A quadratically regularized functional canonical correlation analysis for identifying the global structure of pleiotropy with NGS data

PubMed Central

Zhu, Yun; Fan, Ruzong; Xiong, Momiao

2017-01-01

Investigating the pleiotropic effects of genetic variants can increase statistical power, provide important information to achieve deep understanding of the complex genetic structures of disease, and offer powerful tools for designing effective treatments with fewer side effects. However, the current multiple phenotype association analysis paradigm lacks breadth (number of phenotypes and genetic variants jointly analyzed at the same time) and depth (hierarchical structure of phenotype and genotypes). A key issue for high dimensional pleiotropic analysis is to effectively extract informative internal representation and features from high dimensional genotype and phenotype data. To explore correlation information of genetic variants, effectively reduce data dimensions, and overcome critical barriers in advancing the development of novel statistical methods and computational algorithms for genetic pleiotropic analysis, we proposed a new statistic method referred to as a quadratically regularized functional CCA (QRFCCA) for association analysis which combines three approaches: (1) quadratically regularized matrix factorization, (2) functional data analysis and (3) canonical correlation analysis (CCA). Large-scale simulations show that the QRFCCA has a much higher power than that of the ten competing statistics while retaining the appropriate type 1 errors. To further evaluate performance, the QRFCCA and ten other statistics are applied to the whole genome sequencing dataset from the TwinsUK study. We identify a total of 79 genes with rare variants and 67 genes with common variants significantly associated with the 46 traits using QRFCCA. The results show that the QRFCCA substantially outperforms the ten other statistics. PMID:29040274

Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases

PubMed Central

Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G.; Nalls, Michael A.; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J.; Graff-Radford, Neill R.; Ross, Owen A.; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J.; Halliday, Glenda M.; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K.; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

2016-01-01

The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. PMID:26643944

Ecology has contrasting effects on genetic variation within species versus rates of molecular evolution across species in water beetles.

PubMed

Fujisawa, Tomochika; Vogler, Alfried P; Barraclough, Timothy G

2015-01-22

Comparative analysis is a potentially powerful approach to study the effects of ecological traits on genetic variation and rate of evolution across species. However, the lack of suitable datasets means that comparative studies of correlates of genetic traits across an entire clade have been rare. Here, we use a large DNA-barcode dataset (5062 sequences) of water beetles to test the effects of species ecology and geographical distribution on genetic variation within species and rates of molecular evolution across species. We investigated species traits predicted to influence their genetic characteristics, such as surrogate measures of species population size, latitudinal distribution and habitat types, taking phylogeny into account. Genetic variation of cytochrome oxidase I in water beetles was positively correlated with occupancy (numbers of sites of species presence) and negatively with latitude, whereas substitution rates across species depended mainly on habitat types, and running water specialists had the highest rate. These results are consistent with theoretical predictions from nearly-neutral theories of evolution, and suggest that the comparative analysis using large databases can give insights into correlates of genetic variation and molecular evolution.

Multiple Phenotype Association Tests Using Summary Statistics in Genome-Wide Association Studies

PubMed Central

Liu, Zhonghua; Lin, Xihong

2017-01-01

Summary We study in this paper jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. PMID:28653391

Multiple phenotype association tests using summary statistics in genome-wide association studies.

PubMed

Liu, Zhonghua; Lin, Xihong

2018-03-01

We study in this article jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. © 2017, The International Biometric Society.

Assessing the genetic overlap between BMI and cognitive function

PubMed Central

Marioni, R E; Yang, J; Dykiert, D; Mõttus, R; Campbell, A; Ibrahim-Verbaas, Carla A; Bressler, Jan; Debette, Stephanie; Schuur, Maaike; Smith, Albert V; Davies, Gail; Bennett, David A; Deary, Ian J; Ikram, M Arfan; Launer, Lenore J; Fitzpatrick, Annette L; Seshadri, Sudha; van Duijn, Cornelia M; Mosely Jr, Thomas H; Davies, G; Hayward, C; Porteous, D J; Visscher, P M; Deary, I J

2016-01-01

Obesity and low cognitive function are associated with multiple adverse health outcomes across the life course. They have a small phenotypic correlation (r=−0.11; high body mass index (BMI)−low cognitive function), but whether they have a shared genetic aetiology is unknown. We investigated the phenotypic and genetic correlations between the traits using data from 6815 unrelated, genotyped members of Generation Scotland, an ethnically homogeneous cohort from five sites across Scotland. Genetic correlations were estimated using the following: same-sample bivariate genome-wide complex trait analysis (GCTA)–GREML; independent samples bivariate GCTA–GREML using Generation Scotland for cognitive data and four other samples (n=20 806) for BMI; and bivariate LDSC analysis using the largest genome-wide association study (GWAS) summary data on cognitive function (n=48 462) and BMI (n=339 224) to date. The GWAS summary data were also used to create polygenic scores for the two traits, with within- and cross-trait prediction taking place in the independent Generation Scotland cohort. A large genetic correlation of −0.51 (s.e. 0.15) was observed using the same-sample GCTA–GREML approach compared with −0.10 (s.e. 0.08) from the independent-samples GCTA–GREML approach and −0.22 (s.e. 0.03) from the bivariate LDSC analysis. A genetic profile score using cognition-specific genetic variants accounts for 0.08% (P=0.020) of the variance in BMI and a genetic profile score using BMI-specific variants accounts for 0.42% (P=1.9 × 10−7) of the variance in cognitive function. Seven common genetic variants are significantly associated with both traits at P<5 × 10−5, which is significantly more than expected by chance (P=0.007). All these results suggest there are shared genetic contributions to BMI and cognitive function. PMID:26857597

Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.

PubMed

Duncan, Laramie; Yilmaz, Zeynep; Gaspar, Helena; Walters, Raymond; Goldstein, Jackie; Anttila, Verneri; Bulik-Sullivan, Brendan; Ripke, Stephan; Thornton, Laura; Hinney, Anke; Daly, Mark; Sullivan, Patrick F; Zeggini, Eleftheria; Breen, Gerome; Bulik, Cynthia M

2017-09-01

The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h 2 SNP ]), partitioned heritability, and genetic correlations (r g ) between anorexia nervosa and 159 other phenotypes. Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h 2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort

PubMed Central

Robinson, Elise B.; Kirby, Andrew; Ruparel, Kosha; Yang, Jian; McGrath, Lauren; Anttila, Verneri; Neale, Benjamin M.; Merikangas, Kathleen; Lehner, Thomas; Sleiman, Patrick M.A.; Daly, Mark J.; Gur, Ruben; Gur, Raquel; Hakonarson, Hakon

2014-01-01

The objective of this analysis was to examine the genetic architecture of diverse cognitive abilities in children and adolescents, including the magnitude of common genetic effects and patterns of shared and unique genetic influences. Subjects included 3,689 members of the Philadelphia Neurodevelopmental Cohort, a general population sample of ages 8-21 years who completed an extensive battery of cognitive tests. We used genome-wide complex trait analysis (GCTA) to estimate the SNP-based heritability of each domain, as well as the genetic correlation between all domains that showed significant genetic influence. Several of the individual domains suggested strong influence of common genetic variants (e.g. reading ability, h2g=0.43, p=4e-06; emotion identification, h2g=0.36, p=1e-05; verbal memory, h2g=0.24, p=0.005). The genetic correlations highlighted trait domains that are candidates for joint interrogation in future genetic studies (e.g. language reasoning and spatial reasoning, r(g)=0.72, p=0.007). These results can be used to structure future genetic and neuropsychiatric investigations of diverse cognitive abilities. PMID:25023143

Comment on 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' by Lam et al.

PubMed

Hill, W David

2018-04-01

Intelligence and educational attainment are strongly genetically correlated. This relationship can be exploited by Multi-Trait Analysis of GWAS (MTAG) to add power to Genome-wide Association Studies (GWAS) of intelligence. MTAG allows the user to meta-analyze GWASs of different phenotypes, based on their genetic correlations, to identify association's specific to the trait of choice. An MTAG analysis using GWAS data sets on intelligence and education was conducted by Lam et al. (2017). Lam et al. (2017) reported 70 loci that they described as 'trait specific' to intelligence. This article examines whether the analysis conducted by Lam et al. (2017) has resulted in genetic information about a phenotype that is more similar to education than intelligence.

Multivariate Meta-Analysis of Genetic Association Studies: A Simulation Study

PubMed Central

Neupane, Binod; Beyene, Joseph

2015-01-01

In a meta-analysis with multiple end points of interests that are correlated between or within studies, multivariate approach to meta-analysis has a potential to produce more precise estimates of effects by exploiting the correlation structure between end points. However, under random-effects assumption the multivariate estimation is more complex (as it involves estimation of more parameters simultaneously) than univariate estimation, and sometimes can produce unrealistic parameter estimates. Usefulness of multivariate approach to meta-analysis of the effects of a genetic variant on two or more correlated traits is not well understood in the area of genetic association studies. In such studies, genetic variants are expected to roughly maintain Hardy-Weinberg equilibrium within studies, and also their effects on complex traits are generally very small to modest and could be heterogeneous across studies for genuine reasons. We carried out extensive simulation to explore the comparative performance of multivariate approach with most commonly used univariate inverse-variance weighted approach under random-effects assumption in various realistic meta-analytic scenarios of genetic association studies of correlated end points. We evaluated the performance with respect to relative mean bias percentage, and root mean square error (RMSE) of the estimate and coverage probability of corresponding 95% confidence interval of the effect for each end point. Our simulation results suggest that multivariate approach performs similarly or better than univariate method when correlations between end points within or between studies are at least moderate and between-study variation is similar or larger than average within-study variation for meta-analyses of 10 or more genetic studies. Multivariate approach produces estimates with smaller bias and RMSE especially for the end point that has randomly or informatively missing summary data in some individual studies, when the missing data in the endpoint are imputed with null effects and quite large variance. PMID:26196398

Multivariate Meta-Analysis of Genetic Association Studies: A Simulation Study.

PubMed

Neupane, Binod; Beyene, Joseph

2015-01-01

In a meta-analysis with multiple end points of interests that are correlated between or within studies, multivariate approach to meta-analysis has a potential to produce more precise estimates of effects by exploiting the correlation structure between end points. However, under random-effects assumption the multivariate estimation is more complex (as it involves estimation of more parameters simultaneously) than univariate estimation, and sometimes can produce unrealistic parameter estimates. Usefulness of multivariate approach to meta-analysis of the effects of a genetic variant on two or more correlated traits is not well understood in the area of genetic association studies. In such studies, genetic variants are expected to roughly maintain Hardy-Weinberg equilibrium within studies, and also their effects on complex traits are generally very small to modest and could be heterogeneous across studies for genuine reasons. We carried out extensive simulation to explore the comparative performance of multivariate approach with most commonly used univariate inverse-variance weighted approach under random-effects assumption in various realistic meta-analytic scenarios of genetic association studies of correlated end points. We evaluated the performance with respect to relative mean bias percentage, and root mean square error (RMSE) of the estimate and coverage probability of corresponding 95% confidence interval of the effect for each end point. Our simulation results suggest that multivariate approach performs similarly or better than univariate method when correlations between end points within or between studies are at least moderate and between-study variation is similar or larger than average within-study variation for meta-analyses of 10 or more genetic studies. Multivariate approach produces estimates with smaller bias and RMSE especially for the end point that has randomly or informatively missing summary data in some individual studies, when the missing data in the endpoint are imputed with null effects and quite large variance.

Systematic characterization of Bacillus Genetic Stock Center Bacillus thuringiensis strains using Multi-Locus Sequence Typing.

PubMed

Wang, Kui; Shu, Changlong; Soberón, Mario; Bravo, Alejandra; Zhang, Jie

2018-04-30

The goal of this work was to perform a systematic characterization of Bacillus thuringiensis (Bt) strains from the Bacillus Genetic Stock Center (BGSC) collection using Multi-Locus Sequence Typing (MLST). Different genetic markers of 158 Bacillus thuringiensis (Bt) strains from 73 different serovars stored in the BGSC, that represented 92% of the different Bt serovars of the BGSC were analyzed, the 8% that were not analyzed were not available. In addition, we analyzed 72 Bt strains from 18 serovars available at the pubMLST bcereus database, and Bt strains G03, HBF18 and Bt185, with no H serovars provided by our laboratory. We performed a systematic MLST analysis using seven housekeeping genes (glpF, gmK, ilvD, pta, pur, pycA and tpi) and analyzed correlation of the results of this analysis with strain serovars. The 233 Bt strains analyzed were assigned to 119 STs from which 19 STs were new. Genetic relationships were established by phylogenetic analysis and showed that STs could be grouped in two major Clusters containing 21 sub-groups. We found that a significant number of STs (101 in total) correlated with specific serovars, such as ST13 that corresponded to nine Bt isolates from B. thuringiensis serovar kenyae. However, other serovars showed high genetic variability and correlated with multiple STs; for example, B. thuringiensis serovar morrisoni correlated with 11 different STs. In addition, we found that 16 different STs correlated with multiple serovars (2-4 different serovars); for example, ST12 correlated with B. thuringiensis serovar alesti, dakota, palmanyolensis and sotto/dendrolimus. These data indicated that only partial correspondence between MLST and serotyping can be established. Copyright © 2018 Elsevier Inc. All rights reserved.

A Canonical Correlation Analysis of AIDS Restriction Genes and Metabolic Pathways Identifies Purine Metabolism as a Key Cooperator.

PubMed

Ye, Hanhui; Yuan, Jinjin; Wang, Zhengwu; Huang, Aiqiong; Liu, Xiaolong; Han, Xiao; Chen, Yahong

2016-01-01

Human immunodeficiency virus causes a severe disease in humans, referred to as immune deficiency syndrome. Studies on the interaction between host genetic factors and the virus have revealed dozens of genes that impact diverse processes in the AIDS disease. To resolve more genetic factors related to AIDS, a canonical correlation analysis was used to determine the correlation between AIDS restriction and metabolic pathway gene expression. The results show that HIV-1 postentry cellular viral cofactors from AIDS restriction genes are coexpressed in human transcriptome microarray datasets. Further, the purine metabolism pathway comprises novel host factors that are coexpressed with AIDS restriction genes. Using a canonical correlation analysis for expression is a reliable approach to exploring the mechanism underlying AIDS.

The correlation between reading and mathematics ability at age twelve has a substantial genetic component.

PubMed

Davis, Oliver S P; Band, Gavin; Pirinen, Matti; Haworth, Claire M A; Meaburn, Emma L; Kovas, Yulia; Harlaar, Nicole; Docherty, Sophia J; Hanscombe, Ken B; Trzaskowski, Maciej; Curtis, Charles J C; Strange, Amy; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A Z; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas W; Barroso, Ines; Peltonen, Leena; Dale, Philip S; Petrill, Stephen A; Schalkwyk, Leonard S; Craig, Ian W; Lewis, Cathryn M; Price, Thomas S; Donnelly, Peter; Plomin, Robert; Spencer, Chris C A

2014-07-08

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children's ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child's cognitive abilities at age twelve.

Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.

PubMed

Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G; Nalls, Michael A; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J; Graff-Radford, Neill R; Ross, Owen A; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J; Halliday, Glenda M; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

2016-02-01

The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Integrative analysis of gene expression and copy number alterations using canonical correlation analysis.

PubMed

Soneson, Charlotte; Lilljebjörn, Henrik; Fioretos, Thoas; Fontes, Magnus

2010-04-15

With the rapid development of new genetic measurement methods, several types of genetic alterations can be quantified in a high-throughput manner. While the initial focus has been on investigating each data set separately, there is an increasing interest in studying the correlation structure between two or more data sets. Multivariate methods based on Canonical Correlation Analysis (CCA) have been proposed for integrating paired genetic data sets. The high dimensionality of microarray data imposes computational difficulties, which have been addressed for instance by studying the covariance structure of the data, or by reducing the number of variables prior to applying the CCA. In this work, we propose a new method for analyzing high-dimensional paired genetic data sets, which mainly emphasizes the correlation structure and still permits efficient application to very large data sets. The method is implemented by translating a regularized CCA to its dual form, where the computational complexity depends mainly on the number of samples instead of the number of variables. The optimal regularization parameters are chosen by cross-validation. We apply the regularized dual CCA, as well as a classical CCA preceded by a dimension-reducing Principal Components Analysis (PCA), to a paired data set of gene expression changes and copy number alterations in leukemia. Using the correlation-maximizing methods, regularized dual CCA and PCA+CCA, we show that without pre-selection of known disease-relevant genes, and without using information about clinical class membership, an exploratory analysis singles out two patient groups, corresponding to well-known leukemia subtypes. Furthermore, the variables showing the highest relevance to the extracted features agree with previous biological knowledge concerning copy number alterations and gene expression changes in these subtypes. Finally, the correlation-maximizing methods are shown to yield results which are more biologically interpretable than those resulting from a covariance-maximizing method, and provide different insight compared to when each variable set is studied separately using PCA. We conclude that regularized dual CCA as well as PCA+CCA are useful methods for exploratory analysis of paired genetic data sets, and can be efficiently implemented also when the number of variables is very large.

Human Facial Shape and Size Heritability and Genetic Correlations.

PubMed

Cole, Joanne B; Manyama, Mange; Larson, Jacinda R; Liberton, Denise K; Ferrara, Tracey M; Riccardi, Sheri L; Li, Mao; Mio, Washington; Klein, Ophir D; Santorico, Stephanie A; Hallgrímsson, Benedikt; Spritz, Richard A

2017-02-01

The human face is an array of variable physical features that together make each of us unique and distinguishable. Striking familial facial similarities underscore a genetic component, but little is known of the genes that underlie facial shape differences. Numerous studies have estimated facial shape heritability using various methods. Here, we used advanced three-dimensional imaging technology and quantitative human genetics analysis to estimate narrow-sense heritability, heritability explained by common genetic variation, and pairwise genetic correlations of 38 measures of facial shape and size in normal African Bantu children from Tanzania. Specifically, we fit a linear mixed model of genetic relatedness between close and distant relatives to jointly estimate variance components that correspond to heritability explained by genome-wide common genetic variation and variance explained by uncaptured genetic variation, the sum representing total narrow-sense heritability. Our significant estimates for narrow-sense heritability of specific facial traits range from 28 to 67%, with horizontal measures being slightly more heritable than vertical or depth measures. Furthermore, for over half of facial traits, >90% of narrow-sense heritability can be explained by common genetic variation. We also find high absolute genetic correlation between most traits, indicating large overlap in underlying genetic loci. Not surprisingly, traits measured in the same physical orientation (i.e., both horizontal or both vertical) have high positive genetic correlations, whereas traits in opposite orientations have high negative correlations. The complex genetic architecture of facial shape informs our understanding of the intricate relationships among different facial features as well as overall facial development. Copyright © 2017 by the Genetics Society of America.

Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.

PubMed

Painter, Jodie N; O'Mara, Tracy A; Morris, Andrew P; Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Hodson, Shirley; Jones, Angela; Martin, Nicholas G; Gordon, Scott; Henders, Anjali K; Attia, John; McEvoy, Mark; Holliday, Elizabeth G; Scott, Rodney J; Webb, Penelope M; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Hein, Alexander; Rübner, Matthias; Hall, Per; Czene, Kamila; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo; Lambrechts, Diether; Amant, Frederic; Annibali, Daniela; Depreeuw, Jeroen; Vanderstichele, Adriaan; Goode, Ellen L; Cunningham, Julie M; Dowdy, Sean C; Winham, Stacey J; Trovik, Jone; Hoivik, Erling; Werner, Henrica M J; Krakstad, Camilla; Ashton, Katie; Otton, Geoffrey; Proietto, Tony; Tham, Emma; Mints, Miriam; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Pharoah, Paul D P; Dunning, Alison M; Dennis, Joe; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Zondervan, Krina T; Nyholt, Dale R; MacGregor, Stuart; Montgomery, Grant W; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

2018-05-01

Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (r g  = 0.23, P = 9.3 × 10 -3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10 -3 ) and concordance in effect direction (P = 2.0 × 10 -3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10 -5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10 -8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Evaluation of mature cow weight: genetic correlations with traits used in selection indices, correlated responses, and genetic trends in Nelore cattle.

PubMed

Boligon, A A; Carvalheiro, R; Albuquerque, L G

2013-01-01

Genetic correlations of selection indices and the traits considered in these indices with mature weight (MW) of Nelore females and correlated responses were estimated to determine whether current selection practices will result in an undesired correlated response in MW. Genetic trends for weaning and yearling indices and MW were also estimated. Data from 612,244 Nelore animals born between 1984 and 2010, belonging to different beef cattle evaluation programs from Brazil and Paraguay, were used. The following traits were studied: weaning conformation (WC), weaning precocity (WP), weaning muscling (WM), yearling conformation (YC), yearling precocity (YP), yearling muscling (YM), weaning and yearling indices, BW gain from birth to weaning (BWG), postweaning BW gain (PWG), scrotal circumference (SC), and MW. The variance and covariance components were estimated by Bayesian inference in a multitrait analysis, including all traits in the same analysis, using a nonlinear (threshold) animal model for visual scores and a linear animal model for the other traits. The mean direct heritabilities were 0.21±0.007 (WC), 0.22±0.007 (WP), 0.20±0.007 (WM), 0.43±0.005 (YC), 0.40±0.005 (YP), 0.40±0.005 (YM), 0.17±0.003 (BWG), 0.21±0.004 (PWG), 0.32±0.001 (SC), and 0.44±0.018 (MW). The genetic correlations between MW and weaning and yearling indices were positive and of medium magnitude (0.30±0.01 and 0.31±0.01, respectively). The genetic changes in weaning index, yearling index, and MW, expressed as units of genetic SD per year, were 0.26, 0.27, and 0.01, respectively. The genetic trend for MW was nonsignificant, suggesting no negative correlated response. The selection practice based on the use of sires with high final index giving preference for those better ranked for yearling precocity and muscling than for conformation generates only a minimal correlated response in MW.

Continuity of Genetic and Environmental Influences on Cognition across the Life Span: A Meta-Analysis of Longitudinal Twin and Adoption Studies

PubMed Central

Tucker-Drob, Elliot M.; Briley, Daniel A.

2014-01-01

The longitudinal rank-order stability of cognitive ability increases dramatically over the lifespan. Multiple theoretical perspectives have proposed that genetic and/or environmental mechanisms underlie the longitudinal stability of cognition, and developmental trends therein. However, the patterns of stability of genetic and environmental influences on cognition over the lifespan largely remain poorly understood. We searched for longitudinal studies of cognition that reported raw genetically-informative longitudinal correlations or parameter estimates from longitudinal behavior genetic models. We identified 150 combinations of time points and measures from 15 independent longitudinal samples. In total, longitudinal data came from 4,538 monozygotic twin pairs raised together, 7,777 dizygotic twin pairs raised together, 34 monozygotic twin pairs raised apart, 78 dizygotic twin pairs raised apart, 141 adoptive sibling pairs, and 143 non-adoptive sibling pairs, ranging in age from infancy through late adulthood. At all ages, cross-time genetic correlations and shared environmental correlations were substantially larger than cross-time nonshared environmental correlations. Cross-time correlations for genetic and shared environmental components were low during early childhood, increased sharply over child development, and remained relatively high from adolescence through late adulthood. Cross-time correlations for nonshared environmental components were low across childhood and increased gradually to moderate magnitudes in adulthood. Increasing phenotypic stability over child development was almost entirely mediated by genetic factors. Time-based decay of genetic and shared environmental stability was more pronounced earlier in child development. Results are interpreted in reference to theories of gene-environment interaction and correlation. PMID:24611582

Evaluation of body condition score measured throughout lactation as an indicator of fertility in dairy cattle.

PubMed

Banos, G; Brotherstone, S; Coffey, M P

2004-08-01

Body condition score (BCS) records of primiparous Holstein cows were analyzed both as a single measure per animal and as repeated measures per sire of cow. The former resulted in a single, average, genetic evaluation for each sire, and the latter resulted in separate genetic evaluations per day of lactation. Repeated measure analysis yielded genetic correlations of less than unity between days of lactation, suggesting that BCS may not be the same trait across lactation. Differences between daily genetic evaluations on d 10 or 30 and subsequent daily evaluations were used to assess BCS change at different stages of lactation. Genetic evaluations for BCS level or change were used to estimate genetic correlations between BCS measures and fertility traits in order to assess the capacity of BCS to predict fertility. Genetic correlation estimates with calving interval and non-return rate were consistently higher for daily BCS than single measure BCS evaluations, but results were not always statistically different. Genetic correlations between BCS change and fertility traits were not significantly different from zero. The product of the accuracy of BCS evaluations with their genetic correlation with the UK fertility index, comprising calving interval and non-return rate, was consistently higher for daily than for single BCS evaluations, by 28 to 53%. This product is associated with the conceptual correlated response in fertility from BCS selection and was highest for early (d 10 to 75) evaluations.

Generalist genes and learning disabilities: a multivariate genetic analysis of low performance in reading, mathematics, language and general cognitive ability in a sample of 8000 12-year-old twins.

PubMed

Haworth, Claire M A; Kovas, Yulia; Harlaar, Nicole; Hayiou-Thomas, Marianna E; Petrill, Stephen A; Dale, Philip S; Plomin, Robert

2009-10-01

Our previous investigation found that the same genes influence poor reading and mathematics performance in 10-year-olds. Here we assess whether this finding extends to language and general cognitive disabilities, as well as replicating the earlier finding for reading and mathematics in an older and larger sample. Using a representative sample of 4000 pairs of 12-year-old twins from the UK Twins Early Development Study, we investigated the genetic and environmental overlap between internet-based batteries of language and general cognitive ability tests in addition to tests of reading and mathematics for the bottom 15% of the distribution using DeFries-Fulker extremes analysis. We compared these results to those for the entire distribution. All four traits were highly correlated at the low extreme (average group phenotypic correlation = .58). and in the entire distribution (average phenotypic correlation = .59). Genetic correlations for the low extreme were consistently high (average = .67), and non-shared environmental correlations were modest (average = .23). These results are similar to those seen across the entire distribution (.68 and .23, respectively). The 'Generalist Genes Hypothesis' holds for language and general cognitive disabilities, as well as reading and mathematics disabilities. Genetic correlations were high, indicating a strong degree of overlap in genetic influences on these diverse traits. In contrast, non-shared environmental influences were largely specific to each trait, causing phenotypic differentiation of traits.

Genetic Structure of Bluefin Tuna in the Mediterranean Sea Correlates with Environmental Variables

PubMed Central

Riccioni, Giulia; Stagioni, Marco; Landi, Monica; Ferrara, Giorgia; Barbujani, Guido; Tinti, Fausto

2013-01-01

Background Atlantic Bluefin Tuna (ABFT) shows complex demography and ecological variation in the Mediterranean Sea. Genetic surveys have detected significant, although weak, signals of population structuring; catch series analyses and tagging programs identified complex ABFT spatial dynamics and migration patterns. Here, we tested the hypothesis that the genetic structure of the ABFT in the Mediterranean is correlated with mean surface temperature and salinity. Methodology We used six samples collected from Western and Central Mediterranean integrated with a new sample collected from the recently identified easternmost reproductive area of Levantine Sea. To assess population structure in the Mediterranean we used a multidisciplinary framework combining classical population genetics, spatial and Bayesian clustering methods and a multivariate approach based on factor analysis. Conclusions FST analysis and Bayesian clustering methods detected several subpopulations in the Mediterranean, a result also supported by multivariate analyses. In addition, we identified significant correlations of genetic diversity with mean salinity and surface temperature values revealing that ABFT is genetically structured along two environmental gradients. These results suggest that a preference for some spawning habitat conditions could contribute to shape ABFT genetic structuring in the Mediterranean. However, further studies should be performed to assess to what extent ABFT spawning behaviour in the Mediterranean Sea can be affected by environmental variation. PMID:24260341

Restricted maximum likelihood estimation of genetic principal components and smoothed covariance matrices

PubMed Central

Meyer, Karin; Kirkpatrick, Mark

2005-01-01

Principal component analysis is a widely used 'dimension reduction' technique, albeit generally at a phenotypic level. It is shown that we can estimate genetic principal components directly through a simple reparameterisation of the usual linear, mixed model. This is applicable to any analysis fitting multiple, correlated genetic effects, whether effects for individual traits or sets of random regression coefficients to model trajectories. Depending on the magnitude of genetic correlation, a subset of the principal component generally suffices to capture the bulk of genetic variation. Corresponding estimates of genetic covariance matrices are more parsimonious, have reduced rank and are smoothed, with the number of parameters required to model the dispersion structure reduced from k(k + 1)/2 to m(2k - m + 1)/2 for k effects and m principal components. Estimation of these parameters, the largest eigenvalues and pertaining eigenvectors of the genetic covariance matrix, via restricted maximum likelihood using derivatives of the likelihood, is described. It is shown that reduced rank estimation can reduce computational requirements of multivariate analyses substantially. An application to the analysis of eight traits recorded via live ultrasound scanning of beef cattle is given. PMID:15588566

Heritability and genetic correlation between GERD symptoms severity, metabolic syndrome, and inflammation markers in families living in Mexico City.

PubMed

Reding-Bernal, Arturo; Sánchez-Pedraza, Valentin; Moreno-Macías, Hortensia; Sobrino-Cossio, Sergio; Tejero-Barrera, María Elizabeth; Burguete-García, Ana Isabel; León-Hernández, Mireya; Serratos-Canales, María Fabiola; Duggirala, Ravindranath; López-Alvarenga, Juan Carlos

2017-01-01

The aim of this study was to estimate the heritability (h2) and genetic correlation (ρG) between GERD symptoms severity, metabolic syndrome components, and inflammation markers in Mexican families. Cross-sectional study which included 32 extended families resident in Mexico City. GERD symptoms severity was assessed by the ReQuest in Practice questionnaire. Heritability and genetic correlation were determined using the Sequential Oligogenic Linkage Analysis Routines software. 585 subjects were included, the mean age was 42 (±16.7) years, 57% were women. The heritability of the severity of some GERD symptoms was h2 = 0.27, 0.27, 0.37, and 0.34 (p-value <1.0x10-5) for acidity complaints, lower abdominal complaints, sleep disturbances, and total ReQuest score, respectively. Heritability of metabolic syndrome components ranged from 0.40 for fasting plasma glucose to 0.61 for body mass index and diabetes mellitus. The heritability for fibrinogen and C-reactive protein was 0.64 and 0.38, respectively. Statistically significant genetic correlations were found between acidity complaints and fasting plasma glucose (ρG = 0.40); sleep disturbances and fasting plasma glucose (ρG = 0.36); acidity complaints and diabetes mellitus (ρG = 0.49) and between total ReQuest score and fasting plasma glucose (ρG = 0.43). The rest of metabolic syndrome components did not correlate with GERD symptoms. Genetic factors substantially explain the phenotypic variance of the severity of some GERD symptoms, metabolic syndrome components and inflammation markers. Observed genetic correlations suggest that these phenotypes share common genes. These findings suggest conducting further investigation, as the determination of a linkage analysis in order to identify regions of susceptibility for developing of GERD and metabolic syndrome.

Heritability and genetic correlation between GERD symptoms severity, metabolic syndrome, and inflammation markers in families living in Mexico City

PubMed Central

Reding-Bernal, Arturo; Sánchez-Pedraza, Valentin; Moreno-Macías, Hortensia; Sobrino-Cossio, Sergio; Tejero-Barrera, María Elizabeth; Burguete-García, Ana Isabel; León-Hernández, Mireya; Serratos-Canales, María Fabiola; Duggirala, Ravindranath; López-Alvarenga, Juan Carlos

2017-01-01

Objective The aim of this study was to estimate the heritability (h2) and genetic correlation (ρG) between GERD symptoms severity, metabolic syndrome components, and inflammation markers in Mexican families. Methods Cross-sectional study which included 32 extended families resident in Mexico City. GERD symptoms severity was assessed by the ReQuest in Practice questionnaire. Heritability and genetic correlation were determined using the Sequential Oligogenic Linkage Analysis Routines software. Results 585 subjects were included, the mean age was 42 (±16.7) years, 57% were women. The heritability of the severity of some GERD symptoms was h2 = 0.27, 0.27, 0.37, and 0.34 (p-value <1.0x10-5) for acidity complaints, lower abdominal complaints, sleep disturbances, and total ReQuest score, respectively. Heritability of metabolic syndrome components ranged from 0.40 for fasting plasma glucose to 0.61 for body mass index and diabetes mellitus. The heritability for fibrinogen and C-reactive protein was 0.64 and 0.38, respectively. Statistically significant genetic correlations were found between acidity complaints and fasting plasma glucose (ρG = 0.40); sleep disturbances and fasting plasma glucose (ρG = 0.36); acidity complaints and diabetes mellitus (ρG = 0.49) and between total ReQuest score and fasting plasma glucose (ρG = 0.43). The rest of metabolic syndrome components did not correlate with GERD symptoms. Conclusion Genetic factors substantially explain the phenotypic variance of the severity of some GERD symptoms, metabolic syndrome components and inflammation markers. Observed genetic correlations suggest that these phenotypes share common genes. These findings suggest conducting further investigation, as the determination of a linkage analysis in order to identify regions of susceptibility for developing of GERD and metabolic syndrome. PMID:28582452

Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis.

PubMed

Aschard, Hugues; Kang, Jae H; Iglesias, Adriana I; Hysi, Pirro; Cooke Bailey, Jessica N; Khawaja, Anthony P; Allingham, R Rand; Ashley-Koch, Allison; Lee, Richard K; Moroi, Sayoko E; Brilliant, Murray H; Wollstein, Gadi; Schuman, Joel S; Fingert, John H; Budenz, Donald L; Realini, Tony; Gaasterland, Terry; Scott, William K; Singh, Kuldev; Sit, Arthur J; Igo, Robert P; Song, Yeunjoo E; Hark, Lisa; Ritch, Robert; Rhee, Douglas J; Gulati, Vikas; Haven, Shane; Vollrath, Douglas; Zack, Donald J; Medeiros, Felipe; Weinreb, Robert N; Cheng, Ching-Yu; Chasman, Daniel I; Christen, William G; Pericak-Vance, Margaret A; Liu, Yutao; Kraft, Peter; Richards, Julia E; Rosner, Bernard A; Hauser, Michael A; Klaver, Caroline C W; vanDuijn, Cornelia M; Haines, Jonathan; Wiggs, Janey L; Pasquale, Louis R

2017-11-01

Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 × 10 -27 ) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 × 10 -5 ); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.

Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

PubMed

Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

2016-03-01

Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility disorders were those between BCS and MET in both first and later lactations. Results indicated a limited value of a joint genetic evaluation model for metabolic disease traits and fertility disorders in Canadian Holsteins. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Fatty Acid Diversity is Not Associated with Neutral Genetic Diversity in Native Populations of the Biodiesel Plant Jatropha curcas L.

PubMed

Martínez-Díaz, Yesenia; González-Rodríguez, Antonio; Rico-Ponce, Héctor Rómulo; Rocha-Ramírez, Víctor; Ovando-Medina, Isidro; Espinosa-García, Francisco J

2017-01-01

Jatropha curcas L. (Euphorbiaceae) is a shrub native to Mexico and Central America, which produces seeds with a high oil content that can be converted to biodiesel. The genetic diversity of this plant has been widely studied, but it is not known whether the diversity of the seed oil chemical composition correlates with neutral genetic diversity. The total seed oil content, the diversity of profiles of fatty acids and phorbol esters were quantified, also, the genetic diversity obtained from simple sequence repeats was analyzed in native populations of J. curcas in Mexico. Using the fatty acids profiles, a discriminant analysis recognized three groups of individuals according to geographical origin. Bayesian assignment analysis revealed two genetic groups, while the genetic structure of the populations could not be explained by isolation-by-distance. Genetic and fatty acid profile data were not correlated based on Mantel test. Also, phorbol ester content and genetic diversity were not associated. Multiple linear regression analysis showed that total oil content was associated with altitude and seasonality of temperature. The content of unsaturated fatty acids was associated with altitude. Therefore, the cultivation planning of J. curcas should take into account chemical variation related to environmental factors. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Genetic relationships among body condition score, body weight, milk yield, and fertility in dairy cows.

PubMed

Berry, D P; Buckley, F; Dillon, P; Evans, R D; Rath, M; Veerkamp, R F

2003-06-01

Genetic (co)variances between body condition score (BCS), body weight (BW), milk production, and fertility-related traits were estimated. The data analyzed included 8591 multiparous Holstein-Friesian cows with records for BCS, BW, milk production, and/or fertility from 78 seasonal calving grass-based farms throughout southern Ireland. Of the cows included in the analysis, 4402 had repeated records across the 2 yr of the study. Genetic correlations between level of BCS at different stages of lactation and total lactation milk production were negative (-0.51 to -0.14). Genetic correlations between BW at different stages of lactation and total lactation milk production were all close to zero but became positive (0.01 to 0.39) after adjusting BW for differences in BCS. Body condition score at different stages of lactation correlated favorably with improved fertility; genetic correlations between BCS and pregnant 63 d after the start of breeding season ranged from 0.29 to 0.42. Both BW at different stages of lactation and milk production tended to exhibit negative genetic correlations with pregnant to first service and pregnant 63 d after the start of the breeding season and positive genetic correlations with number of services and the interval from first service to conception. Selection indexes investigated illustrate the possibility of continued selection for increased milk production without any deleterious effects on fertility or average BCS, albeit, genetic merit for milk production would increase at a slower rate.

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

PubMed Central

Davis, Oliver S. P.; Band, Gavin; Pirinen, Matti; Haworth, Claire M. A.; Meaburn, Emma L.; Kovas, Yulia; Harlaar, Nicole; Docherty, Sophia J.; Hanscombe, Ken B.; Trzaskowski, Maciej; Curtis, Charles J. C.; Strange, Amy; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C.; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J.; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A. Z.; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Barroso, Ines; Peltonen, Leena; Dale, Philip S.; Petrill, Stephen A.; Schalkwyk, Leonard S.; Craig, Ian W.; Lewis, Cathryn M.; Price, Thomas S.; Donnelly, Peter; Plomin, Robert; Spencer, Chris C. A.

2014-01-01

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve. PMID:25003214

Genetic analysis of motor milestones attainment in early childhood.

PubMed

Peter, I; Vainder, M; Livshits, G

1999-03-01

The age of attainment for four motor developmental traits, such as turning over, sitting up without support, pulling up to a standing position and walking without support, was examined in 822 children, including 626 siblings from families with 2 to 6 children, 68 pairs of dizygotic twins and 30 pairs of monozygotic twins. Correlation analysis, carried out separately for each type of sibship, showed the highest pairwise correlations in monozygotic twins and the lowest correlation in non-twin siblings for all motor milestones. Variance component analysis was used to decompose the different independent components forming the variation of the studied trait, such as genetic effect, common twin environment, common sib environment and residual factors. The results revealed that the major proportion of the total variance after adjustment for gestation age for the attainment of each motor skill, except pulling up to standing position, is explained by the common twin environment (50.5 to 66.6%), whilst a moderate proportion is explained by additive genetic factors (22.2 to 33.5%). Gestational age was found to be an important predictor of appearance of all motor milestones, affecting delay of 4.5 to 8.6 days for the attainment of the motor abilities for each week of earlier gestation. The age of attainment of the standing position was affected only by shared sibs environment (33.3% of the total variance) and showed no influence of either genetic or common twin environment. Phenotypic between trait correlations were high and significant for all studied traits (range between 0.40 and 0.67, P < 0.01 in all instances). Genetic cross correlations, however, were not easily interpreted and did not show clear variance trends among the different groups of children.

Genetic analysis of a red tilapia (Oreochromis spp.) population undergoing three generations of selection for increased body weight at harvest.

PubMed

Hamzah, Azhar; Thoa, Ngo Phu; Nguyen, Nguyen Hong

2017-11-01

Quantitative genetic analysis was performed on 10,919 data records collected over three generations from the selection programme for increased body weight at harvest in red tilapia (Oreochromis spp.). They were offspring of 224 sires and 226 dams (50 sires and 60 dams per generation, on average). Linear mixed models were used to analyse body traits (weight, length, width and depth), whereas threshold generalised models assuming probit distribution were employed to examine genetic inheritance of survival rate, sexual maturity and body colour. The estimates of heritability for traits studied (body weight, standard length, body width, body depth, body colour, early sexual maturation and survival) across statistical models were moderate to high (0.13-0.45). Genetic correlations among body traits and survival were high and positive (0.68-0.96). Body length and width exhibited negative genetic correlations with body colour (- 0.47 to - 0.25). Sexual maturity was genetically correlated positively with measurements of body traits (weight and length). Direct and correlated genetic responses to selection were measured as estimated breeding values in each generation and expressed in genetic standard deviation units (σ G ). The cumulative improvement achieved for harvest body weight was 1.72 σ G after three generations or 12.5% per generation when the gain was expressed as a percentage of the base population. Selection for improved body weight also resulted in correlated increase in other body traits (length, width and depth) and survival rate (ranging from 0.25 to 0.81 genetic standard deviation units). Avoidance of black spot parent matings also improved the overall red colour of the selected population. It is concluded that the selective breeding programme for red tilapia has succeeded in achieving significant genetic improvement for a range of commercially important traits in this species, and the large genetic variation in body colour and survival also shows that there are prospects for future improvement of these traits in this population of red tilapia.

Analysis of genetic correlations of hip height with selection indices and mature weight in Nelore cattle.

PubMed

Boligon, A A; Carvalheiro, R; Ayres, D R; Albuquerque, L G

2013-02-01

Body size is directly related to the productive and reproductive performance of beef cattle raised under free-range conditions. In an attempt to better plan selection criteria, avoiding extremes in body size, this study estimated the heritabilities and genetic correlations of yearling hip height (YH) and mature hip height (MH) with selection indices obtained at weaning (WI) and yearling (YI) and mature weight (MW). Data from 102,373 Nelore animals born between 1984 and 2010, which belong to 263 farms that participate in genetic evaluation programmes of beef cattle conducted in Brazil and Paraguay, were used. The (co)variance components and genetic parameters were estimated by Bayesian inference in multi-trait analysis using an animal model. The mean heritabilities for YH, MH and MW were 0.56 ± 0.06, 0.47 ± 0.02 and 0.42 ± 0.02, respectively. The genetic correlation of YH with WI (0.13 ± 0.01) and YI (0.11 ± 0.01) was practically zero, whereas a higher correlation was observed with MW (0.22 ± 0.03). Positive genetic correlations of medium magnitude were estimated between MH and WI and YI (0.23 ± 0.01 and 0.43 ± 0.02, respectively). On the other hand, a high genetic correlation (0.68 ± 0.03) was observed between the indicator traits of mature body size (MH and MW). Considering the top 20 % of sire (896 sires) in terms of breeding values for the yearling index, the rank sire correlations between breeding values for MH and MW was 0.62. In general, the results indicate that selection based on WI and YI should not lead to important changes in YH. However, an undesired correlated response in mature cow height is expected, particularly when selection is performed using YI. Therefore, changes in the body structure of Nelore females can be obtained when MH and MW is used as a selection criterion for cows.

Cross-Disorder Genetic Analysis of Tic Disorders, Obsessive-Compulsive, and Hoarding Symptoms.

PubMed

Zilhão, Nuno R; Smit, Dirk J; Boomsma, Dorret I; Cath, Danielle C

2016-01-01

Hoarding, obsessive-compulsive disorder (OCD), and Tourette's disorder (TD) are psychiatric disorders that share symptom overlap, which might partly be the result of shared genetic variation. Population-based twin studies have found significant genetic correlations between hoarding and OCD symptoms, with genetic correlations varying between 0.1 and 0.45. For tic disorders, studies examining these correlations are lacking. Other lines of research, including clinical samples and GWAS or CNV data to explore genetic relationships between tic disorders and OCD, have only found very modest if any shared genetic variation. Our aim was to extend current knowledge on the genetic structure underlying hoarding, OC symptoms (OCS), and lifetime tic symptoms and, in a trivariate analysis, assess the degree of common and unique genetic factors contributing to the etiology of these disorders. Data have been gathered from participants in the Netherlands Twin Register comprising a total of 5293 individuals from a sample of adult monozygotic (n = 2460) and dizygotic (n = 2833) twin pairs (mean age 33.61 years). The data on Hoarding, OCS, and tic symptoms were simultaneously analyzed in Mplus. A liability threshold model was fitted to the twin data, analyzing heritability of phenotypes and of their comorbidity. Following the criteria for a probable clinical diagnosis in all phenotypes, 6.8% of participants had a diagnosis of probable hoarding disorder (HD), 6.3% of OCS, and 12.8% of any probable lifetime tic disorder. Genetic factors explained 50.4, 70.1, and 61.1% of the phenotypic covariance between hoarding-OCS, hoarding-tics, and OCS-tics, respectively. Substantial genetic correlations were observed between hoarding and OCS (0.41), hoarding and tics (0.35), and between OCS and tics (0.37). These results support the contribution of genetic factors in the development of these disorders and their comorbidity. Furthermore, tics were mostly influenced by specific environmental factors unshared with OCS and HD.

Population genetic analysis and bioclimatic modeling in Agave striata in the Chihuahuan Desert indicate higher genetic variation and lower differentiation in drier and more variable environments.

PubMed

Trejo, Laura; Alvarado-Cárdenas, Leonardo O; Scheinvar, Enrique; Eguiarte, Luis E

2016-06-01

Is there an association between bioclimatic variables and genetic variation within species? This question can be approached by a detailed analysis of population genetics parameters along environmental gradients in recently originated species (so genetic drift does not further obscure the patterns). The genus Agave, with more than 200 recent species encompassing a diversity of morphologies and distributional patterns, is an adequate system for such analyses. We studied Agave striata, a widely distributed species from the Chihuahuan Desert, with a distinctive iteroparous reproductive ecology and two recognized subspecies with clear morphological differences. We used population genetic analyses along with bioclimatic studies to understand the effect of environment on the genetic variation and differentiation of this species. We analyzed six populations of the subspecies A. striata subsp. striata, with a southern distribution, and six populations of A. striata subsp. falcata, with a northern distribution, using 48 ISSR loci and a total of 541 individuals (averaging 45 individuals per population). We assessed correlations between population genetics parameters (the levels of genetic variation and differentiation) and the bioclimatic variables of each population. We modeled each subspecies distribution and used linear correlations and multifactorial analysis of variance. Genetic variation (measured as expected heterozygosity) increased at higher latitudes. Higher levels of genetic variation in populations were associated with a higher variation in environmental temperature and lower precipitation. Stronger population differentiation was associated with wetter and more variable precipitation in the southern distribution of the species. The two subspecies have genetic differences, which coincide with their climatic differences and potential distributions. Differences in genetic variation among populations and the genetic differentiation between A. striata subsp. striata and A. striata subsp. falcata is correlated with differences in environmental climatic variables along their distribution. We found two distinct gene pools that suggest active differentiation and perhaps incipient speciation. The detected association between genetic variation and environment variables indicates that climatic variables are playing an important role in the differentiation of A. striata. © 2016 Botanical Society of America.

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

PubMed Central

Lo, Min-Tzu; Hinds, David A.; Tung, Joyce Y.; Franz, Carol; Fan, Chun-Chieh; Wang, Yunpeng; Smeland, Olav B.; Schork, Andrew; Holland, Dominic; Kauppi, Karolina; Sanyal, Nilotpal; Escott-Price, Valentina; Smith, Daniel J.; O'Donovan, Michael; Stefansson, Hreinn; Bjornsdottir, Gyda; Thorgeirsson, Thorgeir E.; Stefansson, Kari; McEvoy, Linda K.; Dale, Anders M.; Andreassen, Ole A.; Chen, Chi-Hua

2017-01-01

Summary Personality is influenced by genetic and environmental factors1, and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N=123,132–260,861). Of these genome-wide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N=5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit/hyperactivity disorder (ADHD), and between openness and schizophrenia/bipolar disorder. The second genetic dimension was closely aligned with extraversion-introversion and grouped neuroticism with internalizing psychopathology (e.g., depression/anxiety). PMID:27918536

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders.

PubMed

Lo, Min-Tzu; Hinds, David A; Tung, Joyce Y; Franz, Carol; Fan, Chun-Chieh; Wang, Yunpeng; Smeland, Olav B; Schork, Andrew; Holland, Dominic; Kauppi, Karolina; Sanyal, Nilotpal; Escott-Price, Valentina; Smith, Daniel J; O'Donovan, Michael; Stefansson, Hreinn; Bjornsdottir, Gyda; Thorgeirsson, Thorgeir E; Stefansson, Kari; McEvoy, Linda K; Dale, Anders M; Andreassen, Ole A; Chen, Chi-Hua

2017-01-01

Personality is influenced by genetic and environmental factors and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132-260,861). Of these genome-wide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422-18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit-hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion-introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety).

Large-scale longitudinal gradients of genetic diversity: a meta-analysis across six phyla in the Mediterranean basin

PubMed Central

Conord, Cyrille; Gurevitch, Jessica; Fady, Bruno

2012-01-01

Biodiversity is the diversity of life at all scales, from genes to ecosystems. Predicting its patterns of variation across the globe is a fundamental issue in ecology and evolution. Diversity within species, that is, genetic diversity, is of prime importance for understanding past and present evolutionary patterns, and highlighting areas where conservation might be a priority. Using published data on the genetic diversity of species whose populations occur in the Mediterranean basin, we calculated a coefficient of correlation between within-population genetic diversity indices and longitude. Using a meta-analysis framework, we estimated the role of biological, ecological, biogeographic, and marker type factors on the strength and magnitude of this correlation in six phylla. Overall, genetic diversity increases from west to east in the Mediterranean basin. This correlation is significant for both animals and plants, but is not uniformly expressed for all groups. It is stronger in the southern than in the northern Mediterranean, in true Mediterranean plants than in plants found at higher elevations, in trees than in other plants, and in bi-parentally and paternally than in maternally inherited DNA makers. Overall, this correlation between genetic diversity and longitude, and its patterns across biological and ecological traits, suggests the role of two non-mutually exclusive major processes that shaped the genetic diversity in the Mediterranean during and after the cold periods of the Pleistocene: east-west recolonization during the Holocene and population size contraction under local Last Glacial Maximum climate in resident western and low elevation Mediterranean populations. PMID:23145344

Pitfalls in genetic analysis of pheochromocytomas/paragangliomas-case report.

PubMed

Canu, Letizia; Rapizzi, Elena; Zampetti, Benedetta; Fucci, Rossella; Nesi, Gabriella; Richter, Susan; Qin, Nan; Giachè, Valentino; Bergamini, Carlo; Parenti, Gabriele; Valeri, Andrea; Ercolino, Tonino; Eisenhofer, Graeme; Mannelli, Massimo

2014-07-01

About 35% of patients with pheochromocytoma/paraganglioma carry a germline mutation in one of the 10 main susceptibility genes. The recent introduction of next-generation sequencing will allow the analysis of all these genes in one run. When positive, the analysis is generally unequivocal due to the association between a germline mutation and a concordant clinical presentation or positive family history. When genetic analysis reveals a novel mutation with no clinical correlates, particularly in the presence of a missense variant, the question arises whether the mutation is pathogenic or a rare polymorphism. We report the case of a 35-year-old patient operated for a pheochromocytoma who turned out to be a carrier of a novel SDHD (succinate dehydrogenase subunit D) missense mutation. With no positive family history or clinical correlates, we decided to perform additional analyses to test the clinical significance of the mutation. We performed in silico analysis, tissue loss of heterozygosity analysis, immunohistochemistry, Western blot analysis, SDH enzymatic assay, and measurement of the succinate/fumarate concentration ratio in the tumor tissue by tandem mass spectrometry. Although the in silico analysis gave contradictory results according to the different methods, all the other tests demonstrated that the SDH complex was conserved and normally active. We therefore came to the conclusion that the variant was a nonpathogenic polymorphism. Advancements in technology facilitate genetic analysis of patients with pheochromocytoma but also offer new challenges to the clinician who, in some cases, needs clinical correlates and/or functional tests to give significance to the results of the genetic assay.

How do emotional restrictions affect the use of humor? A behavior genetic analysis of alexithymia and humor styles.

PubMed

Atkinson, Breanna E; Lipton, Debra; Baughman, Holly M; Schermer, Julie A; Harris, Juliette; Vernon, Philip A

2015-04-01

This article reports the first behavioral genetic study of relationships between alexithymia and four styles of humor: affiliative, self-enhancing, self-defeating, and aggressive. A total of 509 MZ pairs and 264 DZ pairs of twins completed the Toronto Alexithymia Scale-20 (TAS-20) and the Humor Styles Questionnaire (HSQ). Consistent with our predictions, alexithymia correlated negatively with affiliative and self-enhancing humor and positively with self-defeating and aggressive humor. All but one of the 16 phenotypic correlations that we report are significant at the 0.01 level. Also consistent with our predictions, the phenotypic correlations between alexithymia and humor styles were primarily attributable to correlated genetic factors and to a lesser extent to correlated non-shared environmental factors. Correlated shared environmental factors had no significant effect. Implications and limitations of this study are discussed.

LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis.

PubMed

Zheng, Jie; Erzurumluoglu, A Mesut; Elsworth, Benjamin L; Kemp, John P; Howe, Laurence; Haycock, Philip C; Hemani, Gibran; Tansey, Katherine; Laurin, Charles; Pourcain, Beate St; Warrington, Nicole M; Finucane, Hilary K; Price, Alkes L; Bulik-Sullivan, Brendan K; Anttila, Verneri; Paternoster, Lavinia; Gaunt, Tom R; Evans, David M; Neale, Benjamin M

2017-01-15

LD score regression is a reliable and efficient method of using genome-wide association study (GWAS) summary-level results data to estimate the SNP heritability of complex traits and diseases, partition this heritability into functional categories, and estimate the genetic correlation between different phenotypes. Because the method relies on summary level results data, LD score regression is computationally tractable even for very large sample sizes. However, publicly available GWAS summary-level data are typically stored in different databases and have different formats, making it difficult to apply LD score regression to estimate genetic correlations across many different traits simultaneously. In this manuscript, we describe LD Hub - a centralized database of summary-level GWAS results for 173 diseases/traits from different publicly available resources/consortia and a web interface that automates the LD score regression analysis pipeline. To demonstrate functionality and validate our software, we replicated previously reported LD score regression analyses of 49 traits/diseases using LD Hub; and estimated SNP heritability and the genetic correlation across the different phenotypes. We also present new results obtained by uploading a recent atopic dermatitis GWAS meta-analysis to examine the genetic correlation between the condition and other potentially related traits. In response to the growing availability of publicly accessible GWAS summary-level results data, our database and the accompanying web interface will ensure maximal uptake of the LD score regression methodology, provide a useful database for the public dissemination of GWAS results, and provide a method for easily screening hundreds of traits for overlapping genetic aetiologies. The web interface and instructions for using LD Hub are available at http://ldsc.broadinstitute.org/ CONTACT: jie.zheng@bristol.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Genetic analysis of fat-to-protein ratio, milk yield and somatic cell score of Holstein cows in Japan in the first three lactations by using a random regression model.

PubMed

Nishiura, Akiko; Sasaki, Osamu; Aihara, Mitsuo; Takeda, Hisato; Satoh, Masahiro

2015-12-01

We estimated the genetic parameters of fat-to-protein ratio (FPR) and the genetic correlations between FPR and milk yield or somatic cell score in the first three lactations in dairy cows. Data included 3,079,517 test-day records of 201,138 Holstein cows in Japan from 2006 to 2011. Genetic parameters were estimated with a multiple-trait random regression model in which the records within and between parities were treated as separate traits. The phenotypic values of FPR increased soon after parturition and peaked at 10 to 20 days in milk, then decreased slowly in mid- and late lactation. Heritability estimates for FPR yielded moderate values. Genetic correlations of FPR among parities were low in early lactation. Genetic correlations between FPR and milk yield were positive and low in early lactation, but only in the first lactation. Genetic correlations between FPR and somatic cell score were positive in early lactation and decreased to become negative in mid- to late lactation. By using these results for genetic evaluation it should be possible to improve energy balance in dairy cows. © 2015 Japanese Society of Animal Science.

Correlation of genetic risk and messenger RNA expression in a Th17/IL23 pathway analysis in inflammatory bowel disease.

PubMed

Fransen, Karin; van Sommeren, Suzanne; Westra, Harm-Jan; Veenstra, Monique; Lamberts, Letitia E; Modderman, Rutger; Dijkstra, Gerard; Fu, Jingyuan; Wijmenga, Cisca; Franke, Lude; Weersma, Rinse K; van Diemen, Cleo C

2014-05-01

The Th17/IL23 pathway has both genetically and biologically been implicated in the pathogenesis of the inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis. So far, it is unknown whether and how associated risk variants affect expression of the genes encoding for Th17/IL23 pathway proteins. Ten IBD-associated SNPs residing near Th17/IL23 genes were used to construct a genetic risk model in 753 Dutch IBD cases and 1045 controls. In an independent cohort of 40 Crohn's disease, 40 ulcerative colitis, and 40 controls, the genetic risk load and presence of IBD were correlated to quantitative PCR-generated messenger RNA (mRNA) expression of 9 representative Th17/IL23 genes in both unstimulated and PMA/CaLo stimulated peripheral blood mononuclear cells. In 1240 individuals with various immunological diseases with whole genome genotype and mRNA-expression data, we also assessed correlation between genetic risk load and differential mRNA expression and sought for SNPs affecting expression of all currently known Th17/IL23 pathway genes (cis-expression quantitative trait locus). The presence of IBD, but not the genetic risk load, was correlated to differential mRNA expression for IL6 in unstimulated peripheral blood mononuclear cells and to IL23A and RORC in response to stimulation. The cis-expression quantitative trait locus analysis showed little evidence for correlation between genetic risk load and mRNA expression of Th17/IL23 genes, because we identified for only 2 of 22 Th17/IL23 genes a cis-expression quantitative trait locus single nucleotide polymorphism that is also associated to IBD (STAT3 and CCR6). Our results suggest that only the presence of IBD and not the genetic risk load alters mRNA expression levels of IBD-associated Th17/IL23 genes.

Comparative analyses of genetic/epigenetic diversities and structures in a wild barley species (Hordeum brevisubulatum) using MSAP, SSAP and AFLP.

PubMed

Shan, X H; Li, Y D; Liu, X M; Wu, Y; Zhang, M Z; Guo, W L; Liu, B; Yuan, Y P

2012-08-17

We analyzed genetic diversity and population genetic structure of four artificial populations of wild barley (Hordeum brevisubulatum); 96 plants collected from the Songnen Prairie in northeastern China were analyzed using amplified fragment length polymorphism (AFLP), specific-sequence amplified polymorphism (SSAP) and methylation-sensitive amplified polymorphism (MSAP) markers. Indices of (epi-)genetic diversity, (epi-)genetic distance, gene flow, genotype frequency, cluster analysis, PCA analysis and AMOVA analysis generated from MSAP, AFLP and SSAP markers had the same trend. We found a high level of correlation in the artificial populations between MSAP, SSAP and AFLP markers by the Mantel test (r > 0.8). This is incongruent with previous findings showing that there is virtually no correlation between DNA methylation polymorphism and classical genetic variation; the high level of genetic polymorphism could be a result of epigenetic regulation. We compared our results with data from natural populations. The population diversity of the artificial populations was lower. However, different from what was found using AFLP and SSAP, based on MSAP results the methylation polymorphism of the artificial populations was not significantly reduced. This leads us to suggest that the DNA methylation pattern change in H. brevisubulatum populations is not only related to DNA sequence variation, but is also regulated by other controlling systems.

Genetic variation and correlated changes in reproductive performance of a red tilapia line selected for improved growth over three generations.

PubMed

Thoa, Ngo Phu; Hamzah, Azhar; Nguyen, Nguyen Hong

2017-09-01

The present study examines genetic variation and correlated changes in reproductive performance traits in a red tilapia (Oreochromis spp.) population selected over three generations for improved growth. A total of 328 breeding females (offspring of 111 sires and 118 dams) had measurements of body weight prior to spawning (WBS), number of fry at hatching (NFH), total fry weight (TFW) and number of dead fry (NDF) or mortality of fry including unhatched eggs at hatching (MFH). Restricted maximum likelihood (REML) analysis in a multi-trait model showed that there are heritable genetic components for all traits studied. The heritability for WBS was very high (0.80). The estimates for traits related to fecundity (NFH, TFW) and survival (NDF) were low and they were associated with high standard errors. Genetic correlations of WBS with other reproductive performance traits (NFH, TFW and NDF) were generally positive. However, NFH was negatively correlated genetically with TFW. As expected, body measurements during growth stage exhibited strong positive genetic correlations with WBS. The genetic correlations between body traits and reproductive performance (NFH, TFW, NDF) were not significant. Correlated responses in reproductive traits were measured as changes in least squares means between generations or spawning years. Except for WBS that increased with the selection programs, the phenotypic changes in other reproductive traits observed were not statistically significant (P>0.05). It is concluded that the selection program for red tilapia has resulted in very little changes in reproductive performance of the animals after three generations. However, periodic monitoring of genetic changes in fecundity and fitness related traits such as NDF or MFH should be made in selective breeding programs for red tilapia. Copyright © 2017 Elsevier B.V. All rights reserved.

Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size.

PubMed

Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T; Weiss, Kenneth M; Mahaney, Michael C; Rogers, Jeffrey; Cheverud, James M

2018-02-01

Determining the genetic architecture of quantitative traits and genetic correlations among them is important for understanding morphological evolution patterns. We address two questions regarding papionin evolution: (1) what effect do body and cranial size, age, and sex have on phenotypic (V P ) and additive genetic (V A ) variation in baboon crania, and (2) how might additive genetic correlations between craniofacial traits and body mass affect morphological evolution? We use a large captive pedigreed baboon sample to estimate quantitative genetic parameters for craniofacial dimensions (EIDs). Our models include nested combinations of the covariates listed above. We also simulate the correlated response of a given EID due to selection on body mass alone. Covariates account for 1.2-91% of craniofacial V P . EID V A decreases across models as more covariates are included. The median genetic correlation estimate between each EID and body mass is 0.33. Analysis of the multivariate response to selection reveals that observed patterns of craniofacial variation in extant baboons cannot be attributed solely to correlated response to selection on body mass, particularly in males. Because a relatively large proportion of EID V A is shared with body mass variation, different methods of correcting for allometry by statistically controlling for size can alter residual V P patterns. This may conflate direct selection effects on craniofacial variation with those resulting from a correlated response to body mass selection. This shared genetic variation may partially explain how selection for increased body mass in two different papionin lineages produced remarkably similar craniofacial phenotypes. © 2017 Wiley Periodicals, Inc.

Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes.

PubMed

Mosley, Jonathan D; Shoemaker, M Benjamin; Wells, Quinn S; Darbar, Dawood; Shaffer, Christian M; Edwards, Todd L; Bastarache, Lisa; McCarty, Catherine A; Thompson, Will; Chute, Christopher G; Jarvik, Gail P; Crosslin, David R; Larson, Eric B; Kullo, Iftikhar J; Pacheco, Jennifer A; Peissig, Peggy L; Brilliant, Murray H; Linneman, James G; Witte, John S; Denny, Josh C; Roden, Dan M

2017-04-01

One potential use for the PR interval is as a biomarker of disease risk. We hypothesized that quantifying the shared genetic architectures of the PR interval and a set of clinical phenotypes would identify genetic mechanisms contributing to PR variability and identify diseases associated with a genetic predictor of PR variability. We used ECG measurements from the ARIC study (Atherosclerosis Risk in Communities; n=6731 subjects) and 63 genetically modulated diseases from the eMERGE network (Electronic Medical Records and Genomics; n=12 978). We measured pairwise genetic correlations (rG) between PR phenotypes (PR interval, PR segment, P-wave duration) and each of the 63 phenotypes. The PR segment was genetically correlated with atrial fibrillation (rG=-0.88; P =0.0009). An analysis of metabolic phenotypes in ARIC also showed that the P wave was genetically correlated with waist circumference (rG=0.47; P =0.02). A genetically predicted PR interval phenotype based on 645 714 single-nucleotide polymorphisms was associated with atrial fibrillation (odds ratio=0.89 per SD change; 95% confidence interval, 0.83-0.95; P =0.0006). The differing pattern of associations among the PR phenotypes is consistent with analyses that show that the genetic correlation between the P wave and PR segment was not significantly different from 0 (rG=-0.03 [0.16]). The genetic architecture of the PR interval comprises modulators of atrial fibrillation risk and obesity. © 2017 American Heart Association, Inc.

Genetic and environmental integration of the hawkmoth pollination syndrome in Ruellia humilis (Acanthaceae).

PubMed

Heywood, John S; Michalski, Joseph S; McCann, Braden K; Russo, Amber D; Andres, Kara J; Hall, Allison R; Middleton, Tessa C

2017-05-01

The serial homology of floral structures has made it difficult to assess the relative contributions of selection and constraint to floral integration. The interpretation of floral integration may also be clouded by the tacit, but largely untested, assumption that genetic and environmental perturbations affect trait correlations in similar ways. In this study, estimates of both the genetic and environmental correlations between components of the hawkmoth pollination syndrome are presented for chasmogamous flowers of Ruellia humilis , including two levels of control for serial homology. A greenhouse population for quantitative genetic analysis was generated by a partial diallel cross between field-collected plants. An average of 634 chasmogamous flowers were measured for each of eight floral traits that contribute to the hawkmoth syndrome. Genetic correlations (across parents) and environmental correlations (across replicate flowers) were estimated by restricted maximum likelihood. Stigma height, anther height and floral tube length were very tightly integrated in their responses to both genetic and environmental perturbations. The inclusion of floral disc width as a control for serial homology suggests this integration is an adaptive response to correlational selection imposed by pollinators. In contrast, integration of non-homologous traits was low. Furthermore, when comparisons between the dimensions of serially homologous structures were excluded, the genetic and environmental correlation matrices showed little congruence. The results suggest that hawkmoths have imposed strong correlational selection on floral traits involved in the deposition and removal of pollen, and that this is a consequence of stabilizing selection on the relative positions of stigmas and anthers in the face of substantial flower size variation. Low integration of other floral traits, and conflicting patterns of genetic and environmental correlations among these traits, suggest weak or no correlational selection within the range of variability expressed within a population. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Prevalence, heritability and genetic correlations of congenital sensorineural deafness and pigmentation phenotypes in the Border Collie.

PubMed

De Risio, Luisa; Lewis, Tom; Freeman, Julia; de Stefani, Alberta; Matiasek, Lara; Blott, Sarah

2011-06-01

The objectives of this study were to estimate prevalence, heritability and genetic correlations of congenital sensorineural deafness (CSD) and pigmentation phenotypes in the Border Collie. Entire litters of Border Collies that presented to the Animal Health Trust (1994-2008) for assessment of hearing status by brain stem auditory evoked response (BAER) at 4-10 weeks of age were included. Heritability and genetic correlations were estimated using residual maximum likelihood (REML). Of 4143 puppies that met the inclusion criteria, 97.6% had normal hearing status, 2.0% were unilaterally deaf and 0.4% were bilaterally deaf. Heritability of deafness as a trichotomous trait (normal/unilaterally deaf/bilaterally deaf) was estimated at 0.42 using multivariate analysis. Genetic correlations of deafness with iris colour and merle coat colour were 0.58 and 0.26, respectively. These results indicate that there is a significant genetic effect on CSD in Border Collies and that some of the genes determining deafness also influence pigmentation phenotypes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Genetic correlations among and between wool, growth and reproduction traits in Merino sheep.

PubMed

Safari, E; Fogarty, N M; Gilmour, A R; Atkins, K D; Mortimer, S I; Swan, A A; Brien, F D; Greeff, J C; van der Werf, J H J

2007-04-01

Data from seven research resource flocks across Australia were combined to provide accurate estimates of genetic correlations among production traits in Merino sheep. The flocks represented contemporary Australian Merino fine, medium and broad wool strains over the past 30 years. Over 110,000 records were available for analysis for each of the major wool traits, and 50,000 records for reproduction and growth traits with over 2700 sires and 25,000 dams. Individual models developed from the single trait analyses were extended to the various combinations of two-trait models to obtain genetic correlations among six wool traits [clean fleece weight (CFW), greasy fleece weight, fibre diameter (FD), yield, coefficient of variation of fibre diameter and standard deviation of fibre diameter], four growth traits [birth weight, weaning weight, yearling weight (YWT), and hogget weight] and four reproduction traits [fertility, litter size, lambs born per ewe joined, lambs weaned per ewe joined (LW/EJ)]. This study has provided for the first time a comprehensive matrix of genetic correlations among these 14 wool, growth and reproduction traits. The large size of the data set has also provided estimates with very low standard errors. A moderate positive genetic correlation was observed between CFW and FD (0.29 +/- 0.02). YWT was positively correlated with CFW (0.23 +/- 0.04), FD (0.17 +/- 0.04) and LWEJ (0.58 +/- 0.06), while LW/EJ was negatively correlated with CFW (-0.26 +/- 0.05) and positively correlated with FD (0.06 +/- 0.04) and LS (0.68 +/- 0.04). These genetic correlations, together with the estimates of heritability and other parameters provide the basis for more accurate prediction of outcomes in complex sheep-breeding programmes designed to improve several traits.

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types

PubMed Central

Wheeler, William A.; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I.; Lan, Qing; Abnet, Christian C.; Amundadottir, Laufey T.; Figueroa, Jonine D.; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A.; Taylor, Philip R.; Vivo, Immaculata De; McGlynn, Katherine A.; Purdue, Mark P.; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Angelucci, Emanuele; Ansell, Stephen M.; Arici, Cecilia; Armstrong, Bruce K.; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A.; Birmann, Brenda M.; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brinton, Louise; Brooks-Wilson, Angela R.; Bueno-de-Mesquita, H. Bas; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K. C.; Chang, Ellen T.; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C.; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S.; Comperat, Eva; Conde, Lucia; Connors, Joseph M.; Conti, David; Cortessis, Victoria K.; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G.; Ding, Ti; Diver, W. Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J.; Ennas, Maria Grazia; Erickson, Ralph L.; Feychting, Maria; Flanagan, Adrienne M.; Foretova, Lenka; Fraumeni, Joseph F.; Freedman, Neal D.; Beane Freeman, Laura E.; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D.; Gastier-Foster, Julie; Gaudet, Mia M.; Gaziano, J. Michael; Giffen, Carol; Giles, Graham G.; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M.; Haiman, Christopher A.; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R.; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Horn-Ross, Pamela L.; Hosain, G. M. Monawar; Hosgood, H. Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D.; Jackson, Rebecca D.; Jacobs, Eric J.; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R.; Kelly, Rachel S.; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert J.; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M.; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S.; Link, Brian K.; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Lollo, Simonetta Di; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Marchand, Loic Le; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S.; Michaud, Dominique S.; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E.; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E.; Novak, Anne J.; Oberg, Ann L.; Offit, Kenneth; Oh, In-Jae; Olson, Sara H.; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A.; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M.; de Sanjose, Silvia; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K.; Shanafelt, Tait D.; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F.; Smith, Alex; Smith, Martyn T.; Southey, Melissa C.; Spinelli, John J.; Staines, Anthony; Stampfer, Meir; Stern, Marianna C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael S.; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A.; Tinker, Lesley F.; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C.; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M.; Vermeulen, Roel C. H.; Villano, Danylo J.; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J.; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M.; Cerhan, James R.; Ferri, Giovanni M.; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M.; Smedby, Karin E.; Teras, Lauren R.; Vijai, Joseph; Wang, Sophia S.; Brennan, Paul; Caporaso, Neil E.; Hunter, David J.; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T.; Slager, Susan L.; Chanock, Stephen J.; Chatterjee, Nilanjan

2015-01-01

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl 2, on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation. PMID:26464424

Quantitative genetic properties of four measures of deformity in yellowtail kingfish Seriola lalandi Valenciennes, 1833.

PubMed

Nguyen, N H; Whatmore, P; Miller, A; Knibb, W

2016-02-01

The main aim of this study was to estimate the heritability for four measures of deformity and their genetic associations with growth (body weight and length), carcass (fillet weight and yield) and flesh-quality (fillet fat content) traits in yellowtail kingfish Seriola lalandi. The observed major deformities included lower jaw, nasal erosion, deformed operculum and skinny fish on 480 individuals from 22 families at Clean Seas Tuna Ltd. They were typically recorded as binary traits (presence or absence) and were analysed separately by both threshold generalized models and standard animal mixed models. Consistency of the models was evaluated by calculating simple Pearson correlation of breeding values of full-sib families for jaw deformity. Genetic and phenotypic correlations among traits were estimated using a multitrait linear mixed model in ASReml. Both threshold and linear mixed model analysis showed that there is additive genetic variation in the four measures of deformity, with the estimates of heritability obtained from the former (threshold) models on liability scale ranging from 0.14 to 0.66 (SE 0.32-0.56) and from the latter (linear animal and sire) models on original (observed) scale, 0.01-0.23 (SE 0.03-0.16). When the estimates on the underlying liability were transformed to the observed scale (0, 1), they were generally consistent between threshold and linear mixed models. Phenotypic correlations among deformity traits were weak (close to zero). The genetic correlations among deformity traits were not significantly different from zero. Body weight and fillet carcass showed significant positive genetic correlations with jaw deformity (0.75 and 0.95, respectively). Genetic correlation between body weight and operculum was negative (-0.51, P < 0.05). The genetic correlations' estimates of body and carcass traits with other deformity were not significant due to their relatively high standard errors. Our results showed that there are prospects for genetic selection to improve deformity in yellowtail kingfish and that measures of deformity should be included in the recording scheme, breeding objectives and selection index in practical selective breeding programmes due to the antagonistic genetic correlations of deformed jaws with body and carcass performance. © 2015 John Wiley & Sons Ltd.

Genetic distances between popcorn populations based on molecular markers and correlations with heterosis estimates made by diallel analysis of hybrids.

PubMed

Munhoz, R E F; Prioli, A J; Amaral, A T; Scapim, C A; Simon, G A

2009-08-11

Diallel analysis was used to obtain information on combining ability, heterosis, estimates of genetic distances by random amplified polymorphic DNA (RAPD) and on their correlations with heterosis, for the popcorn varieties RS 20, UNB2, CMS 43, CMS 42, Zélia, UEM J1, UEM M2, Beija-Flor, and Viçosa, which were crossed to obtain all possible combinations, without reciprocals. The genitors and the 36 F(1) hybrids were evaluated in field trials in Maringá during two growing seasons in a randomized complete block design with three replications. Based on the results, strategies for further studies were developed, including the construction of composites by joining varieties with high general combining ability for grain yield (UNB2 and CMS 42) with those with high general combining ability for popping expansion (Zélia, RS 20 and UEM M2). Based on the RAPD markers, UEM J1 and Zélia were the most genetically distant and RS 20 and UNB2 were the most similar. The low correlation between heterosis and genetic distances may be explained by the random dispersion of the RAPD markers, which were insufficient for the exploitation of the popcorn genome. We concluded that an association between genetic dissimilarity and heterosis based only on genetic distance is not expected without considering the effect of dominant loci.

Attitudes Toward Genetic Modification Research: An Analysis of the Views of the Sputnik Generation.

ERIC Educational Resources Information Center

Miller, Jon D.

1982-01-01

Utilizing data from the 1977 National Assessment of Educational Progress (NAEP) survey of young adults, summarizes attitudes toward genetic modification research and the demographic, educational, and occupational correlates of these attitudes. (Author/SK)

‘Generalist genes’ and mathematics in 7-year-old twins

PubMed Central

Kovas, Y.; Harlaar, N.; Petrill, S. A.; Plomin, R.

2009-01-01

Mathematics performance at 7 years as assessed by teachers using UK national curriculum criteria has been found to be highly heritable. For almost 3000 pairs of 7-year-old same-sex twins, we used multivariate genetic analysis to investigate the extent to which these genetic effects on mathematics performance overlap with genetic effects on reading and general intelligence (g) as predicted by the ‘generalist genes’ hypothesis. We found substantial genetic overlap between mathematics and reading (genetic correlation=0.74) and between mathematics and g (0.67). These findings support the ‘generalist genes’ hypothesis that most of the genes that contribute to individual differences in mathematics are the same genes that affect reading and g. Nonetheless, the genetic correlations are less than unity and about a third of the genetic variance on mathematics is independent of reading and g, suggesting that there are also some genes whose effects are specific to mathematics. PMID:19319204

Behavioral Actions of Alcohol: Phenotypic Relations from Multivariate Analysis of Mutant Mouse Data

PubMed Central

Blednov, Yuri A.; Mayfield, R. Dayne; Belknap, John; Harris, R. Adron

2012-01-01

Behavioral studies of genetically diverse mice have proven powerful for determining relationships between phenotypes and have been widely used in alcohol research. Most of these studies rely on naturally occurring genetic polymorphisms among inbred strains and selected lines. Another approach is to introduce variation by engineering single gene mutations in mice. We have tested 37 different mutant mice and their wild type controls for a variety (31) of behaviors and have mined this dataset by K-means clustering and analysis of correlations. We found a correlation between a stress-related response (activity in a novel environment) and alcohol consumption and preference for saccharin. We confirmed several relationships detected in earlier genetic studies including positive correlation of alcohol consumption with saccharin consumption, and negative correlations with conditioned taste aversion and alcohol withdrawal severity. Introduction of single gene mutations either eliminated or greatly diminished these correlations. The three tests of alcohol consumption used (continuous two bottle choice, and two limited access tests: Drinking In the Dark and Sustained High Alcohol Consumption) share a relationship with saccharin consumption, but differ from each other in their correlation networks. We suggest that alcohol consumption is controlled by multiple physiological systems where single gene mutations can disrupt the networks of such systems. PMID:22405477

Worldwide analysis of multiple microsatellites: language diversity has a detectable influence on DNA diversity.

PubMed

Belle, Elise M S; Barbujani, Guido

2007-08-01

Previous studies of the correlations between the languages spoken by human populations and the genes carried by the members of those populations have been limited by the small amount of genetic markers available and by approximations in the treatment of linguistic data. In this study we analyzed a large collection of polymorphic microsatellite loci (377), distributed on all autosomes, and used Ruhlen's linguistic classification, to investigate the relative roles of geography and language in shaping the distribution of human DNA diversity at a worldwide scale. For this purpose, we performed three different kinds of analysis: (i) we partitioned genetic variances at three hierarchical levels of population subdivision according to language group by means of a molecular analysis of variance (AMOVA); (ii) we quantified by a series of Mantel's tests the correlation between measures of genetic and linguistic differentiation; and (iii) we tested whether linguistic differences are increased across known zones of increased genetic change between populations. Genetic differences appear to more closely reflect geographic than linguistic differentiation. However, our analyses show that language differences also have a detectable effect on DNA diversity at the genomic level, above and beyond the effects of geographic distance. (c) 2007 Wiley-Liss, Inc.

Breeding of Acrocomia aculeata using genetic diversity parameters and correlations to select accessions based on vegetative, phenological, and reproductive characteristics.

PubMed

Coser, S M; Motoike, S Y; Corrêa, T R; Pires, T P; Resende, M D V

2016-10-17

Macaw palm (Acrocomia aculeata) is a promising species for use in biofuel production, and establishing breeding programs is important for the development of commercial plantations. The aim of the present study was to analyze genetic diversity, verify correlations between traits, estimate genetic parameters, and select different accessions of A. aculeata in the Macaw Palm Germplasm Bank located in Universidade Federal de Viçosa, to develop a breeding program for this species. Accessions were selected based on precocity (PREC), total spathe (TS), diameter at breast height (DBH), height of the first spathe (HFS), and canopy area (CA). The traits were evaluated in 52 accessions during the 2012/2013 season and analyzed by restricted estimation maximum likelihood/best linear unbiased predictor procedures. Genetic diversity resulted in the formation of four groups by Tocher's clustering method. The correlation analysis showed it was possible to have indirect and early selection for the traits PREC and DBH. Estimated genetic parameters strengthened the genetic variability verified by cluster analysis. Narrow-sense heritability was classified as moderate (PREC, TS, and CA) to high (HFS and DBH), resulting in strong genetic control of the traits and success in obtaining genetic gains by selection. Accuracy values were classified as moderate (PREC and CA) to high (TS, HFS, and DBH), reinforcing the success of the selection process. Selection of accessions for PREC, TS, and HFS by the rank-average method permits selection gains of over 100%, emphasizing the successful use of the accessions in breeding programs and obtaining superior genotypes for commercial plantations.

Genetic parameters and path analysis in cowpea genotypes grown in the Cerrado/Pantanal ecotone.

PubMed

Lopes, K V; Teodoro, P E; Silva, F A; Silva, M T; Fernandes, R L; Rodrigues, T C; Faria, T C; Corrêa, A M

2017-05-18

Estimating genetic parameters in plant breeding allows us to know the population potential for selecting and designing strategies that can maximize the achievement of superior genotypes. The objective of this study was to evaluate the genetic potential of a population of 20 cowpea genotypes by estimating genetic parameters and path analysis among the traits to guide the selection strategies. The trial was conducted in randomized block design with four replications. Its morphophysiological components, components of green grain production and dry grain yield were estimated from genetic use and correlations between the traits. Phenotypic correlations were deployed through path analysis into direct and indirect effects of morphophysiological traits and yield components on dry grain yield. There were significant differences (P < 0.01) between the genotypes for most the traits, indicating the presence of genetic variability in the population and the possibility of practicing selection. The population presents the potential for future genetic breeding studies and is highly promising for the selection of traits dry grain yield, the number of grains per pod, and hundred grains mass. A number of grains per green pod is the main determinant trait of dry grain yield that is also influenced by the cultivar cycle and that the selection for the dry grain yield can be made indirectly by selecting the green pod mass and green pod length.

An ecological genetic delineation of local seed-source provenance for ecological restoration

PubMed Central

Krauss, Siegfried L; Sinclair, Elizabeth A; Bussell, John D; Hobbs, Richard J

2013-01-01

An increasingly important practical application of the analysis of spatial genetic structure within plant species is to help define the extent of local provenance seed collection zones that minimize negative impacts in ecological restoration programs. Here, we derive seed sourcing guidelines from a novel range-wide assessment of spatial genetic structure of 24 populations of Banksia menziesii (Proteaceae), a widely distributed Western Australian tree of significance in local ecological restoration programs. An analysis of molecular variance (AMOVA) of 100 amplified fragment length polymorphism (AFLP) markers revealed significant genetic differentiation among populations (ΦPT = 0.18). Pairwise population genetic dissimilarity was correlated with geographic distance, but not environmental distance derived from 15 climate variables, suggesting overall neutrality of these markers with regard to these climate variables. Nevertheless, Bayesian outlier analysis identified four markers potentially under selection, although these were not correlated with the climate variables. We calculated a global R-statistic using analysis of similarities (ANOSIM) to test the statistical significance of population differentiation and to infer a threshold seed collection zone distance of ∼60 km (all markers) and 100 km (outlier markers) when genetic distance was regressed against geographic distance. Population pairs separated by >60 km were, on average, twice as likely to be significantly genetically differentiated than population pairs separated by <60 km, suggesting that habitat-matched sites within a 30-km radius around a restoration site genetically defines a local provenance seed collection zone for B. menziesii. Our approach is a novel probability-based practical solution for the delineation of a local seed collection zone to minimize negative genetic impacts in ecological restoration. PMID:23919158

Genetic Variance in Processing Speed Drives Variation in Aging of Spatial and Memory Abilities

ERIC Educational Resources Information Center

Finkel, Deborah; Reynolds, Chandra A.; McArdle, John J.; Hamagami, Fumiaki; Pedersen, Nancy L.

2009-01-01

Previous analyses have identified a genetic contribution to the correlation between declines with age in processing speed and higher cognitive abilities. The goal of the current analysis was to apply the biometric dual change score model to consider the possibility of temporal dynamics underlying the genetic covariance between aging trajectories…

Genetic analysis of an ephemeral intraspecific hybrid zone in the hypervariable tree, Metrosideros polymorpha, on Hawai'i Island.

PubMed

Stacy, E A; Johansen, J B; Sakishima, T; Price, D K

2016-09-01

Intraspecific hybrid zones involving long-lived woody species are rare and can provide insights into the genetic basis of early-diverging traits in speciation. Within the landscape-dominant Hawaiian tree, Metrosideros polymorpha, are morphologically distinct successional varieties, incana and glaberrima, that dominate new and old lava flows, respectively, below 1200 me on volcanically active Hawai'i Island, with var. glaberrima also extending to higher elevations and bogs. Here, we use morphological measurements on 86 adult trees to document the presence of an incana-glaberrima hybrid zone on the 1855 Mauna Loa lava flow on east Hawai'i Island and parent-offspring analysis of 1311 greenhouse seedlings from 71 crosses involving 72 adults to estimate heritabilities and genetic correlations among vegetative traits. Both the variation in adult leaf pubescence at the site and the consistency between adult and offspring phenotypes suggest the presence of two hybrid classes, F1s and var. incana backcrosses, as would be expected on a relatively young lava flow. Nine nuclear microsatellite loci failed to distinguish parental and hybrid genotypes. All four leaf traits examined showed an additive genetic basis with moderate to strong heritabilities, and genetic correlations were stronger for the more range-restricted var. incana. The differences between varieties in trait values, heritabilities and genetic correlations, coupled with high genetic variation within but low genetic variation between varieties, are consistent with a multi-million-year history of alternating periods of disruptive selection in contrasting environments and admixture in ephemeral hybrid zones. Finally, the contrasting genetic architectures suggest different evolutionary trajectories of leaf traits in these forms.

Genetic analysis of an ephemeral intraspecific hybrid zone in the hypervariable tree, Metrosideros polymorpha, on Hawai‘i Island

PubMed Central

Stacy, E A; Johansen, J B; Sakishima, T; Price, D K

2016-01-01

Intraspecific hybrid zones involving long-lived woody species are rare and can provide insights into the genetic basis of early-diverging traits in speciation. Within the landscape-dominant Hawaiian tree, Metrosideros polymorpha, are morphologically distinct successional varieties, incana and glaberrima, that dominate new and old lava flows, respectively, below 1200 me on volcanically active Hawai‘i Island, with var. glaberrima also extending to higher elevations and bogs. Here, we use morphological measurements on 86 adult trees to document the presence of an incana–glaberrima hybrid zone on the 1855 Mauna Loa lava flow on east Hawai‘i Island and parent–offspring analysis of 1311 greenhouse seedlings from 71 crosses involving 72 adults to estimate heritabilities and genetic correlations among vegetative traits. Both the variation in adult leaf pubescence at the site and the consistency between adult and offspring phenotypes suggest the presence of two hybrid classes, F1s and var. incana backcrosses, as would be expected on a relatively young lava flow. Nine nuclear microsatellite loci failed to distinguish parental and hybrid genotypes. All four leaf traits examined showed an additive genetic basis with moderate to strong heritabilities, and genetic correlations were stronger for the more range-restricted var. incana. The differences between varieties in trait values, heritabilities and genetic correlations, coupled with high genetic variation within but low genetic variation between varieties, are consistent with a multi-million-year history of alternating periods of disruptive selection in contrasting environments and admixture in ephemeral hybrid zones. Finally, the contrasting genetic architectures suggest different evolutionary trajectories of leaf traits in these forms. PMID:27301333

Genetic diversity of popcorn genotypes using molecular analysis.

PubMed

Resh, F S; Scapim, C A; Mangolin, C A; Machado, M F P S; do Amaral, A T; Ramos, H C C; Vivas, M

2015-08-19

In this study, we analyzed dominant molecular markers to estimate the genetic divergence of 26 popcorn genotypes and evaluate whether using various dissimilarity coefficients with these dominant markers influences the results of cluster analysis. Fifteen random amplification of polymorphic DNA primers produced 157 amplified fragments, of which 65 were monomorphic and 92 were polymorphic. To calculate the genetic distances among the 26 genotypes, the complements of the Jaccard, Dice, and Rogers and Tanimoto similarity coefficients were used. A matrix of Dij values (dissimilarity matrix) was constructed, from which the genetic distances among genotypes were represented in a more simplified manner as a dendrogram generated using the unweighted pair-group method with arithmetic average. Clusters determined by molecular analysis generally did not group material from the same parental origin together. The largest genetic distance was between varieties 17 (UNB-2) and 18 (PA-091). In the identification of genotypes with the smallest genetic distance, the 3 coefficients showed no agreement. The 3 dissimilarity coefficients showed no major differences among their grouping patterns because agreement in determining the genotypes with large, medium, and small genetic distances was high. The largest genetic distances were observed for the Rogers and Tanimoto dissimilarity coefficient (0.74), followed by the Jaccard coefficient (0.65) and the Dice coefficient (0.48). The 3 coefficients showed similar estimations for the cophenetic correlation coefficient. Correlations among the matrices generated using the 3 coefficients were positive and had high magnitudes, reflecting strong agreement among the results obtained using the 3 evaluated dissimilarity coefficients.

Genetics and intelligence differences: five special findings.

PubMed

Plomin, R; Deary, I J

2015-02-01

Intelligence is a core construct in differential psychology and behavioural genetics, and should be so in cognitive neuroscience. It is one of the best predictors of important life outcomes such as education, occupation, mental and physical health and illness, and mortality. Intelligence is one of the most heritable behavioural traits. Here, we highlight five genetic findings that are special to intelligence differences and that have important implications for its genetic architecture and for gene-hunting expeditions. (i) The heritability of intelligence increases from about 20% in infancy to perhaps 80% in later adulthood. (ii) Intelligence captures genetic effects on diverse cognitive and learning abilities, which correlate phenotypically about 0.30 on average but correlate genetically about 0.60 or higher. (iii) Assortative mating is greater for intelligence (spouse correlations ~0.40) than for other behavioural traits such as personality and psychopathology (~0.10) or physical traits such as height and weight (~0.20). Assortative mating pumps additive genetic variance into the population every generation, contributing to the high narrow heritability (additive genetic variance) of intelligence. (iv) Unlike psychiatric disorders, intelligence is normally distributed with a positive end of exceptional performance that is a model for 'positive genetics'. (v) Intelligence is associated with education and social class and broadens the causal perspectives on how these three inter-correlated variables contribute to social mobility, and health, illness and mortality differences. These five findings arose primarily from twin studies. They are being confirmed by the first new quantitative genetic technique in a century-Genome-wide Complex Trait Analysis (GCTA)-which estimates genetic influence using genome-wide genotypes in large samples of unrelated individuals. Comparing GCTA results to the results of twin studies reveals important insights into the genetic architecture of intelligence that are relevant to attempts to narrow the 'missing heritability' gap.

Genetics and intelligence differences: five special findings

PubMed Central

Plomin, R; Deary, I J

2015-01-01

Intelligence is a core construct in differential psychology and behavioural genetics, and should be so in cognitive neuroscience. It is one of the best predictors of important life outcomes such as education, occupation, mental and physical health and illness, and mortality. Intelligence is one of the most heritable behavioural traits. Here, we highlight five genetic findings that are special to intelligence differences and that have important implications for its genetic architecture and for gene-hunting expeditions. (i) The heritability of intelligence increases from about 20% in infancy to perhaps 80% in later adulthood. (ii) Intelligence captures genetic effects on diverse cognitive and learning abilities, which correlate phenotypically about 0.30 on average but correlate genetically about 0.60 or higher. (iii) Assortative mating is greater for intelligence (spouse correlations ~0.40) than for other behavioural traits such as personality and psychopathology (~0.10) or physical traits such as height and weight (~0.20). Assortative mating pumps additive genetic variance into the population every generation, contributing to the high narrow heritability (additive genetic variance) of intelligence. (iv) Unlike psychiatric disorders, intelligence is normally distributed with a positive end of exceptional performance that is a model for ‘positive genetics'. (v) Intelligence is associated with education and social class and broadens the causal perspectives on how these three inter-correlated variables contribute to social mobility, and health, illness and mortality differences. These five findings arose primarily from twin studies. They are being confirmed by the first new quantitative genetic technique in a century—Genome-wide Complex Trait Analysis (GCTA)—which estimates genetic influence using genome-wide genotypes in large samples of unrelated individuals. Comparing GCTA results to the results of twin studies reveals important insights into the genetic architecture of intelligence that are relevant to attempts to narrow the ‘missing heritability' gap. PMID:25224258

Genetic parameters of Visual Image Analysis primal cut carcass traits of commercial prime beef slaughter animals.

PubMed

Moore, K L; Mrode, R; Coffey, M P

2017-10-01

Visual Image analysis (VIA) of carcass traits provides the opportunity to estimate carcass primal cut yields on large numbers of slaughter animals. This allows carcases to be better differentiated and farmers to be paid based on the primal cut yields. It also creates more accurate genetic selection due to high volumes of data which enables breeders to breed cattle that better meet the abattoir specifications and market requirements. In order to implement genetic evaluations for VIA primal cut yields, genetic parameters must first be estimated and that was the aim of this study. Slaughter records from the UK prime slaughter population for VIA carcass traits was available from two processing plants. After edits, there were 17 765 VIA carcass records for six primal cut traits, carcass weight as well as the EUROP conformation and fat class grades. Heritability estimates after traits were adjusted for age ranged from 0.32 (0.03) for EUROP fat to 0.46 (0.03) for VIA Topside primal cut yield. Adjusting the VIA primal cut yields for carcass weight reduced the heritability estimates, with estimates of primal cut yields ranging from 0.23 (0.03) for Fillet to 0.29 (0.03) for Knuckle. Genetic correlations between VIA primal cut yields adjusted for carcass weight were very strong, ranging from 0.40 (0.06) between Fillet and Striploin to 0.92 (0.02) between Topside and Silverside. EUROP conformation was also positively correlated with the VIA primal cuts with genetic correlation estimates ranging from 0.59 to 0.84, whereas EUROP fat was estimated to have moderate negative correlations with primal cut yields, estimates ranged from -0.11 to -0.46. Based on these genetic parameter estimates, genetic evaluation of VIA primal cut yields can be undertaken to allow the UK beef industry to select carcases that better meet abattoir specification and market requirements.

Perceived knowledge and clinical comfort with genetics among Taiwanese nurses enrolled in a RN-to-BSN program.

PubMed

Hsiao, Chiu-Yueh; Lee, Shu-Hsin; Chen, Suh-Jen; Lin, Shu-Chin

2013-08-01

Advances in genetics have had a profound impact on health care. Yet, many nurses, as well as other health care providers, have limited genetic knowledge and feel uncomfortable integrating genetics into their practice. Very little is known about perceived genetic knowledge and clinical comfort among Taiwanese nurses enrolled in a Registered Nurse to Bachelor of Science in Nursing program. To examine perceived knowledge and clinical comfort with genetics among Taiwanese nurses enrolled in a Registered Nurse to Bachelor of Science in Nursing program and to assess how genetics has been integrated into their past and current nursing programs. The study also sought to examine correlations among perceived knowledge, integration of genetics into the nursing curriculum, and clinical comfort with genetics. A descriptive, cross-sectional study. Taiwanese nurses enrolled in a Registered Nurse to Bachelor of Science in Nursing program were recruited. A total of 190 of 220 nurses returned the completed survey (86.36% response rate). Descriptive statistics and the Pearson product-moment correlation were used for data analysis. Most nurses indicated limited perceived knowledge and clinical comfort with genetics. Curricular hours focused on genetics in a current nursing program were greater than those in past nursing programs. The use of genetic materials, attendance at genetic workshops and conferences, and clinically relevant genetics in nursing practice significantly related with perceived knowledge and clinical comfort with genetics. However, there were no correlations between prior genetic-based health care, perceived knowledge, and clinical comfort with genetics. This study demonstrated the need for emphasizing genetic education and practice to ensure health-related professionals become knowledgeable about genetic information. Given the rapidly developing genetic revolution, nurses and other health care providers need to utilize genetic discoveries to optimize health outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Marker-based quantitative genetics in the wild?: the heritability and genetic correlation of chemical defenses in eucalyptus.

PubMed

Andrew, R L; Peakall, R; Wallis, I R; Wood, J T; Knight, E J; Foley, W J

2005-12-01

Marker-based methods for estimating heritability and genetic correlation in the wild have attracted interest because traditional methods may be impractical or introduce bias via G x E effects, mating system variation, and sampling effects. However, they have not been widely used, especially in plants. A regression-based approach, which uses a continuous measure of genetic relatedness, promises to be particularly appropriate for use in plants with mixed-mating systems and overlapping generations. Using this method, we found significant narrow-sense heritability of foliar defense chemicals in a natural population of Eucalyptus melliodora. We also demonstrated a genetic basis for the phenotypic correlation underlying an ecological example of conditioned flavor aversion involving different biosynthetic pathways. Our results revealed that heritability estimates depend on the spatial scale of the analysis in a way that offers insight into the distribution of genetic and environmental variance. This study is the first to successfully use a marker-based method to measure quantitative genetic parameters in a tree. We suggest that this method will prove to be a useful tool in other studies and offer some recommendations for future applications of the method.

Ecological correlates of population genetic structure: a comparative approach using a vertebrate metacommunity.

PubMed

Manier, Mollie K; Arnold, Stevan J

2006-12-07

Identifying ecological factors associated with population genetic differentiation is important for understanding microevolutionary processes and guiding the management of threatened populations. We identified ecological correlates of several population genetic parameters for three interacting species (two garter snakes and an anuran) that occupy a common landscape. Using multiple regression analysis, we found that species interactions were more important in explaining variation in population genetic parameters than habitat and nearest-neighbour characteristics. Effective population size was best explained by census size, while migration was associated with differences in species abundance. In contrast, genetic distance was poorly explained by the ecological correlates that we tested, but geographical distance was prominent in models for all species. We found substantially different population dynamics for the prey species relative to the two predators, characterized by larger effective sizes, lower gene flow and a state of migration-drift equilibrium. We also identified an escarpment formed by a series of block faults that serves as a barrier to dispersal for the predators. Our results suggest that successful landscape-level management should incorporate genetic and ecological data for all relevant species, because even closely associated species can exhibit very different population genetic dynamics on the same landscape.

Heritability of Problem Drinking and the Genetic Overlap with Personality in a General Population Sample

PubMed Central

de Moor, Marleen H. M.; Vink, Jacqueline M.; van Beek, Jenny H. D. A.; Geels, Lot M.; Bartels, Meike; de Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.

2011-01-01

This study examined the heritability of problem drinking and investigated the phenotypic and genetic relationships between problem drinking and personality. In a sample of 5,870 twins and siblings and 4,420 additional family members from the Netherlands Twin Register. Data on problem drinking (assessed with the AUDIT and CAGE; 12 items) and personality [NEO Five-Factor Inventory (FFI); 60 items] were collected in 2009/2010 by surveys. Confirmatory factor analysis on the AUDIT and CAGE items showed that the items clustered on two separate but highly correlated (r = 0.74) underlying factors. A higher-order factor was extracted that reflected those aspects of problem drinking that are common to the AUDIT and CAGE, which showed a heritability of 40%. The correlations between problem drinking and the five dimensions of personality were small but significant, ranging from 0.06 for Extraversion to −0.12 for Conscientiousness. All personality dimensions (with broad-sense heritabilities between 32 and 55%, and some evidence for non-additive genetic influences) were genetically correlated with problem drinking. The genetic correlations were small to modest (between |0.12| and |0.41|). Future studies with longitudinal data and DNA polymorphisms are needed to determine the biological mechanisms that underlie the genetic link between problem drinking and personality. PMID:22303371

Geographical structuring of Trypanosoma cruzi populations from Chilean Triatoma infestans triatomines and their genetic relationship with other Latino American counterparts

PubMed Central

Venegas, J; Rojas, T; DÍaz, F; Miranda, S; Jercic, M I; González, C; Coñoepán, W; Pichuantes, S; RodrÍguez, J; Gajardo, M; Sánchez, G

2011-01-01

In order to obtain more information about the population structure of Chilean Trypanosoma cruzi, and their genetic relationship with other Latino American counterparts, we performed the study of T. cruzi samples detected in the midgut content of Triatoma infestans insects from three endemic regions of Chile. The genetic characteristics of these samples were analysed using microsatellite markers and PCR conditions that allow the detection of predominant T. cruzi clones directly in triatomine midgut content. Population genetic analyses using the Fisher’s exact method, analysis of molecular variance (AMOVA) and the determination of FST showed that the northern T. cruzi population sample was genetically differentiated from the two southern population counterparts. Further analysis showed that the cause of this genetic differentiation was the asymmetrical distribution of TcIII T. cruzi predominant clones. Considering all triatomines from the three regions, the most frequent predominant lineages were TcIII (38%), followed by TcI (34%) and hybrid (8%). No TcII lineage was observed along the predominant T. cruzi clones. The best phylogenetic reconstruction using the shared allelic genetic distance was concordant with the population genetic analysis and tree topology previously described studying foreign samples. The correlation studies showed that the lineage TcIII from the III region was genetically differentiated from the other two, and this differentiation was correlated with geographical distance including Chilean and mainly Brazilian samples. It will be interesting to investigate whether this geographical structure may be related with different clinical manifestation of Chagas disease. PMID:22325822

WGCNA: an R package for weighted correlation network analysis

PubMed Central

Langfelder, Peter; Horvath, Steve

2008-01-01

Background Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. Results The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. Conclusion The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at . PMID:19114008

Genetic diversity and relationship of Hedychium from Northeast India as dissected using PCA analysis and hierarchical clustering.

PubMed

Basak, Supriyo; Ramesh, Aadi Moolam; Kesari, Vigya; Parida, Ajay; Mitra, Sudip; Rangan, Latha

2014-12-01

Molecular genetic fingerprints of eleven Hedychium species from Northeast India were developed using PCR based markers. Fifteen inter-simple sequence repeats (ISSRs) and five amplified fragment length polymorphism (AFLP) primers produced 547 polymorphic fragments. Positive correlation (r = 0.46) was observed between the mean genetic similarity and genetic diversity parameters at the inter-species level. AFLP and ISSR markers were able to group the species according to its altitude and intensity of flower aroma. Cophenetic correlation coefficients between the dendrogram and the original similarity matrix were significant for ISSR (r = 0.89) compared to AFLP (r = 0.83) markers. This genetic characterization of Hedychium from Northeast India contributes to the knowledge of genetic structure of the species and can be used to define strategies for their conservation and management.

[A Study of the Relationship Among Genetic Distances, NIR Spectra Distances, and NIR-Based Identification Model Performance of the Seeds of Maize Iinbred Lines].

PubMed

Liu, Xu; Jia, Shi-qiang; Wang, Chun-ying; Liu, Zhe; Gu, Jian-cheng; Zhai, Wei; Li, Shao-ming; Zhang, Xiao-dong; Zhu, De-hai; Huang, Hua-jun; An, Dong

2015-09-01

This paper explored the relationship among genetic distances, NIR spectra distances and NIR-based identification model performance of the seeds of maize inbred lines. Using 3 groups (total 15 pairs) of maize inbred lines whose genetic distaches are different as experimental materials, we calculates the genetic distance between these seeds with SSR markers and uses Euclidean distance between distributed center points of maize NIR spectrum in the PCA space as the distances of NIR spectrum. BPR method is used to build identification model of inbred lines and the identification accuracy is used as a measure of model identification performance. The results showed that, the correlation of genetic distance and spectra distancesis 0.9868, and it has a correlation of 0.9110 with the identification accuracy, which is highly correlated. This means near-Infrared spectrum of seedscan reflect genetic relationship of maize inbred lines. The smaller the genetic distance, the smaller the distance of spectrum, the poorer ability of model to identify. In practical application, near infrared spectrum analysis technology has the potential to be used to analyze maize inbred genetic relations, contributing much to genetic breeding, identification of species, purity sorting and so on. What's more, when creating a NIR-based identification model, the impact of the maize inbred lines which have closer genetic relationship should be fully considered.

Genetic parameters for body condition score, body weight, milk yield, and fertility estimated using random regression models.

PubMed

Berry, D P; Buckley, F; Dillon, P; Evans, R D; Rath, M; Veerkamp, R F

2003-11-01

Genetic (co)variances between body condition score (BCS), body weight (BW), milk yield, and fertility were estimated using a random regression animal model extended to multivariate analysis. The data analyzed included 81,313 BCS observations, 91,937 BW observations, and 100,458 milk test-day yields from 8725 multiparous Holstein-Friesian cows. A cubic random regression was sufficient to model the changing genetic variances for BCS, BW, and milk across different days in milk. The genetic correlations between BCS and fertility changed little over the lactation; genetic correlations between BCS and interval to first service and between BCS and pregnancy rate to first service varied from -0.47 to -0.31, and from 0.15 to 0.38, respectively. This suggests that maximum genetic gain in fertility from indirect selection on BCS should be based on measurements taken in midlactation when the genetic variance for BCS is largest. Selection for increased BW resulted in shorter intervals to first service, but more services and poorer pregnancy rates; genetic correlations between BW and pregnancy rate to first service varied from -0.52 to -0.45. Genetic selection for higher lactation milk yield alone through selection on increased milk yield in early lactation is likely to have a more deleterious effect on genetic merit for fertility than selection on higher milk yield in late lactation.

A new genetic linkage map of barley (Hordeum vulgare L.) facilitates genetic dissection of height and spike length and angle

USDA-ARS?s Scientific Manuscript database

Plant height and spike length and angle are important agronomic traits in the production of barley (Hordeum vulgare L.) due to strong correlations with lodging and disease. The objective of this study was to use QTL analysis to identify genetic regions associated with each trait in a recombinant inb...

Genetic Variability and Population Structure of Disanthus cercidifolius subsp. longipes (Hamamelidaceae) Based on AFLP Analysis

PubMed Central

Yu, Yi; Fan, Qiang; Shen, Rujiang; Guo, Wei; Jin, Jianhua; Cui, Dafang; Liao, Wenbo

2014-01-01

Disanthus cercidifolius subsp. longipes is an endangered species in China. Genetic diversity and structure analysis of this species was investigated using amplified fragments length polymorphism (AFLP) fingerprinting. Nei's gene diversity ranged from 0.1290 to 0.1394. The AMOVA indicated that 75.06% of variation was distributed within populations, while the between-group component 5.04% was smaller than the between populations-within-group component 19.90%. Significant genetic differentiation was detected between populations. Genetic and geographical distances were not correlated. PCA and genetic structure analysis showed that populations from East China were together with those of the Nanling Range. These patterns of genetic diversity and levels of genetic variation may be the result of D. c. subsp. longipes restricted to several isolated habitats and “excess flowers production, but little fruit set”. It is necessary to protect all existing populations of D. c. subsp. longipes in order to preserve as much genetic variation as possible. PMID:25250583

Increasing Relationship Between Negative Emotionality and Conduct Problems During Childhood: A Cross-Sectional Behavioral Genetic Analysis.

PubMed

Hur, Yoon-Mi; Hwang, Sunyung; Chung, Un-Sun

2015-12-01

Age difference in the etiology of the relationship between childhood negative emotionality (NE) and conduct problems (CP) has not been previously investigated. Mothers of 662 pairs of twins completed questions on the emotionality (NE) scale of the EAS temperament survey and the CP scale of the Strengths and Difficulties Questionnaires (SDQ) via a telephone interview. Twin data were analyzed separately in younger (ages 3 to 7 years; mostly pre-schoolers) and older children (ages 8 to 13 years; mostly elementary school children). The phenotypic correlation between NE and CP increased from 0.33 among younger twins to 0.43 among older twins. Bivariate model-fitting analysis was performed to determine age difference in the etiology of the relationship between NE and CP. Among younger twins, the correlation between NE and CP was entirely explained by additive genetic factors common to NE and CP. Among older children, however, a small but significant amount of unique environmental correlation emerged to account for about 47% of the phenotypic correlation between NE and CP. The remaining 53% of the phenotypic correlation was due to shared additive genetic factors. We speculate that environmental factors associated with school adjustment may exert influences on the relationship between NE and CP among elementary school children.

Genome-Wide Association Analysis of Adaptation Using Environmentally Predicted Traits.

PubMed

van Heerwaarden, Joost; van Zanten, Martijn; Kruijer, Willem

2015-10-01

Current methods for studying the genetic basis of adaptation evaluate genetic associations with ecologically relevant traits or single environmental variables, under the implicit assumption that natural selection imposes correlations between phenotypes, environments and genotypes. In practice, observed trait and environmental data are manifestations of unknown selective forces and are only indirectly associated with adaptive genetic variation. In theory, improved estimation of these forces could enable more powerful detection of loci under selection. Here we present an approach in which we approximate adaptive variation by modeling phenotypes as a function of the environment and using the predicted trait in multivariate and univariate genome-wide association analysis (GWAS). Based on computer simulations and published flowering time data from the model plant Arabidopsis thaliana, we find that environmentally predicted traits lead to higher recovery of functional loci in multivariate GWAS and are more strongly correlated to allele frequencies at adaptive loci than individual environmental variables. Our results provide an example of the use of environmental data to obtain independent and meaningful information on adaptive genetic variation.

Targeted Analysis of Whole Genome Sequence Data to Diagnose Genetic Cardiomyopathy

DOE PAGES

Golbus, Jessica R.; Puckelwartz, Megan J.; Dellefave-Castillo, Lisa; ...

2014-09-01

Background—Cardiomyopathy is highly heritable but genetically diverse. At present, genetic testing for cardiomyopathy uses targeted sequencing to simultaneously assess the coding regions of more than 50 genes. New genes are routinely added to panels to improve the diagnostic yield. With the anticipated $1000 genome, it is expected that genetic testing will shift towards comprehensive genome sequencing accompanied by targeted gene analysis. Therefore, we assessed the reliability of whole genome sequencing and targeted analysis to identify cardiomyopathy variants in 11 subjects with cardiomyopathy. Methods and Results—Whole genome sequencing with an average of 37× coverage was combined with targeted analysis focused onmore » 204 genes linked to cardiomyopathy. Genetic variants were scored using multiple prediction algorithms combined with frequency data from public databases. This pipeline yielded 1-14 potentially pathogenic variants per individual. Variants were further analyzed using clinical criteria and/or segregation analysis. Three of three previously identified primary mutations were detected by this analysis. In six subjects for whom the primary mutation was previously unknown, we identified mutations that segregated with disease, had clinical correlates, and/or had additional pathological correlation to provide evidence for causality. For two subjects with previously known primary mutations, we identified additional variants that may act as modifiers of disease severity. In total, we identified the likely pathological mutation in 9 of 11 (82%) subjects. We conclude that these pilot data demonstrate that ~30-40× coverage whole genome sequencing combined with targeted analysis is feasible and sensitive to identify rare variants in cardiomyopathy-associated genes.« less

Clues to unraveling the coral species problem: distinguishing species from geographic variation in Porites across the Pacific with molecular markers and microskeletal traits

PubMed Central

Wellington, Gerrard M.; Fox, George E.; Toonen, Robert J.

2015-01-01

Morphological variation in the geographically widespread coral Porites lobata can make it difficult to distinguish from other massive congeneric species. This morphological variation could be attributed to geographic variability, phenotypic plasticity, or a combination of such factors. We examined genetic and microscopic morphological variability in P. lobata samples from the Galápagos, Easter Island, Tahiti, Fiji, Rarotonga, and Australia. Panamanian P. evermanni specimens were used as a previously established distinct outgroup against which to test genetic and morphological methods of discrimination. We employed a molecular analysis of variance (AMOVA) based on ribosomal internal transcribed spacer region (ITS) sequence, principal component analysis (PCA) of skeletal landmarks, and Mantel tests to compare genetic and morphological variation. Both genetic and morphometric methods clearly distinguished P. lobata and P. evermanni, while significant genetic and morphological variance was attributed to differences among geographic regions for P. lobata. Mantel tests indicate a correlation between genetic and morphological variation for P. lobata across the Pacific. Here we highlight landmark morphometric measures that correlate well with genetic differences, showing promise for resolving species of Porites, one of the most ubiquitous yet challenging to identify architects of coral reefs. PMID:25674364

Genetic integration of molar cusp size variation in baboons

PubMed Central

Koh, Christina; Bates, Elizabeth; Broughton, Elizabeth; Do, Nicholas T.; Fletcher, Zachary; Mahaney, Michael C.; Hlusko, Leslea J.

2010-01-01

Many studies of primate diversity and evolution rely on dental morphology for insight into diet, behavior, and phylogenetic relationships. Consequently, variation in molar cusp size has increasingly become a phenotype of interest. In 2007 we published a quantitative genetic analysis of mandibular molar cusp size variation in baboons. Those results provided more questions than answers, as the pattern of genetic integration did not fit predictions from odontogenesis. To follow up, we expanded our study to include data from the maxillary molar cusps. Here we report on these later analyses, as well as inter-arch comparisons with the mandibular data. We analyzed variation in two-dimensional maxillary molar cusp size using data collected from a captive pedigreed breeding colony of baboons, Papio hamadryas, housed at the Southwest National Primate Research Center. These analyses show that variation in maxillary molar cusp size is heritable and sexually dimorphic. We also estimated additive genetic correlations between cusps on the same crown, homologous cusps along the tooth row, and maxillary and mandibular cusps. The pattern for maxillary molars yields genetic correlations of one between the paracone-metacone and protocone-hypocone. Bivariate analyses of cuspal homologues on adjacent teeth yield correlations that are high or not significantly different from one. Between dental arcades, the non-occluding cusps consistently yield high genetic correlations, especially the metaconid-paracone and metaconid-metacone. This pattern of genetic correlation does not immediately accord with the pattern of development and/or calcification, however these results do follow predictions that can be made from the evolutionary history of the tribosphenic molar. PMID:20034010

Genetic integration of molar cusp size variation in baboons.

PubMed

Koh, Christina; Bates, Elizabeth; Broughton, Elizabeth; Do, Nicholas T; Fletcher, Zachary; Mahaney, Michael C; Hlusko, Leslea J

2010-06-01

Many studies of primate diversity and evolution rely on dental morphology for insight into diet, behavior, and phylogenetic relationships. Consequently, variation in molar cusp size has increasingly become a phenotype of interest. In 2007 we published a quantitative genetic analysis of mandibular molar cusp size variation in baboons. Those results provided more questions than answers, as the pattern of genetic integration did not fit predictions from odontogenesis. To follow up, we expanded our study to include data from the maxillary molar cusps. Here we report on these later analyses, as well as inter-arch comparisons with the mandibular data. We analyzed variation in two-dimensional maxillary molar cusp size using data collected from a captive pedigreed breeding colony of baboons, Papio hamadryas, housed at the Southwest National Primate Research Center. These analyses show that variation in maxillary molar cusp size is heritable and sexually dimorphic. We also estimated additive genetic correlations between cusps on the same crown, homologous cusps along the tooth row, and maxillary and mandibular cusps. The pattern for maxillary molars yields genetic correlations of one between the paracone-metacone and protocone-hypocone. Bivariate analyses of cuspal homologues on adjacent teeth yield correlations that are high or not significantly different from one. Between dental arcades, the nonoccluding cusps consistently yield high genetic correlations, especially the metaconid-paracone and metaconid-metacone. This pattern of genetic correlation does not immediately accord with the pattern of development and/or calcification, however these results do follow predictions that can be made from the evolutionary history of the tribosphenic molar. Copyright 2009 Wiley-Liss, Inc.

Genetic relationships between carcass cut weights predicted from video image analysis and other performance traits in cattle.

PubMed

Pabiou, T; Fikse, W F; Amer, P R; Cromie, A R; Näsholm, A; Berry, D P

2012-09-01

The objective of this study was to quantify the genetic associations between a range of carcass-related traits including wholesale cut weights predicted from video image analysis (VIA) technology, and a range of pre-slaughter performance traits in commercial Irish cattle. Predicted carcass cut weights comprised of cut weights based on retail value: lower value cuts (LVC), medium value cuts (MVC), high value cuts (HVC) and very high value cuts (VHVC), as well as total meat, fat and bone weights. Four main sources of data were used in the genetic analyses: price data of live animals collected from livestock auctions, live-weight data and linear type collected from both commercial and pedigree farms as well as from livestock auctions and weanling quality recorded on-farm. Heritability of carcass cut weights ranged from 0.21 to 0.39. Genetic correlations between the cut traits and the other performance traits were estimated using a series of bivariate sire linear mixed models where carcass cut weights were phenotypically adjusted to a constant carcass weight. Strongest positive genetic correlations were obtained between predicted carcass cut weights and carcass value (min r g(MVC) = 0.35; max r(g(VHVC)) = 0.69), and animal price at both weaning (min r(g(MVC)) = 0.37; max r(g(VHVC)) = 0.66) and post weaning (min r(g(MVC)) = 0.50; max r(g(VHVC)) = 0.67). Moderate genetic correlations were obtained between carcass cut weights and calf price (min r g(HVC) = 0.34; max r g(LVC) = 0.45), weanling quality (min r(g(MVC)) = 0.12; max r (g(VHVC)) = 0.49), linear scores for muscularity at both weaning (hindquarter development: min r(g(MVC)) = -0.06; max r(g(VHVC)) = 0.46), post weaning (hindquarter development: min r(g(MVC)) = 0.23; max r(g(VHVC)) = 0.44). The genetic correlations between total meat weight were consistent with those observed with the predicted wholesale cut weights. Total fat and total bone weights were generally negatively correlated with carcass value, auction prices and weanling quality. Total bone weight was, however, positively correlated with skeletal scores at weaning and post weaning. These results indicate that some traits collected early in life are moderate-to-strongly correlated with carcass cut weights predicted from VIA technology. This information can be used to improve the accuracy of selection for carcass cut weights in national genetic evaluations.

Heritability of circulating growth factors involved in the angiogenesis in healthy human population.

PubMed

Pantsulaia, I; Trofimov, S; Kobyliansky, E; Livshits, G

2004-09-21

The present study examined the extent of genetic and environmental influences on the populational variation of circulating growth factors (VEGF, EGF) involved in angiogenesis in healthy and ethnically homogeneous Caucasian families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 478 healthy individuals aged 18-75 years. Quantitative genetic analysis showed that the VEGF and EGF variation was appreciably attributable to genetic effects, with heritability estimates of 79.9% and 48.4%, respectively. Yet, common environmental factors, shared by members of the same household, also played a significant role (P < 0.01) and explained between 20.1% and 32.6% of the variation. The present study additionally examined the covariations between these molecules and either transforming growth factor-beta 1 (TGF-beta 1) or tissue inhibitors of matrix metalloproteinases 1 (TIMP-1), likewise relevant for angiogenesis. Bivariate analysis revealed significant phenotypic correlations (P < 0.002) between all pairs of variables, thus indicating the possible existence of common genetic and environmental factors. The analysis suggested that the pleiotropic genetic effects were consistently the primary (or even the sole) source of correlation between all pairs of studied molecules. The results of our study affirm the existence of specific and common genetic pathways that commonly determine the greater part of the circulating variation of these molecules.

Genetic association between milk yield, stayability, and mastitis in Holstein cows under tropical conditions.

PubMed

Irano, Natalia; Bignardi, Annaiza Braga; El Faro, Lenira; Santana, Mário Luiz; Cardoso, Vera Lúcia; Albuquerque, Lucia Galvão

2014-03-01

The objective of this study was to estimate genetic parameters for milk yield, stayability, and the occurrence of clinical mastitis in Holstein cows, as well as studying the genetic relationship between them, in order to provide subsidies for the genetic evaluation of these traits. Records from 5,090 Holstein cows with calving varying from 1991 to 2010, were used in the analysis. Two standard multivariate analyses were carried out, one containing the trait of accumulated 305-day milk yields in the first lactation (MY1), stayability (STAY) until the third lactation, and clinical mastitis (CM), as well as the other traits, considering accumulated 305-day milk yields (Y305), STAY, and CM, including the first three lactations as repeated measures for Y305 and CM. The covariance components were obtained by a Bayesian approach. The heritability estimates obtained by multivariate analysis with MY1 were 0.19, 0.28, and 0.13 for MY1, STAY, and CM, respectively, whereas using the multivariate analysis with the Y305, the estimates were 0.19, 0.31, and 0.14, respectively. The genetic correlations between MY1 and STAY, MY1 and CM, and STAY and CM, respectively, were 0.38, 0.12, and -0.49. The genetic correlations between Y305 and STAY, Y305 and CM, and STAY and CM, respectively, were 0.66, -0.25, and -0.52.

Heritability of Nociception IV: Neuropathic pain assays are genetically distinct across methods of peripheral nerve injury

PubMed Central

Young, Erin E.; Costigan, Michael; Herbert, Teri A.; Lariviere, William R.

2013-01-01

Prior genetic correlation analysis of 22 heritable behavioral measures of nociception and hypersensitivity in the mouse identified five genetically distinct pain types. In the present study, we reanalyzed that dataset and included the results of an additional nine assays of nociception and hypersensitivity to: 1) replicate the previously identified five pain types; 2) test whether any of the newly added pain assays represent novel genetically distinct pain types; 3) test the level of genetic relatedness among nine commonly employed neuropathic pain assays. Multivariate analysis of pairwise correlations between assays shows that the newly added zymosan-induced heat hypersensitivity assay does not conform to the two previously identified groups of heat hypersensitivity assays and cyclophosphamide-induced cystitis, the first organ-specific visceral pain model examined, is genetically distinct from other inflammatory assays. The four included mechanical hypersensitivity assays are genetically distinct, and do not comprise a single pain type as previously reported. Among the nine neuropathic pain assays including autotomy, chemotherapy, nerve ligation and spared nerve injury assays, at least four genetically distinct types of neuropathic sensory abnormalities were identified, corresponding to differences in nerve injury method. In addition, two itch assays and Comt genotype were compared to the expanded set of nociception and hypersensitivity assays. Comt genotype was strongly related only to spontaneous inflammatory nociception assays. These results indicate the priority for continued investigation of genetic mechanisms in several assays newly identified to represent genetically distinct pain types. PMID:24071598

Environmental stress alters genetic regulation of novelty seeking in vervet monkeys.

PubMed

Fairbanks, L A; Bailey, J N; Breidenthal, S E; Laudenslager, M L; Kaplan, J R; Jorgensen, M J

2011-08-01

Considerable attention has been paid to identifying genetic influences and gene-environment interactions that increase vulnerability to environmental stressors, with promising but inconsistent results. A nonhuman primate model is presented here that allows assessment of genetic influences in response to a stressful life event for a behavioural trait with relevance for psychopathology. Genetic and environmental influences on free-choice novelty seeking behaviour were assessed in a pedigreed colony of vervet monkeys before and after relocation from a low stress to a higher stress environment. Heritability of novelty seeking scores, and genetic correlations within and between environments were conducted using variance components analysis. The results showed that novelty seeking was markedly inhibited in the higher stress environment, with effects persisting across a 2-year period for adults but not for juveniles. There were significant genetic contributions to novelty seeking scores in each year (h(2) = 0.35-0.43), with high genetic correlations within each environment (rhoG > 0.80) and a lower genetic correlation (rhoG = 0.35, non-significant) between environments. There were also significant genetic contributions to individual change scores from before to after the move (h(2) = 0.48). These results indicate that genetic regulation of novelty seeking was modified by the level of environmental stress, and they support a role for gene-environment interactions in a behavioural trait with relevance for mental health. © 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Correlational selection leads to genetic integration of body size and an attractive plumage trait in dark-eyed juncos.

PubMed

McGlothlin, Joel W; Parker, Patricia G; Nolan, Val; Ketterson, Ellen D

2005-03-01

When a trait's effect on fitness depends on its interaction with other traits, the resultant selection is correlational and may lead to the integration of functionally related traits. In relation to sexual selection, when an ornamental trait interacts with phenotypic quality to determine mating success, correlational sexual selection should generate genetic correlations between the ornament and quality, leading to the evolution of honest signals. Despite its potential importance in the evolution of signal honesty, correlational sexual selection has rarely been measured in natural populations. In the dark-eyed junco (Junco hyemalis), males with experimentally elevated values of a plumage trait (whiteness in the tail or "tail white") are more attractive to females and dominant in aggressive encounters over resources. We used restricted maximum-likelihood analysis of a long-term dataset to measure the heritability of tail white and two components of body size (wing length and tail length), as well as genetic correlations between pairs of these traits. We then used multiple regression to assess directional, quadratic, and correlational selection as they acted on tail white and body size via four components of lifetime fitness (juvenile and adult survival, mating success, and fecundity). We found a positive genetic correlation between tail white and body size (as measured by wing length), which indicates past correlational selection. Correlational selection, which was largely due to sexual selection on males, was also found to be currently acting on the same pair of traits. Larger males with whiter tails sired young with more females, most likely due to a combination of female choice, which favors males with whiter tails, and male-male competition, which favors both tail white and larger body size. To our knowledge, this is the first study to show both genetic correlations between sexually selected traits and currently acting correlational sexual selection, and we suggest that correlational sexual selection frequently may be an important mechanism for maintaining the honesty of sexual signals.

Genetic trends for live weight traits reflect breeding strategies in registered Charolais Farms in Mexico.

PubMed

Parra-Bracamonte, G M; Lopez-Villalobos, N; Morris, S T; Sifuentes-Rincón, A M; Lopez-Bustamante, L A

2016-12-01

Genetic trends are commonly used to verify genetic improvement; however, there are few reports on beef cattle in Mexico. Data from 1998 to 2013 from four Charolais bull breeding farms were examined to verify the genetic responses to different breeding management and selection criteria. Analysis included the comparison of regression lines of breeding values for birth (BW), weaning (WW) and yearling weights (YW), and maternal weaning weight (MWW) on the year of birth of the animals. Results revealed differential genetic progress for BW and YW and indicated that the overall analysis may have diluted the perception of genetic progress from the farmer's point of view. The use of breeding values as a tool for selection is effective to achieve genetic progress, even in negatively correlated traits, such as birth weight and yearling weight.

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

PubMed

Sampson, Joshua N; Wheeler, William A; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I; Lan, Qing; Abnet, Christian C; Amundadottir, Laufey T; Figueroa, Jonine D; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A; Taylor, Philip R; De Vivo, Immaculata; McGlynn, Katherine A; Purdue, Mark P; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L; Angelucci, Emanuele; Ansell, Stephen M; Arici, Cecilia; Armstrong, Bruce K; Arslan, Alan A; Austin, Melissa A; Baris, Dalsu; Barkauskas, Donald A; Bassig, Bryan A; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A; Birmann, Brenda M; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M; Brinton, Louise; Brooks-Wilson, Angela R; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K C; Chang, Ellen T; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S; Comperat, Eva; Conde, Lucia; Connors, Joseph M; Conti, David; Cortessis, Victoria K; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G; Ding, Ti; Diver, W Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J; Ennas, Maria Grazia; Erickson, Ralph L; Feychting, Maria; Flanagan, Adrienne M; Foretova, Lenka; Fraumeni, Joseph F; Freedman, Neal D; Beane Freeman, Laura E; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D; Gastier-Foster, Julie; Gaudet, Mia M; Gaziano, J Michael; Giffen, Carol; Giles, Graham G; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M; Haiman, Christopher A; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R; Holly, Elizabeth A; Hong, Yun-Chul; Hoover, Robert N; Horn-Ross, Pamela L; Hosain, G M Monawar; Hosgood, H Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D; Jackson, Rebecca D; Jacobs, Eric J; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R; Kelly, Rachel S; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M; Klein, Alison P; Klein, Robert J; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S; Link, Brian K; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Di Lollo, Simonetta; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Le Marchand, Loic; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S; Michaud, Dominique S; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E; Novak, Anne J; Oberg, Ann L; Offit, Kenneth; Oh, In-Jae; Olson, Sara H; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H M; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M; Picci, Piero; Pike, Malcolm C; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M; Sanjose, Silvia de; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K; Shanafelt, Tait D; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F; Smith, Alex; Smith, Martyn T; Southey, Melissa C; Spinelli, John J; Staines, Anthony; Stampfer, Meir; Stern, Marianna C; Stevens, Victoria L; Stolzenberg-Solomon, Rachael S; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A; Tinker, Lesley F; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M; Vermeulen, Roel C H; Villano, Danylo J; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E; Wolpin, Brian M; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M; Cerhan, James R; Ferri, Giovanni M; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M; Smedby, Karin E; Teras, Lauren R; Vijai, Joseph; Wang, Sophia S; Brennan, Paul; Caporaso, Neil E; Hunter, David J; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T; Slager, Susan L; Chanock, Stephen J; Chatterjee, Nilanjan

2015-12-01

Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Association between dietary fat intake and insulin resistance in Chinese child twins.

PubMed

Huang, Tao; Beaty, Terri; Li, Ji; Liu, Huijuan; Zhao, Wei; Wang, Youfa

2017-01-01

Dietary fat intake is correlated with increased insulin resistance (IR). However, it is unknown whether gene-diet interaction modulates the association. This study estimated heritability of IR measures and the related genetic correlations with fat intake, and tested whether dietary fat intake modifies the genetic influence on type 2 diabetes (T2D)-related traits in Chinese child twins. We included 622 twins aged 7-15 years (n 311 pairs, 162 monozygotic (MZ), 149 dizygotic (DZ)) from south-eastern China. Dietary factors were measured using FFQ. Structural equation models were fit using Mx statistical package. The intra-class correlation coefficients for all traits related to T2D were higher for MZ twins than for DZ twins. Dietary fat and fasting serum insulin (additive genetic correlation (r A) 0·20; 95 % CI 0·08, 0·43), glucose (r A 0·12; 95 % CI 0·01, 0·40), homoeostasis model of assessment-insulin resistance (Homa-IR) (r A 0·22; 95 % CI 0·10, 0·50) and the quantitative insulin sensitivity check index (Quicki) (r A -0·22; 95 % CI -0·40, 0·04) showed strong genetic correlations. Heritabilities of dietary fat intake, fasting glucose and insulin were estimated to be 52, 70 and 70 %, respectively. More than 70 % of the phenotypic correlations between dietary fat and insulin, glucose, Homa-IR and the Quicki index appeared to be mediated by shared genetic influence. Dietary fat significantly modified additive genetic effects on these quantitative traits associated with T2D. Analysis of Chinese twins yielded high estimates of heritability of dietary fat intake and IR. Genetic factors appear to contribute to a high proportion of the variance for both insulin sensitivity and IR. Dietary fat intake modifies the genetic influence on blood levels of insulin and glucose, Homa-IR and the Quicki index.

Genetic and Environmental Influences on Pulmonary Function and Muscle Strength: The Chinese Twin Study of Aging.

PubMed

Tian, Xiaocao; Xu, Chunsheng; Wu, Yili; Sun, Jianping; Duan, Haiping; Zhang, Dongfeng; Jiang, Baofa; Pang, Zengchang; Li, Shuxia; Tan, Qihua

2017-02-01

Genetic and environmental influences on predictors of decline in daily functioning, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), handgrip, and five-times-sit-to-stand test (FTSST), have not been addressed in the aging Chinese population. We performed classical twin modeling on FEV1, FVC, handgrip, and FTSST in 379 twin pairs (240 MZ and 139 DZ) with median age of 50 years (40-80 years). Data were analyzed by fitting univariate and bivariate twin models to estimate the genetic and environmental influences on these measures of physical function. Heritability was moderate for FEV1, handgrip, and FTSST (55-60%) but insignificant for FVC. Only FVC showed moderate control, with shared environmental factors accounting for about 50% of the total variance. In contrast, all measures of pulmonary function and muscle strength showed modest influences from the unique environment (40-50%). Bivariate analysis showed highly positive genetic correlations between FEV1 and FVC (r G = 1.00), and moderately negative genetic correlations between FTSST and FEV1 (r G = -0.33) and FVC (r G = -0.42). FEV1 and FVC, as well as FEV1 and handgrip, displayed high common environmental correlations (r C = 1.00), and there were moderate correlations between FVC and handgrip (r C = 0.44). FEV1 and FVC showed high unique environmental correlations (r E = 0.76) and low correlations between handgrip and FEV1 (r E = 0.17), FVC (r E = 0.14), and FTSST (r E = -0.13) with positive or negative direction. We conclude that genetic factors contribute significantly to the individual differences in common indicators of daily functioning (FEV1, handgrip, and FTSST). FEV1 and FVC were genetically and environmentally correlated. Pulmonary function and FTSST may share similar sets of genes but in the negative direction. Pulmonary function and muscle strength may have a shared environmental background.

Correlates of genetic monogamy in socially monogamous mammals: insights from Azara's owl monkeys

PubMed Central

Huck, Maren; Fernandez-Duque, Eduardo; Babb, Paul; Schurr, Theodore

2014-01-01

Understanding the evolution of mating systems, a central topic in evolutionary biology for more than 50 years, requires examining the genetic consequences of mating and the relationships between social systems and mating systems. Among pair-living mammals, where genetic monogamy is extremely rare, the extent of extra-group paternity rates has been associated with male participation in infant care, strength of the pair bond and length of the breeding season. This study evaluated the relationship between two of those factors and the genetic mating system of socially monogamous mammals, testing predictions that male care and strength of pair bond would be negatively correlated with rates of extra-pair paternity (EPP). Autosomal microsatellite analyses provide evidence for genetic monogamy in a pair-living primate with bi-parental care, the Azara's owl monkey (Aotus azarae). A phylogenetically corrected generalized least square analysis was used to relate male care and strength of the pair bond to their genetic mating system (i.e. proportions of EPP) in 15 socially monogamous mammalian species. The intensity of male care was correlated with EPP rates in mammals, while strength of pair bond failed to reach statistical significance. Our analyses show that, once social monogamy has evolved, paternal care, and potentially also close bonds, may facilitate the evolution of genetic monogamy. PMID:24648230

Correlates of genetic monogamy in socially monogamous mammals: insights from Azara's owl monkeys.

PubMed

Huck, Maren; Fernandez-Duque, Eduardo; Babb, Paul; Schurr, Theodore

2014-05-07

Understanding the evolution of mating systems, a central topic in evolutionary biology for more than 50 years, requires examining the genetic consequences of mating and the relationships between social systems and mating systems. Among pair-living mammals, where genetic monogamy is extremely rare, the extent of extra-group paternity rates has been associated with male participation in infant care, strength of the pair bond and length of the breeding season. This study evaluated the relationship between two of those factors and the genetic mating system of socially monogamous mammals, testing predictions that male care and strength of pair bond would be negatively correlated with rates of extra-pair paternity (EPP). Autosomal microsatellite analyses provide evidence for genetic monogamy in a pair-living primate with bi-parental care, the Azara's owl monkey (Aotus azarae). A phylogenetically corrected generalized least square analysis was used to relate male care and strength of the pair bond to their genetic mating system (i.e. proportions of EPP) in 15 socially monogamous mammalian species. The intensity of male care was correlated with EPP rates in mammals, while strength of pair bond failed to reach statistical significance. Our analyses show that, once social monogamy has evolved, paternal care, and potentially also close bonds, may facilitate the evolution of genetic monogamy.

A Critical Analysis of IQ Studies of Adopted Children

ERIC Educational Resources Information Center

Richardson, Ken; Norgate, Sarah H.

2006-01-01

The pattern of parent-child correlations in adoption studies has long been interpreted to suggest substantial additive genetic variance underlying variance in IQ. The studies have frequently been criticized on methodological grounds, but those criticisms have not reflected recent perspectives in genetics and developmental theory. Here we apply…

Genetic Determinants of Thrombin Generation and Their Relation to Venous Thrombosis: Results from the GAIT-2 Project

PubMed Central

Martin-Fernandez, Laura; Ziyatdinov, Andrey; Carrasco, Marina; Millon, Juan Antonio; Martinez-Perez, Angel; Vilalta, Noelia; Brunel, Helena; Font, Montserrat; Hamsten, Anders; Souto, Juan Carlos; Soria, José Manuel

2016-01-01

Background Venous thromboembolism (VTE) is a common disease where known genetic risk factors explain only a small portion of the genetic variance. Then, the analysis of intermediate phenotypes, such as thrombin generation assay, can be used to identify novel genetic risk factors that contribute to VTE. Objectives To investigate the genetic basis of distinct quantitative phenotypes of thrombin generation and its relationship to the risk of VTE. Patients/Methods Lag time, thrombin peak and endogenous thrombin potential (ETP) were measured in the families of the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT-2) Project. This sample consisted of 935 individuals in 35 extended families selected through a proband with idiopathic thrombophilia. We performed also genome wide association studies (GWAS) with thrombin generation phenotypes. Results The results showed that 67% of the variation in the risk of VTE is attributable to genetic factors. The heritabilities of lag time, thrombin peak and ETP were 49%, 54% and 52%, respectively. More importantly, we demonstrated also the existence of positive genetic correlations between thrombin peak or ETP and the risk of VTE. Moreover, the major genetic determinant of thrombin generation was the F2 gene. However, other suggestive signals were observed. Conclusions The thrombin generation phenotypes are strongly genetically determined. The thrombin peak and ETP are significantly genetically correlated with the risk of VTE. In addition, F2 was identified as a major determinant of thrombin generation. We reported suggestive signals that might increase our knowledge to explain the variability of this important phenotype. Validation and functional studies are required to confirm GWAS results. PMID:26784699

The relationship of quantitative nuclear morphology to molecular genetic alterations in the adenoma-carcinoma sequence of the large bowel.

PubMed Central

Mulder, J. W.; Offerhaus, G. J.; de Feyter, E. P.; Floyd, J. J.; Kern, S. E.; Vogelstein, B.; Hamilton, S. R.

1992-01-01

The relationship of abnormal nuclear morphology to molecular genetic alterations that are important in colorectal tumorigenesis is unknown. Therefore, Feulgen-stained isolated nuclei from 22 adenomas and 42 carcinomas that had been analyzed for ras gene mutations and allelic deletions on chromosomes 5q, 18q, and 17p were characterized by computerized image analysis. Both nuclear area and the nuclear shape factor representing irregularity correlated with adenoma-carcinoma progression (r = 0.57 and r = 0.52, P < 0.0001), whereas standard nuclear texture, a parameter of chromatin homogeneity, was inversely correlated with progression (r = -0.80, P < 0.0001). The nuclear parameters were strongly interrelated (P < 0.0005). In multivariate analysis, the nuclear parameters were predominantly associated with adenoma-carcinoma progression (P < or = 0.0001) and were not influenced significantly by the individual molecular genetic alterations. Nuclear texture, however, was inversely correlated with fractional allelic loss, a global measure of genetic changes, in carcinomas (r = -0.39, P = 0.011). The findings indicate that nuclear morphology in colorectal neoplasms is strongly related to tumor progression. Nuclear morphology and biologic behavior appear to be influenced by accumulated alterations in cancer-associated genes. Images Figure 1 PMID:1357973

Motivations for genetic testing for lung cancer risk among young smokers.

PubMed

O'Neill, Suzanne C; Lipkus, Isaac M; Sanderson, Saskia C; Shepperd, James; Docherty, Sharron; McBride, Colleen M

2013-11-01

To examine why young people might want to undergo genetic susceptibility testing for lung cancer despite knowing that tested gene variants are associated with small increases in disease risk. The authors used a mixed-method approach to evaluate motives for and against genetic testing and the association between these motivations and testing intentions in 128 college students who smoke. Exploratory factor analysis yielded four reliable factors: Test Scepticism, Test Optimism, Knowledge Enhancement and Smoking Optimism. Test Optimism and Knowledge Enhancement correlated positively with intentions to test in bivariate and multivariate analyses (ps<0.001). Test Scepticism correlated negatively with testing intentions in multivariate analyses (p<0.05). Open-ended questions assessing testing motivations generally replicated themes of the quantitative survey. In addition to learning about health risks, young people may be motivated to seek genetic testing for reasons, such as gaining knowledge about new genetic technologies more broadly.

A multivariate twin study of early literacy in Japanese Kana

PubMed Central

Fujisawa, Keiko K.; Wadsworth, Sally J.; Kakihana, Shinichiro; Olson, Richard K.; DeFries, John C.; Byrne, Brian; Ando, Juko

2013-01-01

This first Japanese twin study of early literacy development investigated the extent to which genetic and environmental factors influence individual differences in prereading skills in 238 pairs of twins at 42 months of age. Twin pairs were individually tested on measures of phonological awareness, kana letter name/sound knowledge, receptive vocabulary, visual perception, nonword repetition, and digit span. Results obtained from univariate behavioral-genetic analyses yielded little evidence for genetic influences, but substantial shared-environmental influences, for all measures. Phenotypic confirmatory factor analysis suggested three correlated factors: phonological awareness, letter name/sound knowledge, and general prereading skills. Multivariate behavioral genetic analyses confirmed relatively small genetic and substantial shared environmental influences on the factors. The correlations among the three factors were mostly attributable to shared environment. Thus, shared environmental influences play an important role in the early reading development of Japanese children. PMID:23997545

International genetic evaluation of Holstein bulls for overall type traits and body condition score.

PubMed

Battagin, M; Forabosco, F; Jakobsen, J H; Penasa, M; Lawlor, T J; Cassandro, M

2012-08-01

The study documents the procedures used to estimate genetic correlations among countries for overall conformation (OCS), overall udder (OUS), overall feet and legs (OFL), and body condition score (BCS) of Holstein sires. Major differences in traits definition are discussed, in addition to the use of international breeding values (IBV) among countries involved in international genetic evaluations, and similarities among countries through hierarchical clustering. Data were available for populations from 20 countries for OCS and OUS, 18 populations for OFL, and 11 populations for BCS. The IBV for overall traits and BCS were calculated using a multi-trait across-country evaluation model. Distance measures, obtained from genetic correlations, were used as input values in the cluster analysis. Results from surveys sent to countries participating in international genetic evaluation for conformation traits showed that different ways of defining traits are used: the overall traits were either computed from linear or composite traits or defined as general characteristics. For BCS, populations were divided into 2 groups: one scored and evaluated BCS, and one used a best predictor. In general, populations were well connected except for Estonia and French Red Holstein. The average number of common bulls for the overall traits ranged from 19 (OCS and OUS of French Red Holstein) to 514 (OFL of United States), and for BCS from 17 (French Red Holstein) to 413 (the Netherlands). The average genetic correlation (range) across countries was 0.75 (0.35 to 0.95), 0.80 (0.41 to 0.95), and 0.68 (0.12 to 0.89) for OCS, OUS, and OFL, respectively. Genetic correlations among countries that used angularity as best predictor for BCS and countries that scored BCS were negative. The cluster analysis provided a clear picture of the countries distances; differences were due to trait definition, trait composition, and weights in overall traits, genetic ties, and genotype by environment interactions. Harmonization of trait definition and increasing genetic ties could improve genetic correlations across countries and reduce the distances. In each national selection index, all countries, except Estonia and New Zealand, included at least one overall trait, whereas none included BCS. Out of 18 countries, 9 have started genomic evaluation of conformation traits. The first were Canada, France, New Zealand, and United States in 2009, followed by Switzerland, Germany, and the Netherlands in 2010, and Australia and Denmark-Finland-Sweden (joint evaluation) in 2011. Six countries are planning to start soon. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genetic analysis of traits affecting the success of embryo transfer in dairy cattle.

PubMed

König, S; Bosselmann, F; von Borstel, U U; Simianer, H

2007-08-01

The primary aim of this study was to estimate variance components for traits related to embryo transfer (ET) by applying generalized linear mixed models (GLMM) for different distributions of traits (normal, binomial, and Poisson) in a synergistic context. Synergistic models were originally developed for traits affected by several genotypes, denoted as maternal, paternal, and direct effects. In the case of ET, the number of flushed ova (FO) only depends on a donor's maternal genetic effect, whereas paternal fertility must be considered for other embryo survival traits, such as the number of transferable embryos (TE), the number of degenerated embryos (DE), the number of unfertilized oocytes (UO), and the percentage of transferable embryos (PTE). Data for these traits were obtained from 4,196 flushes of 2,489 Holstein cows within 4 regions of northwest Germany from January 1998 through October 2004. Estimates of maternal heritability were 0.231 for FO, 0.096 for TE, 0.021 for DE, 0.135 for UO, and 0.099 for PTE, whereas the relative genetic impact of the paternal component was near zero. Estimates of the genetic correlations between the maternal and the paternal component were slightly negative, indicating a genetic antagonism. For the analysis of pregnancy after ET, 8,239 transfers to 6,819 different Holstein-Friesian recipients were considered by applying threshold methodology. The direct heritability for pregnancy in the recipient after ET was 0.056. The relative genetic impact of maternal and paternal components on pregnancy of recipients describing a donor's and a sire's ability to produce viable embryos was below 1%. The genetic correlations of the direct effect of the recipient with the sire of embryos (paternal effect) and the donor cow (maternal effect) for pregnancy after ET were -0.32 and -0.14, respectively. With the exception of FO and PTE (-0.17), estimates of genetic correlations among traits for the maternal site were distinctly positive, especially between FO and TE (0.74). Based on this high genetic correlation and due to the higher heritability for FO, indirect selection on FO will increase selection response in TE by about 22% compared with direct selection on TE. The negative genetic correlation of -0.27 between TE and lactation milk yield indicates the need for development of an index for bull dams in multiple ovulation and embryo transfer (MOET) breeding schemes combining production as well as traits related to ET.

Learning abilities and disabilities: generalist genes in early adolescence.

PubMed

Davis, Oliver S P; Haworth, Claire M A; Plomin, Robert

2009-01-01

The new view of cognitive neuropsychology that considers not just case studies of rare severe disorders but also common disorders, as well as normal variation and quantitative traits, is more amenable to recent advances in molecular genetics, such as genome-wide association studies, and advances in quantitative genetics, such as multivariate genetic analysis. A surprising finding emerging from multivariate quantitative genetic studies across diverse learning abilities is that most genetic influences are shared: they are "generalist", rather than "specialist". We exploited widespread access to inexpensive and fast Internet connections in the United Kingdom to assess over 5000 pairs of 12-year-old twins from the Twins Early Development Study (TEDS) on four distinct batteries: reading, mathematics, general cognitive ability (g) and, for the first time, language. Genetic correlations remain high among all of the measured abilities, with language as highly correlated genetically with g as reading and mathematics. Despite developmental upheaval, generalist genes remain important into early adolescence, suggesting optimal strategies for molecular genetic studies seeking to identify the genes of small effect that influence learning abilities and disabilities.

Clinical subtypes and genetic heterogeneity: of lumping and splitting in Parkinson disease.

PubMed

von Coelln, Rainer; Shulman, Lisa M

2016-12-01

Recent studies on clinical, genetic and pathological heterogeneity of Parkinson disease have renewed the old debate whether we should think of Parkinson disease as one disease with variations, or as a group of independent diseases that happen to present with similar phenotypes. Here, we provide an overview of where the debate is coming from, and how recent findings in clinical subtyping, genetics and clinico-pathological correlation have shaped this controversy over the last few years. New and innovative clinical diagnostic criteria for Parkinson disease have been proposed and await validation. Studies using functional imaging or wearable biosensors, as well as biomarker studies, provide new support for the validity of the traditional clinical subtypes of Parkinson disease (tremor-dominant versus akinetic-rigid or postural instability/gait difficulty). A recent cluster analysis (as unbiased data-driven approach to subtyping) included a wide spectrum of nonmotor variables, and showed correlation of the proposed subtypes with disease progression in a longitudinal analysis. New genetic factors contributing to Parkinson disease susceptibility continue to be identified, including rare mutations causing monogenetic disease, common variants with small effect size and risk factors (like mutations in the gene for glucocerebrosidase) that fall in between the two other categories. Recent studies show some limited correlation between genetic factors and clinical heterogeneity. Despite some variations in patterns of pathology, Lewy bodies are still the hallmark of Parkinson disease, including the vast majority of genetic subgroups. Evidence of clinical, genetic and pathological heterogeneity of Parkinson disease continues to emerge, but clearly defined subtypes that hold up in more than one of these domains remain elusive. For research to identify such subtypes, splitting is likely the way forward; until then, for clinical practice, lumping remains the more pragmatic approach.

Genetic Analysis of Milk Yield in First-Lactation Holstein Friesian in Ethiopia: A Lactation Average vs Random Regression Test-Day Model Analysis

PubMed Central

Meseret, S.; Tamir, B.; Gebreyohannes, G.; Lidauer, M.; Negussie, E.

2015-01-01

The development of effective genetic evaluations and selection of sires requires accurate estimates of genetic parameters for all economically important traits in the breeding goal. The main objective of this study was to assess the relative performance of the traditional lactation average model (LAM) against the random regression test-day model (RRM) in the estimation of genetic parameters and prediction of breeding values for Holstein Friesian herds in Ethiopia. The data used consisted of 6,500 test-day (TD) records from 800 first-lactation Holstein Friesian cows that calved between 1997 and 2013. Co-variance components were estimated using the average information restricted maximum likelihood method under single trait animal model. The estimate of heritability for first-lactation milk yield was 0.30 from LAM whilst estimates from the RRM model ranged from 0.17 to 0.29 for the different stages of lactation. Genetic correlations between different TDs in first-lactation Holstein Friesian ranged from 0.37 to 0.99. The observed genetic correlation was less than unity between milk yields at different TDs, which indicated that the assumption of LAM may not be optimal for accurate evaluation of the genetic merit of animals. A close look at estimated breeding values from both models showed that RRM had higher standard deviation compared to LAM indicating that the TD model makes efficient utilization of TD information. Correlations of breeding values between models ranged from 0.90 to 0.96 for different group of sires and cows and marked re-rankings were observed in top sires and cows in moving from the traditional LAM to RRM evaluations. PMID:26194217

Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network, and pathway analyses

PubMed Central

Kogelman, Lisette J. A.; Pant, Sameer D.; Fredholm, Merete; Kadarmideen, Haja N.

2014-01-01

Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation of haplotype blocks. We built Weighted Interaction SNP Hub (WISH) and differentially wired (DW) networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g., NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g., metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic) obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways that underlie it. PMID:25071839

Variation and Heritability in Hair Diameter and Curvature in an Australian Twin Sample.

PubMed

Ho, Yvonne Y W; Brims, Mark; McNevin, Dennis; Spector, Timothy D; Martin, Nicholas G; Medland, Sarah E

2016-08-01

Hair diameter and curvature are two characteristics of human scalp hair used in forensic contexts. While previous data show that subjective categorization of hair curvature is highly heritable, the heritability of objectively measured curvature and diameter, and variability of hair characteristics within each individual have not yet been studied. The present study measured hair diameter and curvature using an optical fiber diameter analyzer in a sample of 2,332 twins and siblings. Heritability was estimated using maximum likelihood structural equation modeling. Results show sex differences in the magnitude of genetic influence for mean diameter and curvature, with the vast majority of the variance accounted for by genetic effects in males (diameter = 86%, curvature = 53%) and females (diameter = 77%, curvature = 61%). The consistency of diameter (variance within an individual) was also highly heritable, but did not show sex limitation, with 68% of the variance accounted for by genetic factors. Moderate phenotypic correlations were seen between diameter and consistency (r = 0.3) but there was little correlation between diameter and curvature (r = -0.13). A bivariate Cholesky analysis was used to estimate the genetic and environmental correlations between hair diameter and consistency, yielding genetic correlations of r gF = 0.27 for females and r gM = 0.25 for males.

Genetic parameters for different growth scales in GIFT strain of Nile tilapia (Oreochromis niloticus).

PubMed

He, J; Gao, H; Xu, P; Yang, R

2015-12-01

Body weight, length, width and depth at two growth stages were observed for a total of 5015 individuals of GIFT strain, along with a pedigree including 5588 individuals from 104 sires and 162 dams was collected. Multivariate animal models and a random regression model were used to genetically analyse absolute and relative growth scales of these growth traits. In absolute growth scale, the observed growth traits had moderate heritabilities ranging from 0.321 to 0.576, while pairwise ratios between body length, width and depth were lowly inherited and maximum heritability was only 0.146 for length/depth. All genetic correlations were above 0.5 between pairwise growth traits and genetic correlation between length/width and length/depth varied between both growth stages. Based on those estimates, selection index of multiple traits of interest can be formulated in future breeding program to improve genetically body weight and morphology of the GIFT strain. In relative growth scale, heritabilities in relative growths of body length, width and depth to body weight were 0.257, 0.412 and 0.066, respectively, while genetic correlations among these allometry scalings were above 0.8. Genetic analysis for joint allometries of body weight to body length, width and depth will contribute to genetically regulate the growth rate between body shape and body weight. © 2015 Blackwell Verlag GmbH.

Genetic overlap between diagnostic subtypes of ischemic stroke.

PubMed

Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer; Bevan, Steve; Falcone, Guido; Hopewell, Jemma C; Cheng, Yu-Ching; Cotlarciuc, Ioana; Bis, Joshua C; Boerwinkle, Eric; Boncoraglio, Giorgio B; Clarke, Robert; Cole, John W; Fornage, Myriam; Furie, Karen L; Ikram, M Arfan; Jannes, Jim; Kittner, Steven J; Lincz, Lisa F; Maguire, Jane M; Meschia, James F; Mosley, Thomas H; Nalls, Mike A; Oldmeadow, Christopher; Parati, Eugenio A; Psaty, Bruce M; Rothwell, Peter M; Seshadri, Sudha; Scott, Rodney J; Sharma, Pankaj; Sudlow, Cathie; Wiggins, Kerri L; Worrall, Bradford B; Rosand, Jonathan; Mitchell, Braxton D; Dichgans, Martin; Markus, Hugh S; Levi, Christopher; Attia, John; Wray, Naomi R

2015-03-01

Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10(-4)) and profile scores (rg=0.72; 95% confidence interval, 0.52-0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1×10(-7)) for single nucleotide polymorphisms near the opioid receptor μ1 (OPRM1) gene. Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes. © 2015 American Heart Association, Inc.

Bone Strength Estimated by Micro-Finite Element Analysis (µFEA) Is Heritable and Shares Genetic Predisposition With Areal BMD: The Framingham Study.

PubMed

Karasik, David; Demissie, Serkalem; Lu, Darlene; Broe, Kerry E; Boyd, Steven K; Liu, Ching-Ti; Hsu, Yi-Hsiang; Bouxsein, Mary L; Kiel, Douglas P

2017-11-01

Genetic factors contribute to the risk of bone fractures, partly because of effects on bone strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) estimates bone strength using micro-finite element analysis (µFEA). The goal of this study was to investigate if the bone failure load estimated by HR-pQCT-based µFEA is heritable and to what extent it shares genetic regulation with areal bone mineral density (aBMD). Bone microarchitecture was measured by HR-pQCT at the ultradistal tibia and ultradistal radius in adults from the Framingham Heart Study (n = 1087, mean age 72 years; 57% women). Radial and tibial failure load in compression were estimated by µFEA. Femoral neck (FN) and ultradistal forearm (UD) aBMD were measured by dual-energy X-ray absorptiometry (DXA). Heritability (h 2 ) of failure load and aBMD and genetic correlations between them was estimated adjusting for covariates (age and sex). Failure load values at the non-weight-bearing ultradistal radius and at the weight-bearing ultradistal tibia were highly correlated (r = 0.906; p < 0.001). Estimates of h 2 adjusted for covariates were 0.522 for the radius and 0.497 for the tibia. Additional adjustment for height did not impact on the h 2 results, but adjustment for aBMD at the UD and FN somewhat decreased h 2 point estimates: 0.222 and 0.380 for radius and tibia, respectively. In bivariate analysis, there was a high phenotypic and genetic correlation between covariate-adjusted failure load at the radius and UD aBMD (ρ P  = 0.826, ρ G  = 0.954, respectively), whereas environmental correlations were lower (ρ E  = 0.696), all highly significant (p < 0.001). Similar correlations were observed between tibial failure load and femoral neck aBMD (ρ P  = 0.577, ρ G  = 0.703, both p < 0.001; ρ E  = 0.432, p < 0.05). These data from adult members of families from a population-based cohort suggest that bone strength of distal extremities estimated by micro-finite element analysis is heritable and shares some genetic composition with areal BMD, regardless of the skeletal site. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

The role of mutation analysis of the APC gene in the management of FAP patients. A controversial issue.

PubMed

Dodaro, Concetta; Grifasi, Carlo; Florio, Jole; Santangelo, Michele L; Duraturo, Francesca; De Rosa, Marina; Izzo, Paola; Renda, Andrea

A correlation between the location of mutation in the adenomatous polyposis coli (APC) gene and clinical manifestations of familial adenomatous polyposis (FAP) has repeatedly been reported. Some Authors suggest the use of mutational analysis as a guide to select the best surgical option in FAP patients. However, data coming from studies on large series have raised questions on this issue. The aim of this study is to discuss the role of the genetic tests in the management of FAP. A literature review was performed considering only peer-reviewed articles published between 1991-2015. All the studies examined the role of genetic as a guide for surgical management of FAP. Of 363 articles identified, 21 were selected for full-text review. We found different positions with regard the use of genetic tests to determine surgical management of FAP. In particular, while consistent correlations between the APC mutation site and FAP phenotype were observed in large series, 8 studies reported a wide variation of genotypephenotype correlation in patients with the same mutation and they recommended that decisions regarding surgical strategy should be based not only on genotype but also on the clinical factors and the will of the patient who must be fully informed. The decision on the type and the timing of surgery should be based on the assessment of many factors and genotype assessment should be used in combination with clinical data. Disease severity, Familial adenomatous polyposis, Genetic tests, Genotype-phenotype correlations, Surgical management.

Heritability of articular cartilage regeneration and its association with ear wound healing in mice.

PubMed

Rai, Muhammad Farooq; Hashimoto, Shingo; Johnson, Eric E; Janiszak, Kara L; Fitzgerald, Jamie; Heber-Katz, Ellen; Cheverud, James M; Sandell, Linda J

2012-07-01

Emerging evidence suggests that genetic components contribute significantly to cartilage degeneration in osteoarthritis pathophysiology, but little information is available on the genetics of cartilage regeneration. Therefore, this study was undertaken to investigate cartilage regeneration in genetic murine models using common inbred strains and a set of recombinant inbred (RI) lines generated from LG/J (healer of ear wounds) and SM/J (nonhealer) inbred mouse strains. An acute full-thickness cartilage injury was introduced in the trochlear groove of 8-week-old mice (n=265) through microsurgery. Mouse knee joints were sagittally sectioned and stained with toluidine blue to evaluate regeneration. For the ear wound phenotype, a bilateral 2-mm through-and-through puncture was created in 6-week-old mice (n=229), and healing outcomes were measured after 30 days. Broad-sense heritability and genetic correlations were calculated for both phenotypes. Time-course analysis of the RI mouse lines showed no significant regeneration until 16 weeks after surgery; at that time, the strains could be segregated into 3 categories: good, intermediate, and poor healers. Analysis of heritability (H2) showed that both cartilage regeneration (H2=26%; P=0.006) and ear wound closure (H2=53%; P<0.00001) were significantly heritable. The genetic correlations between the two healing phenotypes for common inbred mouse strains (r=0.92) and RI mouse lines (r=0.86) were found to be extremely high. Our findings indicate that articular cartilage regeneration in mice is heritable, the differences between the mouse lines are due to genetic differences, and a strong genetic correlation between the two phenotypes exists, indicating that they plausibly share a common genetic basis. We therefore surmise that LG/J by SM/J intercross mice can be used to dissect the genetic basis of variation in cartilage regeneration. Copyright © 2012 by the American College of Rheumatology.

Quantitative genetic analysis of the bTB diagnostic single intradermal comparative cervical test (SICCT).

PubMed

Tsairidou, Smaragda; Brotherstone, Susan; Coffey, Mike; Bishop, Stephen C; Woolliams, John A

2016-11-24

Bovine tuberculosis (bTB) is a disease of significant economic importance and is a persistent animal health problem with implications for public health worldwide. Control of bTB in the UK has relied on diagnosis through the single intradermal comparative cervical test (SICCT). However, limitations in the sensitivity of this test hinder successful eradication and the control of bTB remains a major challenge. Genetic selection for cattle that are more resistant to bTB infection can assist in bTB control. The aim of this study was to conduct a quantitative genetic analysis of SICCT measurements collected during bTB herd testing. Genetic selection for bTB resistance will be partially informed by SICCT-based diagnosis; therefore it is important to know whether, in addition to increasing bTB resistance, this might also alter genetically the epidemiological characteristics of SICCT. Our main findings are that: (1) the SICCT test is robust at the genetic level, since its hierarchy and comparative nature provide substantial protection against random genetic changes that arise from genetic drift and from correlated responses among its components due to either natural or artificial selection; (2) the comparative nature of SICCT provides effective control for initial skin thickness and age-dependent differences; and (3) continuous variation in SICCT is only lowly heritable and has a weak correlation with SICCT positivity among healthy animals which was not significantly different from zero (P > 0.05). These emerging results demonstrate that genetic selection for bTB resistance is unlikely to change the probability of correctly identifying non-infected animals, i.e. the test's specificity, while reducing the overall number of cases. This study cannot exclude all theoretical risks from selection on resistance to bTB infection but the role of SICCT in disease control is unlikely to be rapidly undermined, with any adverse correlated responses expected to be weak and slow, which allow them to be monitored and managed.

Genetic correlations between the cumulative pseudo-survival rate, milk yield, and somatic cell score during lactation in Holstein cattle in Japan using a random regression model.

PubMed

Sasaki, O; Aihara, M; Nishiura, A; Takeda, H

2017-09-01

Trends in genetic correlations between longevity, milk yield, and somatic cell score (SCS) during lactation in cows are difficult to trace. In this study, changes in the genetic correlations between milk yield, SCS, and cumulative pseudo-survival rate (PSR) during lactation were examined, and the effect of milk yield and SCS information on the reliability of estimated breeding value (EBV) of PSR were determined. Test day milk yield, SCS, and PSR records were obtained for Holstein cows in Japan from 2004 to 2013. A random subset of the data was used for the analysis (825 herds, 205,383 cows). This data set was randomly divided into 5 subsets (162-168 herds, 83,389-95,854 cows), and genetic parameters were estimated in each subset independently. Data were analyzed using multiple-trait random regression animal models including either the residual effect for the whole lactation period (H0), the residual effects for 5 lactation stages (H5), or both of these residual effects (HD). Milk yield heritability increased until 310 to 351 d in milk (DIM) and SCS heritability increased until 330 to 344 DIM. Heritability estimates for PSR increased with DIM from 0.00 to 0.05. The genetic correlation between milk yield and SCS increased negatively to under -0.60 at 455 DIM. The genetic correlation between milk yield and PSR increased until 342 to 355 DIM (0.53-0.57). The genetic correlation between the SCS and PSR was -0.82 to -0.83 at around 180 DIM, and decreased to -0.65 to -0.71 at 455 DIM. The reliability of EBV of PSR for sires with 30 or more recorded daughters was 0.17 to 0.45 when the effects of correlated traits were ignored. The maximum reliability of EBV was observed at 257 (H0) or 322 (HD) DIM. When the correlations of PSR with milk yield and SCS were considered, the reliabilities of PSR estimates increased to 0.31-0.76. The genetic parameter estimates of H5 were the same as those for HD. The rank correlation coefficients of the EBV of PSR between H0 and H5 or HD were greater than 0.9. Additionally, the reliabilities of EBV of PSR of H0 were similar to those for H5 and HD. Therefore, the genetic parameter estimates in H0 were not substantially different from those in H5 and HD. When milk yield and SCS, which were genetically correlated with PSR, were used, the reliability of PSR increased. Estimates of the genetic correlations between PSR and milk yield and between PSR and SCS are useful for management and breeding decisions to extend the herd life of cows. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genetic parameters for sensory traits in longissimus muscle and their associations with tenderness, marbling score, and intramuscular fat in Angus cattle.

PubMed

Mateescu, R G; Garrick, D J; Garmyn, A J; VanOverbeke, D L; Mafi, G G; Reecy, J M

2015-01-01

The objective of this study was to estimate heritabilities for sensory traits and genetic correlations among sensory traits and with marbling score (MS), Warner-Bratzler shear force (WBSF), and intramuscular fat content (IMFC). Samples of LM from 2,285 Angus cattle were obtained and fabricated into steaks for laboratory analysis and 1,720 steaks were analyzed by a trained sensory panel. Restricted maximum likelihood procedures were used to obtain estimates of variance and covariance components under a multitrait animal model. Estimates of heritability for MS, IMFC, WBSF, tenderness, juiciness, and connective tissue traits were 0.67, 0.38, 0.19, 0.18, 0.06, and 0.25, respectively. The genetic correlations of MS with tenderness, juiciness, and connective tissue were estimated to be 0.57 ± 0.14, 1.00 ± 0.17, and 0.49 ± 0.13, all positive and strong. Estimated genetic correlations of IMFC with tenderness, juiciness, and connective tissue were 0.56 ± 0.16, 1.00 ± 0.21, and 0.50 ± 0.15, respectively. The genetic correlations of WBSF with tenderness, juiciness, and connective tissue were all favorable and estimated to be -0.99 ± 0.08, -0.33 ± 0.30 and -0.99 ± 0.07, respectively. Strong and positive genetic correlations were estimated between tenderness and juiciness (0.54 ± 0.28) and between connective tissue and juiciness (0.58 ± 0.26). In general, genetic correlations were large and favorable, which indicated that strong relationships exist and similar gene and gene networks may control MS, IMFC, and juiciness or WBSF, panel tenderness, and connective tissue. The results from this study confirm that MS currently used in selection breeding programs has positive genetic correlations with tenderness and juiciness and, therefore, is an effective indicator trait for the improvement of tenderness and juiciness in beef. This study also indicated that a more objective measure, particularly WBSF, a trait not easy to improve through phenotypic selection, is an excellent candidate trait for genomic selection aimed at improving eating satisfaction.

Reparametrization-based estimation of genetic parameters in multi-trait animal model using Integrated Nested Laplace Approximation.

PubMed

Mathew, Boby; Holand, Anna Marie; Koistinen, Petri; Léon, Jens; Sillanpää, Mikko J

2016-02-01

A novel reparametrization-based INLA approach as a fast alternative to MCMC for the Bayesian estimation of genetic parameters in multivariate animal model is presented. Multi-trait genetic parameter estimation is a relevant topic in animal and plant breeding programs because multi-trait analysis can take into account the genetic correlation between different traits and that significantly improves the accuracy of the genetic parameter estimates. Generally, multi-trait analysis is computationally demanding and requires initial estimates of genetic and residual correlations among the traits, while those are difficult to obtain. In this study, we illustrate how to reparametrize covariance matrices of a multivariate animal model/animal models using modified Cholesky decompositions. This reparametrization-based approach is used in the Integrated Nested Laplace Approximation (INLA) methodology to estimate genetic parameters of multivariate animal model. Immediate benefits are: (1) to avoid difficulties of finding good starting values for analysis which can be a problem, for example in Restricted Maximum Likelihood (REML); (2) Bayesian estimation of (co)variance components using INLA is faster to execute than using Markov Chain Monte Carlo (MCMC) especially when realized relationship matrices are dense. The slight drawback is that priors for covariance matrices are assigned for elements of the Cholesky factor but not directly to the covariance matrix elements as in MCMC. Additionally, we illustrate the concordance of the INLA results with the traditional methods like MCMC and REML approaches. We also present results obtained from simulated data sets with replicates and field data in rice.

Genetic variation and genetic structure of the endangered species Sinowilsonia henryi Hemsi. (Hamamelidaceae) revealed by amplified fragment length polymorphism (AFLP) markers.

PubMed

Zhang, H; Ji, W L; Li, M; Zhou, L Y

2015-10-14

Comprehensive research of genetic variation is crucial in designing conservation strategies for endangered and threatened species. Sinowilsonia henryi Hemsi. is a tertiary relic with a limited geographical distribution in the central and western areas of China. It is endangered because of climate change and habitat fragmentation over the last thousands of years. In this study, amplified fragment length polymorphism markers were utilized to estimate genetic diversity and genetic structure in and among S. henryi. In this study, Nei's genetic diversity and Shannon's information index were found to be 0.192 and 0.325 respectively, indicating a moderate-to-high genetic diversity in species. According to analysis of molecular variation results, 32% of the genetic variation was shown to be partitioned among populations, demonstrating a relatively high genetic divergence; this was supported by principal coordinate analysis and unweighted pair-group method with arithmetic average analysis. Moreover, the Mantel test showed that there was no significant correlation between genetic and geographical distances. The above results can be explained by the effects of habitat fragmentation, history traits, and gene drift. Based on the results, several implications were indicated and suggestions proposed for preservation strategies for this species.

Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.

PubMed

Hughes, Kim; Flynn, Tanya; de Zoysa, Janak; Dalbeth, Nicola; Merriman, Tony R

2014-02-01

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors.

Molecular insight into the association between cartilage regeneration and ear wound healing in genetic mouse models: targeting new genes in regeneration.

PubMed

Rai, Muhammad Farooq; Schmidt, Eric J; McAlinden, Audrey; Cheverud, James M; Sandell, Linda J

2013-11-06

Tissue regeneration is a complex trait with few genetic models available. Mouse strains LG/J and MRL are exceptional healers. Using recombinant inbred strains from a large (LG/J, healer) and small (SM/J, nonhealer) intercross, we have previously shown a positive genetic correlation between ear wound healing, knee cartilage regeneration, and protection from osteoarthritis. We hypothesize that a common set of genes operates in tissue healing and articular cartilage regeneration. Taking advantage of archived histological sections from recombinant inbred strains, we analyzed expression of candidate genes through branched-chain DNA technology directly from tissue lysates. We determined broad-sense heritability of candidates, Pearson correlation of candidates with healing phenotypes, and Ward minimum variance cluster analysis for strains. A bioinformatic assessment of allelic polymorphisms within and near candidate genes was also performed. The expression of several candidates was significantly heritable among strains. Although several genes correlated with both ear wound healing and cartilage healing at a marginal level, the expression of four genes representing DNA repair (Xrcc2, Pcna) and Wnt signaling (Axin2, Wnt16) pathways was significantly positively correlated with both phenotypes. Cluster analysis accurately classified healers and nonhealers for seven out of eight strains based on gene expression. Specific sequence differences between LG/J and SM/J were identified as potential causal polymorphisms. Our study suggests a common genetic basis between tissue healing and osteoarthritis susceptibility. Mapping genetic variations causing differences in diverse healing responses in multiple tissues may reveal generic healing processes in pursuit of new therapeutic targets designed to induce or enhance regeneration and, potentially, protection from osteoarthritis.

A meta-analysis reveals a positive correlation between genetic diversity metrics and environmental status in the long-lived seagrass Posidonia oceanica.

PubMed

Jahnke, Marlene; Olsen, Jeanine L; Procaccini, Gabriele

2015-05-01

The seagrass Posidonia oceanica is a key engineering species structuring coastal marine systems throughout much of the Mediterranean basin. Its decline is of concern, leading to the search for short- and long-term indicators of seagrass health. Using ArcGIS maps from a recent, high-resolution (1-4 km) modelling study of 18 disturbance factors affecting coastal marine systems across the Mediterranean (Micheli et al. 2013, http://globalmarine.nceas.ucsb.edu/mediterranean/), we tested for correlations with genetic diversity metrics (allelic diversity, genotypic/clonal diversity and heterozygosity) in a meta-analysis of 56 meadows. Contrary to initial predictions, weak but significantly positive correlations were found for commercial shipping, organic pollution (pesticides) and cumulative impact. This counterintuitive finding suggests greater resistance and resilience of individuals with higher genetic and genotypic diversity under disturbance (at least for a time) and/or increased sexual reproduction under an intermediate disturbance model. We interpret the absence of low and medium levels of genetic variation at impacted locations as probable local extinctions of individuals that already exceeded their resistance capacity. Alternatively, high diversity at high-impact sites is likely a temporal artefact, reflecting the mismatch with pre-environmental impact conditions, especially because flowering and sexual recruitment are seldom observed. While genetic diversity metrics are a valuable tool for restoration and mitigation, caution must be exercised in the interpretation of correlative patterns as found in this study, because the exceptional longevity of individuals creates a temporal mismatch that may falsely suggest good meadow health status, while gradual deterioration of allelic diversity might go unnoticed. © 2015 John Wiley & Sons Ltd.

Characterization of Gladiolus Germplasm Using Morphological, Physiological, and Molecular Markers.

PubMed

Singh, Niraj; Pal, Ashish K; Roy, R K; Tewari, S K; Tamta, Sushma; Rana, T S

2018-04-01

Estimation of variability and genetic relationships among breeding materials is one of the important strategies in crop improvement programs. Morphological (plant height, spike length, a number of florets/spike), physiological (chlorophyll content, chlorophyll fluorescence, and rapid light curve parameters) and Directed amplification of minisatellite DNA (DAMD) markers were used to investigate the relationships among 50 Gladiolus cultivars. Cluster analysis based on morphological data, physiological characteristics, molecular markers, and cumulative data discriminated all cultivars into seven, five, seven, and six clusters in the unweighted pair-group method using arithmetic mean (UPGMA) dendrogram, respectively. The results of the principal coordinate analysis (PCoA) also supported UPGMA clustering. Variations among the Gladiolus cultivars at phenotypic level could be due to the changes in physiology, environmental conditions, and genetic variability. DAMD analysis using 10 primers produced 120 polymorphic bands with 80% polymorphism showing polymorphic information content (PIC = 0.28), Marker index (MI = 3.37), Nei's gene diversity (h = 0.267), and Shannon's information index (I = 0.407). Plant height showed a positive significant correlation with Spike length and Number of florets/spike (r = 0.729, p < 0.001 and r = 0.448, p = 0.001 respectively). Whereas, Spike length showed positive significant correlation with Number of florets/spike (r = 0.688, p < 0.001) and Chlorophyll content showed positive significant correlation with Electron transport rate (r = 0.863, p < 0.001). Based on significant morphological variations, high physiological performance, high genetic variability, and genetic distances between cultivars, we have been able to identify diverse cultivars of Gladiolus that could be the potential source as breeding material for further genetic improvement in this ornamental crop.

Genetics of human body size and shape: body proportions and indices.

PubMed

Livshits, Gregory; Roset, A; Yakovenko, K; Trofimov, S; Kobyliansky, E

2002-01-01

The study of the genetic component in morphological variables such as body height and weight, head and chest circumference, etc. has a rather long history. However, only a few studies investigated body proportions and configuration. The major aim of the present study was to evaluate the extent of the possible genetic effects on the inter-individual variation of a number of body configuration indices amenable to clear functional interpretation. Two ethnically different pedigree samples were used in the study: (1) Turkmenians (805 individuals) from Central Asia, and (2) Chuvasha (732 individuals) from the Volga riverside, Russian Federation. To achieve the aim of the present study we proposed three new indices, which were subjected to a statistical-genetic analysis using modified version of "FISHER" software. The proposed indices were: (1) an integral index of torso volume (IND#1), an index reflecting a predisposition of body proportions to maintain a balance in a vertical position (IND#2), and an index of skeletal extremities volume (IND#3). Additionally, the first two principal factors (PF1 and PF2) obtained on 19 measurements of body length and breadth were subjected to genetic analysis. Variance decomposition analysis that simultaneously assess the contribution of gender, age, additive genetic effects and effects of environment shared by the nuclear family members, was applied to fit variation of the above three indices, and PF1 and PF2. The raw familial correlation of all study traits and in both samples showed: (1) all marital correlations did not differ significantly from zero; (2) parent-offspring and sibling correlations were all positive and statistically significant. The parameter estimates obtained in variance analyses showed that from 40% to 75% of inter-individual variation of the studied traits (adjusted for age and sex) were attributable to genetic effects. For PF1 and PF2 in both samples, and for IND#2 (in Chuvasha pedigrees), significant common sib environmental effects were also detectable. Genetic factors substantially influence inter-individual differences in body shape and configuration in two studied samples. However, further studies are needed to clarify the extent of pleiotropy and epigenetic effects on various facets of the human physique.

A Genetic Test Predicts Providence Brace Success for Adolescent Idiopathic Scoliosis When Failure Is Defined as Progression to >45 Degrees.

PubMed

Bohl, Daniel D; Telles, Connor J; Ruiz, Ferrin K; Badrinath, Raghav; DeLuca, Peter A; Grauer, Jonathan N

2016-04-01

Retrospective cohort. To determine whether a genetic test is associated with successful Providence bracing for adolescent idiopathic scoliosis (AIS). Genetic factors have been defined that predict the risk of progression of AIS in a polygenic fashion. From these data, a commercially available genetic test, ScoliScore, was developed. It is now used in clinical practice for counseling and to guide clinical management. Bracing is a mainstay of treatment for AIS. Large efforts have been made recently to reduce potential confounding across studies of different braces; however, none of these have considered genetics as a potential confounder. In particular, ScoliScore has not been evaluated in a population undergoing bracing. We conducted a retrospective cohort study in which we identified a population of AIS patients who were initiated with Providence bracing and followed over time. Although these patients did not necessarily fit the commercial indications for ScoliScore, we contacted the patients and obtained a saliva sample from each for genetic analysis. We then tested whether ScoliScore correlated with the outcome of their bracing therapy. We were able to contact and invite 25 eligible subjects, of whom 16 (64.0%) returned samples for laboratory analysis. Patients were followed for an average of 2.3 years (range, 1.1-4 y) after initiation of the Providence brace. Eight patients (50.0%) progressed to >45 degrees, whereas the other 8 patients (50.0%) did not. The mean ScoliScore among those who progressed to >45 degrees was higher than that among those who did not (176 vs. 112, P=0.030). We demonstrate that a genetic test correlates with bracing outcome. It may be appropriate for future bracing studies to include analysis of genetic predisposition to limit potential confounding.

Methods for the survey and genetic analysis of populations

DOEpatents

Ashby, Matthew

2003-09-02

The present invention relates to methods for performing surveys of the genetic diversity of a population. The invention also relates to methods for performing genetic analyses of a population. The invention further relates to methods for the creation of databases comprising the survey information and the databases created by these methods. The invention also relates to methods for analyzing the information to correlate the presence of nucleic acid markers with desired parameters in a sample. These methods have application in the fields of geochemical exploration, agriculture, bioremediation, environmental analysis, clinical microbiology, forensic science and medicine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golbus, Jessica R.; Puckelwartz, Megan J.; Dellefave-Castillo, Lisa

Background—Cardiomyopathy is highly heritable but genetically diverse. At present, genetic testing for cardiomyopathy uses targeted sequencing to simultaneously assess the coding regions of more than 50 genes. New genes are routinely added to panels to improve the diagnostic yield. With the anticipated $1000 genome, it is expected that genetic testing will shift towards comprehensive genome sequencing accompanied by targeted gene analysis. Therefore, we assessed the reliability of whole genome sequencing and targeted analysis to identify cardiomyopathy variants in 11 subjects with cardiomyopathy. Methods and Results—Whole genome sequencing with an average of 37× coverage was combined with targeted analysis focused onmore » 204 genes linked to cardiomyopathy. Genetic variants were scored using multiple prediction algorithms combined with frequency data from public databases. This pipeline yielded 1-14 potentially pathogenic variants per individual. Variants were further analyzed using clinical criteria and/or segregation analysis. Three of three previously identified primary mutations were detected by this analysis. In six subjects for whom the primary mutation was previously unknown, we identified mutations that segregated with disease, had clinical correlates, and/or had additional pathological correlation to provide evidence for causality. For two subjects with previously known primary mutations, we identified additional variants that may act as modifiers of disease severity. In total, we identified the likely pathological mutation in 9 of 11 (82%) subjects. We conclude that these pilot data demonstrate that ~30-40× coverage whole genome sequencing combined with targeted analysis is feasible and sensitive to identify rare variants in cardiomyopathy-associated genes.« less

TreeGenes and CartograTree: Enabling visualization and analysis in forest tree genomics

Treesearch

E.S. Grau; S.A. Demurjian; H.A. Vasquez-Gross; D.G. Gessler; D.B. Neale; J.L. Wegrzyn

2017-01-01

Association studies integrating environmental, phenotypic, and genetic data are key in understanding forest tree resilience to climate change and disease. As genomic resources increase, both in terms of complete reference sequences and magnitude of individuals genotyped, researchers are better equipped to identify correlations between genetic variation and adaptive or...

Seeking the Cause of Correlations among Mental Abilities: Large Twin Analysis in a National Testing Program.

ERIC Educational Resources Information Center

Page, Ellis B.; Jarjoura, David

1979-01-01

A computer scan of ACT Assessment records identified 3,427 sets of twins. The Hardy-Weinberg rule was used to estimate the proportion of monozygotic twins in the sample. Matrices of genetic and environmental influences were produced. The heaviest loadings were clearly in the genetic matrix. (SJL)

Introduction to Protein Structure through Genetic Diseases

ERIC Educational Resources Information Center

Schneider, Tanya L.; Linton, Brian R.

2008-01-01

An illuminating way to learn about protein function is to explore high-resolution protein structures. Analysis of the proteins involved in genetic diseases has been used to introduce students to protein structure and the role that individual mutations can play in the onset of disease. Known mutations can be correlated to changes in protein…

Joint analysis of phenotypic and molecular diversity provides new insights on the genetic variability of the Brazilian physic nut germplasm bank

PubMed Central

Alves, Alexandre Alonso; Bhering, Leonardo Lopes; Rosado, Tatiana Barbosa; Laviola, Bruno Galvêas; Formighieri, Eduardo Fernandes; Cruz, Cosme Damião

2013-01-01

The genetic variability of the Brazilian physic nut (Jatropha curcas) germplasm bank (117 accessions) was assessed using a combination of phenotypic and molecular data. The joint dissimilarity matrix showed moderate correlation with the original matrices of phenotypic and molecular data. However, the correlation between the phenotypic dissimilarity matrix and the genotypic dissimilarity matrix was low. This finding indicated that molecular markers (RAPD and SSR) did not adequately sample the genomic regions that were relevant for phenotypic differentiation of the accessions. The dissimilarity values of the joint dissimilarity matrix were used to measure phenotypic + molecular diversity. This diversity varied from 0 to 1.29 among the 117 accessions, with an average dissimilarity among genotypes of 0.51. Joint analysis of phenotypic and molecular diversity indicated that the genetic diversity of the physic nut germplasm was 156% and 64% higher than the diversity estimated from phenotypic and molecular data, respectively. These results show that Jatropha genetic variability in Brazil is not as limited as previously thought. PMID:24130445

Shared genetic aetiology of puberty timing between sexes and with health-related outcomes

PubMed Central

Day, Felix R.; Bulik-Sullivan, Brendan; Hinds, David A.; Finucane, Hilary K.; Murabito, Joanne M.; Tung, Joyce Y.; Ong, Ken K.; Perry, John R.B.

2015-01-01

Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P=2.7 × 10−70) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (Pheterogeneity=1.6 × 10−12). We find five novel loci for puberty timing (P<5 × 10−8), in addition to nine signals in men that were previously reported in women. Newly implicated genes include two retinoic acid-related receptors, RORB and RXRA, and two genes reportedly disrupted in rare disorders of puberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease. PMID:26548314

Shared genetic aetiology of puberty timing between sexes and with health-related outcomes.

PubMed

Day, Felix R; Bulik-Sullivan, Brendan; Hinds, David A; Finucane, Hilary K; Murabito, Joanne M; Tung, Joyce Y; Ong, Ken K; Perry, John R B

2015-11-09

Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P=2.7 × 10(-70)) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (Pheterogeneity=1.6 × 10(-12)). We find five novel loci for puberty timing (P<5 × 10(-8)), in addition to nine signals in men that were previously reported in women. Newly implicated genes include two retinoic acid-related receptors, RORB and RXRA, and two genes reportedly disrupted in rare disorders of puberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease.

Joint analysis of phenotypic and molecular diversity provides new insights on the genetic variability of the Brazilian physic nut germplasm bank.

PubMed

Alves, Alexandre Alonso; Bhering, Leonardo Lopes; Rosado, Tatiana Barbosa; Laviola, Bruno Galvêas; Formighieri, Eduardo Fernandes; Cruz, Cosme Damião

2013-09-01

The genetic variability of the Brazilian physic nut (Jatropha curcas) germplasm bank (117 accessions) was assessed using a combination of phenotypic and molecular data. The joint dissimilarity matrix showed moderate correlation with the original matrices of phenotypic and molecular data. However, the correlation between the phenotypic dissimilarity matrix and the genotypic dissimilarity matrix was low. This finding indicated that molecular markers (RAPD and SSR) did not adequately sample the genomic regions that were relevant for phenotypic differentiation of the accessions. The dissimilarity values of the joint dissimilarity matrix were used to measure phenotypic + molecular diversity. This diversity varied from 0 to 1.29 among the 117 accessions, with an average dissimilarity among genotypes of 0.51. Joint analysis of phenotypic and molecular diversity indicated that the genetic diversity of the physic nut germplasm was 156% and 64% higher than the diversity estimated from phenotypic and molecular data, respectively. These results show that Jatropha genetic variability in Brazil is not as limited as previously thought.

Inverse Correlation of Population Similarity and Introduction Date for Invasive Ascidians

PubMed Central

Silva, Nathan; Smith, William C.

2008-01-01

The genomes of many marine invertebrates, including the purple sea urchin and the solitary ascidians Ciona intestinalis and Ciona savignyi, show exceptionally high levels of heterozygosity, implying that these populations are highly polymorphic. Analysis of the C. savignyi genome found little evidence to support an elevated mutation rate, but rather points to a large population size contributing to the polymorphism level. In the present study, the relative genetic polymorphism levels in sampled populations of ten different ascidian species were determined using a similarity index generated by AFLP analysis. The goal was to determine the range of polymorphism within the populations of different species, and to uncover factors that may contribute to the high level of polymorphism. We observe that, surprisingly, the levels of polymorphism within these species show a negative correlation with the reported age of invasive populations, and that closely related species show substantially different levels of genetic polymorphism. These findings show exceptions to the assumptions that invasive species start with a low level of genetic polymorphism that increases over time and that closely related species have similar levels of genetic polymorphism. PMID:18575620

Genome-Wide Association Analysis of Adaptation Using Environmentally Predicted Traits

PubMed Central

van Zanten, Martijn

2015-01-01

Current methods for studying the genetic basis of adaptation evaluate genetic associations with ecologically relevant traits or single environmental variables, under the implicit assumption that natural selection imposes correlations between phenotypes, environments and genotypes. In practice, observed trait and environmental data are manifestations of unknown selective forces and are only indirectly associated with adaptive genetic variation. In theory, improved estimation of these forces could enable more powerful detection of loci under selection. Here we present an approach in which we approximate adaptive variation by modeling phenotypes as a function of the environment and using the predicted trait in multivariate and univariate genome-wide association analysis (GWAS). Based on computer simulations and published flowering time data from the model plant Arabidopsis thaliana, we find that environmentally predicted traits lead to higher recovery of functional loci in multivariate GWAS and are more strongly correlated to allele frequencies at adaptive loci than individual environmental variables. Our results provide an example of the use of environmental data to obtain independent and meaningful information on adaptive genetic variation. PMID:26496492

Meta-analysis of correlated traits via summary statistics from GWASs with an application in hypertension.

PubMed

Zhu, Xiaofeng; Feng, Tao; Tayo, Bamidele O; Liang, Jingjing; Young, J Hunter; Franceschini, Nora; Smith, Jennifer A; Yanek, Lisa R; Sun, Yan V; Edwards, Todd L; Chen, Wei; Nalls, Mike; Fox, Ervin; Sale, Michele; Bottinger, Erwin; Rotimi, Charles; Liu, Yongmei; McKnight, Barbara; Liu, Kiang; Arnett, Donna K; Chakravati, Aravinda; Cooper, Richard S; Redline, Susan

2015-01-08

Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci (CHIC2, HOXA-EVX1, IGFBP1/IGFBP3, and CDH17; p < 5.0 × 10(-8)) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p < 5.0 × 10(-7)) were also observed, including CACNA1D and WNT3. Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Genetic parameters of blood β-hydroxybutyrate predicted from milk infrared spectra and clinical ketosis, and their associations with milk production traits in Norwegian Red cows.

PubMed

Belay, T K; Svendsen, M; Kowalski, Z M; Ådnøy, T

2017-08-01

The aim of this study was to estimate genetic parameters for blood β-hydroxybutyrate (BHB) predicted from milk spectra and for clinical ketosis (KET), and to examine genetic association of blood BHB with KET and milk production traits (milk, fat, protein, and lactose yields, and milk fat, protein, and lactose contents). Data on milk traits, KET, and milk spectra were obtained from the Norwegian Dairy Herd Recording System with legal permission from TINE SA (Ås, Norway), the Norwegian Dairy Association that manages the central database. Data recorded up to 120 d after calving were considered. Blood BHB was predicted from milk spectra using a calibration model developed based on milk spectra and blood BHB measured in Polish dairy cows. The predicted blood BHB was grouped based on days in milk into 4 groups and each group was considered as a trait. The milk components for test-day milk samples were obtained by Fourier transform mid-infrared spectrometer with previously developed calibration equations from Foss (Hillerød, Denmark). Veterinarian-recorded KET data within 15 d before calving to 120 d after calving were used. Data were analyzed using univariate or bivariate linear animal models. Heritability estimates for predicted blood BHB at different stages of lactation were moderate, ranging from 0.250 to 0.365. Heritability estimate for KET from univariate analysis was 0.078, and the corresponding average estimate from bivariate analysis with BHB or milk production traits was 0.002. Genetic correlations between BHB traits were higher for adjacent lactation intervals and decreased as intervals were further apart. Predicted blood BHB at first test day was moderately genetically correlated with KET (0.469) and milk traits (ranged from -0.367 with protein content to 0.277 with milk yield), except for milk fat content from across lactation stages that had near zero genetic correlation with BHB (0.033). These genetic correlations indicate that a lower BHB is genetically associated with higher milk protein and lactose contents, but with lower yields of milk, fat, protein, and lactose, and with lower frequency of KET. Estimates of genetic correlation of KET with milk production traits were from -0.333 (with protein content) to 0.178 (with milk yield). Blood BHB can routinely be predicted from milk spectra analyzed from test-day milk samples, and thereby provides a practical alternative for selecting cows with lower susceptibility to ketosis, even though the correlations are moderate. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Understanding the Relation between Anorexia Nervosa and Bulimia Nervosa in a Swedish National Twin Sample

PubMed Central

Bulik, Cynthia M; Thornton, Laura; Root, Tammy L.; Pisetsky, Emily M.; Lichtenstein, Paul; Pedersen, Nancy L.

2010-01-01

Background We present a bivariate twin analysis of anorexia nervosa (AN) and bulimia nervosa (BN) to determine the extent to which shared genetic and environmental factors contribute to liability to these disorders. Method Focusing on females from the Swedish Twin study of Adults: Genes and Environment (STAGE) (N=7000), we calculated heritability estimates for narrow and broad AN and BN and estimated their genetic correlation. Results In the full model, the heritability estimate for narrow AN was (a2 = .57; 95% CI: .00, .81) and for narrow BN (a2 = .62; 95% CI: .08, .70) with the remaining variance accounted for by unique environmental factors. Shared environmental factors estimates were (c2 = .00; 95% CI: .00, .67) for AN and (c2 = .00; 95% CI: .00, .40) for BN. Moderate additive genetic (.46) and unique environmental (.42) correlations between AN and BN were observed. Heritability estimates for broad AN were lower (a2 = .29; 95% CI: .04, .43) than for narrow AN, but estimates for broad BN were similar to narrow BN. The genetic correlation for broad AN and BN was .79 and the unique environmental correlation was .44. Conclusions We highlight the contribution of additive genetic factors to both narrow and broad AN and BN and demonstrate a moderate overlap of both genetic and unique environmental factors that influence the two conditions. Common concurrent and sequential comorbidity of AN and BN can in part be accounted for by shared genetic and environmental influences on liability although independent factors also operative. PMID:19828139

Sparse models for correlative and integrative analysis of imaging and genetic data

PubMed Central

Lin, Dongdong; Cao, Hongbao; Calhoun, Vince D.

2014-01-01

The development of advanced medical imaging technologies and high-throughput genomic measurements has enhanced our ability to understand their interplay as well as their relationship with human behavior by integrating these two types of datasets. However, the high dimensionality and heterogeneity of these datasets presents a challenge to conventional statistical methods; there is a high demand for the development of both correlative and integrative analysis approaches. Here, we review our recent work on developing sparse representation based approaches to address this challenge. We show how sparse models are applied to the correlation and integration of imaging and genetic data for biomarker identification. We present examples on how these approaches are used for the detection of risk genes and classification of complex diseases such as schizophrenia. Finally, we discuss future directions on the integration of multiple imaging and genomic datasets including their interactions such as epistasis. PMID:25218561

Factor analysis in the Genetics of Asthma International Network family study identifies five major quantitative asthma phenotypes.

PubMed

Pillai, S G; Tang, Y; van den Oord, E; Klotsman, M; Barnes, K; Carlsen, K; Gerritsen, J; Lenney, W; Silverman, M; Sly, P; Sundy, J; Tsanakas, J; von Berg, A; Whyte, M; Ortega, H G; Anderson, W H; Helms, P J

2008-03-01

Asthma is a clinically heterogeneous disease caused by a complex interaction between genetic susceptibility and diverse environmental factors. In common with other complex diseases the lack of a standardized scheme to evaluate the phenotypic variability poses challenges in identifying the contribution of genes and environments to disease expression. To determine the minimum number of sets of features required to characterize subjects with asthma which will be useful in identifying important genetic and environmental contributors. Methods Probands aged 7-35 years with physician diagnosed asthma and symptomatic siblings were identified in 1022 nuclear families from 11 centres in six countries forming the Genetics of Asthma International Network. Factor analysis was used to identify distinct phenotypes from questionnaire, clinical, and laboratory data, including baseline pulmonary function, allergen skin prick test (SPT). Five distinct factors were identified:(1) baseline pulmonary function measures [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)], (2) specific allergen sensitization by SPT, (3) self-reported allergies, (4) symptoms characteristic of rhinitis and (5) symptoms characteristic of asthma. Replication in symptomatic siblings was consistent with shared genetic and/or environmental effects, and was robust across age groups, gender, and centres. Cronbach's alpha ranged from 0.719 to 0.983 suggesting acceptable internal scale consistencies. Derived scales were correlated with serum IgE, methacholine PC(20), age and asthma severity (interrupted sleep). IgE correlated with all three atopy-related factors, the strongest with the SPT factor whereas severity only correlated with baseline lung function, and with symptoms characteristic of rhinitis and of asthma. In children and adolescents with established asthma, five distinct sets of correlated patient characteristics appear to represent important aspects of the disease. Factor scores as quantitative traits may be better phenotypes in epidemiological and genetic analyses than those categories derived from the presence or absence of combinations of +ve SPTs and/or elevated IgE.

Beyond the big five: the Dark Triad and the supernumerary personality inventory.

PubMed

Veselka, Livia; Schermer, Julie Aitken; Vernon, Philip A

2011-04-01

The Dark Triad of personality, comprising Machiavellianism, narcissism, and psychopathy, was investigated in relation to the Supernumerary Personality Inventory (SPI) traits, because both sets of variables are predominantly distinct from the Big Five model of personality. Correlational and principal factor analyses were conducted to assess the relations between the Dark Triad and SPI traits. Multivariate behavioral genetic model-fitting analyses were also conducted to determine the correlated genetic and/or environmental underpinnings of the observed phenotypic correlations. Participants were 358 monozygotic and 98 same-sex dizygotic adult twin pairs from North America. As predicted, results revealed significant correlations between the Dark Triad and most SPI traits, and these correlations were primarily attributable to common genetic and non-shared environmental factors, except in the case of Machiavellianism, where shared environmental effects emerged. Three correlated factors were extracted during joint factor analysis of the Dark Triad and SPI traits, as well as a heritable general factor of personality - results that clarified the structure of the Dark Triad construct. It is concluded that the Dark Triad represents an exploitative and antisocial construct that extends beyond the Big Five model and shares a theoretical space with the SPI traits.

Genetic and Environmental Influences on Systemic Markers of Inflammation in Middle-Aged Male Twins

PubMed Central

Su, Shaoyong; Snieder, Harold; Miller, Andrew H.; Ritchie, James; Bremner, J. Douglas; Goldberg, Jack; Dai, Jun; Jones, Linda; Murrah, Nancy V.; Zhao, Jinying; Vaccarino, Viola

2008-01-01

Objectives The aims of this study were to determine the relative influence of genetic and environmental contributions to inflammatory biomarkers, and to what extent correlations among these markers are due to genetic or environmental factors. Methods We performed univariate and multivariate genetic analyses of four inflammatory markers: interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), C-reactive protein (CRP), and fibrinogen, in 166 (88 monozygotic and 78 dizygotic) middle-aged male twin pairs. Results The mean age (±SD) of the twins was 54 (±2.93) years. Heritability was substantial for CRP (0.61, 95% CI: 0.47–0.72) and moderate to fair for IL-6 (0.31, 0.13–0.46), sIL-6R (0.49, 0.30–0.76) and fibrinogen (0.52, 0.34–0.65). IL-6, CRP and fibrinogen showed significant correlations, but not with sIL-6R. Multivariate genetic analysis found that these correlations could be best explained by a common pathway model, where the common factor explained 27%, 73% and 25% of the variance of IL-6, CRP and fibrinogen, respectively. About 46% (95% CI: 21–64%) of the correlations among the three inflammatory markers could be explained by the genetic factors. After adjusting for covariates known to influence inflammation levels, heritability estimates were slightly decreased but the overall results remained similar. Conclusions A significant part of the variation in inflammatory marker levels is due to genetic influences. Furthermore, almost 50% of the shared variance among these biomarkers is due to a common genetic factor which likely plays a key role in the regulation of inflammation. PMID:18243214

Quantitative genetics of circulating Hyaluronic Acid (HA) and its correlation with hand osteoarthritis and obesity-related phenotypes in a community-based sample.

PubMed

Prakash, Jai; Gabdulina, Gulzhan; Trofimov, Svetlana; Livshits, Gregory

2017-09-01

One of the potential molecular biomarkers of osteoarthritis (OA) is hyaluronic acid (HA). HA levels may be related to the severity and progression of OA. However, little is known about the contribution of major risk factors for osteoarthritis, e.g. obesity-related phenotypes and genetics to HA variation. To clarify the quantitative effect of these factors on HA. An ethnically homogeneous sample of 911 apparently healthy European-derived individuals, assessed for radiographic hand osteoarthritis (RHOA), HA, leptin, adiponectin, and several anthropometrical measures of obesity-related phenotypes was studied. Model-based quantitative genetic analysis was used to reveal genetic and shared environmental factors affecting the variation of the study's phenotypes. The HA levels significantly correlated with the age, RHOA, adiponectin, obesity-related phenotypes, and the waist-to-hip ratio. The putative genetic effects contributed significantly to the variation of HA (66.2 ± 9.3%) and they were also significant factors in the variations of all the other studied phenotypes, with the heritability estimate ranging between 0.122 ± 4.4% (WHR) and 45.7 ± 2.2% (joint space narrowing). This is the first study to report heritability estimates of HA variation and its correlation with obesity-related phenotypes, ADP and RHOA. However, the nature of genetic effects on HA and its correlation with other study phenotypes require further clarification.

Genetic structure of Onchidium "struma" (Mollusca: Gastropoda: Eupulmonata) from the coastal area of China based on mtCO I.

PubMed

Zhou, Na; Shen, Heding; Chen, Cheng; Sun, Bianna; Zheng, Pei; Wang, Chengnuan

2016-01-01

The genetic diversity and population genetic structure of Onchidium "struma" were investigated using mitochondrial cytochrome c oxidase subunit I (CO I) gene sequences. A total of 240 individuals representing 10 collection sites from across a large portion of its known range were included in the analysis. Overall, 42 haplotypes were defined and 97 polymorphic sites were observed. The O. "struma" populations had high haplotype diversity (0.9280) and nucleotide diversity (0.0404). We inferred that the early maturity and extensive survival habitat led to high genetic diversity of O. "struma" populations in China. Bayesian analysis and SAMOVA analysis showed significant genetic differentiation among populations and all populations were divided into two groups, (HK and HN) versus (GY, DF, CX, CN, ND and XM). The Mantel test revealed no significant correlation between geographic distance and genetic distance (r = 0.251; p = 0.058). Restricted gene flow caused by a shorter term pelagic veliger stage and limited dispersal potential were inferred to result in genetic differentiation among populations based on nested analysis. HK population might be an invasive species by artificial transplantation.

Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits.

PubMed

Shi, Huwenbo; Mancuso, Nicholas; Spendlove, Sarah; Pasaniuc, Bogdan

2017-11-02

Although genetic correlations between complex traits provide valuable insights into epidemiological and etiological studies, a precise quantification of which genomic regions disproportionately contribute to the genome-wide correlation is currently lacking. Here, we introduce ρ-HESS, a technique to quantify the correlation between pairs of traits due to genetic variation at a small region in the genome. Our approach requires GWAS summary data only and makes no distributional assumption on the causal variant effect sizes while accounting for linkage disequilibrium (LD) and overlapping GWAS samples. We analyzed large-scale GWAS summary data across 36 quantitative traits, and identified 25 genomic regions that contribute significantly to the genetic correlation among these traits. Notably, we find 6 genomic regions that contribute to the genetic correlation of 10 pairs of traits that show negligible genome-wide correlation, further showcasing the power of local genetic correlation analyses. Finally, we report the distribution of local genetic correlations across the genome for 55 pairs of traits that show putative causal relationships. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Longitudinal analysis of direct and indirect effects on average daily gain in rabbits using a structured antedependence model.

PubMed

David, Ingrid; Sánchez, Juan-Pablo; Piles, Miriam

2018-05-10

Indirect genetic effects (IGE) are important components of various traits in several species. Although the intensity of social interactions between partners likely vary over time, very few genetic studies have investigated how IGE vary over time for traits under selection in livestock species. To overcome this issue, our aim was: (1) to analyze longitudinal records of average daily gain (ADG) in rabbits subjected to a 5-week period of feed restriction using a structured antedependence (SAD) model that includes IGE and (2) to evaluate, by simulation, the response to selection when IGE are present and genetic evaluation is based on a SAD model that includes IGE or not. The direct genetic variance for ADG (g/d) increased from week 1 to 3 [from 8.03 to 13.47 (g/d) 2 ] and then decreased [6.20 (g/d) 2 at week 5], while the indirect genetic variance decreased from week 1 to 4 [from 0.43 to 0.22 (g/d) 2 ]. The correlation between the direct genetic effects of different weeks was moderate to high (ranging from 0.46 to 0.86) and tended to decrease with time interval between measurements. The same trend was observed for IGE for weeks 2 to 5 (correlations ranging from 0.62 to 0.91). Estimates of the correlation between IGE of week 1 and IGE of the other weeks did not follow the same pattern and correlations were lower. Estimates of correlations between direct and indirect effects were negative at all times. After seven generations of simulated selection, the increase in ADG from selection on EBV from a SAD model that included IGE was higher (~ 30%) than when those effects were omitted. Indirect genetic effects are larger just after mixing animals at weaning than later in the fattening period, probably because of the establishment of social hierarchy that is generally observed at that time. Accounting for IGE in the selection criterion maximizes genetic progress.

Multivariate modelling of endophenotypes associated with the metabolic syndrome in Chinese twins.

PubMed

Pang, Z; Zhang, D; Li, S; Duan, H; Hjelmborg, J; Kruse, T A; Kyvik, K O; Christensen, K; Tan, Q

2010-12-01

The common genetic and environmental effects on endophenotypes related to the metabolic syndrome have been investigated using bivariate and multivariate twin models. This paper extends the pairwise analysis approach by introducing independent and common pathway models to Chinese twin data. The aim was to explore the common genetic architecture in the development of these phenotypes in the Chinese population. Three multivariate models including the full saturated Cholesky decomposition model, the common factor independent pathway model and the common factor common pathway model were fitted to 695 pairs of Chinese twins representing six phenotypes including BMI, total cholesterol, total triacylglycerol, fasting glucose, HDL and LDL. Performances of the nested models were compared with that of the full Cholesky model. Cross-phenotype correlation coefficients gave clear indication of common genetic or environmental backgrounds in the phenotypes. Decomposition of phenotypic correlation by the Cholesky model revealed that the observed phenotypic correlation among lipid phenotypes had genetic and unique environmental backgrounds. Both pathway models suggest a common genetic architecture for lipid phenotypes, which is distinct from that of the non-lipid phenotypes. The declining performance with model restriction indicates biological heterogeneity in development among some of these phenotypes. Our multivariate analyses revealed common genetic and environmental backgrounds for the studied lipid phenotypes in Chinese twins. Model performance showed that physiologically distinct endophenotypes may follow different genetic regulations.

Correlation analysis of genetic diversity and population structure of Houttuynia cordata Thunb with regard to environment.

PubMed

Zhong, J; Wu, F-C; Qiu, P; Dai, L-J

2016-08-12

To study the levels of genetic diversity, and population structure, of Houttuynia cordata Thunb, the genetic background and relationships of populations were analyzed in terms of environmental factors. The genetic diversity and population structure of H. cordata were investigated using sequence-related amplified polymorphisms and correlation with environmental factors was analyzed using the SPSS software. Two thousand one hundred sixty-three sites were amplified from 41 pairs of primers, 1825 of which were polymorphic, and the percentage of polymorphic loci was 84.37%; the percentage of polymorphic sites was 72.14 and 67.77% at the species and population level, respectively. The observed number of alleles was 1.52 and 1.30 at species and population level, respectively. The effective number of alleles was 1.38 and 1.24 at species and population level, respectively. The Nei's diversity was 0.26 and 0.15 at species and population level, respectively. The Shannon's information index was 0.87 and 0.63 at species and population level, respectively. The genetic differentiation coefficient of populations was 0.51, and 12 populations were divided into three classes based on D = 0.20; the genetic diversities of different populations are correlated at different significance levels (P < 0.05) with environmental factors. Genetic differentiation existed among populations and the populations exhibited heteroplasmy.

Molecular Diversity and Population Structure of a Worldwide Collection of Cultivated Tetraploid Alfalfa (Medicago sativa subsp. sativa L.) Germplasm as Revealed by Microsatellite Markers.

PubMed

Qiang, Haiping; Chen, Zhihong; Zhang, Zhengli; Wang, Xuemin; Gao, Hongwen; Wang, Zan

2015-01-01

Information on genetic diversity and population structure of a tetraploid alfalfa collection might be valuable in effective use of the genetic resources. A set of 336 worldwide genotypes of tetraploid alfalfa (Medicago sativa subsp. sativa L.) was genotyped using 85 genome-wide distributed SSR markers to reveal the genetic diversity and population structure in the alfalfa. Genetic diversity analysis identified a total of 1056 alleles across 85 marker loci. The average expected heterozygosity and polymorphism information content values were 0.677 and 0.638, respectively, showing high levels of genetic diversity in the cultivated tetraploid alfalfa germplasm. Comparison of genetic characteristics across chromosomes indicated regions of chromosomes 2 and 3 had the highest genetic diversity. A higher genetic diversity was detected in alfalfa landraces than that of wild materials and cultivars. Two populations were identified by the model-based population structure, principal coordinate and neighbor-joining analyses, corresponding to China and other parts of the world. However, lack of strictly correlation between clustering and geographic origins suggested extensive germplasm exchanges of alfalfa germplasm across diverse geographic regions. The quantitative analysis of the genetic diversity and population structure in this study could be useful for genetic and genomic analysis and utilization of the genetic variation in alfalfa breeding.

Importance of neutralization sieve analyses when seeking correlates of HIV-1 vaccine efficacy.

PubMed

Montefiori, David C

2014-01-01

This commentary describes a rationale for the use of breakthrough viruses from clinical trial participants to assess neutralizing antibodies as a correlate of HIV-1 vaccine efficacy. The rationale is based on principles of a genetic sieve analysis, where the 2 analyses may be cooperative for delineating neutralizing antibodies as a mechanistic correlate of protection.

Assessment of diversity among populations of Rauvolfia serpentina Benth. Ex. Kurtz. from Southern Western Ghats of India, based on chemical profiling, horticultural traits and RAPD analysis.

PubMed

Nair, Vadakkemuriyil Divya; Raj, Rajan Pillai Dinesh; Panneerselvam, Rajaram; Gopi, Ragupathi

2014-01-01

Genetic, morphological and chemical variations of ten natural populations of Rauvolfia serpentina Benth. Ex. Kurtz. from Southern Western Ghats of India were assessed using RAPD markers reserpine content and morphological traits. An estimate of genetic diversity and differentiation between genotypes of breeding germplasm is of key importance for its improvement. Populations were collected from different geographical regions. Data obtained through three different methods were compared and the correlation among them was estimated. Statistical analysis showed significant differences for all horticultural characteristics among the accessions suggesting that selection for relevant characteristics could be possible. Variation in the content of Reserpine ranges from 0.192 g/100 g (population from Tusharagiri) to 1.312 g/100 g (population from Aryankavu). A high diversity within population and high genetic differentiation among them based on RAPDs were revealed caused both by habitat fragmentation of the low size of most populations and the low level of gene flow among them. The UPGMA dendrogram and PCA analysis based on reserpine content yielded higher separation among populations indicated specific adaptation of populations into clusters each of them including populations closed to their geographical origin. Genetic, chemical and morphological data were correlated based on Mantel test. Given the high differentiation among populations conservation strategies should take into account genetic diversity and chemical variation levels in relation to bioclimatic and geographic location of populations. Our results also indicate that RAPD approach along with horticultural analysis seemed to be best suited for assessing with high accuracy the genetic relationships among distinct R. serpentina accessions. © 2013.

Predictors of Patterns of Alcohol-Related Blackouts Over Time in Youth From the Collaborative Study of the Genetics of Alcoholism: The Roles of Genetics and Cannabis

PubMed Central

Schuckit, Marc A.; Smith, Tom L.; Shafir, Alexandra; Clausen, Peyton; Danko, George; Gonçalves, Priscila Dib; Anthenelli, Robert M.; Chan, Grace; Kuperman, Samuel; Hesselbrock, Michie; Hesselbrock, Victor; Kramer, John; Bucholz, Kathleen K.

2017-01-01

Objective: Alcohol-related blackouts (ARBs) are anterograde amnesias related to heavy alcohol intake seen in about 50% of drinkers. Although a major determinant of ARBs relates to blood alcohol concentrations, additional contributions come from genetic vulnerabilities and possible impacts of cannabis use disorders (CUDs). We evaluated relationships of genetics and cannabis use to latent class trajectories of ARBs in 829 subjects from the Collaborative Study of the Genetics of Alcoholism (COGA). Method: The number of ARBs experienced every 2 years from subjects with average ages of 18 to 25 were entered into a latent class growth analysis in Mplus, and resulting class membership was evaluated in light of baseline characteristics, including CUDs. Correlations of number of ARBs across assessments were also compared for sibling pairs versus unrelated subjects. Results: Latent class growth analysis identified ARB-based Classes 1 (consistent low = 42.5%), 2 (moderate low = 28.3%), 3 (moderate high = 22.9%), and 4 (consistent high = 6.3%). A multinomial logistic regression analysis within latent class growth analysis revealed that baseline CUDs related most closely to Classes 3 and 4. The number of ARBs across time correlated .23 for sibling pairs and -.10 for unrelated subjects. Conclusions: Baseline CUDs related to the most severe latent ARB course over time, even when considered along with other trajectory predictors, including baseline alcohol use disorders and maximum number of drinks. Data indicated significant roles for genetic factors for alcohol use disorder patterns over time. Future research is needed to improve understanding of how cannabis adds to the ARB risk and to find genes that contribute to risks for ARBs among drinkers. PMID:27936363

Sieve analysis in HIV-1 vaccine efficacy trials

PubMed Central

Edlefsen, Paul T.; Gilbert, Peter B.; Rolland, Morgane

2013-01-01

Purpose of review The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. Recent findings The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 and RV144, led to numerous studies in the last five years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Summary Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons while correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection. PMID:23719202

Sieve analysis in HIV-1 vaccine efficacy trials.

PubMed

Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

2013-09-01

The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

Analysis of genetic diversity of Persea bombycina "Som" using RAPD-based molecular markers.

PubMed

Bhau, Brijmohan Singh; Medhi, Kalyani; Das, Ambrish P; Saikia, Siddhartha P; Neog, Kartik; Choudhury, S N

2009-08-01

The utility of RAPD markers in assessing genetic diversity and phenetic relationships in Persea bombycina, a major tree species for golden silk (muga) production, was investigated using 48 genotypes from northeast India. Thirteen RAPD primer combinations generated 93 bands. On average, seven RAPD fragments were amplified per reaction. In a UPGMA phenetic dendrogram based on Jaccard's coefficient, the P. bombycina accessions showed a high level of genetic variation, as indicated by genetic similarity. The grouping in the phenogram was highly consistent, as indicated by high values of cophenetic correlation and high bootstrap values at the key nodes. The accessions were scattered on a plot derived from principal correspondence analysis. The study concluded that the high level of genetic diversity in the P. bombycina accessions may be attributed to the species' outcrossing nature. This study may be useful in identifying diverse genetic stocks of P. bombycina, which may then be conserved on a priority basis.

Determination of epigenetic inheritance, genetic inheritance, and estimation of genome DNA methylation in a full-sib family of Cupressus sempervirens L.

PubMed

Avramidou, Evangelia V; Doulis, Andreas G; Aravanopoulos, Filippos A

2015-05-15

Genetic inheritance and epigenetic inheritance are significant determinants of plant evolution, adaptation and plasticity. We studied inheritance of restriction site polymorphisms by the f-AFLP method and epigenetic DNA cytosine methylation inheritance by the f-MSAP technique. The study involved parents and 190 progeny of a Cupressus sempervirens L. full-sib family. Results from AFLP genetic data revealed that 71.8% of the fragments studied are under Mendelian genetic control, whereas faithful Mendelian inheritance for the MSAP fragments was low (4.29%). Further, MSAP fragment analysis showed that total methylation presented a mean of 28.2%, which was higher than the midparent value, while maternal inheritance was higher (5.65%) than paternal (3.01%). Interestingly de novo methylation in the progeny was high (19.65%) compared to parental methylation. Genetic and epigenetic distances for parents and offspring were not correlated (R(2)=0.0005). Furthermore, we studied correlation of total relative methylation and CG methylation with growth (height, diameter). We found CG/CNG methylation (N: A, C, T) to be positively correlated with height and diameter, while total relative methylation and CG methylation were positively correlated with height. Results are discussed in light of further research needed and of their potential application in breeding. Copyright © 2015 Elsevier B.V. All rights reserved.

Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.

PubMed

Joshi, Peter K; Pirastu, Nicola; Kentistou, Katherine A; Fischer, Krista; Hofer, Edith; Schraut, Katharina E; Clark, David W; Nutile, Teresa; Barnes, Catriona L K; Timmers, Paul R H J; Shen, Xia; Gandin, Ilaria; McDaid, Aaron F; Hansen, Thomas Folkmann; Gordon, Scott D; Giulianini, Franco; Boutin, Thibaud S; Abdellaoui, Abdel; Zhao, Wei; Medina-Gomez, Carolina; Bartz, Traci M; Trompet, Stella; Lange, Leslie A; Raffield, Laura; van der Spek, Ashley; Galesloot, Tessel E; Proitsi, Petroula; Yanek, Lisa R; Bielak, Lawrence F; Payton, Antony; Murgia, Federico; Concas, Maria Pina; Biino, Ginevra; Tajuddin, Salman M; Seppälä, Ilkka; Amin, Najaf; Boerwinkle, Eric; Børglum, Anders D; Campbell, Archie; Demerath, Ellen W; Demuth, Ilja; Faul, Jessica D; Ford, Ian; Gialluisi, Alessandro; Gögele, Martin; Graff, MariaElisa; Hingorani, Aroon; Hottenga, Jouke-Jan; Hougaard, David M; Hurme, Mikko A; Ikram, M Arfan; Jylhä, Marja; Kuh, Diana; Ligthart, Lannie; Lill, Christina M; Lindenberger, Ulman; Lumley, Thomas; Mägi, Reedik; Marques-Vidal, Pedro; Medland, Sarah E; Milani, Lili; Nagy, Reka; Ollier, William E R; Peyser, Patricia A; Pramstaller, Peter P; Ridker, Paul M; Rivadeneira, Fernando; Ruggiero, Daniela; Saba, Yasaman; Schmidt, Reinhold; Schmidt, Helena; Slagboom, P Eline; Smith, Blair H; Smith, Jennifer A; Sotoodehnia, Nona; Steinhagen-Thiessen, Elisabeth; van Rooij, Frank J A; Verbeek, André L; Vermeulen, Sita H; Vollenweider, Peter; Wang, Yunpeng; Werge, Thomas; Whitfield, John B; Zonderman, Alan B; Lehtimäki, Terho; Evans, Michele K; Pirastu, Mario; Fuchsberger, Christian; Bertram, Lars; Pendleton, Neil; Kardia, Sharon L R; Ciullo, Marina; Becker, Diane M; Wong, Andrew; Psaty, Bruce M; van Duijn, Cornelia M; Wilson, James G; Jukema, J Wouter; Kiemeney, Lambertus; Uitterlinden, André G; Franceschini, Nora; North, Kari E; Weir, David R; Metspalu, Andres; Boomsma, Dorret I; Hayward, Caroline; Chasman, Daniel; Martin, Nicholas G; Sattar, Naveed; Campbell, Harry; Esko, Tōnu; Kutalik, Zoltán; Wilson, James F

2017-10-13

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents

PubMed Central

Prom-Wormley, Elizabeth; Eaves, Lindon J.; Rhee, Soo Hyun; Hewitt, John K.; Young, Susan; Corley, Robin; McGue, Matt; Iacono, William G.; Legrand, Lisa; Samek, Diana R.; Murrelle, E. Lenn; Silberg, Judy L.; Miles, Donna R.; Schieken, Richard M.; Beunen, Gaston P.; Thomis, Martine; Rose, Richard J.; Dick, Danielle M.; Boomsma, Dorret I.; Bartels, Meike; Vink, Jacqueline M.; Lichtenstein, Paul; White, Victoria; Kaprio, Jaakko; Neale, Michael C.

2017-01-01

Abstract Introduction: Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation (SI) across adolescence. Methods: Mega-analysis of pooled genetically informative data on SI was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N = 19 313 pairs) between ages 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the United States, Europe, and Australia. Results: Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of SI across developed countries. The estimate of additive genetic contributions to liability of SI increased from approximately 15% to 45% from ages 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to SI at age 13 (70%) and gradually less by age 19 (40%). Conclusions: Both additive genetic and shared environmental factors significantly contribute to variance in SI throughout adolescence. The present study, the largest genetic epidemiological study on SI to date, found consistent results across 11 studies for the etiology of SI. Environmental factors, especially those shared by siblings in a family, primarily influence SI variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. Implications: This is the first study to find evidence of genetic factors in liability to SI at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across studies reflecting similar etiology of liability to initiate smoking across different cultures and time periods. Thus familial factors strongly contribute to individual differences in who starts to smoke with a gradual increase in the impact of genetic factors and a corresponding decrease in that of the shared environment. PMID:27807125

Attitudes to Gun Control in an American Twin Sample: Sex Differences in the Causes of Variation.

PubMed

Eaves, Lindon J; Silberg, Judy L

2017-10-01

The genetic and social causes of individual differences in attitudes to gun control are estimated in a sample of senior male and female twin pairs in the United States. Genetic and environmental parameters were estimated by weighted least squares applied to polychoric correlations for monozygotic (MZ) and dizygotic (DZ) twins of both sexes. The analysis suggests twin similarity for attitudes to gun control in men is entirely genetic while that in women is purely social. Although the volunteer sample is small, the analysis illustrates how the well-tested concepts and methods of genetic epidemiology may be a fertile resource for deepening our scientific understanding of biological and social pathways that affect individual risk to gun violence.

Radiogenomics to characterize regional genetic heterogeneity in glioblastoma

PubMed Central

Hu, Leland S.; Ning, Shuluo; Eschbacher, Jennifer M.; Baxter, Leslie C.; Gaw, Nathan; Ranjbar, Sara; Plasencia, Jonathan; Dueck, Amylou C.; Peng, Sen; Smith, Kris A.; Nakaji, Peter; Karis, John P.; Quarles, C. Chad; Wu, Teresa; Loftus, Joseph C.; Jenkins, Robert B.; Sicotte, Hugues; Kollmeyer, Thomas M.; O'Neill, Brian P.; Elmquist, William; Hoxworth, Joseph M.; Frakes, David; Sarkaria, Jann; Swanson, Kristin R.; Tran, Nhan L.; Li, Jing; Mitchell, J. Ross

2017-01-01

Background Glioblastoma (GBM) exhibits profound intratumoral genetic heterogeneity. Each tumor comprises multiple genetically distinct clonal populations with different therapeutic sensitivities. This has implications for targeted therapy and genetically informed paradigms. Contrast-enhanced (CE)-MRI and conventional sampling techniques have failed to resolve this heterogeneity, particularly for nonenhancing tumor populations. This study explores the feasibility of using multiparametric MRI and texture analysis to characterize regional genetic heterogeneity throughout MRI-enhancing and nonenhancing tumor segments. Methods We collected multiple image-guided biopsies from primary GBM patients throughout regions of enhancement (ENH) and nonenhancing parenchyma (so called brain-around-tumor, [BAT]). For each biopsy, we analyzed DNA copy number variants for core GBM driver genes reported by The Cancer Genome Atlas. We co-registered biopsy locations with MRI and texture maps to correlate regional genetic status with spatially matched imaging measurements. We also built multivariate predictive decision-tree models for each GBM driver gene and validated accuracies using leave-one-out-cross-validation (LOOCV). Results We collected 48 biopsies (13 tumors) and identified significant imaging correlations (univariate analysis) for 6 driver genes: EGFR, PDGFRA, PTEN, CDKN2A, RB1, and TP53. Predictive model accuracies (on LOOCV) varied by driver gene of interest. Highest accuracies were observed for PDGFRA (77.1%), EGFR (75%), CDKN2A (87.5%), and RB1 (87.5%), while lowest accuracy was observed in TP53 (37.5%). Models for 4 driver genes (EGFR, RB1, CDKN2A, and PTEN) showed higher accuracy in BAT samples (n = 16) compared with those from ENH segments (n = 32). Conclusion MRI and texture analysis can help characterize regional genetic heterogeneity, which offers potential diagnostic value under the paradigm of individualized oncology. PMID:27502248

Genome-wide pleiotropy and shared biological pathways for resistance to bovine pathogens

PubMed Central

Zeng, Y.; Yin, T.; Brügemann, K.

2018-01-01

Host genetic architecture is a major factor in resistance to pathogens and parasites. The collection and analysis of sufficient data on both disease resistance and host genetics has, however, been a major obstacle to dissection the genetics of resistance to single or multiple pathogens. A severe challenge in the estimation of heritabilities and genetic correlations from pedigree-based studies has been the confounding effects of the common environment shared among relatives which are difficult to model in pedigree analyses, especially for health traits with low incidence rates. To circumvent this problem we used genome-wide single-nucleotide polymorphism data and implemented the Genomic-Restricted Maximum Likelihood (G-REML) method to estimate the heritabilities and genetic correlations for resistance to 23 different infectious pathogens in calves and cows in populations undergoing natural pathogen challenge. Furthermore, we conducted gene-based analysis and generalized gene-set analysis to understand the biological background of resistance to infectious diseases. The results showed relatively higher heritabilities of resistance in calves than in cows and significant pleiotropy (both positive and negative) among some calf and cow resistance traits. We also found significant pleiotropy between resistance and performance in both calves and cows. Finally, we confirmed the role of the B-lymphocyte pathway as one of the most important biological pathways associated with resistance to all pathogens. These results both illustrate the potential power of these approaches to illuminate the genetics of pathogen resistance in cattle and provide foundational information for future genomic selection aimed at improving the overall production fitness of cattle. PMID:29608619

GENETIC AND ENVIRONMENTAL CONTRIBUTIONS TO THE CO-OCCURRENCE OF DEPRESSIVE PERSONALITY DISORDER AND DSM-IV PERSONALITY DISORDERS

PubMed Central

Ørstavik, Ragnhild E.; Kendler, Kenneth S.; Røysamb, Espen; Czajkowski, Nikolai; Tambs, Kristian; Reichborn-Kjennerud, Ted

2012-01-01

One of the main controversies with regard to depressive personality disorder (DPD) concerns the co-occurrence with the established DSM-IV personality disorders (PDs). The main aim of this study was to examine to what extent DPD and the DSM-IV PDs share genetic and environmental risk factors, using multivariate twin modeling. The DSM-IV Structured Interview for Personality was applied to 2,794 young adult twins. Paranoid PD from Cluster A, borderline PD from Cluster B, and all three PDs from Cluster C were independently and significantly associated with DPD in multiple regression analysis. The genetic correlations between DPD and the other PDs were strong (.53–.83), while the environmental correlations were moderate (.36–.40). Close to 50% of the total variance in DPD was disorder specific. However, only 5% was due to disorder-specific genetic factors, indicating that a substantial part of the genetic vulnerability to DPD also increases the vulnerability to other PDs. PMID:22686231

Genetic and environmental contributions to the co-occurrence of depressive personality disorder and DSM-IV personality disorders.

PubMed

Ørstavik, Ragnhild E; Kendler, Kenneth S; Røysamb, Espen; Czajkowski, Nikolai; Tambs, Kristian; Reichborn-Kjennerud, Ted

2012-06-01

One of the main controversies with regard to depressive personality disorder (DPD) concerns the co-occurrence with the established DSM-IV personality disorders (PDs). The main aim of this study was to examine to what extent DPD and the DSM-IV PDs share genetic and environmental risk factors, using multivariate twin modeling. The DSM-IV Structured Interview for Personality was applied to 2,794 young adult twins. Paranoid PD from Cluster A, borderline PD from Cluster B, and all three PDs from Cluster C were independently and significantly associated with DPD in multiple regression analysis. The genetic correlations between DPD and the other PDs were strong (.53-.83), while the environmental correlations were moderate (.36-.40). Close to 50% of the total variance in DPD was disorder specific. However, only 5% was due to disorder-specific genetic factors, indicating that a substantial part of the genetic vulnerability to DPD also increases the vulnerability to other PDs.

Genetically determined schizophrenia is not associated with impaired glucose homeostasis.

PubMed

Polimanti, Renato; Gelernter, Joel; Stein, Dan J

2018-05-01

Here, we used data from large genome-wide association studies to test the presence of causal relationships, conducting a Mendelian randomization analysis; and shared molecular mechanisms, calculating the genetic correlation, among schizophrenia, type 2 diabetes (T2D), and impaired glucose homeostasis. Although our Mendelian randomization analysis was well-powered, no causal relationship was observed between schizophrenia and T2D, or traits related to glucose impaired homeostasis. Similarly, we did not observe any global genetic overlap among these traits. These findings indicate that there is no causal relationships or shared mechanisms between schizophrenia and impaired glucose homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Results after laparoscopic partial splenectomy for children with hereditary spherocytosis: Are outcomes influenced by genetic mutation?

PubMed

Pugi, Jakob; Carcao, Manuel; Drury, Luke J; Langer, Jacob C

2018-05-01

Laparoscopic partial splenectomy (LPS) theoretically maintains long-term splenic immune function for children with hereditary spherocytosis (HS). Our goal was to review our results after LPS and to determine if specific genetic mutations influence outcome. All children with HS undergoing LPS between 2005 and 2016 were reviewed. Thirty-one children underwent LPS (16 male) at a median age of 9 (range 2-18) years. All experienced an increase in hemoglobin and decrease in reticulocyte count early after LPS and at last follow-up. Twenty-two were sent for genetic analysis. Mutations in α-spectrin, β-spectrin, and Ankyrin were identified in 6, 5, and 11 patients, respectively. Gene mutation was not correlated with complications, perioperative transfusion, length of hospital stay, or median hemoglobin, platelet, or reticulocyte counts. Three children required completion splenectomy at 10.9, 6.9, and 3.2years post-LPS, each with a different gene mutation. LPS is effective in reversing anemia and reducing reticulocytosis. So far less than 10% have required completion splenectomy, and those children did benefit from delaying the risks of asplenia. In this preliminary analysis, genetic mutation did not influence outcome after LPS. A larger multicenter study is necessary to further investigate potential correlations with specific genetic mutations. Prognosis Study. IV. Copyright © 2018. Published by Elsevier Inc.

Genetic relatedness of Trichoderma isolates antagonistic against Fusarium oxysporum f.sp. dianthi inflicting carnation wilt.

PubMed

Shanmugam, V; Sharma, Vivek; Ananthapadmanaban

2008-01-01

Twenty-eight isolates of Trichoderma belonging to four different species were screened in vitro for their antagonistic ability against Fusarium oxysporum f.sp. dianthi causing carnation wilt. Three different levels of antagonism observed in dual plate assay were further confirmed by cell-free culture filtrate experiments. Isolates showing class I level of antagonism produced maximum lytic enzymes, chitinases and beta-1,3-glucanases. Genetic variability of 25 selected isolates was assessed by random amplified polymorphic DNA technique and the amplified products were correlated for their level of antagonism. Unweighed pair-group method with arithmetical averages cluster analysis revealed prominent inter-and intraspecific genetic variation among the isolates. Based on their genetic relationship, the isolates were mainly distributed into 3 major groups representing T. atroviride, T. pseudokoningii and T. harzianum, with 20-35% interspecific dissimilarity. However, the polymorphism shown by the isolates did not correlate to their level of antagonism.

Give 'til it hurts: trade-offs between immunity and male reproductive effort in the decorated cricket, Gryllodes sigillatus.

PubMed

Gershman, S N; Barnett, C A; Pettinger, A M; Weddle, C B; Hunt, J; Sakaluk, S K

2010-04-01

Trade-offs between life-history variables can be manifested at either the phenotypic or genetic level, with vastly different evolutionary consequences. Here, we examined whether male decorated crickets (Gryllodes sigillatus) from eight inbred lines and the outbred founder population from which they were derived, trade-off immune effort [lytic activity, phenoloxidase (PO) activity or encapsulation] to produce spermatophylaxes: costly nuptial food gifts essential for successful sperm transfer. Canonical correlation analysis of the outbred population revealed a trade-off between spermatophylax mass and lytic activity. Analysis of our inbred lines, however, revealed that although PO activity, encapsulation, body mass, spermatophylax mass and ampulla (sperm capsule) mass were all highly heritable, lytic activity was not, and there was, therefore, no negative genetic correlation between lytic activity and spermatophylax mass. Thus, males showed a phenotypic but not a genetic trade-off between spermatophylax mass and lytic activity, suggesting that this trade-off is mediated largely by environmental factors.

Learning Bayesian Networks from Correlated Data

NASA Astrophysics Data System (ADS)

Bae, Harold; Monti, Stefano; Montano, Monty; Steinberg, Martin H.; Perls, Thomas T.; Sebastiani, Paola

2016-05-01

Bayesian networks are probabilistic models that represent complex distributions in a modular way and have become very popular in many fields. There are many methods to build Bayesian networks from a random sample of independent and identically distributed observations. However, many observational studies are designed using some form of clustered sampling that introduces correlations between observations within the same cluster and ignoring this correlation typically inflates the rate of false positive associations. We describe a novel parameterization of Bayesian networks that uses random effects to model the correlation within sample units and can be used for structure and parameter learning from correlated data without inflating the Type I error rate. We compare different learning metrics using simulations and illustrate the method in two real examples: an analysis of genetic and non-genetic factors associated with human longevity from a family-based study, and an example of risk factors for complications of sickle cell anemia from a longitudinal study with repeated measures.

Environmental and genetic factors affecting cow survival of Israeli Holsteins.

PubMed

Weller, J I; Ezra, E

2015-01-01

The objectives were to investigate the effects of various environmental factors that may affect herd-life of Israeli Holsteins, including first-calving age and season, calving ease, number of progeny born, and service sire for first calving in complete and truncated records; and to estimate heritabilities and genetic correlations between herd-life and the other traits included in the Israeli breeding index. The basic data set consisted of 590,869 cows in milk recording herds with first freshening day between 1985 and at least 8 yr before the cut-off date of September 15, 2013. Herd-life was measured as days from first calving to culling. The phenotypic and genetic trends for herd-life were 5.7 and 16.8d/yr. The genetic trend was almost linear, whereas the phenotypic trend showed 4 peaks and 3 valleys. Cows born in February and March had the shortest herd-life, whereas cows born in September had the longest herd-life. Herd-life was maximal with calving age of 23mo, which is 1mo less than the mean calving age, and minimal at 19 and 31mo of calving age. Dystocia and twinning on first-parity calving reduced herd-life by approximately180 and 120d, but the interaction effect increased herd-life by 140d. Heritability for herd-life was 0.14. Despite the fact that the service sire effect was significant in the fixed model analysis, service sire effect accounted for <0.05% of the total variance. In the analysis of 1,431,938 truncated records, the effects of dystocia and twinning rate were very similar but less than 50% of the effects found in the analysis of complete records. Pregnancy at the truncation date increased expected herd-life by 432d. The correlation between actual herd-life and predicted herd-life based on truncated records was 0.44. Genetic correlations between the truncated records and actual herd-life were 0.75 for records truncated after 6mo but approached unity for records truncated after 3 yr. The genetic correlations of herd-life with first-parity milk, fat, and protein production, somatic cell score (SCS), and female fertility were all positive, except for SCS, in which negative values are economically favorable. The highest correlations with herd-life in absolute value were with female fertility and SCS. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Genetic diversity of wild Cynodon dactylon germplasm detected by SRAP markers].

PubMed

Yi, Yang-Jie; Zhang, Xin-Quan; Huang, Lin-Kai; Ling, Yao; Ma, Xiao; Liu, Wei

2008-01-01

Sequence-related amplified polymorphism (SRAP) molecular markers were used to detect the genetic diversity of 32 wild accessions of Cynodon dactylon collected from Sichuan, Chongqing, Guizhou and Tibet, China. The following results were obtained. (1) Fourteen primer pairs produced 132 polymorphic bands, averaged 9.4 bands per primer pair. The percentage of polymorphic bands in average was 79.8%. The Nei's genetic similarity coefficient of the tested accessions ranged from 0.591 to 0.957, and the average Nei's coefficient was 0.759. These results suggested that there was rich genetic diversity among the wild resources of Cynodon dactylon tested. (2) Thirty two wild accessions were clustered into four groups. Moreover, the accessions from the same origin frequently clustered into one group. The findings implied that a correlation among the wild resources, geographical and ecological environment. (3) Genetic differentiation between and within six eco-geographical groups of C. dactylon was estimated by Shannon's diversity index, which showed that 65.56% genetic variance existed within group, and 34.44% genetic variance was among groups. (4) Based on Nei's unbiased measures of genetic identity, UPGMA cluster analysis measures of six eco-geographical groups of Cynodon dactylon, indicated that there was a correlation between genetic differentiation and eco-geographical habits among the groups.

Microfluidics for Single-Cell Genetic Analysis

PubMed Central

Thompson, A. M.; Paguirigan, A. L.; Kreutz, J. E.; Radich, J. P.; Chiu, D. T.

2014-01-01

The ability to correlate single-cell genetic information to cellular phenotypes will provide the kind of detailed insight into human physiology and disease pathways that is not possible to infer from bulk cell analysis. Microfluidic technologies are attractive for single-cell manipulation due to precise handling and low risk of contamination. Additionally, microfluidic single-cell techniques can allow for high-throughput and detailed genetic analyses that increase accuracy and decreases reagent cost compared to bulk techniques. Incorporating these microfluidic platforms into research and clinical laboratory workflows can fill an unmet need in biology, delivering the highly accurate, highly informative data necessary to develop new therapies and monitor patient outcomes. In this perspective, we describe the current and potential future uses of microfluidics at all stages of single-cell genetic analysis, including cell enrichment and capture, single-cell compartmentalization and manipulation, and detection and analyses. PMID:24789374

Elimination of a genetic correlation between the sexes via artificial correlational selection.

PubMed

Delph, Lynda F; Steven, Janet C; Anderson, Ingrid A; Herlihy, Christopher R; Brodie, Edmund D

2011-10-01

Genetic correlations between the sexes can constrain the evolution of sexual dimorphism and be difficult to alter, because traits common to both sexes share the same genetic underpinnings. We tested whether artificial correlational selection favoring specific combinations of male and female traits within families could change the strength of a very high between-sex genetic correlation for flower size in the dioecious plant Silene latifolia. This novel selection dramatically reduced the correlation in two of three selection lines in fewer than five generations. Subsequent selection only on females in a line characterized by a lower between-sex genetic correlation led to a significantly lower correlated response in males, confirming the potential evolutionary impact of the reduced correlation. Although between-sex genetic correlations can potentially constrain the evolution of sexual dimorphism, our findings reveal that these constraints come not from a simple conflict between an inflexible genetic architecture and a pattern of selection working in opposition to it, but rather a complex relationship between a changeable correlation and a form of selection that promotes it. In other words, the form of selection on males and females that leads to sexual dimorphism may also promote the genetic phenomenon that limits sexual dimorphism. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

The correlation between ancestry and color in two cities of Northeast Brazil with contrasting ethnic compositions

PubMed Central

Magalhães da Silva, Thiago; Sandhya Rani, M R; de Oliveira Costa, Gustavo Nunes; Figueiredo, Maria A; Melo, Paulo S; Nascimento, João F; Molyneaux, Neil D; Barreto, Maurício L; Reis, Mitermayer G; Teixeira, M Glória; Blanton, Ronald E

2015-01-01

The degree of admixture in Brazil between historically isolated populations is complex and geographically variable. Studies differ as to what the genetic and phenotypic consequences of this mixing have been. In Northeastern Brazil, we enrolled 522 residents of Salvador and 620 of Fortaleza whose distributions of self-declared color were comparable to those in the national census. Using the program Structure and principal components analysis there was a clear correlation between biogeographic ancestry and categories of skin color. This correlation with African ancestry was stronger in Salvador (r=0.585; P<0.001) than in Fortaleza (r=0.236; P<0.001). In Fortaleza, although self-declared blacks had a greater proportion of European ancestry, they had more African ancestry than the other categories. When the populations were analyzed without pseudoancestors, as in some studies, the relationship of ‘race' to genetic ancestry tended to diffuse or disappear. The inclusion of different African populations also influenced ancestry estimates. The percentage of unlinked ancestry informative markers in linkage disequilibrium, a measure of population structure, was 3–5 times higher in both Brazilian populations than expected by chance. We propose that certain methods, ascertainment bias and population history of the specific populations surveyed can result in failure to demonstrate a correlation between skin color and genetic ancestry. Population structure in Brazil has important implications for genetic studies, but genetic ancestry is irrelevant for how individuals are treated in society, their health, their income or their inclusion. These track more closely with perceived skin color than genetic ancestry. PMID:25293718

Random regression analysis for body weights and main morphological traits in genetically improved farmed tilapia (Oreochromis niloticus).

PubMed

He, Jie; Zhao, Yunfeng; Zhao, Jingli; Gao, Jin; Xu, Pao; Yang, Runqing

2018-02-01

To genetically analyse growth traits in genetically improved farmed tilapia (GIFT), the body weight (BWE) and main morphological traits, including body length (BL), body depth (BD), body width (BWI), head length (HL) and length of the caudal peduncle (CPL), were measured six times in growth duration on 1451 fish from 45 mixed families of full and half sibs. A random regression model (RRM) was used to model genetic changes of the growth traits with days of age and estimate the heritability for any growth point and genetic correlations between pairwise growth points. Using the covariance function based on optimal RRMs, the heritabilities were estimated to be from 0.102 to 0.662 for BWE, 0.157 to 0.591 for BL, 0.047 to 0.621 for BD, 0.018 to 0.577 for BWI, 0.075 to 0.597 for HL and 0.032 to 0.610 for CPL between 60 and 140 days of age. All genetic correlations exceeded 0.5 between pairwise growth points. Moreover, the traits at initial days of age showed less correlation with those at later days of age. With phenotypes observed repeatedly, the model choice showed that the optimal RRMs could more precisely predict breeding values at a specific growth time than repeatability models or multiple trait animal models, which enhanced the efficiency of selection for the BWE and main morphological traits.

Analyzing Association Mapping in Pedigree-Based GWAS Using a Penalized Multitrait Mixed Model

PubMed Central

Liu, Jin; Yang, Can; Shi, Xingjie; Li, Cong; Huang, Jian; Zhao, Hongyu; Ma, Shuangge

2017-01-01

Genome-wide association studies (GWAS) have led to the identification of many genetic variants associated with complex diseases in the past 10 years. Penalization methods, with significant numerical and statistical advantages, have been extensively adopted in analyzing GWAS. This study has been partly motivated by the analysis of Genetic Analysis Workshop (GAW) 18 data, which have two notable characteristics. First, the subjects are from a small number of pedigrees and hence related. Second, for each subject, multiple correlated traits have been measured. Most of the existing penalization methods assume independence between subjects and traits and can be suboptimal. There are a few methods in the literature based on mixed modeling that can accommodate correlations. However, they cannot fully accommodate the two types of correlations while conducting effective marker selection. In this study, we develop a penalized multitrait mixed modeling approach. It accommodates the two different types of correlations and includes several existing methods as special cases. Effective penalization is adopted for marker selection. Simulation demonstrates its satisfactory performance. The GAW 18 data are analyzed using the proposed method. PMID:27247027

Molecular Diversity and Population Structure of a Worldwide Collection of Cultivated Tetraploid Alfalfa (Medicago sativa subsp. sativa L.) Germplasm as Revealed by Microsatellite Markers

PubMed Central

Qiang, Haiping; Chen, Zhihong; Zhang, Zhengli; Wang, Xuemin; Gao, Hongwen; Wang, Zan

2015-01-01

Information on genetic diversity and population structure of a tetraploid alfalfa collection might be valuable in effective use of the genetic resources. A set of 336 worldwide genotypes of tetraploid alfalfa (Medicago sativa subsp. sativa L.) was genotyped using 85 genome-wide distributed SSR markers to reveal the genetic diversity and population structure in the alfalfa. Genetic diversity analysis identified a total of 1056 alleles across 85 marker loci. The average expected heterozygosity and polymorphism information content values were 0.677 and 0.638, respectively, showing high levels of genetic diversity in the cultivated tetraploid alfalfa germplasm. Comparison of genetic characteristics across chromosomes indicated regions of chromosomes 2 and 3 had the highest genetic diversity. A higher genetic diversity was detected in alfalfa landraces than that of wild materials and cultivars. Two populations were identified by the model-based population structure, principal coordinate and neighbor-joining analyses, corresponding to China and other parts of the world. However, lack of strictly correlation between clustering and geographic origins suggested extensive germplasm exchanges of alfalfa germplasm across diverse geographic regions. The quantitative analysis of the genetic diversity and population structure in this study could be useful for genetic and genomic analysis and utilization of the genetic variation in alfalfa breeding. PMID:25901573

Measuring genetic knowledge: a brief survey instrument for adolescents and adults.

PubMed

Fitzgerald-Butt, S M; Bodine, A; Fry, K M; Ash, J; Zaidi, A N; Garg, V; Gerhardt, C A; McBride, K L

2016-02-01

Basic knowledge of genetics is essential for understanding genetic testing and counseling. The lack of a written, English language, validated, published measure has limited our ability to evaluate genetic knowledge of patients and families. Here, we begin the psychometric analysis of a true/false genetic knowledge measure. The 18-item measure was completed by parents of children with congenital heart defects (CHD) (n = 465) and adolescents and young adults with CHD (age: 15-25, n = 196) with a mean total correct score of 12.6 [standard deviation (SD) = 3.5, range: 0-18]. Utilizing exploratory factor analysis, we determined that one to three correlated factors, or abilities, were captured by our measure. Through confirmatory factor analysis, we determined that the two factor model was the best fit. Although it was necessary to remove two items, the remaining items exhibited adequate psychometric properties in a multidimensional item response theory analysis. Scores for each factor were computed, and a sum-score conversion table was derived. We conclude that this genetic knowledge measure discriminates best at low knowledge levels and is therefore well suited to determine a minimum adequate amount of genetic knowledge. However, further reliability testing and validation in diverse research and clinical settings is needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The genetic correlation between height and IQ: shared genes or assortative mating?

PubMed

Keller, Matthew C; Garver-Apgar, Christine E; Wright, Margaret J; Martin, Nicholas G; Corley, Robin P; Stallings, Michael C; Hewitt, John K; Zietsch, Brendan P

2013-04-01

Traits that are attractive to the opposite sex are often positively correlated when scaled such that scores increase with attractiveness, and this correlation typically has a genetic component. Such traits can be genetically correlated due to genes that affect both traits ("pleiotropy") and/or because assortative mating causes statistical correlations to develop between selected alleles across the traits ("gametic phase disequilibrium"). In this study, we modeled the covariation between monozygotic and dizygotic twins, their siblings, and their parents (total N = 7,905) to elucidate the nature of the correlation between two potentially sexually selected traits in humans: height and IQ. Unlike previous designs used to investigate the nature of the height-IQ correlation, the present design accounts for the effects of assortative mating and provides much less biased estimates of additive genetic, non-additive genetic, and shared environmental influences. Both traits were highly heritable, although there was greater evidence for non-additive genetic effects in males. After accounting for assortative mating, the correlation between height and IQ was found to be almost entirely genetic in nature. Model fits indicate that both pleiotropy and assortative mating contribute significantly and about equally to this genetic correlation.

A data-driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome-wide significant genetic loci.

PubMed

Leonenko, Ganna; Di Florio, Arianna; Allardyce, Judith; Forty, Liz; Knott, Sarah; Jones, Lisa; Gordon-Smith, Katherine; Owen, Michael J; Jones, Ian; Walters, James; Craddock, Nick; O'Donovan, Michael C; Escott-Price, Valentina

2018-06-01

The etiologies of bipolar disorder (BD) and schizophrenia include a large number of common risk alleles, many of which are shared across the disorders. BD is clinically heterogeneous and it has been postulated that the pattern of symptoms is in part determined by the particular risk alleles carried, and in particular, that risk alleles also confer liability to schizophrenia influence psychotic symptoms in those with BD. To investigate links between psychotic symptoms in BD and schizophrenia risk alleles we employed a data-driven approach in a genotyped and deeply phenotyped sample of subjects with BD. We used sparse canonical correlation analysis (sCCA) (Witten, Tibshirani, & Hastie, ) to analyze 30 psychotic symptoms, assessed with the OPerational CRITeria checklist, and 82 independent genome-wide significant single nucleotide polymorphisms (SNPs) identified by the Schizophrenia Working group of the Psychiatric Genomics Consortium for which we had data in our BD sample (3,903 subjects). As a secondary analysis, we applied sCCA to larger groups of SNPs, and also to groups of symptoms defined according to a published factor analyses of schizophrenia. sCCA analysis based on individual psychotic symptoms revealed a significant association (p = .033), with the largest weights attributed to a variant on chromosome 3 (rs11411529), chr3:180594593, build 37) and delusions of influence, bizarre behavior and grandiose delusions. sCCA analysis using the same set of SNPs supported association with the same SNP and the group of symptoms defined "factor 3" (p = .012). A significant association was also observed to the "factor 3" phenotype group when we included a greater number of SNPs that were less stringently associated with schizophrenia; although other SNPs contributed to the significant multivariate association result, the greatest weight remained assigned to rs11411529. Our results suggest that the canonical correlation is a useful tool to explore phenotype-genotype relationships. To the best of our knowledge, this is the first study to apply this approach to complex, polygenic psychiatric traits. The sparse canonical correlation approach offers the potential to include a larger number of fine-grained systematic descriptors, and to include genetic markers associated with other disorders that are genetically correlated with BD. © 2018 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Palmar dermatoglyphic patterns in twins.

PubMed

Jacques, S M; Salzano, F M; Penña, H F

1977-01-01

The role of genetic factors in the determination of palmar dermatoglyphic patterns was investigated in a series of 49 MZ and 51 DZ twins, using Spearman's rank correlation and analysis of variance. Both methods indicated that the genetic effect in the distribution of patterns is highest in the interdigital III and lowest in the interdigital IV regions, the hypothenar and thenar showing intermediate values. As for interdigital II, no evaluation of genetic effects was possible using the nonparametric test, but the estimates of genetic variance indicate that inherited factors may play a relatively minor role in the pattern distribution of this area.

Population genetic analysis and trichothecene profiling of Fusarium graminearum from wheat in Uruguay.

PubMed

Pan, D; Mionetto, A; Calero, N; Reynoso, M M; Torres, A; Bettucci, L

2016-03-11

Fusarium graminearum sensu stricto (F. graminearum s.s.) is the major causal agent of Fusarium head blight of wheat worldwide, and contaminates grains with trichothecene mycotoxins that cause serious threats to food safety and animal health. An important aspect of managing this pathogen and reducing mycotoxin contamination of wheat is knowledge regarding its population genetics. Therefore, isolates of F. graminearum s.s. from the major wheat-growing region of Uruguay were analyzed by amplified fragment length polymorphism assays, PCR genotyping, and chemical analysis of trichothecene production. Of the 102 isolates identified as having the 15-ADON genotype via PCR genotyping, all were DON producers, but only 41 strains were also 15-ADON producers, as determined by chemical analysis. The populations were genotypically diverse but genetically similar, with significant genetic exchange occurring between them. Analysis of molecular variance indicated that most of the genetic variability resulted from differences between isolates within populations. Multilocus linkage disequilibrium analysis suggested that the isolates had a panmictic population genetic structure and that there is significant recombination occurs in F. graminearum s.s. In conclusion, tour findings provide the first detailed description of the genetic structure and trichothecene production of populations of F. graminearum s.s. from Uruguay, and expands our understanding of the agroecology of F. graminearum and of the correlation between genotypes and trichothecene chemotypes.

Site-to-site genetic correlations and their implications on breeding zone size and optimum number of progeny test sites for Coastal Douglas-fir.

Treesearch

G.R. Johnson

1997-01-01

Type B genetic correlations were used to examine the relation among geographic differences between sites and their site-to-site genetic (Type B) correlations. Examination of six local breeding zones in Oregon indicated that breeding zones were, for the most part, not too large because few environmental variables were correlated with Type B genetic correlations. The...

Bias due to two-stage residual-outcome regression analysis in genetic association studies.

PubMed

Demissie, Serkalem; Cupples, L Adrienne

2011-11-01

Association studies of risk factors and complex diseases require careful assessment of potential confounding factors. Two-stage regression analysis, sometimes referred to as residual- or adjusted-outcome analysis, has been increasingly used in association studies of single nucleotide polymorphisms (SNPs) and quantitative traits. In this analysis, first, a residual-outcome is calculated from a regression of the outcome variable on covariates and then the relationship between the adjusted-outcome and the SNP is evaluated by a simple linear regression of the adjusted-outcome on the SNP. In this article, we examine the performance of this two-stage analysis as compared with multiple linear regression (MLR) analysis. Our findings show that when a SNP and a covariate are correlated, the two-stage approach results in biased genotypic effect and loss of power. Bias is always toward the null and increases with the squared-correlation between the SNP and the covariate (). For example, for , 0.1, and 0.5, two-stage analysis results in, respectively, 0, 10, and 50% attenuation in the SNP effect. As expected, MLR was always unbiased. Since individual SNPs often show little or no correlation with covariates, a two-stage analysis is expected to perform as well as MLR in many genetic studies; however, it produces considerably different results from MLR and may lead to incorrect conclusions when independent variables are highly correlated. While a useful alternative to MLR under , the two -stage approach has serious limitations. Its use as a simple substitute for MLR should be avoided. © 2011 Wiley Periodicals, Inc.

Genetic diversity and structure of Atta robusta (Hymenoptera, Formicidae, Attini), an endangered species endemic to the restinga ecoregion

PubMed Central

dos Reis, Evelyze Pinheiro; Fernandes Salomão, Tânia Maria; de Oliveira Campos, Lucio Antonio; Tavares, Mara Garcia

2014-01-01

The genetic diversity and structure of the ant Atta robusta were assessed by ISSR (inter-simple sequence repeats) in 72 colonies collected from 10 localities in the Brazilian states of Espírito Santo (48 colonies) and Rio de Janeiro (24 colonies). The ISSR pattern included 67 bands, 51 of them (76.1%) polymorphic. Analysis of molecular variance (AMOVA) revealed a high level (57.4%) of inter-population variation, which suggested a high degree of genetic structure that was confirmed by UPGMA (unweighted pair-group method using an arithmetic average) cluster analysis. The significant correlation between genetic and geographic distances (r = 0.64, p < 0.05) indicated isolation that reflected the distance between locations. Overall, the populations were found to be genetically divergent. This finding indicates the need for management plans to preserve and reduce the risk of extinction of A. robusta. PMID:25249782

Genetic diversity and structure of Atta robusta (Hymenoptera, Formicidae, Attini), an endangered species endemic to the restinga ecoregion.

PubMed

Dos Reis, Evelyze Pinheiro; Fernandes Salomão, Tânia Maria; de Oliveira Campos, Lucio Antonio; Tavares, Mara Garcia

2014-09-01

The genetic diversity and structure of the ant Atta robusta were assessed by ISSR (inter-simple sequence repeats) in 72 colonies collected from 10 localities in the Brazilian states of Espírito Santo (48 colonies) and Rio de Janeiro (24 colonies). The ISSR pattern included 67 bands, 51 of them (76.1%) polymorphic. Analysis of molecular variance (AMOVA) revealed a high level (57.4%) of inter-population variation, which suggested a high degree of genetic structure that was confirmed by UPGMA (unweighted pair-group method using an arithmetic average) cluster analysis. The significant correlation between genetic and geographic distances (r = 0.64, p < 0.05) indicated isolation that reflected the distance between locations. Overall, the populations were found to be genetically divergent. This finding indicates the need for management plans to preserve and reduce the risk of extinction of A. robusta.

Genetic parameters and principal component analysis for egg production from White Leghorn hens.

PubMed

Venturini, G C; Savegnago, R P; Nunes, B N; Ledur, M C; Schmidt, G S; El Faro, L; Munari, D P

2013-09-01

The objectives of this study were to estimate genetic parameters for accumulated egg production over 3-wk periods and for total egg production over 54 wk of egg-laying, and using principal component analysis (PCA), to explore the relationships among the breeding values of these traits to identify the possible genetic relationships present among them and hence to observe which of them could be used as selection criteria for improving egg production. Egg production was measured among 1,512 females of a line of White Leghorn laying hens. The traits analyzed were the number of eggs produced over partial periods of 3 wk, thus totaling 18 partial periods (P1 to P18), and the total number of eggs produced over the period between the 17 and 70 wk of age (PTOT), thus totaling 54 wk of egg production. Estimates of genetic parameters were obtained by means of the restricted maximum likelihood method, using 2-trait animal models. The PCA was done using the breeding values of partial and total egg production. The heritability estimates ranged from 0.05 ± 0.03 (P1 and P8) to 0.27 ± 0.06 (P4) in the 2-trait analysis. The genetic correlations between PTOT and partial periods ranged from 0.19 ± 0.31 (P1) to 1.00 ± 0.05 (P10, P11, and P12). Despite the high genetic correlation, selection of birds based on P10, P11, and P12 did not result in an increase in PTOT because of the low heritability estimates for these periods (0.06 ± 0.03, 0.12 ± 0.04, and 0.10 ± 0.04, respectively). The PCA showed that egg production can be divided genetically into 4 periods, and that P1 and P2 are independent and have little genetic association with the other periods.

Comparative analysis of genetic diversity among Indian populations of Scirpophaga incertulas by ISSR-PCR and RAPD-PCR.

PubMed

Kumar, L S; Sawant, A S; Gupta, V S; Ranjekar, P K

2001-10-01

Genetic variation between 28 Indian populations of the rice pest, Scirpophaga incertulas was evaluated using inter-simple sequence repeats (ISSR)-PCR assay. Nine SSR primers gave rise to 79 amplification products of which 67 were polymorphic. A dendrogram constructed from this data indicates that there is no geographical bias to the clustering and that gene flow between populations appears to be relatively unrestricted, substantiating our earlier conclusion based on the RAPD (random amplified polymorphic DNA) data. The dendrograms obtained using each of these marker systems were poorly correlated with each other as determined by Mantel's test for matrix correlation. Estimates of expected heterozygosity and marker index for each of these marker systems suggests that both these marker systems are equally efficient in determining polymorphisms. Matrix correlation analyses suggest that reliable estimates of genetic variation among the S. incertulas pest populations can be obtained by using RAPDs alone or in combination with ISSRs, but ISSRs alone cannot be used for this purpose.

Detecting Coevolution in Mammalian Sperm–Egg Fusion Proteins

PubMed Central

CLAW, KATRINA G.; GEORGE, RENEE D.; SWANSON, WILLIE J.

2018-01-01

SUMMARY Interactions between sperm and egg proteins can occur physically between gamete surface-binding proteins, and genetically between gamete proteins that work in complementary pathways in which they may not physically interact. Physically interacting sperm–egg proteins have been functionally identified in only a few species, and none have been verified within mammals. Candidate genes on both the sperm and egg surfaces exist, but gene deletion studies do not support functional interactions between these sperm–egg proteins; interacting sperm–egg proteins thus remain elusive. Cooperative gamete proteins undergo rapid evolution, and it is predicted that these sperm–egg proteins will also have correlated evolutionary rates due to compensatory changes on both the sperm and egg. To explore potential physical and genetic interactions in sperm–egg proteins, we sequenced four candidate genes from diverse primate species, and used regression and likelihood methods to test for signatures of coevolution between sperm–egg gene pairs. With both methods, we found that the egg protein CD9 coevolves with the sperm protein IZUMO1, suggesting a physical or genetic interaction occurs between them. With regression analysis, we found that CD9 and CRISP2 have correlated rates of evolution, and with likelihood analysis, that CD9 and CRISP1 have correlated rates. This suggests that the different tests may reflect different levels of interaction, be it physical or genetic. Coevolution tests thus provide an exploratory method for detecting potentially interacting sperm–egg protein pairs. PMID:24644026

Detecting coevolution in mammalian sperm-egg fusion proteins.

PubMed

Claw, Katrina G; George, Renee D; Swanson, Willie J

2014-06-01

Interactions between sperm and egg proteins can occur physically between gamete surface-binding proteins, and genetically between gamete proteins that work in complementary pathways in which they may not physically interact. Physically interacting sperm-egg proteins have been functionally identified in only a few species, and none have been verified within mammals. Candidate genes on both the sperm and egg surfaces exist, but gene deletion studies do not support functional interactions between these sperm-egg proteins; interacting sperm-egg proteins thus remain elusive. Cooperative gamete proteins undergo rapid evolution, and it is predicted that these sperm-egg proteins will also have correlated evolutionary rates due to compensatory changes on both the sperm and egg. To explore potential physical and genetic interactions in sperm-egg proteins, we sequenced four candidate genes from diverse primate species, and used regression and likelihood methods to test for signatures of coevolution between sperm-egg gene pairs. With both methods, we found that the egg protein CD9 coevolves with the sperm protein IZUMO1, suggesting a physical or genetic interaction occurs between them. With regression analysis, we found that CD9 and CRISP2 have correlated rates of evolution, and with likelihood analysis, that CD9 and CRISP1 have correlated rates. This suggests that the different tests may reflect different levels of interaction, be it physical or genetic. Coevolution tests thus provide an exploratory method for detecting potentially interacting sperm-egg protein pairs. © 2014 Wiley Periodicals, Inc.

Multivariate Genetic Correlates of the Auditory Paired Stimuli-Based P2 Event-Related Potential in the Psychosis Dimension From the BSNIP Study.

PubMed

Mokhtari, Mohammadreza; Narayanan, Balaji; Hamm, Jordan P; Soh, Pauline; Calhoun, Vince D; Ruaño, Gualberto; Kocherla, Mohan; Windemuth, Andreas; Clementz, Brett A; Tamminga, Carol A; Sweeney, John A; Keshavan, Matcheri S; Pearlson, Godfrey D

2016-05-01

The complex molecular etiology of psychosis in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is not well defined, presumably due to their multifactorial genetic architecture. Neurobiological correlates of psychosis can be identified through genetic associations of intermediate phenotypes such as event-related potential (ERP) from auditory paired stimulus processing (APSP). Various ERP components of APSP are heritable and aberrant in SZ, PBP and their relatives, but their multivariate genetic factors are less explored. We investigated the multivariate polygenic association of ERP from 64-sensor auditory paired stimulus data in 149 SZ, 209 PBP probands, and 99 healthy individuals from the multisite Bipolar-Schizophrenia Network on Intermediate Phenotypes study. Multivariate association of 64-channel APSP waveforms with a subset of 16 999 single nucleotide polymorphisms (SNPs) (reduced from 1 million SNP array) was examined using parallel independent component analysis (Para-ICA). Biological pathways associated with the genes were assessed using enrichment-based analysis tools. Para-ICA identified 2 ERP components, of which one was significantly correlated with a genetic network comprising multiple linearly coupled gene variants that explained ~4% of the ERP phenotype variance. Enrichment analysis revealed epidermal growth factor, endocannabinoid signaling, glutamatergic synapse and maltohexaose transport associated with P2 component of the N1-P2 ERP waveform. This ERP component also showed deficits in SZ and PBP. Aberrant P2 component in psychosis was associated with gene networks regulating several fundamental biologic functions, either general or specific to nervous system development. The pathways and processes underlying the gene clusters play a crucial role in brain function, plausibly implicated in psychosis. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Genetic and Environmental Influences on the Associations Between Uric Acid Levels and Metabolic Syndrome Over Time.

PubMed

Song, Yun-Mi; Lee, Kayoung

2018-05-02

The longitudinal associations between serum uric acid (UA) levels and metabolic syndrome (MetS) and its components, as well as the shared genetic and environmental correlations between these traits, were evaluated. In a total of 1803 participants (675 men and 1128 women; 695 monozygotic twin individuals, 159 dizygotic twin individuals, and 949 non-twin family members; 44.3 ± 12.8 years old) and 321 monozygotic twin pairs with data on UA levels and MetS components at baseline and follow-up, mixed linear model, conditional logistic regression, and bivariate variance component analysis were conducted. After 3.7 ± 1.4 years, the incident and persistent prevalence of MetS were 5.3% and 11.6%, respectively. UA was positively associated with the concurrent and future number of MetS criteria, blood pressure (BP), and triglyceride (TG) levels, whereas an inverse association was observed between UA and future high-density lipoprotein cholesterol (HDL-C) levels after adjusting for twin and household effects, demographics, health behaviors at baseline, and other confounders according to outcome variables. In the adjusted bivariate analysis, UA had genetic and environmental correlations with the concurrent and future number of MetS criteria, and had genetic correlations with concurrent BP and TG levels and future diastolic BP and HDL-C levels. In the adjusted co-twin control analysis, twins with a higher UA level were more likely to have concurrent MetS [odds ratio (95% confidence interval) 1.59 (1.00-2.53)], high blood glucose levels [1.84 (1.06-3.17)], future MetS [2.35 (1.19-4.64)], and high TG levels [1.52 (1.03-2.24)] than co-twins with a lower UA level. Genetic and environmental factors affect the concurrent and longitudinal associations between UA and MetS as well as some of its components.

Genetic Diversity and Population Structure of Siberian apricot (Prunus sibirica L.) in China

PubMed Central

Li, Ming; Zhao, Zhong; Miao, Xingjun; Zhou, Jingjing

2014-01-01

The genetic diversity and population genetic structure of 252 accessions from 21 Prunus sibirica L. populations were investigated using 10 ISSR, SSR, and SRAP markers. The results suggest that the entire population has a relatively high level of genetic diversity, with populations HR and MY showing very high diversity. A low level of inter-population genetic differentiation and a high level of intra-population genetic differentiation was found, which is supported by a moderate level of gene flow, and largely attributable to the cross-pollination and self-incompatibility reproductive system. A STRUCTURE (model-based program) analysis revealed that the 21 populations can be divided into two main groups, mainly based on geographic differences and genetic exchanges. The entire wild Siberia apricot population in China could be divided into two subgroups, including 107 accessions in subgroup (SG) 1 and 147 accessions in SG 2. A Mantel test revealed a significant positive correlation between genetic and geographic distance matrices, and there was a very significant positive correlation among three marker datasets. Overall, we recommend a combination of conservation measures, with ex situ and in situ conservation that includes the construction of a core germplasm repository and the implement of in situ conservation for populations HR, MY, and ZY. PMID:24384840

Tooth quality in dental fluorosis genetic and environmental factors.

PubMed

Vieira, A P G F; Hanocock, R; Eggertsson, H; Everett, E T; Grynpas, M D

2005-01-01

Dental fluorosis (DF) affects the appearance and structure of tooth enamel and can occur following ingestion of excess fluoride during critical periods of amelogenesis. This tooth malformation may, depending on its severity, influence enamel and dentin microhardness and dentin mineralization. Poor correlation between tooth fluoride (F) concentration and DF severity was shown in some studies, but even when a correlation was present, tooth fluoride concentration explained very little of DF severity. This fact calls into question the generally accepted hypothesis that the main factor responsible for DF severity is tooth fluoride concentration. It has been shown previously that genetic factors (susceptibility to DF) play an important role in DF severity although DF severity relates to individual susceptibility to fluoride exposure (genetics), tooth fluoride concentration relates to fluoride ingestion (environmental). The objective of this study was to investigate the correlation between tooth fluoride concentration, DF severity, and tooth mechanical and materials properties. Three strains of mice (previously shown to have different susceptibility to DF) at weaning were treated with four different levels of F in their water (0, 25, 50, and 100 ppm) for 6 weeks. Mice teeth were tested for fluoride by instrumental neutron activation analysis (INAA), DF severity determined by quantitative light-induced fluorescence [QLF], and tooth quality (enamel and dentin microhardness and dentin mineralization). Tooth fluoride concentration (environment factor) correlated positively with DF severity (QLF) (rs=0.608), fluoride treatment group (rs=0.952). However, tooth fluoride concentration correlated negatively with enamel microhardness (rs=-0.587), dentin microhardness (rs=-0.268) and dentin mineralization (rs=-0.245). Dental fluorosis (genetic factor) severity (QLF) correlated positively with fluoride treatment (rs=0.608) and tooth fluoride concentration (rs=0.583). DF severity correlated negatively with enamel microhardness (rs=-0.564) and dentin microhardness (rs=-0.356). Genetic factors (DF severity) and the environmental factor (fluoride concentration in tooth structure) have similar influence on tooth biomechanical properties, whereas only the environmental factor has an influence on tooth material property (mineralization).

Genetic Overlap Between Schizophrenia and Developmental Psychopathology: Longitudinal and Multivariate Polygenic Risk Prediction of Common Psychiatric Traits During Development.

PubMed

Nivard, Michel G; Gage, Suzanne H; Hottenga, Jouke J; van Beijsterveldt, Catharina E M; Abdellaoui, Abdel; Bartels, Meike; Baselmans, Bart M L; Ligthart, Lannie; Pourcain, Beate St; Boomsma, Dorret I; Munafò, Marcus R; Middeldorp, Christel M

2017-10-21

Several nonpsychotic psychiatric disorders in childhood and adolescence can precede the onset of schizophrenia, but the etiology of this relationship remains unclear. We investigated to what extent the association between schizophrenia and psychiatric disorders in childhood is explained by correlated genetic risk factors. Polygenic risk scores (PRS), reflecting an individual's genetic risk for schizophrenia, were constructed for 2588 children from the Netherlands Twin Register (NTR) and 6127 from the Avon Longitudinal Study of Parents And Children (ALSPAC). The associations between schizophrenia PRS and measures of anxiety, depression, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder/conduct disorder (ODD/CD) were estimated at age 7, 10, 12/13, and 15 years in the 2 cohorts. Results were then meta-analyzed, and a meta-regression analysis was performed to test differences in effects sizes over, age and disorders. Schizophrenia PRS were associated with childhood and adolescent psychopathology. Meta-regression analysis showed differences in the associations over disorders, with the strongest association with childhood and adolescent depression and a weaker association for ODD/CD at age 7. The associations increased with age and this increase was steepest for ADHD and ODD/CD. Genetic correlations varied between 0.10 and 0.25. By optimally using longitudinal data across diagnoses in a multivariate meta-analysis this study sheds light on the development of childhood disorders into severe adult psychiatric disorders. The results are consistent with a common genetic etiology of schizophrenia and developmental psychopathology as well as with a stronger shared genetic etiology between schizophrenia and adolescent onset psychopathology. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

Phylogeographic patterns of Lygus pratensis (Hemiptera: Miridae): Evidence for weak genetic structure and recent expansion in northwest China.

PubMed

Zhang, Li-Juan; Cai, Wan-Zhi; Luo, Jun-Yu; Zhang, Shuai; Wang, Chun-Yi; Lv, Li-Min; Zhu, Xiang-Zhen; Wang, Li; Cui, Jin-Jie

2017-01-01

Lygus pratensis (L.) is an important cotton pest in China, especially in the northwest region. Nymphs and adults cause serious quality and yield losses. However, the genetic structure and geographic distribution of L. pratensis is not well known. We analyzed genetic diversity, geographical structure, gene flow, and population dynamics of L. pratensis in northwest China using mitochondrial and nuclear sequence datasets to study phylogeographical patterns and demographic history. L. pratensis (n = 286) were collected at sites across an area spanning 2,180,000 km2, including the Xinjiang and Gansu-Ningxia regions. Populations in the two regions could be distinguished based on mitochondrial criteria but the overall genetic structure was weak. The nuclear dataset revealed a lack of diagnostic genetic structure across sample areas. Phylogenetic analysis indicated a lack of population level monophyly that may have been caused by incomplete lineage sorting. The Mantel test showed a significant correlation between genetic and geographic distances among the populations based on the mtDNA data. However the nuclear dataset did not show significant correlation. A high level of gene flow among populations was indicated by migration analysis; human activities may have also facilitated insect movement. The availability of irrigation water and ample cotton hosts makes the Xinjiang region well suited for L. pratensis reproduction. Bayesian skyline plot analysis, star-shaped network, and neutrality tests all indicated that L. pratensis has experienced recent population expansion. Climatic changes and extensive areas occupied by host plants have led to population expansion of L. pratensis. In conclusion, the present distribution and phylogeographic pattern of L. pratensis was influenced by climate, human activities, and availability of plant hosts.

Multiple-trait multiple-country genetic evaluation of Holstein bulls for female fertility and milk production traits.

PubMed

Nilforooshan, M A; Jakobsen, J H; Fikse, W F; Berglund, B; Jorjani, H

2014-06-01

The aim of this study was to investigate the effect of including milk yield data in the international genetic evaluation of female fertility traits to reduce or eliminate a possible bias because of across-country selection for milk yield. Data included two female fertility traits from Great Britain, Italy and the Netherlands, together with milk yield data from the same countries and from the United States, because the genetic trends in other countries may be influenced by selection decisions on bulls in the United States. Potentially, female fertility data had been corrected nationally for within-country selection and management biases for milk yield. Using a multiple-trait multiple across-country evaluation (MT-MACE) for the analysis of female fertility traits with milk yield, across-country selection patterns both for female fertility and milk yield can be considered simultaneously. Four analyses were performed; one single-trait multiple across-country evaluation analysis including only milk yield data, one MT-MACE analysis including only female fertility traits, and one MT-MACE analysis including both female fertility and milk yield traits. An additional MT-MACE analysis was performed including both female fertility and milk yield traits, but excluding the United States. By including milk yield traits to the analysis, female fertility reliabilities increased, but not for all bulls in all the countries by trait combinations. The presence of milk yield traits in the analysis did not considerably change the genetic correlations, genetic trends or bull rankings of female fertility traits. Even though the predicted genetic merits of female fertility traits hardly changed by including milk yield traits to the analysis, the change was not equally distributed to the whole data. The number of bulls in common between the two sets of Top 100 bulls for each trait in the two analyses of female fertility traits, with and without the four milk yield traits and their rank correlations were low, not necessarily because of the absence of the US milk yield data. The joint international genetic evaluation of female fertility traits with milk yield is recommended to make use of information on several female fertility traits from different countries simultaneously, to consider selection decisions for milk yield in the genetic evaluation of female fertility traits for obtaining more accurate estimating breeding values (EBV) and to acquire female fertility EBV for bulls evaluated for milk yield, but not for female fertility.

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.

PubMed

Trampush, J W; Yang, M L Z; Yu, J; Knowles, E; Davies, G; Liewald, D C; Starr, J M; Djurovic, S; Melle, I; Sundet, K; Christoforou, A; Reinvang, I; DeRosse, P; Lundervold, A J; Steen, V M; Espeseth, T; Räikkönen, K; Widen, E; Palotie, A; Eriksson, J G; Giegling, I; Konte, B; Roussos, P; Giakoumaki, S; Burdick, K E; Payton, A; Ollier, W; Horan, M; Chiba-Falek, O; Attix, D K; Need, A C; Cirulli, E T; Voineskos, A N; Stefanis, N C; Avramopoulos, D; Hatzimanolis, A; Arking, D E; Smyrnis, N; Bilder, R M; Freimer, N A; Cannon, T D; London, E; Poldrack, R A; Sabb, F W; Congdon, E; Conley, E D; Scult, M A; Dickinson, D; Straub, R E; Donohoe, G; Morris, D; Corvin, A; Gill, M; Hariri, A R; Weinberger, D R; Pendleton, N; Bitsios, P; Rujescu, D; Lahti, J; Le Hellard, S; Keller, M C; Andreassen, O A; Deary, I J; Glahn, D C; Malhotra, A K; Lencz, T

2017-03-01

The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10 -8 ). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium

PubMed Central

Trampush, J W; Yang, M L Z; Yu, J; Knowles, E; Davies, G; Liewald, D C; Starr, J M; Djurovic, S; Melle, I; Sundet, K; Christoforou, A; Reinvang, I; DeRosse, P; Lundervold, A J; Steen, V M; Espeseth, T; Räikkönen, K; Widen, E; Palotie, A; Eriksson, J G; Giegling, I; Konte, B; Roussos, P; Giakoumaki, S; Burdick, K E; Payton, A; Ollier, W; Horan, M; Chiba-Falek, O; Attix, D K; Need, A C; Cirulli, E T; Voineskos, A N; Stefanis, N C; Avramopoulos, D; Hatzimanolis, A; Arking, D E; Smyrnis, N; Bilder, R M; Freimer, N A; Cannon, T D; London, E; Poldrack, R A; Sabb, F W; Congdon, E; Conley, E D; Scult, M A; Dickinson, D; Straub, R E; Donohoe, G; Morris, D; Corvin, A; Gill, M; Hariri, A R; Weinberger, D R; Pendleton, N; Bitsios, P; Rujescu, D; Lahti, J; Le Hellard, S; Keller, M C; Andreassen, O A; Deary, I J; Glahn, D C; Malhotra, A K; Lencz, T

2017-01-01

The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10−8). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness. PMID:28093568

Rapid changes in genetic architecture of behavioural syndromes following colonization of a novel environment.

PubMed

Karlsson Green, K; Eroukhmanoff, F; Harris, S; Pettersson, L B; Svensson, E I

2016-01-01

Behavioural syndromes, that is correlated behaviours, may be a result from adaptive correlational selection, but in a new environmental setting, the trait correlation might act as an evolutionary constraint. However, knowledge about the quantitative genetic basis of behavioural syndromes, and the stability and evolvability of genetic correlations under different ecological conditions, is limited. We investigated the quantitative genetic basis of correlated behaviours in the freshwater isopod Asellus aquaticus. In some Swedish lakes, A. aquaticus has recently colonized a novel habitat and diverged into two ecotypes, presumably due to habitat-specific selection from predation. Using a common garden approach and animal model analyses, we estimated quantitative genetic parameters for behavioural traits and compared the genetic architecture between the ecotypes. We report that the genetic covariance structure of the behavioural traits has been altered in the novel ecotype, demonstrating divergence in behavioural correlations. Thus, our study confirms that genetic correlations behind behaviours can change rapidly in response to novel selective environments. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Genetic evaluation of mastitis liability and recovery through longitudinal analysis of transition probabilities

PubMed Central

2012-01-01

Background Many methods for the genetic analysis of mastitis use a cross-sectional approach, which omits information on, e.g., repeated mastitis cases during lactation, somatic cell count fluctuations, and recovery process. Acknowledging the dynamic behavior of mastitis during lactation and taking into account that there is more than one binary response variable to consider, can enhance the genetic evaluation of mastitis. Methods Genetic evaluation of mastitis was carried out by modeling the dynamic nature of somatic cell count (SCC) within the lactation. The SCC patterns were captured by modeling transition probabilities between assumed states of mastitis and non-mastitis. A widely dispersed SCC pattern generates high transition probabilities between states and vice versa. This method can model transitions to and from states of infection simultaneously, i.e. both the mastitis liability and the recovery process are considered. A multilevel discrete time survival model was applied to estimate breeding values on simulated data with different dataset sizes, mastitis frequencies, and genetic correlations. Results Correlations between estimated and simulated breeding values showed that the estimated accuracies for mastitis liability were similar to those from previously tested methods that used data of confirmed mastitis cases, while our results were based on SCC as an indicator of mastitis. In addition, unlike the other methods, our method also generates breeding values for the recovery process. Conclusions The developed method provides an effective tool for the genetic evaluation of mastitis when considering the whole disease course and will contribute to improving the genetic evaluation of udder health. PMID:22475575

Social isolation, loneliness and depression in young adulthood: a behavioural genetic analysis.

PubMed

Matthews, Timothy; Danese, Andrea; Wertz, Jasmin; Odgers, Candice L; Ambler, Antony; Moffitt, Terrie E; Arseneault, Louise

2016-03-01

To investigate the association between social isolation and loneliness, how they relate to depression, and whether these associations are explained by genetic influences. We used data from the age-18 wave of the Environmental Risk Longitudinal Twin Study, a birth cohort of 1116 same-sex twin pairs born in England and Wales in 1994 and 1995. Participants reported on their levels of social isolation, loneliness and depressive symptoms. We conducted regression analyses to test the differential associations of isolation and loneliness with depression. Using the twin study design, we estimated the proportion of variance in each construct and their covariance that was accounted for by genetic and environmental factors. Social isolation and loneliness were moderately correlated (r = 0.39), reflecting the separateness of these constructs, and both were associated with depression. When entered simultaneously in a regression analysis, loneliness was more robustly associated with depression. We observed similar degrees of genetic influence on social isolation (40 %) and loneliness (38 %), and a smaller genetic influence on depressive symptoms (29 %), with the remaining variance accounted for by the non-shared environment. Genetic correlations of 0.65 between isolation and loneliness and 0.63 between loneliness and depression indicated a strong role of genetic influences in the co-occurrence of these phenotypes. Socially isolated young adults do not necessarily experience loneliness. However, those who are lonely are often depressed, partly because the same genes influence loneliness and depression. Interventions should not only aim at increasing social connections but also focus on subjective feelings of loneliness.

Nonlinear Analysis of Time Series in Genome-Wide Linkage Disequilibrium Data

NASA Astrophysics Data System (ADS)

Hernández-Lemus, Enrique; Estrada-Gil, Jesús K.; Silva-Zolezzi, Irma; Fernández-López, J. Carlos; Hidalgo-Miranda, Alfredo; Jiménez-Sánchez, Gerardo

2008-02-01

The statistical study of large scale genomic data has turned out to be a very important tool in population genetics. Quantitative methods are essential to understand and implement association studies in the biomedical and health sciences. Nevertheless, the characterization of recently admixed populations has been an elusive problem due to the presence of a number of complex phenomena. For example, linkage disequilibrium structures are thought to be more complex than their non-recently admixed population counterparts, presenting the so-called ancestry blocks, admixed regions that are not yet smoothed by the effect of genetic recombination. In order to distinguish characteristic features for various populations we have implemented several methods, some of them borrowed or adapted from the analysis of nonlinear time series in statistical physics and quantitative physiology. We calculate the main fractal dimensions (Kolmogorov's capacity, information dimension and correlation dimension, usually named, D0, D1 and D2). We also have made detrended fluctuation analysis and information based similarity index calculations for the probability distribution of correlations of linkage disequilibrium coefficient of six recently admixed (mestizo) populations within the Mexican Genome Diversity Project [1] and for the non-recently admixed populations in the International HapMap Project [2]. Nonlinear correlations showed up as a consequence of internal structure within the haplotype distributions. The analysis of these correlations as well as the scope and limitations of these procedures within the biomedical sciences are discussed.

Copy number analysis reveals a novel multiexon deletion of the COLQ gene in congenital myasthenia.

PubMed

Wang, Wei; Wu, Yanhong; Wang, Chen; Jiao, Jinsong; Klein, Christopher J

2016-12-01

Congenital myasthenic syndrome (CMS) is genetically and clinically heterogeneous. 1 Despite a considerable number of causal genes discovered, many patients are left without a specific diagnosis after genetic testing. The presumption is that novel genes yet to be discovered will account for the majority of such patients. However, it is also possible that we are neglecting a type of genetic variation: copy number changes (>50 bp) as causal for some of these patients. Next-generation sequencing (NGS) can simultaneously screen all known causal genes 2 and is increasingly being validated to have a potential to identify copy number changes. 3 We present a CMS case who did not receive a genetic diagnosis from previous Sanger sequencing, but through a novel copy number analysis algorithm integrated into our targeted NGS panel, we discovered a novel copy number mutation in the COLQ gene and made a genetic diagnosis. This discovery expands the genotype-phenotype correlation of CMS, leads to improved genetic counsel, and allows for specific pharmacologic treatment. 1 .

Estimation of genetic parameters for reproductive traits in alpacas.

PubMed

Cruz, A; Cervantes, I; Burgos, A; Morante, R; Gutiérrez, J P

2015-12-01

One of the main deficiencies affecting animal breeding programs in Peruvian alpacas is the low reproductive performance leading to low number of animals available to select from, decreasing strongly the selection intensity. Some reproductive traits could be improved by artificial selection, but very few information about genetic parameters exists for these traits in this specie. The aim of this study was to estimate genetic parameters for six reproductive traits in alpacas both in Suri (SU) and Huacaya (HU) ecotypes, as well as their genetic relationship with fiber and morphological traits. Dataset belonging to Pacomarca experimental farm collected between 2000 and 2014 was used. Number of records for age at first service (AFS), age at first calving (AFC), copulation time (CT), pregnancy diagnosis (PD), gestation length (GL), and calving interval (CI) were, respectively, 1704, 854, 19,770, 5874, 4290 and 934. Pedigree consisted of 7742 animals. Regarding reproductive traits, model of analysis included additive and residual random effects for all traits, and also permanent environmental effect for CT, PD, GL and CI traits, with color and year of recording as fixed effects for all the reproductive traits and also age at mating and sex of calf for GL trait. Estimated heritabilities, respectively for HU and SU were 0.19 and 0.09 for AFS, 0.45 and 0.59 for AFC, 0.04 and 0.05 for CT, 0.07 and 0.05 for PD, 0.12 and 0.20 for GL, and 0.14 and 0.09 for CI. Genetic correlations between them ranged from -0.96 to 0.70. No important genetic correlations were found between reproductive traits and fiber or morphological traits in HU. However, some moderate favorable genetic correlations were found between reproductive and either fiber and morphological traits in SU. According to estimated genetic correlations, some reproductive traits might be included as additional selection criteria in HU. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic analysis of litter size, parturition length, and birth assistance requirements in primiparous sows using a joint linear-threshold animal model.

PubMed

Holm, B; Bakken, M; Vangen, O; Rekaya, R

2004-09-01

The aim of this study was to investigate whether selection for number of live born piglets has led to prolonged parturition and increased requirement for birth assistance, resulting in increased numbers of stillborn piglets. Data were collected from 6,718 primiparous Norwegian Landrace sows farrowing between 2001 and 2003. The need for birth assistance was recorded as a binary response. Physical intervention in the birth of piglets and/or hormonal treatment by the farmer was recorded as birth assistance. The duration of the parturition was analyzed as a binary trait (<4 h and >4 h). The statistical model used for analysis included contemporary groups of herd-year, litter breed, season of farrowing, parity in which the sow was born, a regression on the age of sow at farrowing, an additive genetic effect, and a service sire effect. A full Bayesian approach via Gibbs sampling was adopted to estimate the genetic relationships between these four traits. A total chain length of 100,000 iterations was run. The first 10,000 samples were discarded as burn-in, and the remaining 90,000 iterations were retained without thinning for post-Gibbs analysis. The highest direct heritability was estimated for the number of live-born piglets (h2 = 0.07), followed by the duration of farrowing (h2 = 0.05), the need for birth assistance (h2 = 0.05), and the number of stillborn piglets (h2 = 0.04). The genetic correlations revealed that the number of live and stillborn piglets was uncorrelated; however, the number of live piglets born had a moderate genetic correlation to the need for birth assistance (rg = 0.24 +/- 0.01) and duration of farrowing (rg = -0.20 +/- 0.01), whereas the number of stillborn piglets was highly correlated to the need for birth assistance (rg = 0.74 +/- 0.01) and the duration of parturition (rg = 0.66 +/- 0.01). The duration of farrowing and the need for birth assistance were genetically highly correlated (rg = 0.89 +/- 0.00). For all traits, the service sire variance was approximately one quarter in magnitude compared with its respective genetic variance. The results showed that selection for the number of live born piglets is not expected to influence the number of stillborn piglets. Increasing the number of live piglets born through selection should have a slight negative effect on farrowing duration and a minor increase in the need for birth assistance. Sows with a high genetic potential for birth assistance and prolonged parturition were more likely to give birth to greater numbers of stillborn piglets.

The association between intelligence and lifespan is mostly genetic.

PubMed

Arden, Rosalind; Luciano, Michelle; Deary, Ian J; Reynolds, Chandra A; Pedersen, Nancy L; Plassman, Brenda L; McGue, Matt; Christensen, Kaare; Visscher, Peter M

2016-02-01

Several studies in the new field of cognitive epidemiology have shown that higher intelligence predicts longer lifespan. This positive correlation might arise from socioeconomic status influencing both intelligence and health; intelligence leading to better health behaviours; and/or some shared genetic factors influencing both intelligence and health. Distinguishing among these hypotheses is crucial for medicine and public health, but can only be accomplished by studying a genetically informative sample. We analysed data from three genetically informative samples containing information on intelligence and mortality: Sample 1, 377 pairs of male veterans from the NAS-NRC US World War II Twin Registry; Sample 2, 246 pairs of twins from the Swedish Twin Registry; and Sample 3, 784 pairs of twins from the Danish Twin Registry. The age at which intelligence was measured differed between the samples. We used three methods of genetic analysis to examine the relationship between intelligence and lifespan: we calculated the proportion of the more intelligent twins who outlived their co-twin; we regressed within-twin-pair lifespan differences on within-twin-pair intelligence differences; and we used the resulting regression coefficients to model the additive genetic covariance. We conducted a meta-analysis of the regression coefficients across the three samples. The combined (and all three individual samples) showed a small positive phenotypic correlation between intelligence and lifespan. In the combined sample observed r = .12 (95% confidence interval .06 to .18). The additive genetic covariance model supported a genetic relationship between intelligence and lifespan. In the combined sample the genetic contribution to the covariance was 95%; in the US study, 84%; in the Swedish study, 86%, and in the Danish study, 85%. The finding of common genetic effects between lifespan and intelligence has important implications for public health, and for those interested in the genetics of intelligence, lifespan or inequalities in health outcomes including lifespan. © The Author 2015; Published by Oxford University Press on behalf of the International Epidemiological Association.

The association between intelligence and lifespan is mostly genetic

PubMed Central

Arden, Rosalind; Deary, Ian J; Reynolds, Chandra A; Pedersen, Nancy L; Plassman, Brenda L; McGue, Matt; Christensen, Kaare; Visscher, Peter M

2016-01-01

Abstract Background: Several studies in the new field of cognitive epidemiology have shown that higher intelligence predicts longer lifespan. This positive correlation might arise from socioeconomic status influencing both intelligence and health; intelligence leading to better health behaviours; and/or some shared genetic factors influencing both intelligence and health. Distinguishing among these hypotheses is crucial for medicine and public health, but can only be accomplished by studying a genetically informative sample. Methods: We analysed data from three genetically informative samples containing information on intelligence and mortality: Sample 1, 377 pairs of male veterans from the NAS-NRC US World War II Twin Registry; Sample 2, 246 pairs of twins from the Swedish Twin Registry; and Sample 3, 784 pairs of twins from the Danish Twin Registry. The age at which intelligence was measured differed between the samples. We used three methods of genetic analysis to examine the relationship between intelligence and lifespan: we calculated the proportion of the more intelligent twins who outlived their co-twin; we regressed within-twin-pair lifespan differences on within-twin-pair intelligence differences; and we used the resulting regression coefficients to model the additive genetic covariance. We conducted a meta-analysis of the regression coefficients across the three samples. Results: The combined (and all three individual samples) showed a small positive phenotypic correlation between intelligence and lifespan. In the combined sample observed r  = .12 (95% confidence interval .06 to .18). The additive genetic covariance model supported a genetic relationship between intelligence and lifespan. In the combined sample the genetic contribution to the covariance was 95%; in the US study, 84%; in the Swedish study, 86%, and in the Danish study, 85%. Conclusions: The finding of common genetic effects between lifespan and intelligence has important implications for public health, and for those interested in the genetics of intelligence, lifespan or inequalities in health outcomes including lifespan. PMID:26213105

Genetic Evaluation of Dual-Purpose Buffaloes (Bubalus bubalis) in Colombia Using Principal Component Analysis

PubMed Central

Agudelo-Gómez, Divier; Pineda-Sierra, Sebastian; Cerón-Muñoz, Mario Fernando

2015-01-01

Genealogy and productive information of 48621 dual-purpose buffaloes born in Colombia between years 1996 and 2014 was used. The following traits were assessed using one-trait models: milk yield at 270 days (MY270), age at first calving (AFC), weaning weight (WW), and weights at the following ages: first year (W12), 18 months (W18), and 2 years (W24). Direct additive genetic and residual random effects were included in all the traits. Maternal permanent environmental and maternal additive genetic effects were included for WW and W12. The fixed effects were: contemporary group (for all traits), sex (for WW, W12, W18, and W24), parity (for WW, W12, and MY270). Age was included as covariate for WW, W12, W18 and W24. Principal component analysis (PCA) was conducted using the genetic values of 133 breeding males whose breeding-value reliability was higher than 50% for all the traits in order to define the number of principal components (PC) which would explain most of the variation. The highest heritabilities were for W18 and MY270, and the lowest for AFC; with 0.53, 0.23, and 0.17, respectively. The first three PCs represented 66% of the total variance. Correlation of the first PC with meat production traits was higher than 0.73, and it was -0.38 with AFC. Correlations of the second PC with maternal genetic component traits for WW and W12 were above 0.75. The third PC had 0.84 correlation with MY270. PCA is an alternative approach for analyzing traits in dual-purpose buffaloes and reduces the dimension of the traits. PMID:26230093

Genetic and environmental relationships between change in weight and insulin resistance: the Healthy Twin Study.

PubMed

Song, Yun-Mi; Lee, Kayoung; Sung, Joohon

2014-06-01

We aimed to investigate the association between weight change from 20 years of age and insulin resistance (IR), and genetic and environmental relationships between these traits. In 594 Korean twins and family members (209 men, 385 women, 44.0 ± 10.8 years old), the percentage of weight change was calculated using self-reported body weight at 20 years of age and currently measured bodyweight. IR traits were assessed using fasting plasma glucose and insulin, the homeostasis model assessment of IR index (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI). Linear mixed analysis was applied after adjusting for household, body mass index (BMI) at the age of 20 years, age, sex, alcohol, smoking, physical activity, and caloric intake. Heritabilities and genetic and environmental correlations were estimated after adjusting for covariates. In 55 monozygotic twin pairs discordant for HOMA-IR level by >0.3, a conditional logistic regression analysis was conducted regarding weight change. Increases in glucose, insulin, and HOMA-IR and a decrease in QUICKI were associated with a higher percentage of weight change (p < .05). Estimated heritabilities for IR traits were 0.401-0.606 (p < .001). In cross-trait relationships, environmental correlations were -0.43-0.42 (p < .05 for all IR), while genetic correlations were -0.27-0.27 (p < .05 for QUICKI, insulin, and HOMA-IR). In 55 pairs of monozygotic twins, the odds ratio (95% confidence interval) for having a higher level of HOMA-IR was 1.10 (1.03-1.17) with 1% increase in weight change since 20 years old, after adjusting for lifestyle-related factors. In conclusion, both genetic and environmental influences played significant roles in the positive association between weight change from 20 years of age and IR.

Mind the gut: genomic insights to population divergence and gut microbial composition of two marine keystone species.

PubMed

Fietz, Katharina; Rye Hintze, Christian Olaf; Skovrind, Mikkel; Kjærgaard Nielsen, Tue; Limborg, Morten T; Krag, Marcus A; Palsbøll, Per J; Hestbjerg Hansen, Lars; Rask Møller, Peter; Gilbert, M Thomas P

2018-05-02

Deciphering the mechanisms governing population genetic divergence and local adaptation across heterogeneous environments is a central theme in marine ecology and conservation. While population divergence and ecological adaptive potential are classically viewed at the genetic level, it has recently been argued that their microbiomes may also contribute to population genetic divergence. We explored whether this might be plausible along the well-described environmental gradient of the Baltic Sea in two species of sand lance (Ammodytes tobianus and Hyperoplus lanceolatus). Specifically, we assessed both their population genetic and gut microbial composition variation and investigated not only which environmental parameters correlate with the observed variation, but whether host genome also correlates with microbiome variation. We found a clear genetic structure separating the high-salinity North Sea from the low-salinity Baltic Sea sand lances. The observed genetic divergence was not simply a function of isolation by distance, but correlated with environmental parameters, such as salinity, sea surface temperature, and, in the case of A. tobianus, possibly water microbiota. Furthermore, we detected two distinct genetic groups in Baltic A. tobianus that might represent sympatric spawning types. Investigation of possible drivers of gut microbiome composition variation revealed that host species identity was significantly correlated with the microbial community composition of the gut. A potential influence of host genetic factors on gut microbiome composition was further confirmed by the results of a constrained analysis of principal coordinates. The host genetic component was among the parameters that best explain observed variation in gut microbiome composition. Our findings have relevance for the population structure of two commercial species but also provide insights into potentially relevant genomic and microbial factors with regards to sand lance adaptation across the North Sea-Baltic Sea environmental gradient. Furthermore, our findings support the hypothesis that host genetics may play a role in regulating the gut microbiome at both the interspecific and intraspecific levels. As sequencing costs continue to drop, we anticipate that future studies that include full genome and microbiome sequencing will be able to explore the full relationship and its potential adaptive implications for these species.

From cow to cheese: genetic parameters of the flavour fingerprint of cheese investigated by direct-injection mass spectrometry (PTR-ToF-MS).

PubMed

Bergamaschi, Matteo; Cecchinato, Alessio; Biasioli, Franco; Gasperi, Flavia; Martin, Bruno; Bittante, Giovanni

2016-11-16

Volatile organic compounds determine important quality traits in cheese. The aim of this work was to infer genetic parameters of the profile of volatile compounds in cheese as revealed by direct-injection mass spectrometry of the headspace gas from model cheeses that were produced from milk samples from individual cows. A total of 1075 model cheeses were produced using raw whole-milk samples that were collected from individual Brown Swiss cows. Single spectrometry peaks and a combination of these peaks obtained by principal component analysis (PCA) were analysed. Using a Bayesian approach, we estimated genetic parameters for 240 individual spectrometry peaks and for the first ten principal components (PC) extracted from them. Our results show that there is some genetic variability in the volatile compound fingerprint of these model cheeses. Most peaks were characterized by a substantial heritability and for about one quarter of the peaks, heritability (up to 21.6%) was higher than that of the best PC. Intra-herd heritability of the PC ranged from 3.6 to 10.2% and was similar to heritabilities estimated for milk fat, specific fatty acids, somatic cell count and some coagulation parameters in the same population. We also calculated phenotypic correlations between PC (around zero as expected), the corresponding genetic correlations (from -0.79 to 0.86) and correlations between herds and sampling-processing dates (from -0.88 to 0.66), which confirmed that there is a relationship between cheese flavour and the dairy system in which cows are reared. This work reveals the existence of a link between the cow's genetic background and the profile of volatile compounds in cheese. Analysis of the relationships between the volatile organic compound (VOC) content and the sensory characteristics of cheese as perceived by the consumer, and of the genetic basis of these relationships could generate new knowledge that would open up the possibility of controlling and improving the sensory properties of cheese through genetic selection of cows. More detailed investigations are necessary to connect VOC with the sensory properties of cheese and gain a better understanding of the significance of these new phenotypes.

Multi-population Genomic Relationships for Estimating Current Genetic Variances Within and Genetic Correlations Between Populations.

PubMed

Wientjes, Yvonne C J; Bijma, Piter; Vandenplas, Jérémie; Calus, Mario P L

2017-10-01

Different methods are available to calculate multi-population genomic relationship matrices. Since those matrices differ in base population, it is anticipated that the method used to calculate genomic relationships affects the estimate of genetic variances, covariances, and correlations. The aim of this article is to define the multi-population genomic relationship matrix to estimate current genetic variances within and genetic correlations between populations. The genomic relationship matrix containing two populations consists of four blocks, one block for population 1, one block for population 2, and two blocks for relationships between the populations. It is known, based on literature, that by using current allele frequencies to calculate genomic relationships within a population, current genetic variances are estimated. In this article, we theoretically derived the properties of the genomic relationship matrix to estimate genetic correlations between populations and validated it using simulations. When the scaling factor of across-population genomic relationships is equal to the product of the square roots of the scaling factors for within-population genomic relationships, the genetic correlation is estimated unbiasedly even though estimated genetic variances do not necessarily refer to the current population. When this property is not met, the correlation based on estimated variances should be multiplied by a correction factor based on the scaling factors. In this study, we present a genomic relationship matrix which directly estimates current genetic variances as well as genetic correlations between populations. Copyright © 2017 by the Genetics Society of America.

NO RELATIONSHIP BETWEEN INTELLIGENCE AND FACIAL ATTRACTIVENESS IN A LARGE, GENETICALLY INFORMATIVE SAMPLE

PubMed Central

Mitchem, Dorian G.; Zietsch, Brendan P.; Wright, Margaret J.; Martin, Nicholas G.; Hewitt, John K.; Keller, Matthew C.

2015-01-01

Theories in both evolutionary and social psychology suggest that a positive correlation should exist between facial attractiveness and general intelligence, and several empirical observations appear to corroborate this expectation. Using highly reliable measures of facial attractiveness and IQ in a large sample of identical and fraternal twins and their siblings, we found no evidence for a phenotypic correlation between these traits. Likewise, neither the genetic nor the environmental latent factor correlations were statistically significant. We supplemented our analyses of new data with a simple meta-analysis that found evidence of publication bias among past studies of the relationship between facial attractiveness and intelligence. In view of these results, we suggest that previously published reports may have overestimated the strength of the relationship and that the theoretical bases for the predicted attractiveness-intelligence correlation may need to be reconsidered. PMID:25937789

A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents.

PubMed

Maes, Hermine H; Prom-Wormley, Elizabeth; Eaves, Lindon J; Rhee, Soo Hyun; Hewitt, John K; Young, Susan; Corley, Robin; McGue, Matt; Iacono, William G; Legrand, Lisa; Samek, Diana R; Murrelle, E Lenn; Silberg, Judy L; Miles, Donna R; Schieken, Richard M; Beunen, Gaston P; Thomis, Martine; Rose, Richard J; Dick, Danielle M; Boomsma, Dorret I; Bartels, Meike; Vink, Jacqueline M; Lichtenstein, Paul; White, Victoria; Kaprio, Jaakko; Neale, Michael C

2017-04-01

Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation (SI) across adolescence. Mega-analysis of pooled genetically informative data on SI was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N = 19 313 pairs) between ages 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the United States, Europe, and Australia. Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of SI across developed countries. The estimate of additive genetic contributions to liability of SI increased from approximately 15% to 45% from ages 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to SI at age 13 (70%) and gradually less by age 19 (40%). Both additive genetic and shared environmental factors significantly contribute to variance in SI throughout adolescence. The present study, the largest genetic epidemiological study on SI to date, found consistent results across 11 studies for the etiology of SI. Environmental factors, especially those shared by siblings in a family, primarily influence SI variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. This is the first study to find evidence of genetic factors in liability to SI at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across studies reflecting similar etiology of liability to initiate smoking across different cultures and time periods. Thus familial factors strongly contribute to individual differences in who starts to smoke with a gradual increase in the impact of genetic factors and a corresponding decrease in that of the shared environment. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis.

PubMed

Lee, S Hong; Byrne, Enda M; Hultman, Christina M; Kähler, Anna; Vinkhuyzen, Anna A E; Ripke, Stephan; Andreassen, Ole A; Frisell, Thomas; Gusev, Alexander; Hu, Xinli; Karlsson, Robert; Mantzioris, Vasilis X; McGrath, John J; Mehta, Divya; Stahl, Eli A; Zhao, Qiongyi; Kendler, Kenneth S; Sullivan, Patrick F; Price, Alkes L; O'Donovan, Michael; Okada, Yukinori; Mowry, Bryan J; Raychaudhuri, Soumya; Wray, Naomi R; Byerley, William; Cahn, Wiepke; Cantor, Rita M; Cichon, Sven; Cormican, Paul; Curtis, David; Djurovic, Srdjan; Escott-Price, Valentina; Gejman, Pablo V; Georgieva, Lyudmila; Giegling, Ina; Hansen, Thomas F; Ingason, Andrés; Kim, Yunjung; Konte, Bettina; Lee, Phil H; McIntosh, Andrew; McQuillin, Andrew; Morris, Derek W; Nöthen, Markus M; O'Dushlaine, Colm; Olincy, Ann; Olsen, Line; Pato, Carlos N; Pato, Michele T; Pickard, Benjamin S; Posthuma, Danielle; Rasmussen, Henrik B; Rietschel, Marcella; Rujescu, Dan; Schulze, Thomas G; Silverman, Jeremy M; Thirumalai, Srinivasa; Werge, Thomas; Agartz, Ingrid; Amin, Farooq; Azevedo, Maria H; Bass, Nicholas; Black, Donald W; Blackwood, Douglas H R; Bruggeman, Richard; Buccola, Nancy G; Choudhury, Khalid; Cloninger, Robert C; Corvin, Aiden; Craddock, Nicholas; Daly, Mark J; Datta, Susmita; Donohoe, Gary J; Duan, Jubao; Dudbridge, Frank; Fanous, Ayman; Freedman, Robert; Freimer, Nelson B; Friedl, Marion; Gill, Michael; Gurling, Hugh; De Haan, Lieuwe; Hamshere, Marian L; Hartmann, Annette M; Holmans, Peter A; Kahn, René S; Keller, Matthew C; Kenny, Elaine; Kirov, George K; Krabbendam, Lydia; Krasucki, Robert; Lawrence, Jacob; Lencz, Todd; Levinson, Douglas F; Lieberman, Jeffrey A; Lin, Dan-Yu; Linszen, Don H; Magnusson, Patrik K E; Maier, Wolfgang; Malhotra, Anil K; Mattheisen, Manuel; Mattingsdal, Morten; McCarroll, Steven A; Medeiros, Helena; Melle, Ingrid; Milanova, Vihra; Myin-Germeys, Inez; Neale, Benjamin M; Ophoff, Roel A; Owen, Michael J; Pimm, Jonathan; Purcell, Shaun M; Puri, Vinay; Quested, Digby J; Rossin, Lizzy; Ruderfer, Douglas; Sanders, Alan R; Shi, Jianxin; Sklar, Pamela; St Clair, David; Stroup, T Scott; Van Os, Jim; Visscher, Peter M; Wiersma, Durk; Zammit, Stanley; Bridges, S Louis; Choi, Hyon K; Coenen, Marieke J H; de Vries, Niek; Dieud, Philippe; Greenberg, Jeffrey D; Huizinga, Tom W J; Padyukov, Leonid; Siminovitch, Katherine A; Tak, Paul P; Worthington, Jane; De Jager, Philip L; Denny, Joshua C; Gregersen, Peter K; Klareskog, Lars; Mariette, Xavier; Plenge, Robert M; van Laar, Mart; van Riel, Piet

2015-10-01

A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders. We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born. We estimate a small but significant negative SNP-genetic correlation between SZ and RA (-0.046, s.e. 0.026, P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (-0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P = 0.00090). Our results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context.

Correlated changes in body shape after five generations of selection to improve growth rate in a breeding program for Nile tilapia Oreochromis niloticus in Brazil.

PubMed

de Oliveira, Carlos Antonio Lopes; Ribeiro, Ricardo Pereira; Yoshida, Grazyella Massako; Kunita, Natali Miwa; Rizzato, Gabriel Soriani; de Oliveira, Sheila Nogueira; Dos Santos, Alexandra Inês; Nguyen, Nguyen Hong

2016-11-01

Body shape is a commercial trait of great interest as it impacts profit and productivity of aquaculture enterprises. In the present study, we examined correlated changes in two measures of body shape (depth to length ratio, DL-R and ellipticity of mid sagittal plane, EL-H) from a selection program for high daily weight gain in a Nile tilapia population reared in freshwater cages in Brazil. Genetic parameters for body shape and its genetic association with growth traits (body weight and daily gain) were also estimated from 8,725 individuals with growth performance recorded over five generations from 2008 to 2013. Mixed model analysis showed that the selection program resulted in substantial improvement in growth performance (about 4 % genetic gain per generation or per year) and also brought about trivial changes in body shape. The heritabilities ranged from 0.470 to 0.564 for growth traits and 0.180 to 0.289 for body shape. The common family effects were low for all traits studied, accounting for only 3-11 % of total phenotypic variance. The genetic correlations between body shape and growth traits were weak, i.e., -0.385 between EL-H and growth traits and 0.28 between DL-R and body weight or daily gain. Strong and negative genetic association was found between the two body shape traits (rg = --0.955). Harvest body weight and daily gain are essentially the same traits, as indicated by the close to one genetic correlations between the two characters. Our results demonstrated that the selection process to increase growth rate had small, but slowly constant effect in body shape traits; and in the long term, the fish would have become rotund.

New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis

PubMed Central

Lee, S Hong; Byrne, Enda M; Hultman, Christina M; Kähler, Anna; Vinkhuyzen, Anna AE; Ripke, Stephan; Andreassen, Ole A; Frisell, Thomas; Gusev, Alexander; Hu, Xinli; Karlsson, Robert; Mantzioris, Vasilis X; McGrath, John J; Mehta, Divya; Stahl, Eli A; Zhao, Qiongyi; Kendler, Kenneth S; Sullivan, Patrick F; Price, Alkes L; O’Donovan, Michael; Okada, Yukinori; Mowry, Bryan J; Raychaudhuri, Soumya; Wray, Naomi R; Byerley, William; Cahn, Wiepke; Cantor, Rita M; Cichon, Sven; Cormican, Paul; Curtis, David; Djurovic, Srdjan; Escott-Price, Valentina; Gejman, Pablo V; Georgieva, Lyudmila; Giegling, Ina; Hansen, Thomas F; Ingason, Andrés; Kim, Yunjung; Konte, Bettina; Lee, Phil H; McIntosh, Andrew; McQuillin, Andrew; Morris, Derek W; Nöthen, Markus M; O’Dushlaine, Colm; Olincy, Ann; Olsen, Line; Pato, Carlos N; Pato, Michele T; Pickard, Benjamin S; Posthuma, Danielle; Rasmussen, Henrik B; Rietschel, Marcella; Rujescu, Dan; Schulze, Thomas G; Silverman, Jeremy M; Thirumalai, Srinivasa; Werge, Thomas; Agartz, Ingrid; Amin, Farooq; Azevedo, Maria H; Bass, Nicholas; Black, Donald W; Blackwood, Douglas H R; Bruggeman, Richard; Buccola, Nancy G; Choudhury, Khalid; Cloninger, Robert C; Corvin, Aiden; Craddock, Nicholas; Daly, Mark J; Datta, Susmita; Donohoe, Gary J; Duan, Jubao; Dudbridge, Frank; Fanous, Ayman; Freedman, Robert; Freimer, Nelson B; Friedl, Marion; Gill, Michael; Gurling, Hugh; De Haan, Lieuwe; Hamshere, Marian L; Hartmann, Annette M; Holmans, Peter A; Kahn, René S; Keller, Matthew C; Kenny, Elaine; Kirov, George K; Krabbendam, Lydia; Krasucki, Robert; Lawrence, Jacob; Lencz, Todd; Levinson, Douglas F; Lieberman, Jeffrey A; Lin, Dan-Yu; Linszen, Don H; Magnusson, Patrik KE; Maier, Wolfgang; Malhotra, Anil K; Mattheisen, Manuel; Mattingsdal, Morten; McCarroll, Steven A; Medeiros, Helena; Melle, Ingrid; Milanova, Vihra; Myin-Germeys, Inez; Neale, Benjamin M; Ophoff, Roel A; Owen, Michael J; Pimm, Jonathan; Purcell, Shaun M; Puri, Vinay; Quested, Digby J; Rossin, Lizzy; Ruderfer, Douglas; Sanders, Alan R; Shi, Jianxin; Sklar, Pamela; St. Clair, David; Stroup, T Scott; Van Os, Jim; Visscher, Peter M; Wiersma, Durk; Zammit, Stanley; Bridges, S Louis; Choi, Hyon K; Coenen, Marieke JH; de Vries, Niek; Dieud, Philippe; Greenberg, Jeffrey D; Huizinga, Tom WJ; Padyukov, Leonid; Siminovitch, Katherine A; Tak, Paul P; Worthington, Jane; De Jager, Philip L; Denny, Joshua C; Gregersen, Peter K; Klareskog, Lars; Mariette, Xavier; Plenge, Robert M; van Laar, Mart; van Riel, Piet

2015-01-01

Background: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders. Methods: We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born. Results: We estimate a small but significant negative SNP-genetic correlation between SZ and RA (−0.046, s.e. 0.026, P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (−0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P  = 0.00090). Conclusions: Our results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context. PMID:26286434

Familial aggregation and linkage analysis with covariates for metabolic syndrome risk factors.

PubMed

Naseri, Parisa; Khodakarim, Soheila; Guity, Kamran; Daneshpour, Maryam S

2018-06-15

Mechanisms of metabolic syndrome (MetS) causation are complex, genetic and environmental factors are important factors for the pathogenesis of MetS In this study, we aimed to evaluate familial and genetic influences on metabolic syndrome risk factor and also assess association between FTO (rs1558902 and rs7202116) and CETP(rs1864163) genes' single nucleotide polymorphisms (SNP) with low HDL_C in the Tehran Lipid and Glucose Study (TLGS). The design was a cross-sectional study of 1776 members of 227 randomly-ascertained families. Selected families contained at least one affected metabolic syndrome and at least two members of the family had suffered a loss of HDL_C according to ATP III criteria. In this study, after confirming the familial aggregation with intra-trait correlation coefficients (ICC) of Metabolic syndrome (MetS) and the quantitative lipid traits, the genetic linkage analysis of HDL_C was performed using conditional logistic method with adjusted sex and age. The results of the aggregation analysis revealed a higher correlation between siblings than between parent-offspring pairs representing the role of genetic factors in MetS. In addition, the conditional logistic model with covariates showed that the linkage results between HDL_C and three marker, rs1558902, rs7202116 and rs1864163 were significant. In summary, a high risk of MetS was found in siblings confirming the genetic influences of metabolic syndrome risk factor. Moreover, the power to detect linkage increases in the one parameter conditional logistic model regarding the use of age and sex as covariates. Copyright © 2018. Published by Elsevier B.V.

Analysis of HIV-1 intersubtype recombination breakpoints suggests region with high pairing probability may be a more fundamental factor than sequence similarity affecting HIV-1 recombination.

PubMed

Jia, Lei; Li, Lin; Gui, Tao; Liu, Siyang; Li, Hanping; Han, Jingwan; Guo, Wei; Liu, Yongjian; Li, Jingyun

2016-09-21

With increasing data on HIV-1, a more relevant molecular model describing mechanism details of HIV-1 genetic recombination usually requires upgrades. Currently an incomplete structural understanding of the copy choice mechanism along with several other issues in the field that lack elucidation led us to perform an analysis of the correlation between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarity to further explore structural mechanisms. Near full length sequences of URFs from Asia, Europe, and Africa (one sequence/patient), and representative sequences of worldwide CRFs were retrieved from the Los Alamos HIV database. Their recombination patterns were analyzed by jpHMM in detail. Then the relationships between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarities were investigated. Pearson correlation test showed that all URF groups and the CRF group exhibit the same breakpoint distribution pattern. Additionally, the Wilcoxon two-sample test indicated a significant and inexplicable limitation of recombination in regions with high pairing probability. These regions have been found to be strongly conserved across distinct biological states (i.e., strong intersubtype similarity), and genetic similarity has been determined to be a very important factor promoting recombination. Thus, the results revealed an unexpected disagreement between intersubtype similarity and breakpoint distribution, which were further confirmed by genetic similarity analysis. Our analysis reveals a critical conflict between results from natural HIV-1 isolates and those from HIV-1-based assay vectors in which genetic similarity has been shown to be a very critical factor promoting recombination. These results indicate the region with high-pairing probabilities may be a more fundamental factor affecting HIV-1 recombination than sequence similarity in natural HIV-1 infections. Our findings will be relevant in furthering the understanding of HIV-1 recombination mechanisms.

Quantitative maps of genetic interactions in yeast - comparative evaluation and integrative analysis.

PubMed

Lindén, Rolf O; Eronen, Ville-Pekka; Aittokallio, Tero

2011-03-24

High-throughput genetic screening approaches have enabled systematic means to study how interactions among gene mutations contribute to quantitative fitness phenotypes, with the aim of providing insights into the functional wiring diagrams of genetic interaction networks on a global scale. However, it is poorly known how well these quantitative interaction measurements agree across the screening approaches, which hinders their integrated use toward improving the coverage and quality of the genetic interaction maps in yeast and other organisms. Using large-scale data matrices from epistatic miniarray profiling (E-MAP), genetic interaction mapping (GIM), and synthetic genetic array (SGA) approaches, we carried out here a systematic comparative evaluation among these quantitative maps of genetic interactions in yeast. The relatively low association between the original interaction measurements or their customized scores could be improved using a matrix-based modelling framework, which enables the use of single- and double-mutant fitness estimates and measurements, respectively, when scoring genetic interactions. Toward an integrative analysis, we show how the detections from the different screening approaches can be combined to suggest novel positive and negative interactions which are complementary to those obtained using any single screening approach alone. The matrix approximation procedure has been made available to support the design and analysis of the future screening studies. We have shown here that even if the correlation between the currently available quantitative genetic interaction maps in yeast is relatively low, their comparability can be improved by means of our computational matrix approximation procedure, which will enable integrative analysis and detection of a wider spectrum of genetic interactions using data from the complementary screening approaches.

Path analysis of the genetic integration of traits in the sand cricket: a novel use of BLUPs.

PubMed

Roff, D A; Fairbairn, D J

2011-09-01

This study combines path analysis with quantitative genetics to analyse a key life history trade-off in the cricket, Gryllus firmus. We develop a path model connecting five traits associated with the trade-off between flight capability and reproduction and test this model using phenotypic data and estimates of breeding values (best linear unbiased predictors) from a half-sibling experiment. Strong support by both types of data validates our causal model and indicates concordance between the phenotypic and genetic expression of the trade-off. Comparisons of the trade-off between sexes and wing morphs reveal that these discrete phenotypes are not genetically independent and that the evolutionary trajectories of the two wing morphs are more tightly constrained to covary than those of the two sexes. Our results illustrate the benefits of combining a quantitative genetic analysis, which examines statistical correlations between traits, with a path model that focuses upon the causal components of variation. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

Genome-wide association analysis of secondary imaging phenotypes from the Alzheimer's disease neuroimaging initiative study.

PubMed

Zhu, Wensheng; Yuan, Ying; Zhang, Jingwen; Zhou, Fan; Knickmeyer, Rebecca C; Zhu, Hongtu

2017-02-01

The aim of this paper is to systematically evaluate a biased sampling issue associated with genome-wide association analysis (GWAS) of imaging phenotypes for most imaging genetic studies, including the Alzheimer's Disease Neuroimaging Initiative (ADNI). Specifically, the original sampling scheme of these imaging genetic studies is primarily the retrospective case-control design, whereas most existing statistical analyses of these studies ignore such sampling scheme by directly correlating imaging phenotypes (called the secondary traits) with genotype. Although it has been well documented in genetic epidemiology that ignoring the case-control sampling scheme can produce highly biased estimates, and subsequently lead to misleading results and suspicious associations, such findings are not well documented in imaging genetics. We use extensive simulations and a large-scale imaging genetic data analysis of the Alzheimer's Disease Neuroimaging Initiative (ADNI) data to evaluate the effects of the case-control sampling scheme on GWAS results based on some standard statistical methods, such as linear regression methods, while comparing it with several advanced statistical methods that appropriately adjust for the case-control sampling scheme. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessing genetic divergence in interspecific hybrids of Aechmea gomosepala and A. recurvata var. recurvata using inflorescence characteristics and sequence-related amplified polymorphism markers.

PubMed

Zhang, F; Ge, Y Y; Wang, W Y; Shen, X L; Yu, X Y

2012-12-03

Conventional hybridization and selection techniques have aided the development of new ornamental crop cultivars. However, little information is available on the genetic divergence of bromeliad hybrids. In the present study, we investigated the genetic variability in interspecific hybrids of Aechmea gomosepala and A. recurvata var. recurvata using inflorescence characteristics and sequence-related amplified polymorphism (SRAP) markers. The morphological analysis showed that the putative hybrids were intermediate between both parental species with respect to inflorescence characteristics. The 16 SRAP primer combinations yield 265 bands, among which 154 (57.72%) were polymorphic. The genetic similarity was an average of 0.59 and ranged from 0.21 to 0.87, indicating moderate genetic divergence among the hybrids. The unweighted pair group method with arithmetic average (UPGMA)-based cluster analysis distinguished the hybrids from their parents with a genetic distance coefficient of 0.54. The cophenetic correlation was 0.93, indicating a good fit between the dendrogram and the original distance matrix. The two-dimensional plot from the principal coordinate analysis showed that the hybrids were intermediately dispersed between both parents, corresponding to the results of the UPGMA cluster and the morphological analysis. These results suggest that SRAP markers could help to identify breeders, characterize F(1) hybrids of bromeliads at an early stage, and expedite genetic improvement of bromeliad cultivars.

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

PubMed

Savage, Jeanne E; Jansen, Philip R; Stringer, Sven; Watanabe, Kyoko; Bryois, Julien; de Leeuw, Christiaan A; Nagel, Mats; Awasthi, Swapnil; Barr, Peter B; Coleman, Jonathan R I; Grasby, Katrina L; Hammerschlag, Anke R; Kaminski, Jakob A; Karlsson, Robert; Krapohl, Eva; Lam, Max; Nygaard, Marianne; Reynolds, Chandra A; Trampush, Joey W; Young, Hannah; Zabaneh, Delilah; Hägg, Sara; Hansell, Narelle K; Karlsson, Ida K; Linnarsson, Sten; Montgomery, Grant W; Muñoz-Manchado, Ana B; Quinlan, Erin B; Schumann, Gunter; Skene, Nathan G; Webb, Bradley T; White, Tonya; Arking, Dan E; Avramopoulos, Dimitrios; Bilder, Robert M; Bitsios, Panos; Burdick, Katherine E; Cannon, Tyrone D; Chiba-Falek, Ornit; Christoforou, Andrea; Cirulli, Elizabeth T; Congdon, Eliza; Corvin, Aiden; Davies, Gail; Deary, Ian J; DeRosse, Pamela; Dickinson, Dwight; Djurovic, Srdjan; Donohoe, Gary; Conley, Emily Drabant; Eriksson, Johan G; Espeseth, Thomas; Freimer, Nelson A; Giakoumaki, Stella; Giegling, Ina; Gill, Michael; Glahn, David C; Hariri, Ahmad R; Hatzimanolis, Alex; Keller, Matthew C; Knowles, Emma; Koltai, Deborah; Konte, Bettina; Lahti, Jari; Le Hellard, Stephanie; Lencz, Todd; Liewald, David C; London, Edythe; Lundervold, Astri J; Malhotra, Anil K; Melle, Ingrid; Morris, Derek; Need, Anna C; Ollier, William; Palotie, Aarno; Payton, Antony; Pendleton, Neil; Poldrack, Russell A; Räikkönen, Katri; Reinvang, Ivar; Roussos, Panos; Rujescu, Dan; Sabb, Fred W; Scult, Matthew A; Smeland, Olav B; Smyrnis, Nikolaos; Starr, John M; Steen, Vidar M; Stefanis, Nikos C; Straub, Richard E; Sundet, Kjetil; Tiemeier, Henning; Voineskos, Aristotle N; Weinberger, Daniel R; Widen, Elisabeth; Yu, Jin; Abecasis, Goncalo; Andreassen, Ole A; Breen, Gerome; Christiansen, Lene; Debrabant, Birgit; Dick, Danielle M; Heinz, Andreas; Hjerling-Leffler, Jens; Ikram, M Arfan; Kendler, Kenneth S; Martin, Nicholas G; Medland, Sarah E; Pedersen, Nancy L; Plomin, Robert; Polderman, Tinca J C; Ripke, Stephan; van der Sluis, Sophie; Sullivan, Patrick F; Vrieze, Scott I; Wright, Margaret J; Posthuma, Danielle

2018-06-25

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

The nature of schizotypy among multigenerational multiplex schizophrenia families

PubMed Central

Tarbox, Sarah I.; Almasy, Laura; Gur, Raquel E.; Nimgaonkar, Vishwajit L.; Pogue-Geile, Michael F.

2012-01-01

Identification of endophenotypes (Gottesman & Gould, 2003; Gottesman & Shields, 1972) that genetically correlate with schizophrenia and are genetically homogeneous is an important strategy for detecting genes that affect schizophrenia risk. Symptoms of schizotypy may familially correlate with schizophrenia; however, there are critical limitations of the current literature concerning this association. The present study examined the genetic architecture and genetic associations between schizotypy and schizophrenia among multigenerational, multiplex schizophrenia families. Genetic schizotypy factor scales were developed that genetically correlated with schizophrenia, although some relations were unexpected in direction suggesting minimization of “psychotic-like” symptoms. These genetic schizotypy factor scales did not genetically correlate with major depressive disorder or substance dependence indicating specificity to schizophrenia. The results highlight the possibility of significant response bias in schizophrenia families, particularly among close relatives, and suggest an important consideration when acquiring self-report information. This is a topic that deserves future study as the origins of this putative bias in relatives are unclear. In addition, the results support the identification of genetic schizotypy factors as a promising technique for maximizing genetic correlation of endophenotypes with schizophrenia. PMID:22288909

Shared genetic determinants of axial length and height in children: the Guangzhou twin eye study.

PubMed

Zhang, Jian; Hur, Yoon-Mi; Huang, Wenyong; Ding, Xiaohu; Feng, Ke; He, Mingguang

2011-01-01

To describe the association between axial length (AL) and height and to estimate the extent to which shared genetic or environmental factors influence this covariance. Study participants were recruited from the Guangzhou Twin Registry. Axial length was measured using partial coherence laser interferometry. Height was measured with the participants standing without shoes. We computed twin pairwise correlations and cross-twin cross-trait correlations between AL and height for monozygotic and dizygotic twins and performed model-fitting analyses using a multivariate Cholesky model. The right eye was arbitrarily selected to represent AL of participants. Five hundred sixty-five twin pairs (359 monozygotic and 206 dizygotic) aged 7 to 15 years were available for analysis. Phenotypic correlation between AL and height was 0.46 but decreased to 0.19 after adjusting for age, sex, and age × sex interaction. Bivariate Cholesky model-fitting analyses revealed that 89% of phenotypic correlation was due to shared genetic factors and 11% was due to shared random environmental factors, which includes measurement error. Covariance of AL and height is largely attributable to shared genes. Given that AL is a key determinant of myopia, further work is needed to confirm gene sharing between myopia and stature.

Genetic correlations between body weight change and reproduction traits in Merino ewes depend on age.

PubMed

Rose, G; Mulder, H A; van der Werf, J H J; Thompson, A N; van Arendonk, J A M

2014-08-01

Merino sheep in Australia experience periods of variable feed supply. Merino sheep can be bred to be more resilient to this variation by losing less BW when grazing poor quality pasture and gaining more BW when grazing good quality pasture. Therefore, selection on BW change might be economically attractive but correlations with other traits in the breeding objective need to be known. The genetic correlations (rg) between BW, BW change, and reproduction were estimated using records from approximately 7,350 fully pedigreed Merino ewes managed at Katanning in Western Australia. Number of lambs and total weight of lambs born and weaned were measured on approximately 5,300 2-yr-old ewes, approximately 4,900 3-yr-old ewes, and approximately 3,600 4-yr-old ewes. On a proportion of these ewes BW change was measured: approximately 1,950 2-yr-old ewes, approximately 1,500 3-yr-old ewes, and approximately 1,100 4-yr-old ewes. The BW measurements were for 3 periods. The first period was during mating period over 42 d on poor pasture. The second period was during pregnancy over 90 d for ewes that got pregnant on poor and medium quality pasture. The third period was during lactation over 130 d for ewes that weaned a lamb on good quality pasture. Genetic correlations between weight change and reproduction were estimated within age classes. Genetic correlations were tested to be significantly greater magnitude than 0 using likelihood ratio tests. Nearly all BW had significant positive genetic correlations with all reproduction traits. In 2-yr-old ewes, BW change during the mating period had a positive genetic correlation with number of lambs weaned (rg = 0.58); BW change during pregnancy had a positive genetic correlation with total weight of lambs born (rg = 0.33) and a negative genetic correlation with number of lambs weaned (rg = -0.49). All other genetic correlations were not significantly greater magnitude than 0 but estimates of genetic correlations for 3-yr-old ewes were generally consistent with these findings. The direction of the genetic correlations mostly coincided with the energy requirements of the ewes and the stage of maturity of the ewes. In conclusion, optimized selection strategies on BW changes to increase resilience will depend on the genetic correlations with reproduction and are dependent on age.

Laboratory Estimates of Heritabilities and Genetic Correlations in Nature

PubMed Central

Riska, B.; Prout, T.; Turelli, M.

1989-01-01

A lower bound on heritability in a natural environment can be determined from the regression of offspring raised in the laboratory on parents raised in nature. An estimate of additive genetic variance in the laboratory is also required. The estimated lower bounds on heritabilities can sometimes be used to demonstrate a significant genetic correlation between two traits in nature, if their genetic and phenotypic correlations in nature have the same sign, and if sample sizes are large, and heritabilities and phenotypic and genetic correlations are high. PMID:2515111

Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis.

PubMed

van Hulzen, Kimm J E; Scholz, Claus J; Franke, Barbara; Ripke, Stephan; Klein, Marieke; McQuillin, Andrew; Sonuga-Barke, Edmund J; Kelsoe, John R; Landén, Mikael; Andreassen, Ole A; Lesch, Klaus-Peter; Weber, Heike; Faraone, Stephen V; Arias-Vasquez, Alejandro; Reif, Andreas

2017-11-01

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently co-occurring and highly heritable mental health conditions. We hypothesized that BPD cases with an early age of onset (≤21 years old) would be particularly likely to show genetic covariation with ADHD. Genome-wide association study data were available for 4609 individuals with ADHD, 9650 individuals with BPD (5167 thereof with early-onset BPD), and 21,363 typically developing controls. We conducted a cross-disorder genome-wide association study meta-analysis to identify whether the observed comorbidity between ADHD and BPD could be due to shared genetic risks. We found a significant single nucleotide polymorphism-based genetic correlation between ADHD and BPD in the full and age-restricted samples (r Gfull = .64, p = 3.13 × 10 -14 ; r Grestricted = .71, p = 4.09 × 10 -16 ). The meta-analysis between the full BPD sample identified two genome-wide significant (p rs7089973 = 2.47 × 10 -8 ; p rs11756438 = 4.36 × 10 -8 ) regions located on chromosomes 6 (CEP85L) and 10 (TAF9BP2). Restricting the analyses to BPD cases with an early onset yielded one genome-wide significant association (p rs58502974 = 2.11 × 10 -8 ) on chromosome 5 in the ADCY2 gene. Additional nominally significant regions identified contained known expression quantitative trait loci with putative functional consequences for NT5DC1, NT5DC2, and CACNB3 expression, whereas functional predictions implicated ABLIM1 as an allele-specific expressed gene in neuronal tissue. The single nucleotide polymorphism-based genetic correlation between ADHD and BPD is substantial, significant, and consistent with the existence of genetic overlap between ADHD and BPD, with potential differential genetic mechanisms involved in early and later BPD onset. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Radiogenomics to characterize regional genetic heterogeneity in glioblastoma.

PubMed

Hu, Leland S; Ning, Shuluo; Eschbacher, Jennifer M; Baxter, Leslie C; Gaw, Nathan; Ranjbar, Sara; Plasencia, Jonathan; Dueck, Amylou C; Peng, Sen; Smith, Kris A; Nakaji, Peter; Karis, John P; Quarles, C Chad; Wu, Teresa; Loftus, Joseph C; Jenkins, Robert B; Sicotte, Hugues; Kollmeyer, Thomas M; O'Neill, Brian P; Elmquist, William; Hoxworth, Joseph M; Frakes, David; Sarkaria, Jann; Swanson, Kristin R; Tran, Nhan L; Li, Jing; Mitchell, J Ross

2017-01-01

Glioblastoma (GBM) exhibits profound intratumoral genetic heterogeneity. Each tumor comprises multiple genetically distinct clonal populations with different therapeutic sensitivities. This has implications for targeted therapy and genetically informed paradigms. Contrast-enhanced (CE)-MRI and conventional sampling techniques have failed to resolve this heterogeneity, particularly for nonenhancing tumor populations. This study explores the feasibility of using multiparametric MRI and texture analysis to characterize regional genetic heterogeneity throughout MRI-enhancing and nonenhancing tumor segments. We collected multiple image-guided biopsies from primary GBM patients throughout regions of enhancement (ENH) and nonenhancing parenchyma (so called brain-around-tumor, [BAT]). For each biopsy, we analyzed DNA copy number variants for core GBM driver genes reported by The Cancer Genome Atlas. We co-registered biopsy locations with MRI and texture maps to correlate regional genetic status with spatially matched imaging measurements. We also built multivariate predictive decision-tree models for each GBM driver gene and validated accuracies using leave-one-out-cross-validation (LOOCV). We collected 48 biopsies (13 tumors) and identified significant imaging correlations (univariate analysis) for 6 driver genes: EGFR, PDGFRA, PTEN, CDKN2A, RB1, and TP53. Predictive model accuracies (on LOOCV) varied by driver gene of interest. Highest accuracies were observed for PDGFRA (77.1%), EGFR (75%), CDKN2A (87.5%), and RB1 (87.5%), while lowest accuracy was observed in TP53 (37.5%). Models for 4 driver genes (EGFR, RB1, CDKN2A, and PTEN) showed higher accuracy in BAT samples (n = 16) compared with those from ENH segments (n = 32). MRI and texture analysis can help characterize regional genetic heterogeneity, which offers potential diagnostic value under the paradigm of individualized oncology. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Inheritance of Vertebral Number in the Three-Spined Stickleback (Gasterosteus aculeatus)

PubMed Central

Alho, Jussi S.; Leinonen, Tuomas; Merilä, Juha

2011-01-01

Intraspecific variation in the number of vertebrae is taxonomically widespread, and both genetic and environmental factors are known to contribute to this variation. However, the relative importance of genetic versus environmental influences on variation in vertebral number has seldom been investigated with study designs that minimize bias due to non-additive genetic and maternal influences. We used a paternal half-sib design and animal model analysis to estimate heritability and causal components of variance in vertebral number in three-spined sticklebacks (Gasterosteus aculeatus). We found that both the number of vertebrae (h2 = 0.36) and body size (h2 = 0.42) were moderately heritable, whereas the influence of maternal effects was estimated to be negligible. While the number of vertebrae had a positive effect on body size, no evidence for a genetic correlation between body size and vertebral number was detected. However, there was a significant positive environmental correlation between these two traits. Our results support the generalization-in accordance with results from a review of heritability estimates for vertebral number in fish, reptiles and mammals-that the number of vertebrae appears to be moderately to highly heritable in a wide array of species. In the case of the three-spined stickleback, independent evolution of body size and number of vertebrae should be possible given the low genetic correlation between the two traits. PMID:21603609

Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme

PubMed Central

Heiland, Dieter Henrik; Mader, Irina; Schlosser, Pascal; Pfeifer, Dietmar; Carro, Maria Stella; Lange, Thomas; Schwarzwald, Ralf; Vasilikos, Ioannis; Urbach, Horst; Weyerbrock, Astrid

2016-01-01

The goal of this study was to identify correlations between metabolites from proton MR spectroscopy and genetic pathway activity in glioblastoma multiforme (GBM). Twenty patients with primary GBM were analysed by short echo-time chemical shift imaging and genome-wide expression analyses. Weighed Gene Co-Expression Analysis was used for an integrative analysis of imaging and genetic data. N-acetylaspartate, normalised to the contralateral healthy side (nNAA), was significantly correlated to oligodendrocytic and neural development. For normalised creatine (nCr), a group with low nCr was linked to the mesenchymal subtype, while high nCr could be assigned to the proneural subtype. Moreover, clustering of normalised glutamine and glutamate (nGlx) revealed two groups, one with high nGlx being attributed to the neural subtype, and one with low nGlx associated with the classical subtype. Hence, the metabolites nNAA, nCr, and nGlx correlate with a specific gene expression pattern reflecting the previously described subtypes of GBM. Moreover high nNAA was associated with better clinical prognosis, whereas patients with lower nNAA revealed a shorter progression-free survival (PFS). PMID:27350391

Common genetic variants explain the majority of the correlation between height and intelligence: the generation Scotland study.

PubMed

Marioni, Riccardo E; Batty, G David; Hayward, Caroline; Kerr, Shona M; Campbell, Archie; Hocking, Lynne J; Porteous, David J; Visscher, Peter M; Deary, Ian J

2014-03-01

Greater height and higher intelligence test scores are predictors of better health outcomes. Here, we used molecular (single-nucleotide polymorphism) data to estimate the genetic correlation between height and general intelligence (g) in 6,815 unrelated subjects (median age 57, IQR 49-63) from the Generation Scotland: Scottish Family Health Study cohort. The phenotypic correlation between height and g was 0.16 (SE 0.01). The genetic correlation between height and g was 0.28 (SE 0.09) with a bivariate heritability estimate of 0.71. Understanding the molecular basis of the correlation between height and intelligence may help explain any shared role in determining health outcomes. This study identified a modest genetic correlation between height and intelligence with the majority of the phenotypic correlation being explained by shared genetic influences.

A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Paediatric Cohorts

PubMed Central

Groen-Blokhuis, Maria M.; Pourcain, Beate St.; Greven, Corina U.; Pappa, Irene; Tiesler, Carla M.T.; Ang, Wei; Nolte, Ilja M.; Vilor-Tejedor, Natalia; Bacelis, Jonas; Ebejer, Jane L.; Zhao, Huiying; Davies, Gareth E.; Ehli, Erik A.; Evans, David M.; Fedko, Iryna O.; Guxens, Mònica; Hottenga, Jouke-Jan; Hudziak, James J.; Jugessur, Astanand; Kemp, John P.; Krapohl, Eva; Martin, Nicholas G.; Murcia, Mario; Myhre, Ronny; Ormel, Johan; Ring, Susan M.; Standl, Marie; Stergiakouli, Evie; Stoltenberg, Camilla; Thiering, Elisabeth; Timpson, Nicholas J.; Trzaskowski, Maciej; van der Most, Peter J.; Wang, Carol; Nyholt, Dale R.; Medland, Sarah E.; Neale, Benjamin; Jacobsson, Bo; Sunyer, Jordi; Hartman, Catharina A.; Whitehouse, Andrew J.O.; Pennell, Craig E.; Heinrich, Joachim; Plomin, Robert; Smith, George Davey; Tiemeier, Henning; Posthuma, Danielle; Boomsma, Dorret I.

2016-01-01

Objective To elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (< 13 years) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46×10-6 and 2.66×10-6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and improve statistical power for identifying genetic variants. PMID:27663945

Genetic and environmental influences on female sexual orientation, childhood gender typicality and adult gender identity.

PubMed

Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

2011-01-01

Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates--childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation.

Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours.

PubMed

Treur, Jorien L; Gibson, Mark; Taylor, Amy E; Rogers, Peter J; Munafò, Marcus R

2018-04-22

Observationally, higher caffeine consumption is associated with poorer sleep and insomnia. We investigated whether these associations are a result of shared genetic risk factors and/or (possibly bidirectional) causal effects. Summary-level data were available from genome-wide association studies on caffeine intake (n = 91 462), plasma caffeine and caffeine metabolic rate (n = 9876), sleep duration and chronotype (being a "morning" versus an "evening" person) (n = 128 266), and insomnia complaints (n = 113 006). First, genetic correlations were calculated, reflecting the extent to which genetic variants influencing caffeine consumption and those influencing sleep overlap. Next, causal effects were estimated with bidirectional, two-sample Mendelian randomization. This approach utilizes the genetic variants most robustly associated with an exposure variable as an "instrument" to test causal effects. Estimates from individual variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR-Egger regression. We found no clear evidence for a genetic correlation between caffeine intake and sleep duration (rg = 0.000, p = .998), chronotype (rg = 0.086, p = .192) or insomnia complaints (rg = -0.034, p = .700). For plasma caffeine and caffeine metabolic rate, genetic correlations could not be calculated because of the small sample size. Mendelian randomization did not support causal effects of caffeine intake on sleep, or vice versa. There was weak evidence that higher plasma caffeine levels causally decrease the odds of being a morning person. Although caffeine may acutely affect sleep when taken shortly before bedtime, our findings suggest that a sustained pattern of high caffeine consumption is more likely to be associated with poorer sleep through shared environmental factors. Future research should identify such environments, which could aid the development of interventions to improve sleep. © 2018 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

A meta-analysis of heritability of cognitive aging: minding the "missing heritability" gap.

PubMed

Reynolds, Chandra A; Finkel, Deborah

2015-03-01

The etiologies underlying variation in adult cognitive performance and cognitive aging have enjoyed much attention in the literature, but much of that attention has focused on broad factors, principally general cognitive ability. The current review provides meta-analyses of age trends in heritability of specific cognitive abilities and considers the profile of genetic and environmental factors contributing to cognitive aging to address the 'missing heritability' issue. Our findings, based upon evaluating 27 reports in the literature, indicate that verbal ability demonstrated declining heritability, after about age 60, as did spatial ability and perceptual speed more modestly. Trends for general memory, working memory, and spatial ability generally indicated stability, or small increases in heritability in mid-life. Equivocal results were found for executive function. A second meta-analysis then considered the gap between twin-based versus SNP-based heritability derived from population-based GWAS studies. Specifically, we considered twin correlation ratios to agnostically re-evaluate biometrical models across age and by cognitive domain. Results modestly suggest that nonadditive genetic variance may become increasingly important with age, especially for verbal ability. If so, this would support arguments that lower SNP-based heritability estimates result in part from uncaptured non-additive influences (e.g., dominance, gene-gene interactions), and possibly gene-environment (GE) correlations. Moreover, consistent with longitudinal twin studies of aging, as rearing environment becomes a distal factor, increasing genetic variance may result in part from nonadditive genetic influences or possible GE correlations. Sensitivity to life course dynamics is crucial to understanding etiological contributions to adult cognitive performance and cognitive aging.

Genetic and non-genetic correlates of vitamins K and D.

PubMed

Shea, M K; Benjamin, E J; Dupuis, J; Massaro, J M; Jacques, P F; D'Agostino, R B; Ordovas, J M; O'Donnell, C J; Dawson-Hughes, B; Vasan, R S; Booth, S L

2009-04-01

To assess the genetic and nongenetic correlates of circulating measures of vitamins K and D status in a community-based sample of men and women. A cross-sectional study of 1762 participants of the Framingham Offspring Study (919 women; mean age 59 years). Vitamin K status was measured as plasma phylloquinone and serum percent undercarboxylated osteocalcin (ucOC), and vitamin D was measured using plasma 25-hydroxyvitamin D (25(OH)D). Associations between vitamin K status and vitamin D status with biologically plausible nongenetic factors were assessed using stepwise regression. Heritability and linkage were determined using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Nongenetic factors accounted for 20.1 and 12.3% of the variability in plasma phylloquinone in men and women respectively, with triglycerides and phylloquinone intake being the primary correlates. In men 12.2% and in women 14.6% of the variability in %ucOC was explained by nongenetic factors in our models. Heritability estimates for these vitamin K status biomarkers were nonsignificant. Season, vitamin D intake, high-density lipoprotein (HDL) cholesterol and waist circumference explained 24.7% (men) and 24.2% (women) of the variability in plasma 25(OH)D. Of the three vitamins examined, only 25(OH)D was significantly heritable (heritability estimate=28.8%, P<0.01), but linkage analysis of 25(OH)D did not achieve genome-wide significance. Variability in biomarkers of vitamin K status was attributed to nongenetic factors, whereas plasma 25(OH)D was found to be significantly heritable. Further studies are warranted to investigate genetic loci influencing vitamin D status.

Genetic influences on the cognitive biases associated with anxiety and depression symptoms in adolescents.

PubMed

Zavos, Helena M S; Rijsdijk, Frühling V; Gregory, Alice M; Eley, Thalia C

2010-07-01

There is a substantial overlap between genes affecting anxiety and depression. Both anxiety and depression are associated with cognitive biases such as anxiety sensitivity and attributional style. Little, however, is known about the relationship between these variables and whether these too are genetically correlated. Self-reports of anxiety sensitivity, anxiety symptoms, attributional style and depression symptoms were obtained for over 1300 adolescent twin and sibling pairs at two time points. The magnitude of genetic and environmental influences on the measures was examined. Strongest associations were found between anxiety sensitivity and anxiety ratings at both measurement times (r=.70, .72) and between anxiety and depression (r=.62 at both time points). Correlations between the cognitive biases were modest at time 1 (r=-.12) and slightly larger at time 2 (r=-.31). All measures showed moderate genetic influence. Generally genetic correlations reflected phenotypic correlations. Thus the highest genetic correlations were between anxiety sensitivity and anxiety ratings (.86, .87) and between anxiety and depression ratings (.77, .71). Interestingly, depression ratings also showed a high genetic correlation with anxiety sensitivity (.70, .76). Genetic correlations between the cognitive bias measures were moderate (-.31, -.46). The sample consists primarily of twins, there are limitations associated with the twin design. Cognitive biases associated with depression and anxiety are not as genetically correlated as anxiety and depression ratings themselves. Further research into the cognitive processes related to anxiety and depression will facilitate understanding of the relationship between bias and symptoms.

Interspecific analysis of covariance structure in the masticatory apparatus of galagos.

PubMed

Vinyard, Christopher J

2007-01-01

The primate masticatory apparatus (MA) is a functionally integrated set of features, each of which performs important functions in biting, ingestive, and chewing behaviors. A comparison of morphological covariance structure among species for these MA features will help us to further understand the evolutionary history of this region. In this exploratory analysis, the covariance structure of the MA is compared across seven galago species to investigate 1) whether there are differences in covariance structure in this region, and 2) if so, how has this covariation changed with respect to size, MA form, diet, and/or phylogeny? Ten measurements of the MA functionally related to bite force production and load resistance were obtained from 218 adults of seven galago species. Correlation matrices were generated for these 10 dimensions and compared among species via matrix correlations and Mantel tests. Subsequently, pairwise covariance disparity in the MA was estimated as a measure of difference in covariance structure between species. Covariance disparity estimates were correlated with pairwise distances related to differences in body size, MA size and shape, genetic distance (based on cytochrome-b sequences) and percentage of dietary foods to determine whether one or more of these factors is linked to differences in covariance structure. Galagos differ in MA covariance structure. Body size appears to be a major factor correlated with differences in covariance structure among galagos. The largest galago species, Otolemur crassicaudatus, exhibits large differences in body mass and covariance structure relative to other galagos, and thus plays a primary role in creating this association. MA size and shape do not correlate with covariance structure when body mass is held constant. Diet also shows no association. Genetic distance is significantly negatively correlated with covariance disparity when body mass is held constant, but this correlation appears to be a function of the small body size and large genetic distance for Galagoides demidoff. These exploratory results indicate that changing body size may have been a key factor in the evolution of the galago MA.

Advertisement call and genetic structure conservatism: good news for an endangered Neotropical frog

PubMed Central

Costa, William P.; Martins, Lucas B.; Nunes-de-Almeida, Carlos H. L.; Toledo, Luís Felipe

2016-01-01

Background: Many amphibian species are negatively affected by habitat change due to anthropogenic activities. Populations distributed over modified landscapes may be subject to local extinction or may be relegated to the remaining—likely isolated and possibly degraded—patches of available habitat. Isolation without gene flow could lead to variability in phenotypic traits owing to differences in local selective pressures such as environmental structure, microclimate, or site-specific species assemblages. Methods: Here, we tested the microevolution hypothesis by evaluating the acoustic parameters of 349 advertisement calls from 15 males from six populations of the endangered amphibian species Proceratophrys moratoi. In addition, we analyzed the genetic distances among populations and the genetic diversity with a haplotype network analysis. We performed cluster analysis on acoustic data based on the Bray-Curtis index of similarity, using the UPGMA method. We correlated acoustic dissimilarities (calculated by Euclidean distance) with geographical and genetic distances among populations. Results: Spectral traits of the advertisement call of P. moratoi presented lower coefficients of variation than did temporal traits, both within and among males. Cluster analyses placed individuals without congruence in population or geographical distance, but recovered the species topology in relation to sister species. The genetic distance among populations was low; it did not exceed 0.4% for the most distant populations, and was not correlated with acoustic distance. Discussion: Both acoustic features and genetic sequences are highly conserved, suggesting that populations could be connected by recent migrations, and that they are subject to stabilizing selective forces. Although further studies are required, these findings add to a growing body of literature suggesting that this species would be a good candidate for a reintroduction program without negative effects on communication or genetic impact. PMID:27190717

Genetic regulation of the variation of circulating insulin-like growth factors and leptin in human pedigrees.

PubMed

Pantsulaia, Ia; Pantsulaia, I; Trofimov, Svetlana; Kobyliansky, Eugene; Livshits, Gregory

2005-07-01

Recent literature has shown that circulating levels of insulin-like growth factor I (IGF-I) and/or IGF binding proteins (IGF-BPs) may be of importance in the risk assessment of several chronic diseases including cancer, cardiovascular disease, diabetes mellitus and so on. The present study examined the extent of genetic and environmental influences on the populational variation of circulating IGF-I and IGF-BP-1 in apparently healthy and ethnically homogeneous white families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 563 individuals aged 18 to 80 years. Quantitative genetic analysis showed that the IGF-I variation was appreciably attributable to genetic effects (47.1% +/- 9.0%), whereas for IGF-BP-1, only 23.3% +/- 7.8% of the interindividual variation was explained by genetic determinants. Common familial environment factors contributed significantly only to IGF-BP-1 variation (23.3% +/- 7.8%). In addition, we examined the covariations between these molecules and between them and IGF-BP-3 and leptin that were previously studied in the same sample. The analysis revealed that the pleiotropic genetic effects were significant for 2 pairs of traits, namely for IGF-I and IGF-BP-3, and for IGF-BP-1 and leptin. The bivariate heritability estimates were 0.21 +/- 0.04 and 0.15 +/- 0.05. The common environmental factors were consistently a significant source of correlation between all pairs (barring IGF-I and leptin) of the studied molecules; they were the sole predictors of correlation between IGF-I and IGF-BP-1, and between IGF-BP-1 and IGF-BP-3. Our results affirm the existence of specific and common genetic pathways that in combination determine a substantial proportion of the circulating variation of these molecules.

Advertisement call and genetic structure conservatism: good news for an endangered Neotropical frog.

PubMed

Forti, Lucas R; Costa, William P; Martins, Lucas B; Nunes-de-Almeida, Carlos H L; Toledo, Luís Felipe

2016-01-01

Many amphibian species are negatively affected by habitat change due to anthropogenic activities. Populations distributed over modified landscapes may be subject to local extinction or may be relegated to the remaining-likely isolated and possibly degraded-patches of available habitat. Isolation without gene flow could lead to variability in phenotypic traits owing to differences in local selective pressures such as environmental structure, microclimate, or site-specific species assemblages. Here, we tested the microevolution hypothesis by evaluating the acoustic parameters of 349 advertisement calls from 15 males from six populations of the endangered amphibian species Proceratophrys moratoi. In addition, we analyzed the genetic distances among populations and the genetic diversity with a haplotype network analysis. We performed cluster analysis on acoustic data based on the Bray-Curtis index of similarity, using the UPGMA method. We correlated acoustic dissimilarities (calculated by Euclidean distance) with geographical and genetic distances among populations. Spectral traits of the advertisement call of P. moratoi presented lower coefficients of variation than did temporal traits, both within and among males. Cluster analyses placed individuals without congruence in population or geographical distance, but recovered the species topology in relation to sister species. The genetic distance among populations was low; it did not exceed 0.4% for the most distant populations, and was not correlated with acoustic distance. Both acoustic features and genetic sequences are highly conserved, suggesting that populations could be connected by recent migrations, and that they are subject to stabilizing selective forces. Although further studies are required, these findings add to a growing body of literature suggesting that this species would be a good candidate for a reintroduction program without negative effects on communication or genetic impact.

Estimation of test-day model (co)variance components across breeds using New Zealand dairy cattle data.

PubMed

Vanderick, S; Harris, B L; Pryce, J E; Gengler, N

2009-03-01

In New Zealand, a large proportion of cows are currently crossbreds, mostly Holstein-Friesians (HF) x Jersey (JE). The genetic evaluation system for milk yields is considering the same additive genetic effects for all breeds. The objective was to model different additive effects according to parental breeds to obtain first estimates of correlations among breed-specific effects and to study the usefulness of this type of random regression test-day model. Estimates of (co)variance components for purebred HF and JE cattle in purebred herds were computed by using a single-breed model. This analysis showed differences between the 2 breeds, with a greater variability in the HF breed. (Co)variance components for purebred HF and JE and crossbred HF x JE cattle were then estimated by using a complete multibreed model in which computations of complete across-breed (co)variances were simplified by correlating only eigenvectors for HF and JE random regressions of the same order as obtained from the single-breed analysis. Parameter estimates differed more strongly than expected between the single-breed and multibreed analyses, especially for JE. This could be due to differences between animals and management in purebred and non-purebred herds. In addition, the model used only partially accounted for heterosis. The multibreed analysis showed additive genetic differences between the HF and JE breeds, expressed as genetic correlations of additive effects in both breeds, especially in linear and quadratic Legendre polynomials (respectively, 0.807 and 0.604). The differences were small for overall milk production (0.926). Results showed that permanent environmental lactation curves were highly correlated across breeds; however, intraherd lactation curves were also affected by the breed-environment interaction. This result may indicate the existence of breed-specific competition effects that vary through the different lactation stages. In conclusion, a multibreed model similar to the one presented could optimally use the environmental and genetic parameters and provide breed-dependent additive breeding values. This model could also be a useful tool to evaluate crossbred dairy cattle populations like those in New Zealand. However, a routine evaluation would still require the development of an improved methodology. It would also be computationally very challenging because of the simultaneous presence of a large number of breeds.

Genetic analysis of superovulatory response of Holstein cows in Canada.

PubMed

Jaton, C; Koeck, A; Sargolzaei, M; Malchiodi, F; Price, C A; Schenkel, F S; Miglior, F

2016-05-01

Superovulation of dairy cattle is frequently used in Canada. The cost of this protocol is high, and so is the variability of the outcome. Knowing the superovulatory potential of a donor cow could influence the breeder's decision to superovulate it or not. The main objective of this study was to perform a genetic analysis for superovulatory response of Holstein cows in Canada using data recorded by Holstein Canada, and to investigate if these data could be used for genetic evaluation. Data contained the total number of embryos and the number of viable embryos from every successful flushing performed across Canada. After editing, 137,446 records of superovulation performed between 1992 and 2014 were analyzed. A univariate repeatability animal model analysis was performed for both total number of embryos and number of viable embryos. Because both data and residuals did not follow a normal distribution, records were subject to either logarithmic or Anscombe transformation. Using logarithmic transformation, heritability estimates (SE) of 0.15 (0.01) and 0.14 (0.01) were found for total number of embryos and number of viable embryos, respectively. Using Anscombe transformation, heritability estimates (SE) of 0.17 (0.01) and 0.14 (0.01) were found for total number of embryos and number of viable embryos, respectively. The genetic correlation between the 2 traits was estimated at 0.97 using logarithmic transformation and 0.95 using Anscombe transformation. Breeding values were estimated for 54,463 cows, and 3,513 sires. Only estimated breeding values of sires having a reliability higher than 40% were considered for estimated breeding values correlations with other routinely evaluated traits. The results showed that selection for a higher response to superovulation would lead to a slight decrease in milk production, but an improvement for functional traits, including all reproduction traits. In all cases, the estimated correlations are either low or modest. We conclude that genetic selection for increased superovulatory response in donors is possible; daughters of sires with high estimated breeding values for superovulatory response will tend to yield more embryos, whereas the additive effect of service sire seems not to contribute to the variability of the 2 superovulation traits and was not significantly correlated with the additive effect of the donor. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genetic parameters of pelt character, feed efficiency and size traits in Finnish blue fox (Vulpes lagopus).

PubMed

Kempe, R; Koskinen, N; Strandén, I

2013-12-01

Pelt character traits (size, quality, colour clarity, darkness) are important economic traits in blue fox breeding. Better feed efficiency (FE) is another economically important and new breeding goal for fur animals. The purpose of this study was to determine the correlations between pelt character traits, FE and size traits and to estimate genetic parameters for pelt character traits. Pelt size (pSIcm ) had a high positive genetic correlation with animal grading size (gSI), final body weight (BWFin), body length and daily gain (DG), and a moderate correlation with body condition score (BCS). Animal body length and BCS (describing fatness) were considered as genetically different traits. Genetic correlations between pelt quality and size traits were estimated without precision and did not differ from zero, but colour clarity (pCL) had a low antagonistic genetic correlation with FE. Pelt size and DG had a favourable genetic correlation with FE but a fairly high unfavourable genetic correlation with dry matter feed intake. The current emphasis on selection for larger animal and pelt size improves FE indirectly, but selection for larger pelt size favours fast-growing and fat individuals and simultaneously increases feed intake. The detected genetic connections between FE, size, feed intake and pCL should be taken into account in the Finnish blue fox breeding programme. © 2013 Blackwell Verlag GmbH.

Genetic diversity and relatedness within and between species of the genus Oligoryzomys (Rodentia; Sigmodontinae).

PubMed

Trott, A; Callegari-Jacques, S M; Oliveira, L F B; Langguth, A; Mattevi, M S

2007-02-01

A RAPD analysis on six species of the rodent genus Oligoryzomys trapped in a wide area (ranging from 01 degrees N to 32 degrees S) of Brazilian territory was performed in order to determine the levels of genetic variability within and between its populations and species. One-hundred and ninety-three animals were collected in 13 different sites (corresponding to 17 samples) located at Pampas, Atlantic Rain Forest, Cerrado, and Amazon domains. Oligoryzomys sp., O. nigripes (8 populations), O. flavescens (4 populations), O. moojeni, O. stramineus, and O. fornesi were the taxa analyzed. Of the 20 primers tested, 4 generated a total of 75 polymorphic products simultaneously amplified in 151 specimens. Various diversity estimators analyzed showed considerable differences between species and populations, indicating a great genetic variation occurring in the Oligoryzomys taxa investigated. A cluster analysis was made using Nei's standard genetic distances, however, it did not correlate the genetic heterogeneity of the species and populations with the geographical areas.

A novel structure-aware sparse learning algorithm for brain imaging genetics.

PubMed

Du, Lei; Jingwen, Yan; Kim, Sungeun; Risacher, Shannon L; Huang, Heng; Inlow, Mark; Moore, Jason H; Saykin, Andrew J; Shen, Li

2014-01-01

Brain imaging genetics is an emergent research field where the association between genetic variations such as single nucleotide polymorphisms (SNPs) and neuroimaging quantitative traits (QTs) is evaluated. Sparse canonical correlation analysis (SCCA) is a bi-multivariate analysis method that has the potential to reveal complex multi-SNP-multi-QT associations. Most existing SCCA algorithms are designed using the soft threshold strategy, which assumes that the features in the data are independent from each other. This independence assumption usually does not hold in imaging genetic data, and thus inevitably limits the capability of yielding optimal solutions. We propose a novel structure-aware SCCA (denoted as S2CCA) algorithm to not only eliminate the independence assumption for the input data, but also incorporate group-like structure in the model. Empirical comparison with a widely used SCCA implementation, on both simulated and real imaging genetic data, demonstrated that S2CCA could yield improved prediction performance and biologically meaningful findings.

Quantitative genetic analysis of injury liability in infants and toddlers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, K.; Matheny, A.P. Jr.

1995-02-27

A threshold model of latent liability was applied to infant and toddler twin data on total count of injuries sustained during the interval from birth to 36 months of age. A quantitative genetic analysis of estimated twin correlations in injury liability indicated strong genetic dominance effects, but no additive genetic variance was detected. Because interpretations involving overdominance have little research support, the results may be due to low order epistasis or other interaction effects. Boys had more injuries than girls, but this effect was found only for groups whose parents were prompted and questioned in detail about their children`s injuries.more » Activity and impulsivity are two behavioral predictors of childhood injury, and the results are discussed in relation to animal research on infant and adult activity levels, and impulsivity in adult humans. Genetic epidemiological approaches to childhood injury should aid in targeting higher risk children for preventive intervention. 30 refs., 4 figs., 3 tabs.« less

Genetic diversity of Trichomonas vaginalis clinical isolates from Henan province in central China.

PubMed

Mao, Meng; Liu, Hui Li

2015-07-01

Trichomonas vaginalis is a flagellated protozoan parasite that infects the human urogenital tract, causing the most common non-viral, sexually transmitted disease worldwide. In this study, genetic variants of T. vaginalis were identified in Henan Province, China. Fragments of the small subunit of nuclear ribosomal RNA (18S rRNA) were amplified from 32 T. vaginalis isolates obtained from seven regions of Henan Province. Overall, 18 haplotypes were determined from the 18S rRNA sequences. Each sampled population and the total population displayed high haplotype diversity (Hd), accompanied by very low nucleotide diversity (Pi). In these molecular genetic variants, 91.58% genetic variation was derived from intra-regions. Phylogenetic analysis revealed no correlation between phylogeny and geographic distribution. Demographic analysis supported population expansion of T. vaginalis isolates from central China. Our findings showing moderate-to-high genetic variations in the 32 isolates of T. vaginalis provide useful knowledge for monitoring changes in parasite populations for the development of future control strategies.

Consistency of immigrant and country-of-birth suicide rates: a meta-analysis.

PubMed

Voracek, M; Loibl, L M

2008-10-01

Multifaceted evidence (family, twin, adoption, molecular genetic, geographic and surname studies of suicide) suggests genetic risk factors for suicide. Migrant studies are also informative in this context, but underused. In particular, a meta-analysis of the associations of immigrant (IMM) and country-of-birth (COB) suicide rates is unavailable. Thirty-three studies, reporting IMM suicide rates for nearly 50 nationalities in seven host countries (Australia, Austria, Canada, England, the Netherlands, Sweden and the USA), were retrieved. Total-population IMM and COB suicide rates were strongly positively associated (combined rank-order correlation across 20 eligible studies: 0.65, 95% CI: 0.56-0.73, P < 10(-9)). The effect generalized across both sexes, host countries and study periods. Following the logic of the migrant study design of genetic epidemiology, the correspondence of IMM and COB suicide rates is consistent with the assumption of population differences in the prevalence of genetic risk factors for suicide.

Evolution of floral display in Eichhornia paniculata (Pontederiaceae): direct and correlated responses to selection on flower size and number.

PubMed

Worley, A C; Barrett, S C

2000-10-01

Trade-offs between flower size and number seem likely to influence the evolution of floral display and are an important assumption of several theoretical models. We assessed floral trade-offs by imposing two generations of selection on flower size and number in a greenhouse population of bee-pollinated Eichhornia paniculata. We established a control line and two replicate selection lines of 100 plants each for large flowers (S+), small flowers (S-), and many flowers per inflorescence (N+). We compared realized heritabilities and genetic correlations with estimates based on restricted-maximum-likelihood (REML) analysis of pedigrees. Responses to selection confirmed REML heritability estimates (flower size, h2 = 0.48; daily flower number, h2 = 0.10; total flower number, h2 = 0.23). Differences in nectar, pollen, and ovule production between S+ and S- lines supported an overall divergence in investment per flower. Both realized and REML estimates of the genetic correlation between daily and total flower number were r = 1.0. However, correlated responses to selection were inconsistent in their support of a trade-off. In both S- lines, correlated increases in flower number indicated a genetic correlation of r = -0.6 between flower size and number. In contrast, correlated responses in N+ and S+ lines were not significant, although flower size decreased in one N+ line. In addition, REML estimates of genetic correlations between flower size and number were positive, and did not differ from zero when variation in leaf area and age at first flowering were taken into account. These results likely reflect the combined effects of variation in genes controlling the resources available for flowering and genes with opposing effects on flower size and number. Our results suggest that the short-term evolution of floral display is not necessarily constrained by trade-offs between flower size and number, as is often assumed.

Molecular genetic contributions to socioeconomic status and intelligence

PubMed Central

Marioni, Riccardo E.; Davies, Gail; Hayward, Caroline; Liewald, Dave; Kerr, Shona M.; Campbell, Archie; Luciano, Michelle; Smith, Blair H.; Padmanabhan, Sandosh; Hocking, Lynne J.; Hastie, Nicholas D.; Wright, Alan F.; Porteous, David J.; Visscher, Peter M.; Deary, Ian J.

2014-01-01

Education, socioeconomic status, and intelligence are commonly used as predictors of health outcomes, social environment, and mortality. Education and socioeconomic status are typically viewed as environmental variables although both correlate with intelligence, which has a substantial genetic basis. Using data from 6815 unrelated subjects from the Generation Scotland study, we examined the genetic contributions to these variables and their genetic correlations. Subjects underwent genome-wide testing for common single nucleotide polymorphisms (SNPs). DNA-derived heritability estimates and genetic correlations were calculated using the ‘Genome-wide Complex Trait Analyses’ (GCTA) procedures. 21% of the variation in education, 18% of the variation in socioeconomic status, and 29% of the variation in general cognitive ability was explained by variation in common SNPs (SEs ~ 5%). The SNP-based genetic correlations of education and socioeconomic status with general intelligence were 0.95 (SE 0.13) and 0.26 (0.16), respectively. There are genetic contributions to intelligence and education with near-complete overlap between common additive SNP effects on these traits (genetic correlation ~ 1). Genetic influences on socioeconomic status are also associated with the genetic foundations of intelligence. The results are also compatible with substantial environmental contributions to socioeconomic status. PMID:24944428

Molecular genetic contributions to socioeconomic status and intelligence.

PubMed

Marioni, Riccardo E; Davies, Gail; Hayward, Caroline; Liewald, Dave; Kerr, Shona M; Campbell, Archie; Luciano, Michelle; Smith, Blair H; Padmanabhan, Sandosh; Hocking, Lynne J; Hastie, Nicholas D; Wright, Alan F; Porteous, David J; Visscher, Peter M; Deary, Ian J

2014-05-01

Education, socioeconomic status, and intelligence are commonly used as predictors of health outcomes, social environment, and mortality. Education and socioeconomic status are typically viewed as environmental variables although both correlate with intelligence, which has a substantial genetic basis. Using data from 6815 unrelated subjects from the Generation Scotland study, we examined the genetic contributions to these variables and their genetic correlations. Subjects underwent genome-wide testing for common single nucleotide polymorphisms (SNPs). DNA-derived heritability estimates and genetic correlations were calculated using the 'Genome-wide Complex Trait Analyses' (GCTA) procedures. 21% of the variation in education, 18% of the variation in socioeconomic status, and 29% of the variation in general cognitive ability was explained by variation in common SNPs (SEs ~ 5%). The SNP-based genetic correlations of education and socioeconomic status with general intelligence were 0.95 (SE 0.13) and 0.26 (0.16), respectively. There are genetic contributions to intelligence and education with near-complete overlap between common additive SNP effects on these traits (genetic correlation ~ 1). Genetic influences on socioeconomic status are also associated with the genetic foundations of intelligence. The results are also compatible with substantial environmental contributions to socioeconomic status.

Assessing the potential for an ongoing arms race within and between the sexes: selection and heritable variation.

PubMed

Friberg, Urban; Lew, Timothy A; Byrne, Phillip G; Rice, William R

2005-07-01

In promiscuous species, sexual selection generates two opposing male traits: offense (acquiring new mates and supplanting stored sperm) and defense (enforcing fidelity on one's mates and preventing sperm displacement when this fails). Coevolution between these traits requires both additive genetic variation and associated natural selection. Previous work with Drosophila melanogaster found autosomal genetic variation for these traits among inbred lines from a mixture of populations, but only nonheritable genetic variation was found within a single outbred population. These results do not support ongoing antagonistic coevolution between offense and defense, nor between either of these male traits and female reproductive characters. Here we use a new method (hemiclonal analysis) to study genomewide genetic variation in a large outbred laboratory population of D. melanogaster. Hemiclonal analysis estimates the additive genetic variation among random, genomewide haplotypes taken from a large, outbred, locally adapted laboratory population and determines the direction of the selection gradient on this variation. In contrast to earlier studies, we found low but biologically significant heritable variation for defensive and offensive offspring production as well as all their components (P1, fidelity, P2, and remating). Genetic correlations between these traits were substantially different from those reported for inbred lines. A positive genetic correlation was found between defense and offense, demonstrating that some shared genes influence both traits. In addition to this common variation, evidence for unique genetic variation for each trait was also found, supporting an ongoing coevolutionary arms race between defense and offense. Reproductive conflict between males can strongly influence female fitness. Correspondingly, we found genetic variation in both defense and offense that affected female fitness. No evidence was found for intersexual conflict in the context of male defense, but we found substantial intersexual conflict in the context of male offensive sperm competitive ability. These results indicate that conflict between competing males also promotes an associated arms race between the sexes.

Carcass traits of young bulls in dual-purpose cattle: genetic parameters and genetic correlations with veal calf, type and production traits.

PubMed

Croué, I; Fouilloux, M N; Saintilan, R; Ducrocq, V

2017-06-01

The profitability of dual-purpose breeding farms can be increased through genetic improvement of carcass traits. To develop a genetic evaluation of carcass traits of young bulls, breed-specific genetic parameters were estimated in three French dual-purpose breeds. Genetic correlations between these traits and veal calf, type and milk production traits were also estimated. Slaughter performances of 156 226 Montbeliarde, 160 361 Normande and 8691 Simmental young bulls were analyzed with a multitrait animal model. In the three breeds, heritabilities were moderate for carcass weight (0.12 to 0.19±0.01 to 0.04) and carcass conformation (0.21 to 0.26±0.01 to 0.04) and slightly lower for age at slaughter (0.08 to 0.17±0.01 to 0.03). For all three breeds, genetic correlations between carcass weight and carcass conformation were moderate and favorable (0.30 to 0.52±0.03 to 0.13). They were strong and favorable (-0.49 to -0.71±0.05 to 0.15) between carcass weight and age at slaughter. Between age at slaughter and carcass conformation, they were low and unfavorable to moderate and favorable (-0.25 to 0.10±0.06 to 0.18). Heavier young bulls tend to be better conformed and slaughtered earlier. Genetic correlations between corresponding young bulls and veal production traits were moderate and favorable (0.32 to 0.70±0.03 to 0.09), implying that selecting sires for veal calf production leads to select sires producing better young bulls. Genetic correlations between young bull carcass weight and cow size were moderately favorable (0.22 to 0.45±0.04 to 0.10). Young bull carcass conformation had moderate and favorable genetic correlations (0.11 to 0.24±0.04 to 0.10) with cow width but moderate and unfavorable genetic correlations (-0.21 to -0.36±0.03 to 0.08) with cow height. Taller cows tended to produce heavier young bulls and thinner cows to produce less conformed ones. Genetic correlations between carcass traits of young bulls and cow muscularity traits were low to moderate and favorable. Finally, genetic correlations between carcass traits of young bulls and milk production traits were low and unfavorable to moderate and favorable. These results indicate the existence for all three breeds of genetic variability for the genetic improvement of carcass traits of young bulls as well as favorable genetic correlations for their simultaneous selection and no strong unfavorable correlation with milk production traits.

Statistical power and utility of meta-analysis methods for cross-phenotype genome-wide association studies.

PubMed

Zhu, Zhaozhong; Anttila, Verneri; Smoller, Jordan W; Lee, Phil H

2018-01-01

Advances in recent genome wide association studies (GWAS) suggest that pleiotropic effects on human complex traits are widespread. A number of classic and recent meta-analysis methods have been used to identify genetic loci with pleiotropic effects, but the overall performance of these methods is not well understood. In this work, we use extensive simulations and case studies of GWAS datasets to investigate the power and type-I error rates of ten meta-analysis methods. We specifically focus on three conditions commonly encountered in the studies of multiple traits: (1) extensive heterogeneity of genetic effects; (2) characterization of trait-specific association; and (3) inflated correlation of GWAS due to overlapping samples. Although the statistical power is highly variable under distinct study conditions, we found the superior power of several methods under diverse heterogeneity. In particular, classic fixed-effects model showed surprisingly good performance when a variant is associated with more than a half of study traits. As the number of traits with null effects increases, ASSET performed the best along with competitive specificity and sensitivity. With opposite directional effects, CPASSOC featured the first-rate power. However, caution is advised when using CPASSOC for studying genetically correlated traits with overlapping samples. We conclude with a discussion of unresolved issues and directions for future research.

[Genetic diversity and relationships of northern eurasia populations for polymorphic Alu-insertions].

PubMed

Khitrinskaia, I Iu; Khar'kov, V N; Voevoda, M I; Stepanova, V A

2014-01-01

We for the first time have examined the autosomal gene pool of the Siberia, Central Asian and the Far East populations (27 populations of 12 ethnic groups) using a set of polymorphic Alu insertions in the human genome. The results of the analysis testify (i) to a significant level of genetic diversity in the Northern Eurasian populations and (ii) to a considerable differentiation of gene pool in the population of this region. It has been shown that at the CD4 locus, the frequency of Alu (-) is inversely related to the Mongoloid component of the population, the lowest and highest frequencies of the Alu deletion at locus CD4 were recorded respectively in Eskimo (0.012) and Russian and Ukrainian (0.35). The analysis of gene flow proved Caucasoid populations (Russian, Tajik and Uzbek), as well as those of Turkic ethnic groups from the Southern Siberia (Altaians and Tuvinians) and Khanty and Mansy populations to be the recipients of a considerable gene flow from the outside of the concerned population system, as compared with the East Siberian and the Far East ethnic groups. The results of the correlation analysis received with use polymorphic Alu insertion testify to the greatest correlation of genetic distances with anthropological characteristics of populations.

Intracoastal shipping drives patterns of regional population expansion by an invasive marine invertebrate.

PubMed

Darling, John A; Herborg, Leif-Matthias; Davidson, Ian C

2012-10-01

Understanding the factors contributing to expansion of nonnative populations is a critical step toward accurate risk assessment and effective management of biological invasions. Nevertheless, few studies have attempted explicitly to test hypotheses regarding factors driving invasive spread by seeking correlations between patterns of vector movement and patterns of genetic connectivity. Herein, we describe such an attempt for the invasive tunicate Styela clava in the northeastern Pacific. We utilized microsatellite data to estimate gene flow between samples collected throughout the known range of S. clava in the region, and assessed correlation of these estimates with patterns of intracoastal commercial vessel traffic. Our results suggest that recent shipping patterns have contributed to the contemporary distribution of genetic variation. However, the analysis also indicates that other factors-including a complex invasion history and the influence of other vectors-have partially obscured genetic patterns associated with intracoastal population expansion.

Organizational Benchmarks for Test Utilization Performance: An Example Based on Positivity Rates for Genetic Tests.

PubMed

Rudolf, Joseph; Jackson, Brian R; Wilson, Andrew R; Smock, Kristi J; Schmidt, Robert L

2017-04-01

Health care organizations are under increasing pressure to deliver value by improving test utilization management. Many factors, including organizational factors, could affect utilization performance. Past research has focused on the impact of specific interventions in single organizations. The impact of organizational factors is unknown. The objective of this study is to determine whether testing patterns are subject to organizational effects, ie, are utilization patterns for individual tests correlated within organizations. Comparative analysis of ordering patterns (positivity rates for three genetic tests) across 659 organizations. Hierarchical regression was used to assess the impact of organizational factors after controlling for test-level factors (mutation prevalence) and hospital bed size. Test positivity rates were correlated within organizations. Organizations have a statistically significant impact on the positivity rate of three genetic tests. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Genetic grouping strategies in selection efficiency of composite beef cattle ( × ).

PubMed

Petrini, J; Pertile, S F N; Eler, J P; Ferraz, J B S; Mattos, E C; Figueiredo, L G G; Mourão, G B

2015-02-01

The inclusion of genetic groups in sire evaluation has been widely used to represent genetic differences among animals not accounted for by the absence of parentage data. However, the definition of these groups is still arbitrary, and studies assessing the effects of genetic grouping strategies on the selection efficiency are rare. Therefore, the aim in this study was to compare genetic grouping strategies for animals with unknown parentage in prediction of breeding values (EBV). The total of 179,302 records of weaning weight (WW), 29,825 records of scrotal circumference (SC), and 70,302 records of muscling score (MUSC) from Montana Tropical animals, a Brazilian composite beef cattle population, were used. Genetic grouping strategies involving year of birth, sex of the unknown parent, birth farm, breed composition, and their combinations were evaluated. Estimated breeding values were predicted for each approach simulating a loss of genealogy data. Thereafter, these EBV were compared to those obtained in an analysis involving a real relationship matrix to estimate selection efficiency and correlations between EBV and animal rankings. The analysis model included the fixed effects of contemporary groups and class of the dam age at calving, the covariates of additive and nonadditive genetic effects, and age, and the additive genetic effect of animal as random effects. A second model also included the fixed effects of genetic group. The use of genetic groups resulted in means of selection efficiency and correlation of 70.4 to 97.1% and 0.51 to 0.94 for WW, 85.8 to 98.8% and 0.82 to 0.98 for SC, and 85.1 to 98.6% and 0.74 to 0.97 for MUSC, respectively. High selection efficiencies were observed for year of birth and breed composition strategies. The maximum absolute difference in annual genetic gain estimated through the use of complete genealogy and genetic groups were 0.38 kg for WW, 0.02 cm for SC, and 0.01 for MUSC, with lower differences obtained when year of birth was adopted as a genetic group criterion. Grouping strategy must consider selection decisions and the number of genetic groups formed, in the way that genetic groups represent the genetic differences in population and allow an adequate prediction of EBV.

The relationship between genetic and chemotypic diversity in American ginseng (Panax quinquefolius L.).

PubMed

Schlag, Erin M; McIntosh, Marla S

2013-09-01

Ginseng is one of the world's most important herbals used as an adaptogen and a cure for an impressively large range of ailments. Differences in the medicinal properties of ginseng roots have been attributed to variation in ginsenoside composition. In this study, the association between genetic and chemotypic profiles of wild and cultivated American ginseng (Panax quinquefolius L.) roots grown in Maryland was investigated. Ginseng roots were classified into chemotypes based on their relative composition of Re and Rg1. Genetic profiles of these roots were determined from the analysis of 38 polymorphic RAPD markers and used for a cluster analysis of genetic similarities. The close correspondence between chemotype and genetic cluster provides the first DNA-based evidence for the genetic basis of ginsenoside composition. Results of this research are significant for plant breeding and conservation, phytochemical research, and clinical and pharmacological studies. Also, the correlation between RAPD markers and chemotype indicates the potential to use RAPD markers as a reliable and practical method for identification and certification of ginseng roots. Copyright © 2013 Elsevier Ltd. All rights reserved.

The association between lower educational attainment and depression owing to shared genetic effects? Results in ~25,000 subjects.

PubMed

Peyrot, W J; Lee, S H; Milaneschi, Y; Abdellaoui, A; Byrne, E M; Esko, T; de Geus, E J C; Hemani, G; Hottenga, J J; Kloiber, S; Levinson, D F; Lucae, S; Martin, N G; Medland, S E; Metspalu, A; Milani, L; Noethen, M M; Potash, J B; Rietschel, M; Rietveld, C A; Ripke, S; Shi, J; Willemsen, G; Zhu, Z; Boomsma, D I; Wray, N R; Penninx, B W J H

2015-06-01

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14,949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15,138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884,105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120,000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

Comparative physiological and metabolomics analysis of wheat (Triticum aestivum L.) following post-anthesis heat stress

PubMed Central

Beecher, Chris; MacDonald, Greg

2018-01-01

Genetic improvement for stress tolerance requires a solid understanding of biochemical processes involved with different physiological mechanisms and their relationships with different traits. The objective of this study was to demonstrate genetic variability in altered metabolic levels in a panel of six wheat genotypes in contrasting temperature regimes, and to quantify the correlation between those metabolites with different traits. In a controlled environment experiment, heat stress (35:28 ± 0.08°C) was initiated 10 days after anthesis. Flag leaves were collected 10 days after heat treatment to employ an untargeted metabolomics profiling using LC-HRMS based technique called IROA. High temperature stress produced significant genetic variations for cell and thylakoid membrane damage, and yield related traits. 64 known metabolites accumulated 1.5 fold of higher or lower due to high temperature stress. In general, metabolites that increased the most under heat stress (L-tryptophan, pipecolate) showed negative correlation with different traits. Contrary, the metabolites that decreased the most under heat stress (drummondol, anthranilate) showed positive correlation with the traits. Aminoacyl-tRNA biosysnthesis and plant secondary metabolite biosynthesis pathways were most impacted by high temperature stress. The robustness of metabolic change and their relationship with phenotypes renders those metabolites as potential bio-markers for genetic improvement. PMID:29897945

Interactive effects of genotype x environment on the live weight of GIFT Nile tilapias.

PubMed

Oliveira, Sheila N DE; Ribeiro, Ricardo P; Oliveira, Carlos A L DE; Alexandre, Luiz; Oliveira, Aline M S; Lopera-Barrero, Nelson M; Santander, Victor F A; Santana, Renan A C

2017-01-01

In this paper, the existence of a genotype x environment interaction for the average daily weight in GIFT Nile tilapia (Oreochromis niloticus) in different regions in the state of Paraná (Brazil) was analyzed. The heritability results were high in the uni-characteristic analysis: 0.71, 0.72 and 0.67 for the cities of Palotina (PL), Floriano (FL) and Diamond North (DN), respectively. Genetic correlations estimated in bivariate analyzes were weak with values between 0.12 for PL-FL, 0.06 for PL and 0.23 for DN-FL-DN. The Spearman correlation values were low, which indicated a change in ranking in the selection of animals in different environments in the study. There was heterogeneity in the phenotypic variance among the three regions and heterogeneity in the residual variance between PL and DN. The direct genetic gain was greater for the region with a DN value gain of 198.24 g/generation, followed by FL (98.73 g/generation) and finally PL (98.73 g/generation). The indirect genetic gains were lower than 0.37 and greater than 0.02 g/generation. The evidence of the genotype x environment interaction was verified, which indicated the phenotypic heterogeneity of the variances among the three regions, weak genetic correlation and modified rankings in the different environments.

Genetic overlap between impulsivity and alcohol dependence: a large-scale national twin study.

PubMed

Khemiri, L; Kuja-Halkola, R; Larsson, H; Jayaram-Lindström, N

2016-04-01

Alcohol dependence is associated with increased levels of impulsivity, but the genetic and environmental underpinnings of this overlap remain unclear. The purpose of the current study was to investigate the degree to which genetic and environmental factors contribute to the overlap between alcohol dependence and impulsivity. Univariate and bivariate twin model fitting was conducted for alcohol dependence and impulsivity in a national sample of 16 819 twins born in Sweden from 1959 to 1985. The heritability estimate for alcohol dependence was 44% [95% confidence interval (CI) 31-57%] for males and 62% (95% CI 52-72%) for females. For impulsivity, the heritability was 33% (95% CI 30-36%) in males and females. The bivariate twin analysis indicated a statistically significant genetic correlation between alcohol dependence and impulsivity of 0.40 (95% CI 0.23-0.58) in males and 0.20 (95% CI 0.07-0.33) in females. The phenotypic correlation between alcohol dependence and impulsivity was 0.20 and 0.17 for males and females, respectively, and the bivariate heritability was 80% (95% CI 47-117%) for males and 53% (95% CI 19-86%) for females. The remaining variance in all models was accounted for by non-shared environmental factors. The association between alcohol dependence and impulsivity can be partially accounted for by shared genetic factors. The genetic correlation was greater in men compared with women, which may indicate different pathways to the development of alcohol dependence between sexes. The observed genetic overlap has clinical implications regarding treatment and prevention, and partially explains the substantial co-morbidity between alcohol dependence and psychiatric disorders characterized by impulsive behaviour.

Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study.

PubMed

Lee, Miryoung; Czerwinski, Stefan A; Choh, Audrey C; Demerath, Ellen W; Sun, Shumei S; Chumlea, Wm C; Towne, Bradford; Siervogel, Roger M

2006-03-01

Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.

Hemiclonal analysis of interacting phenotypes in male and female Drosophila melanogaster

PubMed Central

2014-01-01

Background Identifying the sources of variation in mating interactions between males and females is important because this variation influences the strength and/or the direction of sexual selection that populations experience. While the origins and effects of variation in male attractiveness and ornamentation have received much scrutiny, the causes and consequences of intraspecific variation in females have been relatively overlooked. We used cytogenetic cloning techniques developed for Drosophila melanogaster to create “hemiclonal” males and females with whom we directly observed sexual interaction between individuals of different known genetic backgrounds and measured subsequent reproductive outcomes. Using this approach, we were able to quantify the genetic contribution of each mate to the observed phenotypic variation in biologically important traits including mating speed, copulation duration, and subsequent offspring production, as well as measure the magnitude and direction of intersexual genetic correlation between female choosiness and male attractiveness. Results We found significant additive genetic variation contributing to mating speed that can be attributed to male genetic identity, female genetic identity, but not their interaction. Furthermore we found that phenotypic variation in copulation duration had a significant male-associated genetic component. Female genetic identity and the interaction between male and female genetic identity accounted for a substantial amount of the observed phenotypic variation in egg size. Although previous research predicts a trade-off between egg size and fecundity, this was not evident in our results. We found a strong negative genetic correlation between female choosiness and male attractiveness, a result that suggests a potentially important role for sexually antagonistic alleles in sexual selection processes in our population. Conclusion These results further our understanding of sexual selection because they identify that genetic identity plays a significant role in phenotypic variation in female behaviour and fecundity. This variation may be potentially due to ongoing sexual conflict found between the sexes for interacting phenotypes. Our unexpected observation of a negative correlation between female choosiness and male attractiveness highlights the need for more explicit theoretical models of genetic covariance to investigate the coevolution of female choosiness and male attractiveness. PMID:24884361

Evaluation of genetic diversity of Panicum turgidum Forssk from Saudi Arabia.

PubMed

Assaeed, Abdulaziz M; Al-Faifi, Sulieman A; Migdadi, Hussein M; El-Bana, Magdy I; Al Qarawi, Abdulaziz A; Khan, Mohammad Altaf

2018-01-01

The genetic diversity of 177 accessions of Panicum turgidum Forssk, representing ten populations collected from four geographical regions in Saudi Arabia, was analyzed using amplified fragment length polymorphism (AFLP) markers. A set of four primer-pairs with two/three selective nucleotides scored 836 AFLP amplified fragments (putative loci/genome landmarks), all of which were polymorphic. Populations collected from the southern region of the country showed the highest genetic diversity parameters, whereas those collected from the central regions showed the lowest values. Analysis of molecular variance (AMOVA) revealed that 78% of the genetic variability was attributable to differences within populations. Pairwise values for population differentiation and genetic structure were statistically significant for all variances. The UPGMA dendrogram, validated by principal coordinate analysis-grouped accessions, corresponded to the geographical origin of the accessions. Mantel's test showed that there was a significant correlation between the genetic and geographical distances ( r  = 0.35, P  < 0.04). In summary, the AFLP assay demonstrated the existence of substantial genetic variation in P. turgidum . The relationship between the genetic diversity and geographical source of P. turgidum populations of Saudi Arabia, as revealed through this comprehensive study, will enable effective resource management and restoration of new areas without compromising adaptation and genetic diversity.

Floral and Vegetative Morphometrics of Five Pleurothallis (Orchidaceae) Species: Correlation with Taxonomy, Phylogeny, Genetic Variability and Pollination Systems

PubMed Central

BORBA, EDUARDO L.; SHEPHERD, GEORGE J.; BERG, CÁSSIO VAN DEN; SEMIR, JOÃO

2002-01-01

Morphometric analyses of vegetative and floral characters were conducted in 21 populations of five Pleurothallis (Orchidaceae) species occurring in Brazilian ‘campo rupestre’ vegetation. A phylogenetic analysis of this species group was also carried out using nuclear ribosomal DNA internal transcribed spacers (ITS1 and ITS2). Results of the ordination and cluster analyses agree with species’ delimitation revealed by taxonomic and allozyme studies. The groups formed in ordination analysis correspond to the pollinator groups determined in a previous pollination study. Relationships among the species in the cluster analysis using only vegetative characters are similar to those found in a previous allozyme study, but those indicated by cluster analysis using only floral characters differ. These results support the hypothesis that floral similarities are due to convergence driven by similar pollination mechanisms, and therefore floral traits may not be good indicators of phylogenetic relationships in this group. The results of the phylogenetic analysis support this conclusion to some extent. There is no correlation between genetic (allozyme) and morphological variability in the populations nor in the way this variability is distributed among conspecific populations. We describe a new subspecies of Pleurothallis ochreata based on differences in vegetative and chemical characters as well as geographic distribution. Absence of differentiation in floral characters, attraction of the same pollinator species, interfertility and genetic similarity support the argument for subspecific rather than specific status. PMID:12197519

Genotype by environment interaction for activity-based estrus traits in relation to production level for Danish Holstein.

PubMed

Ismael, Ahmed; Strandberg, Erling; Berglund, Britt; Kargo, Morten; Fogh, Anders; Løvendahl, Peter

2016-12-01

The objective of this study was to investigate whether genotype by environment interaction exists for female fertility traits and production of energy-corrected milk at 70d in milk (ECM70). Fertility traits considered were the activity-based estrus traits interval from calving to first high activity (CFHA), duration of high activity episode (DHA), as an indicator for first estrus duration, and strength of high activity episode (SHA), as an indicator for first estrus strength. The physical activity traits were derived from electronic activity tags for 11,522 first-parity cows housed in 125 commercial dairy herds. Data were analyzed using a univariate random regression animal model (URRM), by regressing the phenotypic performance on the average herd ECM70 as an environmental gradient. Furthermore, the genetic correlations between CFHA and ECM70 as a function of production level were estimated using a bivariate random regression animal model (BRRM). For all traits, heterogeneity of additive genetic variances and heritability estimates was observed. The heritability estimate for CFHA decreased from 0.25 to 0.10 with increasing production level and the heritability estimate for ECM70 decreased from 0.35 to 0.15 with increasing production level using URRM. The genetic correlation of the same trait in low and high production levels was around 0.74 for CFHA and 0.80 for ECM70 using URRM, but when data were analyzed using the multiple-trait analysis (MT), genetic correlation estimates between low and high production levels were not significantly different from unity. Furthermore, the genetic correlation of SHA between low and high production level was 0.22 using URRM, but the corresponding correlation estimate had large standard error when data were analyzed using MT. The genetic correlation between CFHA and ECM70 as a function of production environment was weak but unfavorable and decreased slightly from 0.09 to 0.04 with increasing production level using BRRM. Moreover, the same trend was observed when the data were analyzed using MT where the genetic correlation between CFHA and ECM70 in the low production environment was 0.29 compared with -0.13 in the high production environment, but these estimates had large standard errors. In conclusion, regardless of the trait used, in relation to average herd ECM70 production, the results indicated no clear evidence of strong genotype by environment interaction that would cause significant re-ranking of sires between low and high production environments. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

What's in a name? Y chromosomes, surnames and the genetic genealogy revolution.

PubMed

King, Turi E; Jobling, Mark A

2009-08-01

Heritable surnames are highly diverse cultural markers of coancestry in human populations. A patrilineal surname is inherited in the same way as the non-recombining region of the Y chromosome and there should, therefore, be a correlation between the two. Studies of Y haplotypes within surnames, mostly of the British Isles, reveal high levels of coancestry among surname cohorts and the influence of confounding factors, including multiple founders for names, non-paternities and genetic drift. Combining molecular genetics and surname analysis illuminates population structure and history, has potential applications in forensic studies and, in the form of 'genetic genealogy', is an area of rapidly growing interest for the public.

Adjusting head circumference for covariates in autism: clinical correlates of a highly heritable continuous trait.

PubMed

Chaste, Pauline; Klei, Lambertus; Sanders, Stephan J; Murtha, Michael T; Hus, Vanessa; Lowe, Jennifer K; Willsey, A Jeremy; Moreno-De-Luca, Daniel; Yu, Timothy W; Fombonne, Eric; Geschwind, Daniel; Grice, Dorothy E; Ledbetter, David H; Lord, Catherine; Mane, Shrikant M; Lese Martin, Christa; Martin, Donna M; Morrow, Eric M; Walsh, Christopher A; Sutcliffe, James S; State, Matthew W; Devlin, Bernie; Cook, Edwin H; Kim, Soo-Jeong

2013-10-15

Brain development follows a different trajectory in children with autism spectrum disorders (ASD) than in typically developing children. A proxy for neurodevelopment could be head circumference (HC), but studies assessing HC and its clinical correlates in ASD have been inconsistent. This study investigates HC and clinical correlates in the Simons Simplex Collection cohort. We used a mixed linear model to estimate effects of covariates and the deviation from the expected HC given parental HC (genetic deviation). After excluding individuals with incomplete data, 7225 individuals in 1891 families remained for analysis. We examined the relationship between HC/genetic deviation of HC and clinical parameters. Gender, age, height, weight, genetic ancestry, and ASD status were significant predictors of HC (estimate of the ASD effect = .2 cm). HC was approximately normally distributed in probands and unaffected relatives, with only a few outliers. Genetic deviation of HC was also normally distributed, consistent with a random sampling of parental genes. Whereas larger HC than expected was associated with ASD symptom severity and regression, IQ decreased with the absolute value of the genetic deviation of HC. Measured against expected values derived from covariates of ASD subjects, statistical outliers for HC were uncommon. HC is a strongly heritable trait, and population norms for HC would be far more accurate if covariates including genetic ancestry, height, and age were taken into account. The association of diminishing IQ with absolute deviation from predicted HC values suggests HC could reflect subtle underlying brain development and warrants further investigation. © 2013 Society of Biological Psychiatry.

Heritability of Boldness and Hypoxia Avoidance in European Seabass, Dicentrarchus labrax.

PubMed

Ferrari, Sébastien; Horri, Khaled; Allal, François; Vergnet, Alain; Benhaim, David; Vandeputte, Marc; Chatain, Béatrice; Bégout, Marie-Laure

2016-01-01

To understand the genetic basis of coping style in European seabass, fish from a full factorial mating (10 females x 50 males) were reared in common garden and individually tagged. Individuals coping style was characterized through behavior tests at four different ages, categorizing fish into proactive or reactive: a hypoxia avoidance test (at 255 days post hatching, dph) and 3 risk-taking tests (at 276, 286 and 304 dph). We observed significant heritability of the coping style, higher for the average of risk-taking scores (h2 = 0.45 ± 0.14) than for the hypoxia avoidance test (h2 = 0.19 ± 0.10). The genetic correlations between the three risk-taking scores were very high (rA = 0.96-0.99) showing that although their repeatability was moderately high (rP = 0.64-0.72), successive risk-taking tests evaluated the same genetic variation. A mild genetic correlation between the results of the hypoxia avoidance test and the average of risk-taking scores (0.45 ± 0.27) suggested that hypoxia avoidance and risk-taking tests do not address exactly the same behavioral and physiological responses. Genetic correlations between weight and risk taking traits showed negative values whatever the test used in our population i.e. reactive individual weights were larger. The results of this quantitative genetic analysis suggest a potential for the development of selection programs based on coping styles that could increase seabass welfare without altering growth performances. Overall, it also contributes to a better understanding of the origin and the significance of individual behavioral differences.

Adjusting head circumference for covariates in autism: clinical correlates of a highly heritable continuous trait

PubMed Central

Chaste, Pauline; Klei, Lambertus; Sanders, Stephan J.; Murtha, Michael T.; Hus, Vanessa; Lowe, Jennifer K.; Willsey, A. Jeremy; Moreno-De-Luca, Daniel; Yu, Timothy W.; Fombonne, Eric; Geschwind, Daniel; Grice, Dorothy E.; Ledbetter, David H.; Lord, Catherine; Mane, Shrikant M.; Martin, Christa Lese; Martin, Donna M.; Morrow, Eric M.; Walsh, Christopher A.; Sutcliffe, James S.; State, Matthew W.; Devlin, Bernie; Cook, Edwin H.; Kim, Soo-Jeong

2013-01-01

BACKGROUND Brain development follows a different trajectory in children with Autism Spectrum Disorders (ASD) than in typically developing children. A proxy for neurodevelopment could be head circumference (HC), but studies assessing HC and its clinical correlates in ASD have been inconsistent. This study investigates HC and clinical correlates in the Simons Simplex Collection cohort. METHODS We used a mixed linear model to estimate effects of covariates and the deviation from the expected HC given parental HC (genetic deviation). After excluding individuals with incomplete data, 7225 individuals in 1891 families remained for analysis. We examined the relationship between HC/genetic deviation of HC and clinical parameters. RESULTS Gender, age, height, weight, genetic ancestry and ASD status were significant predictors of HC (estimate of the ASD effect=0.2cm). HC was approximately normally distributed in probands and unaffected relatives, with only a few outliers. Genetic deviation of HC was also normally distributed, consistent with a random sampling of parental genes. Whereas larger HC than expected was associated with ASD symptom severity and regression, IQ decreased with the absolute value of the genetic deviation of HC. CONCLUSIONS Measured against expected values derived from covariates of ASD subjects, statistical outliers for HC were uncommon. HC is a strongly heritable trait and population norms for HC would be far more accurate if covariates including genetic ancestry, height and age were taken into account. The association of diminishing IQ with absolute deviation from predicted HC values suggests HC could reflect subtle underlying brain development and warrants further investigation. PMID:23746936

Genetic and epigenetic differences associated with environmental gradients in replicate populations of two salt marsh perennials.

PubMed

Foust, C M; Preite, V; Schrey, A W; Alvarez, M; Robertson, M H; Verhoeven, K J F; Richards, C L

2016-04-01

While traits and trait plasticity are partly genetically based, investigating epigenetic mechanisms may provide more nuanced understanding of the mechanisms underlying response to environment. Using AFLP and methylation-sensitive AFLP, we tested the hypothesis that differentiation to habitats along natural salt marsh environmental gradients occurs at epigenetic, but not genetic loci in two salt marsh perennials. We detected significant genetic and epigenetic structure among populations and among subpopulations, but we found multilocus patterns of differentiation to habitat type only in epigenetic variation for both species. In addition, more epigenetic than genetic loci were correlated with habitat in both species. When we analysed genetic and epigenetic variation simultaneously with partial Mantel, we found no correlation between genetic variation and habitat and a significant correlation between epigenetic variation and habitat in Spartina alterniflora. In Borrichia frutescens, we found significant correlations between epigenetic and/or genetic variation and habitat in four of five populations when populations were analysed individually, but there was no significant correlation between genetic or epigenetic variation and habitat when analysed jointly across the five populations. These analyses suggest that epigenetic mechanisms are involved in the response to salt marsh habitats, but also that the relationships among genetic and epigenetic variation and habitat vary by species. Site-specific conditions may also cloud our ability to detect response in replicate populations with similar environmental gradients. Future studies analysing sequence data and the correlation between genetic variation and DNA methylation will be powerful to identify the contributions of genetic and epigenetic response to environmental gradients. © 2016 John Wiley & Sons Ltd.

Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank.

PubMed

Hall, Lynsey S; Adams, Mark J; Arnau-Soler, Aleix; Clarke, Toni-Kim; Howard, David M; Zeng, Yanni; Davies, Gail; Hagenaars, Saskia P; Maria Fernandez-Pujals, Ana; Gibson, Jude; Wigmore, Eleanor M; Boutin, Thibaud S; Hayward, Caroline; Scotland, Generation; Porteous, David J; Deary, Ian J; Thomson, Pippa A; Haley, Chris S; McIntosh, Andrew M

2018-01-10

Few replicable genetic associations for Major Depressive Disorder (MDD) have been identified. Recent studies of MDD have identified common risk variants by using a broader phenotype definition in very large samples, or by reducing phenotypic and ancestral heterogeneity. We sought to ascertain whether it is more informative to maximize the sample size using data from all available cases and controls, or to use a sex or recurrent stratified subset of affected individuals. To test this, we compared heritability estimates, genetic correlation with other traits, variance explained by MDD polygenic score, and variants identified by genome-wide meta-analysis for broad and narrow MDD classifications in two large British cohorts - Generation Scotland and UK Biobank. Genome-wide meta-analysis of MDD in males yielded one genome-wide significant locus on 3p22.3, with three genes in this region (CRTAP, GLB1, and TMPPE) demonstrating a significant association in gene-based tests. Meta-analyzed MDD, recurrent MDD and female MDD yielded equivalent heritability estimates, showed no detectable difference in association with polygenic scores, and were each genetically correlated with six health-correlated traits (neuroticism, depressive symptoms, subjective well-being, MDD, a cross-disorder phenotype and Bipolar Disorder). Whilst stratified GWAS analysis revealed a genome-wide significant locus for male MDD, the lack of independent replication, and the consistent pattern of results in other MDD classifications suggests that phenotypic stratification using recurrence or sex in currently available sample sizes is currently weakly justified. Based upon existing studies and our findings, the strategy of maximizing sample sizes is likely to provide the greater gain.

QTL analysis of root morphology, flowering time, and yield reveals trade-offs in response to drought in Brassica napus.

PubMed

Fletcher, Richard S; Mullen, Jack L; Heiliger, Annie; McKay, John K

2015-01-01

Drought escape and dehydration avoidance represent alternative strategies for drought adaptation in annual crops. The mechanisms underlying these two strategies are reported to have a negative correlation, suggesting a trade-off. We conducted a quantitative trait locus (QTL) analysis of flowering time and root mass, traits representing each strategy, in Brassica napus to understand if a trade-off exists and what the genetic basis might be. Our field experiment used a genotyped population of doubled haploid lines and included both irrigated and rainfed treatments, allowing analysis of plasticity in each trait. We found strong genetic correlations among all traits, suggesting a trade-off among traits may exist. Summing across traits and treatments we found 20 QTLs, but many of these co-localized to two major QTLs, providing evidence that the trade-off is genetically constrained. To understand the mechanistic relationship between root mass, flowering time, and QTLs, we analysed the data by conditioning upon correlated traits. Our results suggest a causal model where such QTLs affect root mass directly as well as through their impacts on flowering time. Additionally, we used draft Brassica genomes to identify orthologues of well characterized Arabidopsis thaliana flowering time genes as candidate genes. This research provides valuable clues to breeding for drought adaptation as it is the first to analyse the inheritance of the root system in B. napus in relation to drought. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Genetic analysis of milk production traits of Tunisian Holsteins using random regression test-day model with Legendre polynomials

PubMed Central

2018-01-01

Objective The objective of this study was to estimate genetic parameters of milk, fat, and protein yields within and across lactations in Tunisian Holsteins using a random regression test-day (TD) model. Methods A random regression multiple trait multiple lactation TD model was used to estimate genetic parameters in the Tunisian dairy cattle population. Data were TD yields of milk, fat, and protein from the first three lactations. Random regressions were modeled with third-order Legendre polynomials for the additive genetic, and permanent environment effects. Heritabilities, and genetic correlations were estimated by Bayesian techniques using the Gibbs sampler. Results All variance components tended to be high in the beginning and the end of lactations. Additive genetic variances for milk, fat, and protein yields were the lowest and were the least variable compared to permanent variances. Heritability values tended to increase with parity. Estimates of heritabilities for 305-d yield-traits were low to moderate, 0.14 to 0.2, 0.12 to 0.17, and 0.13 to 0.18 for milk, fat, and protein yields, respectively. Within-parity, genetic correlations among traits were up to 0.74. Genetic correlations among lactations for the yield traits were relatively high and ranged from 0.78±0.01 to 0.82±0.03, between the first and second parities, from 0.73±0.03 to 0.8±0.04 between the first and third parities, and from 0.82±0.02 to 0.84±0.04 between the second and third parities. Conclusion These results are comparable to previously reported estimates on the same population, indicating that the adoption of a random regression TD model as the official genetic evaluation for production traits in Tunisia, as developed by most Interbull countries, is possible in the Tunisian Holsteins. PMID:28823122

Genetic analysis of milk production traits of Tunisian Holsteins using random regression test-day model with Legendre polynomials.

PubMed

Ben Zaabza, Hafedh; Ben Gara, Abderrahmen; Rekik, Boulbaba

2018-05-01

The objective of this study was to estimate genetic parameters of milk, fat, and protein yields within and across lactations in Tunisian Holsteins using a random regression test-day (TD) model. A random regression multiple trait multiple lactation TD model was used to estimate genetic parameters in the Tunisian dairy cattle population. Data were TD yields of milk, fat, and protein from the first three lactations. Random regressions were modeled with third-order Legendre polynomials for the additive genetic, and permanent environment effects. Heritabilities, and genetic correlations were estimated by Bayesian techniques using the Gibbs sampler. All variance components tended to be high in the beginning and the end of lactations. Additive genetic variances for milk, fat, and protein yields were the lowest and were the least variable compared to permanent variances. Heritability values tended to increase with parity. Estimates of heritabilities for 305-d yield-traits were low to moderate, 0.14 to 0.2, 0.12 to 0.17, and 0.13 to 0.18 for milk, fat, and protein yields, respectively. Within-parity, genetic correlations among traits were up to 0.74. Genetic correlations among lactations for the yield traits were relatively high and ranged from 0.78±0.01 to 0.82±0.03, between the first and second parities, from 0.73±0.03 to 0.8±0.04 between the first and third parities, and from 0.82±0.02 to 0.84±0.04 between the second and third parities. These results are comparable to previously reported estimates on the same population, indicating that the adoption of a random regression TD model as the official genetic evaluation for production traits in Tunisia, as developed by most Interbull countries, is possible in the Tunisian Holsteins.

Genetic factors in familial aggregation of blood pressure of Portuguese nuclear families.

PubMed

Fermino, Rogério César; Seabra, André; Garganta, Rui; Maia, José António Ribeiro

2009-03-01

Despite of the increase in the prevalence of hypertension in Portugal, the importance of genetic factors in blood pressure (BP) has not been studied extensively in our country. To verify the indirect presence of vertical transmission of genetic factors between parents and children in BP values, and to estimate the magnitude of genetic factors contributing for variation in BP values in the population. Sample size comprises 367 individuals (164 parents and 203 children) pertaining the 107 nuclear families participating in 'Familias Activas' project, proceeding from different regions of North Portugal. The BP was measured with Omron model M6 (HEM-7001-E) digital device. SPSS 15.0 was used for data analysis; PEDSTATS was used to verify the structure of each family data. Familial correlations and heritability estimates were computed in FCOR and ASSOC modules of S.A.G.E. version 5.3. For systolic BP (SBP), correlation values were low to moderate (0.21< or = r < or =0.35); for diastolic BP (DBP) values were found to be moderate (0.24< or = r < or =0. 50). Genetic factors explain 43 and 49% of the total variation in SBP and DBP, respectively. A moderate amount of the SBP and the DBP is accounted for by genetic factors.

Epigenetic differentiation and relationship to adaptive genetic divergence in discrete populations of the violet Viola cazorlensis.

PubMed

Herrera, Carlos M; Bazaga, Pilar

2010-08-01

*In plants, epigenetic variations based on DNA methylation are often heritable and could influence the course of evolution. Before this hypothesis can be assessed, fundamental questions about epigenetic variation remain to be addressed in a real-world context, including its magnitude, structuring within and among natural populations, and autonomy in relation to the genetic context. *Extent and patterns of cytosine methylation, and the relationship to adaptive genetic divergence between populations, were investigated for wild populations of the southern Spanish violet Viola cazorlensis (Violaceae) using the methylation-sensitive amplified polymorphism (MSAP) technique, a modification of the amplified fragment length polymorphism method (AFLP) based on the differential sensitivity of isoschizomeric restriction enzymes to site-specific cytosine methylation. *The genome of V. cazorlensis plants exhibited extensive levels of methylation, and methylation-based epigenetic variation was structured into distinct between- and within- population components. Epigenetic differentiation of populations was correlated with adaptive genetic divergence revealed by a Bayesian population-genomic analysis of AFLP data. Significant associations existed at the individual genome level between adaptive AFLP loci and the methylation state of methylation-susceptible MSAP loci. *Population-specific, divergent patterns of correlated selection on epigenetic and genetic individual variation could account for the coordinated epigenetic-genetic adaptive population differentiation revealed by this study.

Distinct evolutionary strategies of human leucocyte antigen loci in pathogen-rich environments

PubMed Central

Sanchez-Mazas, Alicia; Lemaître, Jean-François; Currat, Mathias

2012-01-01

Human leucocyte antigen (HLA) loci have a complex evolution where both stochastic (e.g. genetic drift) and deterministic (natural selection) forces are involved. Owing to their extraordinary level of polymorphism, HLA genes are useful markers for reconstructing human settlement history. However, HLA variation often deviates significantly from neutral expectations towards an excess of genetic diversity. Because HLA molecules play a crucial role in immunity, this observation is generally explained by pathogen-driven-balancing selection (PDBS). In this study, we investigate the PDBS model by analysing HLA allelic diversity on a large database of 535 populations in relation to pathogen richness. Our results confirm that geographical distances are excellent predictors of HLA genetic differentiation worldwide. We also find a significant positive correlation between genetic diversity and pathogen richness at two HLA class I loci (HLA-A and -B), as predicted by PDBS, and a significant negative correlation at one HLA class II locus (HLA-DQB1). Although these effects are weak, as shown by a loss of significance when populations submitted to rapid genetic drift are removed from the analysis, the inverse relationship between genetic diversity and pathogen richness at different loci indicates that HLA genes have adopted distinct evolutionary strategies to provide immune protection in pathogen-rich environments. PMID:22312050

Self-reported psychological demands, skill discretion and decision authority at work: A twin study.

PubMed

Theorell, Töres; De Manzano, Örjan; Lennartsson, Anna-Karin; Pedersen, Nancy L; Ullén, Fredrik

2016-06-01

To examine the contribution of genetic factors to self-reported psychological demands (PD), skill discretion (SD) and decision authority (DA) and the possible importance of such influence on the association between these work variables and depressive symptoms. 11,543 participants aged 27-54 in the Swedish Twin Registry participated in a web survey. First of all, in multiple regressions, phenotypic associations between each one of the three work environment variables and depressive symptoms were analysed. Secondly, by means of classical twin analysis, the genetic contribution to PD, SD and DA was assessed. After this, cross-twin cross-trait correlations were computed between PD, SD and DA, on the one hand, and depressive symptom score, on the other hand. The genetic contribution to self-reported PD, DS and DA ranged from 18% for decision authority to 30% for skill discretion. Cross-twin cross-trait correlations were very weak (r values < .1) and non-significant for dizygotic twins, and we lacked power to analyse the genetic architecture of the phenotypic associations using bivariate twin modelling. However, substantial genetic contribution to these associations seems unlikely. CONCLUSIONS GENETIC CONTRIBUTIONS TO THE SELF-REPORTED WORK ENVIRONMENT SCORES WERE 18-30%. © 2016 the Nordic Societies of Public Health.

Bivariate Heritability of Total and Regional Brain Volumes: the Framingham Study

PubMed Central

DeStefano, Anita L.; Seshadri, Sudha; Beiser, Alexa; Atwood, Larry D.; Massaro, Joe M.; Au, Rhoda; Wolf, Philip A.; DeCarli, Charles

2009-01-01

Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging (MRI) who were free of stroke and other neurological disorders that might influence brain volumes and who were members of families with at least two Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile. Genetic and environmental correlations between traits were obtained from bivariate analysis. Heritability estimates ranging from 0.46 to 0.60, were observed for total brain, white matter hyperintensity, hippocampal, temporal lobe, and lateral ventricular volumes. Moderate, yet significant, heritability was observed for the other measures. Bivariate analyses demonstrated that relationships between brain volume measures, except for white matter hyperintensity, reflected both moderate to strong shared genetic and shared environmental influences. This study confirms strong genetic effects on brain and white matter hyperintensity volumes. These data extend current knowledge by showing that these two different types of MRI measures do not share underlying genetic or environmental influences. PMID:19812462

Methods for meta-analysis of multiple traits using GWAS summary statistics.

PubMed

Ray, Debashree; Boehnke, Michael

2018-03-01

Genome-wide association studies (GWAS) for complex diseases have focused primarily on single-trait analyses for disease status and disease-related quantitative traits. For example, GWAS on risk factors for coronary artery disease analyze genetic associations of plasma lipids such as total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides (TGs) separately. However, traits are often correlated and a joint analysis may yield increased statistical power for association over multiple univariate analyses. Recently several multivariate methods have been proposed that require individual-level data. Here, we develop metaUSAT (where USAT is unified score-based association test), a novel unified association test of a single genetic variant with multiple traits that uses only summary statistics from existing GWAS. Although the existing methods either perform well when most correlated traits are affected by the genetic variant in the same direction or are powerful when only a few of the correlated traits are associated, metaUSAT is designed to be robust to the association structure of correlated traits. metaUSAT does not require individual-level data and can test genetic associations of categorical and/or continuous traits. One can also use metaUSAT to analyze a single trait over multiple studies, appropriately accounting for overlapping samples, if any. metaUSAT provides an approximate asymptotic P-value for association and is computationally efficient for implementation at a genome-wide level. Simulation experiments show that metaUSAT maintains proper type-I error at low error levels. It has similar and sometimes greater power to detect association across a wide array of scenarios compared to existing methods, which are usually powerful for some specific association scenarios only. When applied to plasma lipids summary data from the METSIM and the T2D-GENES studies, metaUSAT detected genome-wide significant loci beyond the ones identified by univariate analyses. Evidence from larger studies suggest that the variants additionally detected by our test are, indeed, associated with lipid levels in humans. In summary, metaUSAT can provide novel insights into the genetic architecture of a common disease or traits. © 2017 WILEY PERIODICALS, INC.

The effects of riverine physical complexity on anadromy and genetic diversity in steelhead or rainbow trout Oncorhynchus mykiss around the Pacific Rim.

PubMed

McPhee, M V; Whited, D C; Kuzishchin, K V; Stanford, J A

2014-07-01

This study explored the relationship between riverine physical complexity, as determined from remotely sensed metrics, and anadromy and genetic diversity in steelhead or rainbow trout Oncorhynchus mykiss. The proportion of anadromy (estimated fraction of individuals within a drainage that are anadromous) was correlated with riverine complexity, but this correlation appeared to be driven largely by a confounding negative relationship between drainage area and the proportion of anadromy. Genetic diversity decreased with latitude, was lower in rivers with only non-anadromous individuals and also decreased with an increasing ratio of floodplain area to total drainage area. Anadromy may be less frequent in larger drainages due to the higher cost of migration associated with reaches farther from the ocean, and the negative relationship between genetic diversity and floodplain area may be due to lower effective population size resulting from greater population fluctuations associated with higher rates of habitat turnover. Ultimately, the relationships between riverine physical complexity and migratory life history or genetic diversity probably depend on the spatial scale of analysis. © 2014 The Fisheries Society of the British Isles.

Genetic diversity patterns of arbuscular mycorrhizal fungi associated with the mycoheterotroph Arachnitis uniflora Phil. (Corsiaceae)

PubMed Central

Acosta, M. Cristina; Cofré, Noelia; Domínguez, Laura S.; Bidartondo, Martin I.; Sérsic, Alicia N.

2017-01-01

Abstract Background and Aims Arachnitis uniflora is a mycoheterotrophic plant that exploits arbuscular mycorrhizal fungi of neighbouring plants. We tested A. uniflora's specificity towards fungi across its large latitudinal range, as well as the role of historical events and current environmental, geographical and altitudinal variables on fungal genetic diversity. Methods Arachnitis uniflora mycorrhizas were sampled at 25 sites. Fungal phylogenetic relationships were reconstructed, genetic diversity was calculated and the main divergent lineages were dated. Phylogeographical analysis was performed with the main fungal clade. Fungal diversity correlations with environmental factors were investigated. Key Results Glomeraceae fungi dominated, with a main clade that likely originated in the Upper Cretaceous and diversified in the Miocene. Two other arbuscular mycorrhizal fungal families not previously known to be targeted by A. uniflora were detected rarely and appear to be facultative associations. High genetic diversity, found in Bolivia and both northern and southern Patagonia, was correlated with temperature, rainfall and soil features. Conclusions Fungal genetic diversity and its distribution can be explained by the ancient evolutionary history of the target fungi and by micro-scale environmental conditions with a geographical mosaic pattern. PMID:28398457

High-Performance Computational Analysis of Glioblastoma Pathology Images with Database Support Identifies Molecular and Survival Correlates.

PubMed

Kong, Jun; Wang, Fusheng; Teodoro, George; Cooper, Lee; Moreno, Carlos S; Kurc, Tahsin; Pan, Tony; Saltz, Joel; Brat, Daniel

2013-12-01

In this paper, we present a novel framework for microscopic image analysis of nuclei, data management, and high performance computation to support translational research involving nuclear morphometry features, molecular data, and clinical outcomes. Our image analysis pipeline consists of nuclei segmentation and feature computation facilitated by high performance computing with coordinated execution in multi-core CPUs and Graphical Processor Units (GPUs). All data derived from image analysis are managed in a spatial relational database supporting highly efficient scientific queries. We applied our image analysis workflow to 159 glioblastomas (GBM) from The Cancer Genome Atlas dataset. With integrative studies, we found statistics of four specific nuclear features were significantly associated with patient survival. Additionally, we correlated nuclear features with molecular data and found interesting results that support pathologic domain knowledge. We found that Proneural subtype GBMs had the smallest mean of nuclear Eccentricity and the largest mean of nuclear Extent, and MinorAxisLength. We also found gene expressions of stem cell marker MYC and cell proliferation maker MKI67 were correlated with nuclear features. To complement and inform pathologists of relevant diagnostic features, we queried the most representative nuclear instances from each patient population based on genetic and transcriptional classes. Our results demonstrate that specific nuclear features carry prognostic significance and associations with transcriptional and genetic classes, highlighting the potential of high throughput pathology image analysis as a complementary approach to human-based review and translational research.

Genetic Factors of Individual Differences in Decision Making in Economic Behavior: A Japanese Twin Study using the Allais Problem.

PubMed

Shikishima, Chizuru; Hiraishi, Kai; Yamagata, Shinji; Ando, Juko; Okada, Mitsuhiro

2015-01-01

Why does decision making differ among individuals? People sometimes make seemingly inconsistent decisions with lower expected (monetary) utility even when objective information of probabilities and reward are provided. It is noteworthy, however, that a certain proportion of people do not provide anomalous responses, choosing the alternatives with higher expected utility, thus appearing to be more "rational." We investigated the genetic and environmental influences on these types of individual differences in decision making using a classical Allais problem task. Participants were 1,199 Japanese adult twins aged 20-47. Univariate genetic analysis revealed that approximately a third of the Allais problem response variance was explained by genetic factors and the rest by environmental factors unique to individuals and measurement error. The environmental factor shared between families did not contribute to the variance. Subsequent multivariate genetic analysis clarified that decision making using the expected utility theory was associated with general intelligence and that the association was largely mediated by the same genetic factor. We approach the mechanism underlying two types of "rational" decision making from the perspective of genetic correlations with cognitive abilities.

Genetic and environmental correlations between subjective wellbeing and experience of life events in adolescence.

PubMed

Wootton, Robyn E; Davis, Oliver S P; Mottershaw, Abigail L; Wang, R Adele H; Haworth, Claire M A

2017-09-01

Some life events appear heritable due to the genetic influence on related behaviours. Shared genetic influence between negative behaviours and negative life events has previously been established. This study investigated whether subjective wellbeing and positive life events were genetically associated. Participants in the Twins Early Development Study (aged 16.32 ± .68 years) completed subjective wellbeing and life events assessments via two separate studies (overlapping N for wellbeing and life events measures ranged from 3527 to 9350). We conducted bivariate twin models between both positive and negative life events with subjective wellbeing and related positive psychological traits including subjective happiness, life satisfaction, optimism, hopefulness and gratitude measured at 16 years. Results suggested that the heritability of life events can partially be explained by shared genetic influences with the wellbeing indicators. Wellbeing traits were positively genetically correlated with positive life events and negatively correlated with negative life events (except curiosity where there was no correlation). Those positive traits that drive behaviour (grit and ambition) showed the highest genetic correlation with life events, whereas the reflective trait gratitude was less correlated. This suggests that gene-environment correlations might explain the observed genetic association between life events and wellbeing. Inheriting propensity for positive traits might cause you to seek environments that lead to positive life events and avoid environments which make negative life events more likely.

A twin-sibling study on the relationship between exercise attitudes and exercise behavior.

PubMed

Huppertz, Charlotte; Bartels, Meike; Jansen, Iris E; Boomsma, Dorret I; Willemsen, Gonneke; de Moor, Marleen H M; de Geus, Eco J C

2014-01-01

Social cognitive models of health behavior propose that individual differences in leisure time exercise behavior are influenced by the attitudes towards exercise. At the same time, large scale twin-family studies show a significant influence of genetic factors on regular exercise behavior. This twin-sibling study aimed to unite these findings by demonstrating that exercise attitudes can be heritable themselves. Secondly, the genetic and environmental cross-trait correlations and the monozygotic (MZ) twin intrapair differences model were used to test whether the association between exercise attitudes and exercise behavior can be causal. Survey data were obtained from 5,095 twins and siblings (18-50 years). A genetic contribution was found for exercise behavior (50 % in males, 43 % in females) and for the six exercise attitude components derived from principal component analysis: perceived benefits (21, 27 %), lack of skills, support and/or resources (45, 48 %), time constraints (25, 30 %), lack of energy (34, 44 %), lack of enjoyment (47, 44 %), and embarrassment (42, 49 %). These components were predictive of leisure time exercise behavior (R(2) = 28 %). Bivariate modeling further showed that all the genetic (0.36 < |rA| < 0.80) and all but two unique environmental (0.00 < |rE| < 0.27) correlations between exercise attitudes and exercise behavior were significantly different from zero, which is a necessary condition for the existence of a causal effect driving the association. The correlations between the MZ twins' difference scores were in line with this finding. It is concluded that exercise attitudes and exercise behavior are heritable, that attitudes and behavior are partly correlated through pleiotropic genetic effects, but that the data are compatible with a causal association between exercise attitudes and behavior.

A Twin-Sibling Study on the Relationship Between Exercise Attitudes and Exercise Behavior

PubMed Central

Bartels, Meike; Jansen, Iris E.; Boomsma, Dorret I.; Willemsen, Gonneke; de Moor, Marleen H. M.; de Geus, Eco J. C.

2013-01-01

Social cognitive models of health behavior propose that individual differences in leisure time exercise behavior are influenced by the attitudes towards exercise. At the same time, large scale twin-family studies show a significant influence of genetic factors on regular exercise behavior. This twin–sibling study aimed to unite these findings by demonstrating that exercise attitudes can be heritable themselves. Secondly, the genetic and environmental cross-trait correlations and the monozygotic (MZ) twin intrapair differences model were used to test whether the association between exercise attitudes and exercise behavior can be causal. Survey data were obtained from 5,095 twins and siblings (18–50 years). A genetic contribution was found for exercise behavior (50 % in males, 43 % in females) and for the six exercise attitude components derived from principal component analysis: perceived benefits (21, 27 %), lack of skills, support and/or resources (45, 48 %), time constraints (25, 30 %), lack of energy (34, 44 %), lack of enjoyment (47, 44 %), and embarrassment (42, 49 %). These components were predictive of leisure time exercise behavior (R2 = 28 %). Bivariate modeling further showed that all the genetic (0.36 <|rA| <0.80) and all but two unique environmental (0.00 <|rE| <0.27) correlations between exercise attitudes and exercise behavior were significantly different from zero, which is a necessary condition for the existence of a causal effect driving the association. The correlations between the MZ twins’ difference scores were in line with this finding. It is concluded that exercise attitudes and exercise behavior are heritable, that attitudes and behavior are partly correlated through pleiotropic genetic effects, but that the data are compatible with a causal association between exercise attitudes and behavior. PMID:24072598

Microsatellite diversity among the primitive tribes of India

PubMed Central

Mukherjee, Malay B.; Tripathy, V.; Colah, R. B.; Solanki, P. K.; Ghosh, K.; Reddy, B. M.; Mohanty, D.

2009-01-01

The present study was undertaken to determine the extent of diversity at 12 microsatellite short tandem repeat (STR) loci in seven primitive tribal populations of India with diverse linguistic and geographic backgrounds. DNA samples of 160 unrelated individuals were analyzed for 12 STR loci by multiplex polymerase chain reaction (PCR). Gene diversity analysis suggested that the average heterozygosity was uniformly high ( >0.7) in these groups and varied from 0.705 to 0.794. The Hardy-Weinberg equilibrium analysis revealed that these populations were in genetic equilibrium at almost all the loci. The overall GST value was high (GST = 0.051; range between 0.026 and 0.098 among the loci), reflecting the degree of differentiation/heterogeneity of seven populations studied for these loci. The cluster analysis and multidimensional scaling of genetic distances reveal two broad clusters of populations, besides Moolu Kurumba maintaining their distinct genetic identity vis-à-vis other populations. The genetic affinity for the three tribes of the Indo-European family could be explained based on geography and Language but not for the four Dravidian tribes as reflected by the NJT and MDS plots. For the overall data, the insignificant MANTEL correlations between genetic, linguistic and geographic distances suggest that the genetic variation among these tribes is not patterned along geographic and/or linguistic lines. PMID:21088716

Language and Traits of Autism Spectrum Conditions: Evidence of Limited Phenotypic and Etiological Overlap

PubMed Central

Taylor, Mark J.; Charman, Tony; Robinson, Elise B.; Hayiou-Thomas, Marianna E.; Happé, Francesca; Dale, Philip S.; Ronald, Angelica

2015-01-01

Language difficulties have historically been viewed as integral to autism spectrum conditions (ASC), leading molecular genetic studies to consider whether ASC and language difficulties have overlapping genetic bases. The extent of genetic, and also environmental, overlap between ASC and language is, however, unclear. We hence conducted a twin study of the concurrent association between autistic traits and receptive language abilities. Internet-based language tests were completed by ~3,000 pairs of twins, while autistic traits were assessed via parent ratings. Twin model fitting explored the association between these measures in the full sample, while DeFries-Fulker analysis tested these associations at the extremes of the sample. Phenotypic associations between language ability and autistic traits were modest and negative. The degree of genetic overlap was also negative, indicating that genetic influences on autistic traits lowered language scores in the full sample (mean genetic correlation = −0.13). Genetic overlap was also low at the extremes of the sample (mean genetic correlation = 0.14), indicating that genetic influences on quantitatively defined language difficulties were largely distinct from those on extreme autistic traits. Variation in language ability and autistic traits were also associated with largely different nonshared environmental influences. Language and autistic traits are influenced by largely distinct etiological factors. This has implications for molecular genetic studies of ASC and understanding the etiology of ASC. Additionally, these findings lend support to forthcoming DSM-5 changes to ASC diagnostic criteria that will see language difficulties separated from the core ASC communication symptoms, and instead listed as a clinical specifier. PMID:25088445

Depth as an Organizing Force in Pocillopora damicornis: Intra-Reef Genetic Architecture

PubMed Central

Gorospe, Kelvin D.; Karl, Stephen A.

2015-01-01

Relative to terrestrial plants, and despite similarities in life history characteristics, the potential for corals to exhibit intra-reef local adaptation in the form of genetic differentiation along an environmental gradient has received little attention. The potential for natural selection to act on such small scales is likely increased by the ability of coral larval dispersal and settlement to be influenced by environmental cues. Here, we combine genetic, spatial, and environmental data for a single patch reef in Kāne‘ohe Bay, O‘ahu, Hawai‘i, USA in a landscape genetics framework to uncover environmental drivers of intra-reef genetic structuring. The genetic dataset consists of near-exhaustive sampling (n = 2352) of the coral, Pocillopora damicornis at our study site and six microsatellite genotypes. In addition, three environmental parameters – depth and two depth-independent temperature indices – were collected on a 4 m grid across 85 locations throughout the reef. We use ordinary kriging to spatially interpolate our environmental data and estimate the three environmental parameters for each colony. Partial Mantel tests indicate a significant correlation between genetic relatedness and depth while controlling for space. These results are also supported by multi-model inference. Furthermore, spatial Principle Component Analysis indicates a statistically significant genetic cline along a depth gradient. Binning the genetic dataset based on size-class revealed that the correlation between genetic relatedness and depth was significant for new recruits and increased for larger size classes, suggesting a possible role of larval habitat selection as well as selective mortality in structuring intra-reef genetic diversity. That both pre- and post-recruitment processes may be involved points to the adaptive role of larval habitat selection in increasing adult survival. The conservation importance of uncovering intra-reef patterns of genetic diversity is discussed. PMID:25806798

Genetic analysis of Holstein cattle populations in Brazil and the United States.

PubMed

Costa, C N; Blake, R W; Pollak, E J; Oltenacu, P A; Quaas, R L; Searle, S R

2000-12-01

Genetic relationships between Brazilian and US Holstein cattle populations were studied using first-lactation records of 305-d mature equivalent (ME) yields of milk and fat of daughters of 705 sires in Brazil and 701 sires in the United States, 358 of which had progeny in both countries. Components of(co)variance and genetic parameters were estimated from all data and from within herd-year standard deviation for milk (HYSD) data files using bivariate and multivariate sire models and DFREML procedures distinguishing the two countries. Sire (residual) variances from all data for milk yield were 51 to 59% (58 to 101%) as large in Brazil as those obtained from half-sisters in the average US herd. Corresponding proportions of the US variance in fat yield that were found in Brazil were 30 to 41% for the sire component of variance and 48 to 80% for the residual. Heritabilities for milk and fat yields from multivariate analysis of all the data were 0.25 and 0.22 in Brazil, and 0.34 and 0.35 in the United States. Genetic correlations between milk and fat were 0.79 in Brazil and 0.62 in the United States. Genetic correlations between countries were 0.85 for milk, 0.88 for fat, 0.55 for milk in Brazil and fat in the US, and 0.67 for fat in Brazil and milk in the United States. Correlated responses in Brazil from sire selection based on the US information increased with average HYSD in Brazil. Largest daughter yield response was predicted from information from half-sisters in low HYSD US herds (0.75 kg/kg for milk; 0.63 kg/kg for fat), which was 14% to 17% greater than estimates from all US herds because the scaling effects were less severe from heterogeneous variances. Unequal daughter response from unequal genetic (co)variances under restrictive Brazilian conditions is evidence for the interaction of genotype and environment. The smaller and variable yield expectations of daughters of US sires in Brazilian environments suggest the need for specific genetic improvement strategies in Brazilian Holstein herds. A US data file restricting daughter information to low HYSD US environments would be a wise choice for across-country evaluation. Procedures to incorporate such foreign evaluations should be explored to improve the accuracy of genetic evaluations for the Brazilian Holstein population.

Teachers' Conceptions About the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

NASA Astrophysics Data System (ADS)

Castéra, Jérémy; Clément, Pierre

2014-02-01

This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed teachers' conceptions. This illustrates that innatism is present in two distinct ways: in relation to individuals (e.g. genetic determinism to justify intellectual likeness between individuals such as twins) or in relation to groups of humans (e.g. genetic determinism to justify gender differences or the superiority of some human ethnic groups). A between-factor analysis discriminates between countries, showing very significant differences. There is more innatism among teachers' conceptions in African countries and Lebanon than in European countries, Brazil and Australia. Among the other controlled parameters, only two are significantly independent of the country: the level of training and the level of knowledge of biology. A co-inertia analysis shows a strong correlation between non-citizen attitudes towards and innatist conceptions of genetic determinism regarding human groups. We discuss these findings and their implications for education.

Genetic parameters of infectious bovine keratoconjunctivitis and its relationship with weight and parasite infestations in Australian tropical Bos taurus cattle.

PubMed

Ali, Abdirahman A; O'Neill, Christopher J; Thomson, Peter C; Kadarmideen, Haja N

2012-07-27

Infectious bovine keratoconjunctivitis (IBK) or 'pinkeye' is an economically important ocular disease that significantly impacts animal performance. Genetic parameters for IBK infection and its genetic and phenotypic correlations with cattle tick counts, number of helminth (unspecified species) eggs per gram of faeces and growth traits in Australian tropically adapted Bos taurus cattle were estimated. Animals were clinically examined for the presence of IBK infection before and after weaning when the calves were 3 to 6 months and 15 to 18 months old, respectively and were also recorded for tick counts, helminth eggs counts as an indicator of intestinal parasites and live weights at several ages including 18 months. Negative genetic correlations were estimated between IBK incidence and weight traits for animals in pre-weaning and post-weaning datasets. Genetic correlations among weight measurements were positive, with moderate to high values. Genetic correlations of IBK incidence with tick counts were positive for the pre-weaning and negative for the post-weaning datasets but negative with helminth eggs counts for the pre-weaning dataset and slightly positive for the post-weaning dataset. Genetic correlations between tick and helminth eggs counts were moderate and positive for both datasets. Phenotypic correlations of IBK incidence with helminth eggs per gram of faeces were moderate and positive for both datasets, but were close to zero for both datasets with tick counts. Our results suggest that genetic selection against IBK incidence in tropical cattle is feasible and that calves genetically prone to acquire IBK infection could also be genetically prone to have a slower growth. The positive genetic correlations among weight traits and between tick and helminth eggs counts suggest that they are controlled by common genes (with pleiotropic effects). Genetic correlations between IBK incidence and tick and helminth egg counts were moderate and opposite between pre-weaning and post-weaning datasets, suggesting that the environmental and (or) maternal effects differ between these two growth phases. This preliminary study provides estimated genetic parameters for IBK incidence, which could be used to design selection and breeding programs for tropical adaptation in beef cattle.

Genetic parameters of infectious bovine keratoconjunctivitis and its relationship with weight and parasite infestations in Australian tropical Bos taurus cattle

PubMed Central

2012-01-01

Background Infectious bovine keratoconjunctivitis (IBK) or ‘pinkeye’ is an economically important ocular disease that significantly impacts animal performance. Genetic parameters for IBK infection and its genetic and phenotypic correlations with cattle tick counts, number of helminth (unspecified species) eggs per gram of faeces and growth traits in Australian tropically adapted Bos taurus cattle were estimated. Methods Animals were clinically examined for the presence of IBK infection before and after weaning when the calves were 3 to 6 months and 15 to 18 months old, respectively and were also recorded for tick counts, helminth eggs counts as an indicator of intestinal parasites and live weights at several ages including 18 months. Results Negative genetic correlations were estimated between IBK incidence and weight traits for animals in pre-weaning and post-weaning datasets. Genetic correlations among weight measurements were positive, with moderate to high values. Genetic correlations of IBK incidence with tick counts were positive for the pre-weaning and negative for the post-weaning datasets but negative with helminth eggs counts for the pre-weaning dataset and slightly positive for the post-weaning dataset. Genetic correlations between tick and helminth eggs counts were moderate and positive for both datasets. Phenotypic correlations of IBK incidence with helminth eggs per gram of faeces were moderate and positive for both datasets, but were close to zero for both datasets with tick counts. Conclusions Our results suggest that genetic selection against IBK incidence in tropical cattle is feasible and that calves genetically prone to acquire IBK infection could also be genetically prone to have a slower growth. The positive genetic correlations among weight traits and between tick and helminth eggs counts suggest that they are controlled by common genes (with pleiotropic effects). Genetic correlations between IBK incidence and tick and helminth egg counts were moderate and opposite between pre-weaning and post-weaning datasets, suggesting that the environmental and (or) maternal effects differ between these two growth phases. This preliminary study provides estimated genetic parameters for IBK incidence, which could be used to design selection and breeding programs for tropical adaptation in beef cattle. PMID:22839739

Genetic parameters for image analysis traits on M. longissimus thoracis and M. trapezius of carcass cross section in Japanese Black steers.

PubMed

Osawa, T; Kuchida, K; Hidaka, S; Kato, T

2008-01-01

In Japan, the degree of marbling in ribeye (M. longissimus thoracis) is evaluated in the beef meat grading process. However, other muscles (e.g., M. trapezius) are also important in determining the meat quality and carcass market prices. The purpose of this study was to estimate genetic parameters for M. longissimus thoracis (M-LONG) and M. trapezius (M-TRAP) of carcass cross section of Japanese Black steers by computer image analysis. The number of records of Japanese Black steers and the number of pedigree records were 2,925 and 10,889, respectively. Digital images of the carcass cross section were taken between the sixth and seventh ribs by photographing equipment. Muscle area (MA), fat area ratio (FAR), overall coarseness of marbling particles (OCM), and coarseness of maximum marbling particle (MMC) in M-LONG and M-TRAP were calculated by image analysis. Genetic parameters for these traits were estimated using the AIREMLF90 program with an animal model. Fixed effects that were included in the model were dates of arrival at the carcass market and slaughter age (mo), and random effects of fattening farms, additive genetic effects and residuals were included in the model. For M-LONG, heritability estimates (+/-SE) were 0.46 +/- 0.06, 0.59 +/- 0.06, 0.47 +/- 0.06, and 0.20 +/- 0.05 for MA, FAR, OCM, and MMC, respectively. Heritability estimates (+/-SE) in M-TRAP were 0.47 +/- 0.06, 0.57 +/- 0.07, 0.49 +/- 0.07, and 0.13 +/- 0.04 for the same traits. Genetic correlations between subcutaneous fat thickness and FAR for M-LONG and M-TRAP were negative (-0.21 and -0.19, respectively). Those correlations between M-LONG and M-TRAP were moderate to high for MA, FAR, OCM, and MMC (0.38, 0.52, 0.39, and 0.60, respectively). These results indicate that other muscles including M-LONG should be evaluated for more efficient genetic improvement.

EvolQG - An R package for evolutionary quantitative genetics

PubMed Central

Melo, Diogo; Garcia, Guilherme; Hubbe, Alex; Assis, Ana Paula; Marroig, Gabriel

2016-01-01

We present an open source package for performing evolutionary quantitative genetics analyses in the R environment for statistical computing. Evolutionary theory shows that evolution depends critically on the available variation in a given population. When dealing with many quantitative traits this variation is expressed in the form of a covariance matrix, particularly the additive genetic covariance matrix or sometimes the phenotypic matrix, when the genetic matrix is unavailable and there is evidence the phenotypic matrix is sufficiently similar to the genetic matrix. Given this mathematical representation of available variation, the \\textbf{EvolQG} package provides functions for calculation of relevant evolutionary statistics; estimation of sampling error; corrections for this error; matrix comparison via correlations, distances and matrix decomposition; analysis of modularity patterns; and functions for testing evolutionary hypotheses on taxa diversification. PMID:27785352

Genetics of the Framingham Heart Study Population

PubMed Central

Govindaraju, Diddahally R.; Cupples, L. Adrienne; Kannel, William B.; O’Donnell, Christopher J.; Atwood, Larry D.; D’Agostino, Ralph B.; Fox, Caroline S.; Larson, Marty; Levy, Daniel; Morabito, Joanne; Vasan, Ramachandran S.; Splansky, Greta Lee; Wolf, Philip A.; Benjamin, Emelia J.

2010-01-01

This article provides an introduction to the Framingham Heart Study (FHS) and the genetic research related to cardiovascular diseases conducted in this unique population1. It briefly describes the origins of the study, the risk factors that contribute to heart disease and the approaches taken to discover the genetic basis of some of these risk factors. The genetic architecture of several biological risk factors has been explained using family studies, segregation analysis, heritability, phenotypic and genetic correlations. Many quantitative trait loci underlying cardiovascular diseases have been discovered using different molecular markers. Additionally, results from genome-wide association studies using 100,000 markers, and the prospects of using 550,000 markers for association studies are presented. Finally, the use of this unique sample in genotype and environment interaction is described. PMID:19010253

A genetic analysis of post-weaning feedlot performance and profitability in Bonsmara cattle.

PubMed

van der Westhuizen, R R; van der Westhuizen, J; Schoeman, S J

2009-02-25

The aim of this study was to identify factors influencing profitability in a feedlot environment and to estimate genetic parameters for and between a feedlot profit function and productive traits measured in growth tests. The heritability estimate of 0.36 for feedlot profitability shows that this trait is genetically inherited and that it can be selected for. The genetic correlations between feedlot profitability and production and efficiency varied from negligible to high. The genetic correlation estimate of -0.92 between feed conversion ratio and feedlot profitability is largely due to the part-whole relationship between these two traits. Consequently, a multiple regression equation was developed to estimate a feed intake value for all performance-tested Bonsmara bulls, which were group fed and whose feed intakes were unknown. These predicted feed intake values enabled the calculation of a post-weaning growth or feedlot profitability value for all tested bulls, even where individual feed intakes were unknown. Subsequently, a feedlot profitability value for each bull was calculated in a favorable economic environment, an average economic environment and in an unfavorable economic environment. The high Pearson and Spearman correlations between the estimate breeding values based on the average economic environment and the other two environments suggested that the average economic environment could be used to calculate estimate breeding values for feedlot profitability. It is therefore not necessary to change the carcass, weaned calf or feed price on a regular basis to allow for possible re-rankings based on estimate breeding values.

Factors that cause genotype by environment interaction and use of a multiple-trait herd-cluster model for milk yield of Holstein cattle from Brazil and Colombia.

PubMed

Cerón-Muñoz, M F; Tonhati, H; Costa, C N; Rojas-Sarmiento, D; Echeverri Echeverri, D M

2004-08-01

Descriptive herd variables (DVHE) were used to explain genotype by environment interactions (G x E) for milk yield (MY) in Brazilian and Colombian production environments and to develop a herd-cluster model to estimate covariance components and genetic parameters for each herd environment group. Data consisted of 180,522 lactation records of 94,558 Holstein cows from 937 Brazilian and 400 Colombian herds. Herds in both countries were jointly grouped in thirds according to 8 DVHE: production level, phenotypic variability, age at first calving, calving interval, percentage of imported semen, lactation length, and herd size. For each DVHE, REML bivariate animal model analyses were used to estimate genetic correlations for MY between upper and lower thirds of the data. Based on estimates of genetic correlations, weights were assigned to each DVHE to group herds in a cluster analysis using the FASTCLUS procedure in SAS. Three clusters were defined, and genetic and residual variance components were heterogeneous among herd clusters. Estimates of heritability in clusters 1 and 3 were 0.28 and 0.29, respectively, but the estimate was larger (0.39) in Cluster 2. The genetic correlations of MY from different clusters ranged from 0.89 to 0.97. The herd-cluster model based on DVHE properly takes into account G x E by grouping similar environments accordingly and seems to be an alternative to simply considering country borders to distinguish between environments.

Molecular genetic analysis of the F11 gene in 14 Turkish patients with factor XI deficiency: identification of novel and recurrent mutations and their inheritance within families.

PubMed

Colakoglu, Seyma; Bayhan, Turan; Tavil, Betül; Keskin, Ebru Yılmaz; Cakir, Volkan; Gümrük, Fatma; Çetin, Mualla; Aytaç, Selin; Berber, Ergul

2018-01-01

Factor XI (FXI) deficiency is an autosomal bleeding disease associated with genetic defects in the F11 gene which cause decreased FXI levels or impaired FXI function. An increasing number of mutations has been reported in the FXI mutation database, most of which affect the serine protease domain of the protein. FXI is a heterogeneous disorder associated with a variable bleeding tendency and a variety of causative F11 gene mutations. The molecular basis of FXI deficiency in 14 patients from ten unrelated families in Turkey was analysed to establish genotype-phenotype correlations and inheritance of the mutations in the patients' families. Fourteen index cases with a diagnosis of FXI deficiency and family members of these patients were enrolled into the study. The patients' F11 genes were amplified by polymerase chain reaction and subjected to direct DNA sequencing analysis. The findings were analysed statistically using bivariate correlations, Pearson's correlation coefficient and the nonparametric Mann-Whitney test. Direct DNA sequencing analysis of the F11 genes revealed that all of the 14 patients had a F11 gene mutation. Eight different mutations were identified in the apple 1, apple 2 or serine protease domains, except one which was a splice site mutation. Six of the mutations were recurrent. Two of the mutations were novel missense mutations, p.Val522Gly and p.Cys581Arg, within the catalytic domain. The p.Trp519Stop mutation was observed in two families whereas all the other mutations were specific to a single family. Identification of mutations confirmed the genetic heterogeneity of FXI deficiency. Most of the patients with mutations did not have any bleeding complications, whereas some had severe bleeding symptoms. Genetic screening for F11 gene mutations is important to decrease the mortality and morbidity rate associated with FXI deficiency, which can be life-threatening if bleeding occurs in tissues with high fibrinolytic activity.

Why do measures of normal and disordered personality correlate? A study of genetic comorbidity.

PubMed

Jang, K L; Livesley, W J

1999-01-01

The genetic and environmental correlations between measures of normal (NEO-FFI) and abnormal personality (Dimensional Assessment of Personality Pathology: DAPP-BQ) were estimated in a sample of 545 volunteer general population twin pairs (269 monozygotic and 276 dizygotic pairs). The largest genetic correlations were observed between the 18 DAPP-BQ dimensions and NEO-FFI neuroticism (range = .05 to .81; median = .48), extraversion (range = -.65 to .33; median = -.28), agreeableness (range = -.65 to .00; median = -.38), and conscientiousness (range = -.76 to .52; median = -.31). The smallest genetic correlations were found between the DAPP-BQ dimensions and NEO-FFI openness (range = -.17 to .20; median = -.04). The environmental correlations are lower in magnitude but show the same pattern of correlations between DAPP-BQ and NEO-FFI scales. These results indicate that these two scales share a common broad-based genetic architecture, whereas the environmental influences show greater scale specificity.

Knowlege of, attitudes toward, and acceptance of genetically modified organisms among prospective teachers of biology, home economics, and grade school in Slovenia.

PubMed

Sorgo, Andrej; Ambrožič-Dolinšek, Jana

2010-05-01

The objective of this study was to investigate knowledge, opinions, and attitudes toward, as well as readiness to accept genetically modified organisms (GMOs) among prospective primary and secondary Slovene teachers. Our findings are that prospective teachers want to take an active role in rejecting or supporting individual GMOs and are aware of the importance of education about genetically modified organism (GMO) items and their potential significance for society. Through cluster analysis, we recognized four clusters of GMOs, separated by degree of genetically modified acceptability. GM plants and microorganisms which are recognized as useful are accepted. They are undecided about organisms used in research or medicine and reject organisms used for food consumption and for fun. There are only weak correlations between knowledge and attitudes and knowledge and acceptance of GMOs, and a strong correlation between attitudes and acceptance. The appropriate strategies and actions for improving university courses in biotechnology are discussed. Copyright © 2010 International Union of Biochemistry and Molecular Biology, Inc.

Meta-analysis of human leukocyte antigen genetic polymorphisms and susceptibility to chronic myelogenous leukemia in Chinese population.

PubMed

Zhang, Min-Yue; Chen, Fang-Yuan; Zhong, Hua

2011-12-01

Human leukocyte antigen (HLA) genetic polymorphisms are assumed to be correlated to the risk of chronic myelogenous leukemia (CML) in various ethnicities. Up to now, no clear consensus has been reached. Our goal is to address this issue in Chinese population. By searching the data in PubMed, Embase and four Chinese databases (prior to July 2010), the association of HLA genetic polymorphisms with CML has been fixed as the research objective. We studied a totality of 12 studies, comprising 2281 CML cases and 41000 health controls. The data demonstrated that HLA-A*11, A*74, HLA-B*40, B*47, B*55 and B*81 alleles were correlated with the increasing risk of CML. Nevertheless, HLA-DRB1*13 allele seemed to contribute to the genetic protection to CML. Conclusively we suggested that certain HLA alleles might be in association with the pathogenesis of CML in Chinese population. Due to little statistical scale, larger studies and particularly in a mono-people background, our hypothesis need to be further investigated in the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Population genetics study of functional brain asymmetry in the native and immigrant populations of northeastern USSR. I. Sex-age distribution and familial data].

PubMed

Solovenchuk, L L; Arshavskiĭ, V V

1988-05-01

Clearly definable polymorphism of hemisphere interrelations represented by three phenotypes was established by the method of EEG cross-correlation analysis. Each phenotype of the three, representing polymorphism, is characterized by marked specificity of perception and the processing of information, which determines certain integral physiological characteristics of individuals. Phenotype frequencies in aboriginal and new-come populations of the North-East of the USSR differ significantly. In comparison with the inhabitants, Moscow Russians of Magadan are significantly closer to aboriginal population, judging by their frequency distribution, and this may be due to the strategy specificity in adaptation of populations to environmental conditions. Significant difference in phenotype frequencies is shown in representatives of both sexes, this being more pronounced in the aboriginal population. The establishment of interhemispheric reaction type by approx. 10th year of individual's life is confirmed. Phenotype frequency correlations, depending on parental phenotype, were analyzed in children. The role of genetic and environmental factors in manifestation of the hemisphere relationship type is discussed. Rationality of the population analysis of hemisphere asymmetry types is grounded, according to the study of behavioural genetics and population adaptation.

Establishing an efficient way to utilize the drought resistance germplasm population in wheat.

PubMed

Wang, Jiancheng; Guan, Yajing; Wang, Yang; Zhu, Liwei; Wang, Qitian; Hu, Qijuan; Hu, Jin

2013-01-01

Drought resistance breeding provides a hopeful way to improve yield and quality of wheat in arid and semiarid regions. Constructing core collection is an efficient way to evaluate and utilize drought-resistant germplasm resources in wheat. In the present research, 1,683 wheat varieties were divided into five germplasm groups (high resistant, HR; resistant, R; moderate resistant, MR; susceptible, S; and high susceptible, HS). The least distance stepwise sampling (LDSS) method was adopted to select core accessions. Six commonly used genetic distances (Euclidean distance, Euclid; Standardized Euclidean distance, Seuclid; Mahalanobis distance, Mahal; Manhattan distance, Manhat; Cosine distance, Cosine; and Correlation distance, Correlation) were used to assess genetic distances among accessions. Unweighted pair-group average (UPGMA) method was used to perform hierarchical cluster analysis. Coincidence rate of range (CR) and variable rate of coefficient of variation (VR) were adopted to evaluate the representativeness of the core collection. A method for selecting the ideal constructing strategy was suggested in the present research. A wheat core collection for the drought resistance breeding programs was constructed by the strategy selected in the present research. The principal component analysis showed that the genetic diversity was well preserved in that core collection.

Correlation analysis for the incubation period of prion disease.

PubMed

Bae, Se-Eun; Jung, Sunghoon; Kim, Ha-Yeon; Son, Hyeon S

2012-07-01

Previous studies have shown that genetic quantitative trait loci (QTL), strain barriers, inoculation dose and inoculation method modulate the incubation period of prion diseases. We examined the relationship between a diverse set of physical, genetic and immunological characteristics and the incubation period of prion disease using correlation analyses. We found that incubation period was highly correlated with brain weight. In addition, mean corpuscular volume and cell size were strongly correlated with incubation period, indicating that the physical magnitude of prion-infected organs or individual cells may be important in determining the incubation period. Given the same prion inoculation dose, animals with a lower brain weight, mean corpuscular volume or cell size may experience more virulent disease, as the effective concentration of abnormal prion, which might regulate the attachment rate of prions to aggregates, is increased with smaller capacity of brains and cells. This is partly consistent with previous theoretical modeling. The strong correlations between incubation period and physical properties of the brain and cells in this study suggest that the mechanism underlying prion disease pathology may be physical, indicating that the incubation process is governed by simple chemical stoichiometry.

Testing for biases in selection on avian reproductive traits and partitioning direct and indirect selection using quantitative genetic models.

PubMed

Reed, Thomas E; Gienapp, Phillip; Visser, Marcel E

2016-10-01

Key life history traits such as breeding time and clutch size are frequently both heritable and under directional selection, yet many studies fail to document microevolutionary responses. One general explanation is that selection estimates are biased by the omission of correlated traits that have causal effects on fitness, but few valid tests of this exist. Here, we show, using a quantitative genetic framework and six decades of life-history data on two free-living populations of great tits Parus major, that selection estimates for egg-laying date and clutch size are relatively unbiased. Predicted responses to selection based on the Robertson-Price Identity were similar to those based on the multivariate breeder's equation (MVBE), indicating that unmeasured covarying traits were not missing from the analysis. Changing patterns of phenotypic selection on these traits (for laying date, linked to climate change) therefore reflect changing selection on breeding values, and genetic constraints appear not to limit their independent evolution. Quantitative genetic analysis of correlational data from pedigreed populations can be a valuable complement to experimental approaches to help identify whether apparent associations between traits and fitness are biased by missing traits, and to parse the roles of direct versus indirect selection across a range of environments. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Genetic linkage of hyperglycemia and dyslipidemia in an intercross between BALB/cJ and SM/J Apoe-deficient mouse strains.

PubMed

Wang, Qian; Grainger, Andrew T; Manichaikul, Ani; Farber, Emily; Onengut-Gumuscu, Suna; Shi, Weibin

2015-11-10

Individuals with dyslipidemia often develop type 2 diabetes, and diabetic patients often have dyslipidemia. It remains to be determined whether there are genetic connections between the 2 disorders. A female F2 cohort, generated from BALB/cJ (BALB) and SM/J (SM) Apoe-deficient (Apoe(-/-)) strains, was started on a Western diet at 6 weeks of age and maintained on the diet for 12 weeks. Fasting plasma glucose and lipid levels were measured before and after 12 weeks of Western diet. 144 genetic markers across the entire genome were used for quantitative trait locus (QTL) analysis. One significant QTL on chromosome 9, named Bglu17 [26.4 cM, logarithm of odds ratio (LOD): 5.4], and 3 suggestive QTLs were identified for fasting glucose levels. The suggestive QTL near the proximal end of chromosome 9 (2.4 cM, LOD: 3.12) was replicated at both time points and named Bglu16. Bglu17 coincided with a significant QTL for HDL (high-density lipoprotein) and a suggestive QTL for non-HDL cholesterol levels. Plasma glucose levels were inversely correlated with HDL but positively correlated with non-HDL cholesterol levels in F2 mice on either chow or Western diet. A significant correlation between fasting glucose and triglyceride levels was also observed on the Western diet. Haplotype analysis revealed that "lipid genes" Sik3, Apoa1, and Apoc3 were probable candidates for Bglu17. We have identified multiple QTLs for fasting glucose and lipid levels. The colocalization of QTLs for both phenotypes and the sharing of potential candidate genes demonstrate genetic connections between dyslipidemia and type 2 diabetes.

Genetic evaluation of recombinant inbred lines of rice (Oryza sativa L.) for grain zinc concentrations, yield related traits and identification of associated SSR markers.

PubMed

Bekele, Berhanu D; Naveen, G K; Rakhi, S; Shashidhar, H E

2013-12-01

The objectives of the present study were to evaluate genetic variability parameters, correlations that exist for grain Zn concentration and yield related traits and identification of SSR markers linked to these traits in rice. One hundred seventy six Recombinant Inbred Lines (RILs) of Azucena X Moromutant were grown at University of Agricultural Sciences, Bangalore in augmented experimental design during wet seasons of 2010 and 2011. The study revealed significant genetic variability for all the traits. Grain yield per plant and grain zinc concentration showed higher phenotypic and genotypic co-efficient of variation. Significant positive correlation was observed for grain yield per plant with number of productive tillers per plant (r = 0.5) and number of tillers per plant (r = 0.4). Grain zinc concentration showed negative correlation with grain yield per plant (r = - 0.27). The path-coefficient analysis indicated the positive direct effect of number of productive tillers per plant on grain yield per plant (0.514). Grain zinc concentration showed negative direct effect on grain yield per plant (-0.186). Single-marker analysis using 26 SSR markers on RILs mapping population showed that RM212, RM263, RM6832, RM152, RM21, RM234 and RM3331 had association with grain zinc concentration and other yield related traits. But validation of these markers on fifty two rice genotypes showed that only three markers RM263, RM152 and RM21 had association with grain zinc concentration. Therefore, the genetic information generated and molecular markers identified from this study could be used for zinc biofortification programmes in rice.

High levels of bcl-2 protein expression do not correlate with genetic abnormalities but predict worse prognosis in patients with lymphoblastic lymphoma.

PubMed

Gu, Yajun; Pan, Yi; Meng, Bin; Guan, Bingxin; Fu, Kai; Sun, Baocun; Zheng, Fang

2013-06-01

We aimed to investigate bcl-2, bcl-6, and c-myc rearrangements in patients with lymphoblastic lymphoma (LBL), especially focus on the correlation of protein expression with genetic abnormalities. Moreover, their prognostic significance was further analyzed in LBL. Protein expression and genetic abnormalities of bcl-2, bcl-6, and c-myc were investigated in microarrayed tumors from 33 cases of T cell LBL and eight cases of B cell lineage. Immunohistochemical (IHC) staining was performed to evaluate protein expression, including bcl-2, bcl-6, c-myc, TdT, CD1α, CD34, Ki-67, PAX-5, CD2, CD3, CD4, CD8, and CD20. Genetic abnormalities of bcl-2, bcl-6, and c-myc were detected by dual color fluorescence in situ hybridization (FISH). Bcl-2 protein was positive in 51.2 % (21/41) of the patients, bcl-6 protein in 7.3 % (three out of 41), and c-myc protein in 78.0 % (32/41). Bcl-2 breakpoint was found in two cases by FISH analysis. There was no evidence of bcl-6 or c-myc rearrangement in patients with LBL. However, both gene gain and loss events occurred in bcl-2, bcl-6, and c-myc. A univariate analysis showed that stage III or IV, elevated lactate dehydrogenase (LDH), and positivity for bcl-2 protein were associated with shorter survival (p<0.05). Enhanced protein expression and detectable genetic abnormalities of bcl-2, bcl-6, and c-myc were observed in patients with LBL. No statistical correlation was found between IHC results and cytogenetic findings. Stage III or IV, elevated LDH, and positivity for bcl-2 protein were identified as adverse prognostic factors. The patients with more adverse factors would have increasingly worse prognosis.

Identification of homogeneous genetic architecture of multiple genetically correlated traits by block clustering of genome-wide associations.

PubMed

Gupta, Mayetri; Cheung, Ching-Lung; Hsu, Yi-Hsiang; Demissie, Serkalem; Cupples, L Adrienne; Kiel, Douglas P; Karasik, David

2011-06-01

Genome-wide association studies (GWAS) using high-density genotyping platforms offer an unbiased strategy to identify new candidate genes for osteoporosis. It is imperative to be able to clearly distinguish signal from noise by focusing on the best phenotype in a genetic study. We performed GWAS of multiple phenotypes associated with fractures [bone mineral density (BMD), bone quantitative ultrasound (QUS), bone geometry, and muscle mass] with approximately 433,000 single-nucleotide polymorphisms (SNPs) and created a database of resulting associations. We performed analysis of GWAS data from 23 phenotypes by a novel modification of a block clustering algorithm followed by gene-set enrichment analysis. A data matrix of standardized regression coefficients was partitioned along both axes--SNPs and phenotypes. Each partition represents a distinct cluster of SNPs that have similar effects over a particular set of phenotypes. Application of this method to our data shows several SNP-phenotype connections. We found a strong cluster of association coefficients of high magnitude for 10 traits (BMD at several skeletal sites, ultrasound measures, cross-sectional bone area, and section modulus of femoral neck and shaft). These clustered traits were highly genetically correlated. Gene-set enrichment analyses indicated the augmentation of genes that cluster with the 10 osteoporosis-related traits in pathways such as aldosterone signaling in epithelial cells, role of osteoblasts, osteoclasts, and chondrocytes in rheumatoid arthritis, and Parkinson signaling. In addition to several known candidate genes, we also identified PRKCH and SCNN1B as potential candidate genes for multiple bone traits. In conclusion, our mining of GWAS results revealed the similarity of association results between bone strength phenotypes that may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in identifying novel genes and pathways that underlie several correlated phenotypes, as well as in deciphering genetic and phenotypic modularity underlying osteoporosis risk. Copyright © 2011 American Society for Bone and Mineral Research.

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy.

PubMed

Iarossi, Giancarlo; Bertelli, Matteo; Maltese, Paolo Enrico; Gusson, Elena; Marchini, Giorgio; Bruson, Alice; Benedetti, Sabrina; Volpetti, Sabrina; Catena, Gino; Buzzonetti, Luca; Ziccardi, Lucia

2017-01-01

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7-19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4 , LRP5 , TSPAN12 , and NDP . Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands ( NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy

PubMed Central

Marchini, Giorgio; Volpetti, Sabrina; Catena, Gino

2017-01-01

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7–19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family. PMID:28758032

Genetic variation and phylogeographic structure of the cotton aphid, Aphis gossypii, based on mitochondrial DNA and microsatellite markers.

PubMed

Wang, Xing-Ya; Yang, Xian-Ming; Lu, Bin; Zhou, Li-Hong; Wu, Kong-Ming

2017-05-15

Aphis gossypii, one of the most important agricultural pests in the world, can cause serious economic losses in the main crop-producing areas. To clarify issues such as the genetic differentiation, genetic structure, and demographic history of A. gossypii populations, we used 10 nuclear microsatellite loci (SSR) and two mitochondrial gene sequences (COI and Cytb) to investigate genetic diversity and population structure of A. gossypii populations that were collected from 33 sampling sites in China from different climatic zones. SSR and mtDNA data suggested low to moderate levels of genetic diversity. A star-shaped network of mtDNA haplotypes indicated that the maternal ancestor of China cotton aphids likely originated in Xinjiang. The POPTREE, STRUCTURE and principal coordinate analysis (PCoA) revealed two genetic clusters: an eastern and a western region group. Isolation by distance (IBD) results showed a positive correlation between geographic distance and genetic distance in the vast eastern region but not in the western region. Neutrality testing and mismatch distribution analysis provided strong evidence for a recent rapid expansion in most populations. Genetic bottleneck was not detected in A. gossypii populations of China. The present work can help us to develop strategies for managing this pest.

Multivariate random regression analysis for body weight and main morphological traits in genetically improved farmed tilapia (Oreochromis niloticus).

PubMed

He, Jie; Zhao, Yunfeng; Zhao, Jingli; Gao, Jin; Han, Dandan; Xu, Pao; Yang, Runqing

2017-11-02

Because of their high economic importance, growth traits in fish are under continuous improvement. For growth traits that are recorded at multiple time-points in life, the use of univariate and multivariate animal models is limited because of the variable and irregular timing of these measures. Thus, the univariate random regression model (RRM) was introduced for the genetic analysis of dynamic growth traits in fish breeding. We used a multivariate random regression model (MRRM) to analyze genetic changes in growth traits recorded at multiple time-point of genetically-improved farmed tilapia. Legendre polynomials of different orders were applied to characterize the influences of fixed and random effects on growth trajectories. The final MRRM was determined by optimizing the univariate RRM for the analyzed traits separately via penalizing adaptively the likelihood statistical criterion, which is superior to both the Akaike information criterion and the Bayesian information criterion. In the selected MRRM, the additive genetic effects were modeled by Legendre polynomials of three orders for body weight (BWE) and body length (BL) and of two orders for body depth (BD). By using the covariance functions of the MRRM, estimated heritabilities were between 0.086 and 0.628 for BWE, 0.155 and 0.556 for BL, and 0.056 and 0.607 for BD. Only heritabilities for BD measured from 60 to 140 days of age were consistently higher than those estimated by the univariate RRM. All genetic correlations between growth time-points exceeded 0.5 for either single or pairwise time-points. Moreover, correlations between early and late growth time-points were lower. Thus, for phenotypes that are measured repeatedly in aquaculture, an MRRM can enhance the efficiency of the comprehensive selection for BWE and the main morphological traits.

Relative Contribution of Genetic and Non-genetic Modifiers to Intestinal Obstruction in Cystic Fibrosis

PubMed Central

Blackman, Scott M.; Deering-Brose, Rebecca; McWilliams, Rita; Naughton, Kathleen; Coleman, Barbara; Lai, Teresa; Algire, Marilyn; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Fallin, M. Daniele; West, Kristen; Arking, Dan E.; Chakravarti, Aravinda; Cutler, David J.; Cutting, Garry R

2006-01-01

Background & Aims Neonatal intestinal obstruction (meconium ileus or MI) occurs in 15% of patients with cystic fibrosis (CF). Our aim was to determine the relative contribution of genetic and non-genetic modifiers to the development of this major complication of CF. Methods Using clinical data and DNA collected by the CF Twin and Sibling Study, 65 monozygous twin pairs, 23 dizygous twin/triplet sets, and 349 sets of siblings with CF were analyzed for MI status, significant covariates, and genome-wide linkage. Results Specific mutations in CFTR, the gene responsible for CF, correlated with MI indicating a role for CFTR genotype. Monozygous twins showed substantially greater concordance for MI than dizygous twins and siblings (p=1×10−5) demonstrating that modifier genes independent of CFTR contribute substantially to this trait. Regression analysis revealed that MI was correlated with distal intestinal obstruction syndrome (DIOS; p=8×10−4). Unlike MI, concordance analysis indicated that the risk for development of DIOS in CF patients is primarily due to non-genetic factors. Regions of suggestive linkage (logarithm of the odds of linkage >2.0) for modifier genes that cause MI (chromosomes 4q35.1, 8p23.1, and 11q25) or protect from MI (chromosomes 20p11.22 and 21q22.3) were identified by genome-wide analyses. These analyses did not support the existence of a major modifier gene within the CFM1 region on chromosome 19 that had previously been linked to MI. Conclusions The CFTR gene along with two or more modifier genes are the major determinants of intestinal obstruction in newborn CF patients, while intestinal obstruction in older CF patients is primarily due to non-genetic factors. PMID:17030173

Assessment of the Genetic Diversity of Different Job's Tears (Coix lacryma-jobi L.) Accessions and the Active Composition and Anticancer Effect of Its Seed Oil

PubMed Central

Xi, Xiu-Jie; Zhu, Yun-Guo; Tong, Ying-Peng; Yang, Xiao-Ling; Tang, Nan-Nan; Ma, Shu-Min; Li, Shan; Cheng, Zhou

2016-01-01

Job’s tears (Coix lachryma-jobi L.) is an important crop used as food and herbal medicine in Asian countries. A drug made of Job’s tears seed oil has been clinically applied to treat multiple cancers. In this study, the genetic diversity of Job’s tears accessions and the fatty acid composition, triglyceride composition, and anti-proliferative effect of Job’s tears seed oil were analyzed using morphological characteristics and ISSR markers, GC-MS, HPLC-ELSD, and the MTT method. ISSR analysis demonstrated low genetic diversity of Job’s tears at the species level (h = 0.21, I = 0.33) and the accession level (h = 0.07, I = 0.10), and strong genetic differentiation (GST = 0.6702) among all accessions. It also clustered the 11 accessions into three cultivated clades corresponding with geographical locations and two evidently divergent wild clades. The grouping patterns based on morphological characteristics and chemical profiles were in accordance with those clustered by ISSR analysis. Significant differences in morphological characteristics, fatty acid composition, triglyceride composition, and inhibition rates of seed oil were detected among different accessions, which showed a highly significant positive correlation with genetic variation. These results suggest that the seed morphological characteristics, fatty acid composition, and triglyceride composition may be mainly attributed to genetic factors. The proportion of palmitic acid and linoleic acid to oleic acid displayed a highly significant positive correlation with the inhibition rates of Job’s tears seed oil for T24 cells, and thus can be an important indicator for quality control for Job’s tears. PMID:27070310

Natural variation in stomatal abundance of Arabidopsis thaliana includes cryptic diversity for different developmental processes

PubMed Central

Delgado, Dolores; Alonso-Blanco, Carlos; Fenoll, Carmen; Mena, Montaña

2011-01-01

Background and Aims Current understanding of stomatal development in Arabidopsis thaliana is based on mutations producing aberrant, often lethal phenotypes. The aim was to discover if naturally occurring viable phenotypes would be useful for studying stomatal development in a species that enables further molecular analysis. Methods Natural variation in stomatal abundance of A. thaliana was explored in two collections comprising 62 wild accessions by surveying adaxial epidermal cell-type proportion (stomatal index) and density (stomatal and pavement cell density) traits in cotyledons and first leaves. Organ size variation was studied in a subset of accessions. For all traits, maternal effects derived from different laboratory environments were evaluated. In four selected accessions, distinct stomatal initiation processes were quantitatively analysed. Key Results and Conclusions Substantial genetic variation was found for all six stomatal abundance-related traits, which were weakly or not affected by laboratory maternal environments. Correlation analyses revealed overall relationships among all traits. Within each organ, stomatal density highly correlated with the other traits, suggesting common genetic bases. Each trait correlated between organs, supporting supra-organ control of stomatal abundance. Clustering analyses identified accessions with uncommon phenotypic patterns, suggesting differences among genetic programmes controlling the various traits. Variation was also found in organ size, which negatively correlated with cell densities in both organs and with stomatal index in the cotyledon. Relative proportions of primary and satellite lineages varied among the accessions analysed, indicating that distinct developmental components contribute to natural diversity in stomatal abundance. Accessions with similar stomatal indices showed different lineage class ratios, revealing hidden developmental phenotypes and showing that genetic determinants of primary and satellite lineage initiation combine in several ways. This first systematic, comprehensive natural variation survey for stomatal abundance in A. thaliana reveals cryptic developmental genetic variation, and provides relevant relationships amongst stomatal traits and extreme or uncommon accessions as resources for the genetic dissection of stomatal development. PMID:21447490

Genetic correlations between mature cow weight and productive and reproductive traits in Nellore cattle.

PubMed

Regatieri, I C; Boligon, A A; Baldi, F; Albuquerque, L G

2012-08-29

We investigated genetic associations between mature cow weight (MW) and weaning weight (WW), yearling weight (YW), weight gain from birth to weaning (GBW), weight gain from weaning to yearling (GWY), weaning hip height (WHH), yearling hip height (YHH), scrotal circumference (SC), and age at first calving (AFC). Data from 127,104 Nellore animals born between 1993 and 2006, belonging to Agropecuária Jacarezinho Ltda., were analyzed. (Co)variance components were obtained by the restricted maximum likelihood method, applying an animal model in a multi-traits analysis. The model included direct genetic and residual effects as random effects, the fixed effects of contemporary group, and the linear and quadratic effects of animal age at recording (except for AFC, GBW, and GWY) and age of cow at calving as covariates (except for MW). The numbers of days from birth to weaning and from weaning to yearling were included as covariates for GBW and GWY, respectively. Estimated direct heritabilities were 0.43 ± 0.02 (MW), 0.33 ± 0.01 (WW), 0.36 ± 0.01 (YW), 0.28 ± 0.02 (GBW), 0.31 ± 0.01 (GWY), 0.44 ± 0.02 (WHH), 0.48 ± 0.02 (YHH), 0.44 ± 0.01 (SC), and 0.16 ± 0.03 (AFC). Genetic correlations between MW and productive traits were positive and of medium to high magnitude (ranging from 0.47 ± 0.03 to 0.71 ± 0.01). A positive and low genetic correlation was observed between MW and SC (0.24 ± 0.04). A negative genetic correlation (-0.19 ± 0.03) was estimated between MW and AFC. Selection to increase weight or weight gains at any age, as well as hip height, will change MW in the same direction. Selection for higher SC may lead to a long-term increase in MW. The AFC can be included in selection indices to improve the reproductive performance of beef cattle without significant changes in MW.

Statistical Analysis of Big Data on Pharmacogenomics

PubMed Central

Fan, Jianqing; Liu, Han

2013-01-01

This paper discusses statistical methods for estimating complex correlation structure from large pharmacogenomic datasets. We selectively review several prominent statistical methods for estimating large covariance matrix for understanding correlation structure, inverse covariance matrix for network modeling, large-scale simultaneous tests for selecting significantly differently expressed genes and proteins and genetic markers for complex diseases, and high dimensional variable selection for identifying important molecules for understanding molecule mechanisms in pharmacogenomics. Their applications to gene network estimation and biomarker selection are used to illustrate the methodological power. Several new challenges of Big data analysis, including complex data distribution, missing data, measurement error, spurious correlation, endogeneity, and the need for robust statistical methods, are also discussed. PMID:23602905

[Correlation between genetic differences of mates and pathogenicity of Schistosoma japonicum in definitive host].

PubMed

Wen-Qiao, Huang; Yuan-Jian, Zhu; Da-Bing, Lv; Xia, Zhou; Ying-Nan, Yang; Hong-Xiang, Zhu-Ge

2016-05-24

To explore the correlation between the genetic dissimilarity and heterozygosity of mates and the pathogenicity of Schistosoma japonicum in the definitive host. By using seven microsatellite loci markers, S. japonicum genotyping of sixteen pairs randomly mated was performed, the genetic dissimilarity and heterozygosity were calculated between the mates, and the correlation between the genetic dissimilarity and heterozygosity of the mates and the pathogenicity of S. japonicum in the definitive host was evaluated. There was a significant correlation between the genetic similarity of S. japonicum mates and the mean number of eggs per worm pair in the liver and intestinal tissue ( r = 0.501 6, P < 0.05; r = 0.796 5, P < 0.01, respectively) and the hatching rate of deposited eggs in the liver ( r = 0.508 3, P < 0.05), respectively. There was no correlation between the genetic similarity of the mates and hepatosplenomegaly per worm pair ( r = 0.109 5, P > 0.05; r = 0.265 3, P > 0.05, respectively) and the average diameter of granuloma in the liver ( r = -0.272 7, P > 0.05), respectively. There was no correlation between the heterozygosity of the mates and all the pathological parameters of S. japonicum in the definitive host ( P > 0.05). There is the correlation between the genetic dissimilarity of the mates and the pathogenicity of S. japonicum in the definitive host, and the genetic dissimilarity is greater, pathogenicity is weaker. There is no correlation between heterozygosity of the mates and the pathogenicity of S. japonicum in the definitive host.

Imaging genetics approach to predict progression of Parkinson's diseases.

PubMed

Mansu Kim; Seong-Jin Son; Hyunjin Park

2017-07-01

Imaging genetics is a tool to extract genetic variants associated with both clinical phenotypes and imaging information. The approach can extract additional genetic variants compared to conventional approaches to better investigate various diseased conditions. Here, we applied imaging genetics to study Parkinson's disease (PD). We aimed to extract significant features derived from imaging genetics and neuroimaging. We built a regression model based on extracted significant features combining genetics and neuroimaging to better predict clinical scores of PD progression (i.e. MDS-UPDRS). Our model yielded high correlation (r = 0.697, p <; 0.001) and low root mean squared error (8.36) between predicted and actual MDS-UPDRS scores. Neuroimaging (from 123 I-Ioflupane SPECT) predictors of regression model were computed from independent component analysis approach. Genetic features were computed using image genetics approach based on identified neuroimaging features as intermediate phenotypes. Joint modeling of neuroimaging and genetics could provide complementary information and thus have the potential to provide further insight into the pathophysiology of PD. Our model included newly found neuroimaging features and genetic variants which need further investigation.

Variances and correlations of milk production, fertility, longevity, and type traits over time in Australian Holstein cattle.

PubMed

Haile-Mariam, M; Pryce, J E

2015-10-01

When using historical data, it is often assumed that the genetic correlation of the same trait recorded at different time points is reasonably close to 1. However, selection and possible changes in trait definitions means that this may not necessarily be the case. Regularly monitoring genetic parameters over time is important, as changes could reduce the accuracy of genetic evaluations. About 20 yr (1993 to 2012) of data on milk yield as well as functional and type traits from Australian Holstein dairy cattle were analyzed to assess changes in genetic correlations within and among traits over time by considering 2 traits at a time using linear random regression (RR) and multitrait (MT) models. Both residual and genetic variances for milk yield traits and calving interval (CI) increased over time, with the highest increase observed for protein yield. For most type traits some fluctuations over time were noted in both the residual and additive genetic variances. Genetic correlations among survival (i.e., from first to second lactation), milk yield traits, CI, and some type traits varied over time. The genetic correlation of the same trait (e.g., protein yield, fat yield, and some type traits) measured in different years was also less than 1.0 (0.1-0.9), which is likely to be due to selection or changes in trait definitions. Estimates of parameters from the RR model were generally similar to those from MT models that considered the same trait recorded in different year groups as different traits. However, in the case of survival and CI (i.e., lowly heritable traits), the genetic correlations over time obtained from the MT model were lower (0.21 to 0.75) than those from the RR models (0.9-1.0). Genetic correlations of survival with milk, fat, and protein yields declined from ~0.4 to 0.5 at the beginning of the study period (1993/94) to zero or negative at the end (2009/10), whereas the correlation between CI and milk yield became more unfavorable and increased from 0.3 to 0.5 over the same time period. The same pattern was observed for the genetic correlation between survival and CI, which also became more unfavorable over time and increased from 0.67 to 0.87 in absolute value. The genetic correlations of survival with type traits, such as angularity and body depth, decreased from near zero to negative (-0.3 to -0.4). But genetic correlations between pin set and survival showed less variation (0.2-0.3) over time. Similarly the genetic correlation of CI with body depth and angularity became more antagonistic over time. Over time the importance of traits such as milk yield and overall type as criteria for culling decreased, whereas the importance of fertility and possible disease incidence increased, implying that there has been a switch from voluntary to involuntary reasons dominating culling decisions. Changes in genetic correlations of the same trait and among traits over time have important implications on the accuracy of prediction of traits, such as survival and CI, which often rely on other traits as predictors and ultimately on the accuracy of genetic evaluations (traditional and genomic), and also the prediction of response to selection. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Social network analysis of the genetic structure of Pacific islanders.

PubMed

Terrell, John Edward

2010-05-01

Social network analysis (SNA) is a body of theory and a set of relatively new computer-aided techniques used in the analysis and study of relational data. Recent studies of autosomal markers from over 40 human populations in the south-western Pacific have further documented the remarkable degree of genetic diversity in this part of the world. I report additional analysis using SNA methods contributing new controlled observations on the structuring of genetic diversity among these islanders. These SNA mappings are then compared with model-based network expectations derived from the geographic distances among the same populations. Previous studies found that genetic divergence among island Melanesian populations is organised by island, island size/topography, and position (coastal vs. inland), and that similarities observed correlate only weakly with an isolation-by-distance model. Using SNA methods, however, improves the resolution of among population comparison, and suggests that isolation by distance constrained by social networks together with position (coastal/inland) accounts for much of the population structuring observed. The multilocus data now available is also in accord with current thinking on the impact of major biogeographical transformations on prehistoric colonisation and post-settlement human interaction in Oceania.

Genetic and Environmental Influences on Female Sexual Orientation, Childhood Gender Typicality and Adult Gender Identity

PubMed Central

Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

2011-01-01

Background Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates – childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Methodology/Principal Findings Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. Conclusions/Significance This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation. PMID:21760939

Effects of landscape features on population genetic variation of a tropical stream fish, Stone lapping minnow, Garra cambodgiensis, in the upper Nan River drainage basin, northern Thailand.

PubMed

Jaisuk, Chaowalee; Senanan, Wansuk

2018-01-01

Spatial genetic variation of river-dwelling freshwater fishes is typically affected by the historical and contemporary river landscape as well as life-history traits. Tropical river and stream landscapes have endured extended geological change, shaping the existing pattern of genetic diversity, but were not directly affected by glaciation. Thus, spatial genetic variation of tropical fish populations should look very different from the pattern observed in temperate fish populations. These data are becoming important for designing appropriate management and conservation plans, as these aquatic systems are undergoing intense development and exploitation. This study evaluated the effects of landscape features on population genetic diversity of Garra cambodgiensis, a stream cyprinid , in eight tributary streams in the upper Nan River drainage basin ( n  = 30-100 individuals/location), Nan Province, Thailand. These populations are under intense fishing pressure from local communities. Based on 11 microsatellite loci, we detected moderate genetic diversity within eight population samples (average number of alleles per locus = 10.99 ± 3.00; allelic richness = 10.12 ± 2.44). Allelic richness within samples and stream order of the sampling location were negatively correlated ( P  < 0.05). We did not detect recent bottleneck events in these populations, but we did detect genetic divergence among populations (Global F ST = 0.022, P  < 0.01). The Bayesian clustering algorithms (TESS and STRUCTURE) suggested that four to five genetic clusters roughly coincide with sub-basins: (1) headwater streams/main stem of the Nan River, (2) a middle tributary, (3) a southeastern tributary and (4) a southwestern tributary. We observed positive correlation between geographic distance and linearized F ST ( P  < 0.05), and the genetic differentiation pattern can be moderately explained by the contemporary stream network (STREAMTREE analysis, R 2 = 0.75). The MEMGENE analysis suggested genetic division between northern (genetic clusters 1 and 2) and southern (clusters 3 and 4) sub-basins. We observed a high degree of genetic admixture in each location, highlighting the importance of natural flooding patterns and possible genetic impacts of supplementary stocking. Insights obtained from this research advance our knowledge of the complexity of a tropical stream system, and guide current conservation and restoration efforts for this species in Thailand.

Estimation of Genetic Parameters from Longitudinal Records of Body Weight of Berkshire Pigs

PubMed Central

Lee, Dong-Hee; Do, Chang-Hee

2012-01-01

Direct and maternal genetic heritabilities and their correlations with body weight at 5 stages in the life span of purebred Berkshire pigs, from birth to harvest, were estimated to scrutinize body weight development with the records for 5,088 purebred Berkshire pigs in a Korean farm, using the REML based on an animal model. Body weights were measured at birth (Birth), at weaning (Weaning: mean 22.9 d), at the beginning of a performance test (On: mean 72.7 d), at the end of a performance test (Off: mean 152.4 d), and at harvest (Finish: mean 174.3 d). Ordinary polynomials and Legendre with order 1, 2, and 3 were adopted to adjust body weight with age in the multivariate animal models. Legendre with order 3 fitted best concerning prediction error deviation (PED) and yielded the lowest AIC for multivariate analysis of longitudinal body weights. Direct genetic correlations between body weight at Birth and body weight at Weaning, On, Off, and Finish were 0.48, 0.36, 0.10, and 0.10, respectively. The estimated maternal genetic correlations of body weight at Finish with body weight at Birth, Weaning, On, and Off were 0.39, 0.49, 0.65, and 0.90, respectively. Direct genetic heritabilities progressively increased from birth to harvest and were 0.09, 0.11, 0.20, 0.31, and 0.43 for body weight at Birth, Weaning, On, Off, and Finish, respectively. Maternal genetic heritabilities generally decreased and were 0.26, 0.34, 0.15, 0.10, and 0.10 for body weight at Birth, Weaning, On, Off, and Finish, respectively. As pigs age, maternal genetic effects on growth are reduced and pigs begin to rely more on the expression of their own genes. Although maternal genetic effects on body weight may not be large, they are sustained through life. PMID:25049624

Can metamorphosis survival during larval development in spiny lobster Sagmariasus verreauxi be improved through quantitative genetic inheritance?

PubMed

Nguyen, Nguyen H; Fitzgibbon, Quinn P; Quinn, Jane; Smith, Greg; Battaglene, Stephen; Knibb, Wayne

2018-05-04

One of the major impediments to spiny lobster aquaculture is the high cost of hatchery production due to the long and complex larval cycle and poor survival during the many moult stages, especially at metamorphosis. We examined if the key trait of larval survival can be improved through selection by determining if genetic variance exists for this trait. Specifically, we report, for the first time, genetic parameters (heritability and correlations) for early survival rates recorded at five larval phases; early-phyllosoma stages (instars 1-6; S1), mid-phyllosoma stages (instars; 7-12; S2), late-phyllosoma stages (instars 13-17; S3), metamorphosis (S4) and puerulus stage (S5) in hatchery-reared spiny lobster Sagmariasus verreauxi. The data were collected from a total of 235,060 larvae produced from 18 sires and 30 dams over nine years (2006 to 2014). Parentage of the offspring and full-sib families was verified using ten microsatellite markers. Analysis of variance components showed that the estimates of heritability for all the five phases of larval survival obtained from linear mixed model were generally similar to those obtained from threshold logistic generalised models (0.03-0.47 vs. 0.01-0.50). The heritability estimates for survival traits recorded in the early larval phases (S1 and S2) were higher than those estimated in later phases (S3, S4 and S5). The existence of the additive genetic component in larval survival traits indicate that they could be improved through selection. Both phenotypic and genetic correlations among the five survival measures studied were moderate to high and positive. The genetic associations between successive rearing periods were stronger than those that are further apart. Our estimates of heritability and genetic correlations reported here in a spiny lobster species indicate that improvement in the early survival especially during metamorphosis can be achieved through genetic selection in this highly economic value species.

A classical twin study of PTSD symptoms and resilience: Evidence for a single spectrum of vulnerability to traumatic stress.

PubMed

Wolf, Erika J; Miller, Mark W; Sullivan, Danielle R; Amstadter, Ananda B; Mitchell, Karen S; Goldberg, Jack; Magruder, Kathryn M

2018-02-01

To examine shared genetic and environmental risk factors across PTSD symptoms and resilience. Classical twin study of 2010-2012 survey data conducted among 3,318 male twin pairs in the Vietnam Era Twin Registry. Analyses included: (a) estimates of genetic and environmental influences on PTSD symptom severity (as measured by the PTSD Checklist) and resilience (assessed with the Connor-Davidson Resilience Scale-10); (b) development of a latent model of traumatic stress, spanning both PTSD and resilience; and (c) estimates of genetic and environmental influences on this spectrum. The heritability of PTSD was 49% and of resilience was 25%. PTSD and resilience were correlated at r = -.59, and 59% of this correlation was attributable to a single genetic factor, whereas the remainder was due to a single non-shared environment factor. Resilience was also influenced by common and unique environmental factors not shared with PTSD, but there was no genetic factor specific to resilience. Confirmatory factor analysis supported the Development of a revised phenotype reflecting the broader dimension of traumatic stress, with biometric models suggesting increased heritability (66%) of this spectrum compared to PTSD or resilience individually. Genetic factors contribute to a single spectrum of traumatic stress reflecting resilience at one end and high symptom severity at the other. This carries implications for phenotype refinement in the search for molecular genetic markers of trauma-related psychopathology. Rather than focusing only on genetic risk for PTSD, molecular genetics research may benefit from evaluation of the broader spectrum of traumatic stress. © 2017 Wiley Periodicals, Inc.

Inherited behavioral susceptibility to adiposity in infancy: a multivariate genetic analysis of appetite and weight in the Gemini birth cohort.

PubMed

Llewellyn, Clare H; van Jaarsveld, Cornelia H M; Plomin, Robert; Fisher, Abigail; Wardle, Jane

2012-03-01

The behavioral susceptibility model proposes that inherited differences in traits such as appetite confer differential risk of weight gain and contribute to the heritability of weight. Evidence that the FTO gene may influence weight partly through its effects on appetite supports this model, but testing the behavioral pathways for multiple genes with very small effects is not feasible. Twin analyses make it possible to get a broad-based estimate of the extent of shared genetic influence between appetite and weight. The objective was to use multivariate twin analyses to test the hypothesis that associations between appetite and weight are underpinned by shared genetic effects. Data were from Gemini, a population-based birth cohort of twins (n = 4804) born in 2007. Infant weights at 3 mo were taken from the records of health professionals. Appetite was assessed at 3 mo for the milk-feeding period by using the Baby Eating Behaviour Questionnaire (BEBQ), a parent-reported measure of appetite [enjoyment of food, food responsiveness, slowness in eating (SE), satiety responsiveness (SR), and appetite size (AS)]. Multivariate quantitative genetic modeling was used to test for shared genetic influences. Significant correlations were found between all BEBQ traits and weight. Significant shared genetic influence was identified for weight with SE, SR, and AS; genetic correlations were between 0.22 and 0.37. Shared genetic effects explained 41-45% of these phenotypic associations. Differences in weight in infancy may be due partly to genetically determined differences in appetitive traits that confer differential susceptibility to obesogenic environments.

On the Genetic and Environmental Correlations between Trait Emotional Intelligence and Vocational Interest Factors.

PubMed

Schermer, Julie Aitken; Petrides, Konstantinos V; Vernon, Philip A

2015-04-01

The phenotypic (observed), genetic, and environmental correlations were examined in a sample of adult twins between the four factors and global score of the trait emotional intelligence questionnaire (TEIQue) and the seven vocational interest factors of the Jackson Career Explorer (JCE). Multiple significant correlations were found involving the work style vocational interest factor (consisting of job security, stamina, accountability, planfulness, and interpersonal confidence) and the social vocational interest factor (which included interests in the social sciences, personal services, teaching, social services, and elementary education), both of which correlated significantly with all of the TEIQue variables (well-being, self-control, emotionality, sociability, and global trait EI). Following bivariate genetic analyses, most of the significant phenotypic correlations were found to also have significant genetic correlations as well as significant non-shared (unique) environmental correlations.

GWAS-based pathway analysis differentiates between fluid and crystallized intelligence.

PubMed

Christoforou, A; Espeseth, T; Davies, G; Fernandes, C P D; Giddaluru, S; Mattheisen, M; Tenesa, A; Harris, S E; Liewald, D C; Payton, A; Ollier, W; Horan, M; Pendleton, N; Haggarty, P; Djurovic, S; Herms, S; Hoffman, P; Cichon, S; Starr, J M; Lundervold, A; Reinvang, I; Steen, V M; Deary, I J; Le Hellard, S

2014-09-01

Cognitive abilities vary among people. About 40-50% of this variability is due to general intelligence (g), which reflects the positive correlation among individuals' scores on diverse cognitive ability tests. g is positively correlated with many life outcomes, such as education, occupational status and health, motivating the investigation of its underlying biology. In psychometric research, a distinction is made between general fluid intelligence (gF) - the ability to reason in novel situations - and general crystallized intelligence (gC) - the ability to apply acquired knowledge. This distinction is supported by developmental and cognitive neuroscience studies. Classical epidemiological studies and recent genome-wide association studies (GWASs) have established that these cognitive traits have a large genetic component. However, no robust genetic associations have been published thus far due largely to the known polygenic nature of these traits and insufficient sample sizes. Here, using two GWAS datasets, in which the polygenicity of gF and gC traits was previously confirmed, a gene- and pathway-based approach was undertaken with the aim of characterizing and differentiating their genetic architecture. Pathway analysis, using genes selected on the basis of relaxed criteria, revealed notable differences between these two traits. gF appeared to be characterized by genes affecting the quantity and quality of neurons and therefore neuronal efficiency, whereas long-term depression (LTD) seemed to underlie gC. Thus, this study supports the gF-gC distinction at the genetic level and identifies functional annotations and pathways worthy of further investigation. © 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Short communication: Estimates of heritabilities and genetic correlations among milk fatty acid unsaturation indices in Canadian Holsteins.

PubMed

Bilal, G; Cue, R I; Mustafa, A F; Hayes, J F

2012-12-01

The objectives of the present study were to estimate genetic parameters of milk fatty acid unsaturation indices in Canadian Holsteins. Data were available on milk fatty acid composition of 2,573 Canadian Holstein cows from 46 commercial herds enrolled in the Québec Dairy Production Centre of Expertise, Valacta (Sainte-Anne-de-Bellevue, Quebec, Canada). Individual fatty acid percentages (g/100 g of total fatty acids) were determined for each milk sample by gas chromatography. The unsaturation indices were calculated as the ratio of an unsaturated fatty acid to the sum of that unsaturated fatty acid and its corresponding substrate fatty acid, multiplied by 100. A mixed linear model was fitted under REML for the statistical analysis of milk fatty acid unsaturation indices. The statistical model included the fixed effects of parity, age at calving, and stage of lactation, each nested within parity, and the random effects of herd-year-season of calving, animal, and residual. Estimates of heritabilities for the C14, C16, C18, conjugated linoleic acid, and total unsaturation indices were 0.48, 0.25, 0.29, 0.14, and 0.19, respectively. Phenotypic and genetic correlation estimates among unsaturation indices were all positive and ranged from 0.20 to 0.65 and 0.23 to 0.81, respectively. The estimates of heritabilities and genetic correlations for milk fatty acid unsaturation indices suggest that genetic variation exists among cows in milk fatty acid unsaturation, and the proportions of desirable unsaturated fatty acids from a human health point of view may be increased in bovine milk through genetic selection. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The intergenerational correlation in weight: How genetic resemblance reveals the social role of families*

PubMed Central

Martin, Molly A.

2009-01-01

According to behavioral genetics research, the intergenerational correlation in weight derives solely from shared genetic predispositions, but complete genetic determinism contradicts the scientific consensus that social and behavioral change underlies the modern obesity epidemic. To address this conundrum, this article utilizes sibling data from the National Longitudinal Study of Adolescent Health and extends structural equation sibling models to incorporate siblings’ genetic relationships to explore the role of families’ social characteristics for adolescent weight. The article is the first to demonstrate that the association between parents’ obesity and adolescent weight is both social and genetic. Furthermore, by incorporating genetic information, the shared and social origins of the correlation between inactivity and weight are better revealed. PMID:19569401

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia

PubMed Central

Lee, Phil H.; Baker, Justin T.; Holmes, Avram J.; Jahanshad, Neda; Ge, Tian; Jung, Jae-Yoon; Cruz, Yanela; Manoach, Dara S.; Hibar, Derrek P.; Faskowitz, Joshua; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicolas H.; Wright, Margaret J.; Öngür, Dost; Buckner, Randy; Roffman, Joshua; Thompson, Paul M.; Smoller, Jordan W.

2016-01-01

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide SNP and neuroimaging data from 1,750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (FDR=10%). In particular, intracranial volume (ICV) and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder. PMID:27725656

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

PubMed

Lee, P H; Baker, J T; Holmes, A J; Jahanshad, N; Ge, T; Jung, J-Y; Cruz, Y; Manoach, D S; Hibar, D P; Faskowitz, J; McMahon, K L; de Zubicaray, G I; Martin, N H; Wright, M J; Öngür, D; Buckner, R; Roffman, J; Thompson, P M; Smoller, J W

2016-12-01

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.

Patterns of Post-Glacial Genetic Differentiation in Marginal Populations of a Marine Microalga

PubMed Central

Tahvanainen, Pia; Alpermann, Tilman J.; Figueroa, Rosa Isabel; John, Uwe; Hakanen, Päivi; Nagai, Satoshi; Blomster, Jaanika; Kremp, Anke

2012-01-01

This study investigates the genetic structure of an eukaryotic microorganism, the toxic dinoflagellate Alexandrium ostenfeldii, from the Baltic Sea, a geologically young and ecologically marginal brackish water estuary which is predicted to support evolution of distinct, genetically impoverished lineages of marine macroorganisms. Analyses of the internal transcribed spacer (ITS) sequences and Amplified Fragment Length Polymorphism (AFLP) of 84 A. ostenfeldii isolates from five different Baltic locations and multiple external sites revealed that Baltic A. ostenfeldii is phylogenetically differentiated from other lineages of the species and micro-geographically fragmented within the Baltic Sea. Significant genetic differentiation (F ST) between northern and southern locations was correlated to geographical distance. However, instead of discrete genetic units or continuous genetic differentiation, the analysis of population structure suggests a complex and partially hierarchic pattern of genetic differentiation. The observed pattern suggests that initial colonization was followed by local differentiation and varying degrees of dispersal, most likely depending on local habitat conditions and prevailing current systems separating the Baltic Sea populations. Local subpopulations generally exhibited low levels of overall gene diversity. Association analysis suggests predominately asexual reproduction most likely accompanied by frequency shifts of clonal lineages during planktonic growth. Our results indicate that the general pattern of genetic differentiation and reduced genetic diversity of Baltic populations found in large organisms also applies to microscopic eukaryotic organisms. PMID:23300940

Genetic diversity and structure of the threatened species Sinopodophyllum hexandrum (Royle) Ying.

PubMed

Liu, W; Wang, J; Yin, D X; Yang, M; Wang, P; Han, Q S; Ma, Q Q; Liu, J J; Wang, J X

2016-06-10

Sinopodophyllum hexandrum is an important medicinal plant that has been listed as an endangered species, making the conservation of its genetic diversity a priority. Therefore, the genetic diversity and population structure of S. hexandrum was investigated through inter-simple sequence repeat analysis of eight natural populations. Eleven selected primers generated 141 discernible fragments. The percentage of polymorphic bands was 37.59% at the species level, and 7.66-24.32% at the population level. Genetic diversity of S. hexandrum was low within populations (average HE = 0.0366), but higher at the species level (HE = 0.0963). Clear structure and high genetic differentiation were detected between populations using unweighted pair groups mean arithmetic and principle coordinate analysis. Clustering approaches clustered the eight sampled populations into three major groups, and AMOVA confirmed there to be significant variation between populations (63.27%). Genetic differentiation may have arisen through limited gene flow (Nm = 0.3317) in this species. Isolation by distance among populations was determined by comparing genetic distance versus geographical distance using the Mantel test. The results revealed no correlation between spatial pattern and geographic location. Given the low within-population genetic diversity, high differentiation among populations, and the increasing anthropogenic pressure on this species, in situ conservation measures, in addition to sampling and ex situ preservation, are recommended to preserve S. hexandrum populations and to retain their genetic diversity.

Patterns of post-glacial genetic differentiation in marginal populations of a marine microalga.

PubMed

Tahvanainen, Pia; Alpermann, Tilman J; Figueroa, Rosa Isabel; John, Uwe; Hakanen, Päivi; Nagai, Satoshi; Blomster, Jaanika; Kremp, Anke

2012-01-01

This study investigates the genetic structure of an eukaryotic microorganism, the toxic dinoflagellate Alexandrium ostenfeldii, from the Baltic Sea, a geologically young and ecologically marginal brackish water estuary which is predicted to support evolution of distinct, genetically impoverished lineages of marine macroorganisms. Analyses of the internal transcribed spacer (ITS) sequences and Amplified Fragment Length Polymorphism (AFLP) of 84 A. ostenfeldii isolates from five different Baltic locations and multiple external sites revealed that Baltic A. ostenfeldii is phylogenetically differentiated from other lineages of the species and micro-geographically fragmented within the Baltic Sea. Significant genetic differentiation (F(ST)) between northern and southern locations was correlated to geographical distance. However, instead of discrete genetic units or continuous genetic differentiation, the analysis of population structure suggests a complex and partially hierarchic pattern of genetic differentiation. The observed pattern suggests that initial colonization was followed by local differentiation and varying degrees of dispersal, most likely depending on local habitat conditions and prevailing current systems separating the Baltic Sea populations. Local subpopulations generally exhibited low levels of overall gene diversity. Association analysis suggests predominately asexual reproduction most likely accompanied by frequency shifts of clonal lineages during planktonic growth. Our results indicate that the general pattern of genetic differentiation and reduced genetic diversity of Baltic populations found in large organisms also applies to microscopic eukaryotic organisms.

Genetic Correlation Analysis Suggests Association between Increased Self-Reported Sleep Duration in Adults and Schizophrenia and Type 2 Diabetes.

PubMed

Byrne, Enda M; Gehrman, Philip R; Trzaskowski, Maciej; Tiemeier, Henning; Pack, Allan I

2016-10-01

We sought to examine how much of the heritability of self-report sleep duration is tagged by common genetic variation in populations of European ancestry and to test if the common variants contributing to sleep duration are also associated with other diseases and traits. We utilized linkage disequilibrium (LD)-score regression to estimate the heritability tagged by common single nucleotide polymorphisms (SNPs) in the CHARGE consortium genome-wide association study (GWAS) of self-report sleep duration. We also used bivariate LD-score regression to investigate the genetic correlation of sleep duration with other publicly available GWAS datasets. We show that 6% (SE = 1%) of the variance in self-report sleep duration in the CHARGE study is tagged by common SNPs in European populations. Furthermore, we find evidence of a positive genetic correlation (rG) between sleep duration and type 2 diabetes (rG = 0.26, P = 0.02), and between sleep duration and schizophrenia (rG = 0.19, P = 0.01). Our results show that increased sample sizes will identify more common variants for self-report sleep duration; however, the heritability tagged is small when compared to other traits and diseases. These results also suggest that those who carry variants that increase risk to type 2 diabetes and schizophrenia are more likely to report longer sleep duration. © 2016 Associated Professional Sleep Societies, LLC.

Genetic parameters for milk coagulation properties in Estonian Holstein cows.

PubMed

Vallas, M; Bovenhuis, H; Kaart, T; Pärna, K; Kiiman, H; Pärna, E

2010-08-01

The objective of this study was to estimate heritabilities and repeatabilities for milk coagulation traits [milk coagulation time (RCT) and curd firmness (E(30))] and genetic and phenotypic correlations between milk yield and composition traits (milk fat percentage and protein percentage, urea, somatic cell count, pH) in first-lactation Estonian Holstein dairy cattle. A total of 17,577 test-day records from 4,191 Estonian Holstein cows in 73 herds across the country were collected during routine milk recordings. Measurements of RCT and E(30) determined with the Optigraph (Ysebaert, Frepillon, France) are based on an optical signal in the near-infrared region. The cows had at least 3 measurements taken during the period from April 2005 to January 2009. Data were analyzed using a repeatability animal model. There was substantial variation in milk coagulation traits with a coefficient of variation of 27% for E(30) and 9% for the log-transformed RCT. The percentage of variation explained by herd was 3% for E(30) and 4% for RCT, suggesting that milk coagulation traits are not strongly affected by herd conditions (e.g., feeding). Heritability was 0.28 for RCT and 0.41 for E(30), and repeatability estimates were 0.45 and 0.50, respectively. Genetic correlation between both milk coagulation traits was negligible, suggesting that RCT and E(30) have genetically different foundations. Milk coagulation time had a moderately high positive genetic (0.69) and phenotypic (0.61) correlation with milk pH indicating that a high pH is related to a less favorable RCT. Curd firmness had a moderate positive genetic (0.48) and phenotypic (0.45) correlation with the protein percentage. Therefore, a high protein percentage is associated with favorable curd firmness. All reported genetic parameters were statistically significantly different from zero. Additional univariate random regression analysis for milk coagulation traits yielded slightly higher average heritabilities of 0.38 and 0.47 for RCT and E(30) compared with the heritabilities of the repeatability model. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Diversity and population structure of a dominant deciduous tree based on morphological and genetic data

PubMed Central

Zhang, Qin-di; Jia, Rui-Zhi; Meng, Chao; Ti, Chao-Wen; Wang, Yi-Ling

2015-01-01

Knowledge of the genetic diversity and structure of tree species across their geographic ranges is essential for sustainable use and management of forest ecosystems. Acer grosseri Pax., an economically and ecologically important maple species, is mainly distributed in North China. In this study, the genetic diversity and population differentiation of 24 natural populations of this species were evaluated using sequence-related amplified polymorphism markers and morphological characters. The results show that highly significant differences occurred in 32 morphological traits. The coefficient of variation of 34 characters was 18.19 %. Principal component analysis indicated that 18 of 34 traits explained 60.20 % of the total variance. The phenotypic differentiation coefficient (VST) was 36.06 % for all morphological traits. The Shannon–Wiener index of 34 morphological characters was 6.09, while at the population level, it was 1.77. The percentage of polymorphic bands of all studied A. grosseri populations was 82.14 %. Nei's gene diversity (He) and Shannon's information index (I) were 0.35 and 0.50, respectively. Less genetic differentiation was detected among the natural populations (GST = 0.20, ΦST = 0.10). Twenty-four populations of A. grosseri formed two main clusters, which is consistent with morphological cluster analysis. Principal coordinates analysis and STRUCTURE analysis supported the UPGMA-cluster dendrogram. There was no significant correlation between genetic and geographical distances among populations. Both molecular and morphological data suggested that A. grosseri is rich in genetic diversity. The high level of genetic variation within populations could be affected by the biological characters, mating system and lifespan of A. grosseri, whereas the lower genetic diversity among populations could be caused by effective gene exchange, selective pressure from environmental heterogeneity and the species' geographical range. PMID:26311734

Genetics of alternative definitions of feed efficiency in grazing lactating dairy cows.

PubMed

Hurley, A M; López-Villalobos, N; McParland, S; Lewis, E; Kennedy, E; O'Donovan, M; Burke, J L; Berry, D P

2017-07-01

The objective of the present study was to estimate genetic parameters across lactation for measures of energy balance (EB) and a range of feed efficiency variables as well as to quantify the genetic inter-relationships between them. Net energy intake (NEI) from pasture and concentrate intake was estimated up to 8 times per lactation for 2,481 lactations from 1,274 Holstein-Friesian cows. A total of 8,134 individual feed intake measurements were used. Efficiency traits were either ratio based or residual based; the latter were derived from least squares regression models. Residual energy intake (REI) was defined as NEI minus predicted energy requirements [e.g., net energy of lactation (NE L ), maintenance, and body tissue anabolism] or supplied from body tissue mobilization; residual energy production was defined as the difference between actual NE L and predicted NE L based on NEI, maintenance, and body tissue anabolism/catabolism. Energy conversion efficiency was defined as NE L divided by NEI. Random regression animal models were used to estimate residual, additive genetic, and permanent environmental (co)variances across lactation. Heritability across lactation stages varied from 0.03 to 0.36 for all efficiency traits. Within-trait genetic correlations tended to weaken as the interval between lactation stages compared lengthened for EB, REI, residual energy production, and NEI. Analysis of eigenvalues and associated eigenfunctions for EB and the efficiency traits indicate the ability to genetically alter the profile of these lactation curves to potentially improve dairy cow efficiency differently at different stages of lactation. Residual energy intake and EB were moderately to strongly genetically correlated with each other across lactation (genetic correlations ranged from 0.45 to 0.90), indicating that selection for lower REI alone (i.e., deemed efficient cows) would favor cows with a compromised energy status; nevertheless, selection for REI within a holistic breeding goal could be used to overcome such antagonisms. The smallest (8.90% of genetic variance) and middle (11.22% of genetic variance) eigenfunctions for REI changed sign during lactation, indicating the potential to alter the shape of the REI lactation profile. Results from the present study suggest exploitable genetic variation exists for a range of efficiency traits, and the magnitude of this variation is sufficiently large to justify consideration of the feed efficiency complex in future dairy breeding goals. Moreover, it is possible to alter the trajectories of the efficiency traits to suit a particular breeding objective, although this relies on very precise across-parity genetic parameter estimates, including genetic correlations with health and fertility traits (as well as other traits). Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genetic Variation and Geographic Differentiation Among Populations of the Nonmigratory Agricultural Pest Oedaleus infernalis (Orthoptera: Acridoidea) in China

PubMed Central

Sun, Wei; Dong, Hui; Gao, Yue-Bo; Su, Qian-Fu; Qian, Hai-Tao; Bai, Hong-Yan; Zhang, Zhu-Ting; Cong, Bin

2015-01-01

The nonmigratory grasshopper Oedaleus infernalis Saussure (Orthoptera : Acridoidea) is an agricultural pest to crops and forage grasses over a wide natural geographical distribution in China. The genetic diversity and genetic variation among 10 geographically separated populations of O. infernalis was assessed using polymerase chain reaction-based molecular markers, including the intersimple sequence repeat and mitochondrial cytochrome oxidase sequences. A high level of genetic diversity was detected among these populations from the intersimple sequence repeat (H: 0.2628, I: 0.4129, Hs: 0.2130) and cytochrome oxidase analyses (Hd: 0.653). There was no obvious geographical structure based on an unweighted pair group method analysis and median-joining network. The values of FST, θII, and Gst estimated in this study are low, and the gene flow is high (Nm > 4). Analysis of the molecular variance suggested that most of the genetic variation occurs within populations, whereas only a small variation takes place between populations. No significant correlation was found between the genetic distance and geographical distance. Overall, our results suggest that the geographical distance plays an unimpeded role in the gene flow among O. infernalis populations. PMID:26496789

Epilepsy may be the major risk factor of mental retardation in children with tuberous sclerosis: A retrospective cohort study.

PubMed

Wang, Yang-Yang; Pang, Ling-Yu; Ma, Shu-Fang; Zhang, Meng-Na; Liu, Li-Ying; Zou, Li-Ping

2017-12-01

Mental retardation (MR) is one of the most common cognitive comorbidities in children with tuberous sclerosis, and there are enormous studies about its risk factors. The genetic difference and the severity of epilepsy are the two main factors, but their weight in the occurrence of MR is still unclear. Two hundred twenty-three patients with tuberous sclerosis who received intelligence assessment, genetic mutation analysis, and the epilepsy severity assessment were included in our study. Genotype-neurocognitive phenotype correlations and epilepsy-neurocognitive phenotype correlations were analyzed by binary logistic regression analysis. No statistical significant result was found on genotype-neurocognitive phenotype correlations, which contrasted the previous report. The prevalence of MR was 50.0% for the patients with tuberous sclerosis complex-1 (TSC1) mutation, 54.5% for TSC2 (p=0.561), 54.7% for patients with protein-truncating (PT) and 50.0% for patients with nontruncating (NT) (p=0.791), and 54.3% for patients with family history and 53.7% for patients without family history (p=0.748). Statistical significant results were found on epilepsy-neurocognitive phenotype correlations, both on E-chess score (p=0.01) and the occurrence of infantile spasms (p=0.014), which was consistent to the previous study. For children with tuberous sclerosis, instead of genetic factors, epilepsy may play the main role for the presence of mental retardation. Patients with mental retardation tend to have earlier seizure attack, take more AEDs, have more seizure types, and have higher seizure frequency. Among the four cognitive functions in Denver II, social ability and language ability are more vulnerable to be influenced than fine and gross motor ability. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel mutations and their genotype-phenotype correlations in patients with Noonan syndrome, using next-generation sequencing.

PubMed

Tafazoli, Alireza; Eshraghi, Peyman; Pantaleoni, Francesca; Vakili, Rahim; Moghaddassian, Morteza; Ghahraman, Martha; Muto, Valentina; Paolacci, Stefano; Golyan, Fatemeh Fardi; Abbaszadegan, Mohammad Reza

2018-03-01

Noonan Syndrome (NS) is an autosomal dominant disorder with many variable and heterogeneous conditions. The genetic basis for 20-30% of cases is still unknown. This study evaluates Iranian Noonan patients both clinically and genetically for the first time. Mutational analysis of PTPN11 gene was performed in 15 Iranian patients, using PCR and Sanger sequencing at phase one. Then, as phase two, Next Generation Sequencing (NGS) in the form of targeted resequencing was utilized for analysis of exons from other related genes. Homology modelling for the novel founded mutations was performed as well. The genotype, phenotype correlation was done according to the molecular findings and clinical features. Previously reported mutation (p.N308D) in some patients and a novel mutation (p.D155N) in one of the patients were identified in phase one. After applying NGS methods, known and new variants were found in four patients in other genes, including: CBL (p. V904I), KRAS (p. L53W), SOS1 (p. I1302V), and SOS1 (p. R552G). Structural studies of two deduced novel mutations in related genes revealed deficiencies in the mutated proteins. Following genotype, phenotype correlation, a new pattern of the presence of intellectual disability in two patients was registered. NS shows strong variable expressivity along the high genetic heterogeneity especially in distinct populations and ethnic groups. Also possibly unknown other causative genes may be exist. Obviously, more comprehensive and new technologies like NGS methods are the best choice for detection of molecular defects in patients for genotype, phenotype correlation and disease management. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Correlation Analysis of Genetic Admixture and Social Identification with Body Mass Index in a Native American Community

PubMed Central

Norden-Krichmar, Trina M.; Gizer, Ian R.; Libiger, Ondrej; Wilhelmsen, Kirk C.; Ehlers, Cindy L.; Schork, Nicholas J.

2014-01-01

Objectives Body mass index (BMI) is a well-known measure of obesity with a multitude of genetic and non-genetic determinants. Identifying the underlying factors associated with BMI is difficult because of its multifactorial etiology that varies as a function of geoethnic background and socioeconomic setting. Thus, we pursued a study exploring the influence of the degree of Native American admixture on BMI (as well as weight and height individually) in a community sample of Native Americans (n=846) while accommodating a variety of socioeconomic and cultural factors. Methods Participants’ degree of Native American (NA) ancestry was estimated using a genome-wide panel of markers. The participants also completed an extensive survey of cultural and social identity measures: the Indian Culture Scale (ICS) and the Orthogonal Cultural Identification Scale (OCIS). Multiple linear regression was used to examine the relation between these measures and BMI. Results Our results suggest that BMI is correlated positively with the proportion of NA ancestry. Age was also significantly associated with BMI, while gender and socioeconomic measures (education and income) were not. For the two cultural identity measures, the ICS showed a positive correlation with BMI, while OCIS was not associated with BMI. Conclusions Taken together, these results suggest that genetic and cultural environmental factors, rather than socioeconomic factors, account for a substantial proportion of variation in BMI in this population. Further, significant correlations between degree of NA ancestry and BMI suggest that admixture mapping may be appropriate to identify loci associated with BMI in this population. PMID:24757035

Population structure, migration, and diversifying selection in the Netherlands

PubMed Central

Abdellaoui, Abdel; Hottenga, Jouke-Jan; Knijff, Peter de; Nivard, Michel G; Xiao, Xiangjun; Scheet, Paul; Brooks, Andrew; Ehli, Erik A; Hu, Yueshan; Davies, Gareth E; Hudziak, James J; Sullivan, Patrick F; van Beijsterveldt, Toos; Willemsen, Gonneke; de Geus, Eco J; Penninx, Brenda W J H; Boomsma, Dorret I

2013-01-01

Genetic variation in a population can be summarized through principal component analysis (PCA) on genome-wide data. PCs derived from such analyses are valuable for genetic association studies, where they can correct for population stratification. We investigated how to capture the genetic population structure in a well-characterized sample from the Netherlands and in a worldwide data set and examined whether (1) removing long-range linkage disequilibrium (LD) regions and LD-based SNP pruning significantly improves correlations between PCs and geography and (2) whether genetic differentiation may have been influenced by migration and/or selection. In the Netherlands, three PCs showed significant correlations with geography, distinguishing between: (1) North and South; (2) East and West; and (3) the middle-band and the rest of the country. The third PC only emerged with minimized LD, which also significantly increased correlations with geography for the other two PCs. In addition to geography, the Dutch North–South PC showed correlations with genome-wide homozygosity (r=0.245), which may reflect a serial-founder effect due to northwards migration, and also with height (♂: r=0.142, ♀: r=0.153). The divergence between subpopulations identified by PCs is partly driven by selection pressures. The first three PCs showed significant signals for diversifying selection (545 SNPs - the majority within 184 genes). The strongest signal was observed between North and South for the functional SNP in HERC2 that determines human blue/brown eye color. Thus, this study demonstrates how to increase ancestry signals in a relatively homogeneous population and how those signals can reveal evolutionary history. PMID:23531865

Three-way parallel independent component analysis for imaging genetics using multi-objective optimization.

PubMed

Ulloa, Alvaro; Jingyu Liu; Vergara, Victor; Jiayu Chen; Calhoun, Vince; Pattichis, Marios

2014-01-01

In the biomedical field, current technology allows for the collection of multiple data modalities from the same subject. In consequence, there is an increasing interest for methods to analyze multi-modal data sets. Methods based on independent component analysis have proven to be effective in jointly analyzing multiple modalities, including brain imaging and genetic data. This paper describes a new algorithm, three-way parallel independent component analysis (3pICA), for jointly identifying genomic loci associated with brain function and structure. The proposed algorithm relies on the use of multi-objective optimization methods to identify correlations among the modalities and maximally independent sources within modality. We test the robustness of the proposed approach by varying the effect size, cross-modality correlation, noise level, and dimensionality of the data. Simulation results suggest that 3p-ICA is robust to data with SNR levels from 0 to 10 dB and effect-sizes from 0 to 3, while presenting its best performance with high cross-modality correlations, and more than one subject per 1,000 variables. In an experimental study with 112 human subjects, the method identified links between a genetic component (pointing to brain function and mental disorder associated genes, including PPP3CC, KCNQ5, and CYP7B1), a functional component related to signal decreases in the default mode network during the task, and a brain structure component indicating increases of gray matter in brain regions of the default mode region. Although such findings need further replication, the simulation and in-vivo results validate the three-way parallel ICA algorithm presented here as a useful tool in biomedical data decomposition applications.

The Genetics Concept Assessment: a new concept inventory for gauging student understanding of genetics.

PubMed

Smith, Michelle K; Wood, William B; Knight, Jennifer K

2008-01-01

We have designed, developed, and validated a 25-question Genetics Concept Assessment (GCA) to test achievement of nine broad learning goals in majors and nonmajors undergraduate genetics courses. Written in everyday language with minimal jargon, the GCA is intended for use as a pre- and posttest to measure student learning gains. The assessment was reviewed by genetics experts, validated by student interviews, and taken by >600 students at three institutions. Normalized learning gains on the GCA were positively correlated with averaged exam scores, suggesting that the GCA measures understanding of topics relevant to instructors. Statistical analysis of our results shows that differences in the item difficulty and item discrimination index values between different questions on pre- and posttests can be used to distinguish between concepts that are well or poorly learned during a course.

Personality and divorce: a genetic analysis.

PubMed

Jocklin, V; McGue, M; Lykken, D T

1996-08-01

M. McGue and D.T. Lykken (1992) found that divorce risk was, to a substantial degree, genetically mediated; prior research has identified numerous social and psychological factors that affect divorce risk (G.C. Kitson, K.B. Barbi, & M.J. Roach, 1985). The present study attempted to link these domains by examining the extent to which genetic influences on one such psychological factor, personality, explain divorce risk heritability. A sample of adult twins from the Minnesota Twin Registry completed a marital history questionnaire and the Multidimensional Personality Questionnaire (A. Tellegen, 1982). Positive Emotionality and Negative Emotionality factors were positively related to divorce risk, whereas Constraint was negatively related. In women and men, respectively, 30% and 42% of the heritability of divorce risk consisted of genetic factors affecting personality and divorce risk correlated largely as a result of these common genetic influences.

The Genetics Concept Assessment: A New Concept Inventory for Gauging Student Understanding of Genetics

PubMed Central

Wood, William B.; Knight, Jennifer K.

2008-01-01

We have designed, developed, and validated a 25-question Genetics Concept Assessment (GCA) to test achievement of nine broad learning goals in majors and nonmajors undergraduate genetics courses. Written in everyday language with minimal jargon, the GCA is intended for use as a pre- and posttest to measure student learning gains. The assessment was reviewed by genetics experts, validated by student interviews, and taken by >600 students at three institutions. Normalized learning gains on the GCA were positively correlated with averaged exam scores, suggesting that the GCA measures understanding of topics relevant to instructors. Statistical analysis of our results shows that differences in the item difficulty and item discrimination index values between different questions on pre- and posttests can be used to distinguish between concepts that are well or poorly learned during a course. PMID:19047428

Heritability and genetic correlations of personality traits in a wild population of yellow-bellied marmots (Marmota flaviventris).

PubMed

Petelle, M B; Martin, J G A; Blumstein, D T

2015-10-01

Describing and quantifying animal personality is now an integral part of behavioural studies because individually distinctive behaviours have ecological and evolutionary consequences. Yet, to fully understand how personality traits may respond to selection, one must understand the underlying heritability and genetic correlations between traits. Previous studies have reported a moderate degree of heritability of personality traits, but few of these studies have either been conducted in the wild or estimated the genetic correlations between personality traits. Estimating the additive genetic variance and covariance in the wild is crucial to understand the evolutionary potential of behavioural traits. Enhanced environmental variation could reduce heritability and genetic correlations, thus leading to different evolutionary predictions. We estimated the additive genetic variance and covariance of docility in the trap, sociability (mirror image stimulation), and exploration and activity in two different contexts (open-field and mirror image simulation experiments) in a wild population of yellow-bellied marmots (Marmota flaviventris). We estimated both heritability of behaviours and of personality traits and found nonzero additive genetic variance in these traits. We also found nonzero maternal, permanent environment and year effects. Finally, we found four phenotypic correlations between traits, and one positive genetic correlation between activity in the open-field test and sociability. We also found permanent environment correlations between activity in both tests and docility and exploration in the MIS test. This is one of a handful of studies to adopt a quantitative genetic approach to explain variation in personality traits in the wild and, thus, provides important insights into the potential variance available for selection. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Shared genetic contributions of fruit and vegetable consumption with BMI in families 20 y after sharing a household.

PubMed

Martin, Lisa J; Lee, Seung-Yeon; Couch, Sarah C; Morrison, John; Woo, Jessica G

2011-10-01

Obesity has a strong genetic basis, but the identification of genetic variants has not resulted in improved clinical care. However, phenotypes that influence weight, such as diet, may have shared underpinnings with obesity. Interestingly, diet also has a genetic basis. Thus, we hypothesized that the genetic underpinnings of diet may partially overlap with the genetics of obesity. Our objective was to determine whether dietary intake and BMI share heritable components in adulthood. We used a cross-sectional cohort of parents and adult offspring (n = 1410) from the Princeton Follow-up Study. Participants completed Block food-frequency questionnaires 15-27 y after sharing a household. Heritability of dietary intakes was estimated by using variance components analysis. Bivariate genetic analyses were used to estimate the shared effects between BMI and heritable dietary intakes. Fruit, vegetable, and protein consumption exhibited moderate heritability [(mean ± SE) 0.26 ± 0.06, 0.32 ± 0.06, and 0.21 ± 0.06, respectively; P < 0.001], but other dietary intakes were modest (h(2) < 0.2). Only fruit and vegetable consumption exhibited genetic correlations with BMI (ρ(g) = -0.28 ± 0.13 and -0.30 ± 0.13, respectively; P < 0.05). Phenotypic correlations with BMI were not significant. We showed that fruit, vegetable, and protein intakes are moderately heritable and that fruit and vegetable consumption shares underlying genetic effects with BMI in adulthood, which suggests that individuals genetically predisposed to low fruit and vegetable consumption may be predisposed to higher BMI. Thus, obese individuals who have low fruit and vegetable consumption may require targeted interventions that go beyond low-calorie, plant-based programs for weight management.

Genetic Variation of Beet Armyworm (Lepidoptera: Noctuidae) Populations Detected Using Microsatellite Markers in Iran.

PubMed

Golikhajeh, Neshat; Naseri, Bahram; Razmjou, Jabraeil; Hosseini, Reza; Aghbolaghi, Marzieh Asadi

2018-05-28

In order to understand the population genetic diversity and structure of Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), a serious pest of sugar beet in Iran and the world, we genotyped 133 individuals from seven regions in Iran using four microsatellite loci. Significant difference was seen between the observed and expected heterozygosity in all loci. A lower observed heterozygosity than expected heterozygosity indicated a low heterozygosity in these populations. The value of F showed a high genetic differentiation, so that the mean of Fst was 0.21. Molecular analysis variance showed significant differences within and among populations with group variance accounted for 71 and 21%, respectively. No correlation was found between pair-wise Fst and geographic distance by Mantel test. Bayesian clustering analysis grouped all regions to two clusters. These data suggested that a combination of different factors, such as geographic distance, environmental condition, and physiological behavior in addition to genetic factors, could play an important role in forming variation within and between S. exigua populations.

Ndufs4 related Leigh syndrome: A case report and review of the literature.

PubMed

Ortigoza-Escobar, Juan Darío; Oyarzabal, Alfonso; Montero, Raquel; Artuch, Rafael; Jou, Cristina; Jiménez, Cecilia; Gort, Laura; Briones, Paz; Muchart, Jordi; López-Gallardo, Ester; Emperador, Sonia; Pesini, Eduardo Ruiz; Montoya, Julio; Pérez, Belén; Rodríguez-Pombo, Pilar; Pérez-Dueñas, Belén

2016-05-01

The genetic causes of Leigh syndrome are heterogeneous, with a poor correlation between the phenotype and genotype. Here, we present a patient with an NDUFS4 mutation to expand the clinical and biochemical spectrum of the disease. A combined defect in the CoQ, PDH and RCC activities in our patient was due to an inappropriate assembly of the RCC complex I (CI), which was confirmed using Blue-Native polyacrylamide gel electrophoresis (BN-PAGE) analysis. Targeted exome sequencing analysis allowed for the genetic diagnosis of this patient. We reviewed 198 patients with 24 different genetic defects causing RCC I deficiency and compared them to 22 NDUFS4 patients. We concluded that NDUFS4-related Leigh syndrome is invariably linked to an early onset severe phenotype that results in early death. Some data, including the clinical phenotype, neuroimaging and biochemical findings, can guide the genetic study in patients with RCC I deficiency. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study.

PubMed

Strauss, David G; Vicente, Jose; Johannesen, Lars; Blinova, Ksenia; Mason, Jay W; Weeke, Peter; Behr, Elijah R; Roden, Dan M; Woosley, Ray; Kosova, Gulum; Rosenberg, Michael A; Newton-Cheh, Christopher

2017-04-04

Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs. Genetic analysis of 22 subjects was performed in a secondary analysis of a randomized, double-blind, placebo-controlled, crossover trial of 3 QT-prolonging drugs with 15 time-matched QT and plasma drug concentration measurements. Subjects received single doses of dofetilide, quinidine, ranolazine, and placebo. The outcome was the correlation between a genetic QT score comprising 61 common genetic variants and the slope of an individual subject's drug-induced increase in heart rate-corrected QT (QTc) versus drug concentration. The genetic QT score was correlated with drug-induced QTc prolongation. Among white subjects, genetic QT score explained 30% of the variability in response to dofetilide ( r =0.55; 95% confidence interval, 0.09-0.81; P =0.02), 23% in response to quinidine ( r =0.48; 95% confidence interval, -0.03 to 0.79; P =0.06), and 27% in response to ranolazine ( r =0.52; 95% confidence interval, 0.05-0.80; P =0.03). Furthermore, the genetic QT score was a significant predictor of drug-induced torsade de pointes in an independent sample of 216 cases compared with 771 controls ( r 2 =12%, P =1×10 -7 ). We demonstrate that a genetic QT score comprising 61 common genetic variants explains a significant proportion of the variability in drug-induced QT prolongation and is a significant predictor of drug-induced torsade de pointes. These findings highlight an opportunity for recent genetic discoveries to improve individualized risk-benefit assessment for pharmacological therapies. Replication of these findings in larger samples is needed to more precisely estimate variance explained and to establish the individual variants that drive these effects. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01873950. © 2017 American Heart Association, Inc.

Results from six generations of selection for intramuscular fat in Duroc swine using real-time ultrasound. II. Genetic parameters and trends.

PubMed

Schwab, C R; Baas, T J; Stalder, K J

2010-01-01

Design of breeding programs requires knowledge of variance components that exist for traits included in specific breeding goals and the genetic relationships that exist among traits of economic importance. A study was conducted to evaluate direct and correlated genetic responses to selection for intramuscular fat (IMF) and to estimate genetic parameters for economically important traits in Duroc swine. Forty gilts were purchased from US breeders and randomly mated for 2 generations to boars available in regional boar studs to develop a base population of 56 litters. Littermate pairs of gilts from this population were randomly assigned to a select line (SL) or control line (CL) and mated to the same boar to establish genetic ties between lines. In the SL, the top 10 boars and 75 gilts were selected based on IMF EBV obtained from a bivariate animal model that included IMF evaluated on the carcass and IMF predicted via ultrasound. One boar from each sire family and 50 to 60 gilts representing all sire families were randomly selected to maintain the CL. Carcass and ultrasound IMF were both moderately heritable (0.31 and 0.38, respectively). Moderate to high genetic relationships were estimated among carcass backfat and meat quality measures of IMF, Instron tenderness, and objective loin muscle color. Based on estimates obtained in this study, more desirable genetic merit for pH is associated with greater genetic value for loin color, tenderness, and sensory characteristics. Intramuscular fat measures obtained on the carcass and predicted using ultrasound technology were highly correlated (r(g) = 0.86 from a 12-trait analysis; r(g) = 0.90 from a 5-trait analysis). Estimated genetic relationships among IMF measures and other traits evaluated were generally consistent. Intramuscular fat measures were also genetically associated with Instron tenderness and flavor score in a desirable direction. Direct genetic response in IMF measures observed in the SL corresponded to a significant decrease in EBV for carcass loin muscle area (-0.90 cm(2) per generation) and an increase in carcass backfat EBV (0.98 mm per generation). Selection for IMF has led to more desirable EBV for objective tenderness and has had an adverse effect on additive genetic merit for objective loin color.

Heritability and genetic integration of tooth size in the South Carolina Gullah.

PubMed

Stojanowski, Christopher M; Paul, Kathleen S; Seidel, Andrew C; Duncan, William N; Guatelli-Steinberg, Debbie

2017-11-01

This article provides estimates of narrow-sense heritability and genetic pleiotropy for mesiodistal tooth dimensions for a sample of 20th century African American individuals. Results inform biological distance analysis and offer insights into patterns of integration in the human dentition. Maximum mesiodistal crown dimensions were measured using Hillson-FitzGerald calipers on 469 stone dental casts from the Menegaz-Bock Collection. Narrow-sense heritability estimates and genetic and phenotypic correlations were estimated using SOLAR 8.1.1 with covariate screening for age, sex, age*sex interaction, and birth year. Heritability estimates were moderate (∼0.10 - 0.90; h 2 mean = 0.51) for most measured variables with sex as the only significant covariate. Patterns of genetic correlation indicate strong integration across tooth classes, except molars. Comparison of these results to previously published work suggests lower overall heritability relative to other human populations and much stronger genetic integration across tooth classes than obtained from nonhuman primate genetic pleiotropy estimates. These results suggest that the high heritabilities previously published may reflect overestimates inherent in previous study designs; as such the standard estimate of 0.55 used in biodistance analyses may not be appropriate. For the Gullah, isolation and endogamy coupled with elevated levels of physiological and economic stress may suppress narrow-sense heritability estimates. Pleiotropy analyses suggest a more highly integrated dentition in humans than in other mammals. © 2017 Wiley Periodicals, Inc.

Genetic relationship between growth and reproductive traits in Nellore cattle.

PubMed

Santana, M L; Eler, J P; Ferraz, J B S; Mattos, E C

2012-04-01

The objective of this study was to evaluate the genetic relationship between postweaning weight gain (PWG), heifer pregnancy (HP), scrotal circumference (SC) at 18 months of age, stayability at 6 years of age (STAY) and finishing visual score at 18 months of age (PREC), and to determine the potential of these traits as selection criteria for the genetic improvement of growth and reproduction in Nellore cattle. The HP was defined as the observation that a heifer conceived and remained pregnant, which was assessed by rectal palpation at 60 days. The STAY was defined as whether or not a cow calved every year up to the age of 6 years, given that she was provided the opportunity to breed. The Bayesian linear-threshold analysis via the Gibbs sampler was used to estimate the variance and covariance components applying a multitrait model. Posterior mean estimates of direct heritability were 0.15 ± 0.00, 0.42 ± 0.02, 0.49 ± 0.01, 0.11 ± 0.01 and 0.19 ± 0.00 for PWG, HP, SC, STAY and PREC, respectively. The genetic correlations between traits ranged from 0.17 to 0.62. The traits studied generally have potential for use as selection criteria in genetic breeding programs. The genetic correlations between all traits show that selection for one of these traits does not imply the loss of the others.

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

NASA Astrophysics Data System (ADS)

McLaughlin, Russell L.; Schijven, Dick; van Rheenen, Wouter; van Eijk, Kristel R.; O'Brien, Margaret; Kahn, René S.; Ophoff, Roel A.; Goris, An; Bradley, Daniel G.; Al-Chalabi, Ammar; van den Berg, Leonard H.; Luykx, Jurjen J.; Hardiman, Orla; Veldink, Jan H.; Shatunov, Aleksey; Dekker, Annelot M.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.; van Doormaal, Perry T. C.; Sproviero, William; Jones, Ashley R.; Nicholson, Garth A.; Rowe, Dominic B.; Pamphlett, Roger; Kiernan, Matthew C.; Bauer, Denis; Kahlke, Tim; Williams, Kelly; Eftimov, Filip; Fogh, Isabella; Ticozzi, Nicola; Lin, Kuang; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S.; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E.; Shaw, Pamela J.; Hardy, John; Orrell, Richard W.; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Petri, Susanne; Abdulla, Susanna; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; van Deerlin, Vivianna M.; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Basak, Nazli; Meitinger, Thomas; Lichtner, Peter; Blagojevic-Radivojkov, Milena; Andres, Christian R.; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A. M.; Saker-Delye, Safa; Dürr, Alexandra; Wood, Nicholas; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöuthen, Markus M.; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; van der Kooi, Anneke J.; de Visser, Marianne; Weber, Markus; Shaw, Christopher E.; Smith, Bradley N.; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P.; D'Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simon; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Blair, Ian; Leigh, P. Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C.; Weishaupt, Jochen H.; Robberecht, Wim; van Damme, Philip; Brown, Robert H.; Glass, Jonathan; Landers, John E.; Andersen, Peter M.; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; van Es, Michael A.; Pasterkamp, R. Jeroen; Lewis, Cathryn M.; Breen, Gerome; Ripke, Stephan; Neale, Benjamin M.; Corvin, Aiden; Walters, James T. R.; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A.; Huang, Hailiang; Pers, Tune H.; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A.; Begemann, Martin; Belliveau, Richard A.; Bene, Judit; Bergen, Sarah E.; Bevilacqua, Elizabeth; Bigdeli, Tim B.; Black, Donald W.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberley D.; Chan, Raymond C. K.; Chan, Ronald Y. L.; Chen, Eric Y. H.; Cheng, Wei; Cheung, Eric F. C.; Chong, Siow Ann; Cloninger, C. Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; Del Favero, Jurgen; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H.; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Friedman, Joseph I.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Giegling, Ina; Giusti-Rodríguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V.; Hougaard, David M.; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kennedy, James L.; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A.; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K.; Laurent, Claudine; Lee, Jimmy; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M.; Lubinski, Jan; Lönnqvist, Jouko; Macek, Milan; Magnusson, Patrik K. E.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Mors, Ole; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Müller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O'Callaghan, Eadbhard; O'Dushlaine, Colm; O'Neill, F. Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; van Os, Jim; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T.; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O.; Pietiläinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Price, Alkes; Pulver, Ann E.; Purcell, Shaun M.; Quested, Digby; Rasmussen, Henrik B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Schall, Ulrich; Schubert, Christian R.; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M.; Sim, Kang; Slominsky, Petr; Smoller, Jordan W.; So, Hon-Cheong; Spencer, Chris C. A.; Stahl, Eli A.; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Söderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tosato, Sarah; Veijola, Juha; Waddington, John; Walsh, Dermot; Wang, Dai; Wang, Qiang; Webb, Bradley T.; Weiser, Mark; Wildenauer, Dieter B.; Williams, Nigel M.; Williams, Stephanie; Witt, Stephanie H.; Wolen, Aaron R.; Wong, Emily H. M.; Wormley, Brandon K.; Xi, Hualin Simon; Zai, Clement C.; Zheng, Xuebin; Zimprich, Fritz; Wray, Naomi R.; Stefansson, Kari; Visscher, Peter M.; Adolfsson, Rolf; Andreassen, Ole A.; Blackwood, Douglas H. R.; Bramon, Elvira; Buxbaum, Joseph D.; Børglum, Anders D.; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Esko, Tõnu; Gejman, Pablo V.; Gill, Michael; Gurling, Hugh; Hultman, Christina M.; Iwata, Nakao; Jablensky, Assen V.; Jönsson, Erik G.; Kendler, Kenneth S.; Kirov, George; Knight, Jo; Lencz, Todd; Levinson, Douglas F.; Li, Qingqin S.; Liu, Jianjun; Malhotra, Anil K.; McCarroll, Steven A.; McQuillin, Andrew; Moran, Jennifer L.; Mortensen, Preben B.; Mowry, Bryan J.; Owen, Michael J.; Palotie, Aarno; Pato, Carlos N.; Petryshen, Tracey L.; Posthuma, Danielle; Riley, Brien P.; Rujescu, Dan; Sham, Pak C.; Sklar, Pamela; St Clair, David; Weinberger, Daniel R.; Wendland, Jens R.; Werge, Thomas; Daly, Mark J.; Sullivan, Patrick F.; O'Donovan, Michael C.

2017-03-01

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6 P=1 × 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia.

PubMed

McLaughlin, Russell L; Schijven, Dick; van Rheenen, Wouter; van Eijk, Kristel R; O'Brien, Margaret; Kahn, René S; Ophoff, Roel A; Goris, An; Bradley, Daniel G; Al-Chalabi, Ammar; van den Berg, Leonard H; Luykx, Jurjen J; Hardiman, Orla; Veldink, Jan H

2017-03-21

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10 -4 ) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10 -7 ). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.

Genetic relationships between detailed reproductive traits and performance traits in Holstein-Friesian dairy cattle.

PubMed

Carthy, T R; Ryan, D P; Fitzgerald, A M; Evans, R D; Berry, D P

2016-02-01

The objective of the study was to estimate the genetic relationships between detailed reproductive traits derived from ultrasound examination of the reproductive tract and a range of performance traits in Holstein-Friesian dairy cows. The performance traits investigated included calving performance, milk production, somatic cell score (i.e., logarithm transformation of somatic cell count), carcass traits, and body-related linear type traits. Detailed reproductive traits included (1) resumed cyclicity at the time of examination, (2) multiple ovulations, (3) early ovulation, (4) heat detection, (5) ovarian cystic structures, (6) embryo loss, and (7) uterine score, measured on a 1 (little or no fluid with normal tone) to 4 (large quantity of fluid with a flaccid tone) scale, based on the tone of the uterine wall and the quantity of fluid present in the uterus. (Co)variance components were estimated using a repeatability animal linear mixed model. Genetic merit for greater milk, fat, and protein yield was associated with a reduced ability to resume cyclicity postpartum (genetic correlations ranged from -0.25 to -0.15). Higher genetic merit for milk yield was also associated with a greater genetic susceptibility to multiple ovulations. Genetic predisposition to elevated somatic cell score was associated with a decreased likelihood of cyclicity postpartum (genetic correlation of -0.32) and a greater risk of both multiple ovulations (genetic correlation of 0.25) and embryo loss (genetic correlation of 0.32). Greater body condition score was genetically associated with an increased likelihood of resumption of cyclicity postpartum (genetic correlation of 0.52). Genetically heavier, fatter carcasses with better conformation were also associated with an increased likelihood of resumed cyclicity by the time of examination (genetic correlations ranged from 0.24 to 0.41). Genetically heavier carcasses were associated with an inferior uterine score as well as a greater predisposition to embryo loss. Despite the overall antagonistic relationship between reproductive performance and both milk and carcass traits, not all detailed aspects of reproduction performance exhibited an antagonistic relationship. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genetic diversity patterns of arbuscular mycorrhizal fungi associated with the mycoheterotroph Arachnitis uniflora Phil. (Corsiaceae).

PubMed

Renny, Mauricio; Acosta, M Cristina; Cofré, Noelia; Domínguez, Laura S; Bidartondo, Martin I; Sérsic, Alicia N

2017-06-01

Arachnitis uniflora is a mycoheterotrophic plant that exploits arbuscular mycorrhizal fungi of neighbouring plants. We tested A. uniflora 's specificity towards fungi across its large latitudinal range, as well as the role of historical events and current environmental, geographical and altitudinal variables on fungal genetic diversity. Arachnitis uniflora mycorrhizas were sampled at 25 sites. Fungal phylogenetic relationships were reconstructed, genetic diversity was calculated and the main divergent lineages were dated. Phylogeographical analysis was performed with the main fungal clade. Fungal diversity correlations with environmental factors were investigated. Glomeraceae fungi dominated, with a main clade that likely originated in the Upper Cretaceous and diversified in the Miocene. Two other arbuscular mycorrhizal fungal families not previously known to be targeted by A. uniflora were detected rarely and appear to be facultative associations. High genetic diversity, found in Bolivia and both northern and southern Patagonia, was correlated with temperature, rainfall and soil features. Fungal genetic diversity and its distribution can be explained by the ancient evolutionary history of the target fungi and by micro-scale environmental conditions with a geographical mosaic pattern. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

An experimental analysis of the heritability of variation in glucocorticoid concentrations in a wild avian population

PubMed Central

Jenkins, Brittany R.; Vitousek, Maren N.; Hubbard, Joanna K.; Safran, Rebecca J.

2014-01-01

Glucocorticoid hormones (CORT) are predicted to promote adaptation to variable environments, yet little is known about the potential for CORT secretion patterns to respond to selection in free-living populations. We assessed the heritable variation underlying differences in hormonal phenotypes using a cross-foster experimental design with nestling North American barn swallows (Hirundo rustica erythrogaster). Using a bivariate animal model, we partitioned variance in baseline and stress-induced CORT concentrations into their additive genetic and rearing environment components and estimated their genetic correlation. Both baseline and stress-induced CORT were heritable with heritability of 0.152 and 0.343, respectively. We found that the variation in baseline CORT was best explained by rearing environment, whereas the variation in stress-induced CORT was contributed to by a combination of genetic and environmental factors. Further, we did not detect a genetic correlation between these two hormonal traits. Although rearing environment appears to play an important role in the secretion of both types of CORT, our results suggest that stress-induced CORT levels are underlain by greater additive genetic variance compared with baseline CORT levels. Accordingly, we infer that the glucocorticoid response to stress has a greater potential for evolutionary change in response to selection compared with baseline glucocorticoid secretion patterns. PMID:25056627

Genetic diversity and geographic differentiation analysis of duckweed using inter-simple sequence repeat markers.

PubMed

Xue, Huiling; Xiao, Yao; Jin, Yanling; Li, Xinbo; Fang, Yang; Zhao, Hai; Zhao, Yun; Guan, Jiafa

2012-01-01

Duckweed, with rapid growth rate and high starch content, is a new alternate feedstock for bioethanol production. The genetic diversity among 27 duckweed populations of seven species in genus Lemna and Spirodela from China and Vietnam was analyzed by ISSR-PCR. Eight ISSR primers generating a reproducible amplification banding pattern had been screened. 89 polymorphic bands were scored out of the 92 banding patterns of 16 Lemna populations, accounting for 96.74% of the polymorphism. 98 polymorphic bands of 11 Spirodela populations were scored out of 99 banding patterns, and the polymorphism was 98.43%. The genetic distance of Lemna varied from 0.127 to 0.784, and from 0.138 to 0.902 for Spirodela, which indicated a high level of genetic variation among the populations studied. The unweighted pair group method with arithmetic average (UPGMA) cluster analysis corresponded well with the genetic distance. Populations from Sichuan China grouped together and so did the populations from Vietnam, which illuminated populations collected from the same region clustered into one group. Especially, the only one population from Tibet was included in subgroup A2 alone. Clustering analysis indicated that the geographic differentiation of collected sites correlated closely with the genetic differentiation of duckweeds. The results suggested that geographic differentiation had great influence on genetic diversity of duckweed in China and Vietnam at the regional scale. This study provided primary guidelines for collection, conservation, characterization of duckweed resources for bioethanol production etc.

Genetic conflict between sexual signalling and juvenile survival in the three-spined stickleback.

PubMed

Kim, Sin-Yeon; Velando, Alberto

2016-02-29

Secondary sexual traits and mating preferences may evolve in part because the offspring of attractive males inherit attractiveness and other genetically correlated traits such as fecundity and viability. A problem regarding these indirect genetic mechanisms is how sufficient genetic variation in the traits subject to sexual selection is maintained within a population. Here we explored the additive genetic correlations between carotenoid-based male ornament colouration, female fecundity and juvenile survival rate in the three-spined stickleback (Gasterosteus aculeatus) to test the possibility that attractiveness genes reduce important fitness components in the bearers not expressing the sexual trait. Male sexual attractiveness (i.e., red nuptial colouration) as well as female fecundity and juvenile viability showed heritable variations in the three-spined stickleback. Thus, females can gain indirect benefits by mating with an attractive male. There was a strong positive genetic correlation between female fecundity and juvenile viability. However, red sexual signal of male sticklebacks was negatively genetically correlated with juvenile survival, suggesting genetic conflict between attractiveness and viability. There was no significant correlation between attractiveness of brothers and fecundity of sisters, suggesting no intra-locus sexual conflict. The negative effects of mating with a colourful male on offspring viability may contribute to maintaining the heritable variation under strong directional sexual selection. The strength of indirect sexual selection may be weaker than previously thought due to the hidden genetic conflicts.

Multilevel analysis of ADHD, anxiety and depression symptoms aggregation in families.

PubMed

Segenreich, Daniel; Paez, Marina Silva; Regalla, Maria Angélica; Fortes, Dídia; Faraone, Stephen V; Sergeant, Joseph; Mattos, Paulo

2015-05-01

A strong genetic role in the etiology of attention-deficit hyperactivity disorder (ADHD) has been demonstrated by several studies using different methodologies. Shortcomings of genetic studies often include the lack of golden standard practices for diagnosis for ADHD, the use of categorical instead of a dimensional approach, and the disregard for assortative mating phenomenon in parents. The current study aimed to overcome these shortcomings and analyze data through a novel statistical approach, using multilevel analyses with Bayesian procedures and a specific mathematical model, which takes into account data with an elevated number of zero responses (expected in samples with few or no ADHD symptoms). Correlations of parental clinical variables (ADHD, anxiety and depression) to offspring psychopathology may vary according to gender and type of symptoms. We aimed to investigate how those variables interact within each other. One hundred families, comprising a proband child or adolescent with ADHD or a typically developing child or adolescent were included and all family members (both biological parents, the proband child or adolescent and their sibling) were examined through semi-structured interviews using DSM-IV criteria. Results indicated that: (a) maternal clinical variables (ADHD, anxiety and depression) were more correlated with offspring variables than paternal ones; (b) maternal inattention (but not hyperactivity) was correlated with both inattention and hyperactivity in the offspring; (c) maternal anxiety was correlated with offspring inattention; on the other hand, maternal inattention was correlated with anxiety in the offspring. Although a family study design limits the possibility of revealing causality and cannot disentangle genetic and environmental factors, our findings suggest that ADHD, anxiety and depression are variables that correlate in families and should be addressed together. Maternal variables significantly correlated with offspring variables, but the paternal variables did not.

Inferring Geographic Coordinates of Origin for Europeans Using Small Panels of Ancestry Informative Markers

PubMed Central

Paschou, Peristera

2010-01-01

Recent large-scale studies of European populations have demonstrated the existence of population genetic structure within Europe and the potential to accurately infer individual ancestry when information from hundreds of thousands of genetic markers is used. In fact, when genomewide genetic variation of European populations is projected down to a two-dimensional Principal Components Analysis plot, a surprising correlation with actual geographic coordinates of self-reported ancestry has been reported. This substructure can hamper the search of susceptibility genes for common complex disorders leading to spurious correlations. The identification of genetic markers that can correct for population stratification becomes therefore of paramount importance. Analyzing 1,200 individuals from 11 populations genotyped for more than 500,000 SNPs (Population Reference Sample), we present a systematic exploration of the extent to which geographic coordinates of origin within Europe can be predicted, with small panels of SNPs. Markers are selected to correlate with the top principal components of the dataset, as we have previously demonstrated. Performing thorough cross-validation experiments we show that it is indeed possible to predict individual ancestry within Europe down to a few hundred kilometers from actual individual origin, using information from carefully selected panels of 500 or 1,000 SNPs. Furthermore, we show that these panels can be used to correctly assign the HapMap Phase 3 European populations to their geographic origin. The SNPs that we propose can prove extremely useful in a variety of different settings, such as stratification correction or genetic ancestry testing, and the study of the history of European populations. PMID:20805874

Convergent genetic and expression data implicate immunity in Alzheimer's disease

PubMed Central

Jones, Lesley; Lambert, Jean-Charles; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Vedernikov, Alexey; Escott-Price, Valentina; Stone, Timothy; Richards, Alexander; Bellenguez, Céline; Ibrahim-Verbaas, Carla A; Naj, Adam C; Sims, Rebecca; Gerrish, Amy; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letteneur, Luc; Kornhuber, Johanes; Tárraga, Lluís; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Emilsson, Valur; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Kehoe, Pat; Rogaeva, Ekaterina; Gallacher, John; George-Hyslop, Peter St; Clarimon, Jordi; Lleὀ, Alberti; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petra; Collinge, John; Sorbi, Sandro; Garcia, Florentino Sanchez; Fox, Nick; Hardy, John; Naranjo, Maria Candida Deniz; Razquin, Cristina; Bosco, Paola; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Moebus, Susanne; Mecocci, Patrizia; del Zompo, Maria; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Jessen, Frank; Dichgans, Martin; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alavarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee FAG; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John SK; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Pastor, Pau; Schmidt, Reinhold; Rujescu, Dan; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Haines, Jonathan L; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broekhoven, Christine; Ramirez, Alfredo; Schellenberg, Gerard D; Seshadri, Sudha; Amouyel, Philippe; Holmans, Peter A

2015-01-01

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics. PMID:25533204

Genotype-phenotype association study via new multi-task learning model

PubMed Central

Huo, Zhouyuan; Shen, Dinggang

2018-01-01

Research on the associations between genetic variations and imaging phenotypes is developing with the advance in high-throughput genotype and brain image techniques. Regression analysis of single nucleotide polymorphisms (SNPs) and imaging measures as quantitative traits (QTs) has been proposed to identify the quantitative trait loci (QTL) via multi-task learning models. Recent studies consider the interlinked structures within SNPs and imaging QTs through group lasso, e.g. ℓ2,1-norm, leading to better predictive results and insights of SNPs. However, group sparsity is not enough for representing the correlation between multiple tasks and ℓ2,1-norm regularization is not robust either. In this paper, we propose a new multi-task learning model to analyze the associations between SNPs and QTs. We suppose that low-rank structure is also beneficial to uncover the correlation between genetic variations and imaging phenotypes. Finally, we conduct regression analysis of SNPs and QTs. Experimental results show that our model is more accurate in prediction than compared methods and presents new insights of SNPs. PMID:29218896

Cluster analysis reveals subclinical subgroups with shared autistic and schizotypal traits.

PubMed

Ford, Talitha C; Apputhurai, Pragalathan; Meyer, Denny; Crewther, David P

2018-07-01

Autism and schizophrenia spectrum research is typically based on coarse diagnostic classification, which overlooks individual variation within clinical groups. This method limits the identification of underlying cognitive, genetic and neural correlates of specific symptom dimensions. This study, therefore, aimed to identify homogenous subclinical subgroups of specific autistic and schizotypal traits dimensions, that may be utilised to establish more effective diagnostic and treatment practices. Latent profile analysis of subscale scores derived from an autism-schizotypy questionnaire, completed by 1678 subclinical adults aged 18-40 years (1250 females), identified a local optimum of eight population clusters: High, Moderate and Low Psychosocial Difficulties; High, Moderate and Low Autism-Schizotypy; High Psychosis-Proneness; and Moderate Schizotypy. These subgroups represent the convergent and discriminant dimensions of autism and schizotypy in the subclinical population, and highlight the importance of examining subgroups of specific symptom characteristics across these spectra in order to identify the underlying genetic and neural correlates that can be utilised to advance diagnostic and treatment practices. Copyright © 2018 Elsevier B.V. All rights reserved.

Convergent genetic and expression data implicate immunity in Alzheimer's disease.

PubMed

2015-06-01

Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10(-11)), cholesterol transport (P = 2.96 × 10(-9)), and proteasome-ubiquitin activity (P = 1.34 × 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. Copyright © 2015. Published by Elsevier Inc.

Rapid independent trait evolution despite a strong pleiotropic genetic correlation.

PubMed

Conner, Jeffrey K; Karoly, Keith; Stewart, Christy; Koelling, Vanessa A; Sahli, Heather F; Shaw, Frank H

2011-10-01

Genetic correlations are the most commonly studied of all potential constraints on adaptive evolution. We present a comprehensive test of constraints caused by genetic correlation, comparing empirical results to predictions from theory. The additive genetic correlation between the filament and the corolla tube in wild radish flowers is very high in magnitude, is estimated with good precision (0.85 ± 0.06), and is caused by pleiotropy. Thus, evolutionary changes in the relative lengths of these two traits should be constrained. Still, artificial selection produced rapid evolution of these traits in opposite directions, so that in one replicate relative to controls, the difference between them increased by six standard deviations in only nine generations. This would result in a 54% increase in relative fitness on the basis of a previous estimate of natural selection in this population, and it would produce the phenotypes found in the most extreme species in the family Brassicaceae in less than 100 generations. These responses were within theoretical expectations and were much slower than if the genetic correlation was zero; thus, there was evidence for constraint. These results, coupled with comparable results from other species, show that evolution can be rapid despite the constraints caused by genetic correlations.

Genetic and environmental contributions to children's prosocial behavior: brief review and new evidence from a reanalysis of experimental twin data.

PubMed

Knafo-Noam, Ariel; Vertsberger, Dana; Israel, Salomon

2018-04-01

Children's prosocial behaviors show considerable variability. Here we discuss the genetic and environmental contributions to individual differences in children's prosocial behavior. Twin research systematically shows, at least from the age of 3 years, a genetic contribution to individual differences in prosocial behavior, both questionnaire-based and observed. This finding is demonstrated across a wide variety of cultures. We discuss the possibility that different prosocial behaviors have different genetic etiologies. A re-analysis of past twin data shows that sharing and comforting are affected by overlapping genetic factors at age 3.5 years. In contrast, the association between helping and comforting is attributed to environmental factors. The few molecular genetic studies of children's prosocial behavior are reviewed, and we point out genome-wide and polygenic methods as a key future direction. Finally, we discuss the interplay of genetic and environmental factors, focusing on both gene×environment interactions and gene-environment correlations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic variation of Taenia pisiformis collected from Sichuan, China, based on the mitochondrial cytochrome B gene.

PubMed

Yang, Deying; Ren, Yongjun; Fu, Yan; Xie, Yue; Nie, Huaming; Nong, Xiang; Gu, Xiaobin; Wang, Shuxian; Peng, Xuerong; Yang, Guangyou

2013-08-01

Taenia pisiformis is one of the most important parasites of canines and rabbits. T. pisiformis cysticercus (the larval stage) causes severe damage to rabbit breeding, which results in huge economic losses. In this study, the genetic variation of T. pisiformis was determined in Sichuan Province, China. Fragments of the mitochondrial cytochrome b (cytb) (922 bp) gene were amplified in 53 isolates from 8 regions of T. pisiformis. Overall, 12 haplotypes were found in these 53 cytb sequences. Molecular genetic variations showed 98.4% genetic variation derived from intra-region. FST and Nm values suggested that 53 isolates were not genetically differentiated and had low levels of genetic diversity. Neutrality indices of the cytb sequences showed the evolution of T. pisiformis followed a neutral mode. Phylogenetic analysis revealed no correlation between phylogeny and geographic distribution. These findings indicate that 53 isolates of T. pisiformis keep a low genetic variation, which provide useful knowledge for monitoring changes in parasite populations for future control strategies.

Analysis of Genetic Diversity and Structure Pattern of Indigofera Pseudotinctoria in Karst Habitats of the Wushan Mountains Using AFLP Markers.

PubMed

Fan, Yan; Zhang, Chenglin; Wu, Wendan; He, Wei; Zhang, Li; Ma, Xiao

2017-10-16

Indigofera pseudotinctoria Mats is an agronomically and economically important perennial legume shrub with a high forage yield, protein content and strong adaptability, which is subject to natural habitat fragmentation and serious human disturbance. Until now, our knowledge of the genetic relationships and intraspecific genetic diversity for its wild collections is still poor, especially at small spatial scales. Here amplified fragment length polymorphism (AFLP) technology was employed for analysis of genetic diversity, differentiation, and structure of 364 genotypes of I. pseudotinctoria from 15 natural locations in Wushan Montain, a highly structured mountain with typical karst landforms in Southwest China. We also tested whether eco-climate factors has affected genetic structure by correlating genetic diversity with habitat features. A total of 515 distinctly scoreable bands were generated, and 324 of them were polymorphic. The polymorphic information content (PIC) ranged from 0.694 to 0.890 with an average of 0.789 per primer pair. On species level, Nei's gene diversity ( H j ), the Bayesian genetic diversity index ( H B ) and the Shannon information index ( I ) were 0.2465, 0.2363 and 0.3772, respectively. The high differentiation among all sampling sites was detected ( F ST = 0.2217, G ST = 0.1746, G' ST = 0.2060, θ B = 0.1844), and instead, gene flow among accessions ( N m = 1.1819) was restricted. The population genetic structure resolved by the UPGMA tree, principal coordinate analysis, and Bayesian-based cluster analyses irrefutably grouped all accessions into two distinct clusters, i.e., lowland and highland groups. The population genetic structure resolved by the UPGMA tree, principal coordinate analysis, and Bayesian-based cluster analyses irrefutably grouped all accessions into two distinct clusters, i.e., lowland and highland groups. This structure pattern may indicate joint effects by the neutral evolution and natural selection. Restricted N m was observed across all accessions, and genetic barriers were detected between adjacent accessions due to specifically geographical landform.

Genetic correlations between dressage, show jumping and studbook-entry inspection traits in a process of specialization in Dutch Warmblood horses.

PubMed

Rovere, G; Ducro, B J; van Arendonk, J A M; Norberg, E; Madsen, P

2017-04-01

Sport performance in dressage and show jumping are two important traits in the breeding goals of many studbooks. To determine the optimum selection scheme for jumping and dressage, knowledge is needed on the genetic correlation between both disciplines and between traits measured early in life and performance in competition in each discipline. This study aimed to estimate genetic parameters to support decision-making on specialization of breeding horses for dressage and show jumping in Dutch warmblood horses. Genetic correlations between performance of horses in dressage and show jumping were estimated as well as the genetic correlation between traits recorded during studbook-entry inspections and performance in dressage and show jumping competitions. The information on competition comprised the performance of 82 694 horses in dressage and 62 072 horses in show jumping, recorded in the period 1993-2012. For 26 056 horses, information was available for both disciplines. The information on traits recorded at studbook-entry inspections comprised 62 628 horses, recorded in the period 1992-2013. Genetic parameters were estimated from the whole dataset and from a subset without horses recorded in both disciplines. Additionally, the genetic parameters were estimated in three different time periods defined by horses' birth year. The genetic correlation between dressage and show jumping in the whole dataset was -0.23, and it was -0.03 when it was estimated from horses recorded in only one discipline. The genetic correlation between dressage and show jumping was more negative in the most recent time period in all the cases. The more negative correlation between disciplines in more recent time periods was not reflected in changes in the correlations between competitions traits and the traits recorded in the studbook-first inspection. These results suggest that a breeding programme under specialization might be most effective defining two separate aggregate breeding goals for each of the disciplines. © 2016 Blackwell Verlag GmbH.

The influence of genetic drift and selection on quantitative traits in a plant pathogenic fungus.

PubMed

Stefansson, Tryggvi S; McDonald, Bruce A; Willi, Yvonne

2014-01-01

Genetic drift and selection are ubiquitous evolutionary forces acting to shape genetic variation in populations. While their relative importance has been well studied in plants and animals, less is known about their relative importance in fungal pathogens. Because agro-ecosystems are more homogeneous environments than natural ecosystems, stabilizing selection may play a stronger role than genetic drift or diversifying selection in shaping genetic variation among populations of fungal pathogens in agro-ecosystems. We tested this hypothesis by conducting a QST/FST analysis using agricultural populations of the barley pathogen Rhynchosporium commune. Population divergence for eight quantitative traits (QST) was compared with divergence at eight neutral microsatellite loci (FST) for 126 pathogen strains originating from nine globally distributed field populations to infer the effects of genetic drift and types of selection acting on each trait. Our analyses indicated that five of the eight traits had QST values significantly lower than FST, consistent with stabilizing selection, whereas one trait, growth under heat stress (22°C), showed evidence of diversifying selection and local adaptation (QST>FST). Estimates of heritability were high for all traits (means ranging between 0.55-0.84), and average heritability across traits was negatively correlated with microsatellite gene diversity. Some trait pairs were genetically correlated and there was significant evidence for a trade-off between spore size and spore number, and between melanization and growth under benign temperature. Our findings indicate that many ecologically and agriculturally important traits are under stabilizing selection in R. commune and that high within-population genetic variation is maintained for these traits.

Genetic structure of wild boar (Sus scrofa) populations from East Asia based on microsatellite loci analyses

PubMed Central

2014-01-01

Background Wild boar, Sus scrofa, is an extant wild ancestor of the domestic pig as an agro-economically important mammal. Wild boar has a worldwide distribution with its geographic origin in Southeast Asia, but genetic diversity and genetic structure of wild boar in East Asia are poorly understood. To characterize the pattern and amount of genetic variation and population structure of wild boar in East Asia, we genotyped and analyzed microsatellite loci for a total of 238 wild boar specimens from ten locations across six countries in East and Southeast Asia. Results Our data indicated that wild boar populations in East Asia are genetically diverse and structured, showing a significant correlation of genetic distance with geographic distance and implying a low level of gene flow at a regional scale. Bayesian-based clustering analysis was indicative of seven inferred genetic clusters in which wild boars in East Asia are geographically structured. The level of genetic diversity was relatively high in wild boars from Southeast Asia, compared with those from Northeast Asia. This gradient pattern of genetic diversity is consistent with an assumed ancestral population of wild boar in Southeast Asia. Genetic evidences from a relationship tree and structure analysis suggest that wild boar in Jeju Island, South Korea have a distinct genetic background from those in mainland Korea. Conclusions Our results reveal a diverse pattern of genetic diversity and the existence of genetic differentiation among wild boar populations inhabiting East Asia. This study highlights the potential contribution of genetic variation of wild boar to the high genetic diversity of local domestic pigs during domestication in East Asia. PMID:25034725

Genetic Relationships Between Schizophrenia, Bipolar Disorder, and Schizoaffective Disorder

PubMed Central

Cardno, Alastair G.

2014-01-01

There is substantial evidence for partial overlap of genetic influences on schizophrenia and bipolar disorder, with family, twin, and adoption studies showing a genetic correlation between the disorders of around 0.6. Results of genome-wide association studies are consistent with commonly occurring genetic risk variants, contributing to both the shared and nonshared aspects, while studies of large, rare chromosomal structural variants, particularly copy number variants, show a stronger influence on schizophrenia than bipolar disorder to date. Schizoaffective disorder has been less investigated but shows substantial familial overlap with both schizophrenia and bipolar disorder. A twin analysis is consistent with genetic influences on schizoaffective episodes being entirely shared with genetic influences on schizophrenic and manic episodes, while association studies suggest the possibility of some relatively specific genetic influences on broadly defined schizoaffective disorder, bipolar subtype. Further insights into genetic relationships between these disorders are expected as studies continue to increase in sample size and in technical and analytical sophistication, information on phenotypes beyond clinical diagnoses are increasingly incorporated, and approaches such as next-generation sequencing identify additional types of genetic risk variant. PMID:24567502

Self-fertilization is the main sexual reproduction mechanism in native wine yeast populations.

PubMed

Cubillos, Francisco A; Vásquez, Claudia; Faugeron, Sylvain; Ganga, Angélica; Martínez, Claudio

2009-01-01

Saccharomyces cerevisiae is a model eukaryotic organism for classical genetics and genomics, and yet its ecology is still largely unknown. In this work, a population genetic analysis was performed on five yeast populations isolated from wine-making areas with different enological practices using simple sequence repeats and restriction fragment length polymorphism of mitochondrial DNA as molecular markers on 292 strains. In accordance with other studies, genome size estimation suggests that native S. cerevisiae strains are mainly homothallic and diploids. Analysis of mtDNA data showed that yeast populations from nonindustrial areas have 40% higher genetic diversity than populations isolated from industrial areas, demonstrating that industrial enological practices are likely to affect native yeast populations negatively by reducing its biodiversity. On the other hand, genetic differentiation analysis based on their microsatellite showed no correlation between genetic and geographic distance and a nonsignificant value when a Mantel test was applied. Finally, in the five populations studied, positive inbreeding (F(is)) values from 0.4 to 0.75, a low but significant level of linkage disequilibrium and a high number of multilocus genotypes were detected. These results strongly advocate that sexual reproduction is frequent enough to erase clonal signature in natural populations and that self-fertilization is the main mating system.

Phenotypic and genetic associations between the big five and trait emotional intelligence.

PubMed

Vernon, Philip A; Villani, Vanessa C; Schermer, Julie Aitken; Petrides, K V

2008-10-01

This study reports the first behavioral genetic investigation of the extent to which genetic and/or environmental factors contribute to the relationship between the Big Five personality factors and trait emotional intelligence. 213 pairs of adult monozygotic twins and 103 pairs of same-sex dizygotic twins completed the NEO-PI-R and the Trait Emotional Intelligence Questionnaire (TEIQue). Replicating previous non-twin studies, many significant phenotypic correlations were found between the Big Five factors - especially Neuroticism, Extraversion, and Conscientiousness - and the facets, factors, and global scores derived from the TEIQue. Bivariate behavioral genetic model-fitting analyses revealed that these phenotypic correlations were primarily attributable to correlated genetic factors and secondarily to correlated non-shared environmental factors. The results support the feasibility of incorporating EI as a trait within existing personality taxonomies.

Estimates of genetic parameters, genetic trends, and inbreeding in a crossbred dairy sheep research flock in the United States.

PubMed

Murphy, T W; Berger, Y M; Holman, P W; Baldin, M; Burgett, R L; Thomas, D L

2017-10-01

For the past 2 decades, the Spooner Agriculture Research Station (ARS) of the University of Wisconsin-Madison operated the only dairy sheep research flock in North America. The objectives of the present study were to 1) obtain estimates of genetic parameters for lactation and reproductive traits in dairy ewes, 2) estimate the amount of genetic change in these traits over time, and 3) quantify the level of inbreeding in this flock over the last 20 yr. Multiple-trait repeatability models (MTRM) were used to analyze ewe traits through their first 6 parities. The first MTRM jointly analyzed milk (180-d-adjusted milk yield [180d MY]), fat (180-d-adjusted fat yield [180d FY]), and protein (180-d-adjusted protein yield [180d PY]) yields adjusted to 180 d of lactation; number of lambs born per ewe lambing (NLB); and lactation average test-day somatic cell score (LSCS). A second MTRM analyzed 180d MY, NLB, LSCS, and percentage milk fat (%F) and percentage milk protein (%P). The 3 yield traits were moderately heritable (0.26 to 0.32) and strongly genetically correlated (0.91 to 0.96). Percentage milk fat and %P were highly heritable (0.53 and 0.61, respectively) and moderately genetically correlated (0.61). Milk yield adjusted to 180 d was negatively genetically correlated with %F and %P (-0.31 and -0.34, respectively). Ewe prolificacy was not significantly ( > 0.67) genetically correlated with yield traits, %P, or LSCS but lowly negatively correlated with %F (-0.26). Lactation somatic cell score was unfavorably genetically correlated with yield traits (0.28 to 0.39) but not significantly ( > 0.09) correlated with %F, %P, and NLB. Within-trait multiple-trait models through the first 4 parities revealed that 180d MY, 180d FY, 180d PY, %F, and %P were strongly genetically correlated across parity (0.67 to 1.00). However, the genetic correlations across parity for NLB and LSCS were somewhat lower (0.51 to 0.96). Regressing predicted breeding values for 180d MY, without and with the addition of breed effects, on ewe year of birth revealed a positive genetic gain of 2.30 and 6.24 kg/yr, respectively, over the past 20 yr in this flock. Inbreeding coefficients of ewes with an extended pedigree ranged from 0.0 to 0.29, with an average of 0.07. To optimize genetic gains and avoid excessive inbreeding, the development of a national genetic improvement program should be a top priority for the growing dairy sheep industry.

Computer image analysis traits of cross-sectioned dry-cured hams: a genetic analysis.

PubMed

Bonfatti, V; Cecchinato, A; Sturaro, E; Gallo, L; Carnier, P

2011-08-01

The aims of this study were to estimate genetic parameters of image analysis traits of cross-sectioned dry-cured hams and carcass weight (CW) and to investigate effects of some nongenetic sources of variation on these traits. Computer image analysis (CIA) had been carried out for digital images of the cross-section of 1,319 San Daniele dry-cured hams. The cross-sectional area (SA, cm(2)); the average thickness of subcutaneous fat (FT, cm); and the proportions of lean (LA, %), fat-eye (FEA, %), and subcutaneous fat area (SCF, %) to SA, and of biceps femoris (BFA, %) and semitendinosus muscle area (STA, %) to LA were recorded. Bivariate analyses were carried out for pairs of traits for estimation of genetic parameters using Bayesian methodology and linear models. Linear models included the nongenetic effects of slaughter groups and sex and the additive genetic effects of pigs and their ancestors (1,888 animals). Variation of FEA was nearly 4-fold that of SA and LA. Variation of CIA traits due to sex effect was not large, whereas slaughter group effects were relevant sources of variation for all traits. For all traits, with the exception of FEA, the posterior probability for the true heritability being greater than 0.1, was greater than 0.95. Point estimates of heritabilities for FT and SCF were 0.42 and 0.51, respectively. Heritability estimates for FEA, LA, BFA, and STA were 0.13, 0.44, 0.44, and 0.36, respectively. The genetic correlations between CW and CIA traits were positive and large for SA (0.86), positive and moderate for FT, FEA, and STA (0.47, 0.40, and 0.45, respectively) and negative with LA (-0.28). Although FEA, FT, and SCF were all measures of the extent of fat deposition in the ham, the genetic correlations between FT or SCF and FEA were very low. A very large estimate (0.74) was obtained for the genetic relationship between SA and FEA, suggesting that reduction of ham roundness through selective breeding would be beneficial for decreasing FEA. On the basis of the estimated parameters, genetic selection is expected to be effective in changing size of fatty and lean areas of the cross-section of dry-cured hams. Causes related to the abnormal development of the fat-eye depot remain unknown, but this study provided evidence that influences of polygenic effects on phenotypic variation of FEA are limited. © 2011 American Society of Animal Science. All rights reserved.

Network-based analysis of genotype-phenotype correlations between different inheritance modes.

PubMed

Hao, Dapeng; Li, Chuanxing; Zhang, Shaojun; Lu, Jianping; Jiang, Yongshuai; Wang, Shiyuan; Zhou, Meng

2014-11-15

Recent studies on human disease have revealed that aberrant interaction between proteins probably underlies a substantial number of human genetic diseases. This suggests a need to investigate disease inheritance mode using interaction, and based on which to refresh our conceptual understanding of a series of properties regarding inheritance mode of human disease. We observed a strong correlation between the number of protein interactions and the likelihood of a gene causing any dominant diseases or multiple dominant diseases, whereas no correlation was observed between protein interaction and the likelihood of a gene causing recessive diseases. We found that dominant diseases are more likely to be associated with disruption of important interactions. These suggest inheritance mode should be understood using protein interaction. We therefore reviewed the previous studies and refined an interaction model of inheritance mode, and then confirmed that this model is largely reasonable using new evidences. With these findings, we found that the inheritance mode of human genetic diseases can be predicted using protein interaction. By integrating the systems biology perspectives with the classical disease genetics paradigm, our study provides some new insights into genotype-phenotype correlations. haodapeng@ems.hrbmu.edu.cn or biofomeng@hotmail.com Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genetic diversity studies and identification of SSR markers associated with Fusarium wilt (Fusarium udum) resistance in cultivated pigeonpea (Cajanus cajan).

PubMed

Singh, A K; Rai, V P; Chand, R; Singh, R P; Singh, M N

2013-01-01

Genetic diversity and identification of simple sequence repeat markers correlated with Fusarium wilt resistance was performed in a set of 36 elite cultivated pigeonpea genotypes differing in levels of resistance to Fusarium wilt. Twenty-four polymorphic sequence repeat markers were screened across these genotypes, and amplified a total of 59 alleles with an average high polymorphic information content value of 0.52. Cluster analysis, done by UPGMA and PCA, grouped the 36 pigeonpea genotypes into two main clusters according to their Fusarium wilt reaction. Based on the Kruskal-Wallis ANOVA and simple regression analysis, six simple sequence repeat markers were found to be significantly associated with Fusarium wilt resistance. The phenotypic variation explained by these markers ranged from 23.7 to 56.4%. The present study helps in finding out feasibility of prescreened SSR markers to be used in genetic diversity analysis and their potential association with disease resistance.

Integrating Nonadditive Genomic Relationship Matrices into the Study of Genetic Architecture of Complex Traits.

PubMed

Nazarian, Alireza; Gezan, Salvador A

2016-03-01

The study of genetic architecture of complex traits has been dramatically influenced by implementing genome-wide analytical approaches during recent years. Of particular interest are genomic prediction strategies which make use of genomic information for predicting phenotypic responses instead of detecting trait-associated loci. In this work, we present the results of a simulation study to improve our understanding of the statistical properties of estimation of genetic variance components of complex traits, and of additive, dominance, and genetic effects through best linear unbiased prediction methodology. Simulated dense marker information was used to construct genomic additive and dominance matrices, and multiple alternative pedigree- and marker-based models were compared to determine if including a dominance term into the analysis may improve the genetic analysis of complex traits. Our results showed that a model containing a pedigree- or marker-based additive relationship matrix along with a pedigree-based dominance matrix provided the best partitioning of genetic variance into its components, especially when some degree of true dominance effects was expected to exist. Also, we noted that the use of a marker-based additive relationship matrix along with a pedigree-based dominance matrix had the best performance in terms of accuracy of correlations between true and estimated additive, dominance, and genetic effects. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic correlations and the evolution of photoperiodic time measurement within a local population of the pitcher-plant mosquito, Wyeomyia smithii

PubMed Central

Bradshaw, W E; Emerson, K J; Holzapfel, C M

2012-01-01

The genetic relationship between the daily circadian clock and the seasonal photoperiodic timer remains a subject of intense controversy. In Wyeomyia smithii, the critical photoperiod (an overt expression of the photoperiodic timer) evolves independently of the rhythmic response to the Nanda–Hamner protocol (an overt expression of the daily circadian clock) over a wide geographical range in North America. Herein, we focus on these two processes within a single local population in which there is a negative genetic correlation between them. We show that antagonistic selection against this genetic correlation rapidly breaks it down and, in fact, reverses its sign, showing that the genetic correlation is due primarily to linkage and not to pleiotropy. This rapid reversal of the genetic correlation within a small, single population means that it is difficult to argue that circadian rhythmicity forms the necessary, causal basis for the adaptive divergence of photoperiodic time measurement within populations or for the evolution of photoperiodic time measurement among populations over a broad geographical gradient of seasonal selection. PMID:22072069

Morphoagronomic and molecular profiling of Capsicum spp from southwest Mato Grosso, Brazil.

PubMed

Campos, A L; Marostega, T N; Cabral, N S S; Araújo, K L; Serafim, M E; Seabra-Júnior, S; Sudré, C P; Rodrigues, R; Neves, L G

2016-07-15

The genus Capsicum ranks as the second most exported vegetable in Brazil, which is also considered to be a center of diversity for this genus. The aim of this study was to rescue genetic variability in the genus Capsicum in the southwest region of Mato Grosso, and to characterize and estimate the genetic diversity of accessions based on morphoagronomic descriptors and inter-simple sequence repeat molecular markers. Data were obtained following the criteria of the International Plant Genetic Resources Institute, renamed Bioversity International for Capsicum. Data were analyzed using different multivariate statistical techniques. An array of binary data was used to analyze molecular data, and the arithmetic complement of the Jaccard index was used to estimate the genetic dissimilarity among accessions. Six well-defined groups were formed based on the morphological characterization. The most divergent accessions were 142 and 126, with 125 and 126 being the most similar. The groups formed following agronomic characterization differed from those formed by morphological characterization, and there was a need to subdivide the groups for better distinction of accessions. Based on molecular analysis, accessions were divided into two groups, and there was also a need to subdivide the groups. Based on joint analysis (morphological + agronomic + molecular), six groups were formed with no duplicates. For all groups, the cophenetic correlation coefficient was higher than 0.8. These results provide useful information for the better management of the work collection. All correlations between the combined distance matrix were significant by the Mantel test.

Genetics of variation in HOMA-IR and cardiovascular risk factors in Mexican-Americans.

PubMed

Voruganti, V Saroja; Lopez-Alvarenga, Juan C; Nath, Subrata D; Rainwater, David L; Bauer, Richard; Cole, Shelley A; Maccluer, Jean W; Blangero, John; Comuzzie, Anthony G

2008-03-01

Insulin resistance is a major biochemical defect underlying the pathogenesis of cardiovascular disease (CVD). Mexican-Americans are known to have an unfavorable cardiovascular profile. Thus, the aim of this study was to investigate the genetic effect on variation in HOMA-IR and to evaluate its genetic correlations with other phenotypes related to risk of CVD in Mexican-Americans. The homeostatic model assessment method (HOMA-IR) is one of several approaches that are used to measure insulin resistance and was used here to generate a quantitative phenotype for genetic analysis. For 644 adults who had participated in the San Antonio Family Heart Study (SAFHS), estimates of genetic contribution were computed using a variance components method implemented in SOLAR. Traits that exhibited significant heritabilities were body mass index (BMI) (h (2) = 0.43), waist circumference (h (2) = 0.48), systolic blood pressure (h (2) = 0.30), diastolic blood pressure (h (2) = 0.21), pulse pressure (h (2) = 0.32), triglycerides (h (2) = 0.51), LDL cholesterol (h (2) = 0.31), HDL cholesterol (h (2) = 0.24), C-reactive protein (h (2) = 0.17), and HOMA-IR (h (2) = 0.33). A genome-wide scan for HOMA-IR revealed significant evidence of linkage on chromosome 12q24 (close to PAH (phenylalanine hydroxylase), LOD = 3.01, p < 0.001). Bivariate analyses demonstrated significant genetic correlations (p < 0.05) of HOMA-IR with BMI (rho (G) = 0.36), waist circumference (rho (G) = 0.47), pulse pressure (rho (G) = 0.39), and HDL cholesterol (rho (G) = -0.18). Identification of significant linkage for HOMA-IR on chromosome 12q replicates previous family-based studies reporting linkage of phenotypes associated with type 2 diabetes in the same chromosomal region. Significant genetic correlations between HOMA-IR and phenotypes related to CVD risk factors suggest that a common set of gene(s) influence the regulation of these phenotypes.

Stability in and correlation between factors influencing genetic quality of seed lots in seed orchard of Pinus tabuliformis Carr. over a 12-year span.

PubMed

Li, Wei; Wang, Xiaoru; Li, Yue

2011-01-01

Coniferous seed orchards require a long period from initial seed harvest to stable seed production. Differential reproductive success and asynchrony are among the main factors for orchard crops year-to-year variation in terms of parental gametic contribution and ultimately the genetic gain. It is fundamental in both making predictions about the genetic composition of the seed crop and decisions about orchard roguing and improved seed orchard establishment. In this paper, a primary Chinese pine seed orchard with 49 clones is investigated for stability, variation and correlation analysis of factors which influence genetic quality of the seed lots from initial seed harvest to the stable seed production over a 12 years span. Results indicated that the reproductive synchrony index of pollen shedding has shown to be higher than that of the strobili receptivity, and both can be drastically influenced by the ambient climate factors. Reproductive synchrony index of the clones has certain relative stability and it could be used as an indication of the seed orchard status during maturity stage; clones in the studied orchard have shown extreme differences in terms of the gametic and genetic contribution to the seed crop at the orchard's early production phase specifically when they severe as either female or male parents. Those differences are closely related to clonal sex tendency at the time of orchard's initial reproduction. Clonal gamete contribution as male and female parent often has a negative correlation. Clone utilization as pollen, seed or both pollen and seed donors should consider the role it would play in the seed crop; due to numerous factors influencing on the mating system in seed orchards, clonal genetic contribution as male parent is uncertain, and it has major influence on the genetic composition in the seed orchard during the initial reproductive and seed production phase.

Cross-validation analysis for genetic evaluation models for ranking in endurance horses.

PubMed

García-Ballesteros, S; Varona, L; Valera, M; Gutiérrez, J P; Cervantes, I

2018-01-01

Ranking trait was used as a selection criterion for competition horses to estimate racing performance. In the literature the most common approaches to estimate breeding values are the linear or threshold statistical models. However, recent studies have shown that a Thurstonian approach was able to fix the race effect (competitive level of the horses that participate in the same race), thus suggesting a better prediction accuracy of breeding values for ranking trait. The aim of this study was to compare the predictability of linear, threshold and Thurstonian approaches for genetic evaluation of ranking in endurance horses. For this purpose, eight genetic models were used for each approach with different combinations of random effects: rider, rider-horse interaction and environmental permanent effect. All genetic models included gender, age and race as systematic effects. The database that was used contained 4065 ranking records from 966 horses and that for the pedigree contained 8733 animals (47% Arabian horses), with an estimated heritability around 0.10 for the ranking trait. The prediction ability of the models for racing performance was evaluated using a cross-validation approach. The average correlation between real and predicted performances across genetic models was around 0.25 for threshold, 0.58 for linear and 0.60 for Thurstonian approaches. Although no significant differences were found between models within approaches, the best genetic model included: the rider and rider-horse random effects for threshold, only rider and environmental permanent effects for linear approach and all random effects for Thurstonian approach. The absolute correlations of predicted breeding values among models were higher between threshold and Thurstonian: 0.90, 0.91 and 0.88 for all animals, top 20% and top 5% best animals. For rank correlations these figures were 0.85, 0.84 and 0.86. The lower values were those between linear and threshold approaches (0.65, 0.62 and 0.51). In conclusion, the Thurstonian approach is recommended for the routine genetic evaluations for ranking in endurance horses.

Alignment-free genetic sequence comparisons: a review of recent approaches by word analysis

PubMed Central

Steele, Joe; Bastola, Dhundy

2014-01-01

Modern sequencing and genome assembly technologies have provided a wealth of data, which will soon require an analysis by comparison for discovery. Sequence alignment, a fundamental task in bioinformatics research, may be used but with some caveats. Seminal techniques and methods from dynamic programming are proving ineffective for this work owing to their inherent computational expense when processing large amounts of sequence data. These methods are prone to giving misleading information because of genetic recombination, genetic shuffling and other inherent biological events. New approaches from information theory, frequency analysis and data compression are available and provide powerful alternatives to dynamic programming. These new methods are often preferred, as their algorithms are simpler and are not affected by synteny-related problems. In this review, we provide a detailed discussion of computational tools, which stem from alignment-free methods based on statistical analysis from word frequencies. We provide several clear examples to demonstrate applications and the interpretations over several different areas of alignment-free analysis such as base–base correlations, feature frequency profiles, compositional vectors, an improved string composition and the D2 statistic metric. Additionally, we provide detailed discussion and an example of analysis by Lempel–Ziv techniques from data compression. PMID:23904502

Genetic diversity and structure of Sinopodophyllum hexandrum (Royle) Ying in the Qinling Mountains, China.

PubMed

Liu, Wei; Yin, Dongxue; Liu, Jianjun; Li, Na

2014-01-01

Sinopodophyllum hexandrum is an important medicinal plant whose genetic diversity must be conserved because it is endangered. The Qinling Mts. are a S. hexandrum distribution area that has unique environmental features that highly affect the evolution of the species. To provide the reference data for evolutionary and conservation studies, the genetic diversity and population structure of S. hexandrum in its overall natural distribution areas in the Qinling Mts. were investigated through inter-simple sequence repeats analysis of 32 natural populations. The 11 selected primers generated a total of 135 polymorphic bands. S. hexandrum genetic diversity was low within populations (average He = 0.0621), but higher at the species level (He = 0.1434). Clear structure and high genetic differentiation among populations were detected by using the unweighted pair group method for arithmetic averages, principle coordinate analysis and Bayesian clustering. The clustering approaches supported a division of the 32 populations into three major groups, for which analysis of molecular variance confirmed significant variation (63.27%) among populations. The genetic differentiation may have been attributed to the limited gene flow (Nm = 0.3587) in the species. Isolation by distance among populations was determined by comparing genetic distance versus geographic distance by using the Mantel test. Result was insignificant (r = 0.212, P = 0.287) at 0.05, showing that their spatial pattern and geographic locations are not correlated. Given the low within-population genetic diversity, high differentiation among populations and the increasing anthropogenic pressure on the species, in situ conservation measures were recommended to preserve S. hexandrum in Qinling Mts., and other populations must be sampled to retain as much genetic diversity of the species to achieve ex situ preservation as a supplement to in situ conservation.

Genetic Diversity and Structure of Sinopodophyllum hexandrum (Royle) Ying in the Qinling Mountains, China

PubMed Central

Liu, Wei; Yin, Dongxue; Liu, Jianjun; Li, Na

2014-01-01

Sinopodophyllum hexandrum is an important medicinal plant whose genetic diversity must be conserved because it is endangered. The Qinling Mts. are a S. hexandrum distribution area that has unique environmental features that highly affect the evolution of the species. To provide the reference data for evolutionary and conservation studies, the genetic diversity and population structure of S. hexandrum in its overall natural distribution areas in the Qinling Mts. were investigated through inter-simple sequence repeats analysis of 32 natural populations. The 11 selected primers generated a total of 135 polymorphic bands. S. hexandrum genetic diversity was low within populations (average He = 0.0621), but higher at the species level (He = 0.1434). Clear structure and high genetic differentiation among populations were detected by using the unweighted pair group method for arithmetic averages, principle coordinate analysis and Bayesian clustering. The clustering approaches supported a division of the 32 populations into three major groups, for which analysis of molecular variance confirmed significant variation (63.27%) among populations. The genetic differentiation may have been attributed to the limited gene flow (Nm = 0.3587) in the species. Isolation by distance among populations was determined by comparing genetic distance versus geographic distance by using the Mantel test. Result was insignificant (r = 0.212, P = 0.287) at 0.05, showing that their spatial pattern and geographic locations are not correlated. Given the low within-population genetic diversity, high differentiation among populations and the increasing anthropogenic pressure on the species, in situ conservation measures were recommended to preserve S. hexandrum in Qinling Mts., and other populations must be sampled to retain as much genetic diversity of the species to achieve ex situ preservation as a supplement to in situ conservation. PMID:25333788

Proton Nuclear Magnetic Resonance-Spectroscopic Discrimination of Wines Reflects Genetic Homology of Several Different Grape (V. vinifera L.) Cultivars.

PubMed

Hu, Boran; Yue, Yaqing; Zhu, Yong; Wen, Wen; Zhang, Fengmin; Hardie, Jim W

2015-01-01

Proton nuclear magnetic resonance spectroscopy coupled multivariate analysis (1H NMR-PCA/PLS-DA) is an important tool for the discrimination of wine products. Although 1H NMR has been shown to discriminate wines of different cultivars, a grape genetic component of the discrimination has been inferred only from discrimination of cultivars of undefined genetic homology and in the presence of many confounding environmental factors. We aimed to confirm the influence of grape genotypes in the absence of those factors. We applied 1H NMR-PCA/PLS-DA and hierarchical cluster analysis (HCA) to wines from five, variously genetically-related grapevine (V. vinifera) cultivars; all grown similarly on the same site and vinified similarly. We also compared the semi-quantitative profiles of the discriminant metabolites of each cultivar with previously reported chemical analyses. The cultivars were clearly distinguishable and there was a general correlation between their grouping and their genetic homology as revealed by recent genomic studies. Between cultivars, the relative amounts of several of the cultivar-related discriminant metabolites conformed closely with reported chemical analyses. Differences in grape-derived metabolites associated with genetic differences alone are a major source of 1H NMR-based discrimination of wines and 1H NMR has the capacity to discriminate between very closely related cultivars. The study confirms that genetic variation among grape cultivars alone can account for the discrimination of wine by 1H NMR-PCA/PLS and indicates that 1H NMR spectra of wine of single grape cultivars may in future be used in tandem with hierarchical cluster analysis to elucidate genetic lineages and metabolomic relations of grapevine cultivars. In the absence of genetic information, for example, where predecessor varieties are no longer extant, this may be a particularly useful approach.

Waterfalls drive parallel evolution in a freshwater goby

PubMed Central

Kano, Yuichi; Nishida, Shin; Nakajima, Jun

2012-01-01

Waterfalls may affect fish distribution and genetic structure within drainage networks even to the extent of leading evolutionary events. Here, parallel evolution was studied by focusing on waterfall and the landlocked freshwater goby Rhinogobius sp. YB (YB), which evolved from amphidromous R. brunneus (BR). The fish fauna was surveyed at 30 sites in 11 rivers on Iriomote Island, Japan, the geography of which was characterized by terraces/tablelands with many waterfalls. We found that all YB individuals were distributed only above waterfalls (height 6.8–58.7 m), whereas BR, and other fishes, were mostly distributed below waterfalls. Mitochondrial DNA analysis showed that every YB local population above the waterfall was independently evolved from BR. In contrast, cluster analysis of nine morphological characters, such as fin color and body pattern, showed that the morphology of YB individuals held a similarity beyond the genetic divergence, suggesting parallel evolution has occurred relating to their morphology. Genetic distance between each YB local population and BR was significantly correlated with waterfall height (r2 = 0.94), suggesting that the waterfalls have been heightened due to the constant geological erosion and that their height represents the isolation period of YB local populations from BR (ca. 11,000–88,000 years). Each local population of BR was once landlocked in upstream by waterfall formation, consequently evolving to YB in each site. Although the morphology of YB had a high degree of similarity among local populations, finer scale analysis showed that the morphology of YB was significantly correlated with the genetic distance from BR. Consequently, there could be simultaneous multiple phases of allopatric/parallel evolution of the goby due to variations in waterfall height on this small island. PMID:22957183

Y-Chromosomal Diversity in Europe Is Clinal and Influenced Primarily by Geography, Rather than by Language

PubMed Central

Rosser, Zoë H.; Zerjal, Tatiana; Hurles, Matthew E.; Adojaan, Maarja; Alavantic, Dragan; Amorim, António; Amos, William; Armenteros, Manuel; Arroyo, Eduardo; Barbujani, Guido; Beckman, Gunhild; Beckman, Lars; Bertranpetit, Jaume; Bosch, Elena; Bradley, Daniel G.; Brede, Gaute; Cooper, Gillian; Côrte-Real, Helena B. S. M.; de Knijff, Peter; Decorte, Ronny; Dubrova, Yuri E.; Evgrafov, Oleg; Gilissen, Anja; Glisic, Sanja; Gölge, Mukaddes; Hill, Emmeline W.; Jeziorowska, Anna; Kalaydjieva, Luba; Kayser, Manfred; Kivisild, Toomas; Kravchenko, Sergey A.; Krumina, Astrida; Kučinskas, Vaidutis; Lavinha, João; Livshits, Ludmila A.; Malaspina, Patrizia; Maria, Syrrou; McElreavey, Ken; Meitinger, Thomas A.; Mikelsaar, Aavo-Valdur; Mitchell, R. John; Nafa, Khedoudja; Nicholson, Jayne; Nørby, Søren; Pandya, Arpita; Parik, Jüri; Patsalis, Philippos C.; Pereira, Luísa; Peterlin, Borut; Pielberg, Gerli; Prata, Maria João; Previderé, Carlo; Roewer, Lutz; Rootsi, Siiri; Rubinsztein, D. C.; Saillard, Juliette; Santos, Fabrício R.; Stefanescu, Gheorghe; Sykes, Bryan C.; Tolun, Aslihan; Villems, Richard; Tyler-Smith, Chris; Jobling, Mark A.

2000-01-01

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift. PMID:11078479

Genetic parameters for carcass and meat quality traits and their relationships to liveweight and wool production in hogget Merino rams.

PubMed

Greeff, J C; Safari, E; Fogarty, N M; Hopkins, D L; Brien, F D; Atkins, K D; Mortimer, S I; van der Werf, J H J

2008-06-01

Genetic parameters for carcass and meat quality traits of about 18-month-old Merino rams (n = 5870), the progeny of 543 sires from three research resource flocks, were estimated. The estimates of heritability for hot carcass weight (HCW) and the various fat and muscle dimension measurements were moderate and ranged from 0.20 to 0.37. The brightness of meat (colour L*, 0.18 +/- 0.03 standard error) and meat pH (0.22 +/- 0.03) also had moderate estimates of heritability, although meat relative redness (colour a*, 0.10 +/- 0.03) and relative yellowness (colour b*, 0.10 +/- 0.03) were lower. Heritability estimates for live weights were moderate and ranged from 0.29 to 0.41 with significant permanent maternal environmental effects (0.13 to 0.10). The heritability estimates for the hogget wool traits were moderate to high and ranged from 0.27 to 0.60. The ultrasound measurements of fat depth (FATUS) and eye muscle depth (EMDUS) on live animals were highly genetically correlated with the corresponding carcass measurements (0.69 +/- 0.09 FATC and 0.77 +/- 0.07 EMD). Carcass tissue depth (FATGR) had moderate to low genetic correlations with carcass muscle measurements [0.18 +/- 0.10 EMD and 0.05 +/- 0.10 eye muscle area (EMA)], while those with FATC were negative. The genetic correlation between EMD and eye muscle width (EMW) was 0.41 +/- 0.08, while EMA was highly correlated with EMD (0.89 +/- 0.0) and EMW (0.78 +/- 0.04). The genetic correlations for muscle colour with muscle measurements were moderately negative, while those with fat measurements were close to zero. Meat pH was positively correlated with muscle measurements (0.14 to 0.17) and negatively correlated with fat measurements (-0.06 to -0.18). EMDUS also showed a similar pattern of correlations to EMD with meat quality indicator traits, although FATUS had positive correlations with these traits which were generally smaller than their standard error. The genetic correlations among the meat colour traits were high and positive while those with meat pH were high and negative, which were all in the favourable direction. Generally, phenotypic correlations were similar or slightly lower than the corresponding genetic correlations. There were generally small to moderate negative genetic correlations between clean fleece weight (CFW) and carcass fat traits while those with muscle traits were close to zero. As the Merino is already a relatively lean breed, this implies that particular attention should be given to this relationship in Merino breeding programmes to prevent the reduction of fat reserves as a correlated response to selection for increased fleece weight. The ultrasound scan traits generally showed a similar pattern to the corresponding carcass fat and muscle traits. There was a small unfavourable genetic correlation between CFW and meat pH (0.19 +/- 0.07).

What can genes tell us about the relationship between education and health?

PubMed

Boardman, Jason D; Domingue, Benjamin W; Daw, Jonathan

2015-02-01

We use genome wide data from respondents of the Health and Retirement Study (HRS) to evaluate the possibility that common genetic influences are associated with education and three health outcomes: depression, self-rated health, and body mass index. We use a total of 1.7 million single nucleotide polymorphisms obtained from the Illumina HumanOmni2.5-4v1 chip from 4233 non-Hispanic white respondents to characterize genetic similarities among unrelated persons in the HRS. We then used the Genome Wide Complex Trait Analysis (GCTA) toolkit, to estimate univariate and bivariate heritability. We provide evidence that education (h(2) = 0.33), BMI (h(2) = 0.43), depression (h(2) = 0.19), and self-rated health (h(2) = 0.18) are all moderately heritable phenotypes. We also provide evidence that some of the correlation between depression and education as well as self-rated health and education is due to common genetic factors associated with one or both traits. We find no evidence that the correlation between education and BMI is influenced by common genetic factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Correlation analysis for the incubation period of prion disease

PubMed Central

Bae, Se-Eun; Jung, Sunghoon; Kim, Ha-Yeon; Son, Hyeon S.

2012-01-01

Previous studies have shown that genetic quantitative trait loci (QTL), strain barriers, inoculation dose and inoculation method modulate the incubation period of prion diseases. We examined the relationship between a diverse set of physical, genetic and immunological characteristics and the incubation period of prion disease using correlation analyses. We found that incubation period was highly correlated with brain weight. In addition, mean corpuscular volume and cell size were strongly correlated with incubation period, indicating that the physical magnitude of prion-infected organs or individual cells may be important in determining the incubation period. Given the same prion inoculation dose, animals with a lower brain weight, mean corpuscular volume or cell size may experience more virulent disease, as the effective concentration of abnormal prion, which might regulate the attachment rate of prions to aggregates, is increased with smaller capacity of brains and cells. This is partly consistent with previous theoretical modeling. The strong correlations between incubation period and physical properties of the brain and cells in this study suggest that the mechanism underlying prion disease pathology may be physical, indicating that the incubation process is governed by simple chemical stoichiometry. PMID:22561168

Integrating Genomic Analysis with the Genetic Basis of Gene Expression: Preliminary Evidence of the Identification of Causal Genes for Cardiovascular and Metabolic Traits Related to Nutrition in Mexicans123

PubMed Central

Bastarrachea, Raúl A.; Gallegos-Cabriales, Esther C.; Nava-González, Edna J.; Haack, Karin; Voruganti, V. Saroja; Charlesworth, Jac; Laviada-Molina, Hugo A.; Veloz-Garza, Rosa A.; Cardenas-Villarreal, Velia Margarita; Valdovinos-Chavez, Salvador B.; Gomez-Aguilar, Patricia; Meléndez, Guillermo; López-Alvarenga, Juan Carlos; Göring, Harald H. H.; Cole, Shelley A.; Blangero, John; Comuzzie, Anthony G.; Kent, Jack W.

2012-01-01

Whole-transcriptome expression profiling provides novel phenotypes for analysis of complex traits. Gene expression measurements reflect quantitative variation in transcript-specific messenger RNA levels and represent phenotypes lying close to the action of genes. Understanding the genetic basis of gene expression will provide insight into the processes that connect genotype to clinically significant traits representing a central tenet of system biology. Synchronous in vivo expression profiles of lymphocytes, muscle, and subcutaneous fat were obtained from healthy Mexican men. Most genes were expressed at detectable levels in multiple tissues, and RNA levels were correlated between tissue types. A subset of transcripts with high reliability of expression across tissues (estimated by intraclass correlation coefficients) was enriched for cis-regulated genes, suggesting that proximal sequence variants may influence expression similarly in different cellular environments. This integrative global gene expression profiling approach is proving extremely useful for identifying genes and pathways that contribute to complex clinical traits. Clearly, the coincidence of clinical trait quantitative trait loci and expression quantitative trait loci can help in the prioritization of positional candidate genes. Such data will be crucial for the formal integration of positional and transcriptomic information characterized as genetical genomics. PMID:22797999

Latitude delineates patterns of biogeography in terrestrial Streptomyces.

PubMed

Choudoir, Mallory J; Doroghazi, James R; Buckley, Daniel H

2016-12-01

The biogeography of Streptomyces was examined at regional spatial scales to identify factors that govern patterns of microbial diversity. Streptomyces are spore forming filamentous bacteria which are widespread in soil. Streptomyces strains were isolated from perennial grass habitats sampled across a spatial scale of more than 6000 km. Previous analysis of this geographically explicit culture collection provided evidence for a latitudinal diversity gradient in Streptomyces species. Here the hypothesis that this latitudinal diversity gradient is a result of evolutionary dynamics associated with historical demographic processes was evaluated. Historical demographic phenomena have genetic consequences that can be evaluated through analysis of population genetics. Population genetic approaches were applied to analyze population structure in six of the most numerically abundant and geographically widespread Streptomyces phylogroups from our culture collection. Streptomyces population structure varied at regional spatial scales, and allelic diversity correlated with geographic distance. In addition, allelic diversity and gene flow are partitioned by latitude. Finally, it was found that nucleotide diversity within phylogroups was negatively correlated with latitude. These results indicate that phylogroup diversification is constrained by dispersal limitation at regional spatial scales, and they are consistent with the hypothesis that historical demographic processes have influenced the contemporary biogeography of Streptomyces. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Molecular variability among isolates of Fusarium oxysporum associated with root rot disease of Agave tequilana.

PubMed

Vega-Ramos, Karla L; Uvalle-Bueno, J Xavier; Gómez-Leyva, Juan F

2013-04-01

In this study, 115 isolates of Fusarium oxysporum from roots of Agave tequilana Weber cv azul plants and soil in commercial plantations in western Mexico were characterized using morphological and molecular methods. Genetic analyses of monosporic isolates included restriction enzyme analysis of rDNA (ARDRA) using HaeIII and HinfI, and genetic diversity was determined using Box-PCR molecular markers. Box-PCR analysis generated 14 groups. The groups correlated highly with the geographic location of the isolate and sample type. These results demonstrate the usefulness of ARDRA and Box-PCR techniques in the molecular characterization of the Fusarium genus for the discrimination of pathogenic isolates.

Behavioral and Molecular Genetics of Reading-Related AM and FM Detection Thresholds.

PubMed

Bruni, Matthew; Flax, Judy F; Buyske, Steven; Shindhelm, Amber D; Witton, Caroline; Brzustowicz, Linda M; Bartlett, Christopher W

2017-03-01

Auditory detection thresholds for certain frequencies of both amplitude modulated (AM) and frequency modulated (FM) dynamic auditory stimuli are associated with reading in typically developing and dyslexic readers. We present the first behavioral and molecular genetic characterization of these two auditory traits. Two extant extended family datasets were given reading tasks and psychoacoustic tasks to determine FM 2 Hz and AM 20 Hz sensitivity thresholds. Univariate heritabilities were significant for both AM (h 2  = 0.20) and FM (h 2  = 0.29). Bayesian posterior probability of linkage (PPL) analysis found loci for AM (12q, PPL = 81 %) and FM (10p, PPL = 32 %; 20q, PPL = 65 %). Bivariate heritability analyses revealed that FM is genetically correlated with reading, while AM was not. Bivariate PPL analysis indicates that FM loci (10p, 20q) are not also associated with reading.

Alcohol use disorder and divorce: Evidence for a genetic correlation in a population-based Swedish sample

PubMed Central

Salvatore, Jessica E.; Lönn, Sara Larsson; Sundquist, Jan; Lichtenstein, Paul; Sundquist, Kristina; Kendler, Kenneth S.

2016-01-01

Aims We tested the association between alcohol use disorder (AUD) and divorce; estimated the genetic and environmental influences on divorce; estimated how much genetic and environmental influences accounted for covariance between AUD and divorce; and estimated latent genetic and environmental correlations between AUD and divorce. We tested sex differences in these effects. Design We identified twin and sibling pairs with AUD and divorce information in Swedish national registers. We described the association between AUD and divorce using tetrachorics; and used twin and sibling models to estimate genetic and environmental influences on divorce, on the covariance between AUD and divorce, and the latent genetic and environmental correlations between AUD and divorce. Setting Sweden. Participants 670,836 individuals (53% male) born 1940–1965. Measurements Lifetime measures of AUD and divorce. Findings AUD and divorce were strongly related (estimates [95% CIs]: males: rtet = +0.44 [0.43, 0.45]; females rtet = +0.37 [0.36, 0.38]). Genetic factors accounted for a modest proportion of the variance in divorce (males: 21.3% [7.6, 28.5]; females: 31.0% [18.8, 37.1]). Genetic factors accounted for most of the covariance between AUD and divorce (males: 52.0% [48.8, 67.9]; females: 53.74% [17.6, 54.5]), followed by nonshared environmental factors (males: 45.0% [37.5, 54.9]; females: 41.6% [40.3, 60.2]). Shared environmental factors accounted for a negligible proportion of the covariance (males: 3.0% [−3.0, 13.5]; females: 4.75%, [0.0, 6.6].) The AUD-divorce genetic correlations were high (males: rA = +0.76 [0.53, 0.90]; females +0.52 [0.24, 0.67]). The nonshared environmental correlations were modest (males: rE = +0.32 [0.31, 0.40]; females: +0.27 [0.27, 0.36]). Conclusions Divorce and alcohol use disorder (AUD) are strongly correlated in the Swedish population, and the heritability of divorce is consistent with previous studies. Covariation between AUD and divorce results from overlapping genetic and nonshared environmental factors. Latent genetic and nonshared environmental correlations for AUD and divorce are high and moderate. PMID:27981669

Genetic parameters for carcass weight, conformation and fat in five beef cattle breeds.

PubMed

Kause, A; Mikkola, L; Strandén, I; Sirkko, K

2015-01-01

Profitability of beef production can be increased by genetically improving carcass traits. To construct breeding value evaluations for carcass traits, breed-specific genetic parameters were estimated for carcass weight, carcass conformation and carcass fat in five beef cattle breeds in Finland (Hereford, Aberdeen Angus, Simmental, Charolais and Limousin). Conformation and fat were visually scored using the EUROP carcass classification. Each breed was separately analyzed using a multitrait animal model. A total of 6879-19 539 animals per breed had phenotypes. For the five breeds, heritabilities were moderate for carcass weight (h 2=0.39 to 0.48, s.e.=0.02 to 0.04) and slightly lower for conformation (h 2=0.30 to 0.44, s.e.=0.02 to 0.04) and carcass fat (h 2=0.29 to 0.44, s.e.=0.02 to 0.04). The genetic correlation between carcass weight and conformation was favorable in all breeds (r G=0.37 to 0.53, s.e.=0.04 to 0.05), heavy carcasses being genetically more conformed. The phenotypic correlation between carcass weight and carcass fat was moderately positive in all breeds (r P=0.21 to 0.32), implying that increasing carcass weight was related to increasing fat levels. The respective genetic correlation was the strongest in Hereford (r G=0.28, s.e.=0.05) and Angus (r G=0.15, s.e.=0.05), the two small body-sized British breeds with the lowest conformation and the highest fat level. The correlation was weaker in the other breeds (r G=0.08 to 0.14). For Hereford, Angus and Simmental, more conformed carcasses were phenotypically fatter (r P=0.11 to 0.15), but the respective genetic correlations were close to zero (r G=-0.05 to 0.04). In contrast, in the two large body-sized and muscular French breeds, the genetic correlation between conformation and fat was negative and the phenotypic correlation was close to zero or negative (Charolais: r G=-0.18, s.e.=0.06, r P=0.02; Limousin: r G=-0.56, s.e.=0.04, r P=-0.13). The results indicate genetic variation for the genetic improvement of the carcass traits, favorable correlations for the simultaneous improvement of carcass weight and conformation in all breeds, and breed differences in the correlations of carcass fat.

The Genetic Architecture of Interspecific Variation in Mimulus

PubMed Central

Macnair, M. R.; Cumbes, Q. J.

1989-01-01

The genetic architecture of various floral and morphological differences between Mimulus cupriphilus and Mimulus guttatus is investigated. M. cupriphilus is believed to have speciated from M. guttatus in the recent past. The two parent species, the F(1) and F(2), and two backcrosses were grown and scored for 23 different characters. The analysis of means revealed significant epistasis for a number of the floral characters, particularly those involving the length of parts. Dominance was generally toward M. guttatus, except for the characters related to flowering time. Analysis of the genetic correlations between characters revealed that there were at least four different polygenic genetic systems, governing flowering time, size of flower, number of spots on the corolla, and general size. An analysis of minimum gene number suggested that there were at least 3-7 genes controlling floral size, and a different three controlling floral spot number. Two other characters, corolla lobe shape and stem color, were produced by independent major gene differences. Annuality was also shown to be heritable. The two species appear to utilize the same gene for copper tolerance. The results are discussed in the light of current theories of speciation. PMID:17246497

Genetic correlations between body condition scores and fertility in dairy cattle using bivariate random regression models.

PubMed

De Haas, Y; Janss, L L G; Kadarmideen, H N

2007-10-01

Genetic correlations between body condition score (BCS) and fertility traits in dairy cattle were estimated using bivariate random regression models. BCS was recorded by the Swiss Holstein Association on 22,075 lactating heifers (primiparous cows) from 856 sires. Fertility data during first lactation were extracted for 40,736 cows. The fertility traits were days to first service (DFS), days between first and last insemination (DFLI), calving interval (CI), number of services per conception (NSPC) and conception rate to first insemination (CRFI). A bivariate model was used to estimate genetic correlations between BCS as a longitudinal trait by random regression components, and daughter's fertility at the sire level as a single lactation measurement. Heritability of BCS was 0.17, and heritabilities for fertility traits were low (0.01-0.08). Genetic correlations between BCS and fertility over the lactation varied from: -0.45 to -0.14 for DFS; -0.75 to 0.03 for DFLI; from -0.59 to -0.02 for CI; from -0.47 to 0.33 for NSPC and from 0.08 to 0.82 for CRFI. These results show (genetic) interactions between fat reserves and reproduction along the lactation trajectory of modern dairy cows, which can be useful in genetic selection as well as in management. Maximum genetic gain in fertility from indirect selection on BCS should be based on measurements taken in mid lactation when the genetic variance for BCS is largest, and the genetic correlations between BCS and fertility is strongest.

Common Psychiatric Disorders and Caffeine Use, Tolerance, and Withdrawal: An Examination of Shared Genetic and Environmental Effects

PubMed Central

Bergin, Jocilyn E.; Kendler, Kenneth S.

2012-01-01

Background Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Method Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. Results GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation = 0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. Conclusions There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes. PMID:22854069

Common psychiatric disorders and caffeine use, tolerance, and withdrawal: an examination of shared genetic and environmental effects.

PubMed

Bergin, Jocilyn E; Kendler, Kenneth S

2012-08-01

Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation=0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes.

Assessing Multivariate Constraints to Evolution across Ten Long-Term Avian Studies

PubMed Central

Teplitsky, Celine; Tarka, Maja; Møller, Anders P.; Nakagawa, Shinichi; Balbontín, Javier; Burke, Terry A.; Doutrelant, Claire; Gregoire, Arnaud; Hansson, Bengt; Hasselquist, Dennis; Gustafsson, Lars; de Lope, Florentino; Marzal, Alfonso; Mills, James A.; Wheelwright, Nathaniel T.; Yarrall, John W.; Charmantier, Anne

2014-01-01

Background In a rapidly changing world, it is of fundamental importance to understand processes constraining or facilitating adaptation through microevolution. As different traits of an organism covary, genetic correlations are expected to affect evolutionary trajectories. However, only limited empirical data are available. Methodology/Principal Findings We investigate the extent to which multivariate constraints affect the rate of adaptation, focusing on four morphological traits often shown to harbour large amounts of genetic variance and considered to be subject to limited evolutionary constraints. Our data set includes unique long-term data for seven bird species and a total of 10 populations. We estimate population-specific matrices of genetic correlations and multivariate selection coefficients to predict evolutionary responses to selection. Using Bayesian methods that facilitate the propagation of errors in estimates, we compare (1) the rate of adaptation based on predicted response to selection when including genetic correlations with predictions from models where these genetic correlations were set to zero and (2) the multivariate evolvability in the direction of current selection to the average evolvability in random directions of the phenotypic space. We show that genetic correlations on average decrease the predicted rate of adaptation by 28%. Multivariate evolvability in the direction of current selection was systematically lower than average evolvability in random directions of space. These significant reductions in the rate of adaptation and reduced evolvability were due to a general nonalignment of selection and genetic variance, notably orthogonality of directional selection with the size axis along which most (60%) of the genetic variance is found. Conclusions These results suggest that genetic correlations can impose significant constraints on the evolution of avian morphology in wild populations. This could have important impacts on evolutionary dynamics and hence population persistence in the face of rapid environmental change. PMID:24608111

Genome-wide analysis in UK Biobank identifies four loci associated with mood instability and genetic correlation with major depressive disorder, anxiety disorder and schizophrenia.

PubMed

Ward, Joey; Strawbridge, Rona J; Bailey, Mark E S; Graham, Nicholas; Ferguson, Amy; Lyall, Donald M; Cullen, Breda; Pidgeon, Laura M; Cavanagh, Jonathan; Mackay, Daniel F; Pell, Jill P; O'Donovan, Michael; Escott-Price, Valentina; Smith, Daniel J

2017-11-30

Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD). We conducted a genome-wide association study (GWAS) of mood instability in 53,525 cases and 60,443 controls from UK Biobank, identifying four independently associated loci (on chromosomes 8, 9, 14 and 18), and a common single-nucleotide polymorphism (SNP)-based heritability estimate of ~8%. We found a strong genetic correlation between mood instability and MDD (r g  = 0.60, SE = 0.07, p = 8.95 × 10 -17 ) and a small but significant genetic correlation with both schizophrenia (r g  = 0.11, SE = 0.04, p = 0.01) and anxiety disorders (r g  = 0.28, SE = 0.14, p = 0.04), although no genetic correlation with BD, ADHD or PTSD was observed. Several genes at the associated loci may have a role in mood instability, including the DCC netrin 1 receptor (DCC) gene, eukaryotic translation initiation factor 2B subunit beta (eIF2B2), placental growth factor (PGF) and protein tyrosine phosphatase, receptor type D (PTPRD). Strengths of this study include the very large sample size, but our measure of mood instability may be limited by the use of a single question. Overall, this work suggests a polygenic basis for mood instability. This simple measure can be obtained in very large samples; our findings suggest that doing so may offer the opportunity to illuminate the fundamental biology of mood regulation.

External validity of a hierarchical dimensional model of child and adolescent psychopathology: Tests using confirmatory factor analyses and multivariate behavior genetic analyses.

PubMed

Waldman, Irwin D; Poore, Holly E; van Hulle, Carol; Rathouz, Paul J; Lahey, Benjamin B

2016-11-01

Several recent studies of the hierarchical phenotypic structure of psychopathology have identified a General psychopathology factor in addition to the more expected specific Externalizing and Internalizing dimensions in both youth and adult samples and some have found relevant unique external correlates of this General factor. We used data from 1,568 twin pairs (599 MZ & 969 DZ) age 9 to 17 to test hypotheses for the underlying structure of youth psychopathology and the external validity of the higher-order factors. Psychopathology symptoms were assessed via structured interviews of caretakers and youth. We conducted phenotypic analyses of competing structural models using Confirmatory Factor Analysis and used Structural Equation Modeling and multivariate behavior genetic analyses to understand the etiology of the higher-order factors and their external validity. We found that both a General factor and specific Externalizing and Internalizing dimensions are necessary for characterizing youth psychopathology at both the phenotypic and etiologic levels, and that the 3 higher-order factors differed substantially in the magnitudes of their underlying genetic and environmental influences. Phenotypically, the specific Externalizing and Internalizing dimensions were slightly negatively correlated when a General factor was included, which reflected a significant inverse correlation between the nonshared environmental (but not genetic) influences on Internalizing and Externalizing. We estimated heritability of the general factor of psychopathology for the first time. Its moderate heritability suggests that it is not merely an artifact of measurement error but a valid construct. The General, Externalizing, and Internalizing factors differed in their relations with 3 external validity criteria: mother's smoking during pregnancy, parent's harsh discipline, and the youth's association with delinquent peers. Multivariate behavior genetic analyses supported the external validity of the 3 higher-order factors by suggesting that the General, Externalizing, and Internalizing factors were correlated with peer delinquency and parent's harsh discipline for different etiologic reasons. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Determination of genetic diversity among Saccharina germplasm using ISSR and RAPD markers.

PubMed

Cui, Cuiju; Li, Yan; Liu, Yanling; Li, Xiaojie; Luo, Shiju; Zhang, Zhuangzhi; Wu, Ruina; Liang, Guangjin; Sun, Juan; Peng, Jie; Tian, Pingping

2017-02-01

Various species of genus Saccharina are economically important brown macroalgae cultivated in China. The genetic background of the conserved Saccharina germplasm was not clear. In this report, DNA-based molecular markers such as inter simple sequence repeats (ISSR) and random amplified polymorphic DNA (RAPD) were used to assess the genetic diversity and phylogenetic relationships among 48 Saccharina germplasms. A total of 50 ISSR and 50 RAPD primers were tested, of which only 33 polymorphic primers (17 ISSR and 16 RAPD) had an amplified clear and reproducible profile, and could be used. Seventeen ISSR primers yielded a total of 262 bands, of which 256 were polymorphic, and 15.06 polymorphic bands per primer were amplified from 48 kelp gametophytes. Sixteen RAPD primers produced 355 bands, of which 352 were polymorphic, and 22 polymorphic bands per primer were observed across 48 individuals. The simple matching coefficient of ISSR, RAPD and pooled ISSR and RAPD dendrograms ranged from 0.568 to 0.885, 0.670 to 0.873, and 0.667 to 0.862, revealing high genetic diversity. Based on the unweighted pair group method with the arithmetic averaging algorithm (UPGMA) cluster analysis and the principal components analysis (PCA) of ISSR data, the 48 gametophytes were divided into three main groups. The Mantel test revealed a similar polymorphism distribution pattern between ISSR and RAPD markers, the correlation coefficient r was 0.62, and the results indicated that both ISSR and RAPD markers were effective to assess the selected gametophytes, while matrix correlation of the ISSR marker system (r=0.78) was better than that of the RAPD marker system (r=0.64). Genetic analysis data from this study were helpful in understanding the genetic relationships among the selected 17 kelp varieties (or lines) and provided guidance for molecular-assisted selection for parental gametophytes of hybrid kelp breeding. Copyright © 2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Correlation of physical and genetic maps of human chromosome 16

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sutherland, G.R.

1991-01-01

This project aimed to divide chromosome 16 into approximately 50 intervals of {approximately}2Mb in size by constructing a series of mouse/human somatic cell hybrids each containing a rearranged chromosome 16. Using these hybrids, DNA probes would be regionally mapped by Southern blot or PCR analysis. Preference would be given to mapping probes which demonstrated polymorphisms for which the CEPH panel of families had been typed. This would allow a correlation of the physical and linkage maps of this chromosome. The aims have been substantially achieved. 49 somatic cell hybrids have been constructed which have allowed definition of 46, and potentiallymore » 57, different physical intervals on the chromosome. 164 loci have been fully mapped into these intervals. A correlation of the physical and genetic maps of the chromosome is in an advanced stage of preparation. The somatic cell hybrids constructed have been widely distributed to groups working on chromosome 16 and other genome projects.« less

Correlation of physical and genetic maps of human chromosome 16. Annual progress report, October 1, 1990--July 31, 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sutherland, G.R.

1991-12-31

This project aimed to divide chromosome 16 into approximately 50 intervals of {approximately}2Mb in size by constructing a series of mouse/human somatic cell hybrids each containing a rearranged chromosome 16. Using these hybrids, DNA probes would be regionally mapped by Southern blot or PCR analysis. Preference would be given to mapping probes which demonstrated polymorphisms for which the CEPH panel of families had been typed. This would allow a correlation of the physical and linkage maps of this chromosome. The aims have been substantially achieved. 49 somatic cell hybrids have been constructed which have allowed definition of 46, and potentiallymore » 57, different physical intervals on the chromosome. 164 loci have been fully mapped into these intervals. A correlation of the physical and genetic maps of the chromosome is in an advanced stage of preparation. The somatic cell hybrids constructed have been widely distributed to groups working on chromosome 16 and other genome projects.« less

Genetic interrelationships among phosphorus, nitrogen, calcium, and energy bioavailability in a growing chicken population.

PubMed

Ankra-Badu, G A; Pesti, G M; Aggrey, S E

2010-11-01

A random-mating population was used to study the genetic interrelationship between phytate P (PPB), Ca (CaB), N (NB), and energy bioavailability (EB), BW at 4 wk of age, relative growth (RG), and feed conversion ratio (FCR). Heritability estimates for PPB, CaB, NB, and EB were 0.09, 0.13, 0.16, and 0.10, respectively, and those of BW, RG, and FCR were 0.66, 0.15, and 0.10, respectively. Genetic correlations between PPB and BW, and FCR were moderate and negative, suggesting that improvement in PPB will impair growth. The genetic correlations between PPB and CaB, and EB and RG were positive and moderate, indicating that improvement in PPB would also lead to improved CaB, EB, and RG. Energy bioavailability was positively correlated with CaB, NB, PPB, and BW. Even though the genetic correlation between EB and the other traits measured, except RG and FCR, ranged from low to moderate, improving the ability of birds to utilize caloric energy in the feed would consequently improve PPB as well as growth. Improving PPB would reduce the amount of P in excreta and provide an additional savings if exogenous phytase were not added to poultry feed. The genetic correlation between PPB and NB was low but positive, whereas NB had a positive genetic correlation with BW. Therefore, selecting on NB will result in positive correlated responses in BW and PPB. Improving PPB and NB will not only improve productivity, but also reduce the polluting effects of P and N on the environment.

Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study.

PubMed

Cadby, Gemma; Melton, Phillip E; McCarthy, Nina S; Almeida, Marcio; Williams-Blangero, Sarah; Curran, Joanne E; VandeBerg, John L; Hui, Jennie; Beilby, John; Musk, A W; James, Alan L; Hung, Joseph; Blangero, John; Moses, Eric K

2018-01-01

Over two billion adults are overweight or obese and therefore at an increased risk of cardiometabolic syndrome (CMS). Obesity-related anthropometric traits genetically correlated with CMS may provide insight into CMS aetiology. The aim of this study was to utilise an empirically derived genetic relatedness matrix to calculate heritabilities and genetic correlations between CMS and anthropometric traits to determine whether they share genetic risk factors (pleiotropy). We used genome-wide single nucleotide polymorphism (SNP) data on 4671 Busselton Health Study participants. Exploiting both known and unknown relatedness, empirical kinship probabilities were estimated using these SNP data. General linear mixed models implemented in SOLAR were used to estimate narrow-sense heritabilities (h 2 ) and genetic correlations (r g ) between 15 anthropometric and 9 CMS traits. Anthropometric traits were adjusted by body mass index (BMI) to determine whether the observed genetic correlation was independent of obesity. After adjustment for multiple testing, all CMS and anthropometric traits were significantly heritable (h 2 range 0.18-0.57). We identified 50 significant genetic correlations (r g range: - 0.37 to 0.75) between CMS and anthropometric traits. Five genetic correlations remained significant after adjustment for BMI [high density lipoprotein cholesterol (HDL-C) and waist-hip ratio; triglycerides and waist-hip ratio; triglycerides and waist-height ratio; non-HDL-C and waist-height ratio; insulin and iliac skinfold thickness]. This study provides evidence for the presence of potentially pleiotropic genes that affect both anthropometric and CMS traits, independently of obesity.

The potential for using canopy spectral reflectance as an indirect selection tool for yield improvement in winter wheat

NASA Astrophysics Data System (ADS)

Prasad, Bishwajit

Scope and methods of study. Complementing breeding effort by deploying alternative methods of identifying higher yielding genotypes in a wheat breeding program is important for obtaining greater genetic gains. Spectral reflectance indices (SRI) are one of the many indirect selection tools that have been reported to be associated with different physiological process of wheat. A total of five experiments (a set of 25 released cultivars from winter wheat breeding programs of the U.S. Great Plains and four populations of randomly derived recombinant inbred lines having 25 entries in each population) were conducted in two years under Great Plains winter wheat rainfed environments at Oklahoma State University research farms. Grain yield was measured in each experiment and biomass was measured in three experiments at three growth stages (booting, heading, and grainfilling). Canopy spectral reflectance was measured at three growth stages and eleven SRI were calculated. Correlation (phenotypic and genetic) between grain yield and SRI, biomass and SRI, heritability (broad sense) of the SRI and yield, response to selection and correlated response, relative selection efficiency of the SRI, and efficiency in selecting the higher yielding genotypes by the SRI were assessed. Findings and conclusions. The genetic correlation coefficients revealed that the water based near infrared indices (WI and NWI) were strongly associated with grain yield and biomass production. The regression analysis detected a linear relationship between the water based indices with grain yield and biomass. The two newly developed indices (NWI-3 and NWI-4) gave higher broad sense heritability than grain yield, higher direct response to selection compared to grain yield, correlated response equal to or higher than direct response for grain yield, relative selection efficiency greater than one, and higher efficiency in selecting higher yielding genotypes. Based on the overall genetic analysis required to establish any trait as an efficient indirect selection tool, the water based SRI (especially NWI-3 and NWI-4) have the potential to complement the classical breeding effort for selecting genotypes with higher yield potential in a winter wheat breeding program.

Genetic covariance components within and among linear type traits differ among contrasting beef cattle breeds.

PubMed

Doyle, Jennifer L; Berry, Donagh P; Walsh, Siobhan W; Veerkamp, Roel F; Evans, Ross D; Carthy, Tara R

2018-05-04

Linear type traits describing the skeletal, muscular, and functional characteristics of an animal are routinely scored on live animals in both the dairy and beef cattle industries. Previous studies have demonstrated that genetic parameters for certain performance traits may differ between breeds; no study, however, has attempted to determine if differences exist in genetic parameters of linear type traits among breeds or sexes. Therefore, the objective of the present study was to determine if genetic covariance components for linear type traits differed among five contrasting cattle breeds, and to also investigate if these components differed by sex. A total of 18 linear type traits scored on 3,356 Angus (AA), 31,049 Charolais (CH), 3,004 Hereford (HE), 35,159 Limousin (LM), and 8,632 Simmental (SI) were used in the analysis. Data were analyzed using animal linear mixed models which included the fixed effects of sex of the animal (except in the investigation into the presence of sexual dimorphism), age at scoring, parity of the dam, and contemporary group of herd-date of scoring. Differences (P < 0.05) in heritability estimates, between at least two breeds, existed for 13 out of 18 linear type traits. Differences (P < 0.05) also existed between the pairwise within-breed genetic correlations among the linear type traits. Overall, the linear type traits in the continental breeds (i.e., CH, LM, SI) tended to have similar heritability estimates to each other as well as similar genetic correlations among the same pairwise traits, as did the traits in the British breeds (i.e., AA, HE). The correlation between a linear function of breeding values computed conditional on covariance parameters estimated from the CH breed with a linear function of breeding values computed conditional on covariance parameters estimated from the other breeds was estimated. Replacing the genetic covariance components estimated in the CH breed with those of the LM had least effect but the impact was considerable when the genetic covariance components of the AA were used. Genetic correlations between the same linear type traits in the two sexes were all close to unity (≥0.90) suggesting little advantage in considering these as separate traits for males and females. Results for the present study indicate the potential increase in accuracy of estimated breeding value prediction from considering, at least, the British breed traits separate to continental breed traits.

Endocrine profile and phenotype-(epi)genotype correlation in Spanish patients with pseudohypoparathyroidism.

PubMed

Fernández-Rebollo, Eduardo; Lecumberri, Beatriz; Gaztambide, Sonia; Martinez-Indart, Lorea; Perez de Nanclares, Guiomar; Castaño, Luis

2013-05-01

Recent advances in genetics and epigenetics have revealed an overlap between molecular and clinical features of pseudohypoparathyroidism (PHP) subtypes, broadening the previous spectrum of PHP genotype-phenotype correlations and indicating limitations of the current classification of the disease. The aim of the study was to screen patients with clinical diagnoses of PHP type I or pseudo-PHP for underlying molecular defects and explore possible correlations between molecular findings and clinical features. We investigated the GNAS locus at the molecular level in 72 affected patients (46 women and 26 men) from 56 nonrelated families. Clinical data were obtained for 63 of these patients (38 women and 25 men). The molecular analysis showed that 35 patients carried structural mutations, 32 had loss of methylation, and 2 had a 2q37 deletion but did not reveal any (epi)mutation for 3 patients. Comparing these results and the clinical data, we observed that a younger age at diagnosis was associated with structural defects at the GNAS gene and epigenetic defects with a diagnosis later in life (9.19 ± 1.64 vs 24.57 ± 2.28 years, P < .0001). This first global review of PHP in Spain highlights the importance of a detailed clinical and genetic study of each patient and the integrated analysis of the findings from the two approaches. It may also help geneticists and clinicians to raise the suspicion of PHP earlier, reach more accurate diagnoses, and provide patients with PHP and their families with useful genetic information and counseling, thereby improving outcomes and quality of life.

Black Americans: A Psychological Analysis.

ERIC Educational Resources Information Center

Baughman, E. Earl

Contents of this book include: (1) The Concept of Race-Black, Negro, Afro-American, Colored?; Social versus Biological Definitions of Race; and Confounding Race and Social Class; (2) Intelligence-Black-White Differences in IQ: age and sex differences, the genetic explanation, the environmental explanation, family correlates of IQ, and a personal…

Filtering genetic variants and placing informative priors based on putative biological function.

PubMed

Friedrichs, Stefanie; Malzahn, Dörthe; Pugh, Elizabeth W; Almeida, Marcio; Liu, Xiao Qing; Bailey, Julia N

2016-02-03

High-density genetic marker data, especially sequence data, imply an immense multiple testing burden. This can be ameliorated by filtering genetic variants, exploiting or accounting for correlations between variants, jointly testing variants, and by incorporating informative priors. Priors can be based on biological knowledge or predicted variant function, or even be used to integrate gene expression or other omics data. Based on Genetic Analysis Workshop (GAW) 19 data, this article discusses diversity and usefulness of functional variant scores provided, for example, by PolyPhen2, SIFT, or RegulomeDB annotations. Incorporating functional scores into variant filters or weights and adjusting the significance level for correlations between variants yielded significant associations with blood pressure traits in a large family study of Mexican Americans (GAW19 data set). Marker rs218966 in gene PHF14 and rs9836027 in MAP4 significantly associated with hypertension; additionally, rare variants in SNUPN significantly associated with systolic blood pressure. Variant weights strongly influenced the power of kernel methods and burden tests. Apart from variant weights in test statistics, prior weights may also be used when combining test statistics or to informatively weight p values while controlling false discovery rate (FDR). Indeed, power improved when gene expression data for FDR-controlled informative weighting of association test p values of genes was used. Finally, approaches exploiting variant correlations included identity-by-descent mapping and the optimal strategy for joint testing rare and common variants, which was observed to depend on linkage disequilibrium structure.

Adoptive Parent Hostility and Children’s Peer Behavior Problems: Examining the Role of Genetically-Informed Child Attributes on Adoptive Parent Behavior

PubMed Central

Elam, Kit K.; Harold, Gordon T.; Neiderhiser, Jenae M.; Reiss, David; Shaw, Daniel S.; Natsuaki, Misaki N.; Gaysina, Darya; Barrett, Doug; Leve, Leslie D.

2014-01-01

Socially disruptive behavior during peer interactions in early childhood is detrimental to children’s social, emotional, and academic development. Few studies have investigated the developmental underpinnings of children’s socially disruptive behavior using genetically-sensitive research designs that allow examination of parent-on-child and child-on-parent (evocative genotype-environment correlation) effects when examining family process and child outcome associations. Using an adoption-at-birth design, the present study controlled for passive genotype-environment correlation and directly examined evocative genotype-environment correlation (rGE) while examining the associations between family processes and children’s peer behavior. Specifically, the present study examined the evocative effect of genetic influences underlying toddler low social motivation on mother-child and father-child hostility, and the subsequent influence of parent hostility on disruptive peer behavior during the preschool period. Participants were 316 linked triads of birth mothers, adoptive parents, and adopted children. Path analysis showed that birth mother low behavioral motivation predicted toddler low social motivation, which predicted both adoptive mother-child and father-child hostility, suggesting the presence of an evocative genotype-environment association. In addition, both mother-child and father-child hostility predicted children’s later disruptive peer behavior. Results highlight the importance of considering genetically-influenced child attributes on parental hostility that in turn link to later child social behavior. Implications for intervention programs focusing on early family processes and the precursors of disrupted child social development are discussed. PMID:24364829

Assessment of genetic diversity among Indian potato (Solanum tuberosum L.) collection using microsatellite and retrotransposon based marker systems.

PubMed

Sharma, Vishakha; Nandineni, Madhusudan R

2014-04-01

Potato (Solanum tuberosum) is an important non-cereal crop throughout the world and is highly recommended for ensuring global food security. Owing to the complexities in genetics and inheritance pattern of potato, the conventional method of cross breeding for developing improved varieties has been difficult. Identification and tagging of desirable traits with informative molecular markers would aid in the development of improved varieties. Insertional polymorphism of copia-like and gypsy-like long terminal repeat retrotransposons (RTN) were investigated among 47 potato varieties from India using Inter-Retrotransposon Amplified Polymorphism (IRAP) and Retrotransposon Microsatellite Amplified Polymorphism (REMAP) marker techniques and were compared with the DNA profiles obtained with simple sequence repeats (SSRs). The genetic polymorphism, efficiency of polymorphism and effectiveness of marker systems were evaluated to assess the extent of genetic diversity among Indian potato varieties. A total of 139 polymorphic SSR alleles, 270 IRAP and 98 REMAP polymorphic bands, showing polymorphism of 100%, 87.9% and 68.5%, respectively, were used for detailed characterization of the genetic relationships among potato varieties by using cluster analysis and principal coordinate analysis (PCoA). IRAP analysis resulted in the highest number of polymorphic bands with an average of 15 polymorphic bands per assay unit when compared to the other two marker systems. Based on pair-wise comparison, the genetic similarity was calculated using Dice similarity coefficient. The SSRs showed a wide range in genetic similarity values (0.485-0.971) as compared to IRAP (0.69-0.911) and REMAP (0.713-0.947). A Mantel's matrix correspondence test showed a high positive correlation (r=0.6) between IRAP and REMAP, an intermediate value (r=0.58) for IRAP and SSR and the lowest value (r=0.17) for SSR and REMAP. Statistically significant cophenetic correlation coefficient values, of 0.961, 0.941 and 0.905 were observed for REMAP, IRAP and SSR, respectively. The widespread presence and distinct DNA profiles for copia-like and gypsy-like RTNs in the examined genotypes indicate that these elements are active in the genome and may have even contributed to the potato genome organization. Although the three marker systems were capable of distinguishing all the 47 varieties; high reproducibility, low cost and ease of DNA profiling data collection make IRAP and REMAP markers highly efficient whole-genome scanning molecular probes for population genetic studies. Information obtained from the present study regarding the genetic association and distinctiveness provides an useful guide for selection of germplasm for plant breeding and conservation efforts. Copyright © 2014. Published by Elsevier Inc.

[Transciptome among Mexicans: a large scale methodology to analyze the genetics expression profile of simultaneous samples in muscle, adipose tissue and lymphocytes obtained from the same individual].

PubMed

Bastarrachea, Raúl A; López-Alvarenga, Juan Carlos; Kent, Jack W; Laviada-Molina, Hugo A; Cerda-Flores, Ricardo M; Calderón-Garcidueñas, Ana Laura; Torres-Salazar, Amada; Torres-Salazar, Amanda; Nava-González, Edna J; Solis-Pérez, Elizabeth; Gallegos-Cabrales, Esther C; Cole, Shelley A; Comuzzie, Anthony G

2008-01-01

We describe the methodology used to analyze multiple transcripts using microarray techniques in simultaneous biopsies of muscle, adipose tissue and lymphocytes obtained from the same individual as part of the standard protocol of the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. We recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent letter. Subjects participated in a clinical examination that included anthropometric and body composition measurements, muscle biopsies (vastus lateralis) subcutaneous fat biopsies anda blood draw. All samples provided sufficient amplified RNA for microarray analysis. Total RNA was extracted from the biopsy samples and amplified for analysis. Of the 48,687 transcript targets queried, 39.4% were detectable in a least one of the studied tissues. Leptin was not detectable in lymphocytes, weakly expressed in muscle, but overexpressed and highly correlated with BMI in subcutaneous fat. Another example was GLUT4, which was detectable only in muscle and not correlated with BMI. Expression level concordance was 0.7 (p< 0.001) for the three tissues studied. We demonstrated the feasibility of carrying out simultaneous analysis of gene expression in multiple tissues, concordance of genetic expression in different tissues, and obtained confidence that this method corroborates the expected biological relationships among LEPand GLUT4. TheGEMM study will provide a broad and valuable overview on metabolic diseases, including obesity and type 2 diabetes.

Familial occurrence of cervical artery dissection--coincidence or sign of familial predisposition?

PubMed

Grond-Ginsbach, Caspar; de Freitas, Gabriel R; Campos, Cynthia R; Thie, Andreas; Caso, Valeria; Machetanz, Jochen; Kloss, Manja

2012-01-01

BACKGROUNDAND PURPOSE: The etiology of spontaneous cervical artery dissection (CeAD) is poorly understood in most patients. Mild cervical trauma preceding the dissection event is a common finding, but many CeAD occur spontaneously. It is likely that genetic factors may increase the risk for CeAD. However, familial cases are excedingly rare. Familial clustering of CeAD may be accidental or associated with genetic or environmental risk factors shared between affected relatives. In this explorative study, we aim to show that specific risk factors for familial CeAD exist. Age of onset, sex, affected artery and number of recurrent CeAD were documented for familial patients and compared with published findings from patients with sporadic CeAD. Concordance of age, sex and dissected artery within the families was analyzed by correlation analysis and by analysis of variance or Kruskal-Wallis testing. The study sample consisted of 9 new patients with a family history of CeAD enrolled in the Neurology Department of the University of Heidelberg or referred to Heidelberg from other centers. The study sample also included published findings from another 23 patients, in total 32 patients. The mean age of the patients with familial CeAD at their first dissections was 38.4 ± 13.3 years. Twenty (62.5%) patients were female and 12 patients (37.5%) suffered multiple dissections. Four patients (12.5%) presented with recurrent dissections after >1 year. Patients with a familial history of CeAD were younger (p = 0.023) and presented more often with multiple dissections (p = 0.024) and recurrent dissections (p = 0.018). Age at the first event (correlation analysis p = 0.026; analysis of variance p = 0.029) and site of the dissection (correlation analysis p = 0.032; Kruskal-Wallis test p = 0.018) differed between the families, and there was no concordance of gender of affected family members (correlation analysis p = 0.500; Kruskal-Wallis test p = 0.211). The high prevalence of multiple dissection events and of long-term (>1 year) recurrent dissections in patients with a familial history of CeAD indicates that a specific predisposition for familial CeAD exists. Since age of onset and affected vessel differ between families, the risk profile for familial CeAD is heterogeneous. A large-scale (whole exome) sequencing analysis of 14 patients from 7 of the analyzed families is currently being performed in order to identify causative genetic variants. Copyright © 2012 S. Karger AG, Basel.

DNA-based methods of geochemical prospecting

DOEpatents

Ashby, Matthew [Mill Valley, CA

2011-12-06

The present invention relates to methods for performing surveys of the genetic diversity of a population. The invention also relates to methods for performing genetic analyses of a population. The invention further relates to methods for the creation of databases comprising the survey information and the databases created by these methods. The invention also relates to methods for analyzing the information to correlate the presence of nucleic acid markers with desired parameters in a sample. These methods have application in the fields of geochemical exploration, agriculture, bioremediation, environmental analysis, clinical microbiology, forensic science and medicine.

Identification of kin structure among Guam rail founders: a comparison of pedigrees and DNA profiles

USGS Publications Warehouse

Haig, Susan M.; Ballou, J.D.; Casna, N.J.

1994-01-01

Kin structure among founders can have a significant effect on subsequent population structure. Here we use the correlation between DNA profile similarity and relatedness calculated from pedigrees to test hypotheses regarding kin structure among founders to the captive Guam rail (Rallus owstoni) population. Five different pedigrees were generated under the following hypotheses: (i) founders are unrelated; (ii) founders are unrelated except for same-nest chicks; (iii) founders from the same major site are siblings; (iv) founders from the same local site are siblings; and (v) founders are related as defined by a UPGMA cluster analysis of DNA similarity data. Relatedness values from pedigrees 1, 2 and 5 had the highest correlation with DNA similarity but the correlation between relatedness and similarity were not significantly different among pedigrees. Pedigree 5 resulted in the highest correlation overall when using only relatedness values that changed as a result of different founder hypotheses. Thus, founders were assigned relatedness based on pedigree 5 because it had the highest correlations with DNA similarity, was the most conservative approach, and incorporated all field data. The analyses indicated that estimating relatedness using DNA profiles remains problematic, therefore we compared mean kinship, a measure of genetic importance, with mean DNA profile similarity to determine if genetic importance among individuals could be determined via use of DNA profiles alone. The significant correlation suggests this method may provide more information about population structure than was previously thought. Thus, DNA profiles can provide a reasonable explanation for founder relatedness and mean DNA profile similarity may be helpful in determining relative genetic importance of individuals when detailed pedigrees are absent.

Molecular genetic analysis of the F11 gene in 14 Turkish patients with factor XI deficiency: identification of novel and recurrent mutations and their inheritance within families

PubMed Central

Colakoglu, Seyma; Bayhan, Turan; Tavil, Betül; Keskin, Ebru Yılmaz; Cakir, Volkan; Gümrük, Fatma; Çetin, Mualla; Aytaç, Selin; Berber, Ergul

2018-01-01

Background Factor XI (FXI) deficiency is an autosomal bleeding disease associated with genetic defects in the F11 gene which cause decreased FXI levels or impaired FXI function. An increasing number of mutations has been reported in the FXI mutation database, most of which affect the serine protease domain of the protein. FXI is a heterogeneous disorder associated with a variable bleeding tendency and a variety of causative F11 gene mutations. The molecular basis of FXI deficiency in 14 patients from ten unrelated families in Turkey was analysed to establish genotype-phenotype correlations and inheritance of the mutations in the patients’ families. Material and methods Fourteen index cases with a diagnosis of FXI deficiency and family members of these patients were enrolled into the study. The patients’ F11 genes were amplified by polymerase chain reaction and subjected to direct DNA sequencing analysis. The findings were analysed statistically using bivariate correlations, Pearson’s correlation coefficient and the nonparametric Mann-Whitney test. Results Direct DNA sequencing analysis of the F11 genes revealed that all of the 14 patients had a F11 gene mutation. Eight different mutations were identified in the apple 1, apple 2 or serine protease domains, except one which was a splice site mutation. Six of the mutations were recurrent. Two of the mutations were novel missense mutations, p.Val522Gly and p.Cys581Arg, within the catalytic domain. The p.Trp519Stop mutation was observed in two families whereas all the other mutations were specific to a single family. Discussion Identification of mutations confirmed the genetic heterogeneity of FXI deficiency. Most of the patients with mutations did not have any bleeding complications, whereas some had severe bleeding symptoms. Genetic screening for F11 gene mutations is important to decrease the mortality and morbidity rate associated with FXI deficiency, which can be life-threatening if bleeding occurs in tissues with high fibrinolytic activity. PMID:27723456

Natural selection and inheritance of breeding time and clutch size in the collared flycatcher.

PubMed

Sheldon, B C; Kruuk, L E B; Merilä, J

2003-02-01

Many characteristics of organisms in free-living populations appear to be under directional selection, possess additive genetic variance, and yet show no evolutionary response to selection. Avian breeding time and clutch size are often-cited examples of such characters. We report analyses of inheritance of, and selection on, these traits in a long-term study of a wild population of the collared flycatcher Ficedula albicollis. We used mixed model analysis with REML estimation ("animal models") to make full use of the information in complex multigenerational pedigrees. Heritability of laying date, but not clutch size, was lower than that estimated previously using parent-offspring regressions, although for both traits there was evidence of substantial additive genetic variance (h2 = 0.19 and 0.29, respectively). Laying date and clutch size were negatively genetically correlated (rA = -0.41 +/- 0.09), implying that selection on one of the traits would cause a correlated response in the other, but there was little evidence to suggest that evolution of either trait would be constrained by correlations with other phenotypic characters. Analysis of selection on these traits in females revealed consistent strong directional fecundity selection for earlier breeding at the level of the phenotype (beta = -0.28 +/- 0.03), but little evidence for stabilising selection on breeding time. We found no evidence that clutch size was independently under selection. Analysis of fecundity selection on breeding values for laying date, estimated from an animal model, indicated that selection acts directly on additive genetic variance underlying breeding time (beta = -0.20 +/- 0.04), but not on clutch size (beta = 0.03 +/- 0.05). In contrast, selection on laying date via adult female survival fluctuated in sign between years, and was opposite in sign for selection on phenotypes (negative) and breeding values (positive). Our data thus suggest that any evolutionary response to selection on laying date is partially constrained by underlying life-history trade-offs, and illustrate the difficulties in using purely phenotypic measures and incomplete fitness estimates to assess evolution of life-history trade-offs. We discuss some of the difficulties associated with understanding the evolution of laying date and clutch size in natural populations.

Genetic diversity, population structure, and correlations between locally adapted zebu and taurine breeds in Brazil using SNP markers.

PubMed

Campos, Bárbara Machado; do Carmo, Adriana Santana; do Egito, Andrea Alves; da Mariante, Arthur Silva; do Albuquerque, Maria Socorro Muaés; de Gouveia, João José Simoni; Malhado, Carlos Henrique Mendes; Verardo, Lucas Lima; da Silva, Marcos Vinícius Gualberto Barbosa; Carneiro, Paulo Luiz Souza

2017-12-01

Genetic diversity is one of the most important issues in studies on conservation of cattle breeds and endangered species. The objective of this study was to estimate the levels of genetic differentiation between locally adapted taurine (Bos taurus taurus) and zebu (Bos taurus indicus) breeds in Brazil, which were genotyped for more than 777,000 SNPs. The fixation index (F ST ), principal component analysis (PCA), and Bayesian clustering were estimated. The F ST highlighted genetic differentiation between taurine and zebu breeds. The taurine lines, Caracu and Caracu Caldeano, had significant genetic differentiation (F ST close to 5%) despite their recent selection for different uses (meat and milk). This genetic variability can be used for conservation of locally adapted animals, as well as for breeding programs on zebu breeds. Introgression of zebu in locally adapted breeds was identified, especially in Curraleiro Pé-Duro breed. The Gyr breed, however, had low breed purity at genomic level due to its very heterogeneous mixing pattern.

Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality.

PubMed

Eppinga, Ruben N; Hagemeijer, Yanick; Burgess, Stephen; Hinds, David A; Stefansson, Kari; Gudbjartsson, Daniel F; van Veldhuisen, Dirk J; Munroe, Patricia B; Verweij, Niek; van der Harst, Pim

2016-12-01

Resting heart rate is a heritable trait correlated with life span. Little is known about the genetic contribution to resting heart rate and its relationship with mortality. We performed a genome-wide association discovery and replication analysis starting with 19.9 million genetic variants and studying up to 265,046 individuals to identify 64 loci associated with resting heart rate (P < 5 × 10 -8 ); 46 of these were novel. We then used the genetic variants identified to study the association between resting heart rate and all-cause mortality. We observed that a genetically predicted resting heart rate increase of 5 beats per minute was associated with a 20% increase in mortality risk (hazard ratio 1.20, 95% confidence interval 1.11-1.28, P = 8.20 × 10 -7 ) translating to a reduction in life expectancy of 2.9 years for males and 2.6 years for females. Our findings provide evidence for shared genetic predictors of resting heart rate and all-cause mortality.

Estimates of Heritability for Growth and Shell Color Traits and Their Genetic Correlations in the Black Shell Strain of Pacific Oyster Crassostrea gigas.

PubMed

Xu, Lan; Li, Qi; Yu, Hong; Kong, Lingfeng

2017-10-01

The Pacific oyster Crassostrea gigas has been introduced widely and massively and became an economically important aquaculture species on a global scale. We estimated heritabilities of growth and shell color traits and their genetic correlations in black shell strain of C. gigas. Analyses were performed on 22 full-sib families in a nested mating design including 410 individuals at harvest (24 months of age). The parentage assignment was inferred based on four panels of multiplex PCR markers including 10 microsatellite loci and 94.9% of the offspring were unambiguously assigned to single parent pairs. The Spearman correlation test (r = - 0.992, P < 0.001) demonstrated the high consistency of the shell pigmentation (SP) and L* and their same efficacy in shell color measurements. The narrow-sense heritability estimated under the animal model analysis was 0.18 ± 0.12 for shell height, 0.25 ± 0.16 for shell length, 0.10 ± 0.09 for shell width, 0.42 ± 0.20 for total weight, 0.32 ± 0.18 for shell weight, and 0.68 ± 0.16 for L*, 0.69 ± 0.16 for shell pigmentation, respectively. The considerable additive genetic variation in growth and shell color traits will make it feasible to produce genetic improvements for these traits in selective breeding program. High genetic and phenotypic correlations were found among growth traits and among shell color traits. To optimize a selection strategy for both fast growth and pure dark shell strain of C. gigas, it is proposed to take both total weight and black shell as joint objective traits in selective breeding program. Our study offers an important reference in the process of selective breeding in black shell color stain of C. gigas and will facilitate to develop favorable breeding strategies of genetic improvements for this economically important strain.

Short communication: Genetic characterization of digital cushion thickness.

PubMed

Oikonomou, G; Banos, G; Machado, V; Caixeta, L; Bicalho, R C

2014-01-01

Dairy cow lameness is a serious animal welfare issue. It is also a significant cause of economic losses, reducing reproductive efficiency and milk production and increasing culling rates. The digital cushion is a complex structure composed mostly of adipose tissue located underneath the distal phalanx and has recently been phenotypically associated with incidence of claw horn disruption lesions (CHDL); namely, sole ulcers and white line disease. The objective of this study was to characterize digital cushion thickness genetically and to investigate its association with body condition score (BCS), locomotion score (LOCO), CHDL, and milk production. Data were collected from 1 large closely monitored commercial dairy farm located in upstate New York; 923 dairy cows were used. Before trimming, the following data were collected by a member of the research team: BCS, cow height measurement, and LOCO. Presence or not of CHDL (sole ulcer or white line disease, or both) was recorded at trimming. Immediately after the cows were hoof trimmed, they underwent digital sonographic B-mode examination for the measurement of digital cushion thickness. Factors such as parity number, stage of lactation, calving date, mature-equivalent 305-d milk yield (ME305MY), and pedigree information were obtained from the farm's dairy management software (DairyCOMP 305; Valley Agricultural Software, Tulare, CA). Univariate animal models were used to obtain variance component estimations for each studied trait (CHDL, BCS, digital cushion thickness average, LOCO, height, and ME305MY) and a 6-variate analysis was conducted to estimate the genetic, residual, and phenotypic correlations between the studied traits. The heritability estimate of DCTA was 0.33±0.09, whereas a statistically significant genetic correlation was estimated between DCTA and CHDL (-0.60±0.29). Of the other genetic correlations, significant estimates were derived for BCS with LOCO (-0.49±0.19) and ME305MY (-0.48±0.20). Digital cushion thickness is moderately heritable and genetically strongly correlated with CHDL. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Differential detection of genetic Loci underlying stem and root lignin content in Populus.

PubMed

Yin, Tongming; Zhang, Xinye; Gunter, Lee; Priya, Ranjan; Sykes, Robert; Davis, Mark; Wullschleger, Stan D; Tuskan, Gerald A

2010-11-22

In this study, we established a comprehensive genetic map with a large number of progeny from a three-generation hybrid Populus intercross, and phenotyped the lignin content, S/G ratio and 28 cell wall subcomponents both in stems and roots for the mapping individuals. Phenotypic analysis revealed that lignin content and syringyl-to-guaiacyl (S/G) ratio using pyrolysis molecular beam mass spectroscopy (pyMBMS) varied among mapping individuals. Phenotypic analysis revealed that stem lignin content is significantly higher than that in root and the quantified traits can be classified into four distinct groups, with strong correlations observed among components within organs. Altogether, 179 coordinating QTLs were detected, and they were co-localized into 49 genetic loci, 27 of which appear to be pleiotropic. Many of the detected genetic loci were detected differentially in stem and root. This is the first report of separate genetic loci controlling cell wall phenotypes above and below ground. These results suggest that it may be possible to modify lignin content and composition via breed and/or engineer as a means of simultaneously improving Populus for cellulosic ethanol production and carbon sequestration.

Short communication: Genetic association between schizophrenia and cannabis use.

PubMed

Verweij, Karin J H; Abdellaoui, Abdel; Nivard, Michel G; Sainz Cort, Alberto; Ligthart, Lannie; Draisma, Harmen H M; Minică, Camelia C; Gillespie, Nathan A; Willemsen, Gonneke; Hottenga, Jouke-Jan; Boomsma, Dorret I; Vink, Jacqueline M

2017-02-01

Previous studies have shown a relationship between schizophrenia and cannabis use. As both traits are substantially heritable, a shared genetic liability could explain the association. We use two recently developed genomics methods to investigate the genetic overlap between schizophrenia and cannabis use. Firstly, polygenic risk scores for schizophrenia were created based on summary statistics from the largest schizophrenia genome-wide association (GWA) meta-analysis to date. We analysed the association between these schizophrenia polygenic scores and multiple cannabis use phenotypes (lifetime use, regular use, age at initiation, and quantity and frequency of use) in a sample of 6,931 individuals. Secondly, we applied LD-score regression to the GWA summary statistics of schizophrenia and lifetime cannabis use to calculate the genome-wide genetic correlation. Polygenic risk scores for schizophrenia were significantly (α<0.05) associated with five of the eight cannabis use phenotypes, including lifetime use, regular use, and quantity of use, with risk scores explaining up to 0.5% of the variance. Associations were not significant for age at initiation of use and two measures of frequency of use analyzed in lifetime users only, potentially because of reduced power due to a smaller sample size. The LD-score regression revealed a significant genetic correlation of r g =0.22 (SE=0.07, p=0.003) between schizophrenia and lifetime cannabis use. Common genetic variants underlying schizophrenia and lifetime cannabis use are partly overlapping. Individuals with a stronger genetic predisposition to schizophrenia are more likely to initiate cannabis use, use cannabis more regularly, and consume more cannabis over their lifetime. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Heritable Environmental Variance Causes Nonlinear Relationships Between Traits: Application to Birth Weight and Stillbirth of Pigs

PubMed Central

Mulder, Herman A.; Hill, William G.; Knol, Egbert F.

2015-01-01

There is recent evidence from laboratory experiments and analysis of livestock populations that not only the phenotype itself, but also its environmental variance, is under genetic control. Little is known about the relationships between the environmental variance of one trait and mean levels of other traits, however. A genetic covariance between these is expected to lead to nonlinearity between them, for example between birth weight and survival of piglets, where animals of extreme weights have lower survival. The objectives were to derive this nonlinear relationship analytically using multiple regression and apply it to data on piglet birth weight and survival. This study provides a framework to study such nonlinear relationships caused by genetic covariance of environmental variance of one trait and the mean of the other. It is shown that positions of phenotypic and genetic optima may differ and that genetic relationships are likely to be more curvilinear than phenotypic relationships, dependent mainly on the environmental correlation between these traits. Genetic correlations may change if the population means change relative to the optimal phenotypes. Data of piglet birth weight and survival show that the presence of nonlinearity can be partly explained by the genetic covariance between environmental variance of birth weight and survival. The framework developed can be used to assess effects of artificial and natural selection on means and variances of traits and the statistical method presented can be used to estimate trade-offs between environmental variance of one trait and mean levels of others. PMID:25631318

Genetic effects influencing risk for major depressive disorder in China and Europe.

PubMed

Bigdeli, T B; Ripke, S; Peterson, R E; Trzaskowski, M; Bacanu, S-A; Abdellaoui, A; Andlauer, T F M; Beekman, A T F; Berger, K; Blackwood, D H R; Boomsma, D I; Breen, G; Buttenschøn, H N; Byrne, E M; Cichon, S; Clarke, T-K; Couvy-Duchesne, B; Craddock, N; de Geus, E J C; Degenhardt, F; Dunn, E C; Edwards, A C; Fanous, A H; Forstner, A J; Frank, J; Gill, M; Gordon, S D; Grabe, H J; Hamilton, S P; Hardiman, O; Hayward, C; Heath, A C; Henders, A K; Herms, S; Hickie, I B; Hoffmann, P; Homuth, G; Hottenga, J-J; Ising, M; Jansen, R; Kloiber, S; Knowles, J A; Lang, M; Li, Q S; Lucae, S; MacIntyre, D J; Madden, P A F; Martin, N G; McGrath, P J; McGuffin, P; McIntosh, A M; Medland, S E; Mehta, D; Middeldorp, C M; Milaneschi, Y; Montgomery, G W; Mors, O; Müller-Myhsok, B; Nauck, M; Nyholt, D R; Nöthen, M M; Owen, M J; Penninx, B W J H; Pergadia, M L; Perlis, R H; Peyrot, W J; Porteous, D J; Potash, J B; Rice, J P; Rietschel, M; Riley, B P; Rivera, M; Schoevers, R; Schulze, T G; Shi, J; Shyn, S I; Smit, J H; Smoller, J W; Streit, F; Strohmaier, J; Teumer, A; Treutlein, J; Van der Auwera, S; van Grootheest, G; van Hemert, A M; Völzke, H; Webb, B T; Weissman, M M; Wellmann, J; Willemsen, G; Witt, S H; Levinson, D F; Lewis, C M; Wray, N R; Flint, J; Sullivan, P F; Kendler, K S

2017-03-28

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log 10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Genetic effects influencing risk for major depressive disorder in China and Europe

PubMed Central

Bigdeli, T B; Ripke, S; Peterson, R E; Trzaskowski, M; Bacanu, S-A; Abdellaoui, A; Andlauer, T F M; Beekman, A T F; Berger, K; Blackwood, D H R; Boomsma, D I; Breen, G; Buttenschøn, H N; Byrne, E M; Cichon, S; Clarke, T-K; Couvy-Duchesne, B; Craddock, N; de Geus, E J C; Degenhardt, F; Dunn, E C; Edwards, A C; Fanous, A H; Forstner, A J; Frank, J; Gill, M; Gordon, S D; Grabe, H J; Hamilton, S P; Hardiman, O; Hayward, C; Heath, A C; Henders, A K; Herms, S; Hickie, I B; Hoffmann, P; Homuth, G; Hottenga, J-J; Ising, M; Jansen, R; Kloiber, S; Knowles, J A; Lang, M; Li, Q S; Lucae, S; MacIntyre, D J; Madden, P A F; Martin, N G; McGrath, P J; McGuffin, P; McIntosh, A M; Medland, S E; Mehta, D; Middeldorp, C M; Milaneschi, Y; Montgomery, G W; Mors, O; Müller-Myhsok, B; Nauck, M; Nyholt, D R; Nöthen, M M; Owen, M J; Penninx, B W J H; Pergadia, M L; Perlis, R H; Peyrot, W J; Porteous, D J; Potash, J B; Rice, J P; Rietschel, M; Riley, B P; Rivera, M; Schoevers, R; Schulze, T G; Shi, J; Shyn, S I; Smit, J H; Smoller, J W; Streit, F; Strohmaier, J; Teumer, A; Treutlein, J; Van der Auwera, S; van Grootheest, G; van Hemert, A M; Völzke, H; Webb, B T; Weissman, M M; Wellmann, J; Willemsen, G; Witt, S H; Levinson, D F; Lewis, C M; Wray, N R; Flint, J; Sullivan, P F; Kendler, K S

2017-01-01

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies. PMID:28350396

Shared Genetic Architecture in the Relationship between Adult Stature and Subclinical Coronary Artery Atherosclerosis

PubMed Central

Cassidy-Bushrow, Andrea E.; Bielak, Lawrence F.; Sheedy, Patrick F.; Turner, Stephen T.; Chu, Julia S.; Peyser, Patricia A.

2011-01-01

Background Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. Methods 877 asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Results Adult height was significantly and inversely associated with CAC score (P=0.01). After adjusting for age, sex, and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P=0.001) and -1 (P<0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P=0.024). Conclusions Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. PMID:21937044

Shared genetic architecture in the relationship between adult stature and subclinical coronary artery atherosclerosis.

PubMed

Cassidy-Bushrow, Andrea E; Bielak, Lawrence F; Sheedy, Patrick F; Turner, Stephen T; Chu, Julia S; Peyser, Patricia A

2011-12-01

Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. 877 Asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Adult height was significantly and inversely associated with CAC score (P = 0.01). After adjusting for age, sex and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P = 0.001) and -1 (P < 0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P = 0.024). Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Genetic rhetoric: Science, authority, and genes

NASA Astrophysics Data System (ADS)

Shea, Elizabeth Parthenia

This dissertation is an analysis of how the cultural authority of genetics works through language. An analysis of the rhetorical construction of knowledge and authority in cultural contexts, the study is intended to contribute to a larger discussion aimed at keeping the intersections of science and culture within the realm of rhetoric, that is within the realm of communication and dialogue. Of special concern is the influence of genetic rhetoric on the cultural momentum of biological determinism to explain away social organization, class inequalities, racial differences, gender differences, and stigmatized behaviors by rooting them in the construct of the biological individual. This study separates questions of legitimacy from questions of authority and focuses on the way that authority of genetics works through language. With authority defined as the function of resisting challenges to legitimacy and/or power, the study consists of three parts. First, a historical analysis of the terms science, genetics, and gene, shows how these words came to refer not only to areas and objects of study but also to sources of epistemological legitimacy outside culture and language. The relationships between these words and their referents are examined in socio-historical context to illustrate how the function of signaling authority was inscribed in the literal definition of these terms. Second, introductory chapters of contemporary Genetics textbooks are examined. In these texts the foundations of legitimacy associated with genetics and science are maintained as the authors articulate idealized views of science and genetics in relation to society. Finally, articles in the popular press reporting on and discussing recent research correlating genetics and homosexuality are examined. The popular press reports of "gay gene" research serve as textual examples of figurative representations of genetics concepts shaping discourse about social issues. I argue that the cultural authority of genetics, as well as the power of science to shape culture, is not necessarily a matter of the persuasiveness of material truths but rather a mobilization of rhetorical figures that are linked to but not literally representing ideas of material truth.

Correlation and path analysis of biomass sorghum production.

PubMed

Vendruscolo, T P S; Barelli, M A A; Castrillon, M A S; da Silva, R S; de Oliveira, F T; Corrêa, C L; Zago, B W; Tardin, F D

2016-12-23

Sorghum biomass is an interesting raw material for bioenergy production due to its versatility, potential of being a renewable energy source, and low-cost of production. The objective of this study was to evaluate the genetic variability of biomass sorghum genotypes and to estimate genotypic, phenotypic, and environmental correlations, and direct and indirect effects of seven agronomic traits through path analysis. Thirty-four biomass sorghum genotypes and two forage sorghum genotypes were cultivated in a randomized block design with three replicates. The following morpho-agronomic traits were evaluated: flowering date, stem diameter, number of stems, plant height, number of leaves, green mass production, and dry matter production. There were significant differences at the 1% level for all traits. The highest genotypic correlation was found between the traits green mass production and dry matter production. The path analysis demonstrated that green mass production and number of leaves can assist in the selection of dry matter production.

Genetic alterations of hepatocellular carcinoma by random amplified polymorphic DNA analysis and cloning sequencing of tumor differential DNA fragment

PubMed Central

Xian, Zhi-Hong; Cong, Wen-Ming; Zhang, Shu-Hui; Wu, Meng-Chao

2005-01-01

AIM: To study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments. METHODS: DNA isolated from tumors and corresponding noncancerous liver tissues of 56 HCC patients was amplified by random amplified polymorphic DNA (RAPD) with 10 random 10-mer arbitrary primers. The RAPD bands showing obvious differences in tumor tissue DNA corresponding to that of normal tissue were separated, purified, cloned and sequenced. DNA sequences were analyzed and compared with GenBank data. RESULTS: A total of 56 cases of HCC were demonstrated to have genetic alterations, which were detected by at least one primer. The detestability of genetic alterations ranged from 20% to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor size, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with genetic alterations on certain primers. A band with a higher intensity of 480 bp or so amplified fragments in tumor DNA relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4. Sequence analysis of these fragments showed 91% homology with Homo sapiens double homeobox protein DUX10 gene. CONCLUSION: Genetic alterations are a frequent event in HCC, and tumor related DNA fragments have been found in this study, which may be associated with hepatocarcin-ogenesis. RAPD is an effective method for the identification and analysis of genetic alterations in HCC, and may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis. PMID:15996039

Genetic, epigenetic, and HPLC fingerprint differentiation between natural and ex situ populations of Rhodiola sachalinensis from Changbai Mountain, China.

PubMed

Zhao, Wei; Shi, Xiaozheng; Li, Jiangnan; Guo, Wei; Liu, Chengbai; Chen, Xia

2014-01-01

Rhodiola sachalinensis is an endangered species with important medicinal value. We used inter-simple sequence repeat (ISSR) and methylation-sensitive amplified polymorphism (MSAP) markers to analyze genetic and epigenetic differentiation in different populations of R. sachalinensis, including three natural populations and an ex situ population. Chromatographic fingerprint was used to reveal HPLC fingerprint differentiation. According to our results, the ex situ population of R. sachalinensis has higher level genetic diversity and greater HPLC fingerprint variation than natural populations, but shows lower epigenetic diversity. Most genetic variation (54.88%) was found to be distributed within populations, and epigenetic variation was primarily distributed among populations (63.87%). UPGMA cluster analysis of ISSR and MSAP data showed identical results, with individuals from each given population grouping together. The results of UPGMA cluster analysis of HPLC fingerprint patterns was significantly different from results obtained from ISSR and MSAP data. Correlation analysis revealed close relationships among altitude, genetic structure, epigenetic structure, and HPLC fingerprint patterns (R2 = 0.98 for genetic and epigenetic distance; R2 = 0.90 for DNA methylation level and altitude; R2 = -0.95 for HPLC fingerprint and altitude). Taken together, our results indicate that ex situ population of R. sachalinensis show significantly different genetic and epigenetic population structures and HPLC fingerprint patterns. Along with other potential explanations, these findings suggest that the ex situ environmental factors caused by different altitude play an important role in keeping hereditary characteristic of R. sachalinensis.

Genetic, Epigenetic, and HPLC Fingerprint Differentiation between Natural and Ex Situ Populations of Rhodiola sachalinensis from Changbai Mountain, China

PubMed Central

Zhao, Wei; Shi, Xiaozheng; Li, Jiangnan; Guo, Wei; Liu, Chengbai; Chen, Xia

2014-01-01

Rhodiola sachalinensis is an endangered species with important medicinal value. We used inter-simple sequence repeat (ISSR) and methylation-sensitive amplified polymorphism (MSAP) markers to analyze genetic and epigenetic differentiation in different populations of R. sachalinensis, including three natural populations and an ex situ population. Chromatographic fingerprint was used to reveal HPLC fingerprint differentiation. According to our results, the ex situ population of R. sachalinensis has higher level genetic diversity and greater HPLC fingerprint variation than natural populations, but shows lower epigenetic diversity. Most genetic variation (54.88%) was found to be distributed within populations, and epigenetic variation was primarily distributed among populations (63.87%). UPGMA cluster analysis of ISSR and MSAP data showed identical results, with individuals from each given population grouping together. The results of UPGMA cluster analysis of HPLC fingerprint patterns was significantly different from results obtained from ISSR and MSAP data. Correlation analysis revealed close relationships among altitude, genetic structure, epigenetic structure, and HPLC fingerprint patterns (R2 = 0.98 for genetic and epigenetic distance; R2 = 0.90 for DNA methylation level and altitude; R2 = –0.95 for HPLC fingerprint and altitude). Taken together, our results indicate that ex situ population of R. sachalinensis show significantly different genetic and epigenetic population structures and HPLC fingerprint patterns. Along with other potential explanations, these findings suggest that the ex situ environmental factors caused by different altitude play an important role in keeping hereditary characteristic of R. sachalinensis. PMID:25386983

Genetic Relationship of Productive Life, Production and Type Traits of Korean Holsteins at Early Lactations

PubMed Central

Wasana, Nidarshani; Cho, GwangHyun; Park, SuBong; Kim, SiDong; Choi, JaeGwan; Park, ByungHo; Park, ChanHyuk; Do, ChangHee

2015-01-01

The present study was performed to study the genetic relationship of productive life with production and type traits of Korean Holsteins at first three lactations. The data for the analysis from 56,054, 28,997, and 11,816 animals of first, second and third parity cows which were born from 2006 to 2011 were collected by Dairy Cattle Improvement Center, National Agricultural Co-operative Federation. Milk, protein and fat yields adjusted for 305 days and average somatic cell score considered as production traits and analyzed type traits were stature, strength, body depth, dairy form, rump angle, rump width, rear leg side view, foot angle, front attachment placement, rear attachment height, rear attachment width, udder cleft, udder depth, front teat placement and front teat length. A multi trait genetic analysis was performed using Wombat program with restricted maximum likelihood animal model composed of fixed effect of birth year, farm and the random effect of animal and random residual effect according to the traits. Heritability estimates of productive life were between 0.06 and 0.13. Genetic and phenotypic correlations between production and productive life traits ranged from 0.35 to 0.04 for milk, 0.16 to 0.05 for protein and 0.18 to 0.02 f 15-0034 (2nd) 150520 or fat. Somatic cells score showed a negative genetic and phenotypic correlation with productive life and also udder type traits, indicating that the selection for higher udder traits will likely to improve resistance to mastitis and persistence in the herd. Among all dairy form type traits, udder characters such as udder cleft showed a significant relationship with productive life. However, a specific change of heritabilities or correlations were not observed with the change of parity. Moreover, further studies are needed to further confirm the significance of the above traits and the effect of parity on above relationships in order to minimize both voluntary and involuntary culling rates while improving herd health and maintaining high yielding dairy cows. PMID:26194223

Genetic Relationship of Productive Life, Production and Type Traits of Korean Holsteins at Early Lactations.

PubMed

Wasana, Nidarshani; Cho, GwangHyun; Park, SuBong; Kim, SiDong; Choi, JaeGwan; Park, ByungHo; Park, ChanHyuk; Do, ChangHee

2015-09-01

The present study was performed to study the genetic relationship of productive life with production and type traits of Korean Holsteins at first three lactations. The data for the analysis from 56,054, 28,997, and 11,816 animals of first, second and third parity cows which were born from 2006 to 2011 were collected by Dairy Cattle Improvement Center, National Agricultural Co-operative Federation. Milk, protein and fat yields adjusted for 305 days and average somatic cell score considered as production traits and analyzed type traits were stature, strength, body depth, dairy form, rump angle, rump width, rear leg side view, foot angle, front attachment placement, rear attachment height, rear attachment width, udder cleft, udder depth, front teat placement and front teat length. A multi trait genetic analysis was performed using Wombat program with restricted maximum likelihood animal model composed of fixed effect of birth year, farm and the random effect of animal and random residual effect according to the traits. Heritability estimates of productive life were between 0.06 and 0.13. Genetic and phenotypic correlations between production and productive life traits ranged from 0.35 to 0.04 for milk, 0.16 to 0.05 for protein and 0.18 to 0.02 f 15-0034 (2nd) 150520 or fat. Somatic cells score showed a negative genetic and phenotypic correlation with productive life and also udder type traits, indicating that the selection for higher udder traits will likely to improve resistance to mastitis and persistence in the herd. Among all dairy form type traits, udder characters such as udder cleft showed a significant relationship with productive life. However, a specific change of heritabilities or correlations were not observed with the change of parity. Moreover, further studies are needed to further confirm the significance of the above traits and the effect of parity on above relationships in order to minimize both voluntary and involuntary culling rates while improving herd health and maintaining high yielding dairy cows.

An alternative covariance estimator to investigate genetic heterogeneity in populations.

PubMed

Heslot, Nicolas; Jannink, Jean-Luc

2015-11-26

For genomic prediction and genome-wide association studies (GWAS) using mixed models, covariance between individuals is estimated using molecular markers. Based on the properties of mixed models, using available molecular data for prediction is optimal if this covariance is known. Under this assumption, adding individuals to the analysis should never be detrimental. However, some empirical studies showed that increasing training population size decreased prediction accuracy. Recently, results from theoretical models indicated that even if marker density is high and the genetic architecture of traits is controlled by many loci with small additive effects, the covariance between individuals, which depends on relationships at causal loci, is not always well estimated by the whole-genome kinship. We propose an alternative covariance estimator named K-kernel, to account for potential genetic heterogeneity between populations that is characterized by a lack of genetic correlation, and to limit the information flow between a priori unknown populations in a trait-specific manner. This is similar to a multi-trait model and parameters are estimated by REML and, in extreme cases, it can allow for an independent genetic architecture between populations. As such, K-kernel is useful to study the problem of the design of training populations. K-kernel was compared to other covariance estimators or kernels to examine its fit to the data, cross-validated accuracy and suitability for GWAS on several datasets. It provides a significantly better fit to the data than the genomic best linear unbiased prediction model and, in some cases it performs better than other kernels such as the Gaussian kernel, as shown by an empirical null distribution. In GWAS simulations, alternative kernels control type I errors as well as or better than the classical whole-genome kinship and increase statistical power. No or small gains were observed in cross-validated prediction accuracy. This alternative covariance estimator can be used to gain insight into trait-specific genetic heterogeneity by identifying relevant sub-populations that lack genetic correlation between them. Genetic correlation can be 0 between identified sub-populations by performing automatic selection of relevant sets of individuals to be included in the training population. It may also increase statistical power in GWAS.

Genetic and environmental influences on the comorbidity between depression, panic disorder, agoraphobia and social phobia: A twin study

PubMed Central

Mosing, Miriam A.; Gordon, Scott D.; Medland, Sarah E.; Statham, Dixie J.; Nelson, Elliot C.; Heath, Andrew C.; Martin, Nicholas G.; Wray, Naomi R.

2011-01-01

Background Major depression (MD) and anxiety disorders such as panic disorder (PD), agoraphobia (AG) and social phobia (SP) are heritable and highly comorbid. However, the relative importance of genetic and environmental aetiology of the covariation between these disorders, particularly the relationship between PD and AG is less clear. Methods The present study measured MD, PD and AG in a population sample of 5440 twin pairs and 1245 single twins, about 45% of whom were also scored for SP. Prevalences, within individual comorbidity and twin odds ratios for comorbidity are reported. A behavioural genetic analysis of the four disorders using the classical twin design was conducted. Results Odds ratios for MD, PD, AG, and SP in twins of individuals diagnosed with one of the four disorders were increased. Heritability estimates under a threshold-liability model for MD, PD, AG, and SP respectively were 0.33 (CI:0.30–0.42), 0.38 (CI:0.24–0.55), 0.48 (CI:0.37–0.65) of, and 0.39 (CI:0.16–0.65), with no evidence for any variance explained by the common environment shared by twins. We find that a common genetic factor explains a moderate proportion of variance in these four disorders. The genetic correlation between PD and AG was 0.83. Conclusion MD, PD, AG, and SP strongly co-aggregate within families and common genetic factors explain a moderate proportion of variance in these four disorders. The high genetic correlation between PD and AG and the increased odds ratio for PD and AG in siblings of those with AG without PD suggests a common genetic aetiology for PD and AG. PMID:19750555

Genetic and environmental influences on the co-morbidity between depression, panic disorder, agoraphobia, and social phobia: a twin study.

PubMed

Mosing, Miriam A; Gordon, Scott D; Medland, Sarah E; Statham, Dixie J; Nelson, Elliot C; Heath, Andrew C; Martin, Nicholas G; Wray, Naomi R

2009-01-01

Major depression (MD) and anxiety disorders such as panic disorder (PD), agoraphobia (AG), and social phobia (SP) are heritable and highly co-morbid. However, the relative importance of genetic and environmental etiology of the covariation between these disorders, particularly the relationship between PD and AG, is less clear. This study measured MD, PD, and AG in a population sample of 5,440 twin pairs and 1,245 single twins, about 45% of whom were also scored for SP. Prevalences, within individual co-morbidity and twin odds ratios for co-morbidity, are reported. A behavioral genetic analysis of the four disorders using the classical twin design was conducted. Odds ratios for MD, PD, AG, and SP in twins of individuals diagnosed with one of the four disorders were increased. Heritability estimates under a threshold-liability model for MD, PD, AG, and SP respectively were .33 (CI: 0.30-0.42), .38 (CI: 0.24-0.55), .48 (CI: 0.37-0.65), and .39 (CI: 0.16-0.65), with no evidence for any variance explained by the common environment shared by twins. We find that a common genetic factor explains a moderate proportion of variance in these four disorders. The genetic correlation between PD and AG was .83. MD, PD, AG, and SP strongly co-aggregate within families and common genetic factors explain a moderate proportion of variance in these four disorders. The high genetic correlation between PD and AG and the increased odds ratio for PD and AG in siblings of those with AG without PD suggests a common genetic etiology for PD and AG.

Analysis of a genetically structured variance heterogeneity model using the Box-Cox transformation.

PubMed

Yang, Ye; Christensen, Ole F; Sorensen, Daniel

2011-02-01

Over recent years, statistical support for the presence of genetic factors operating at the level of the environmental variance has come from fitting a genetically structured heterogeneous variance model to field or experimental data in various species. Misleading results may arise due to skewness of the marginal distribution of the data. To investigate how the scale of measurement affects inferences, the genetically structured heterogeneous variance model is extended to accommodate the family of Box-Cox transformations. Litter size data in rabbits and pigs that had previously been analysed in the untransformed scale were reanalysed in a scale equal to the mode of the marginal posterior distribution of the Box-Cox parameter. In the rabbit data, the statistical evidence for a genetic component at the level of the environmental variance is considerably weaker than that resulting from an analysis in the original metric. In the pig data, the statistical evidence is stronger, but the coefficient of correlation between additive genetic effects affecting mean and variance changes sign, compared to the results in the untransformed scale. The study confirms that inferences on variances can be strongly affected by the presence of asymmetry in the distribution of data. We recommend that to avoid one important source of spurious inferences, future work seeking support for a genetic component acting on environmental variation using a parametric approach based on normality assumptions confirms that these are met.

Characterization of Movement Disorder Phenomenology in Genetically Proven, Familial Frontotemporal Lobar Degeneration: A Systematic Review and Meta-Analysis.

PubMed

Gasca-Salas, Carmen; Masellis, Mario; Khoo, Edwin; Shah, Binit B; Fisman, David; Lang, Anthony E; Kleiner-Fisman, Galit

2016-01-01

Mutations in granulin (PGRN) and tau (MAPT), and hexanucleotide repeat expansions near the C9orf72 genes are the most prevalent genetic causes of frontotemporal lobar degeneration. Although behavior, language and movement presentations are common, the relationship between genetic subgroup and movement disorder phenomenology is unclear. We conducted a systematic review and meta-analysis of the literature characterizing the spectrum and prevalence of movement disorders in genetic frontotemporal lobar degeneration. Electronic databases were searched using terms related to frontotemporal lobar degeneration and movement disorders. Articles were included when cases had a proven genetic cause. Study-specific prevalence estimates for clinical features were transformed using Freeman-Tukey arcsine transformation, allowing for pooled estimates of prevalence to be generated using random-effects models. The mean age at onset was earlier in those with MAPT mutations compared to PGRN (p<0.001) and C9orf72 (p = 0.024). 66.5% of subjects had an initial non-movement presentation that was most likely a behavioral syndrome (35.7%). At any point during the disease, parkinsonism was the most common movement syndrome reported in 79.8% followed by progressive supranuclear palsy (PSPS) and corticobasal (CBS) syndromes in 12.2% and 10.7%, respectively. The prevalence of movement disorder as initial presentation was higher in MAPT subjects (35.8%) compared to PGRN subjects (10.1). In those with a non-movement presentation, language disorder was more common in PGRN subjects (18.7%) compared to MAPT subjects (5.4%). This represents the first systematic review and meta-analysis of the occurrence of movement disorder phenomenology in genetic frontotemporal lobar degeneration. Standardized prospective collection of clinical information in conjunction with genetic characterization will be crucial for accurate clinico-genetic correlation.

Characterization of Movement Disorder Phenomenology in Genetically Proven, Familial Frontotemporal Lobar Degeneration: A Systematic Review and Meta-Analysis

PubMed Central

Gasca-Salas, Carmen; Masellis, Mario; Khoo, Edwin; Shah, Binit B.; Fisman, David; Lang, Anthony E.; Kleiner-Fisman, Galit

2016-01-01

Background Mutations in granulin (PGRN) and tau (MAPT), and hexanucleotide repeat expansions near the C9orf72 genes are the most prevalent genetic causes of frontotemporal lobar degeneration. Although behavior, language and movement presentations are common, the relationship between genetic subgroup and movement disorder phenomenology is unclear. Objective We conducted a systematic review and meta-analysis of the literature characterizing the spectrum and prevalence of movement disorders in genetic frontotemporal lobar degeneration. Methods Electronic databases were searched using terms related to frontotemporal lobar degeneration and movement disorders. Articles were included when cases had a proven genetic cause. Study-specific prevalence estimates for clinical features were transformed using Freeman-Tukey arcsine transformation, allowing for pooled estimates of prevalence to be generated using random-effects models. Results The mean age at onset was earlier in those with MAPT mutations compared to PGRN (p<0.001) and C9orf72 (p = 0.024). 66.5% of subjects had an initial non-movement presentation that was most likely a behavioral syndrome (35.7%). At any point during the disease, parkinsonism was the most common movement syndrome reported in 79.8% followed by progressive supranuclear palsy (PSPS) and corticobasal (CBS) syndromes in 12.2% and 10.7%, respectively. The prevalence of movement disorder as initial presentation was higher in MAPT subjects (35.8%) compared to PGRN subjects (10.1). In those with a non-movement presentation, language disorder was more common in PGRN subjects (18.7%) compared to MAPT subjects (5.4%). Summary This represents the first systematic review and meta-analysis of the occurrence of movement disorder phenomenology in genetic frontotemporal lobar degeneration. Standardized prospective collection of clinical information in conjunction with genetic characterization will be crucial for accurate clinico-genetic correlation. PMID:27100392

A Whole Genome DArTseq and SNP Analysis for Genetic Diversity Assessment in Durum Wheat from Central Fertile Crescent

PubMed Central

Shahid, Muhammad Qasim; Çiftçi, Vahdettin; E. Sáenz de Miera, Luis; Aasim, Muhammad; Nadeem, Muhammad Azhar; Aktaş, Husnu; Özkan, Hakan; Hatipoğlu, Rüştü

2017-01-01

Until now, little attention has been paid to the geographic distribution and evaluation of genetic diversity of durum wheat from the Central Fertile Crescent (modern-day Turkey and Syria). Turkey and Syria are considered as primary centers of wheat diversity, and thousands of locally adapted wheat landraces are still present in the farmers’ small fields. We planned this study to evaluate the genetic diversity of durum wheat landraces from the Central Fertile Crescent by genotyping based on DArTseq and SNP analysis. A total of 39,568 DArTseq and 20,661 SNP markers were used to characterize the genetic characteristic of 91 durum wheat land races. Clustering based on Neighbor joining analysis, principal coordinate as well as Bayesian model implemented in structure, clearly showed that the grouping pattern is not associated with the geographical distribution of the durum wheat due to the mixing of the Turkish and Syrian landraces. Significant correlation between DArTseq and SNP markers was observed in the Mantel test. However, we detected a non-significant relationship between geographical coordinates and DArTseq (r = -0.085) and SNP (r = -0.039) loci. These results showed that unconscious farmer selection and lack of the commercial varieties might have resulted in the exchange of genetic material and this was apparent in the genetic structure of durum wheat in Turkey and Syria. The genomic characterization presented here is an essential step towards a future exploitation of the available durum wheat genetic resources in genomic and breeding programs. The results of this study have also depicted a clear insight about the genetic diversity of wheat accessions from the Central Fertile Crescent. PMID:28099442

Genetic Structure and Relationship Analysis of an Association Population in Jute (Corchorus spp.) Evaluated by SSR Markers

PubMed Central

Zhang, Liwu; Yuan, Minhang; Tao, Aifen; Xu, Jiantang; Lin, Lihui; Fang, Pingping; Qi, Jianmin

2015-01-01

Population structure and relationship analysis is of great importance in the germplasm utilization and association mapping. Jute, comprised of white jute (C. capsularis L) and dark jute (C. olitorius L), is second to cotton in its commercial significance in the world. Here, we assessed the genetic structure and relationship in a panel of 159 jute accessions from 11 countries and regions using 63 SSRs. The structure analysis divided the 159 jute accessions from white and dark jute into Co and Cc group, further into Co1, Co2, Cc1 and Cc2 subgroups. Out of Cc1 subgroup, 81 accessions were from China and the remaining 10 accessions were from India (2), Japan (5), Thailand, Vietnam (2) and Pakistan (1). Out of Cc2 subgroup, 35 accessions were from China, and the remaining 3 accessions were from India, Pakistan and Thailand respectively. It can be inferred that the genetic background of these jute accessions was not always correlative with their geographical regions. Similar results were found in Co1 and Co2 subgroups. Analysis of molecular variance revealed 81% molecular variation between groups but it was low (19%) within subgroups, which further confirmed the genetic differentiation between the two groups. The genetic relationship analysis showed that the most diverse genotypes were Maliyeshengchangguo and Changguozhongyueyin in dark jute, BZ-2-2, Aidianyehuangma, Yangjuchiyuanguo, Zijinhuangma and Jute 179 in white jute, which could be used as the potential parents in breeding programs for jute improvement. These results would be very useful for association studies and breeding in jute. PMID:26035301

Genetic Structure and Relationship Analysis of an Association Population in Jute (Corchorus spp.) Evaluated by SSR Markers.

PubMed

Zhang, Liwu; Yuan, Minhang; Tao, Aifen; Xu, Jiantang; Lin, Lihui; Fang, Pingping; Qi, Jianmin

2015-01-01

Population structure and relationship analysis is of great importance in the germplasm utilization and association mapping. Jute, comprised of white jute (C. capsularis L) and dark jute (C. olitorius L), is second to cotton in its commercial significance in the world. Here, we assessed the genetic structure and relationship in a panel of 159 jute accessions from 11 countries and regions using 63 SSRs. The structure analysis divided the 159 jute accessions from white and dark jute into Co and Cc group, further into Co1, Co2, Cc1 and Cc2 subgroups. Out of Cc1 subgroup, 81 accessions were from China and the remaining 10 accessions were from India (2), Japan (5), Thailand, Vietnam (2) and Pakistan (1). Out of Cc2 subgroup, 35 accessions were from China, and the remaining 3 accessions were from India, Pakistan and Thailand respectively. It can be inferred that the genetic background of these jute accessions was not always correlative with their geographical regions. Similar results were found in Co1 and Co2 subgroups. Analysis of molecular variance revealed 81% molecular variation between groups but it was low (19%) within subgroups, which further confirmed the genetic differentiation between the two groups. The genetic relationship analysis showed that the most diverse genotypes were Maliyeshengchangguo and Changguozhongyueyin in dark jute, BZ-2-2, Aidianyehuangma, Yangjuchiyuanguo, Zijinhuangma and Jute 179 in white jute, which could be used as the potential parents in breeding programs for jute improvement. These results would be very useful for association studies and breeding in jute.

Geographic separation of domestic and wild strains of Toxoplasma gondii in French Guiana correlates with a monomorphic version of chromosome1a.

PubMed

Khan, Asis; Ajzenberg, Daniel; Mercier, Aurélien; Demar, Magalie; Simon, Stéphane; Dardé, Marie Laure; Wang, Qiuling; Verma, Shiv Kumar; Rosenthal, Benjamin M; Dubey, Jitender P; Sibley, L David

2014-09-01

Previous studies have stressed the genetic divergence and high pathogenicity of strains of T. gondii from French Guiana. Although strains from coastal, human adapted environments (so called anthropized) resemble those found in other regions of the Caribbean, strains collected from inland jungle environment are genetically quite diverse. To better understand the composition of these distinct strain types, we undertook a more in depth analysis of T. gondii strains from French Guiana including profiling of chromosome 1a (Chr1a), which is often shared as a single monomorphic haplotype among lineages that are otherwise genetically distinct. Comparison of intron sequences from selectively neutral genes indicated that anthropized strains were most closely related to clonal type III strains from North America, although wider RFLP analysis revealed that they are natural hybrids. In contrast, strains isolated from the jungle were genetically very diverse. Remarkably, nearly all anthropized strains contained the monomorphic version of Chr1a while wild stains were extremely divergent. The presence of the monomorphic Chr1a strongly correlated with greater transmission in domestic cats, although there were several exceptions, indicating that other factors also contribute. Anthropized strains also varied in their virulence in laboratory mice, and this pattern could not be explained by the simple combination of previously identified virulence factors, indicating that other genetic determinants influence pathogenicity. Our studies underscore the marked genetic separation of anthropized and wild strains of T. gondii in French Guiana and provide additional evidence that the presence of Chr1a is associated with successful expansion of widely different lineages within diverse geographic areas. The predominance of Chr1a among strains in the anthropized environment suggests that it may confer an advantage for transmission in this environment, and thus potentially contribute to the spread of pathogenecity determinants.

Geographic Separation of Domestic and Wild Strains of Toxoplasma gondii in French Guiana Correlates with a Monomorphic Version of Chromosome1a

PubMed Central

Khan, Asis; Ajzenberg, Daniel; Mercier, Aurélien; Demar, Magalie; Simon, Stéphane; Dardé, Marie Laure; Wang, Qiuling; Verma, Shiv Kumar; Rosenthal, Benjamin M.; Dubey, Jitender P.; Sibley, L. David

2014-01-01

Background Previous studies have stressed the genetic divergence and high pathogenicity of strains of T. gondii from French Guiana. Although strains from coastal, human adapted environments (so called anthropized) resemble those found in other regions of the Caribbean, strains collected from inland jungle environment are genetically quite diverse. To better understand the composition of these distinct strain types, we undertook a more in depth analysis of T. gondii strains from French Guiana including profiling of chromosome 1a (Chr1a), which is often shared as a single monomorphic haplotype among lineages that are otherwise genetically distinct. Methodology/Principal Findings Comparison of intron sequences from selectively neutral genes indicated that anthropized strains were most closely related to clonal type III strains from North America, although wider RFLP analysis revealed that they are natural hybrids. In contrast, strains isolated from the jungle were genetically very diverse. Remarkably, nearly all anthropized strains contained the monomorphic version of Chr1a while wild stains were extremely divergent. The presence of the monomorphic Chr1a strongly correlated with greater transmission in domestic cats, although there were several exceptions, indicating that other factors also contribute. Anthropized strains also varied in their virulence in laboratory mice, and this pattern could not be explained by the simple combination of previously identified virulence factors, indicating that other genetic determinants influence pathogenicity. Conclusions/Significance Our studies underscore the marked genetic separation of anthropized and wild strains of T. gondii in French Guiana and provide additional evidence that the presence of Chr1a is associated with successful expansion of widely different lineages within diverse geographic areas. The predominance of Chr1a among strains in the anthropized environment suggests that it may confer an advantage for transmission in this environment, and thus potentially contribute to the spread of pathogenecity determinants. PMID:25233228

Environmental and genetic sources of diversification in the timing of seed germination: implications for the evolution of bet hedging.

PubMed

Simons, Andrew M; Johnston, Mark O

2006-11-01

Environmental variation that is not predictably related to cues is expected to drive the evolution of bet-hedging strategies. The high variance observed in the timing of seed germination has led to it being the most cited diversification strategy in the theoretical bet-hedging literature. Despite this theoretical focus, virtually nothing is known about the mechanisms responsible for the generation of individual-level diversification. Here we report analyses of sources of variation in timing of germination within seasons, germination fraction over two generations and three sequential seasons, and the genetic correlation structure of these traits using almost 10,000 seeds from more than 100 genotypes of the monocarpic perennial Lobelia inflata. Microenvironmental analysis of time to germination suggests that extreme sensitivity to environmental gradients, or microplasticity, even within a homogeneous growth chamber, may act as an effective individual-level diversification mechanism and explains more than 30% of variance in time to germination. The heritability of within-season timing of germination was low (h(2) = 0.07) but significant under homogeneous conditions. Consistent with individual-level diversification, this low h(2) was attributable not to low additive genetic variance, but to an unusually high coefficient of residual variation in time to germination. Despite high power to detect additive genetic variance in within-season diversification, it was low and indistinguishable from zero. Restricted maximum likelihood detected significant genetic variation for germination fraction (h(2) = 0.18) under homogeneous conditions. Unexpectedly, this heritability was positive when measured within a generation by sibling analysis and negative when measured across generations by offspring-on-parent regression. The consistency of dormancy fraction over multiple delays, a major premise of Cohen's classic model, was supported by a strong genetic correlation (r = 0.468) observed for a cohort's germination fraction over two seasons. We discuss implications of the results for the evolution of bet hedging and highlight the need for further empirical study of the causal components of diversification.

Genetic diversity and gene differentiation among ten species of Zingiberaceae from Eastern India.

PubMed

Mohanty, Sujata; Panda, Manoj Kumar; Acharya, Laxmikanta; Nayak, Sanghamitra

2014-08-01

In the present study, genetic fingerprints of ten species of Zingiberaceae from eastern India were developed using PCR-based markers. 19 RAPD (Rapid Amplified polymorphic DNA), 8 ISSR (Inter Simple Sequence Repeats) and 8 SSR (Simple Sequence Repeats) primers were used to elucidate genetic diversity important for utilization, management and conservation. These primers produced 789 loci, out of which 773 loci were polymorphic (including 220 unique loci) and 16 monomorphic loci. Highest number of bands amplified (263) in Curcuma caesia whereas lowest (209) in Zingiber cassumunar. Though all the markers discriminated the species effectively, analysis of combined data of all markers resulted in better distinction of individual species. Highest number of loci was amplified with SSR primers with resolving power in a range of 17.4-39. Dendrogram based on three molecular data using unweighted pair group method with arithmetic mean classified all the species into two clusters. Mantle matrix correspondence test revealed high matrix correlation in all the cases. Correlation values for RAPD, ISSR and SSR were 0.797, 0.84 and 0.8, respectively, with combined data. In both the genera wild and cultivated species were completely separated from each other at genomic level. It also revealed distinct genetic identity between species of Curcuma and Zingiber. High genetic diversity documented in the present study provides a baseline data for optimization of conservation and breeding programme of the studied zingiberacious species.

Description and Validation of a Dynamical Systems Model of Presynaptic Serotonin Function: Genetic Variation, Brain Activation and Impulsivity

PubMed Central

Stoltenberg, Scott F.; Nag, Parthasarathi

2010-01-01

Despite more than a decade of empirical work on the role of genetic polymorphisms in the serotonin system on behavior, the details across levels of analysis are not well understood. We describe a mathematical model of the genetic control of presynaptic serotonergic function that is based on control theory, implemented using systems of differential equations, and focused on better characterizing pathways from genes to behavior. We present the results of model validation tests that include the comparison of simulation outcomes with empirical data on genetic effects on brain response to affective stimuli and on impulsivity. Patterns of simulated neural firing were consistent with recent findings of additive effects of serotonin transporter and tryptophan hydroxylase-2 polymorphisms on brain activation. In addition, simulated levels of cerebral spinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) were negatively correlated with Barratt Impulsiveness Scale (Version 11) Total scores in college students (r = −.22, p = .002, N = 187), which is consistent with the well-established negative correlation between CSF 5-HIAA and impulsivity. The results of the validation tests suggest that the model captures important aspects of the genetic control of presynaptic serotonergic function and behavior via brain activation. The proposed model can be: (1) extended to include other system components, neurotransmitter systems, behaviors and environmental influences; (2) used to generate testable hypotheses. PMID:20111992

Genetic Variance in the SES-IQ Correlation.

ERIC Educational Resources Information Center

Eckland, Bruce K.

1979-01-01

Discusses questions dealing with genetic aspects of the correlation between IQ and socioeconomic status (SES). Questions include: How does assortative mating affect the genetic variance of IQ? Is the relationship between an individual's IQ and adult SES a causal one? And how can IQ research improve schools and schooling? (Author/DB)

Genetic Stability of Cognitive Development from Childhood to Adulthood.

ERIC Educational Resources Information Center

DeFries, J. C.; And Others

1987-01-01

A path model of genetic and family environmental transmission was fitted to published twin correlations and to general cognitive ability data from adoptive and nonadoptive families in which children were tested yearly through the fourth year. Longitudinal genetic correlations from infancy to adulthood were modeled explicitly, as were effects of…

Correlated responses to clonal selection in populations of Daphnia pulicaria: mechanisms of genetic correlation and the creative power of sex.

PubMed

Dudycha, Jeffry L; Snoke-Smith, Margaret; Alía, Ricardo

2013-02-01

Genetic correlations among traits alter evolutionary trajectories due to indirect selection. Pleiotropy, chance linkage, and selection can all lead to genetic correlations, but have different consequences for phenotypic evolution. We sought to assess the mechanisms contributing to correlations with size at maturity in the cyclic parthenogen Daphnia pulicaria. We selected on size in each of four populations that differ in the frequency of sex, and evaluated correlated responses in a life table. Size at advanced adulthood, reproductive output, and adult growth rate clearly showed greater responses in high-sex populations, with a similar pattern in neonate size and r. This pattern is expected only when trait correlations are favored by selection and the frequency of sex favors the creation and demographic expansion of highly fit clones. Juvenile growth and age at maturity did not diverge consistently. The inter-clutch interval appeared to respond more strongly in low-sex populations, but this was not statistically significant. Our data support the hypothesis that correlated selection is the strongest driver of genetic correlations, and suggest that in organisms with both sexual and asexual reproduction, adaptation can be enhanced by recombination.

Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium

PubMed Central

Stringer, S; Minică, C C; Verweij, K J H; Mbarek, H; Bernard, M; Derringer, J; van Eijk, K R; Isen, J D; Loukola, A; Maciejewski, D F; Mihailov, E; van der Most, P J; Sánchez-Mora, C; Roos, L; Sherva, R; Walters, R; Ware, J J; Abdellaoui, A; Bigdeli, T B; Branje, S J T; Brown, S A; Bruinenberg, M; Casas, M; Esko, T; Garcia-Martinez, I; Gordon, S D; Harris, J M; Hartman, C A; Henders, A K; Heath, A C; Hickie, I B; Hickman, M; Hopfer, C J; Hottenga, J J; Huizink, A C; Irons, D E; Kahn, R S; Korhonen, T; Kranzler, H R; Krauter, K; van Lier, P A C; Lubke, G H; Madden, P A F; Mägi, R; McGue, M K; Medland, S E; Meeus, W H J; Miller, M B; Montgomery, G W; Nivard, M G; Nolte, I M; Oldehinkel, A J; Pausova, Z; Qaiser, B; Quaye, L; Ramos-Quiroga, J A; Richarte, V; Rose, R J; Shin, J; Stallings, M C; Stiby, A I; Wall, T L; Wright, M J; Koot, H M; Paus, T; Hewitt, J K; Ribasés, M; Kaprio, J; Boks, M P; Snieder, H; Spector, T; Munafò, M R; Metspalu, A; Gelernter, J; Boomsma, D I; Iacono, W G; Martin, N G; Gillespie, N A; Derks, E M; Vink, J M

2016-01-01

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40–48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13–20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10−8) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use. PMID:27023175

Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias.

PubMed

Beecham, Gary W; Hamilton, Kara; Naj, Adam C; Martin, Eden R; Huentelman, Matt; Myers, Amanda J; Corneveaux, Jason J; Hardy, John; Vonsattel, Jean-Paul; Younkin, Steven G; Bennett, David A; De Jager, Philip L; Larson, Eric B; Crane, Paul K; Kamboh, M Ilyas; Kofler, Julia K; Mash, Deborah C; Duque, Linda; Gilbert, John R; Gwirtsman, Harry; Buxbaum, Joseph D; Kramer, Patricia; Dickson, Dennis W; Farrer, Lindsay A; Frosch, Matthew P; Ghetti, Bernardino; Haines, Jonathan L; Hyman, Bradley T; Kukull, Walter A; Mayeux, Richard P; Pericak-Vance, Margaret A; Schneider, Julie A; Trojanowski, John Q; Reiman, Eric M; Schellenberg, Gerard D; Montine, Thomas J

2014-09-01

Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI). Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE). GalNAc transferase 7 (GALNT7), ATP-Binding Cassette, Sub-Family G (WHITE), Member 1 (ABCG1), and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2) was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related dementias.

Testing Genetic Pleiotropy with GWAS Summary Statistics for Marginal and Conditional Analyses.

PubMed

Deng, Yangqing; Pan, Wei

2017-12-01

There is growing interest in testing genetic pleiotropy, which is when a single genetic variant influences multiple traits. Several methods have been proposed; however, these methods have some limitations. First, all the proposed methods are based on the use of individual-level genotype and phenotype data; in contrast, for logistical, and other, reasons, summary statistics of univariate SNP-trait associations are typically only available based on meta- or mega-analyzed large genome-wide association study (GWAS) data. Second, existing tests are based on marginal pleiotropy, which cannot distinguish between direct and indirect associations of a single genetic variant with multiple traits due to correlations among the traits. Hence, it is useful to consider conditional analysis, in which a subset of traits is adjusted for another subset of traits. For example, in spite of substantial lowering of low-density lipoprotein cholesterol (LDL) with statin therapy, some patients still maintain high residual cardiovascular risk, and, for these patients, it might be helpful to reduce their triglyceride (TG) level. For this purpose, in order to identify new therapeutic targets, it would be useful to identify genetic variants with pleiotropic effects on LDL and TG after adjusting the latter for LDL; otherwise, a pleiotropic effect of a genetic variant detected by a marginal model could simply be due to its association with LDL only, given the well-known correlation between the two types of lipids. Here, we develop a new pleiotropy testing procedure based only on GWAS summary statistics that can be applied for both marginal analysis and conditional analysis. Although the main technical development is based on published union-intersection testing methods, care is needed in specifying conditional models to avoid invalid statistical estimation and inference. In addition to the previously used likelihood ratio test, we also propose using generalized estimating equations under the working independence model for robust inference. We provide numerical examples based on both simulated and real data, including two large lipid GWAS summary association datasets based on ∼100,000 and ∼189,000 samples, respectively, to demonstrate the difference between marginal and conditional analyses, as well as the effectiveness of our new approach. Copyright © 2017 by the Genetics Society of America.

Huntington disease - another chapter rewritten

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nance, M.A.

1996-07-01

To those of us who began life when humans had 48 chromosomes and who began working in genetics when the (by then 46) chromosomes had no bands and chromosome 4 could not reliably be distinguished from chromosome 5, the mere ability to diagnose and correlate the clinical phenotypes of genetic disorders with their molecular genotypes is a source of continuing astonishment and pleasure. Indeed, molecular genetic analysis of neurogenetic disorders such as Huntington disease (HD) has provided a steady stream of challenges and surprises to all who believe the genetic principles that they were taught about these disorders. The papermore » by Rubinsztein et al. in this issue of the Journal highlights yet another surprise, which was adumbrated even in the initial paper announcing the discovery of the HD gene: incomplete penetrance of HD gene mutations. 59 refs., 1 fig.« less

Evidence that pairing with genetically similar mates is maladaptive in a monogamous bird

USGS Publications Warehouse

Mulard, Hervé; Danchin, E.; Talbot, S.L.; Ramey, A.M.; Hatch, Shyla A.; White, J.F.; Helfenstein, F.; Wagner, R.H.

2009-01-01

Background. Evidence of multiple genetic criteria of mate choice is accumulating in numerous taxa. In many species, females have been shown to pair with genetically dissimilar mates or with extra-pair partners that are more genetically compatible than their social mates, thereby increasing their offsprings' heterozygosity which often correlates with offspring fitness. While most studies have focused on genetically promiscuous species, few studies have addressed genetically monogamous species, in which mate choice tends to be mutual. Results. Here, we used microsatellite markers to assess individual global heterozygosity and genetic similarity of pairs in a socially and genetically monogamous seabird, the black-legged kittiwake Rissa tridactyla. We found that pairs were more genetically dissimilar than expected by chance. We also identified fitness costs of breeding with genetically similar partners: (i) genetic similarity of pairs was negatively correlated with the number of chicks hatched, and (ii) offspring heterozygosity was positively correlated with growth rate and survival. Conclusion. These findings provide evidence that breeders in a genetically monogamous species may avoid the fitness costs of reproducing with a genetically similar mate. In such species that lack the opportunity to obtain extra-pair fertilizations, mate choice may therefore be under high selective pressure. ?? 2009 Mulard et al; licensee BioMed Central Ltd.