Defining genetic and chemical diversity in wheat grain by 1H-NMR spectroscopy of polar metabolites.

PubMed

Shewry, Peter R; Corol, Delia I; Jones, Huw D; Beale, Michael H; Ward, Jane L

2017-07-01

The application of high-throughput 1H nuclear magnetic resonance (1H-NMR) of unpurified extracts to determine genetic diversity and the contents of polar components in grain of wheat. Milled whole wheat grain was extracted with 80:20 D 2 O:CD 3 OD containing 0.05% d 4 -trimethylsilylpropionate. 1H-NMR spectra were acquired under automation at 300°K using an Avance Spectrometer operating at 600.0528 MHz. Regions for individual metabolites were identified by comparison to a library of known standards run under identical conditions. The individual 1H-NMR peaks or levels of known metabolites were then compared by Principal Component Analysis using SIMCA-P software. High-throughput 1H-NMR is an excellent tool to compare the extent of genetic diversity within and between wheat species, and to quantify specific components (including glycine betaine, choline, and asparagine) in individual genotypes. It can also be used to monitor changes in composition related to environmental factors and to support comparisons of the substantial equivalence of transgenic lines. © 2017 Rothamsted Research. Molecular Nutrition & Food Research Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Genealogical Interpretation of Principal Components Analysis

PubMed Central

McVean, Gil

2009-01-01

Principal components analysis, PCA, is a statistical method commonly used in population genetics to identify structure in the distribution of genetic variation across geographical location and ethnic background. However, while the method is often used to inform about historical demographic processes, little is known about the relationship between fundamental demographic parameters and the projection of samples onto the primary axes. Here I show that for SNP data the projection of samples onto the principal components can be obtained directly from considering the average coalescent times between pairs of haploid genomes. The result provides a framework for interpreting PCA projections in terms of underlying processes, including migration, geographical isolation, and admixture. I also demonstrate a link between PCA and Wright's fst and show that SNP ascertainment has a largely simple and predictable effect on the projection of samples. Using examples from human genetics, I discuss the application of these results to empirical data and the implications for inference. PMID:19834557

A Model of Compound Heterozygous, Loss-of-Function Alleles Is Broadly Consistent with Observations from Complex-Disease GWAS Datasets

PubMed Central

Sanjak, Jaleal S.; Long, Anthony D.; Thornton, Kevin R.

2017-01-01

The genetic component of complex disease risk in humans remains largely unexplained. A corollary is that the allelic spectrum of genetic variants contributing to complex disease risk is unknown. Theoretical models that relate population genetic processes to the maintenance of genetic variation for quantitative traits may suggest profitable avenues for future experimental design. Here we use forward simulation to model a genomic region evolving under a balance between recurrent deleterious mutation and Gaussian stabilizing selection. We consider multiple genetic and demographic models, and several different methods for identifying genomic regions harboring variants associated with complex disease risk. We demonstrate that the model of gene action, relating genotype to phenotype, has a qualitative effect on several relevant aspects of the population genetic architecture of a complex trait. In particular, the genetic model impacts genetic variance component partitioning across the allele frequency spectrum and the power of statistical tests. Models with partial recessivity closely match the minor allele frequency distribution of significant hits from empirical genome-wide association studies without requiring homozygous effect sizes to be small. We highlight a particular gene-based model of incomplete recessivity that is appealing from first principles. Under that model, deleterious mutations in a genomic region partially fail to complement one another. This model of gene-based recessivity predicts the empirically observed inconsistency between twin and SNP based estimated of dominance heritability. Furthermore, this model predicts considerable levels of unexplained variance associated with intralocus epistasis. Our results suggest a need for improved statistical tools for region based genetic association and heritability estimation. PMID:28103232

Guided Exploration of Genomic Risk for Gray Matter Abnormalities in Schizophrenia Using Parallel Independent Component Analysis with Reference

PubMed Central

Chen, Jiayu; Calhoun, Vince D.; Pearlson, Godfrey D.; Perrone-Bizzozero, Nora; Sui, Jing; Turner, Jessica A.; Bustillo, Juan R; Ehrlich, Stefan; Sponheim, Scott R.; Cañive, José M.; Ho, Beng-Choon; Liu, Jingyu

2013-01-01

One application of imaging genomics is to explore genetic variants associated with brain structure and function, presenting a new means of mapping genetic influences on mental disorders. While there is growing interest in performing genome-wide searches for determinants, it remains challenging to identify genetic factors of small effect size, especially in limited sample sizes. In an attempt to address this issue, we propose to take advantage of a priori knowledge, specifically to extend parallel independent component analysis (pICA) to incorporate a reference (pICA-R), aiming to better reveal relationships between hidden factors of a particular attribute. The new approach was first evaluated on simulated data for its performance under different configurations of effect size and dimensionality. Then pICA-R was applied to a 300-participant (140 schizophrenia (SZ) patients versus 160 healthy controls) dataset consisting of structural magnetic resonance imaging (sMRI) and single nucleotide polymorphism (SNP) data. Guided by a reference SNP set derived from ANK3, a gene implicated by the Psychiatric Genomic Consortium SZ study, pICA-R identified one pair of SNP and sMRI components with a significant loading correlation of 0.27 (p = 1.64×10−6). The sMRI component showed a significant group difference in loading parameters between patients and controls (p = 1.33×10−15), indicating SZ-related reduction in gray matter concentration in prefrontal and temporal regions. The linked SNP component also showed a group difference (p = 0.04) and was predominantly contributed to by 1,030 SNPs. The effect of these top contributing SNPs was verified using association test results of the Psychiatric Genomic Consortium SZ study, where the 1,030 SNPs exhibited significant SZ enrichment compared to the whole genome. In addition, pathway analyses indicated the genetic component majorly relating to neurotransmitter and nervous system signaling pathways. Given the simulation and experiment results, pICA-R may prove a promising multivariate approach for use in imaging genomics to discover reliable genetic risk factors under a scenario of relatively high dimensionality and small effect size. PMID:23727316

Genetic component of sensitivity to heat stress for nonreturn rate of Brazilian Holstein cattle.

PubMed

Santana, M L; Bignardi, A B; Stefani, G; El Faro, L

2017-08-01

The objectives of the present study were: 1) to investigate variation in the genetic component of heat stress for nonreturn rate at 56 days after first artificial insemination (NR56); 2) to identify and characterize the genotype by environment interaction (G × E) due to heat stress for NR56 of Brazilian Holstein cattle. A linear random regression model (reaction norm model) was applied to 51,748 NR56 records of 28,595 heifers and multiparous cows. The decline in NR56 due to heat stress was more pronounced in milking cows compared to heifers. The age of females at first artificial insemination and temperature-humidity index (THI) exerted an important influence on the genetic parameters of NR56. Several evidence of G × E on NR56 were found as the high slope/intercept ratio and frequent intersection of reaction norms. Additionally, the genetic correlation between NR56 at opposite extremes of the THI scale reached estimates below zero, indicating that few of the same genes are responsible for NR56 under conditions of thermoneutrality and heat stress. The genetic evaluation and selection for NR56 in Holstein cattle reared under (sub)tropical conditions should therefore take into consideration the genetic variation on age at insemination and G × E due to heat stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Concerted evolution of life stage performances signals recent selection on yeast nitrogen use.

PubMed

Ibstedt, Sebastian; Stenberg, Simon; Bagés, Sara; Gjuvsland, Arne B; Salinas, Francisco; Kourtchenko, Olga; Samy, Jeevan K A; Blomberg, Anders; Omholt, Stig W; Liti, Gianni; Beltran, Gemma; Warringer, Jonas

2015-01-01

Exposing natural selection driving phenotypic and genotypic adaptive differentiation is an extraordinary challenge. Given that an organism's life stages are exposed to the same environmental variations, we reasoned that fitness components, such as the lag, rate, and efficiency of growth, directly reflecting performance in these life stages, should often be selected in concert. We therefore conjectured that correlations between fitness components over natural isolates, in a particular environmental context, would constitute a robust signal of recent selection. Critically, this test for selection requires fitness components to be determined by different genetic loci. To explore our conjecture, we exhaustively evaluated the lag, rate, and efficiency of asexual population growth of natural isolates of the model yeast Saccharomyces cerevisiae in a large variety of nitrogen-limited environments. Overall, fitness components were well correlated under nitrogen restriction. Yeast isolates were further crossed in all pairwise combinations and coinheritance of each fitness component and genetic markers were traced. Trait variations tended to map to quantitative trait loci (QTL) that were private to a single fitness component. We further traced QTLs down to single-nucleotide resolution and uncovered loss-of-function mutations in RIM15, PUT4, DAL1, and DAL4 as the genetic basis for nitrogen source use variations. Effects of SNPs were unique for a single fitness component, strongly arguing against pleiotropy between lag, rate, and efficiency of reproduction under nitrogen restriction. The strong correlations between life stage performances that cannot be explained by pleiotropy compellingly support adaptive differentiation of yeast nitrogen source use and suggest a generic approach for detecting selection. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic component of flammability variation in a Mediterranean shrub.

PubMed

Moreira, B; Castellanos, M C; Pausas, J G

2014-03-01

Recurrent fires impose a strong selection pressure in many ecosystems worldwide. In such ecosystems, plant flammability is of paramount importance because it enhances population persistence, particularly in non-resprouting species. Indeed, there is evidence of phenotypic divergence of flammability under different fire regimes. Our general hypothesis is that flammability-enhancing traits are adaptive; here, we test whether they have a genetic component. To test this hypothesis, we used the postfire obligate seeder Ulex parviflorus from sites historically exposed to different fire recurrence. We associated molecular variation in potentially adaptive loci detected with a genomic scan (using AFLP markers) with individual phenotypic variability in flammability across fire regimes. We found that at least 42% of the phenotypic variation in flammability was explained by the genetic divergence in a subset of AFLP loci. In spite of generalized gene flow, the genetic variability was structured by differences in fire recurrence. Our results provide the first field evidence supporting that traits enhancing plant flammability have a genetic component and thus can be responding to natural selection driven by fire. These results highlight the importance of flammability as an adaptive trait in fire-prone ecosystems. © 2014 John Wiley & Sons Ltd.

Genetic diversity among 16 genotypes of Coffea arabica in the Brazilian cerrado.

PubMed

Machado, C M S; Pimentel, N S; Golynsk, A; Ferreira, A; Vieira, H D; Partelli, F L

2017-09-21

For the selection of coffee plants that have favorable characteristics, it is necessary to evaluate variables related to production. Knowledge of the genetic divergence of arabica coffee is of extreme importance, as this knowledge can be associated with plant breeding programs in order to combine genetic divergence with good productive performance. The objective of this study was to evaluate the genetic divergence among 16 genotypes of Coffea arabica with the purpose of identifying the most dissimilar genotypes for the establishment of breeding programs and adaptation to the Brazilian cerrado. The genetic divergence was evaluated using multivariate procedures, the analysis of the average grouping unweighted pair group method with arithmetic mean (UPGMA) and main components in 2013 and 2014. Eight characters were evaluated in an experiment conducted in Morrinhos, Goiás. The presence of genetic divergence among the 16 C. arabica genotypes under cerrado conditions was recorded. The formation of UPGMA groups for the evaluated characteristics was pertinent due to the number of genotypes. The first three major components accounted for 81.77% of the total variance. The genotype H-419-3-4-4-13(C-241) of low size was the most divergent, followed by Catucaí 2 SL and Catiguá MG2, according to the main components.

Great influence of geographic isolation on the genetic differentiation of Myriophyllum spicatum under a steep environmental gradient

PubMed Central

Wu, Zhigang; Yu, Dan; Wang, Zhong; Li, Xing; Xu, Xinwei

2015-01-01

Understanding how natural processes affect population genetic structures is an important issue in evolutionary biology. One effective method is to assess the relative importance of environmental and geographical factors in the genetic structure of populations. In this study, we examined the spatial genetic variation of thirteen Myriophyllum spicatum populations from the Qinghai-Tibetan Plateau (QTP) and adjacent highlands (Yunnan-Guizhou Plateau, YGP) by using microsatellite loci and environmental and geographical factors. Bioclim layers, hydrological properties and elevation were considered as environmental variables and reduced by principal component analysis. The genetic isolation by geographic distance (IBD) was tested by Mantel tests and the relative importance of environmental variables on population genetic differentiation was determined by a partial Mantel test and multiple matrix regression with randomization (MMRR). Two genetic clusters corresponding to the QTP and YGP were identified. Both tests and MMRR revealed a significant and strong correlation between genetic divergence and geographic isolation under the influence of environmental heterogeneity at the overall and finer spatial scales. Our findings suggested the dominant role of geography on the evolution of M. spicatum under a steep environmental gradient in the alpine landscape as a result of dispersal limitation and genetic drift. PMID:26494202

Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.

PubMed

Joslyn, Geoff; Brush, Gerry; Robertson, Margaret; Smith, Tom L; Kalmijn, Jelger; Schuckit, Marc; White, Raymond L

2008-12-23

As with other genetically complex common psychiatric and medical conditions, multiple genetic and environmental components contribute to alcohol use disorders (AUDs), which can confound attempts to identify genetic components. Intermediate phenotypes are often more closely correlated with underlying biology and have often proven invaluable in genetic studies. Level of response (LR) to alcohol is an intermediate phenotype for AUDs, and individuals with a low LR are at increased risk. A high rate of concurrent alcohol and nicotine use and dependence suggests that these conditions may share biochemical and genetic mechanisms. Genetic association studies indicate that a genetic locus, which includes the CHRNA5-CHRNA3-CHRNB4 gene cluster, plays a role in nicotine consumption and dependence. Genetic association with alcohol dependence was also recently shown. We show here that two of the markers from the nicotine studies also show an association (multiple testing corrected P < 0.025) with several LR phenotypes in a sample of 367 siblings. Additional markers in the region were analyzed and shown to be located in a 250-kb expanse of high linkage disequilibrium containing three additional genes. These findings indicate that LR intermediate phenotypes have utility in genetic approaches to AUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.

Circulating anti-Mullerian hormone levels in adult men are under a strong genetic influence.

PubMed

Pietiläinen, Kirsi H; Kaprio, Jaakko; Vaaralahti, Kirsi; Rissanen, Aila; Raivio, Taneli

2012-01-01

The determinants of serum anti-Müllerian hormone (AMH) levels in adult men remain unclear. The objective of the study was to investigate the genetic and environmental components in determining postpubertal AMH levels in healthy men. Serum AMH levels, body mass index (BMI), and fat mass (dual energy x-ray absorptiometry) were measured in 64 healthy male (23 monozygotic and 41 dizygotic) twin pairs. Postpubertal AMH levels were highly genetically determined (broad sense heritability 0.92, 95% confidence interval 0.83-0.96). AMH correlated negatively with BMI (r = -0.26, P = 0.030) and fat mass (r = -0.23, P = 0.048). As AMH, BMI had a high heritability (0.68, 95% confidence interval 0.39-0.83), but no genetic correlation was observed between them. AMH levels in men after puberty are under a strong genetic influence. Twin modeling suggests that AMH and BMI are influenced by different sets of genes.

The genetics of human obesity.

PubMed

Xia, Qianghua; Grant, Struan F A

2013-04-01

It has long been known that there is a genetic component to obesity, and that characterizing this underlying factor would likely offer the possibility of better intervention in the future. Monogenic obesity has proved to be relatively straightforward, with a combination of linkage analysis and mouse models facilitating the identification of multiple genes. In contrast, genome-wide association studies have successfully revealed a variety of genetic loci associated with the more common form of obesity, allowing for very strong consensus on the underlying genetic architecture of the phenotype for the first time. Although a number of significant findings have been made, it appears that very little of the apparent heritability of body mass index has actually been explained to date. New approaches for data analyses and advances in technology will be required to uncover the elusive missing heritability, and to aid in the identification of the key causative genetic underpinnings of obesity. © 2013 New York Academy of Sciences.

Selection against variants in the genome associated with educational attainment.

PubMed

Kong, Augustine; Frigge, Michael L; Thorleifsson, Gudmar; Stefansson, Hreinn; Young, Alexander I; Zink, Florian; Jonsdottir, Gudrun A; Okbay, Aysu; Sulem, Patrick; Masson, Gisli; Gudbjartsson, Daniel F; Helgason, Agnar; Bjornsdottir, Gyda; Thorsteinsdottir, Unnur; Stefansson, Kari

2017-01-31

Epidemiological and genetic association studies show that genetics play an important role in the attainment of education. Here, we investigate the effect of this genetic component on the reproductive history of 109,120 Icelanders and the consequent impact on the gene pool over time. We show that an educational attainment polygenic score, POLY EDU, constructed from results of a recent study is associated with delayed reproduction (P < 10 -100 ) and fewer children overall. The effect is stronger for women and remains highly significant after adjusting for educational attainment. Based on 129,808 Icelanders born between 1910 and 1990, we find that the average POLY EDU has been declining at a rate of ∼0.010 standard units per decade, which is substantial on an evolutionary timescale. Most importantly, because POLY EDU only captures a fraction of the overall underlying genetic component the latter could be declining at a rate that is two to three times faster.

Selection against variants in the genome associated with educational attainment

PubMed Central

Kong, Augustine; Frigge, Michael L.; Thorleifsson, Gudmar; Stefansson, Hreinn; Young, Alexander I.; Zink, Florian; Jonsdottir, Gudrun A.; Sulem, Patrick; Masson, Gisli; Gudbjartsson, Daniel F.; Helgason, Agnar; Bjornsdottir, Gyda; Thorsteinsdottir, Unnur; Stefansson, Kari

2017-01-01

Epidemiological and genetic association studies show that genetics play an important role in the attainment of education. Here, we investigate the effect of this genetic component on the reproductive history of 109,120 Icelanders and the consequent impact on the gene pool over time. We show that an educational attainment polygenic score, POLYEDU, constructed from results of a recent study is associated with delayed reproduction (P < 10−100) and fewer children overall. The effect is stronger for women and remains highly significant after adjusting for educational attainment. Based on 129,808 Icelanders born between 1910 and 1990, we find that the average POLYEDU has been declining at a rate of ∼0.010 standard units per decade, which is substantial on an evolutionary timescale. Most importantly, because POLYEDU only captures a fraction of the overall underlying genetic component the latter could be declining at a rate that is two to three times faster. PMID:28096410

Distribution of lod scores in oligogenic linkage analysis.

PubMed

Williams, J T; North, K E; Martin, L J; Comuzzie, A G; Göring, H H; Blangero, J

2001-01-01

In variance component oligogenic linkage analysis it can happen that the residual additive genetic variance bounds to zero when estimating the effect of the ith quantitative trait locus. Using quantitative trait Q1 from the Genetic Analysis Workshop 12 simulated general population data, we compare the observed lod scores from oligogenic linkage analysis with the empirical lod score distribution under a null model of no linkage. We find that zero residual additive genetic variance in the null model alters the usual distribution of the likelihood-ratio statistic.

Molecular Analysis Research at Community College of Philadelphia

DTIC Science & Technology

2015-09-21

projects presented below fall under the category of "molecular genetics ", as presented in ARO Solicitation Number W911NF-12-R-0012-01. These projects...role of the GADD45 family of genes in innate immunity and sepsis. In addition to studying genetic components of the molecular response of myeloid...Equipment in left  column, procedure in right column.  kinetics of these molecular signaling pathways in genetic variants (gene KO models) has yet to

Detection of mastitis in dairy cattle by use of mixture models for repeated somatic cell scores: a Bayesian approach via Gibbs sampling.

PubMed

Odegård, J; Jensen, J; Madsen, P; Gianola, D; Klemetsdal, G; Heringstad, B

2003-11-01

The distribution of somatic cell scores could be regarded as a mixture of at least two components depending on a cow's udder health status. A heteroscedastic two-component Bayesian normal mixture model with random effects was developed and implemented via Gibbs sampling. The model was evaluated using datasets consisting of simulated somatic cell score records. Somatic cell score was simulated as a mixture representing two alternative udder health statuses ("healthy" or "diseased"). Animals were assigned randomly to the two components according to the probability of group membership (Pm). Random effects (additive genetic and permanent environment), when included, had identical distributions across mixture components. Posterior probabilities of putative mastitis were estimated for all observations, and model adequacy was evaluated using measures of sensitivity, specificity, and posterior probability of misclassification. Fitting different residual variances in the two mixture components caused some bias in estimation of parameters. When the components were difficult to disentangle, so were their residual variances, causing bias in estimation of Pm and of location parameters of the two underlying distributions. When all variance components were identical across mixture components, the mixture model analyses returned parameter estimates essentially without bias and with a high degree of precision. Including random effects in the model increased the probability of correct classification substantially. No sizable differences in probability of correct classification were found between models in which a single cow effect (ignoring relationships) was fitted and models where this effect was split into genetic and permanent environmental components, utilizing relationship information. When genetic and permanent environmental effects were fitted, the between-replicate variance of estimates of posterior means was smaller because the model accounted for random genetic drift.

Genetic Variation of Morphological Traits and Transpiration in an Apple Core Collection under Well-Watered Conditions: Towards the Identification of Morphotypes with High Water Use Efficiency.

PubMed

Lopez, Gerardo; Pallas, Benoît; Martinez, Sébastien; Lauri, Pierre-Éric; Regnard, Jean-Luc; Durel, Charles-Éric; Costes, Evelyne

2015-01-01

Water use efficiency (WUE) is a quantitative measurement which improvement is a major issue in the context of global warming and restrictions in water availability for agriculture. In this study, we aimed at studying the variation and genetic control of WUE and the respective role of its components (plant biomass and transpiration) in a perennial fruit crop. We explored an INRA apple core collection grown in a phenotyping platform to screen one-year-old scions for their accumulated biomass, transpiration and WUE under optimal growing conditions. Plant biomass was decompose into morphological components related to either growth or organ expansion. For each trait, nine mixed models were evaluated to account for the genetic effect and spatial heterogeneity inside the platform. The Best Linear Unbiased Predictors of genetic values were estimated after model selection. Mean broad-sense heritabilities were calculated from variance estimates. Heritability values indicated that biomass (0.76) and WUE (0.73) were under genetic control. This genetic control was lower in plant transpiration with an heritability of 0.54. Across the collection, biomass accounted for 70% of the WUE variability. A Hierarchical Ascendant Classification of the core collection indicated the existence of six groups of genotypes with contrasting morphology and WUE. Differences between morphotypes were interpreted as resulting from differences in the main processes responsible for plant growth: cell division leading to the generation of new organs and cell elongation leading to organ dimension. Although further studies will be necessary on mature trees with more complex architecture and multiple sinks such as fruits, this study is a first step for improving apple plant material for the use of water.

Genetic Variation of Morphological Traits and Transpiration in an Apple Core Collection under Well-Watered Conditions: Towards the Identification of Morphotypes with High Water Use Efficiency

PubMed Central

Lopez, Gerardo; Pallas, Benoît; Martinez, Sébastien; Lauri, Pierre-Éric; Regnard, Jean-Luc; Durel, Charles-Éric; Costes, Evelyne

2015-01-01

Water use efficiency (WUE) is a quantitative measurement which improvement is a major issue in the context of global warming and restrictions in water availability for agriculture. In this study, we aimed at studying the variation and genetic control of WUE and the respective role of its components (plant biomass and transpiration) in a perennial fruit crop. We explored an INRA apple core collection grown in a phenotyping platform to screen one-year-old scions for their accumulated biomass, transpiration and WUE under optimal growing conditions. Plant biomass was decompose into morphological components related to either growth or organ expansion. For each trait, nine mixed models were evaluated to account for the genetic effect and spatial heterogeneity inside the platform. The Best Linear Unbiased Predictors of genetic values were estimated after model selection. Mean broad-sense heritabilities were calculated from variance estimates. Heritability values indicated that biomass (0.76) and WUE (0.73) were under genetic control. This genetic control was lower in plant transpiration with an heritability of 0.54. Across the collection, biomass accounted for 70% of the WUE variability. A Hierarchical Ascendant Classification of the core collection indicated the existence of six groups of genotypes with contrasting morphology and WUE. Differences between morphotypes were interpreted as resulting from differences in the main processes responsible for plant growth: cell division leading to the generation of new organs and cell elongation leading to organ dimension. Although further studies will be necessary on mature trees with more complex architecture and multiple sinks such as fruits, this study is a first step for improving apple plant material for the use of water. PMID:26717192

G-Protein Genomic Association With Normal Variation in Gray Matter Density

PubMed Central

Chen, Jiayu; Calhoun, Vince D.; Arias-Vasquez, Alejandro; Zwiers, Marcel P.; van Hulzen, Kimm; Fernández, Guillén; Fisher, Simon E.; Franke, Barbara; Turner, Jessica A.; Liu, Jingyu

2017-01-01

While detecting genetic variations underlying brain structures helps reveal mechanisms of neural disorders, high data dimensionality poses a major challenge for imaging genomic association studies. In this work, we present the application of a recently proposed approach, parallel independent component analysis with reference (pICA-R), to investigate genomic factors potentially regulating gray matter variation in a healthy population. This approach simultaneously assesses many variables for an aggregate effect and helps to elicit particular features in the data. We applied pICA-R to analyze gray matter density (GMD) images (274,131 voxels) in conjunction with single nucleotide polymorphism (SNP) data (666,019 markers) collected from 1,256 healthy individuals of the Brain Imaging Genetics (BIG) study. Guided by a genetic reference derived from the gene GNA14, pICA-R identified a significant SNP-GMD association (r = −0.16, P = 2.34 × 10−8), implying that subjects with specific genotypes have lower localized GMD. The identified components were then projected to an independent dataset from the Mind Clinical Imaging Consortium (MCIC) including 89 healthy individuals, and the obtained loadings again yielded a significant SNP-GMD association (r = −0.25, P = 0.02). The imaging component reflected GMD variations in frontal, precuneus, and cingulate regions. The SNP component was enriched in genes with neuronal functions, including synaptic plasticity, axon guidance, molecular signal transduction via PKA and CREB, highlighting the GRM1, PRKCH, GNA12, and CAMK2B genes. Collectively, our findings suggest that GNA12 and GNA14 play a key role in the genetic architecture underlying normal GMD variation in frontal and parietal regions. PMID:26248772

Genetic parameters for milk fatty acids, milk yield and quality traits of a Holstein cattle population reared under tropical conditions.

PubMed

Petrini, J; Iung, L H S; Rodriguez, M A P; Salvian, M; Pértille, F; Rovadoscki, G A; Cassoli, L D; Coutinho, L L; Machado, P F; Wiggans, G R; Mourão, G B

2016-10-01

Information about genetic parameters is essential for selection decisions and genetic evaluation. These estimates are population specific; however, there are few studies with dairy cattle populations reared under tropical and sub-tropical conditions. Thus, the aim was to obtain estimates of heritability and genetic correlations for milk yield and quality traits using pedigree and genomic information from a Holstein population maintained in a tropical environment. Phenotypic records (n = 36 457) of 4203 cows as well as the genotypes for 57 368 single nucleotide polymorphisms from 755 of these cows were used. Covariance components were estimated using the restricted maximum likelihood method under a mixed animal model, considering a pedigree-based relationship matrix or a combined pedigree-genomic matrix. High heritabilities (around 0.30) were estimated for lactose and protein content in milk whereas moderate values (between 0.19 and 0.26) were obtained for percentages of fat, saturated fatty acids and palmitic acid in milk. Genetic correlations ranging from -0.38 to -0.13 were determined between milk yield and composition traits. The smaller estimates compared to other similar studies can be due to poor environmental conditions, which may reduce genetic variability. These results highlight the importance in using genetic parameters estimated in the population under evaluation for selection decisions. © 2016 Blackwell Verlag GmbH.

A propensity score approach to correction for bias due to population stratification using genetic and non-genetic factors.

PubMed

Zhao, Huaqing; Rebbeck, Timothy R; Mitra, Nandita

2009-12-01

Confounding due to population stratification (PS) arises when differences in both allele and disease frequencies exist in a population of mixed racial/ethnic subpopulations. Genomic control, structured association, principal components analysis (PCA), and multidimensional scaling (MDS) approaches have been proposed to address this bias using genetic markers. However, confounding due to PS can also be due to non-genetic factors. Propensity scores are widely used to address confounding in observational studies but have not been adapted to deal with PS in genetic association studies. We propose a genomic propensity score (GPS) approach to correct for bias due to PS that considers both genetic and non-genetic factors. We compare the GPS method with PCA and MDS using simulation studies. Our results show that GPS can adequately adjust and consistently correct for bias due to PS. Under no/mild, moderate, and severe PS, GPS yielded estimated with bias close to 0 (mean=-0.0044, standard error=0.0087). Under moderate or severe PS, the GPS method consistently outperforms the PCA method in terms of bias, coverage probability (CP), and type I error. Under moderate PS, the GPS method consistently outperforms the MDS method in terms of CP. PCA maintains relatively high power compared to both MDS and GPS methods under the simulated situations. GPS and MDS are comparable in terms of statistical properties such as bias, type I error, and power. The GPS method provides a novel and robust tool for obtaining less-biased estimates of genetic associations that can consider both genetic and non-genetic factors. 2009 Wiley-Liss, Inc.

ViSEN: methodology and software for visualization of statistical epistasis networks

PubMed Central

Hu, Ting; Chen, Yuanzhu; Kiralis, Jeff W.; Moore, Jason H.

2013-01-01

The non-linear interaction effect among multiple genetic factors, i.e. epistasis, has been recognized as a key component in understanding the underlying genetic basis of complex human diseases and phenotypic traits. Due to the statistical and computational complexity, most epistasis studies are limited to interactions with an order of two. We developed ViSEN to analyze and visualize epistatic interactions of both two-way and three-way. ViSEN not only identifies strong interactions among pairs or trios of genetic attributes, but also provides a global interaction map that shows neighborhood and clustering structures. This visualized information could be very helpful to infer the underlying genetic architecture of complex diseases and to generate plausible hypotheses for further biological validations. ViSEN is implemented in Java and freely available at https://sourceforge.net/projects/visen/. PMID:23468157

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose

PubMed Central

Auld, Stuart K. J. R; Edel, Kai H.; Little, Tom J.

2013-01-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. PMID:23025616

Multi-scale genetic dynamic modelling II: application to synthetic biology: an algorithmic Markov chain based approach.

PubMed

Kirkilionis, Markus; Janus, Ulrich; Sbano, Luca

2011-09-01

We model in detail a simple synthetic genetic clock that was engineered in Atkinson et al. (Cell 113(5):597-607, 2003) using Escherichia coli as a host organism. Based on this engineered clock its theoretical description uses the modelling framework presented in Kirkilionis et al. (Theory Biosci. doi: 10.1007/s12064-011-0125-0 , 2011, this volume). The main goal of this accompanying article was to illustrate that parts of the modelling process can be algorithmically automatised once the model framework we called 'average dynamics' is accepted (Sbano and Kirkilionis, WMI Preprint 7/2007, 2008c; Kirkilionis and Sbano, Adv Complex Syst 13(3):293-326, 2010). The advantage of the 'average dynamics' framework is that system components (especially in genetics) can be easier represented in the model. In particular, if once discovered and characterised, specific molecular players together with their function can be incorporated. This means that, for example, the 'gene' concept becomes more clear, for example, in the way the genetic component would react under different regulatory conditions. Using the framework it has become a realistic aim to link mathematical modelling to novel tools of bioinformatics in the future, at least if the number of regulatory units can be estimated. This should hold in any case in synthetic environments due to the fact that the different synthetic genetic components are simply known (Elowitz and Leibler, Nature 403(6767):335-338, 2000; Gardner et al., Nature 403(6767):339-342, 2000; Hasty et al., Nature 420(6912):224-230, 2002). The paper illustrates therefore as a necessary first step how a detailed modelling of molecular interactions with known molecular components leads to a dynamic mathematical model that can be compared to experimental results on various levels or scales. The different genetic modules or components are represented in different detail by model variants. We explain how the framework can be used for investigating other more complex genetic systems in terms of regulation and feedback.

The infinitesimal model: Definition, derivation, and implications.

PubMed

Barton, N H; Etheridge, A M; Véber, A

2017-12-01

Our focus here is on the infinitesimal model. In this model, one or several quantitative traits are described as the sum of a genetic and a non-genetic component, the first being distributed within families as a normal random variable centred at the average of the parental genetic components, and with a variance independent of the parental traits. Thus, the variance that segregates within families is not perturbed by selection, and can be predicted from the variance components. This does not necessarily imply that the trait distribution across the whole population should be Gaussian, and indeed selection or population structure may have a substantial effect on the overall trait distribution. One of our main aims is to identify some general conditions on the allelic effects for the infinitesimal model to be accurate. We first review the long history of the infinitesimal model in quantitative genetics. Then we formulate the model at the phenotypic level in terms of individual trait values and relationships between individuals, but including different evolutionary processes: genetic drift, recombination, selection, mutation, population structure, …. We give a range of examples of its application to evolutionary questions related to stabilising selection, assortative mating, effective population size and response to selection, habitat preference and speciation. We provide a mathematical justification of the model as the limit as the number M of underlying loci tends to infinity of a model with Mendelian inheritance, mutation and environmental noise, when the genetic component of the trait is purely additive. We also show how the model generalises to include epistatic effects. We prove in particular that, within each family, the genetic components of the individual trait values in the current generation are indeed normally distributed with a variance independent of ancestral traits, up to an error of order 1∕M. Simulations suggest that in some cases the convergence may be as fast as 1∕M. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Multi-system Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees

PubMed Central

Fears, Scott C.; Service, Susan K.; Kremeyer, Barbara; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Ramirez, Margarita; Castrillón, Gabriel; Gomez-Franco, Juliana; Lopez, Maria C.; Montoya, Gabriel; Montoya, Patricia; Aldana, Ileana; Teshiba, Terri M.; Abaryan, Zvart; Al-Sharif, Noor B.; Ericson, Marissa; Jalbrzikowski, Maria; Luykx, Jurjen J.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori; Bartzokis, George; Escobar, Javier; Glahn, David C.; Ospina-Duque, Jorge; Risch, Neil; Ruiz-Linares, Andrés; Thompson, Paul M.; Cantor, Rita M.; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Freimer, Nelson B.; Bearden, Carrie E.

2014-01-01

IMPORTANCE Genetic factors contribute to risk for bipolar disorder (BP), yet its pathogenesis remains poorly understood. A focus on measuring multi-system quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that impact on BP as well as its component phenotypes. OBJECTIVE To identify quantitative neurocognitive, temperament-related, and neuroanatomic phenotypes that appear heritable and associated with severe bipolar disorder (BP-I), and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk. DESIGN Multi-generational pedigree study in two closely related, genetically isolated populations: the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (ANT). PARTICIPANTS 738 individuals, all from CVCR and ANT pedigrees, of whom 181 are affected with BP-I. MAIN OUTCOME MEASURE Familial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) phenotypes. RESULTS Seventy-five percent (126) of the phenotypes investigated were significantly heritable, and 31% (53) were associated with BP-I. About 1/4 of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions, and volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture. CONCLUSIONS AND RELEVANCE This is the most extensive investigation of BP-relevant component phenotypes to date. Our results identify brain and behavioral quantitative traits that appear to be genetically influenced and show a pattern of BP-I-association within families that is consistent with expectations from case-control studies. Together these phenotypes provide a basis for identifying loci contributing to BP-I risk and for genetic dissection of the disorder. PMID:24522887

Navigation by environmental geometry: the use of zebrafish as a model.

PubMed

Lee, Sang Ah; Vallortigara, Giorgio; Flore, Michele; Spelke, Elizabeth S; Sovrano, Valeria A

2013-10-01

Sensitivity to environmental shape in spatial navigation has been found, at both behavioural and neural levels, in virtually every species tested, starting early in development. Moreover, evidence that genetic deletions can cause selective deficits in such navigation behaviours suggests a genetic basis to navigation by environmental geometry. Nevertheless, the geometric computations underlying navigation have not been specified in any species. The present study teases apart the geometric components within the traditionally used rectangular enclosure and finds that zebrafish selectively represent distance and directional relationships between extended boundary surfaces. Similar behavioural results in geometric navigation tasks with human children provide prima facie evidence for similar underlying cognitive computations and open new doors for probing the genetic foundations that give rise to these computations.

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).

Research advances on microbial genetics in China in 2015.

PubMed

Xie, Jian-ping; Han, Yu-bo; Liu, Gang; Bai, Lin-quan

2016-09-01

In 2015, there are significant progresses in many aspects of the microbial genetics in China. To showcase the contribution of Chinese scientists in microbial genetics, this review surveys several notable progresses in microbial genetics made largely by Chinese scientists, and some key findings are highlighted. For the basic microbial genetics, the components, structures and functions of many macromolecule complexes involved in gene expression regulation have been elucidated. Moreover, the molecular basis underlying the recognition of foreign nucleic acids by microbial immune systems was unveiled. We also illustrated the biosynthetic pathways and regulators of multiple microbial compounds, novel enzyme reactions, and new mechanisms regulating microbial gene expression. And new findings were obtained in the microbial development, evolution and population genetics. For the industrial microbiology, more understanding on the molecular basis of the microbial factory has been gained. For the pathogenic microbiology, the genetic circuits of several pathogens were depicted, and significant progresses were achieved for understanding the pathogen-host interaction and revealing the genetic mechanisms underlying antimicrobial resistance, emerging pathogens and environmental microorganisms at the genomic level. In future, the genetic diversity of microbes can be used to obtain specific products, while gut microbiome is gathering momentum.

The role of genetic testing in epilepsy diagnosis and management.

PubMed

Weber, Yvonne G; Biskup, Saskia; Helbig, Katherine L; Von Spiczak, Sarah; Lerche, Holger

2017-08-01

Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. More than 500 epilepsy-associated genes have been described in the literature. Most of these genes play an important role in neuronal excitability, cortical development or synaptic transmission. A growing number of genetic variations have implications on diagnosis and prognostic or therapeutic advice in terms of a personalized medicine. Area covered: The review presents the different forms of genetic epilepsies with respect to their underlying genetic and functional pathophysiology and aims to give advice for recommended genetic testing. Moreover, it discusses ethical and legal guidelines, costs and technical limitations which should be considered. Expert commentary: Genetic testing is an important component in the diagnosis and treatment of many forms of epilepsy.

Phenotypic and genetic structure of traits delineating personality disorder.

PubMed

Livesley, W J; Jang, K L; Vernon, P A

1998-10-01

The evidence suggests that personality traits are hierarchically organized with more specific or lower-order traits combining to form more generalized higher-order traits. Agreement exists across studies regarding the lower-order traits that delineate personality disorder but not the higher-order traits. This study seeks to identify the higher-order structure of personality disorder by examining the phenotypic and genetic structures underlying lower-order traits. Eighteen lower-order traits were assessed using the Dimensional Assessment of Personality Disorder-Basic Questionnaire in samples of 656 personality disordered patients, 939 general population subjects, and a volunteer sample of 686 twin pairs. Principal components analysis yielded 4 components, labeled Emotional Dysregulation, Dissocial Behavior, Inhibitedness, and Compulsivity, that were similar across the 3 samples. Multivariate genetic analyses also yielded 4 genetic and environmental factors that were remarkably similar to the phenotypic factors. Analysis of the residual heritability of the lower-order traits when the effects of the higher-order factors were removed revealed a substantial residual heritable component for 12 of the 18 traits. The results support the following conclusions. First, the stable structure of traits across clinical and nonclinical samples is consistent with dimensional representations of personality disorders. Second, the higher-order traits of personality disorder strongly resemble dimensions of normal personality. This implies that a dimensional classification should be compatible with normative personality. Third, the residual heritability of the lower-order traits suggests that the personality phenotypes are based on a large number of specific genetic components.

Genetic Factors Influence Serological Measures of Common Infections

PubMed Central

Rubicz, Rohina; Leach, Charles T.; Kraig, Ellen; Dhurandhar, Nikhil V.; Duggirala, Ravindranath; Blangero, John; Yolken, Robert; Göring, Harald H.H.

2011-01-01

Background/Aims Antibodies against infectious pathogens provide information on past or present exposure to infectious agents. While host genetic factors are known to affect the immune response, the influence of genetic factors on antibody levels to common infectious agents is largely unknown. Here we test whether antibody levels for 13 common infections are significantly heritable. Methods IgG antibodies to Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii, adenovirus 36 (Ad36), hepatitis A virus, influenza A and B, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV)-1 and −2, human herpesvirus-6, and varicella zoster virus were determined for 1,227 Mexican Americans. Both quantitative and dichotomous (seropositive/seronegative) traits were analyzed. Influences of genetic and shared environmental factors were estimated using variance components pedigree analysis, and sharing of underlying genetic factors among traits was investigated using bivariate analyses. Results Serological phenotypes were significantly heritable for most pathogens (h2 = 0.17–0.39), except for Ad36 and HSV-2. Shared environment was significant for several pathogens (c2 = 0.10–0.32). The underlying genetic etiology appears to be largely different for most pathogens. Conclusions Our results demonstrate, for the first time for many of these pathogens, that individual genetic differences of the human host contribute substantially to antibody levels to many common infectious agents, providing impetus for the identification of underlying genetic variants, which may be of clinical importance. PMID:21996708

Quantitative genetics of immunity and life history under different photoperiods.

PubMed

Hammerschmidt, K; Deines, P; Wilson, A J; Rolff, J

2012-05-01

Insects with complex life-cycles should optimize age and size at maturity during larval development. When inhabiting seasonal environments, organisms have limited reproductive periods and face fundamental decisions: individuals that reach maturity late in season have to either reproduce at a small size or increase their growth rates. Increasing growth rates is costly in insects because of higher juvenile mortality, decreased adult survival or increased susceptibility to parasitism by bacteria and viruses via compromised immune function. Environmental changes such as seasonality can also alter the quantitative genetic architecture. Here, we explore the quantitative genetics of life history and immunity traits under two experimentally induced seasonal environments in the cricket Gryllus bimaculatus. Seasonality affected the life history but not the immune phenotypes. Individuals under decreasing day length developed slower and grew to a bigger size. We found ample additive genetic variance and heritability for components of immunity (haemocyte densities, proPhenoloxidase activity, resistance against Serratia marcescens), and for the life history traits, age and size at maturity. Despite genetic covariance among traits, the structure of G was inconsistent with genetically based trade-off between life history and immune traits (for example, a strong positive genetic correlation between growth rate and haemocyte density was estimated). However, conditional evolvabilities support the idea that genetic covariance structure limits the capacity of individual traits to evolve independently. We found no evidence for G × E interactions arising from the experimentally induced seasonality.

BREEDING AND GENETICS SYMPOSIUM: Resilience and lessons from studies in genetics of heat stress.

PubMed

Misztal, I

2017-04-01

Production environments are expected to change, mostly to a hotter climate but also possibly more extreme and drier. Can the current generation of farm animals cope with the changes or should it be specifically selected for changing conditions? In general, genetic selection produces animals with a smaller environmental footprint but also with smaller environmental flexibility. Some answers are coming from heat-stress research across species, with heat tolerance partly understood as a greater environmental flexibility. Specific studies in various species show the complexities of defining and selecting for heat tolerance. In Holsteins, the genetic component for effect of heat stress on production approximately doubles in second and quadruples in third parity. Cows with elevated body temperature have the greatest production under heat stress but probably are at risk for increased mortality. In hot but less intensive environments, the effect of heat stress on production is minimal, although the negative effect on fertility remains. Mortality peaks under heat stress and increases with parity. In Angus, the effect of heat stress is stronger only in selected regions, probably because of adaptation of calving seasons to local conditions and crossbreeding. Genetically, the direct effect shows variability because of heat stress, but the maternal effect does not, probably because dams shield calves from environmental challenges. In pigs, the effect of heat stress is strong for commercial farms but almost nothing for nucleus farms, which have lower pig density and better heat abatement. Under intensive management, heat stress is less evident in drier environments because of more efficient cooling. A genetic component of heat stress exists, but it is partly masked by improving management and selection based on data from elite farms. Genetic selection may provide superior identification of heat-tolerant animals, but a few cycles may be needed for clear results. Also, simple traits exist that are strongly related to heat stress (e.g., slick hair in dairy cattle and shedding intensity in Angus). Defining resilience may be difficult, especially when masked by improving environment. Under climate change, the current selection strategies may be adequate if they 1) are accompanied by constantly improving management, 2) use commercial data, and 3) include traits important under climate change (e.g., mortality).

Genetic surgery - a right strategy to attack cancer.

PubMed

Sverdlov, Eugene D

2011-12-01

The approaches now united under the term "gene therapy" can be divided into two broad strategies: (1) strategy using the ideology of molecular targeted therapy, but with genes in the role of agents targeted at certain molecular component(s) or pathways presumably crucial for cancer maintenance; (ii) strategy aimed at the destruction of tumors as a whole exploiting the features shared by all cancers, for example relatively fast mitotic cell division. While the first strategy is "true" gene therapy, the second one, as e.g. suicide gene therapy, is more like genetic surgery, when a surgeon just cuts off a tumor being not interested in subtle genetic mechanisms of cancer emergence and progression. This approach inherits the ideology of chemotherapy but escapes its severe toxic effects due to intracellular formation of toxic agents. Genetic surgery seems to be the most appropriate approach to combat cancer, and its simplicity is paradoxically adequate to the super-complexity of tumors. The review consists of three parts: (i) analysis of the reasons of tumor supercomplexity and fatally inevitable failure of molecular targeted therapy, (ii) general principles of the genetic surgery strategy, and (iii) examples of genetic surgery approaches with analysis of their drawbacks and the ways for their improvement.

Genetic variation of the riparian pioneer tree species populus nigra. II. Variation In susceptibility to the foliar rust melampsora larici-populina

PubMed

Legionnet; Muranty; Lefevre

1999-04-01

Partial resistance of Populus nigra L. to three races of the foliar rust Melampsora larici-populina Kleb. was studied in a field trial and in laboratory tests, using a collection of P. nigra originating from different places throughout France. No total resistance was found. The partial resistance was split into epidemiological components, which proved to be under genetic control. Various patterns of association of epidemiological components values were found. Principal components analysis revealed their relationships. Only 24% of the variance of the field susceptibility could be explained by the variation of the epidemiological components of susceptibility. This variable was significantly correlated with susceptibility to the most ancient and widespread race of the pathogen, and with the variables related to the size of the lesions of the different races. Analysis of variance showed significant differences in susceptibility between regions and between stands within one region. Up to 20% of variation was between regions, and up to 22% between stands, so that these genetic factors appeared to be more differentiated than the neutral diversity (up to 3.5% Legionnet & Lefevre, 1996). However, no clear pattern of geographical distribution of diversity was detected.

Sexually antagonistic selection on genetic variation underlying both male and female same-sex sexual behavior.

PubMed

Berger, David; You, Tao; Minano, Maravillas R; Grieshop, Karl; Lind, Martin I; Arnqvist, Göran; Maklakov, Alexei A

2016-05-13

Intralocus sexual conflict, arising from selection for different alleles at the same locus in males and females, imposes a constraint on sex-specific adaptation. Intralocus sexual conflict can be alleviated by the evolution of sex-limited genetic architectures and phenotypic expression, but pleiotropic constraints may hinder this process. Here, we explored putative intralocus sexual conflict and genetic (co)variance in a poorly understood behavior with near male-limited expression. Same-sex sexual behaviors (SSBs) generally do not conform to classic evolutionary models of adaptation but are common in male animals and have been hypothesized to result from perception errors and selection for high male mating rates. However, perspectives incorporating sex-specific selection on genes shared by males and females to explain the expression and evolution of SSBs have largely been neglected. We performed two parallel sex-limited artificial selection experiments on SSB in male and female seed beetles, followed by sex-specific assays of locomotor activity and male sex recognition (two traits hypothesized to be functionally related to SSB) and adult reproductive success (allowing us to assess fitness consequences of genetic variance in SSB and its correlated components). Our experiments reveal both shared and sex-limited genetic variance for SSB. Strikingly, genetically correlated responses in locomotor activity and male sex-recognition were associated with sexually antagonistic fitness effects, but these effects differed qualitatively between male and female selection lines, implicating intralocus sexual conflict at both male- and female-specific genetic components underlying SSB. Our study provides experimental support for the hypothesis that widespread pleiotropy generates pervasive intralocus sexual conflict governing the expression of SSBs, suggesting that SSB in one sex can occur due to the expression of genes that carry benefits in the other sex.

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.

Navigation by environmental geometry: the use of zebrafish as a model

PubMed Central

Lee, Sang Ah; Vallortigara, Giorgio; Flore, Michele; Spelke, Elizabeth S.; Sovrano, Valeria A.

2013-01-01

SUMMARY Sensitivity to environmental shape in spatial navigation has been found, at both behavioural and neural levels, in virtually every species tested, starting early in development. Moreover, evidence that genetic deletions can cause selective deficits in such navigation behaviours suggests a genetic basis to navigation by environmental geometry. Nevertheless, the geometric computations underlying navigation have not been specified in any species. The present study teases apart the geometric components within the traditionally used rectangular enclosure and finds that zebrafish selectively represent distance and directional relationships between extended boundary surfaces. Similar behavioural results in geometric navigation tasks with human children provide prima facie evidence for similar underlying cognitive computations and open new doors for probing the genetic foundations that give rise to these computations. PMID:23788708

Factors affecting commercial application of embryo technologies in dairy cattle in Europe--a modelling approach.

PubMed

van Arendonk, Johan A M; Bijma, Piter

2003-01-15

Reproductive techniques have a major impact on the structure of breeding programmes, the rate of genetic gain and dissemination of genetic gain in populations. This manuscript reviews the impact of reproductive technologies on the underlying components of genetic gain and inbreeding with special reference to the role of female reproductive technology. Evaluation of alternative breeding schemes should be based on genetic gain while constraining inbreeding. Optimum breeding schemes can be characterised by: decreased importance of sib information; increased accuracy at the expense of intensity; and a factorial mating strategy. If large-scale embryo cloning becomes feasible, this will have a small impact on the rate of genetic gain but will have a large impact on the structure of breeding programmes.

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose.

PubMed

Auld, Stuart K J R; Edel, Kai H; Little, Tom J

2012-10-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Human-directed social behaviour in dogs shows significant heritability.

PubMed

Persson, M E; Roth, L S V; Johnsson, M; Wright, D; Jensen, P

2015-04-01

Through domestication and co-evolution with humans, dogs have developed abilities to attract human attention, e.g. in a manner of seeking assistance when faced with a problem solving task. The aims of this study were to investigate within breed variation in human-directed contact seeking in dogs and to estimate its genetic basis. To do this, 498 research beagles, bred and kept under standardized conditions, were tested in an unsolvable problem task. Contact seeking behaviours recorded included both eye contact and physical interactions. Behavioural data was summarized through a principal component analysis, resulting in four components: test interactions, social interactions, eye contact and physical contact. Females scored significantly higher on social interactions and physical contact and age had an effect on eye contact scores. Narrow sense heritabilities (h(2) ) of the two largest components were estimated at 0.32 and 0.23 but were not significant for the last two components. These results show that within the studied dog population, behavioural variation in human-directed social behaviours was sex dependent and that the utilization of eye contact seeking increased with age and experience. Hence, heritability estimates indicate a significant genetic contribution to the variation found in human-directed social interactions, suggesting that social skills in dogs have a genetic basis, but can also be shaped and enhanced through individual experiences. This research gives the opportunity to further investigate the genetics behind dogs' social skills, which could also play a significant part into research on human social disorders such as autism. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

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.

Molecular Genetics of Pigment Dispersion Syndrome and Pigmentary Glaucoma: New Insights into Mechanisms

PubMed Central

2018-01-01

We explore the ideas and advances surrounding the genetic basis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). As PG is the leading cause of nontraumatic blindness in young adults and current tailored interventions have proven ineffective, a better understanding of the underlying causes of PDS, PG, and their relationship is essential. Despite PDS being a subclinical disease, a large proportion of patients progress to PG with associated vision loss. Decades of research have supported a genetic component both for PDS and conversion to PG. We review the body of evidence supporting a genetic basis in humans and animal models and reevaluate classical mechanisms of PDS/PG considering this new evidence. PMID:29780638

Molecular Genetics of Pigment Dispersion Syndrome and Pigmentary Glaucoma: New Insights into Mechanisms.

PubMed

Lahola-Chomiak, Adrian A; Walter, Michael A

2018-01-01

We explore the ideas and advances surrounding the genetic basis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). As PG is the leading cause of nontraumatic blindness in young adults and current tailored interventions have proven ineffective, a better understanding of the underlying causes of PDS, PG, and their relationship is essential. Despite PDS being a subclinical disease, a large proportion of patients progress to PG with associated vision loss. Decades of research have supported a genetic component both for PDS and conversion to PG. We review the body of evidence supporting a genetic basis in humans and animal models and reevaluate classical mechanisms of PDS/PG considering this new evidence.

[Analytic methods for seed models with genotype x environment interactions].

PubMed

Zhu, J

1996-01-01

Genetic models with genotype effect (G) and genotype x environment interaction effect (GE) are proposed for analyzing generation means of seed quantitative traits in crops. The total genetic effect (G) is partitioned into seed direct genetic effect (G0), cytoplasm genetic of effect (C), and maternal plant genetic effect (Gm). Seed direct genetic effect (G0) can be further partitioned into direct additive (A) and direct dominance (D) genetic components. Maternal genetic effect (Gm) can also be partitioned into maternal additive (Am) and maternal dominance (Dm) genetic components. The total genotype x environment interaction effect (GE) can also be partitioned into direct genetic by environment interaction effect (G0E), cytoplasm genetic by environment interaction effect (CE), and maternal genetic by environment interaction effect (GmE). G0E can be partitioned into direct additive by environment interaction (AE) and direct dominance by environment interaction (DE) genetic components. GmE can also be partitioned into maternal additive by environment interaction (AmE) and maternal dominance by environment interaction (DmE) genetic components. Partitions of genetic components are listed for parent, F1, F2 and backcrosses. A set of parents, their reciprocal F1 and F2 seeds is applicable for efficient analysis of seed quantitative traits. MINQUE(0/1) method can be used for estimating variance and covariance components. Unbiased estimation for covariance components between two traits can also be obtained by the MINQUE(0/1) method. Random genetic effects in seed models are predictable by the Adjusted Unbiased Prediction (AUP) approach with MINQUE(0/1) method. The jackknife procedure is suggested for estimation of sampling variances of estimated variance and covariance components and of predicted genetic effects, which can be further used in a t-test for parameter. Unbiasedness and efficiency for estimating variance components and predicting genetic effects are tested by Monte Carlo simulations.

Dominance Genetic Variance for Traits Under Directional Selection in Drosophila serrata

PubMed Central

Sztepanacz, Jacqueline L.; Blows, Mark W.

2015-01-01

In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait–fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. PMID:25783700

Dominance genetic variance for traits under directional selection in Drosophila serrata.

PubMed

Sztepanacz, Jacqueline L; Blows, Mark W

2015-05-01

In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait-fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. Copyright © 2015 by the Genetics Society of America.

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

Cryptic Genetic Variation for Arabidopsis thaliana Seed Germination Speed in a Novel Salt Stress Environment

PubMed Central

Yuan, Wei; Flowers, Jonathan M.; Sahraie, Dustin J.; Purugganan, Michael D.

2016-01-01

The expansion of species ranges frequently necessitates responses to novel environments. In plants, the ability of seeds to disperse to marginal areas relies in part to its ability to germinate under stressful conditions. Here we examine the genetic architecture of Arabidopsis thaliana germination speed under a novel, saline environment, using an Extreme QTL (X-QTL) mapping platform we previously developed. We find that early germination in normal and salt conditions both rely on a QTL on the distal arm of chromosome 4, but we also find unique QTL on chromosomes 1, 2, 4, and 5 that are specific to salt stress environments. Moreover, different QTLs are responsible for early vs. late germination, suggesting a temporal component to the expression of life history under these stress conditions. Our results indicate that cryptic genetic variation exists for responses to a novel abiotic stress, which may suggest a role of such variation in adaptation to new climactic conditions or growth environments. PMID:27543295

Common polygenic variation contributes to risk of schizophrenia that overlaps with bipolar disorder

PubMed Central

2013-01-01

Schizophrenia (SCZ) is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits with heritability estimated at up to 80%1,2. We adopted two analytic approaches to determine the extent to which common genetic variation underlies risk of SCZ using genome-wide association study (GWAS) data from 3,322 European individuals with SCZ and 3,587 controls. First, we implicate the major histocompatibility complex (MHC). Second, we provide molecular genetic evidence for a substantial polygenic component to risk of SCZ involving thousands of common alleles of very small effect. We show that this component also contributes to risk of bipolar disorder (BPD), but not to multiple non-psychiatric diseases. PMID:19571811

Quantitative disease resistance: dissection and adoption in maize

USDA-ARS?s Scientific Manuscript database

Maize is the world’s most widely cultivated crop, providing food, feed, and biofuel. Maize production is constantly threatened by the presence of devastating pathogens worldwide. Characterization of the genetic components underlying disease resistance is a major research area in maize which is highl...

Discovering Hematopoietic Mechanisms Through Genome-Wide Analysis of GATA Factor Chromatin Occupancy

PubMed Central

Fujiwara, Tohru; O'Geen, Henriette; Keles, Sunduz; Blahnik, Kimberly; Linnemann, Amelia K.; Kang, Yoon-A; Choi, Kyunghee; Farnham, Peggy J.; Bresnick, Emery H.

2009-01-01

SUMMARY GATA factors interact with simple DNA motifs (WGATAR) to regulate critical processes, including hematopoiesis, but very few WGATAR motifs are occupied in genomes. Given the rudimentary knowledge of mechanisms underlying this restriction, and how GATA factors establish genetic networks, we used ChIP-seq to define GATA-1 and GATA-2 occupancy genome-wide in erythroid cells. Coupled with genetic complementation analysis and transcriptional profiling, these studies revealed a rich collection of targets containing a characteristic binding motif of greater complexity than WGATAR. GATA factors occupied loci encoding multiple components of the Scl/TAL1 complex, a master regulator of hematopoiesis and leukemogenic target. Mechanistic analyses provided evidence for cross-regulatory and autoregulatory interactions among components of this complex, including GATA-2 induction of the hematopoietic corepressor ETO-2 and an ETO-2 negative autoregulatory loop. These results establish fundamental principles underlying GATA factor mechanisms in chromatin and illustrate a complex network of considerable importance for the control of hematopoiesis. PMID:19941826

Disruptions in Energy Balance: Does Nature overcome Nurture?

PubMed Central

Fernández, José R.; Casazza, Krista; Divers, Jasmin; López-Alarcón, Mardya

2008-01-01

Fat accumulation, in general, is the result of a breakdown in the homeostatic regulation of energy balance. Although, the specific factors influencing the disruption of energy balance and why these factors affect individuals differently are not completely understood, numerous studies have identified multiple contributors. Environmental components influence food acquisition, eating, and lifestyle habits. However, the variability in obesity-related outcomes observed among individuals placed in similar controlled environments support the notion that genetic components also wield some control. Multiple genetic regions have been associated with measures related to energy balance; however, the replication of these genetic contributors to energy intake and energy expenditure in humans is relatively small perhaps because of the heterogeneity of human populations. Genetic tools such as genetic admixture account for individual’s genetic background in gene association studies, reducing the confounding effect of population stratification, and promise to be a relevant tool on the identification of genetic contributions to energy balance, particularly among individuals of diverse racial/ethnic backgrounds. Although it has been recognized that genes are expressed according to environmental influences, the search toward the understanding of nature and nurture in obesity will require the detailed study of the effect of genes under diverse physiologic and behavioral environments. It is evident that more research is needed to elucidate the methodological and statistical issues that underlie the interactions between genes and environments in obesity and its related comorbidities. PMID:18096193

Influence of ethnic traditional cultures on genetic diversity of rice landraces under on-farm conservation in southwest China.

PubMed

Wang, Yanjie; Wang, Yanli; Sun, Xiaodong; Caiji, Zhuoma; Yang, Jingbiao; Cui, Di; Cao, Guilan; Ma, Xiaoding; Han, Bing; Xue, Dayuan; Han, Longzhi

2016-10-27

Crop genetic resources are important components of biodiversity. However, with the large-scale promotion of mono-cropping, genetic diversity has largely been lost. Ex-situ conservation approaches were widely used to protect traditional crop varieties worldwide. However, this method fails to maintain the dynamic evolutionary processes of crop genetic resources in their original habitats, leading to genetic diversity reduction and even loss of the capacity of resistance to new diseases and pests. Therefore, on-farm conservation has been considered a crucial complement to ex-situ conservation. This study aimed at clarifying the genetic diversity differences between ex-situ conservation and on-farm conservation and to exploring the influence of traditional cultures on genetic diversity of rice landraces under on-farm conservation. The conservation status of rice landrace varieties, including Indica and Japonica, non-glutinous rice (Oryza sativa) and glutinous rice (Oryza sativa var. glutinosa Matsum), was obtained through ethno-biology investigation method in 12 villages of ethnic groups from Guizhou, Yunnan and Guangxi provinces of China. The genetic diversity between 24 pairs of the same rice landraces from different times were compared using simple sequence repeat (SSR) molecular markers technology. The landrace paris studied were collected in 1980 and maintained ex-situ, while 2014 samples were collected on-farm in southwest of China. The results showed that many varieties of rice landraces have been preserved on-farm by local farmers for hundreds or thousands of years. The number of alleles (Na), effective number of alleles (Ne), Nei genetic diversity index (He) and Shannon information index (I) of rice landraces were significantly higher by 12.3-30.4 % under on-farm conservation than under ex-situ conservation. Compared with the ex-situ conservation approach, rice landraces under on-farm conservation programs had more alleles and higher genetic diversity. In every site we investigated, ethnic traditional cultures play a positive influence on rice landrace variety diversity and genetic diversity. Most China's rice landraces were conserved in the ethnic areas of southwest China. On-farm conservation can effectively promote the allelic variation and increase the genetic diversity of rice landraces over the past 35 years. Moreover, ethnic traditional culture practices are a crucial foundation to increase genetic diversity of rice landraces and implement on-farm conservation.

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli

PubMed Central

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-01-01

Individual genetic variation affects gene expression in response to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness QTLs; reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant acts as an activator of the antiviral response; using RNAi, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli. PMID:23503680

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.

PubMed

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex K; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-04-01

Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

Genetic structure characterization of Chileans reflects historical immigration patterns.

PubMed

Eyheramendy, Susana; Martinez, Felipe I; Manevy, Federico; Vial, Cecilia; Repetto, Gabriela M

2015-03-17

Identifying the ancestral components of genomes of admixed individuals helps uncovering the genetic basis of diseases and understanding the demographic history of populations. We estimate local ancestry on 313 Chileans and assess the contribution from three continental populations. The distribution of ancestry block-length suggests an average admixing time around 10 generations ago. Sex-chromosome analyses confirm imbalanced contribution of European men and Native-American women. Previously known genes under selection contain SNPs showing large difference in allele frequencies. Furthermore, we show that assessing ancestry is harder at SNPs with higher recombination rates and easier at SNPs with large difference in allele frequencies at the ancestral populations. Two observations, that African ancestry proportions systematically decrease from North to South, and that European ancestry proportions are highest in central regions, show that the genetic structure of Chileans is under the influence of a diffusion process leading to an ancestry gradient related to geography.

Genetic structure characterization of Chileans reflects historical immigration patterns

PubMed Central

Eyheramendy, Susana; Martinez, Felipe I.; Manevy, Federico; Vial, Cecilia; Repetto, Gabriela M.

2015-01-01

Identifying the ancestral components of genomes of admixed individuals helps uncovering the genetic basis of diseases and understanding the demographic history of populations. We estimate local ancestry on 313 Chileans and assess the contribution from three continental populations. The distribution of ancestry block-length suggests an average admixing time around 10 generations ago. Sex-chromosome analyses confirm imbalanced contribution of European men and Native-American women. Previously known genes under selection contain SNPs showing large difference in allele frequencies. Furthermore, we show that assessing ancestry is harder at SNPs with higher recombination rates and easier at SNPs with large difference in allele frequencies at the ancestral populations. Two observations, that African ancestry proportions systematically decrease from North to South, and that European ancestry proportions are highest in central regions, show that the genetic structure of Chileans is under the influence of a diffusion process leading to an ancestry gradient related to geography. PMID:25778948

Unlinked Mendelian inheritance of red and black pigmentation in snakes: Implications for Batesian mimicry.

PubMed

Davis Rabosky, Alison R; Cox, Christian L; Rabosky, Daniel L

2016-04-01

Identifying the genetic basis of mimetic signals is critical to understanding both the origin and dynamics of mimicry over time. For species not amenable to large laboratory breeding studies, widespread color polymorphism across natural populations offers a powerful way to assess the relative likelihood of different genetic systems given observed phenotypic frequencies. We classified color phenotype for 2175 ground snakes (Sonora semiannulata) across the continental United States to analyze morph ratios and test among competing hypotheses about the genetic architecture underlying red and black coloration in coral snake mimics. We found strong support for a two-locus model under simple Mendelian inheritance, with red and black pigmentation being controlled by separate loci. We found no evidence of either linkage disequilibrium between loci or sex linkage. In contrast to Batesian mimicry systems such as butterflies in which all color signal components are linked into a single "supergene," our results suggest that the mimetic signal in colubrid snakes can be disrupted through simple recombination and that color evolution is likely to involve discrete gains and losses of each signal component. Both outcomes are likely to contribute to the exponential increase in rates of color evolution seen in snake mimicry systems over insect systems. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Why do some like it hot? Genetic and environmental contributions to the pleasantness of oral pungency.

PubMed

Törnwall, Outi; Silventoinen, Karri; Kaprio, Jaakko; Tuorila, Hely

2012-10-10

Although potential environmental influences on hedonic responses to oral pungency have been identified, little is known of the possible role of genetics underlying these responses. We explored the contribution of genetic and environmental influences on the pleasantness of oral pungency and spicy foods. Respondents were young adult Finnish twins (n=331, 21-25 years), including 47 complete monozygotic and 93 dizygotic twin pairs and 51 twin individuals without their co-twin. Pleasantness and intensity of strawberry jelly spiked with capsaicin (0.0001% w/v) relative to untainted strawberry jelly were rated. Furthermore, pleasantness of spicy foods and oral pungency caused by spices were rated based on food names in a questionnaire. Respondents were grouped as non-likers, medium-likers, and likers by their pleasantness responses to capsaicin spiked jelly. The contribution of genetic and environmental factors to variation and co-variation of the pleasantness traits was analyzed using quantitative genetic modeling. The non-likers perceived oral pungency as more intense (sensory) and rated pleasantness of spicy foods and pungent sensations caused by spices (questionnaire) as less pleasant than the likers. Genetic factors accounted for 18-58% of the variation in the pleasantness of oral pungency, spicy foods and pungent sensations. The rest was due to environmental factors. All pleasantness traits (sensory and questionnaire based) were shown to share a common genetic variance. This indicates that an underlying genetic aptitude to like oral pungency, and spicy foods exists and it is expressed in these measures. The findings broaden the understanding of the diverse nature of individual food preferences and motivate further search for the underlying genetic components of oral pungency. Copyright © 2012. Published by Elsevier Inc.

Environmental quality and evolutionary potential: lessons from wild populations

PubMed Central

Charmantier, Anne; Garant, Dany

2005-01-01

An essential requirement to determine a population's potential for evolutionary change is to quantify the amount of genetic variability expressed for traits under selection. Early investigations in laboratory conditions showed that the magnitude of the genetic and environmental components of phenotypic variation can change with environmental conditions. However, there is no consensus as to how the expression of genetic variation is sensitive to different environmental conditions. Recently, the study of quantitative genetics in the wild has been revitalized by new pedigree analyses based on restricted maximum likelihood, resulting in a number of studies investigating these questions in wild populations. Experimental manipulation of environmental quality in the wild, as well as the use of naturally occurring favourable or stressful environments, has broadened the treatment of different taxa and traits. Here, we conduct a meta-analysis on recent studies comparing heritability in favourable versus unfavourable conditions in non-domestic and non-laboratory animals. The results provide evidence for increased heritability in more favourable conditions, significantly so for morphometric traits but not for traits more closely related to fitness. We discuss how these results are explained by underlying changes in variance components, and how they represent a major step in our understanding of evolutionary processes in wild populations. We also show how these trends contrast with the prevailing view resulting mainly from laboratory experiments on Drosophila. Finally, we underline the importance of taking into account the environmental variation in models predicting quantitative trait evolution. PMID:16011915

Mapping quantitative trait loci associated with chilling requirement, heat requirement and bloom date in peach [Prunus persica (L.) Batsch

USDA-ARS?s Scientific Manuscript database

Chilling requirement (CR), together with heat requirement (HR), determines blooming date (BD) and climatic distribution of genotypes of temperate tree species. However, information on the genetic components underlying these important traits remains unknown or fragmentary. Here the identification o...

New genetic tools to improve citrus fruit quality and drive consumer demand

USDA-ARS?s Scientific Manuscript database

Chemical and genomic dissection of important components underlying fruit quality has led toward the development of new tools to make the creation and selection of citrus cultivars improved in quality attributes more targeted and efficient. The use of SNP platforms and other technologies have resulte...

Detecting epistasis with the marginal epistasis test in genetic mapping studies of quantitative traits

PubMed Central

Zeng, Ping; Mukherjee, Sayan; Zhou, Xiang

2017-01-01

Epistasis, commonly defined as the interaction between multiple genes, is an important genetic component underlying phenotypic variation. Many statistical methods have been developed to model and identify epistatic interactions between genetic variants. However, because of the large combinatorial search space of interactions, most epistasis mapping methods face enormous computational challenges and often suffer from low statistical power due to multiple test correction. Here, we present a novel, alternative strategy for mapping epistasis: instead of directly identifying individual pairwise or higher-order interactions, we focus on mapping variants that have non-zero marginal epistatic effects—the combined pairwise interaction effects between a given variant and all other variants. By testing marginal epistatic effects, we can identify candidate variants that are involved in epistasis without the need to identify the exact partners with which the variants interact, thus potentially alleviating much of the statistical and computational burden associated with standard epistatic mapping procedures. Our method is based on a variance component model, and relies on a recently developed variance component estimation method for efficient parameter inference and p-value computation. We refer to our method as the “MArginal ePIstasis Test”, or MAPIT. With simulations, we show how MAPIT can be used to estimate and test marginal epistatic effects, produce calibrated test statistics under the null, and facilitate the detection of pairwise epistatic interactions. We further illustrate the benefits of MAPIT in a QTL mapping study by analyzing the gene expression data of over 400 individuals from the GEUVADIS consortium. PMID:28746338

The effects of r- and K-selection on components of variance for two quantitative traits.

PubMed

Long, T; Long, G

1974-03-01

The genetic and environmental components of variance for two quantitative characters were measured in the descendants of Drosophila melanogaster populations which had been grown for several generations at densities of 100, 200, 300, and 400 eggs per vial. Populations subject to intermediate densities had a greater proportion of phenotypic variance available for selection than populations from either extreme. Selection on either character would be least effective under pure r-selection, a frequent attribute of selection programs.

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.

The genetics of normal and defective color vision

PubMed Central

Neitz, Jay; Neitz, Maureen

2011-01-01

The contributions of genetics research to the science of normal and defective color vision over the previous few decades are reviewed emphasizing the developments in the 25 years since the last anniversary issue of Vision Research. Understanding of the biology underlying color vision has been vaulted forward through the application of the tools of molecular genetics. For all their complexity, the biological processes responsible for color vision are more accessible than for many other neural systems. This is partly because of the wealth of genetic variations that affect color perception, both within and across species, and because components of the color vision system lend themselves to genetic manipulation. Mutations and rearrangements in the genes encoding the long, middle, and short wavelength sensitive cone pigments are responsible for color vision deficiencies and mutations have been identified that affect the number of cone types, the absorption spectrum of the pigments, the functionality and viability of the cones, and the topography of the cone mosaic. The addition of an opsin gene, as occurred in the evolution of primate color vision, and has been done in experimental animals can produce expanded color vision capacities and this has provided insight into the underlying neural circuitry. PMID:21167193

Mendelian Diseases and Conditions in Croatian Island Populations: Historic Records and New Insights

PubMed Central

Saftić, Vanja; Rudan, Diana; Zgaga, Lina

2006-01-01

Among Croatian islands, there are several which are known for unusual autochthonous diseases and specific medical conditions that result from the reproductive isolation and specific population genetic structure. These populations are characterized by high degree of genetic isolation, consanguinity, and inbreeding. The reported diseases include Mal de Meleda on Mljet island, hereditary dwarfism on Krk island, familial learning disability on Susak island, familial ovarian cancer on Lastovo island, and several other rare diseases and conditions inherited in Mendelian fashion. We present a historical perspective on how these conditions were first described, interpreted, and assessed. We reviewed the information obtained through genetic research in the past several years, when the genetic etiology of some of these conditions was explained. The disease gene causing Mal de Meleda was first localized at 8q chromosome, and mutations in the ARS (component B) gene encoding SLURP-1 (secreted mammalian Ly-6/uPAR-related protein 1) protein were identified subsequently. The genetic etiology of dwarfism on the island of Krk is explained by a mutation in the PROP1 gene, responsible for the short stature. The search for mutations underlying other monogenic diseases in Croatian islands is under way. PMID:16909451

The distribution of genetic variance across phenotypic space and the response to selection.

PubMed

Blows, Mark W; McGuigan, Katrina

2015-05-01

The role of adaptation in biological invasions will depend on the availability of genetic variation for traits under selection in the new environment. Although genetic variation is present for most traits in most populations, selection is expected to act on combinations of traits, not individual traits in isolation. The distribution of genetic variance across trait combinations can be characterized by the empirical spectral distribution of the genetic variance-covariance (G) matrix. Empirical spectral distributions of G from a range of trait types and taxa all exhibit a characteristic shape; some trait combinations have large levels of genetic variance, while others have very little genetic variance. In this study, we review what is known about the empirical spectral distribution of G and show how it predicts the response to selection across phenotypic space. In particular, trait combinations that form a nearly null genetic subspace with little genetic variance respond only inconsistently to selection. We go on to set out a framework for understanding how the empirical spectral distribution of G may differ from the random expectations that have been developed under random matrix theory (RMT). Using a data set containing a large number of gene expression traits, we illustrate how hypotheses concerning the distribution of multivariate genetic variance can be tested using RMT methods. We suggest that the relative alignment between novel selection pressures during invasion and the nearly null genetic subspace is likely to be an important component of the success or failure of invasion, and for the likelihood of rapid adaptation in small populations in general. © 2014 John Wiley & Sons Ltd.

Does selection in a challenging environment produce Nile tilapia genotypes that can thrive in a range of production systems?

PubMed

Thoa, Ngo Phu; Ninh, Nguyen Huu; Knibb, Wayne; Nguyen, Nguyen Hong

2016-02-19

This study assessed whether selection for high growth in a challenging environment of medium salinity produces tilapia genotypes that perform well across different production environments. We estimated the genetic correlations between trait expressions in saline and freshwater using a strain of Nile tilapia selected for fast growth under salinity water of 15-20 ppt. We also estimated the heritability and genetic correlations for new traits of commercial importance (sexual maturity, feed conversion ratio, deformity and gill condition) in a full pedigree comprising 36,145 fish. The genetic correlations for the novel characters between the two environments were 0.78-0.99, suggesting that the effect of genotype by environment interaction was not biologically important. Across the environments, the heritability for body weight was moderate to high (0.32-0.62), indicating that this population will continue responding to future selection. The estimates of heritability for sexual maturity and survival were low but significant. The additive genetic components also exist for FCR, gill condition and deformity. Genetic correlations of harvest body weight with sexual maturity were positive and those between harvest body weight with FCR were negative. Our results indicate that the genetic line selected under a moderate saline water environment can be cultured successfully in freshwater systems.

Education and alcohol use: A study of gene-environment interaction in young adulthood.

PubMed

Barr, Peter B; Salvatore, Jessica E; Maes, Hermine; Aliev, Fazil; Latvala, Antti; Viken, Richard; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M

2016-08-01

The consequences of heavy alcohol use remain a serious public health problem. Consistent evidence has demonstrated that both genetic and social influences contribute to alcohol use. Research on gene-environment interaction (GxE) has also demonstrated that these social and genetic influences do not act independently. Instead, certain environmental contexts may limit or exacerbate an underlying genetic predisposition. However, much of the work on GxE and alcohol use has focused on adolescence and less is known about the important environmental contexts in young adulthood. Using data from the young adult wave of the Finnish Twin Study, FinnTwin12 (N = 3402), we used biometric twin modeling to test whether education moderated genetic risk for alcohol use as assessed by drinking frequency and intoxication frequency. Education is important because it offers greater access to personal resources and helps determine one's position in the broader stratification system. Results from the twin models show that education did not moderate genetic variance components and that genetic risk was constant across levels of education. Instead, education moderated environmental variance so that under conditions of low education, environmental influences explained more of the variation in alcohol use outcomes. The implications and limitations of these results are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Education and Alcohol Use: A Study of Gene-Environment Interaction in Young Adulthood

PubMed Central

Barr, Peter B.; Salvatore, Jessica E.; Maes, Hermine; Aliev, Fazil; Latvala, Antti; Viken, Richard; Rose, Richard J.; Kaprio, Jaakko; Dick, Danielle M.

2016-01-01

The consequences of heavy alcohol use remain a serious public health problem. Consistent evidence has demonstrated that both genetic and social influences contribute to alcohol use. Research on gene-environment interaction (GxE) has also demonstrated that these social and genetic influences do not act independently. Instead, certain environmental contexts may limit or exacerbate an underlying genetic predisposition. However, much of the work on GxE and alcohol use has focused on adolescence and less is known about the important environmental contexts in young adulthood. Using data from the young adult wave of the Finnish Twin Study, FinnTwin12 (N=3,402), we used biometric twin modeling to test whether education moderated genetic risk for alcohol use as assessed by drinking frequency and intoxication frequency. Education is important because it offers greater access to personal resources and helps determine one’s position in the broader stratification system. Results from the twin models show that education did not moderate genetic variance components and that genetic risk was constant across levels of education. Instead, education moderated environmental variance so that under conditions of low education, environmental influences explained more of the variation in alcohol use outcomes. The implications and limitations of these results are discussed. PMID:27367897

Working Memory and Parent-Rated Components of Attention in Middle Childhood: A Behavioral Genetic Study

PubMed Central

Deater-Deckard, Kirby; Cutting, Laurie; Thompson, Lee A.; Petrill, Stephen A.

2012-01-01

The purpose of the current study was to investigate potential genetic and environmental correlations between working memory and three behavioral aspects of the attention network (i.e., executive, alerting, and orienting) using a twin design. Data were from 90 monozygotic (39% male) and 112 same-sex dizygotic (41% male) twins. Individual differences in working memory performance (digit span) and parent-rated measures of executive, alerting, and orienting attention included modest to moderate genetic variance, modest shared environmental variance, and modest to moderate nonshared environmental variance. As hypothesized, working memory performance was correlated with executive and alerting attention, but not orienting attention. The correlation between working memory, executive attention, and alerting attention was completely accounted for by overlapping genetic covariance, suggesting a common genetic mechanism or mechanisms underlying the links between working memory and certain parent-rated indicators of attentive behavior. PMID:21948215

The underlying process of early ecological and genetic differentiation in a facultative mutualistic Sinorhizobium meliloti population.

PubMed

Toro, Nicolás; Villadas, Pablo J; Molina-Sánchez, María Dolores; Navarro-Gómez, Pilar; Vinardell, José M; Cuesta-Berrio, Lidia; Rodríguez-Carvajal, Miguel A

2017-04-06

The question of how genotypic and ecological units arise and spread in natural microbial populations remains controversial in the field of evolutionary biology. Here, we investigated the early stages of ecological and genetic differentiation in a highly clonal sympatric Sinorhizobium meliloti population. Whole-genome sequencing revealed that a large DNA region of the symbiotic plasmid pSymB was replaced in some isolates with a similar synteny block carrying densely clustered SNPs and displaying gene acquisition and loss. Two different versions of this genomic island of differentiation (GID) generated by multiple genetic exchanges over time appear to have arisen recently, through recombination in a particular clade within this population. In addition, these isolates display resistance to phages from the same geographic region, probably due to the modification of surface components by the acquired genes. Our results suggest that an underlying process of early ecological and genetic differentiation in S. meliloti is primarily triggered by acquisition of genes that confer resistance to soil phages within particular large genomic DNA regions prone to recombination.

Characterising variation in wheat traits under hostile soil conditions in India

PubMed Central

Khokhar, Jaswant S.; Sareen, Sindhu; Tyagi, Bhudeva S.; Singh, Gyanendra; Chowdhury, Apurba K.; Dhar, Tapamay; Singh, Vinod; King, Ian P.; Young, Scott D.

2017-01-01

Intensive crop breeding has increased wheat yields and production in India. Wheat improvement in India typically involves selecting yield and component traits under non-hostile soil conditions at regional scales. The aim of this study is to quantify G*E interactions on yield and component traits to further explore site-specific trait selection for hostile soils. Field experiments were conducted at six sites (pH range 4.5–9.5) in 2013–14 and 2014–15, in three agro-climatic regions of India. At each site, yield and component traits were measured on 36 genotypes, representing elite varieties from a wide genetic background developed for different regions. Mean grain yields ranged from 1.0 to 5.5 t ha-1 at hostile and non-hostile sites, respectively. Site (E) had the largest effect on yield and component traits, however, interactions between genotype and site (G*E) affected most traits to a greater extent than genotype alone. Within each agro-climatic region, yield and component traits correlated positively between hostile and non-hostile sites. However, some genotypes performed better under hostile soils, with site-specific relationships between yield and component traits, which supports the value of ongoing site-specific selection activities. PMID:28604800

Dissecting the Phenotypic Components of Crop Plant Growth and Drought Responses Based on High-Throughput Image Analysis[W][OPEN

PubMed Central

Chen, Dijun; Neumann, Kerstin; Friedel, Swetlana; Kilian, Benjamin; Chen, Ming; Altmann, Thomas; Klukas, Christian

2014-01-01

Significantly improved crop varieties are urgently needed to feed the rapidly growing human population under changing climates. While genome sequence information and excellent genomic tools are in place for major crop species, the systematic quantification of phenotypic traits or components thereof in a high-throughput fashion remains an enormous challenge. In order to help bridge the genotype to phenotype gap, we developed a comprehensive framework for high-throughput phenotype data analysis in plants, which enables the extraction of an extensive list of phenotypic traits from nondestructive plant imaging over time. As a proof of concept, we investigated the phenotypic components of the drought responses of 18 different barley (Hordeum vulgare) cultivars during vegetative growth. We analyzed dynamic properties of trait expression over growth time based on 54 representative phenotypic features. The data are highly valuable to understand plant development and to further quantify growth and crop performance features. We tested various growth models to predict plant biomass accumulation and identified several relevant parameters that support biological interpretation of plant growth and stress tolerance. These image-based traits and model-derived parameters are promising for subsequent genetic mapping to uncover the genetic basis of complex agronomic traits. Taken together, we anticipate that the analytical framework and analysis results presented here will be useful to advance our views of phenotypic trait components underlying plant development and their responses to environmental cues. PMID:25501589

Genetic and environmental contributions to body mass index: comparative analysis of monozygotic twins, dizygotic twins and same-age unrelated siblings.

PubMed

Segal, N L; Feng, R; McGuire, S A; Allison, D B; Miller, S

2009-01-01

Earlier studies have established that a substantial percentage of variance in obesity-related phenotypes is explained by genetic components. However, only one study has used both virtual twins (VTs) and biological twins and was able to simultaneously estimate additive genetic, non-additive genetic, shared environmental and unshared environmental components in body mass index (BMI). Our current goal was to re-estimate four components of variance in BMI, applying a more rigorous model to biological and virtual multiples with additional data. Virtual multiples share the same family environment, offering unique opportunities to estimate common environmental influence on phenotypes that cannot be separated from the non-additive genetic component using only biological multiples. Data included 929 individuals from 164 monozygotic twin pairs, 156 dizygotic twin pairs, five triplet sets, one quadruplet set, 128 VT pairs, two virtual triplet sets and two virtual quadruplet sets. Virtual multiples consist of one biological child (or twins or triplets) plus one same-aged adoptee who are all raised together since infancy. We estimated the additive genetic, non-additive genetic, shared environmental and unshared random components in BMI using a linear mixed model. The analysis was adjusted for age, age(2), age(3), height, height(2), height(3), gender and race. Both non-additive genetic and common environmental contributions were significant in our model (P-values<0.0001). No significant additive genetic contribution was found. In all, 63.6% (95% confidence interval (CI) 51.8-75.3%) of the total variance of BMI was explained by a non-additive genetic component, 25.7% (95% CI 13.8-37.5%) by a common environmental component and the remaining 10.7% by an unshared component. Our results suggest that genetic components play an essential role in BMI and that common environmental factors such as diet or exercise also affect BMI. This conclusion is consistent with our earlier study using a smaller sample and shows the utility of virtual multiples for separating non-additive genetic variance from common environmental variance.

Dissection of K+ currents in Caenorhabditis elegans muscle cells by genetics and RNA interference

PubMed Central

Santi, C. M.; Yuan, A.; Fawcett, G.; Wang, Z.-W.; Butler, A.; Nonet, M. L.; Wei, A.; Rojas, P.; Salkoff, L.

2003-01-01

GFP-promoter experiments have previously shown that at least nine genes encoding potassium channel subunits are expressed in Caenorhabditis elegans muscle. By using genetic, RNA interference, and physiological techniques we revealed the molecular identity of the major components of the outward K+ currents in body wall muscle cells in culture. We found that under physiological conditions, outward current is dominated by the products of only two genes, Shaker (Kv1) and Shal (Kv4), both expressing voltage-dependent potassium channels. Other channels may be held in reserve to respond to particular circumstances. Because GFP-promoter experiments indicated that slo-2 expression is prominent, we created a deletion mutant to identify the SLO-2 current in vivo. In both whole-cell and single-channel modes, in vivo SLO-2 channels were active only when intracellular Ca2+ and Cl- were raised above normal physiological conditions, as occurs during hypoxia. Under such conditions, SLO-2 is the largest outward current, contributing up to 87% of the total current. Other channels are present in muscle, but our results suggest that they are unlikely to contribute a large outward component under physiological conditions. However, they, too, may contribute currents conditional on other factors. Hence, the picture that emerges is of a complex membrane with a small number of household conductances functioning under normal circumstances, but with additional conductances that are activated during unusual circumstances. PMID:14612577

A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis

PubMed Central

Lucarelli, Marco; Bruno, Sabina Maria; Pierandrei, Silvia; Ferraguti, Giampiero; Stamato, Antonella; Narzi, Fabiana; Amato, Annalisa; Cimino, Giuseppe; Bertasi, Serenella; Quattrucci, Serena; Strom, Roberto

2015-01-01

Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype–phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype–phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype–phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway. PMID:25910067

Birth, death, and replacement of karyopherins in Drosophila.

PubMed

Phadnis, Nitin; Hsieh, Emily; Malik, Harmit S

2012-05-01

Nucleocytoplasmic transport is a broadly conserved process across eukaryotes. Despite its essential function and conserved mechanism, components of the nuclear transport apparatus have been implicated in genetic conflicts in Drosophila, especially in the male germ line. The best understood case is represented by a truncated RanGAP gene duplication that is part of the segregation distorter system in Drosophila melanogaster. Consistent with the hypothesis that the nuclear transport pathway is at the heart of mediating genetic conflicts, both nucleoporins and directionality imposing components of nuclear transport have previously been shown to evolve under positive selection. Here, we present a comprehensive phylogenomic analysis of importins (karyopherins) in Drosophila evolution. Importins are adaptor molecules that physically mediate the transport of cargo molecules and comprise the third component of the nuclear transport apparatus. We find that importins have been repeatedly gained and lost throughout various stages of Drosophila evolution, including two intriguing examples of an apparently coincident loss and gain of nonorthologous and noncanonical importin-α. Although there are a few signatures of episodic positive selection, genetic innovation in importin evolution is more evident in patterns of recurrent gene birth and loss specifically for function in Drosophila testes, which is consistent with their role in supporting host genomes defense against segregation distortion.

Genetic framework for GATA factor function in vascular biology.

PubMed

Linnemann, Amelia K; O'Geen, Henriette; Keles, Sunduz; Farnham, Peggy J; Bresnick, Emery H

2011-08-16

Vascular endothelial dysfunction underlies the genesis and progression of numerous diseases. Although the GATA transcription factor GATA-2 is expressed in endothelial cells and is implicated in coronary heart disease, it has been studied predominantly as a master regulator of hematopoiesis. Because many questions regarding GATA-2 function in the vascular biology realm remain unanswered, we used ChIP sequencing and loss-of-function strategies to define the GATA-2-instigated genetic network in human endothelial cells. In contrast to erythroid cells, GATA-2 occupied a unique target gene ensemble consisting of genes encoding key determinants of endothelial cell identity and inflammation. GATA-2-occupied sites characteristically contained motifs that bind activator protein-1 (AP-1), a pivotal regulator of inflammatory genes. GATA-2 frequently occupied the same chromatin sites as c-JUN and c-FOS, heterodimeric components of AP-1. Although all three components were required for maximal AP-1 target gene expression, GATA-2 was not required for AP-1 chromatin occupancy. GATA-2 conferred maximal phosphorylation of chromatin-bound c-JUN at Ser-73, which stimulates AP-1-dependent transactivation, in a chromosomal context-dependent manner. This work establishes a link between a GATA factor and inflammatory genes, mechanistic insights underlying GATA-2-AP-1 cooperativity and a rigorous genetic framework for understanding GATA-2 function in normal and pathophysiological vascular states.

Mitochondrial Recombination Reveals Mito-Mito Epistasis in Yeast.

PubMed

Wolters, John F; Charron, Guillaume; Gaspary, Alec; Landry, Christian R; Fiumera, Anthony C; Fiumera, Heather L

2018-05-01

Genetic variation in mitochondrial DNA (mtDNA) provides adaptive potential although the underlying genetic architecture of fitness components within mtDNAs is not known. To dissect functional variation within mtDNAs, we first identified naturally occurring mtDNAs that conferred high or low fitness in Saccharomyces cerevisiae by comparing growth in strains containing identical nuclear genotypes but different mtDNAs. During respiratory growth under temperature and oxidative stress conditions, mitotype effects were largely independent of nuclear genotypes even in the presence of mito-nuclear interactions. Recombinant mtDNAs were generated to determine fitness components within high- and low-fitness mtDNAs. Based on phenotypic distributions of isogenic strains containing recombinant mtDNAs, we found that multiple loci contributed to mitotype fitness differences. These mitochondrial loci interacted in epistatic, nonadditive ways in certain environmental conditions. Mito-mito epistasis ( i.e. , nonadditive interactions between mitochondrial loci) influenced fitness in progeny from four different crosses, suggesting that mito-mito epistasis is a widespread phenomenon in yeast and other systems with recombining mtDNAs. Furthermore, we found that interruption of coadapted mito-mito interactions produced recombinant mtDNAs with lower fitness. Our results demonstrate that mito-mito epistasis results in functional variation through mitochondrial recombination in fungi, providing modes for adaptive evolution and the generation of mito-mito incompatibilities. Copyright © 2018 by the Genetics Society of America.

The genetics of pre-eclampsia and other hypertensive disorders of pregnancy

PubMed Central

Williams, Paula J.; Broughton Pipkin, Fiona

2011-01-01

Hypertension is the most frequent medical complication occurring during pregnancy. In this chapter, we aim to address the genetic contribution to these disorders, with specific focus on pre-eclampsia. The pathogenic mechanisms underlying pre-eclampsia remain to be elucidated; however, immune maladaptation, inadequate placental development and trophoblast invasion, placental ischaemia, oxidative stress and thrombosis are all thought to represent key factors in the development of disease. Furthermore, all of these components have genetic factors that may be involved in the pathogenic changes occurring. The familial nature of pre-eclampsia has been known for many years and, as such, extensive genetic research has been carried out in this area using strategies that include candidate gene studies and linkage analysis. Interactions between fetal and maternal genotypes, the effect of environmental factors, and epistasis will also be considered. PMID:21429808

Large scale q-PCR reveals maize transcription factors that are regulated under water deficit in a tissue-specific manner

USDA-ARS?s Scientific Manuscript database

Water deficit stress is a major component of agricultural drought events and contributes greatly to yield loss in all crops. Genetic modification to improve water deficit tolerance is an obvious strategy to mitigate this problem and an understanding of the mechanism of adaptation to water deficit is...

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette Syndrome and Obsessive-Compulsive Disorder

PubMed Central

Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Fagerness, Jesen A.; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Cardona Silgado, Julio C.; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M.J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosário, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Valencia Duarte, Ana V.; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Walkup, John; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G.M.; Yao, Yin; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Rouleau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson; Stewart, S. Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.

2014-01-01

Obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS) are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. Here, we report a combined genome-wide association study (GWAS) of TS and OCD in 2723 cases (1310 with OCD, 834 with TS, 579 with OCD plus TS/chronic tics (CT)), 5667 ancestry-matched controls, and 290 OCD parent-child trios. Although no individual single nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels, i.e. expression quantitative loci (eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10−4), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, TS had a smaller, non-significant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and TS/CT were included in the analysis (p=0.01). Previous work has shown that TS and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of TS and OCD. Furthermore, OCD with co-occurring TS/CT may have different underlying genetic susceptibility compared to OCD alone. PMID:25158072

Investigating the genetic basis of theory of mind (ToM): the role of catechol-O-methyltransferase (COMT) gene polymorphisms.

PubMed

Xia, Haiwei; Wu, Nan; Su, Yanjie

2012-01-01

The ability to deduce other persons' mental states and emotions which has been termed 'theory of mind (ToM)' is highly heritable. First molecular genetic studies focused on some dopamine-related genes, while the genetic basis underlying different components of ToM (affective ToM and cognitive ToM) remain unknown. The current study tested 7 candidate polymorphisms (rs4680, rs4633, rs2020917, rs2239393, rs737865, rs174699 and rs59938883) on the catechol-O-methyltransferase (COMT) gene. We investigated how these polymorphisms relate to different components of ToM. 101 adults participated in our study; all were genetically unrelated, non-clinical and healthy Chinese subjects. Different ToM tasks were applied to detect their theory of mind ability. The results showed that the COMT gene rs2020917 and rs737865 SNPs were associated with cognitive ToM performance, while the COMT gene rs5993883 SNP was related to affective ToM, in which a significant gender-genotype interaction was found (p = 0.039). Our results highlighted the contribution of DA-related COMT gene on ToM performance. Moreover, we found out that the different SNP at the same gene relates to the discriminative aspect of ToM. Our research provides some preliminary evidence to the genetic basis of theory of mind which still awaits further studies.

The genetic basis of female multiple mating in a polyandrous livebearing fish

PubMed Central

Evans, Jonathan P; Gasparini, Clelia

2013-01-01

The widespread occurrence of female multiple mating (FMM) demands evolutionary explanation, particularly in the light of the costs of mating. One explanation encapsulated by “good sperm” and “sexy-sperm” (GS-SS) theoretical models is that FMM facilitates sperm competition, thus ensuring paternity by males that pass on genes for elevated sperm competitiveness to their male offspring. While support for this component of GS-SS theory is accumulating, a second but poorly tested assumption of these models is that there should be corresponding heritable genetic variation in FMM – the proposed mechanism of postcopulatory preferences underlying GS-SS models. Here, we conduct quantitative genetic analyses on paternal half-siblings to test this component of GS-SS theory in the guppy (Poecilia reticulata), a freshwater fish with some of the highest known rates of FMM in vertebrates. As with most previous quantitative genetic analyses of FMM in other species, our results reveal high levels of phenotypic variation in this trait and a correspondingly low narrow-sense heritability (h2 = 0.11). Furthermore, although our analysis of additive genetic variance in FMM was not statistically significant (probably owing to limited statistical power), the ensuing estimate of mean-standardized additive genetic variance (IA = 0.7) was nevertheless relatively low compared with estimates published for life-history traits across a broad range of taxa. Our results therefore add to a growing body of evidence that FMM is characterized by relatively low additive genetic variation, thus apparently contradicting GS-SS theory. However, we qualify this conclusion by drawing attention to potential deficiencies in most designs (including ours) that have tested for genetic variation in FMM, particularly those that fail to account for intersexual interactions that underlie FMM in many systems. PMID:23403856

Evaluating methods to visualize patterns of genetic differentiation on a landscape.

PubMed

House, Geoffrey L; Hahn, Matthew W

2018-05-01

With advances in sequencing technology, research in the field of landscape genetics can now be conducted at unprecedented spatial and genomic scales. This has been especially evident when using sequence data to visualize patterns of genetic differentiation across a landscape due to demographic history, including changes in migration. Two recent model-based visualization methods that can highlight unusual patterns of genetic differentiation across a landscape, SpaceMix and EEMS, are increasingly used. While SpaceMix's model can infer long-distance migration, EEMS' model is more sensitive to short-distance changes in genetic differentiation, and it is unclear how these differences may affect their results in various situations. Here, we compare SpaceMix and EEMS side by side using landscape genetics simulations representing different migration scenarios. While both methods excel when patterns of simulated migration closely match their underlying models, they can produce either un-intuitive or misleading results when the simulated migration patterns match their models less well, and this may be difficult to assess in empirical data sets. We also introduce unbundled principal components (un-PC), a fast, model-free method to visualize patterns of genetic differentiation by combining principal components analysis (PCA), which is already used in many landscape genetics studies, with the locations of sampled individuals. Un-PC has characteristics of both SpaceMix and EEMS and works well with simulated and empirical data. Finally, we introduce msLandscape, a collection of tools that streamline the creation of customizable landscape-scale simulations using the popular coalescent simulator ms and conversion of the simulated data for use with un-PC, SpaceMix and EEMS. © 2017 John Wiley & Sons Ltd.

Whole genome sequences of two octogenarians with sustained cognitive abilities

PubMed Central

Nickles, Dorothee; Madireddy, Lohith; Patel, Nihar; Isobe, Noriko; Miller, Bruce L.; Baranzini, Sergio E.; Kramer, Joel H.; Oksenberg, Jorge R.

2014-01-01

Although numerous genetic variants affecting aging and mortality have been identified, e.g. APOE ε4, the genetic component influencing cognitive aging has not been fully defined yet. A better knowledge of the genetics of aging will prove helpful in understanding the underlying biological processes. Here, we describe the whole genome sequences of two female octogenarians. We provide the repertoire of genomic variants that the two octogenarians have in common. We also describe the overlap with the previously reported genomes of two supercentenarians - individuals aged ≥ 110 years. We assessed the genetic disease propensities of the octogenarians and non-aged control genomes and could not find support for the hypothesis that long-lived healthy individuals might exhibit greater genetic fitness than the general population. Furthermore, there is no evidence for an accumulation of previously described variants promoting longevity in the two octogenarians. These findings suggest that genetic fitness, as currently defined, is not the sole factor enabling an increased lifespan. We identified a number of healthy-cognitive-aging candidate genetic loci awaiting confirmation in larger studies. PMID:25618617

Whole genome sequences of 2 octogenarians with sustained cognitive abilities.

PubMed

Nickles, Dorothee; Madireddy, Lohith; Patel, Nihar; Isobe, Noriko; Miller, Bruce L; Baranzini, Sergio E; Kramer, Joel H; Oksenberg, Jorge R

2015-03-01

Although numerous genetic variants affecting aging and mortality have been identified, for example, apolipoprotein E ε4, the genetic component influencing cognitive aging has not been fully defined yet. A better knowledge of the genetics of aging will prove helpful in understanding the underlying biological processes. Here, we describe the whole genome sequences of 2 female octogenarians. We provide the repertoire of genomic variants that the 2 octogenarians have in common. We also describe the overlap with the previously reported genomes of 2 supercentenarians—individuals aged ≥110 years. We assessed the genetic disease propensities of the octogenarians and non-aged control genomes and could not find support for the hypothesis that long-lived healthy individuals might exhibit greater genetic fitness than the general population. Furthermore, there is no evidence for an accumulation of previously described variants promoting longevity in the 2 octogenarians. These findings suggest that genetic fitness, as currently defined, is not the sole factor enabling an increased life span. We identified a number of healthy-cognitive-aging candidate genetic loci awaiting confirmation in larger studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Sex-specific genetic variances in life-history and morphological traits of the seed beetle Callosobruchus maculatus.

PubMed

Hallsson, Lára R; Björklund, Mats

2012-01-01

Knowledge of heritability and genetic correlations are of central importance in the study of adaptive trait evolution and genetic constraints. We use a paternal half-sib-full-sib breeding design to investigate the genetic architecture of three life-history and morphological traits in the seed beetle, Callosobruchus maculatus. Heritability was significant for all traits under observation and genetic correlations between traits (r(A)) were low. Interestingly, we found substantial sex-specific genetic effects and low genetic correlations between sexes (r(MF)) in traits that are only moderately (weight at emergence) to slightly (longevity) sexually dimorphic. Furthermore, we found an increased sire ([Formula: see text]) compared to dam ([Formula: see text]) variance component within trait and sex. Our results highlight that the genetic architecture even of the same trait should not be assumed to be the same for males and females. Furthermore, it raises the issue of the presence of unnoticed environmental effects that may inflate estimates of heritability. Overall, our study stresses the fact that estimates of quantitative genetic parameters are not only population, time, environment, but also sex specific. Thus, extrapolation between sexes and studies should be treated with caution.

Sex-specific genetic variances in life-history and morphological traits of the seed beetle Callosobruchus maculatus

PubMed Central

Hallsson, Lára R; Björklund, Mats

2012-01-01

Knowledge of heritability and genetic correlations are of central importance in the study of adaptive trait evolution and genetic constraints. We use a paternal half-sib-full-sib breeding design to investigate the genetic architecture of three life-history and morphological traits in the seed beetle, Callosobruchus maculatus. Heritability was significant for all traits under observation and genetic correlations between traits (rA) were low. Interestingly, we found substantial sex-specific genetic effects and low genetic correlations between sexes (rMF) in traits that are only moderately (weight at emergence) to slightly (longevity) sexually dimorphic. Furthermore, we found an increased sire () compared to dam () variance component within trait and sex. Our results highlight that the genetic architecture even of the same trait should not be assumed to be the same for males and females. Furthermore, it raises the issue of the presence of unnoticed environmental effects that may inflate estimates of heritability. Overall, our study stresses the fact that estimates of quantitative genetic parameters are not only population, time, environment, but also sex specific. Thus, extrapolation between sexes and studies should be treated with caution. PMID:22408731

Population growth of the floricolous yeast Metschnikowia reukaufii: effects of nectar host, yeast genotype, and host × genotype interaction.

PubMed

Herrera, Carlos M

2014-05-01

Genetic diversity and genotypic diversity of wild populations of the floricolous yeast Metschnikowia reukaufii exhibit a strong host-mediated component, with genotypes being nonrandomly distributed among flowers of different plant species. To unravel the causal mechanism of this pattern of host-mediated genetic diversity, this paper examines experimentally whether floral nectars of different host plants differ in their quality as a growing substrate for M. reukaufii and also whether genetically distinct yeast strains differ in their relative ability to thrive in nectars of different species (host × genotype interaction). Genetically distinct M. reukaufii strains were grown in natural nectar of different hosts under controlled conditions. Population growth varied widely among nectar hosts, revealing that different host plants provided microhabitats of different quality for M. reukaufii. Different M. reukaufii strains responded in different ways to interspecific nectar variation, and variable growth responses were significantly associated with genetic differences between strains, thus leading to a significant host × genotype interaction. Results of this study provide support for the diversifying selection hypothesis as the underlying mechanism preserving high genetic diversity in wild M. reukaufii populations and also suggest that consequences of functional plant-pollinator diversity may surpass the domain of the mutualistic organisms to implicate associated microorganisms. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Does selection in a challenging environment produce Nile tilapia genotypes that can thrive in a range of production systems?

PubMed Central

Thoa, Ngo Phu; Ninh, Nguyen Huu; Knibb, Wayne; Nguyen, Nguyen Hong

2016-01-01

This study assessed whether selection for high growth in a challenging environment of medium salinity produces tilapia genotypes that perform well across different production environments. We estimated the genetic correlations between trait expressions in saline and freshwater using a strain of Nile tilapia selected for fast growth under salinity water of 15–20 ppt. We also estimated the heritability and genetic correlations for new traits of commercial importance (sexual maturity, feed conversion ratio, deformity and gill condition) in a full pedigree comprising 36,145 fish. The genetic correlations for the novel characters between the two environments were 0.78–0.99, suggesting that the effect of genotype by environment interaction was not biologically important. Across the environments, the heritability for body weight was moderate to high (0.32–0.62), indicating that this population will continue responding to future selection. The estimates of heritability for sexual maturity and survival were low but significant. The additive genetic components also exist for FCR, gill condition and deformity. Genetic correlations of harvest body weight with sexual maturity were positive and those between harvest body weight with FCR were negative. Our results indicate that the genetic line selected under a moderate saline water environment can be cultured successfully in freshwater systems. PMID:26892814

A Genome-Wide Association Study Identifies Genetic Variants Associated with Mathematics Ability

PubMed Central

Chen, Huan; Gu, Xiao-hong; Zhou, Yuxi; Ge, Zeng; Wang, Bin; Siok, Wai Ting; Wang, Guoqing; Huen, Michael; Jiang, Yuyang; Tan, Li-Hai; Sun, Yimin

2017-01-01

Mathematics ability is a complex cognitive trait with polygenic heritability. Genome-wide association study (GWAS) has been an effective approach to investigate genetic components underlying mathematic ability. Although previous studies reported several candidate genetic variants, none of them exceeded genome-wide significant threshold in general populations. Herein, we performed GWAS in Chinese elementary school students to identify potential genetic variants associated with mathematics ability. The discovery stage included 494 and 504 individuals from two independent cohorts respectively. The replication stage included another cohort of 599 individuals. In total, 28 of 81 candidate SNPs that met validation criteria were further replicated. Combined meta-analysis of three cohorts identified four SNPs (rs1012694, rs11743006, rs17778739 and rs17777541) of SPOCK1 gene showing association with mathematics ability (minimum p value 5.67 × 10−10, maximum β −2.43). The SPOCK1 gene is located on chromosome 5q31.2 and encodes a highly conserved glycoprotein testican-1 which was associated with tumor progression and prognosis as well as neurogenesis. This is the first study to report genome-wide significant association of individual SNPs with mathematics ability in general populations. Our preliminary results further supported the role of SPOCK1 during neurodevelopment. The genetic complexities underlying mathematics ability might contribute to explain the basis of human cognition and intelligence at genetic level. PMID:28155865

A Genome-Wide Association Study Identifies Genetic Variants Associated with Mathematics Ability.

PubMed

Chen, Huan; Gu, Xiao-Hong; Zhou, Yuxi; Ge, Zeng; Wang, Bin; Siok, Wai Ting; Wang, Guoqing; Huen, Michael; Jiang, Yuyang; Tan, Li-Hai; Sun, Yimin

2017-02-03

Mathematics ability is a complex cognitive trait with polygenic heritability. Genome-wide association study (GWAS) has been an effective approach to investigate genetic components underlying mathematic ability. Although previous studies reported several candidate genetic variants, none of them exceeded genome-wide significant threshold in general populations. Herein, we performed GWAS in Chinese elementary school students to identify potential genetic variants associated with mathematics ability. The discovery stage included 494 and 504 individuals from two independent cohorts respectively. The replication stage included another cohort of 599 individuals. In total, 28 of 81 candidate SNPs that met validation criteria were further replicated. Combined meta-analysis of three cohorts identified four SNPs (rs1012694, rs11743006, rs17778739 and rs17777541) of SPOCK1 gene showing association with mathematics ability (minimum p value 5.67 × 10 -10 , maximum β -2.43). The SPOCK1 gene is located on chromosome 5q31.2 and encodes a highly conserved glycoprotein testican-1 which was associated with tumor progression and prognosis as well as neurogenesis. This is the first study to report genome-wide significant association of individual SNPs with mathematics ability in general populations. Our preliminary results further supported the role of SPOCK1 during neurodevelopment. The genetic complexities underlying mathematics ability might contribute to explain the basis of human cognition and intelligence at genetic level.

Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13.

PubMed

Nurmi, Erika L; Dowd, Michael; Tadevosyan-Leyfer, Ovsanna; Haines, Jonathan L; Folstein, Susan E; Sutcliffe, James S

2003-07-01

Autism displays a remarkably high heritability but a complex genetic etiology. One approach to identifying susceptibility loci under these conditions is to define more homogeneous subsets of families on the basis of genetically relevant phenotypic or biological characteristics that vary from case to case. The authors performed a principal components analysis, using items from the Autism Diagnostic Interview, which resulted in six clusters of variables, five of which showed significant sib-sib correlation. The utility of these phenotypic subsets was tested in an exploratory genetic analysis of the autism candidate region on chromosome 15q11-q13. When the Collaborative Linkage Study of Autism sample was divided, on the basis of mean proband score for the "savant skills" cluster, the heterogeneity logarithm of the odds under a recessive model at D15S511, within the GABRB3 gene, increased from 0.6 to 2.6 in the subset of families in which probands had greater savant skills. These data are consistent with the genetic contribution of a 15q locus to autism susceptibility in a subset of affected individuals exhibiting savant skills. Similar types of skills have been noted in individuals with Prader-Willi syndrome, which results from deletions of this chromosomal region.

Wild rodents as a model to discover genes and pathways underlying natural variation in infectious disease susceptibility.

PubMed

Turner, A K; Paterson, S

2013-11-01

Individuals vary in their susceptibility to infectious disease, and it is now well established that host genetic factors form a major component of this variation. The discovery of genes underlying susceptibility has the potential to lead to improved disease control, through the identification and management of vulnerable individuals and the discovery of novel therapeutic targets. Laboratory rodents have proved invaluable for ascertaining the function of genes involved in immunity to infection. However, these captive animals experience conditions very different to the natural environment, lacking the genetic diversity and environmental pressures characteristic of natural populations, including those of humans. It has therefore often proved difficult to translate basic laboratory research to the real world. In order to further our understanding of the genetic basis of infectious disease resistance, and the evolutionary forces that drive variation in susceptibility, we propose that genetic research traditionally conducted on laboratory animals is expanded to the more ecologically valid arena of natural populations. In this article, we highlight the potential of using wild rodents as a new resource for biomedical research, to link the functional genetic knowledge gained from laboratory rodents with the variation in infectious disease susceptibility observed in humans and other natural populations. © 2013 John Wiley & Sons Ltd.

The genetics of normal and defective color vision.

PubMed

Neitz, Jay; Neitz, Maureen

2011-04-13

The contributions of genetics research to the science of normal and defective color vision over the previous few decades are reviewed emphasizing the developments in the 25years since the last anniversary issue of Vision Research. Understanding of the biology underlying color vision has been vaulted forward through the application of the tools of molecular genetics. For all their complexity, the biological processes responsible for color vision are more accessible than for many other neural systems. This is partly because of the wealth of genetic variations that affect color perception, both within and across species, and because components of the color vision system lend themselves to genetic manipulation. Mutations and rearrangements in the genes encoding the long, middle, and short wavelength sensitive cone pigments are responsible for color vision deficiencies and mutations have been identified that affect the number of cone types, the absorption spectra of the pigments, the functionality and viability of the cones, and the topography of the cone mosaic. The addition of an opsin gene, as occurred in the evolution of primate color vision, and has been done in experimental animals can produce expanded color vision capacities and this has provided insight into the underlying neural circuitry. Copyright © 2010 Elsevier Ltd. All rights reserved.

Art meets science: The Cosmopolitan Chicken Research Project.

PubMed

Stinckens, A; Vereijken, A; Ons, E; Konings, P; Van As, P; Cuppens, H; Moreau, Y; Sakai, R; Aerts, J; Goddeeris, B; Buys, N; Vanmechelen, K; Cassiman, J J

2015-01-01

The Cosmopolitan Chicken Project is an artistic undertaking of renowned artist Koen Vanmechelen. In this project, the artist interbreeds domestic chickens from different countries aiming at the creation of a true Cosmopolitan Chicken as a symbol for global diversity. The unifying theme is the chicken and the egg, symbols that link scientific, political, philosophical and ethical issues. The Cosmopolitan Chicken Research Project is the scientific component of this artwork. Based on state of the art genomic techniques, the project studies the effect of the crossing of chickens on the genetic diversity. Also, this research is potentially applicable to the human population. The setup of the CC®P is quite different from traditional breeding experiments: starting from the crossbreed of two purebred chickens (Mechelse Koekoek x Poule de Bresse), every generation is crossed with a few animals from another breed. For 26 of these purebred and crossbred populations, genetic diversity was measured (1) under the assumption that populations were sufficiently large to maintain all informative SNP within a generation and (2) under the circumstances of the CCP breeding experiment. Under the first assumption, a steady increase in genetic diversity was witnessed over the consecutive generations, thus indeed indicating the creation of a "Cosmopolitan Chicken Genome". However, under the conditions of the CCP, which reflects the reality within the human population, diversity is seen to fluctuate within given boundaries instead of steadily increasing. A reflection on this might be that this is because, in humans, an evolutionary optimum in genetic diversity is reached. Key words.

Random sex determination: When developmental noise tips the sex balance.

PubMed

Perrin, Nicolas

2016-12-01

Sex-determining factors are usually assumed to be either genetic or environmental. The present paper aims at drawing attention to the potential contribution of developmental noise, an important but often-neglected component of phenotypic variance. Mutual inhibitions between male and female pathways make sex a bistable equilibrium, such that random fluctuations in the expression of genes at the top of the cascade are sufficient to drive individual development toward one or the other stable state. Evolutionary modeling shows that stochastic sex determinants should resist elimination by genetic or environmental sex determinants under ecologically meaningful settings. On the empirical side, many sex-determination systems traditionally considered as environmental or polygenic actually provide evidence for large components of stochasticity. In reviewing the field, I argue that sex-determination systems should be considered within a three-ends continuum, rather than the classical two-ends continuum. © 2016 WILEY Periodicals, Inc.

Congenital hearing loss

PubMed Central

Korver, Anna M. H.; Smith, Richard J. H.; Van Camp, Guy; Schleiss, Mark R.; Bitner-Glindzicz, Maria A. K.; Lustig, Lawrence R.; Usami, Shin-ichi; Boudewyns, An N.

2017-01-01

Congenital hearing loss (hearing loss present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing-screening programmes enable early detection; early intervention will prevent delays in speech and language development and have long-lasting beneficial effects on social and emotional development and quality of life. A hearing loss diagnosis is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision-making and guide prevention and (genetic) counseling. Management options include specific antimicrobial therapies, surgical treatment of cranio-facial abnormalities and hearing aids. An improved understanding of the pathophysiology and molecular mechanisms underlying hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies. PMID:28079113

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

PubMed

Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Neale, Benjamin M; Davis, Lea K; Gamazon, Eric R; Derks, Eske M; Evans, Patrick; Edlund, Christopher K; Crane, Jacquelyn; Fagerness, Jesen A; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O Joseph; Black, Donald W; Bloch, Michael H; Brentani, Helena; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Campbell, Desmond D; Cappi, Carolina; Silgado, Julio C Cardona; Cavallini, Maria C; Chavira, Denise A; Chouinard, Sylvain; Cook, Edwin H; Cookson, M R; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L; Girard, Simon L; Grabe, Hans J; Grados, Marco A; Greenberg, Benjamin D; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A; Hemmings, Sian M J; Herrera, Luis D; Hezel, Dianne M; Hoekstra, Pieter J; Jankovic, Joseph; Kennedy, James L; King, Robert A; Konkashbaev, Anuar I; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T; Mesa Restrepo, Sandra C; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L; Naarden, Allan L; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A; Pakstis, Andrew J; Pato, Michele T; Pato, Carlos N; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L; Renner, Tobias; Reus, Victor I; Richter, Margaret A; Riddle, Mark A; Robertson, Mary M; Romero, Roxana; Rosário, Maria C; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S; Samuels, Jack; Sandor, Paul; Service, Susan K; Sheppard, Brooke; Singer, Harvey S; Smit, Jan H; Stein, Dan J; Strengman, Eric; Tischfield, Jay A; Turiel, Maurizio; Valencia Duarte, Ana V; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R; Westenberg, Herman G M; Shugart, Yin Yao; Hounie, Ana G; Miguel, Euripedes C; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C; McMahon, William; Posthuma, Danielle; Oostra, Ben A; Nestadt, Gerald; Rouleau, Guy A; Purcell, Shaun; Jenike, Michael A; Heutink, Peter; Hanna, Gregory L; Conti, David V; Arnold, Paul D; Freimer, Nelson B; Stewart, S Evelyn; Knowles, James A; Cox, Nancy J; Pauls, David L

2015-01-01

Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01). Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.

The Brazilian contribution to Attention-Deficit/Hyperactivity Disorder molecular genetics in children and adolescents

PubMed Central

Genro, Júlia Pasqualini; Roman, Tatiana; Rohde, Luis Augusto; Hutz, Mara Helena

2012-01-01

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric condition of children worldwide. This disorder is defined by a combination of symptoms of inattention and hyperactivity/impulsivity. Diagnosis is based on a sufficient number of symptoms causing impairment in these two domains determining several problems in personal and academic life. Although genetic and environmental factors are important in ADHD etiology, how these factors influence the brain and consequently behavior is still under debate. It seems to be consensus that a frontosubcortical dysfunction is responsible, at least in part, for the ADHD phenotype spectrum. The main results from association and pharmacogenetic studies performed in Brazil are discussed. The investigations performed so far on ADHD genetics in Brazil and elsewhere are far from conclusive. New plausible biological hypotheses linked to neurotransmission and neurodevelopment, as well as new analytic approaches are needed to fully disclose the genetic component of the disorder. PMID:23411749

Genetic and environmental melanoma models in fish

PubMed Central

Patton, E Elizabeth; Mitchell, David L; Nairn, Rodney S

2010-01-01

Experimental animal models are extremely valuable for the study of human diseases, especially those with underlying genetic components. The exploitation of various animal models, from fruitflies to mice, has led to major advances in our understanding of the etiologies of many diseases, including cancer. Cutaneous malignant melanoma is a form of cancer for which both environmental insult (i.e., UV) and hereditary predisposition are major causative factors. Fish melanoma models have been used in studies of both spontaneous and induced melanoma formation. Genetic hybrids between platyfish and swordtails, different species of the genus Xiphophorus, have been studied since the 1920s to identify genetic determinants of pigmentation and melanoma formation. Recently, transgenesis has been used to develop zebrafish and medaka models for melanoma research. This review will provide a historical perspective on the use of fish models in melanoma research, and an updated summary of current and prospective studies using these unique experimental systems. PMID:20230482

Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion

PubMed Central

Weaver, Cole A.; Miller, Steven F.; da Fontoura, Clarissa S. G.; Wehby, George L.; Amendt, Brad A.; Holton, Nathan E.; Allareddy, Veeratrishul; Southard, Thomas E.; Moreno Uribe, Lina M.

2017-01-01

Introduction Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes, DUSP6, ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion. Methods Pretreatment dental casts or cone-beam computed tomographic images from 300 healthy subjects were digitized with 48 landmarks. The 3-dimensional coordinate data were submitted to a geometric morphometric approach along with principal component analysis to generate continuous phenotypes including symmetric and asymmetric components of dentoalveolar shape variation, fluctuating asymmetry, and size. The subjects were genotyped for 222 single-nucleotide polymorphisms in 82 genes/loci, and phenotpye-genotype associations were tested via multivariate linear regression. Results Principal component analysis of symmetric variation identified 4 components that explained 68% of the total variance and depicted anteroposterior, vertical, and transverse dentoalveolar discrepancies. Suggestive associations (P < 0.05) were identified with PITX2, SNAI3, 11q22.2-q22.3, 4p16.1, ISL1, and FGF8. Principal component analysis for asymmetric variations identified 4 components that explained 51% of the total variations and captured left-to-right discrepancies resulting in midline deviations, unilateral crossbites, and ectopic eruptions. Suggestive associations were found with TBX1 AJUBA, SNAI3 SATB2, TP63, and 1p22.1. Fluctuating asymmetry was associated with BMP3 and LATS1. Associations for SATB2 and BMP3 with asymmetric variations remained significant after the Bonferroni correction (P <0.00022). Suggestive associations were found for centroid size, a proxy for dentoalveolar size variation with 4p16.1 and SNAI1. Conclusions Specific genetic pathways associated with 3-dimensional dentoalveolar phenotypic variation in malocclusions were identified. PMID:28257739

Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate

PubMed Central

Pineda, David A.; Lopera, Francisco; Puerta, Isabel C.; Trujillo-Orrego, Natalia; Aguirre-Acevedo, Daniel C.; Hincapié-Henao, Liliana; Arango, Clara P.; Acosta, Maria T.; Holzinger, Sandra I.; Palacio, Juan David; Pineda-Alvarez, Daniel E.; Velez, Jorge I.; Martinez, Ariel F.; Lewis, John E.

2014-01-01

Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association. PMID:21779842

The effects of intraspecific competition and stabilizing selection on a polygenic trait.

PubMed Central

Bürger, Reinhard; Gimelfarb, Alexander

2004-01-01

The equilibrium properties of an additive multilocus model of a quantitative trait under frequency- and density-dependent selection are investigated. Two opposing evolutionary forces are assumed to act: (i) stabilizing selection on the trait, which favors genotypes with an intermediate phenotype, and (ii) intraspecific competition mediated by that trait, which favors genotypes whose effect on the trait deviates most from that of the prevailing genotypes. Accordingly, fitnesses of genotypes have a frequency-independent component describing stabilizing selection and a frequency- and density-dependent component modeling competition. We study how the equilibrium structure, in particular, number, degree of polymorphism, and genetic variance of stable equilibria, is affected by the strength of frequency dependence, and what role the number of loci, the amount of recombination, and the demographic parameters play. To this end, we employ a statistical and numerical approach, complemented by analytical results, and explore how the equilibrium properties averaged over a large number of genetic systems with a given number of loci and average amount of recombination depend on the ecological and demographic parameters. We identify two parameter regions with a transitory region in between, in which the equilibrium properties of genetic systems are distinctively different. These regions depend on the strength of frequency dependence relative to pure stabilizing selection and on the demographic parameters, but not on the number of loci or the amount of recombination. We further study the shape of the fitness function observed at equilibrium and the extent to which the dynamics in this model are adaptive, and we present examples of equilibrium distributions of genotypic values under strong frequency dependence. Consequences for the maintenance of genetic variation, the detection of disruptive selection, and models of sympatric speciation are discussed. PMID:15280253

Estimation of genetic parameters and response to selection for a continuous trait subject to culling before testing.

PubMed

Arnason, T; Albertsdóttir, E; Fikse, W F; Eriksson, S; Sigurdsson, A

2012-02-01

The consequences of assuming a zero environmental covariance between a binary trait 'test-status' and a continuous trait on the estimates of genetic parameters by restricted maximum likelihood and Gibbs sampling and on response from genetic selection when the true environmental covariance deviates from zero were studied. Data were simulated for two traits (one that culling was based on and a continuous trait) using the following true parameters, on the underlying scale: h² = 0.4; r(A) = 0.5; r(E) = 0.5, 0.0 or -0.5. The selection on the continuous trait was applied to five subsequent generations where 25 sires and 500 dams produced 1500 offspring per generation. Mass selection was applied in the analysis of the effect on estimation of genetic parameters. Estimated breeding values were used in the study of the effect of genetic selection on response and accuracy. The culling frequency was either 0.5 or 0.8 within each generation. Each of 10 replicates included 7500 records on 'test-status' and 9600 animals in the pedigree file. Results from bivariate analysis showed unbiased estimates of variance components and genetic parameters when true r(E) = 0.0. For r(E) = 0.5, variance components (13-19% bias) and especially (50-80%) were underestimated for the continuous trait, while heritability estimates were unbiased. For r(E) = -0.5, heritability estimates of test-status were unbiased, while genetic variance and heritability of the continuous trait together with were overestimated (25-50%). The bias was larger for the higher culling frequency. Culling always reduced genetic progress from selection, but the genetic progress was found to be robust to the use of wrong parameter values of the true environmental correlation between test-status and the continuous trait. Use of a bivariate linear-linear model reduced bias in genetic evaluations, when data were subject to culling. © 2011 Blackwell Verlag GmbH.

Reaching a Consensus on the Definition of Genetic Literacy that Is Required from a Twenty-First-Century Citizen

NASA Astrophysics Data System (ADS)

Boerwinkel, Dirk Jan; Yarden, Anat; Waarlo, Arend Jan

2017-12-01

To determine what knowledge of genetics is needed for decision-making on genetic-related issues, a consensus-reaching approach was used. An international group of 57 experts, involved in teaching, studying, or developing genetic education and communication or working with genetic applications in medicine, agriculture, or forensics, answered the questions: "What knowledge of genetics is relevant to those individuals not professionally involved in science?" and "Why is this knowledge relevant?" The answers were classified in different knowledge components following the PISA 2015 science framework. During a workshop with the participants, the results were discussed and applied to seven cases in which genetic knowledge is relevant for decision-making. The analysis of these discussions resulted in a revised framework consisting of nine conceptual knowledge components, three sociocultural components, and four epistemic components. The framework can be used in curricular decisions; its open character allows for including new technologies and applications and facilitates comparisons of different cases.

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 of female extra-pair paternity rate in song sparrows (Melospiza melodia)

PubMed Central

Reid, Jane M.; Arcese, Peter; Sardell, Rebecca J.; Keller, Lukas F.

2011-01-01

The forces driving the evolution of extra-pair reproduction in socially monogamous animals remain widely debated and unresolved. One key hypothesis is that female extra-pair reproduction evolves through indirect genetic benefits, reflecting increased additive genetic value of extra-pair offspring. Such evolution requires that a female's propensity to produce offspring that are sired by an extra-pair male is heritable. However, additive genetic variance and heritability in female extra-pair paternity (EPP) rate have not been quantified, precluding accurate estimation of the force of indirect selection. Sixteen years of comprehensive paternity and pedigree data from socially monogamous but genetically polygynandrous song sparrows (Melospiza melodia) showed significant additive genetic variance and heritability in the proportion of a female's offspring that was sired by an extra-pair male, constituting major components of the genetic architecture required for extra-pair reproduction to evolve through indirect additive genetic benefits. However, estimated heritabilities were moderately small (0.12 and 0.18 on the observed and underlying latent scales, respectively). The force of selection on extra-pair reproduction through indirect additive genetic benefits may consequently be relatively weak. However, the additive genetic variance and non-zero heritability observed in female EPP rate allow for multiple further genetic mechanisms to drive and constrain mating system evolution. PMID:20980302

Analytical criteria for performance characteristics of IgE binding methods for evaluating safety of biotech food products.

PubMed

Holzhauser, Thomas; Ree, Ronald van; Poulsen, Lars K; Bannon, Gary A

2008-10-01

There is detailed guidance on how to perform bioinformatic analyses and enzymatic degradation studies for genetically modified crops under consideration for approval by regulatory agencies; however, there is no consensus in the scientific community on the details of how to perform IgE serum studies. IgE serum studies are an important safety component to acceptance of genetically modified crops when the introduced protein is novel, the introduced protein is similar to known allergens, or the crop is allergenic. In this manuscript, we describe the characteristics of the reagents, validation of assay performance, and data analysis necessary to optimize the information obtained from serum testing of novel proteins and genetically modified (GM) crops and to make results more accurate and comparable between different investigations.

Network-assisted crop systems genetics: network inference and integrative analysis.

PubMed

Lee, Tak; Kim, Hyojin; Lee, Insuk

2015-04-01

Although next-generation sequencing (NGS) technology has enabled the decoding of many crop species genomes, most of the underlying genetic components for economically important crop traits remain to be determined. Network approaches have proven useful for the study of the reference plant, Arabidopsis thaliana, and the success of network-based crop genetics will also require the availability of a genome-scale functional networks for crop species. In this review, we discuss how to construct functional networks and elucidate the holistic view of a crop system. The crop gene network then can be used for gene prioritization and the analysis of resequencing-based genome-wide association study (GWAS) data, the amount of which will rapidly grow in the field of crop science in the coming years. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prioritizing the Components of Vulnerability: A Genetic Algorithm Minimization of Flood Risk

NASA Astrophysics Data System (ADS)

Bongolan, Vena Pearl; Ballesteros, Florencio; Baritua, Karessa Alexandra; Junne Santos, Marie

2013-04-01

We define a flood resistant city as an optimal arrangement of communities according to their traits, with the goal of minimizing the flooding vulnerability via a genetic algorithm. We prioritize the different components of flooding vulnerability, giving each component a weight, thus expressing vulnerability as a weighted sum. This serves as the fitness function for the genetic algorithm. We also allowed non-linear interactions among related but independent components, viz, poverty and mortality rate, and literacy and radio/ tv penetration. The designs produced reflect the relative importance of the components, and we observed a synchronicity between the interacting components, giving us a more consistent design.

Circadian Rhythms, Sleep Deprivation, and Human Performance

PubMed Central

Goel, Namni; Basner, Mathias; Rao, Hengyi; Dinges, David F.

2014-01-01

Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep–wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance. Endogenous circadian rhythms in neurobehavioral functions, including physiological alertness and cognitive performance, have been demonstrated using special laboratory protocols that reveal the interaction of the biological clock with the sleep homeostatic drive. Individual differences in circadian rhythms and genetic and other components underlying such differences also influence waking neurobehavioral functions. Both acute total sleep deprivation and chronic sleep restriction increase homeostatic sleep drive and degrade waking neurobehavioral functions as reflected in sleepiness, attention, cognitive speed, and memory. Recent evidence indicating a high degree of stability in neurobehavioral responses to sleep loss suggests that these trait-like individual differences are phenotypic and likely involve genetic components, including circadian genes. Recent experiments have revealed both sleep homeostatic and circadian effects on brain metabolism and neural activation. Investigation of the neural and genetic mechanisms underlying the dynamically complex interaction between sleep homeostasis and circadian systems is beginning. A key goal of this work is to identify biomarkers that accurately predict human performance in situations in which the circadian and sleep homeostatic systems are perturbed. PMID:23899598

Deep-Learning Convolutional Neural Networks Accurately Classify Genetic Mutations in Gliomas.

PubMed

Chang, P; Grinband, J; Weinberg, B D; Bardis, M; Khy, M; Cadena, G; Su, M-Y; Cha, S; Filippi, C G; Bota, D; Baldi, P; Poisson, L M; Jain, R; Chow, D

2018-05-10

The World Health Organization has recently placed new emphasis on the integration of genetic information for gliomas. While tissue sampling remains the criterion standard, noninvasive imaging techniques may provide complimentary insight into clinically relevant genetic mutations. Our aim was to train a convolutional neural network to independently predict underlying molecular genetic mutation status in gliomas with high accuracy and identify the most predictive imaging features for each mutation. MR imaging data and molecular information were retrospectively obtained from The Cancer Imaging Archives for 259 patients with either low- or high-grade gliomas. A convolutional neural network was trained to classify isocitrate dehydrogenase 1 ( IDH1 ) mutation status, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase ( MGMT ) promotor methylation status. Principal component analysis of the final convolutional neural network layer was used to extract the key imaging features critical for successful classification. Classification had high accuracy: IDH1 mutation status, 94%; 1p/19q codeletion, 92%; and MGMT promotor methylation status, 83%. Each genetic category was also associated with distinctive imaging features such as definition of tumor margins, T1 and FLAIR suppression, extent of edema, extent of necrosis, and textural features. Our results indicate that for The Cancer Imaging Archives dataset, machine-learning approaches allow classification of individual genetic mutations of both low- and high-grade gliomas. We show that relevant MR imaging features acquired from an added dimensionality-reduction technique demonstrate that neural networks are capable of learning key imaging components without prior feature selection or human-directed training. © 2018 by American Journal of Neuroradiology.

Genetic linkage analysis of schizophrenia using chromosome 11q13-24 markers in Israeli pedigrees

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

Mulcrone, J.; Marchblanks, R.; Whatley, S.A.

It is generally agreed that there is a genetic component in the etiology of schizophrenia which may be tested by the application of linkage analysis to multiply-affected families. One genetic region of interest is the long arm of chromosome 11 because of previously reported associations of genetic variation in this region with schizophrenia, and because of the fact that it contains the locus for the dopamine D2 receptor gene. In this study we have examined the segregation of schizophrenia with microsatellite dinucleotide repeat DNA markers along chromosome 11q in 5 Israeli families multiply-affected for schizophrenia. The hypothesis of linkage undermore » genetic homogeneity of causation was tested under a number of genetic models. Linkage analysis provided no evidence for significant causal mutations within the region bounded by INT and D11S420 on chromosome 11q. It is still possible, however, that a gene of major effect exists in this region, either with low penetrance or with heterogeneity. 32 refs., 2 figs., 4 tabs.« less

On the validity of within-nuclear-family genetic association analysis in samples of extended families.

PubMed

Bureau, Alexandre; Duchesne, Thierry

2015-12-01

Splitting extended families into their component nuclear families to apply a genetic association method designed for nuclear families is a widespread practice in familial genetic studies. Dependence among genotypes and phenotypes of nuclear families from the same extended family arises because of genetic linkage of the tested marker with a risk variant or because of familial specificity of genetic effects due to gene-environment interaction. This raises concerns about the validity of inference conducted under the assumption of independence of the nuclear families. We indeed prove theoretically that, in a conditional logistic regression analysis applicable to disease cases and their genotyped parents, the naive model-based estimator of the variance of the coefficient estimates underestimates the true variance. However, simulations with realistic effect sizes of risk variants and variation of this effect from family to family reveal that the underestimation is negligible. The simulations also show the greater efficiency of the model-based variance estimator compared to a robust empirical estimator. Our recommendation is therefore, to use the model-based estimator of variance for inference on effects of genetic variants.

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.

Female guppies agree to differ: phenotypic and genetic variation in mate-choice behavior and the consequences for sexual selection.

PubMed

Brooks, R; Endler, J A

2001-08-01

Variation among females in mate choice may influence evolution by sexual selection. The genetic basis of this variation is of interest because the elaboration of mating preferences requires additive genetic variation in these traits. Here we measure the repeatability and heritability of two components of female choosiness (responsiveness and discrimination) and of female preference functions for the multiple ornaments borne by male guppies (Poecilia reticulata). We show that there is significant repeatable variation in both components of choosiness and in some preference functions but not in others. There appear to be several male ornaments that females find uniformly attractive and others for which females differ in preference. One consequence is that there is no universally attractive male phenotype. Only responsiveness shows significant additive genetic variation. Variation in responsiveness appears to mask variation in discrimination and some preference functions and may be the most biologically relevant source of phenotypic and genetic variation in mate-choice behavior. To test the potential evolutionary importance of the phenotypic variation in mate choice that we report, we estimated the opportunity for and the intensity of sexual selection under models of mate choice that excluded and that incorporated individual female variation. We then compared these estimates with estimates based on measured mating success. Incorporating individual variation in mate choice generally did not predict the outcome of sexual selection any better than models that ignored such variation.

Nature vs nurture: are leaders born or made? A behavior genetic investigation of leadership style.

PubMed

Johnson, A M; Vernon, P A; McCarthy, J M; Molson, M; Harris, J A; Jang, K L

1998-12-01

With the recent resurgence in popularity of trait theories of leadership, it is timely to consider the genetic determination of the multiple factors comprising the leadership construct. Individual differences in personality traits have been found to be moderately to highly heritable, and so it follows that if there are reliable personality trait differences between leaders and non-leaders, then there may be a heritable component to these individual differences. Despite this connection between leadership and personality traits, however, there are no studies of the genetic basis of leadership using modern behavior genetic methodology. The present study proposes to address the lack of research in this area by examining the heritability of leadership style, as measured by self-report psychometric inventories. The Multifactor Leadership Questionnaire (MLQ), the Leadership Ability Evaluation, and the Adjective Checklist were completed by 247 adult twin pairs (183 monozygotic and 64 same-sex dizygotic). Results indicated that most of the leadership dimensions examined in this study are heritable, as are two higher level factors (resembling transactional and transformational leadership) derived from an obliquely rotated principal components factors analysis of the MLQ. Univariate analyses suggested that 48% of the variance in transactional leadership may be explained by additive heritability, and 59% of the variance in transformational leadership may be explained by non-additive (dominance) heritability. Multivariate analyses indicated that most of the variables studied shared substantial genetic covariance, suggesting a large overlap in the underlying genes responsible for the leadership dimensions.

Genetic and Environmental Effects on Weight, Height, and BMI Under 18 Years in a Chinese Population-Based Twin Sample.

PubMed

Liu, Qingqing; Yu, Canqing; Gao, Wenjing; Cao, Weihua; Lyu, Jun; Wang, Shengfeng; Pang, Zengchang; Cong, Liming; Dong, Zhong; Wu, Fan; Wang, Hua; Wu, Xianping; Jiang, Guohong; Wang, Binyou; Li, Liming

2015-10-01

This study examined the genetic and environmental effects on variances in weight, height, and body mass index (BMI) under 18 years in a population-based sample from China. We selected 6,644 monozygotic and 5,969 dizygotic twin pairs from the Chinese National Twin Registry (CNTR) aged under 18 years (n = 12,613). Classic twin analyses with sex limitation were used to estimate the genetic and environmental components of weight, height, and BMI in six age groups. Sex-limitation of genetic and shared environmental effects was observed, especially when puberty begins. Heritability for weight, height, and BMI was low at 0-2 years old (less than 20% for both sexes) but increased over time, accounting for half or more of the variance in the 15-17 year age group for boys. For girls, heritabilities for weight, height and BMI was maintained at approximately 30% after puberty. Common environmental effects on all body measures were high for girls (59-87%) and presented a small peak during puberty. Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in the pre-adolescent period and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. Further studies about puberty-related genes and social environment are needed to clarify the mechanism of sex differences.

Roles of vascular and metabolic components in cognitive dysfunction of Alzheimer disease: short- and long-term modification by non-genetic risk factors.

PubMed

Sato, Naoyuki; Morishita, Ryuichi

2013-11-05

It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD). Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of (1) compromised vascular reactivity, (2) vascular lesions, (3) hypo/hyperglycemia, and (4) exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. β-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: (1) functional MRI or SPECT for cerebrovascular reactivity, (2) MRI for ischemic lesions and atrophy, (3) clinical episodes of hypoglycemia and hyperglycemia, (4) amyloid-PET and tau-PET for pathological features of AD, would be required.

Genetic covariance between components of male reproductive success: within-pair vs. extra-pair paternity in song sparrows

PubMed Central

Reid, J M; Arcese, P; Losdat, S

2014-01-01

The evolutionary trajectories of reproductive systems, including both male and female multiple mating and hence polygyny and polyandry, are expected to depend on the additive genetic variances and covariances in and among components of male reproductive success achieved through different reproductive tactics. However, genetic covariances among key components of male reproductive success have not been estimated in wild populations. We used comprehensive paternity data from socially monogamous but genetically polygynandrous song sparrows (Melospiza melodia) to estimate additive genetic variance and covariance in the total number of offspring a male sired per year outside his social pairings (i.e. his total extra-pair reproductive success achieved through multiple mating) and his liability to sire offspring produced by his socially paired female (i.e. his success in defending within-pair paternity). Both components of male fitness showed nonzero additive genetic variance, and the estimated genetic covariance was positive, implying that males with high additive genetic value for extra-pair reproduction also have high additive genetic propensity to sire their socially paired female's offspring. There was consequently no evidence of a genetic or phenotypic trade-off between male within-pair paternity success and extra-pair reproductive success. Such positive genetic covariance might be expected to facilitate ongoing evolution of polygyny and could also shape the ongoing evolution of polyandry through indirect selection. PMID:25186454

Genetic architecture of male sterility and segregation distortion in Drosophila pseudoobscura Bogota-USA hybrids.

PubMed

Phadnis, Nitin

2011-11-01

Understanding the genetic basis of reproductive isolation between recently diverged species is a central problem in evolutionary genetics. Here, I present analyses of the genetic architecture underlying hybrid male sterility and segregation distortion between the Bogota and USA subspecies of Drosophila pseudoobscura. Previously, a single gene, Overdrive (Ovd), was shown to be necessary but not sufficient for both male sterility and segregation distortion in F(1) hybrids between these subspecies, requiring several interacting partner loci for full manifestation of hybrid phenomena. I map these partner loci separately on the Bogota X chromosome and USA autosomes using a combination of different mapping strategies. I find that hybrid sterility involves a single hybrid incompatibility of at least seven interacting partner genes that includes three large-effect loci. Segregation distortion involves three loci on the Bogota X chromosome and one locus on the autosomes. The genetic bases of hybrid sterility and segregation distortion are at least partially--but not completely--overlapping. My results lay the foundation for fine-mapping experiments to identify the complete set of genes that interact with Overdrive. While individual genes that cause hybrid sterility or inviability have been identified in a few cases, my analysis provides a comprehensive look at the genetic architecture of all components of a hybrid incompatibility underlying F(1) hybrid sterility. Such an analysis would likely be unfeasible for most species pairs due to their divergence time and emphasizes the importance of young species pairs such as the D. pseudoobscura subspecies studied here.

Genetic information and ecosystem health: arguments for the application of chaos theory to identify boundary conditions for ecosystem management.

PubMed Central

Stomp, A M

1994-01-01

To meet the demands for goods and services of an exponentially growing human population, global ecosystems will come under increasing human management. The hallmark of successful ecosystem management will be long-term ecosystem stability. Ecosystems and the genetic information and processes which underlie interactions of organisms with the environment in populations and communities exhibit behaviors which have nonlinear characteristics. Nonlinear mathematical formulations describing deterministic chaos have been used successfully to model such systems in physics, chemistry, economics, physiology, and epidemiology. This approach can be extended to ecotoxicology and can be used to investigate how changes in genetic information determine the behavior of populations and communities. This article seeks to provide the arguments for such an approach and to give initial direction to the search for the boundary conditions within which lies ecosystem stability. The identification of a theoretical framework for ecotoxicology and the parameters which drive the underlying model is a critical component in the formulation of a prioritized research agenda and appropriate ecosystem management policy and regulation. PMID:7713038

A genetic survey of Salvinia minima in the southern United States

USGS Publications Warehouse

Madeira, Paul T.; Jacono, C.C.; Tipping, Phil; Van, Thai K.; Center, Ted D.

2003-01-01

The genetic relationships among 68 samples of Salvinia minima (Salviniaceae) were investigated using RAPD analysis. Neighbor joining, principle components, and AMOVA analyses were used to detect differences among geographically referenced samples within and outside of Florida. Genetic distances (Nei and Li) range up to 0.48, although most are under 0.30, still relatively high levels for an introduced, clonally reproducing plant. Despite the diversity AMOVA analysis yielded no indication that the Florida plants, as a group, were significantly different from the plants sampled elsewhere in its adventive, North American range. A single, genetically dissimilar population probably exists in the recent (1998) horticultural introduction to Mississippi. When the samples were grouped into 10 regional (but artificial) units and analyzed using AMOVA the between region variance was only 7.7%. Genetic similarity among these regions may indicate introduction and dispersal from common sources. The reduced aggressiveness of Florida populations (compared to other states) may be due to herbivory. The weevil Cyrtobagous salviniae, a selective feeder, is found in Florida but not other states. The genetic similarity also suggests that there are no obvious genetic obstacles to the establishment or efficacy of C. salviniae as a biological control agent on S. minima outside of Florida.

Silencing Nicotiana attenuata LHY and ZTL alters circadian rhythms in flowers

PubMed Central

Yon, Felipe; Joo, Youngsung; Cortés Llorca, Lucas; Rothe, Eva; Baldwin, Ian T.; Kim, Sang-Gyu

2016-01-01

Summary The rhythmic opening/closing and volatile emissions of flowers is known to attract pollinators at specific times. That these rhythms are maintained under constant light or dark conditions suggests a circadian clock involvement. Although a forward and reverse genetic approach led to the identification of core circadian clock components in Arabidopsis thaliana, involvement of these clock components for floral rhythms remained untested likely due to weak diurnal rhythms in A. thaliana flowers.Here we addressed the role of these core clock components in the flowers of the wild tobacco Nicotiana attenuata, whose flowers open at night, emit benzyl acetone (BA) scents, and move vertically through a 140° arc.We first measured N. attenuata floral rhythms under constant light conditions. The results suggest that the circadian clock controls flower opening, BA emission, and pedicel movement, but not flower closing.We generated transgenic N. attenuata lines silenced in the homologous genes of Arabidopsis LATE ELONGATED HYPOCOTYL (LHY) and ZEITLUPE (ZTL), which are known as a core clock component. Silencing NaLHY and NaZTL strongly altered floral rhythms in different ways, indicating that conserved clock components in N. attenuata coordinate these floral rhythms. PMID:26439540

The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project.

PubMed

Blokland, Gabriëlla A M; Del Re, Elisabetta C; Mesholam-Gately, Raquelle I; Jovicich, Jorge; Trampush, Joey W; Keshavan, Matcheri S; DeLisi, Lynn E; Walters, James T R; Turner, Jessica A; Malhotra, Anil K; Lencz, Todd; Shenton, Martha E; Voineskos, Aristotle N; Rujescu, Dan; Giegling, Ina; Kahn, René S; Roffman, Joshua L; Holt, Daphne J; Ehrlich, Stefan; Kikinis, Zora; Dazzan, Paola; Murray, Robin M; Di Forti, Marta; Lee, Jimmy; Sim, Kang; Lam, Max; Wolthusen, Rick P F; de Zwarte, Sonja M C; Walton, Esther; Cosgrove, Donna; Kelly, Sinead; Maleki, Nasim; Osiecki, Lisa; Picchioni, Marco M; Bramon, Elvira; Russo, Manuela; David, Anthony S; Mondelli, Valeria; Reinders, Antje A T S; Falcone, M Aurora; Hartmann, Annette M; Konte, Bettina; Morris, Derek W; Gill, Michael; Corvin, Aiden P; Cahn, Wiepke; Ho, New Fei; Liu, Jian Jun; Keefe, Richard S E; Gollub, Randy L; Manoach, Dara S; Calhoun, Vince D; Schulz, S Charles; Sponheim, Scott R; Goff, Donald C; Buka, Stephen L; Cherkerzian, Sara; Thermenos, Heidi W; Kubicki, Marek; Nestor, Paul G; Dickie, Erin W; Vassos, Evangelos; Ciufolini, Simone; Reis Marques, Tiago; Crossley, Nicolas A; Purcell, Shaun M; Smoller, Jordan W; van Haren, Neeltje E M; Toulopoulou, Timothea; Donohoe, Gary; Goldstein, Jill M; Seidman, Larry J; McCarley, Robert W; Petryshen, Tracey L

2018-05-01

Schizophrenia has a large genetic component, and the pathways from genes to illness manifestation are beginning to be identified. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) Consortium aims to clarify the role of genetic variation in brain abnormalities underlying schizophrenia. This article describes the GENUS Consortium sample collection. We identified existing samples collected for schizophrenia studies consisting of patients, controls, and/or individuals at familial high-risk (FHR) for schizophrenia. Samples had single nucleotide polymorphism (SNP) array data or genomic DNA, clinical and demographic data, and neuropsychological and/or brain magnetic resonance imaging (MRI) data. Data were subjected to quality control procedures at a central site. Sixteen research groups contributed data from 5199 psychosis patients, 4877 controls, and 725 FHR individuals. All participants have relevant demographic data and all patients have relevant clinical data. The sex ratio is 56.5% male and 43.5% female. Significant differences exist between diagnostic groups for premorbid and current IQ (both p<1×10 -10 ). Data from a diversity of neuropsychological tests are available for 92% of participants, and 30% have structural MRI scans (half also have diffusion-weighted MRI scans). SNP data are available for 76% of participants. The ancestry composition is 70% European, 20% East Asian, 7% African, and 3% other. The Consortium is investigating the genetic contribution to brain phenotypes in a schizophrenia sample collection of >10,000 participants. The breadth of data across clinical, genetic, neuropsychological, and MRI modalities provides an important opportunity for elucidating the genetic basis of neural processes underlying schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

An integrated multi-layered analysis of the metabolic networks of different tissues uncovers key genetic components of primary metabolism in maize.

PubMed

Wen, Weiwei; Jin, Min; Li, Kun; Liu, Haijun; Xiao, Yingjie; Zhao, Mingchao; Alseekh, Saleh; Li, Wenqiang; de Abreu E Lima, Francisco; Brotman, Yariv; Willmitzer, Lothar; Fernie, Alisdair R; Yan, Jianbing

2018-03-01

Primary metabolism plays a pivotal role in normal plant growth, development and reproduction. As maize is a major crop worldwide, the primary metabolites produced by maize plants are of immense importance from both calorific and nutritional perspectives. Here a genome-wide association study (GWAS) of 61 primary metabolites using a maize association panel containing 513 inbred lines identified 153 significant loci associated with the level of these metabolites in four independent tissues. The genome-wide expression level of 760 genes was also linked with metabolite levels within the same tissue. On average, the genetic variants at each locus or transcriptional variance of each gene identified here were estimated to have a minor effect (4.4-7.8%) on primary metabolic variation. Thirty-six loci or genes were prioritized as being worthy of future investigation, either with regard to functional characterization or for their utility for genetic improvement. This target list includes the well-known opaque 2 (O2) and lkr/sdh genes as well as many less well-characterized genes. During our investigation of these 36 loci, we analyzed the genetic components and variations underlying the trehalose, aspartate and aromatic amino acid pathways, thereby functionally characterizing four genes involved in primary metabolism in maize. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Analysis of conditional genetic effects and variance components in developmental genetics.

PubMed

Zhu, J

1995-12-01

A genetic model with additive-dominance effects and genotype x environment interactions is presented for quantitative traits with time-dependent measures. The genetic model for phenotypic means at time t conditional on phenotypic means measured at previous time (t-1) is defined. Statistical methods are proposed for analyzing conditional genetic effects and conditional genetic variance components. Conditional variances can be estimated by minimum norm quadratic unbiased estimation (MINQUE) method. An adjusted unbiased prediction (AUP) procedure is suggested for predicting conditional genetic effects. A worked example from cotton fruiting data is given for comparison of unconditional and conditional genetic variances and additive effects.

Analysis of Conditional Genetic Effects and Variance Components in Developmental Genetics

PubMed Central

Zhu, J.

1995-01-01

A genetic model with additive-dominance effects and genotype X environment interactions is presented for quantitative traits with time-dependent measures. The genetic model for phenotypic means at time t conditional on phenotypic means measured at previous time (t - 1) is defined. Statistical methods are proposed for analyzing conditional genetic effects and conditional genetic variance components. Conditional variances can be estimated by minimum norm quadratic unbiased estimation (MINQUE) method. An adjusted unbiased prediction (AUP) procedure is suggested for predicting conditional genetic effects. A worked example from cotton fruiting data is given for comparison of unconditional and conditional genetic variances and additive effects. PMID:8601500

Social neuroscience and its potential contribution to psychiatry

PubMed Central

Cacioppo, John T; Cacioppo, Stephanie; Dulawa, Stephanie; Palmer, Abraham A

2014-01-01

Most mental disorders involve disruptions of normal social behavior. Social neuroscience is an interdisciplinary field devoted to understanding the biological systems underlying social processes and behavior, and the influence of the social environment on biological processes, health and well-being. Research in this field has grown dramatically in recent years. Active areas of research include brain imaging studies in normal children and adults, animal models of social behavior, studies of stroke patients, imaging studies of psychiatric patients, and research on social determinants of peripheral neural, neuroendocrine and immunological processes. Although research in these areas is proceeding along largely independent trajectories, there is increasing evidence for connections across these trajectories. We focus here on the progress and potential of social neuroscience in psychiatry, including illustrative evidence for a rapid growth of neuroimaging and genetic studies of mental disorders. We also argue that neuroimaging and genetic research focused on specific component processes underlying social living is needed. PMID:24890058

Combining genetic and physiological data to identify predictors of lifetime reproductive success and the effect of selection on these predictors on underlying fertility traits.

PubMed

Dennis, N A; Stachowicz, K; Visser, B; Hely, F S; Berg, D K; Friggens, N C; Amer, P R; Meier, S; Burke, C R

2018-04-01

Fertility of the dairy cow relies on complex interactions between genetics, physiology, and management. Mathematical modeling can combine a range of information sources to facilitate informed predictions of cow fertility in scenarios that are difficult to evaluate empirically. We have developed a stochastic model that incorporates genetic and physiological data from more than 70 published reports on a wide range of fertility-related traits in dairy cattle. The model simulates pedigree, random mating, genetically correlated traits (in the form of breeding values for traits such as hours in estrus, estrous cycle length, age at puberty, milk yield, and so on), and interacting environmental variables. This model was used to generate a large simulated data set (200,000 cows replicated 100 times) of herd records within a seasonal dairy production system (based on an average New Zealand system). Using these simulated data, we investigated the genetic component of lifetime reproductive success (LRS), which, in reality, would be impractical to assess empirically. We defined LRS as the total number of times, during her lifetime, a cow calved within the first 42 d of the calving season. Sire estimated breeding values for LRS and other traits were calculated using simulated daughter records. Daughter pregnancy rate in the first lactation (PD_1) was the strongest single predictor of a sire's genetic merit for LRS (R 2 = 0.81). A simple predictive model containing PD_1, calving date for the second season and calving rate in the first season provided a good estimate of sire LRS (R 2 = 0.97). Daughters from sires with extremely high (n = 99,995 daughters, sire LRS = +0.70) or low (n = 99,635 daughters, sire LRS = -0.73) LRS estimated breeding values were compared over a single generation. Of the 14 underlying component traits of fertility, 12 were divergent between the 2 lines. This suggests that genetic variation in female fertility has a complex and multifactorial genetic basis. When simulated phenotypes were compared, daughters of the high LRS sires (HiFERT) reached puberty 44.5 d younger and calved ∼14 d younger at each parity than daughters from low LRS sires (LoFERT). Despite having a much lower genetic potential for milk production (-400 L/lactation) than LoFERT cows, HiFERT cows produced 33% more milk over their lifetime due to additional lactations before culling. In summary, this simulation model suggests that LRS contributes substantially to cow productivity, and novel selection criteria would facilitate a more accurate prediction at a younger age. The Authors. Published by FASS Inc. 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/).

Application of molecular genetic tools for forest pathology

Treesearch

Mee-Sook Kim; John Hanna; Amy Ross-Davis; Ned Klopfenstein

2012-01-01

In recent years, advances in molecular genetics have provided powerful tools to address critical issues in forest pathology to help promote resilient forests. Although molecular genetic tools are initially applied to understand individual components of forest pathosystems, forest pathosystems involve dynamic interactions among biotic and abiotic components of the...

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

Eye growth and myopia development: Unifying theory and Matlab model.

PubMed

Hung, George K; Mahadas, Kausalendra; Mohammad, Faisal

2016-03-01

The aim of this article is to present an updated unifying theory of the mechanisms underlying eye growth and myopia development. A series of model simulation programs were developed to illustrate the mechanism of eye growth regulation and myopia development. Two fundamental processes are presumed to govern the relationship between physiological optics and eye growth: genetically pre-programmed signaling and blur feedback. Cornea/lens is considered to have only a genetically pre-programmed component, whereas eye growth is considered to have both a genetically pre-programmed and a blur feedback component. Moreover, based on the Incremental Retinal-Defocus Theory (IRDT), the rate of change of blur size provides the direction for blur-driven regulation. The various factors affecting eye growth are shown in 5 simulations: (1 - unregulated eye growth): blur feedback is rendered ineffective, as in the case of form deprivation, so there is only genetically pre-programmed eye growth, generally resulting in myopia; (2 - regulated eye growth): blur feedback regulation demonstrates the emmetropization process, with abnormally excessive or reduced eye growth leading to myopia and hyperopia, respectively; (3 - repeated near-far viewing): simulation of large-to-small change in blur size as seen in the accommodative stimulus/response function, and via IRDT as well as nearwork-induced transient myopia (NITM), leading to the development of myopia; (4 - neurochemical bulk flow and diffusion): release of dopamine from the inner plexiform layer of the retina, and the subsequent diffusion and relay of neurochemical cascade show that a decrease in dopamine results in a reduction of proteoglycan synthesis rate, which leads to myopia; (5 - Simulink model): model of genetically pre-programmed signaling and blur feedback components that allows for different input functions to simulate experimental manipulations that result in hyperopia, emmetropia, and myopia. These model simulation programs (available upon request) can provide a useful tutorial for the general scientist and serve as a quantitative tool for researchers in eye growth and myopia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection

PubMed Central

Lambros, Maryou B; Campion-Flora, Adriana; Rodrigues, Daniel Nava; Gauthier, Arnaud; Cabral, Cecilia; Pawar, Vidya; Mackay, Alan; A’Hern, Roger; Marchiò, Caterina; Palacios, Jose; Natrajan, Rachael; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCIS and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDCs were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridisation (aCGH), and Sequenom MassARRAY (Oncocarta v1.0 panel). Fluorescence in situ hybridisation and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCIS and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (i.e. 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case, the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations. PMID:22252965

Translating effects of inbreeding depression on component vital rates to overall population growth in endangered bighorn sheep.

PubMed

Johnson, Heather E; Mills, L Scott; Wehausen, John D; Stephenson, Thomas R; Luikart, Gordon

2011-12-01

Evidence of inbreeding depression is commonly detected from the fitness traits of animals, yet its effects on population growth rates of endangered species are rarely assessed. We examined whether inbreeding depression was affecting Sierra Nevada bighorn sheep (Ovis canadensis sierrae), a subspecies listed as endangered under the U.S. Endangered Species Act. Our objectives were to characterize genetic variation in this subspecies; test whether inbreeding depression affects bighorn sheep vital rates (adult survival and female fecundity); evaluate whether inbreeding depression may limit subspecies recovery; and examine the potential for genetic management to increase population growth rates. Genetic variation in 4 populations of Sierra Nevada bighorn sheep was among the lowest reported for any wild bighorn sheep population, and our results suggest that inbreeding depression has reduced adult female fecundity. Despite this population sizes and growth rates predicted from matrix-based projection models demonstrated that inbreeding depression would not substantially inhibit the recovery of Sierra Nevada bighorn sheep populations in the next approximately 8 bighorn sheep generations (48 years). Furthermore, simulations of genetic rescue within the subspecies did not suggest that such activities would appreciably increase population sizes or growth rates during the period we modeled (10 bighorn sheep generations, 60 years). Only simulations that augmented the Mono Basin population with genetic variation from other subspecies, which is not currently a management option, predicted significant increases in population size. Although we recommend that recovery activities should minimize future losses of genetic variation, genetic effects within these endangered populations-either negative (inbreeding depression) or positive (within subspecies genetic rescue)-appear unlikely to dramatically compromise or stimulate short-term conservation efforts. The distinction between detecting the effects of inbreeding depression on a component vital rate (e.g., fecundity) and the effects of inbreeding depression on population growth underscores the importance of quantifying inbreeding costs relative to population dynamics to effectively manage endangered populations. ©2011 Society for Conservation Biology.

Gene-by-environment interactions that disrupt mitochondrial homeostasis cause neurodegeneration in C. elegans Parkinson's models.

PubMed

Kim, Hanna; Perentis, Rylee J; Caldwell, Guy A; Caldwell, Kim A

2018-05-10

Parkinson's disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons. Initial characterization of this environmental factor indicated that neurodegeneration occurs through a combination of oxidative stress, mitochondrial complex I impairment, and proteostatic disruption. Here we present extended evidence to elucidate the interaction between this bacterial metabolite and mitochondrial dysfunction in the development of DA neurodegeneration. We demonstrate that it causes a time-dependent increase in mitochondrial fragmentation through concomitant changes in the gene expression of mitochondrial fission and fusion components. In particular, the outer mitochondrial membrane fission and fusion genes, drp-1 (a dynamin-related GTPase) and fzo-1 (a mitofusin homolog), are up- and down-regulated, respectively. Additionally, eat-3, an inner mitochondrial membrane fusion component, an OPA1 homolog, is also down regulated. These changes are associated with a metabolite-induced decline in mitochondrial membrane potential and enhanced DA neurodegeneration that is dependent on PINK-1 function. Genetic analysis also indicates an association between the cell death pathway and drp-1 following S. ven exposure. Metabolite-induced neurotoxicity can be suppressed by DA-neuron-specific RNAi knockdown of eat-3. AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) ameliorated metabolite- or PINK-1-induced neurotoxicity; however, it enhanced neurotoxicity under normal conditions. These studies underscore the critical role of mitochondrial dynamics in DA neurodegeneration. Moreover, given the largely undefined environmental components of PD etiology, these results highlight a response to an environmental factor that defines distinct mechanisms underlying a potential contributor to the progressive DA neurodegeneration observed in PD.

Encephaloceles

MedlinePlus

... and seizures. Some affected children may have normal intelligence. There is a genetic component to the condition; ... and seizures. Some affected children may have normal intelligence. There is a genetic component to the condition; ...

Polygenic influences on dyslipidemias.

PubMed

Dron, Jacqueline S; Hegele, Robert A

2018-04-01

Rare large-effect genetic variants underlie monogenic dyslipidemias, whereas common small-effect genetic variants - single nucleotide polymorphisms (SNPs) - have modest influences on lipid traits. Over the past decade, these small-effect SNPs have been shown to cumulatively exert consistent effects on lipid phenotypes under a polygenic framework, which is the focus of this review. Several groups have reported polygenic risk scores assembled from lipid-associated SNPs, and have applied them to their respective phenotypes. For lipid traits in the normal population distribution, polygenic effects quantified by a score that integrates several common polymorphisms account for about 20-30% of genetic variation. Among individuals at the extremes of the distribution, that is, those with clinical dyslipidemia, the polygenic component includes both rare variants with large effects and common polymorphisms: depending on the trait, 20-50% of susceptibility can be accounted for by this assortment of genetic variants. Accounting for polygenic effects increases the numbers of dyslipidemic individuals who can be explained genetically, but a substantial proportion of susceptibility remains unexplained. Whether documenting the polygenic basis of dyslipidemia will affect outcomes in clinical trials or prospective observational studies remains to be determined.

Mate choice theory and the mode of selection in sexual populations.

PubMed

Carson, Hampton L

2003-05-27

Indirect new data imply that mate and/or gamete choice are major selective forces driving genetic change in sexual populations. The system dictates nonrandom mating, an evolutionary process requiring both revised genetic theory and new data on heritability of characters underlying Darwinian fitness. Successfully reproducing individuals represent rare selections from among vigorous, competing survivors of preadult natural selection. Nonrandom mating has correlated demographic effects: reduced effective population size, inbreeding, low gene flow, and emphasis on deme structure. Characters involved in choice behavior at reproduction appear based on quantitative trait loci. This variability serves selection for fitness within the population, having only an incidental relationship to the origin of genetically based reproductive isolation between populations. The claim that extensive hybridization experiments with Drosophila indicate that selection favors a gradual progression of "isolating mechanisms" is flawed, because intra-group random mating is assumed. Over deep time, local sexual populations are strong, independent genetic systems that use rich fields of variable polygenic components of fitness. The sexual reproduction system thus particularizes, in small subspecific populations, the genetic basis of the grand adaptive sweep of selective evolutionary change, much as Darwin proposed.

Heritability of Attractiveness to Mosquitoes

PubMed Central

Fernández-Grandon, G. Mandela; Gezan, Salvador A.; Armour, John A. L.; Pickett, John A.; Logan, James G.

2015-01-01

Female mosquitoes display preferences for certain individuals over others, which is determined by differences in volatile chemicals produced by the human body and detected by mosquitoes. Body odour can be controlled genetically but the existence of a genetic basis for differential attraction to insects has never been formally demonstrated. This study investigated heritability of attractiveness to mosquitoes by evaluating the response of Aedes aegypti (=Stegomyia aegypti) mosquitoes to odours from the hands of identical and non-identical twins in a dual-choice assay. Volatiles from individuals in an identical twin pair showed a high correlation in attractiveness to mosquitoes, while non-identical twin pairs showed a significantly lower correlation. Overall, there was a strong narrow-sense heritability of 0.62 (SE 0.124) for relative attraction and 0.67 (0.354) for flight activity based on the average of ten measurements. The results demonstrate an underlying genetic component detectable by mosquitoes through olfaction. Understanding the genetic basis for attractiveness could create a more informed approach to repellent development. PMID:25901606

Selection and constraints on offspring size-number trade-offs in sand lizards (Lacerta agilis).

PubMed

Ljungström, G; Stjernstedt, M; Wapstra, E; Olsson, M

2016-05-01

The trade-off between offspring size and number is a central component of life-history theory, postulating that larger investment into offspring size inevitably decreases offspring number. This trade-off is generally discussed in terms of genetic, physiological or morphological constraints; however, as among-individual differences can mask individual trade-offs, the underlying mechanisms may be difficult to reveal. In this study, we use multivariate analyses to investigate whether there is a trade-off between offspring size and number in a population of sand lizards by separating among- and within-individual patterns using a 15-year data set collected in the wild. We also explore the ecological and evolutionary causes and consequences of this trade-off by investigating how a female's resource (condition)- vs. age-related size (snout-vent length) influences her investment into offspring size vs. number (OSN), whether these traits are heritable and under selection and whether the OSN trade-off has a genetic component. We found a negative correlation between offspring size and number within individual females and physical constraints (size of body cavity) appear to limit the number of eggs that a female can produce. This suggests that the OSN trade-off occurs due to resource constraints as a female continues to grow throughout life and, thus, produces larger clutches. In contrast to the assumptions of classic OSN theory, we did not detect selection on offspring size; however, there was directional selection for larger clutch sizes. The repeatabilities of both offspring size and number were low and we did not detect any additive genetic variance in either trait. This could be due to strong selection (past or current) on these life-history traits, or to insufficient statistical power to detect significant additive genetic effects. Overall, the findings of this study are an important illustration of how analyses of within-individual patterns can reveal trade-offs and their underlying causes, with potential evolutionary and ecological consequences that are otherwise hidden by among-individual variation. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

The genetic pleiotropy of musculoskeletal aging

PubMed Central

Karasik, David; Cohen-Zinder, Miri

2012-01-01

Musculoskeletal aging is detrimental to multiple bodily functions and starts early, probably in the fourth decade of an individual's life. Sarcopenia is a health problem that is expected to only increase as a greater portion of the population lives longer; prevalence of the related musculoskeletal diseases is similarly expected to increase. Unraveling the biological and biomechanical associations and molecular mechanisms underlying these diseases represents a formidable challenge. There are two major problems making disentangling the biological complexity of musculoskeletal aging difficult: (a) it is a systemic, rather than “compartmental,” problem, which should be approached accordingly, and (b) the aging per se is neither well defined nor reliably measurable. A unique challenge of studying any age-related condition is a need of distinguishing between the “norm” and “pathology,” which are interwoven throughout the aging organism. We argue that detecting genes with pleiotropic functions in musculoskeletal aging is needed to provide insights into the potential biological mechanisms underlying inter-individual differences insusceptibility to the musculoskeletal diseases. However, exploring pleiotropic relationships among the system's components is challenging both methodologically and conceptually. We aimed to focus on genetic aspects of the cross-talk between muscle and its “neighboring” tissues and organs (tendon, bone, and cartilage), and to explore the role of genetics to find the new molecular links between skeletal muscle and other parts of the “musculoskeleton.” Identification of significant genetic variants underlying the musculoskeletal system's aging is now possible more than ever due to the currently available advanced genomic technologies. In summary, a “holistic” genetic approach is needed to study the systems's normal functioning and the disease predisposition in order to improve musculoskeletal health. PMID:22934054

Time scale matters: genetic analysis does not support adaptation-by-time as the mechanism for adaptive seasonal declines in kokanee reproductive life span

PubMed Central

Morbey, Yolanda E; Jensen, Evelyn L; Russello, Michael A

2014-01-01

Seasonal declines of fitness-related traits are often attributed to environmental effects or individual-level decisions about reproductive timing and effort, but genetic variation may also play a role. In populations of Pacific salmon (Oncorhynchus spp.), seasonal declines in reproductive life span have been attributed to adaptation-by-time, in which divergent selection for different traits occurs among reproductively isolated temporal components of a population. We evaluated this hypothesis in kokanee (freshwater obligate Oncorhynchus nerka) by testing for temporal genetic structure in neutral and circadian-linked loci. We detected no genetic differences in presumably neutral loci among kokanee with different arrival and maturation dates within a spawning season. Similarly, we detected no temporal genetic structure in OtsClock1b, Omy1009uw, or OmyFbxw11, candidate loci associated with circadian function. The genetic evidence from this study and others indicates a lack of support for adaptation-by-time as an important evolutionary mechanism underlying seasonal declines in reproductive life span and a need for greater consideration of other mechanisms such as time-dependent, adaptive adjustment of reproductive effort. PMID:25478160

Hereditary melanoma and predictive genetic testing: why not?

PubMed

Riedijk, S R; de Snoo, F A; van Dijk, S; Bergman, W; van Haeringen, A; Silberg, S; van Elderen, T M T; Tibben, A

2005-09-01

Since p16-Leiden presymptomatic testing for hereditary melanoma has become available in the Netherlands, the benefits and risks of offering such testing are evaluated. The current paper investigated why the non-participants were reluctant to participate in genetic testing. Sixty six eligible individuals, who were knowledgeable about the test but had not participated in genetic testing by January 2003, completed a self-report questionnaire assessing motivation, anxiety, family dynamics, risk knowledge and causal attributions. Non-participants reported anxiety levels below clinical significance. A principal components analysis on reasons for non-participation distinguished two underlying motives: emotional and rational motivation. Rational motivation for non-participation was associated with more accurate risk knowledge, the inclination to preselect mutation carriers within the family and lower scores on anxiety. Emotional motivation for non-participation was associated with disease misperceptions, hesitation to communicate unfavourable test results within the family and higher scores on anxiety. Rational and emotional motivation for non-participation in the genetic test for hereditary melanoma was found. Emotionally motivated individuals may be reluctant to disseminate genetic risk information. Rationally motivated individuals were better informed than emotionally motivated individuals. It is suggested that a leaflet is added to the invitation letter to enhance informed decision-making about genetic testing.

Human genetics as a tool to identify progranulin regulators.

PubMed

Nicholson, Alexandra M; Finch, NiCole A; Rademakers, Rosa

2011-11-01

Frontotemporal lobar degeneration (FTLD) is a common neurodegenerative disorder that predominantly affects individuals under the age of 65. It is known that the most common pathological subtype is FTLD with TAR DNA-binding protein 43 inclusions (FTLD-TDP). FTLD has a strong genetic component with about 50% of cases having a positive family history. Mutations identified in the progranulin gene (GRN) have been shown to cause FTLD-TDP as a result of progranulin haploinsufficiency. These findings suggest a progranulin-dependent mechanism in this pathological FTLD subtype. Thus, identifying regulators of progranulin levels is essential for new therapies and treatments for FTLD and related disorders. In this review, we discuss the role of genetic studies in identifying progranulin regulators, beginning with the discovery of pathogenic GRN mutations and additional GRN risk variants. We also cover more recent genetic advances, including the detection of variants in the transmembrane protein 106 B gene that increase FTLD-TDP risk presumably by modulating progranulin levels and the identification of a potential progranulin receptor, sortilin. This review highlights the importance of genetic studies in the context of FTLD and further emphasizes the need for future genetic and cell biology research to continue the effort in finding a cure for progranulin-related diseases.

Genetic Architecture of Male Sterility and Segregation Distortion in Drosophila pseudoobscura Bogota–USA Hybrids

PubMed Central

Phadnis, Nitin

2011-01-01

Understanding the genetic basis of reproductive isolation between recently diverged species is a central problem in evolutionary genetics. Here, I present analyses of the genetic architecture underlying hybrid male sterility and segregation distortion between the Bogota and USA subspecies of Drosophila pseudoobscura. Previously, a single gene, Overdrive (Ovd), was shown to be necessary but not sufficient for both male sterility and segregation distortion in F1 hybrids between these subspecies, requiring several interacting partner loci for full manifestation of hybrid phenomena. I map these partner loci separately on the Bogota X chromosome and USA autosomes using a combination of different mapping strategies. I find that hybrid sterility involves a single hybrid incompatibility of at least seven interacting partner genes that includes three large-effect loci. Segregation distortion involves three loci on the Bogota X chromosome and one locus on the autosomes. The genetic bases of hybrid sterility and segregation distortion are at least partially—but not completely—overlapping. My results lay the foundation for fine-mapping experiments to identify the complete set of genes that interact with Overdrive. While individual genes that cause hybrid sterility or inviability have been identified in a few cases, my analysis provides a comprehensive look at the genetic architecture of all components of a hybrid incompatibility underlying F1 hybrid sterility. Such an analysis would likely be unfeasible for most species pairs due to their divergence time and emphasizes the importance of young species pairs such as the D. pseudoobscura subspecies studied here. PMID:21900263

Panmictic and Clonal Evolution on a Single Patchy Resource Produces Polymorphic Foraging Guilds

PubMed Central

Getz, Wayne M.; Salter, Richard; Lyons, Andrew J.; Sippl-Swezey, Nicolas

2015-01-01

We develop a stochastic, agent-based model to study how genetic traits and experiential changes in the state of agents and available resources influence individuals’ foraging and movement behaviors. These behaviors are manifest as decisions on when to stay and exploit a current resource patch or move to a particular neighboring patch, based on information of the resource qualities of the patches and the anticipated level of intraspecific competition within patches. We use a genetic algorithm approach and an individual’s biomass as a fitness surrogate to explore the foraging strategy diversity of evolving guilds under clonal versus hermaphroditic sexual reproduction. We first present the resource exploitation processes, movement on cellular arrays, and genetic algorithm components of the model. We then discuss their implementation on the Nova software platform. This platform seamlessly combines the dynamical systems modeling of consumer-resource interactions with agent-based modeling of individuals moving over a landscapes, using an architecture that lays transparent the following four hierarchical simulation levels: 1.) within-patch consumer-resource dynamics, 2.) within-generation movement and competition mitigation processes, 3.) across-generation evolutionary processes, and 4.) multiple runs to generate the statistics needed for comparative analyses. The focus of our analysis is on the question of how the biomass production efficiency and the diversity of guilds of foraging strategy types, exploiting resources over a patchy landscape, evolve under clonal versus random hermaphroditic sexual reproduction. Our results indicate greater biomass production efficiency under clonal reproduction only at higher population densities, and demonstrate that polymorphisms evolve and are maintained under random mating systems. The latter result questions the notion that some type of associative mating structure is needed to maintain genetic polymorphisms among individuals exploiting a common patchy resource on an otherwise spatially homogeneous landscape. PMID:26274613

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.

Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma.

PubMed

Horvai, Andrew E; DeVries, Sandy; Roy, Ritu; O'Donnell, Richard J; Waldman, Frederic

2009-11-01

Liposarcoma represents a unique model insofar as some well-differentiated liposarcomas progress to non-lipogenic, so-called 'dedifferentiated,' forms. The well-differentiated and dedifferentiated family of liposarcomas demonstrates amplification of the chromosome subregion 12q13-q15 with resultant amplification of the MDM2 and CDK4 genes. However, the specific genetic changes that distinguish between well-differentiated and dedifferentiated liposarcomas are less well understood. To study the genetic changes in dedifferentiated liposarcomas, paired well-differentiated and dedifferentiated components of 29 tumors were analyzed separately by array-based comparative genomic hybridization. A bacterial artificial chromosome array at approximately 1-Mb resolution was used. The genetic changes were compared with clinical presentation, grade of the dedifferentiated component and overexpression of MDM2 and CDK4. Most tumors (n=21, 72%) were retroperitoneal, with both components present at initial diagnosis (n=25, 86%). Eight tumors (28%) were classified as low-grade dedifferentiation. In four cases (14%), a well-differentiated liposarcoma preceded the presentation of the dedifferentiated tumor by 1-5 years. 12q13-q15 was amplified in all tumors. Using unsupervised hierarchical clustering of copy-number changes, all but two tumors showed close similarities between well-differentiated and dedifferentiated components, and segregated as pairs. Dedifferentiated components had more total amplifications (P=0.008) and a trend for gain at 19q13.2, but no genetic changes were significant in distinguishing between the two components. High-level amplifications of 1p21-32 (n=7, 24%), 1q21-23 (n=9, 31%), 6q23-24 (n=6, 21%) and 12q24 (n=3, 10%) were common, but none significantly correlated with differentiation. Presentation and grade correlated with the frequency of changes at a number of genetic loci (P<0.001), whereas CDK4 immunostaining showed negative correlation with 12q13.13 amplification. The genotypic similarity, at the limit of the array's resolution, between components implies that most genetic changes precede phenotypic 'progression,' early in tumorigenesis. The relationship between genetic changes and presentation or grade may reflect differences in factors that control genomic instability or the background genotype of the tumor.

Parenting Interacts with Oxytocin Polymorphisms to Predict Adolescent Social Anxiety Symptom Development: A Novel Polygenic Approach.

PubMed

Nelemans, Stefanie A; van Assche, Evelien; Bijttebier, Patricia; Colpin, Hilde; van Leeuwen, Karla; Verschueren, Karine; Claes, Stephan; van den Noortgate, Wim; Goossens, Luc

2018-04-26

Guided by a developmental psychopathology framework, research has increasingly focused on the interplay of genetics and environment as a predictor of different forms of psychopathology, including social anxiety. In these efforts, the polygenic nature of complex phenotypes such as social anxiety is increasingly recognized, but studies applying polygenic approaches are still scarce. In this study, we applied Principal Covariates Regression as a novel approach to creating polygenic components for the oxytocin system, which has recently been put forward as particularly relevant to social anxiety. Participants were 978 adolescents (49.4% girls; M age T 1  = 13.8 years). Across 3 years, questionnaires were used to assess adolescent social anxiety symptoms and multi-informant reports of parental psychological control and autonomy support. All adolescents were genotyped for 223 oxytocin single nucleotide polymorphisms (SNPs) in 14 genes. Using Principal Covariates Regression, these SNPs could be reduced to five polygenic components. Four components reflected the underlying linkage disequilibrium and ancestry structure, whereas the fifth component, which consisted of small contributions of many SNPs across multiple genes, was strongly positively associated with adolescent social anxiety symptoms, pointing to an index of genetic risk. Moreover, significant interactions were found with this polygenic component and the environmental variables of interest. Specifically, adolescents who scored high on this polygenic component and experienced less adequate parenting (i.e., high psychological control or low autonomy support) showed the highest levels of social anxiety. Implications of these findings are discussed in the context of individual-by-environment models.

Telomerase RNA Component (TERC) genetic variants interact with the mediterranean diet modifying the inflammatory status and its relationship with aging: CORDIOPREV study

USDA-ARS?s Scientific Manuscript database

Background: Leukocyte telomere length (LTL) attrition has been associated with age-related diseases. Telomerase RNA Component (TERC) genetic variants have been associated with LTL; whereas fatty acids (FAs) can interact with genetic factors and influence in aging. We explore whether variability at t...

Application of molecular genetic tools to studies of forest pathosystems [Chapter 2

Treesearch

Mee-Sook Kim; Ned B. Klopfenstein; Richard C. Hamelin

2005-01-01

The use of molecular genetics in forest pathology has greatly increased over the past 10 years. For the most part, molecular genetic tools were initially developed to focus on individual components (e.g., pathogen, host) of forest pathosystems. As part of broader forest ecosystem complexes, forest pathosystems involve dynamic interactions among living components (e.g...

Signatures of adaptation in the weedy rice genome.

PubMed

Li, Lin-Feng; Li, Ya-Ling; Jia, Yulin; Caicedo, Ana L; Olsen, Kenneth M

2017-05-01

Crop domestication provided the calories that fueled the rise of civilization. For many crop species, domestication was accompanied by the evolution of weedy crop relatives, which aggressively outcompete crops and reduce harvests. Understanding the genetic mechanisms that underlie the evolution of weedy crop relatives is critical for agricultural weed management and food security. Here we use whole-genome sequences to examine the origin and adaptation of the two major strains of weedy rice found in the United States. We find that de-domestication from cultivated ancestors has had a major role in their evolution, with relatively few genetic changes required for the emergence of weediness traits. Weed strains likely evolved both early and late in the history of rice cultivation and represent an under-recognized component of the domestication process. Genomic regions identified here that show evidence of selection can be considered candidates for future genetic and functional analyses for rice improvement.

Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice

PubMed Central

Tanger, Paul; Klassen, Stephen; Mojica, Julius P.; Lovell, John T.; Moyers, Brook T.; Baraoidan, Marietta; Naredo, Maria Elizabeth B.; McNally, Kenneth L.; Poland, Jesse; Bush, Daniel R.; Leung, Hei; Leach, Jan E.; McKay, John K.

2017-01-01

To ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. Here we demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor-intensive measures of flowering time, height, biomass, grain yield, and harvest index. Genetic mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution. PMID:28220807

Quantitative genetics

USDA-ARS?s Scientific Manuscript database

The majority of economically important traits targeted for cotton improvement are quantitatively inherited. In this chapter, the current state of cotton quantitative genetics is described and separated into four components. These components include: 1) traditional quantitative inheritance analysis, ...

A Dynamic Network Model to Explain the Development of Excellent Human Performance

PubMed Central

Den Hartigh, Ruud J. R.; Van Dijk, Marijn W. G.; Steenbeek, Henderien W.; Van Geert, Paul L. C.

2016-01-01

Across different domains, from sports to science, some individuals accomplish excellent levels of performance. For over 150 years, researchers have debated the roles of specific nature and nurture components to develop excellence. In this article, we argue that the key to excellence does not reside in specific underlying components, but rather in the ongoing interactions among the components. We propose that excellence emerges out of dynamic networks consisting of idiosyncratic mixtures of interacting components such as genetic endowment, motivation, practice, and coaching. Using computer simulations we demonstrate that the dynamic network model accurately predicts typical properties of excellence reported in the literature, such as the idiosyncratic developmental trajectories leading to excellence and the highly skewed distributions of productivity present in virtually any achievement domain. Based on this novel theoretical perspective on excellent human performance, this article concludes by suggesting policy implications and directions for future research. PMID:27148140

Gene ontology analysis of pairwise genetic associations in two genome-wide studies of sporadic ALS.

PubMed

Kim, Nora Chung; Andrews, Peter C; Asselbergs, Folkert W; Frost, H Robert; Williams, Scott M; Harris, Brent T; Read, Cynthia; Askland, Kathleen D; Moore, Jason H

2012-07-28

It is increasingly clear that common human diseases have a complex genetic architecture characterized by both additive and nonadditive genetic effects. The goal of the present study was to determine whether patterns of both additive and nonadditive genetic associations aggregate in specific functional groups as defined by the Gene Ontology (GO). We first estimated all pairwise additive and nonadditive genetic effects using the multifactor dimensionality reduction (MDR) method that makes few assumptions about the underlying genetic model. Statistical significance was evaluated using permutation testing in two genome-wide association studies of ALS. The detection data consisted of 276 subjects with ALS and 271 healthy controls while the replication data consisted of 221 subjects with ALS and 211 healthy controls. Both studies included genotypes from approximately 550,000 single-nucleotide polymorphisms (SNPs). Each SNP was mapped to a gene if it was within 500 kb of the start or end. Each SNP was assigned a p-value based on its strongest joint effect with the other SNPs. We then used the Exploratory Visual Analysis (EVA) method and software to assign a p-value to each gene based on the overabundance of significant SNPs at the α = 0.05 level in the gene. We also used EVA to assign p-values to each GO group based on the overabundance of significant genes at the α = 0.05 level. A GO category was determined to replicate if that category was significant at the α = 0.05 level in both studies. We found two GO categories that replicated in both studies. The first, 'Regulation of Cellular Component Organization and Biogenesis', a GO Biological Process, had p-values of 0.010 and 0.014 in the detection and replication studies, respectively. The second, 'Actin Cytoskeleton', a GO Cellular Component, had p-values of 0.040 and 0.046 in the detection and replication studies, respectively. Pathway analysis of pairwise genetic associations in two GWAS of sporadic ALS revealed a set of genes involved in cellular component organization and actin cytoskeleton, more specifically, that were not reported by prior GWAS. However, prior biological studies have implicated actin cytoskeleton in ALS and other motor neuron diseases. This study supports the idea that pathway-level analysis of GWAS data may discover important associations not revealed using conventional one-SNP-at-a-time approaches.

Genetic architecture of the Delis-Kaplan Executive Function System Trail Making Test: evidence for distinct genetic influences on executive function.

PubMed

Vasilopoulos, Terrie; Franz, Carol E; Panizzon, Matthew S; Xian, Hong; Grant, Michael D; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C; Kremen, William S

2012-03-01

To examine how genes and environments contribute to relationships among Trail Making Test (TMT) conditions and the extent to which these conditions have unique genetic and environmental influences. Participants included 1,237 middle-aged male twins from the Vietnam Era Twin Study of Aging. The Delis-Kaplan Executive Function System TMT included visual searching, number and letter sequencing, and set-shifting components. Phenotypic correlations among TMT conditions ranged from 0.29 to 0.60, and genes accounted for the majority (58-84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. A common genetic factor, most likely representing a combination of speed and sequencing, accounted for most of the correlation among TMT 1-4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in nonpatient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes.

Relationship between polycystic ovary syndrome and ancestry in European Americans.

PubMed

Bjonnes, Andrew C; Saxena, Richa; Welt, Corrine K

2016-12-01

To determine whether European Americans with polycystic ovary syndrome (PCOS) exhibit genetic differences associated with PCOS status and phenotypic features. Case-control association study in European Americans. Academic center. Women with PCOS diagnosed with the use of the National Institutes of Health criteria (n = 532) and control women with regular menstrual cycles and no evidence of hyperandrogenism (n = 432). Blood was drawn for measurement of sex steroids, metabolic parameters, and genotyping. Associations among PCOS status, phenotype, and genetic background identified with the use of principal component analysis. Principal component analysis identified five principal components (PCs). PC1 captured northwest-to-southeast European genetic variation and was associated with PCOS status. Acanthosis was associated with southern European ancestry, and larger waist:hip ratio was associated with northern European ancestry. PC2 was associated with east-to-west European genetic variation and cholesterol levels. These data provide evidence for genetic influence based on European ethnicity in women with PCOS. There is also evidence for a genetic component in the phenotypic features of PCOS within a mixed European population. The data point to the need to control for population stratification in genetic studies in women of mixed European ethnicity. They also emphasize the need for better studies of PCOS prevalence and phenotype as a function of genetic background. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The Relationship Between Polycystic Ovary Syndrome and Ancestry in European Americans

PubMed Central

Bjonnes, Andrew C.; Saxena, Richa; Welt, Corrine K.

2016-01-01

Objective To determine whether European Americans with PCOS would exhibit genetic differences associated with PCOS status and phenotypic features. Design The study was a case-control association study in European Americans. Setting Subjects were studied in an academic center. Subjects Women with PCOS diagnosed using the NIH criteria (n=532) and controls with regular menstrual cycles and no evidence of hyperandrogenism (n=432) were studied. Interventions Blood was drawn for measurement of sex steroids, metabolic parameters and genotyping. Main outcome measure Associations were identified between PCOS status, phenotype and genetic background determined using principal components. Results Principal component analysis identified 5 principal components (PCs). PC1 captured northwest to southeast European genetic variation and was associated with PCOS status. Acanthosis was associated with southern European ancestry, while larger waist:hip ratio was associated with northern European ancestry. PC2 was associated with east to west European genetic variation and cholesterol levels. Conclusions These data provide evidence for genetic influence based on European ethnicity in women with PCOS. There is also evidence for a genetic component in the phenotypic features of PCOS within a mixed European population. The data point to the need to control for population stratification in genetic studies in women of mixed European ethnicity. They also emphasize the need for better studies of PCOS prevalence and phenotype as a function of genetic background. PMID:27666562

Silencing Nicotiana attenuata LHY and ZTL alters circadian rhythms in flowers.

PubMed

Yon, Felipe; Joo, Youngsung; Cortés Llorca, Lucas; Rothe, Eva; Baldwin, Ian T; Kim, Sang-Gyu

2016-02-01

The rhythmic opening/closing and volatile emissions of flowers are known to attract pollinators at specific times. That these rhythms are maintained under constant light or dark conditions suggests a circadian clock involvement. Although a forward and reverse genetic approach has led to the identification of core circadian clock components in Arabidopsis thaliana, the involvement of these clock components in floral rhythms has remained untested, probably because of the weak diurnal rhythms in A. thaliana flowers. Here, we addressed the role of these core clock components in the flowers of the wild tobacco Nicotiana attenuata, whose flowers open at night, emit benzyl acetone (BA) scents and move vertically through a 140° arc. We first measured N. attenuata floral rhythms under constant light conditions. The results suggest that the circadian clock controls flower opening, BA emission and pedicel movement, but not flower closing. We generated transgenic N. attenuata lines silenced in the homologous genes of Arabidopsis LATE ELONGATED HYPOCOTYL (LHY) and ZEITLUPE (ZTL), which are known to be core clock components. Silencing NaLHY and NaZTL strongly altered floral rhythms in different ways, indicating that conserved clock components in N. attenuata coordinate these floral rhythms. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Transcriptional and functional characterization of genetic elements involved in galacto-oligosaccharide utilization by Bifidobacterium breve UCC2003.

PubMed

O'Connell Motherway, Mary; Kinsella, Michael; Fitzgerald, Gerald F; van Sinderen, Douwe

2013-01-01

Several prebiotics, such as inulin, fructo-oligosaccharides and galacto-oligosaccharides, are widely used commercially in foods and there is convincing evidence, in particular for galacto-oligosaccharides, that prebiotics can modulate the microbiota and promote bifidobacterial growth in the intestinal tract of infants and adults. In this study we describe the identification and functional characterization of the genetic loci responsible for the transport and metabolism of purified galacto-oligosaccharides (PGOS) by Bifidobacterium breve UCC2003. We further demonstrate that an extracellular endogalactanase specified by several B. breve strains, including B. breve UCC2003, is essential for partial degradation of PGOS components with a high degree of polymerization. These partially hydrolysed PGOS components are presumed to be transported into the bifidobacterial cell via various ABC transport systems and sugar permeases where they are further degraded to galactose and glucose monomers that feed into the bifid shunt. This work significantly advances our molecular understanding of bifidobacterial PGOS metabolism and its associated genetic machinery to utilize this prebiotic. © 2012 The Authors. Published by Society for Applied Microbiology and Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Mixed model approaches for diallel analysis based on a bio-model.

PubMed

Zhu, J; Weir, B S

1996-12-01

A MINQUE(1) procedure, which is minimum norm quadratic unbiased estimation (MINQUE) method with 1 for all the prior values, is suggested for estimating variance and covariance components in a bio-model for diallel crosses. Unbiasedness and efficiency of estimation were compared for MINQUE(1), restricted maximum likelihood (REML) and MINQUE theta which has parameter values for the prior values. MINQUE(1) is almost as efficient as MINQUE theta for unbiased estimation of genetic variance and covariance components. The bio-model is efficient and robust for estimating variance and covariance components for maternal and paternal effects as well as for nuclear effects. A procedure of adjusted unbiased prediction (AUP) is proposed for predicting random genetic effects in the bio-model. The jack-knife procedure is suggested for estimation of sampling variances of estimated variance and covariance components and of predicted genetic effects. Worked examples are given for estimation of variance and covariance components and for prediction of genetic merits.

Molecular Mechanisms Underlying Genomic Instability in Brca-Deficient Cells

DTIC Science & Technology

2012-03-01

Fanconi anemia pathway for ICL repair. BRCA1 therefore has two separate roles in ICL repair that can be modulated by manipulating NHEJ, whereas FANCD2...repair pathway comprising at least 15 gene products. Mutation of any of these genes causes the human disease Fanconi anemia (FA), which is associated...genetic deficiency in components of the Fanconi anemia (FA) pathway (Wang, 2007). Cells from FA patients, or knockout mice with deficiencies in the FA

Genetic Basis of Sjögren's Syndrome. How Strong is the Evidence?

PubMed Central

Anaya, Juan-Manuel; Delgado-Vega, Angélica María; Castiblanco, John

2006-01-01

Sjögren's syndrome (SS) is a late-onset chronic autoimmune disease (AID) affecting the exocrine glands, mainly the salivary and lachrymal. Genetic studies on twins with primary SS have not been performed, and only a few case reports describing twins have been published. The prevalence of primary SS in siblings has been estimated to be 0.09% while the reported general prevalence of the disease is approximately 0.1%. The observed aggregation of AIDs in families of patients with primary SS is nevertheless supportive for a genetic component in its etiology. In the absence of chromosomal regions identified by linkage studies, research has focused on candidate gene approaches (by biological plausibility) rather than on positional approaches. Ancestral haplotype 8.1 as well as TNF, IL10 and SSA1 loci have been consistently associated with the disease although they are not specific for SS. In this review, the genetic component of SS is discussed on the basis of three known observations: (a) age at onset and sex-dependent presentation, (b) familial clustering of the disease, and (c) dissection of the genetic component. Since there is no strong evidence for a specific genetic component in SS, a large international and collaborative study would be suitable to assess the genetics of this disorder. PMID:17162364

Males and Females Contribute Unequally to Offspring Genetic Diversity in the Polygynandrous Mating System of Wild Boar

PubMed Central

Pérez-González, Javier; Costa, Vânia; Santos, Pedro; Slate, Jon; Carranza, Juan; Fernández-Llario, Pedro; Zsolnai, Attila; Monteiro, Nuno M.; Anton, István; Buzgó, József; Varga, Gyula; Beja-Pereira, Albano

2014-01-01

The maintenance of genetic diversity across generations depends on both the number of reproducing males and females. Variance in reproductive success, multiple paternity and litter size can all affect the relative contributions of male and female parents to genetic variation of progeny. The mating system of the wild boar (Sus scrofa) has been described as polygynous, although evidence of multiple paternity in litters has been found. Using 14 microsatellite markers, we evaluated the contribution of males and females to genetic variation in the next generation in independent wild boar populations from the Iberian Peninsula and Hungary. Genetic contributions of males and females were obtained by distinguishing the paternal and maternal genetic component inherited by the progeny. We found that the paternally inherited genetic component of progeny was more diverse than the maternally inherited component. Simulations showed that this finding might be due to a sampling bias. However, after controlling for the bias by fitting both the genetic diversity in the adult population and the number of reproductive individuals in the models, paternally inherited genotypes remained more diverse than those inherited maternally. Our results suggest new insights into how promiscuous mating systems can help maintain genetic variation. PMID:25541986

Genetic determinism of anatomical and hydraulic traits within an apple progeny.

PubMed

Lauri, Pierre-Éric; Gorza, Olivier; Cochard, Hervé; Martinez, Sébastien; Celton, Jean-Marc; Ripetti, Véronique; Lartaud, Marc; Bry, Xavier; Trottier, Catherine; Costes, Evelyne

2011-08-01

The apple tree is known to have an isohydric behaviour, maintaining rather constant leaf water potential in soil with low water status and/or under high evaporative demand. However, little is known on the xylem water transport from roots to leaves from the two perspectives of efficiency and safety, and on its genetic variability. We analysed 16 traits related to hydraulic efficiency and safety, and anatomical traits in apple stems, and the relationships between them. Most variables were found heritable, and we investigated the determinism underlying their genetic control through a quantitative trait loci (QTL) analysis on 90 genotypes from the same progeny. Principal component analysis (PCA) revealed that all traits related to efficiency, whether hydraulic conductivity, vessel number and area or wood area, were included in the first PC, whereas the second PC included the safety variables, thus confirming the absence of trade-off between these two sets of traits. Our results demonstrated that clustered variables were characterized by common genomic regions. Together with previous results on the same progeny, our study substantiated that hydraulic efficiency traits co-localized with traits identified for tree growth and fruit production. © 2011 Blackwell Publishing Ltd.

Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease

PubMed Central

Do, Chuong B.; Tung, Joyce Y.; Dorfman, Elizabeth; Kiefer, Amy K.; Drabant, Emily M.; Francke, Uta; Mountain, Joanna L.; Goldman, Samuel M.; Tanner, Caroline M.; Langston, J. William; Wojcicki, Anne; Eriksson, Nicholas

2011-01-01

Although the causes of Parkinson's disease (PD) are thought to be primarily environmental, recent studies suggest that a number of genes influence susceptibility. Using targeted case recruitment and online survey instruments, we conducted the largest case-control genome-wide association study (GWAS) of PD based on a single collection of individuals to date (3,426 cases and 29,624 controls). We discovered two novel, genome-wide significant associations with PD–rs6812193 near SCARB2 (, ) and rs11868035 near SREBF1/RAI1 (, )—both replicated in an independent cohort. We also replicated 20 previously discovered genetic associations (including LRRK2, GBA, SNCA, MAPT, GAK, and the HLA region), providing support for our novel study design. Relying on a recently proposed method based on genome-wide sharing estimates between distantly related individuals, we estimated the heritability of PD to be at least 0.27. Finally, using sparse regression techniques, we constructed predictive models that account for 6%–7% of the total variance in liability and that suggest the presence of true associations just beyond genome-wide significance, as confirmed through both internal and external cross-validation. These results indicate a substantial, but by no means total, contribution of genetics underlying susceptibility to both early-onset and late-onset PD, suggesting that, despite the novel associations discovered here and elsewhere, the majority of the genetic component for Parkinson's disease remains to be discovered. PMID:21738487

Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries.

PubMed

Lee, Yi-Ying; Hsu, Chih-Yuan; Lin, Ling-Jiun; Chang, Chih-Chun; Cheng, Hsiao-Chun; Yeh, Tsung-Hsien; Hu, Rei-Hsing; Lin, Che; Xie, Zhen; Chen, Bor-Sen

2013-10-27

Synthetic genetic transistors are vital for signal amplification and switching in genetic circuits. However, it is still problematic to efficiently select the adequate promoters, Ribosome Binding Sides (RBSs) and inducer concentrations to construct a genetic transistor with the desired linear amplification or switching in the Input/Output (I/O) characteristics for practical applications. Three kinds of promoter-RBS libraries, i.e., a constitutive promoter-RBS library, a repressor-regulated promoter-RBS library and an activator-regulated promoter-RBS library, are constructed for systematic genetic circuit design using the identified kinetic strengths of their promoter-RBS components.According to the dynamic model of genetic transistors, a design methodology for genetic transistors via a Genetic Algorithm (GA)-based searching algorithm is developed to search for a set of promoter-RBS components and adequate concentrations of inducers to achieve the prescribed I/O characteristics of a genetic transistor. Furthermore, according to design specifications for different types of genetic transistors, a look-up table is built for genetic transistor design, from which we could easily select an adequate set of promoter-RBS components and adequate concentrations of external inducers for a specific genetic transistor. This systematic design method will reduce the time spent using trial-and-error methods in the experimental procedure for a genetic transistor with a desired I/O characteristic. We demonstrate the applicability of our design methodology to genetic transistors that have desirable linear amplification or switching by employing promoter-RBS library searching.

Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries

PubMed Central

2013-01-01

Background Synthetic genetic transistors are vital for signal amplification and switching in genetic circuits. However, it is still problematic to efficiently select the adequate promoters, Ribosome Binding Sides (RBSs) and inducer concentrations to construct a genetic transistor with the desired linear amplification or switching in the Input/Output (I/O) characteristics for practical applications. Results Three kinds of promoter-RBS libraries, i.e., a constitutive promoter-RBS library, a repressor-regulated promoter-RBS library and an activator-regulated promoter-RBS library, are constructed for systematic genetic circuit design using the identified kinetic strengths of their promoter-RBS components. According to the dynamic model of genetic transistors, a design methodology for genetic transistors via a Genetic Algorithm (GA)-based searching algorithm is developed to search for a set of promoter-RBS components and adequate concentrations of inducers to achieve the prescribed I/O characteristics of a genetic transistor. Furthermore, according to design specifications for different types of genetic transistors, a look-up table is built for genetic transistor design, from which we could easily select an adequate set of promoter-RBS components and adequate concentrations of external inducers for a specific genetic transistor. Conclusion This systematic design method will reduce the time spent using trial-and-error methods in the experimental procedure for a genetic transistor with a desired I/O characteristic. We demonstrate the applicability of our design methodology to genetic transistors that have desirable linear amplification or switching by employing promoter-RBS library searching. PMID:24160305

Etiological Distinction of Working Memory Components in Relation to Mathematics

PubMed Central

Lukowski, Sarah L.; Soden, Brooke; Hart, Sara A.; Thompson, Lee A.; Kovas, Yulia; Petrill, Stephen A.

2014-01-01

Working memory has been consistently associated with mathematics achievement, although the etiology of these relations remains poorly understood. The present study examined the genetic and environmental underpinnings of math story problem solving, timed calculation, and untimed calculation alongside working memory components in 12-year-old monozygotic (n = 105) and same-sex dizygotic (n = 143) twin pairs. Results indicated significant phenotypic correlation between each working memory component and all mathematics outcomes (r = 0.18 – 0.33). Additive genetic influences shared between the visuo-spatial sketchpad and mathematics achievement was significant, accounting for roughly 89% of the observed correlation. In addition, genetic covariance was found between the phonological loop and math story problem solving. In contrast, despite there being a significant observed relationship between phonological loop and timed and untimed calculation, there was no significant genetic or environmental covariance between the phonological loop and timed or untimed calculation skills. Further analyses indicated that genetic overlap between the visuo-spatial sketchpad and math story problem solving and math fluency was distinct from general genetic factors, whereas g, phonological loop, and mathematics shared generalist genes. Thus, although each working memory component was related to mathematics, the etiology of their relationships may be distinct. PMID:25477699

Possibility of modifying the growth trajectory in Raeini Cashmere goat.

PubMed

Ghiasi, Heydar; Mokhtari, M S

2018-03-27

The objective of this study was to investigate the possibility of modifying the growth trajectory in Raeini Cashmere goat breed. In total, 13,193 records on live body weight collected from 4788 Raeini Cashmere goats were used. According to Akanke's information criterion (AIC), the sing-trait random regression model included fourth-order Legendre polynomial for direct and maternal genetic effect; maternal and individual permanent environmental effect was the best model for estimating (co)variance components. The matrices of eigenvectors for (co)variances between random regression coefficients of direct additive genetic were used to calculate eigenfunctions, and different eigenvector indices were also constructed. The obtained results showed that the first eigenvalue explained 79.90% of total genetic variance. Therefore, changing the body weights applying the first eigenfunction will be obtained rapidly. Selection based on the first eigenvector will cause favorable positive genetic gains for all body weight considered from birth to 12 months of age. For modifying the growth trajectory in Raeini Cashmere goat, the selection should be based on the second eigenfunction. The second eigenvalue accounted for 14.41% of total genetic variance for body weights that is low in comparison with genetic variance explained by the first eigenvalue. The complex patterns of genetic change in growth trajectory observed under the third and fourth eigenfunction and low amount of genetic variance explained by the third and fourth eigenvalues.

Genetic gains from selection for fiber traits in Gossypium hirsutum L.

PubMed

de Faria, G M P; Sanchez, C F B; de Carvalho, L P; da Silva Oliveira, M; Cruz, C D

2016-11-21

Brazil is among the five largest producers of cotton in the world, cultivating the species Gossypium hirsutum L. r. latifolium Hutch. The cultivars should have good fiber quality as well as yield. Genetic improvement of fiber traits requires the study of the genetic structure of the populations under improvement, leading to the identification of promising parent plants. To this end, it is important to acquire some information, such as estimates of genetic variance components and heritability coefficients, which will support the appropriate choice of the breeding strategy to be employed as well as enable the estimation of gains from selection. This study aimed to evaluate some agronomic characteristics, such as fiber quality and yield, estimating genetic parameters for the purpose of predicting earnings. Twelve cultivars of cotton, including four male progenitors (CNPA 01-42, BRS Verde, Glandless, and Okra leaf) and eight female progenitors (Delta opal, CNPA 7H, Aroeira, Antares, Sucupira, Facual, Precoce 3, and CNPA 8H), were used in performing crosses according to design I, proposed by Comstock and Robinson (1948). The experimental design was a randomized block with four replications. We observed genetic variability among all traits as well as higher efficiency of selection for the gains related to traits. Our results showed that the combined selection presented the highest genetic gains for all traits. For fiber length, the female/male selection and the combined selection resulted in the highest genetic gain.

The contributions of admixture and genetic drift to diversity among post-contact populations in the Americas.

PubMed

Koehl, Anthony J; Long, Jeffrey C

2018-02-01

We present a model that partitions Nei's minimum genetic distance between admixed populations into components of admixture and genetic drift. We applied this model to 17 admixed populations in the Americas to examine how admixture and drift have contributed to the patterns of genetic diversity. We analyzed 618 short tandem repeat loci in 949 individuals from 49 population samples. Thirty-two samples serve as proxies for continental ancestors. Seventeen samples represent admixed populations: (4) African-American and (13) Latin American. We partition genetic distance, and then calculate fixation indices and principal coordinates to interpret our results. A computer simulation confirms that our method correctly estimates drift and admixture components of genetic distance when the assumptions of the model are met. The partition of genetic distance shows that both admixture and genetic drift contribute to patterns of genetic diversity. The admixture component of genetic distance provides evidence for two distinct axes of continental ancestry. However, the genetic distances show that ancestry contributes to only one axis of genetic differentiation. The genetic distances among the 13 Latin American populations in this analysis show contributions from both differences in ancestry and differences in genetic drift. By contrast, the genetic distances among the four African American populations in this analysis owe mostly to genetic drift because these groups have similar fractions of European and African ancestry. The genetic structure of admixed populations in the Americas reflects more than admixture. We show that the history of serial founder effects constrains the impact of admixture on allele frequencies to a single dimension. Genetic drift in the admixed populations imposed a new level of genetic structure onto that created by admixture. © 2017 Wiley Periodicals, Inc.

The Genetic Components of Verbal Divergent Thinking and Short Term Memory.

ERIC Educational Resources Information Center

Pezzullo, Thomas R.; Madaus, George F.

A study of twins was conducted to determine the presence of an hereditary component in short term memory and in three aspects of verbal divergent thinking--flexibility, fluency, and originality. Results showed the existence of a significant genetic component in the trait of short term memory, while none was found in verbal divergent thinking. (AG)

Multiple components in restriction enzyme digests of mammalian (insectivore), avian and reptilian genomic DNA hybridize with murine immunoglobulin VH probes.

PubMed

Litman, G W; Berger, L; Jahn, C L

1982-06-11

High molecular weight genomic DNAs isolated from an insectivore, Tupaia, and a representative reptilian, Caiman, and avian, Gallus, were digested with restriction endonucleases transferred to nitrocellulose and hybridized with nick-translated probes of murine VH genes. The derivations of the probes designated S107V (1) and mu 107V (2,3) have been described previously. Under conditions of reduced stringency, multiple hybridizing components were observed with Tupaia and Caiman; only mu mu 107V exhibited significant hybridization with the separated fragments of Gallus DNA. The nick-translated S107V probe was digested with Fnu4H1 and subinserts corresponding to the 5' and 3' regions both detected multiple hybridizing components in Tupaia and Caiman DNA. A 5' probe lacking the leader sequence identified the same components as the intact 5' probe, suggesting that VH coding regions distant as the reptilians may possess multiple genetic components which exhibit significant homology with murine immunoglobulin in VH regions.

Multiple components in restriction enzyme digests of mammalian (insectivore), avian and reptilian genomic DNA hybridize with murine immunoglobulin VH probes.

PubMed Central

Litman, G W; Berger, L; Jahn, C L

1982-01-01

High molecular weight genomic DNAs isolated from an insectivore, Tupaia, and a representative reptilian, Caiman, and avian, Gallus, were digested with restriction endonucleases transferred to nitrocellulose and hybridized with nick-translated probes of murine VH genes. The derivations of the probes designated S107V (1) and mu 107V (2,3) have been described previously. Under conditions of reduced stringency, multiple hybridizing components were observed with Tupaia and Caiman; only mu mu 107V exhibited significant hybridization with the separated fragments of Gallus DNA. The nick-translated S107V probe was digested with Fnu4H1 and subinserts corresponding to the 5' and 3' regions both detected multiple hybridizing components in Tupaia and Caiman DNA. A 5' probe lacking the leader sequence identified the same components as the intact 5' probe, suggesting that VH coding regions distant as the reptilians may possess multiple genetic components which exhibit significant homology with murine immunoglobulin in VH regions. Images PMID:6285298

Genetic Architecture of Natural Variation Underlying Adult Foraging Behavior That Is Essential for Survival of Drosophila melanogaster.

PubMed

Lee, Yuh Chwen G; Yang, Qian; Chi, Wanhao; Turkson, Susie A; Du, Wei A; Kemkemer, Claus; Zeng, Zhao-Bang; Long, Manyuan; Zhuang, Xiaoxi

2017-05-01

Foraging behavior is critical for the fitness of individuals. However, the genetic basis of variation in foraging behavior and the evolutionary forces underlying such natural variation have rarely been investigated. We developed a systematic approach to assay the variation in survival rate in a foraging environment for adult flies derived from a wild Drosophila melanogaster population. Despite being such an essential trait, there is substantial variation of foraging behavior among D. melanogaster strains. Importantly, we provided the first evaluation of the potential caveats of using inbred Drosophila strains to perform genome-wide association studies on life-history traits, and concluded that inbreeding depression is unlikely a major contributor for the observed large variation in adult foraging behavior. We found that adult foraging behavior has a strong genetic component and, unlike larval foraging behavior, depends on multiple loci. Identified candidate genes are enriched in those with high expression in adult heads and, demonstrated by expression knock down assay, are involved in maintaining normal functions of the nervous system. Our study not only identified candidate genes for foraging behavior that is relevant to individual fitness, but also shed light on the initial stage underlying the evolution of the behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The Genetic Basis of Natural Variation in Kernel Size and Related Traits Using a Four-Way Cross Population in Maize.

PubMed

Chen, Jiafa; Zhang, Luyan; Liu, Songtao; Li, Zhimin; Huang, Rongrong; Li, Yongming; Cheng, Hongliang; Li, Xiantang; Zhou, Bo; Wu, Suowei; Chen, Wei; Wu, Jianyu; Ding, Junqiang

2016-01-01

Kernel size is an important component of grain yield in maize breeding programs. To extend the understanding on the genetic basis of kernel size traits (i.e., kernel length, kernel width and kernel thickness), we developed a set of four-way cross mapping population derived from four maize inbred lines with varied kernel sizes. In the present study, we investigated the genetic basis of natural variation in seed size and other components of maize yield (e.g., hundred kernel weight, number of rows per ear, number of kernels per row). In total, ten QTL affecting kernel size were identified, three of which (two for kernel length and one for kernel width) had stable expression in other components of maize yield. The possible genetic mechanism behind the trade-off of kernel size and yield components was discussed.

The Genetic Basis of Natural Variation in Kernel Size and Related Traits Using a Four-Way Cross Population in Maize

PubMed Central

Liu, Songtao; Li, Zhimin; Huang, Rongrong; Li, Yongming; Cheng, Hongliang; Li, Xiantang; Zhou, Bo; Wu, Suowei; Chen, Wei; Wu, Jianyu; Ding, Junqiang

2016-01-01

Kernel size is an important component of grain yield in maize breeding programs. To extend the understanding on the genetic basis of kernel size traits (i.e., kernel length, kernel width and kernel thickness), we developed a set of four-way cross mapping population derived from four maize inbred lines with varied kernel sizes. In the present study, we investigated the genetic basis of natural variation in seed size and other components of maize yield (e.g., hundred kernel weight, number of rows per ear, number of kernels per row). In total, ten QTL affecting kernel size were identified, three of which (two for kernel length and one for kernel width) had stable expression in other components of maize yield. The possible genetic mechanism behind the trade-off of kernel size and yield components was discussed. PMID:27070143

Spectral reflectance indices as a selection criterion for yield improvement in wheat

NASA Astrophysics Data System (ADS)

Babar, Md. Ali

2005-11-01

Scope and methods of study. Yield in wheat ( Triticum aestivum L.) is a complex trait and influenced by many environmental factors, and yield improvement is a daunting task for wheat breeders. Spectral reflectance indices (SRIs) have been used to study different physiological traits in wheat. SRIs have the potential to differentiate genotypes for grain yield. SRIs strongly associated with grain yield can be used to achieve effective genetic gain in wheat under different environments. Three experiments (15 adapted genotypes, 25 and 36 random sister lines derived from two different crosses) under irrigated conditions, and three experiments (each with 30 advanced genotypes) under water-limited conditions were conducted in three successive years in Northwest Mexico at the CIMMYT (International Maize and wheat Improvement Center) experimental station. SRIs and different agronomic data were collected for three years, and biomass was harvested for two years. Phenotypic and genetic correlations between SRIs and grain yield, between SRIs and biomass, realized and broad sense heritability, direct and correlated selection responses for grain yield, and SRIs were calculated. Findings and conclusion. Seven SRIs were calculated, and three near infrared based indices (WI, NWI-1 and NWI-2) showed higher level of genetic and phenotypic correlations with grain yield, yield components and biomass than other SRIs (PRI, RNDVI, GNDVI, and SR) under both irrigated and water limiting environments. Moderate to high realized and broad sense heritability, and selection response were demonstrated by the three NIR based indices. High efficiency of correlated response for yield estimation was demonstrated by the three NIR based indices. The ratio between the correlated response to grain yield based on the three NIR based indices and direct selection response for grain yield was very close to one. The NIR based indices showed very high accuracy in selecting superior genotypes for grain yield under both well-watered and water-limited conditions. These results demonstrated that effective genetic gain in grain yield improvement can be achieved by making selections with the three NIR based indices.

The albino chick as a model for studying ocular developmental anomalies, including refractive errors, associated with albinism.

PubMed

Rymer, Jodi; Choh, Vivian; Bharadwaj, Shrikant; Padmanabhan, Varuna; Modilevsky, Laura; Jovanovich, Elizabeth; Yeh, Brenda; Zhang, Zhan; Guan, Huanxian; Payne, W; Wildsoet, Christine F

2007-10-01

Albinism is associated with a variety of ocular anomalies including refractive errors. The purpose of this study was to investigate the ocular development of an albino chick line. The ocular development of both albino and normally pigmented chicks was monitored using retinoscopy to measure refractive errors and high frequency A-scan ultrasonography to measure axial ocular dimensions. Functional tests included an optokinetic nystagmus paradigm to assess visual acuity, and flash ERGs to assess retinal function. The underlying genetic abnormality was characterized using a gene microarray, PCR and a tyrosinase assay. The ultrastructure of the retinal pigment epithelium (RPE) was examined using transmission electron microscopy. PCR confirmed that the genetic abnormality in this line is a deletion in exon 1 of the tyrosinase gene. Tyrosinase gene expression in isolated RPE cells was minimally detectable, and there was minimal enzyme activity in albino feather bulbs. The albino chicks had pink eyes and their eyes transilluminated, reflecting the lack of melanin in all ocular tissues. All three main components, anterior chamber, crystalline lens and vitreous chamber, showed axial expansion over time in both normal and albino animals, but the anterior chambers of albino chicks were consistently shallower than those of normal chicks, while in contrast, their vitreous chambers were longer. Albino chicks remained relatively myopic, with higher astigmatism than the normally pigmented chicks, even though both groups underwent developmental emmetropization. Albino chicks had reduced visual acuity yet the ERG a- and b-wave components had larger amplitudes and shorter than normal implicit times. Developmental emmetropization occurs in the albino chick but is impaired, likely because of functional abnormalities in the RPE and/or retina as well as optical factors. In very young chicks the underlying genetic mutation may also contribute to refractive error and eye shape abnormalities.

Gene Ontology-Based Analysis of Zebrafish Omics Data Using the Web Tool Comparative Gene Ontology.

PubMed

Ebrahimie, Esmaeil; Fruzangohar, Mario; Moussavi Nik, Seyyed Hani; Newman, Morgan

2017-10-01

Gene Ontology (GO) analysis is a powerful tool in systems biology, which uses a defined nomenclature to annotate genes/proteins within three categories: "Molecular Function," "Biological Process," and "Cellular Component." GO analysis can assist in revealing functional mechanisms underlying observed patterns in transcriptomic, genomic, and proteomic data. The already extensive and increasing use of zebrafish for modeling genetic and other diseases highlights the need to develop a GO analytical tool for this organism. The web tool Comparative GO was originally developed for GO analysis of bacterial data in 2013 ( www.comparativego.com ). We have now upgraded and elaborated this web tool for analysis of zebrafish genetic data using GOs and annotations from the Gene Ontology Consortium.

Molecular Genetic Analysis of Phototropism in Arabidopsis

PubMed Central

Sakai, Tatsuya; Haga, Ken

2012-01-01

Plant life is strongly dependent on the environment, and plants regulate their growth and development in response to many different environmental stimuli. One of the regulatory mechanisms involved in these responses is phototropism, which allows plants to change their growth direction in response to the location of the light source. Since the study of phototropism by Darwin, many physiological studies of this phenomenon have been published. Recently, molecular genetic analyses of Arabidopsis have begun to shed light on the molecular mechanisms underlying this response system, including phototropin blue light photoreceptors, phototropin signaling components, auxin transporters, auxin action mechanisms and others. This review highlights some of the recent progress that has been made in further elucidating the phototropic response, with particular emphasis on mutant phenotypes. PMID:22864452

Molecular genetic analysis of phototropism in Arabidopsis.

PubMed

Sakai, Tatsuya; Haga, Ken

2012-09-01

Plant life is strongly dependent on the environment, and plants regulate their growth and development in response to many different environmental stimuli. One of the regulatory mechanisms involved in these responses is phototropism, which allows plants to change their growth direction in response to the location of the light source. Since the study of phototropism by Darwin, many physiological studies of this phenomenon have been published. Recently, molecular genetic analyses of Arabidopsis have begun to shed light on the molecular mechanisms underlying this response system, including phototropin blue light photoreceptors, phototropin signaling components, auxin transporters, auxin action mechanisms and others. This review highlights some of the recent progress that has been made in further elucidating the phototropic response, with particular emphasis on mutant phenotypes.

Construction, characterization and application of molecular tools for metabolic engineering of Synechocystis sp.

PubMed

Qi, Fengxia; Yao, Lun; Tan, Xiaoming; Lu, Xuefeng

2013-10-01

An integrative gene expression system has been constructed for the directional assembly of biological components in Synechocystis PCC6803. We have characterized 11 promoter parts with various expression efficiencies for genetic engineering of Synechocystis for the production of fatty alcohols. This was achieved by integrating several genetic modifications including the expression of multiple-copies of fatty acyl-CoA reductase (FAR) under the control of strong promoters, disruption of the competing pathways for poly-β-hydroxybutyrate and glycogen synthesis, and for peptide truncation of the FAR. In shake-flask cultures, the production of fatty alcohols was significantly improved with a yield of 761 ± 216 μg/g cell dry weight in Synechocystis, which is the highest reported to date.

Advances in cereal genomics and applications in crop breeding.

PubMed

Varshney, Rajeev K; Hoisington, David A; Tyagi, Akhilesh K

2006-11-01

Recent advances in cereal genomics have made it possible to analyse the architecture of cereal genomes and their expressed components, leading to an increase in our knowledge of the genes that are linked to key agronomically important traits. These studies have used molecular genetic mapping of quantitative trait loci (QTL) of several complex traits that are important in breeding. The identification and molecular cloning of genes underlying QTLs offers the possibility to examine the naturally occurring allelic variation for respective complex traits. Novel alleles, identified by functional genomics or haplotype analysis, can enrich the genetic basis of cultivated crops to improve productivity. Advances made in cereal genomics research in recent years thus offer the opportunities to enhance the prediction of phenotypes from genotypes for cereal breeding.

Hemiclonal analysis reveals significant genetic, environmental and genotype x environment effects on sperm size in Drosophila melanogaster.

PubMed

Morrow, E H; Leijon, A; Meerupati, A

2008-11-01

Spermatozoa are the most diverse of all animal cells. Variation in size alone is enormous and yet there are still no clear evolutionary explanations that can account for such diversity. The basic genetics of sperm form is also poorly understood, although sperm size is known to have a strong genetic component. Here, using hemiclonal analysis of Drosophila melanogaster, we demonstrate that there is not only a significant additive genetic component contributing to phenotypic variation in sperm length but also a significant environmental effect. Furthermore, the plasticity of sperm size has a significant genetic component to it (a genotype x environment interaction). A genotype x environment interaction could contribute to the maintenance of the substantial genetic variation in this trait and thereby explain the persistent inter-male differences in sperm size seen in numerous taxa. We suggest that the low conditional dependence and high heritability but low evolvability (the coefficient of additive genetic variation) of sperm length is more consistent with a history of stabilizing selection rather than either sexual selection or strong directional selection.

Genetic Variation in Complement Component 2 of the Classical Complement Pathway is Associated with Increased Mortality and Infection: A Study of 627 Trauma Patients

PubMed Central

Morris, John A.; Francois, Cedric; Olson, Paul K.; Cotton, Bryan A.; Summar, Marshall; Jenkins, Judith M.; Norris, Patrick R.; Moore, Jason H.; Williams, Anna E.; McNew, Brent S.; Canter, Jeffrey A.

2009-01-01

Trauma is a disease of inflammation. Complement Component 2 (C2) is a protease involved in activation of complement through the classical pathway and has been implicated in a variety of chronic inflammatory diseases. We hypothesized that genetic variation in C2 (E318D) identifies a high-risk subgroup of trauma patients reflecting increased mortality and infection (Ventilator associated pneumonia: VAP). Consequently, genetic variation in C2 may stratify patient risk and illuminate underlying mechanisms for therapeutic intervention. Methods DNA samples from 702 trauma patients were genotyped for C2 E318D and linked with covariates (age: mean 42.8 years, gender: 74% male, ethnicity: 80% Caucasian, mechanism: 84% blunt, ISS: mean 25.0, admission lactate: mean 3.13 mEq/L) and outcomes: mortality 9.9% and VAP: 18.5%. VAP was defined by quantitative bronchoalveolar lavage (>104). Multivariate regression determined the relationship of genotype and covariates to risk of death and VAP. However, patients with ISS ≥ 45 were excluded from the multivariate analysis, as magnitude of injury overwhelms genetics and covariates in determining outcome. Results 52 patients (8.3%) had the high-risk heterozygous genotype, associated with a significant increase in mortality and VAP. Conclusion In 702 trauma patients, 8.3% had a high-risk genetic variation in C2 associated with increased mortality (OR=2.65) and infection (OR=2.00). This variation: 1) Identifies a previously unknown high risk group for infection and mortality; 2) Can be determined on admission; 3) May provide opportunity for early therapeutic intervention; and 4) Requires validation in a distinct cohort of patients. PMID:19430225

Natural variation and the capacity to adapt to ocean acidification in the keystone sea urchin Strongylocentrotus purpuratus.

PubMed

Kelly, Morgan W; Padilla-Gamiño, Jacqueline L; Hofmann, Gretchen E

2013-08-01

A rapidly growing body of literature documents the potential negative effects of CO2 -driven ocean acidification (OA) on marine organisms. However, nearly all this work has focused on the effects of future conditions on modern populations, neglecting the role of adaptation. Rapid evolution can alter demographic responses to environmental change, ultimately affecting the likelihood of population persistence, but the capacity for adaptation will differ among populations and species. Here, we measure the capacity of the ecologically important purple sea urchin Strongylocentrotus purpuratus to adapt to OA, using a breeding experiment to estimate additive genetic variance for larval size (an important component of fitness) under future high-pCO2 /low-pH conditions. Although larvae reared under future conditions were smaller than those reared under present-day conditions, we show that there is also abundant genetic variation for body size under elevated pCO2 , indicating that this trait can evolve. The observed heritability of size was 0.40 ± 0.32 (95% CI) under low pCO2 , and 0.50 ± 0.30 under high-pCO2 conditions. Accounting for the observed genetic variation in models of future larval size and demographic rates substantially alters projections of performance for this species in the future ocean. Importantly, our model shows that after incorporating the effects of adaptation, the OA-driven decrease in population growth rate is up to 50% smaller, than that predicted by the 'no-adaptation' scenario. Adults used in the experiment were collected from two sites on the coast of the Northeast Pacific that are characterized by different pH regimes, as measured by autonomous sensors. Comparing results between sites, we also found subtle differences in larval size under high-pCO2 rearing conditions, consistent with local adaptation to carbonate chemistry in the field. These results suggest that spatially varying selection may help to maintain genetic variation necessary for adaptation to future OA. © 2013 John Wiley & Sons Ltd.

Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms

PubMed Central

Mahoney, J. Matthew; Taroni, Jaclyn; Martyanov, Viktor; Wood, Tammara A.; Greene, Casey S.; Pioli, Patricia A.; Hinchcliff, Monique E.; Whitfield, Michael L.

2015-01-01

Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6–12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes using a gene-gene interaction network, and place the genetic risk loci in the context of the intrinsic subsets. To identify gene expression modules common to three independent datasets from three different clinical centers, we developed a consensus clustering procedure based on mutual information of partitions, an information theory concept, and performed a meta-analysis of these genome-wide gene expression datasets. We created a gene-gene interaction network of the conserved molecular features across the intrinsic subsets and analyzed their connections with SSc-associated genetic polymorphisms. The network is composed of distinct, but interconnected, components related to interferon activation, M2 macrophages, adaptive immunity, extracellular matrix remodeling, and cell proliferation. The network shows extensive connections between the inflammatory- and fibroproliferative-specific genes. The network also shows connections between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and several human leukocyte antigen (HLA) genes. Our analyses suggest that the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically interconnected and related to a patients underlying genetic risk. PMID:25569146

Lifestyle Cardiovascular Risk Score, Genetic Risk Score, and Myocardial Infarction in Hispanic/Latino Adults Living in Costa Rica.

PubMed

Sotos-Prieto, Mercedes; Baylin, Ana; Campos, Hannia; Qi, Lu; Mattei, Josiemer

2016-12-20

A lifestyle cardiovascular risk score (LCRS) and a genetic risk score (GRS) have been independently associated with myocardial infarction (MI) in Hispanics/Latinos. Interaction or joint association between these scores has not been examined. Thus, our aim was to assess interactive and joint associations between LCRS and GRS, and each individual lifestyle risk factor, on likelihood of MI. Data included 1534 Costa Rican adults with nonfatal acute MI and 1534 matched controls. The LCRS used estimated coefficients as weights for each factor: unhealthy diet, physical inactivity, smoking, elevated waist:hip ratio, low/high alcohol intake, low socioeconomic status. The GRS included 14 MI-associated risk alleles. Conditional logistic regressions were used to calculate adjusted odds ratios. The odds ratios for MI were 2.72 (2.33, 3.17) per LCRS unit and 1.13 (95% CI 1.06, 1.21) per GRS unit. A significant joint association for highest GRS tertile and highest LCRS tertile and odds of MI was detected (odds ratio=5.43 [3.71, 7.94]; P<1.00×10 -7 ), compared to both lowest tertiles. The odds ratios were 1.74 (1.22, 2.49) under optimal lifestyle and unfavorable genetic profile, and 5.02 (3.46, 7.29) under unhealthy lifestyle but advantageous genetic profile. Significant joint associations were observed for the highest GRS tertile and the highest of each lifestyle component risk category. The interaction term was nonsignificant (P=0.33). Lifestyle risk factors and genetics are jointly associated with higher odds of MI among Hispanics/Latinos. Individual and combined lifestyle risk factors showed stronger associations. Efforts to improve lifestyle behaviors could help prevent MI regardless of genetic susceptibility. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Patterns of Genetic Structure and Linkage Disequilibrium in a Large Collection of Pea Germplasm

PubMed Central

Siol, Mathieu; Jacquin, Françoise; Chabert-Martinello, Marianne; Smýkal, Petr; Le Paslier, Marie-Christine; Aubert, Grégoire; Burstin, Judith

2017-01-01

Pea (Pisum sativum, L.) is a major pulse crop used both for animal and human alimentation. Owing to its association with nitrogen-fixing bacteria, it is also a valuable component for low-input cropping systems. To evaluate the genetic diversity and the scale of linkage disequilibrium (LD) decay in pea, we genotyped a collection of 917 accessions, gathering elite cultivars, landraces, and wild relatives using an array of ∼13,000 single nucleotide polymorphisms (SNP). Genetic diversity is broadly distributed across three groups corresponding to wild/landraces peas, winter types, and spring types. At a finer subdivision level, genetic groups relate to local breeding programs and type usage. LD decreases steeply as genetic distance increases. When considering subsets of the data, LD values can be higher, even if the steep decay remains. We looked for genomic regions exhibiting high level of differentiation between wild/landraces, winter, and spring pea, respectively. Two regions on linkage groups 5 and 6 containing 33 SNPs exhibit stronger differentiation between winter and spring peas than would be expected under neutrality. Interestingly, QTL for resistance to cold acclimation and frost resistance have been identified previously in the same regions. PMID:28611254

The big five personality traits: psychological entities or statistical constructs?

PubMed

Franić, Sanja; Borsboom, Denny; Dolan, Conor V; Boomsma, Dorret I

2014-11-01

The present study employed multivariate genetic item-level analyses to examine the ontology and the genetic and environmental etiology of the Big Five personality dimensions, as measured by the NEO Five Factor Inventory (NEO-FFI) [Costa and McCrae, Revised NEO personality inventory (NEO PI-R) and NEO five-factor inventory (NEO-FFI) professional manual, 1992; Hoekstra et al., NEO personality questionnaires NEO-PI-R, NEO-FFI: manual, 1996]. Common and independent pathway model comparison was used to test whether the five personality dimensions fully mediate the genetic and environmental effects on the items, as would be expected under the realist interpretation of the Big Five. In addition, the dimensionalities of the latent genetic and environmental structures were examined. Item scores of a population-based sample of 7,900 adult twins (including 2,805 complete twin pairs; 1,528 MZ and 1,277 DZ) on the Dutch version of the NEO-FFI were analyzed. Although both the genetic and the environmental covariance components display a 5-factor structure, applications of common and independent pathway modeling showed that they do not comply with the collinearity constraints entailed in the common pathway model. Implications for the substantive interpretation of the Big Five are discussed.

Efficient experimental design of high-fidelity three-qubit quantum gates via genetic programming

NASA Astrophysics Data System (ADS)

Devra, Amit; Prabhu, Prithviraj; Singh, Harpreet; Arvind; Dorai, Kavita

2018-03-01

We have designed efficient quantum circuits for the three-qubit Toffoli (controlled-controlled-NOT) and the Fredkin (controlled-SWAP) gate, optimized via genetic programming methods. The gates thus obtained were experimentally implemented on a three-qubit NMR quantum information processor, with a high fidelity. Toffoli and Fredkin gates in conjunction with the single-qubit Hadamard gates form a universal gate set for quantum computing and are an essential component of several quantum algorithms. Genetic algorithms are stochastic search algorithms based on the logic of natural selection and biological genetics and have been widely used for quantum information processing applications. We devised a new selection mechanism within the genetic algorithm framework to select individuals from a population. We call this mechanism the "Luck-Choose" mechanism and were able to achieve faster convergence to a solution using this mechanism, as compared to existing selection mechanisms. The optimization was performed under the constraint that the experimentally implemented pulses are of short duration and can be implemented with high fidelity. We demonstrate the advantage of our pulse sequences by comparing our results with existing experimental schemes and other numerical optimization methods.

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.

Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases.

PubMed

Hellenthal, Nicole; Gaertner-Rommel, Anna; Klauke, Bärbel; Paluszkiewicz, Lech; Stuhr, Markus; Kerner, Thoralf; Farr, Martin; Püschel, Klaus; Milting, Hendrik

2017-11-01

Coronary artery disease accounts for the majority of sudden cardiac deaths (SCD) in the older population whereas cardiomyopathies and arrhythmogenic abnormalities predominate in younger SCD victims (<35 years) with a significant genetic component. The elucidation of the pathogenetic cause of death might be relevant for the prevention of further deaths within affected families. Aim of this study was to determine the portion of underlying genetic heart diseases among unexplained putative SCD cases from a large German forensic department. We included 10 forensic cases of sudden unexplained death (SUD) victims aged 19-40 years, who died by SCD due to forensic autopsy. DNA was analysed by next generation panel sequencing of 174 candidate genes for channelopathies and cardiomyopathies. Cardiological examinations, genetic counselling, and subsequent genetic testing were offered to all affected families. We identified within 1 year 10 cases of SUD among 172 forensic cases. Evidence for a genetic disposition was found in 8 of 10 (80%) cases, with pathogenic mutations in 3 and variants of uncertain significance in 5 of SCD cases. Subsequent selective screening of family members revealed two additional mutation carriers. The study provides strong evidence that molecular genetics improves the post mortem diagnosis of fatal genetic heart diseases among SUD victims. Molecular genetics should be integrated in forensic and pathological routine practice. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

When intracellular logistics fails--genetic defects in membrane trafficking.

PubMed

Olkkonen, Vesa M; Ikonen, Elina

2006-12-15

The number of human genetic disorders shown to be due to defects in membrane trafficking has greatly increased during the past five years. Defects have been identified in components involved in sorting of cargo into transport carriers, vesicle budding and scission, movement of vesicles along cytoskeletal tracks, as well as in vesicle tethering, docking and fusion at the target membrane. The nervous system is extremely sensitive to such disturbances of the membrane trafficking machinery, and the majority of these disorders display neurological defects--particularly diseases affecting the motility of transport carriers along cytoskeletal tracks. In several disorders, defects in a component that represents a fundamental part of the trafficking machinery fail to cause global transport defects but result in symptoms limited to specific cell types and transport events; this apparently reflects the redundancy of the transport apparatus. In groups of closely related diseases such as Hermansky-Pudlak and Griscelli syndromes, identification of the underlying gene defects has revealed groups of genes in which mutations lead to similar phenotypic consequences. New functionally linked trafficking components and regulatory mechanisms have thus been discovered. Studies of the gene defects in trafficking disorders therefore not only open avenues for new therapeutic approaches but also significantly contribute to our knowledge of the fundamental mechanisms of intracellular membrane transport.

Genetics of human body size and shape: pleiotropic and independent genetic determinants of adiposity.

PubMed

Livshits, G; Yakovenko, K; Ginsburg, E; Kobyliansky, E

1998-01-01

The present study utilized pedigree data from three ethnically different populations of Kirghizstan, Turkmenia and Chuvasha. Principal component analysis was performed on a matrix of genetic correlations between 22 measures of adiposity, including skinfolds, circumferences and indices. Findings are summarized as follows: (1) All three genetic matrices were not positive definite and the first four factors retained even after exclusion RG > or = 1.0, explained from 88% to 97% of the total additive genetic variation in the 22 trials studied. This clearly emphasizes the massive involvement of pleiotropic gene effects in the variability of adiposity traits. (2) Despite the quite natural differences in pairwise correlations between the adiposity traits in the three ethnically different samples under study, factor analysis revealed a common basic pattern of covariability for the adiposity traits. In each of the three samples, four genetic factors were retained, namely, the amount of subcutaneous fat, the total body obesity, the pattern of distribution of subcutaneous fat and the central adiposity distribution. (3) Genetic correlations between the retained four factors were virtually non-existent, suggesting that several independent genetic sources may be governing the variation of adiposity traits. (4) Variance decomposition analysis on the obtained genetic factors leaves no doubt regarding the substantial familial and (most probably genetic) effects on variation of each factor in each studied population. The similarity of results in the three different samples indicates that the findings may be deemed valid and reliable descriptions of the genetic variation and covariation pattern of adiposity traits in the human species.

Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

PubMed

Pes, Giovanni Mario; Delitala, Alessandro Palmerio; Errigo, Alessandra; Delitala, Giuseppe; Dore, Maria Pina

2016-06-01

Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers) showed a faster beta-cells failure and PC-3 (characterized mostly by gender and high triglycerides) and PC-4 (high cholesterol) showed a slower beta-cells failure. PC-1 (including dislipidemia and other metabolic dysfunctions), showed a mild beta-cells failure. In conclusion variable clustering might be consistent with different pathogenic pathways and/or distinct immune mechanisms in LADA and could potentially help physicians improve the clinical management of these patients.

Common heritable effects underpin concerns over norm maintenance and in-group favoritism: evidence from genetic analyses of right-wing authoritarianism and traditionalism.

PubMed

Lewis, Gary J; Bates, Timothy C

2014-08-01

Research has shown that in-group favoritism is associated with concerns over the maintenance of social norms. Here we present two studies examining whether genetic factors underpin this association. A classical twin design was used to decompose phenotypic variance into genetic and environmental components in two studies. Study 1 used 812 pairs of adult U.S. twins from the nationally representative MIDUS II sample. Study 2 used 707 pairs of middle-age twins from the Minnesota Twin Registry. In-group favoritism was measured with scales tapping preferences for in-group (vs. out-group) individuals; norm concerns were measured with the Multidimensional Personality Questionnaire-Traditionalism (Study 1) and Right-Wing Authoritarianism (RWA; Study 2) scales. In Study 1, heritable effects underlying traditionalism were moderately (c. 35%) overlapping with the genetic variance underpinning in-group favoritism. In Study 2, heritable influences on RWA were entirely shared with the heritable effects on in-group favoritism. Moreover, we observed that Big Five Openness shared common genetic links to both RWA and in-group favoritism. These results suggest that, at the genetic level, in-group favoritism is linked with a system related to concern over normative social practices, which is, in turn, partially associated with trait Openness. © 2013 Wiley Periodicals, Inc.

HUMAN GENETICS AS A TOOL TO IDENTIFY PROGRANULIN REGULATORS

PubMed Central

Nicholson, Alexandra M.; Finch, NiCole A.; Rademakers, Rosa

2012-01-01

Frontotemporal lobar degeneration (FTLD) is a common neurodegenerative disorder that predominantly affects individuals under the age of 65. It is known that the most common pathological subtype is FTLD with TAR DNA-binding protein 43 inclusions (FTLD-TDP). FTLD has a strong genetic component with about 50% of cases having a positive family history. Mutations identified in the progranulin gene (GRN) have been shown to cause FTLD-TDP as a result of progranulin haploinsufficiency. These findings suggest a progranulin-dependent mechanism in this pathological FTLD subtype. Thus, identifying regulators of progranulin levels is essential for new therapies and treatments for FTLD and related disorders. In this review, we discuss the role of genetic studies in identifying progranulin regulators, beginning with the discovery of pathogenic GRN mutations and additional GRN risk variants. We also cover more recent genetic advances, including the detection of variants in the transmembrane protein 106 B gene that increase FTLD-TDP risk presumably by modulating progranulin levels and the identification of a potential progranulin receptor, sortilin. This review highlights the importance of genetic studies in the context of FTLD and further emphasizes the need for future genetic and cell biology research to continue the effort in finding a cure for progranulin-related diseases. PMID:21626010

A gentic survey of Salvinia minima in the southern United States

USGS Publications Warehouse

Madeira, Paul T.; Jacono, Colette C.; Tipping, Phil; Van, Thai K.; Center, Ted D.

2003-01-01

The genetic relationships among 68 samples of Salvinia minima (Salviniaceae) were investigated using RAPD analysis. Neighbor joining, principle components, and AMOVA analyses were used to detect differences among geographically referenced samples within and outside of Florida. Genetic distances (Nei and Li) range up to 0.48, although most are under 0.30, still relatively high levels for an introduced, clonally reproducing plant. Despite the diversity AMOVA analysis yielded no indication that the Florida plants, as a group, were significantly different from the plants sampled elsewhere in its adventive, North American range. A single, genetically dissimilar population probably exists in the recent (1998) horticultural introduction to Mississippi. When the samples were grouped into 10 regional (but artificial) units and analyzed using AMOVA the between region variance was only 7.7%. Genetic similarity among these regions may indicate introduction and dispersal from common sources. The reduced aggressiveness of Florida populations (compared to other states) may be due to herbivory. The weevilCyrtobagous salviniae, a selective feeder, is found in Florida but not other states. The genetic similarity also suggests that there are no obvious genetic obstacles to the establishment or efficacy of C. salviniae as a biological control agent on S. minimaoutside of Florida.

Genetics, systems, and alcohol.

PubMed

McClearn, G E

1993-03-01

Under a variety of rubrics (e.g., complexity, self-constructing systems, dissipative structures), interest has recently burgeoned in applying principles of complex systems to a wide variety of scientific issues. A major concern is with emergent properties of systems not derivable from the properties of components of the systems. In this paper, some elementary aspects of "systems" considerations are applied to phenomena of alcohol pharmacogenetics. It is likely that whole new families of informative phenotypes can be generated by this approach.

The common molecular players in plant hormone crosstalk and signaling.

PubMed

Ohri, Puja; Bhardwaj, Renu; Bali, Shagun; Kaur, Ravinderjit; Jasrotia, Shivam; Khajuria, Anjali; Parihar, Ripu D

2015-01-01

Plant growth and development is under the control of mutual interactions among plant hormones. The five classical categories of plant hormones include auxins, cytokinins, gibberellins, abscisic acid and ethylene. Additionally, newer classes of plant hormones have been recognized like brassinosteroids, jasmonic acid, salicylic acid and polyamines. These hormones play significant roles in regulating the plant growth and development. Various receptors and key signaling components of these hormones have been studied and identified. At genetic level, crosstalk among the various plant hormones is found to be antagonistic or synergistic. In addition, components of signaling pathway of one plant hormone interact with the signaling components of other hormone. Thus, an attempt has been made to review the literature regarding the role of plant hormones in plant physiology and the common molecular players in their signaling and crosstalk.

Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression.

PubMed

Zeng, Yanni; Navarro, Pau; Xia, Charley; Amador, Carmen; Fernandez-Pujals, Ana M; Thomson, Pippa A; Campbell, Archie; Nagy, Reka; Clarke, Toni-Kim; Hafferty, Jonathan D; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

2016-12-01

Both genetic and environmental factors contribute to risk of depression, but estimates of their relative contributions are limited. Commonalities between clinically-assessed major depressive disorder (MDD) and self-declared depression (SDD) are also unclear. Using data from a large Scottish family-based cohort (GS:SFHS, N=19,994), we estimated the genetic and environmental variance components for MDD and SDD. The components representing the genetic effect associated with genome-wide common genetic variants (SNP heritability), the additional pedigree-associated genetic effect and non-genetic effects associated with common environments were estimated in a linear mixed model (LMM). Both MDD and SDD had significant contributions from components representing the effect from common genetic variants, the additional genetic effect associated with the pedigree and the common environmental effect shared by couples. The estimate of correlation between SDD and MDD was high (r=1.00, se=0.20) for common-variant-associated genetic effect and lower for the additional genetic effect from the pedigree (r=0.57, se=0.08) and the couple-shared environmental effect (r=0.53, se=0.22). Both genetics and couple-shared environmental effects were major factors influencing liability to depression. SDD may provide a scalable alternative to MDD in studies seeking to identify common risk variants. Rarer variants and environmental effects may however differ substantially according to different definitions of depression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Severe infectious diseases of childhood as monogenic inborn errors of immunity

PubMed Central

Casanova, Jean-Laurent

2015-01-01

This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications. PMID:26621750

A cognitive characterization of dyscalculia in Turner syndrome.

PubMed

Bruandet, Marie; Molko, Nicolas; Cohen, Laurent; Dehaene, Stanislas

2004-01-01

Current theories of number processing postulate that the human abilities for arithmetic are based on cerebral circuits that are partially laid down under genetic control and later modified by schooling and education. This view predicts the existence of genetic diseases that interfere specifically with components of the number system. Here, we investigate whether Turner syndrome (TS) corresponds to this definition. TS is a genetic disorder which affects one woman in 2500 and is characterized by partial or complete absence of one X chromosome. In addition to well-characterized physical and hormonal dysfunction, TS patients exhibit cognitive deficits including dyscalculia. We tested 12 women with Turner syndrome and 13 control subjects on a cognitive battery including arithmetical tests (addition, subtraction, multiplication, division) as well as tests of the understanding of numerosity and quantity (cognitive estimation, estimation, comparison, bisection, subitizing/counting). Impairments were observed in cognitive estimation, subitizing, and calculation. We examine whether these deficits can be attributed to a single source, and discuss the possible implications of hormonal and genetic factors in the neuropsychological profile of TS patients.

Genetic Architecture of the Delis-Kaplan Executive Function System Trail Making Test: Evidence for Distinct Genetic Influences on Executive Function

PubMed Central

Vasilopoulos, Terrie; Franz, Carol E.; Panizzon, Matthew S.; Xian, Hong; Grant, Michael D.; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C.; Kremen, William S.

2012-01-01

Objective To examine how genes and environments contribute to relationships among Trail Making test conditions and the extent to which these conditions have unique genetic and environmental influences. Method Participants included 1237 middle-aged male twins from the Vietnam-Era Twin Study of Aging (VESTA). The Delis-Kaplan Executive Function System Trail Making test included visual searching, number and letter sequencing, and set-shifting components. Results Phenotypic correlations among Trails conditions ranged from 0.29 – 0.60, and genes accounted for the majority (58–84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set-shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. Conclusions A common genetic factor, most likely representing a combination of speed and sequencing accounted for most of the correlation among Trails 1–4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set-shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in non-patient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes. PMID:22201299

Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States.

PubMed

Kim, Jong Wook; Abudayyeh, Omar O; Yeerna, Huwate; Yeang, Chen-Hsiang; Stewart, Michelle; Jenkins, Russell W; Kitajima, Shunsuke; Konieczkowski, David J; Medetgul-Ernar, Kate; Cavazos, Taylor; Mah, Clarence; Ting, Stephanie; Van Allen, Eliezer M; Cohen, Ofir; Mcdermott, John; Damato, Emily; Aguirre, Andrew J; Liang, Jonathan; Liberzon, Arthur; Alexe, Gabriella; Doench, John; Ghandi, Mahmoud; Vazquez, Francisca; Weir, Barbara A; Tsherniak, Aviad; Subramanian, Aravind; Meneses-Cime, Karina; Park, Jason; Clemons, Paul; Garraway, Levi A; Thomas, David; Boehm, Jesse S; Barbie, David A; Hahn, William C; Mesirov, Jill P; Tamayo, Pablo

2017-08-23

The systematic sequencing of the cancer genome has led to the identification of numerous genetic alterations in cancer. However, a deeper understanding of the functional consequences of these alterations is necessary to guide appropriate therapeutic strategies. Here, we describe Onco-GPS (OncoGenic Positioning System), a data-driven analysis framework to organize individual tumor samples with shared oncogenic alterations onto a reference map defined by their underlying cellular states. We applied the methodology to the RAS pathway and identified nine distinct components that reflect transcriptional activities downstream of RAS and defined several functional states associated with patterns of transcriptional component activation that associates with genomic hallmarks and response to genetic and pharmacological perturbations. These results show that the Onco-GPS is an effective approach to explore the complex landscape of oncogenic cellular states across cancers, and an analytic framework to summarize knowledge, establish relationships, and generate more effective disease models for research or as part of individualized precision medicine paradigms. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test

PubMed Central

Lionel, Anath C; Costain, Gregory; Monfared, Nasim; Walker, Susan; Reuter, Miriam S; Hosseini, S Mohsen; Thiruvahindrapuram, Bhooma; Merico, Daniele; Jobling, Rebekah; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Sung, Wilson W L; Wang, Zhuozhi; Bikangaga, Peter; Boelman, Cyrus; Carter, Melissa T; Cordeiro, Dawn; Cytrynbaum, Cheryl; Dell, Sharon D; Dhir, Priya; Dowling, James J; Heon, Elise; Hewson, Stacy; Hiraki, Linda; Inbar-Feigenberg, Michal; Klatt, Regan; Kronick, Jonathan; Laxer, Ronald M; Licht, Christoph; MacDonald, Heather; Mercimek-Andrews, Saadet; Mendoza-Londono, Roberto; Piscione, Tino; Schneider, Rayfel; Schulze, Andreas; Silverman, Earl; Siriwardena, Komudi; Snead, O Carter; Sondheimer, Neal; Sutherland, Joanne; Vincent, Ajoy; Wasserman, Jonathan D; Weksberg, Rosanna; Shuman, Cheryl; Carew, Chris; Szego, Michael J; Hayeems, Robin Z; Basran, Raveen; Stavropoulos, Dimitri J; Ray, Peter N; Bowdin, Sarah; Meyn, M Stephen; Cohn, Ronald D; Scherer, Stephen W; Marshall, Christian R

2018-01-01

Purpose Genetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use. Methods We prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing. Results WGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24% P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A. Conclusion WGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort. PMID:28771251

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.

PubMed

Lionel, Anath C; Costain, Gregory; Monfared, Nasim; Walker, Susan; Reuter, Miriam S; Hosseini, S Mohsen; Thiruvahindrapuram, Bhooma; Merico, Daniele; Jobling, Rebekah; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Sung, Wilson W L; Wang, Zhuozhi; Bikangaga, Peter; Boelman, Cyrus; Carter, Melissa T; Cordeiro, Dawn; Cytrynbaum, Cheryl; Dell, Sharon D; Dhir, Priya; Dowling, James J; Heon, Elise; Hewson, Stacy; Hiraki, Linda; Inbar-Feigenberg, Michal; Klatt, Regan; Kronick, Jonathan; Laxer, Ronald M; Licht, Christoph; MacDonald, Heather; Mercimek-Andrews, Saadet; Mendoza-Londono, Roberto; Piscione, Tino; Schneider, Rayfel; Schulze, Andreas; Silverman, Earl; Siriwardena, Komudi; Snead, O Carter; Sondheimer, Neal; Sutherland, Joanne; Vincent, Ajoy; Wasserman, Jonathan D; Weksberg, Rosanna; Shuman, Cheryl; Carew, Chris; Szego, Michael J; Hayeems, Robin Z; Basran, Raveen; Stavropoulos, Dimitri J; Ray, Peter N; Bowdin, Sarah; Meyn, M Stephen; Cohn, Ronald D; Scherer, Stephen W; Marshall, Christian R

2018-04-01

PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use.MethodsWe prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing.ResultsWGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24%; P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A.ConclusionWGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.

[Genetic study on somatotype of child and adolescent twins in Han nationality].

PubMed

Li, Yu-Ling; Ji, Cheng-Ye; Lu, Shun-Hua; Suo, Li-Ya; Chen, Tian-Jiao

2006-11-01

To assess the genetic and environmental influences on the somatotype of children and adolescents, and the effects of sex and age. The components of somatotype were calculated by using Heather-Cater method in a total of 376 twin pairs of Han nationality, including 245 monozygotic (MZ) and 131 like-sex dizygotic (DZ) twin pairs aged 6 to 18 years. Model-fitting method by Mx package was performed to evaluate the proportion of variance components and to analyze the effects of sex and age on each component of somatotype using the adjusted data for other two somatotype components. The heritability of each component in different development periods divided by growth spurt was also evaluated. The estimated heritabilities of endomorphic, mesomorphic and ectomorphic components were 0.45, 0.80, 0.44 in boys, 0.82, 0.79 and 0.81 in girls respectively after adjusting age. In boys, the heritability of endomorphic component during late puberty was significantly higher than that during pre-puberty (t = 4.99, P < 0.01) and puberty (t = 6.16, P < 0.01), while the heritability of ectomorphic component during late puberty was significantly lower than that during pre-puberty (t = 3.35, P < 0.01) and puberty (t = 4.12, P < 0.01). In girls, the heritability of endomorphic (t = 2.77, P < 0.01) or mesomorphic (t = 2.08, P < 0.05) component during pre-puberty was significantly higher than that in early puberty. The genetic influence on somatotype of girls should be much more than that of boys, especially on the endomorphic and ectomorphic components. For boys, the mesomorphic component is mainly determined by genetic factors, but the other components are mainly affected by environmental ones. The effects of the development periods on the heritability of somatotype should be paid much attention to.

Phenotypic Stability of Zea mays Grain Yield and Its Attributing Traits under Drought Stress

PubMed Central

Ali, Fawad; Ahsan, Muhammad; Ali, Qurban; Kanwal, Naila

2017-01-01

Phenotypic stability under stress environment facilitate the fitness of genotype and opens new horizons to explore the cryptic genetic variation. Variation in tolerance to drought stress, a major grain yield constraint to global maize production, was identified, at the phenotypic and genotypic level. Here we found a prominent hybrid H9 that showed fitness over four growing seasons for grain yield under water stress conditions. Genotypic and phenotypic correlation of yield attributing traits over four seasons demonstrated that cobs per plant, 100 seed weight, number of grains rows per cob, total dry matter, cob diameter had positive association (r2 = 0.3–0.9) to grain yield. The perturbation was found for chlorophyll content as it showed moderate to strong association (P < 0.01) over four seasons, might be due to environment or genotype dependent. Highest heritability (95%) and genetic advance (79%) for grain yield was found in H9 over four consecutive crop growing seasons. Combined analysis over four seasons showed that studied variables together explained 85% of total variation in dependent structure (grain yield) obtained by Principal component analysis. This significant finding is the best example of phenotypic stability of grain yield in H9 and made it best fitted for grain yield under drought stress scenario. Detailed genetic analysis of H9 will help us to identify significant loci and alleles that made H9 the best fitted and it could serve as a potential source to generate novel transgressive levels of tolerance for drought stress in arid/semiarid regions. PMID:28878785

Phenotypic Stability of Zea mays Grain Yield and Its Attributing Traits under Drought Stress.

PubMed

Ali, Fawad; Ahsan, Muhammad; Ali, Qurban; Kanwal, Naila

2017-01-01

Phenotypic stability under stress environment facilitate the fitness of genotype and opens new horizons to explore the cryptic genetic variation. Variation in tolerance to drought stress, a major grain yield constraint to global maize production, was identified, at the phenotypic and genotypic level. Here we found a prominent hybrid H 9 that showed fitness over four growing seasons for grain yield under water stress conditions. Genotypic and phenotypic correlation of yield attributing traits over four seasons demonstrated that cobs per plant, 100 seed weight, number of grains rows per cob, total dry matter, cob diameter had positive association ( r 2 = 0.3-0.9) to grain yield. The perturbation was found for chlorophyll content as it showed moderate to strong association ( P < 0.01) over four seasons, might be due to environment or genotype dependent. Highest heritability (95%) and genetic advance (79%) for grain yield was found in H 9 over four consecutive crop growing seasons. Combined analysis over four seasons showed that studied variables together explained 85% of total variation in dependent structure (grain yield) obtained by Principal component analysis. This significant finding is the best example of phenotypic stability of grain yield in H 9 and made it best fitted for grain yield under drought stress scenario. Detailed genetic analysis of H 9 will help us to identify significant loci and alleles that made H 9 the best fitted and it could serve as a potential source to generate novel transgressive levels of tolerance for drought stress in arid/semiarid regions.

Speed, Variability, and Timing of Motor Output in ADHD: Which Measures are Useful for Endophenotypic Research?

PubMed Central

Altink, Marieke E.; Oosterlaan, Jaap; Beem, Leo; Buschgens, Cathelijne J. M.; Buitelaar, Jan; Sergeant, Joseph A.

2007-01-01

Attention-Deficit/Hyperactivity Disorder (ADHD) shares a genetic basis with motor coordination problems and probably motor timing problems. In line with this, comparable problems in motor timing should be observed in first degree relatives and might, therefore, form a suitable endophenotypic candidate. This hypothesis was investigated in 238 ADHD-families (545 children) and 147 control-families (271 children). A motor timing task was administered, in which children had to produce a 1,000 ms interval. In addition to this task, two basic motor tasks were administered to examine speed and variability of motor output, when no timing component was required. Results indicated that variability in motor timing is a useful endophenotypic candidate: It was clearly associated with ADHD, it was also present in non-affected siblings, and it correlated within families. Accuracy (under- versus over-production) in motor timing appeared less useful: Even though accuracy was associated with ADHD (probands and affected siblings had a tendency to under-produce the 1,000 ms interval compared to controls), non-affected siblings did not differ from controls and sibling correlations were only marginally significant. Slow and variable motor output without timing component also appears present in ADHD, but not in non-affected siblings, suggesting these deficits not to be related to a familial vulnerability for ADHD. Deficits in motor timing could not be explained by deficits already present in basic motor output without a timing component. This suggests abnormalities in motor timing were predominantly related to deficient motor timing processes and not to general deficient motor functioning. The finding that deficits in motor timing run in ADHD-families suggests this to be a fruitful domain for further exploration in relation to the genetic underpinnings of ADHD. PMID:18071893

Genetic Counseling as an Educational Process.

ERIC Educational Resources Information Center

Eddy, James M.; St. Pierre, Richard

Historically genetic counseling programs have not included strong educational components or sound educational foundations. This paper deals with some of the drawbacks of current genetic counseling programs and the implications for education in the genetic counseling process. The author adopts a broad definition of genetic counseling which…

Genetics Home Reference: adiposis dolorosa

MedlinePlus

... are some genetic conditions more common in particular ethnic groups? Genetic Changes The cause of adiposis dolorosa is unknown. The condition is thought to have a genetic component because a few families with multiple affected family members have been reported. ...

Applications of machine learning and data mining methods to detect associations of rare and common variants with complex traits.

PubMed

Lu, Ake Tzu-Hui; Austin, Erin; Bonner, Ashley; Huang, Hsin-Hsiung; Cantor, Rita M

2014-09-01

Machine learning methods (MLMs), designed to develop models using high-dimensional predictors, have been used to analyze genome-wide genetic and genomic data to predict risks for complex traits. We summarize the results from six contributions to our Genetic Analysis Workshop 18 working group; these investigators applied MLMs and data mining to analyses of rare and common genetic variants measured in pedigrees. To develop risk profiles, group members analyzed blood pressure traits along with single-nucleotide polymorphisms and rare variant genotypes derived from sequence and imputation analyses in large Mexican American pedigrees. Supervised MLMs included penalized regression with varying penalties, support vector machines, and permanental classification. Unsupervised MLMs included sparse principal components analysis and sparse graphical models. Entropy-based components analyses were also used to mine these data. None of the investigators fully capitalized on the genetic information provided by the complete pedigrees. Their approaches either corrected for the nonindependence of the individuals within the pedigrees or analyzed only those who were independent. Some methods allowed for covariate adjustment, whereas others did not. We evaluated these methods using a variety of metrics. Four contributors conducted primary analyses on the real data, and the other two research groups used the simulated data with and without knowledge of the underlying simulation model. One group used the answers to the simulated data to assess power and type I errors. Although the MLMs applied were substantially different, each research group concluded that MLMs have advantages over standard statistical approaches with these high-dimensional data. © 2014 WILEY PERIODICALS, INC.

Bayesian Genomic Prediction with Genotype × Environment Interaction Kernel Models

PubMed Central

Cuevas, Jaime; Crossa, José; Montesinos-López, Osval A.; Burgueño, Juan; Pérez-Rodríguez, Paulino; de los Campos, Gustavo

2016-01-01

The phenomenon of genotype × environment (G × E) interaction in plant breeding decreases selection accuracy, thereby negatively affecting genetic gains. Several genomic prediction models incorporating G × E have been recently developed and used in genomic selection of plant breeding programs. Genomic prediction models for assessing multi-environment G × E interaction are extensions of a single-environment model, and have advantages and limitations. In this study, we propose two multi-environment Bayesian genomic models: the first model considers genetic effects (u) that can be assessed by the Kronecker product of variance–covariance matrices of genetic correlations between environments and genomic kernels through markers under two linear kernel methods, linear (genomic best linear unbiased predictors, GBLUP) and Gaussian (Gaussian kernel, GK). The other model has the same genetic component as the first model (u) plus an extra component, f, that captures random effects between environments that were not captured by the random effects u. We used five CIMMYT data sets (one maize and four wheat) that were previously used in different studies. Results show that models with G × E always have superior prediction ability than single-environment models, and the higher prediction ability of multi-environment models with u and f over the multi-environment model with only u occurred 85% of the time with GBLUP and 45% of the time with GK across the five data sets. The latter result indicated that including the random effect f is still beneficial for increasing prediction ability after adjusting by the random effect u. PMID:27793970

Bayesian Genomic Prediction with Genotype × Environment Interaction Kernel Models.

PubMed

Cuevas, Jaime; Crossa, José; Montesinos-López, Osval A; Burgueño, Juan; Pérez-Rodríguez, Paulino; de Los Campos, Gustavo

2017-01-05

The phenomenon of genotype × environment (G × E) interaction in plant breeding decreases selection accuracy, thereby negatively affecting genetic gains. Several genomic prediction models incorporating G × E have been recently developed and used in genomic selection of plant breeding programs. Genomic prediction models for assessing multi-environment G × E interaction are extensions of a single-environment model, and have advantages and limitations. In this study, we propose two multi-environment Bayesian genomic models: the first model considers genetic effects [Formula: see text] that can be assessed by the Kronecker product of variance-covariance matrices of genetic correlations between environments and genomic kernels through markers under two linear kernel methods, linear (genomic best linear unbiased predictors, GBLUP) and Gaussian (Gaussian kernel, GK). The other model has the same genetic component as the first model [Formula: see text] plus an extra component, F: , that captures random effects between environments that were not captured by the random effects [Formula: see text] We used five CIMMYT data sets (one maize and four wheat) that were previously used in different studies. Results show that models with G × E always have superior prediction ability than single-environment models, and the higher prediction ability of multi-environment models with [Formula: see text] over the multi-environment model with only u occurred 85% of the time with GBLUP and 45% of the time with GK across the five data sets. The latter result indicated that including the random effect f is still beneficial for increasing prediction ability after adjusting by the random effect [Formula: see text]. Copyright © 2017 Cuevas et al.

Selection on plant male function genes identifies candidates for reproductive isolation of yellow monkeyflowers.

PubMed

Aagaard, Jan E; George, Renee D; Fishman, Lila; Maccoss, Michael J; Swanson, Willie J

2013-01-01

Understanding the genetic basis of reproductive isolation promises insight into speciation and the origins of biological diversity. While progress has been made in identifying genes underlying barriers to reproduction that function after fertilization (post-zygotic isolation), we know much less about earlier acting pre-zygotic barriers. Of particular interest are barriers involved in mating and fertilization that can evolve extremely rapidly under sexual selection, suggesting they may play a prominent role in the initial stages of reproductive isolation. A significant challenge to the field of speciation genetics is developing new approaches for identification of candidate genes underlying these barriers, particularly among non-traditional model systems. We employ powerful proteomic and genomic strategies to study the genetic basis of conspecific pollen precedence, an important component of pre-zygotic reproductive isolation among yellow monkeyflowers (Mimulus spp.) resulting from male pollen competition. We use isotopic labeling in combination with shotgun proteomics to identify more than 2,000 male function (pollen tube) proteins within maternal reproductive structures (styles) of M. guttatus flowers where pollen competition occurs. We then sequence array-captured pollen tube exomes from a large outcrossing population of M. guttatus, and identify those genes with evidence of selective sweeps or balancing selection consistent with their role in pollen competition. We also test for evidence of positive selection on these genes more broadly across yellow monkeyflowers, because a signal of adaptive divergence is a common feature of genes causing reproductive isolation. Together the molecular evolution studies identify 159 pollen tube proteins that are candidate genes for conspecific pollen precedence. Our work demonstrates how powerful proteomic and genomic tools can be readily adapted to non-traditional model systems, allowing for genome-wide screens towards the goal of identifying the molecular basis of genetically complex traits.

The capture of heritable variation for genetic quality through social competition.

PubMed

Wolf, Jason B; Harris, W Edwin; Royle, Nick J

2008-09-01

In theory, females of many species choose mates based on traits that are indicators of male genetic quality. A fundamental question in evolutionary biology is why genetic variation for such indicator traits persists despite strong persistent selection imposed by female preference, which is known as the lek paradox. One potential solution to the lek paradox suggests that the traits that are targets of mate choice should evolve condition-dependent expression and that condition should have a large genetic variance. Condition is expected to exhibit high genetic variance because it is affected by a large number of physiological processes and hence, condition-dependent traits should 'capture' variation contributed by a large number of loci. We suggest that a potentially important cause of variation in condition is competition for limited resources. Here, we discuss a pair of models to analyze the evolutionary genetics of traits affected by success in social competition for resources. We show that competition can contribute to genetic variation of 'competition-dependent' traits that have fundamentally different evolutionary properties than other sources of variation. Competition dependence can make traits honest indicators of genetic quality by revealing the relative competitive ability of males, can provide a component of heritable variation that does not contribute to trait evolution, and can help maintain heritable variation under directional selection. Here we provide a general introduction to the concept of competition dependence and briefly introduce two models to demonstrate the potential evolutionary consequences of competition-dependent trait expression.

Unraveling additive from nonadditive effects using genomic relationship matrices.

PubMed

Muñoz, Patricio R; Resende, Marcio F R; Gezan, Salvador A; Resende, Marcos Deon Vilela; de Los Campos, Gustavo; Kirst, Matias; Huber, Dudley; Peter, Gary F

2014-12-01

The application of quantitative genetics in plant and animal breeding has largely focused on additive models, which may also capture dominance and epistatic effects. Partitioning genetic variance into its additive and nonadditive components using pedigree-based models (P-genomic best linear unbiased predictor) (P-BLUP) is difficult with most commonly available family structures. However, the availability of dense panels of molecular markers makes possible the use of additive- and dominance-realized genomic relationships for the estimation of variance components and the prediction of genetic values (G-BLUP). We evaluated height data from a multifamily population of the tree species Pinus taeda with a systematic series of models accounting for additive, dominance, and first-order epistatic interactions (additive by additive, dominance by dominance, and additive by dominance), using either pedigree- or marker-based information. We show that, compared with the pedigree, use of realized genomic relationships in marker-based models yields a substantially more precise separation of additive and nonadditive components of genetic variance. We conclude that the marker-based relationship matrices in a model including additive and nonadditive effects performed better, improving breeding value prediction. Moreover, our results suggest that, for tree height in this population, the additive and nonadditive components of genetic variance are similar in magnitude. This novel result improves our current understanding of the genetic control and architecture of a quantitative trait and should be considered when developing breeding strategies. Copyright © 2014 by the Genetics Society of America.

Summarizing techniques that combine three non-parametric scores to detect disease-associated 2-way SNP-SNP interactions.

PubMed

Sengupta Chattopadhyay, Amrita; Hsiao, Ching-Lin; Chang, Chien Ching; Lian, Ie-Bin; Fann, Cathy S J

2014-01-01

Identifying susceptibility genes that influence complex diseases is extremely difficult because loci often influence the disease state through genetic interactions. Numerous approaches to detect disease-associated SNP-SNP interactions have been developed, but none consistently generates high-quality results under different disease scenarios. Using summarizing techniques to combine a number of existing methods may provide a solution to this problem. Here we used three popular non-parametric methods-Gini, absolute probability difference (APD), and entropy-to develop two novel summary scores, namely principle component score (PCS) and Z-sum score (ZSS), with which to predict disease-associated genetic interactions. We used a simulation study to compare performance of the non-parametric scores, the summary scores, the scaled-sum score (SSS; used in polymorphism interaction analysis (PIA)), and the multifactor dimensionality reduction (MDR). The non-parametric methods achieved high power, but no non-parametric method outperformed all others under a variety of epistatic scenarios. PCS and ZSS, however, outperformed MDR. PCS, ZSS and SSS displayed controlled type-I-errors (<0.05) compared to GS, APDS, ES (>0.05). A real data study using the genetic-analysis-workshop 16 (GAW 16) rheumatoid arthritis dataset identified a number of interesting SNP-SNP interactions. © 2013 Elsevier B.V. All rights reserved.

A kernel regression approach to gene-gene interaction detection for case-control studies.

PubMed

Larson, Nicholas B; Schaid, Daniel J

2013-11-01

Gene-gene interactions are increasingly being addressed as a potentially important contributor to the variability of complex traits. Consequently, attentions have moved beyond single locus analysis of association to more complex genetic models. Although several single-marker approaches toward interaction analysis have been developed, such methods suffer from very high testing dimensionality and do not take advantage of existing information, notably the definition of genes as functional units. Here, we propose a comprehensive family of gene-level score tests for identifying genetic elements of disease risk, in particular pairwise gene-gene interactions. Using kernel machine methods, we devise score-based variance component tests under a generalized linear mixed model framework. We conducted simulations based upon coalescent genetic models to evaluate the performance of our approach under a variety of disease models. These simulations indicate that our methods are generally higher powered than alternative gene-level approaches and at worst competitive with exhaustive SNP-level (where SNP is single-nucleotide polymorphism) analyses. Furthermore, we observe that simulated epistatic effects resulted in significant marginal testing results for the involved genes regardless of whether or not true main effects were present. We detail the benefits of our methods and discuss potential genome-wide analysis strategies for gene-gene interaction analysis in a case-control study design. © 2013 WILEY PERIODICALS, INC.

Patterns of population structure and environmental associations to aridity across the range of loblolly pine (Pinus taeda L., Pinaceae).

PubMed

Eckert, Andrew J; van Heerwaarden, Joost; Wegrzyn, Jill L; Nelson, C Dana; Ross-Ibarra, Jeffrey; González-Martínez, Santíago C; Neale, David B

2010-07-01

Natural populations of forest trees exhibit striking phenotypic adaptations to diverse environmental gradients, thereby making them appealing subjects for the study of genes underlying ecologically relevant phenotypes. Here, we use a genome-wide data set of single nucleotide polymorphisms genotyped across 3059 functional genes to study patterns of population structure and identify loci associated with aridity across the natural range of loblolly pine (Pinus taeda L.). Overall patterns of population structure, as inferred using principal components and Bayesian cluster analyses, were consistent with three genetic clusters likely resulting from expansions out of Pleistocene refugia located in Mexico and Florida. A novel application of association analysis, which removes the confounding effects of shared ancestry on correlations between genetic and environmental variation, identified five loci correlated with aridity. These loci were primarily involved with abiotic stress response to temperature and drought. A unique set of 24 loci was identified as F(ST) outliers on the basis of the genetic clusters identified previously and after accounting for expansions out of Pleistocene refugia. These loci were involved with a diversity of physiological processes. Identification of nonoverlapping sets of loci highlights the fundamental differences implicit in the use of either method and suggests a pluralistic, yet complementary, approach to the identification of genes underlying ecologically relevant phenotypes.

Plant twitter: ligands under 140 amino acids enforcing stomatal patterning.

PubMed

Rychel, Amanda L; Peterson, Kylee M; Torii, Keiko U

2010-05-01

Stomata are an essential land plant innovation whose patterning and density are under genetic and environmental control. Recently, several putative ligands have been discovered that influence stomatal density, and they all belong to the epidermal patterning factor-like family of secreted cysteine-rich peptides. Two of these putative ligands, EPF1 and EPF2, are expressed exclusively in the stomatal lineage cells and negatively regulate stomatal density. A third, EPFL6 or CHALLAH, is also a negative regulator of density, but is expressed subepidermally in the hypocotyl. A fourth, EPFL9 or STOMAGEN, is expressed in the mesophyll tissues and is a positive regulator of density. Genetic evidence suggests that these ligands may compete for the same receptor complex. Proper stomatal patterning is likely to be an intricate process involving ligand competition, regional specificity, and communication between tissue layers. EPFL-family genes exist in the moss Physcomitrella patens, the lycophyte Selaginella moellendorffii, and rice, Oryza sativa, and their sequence analysis yields several genes some of which are related to EPF1, EPF2, EPFL6, and EPFL9. Presence of these EPFL family members in the basal land plants suggests an exciting hypothesis that the genetic components for stomatal patterning originated early in land plant evolution.

Positive Traits in the Bipolar Spectrum: The Space between Madness and Genius

PubMed Central

Greenwood, Tiffany A.

2017-01-01

Bipolar disorder is a severe, lifelong mood disorder for which little is currently understood of the genetic mechanisms underlying risk. By examining related dimensional phenotypes, we may further our understanding of the disorder. Creativity has a historical connection with the bipolar spectrum and is particularly enhanced among unaffected first-degree relatives and those with bipolar spectrum traits. This suggests that some aspects of the bipolar spectrum may confer advantages, while more severe expressions of symptoms negatively influence creative accomplishment. Creativity is a complex, multidimensional construct with both cognitive and affective components, many of which appear to reflect a shared genetic vulnerability with bipolar disorder. It is suggested that a subset of bipolar risk variants confer advantages as positive traits according to an inverted-U-shaped curve with clinically unaffected allele carriers benefitting from the positive traits and serving to maintain the risk alleles in the population. The association of risk genes with creativity in healthy individuals (e.g., NRG1), as well as an overall sharing of common genetic variation between bipolar patients and creative individuals, provides support for this model. Current findings are summarized from a multidisciplinary perspective to demonstrate the feasibility of research in this area to reveal the mechanisms underlying illness. PMID:28277566

Strains and stressors: an analysis of touchscreen learning in genetically diverse mouse strains.

PubMed

Graybeal, Carolyn; Bachu, Munisa; Mozhui, Khyobeni; Saksida, Lisa M; Bussey, Timothy J; Sagalyn, Erica; Williams, Robert W; Holmes, Andrew

2014-01-01

Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal) in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of "reversal learning," "motivation-related late reversal learning," "discrimination learning," "speed to respond," and "motivation during discrimination." Together, these findings provide a valuable reference to inform the choice of strains and genetic backgrounds in future studies using touchscreen-based tasks.

Shared influence of pathogen and host genetics on a trade-off between latent period and spore production capacity in the wheat pathogen, Puccinia triticina.

PubMed

Pariaud, Bénédicte; Berg, Femke; Bosch, Frank; Powers, Stephen J; Kaltz, Oliver; Lannou, Christian

2013-02-01

Crop pathogens are notorious for their rapid adaptation to their host. We still know little about the evolution of their life cycles and whether there might be trade-offs between fitness components, limiting the evolutionary potential of these pathogens. In this study, we explored a trade-off between spore production capacity and latent period in Puccinia triticina, a fungal pathogen causing leaf rust on wheat. Using a simple multivariate (manova) technique, we showed that the covariance between the two traits is under shared control of host and pathogen, with contributions from host genotype (57%), pathogen genotype (18.4%) and genotype × genotype interactions (12.5%). We also found variation in sign and strength of genetic correlations for the pathogen, when measured on different host varieties. Our results suggest that these important pathogen life-history traits do not freely respond to directional selection and that precise evolutionary trajectories are contingent on the genetic identity of the interacting host and pathogen.

Genetic Architecture of Skin and Eye Color in an African-European Admixed Population

PubMed Central

Beleza, Sandra; Johnson, Nicholas A.; Candille, Sophie I.; Absher, Devin M.; Coram, Marc A.; Lopes, Jailson; Campos, Joana; Araújo, Isabel Inês; Anderson, Tovi M.; Vilhjálmsson, Bjarni J.; Nordborg, Magnus; Correia e Silva, António; Shriver, Mark D.; Rocha, Jorge

2013-01-01

Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3×10−62, SLC24A5 P = 9.6×10−9) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4×10−27, TYR P = 1.1×10−9, APBA2[OCA2] P = 1.5×10−8, SLC45A2 P = 6×10−9) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (∼44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ∼70% of the estimated heritability. PMID:23555287

Methodological framework for projecting the potential loss of intraspecific genetic diversity due to global climate change

PubMed Central

2012-01-01

Background While research on the impact of global climate change (GCC) on ecosystems and species is flourishing, a fundamental component of biodiversity – molecular variation – has not yet received its due attention in such studies. Here we present a methodological framework for projecting the loss of intraspecific genetic diversity due to GCC. Methods The framework consists of multiple steps that combines 1) hierarchical genetic clustering methods to define comparable units of inference, 2) species accumulation curves (SAC) to infer sampling completeness, and 3) species distribution modelling (SDM) to project the genetic diversity loss under GCC. We suggest procedures for existing data sets as well as specifically designed studies. We illustrate the approach with two worked examples from a land snail (Trochulus villosus) and a caddisfly (Smicridea (S.) mucronata). Results Sampling completeness was diagnosed on the third coarsest haplotype clade level for T. villosus and the second coarsest for S. mucronata. For both species, a substantial species range loss was projected under the chosen climate scenario. However, despite substantial differences in data set quality concerning spatial sampling and sampling depth, no loss of haplotype clades due to GCC was predicted for either species. Conclusions The suggested approach presents a feasible method to tap the rich resources of existing phylogeographic data sets and guide the design and analysis of studies explicitly designed to estimate the impact of GCC on a currently still neglected level of biodiversity. PMID:23176586

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 variation and biogeography of the spotted gar Lepisosteus oculatus from core and peripheral populations.

PubMed

David, Solomon R; Wright, Jeremy J

2017-11-01

The spotted gar (Lepisosteus oculatus) shows a disjunct natural distribution, with a core population extending from the central Mississippi River Basin to the U.S. gulf coast and a peripheral population in the southern Great Lakes Basin. Despite significant conservation concerns for this species in the Great Lakes watersheds where it occurs, few genetic examinations and comparisons of these populations have been performed. We investigated inter- and intrapopulational variation in several mitochondrial genetic markers (cytochrome oxidase subunit I, COI; cytochrome oxidase subunit II, COII; and 16S rRNA, 16S) from spotted gars taken from core and peripheral populations. Genetic diversity was highest in the Mississippi River Basin and lowest in the Great Lakes Basin, while the Nueces River Basin (Texas) population showed the greatest level of divergence from other populations. Average genetic distance among core and peripheral populations was over an order of magnitude less than that seen between L. oculatus and its sister species, the Florida gar (L. platyrhincus), although a significant correlation was found between genetic and geographical distance in L. oculatus. Genetic divergence in spotted gars is likely to be related to a combination of geographic isolation and founder effects associated with recent colonization following glacial retreat. Despite its apparent lack of significant genetic differentiation or haplotype diversity, the Great Lakes population of spotted gars has previously been shown to be a unique component of the species, and additional studies are needed to determine the genetic mechanisms underlying regional adaptations as well as potential morphological differentiation among spotted gar populations. © 2017 Wiley Periodicals, Inc.

Evolving Tale of TCPs: New Paradigms and Old Lacunae

PubMed Central

Dhaka, Namrata; Bhardwaj, Vasudha; Sharma, Manoj K.; Sharma, Rita

2017-01-01

Teosinte Branched1/Cycloidea/Proliferating cell factors (TCP) genes are key mediators of genetic innovations underlying morphological novelties, stress adaptation, and evolution of immune response in plants. They have a remarkable ability to integrate and translate diverse endogenous, and environmental signals with high fidelity. Compilation of studies, aimed at elucidating the mechanism of TCP functions, shows that it takes an amalgamation and interplay of several different factors, regulatory processes and pathways, instead of individual components, to achieve the incredible functional diversity and specificity, demonstrated by TCP proteins. Through this minireview, we provide a brief description of key structural features and molecular components, known so far, that operate this conglomerate, and highlight the important conceptual challenges and lacunae in TCP research. PMID:28421104

Evolving Tale of TCPs: New Paradigms and Old Lacunae.

PubMed

Dhaka, Namrata; Bhardwaj, Vasudha; Sharma, Manoj K; Sharma, Rita

2017-01-01

Teosinte Branched1/Cycloidea/Proliferating cell factors (TCP) genes are key mediators of genetic innovations underlying morphological novelties, stress adaptation, and evolution of immune response in plants. They have a remarkable ability to integrate and translate diverse endogenous, and environmental signals with high fidelity. Compilation of studies, aimed at elucidating the mechanism of TCP functions, shows that it takes an amalgamation and interplay of several different factors, regulatory processes and pathways, instead of individual components, to achieve the incredible functional diversity and specificity, demonstrated by TCP proteins. Through this minireview, we provide a brief description of key structural features and molecular components, known so far, that operate this conglomerate, and highlight the important conceptual challenges and lacunae in TCP research.

Evidence for a genetic component in familial sarcoidosis

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

Rybicki, B.A.; Harrington, D.; Major, M.

1994-09-01

Sarcoidosis is a disease with reported familial clustering, but a putative hereditary component has not been established. We analyzed 33 sarcoid index cases with a positive family history and their 596 1st and 2nd degree relatives to determine if the distribution of disease was consistent with a genetic etiology. Prevalence of sarcoidosis was twice as high in 1st degree relatives of index cases compared to 2nd degree relatives (8.5% vs. 3.9%; p=0.016). Recurrence risk ratios (defined as the risk of disease in relatives divided by the population prevalence) were calculated in 2nd degree relatives after making an ascertainment correction. Amore » single gene model fit the observed results better than a polygenic model for a range of sarcoidosis prevalance. A greater shared environment among siblings compared to parents and offspring did not appear to increase risk of sarcoidosis based on a higher prevalance of disease in the latter (7.1% vs. 10.7%; p=0.313). However, the age of diagnosis in affected parent-offspring pairs was more consistent with a combined genetic and environmental etiology than either component alone. In summary, these results suggest a genetic component, possibly a single gene, increases disease risk in family members of sarcoidosis cases. A segregation analysis is planned to more thoroughly evaluate the evidence for both genetic and non-genetic transmission of sarcoidosis in these families.« less

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.

Evolution, revolution and heresy in the genetics of infectious disease susceptibility

PubMed Central

Hill, Adrian V. S.

2012-01-01

Infectious pathogens have long been recognized as potentially powerful agents impacting on the evolution of human genetic diversity. Analysis of large-scale case–control studies provides one of the most direct means of identifying human genetic variants that currently impact on susceptibility to particular infectious diseases. For over 50 years candidate gene studies have been used to identify loci for many major causes of human infectious mortality, including malaria, tuberculosis, human immunodeficiency virus/acquired immunodeficiency syndrome, bacterial pneumonia and hepatitis. But with the advent of genome-wide approaches, many new loci have been identified in diverse populations. Genome-wide linkage studies identified a few loci, but genome-wide association studies are proving more successful, and both exome and whole-genome sequencing now offer a revolutionary increase in power. Opinions differ on the extent to which the genetic component to common disease susceptibility is encoded by multiple high frequency or rare variants, and the heretical view that most infectious diseases might even be monogenic has been advocated recently. Review of findings to date suggests that the genetic architecture of infectious disease susceptibility may be importantly different from that of non-infectious diseases, and it is suggested that natural selection may be the driving force underlying this difference. PMID:22312051

Genetic correlation between autistic traits and IQ in a population-based sample of twins with autism spectrum disorders (ASDs).

PubMed

Nishiyama, Takeshi; Taniai, Hiroko; Taniai, Hitomi; Miyachi, Taishi; Ozaki, Koken; Tomita, Makoto; Sumi, Satoshi

2009-01-01

Although there is accumulating evidence that intelligence quotient (IQ) indexes some aspects of the autistic spectrum disorders (ASDs), the causal relationship between autistic traits and IQ remains controversial. We examined the sources of covariation between autistic traits and IQ. As males have a four times greater risk of ASDs than females, gender-specific effects were also explored. Autistic traits and IQ were assessed in 45 twin male-male, female-female and opposite-sex pairs ascertained by the regional screening system in Nagoya, Japan. Sex-limited Cholesky structural equation models were used to decompose the correlations between autistic traits and IQ into genetic and environmental components, including sex-specific factors. Genetic correlations between autistic traits and IQ were high and not significantly different between boys and girls (-0.94 and -0.95, respectively), but genetic factors underlying the autistic traits were not entirely shared with the IQ. The individual-specific environmental correlation between autistic traits and IQ was estimated at -0.29 for boys and -0.59 for girls. There is a substantial overlap between the genetic factors that influence individual variation in autistic traits and IQ, irrespective of gender. The individual life experiences that increase autistic traits, however, have a moderate overlap with those that contribute to individual IQs.

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

Comparative Analysis of Metabolic Syndrome Components in over 15,000 African Americans Identifies Pleiotropic Variants: Results from the PAGE Study

PubMed Central

Carty, Cara L.; Bhattacharjee, Samsiddhi; Haessler, Jeff; Cheng, Iona; Hindorff, Lucia A.; Aroda, Vanita; Carlson, Christopher S.; Hsu, Chun-Nan; Wilkens, Lynne; Liu, Simin; Selvin, Elizabeth; Jackson, Rebecca; North, Kari E.; Peters, Ulrike; Pankow, James S.; Chatterjee, Nilanjan; Kooperberg, Charles

2014-01-01

Background Metabolic syndrome (MetS) refers to the clustering of cardio-metabolic risk factors including dyslipidemia, central adiposity, hypertension and hyperglycemia in individuals. Identification of pleiotropic genetic factors associated with MetS traits may shed light on key pathways or mediators underlying MetS. Methods and Results Using the Metabochip array in 15,148 African Americans (AA) from the PAGE Study, we identify susceptibility loci and investigate pleiotropy among genetic variants using a subset-based meta-analysis method, ASsociation-analysis-based-on-subSETs (ASSET). Unlike conventional models which lack power when associations for MetS components are null or have opposite effects, ASSET uses one-sided tests to detect positive and negative associations for components separately and combines tests accounting for correlations among components. With ASSET, we identify 27 SNPs in 1 glucose and 4 lipids loci (TCF7L2, LPL, APOA5, CETP, LPL, APOC1/APOE/TOMM40) significantly associated with MetS components overall, all P< 2.5e-7, the Bonferroni adjusted P-value. Three loci replicate in a Hispanic population, n=5172. A novel AA-specific variant, rs12721054/APOC1, and rs10096633/LPL are associated with ≥3 MetS components. We find additional evidence of pleiotropy for APOE, TOMM40, TCF7L2 and CETP variants, many with opposing effects; e.g. the same rs7901695/TCF7L2 allele is associated with increased odds of high glucose and decreased odds of central adiposity. Conclusions We highlight a method to increase power in large-scale genomic association analyses, and report a novel variant associated with all MetS components in AA. We also identify pleiotropic associations that may be clinically useful in patient risk profiling and for informing translational research of potential gene targets and medications. PMID:25023634

Analysis of metabolic syndrome components in >15 000 african americans identifies pleiotropic variants: results from the population architecture using genomics and epidemiology study.

PubMed

Carty, Cara L; Bhattacharjee, Samsiddhi; Haessler, Jeff; Cheng, Iona; Hindorff, Lucia A; Aroda, Vanita; Carlson, Christopher S; Hsu, Chun-Nan; Wilkens, Lynne; Liu, Simin; Selvin, Elizabeth; Jackson, Rebecca; North, Kari E; Peters, Ulrike; Pankow, James S; Chatterjee, Nilanjan; Kooperberg, Charles

2014-08-01

Metabolic syndrome (MetS) refers to the clustering of cardiometabolic risk factors, including dyslipidemia, central adiposity, hypertension, and hyperglycemia, in individuals. Identification of pleiotropic genetic factors associated with MetS traits may shed light on key pathways or mediators underlying MetS. Using the Metabochip array in 15 148 African Americans from the Population Architecture using Genomics and Epidemiology (PAGE) study, we identify susceptibility loci and investigate pleiotropy among genetic variants using a subset-based meta-analysis method, ASsociation-analysis-based-on-subSETs (ASSET). Unlike conventional models that lack power when associations for MetS components are null or have opposite effects, Association-analysis-based-on-subsets uses 1-sided tests to detect positive and negative associations for components separately and combines tests accounting for correlations among components. With Association-analysis-based-on-subsets, we identify 27 single nucleotide polymorphisms in 1 glucose and 4 lipids loci (TCF7L2, LPL, APOA5, CETP, and APOC1/APOE/TOMM40) significantly associated with MetS components overall, all P<2.5e-7, the Bonferroni adjusted P value. Three loci replicate in a Hispanic population, n=5172. A novel African American-specific variant, rs12721054/APOC1, and rs10096633/LPL are associated with ≥3 MetS components. We find additional evidence of pleiotropy for APOE, TOMM40, TCF7L2, and CETP variants, many with opposing effects (eg, the same rs7901695/TCF7L2 allele is associated with increased odds of high glucose and decreased odds of central adiposity). We highlight a method to increase power in large-scale genomic association analyses and report a novel variant associated with all MetS components in African Americans. We also identify pleiotropic associations that may be clinically useful in patient risk profiling and for informing translational research of potential gene targets and medications. © 2014 American Heart Association, Inc.

The evolution of trade-offs under directional and correlational selection.

PubMed

Roff, Derek A; Fairbairn, Daphne J

2012-08-01

Using quantitative genetic theory, we develop predictions for the evolution of trade-offs in response to directional and correlational selection. We predict that directional selection favoring an increase in one trait in a trade-off will result in change in the intercept but not the slope of the trade-off function, with the mean value of the selected trait increasing and that of the correlated trait decreasing. Natural selection will generally favor an increase in some combination of trait values, which can be represented as directional selection on an index value. Such selection induces both directional and correlational selection on the component traits. Theory predicts that selection on an index value will also change the intercept but not the slope of the trade-off function but because of correlational selection, the direction of change in component traits may be in the same or opposite directions. We test these predictions using artificial selection on the well-established trade-off between fecundity and flight capability in the cricket, Gryllus firmus and compare the empirical results with a priori predictions made using genetic parameters from a separate half-sibling experiment. Our results support the predictions and illustrate the complexity of trade-off evolution when component traits are subject to both directional and correlational selection. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Overview of the Genetics of Alcohol Use Disorder

PubMed Central

Tawa, Elisabeth A.; Hall, Samuel D.; Lohoff, Falk W.

2016-01-01

Aims Alcohol Use Disorder (AUD) is a chronic psychiatric illness characterized by harmful drinking patterns leading to negative emotional, physical, and social ramifications. While the underlying pathophysiology of AUD is poorly understood, there is substantial evidence for a genetic component; however, identification of universal genetic risk variants for AUD has been difficult. Recent efforts in the search for AUD susceptibility genes will be reviewed in this article. Methods In this review, we provide an overview of genetic studies on AUD, including twin studies, linkage studies, candidate gene studies, and genome-wide association studies (GWAS). Results Several potential genetic susceptibility factors for AUD have been identified, but the genes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), have been found to be protective against the development of AUD. GWAS have also identified a heterogeneous list of SNPs associated with AUD and alcohol-related phenotypes, emphasizing the complexity and heterogeneity of the disorder. In addition, many of these findings have small effect sizes when compared to alcohol metabolism genes, and biological relevance is often unknown. Conclusions Although studies spanning multiple approaches have suggested a genetic basis for AUD, identification of the genetic risk variants has been challenging. Some promising results are emerging from GWAS studies; however, larger sample sizes are needed to improve GWAS results and resolution. As the field of genetics is rapidly developing, whole genome sequencing could soon become the new standard of interrogation of the genes and neurobiological pathways which contribute to the complex phenotype of AUD. Short summary This review examines the genetic underpinnings of Alcohol Use Disorder (AUD), with an emphasis on GWAS approaches for identifying genetic risk variants. The most promising results associated with AUD and alcohol-related phenotypes have included SNPs of the alcohol metabolism genes ADH and ALDH. PMID:27445363

Applying landscape genomic tools to forest management and restoration of Hawaiian koa (Acacia koa) in a changing environment.

PubMed

Gugger, Paul F; Liang, Christina T; Sork, Victoria L; Hodgskiss, Paul; Wright, Jessica W

2018-02-01

Identifying and quantifying the importance of environmental variables in structuring population genetic variation can help inform management decisions for conservation, restoration, or reforestation purposes, in both current and future environmental conditions. Landscape genomics offers a powerful approach for understanding the environmental factors that currently associate with genetic variation, and given those associations, where populations may be most vulnerable under future environmental change. Here, we applied genotyping by sequencing to generate over 11,000 single nucleotide polymorphisms from 311 trees and then used nonlinear, multivariate environmental association methods to examine spatial genetic structure and its association with environmental variation in an ecologically and economically important tree species endemic to Hawaii, Acacia koa . Admixture and principal components analyses showed that trees from different islands are genetically distinct in general, with the exception of some genotypes that match other islands, likely as the result of recent translocations. Gradient forest and generalized dissimilarity models both revealed a strong association between genetic structure and mean annual rainfall. Utilizing a model for projected future climate on the island of Hawaii, we show that predicted changes in rainfall patterns may result in genetic offset, such that trees no longer may be genetically matched to their environment. These findings indicate that knowledge of current and future rainfall gradients can provide valuable information for the conservation of existing populations and also help refine seed transfer guidelines for reforestation or replanting of koa throughout the state.

Should I Perform Genetic Testing? A Qualitative Look into the Decision Making Considerations of Religious Israeli Undergraduate Students.

PubMed

Siani, Merav; Assaraf, Orit Ben-Zvi

2016-10-01

The aim of this study is to draw a picture of the concerns that guide the decision making of Israeli religious undergraduate students and the complex considerations they take into account while facing the need to have genetic testing or to attend a genetic counseling session. We examined how the religious affiliation of the students influences their perceptions toward genetics and how these are expressed. Qualitative data were collected from 51 semi-structured interviews with students, in which recurring themes were identified using 'thematic analysis.' The codes from the thematic analysis were obtained according to 'grounded theory'. Our results show that religious undergraduate students' decision making in these issues is influenced by factors that fall under three main categories: knowledge and perceptions, values, and norms. In order to include all the components of influence, we created the Triple C model: "Culture influences Choices towards genetic Counseling" which aims to generalize the complex decision making considerations that we detected. Our model places religion, as part of culture, as its central point of influence that impacts all three of the main categories we detected. It also traces the bidirectional influences that each of these main categories have on one another. Using this model may help identify the sociocultural differences between different types of patients, helping genetic counselors to better assist them in addressing their genetic status by tailoring the counseling more specifically to the patient's cultural uniqueness.

Genetics Home Reference: nonsyndromic aplasia cutis congenita

MedlinePlus

... are some genetic conditions more common in particular ethnic groups? Genetic Changes Nonsyndromic aplasia cutis congenita can have different causes, and often the cause is unknown. Because the condition is sometimes found in multiple members of a family, it is thought to have a genetic component; ...

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

Innovations in human genetics education. Incorporation of genetics into a problem-based medical school curriculum.

PubMed Central

Swinford, A E; McKeag, D B

1990-01-01

There has been recent interest in the development of problem-based human genetics curricula in U.S. medical schools. The College of Human Medicine at Michigan State University has had a problem-based curriculum since 1974. The vertical integration of genetics within the problem-based curriculum, called "Track II," has recently been revised. On first inspection, the curriculum appeared to lack a significant genetics component; however, on further analysis it was found that many genetics concepts were covered in the biochemistry, microbiology, pathology, and clinical science components. Both basic science concepts and clinical applications of genetics are covered in the curriculum by providing appropriate references for basic concepts and including inherited conditions within the differential diagnosis in the cases studied. Evaluations consist of a multiple-choice content exam and a modified essay exam based on a clinical case, allowing evaluation of both basic concepts and problem-solving ability. This curriculum prepares students to use genetics in a clinical context in their future careers. PMID:2220816

Identification of small non-coding RNA classes expressed in swine whole blood during HP-PRRSV infection

USDA-ARS?s Scientific Manuscript database

It has been established that reduced susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) has a genetic component. This genetic component may take the form of small non-coding RNAs (sncRNA), which are molecules that function as regulators of gene expression. Various sncRNAs ...

Genetics of fat intake in the determination of body mass.

PubMed

Chmurzynska, Agata; Mlodzik, Monika A

2017-06-01

Body mass and fat intake are multifactorial traits that have genetic and environmental components. The gene with the greatest effect on body mass is FTO (fat mass and obesity-associated), but several studies have shown that the effect of FTO (and of other genes) on body mass can be modified by the intake of nutrients. The so-called gene-environment interactions may also be important for the effectiveness of weight-loss strategies. Food choices, and thus fat intake, depend to some extent on individual preferences. The most important biological component of food preference is taste, and the role of fat sensitivity in fat intake has recently been pointed out. Relatively few studies have analysed the genetic components of fat intake or fatty acid sensitivity in terms of their relation to obesity. It has been proposed that decreased oral fatty acid sensitivity leads to increased fat intake and thus increased body mass. One of the genes that affect fatty acid sensitivity is CD36 (cluster of differentiation 36). However, little is known so far about the genetic component of fat sensing. We performed a literature review to identify the state of knowledge regarding the genetics of fat intake and its relation to body-mass determination, and to identify the priorities for further investigations.

Nontraditional inheritance: Genetics and the nature of science, now titled, The puzzle of inheritance: Genetics and the methods of science. Final report

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

McInerney, J.D.

1998-08-31

This project led to the development of an instructional module designed for use in high school biology classes. The module contains two major components. The first is an overview for teachers, which introduces the module, describes the Human Genome Project, and addresses issues in the philosophy of science and some of the ethical, legal, and social implications of research in genetics. It provides a survey of fundamental genetics concepts and of new, nontraditional concepts of inheritance. The second component provides six instructional activities appropriate for high school or introductory college students.

The clinical maze of mitochondrial neurology

PubMed Central

DiMauro, Salvatore; Schon, Eric A.; Carelli, Valerio; Hirano, Michio

2014-01-01

Mitochondrial diseases involve the respiratory chain, which is under the dual control of nuclear and mitochondrial DNA (mtDNA). The complexity of mitochondrial genetics provides one explanation for the clinical heterogeneity of mitochondrial diseases, but our understanding of disease pathogenesis remains limited. Classification of Mendelian mitochondrial encephalomyopathies has been laborious, but whole-exome sequencing studies have revealed unexpected molecular aetiologies for both typical and atypical mitochondrial disease phenotypes. Mendelian mitochondrial defects can affect five components of mitochondrial biology: subunits of respiratory chain complexes (direct hits); mitochondrial assembly proteins; mtDNA translation; phospholipid composition of the inner mitochondrial membrane; or mitochondrial dynamics. A sixth category—defects of mtDNA maintenance—combines features of Mendelian and mitochondrial genetics. Genetic defects in mitochondrial dynamics are especially important in neurology as they cause optic atrophy, hereditary spastic paraplegia, and Charcot–Marie–Tooth disease. Therapy is inadequate and mostly palliative, but promising new avenues are being identified. Here, we review current knowledge on the genetics and pathogenesis of the six categories of mitochondrial disorders outlined above, focusing on their salient clinical manifestations and highlighting novel clinical entities. An outline of diagnostic clues for the various forms of mitochondrial disease, as well as potential therapeutic strategies, is also discussed. PMID:23835535

The Three Domains of Conservation Genetics: Case Histories from Hawaiian Waters.

PubMed

Bowen, Brian W

2016-07-01

The scientific field of conservation biology is dominated by 3 specialties: phylogenetics, ecology, and evolution. Under this triad, phylogenetics is oriented towards the past history of biodiversity, conserving the divergent branches in the tree of life. The ecological component is rooted in the present, maintaining the contemporary life support systems for biodiversity. Evolutionary conservation (as defined here) is concerned with preserving the raw materials for generating future biodiversity. All 3 domains can be documented with genetic case histories in the waters of the Hawaiian Archipelago, an isolated chain of volcanic islands with 2 types of biodiversity: colonists, and new species that arose from colonists. This review demonstrates that 1) phylogenetic studies have identified previously unknown branches in the tree of life that are endemic to Hawaiian waters; 2) population genetic surveys define isolated marine ecosystems as management units, and 3) phylogeographic analyses illustrate the pathways of colonization that can enhance future biodiversity. Conventional molecular markers have advanced all 3 domains in conservation biology over the last 3 decades, and recent advances in genomics are especially valuable for understanding the foundations of future evolutionary diversity. © The American Genetic Association. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Efficient strategy for detecting gene × gene joint action and its application in schizophrenia.

PubMed

Won, Sungho; Kwon, Min-Seok; Mattheisen, Manuel; Park, Suyeon; Park, Changsoon; Kihara, Daisuke; Cichon, Sven; Ophoff, Roel; Nöthen, Markus M; Rietschel, Marcella; Baur, Max; Uitterlinden, Andre G; Hofmann, A; Lange, Christoph

2014-01-01

We propose a new approach to detect gene × gene joint action in genome-wide association studies (GWASs) for case-control designs. This approach offers an exhaustive search for all two-way joint action (including, as a special case, single gene action) that is computationally feasible at the genome-wide level and has reasonable statistical power under most genetic models. We found that the presence of any gene × gene joint action may imply differences in three types of genetic components: the minor allele frequencies and the amounts of Hardy-Weinberg disequilibrium may differ between cases and controls, and between the two genetic loci the degree of linkage disequilibrium may differ between cases and controls. Using Fisher's method, it is possible to combine the different sources of genetic information in an overall test for detecting gene × gene joint action. The proposed statistical analysis is efficient and its simplicity makes it applicable to GWASs. In the current study, we applied the proposed approach to a GWAS on schizophrenia and found several potential gene × gene interactions. Our application illustrates the practical advantage of the proposed method. © 2013 WILEY PERIODICALS, INC.

Enamel formation and amelogenesis imperfecta.

PubMed

Hu, Jan C-C; Chun, Yong-Hee P; Al Hazzazzi, Turki; Simmer, James P

2007-01-01

Dental enamel is the epithelial-derived hard tissue covering the crowns of teeth. It is the most highly mineralized and hardest tissue in the body. Dental enamel is acellular and has no physiological means of repair outside of the protective and remineralization potential provided by saliva. Enamel is comprised of highly organized hydroxyapatite crystals that form in a defined extracellular space, the contents of which are supplied and regulated by ameloblasts. The entire process is under genetic instruction. The genetic control of amelogenesis is poorly understood, but requires the activities of multiple components that are uniquely important for dental enamel formation. Amelogenesis imperfecta (AI) is a collective designation for the variety of inherited conditions displaying isolated enamel malformations, but the designation is also used to indicate the presence of an enamel phenotype in syndromes. Recently, genetic studies have demonstrated the importance of genes encoding enamel matrix proteins in the etiology of isolated AI. Here we review the essential elements of dental enamel formation and the results of genetic analyses that have identified disease-causing mutations in genes encoding enamel matrix proteins. In addition, we provide a fresh perspective on the roles matrix proteins play in catalyzing the biomineralization of dental enamel. Copyright 2007 S. Karger AG, Basel.

Multivariate Cholesky models of human female fertility patterns in the NLSY.

PubMed

Rodgers, Joseph Lee; Bard, David E; Miller, Warren B

2007-03-01

Substantial evidence now exists that variables measuring or correlated with human fertility outcomes have a heritable component. In this study, we define a series of age-sequenced fertility variables, and fit multivariate models to account for underlying shared genetic and environmental sources of variance. We make predictions based on a theory developed by Udry [(1996) Biosocial models of low-fertility societies. In: Casterline, JB, Lee RD, Foote KA (eds) Fertility in the United States: new patterns, new theories. The Population Council, New York] suggesting that biological/genetic motivations can be more easily realized and measured in settings in which fertility choices are available. Udry's theory, along with principles from molecular genetics and certain tenets of life history theory, allow us to make specific predictions about biometrical patterns across age. Consistent with predictions, our results suggest that there are different sources of genetic influence on fertility variance at early compared to later ages, but that there is only one source of shared environmental influence that occurs at early ages. These patterns are suggestive of the types of gene-gene and gene-environment interactions for which we must account to better understand individual differences in fertility outcomes.

Highly Pathogenic H5N1 Avian Influenza Viruses Exhibit Few Barriers to Gene Flow in Vietnam

PubMed Central

Carrel, Margaret; Wan, Xiu-Feng; Nguyen, Tung; Emch, Michael

2013-01-01

Locating areas where genetic change is inhibited can illuminate underlying processes that drive evolution of pathogens. The persistence of highly pathogenic H5N1 avian influenza in Vietnam since 2003, and the continuous molecular evolution of Vietnamese avian influenza viruses, indicates that local environmental factors are supportive not only of incidence but also of viral adaptation. This article explores whether gene flow is constant across Vietnam, or whether there exist boundary areas where gene flow exhibits discontinuity. Using a dataset of 125 highly pathogenic H5N1 avian influenza viruses, principal components analysis and wombling analysis are used to indicate the location, magnitude, and statistical significance of genetic boundaries. Results show that a small number of geographically minor boundaries to gene flow in highly pathogenic H5N1 avian influenza viruses exist in Vietnam, but that overall there is little division in genetic exchange. This suggests that differences in genetic characteristics of viruses from one region to another are not the result of barriers to H5N1 viral exchange in Vietnam, and that H5N1 avian influenza is able to spread relatively unimpeded across the country. PMID:22350419

Evolutionary genetics of maternal effects

PubMed Central

Wolf, Jason B.; Wade, Michael J.

2016-01-01

Maternal genetic effects (MGEs), where genes expressed by mothers affect the phenotype of their offspring, are important sources of phenotypic diversity in a myriad of organisms. We use a single‐locus model to examine how MGEs contribute patterns of heritable and nonheritable variation and influence evolutionary dynamics in randomly mating and inbreeding populations. We elucidate the influence of MGEs by examining the offspring genotype‐phenotype relationship, which determines how MGEs affect evolutionary dynamics in response to selection on offspring phenotypes. This approach reveals important results that are not apparent from classic quantitative genetic treatments of MGEs. We show that additive and dominance MGEs make different contributions to evolutionary dynamics and patterns of variation, which are differentially affected by inbreeding. Dominance MGEs make the offspring genotype‐phenotype relationship frequency dependent, resulting in the appearance of negative frequency‐dependent selection, while additive MGEs contribute a component of parent‐of‐origin dependent variation. Inbreeding amplifies the contribution of MGEs to the additive genetic variance and, therefore enhances their evolutionary response. Considering evolutionary dynamics of allele frequency change on an adaptive landscape, we show that this landscape differs from the mean fitness surface, and therefore, under some condition, fitness peaks can exist but not be “available” to the evolving population. PMID:26969266

A new method of linkage analysis using LOD scores for quantitative traits supports linkage of monoamine oxidase activity to D17S250 in the Collaborative Study on the Genetics of Alcoholism pedigrees.

PubMed

Curtis, David; Knight, Jo; Sham, Pak C

2005-09-01

Although LOD score methods have been applied to diseases with complex modes of inheritance, linkage analysis of quantitative traits has tended to rely on non-parametric methods based on regression or variance components analysis. Here, we describe a new method for LOD score analysis of quantitative traits which does not require specification of a mode of inheritance. The technique is derived from the MFLINK method for dichotomous traits. A range of plausible transmission models is constructed, constrained to yield the correct population mean and variance for the trait but differing with respect to the contribution to the variance due to the locus under consideration. Maximized LOD scores under homogeneity and admixture are calculated, as is a model-free LOD score which compares the maximized likelihoods under admixture assuming linkage and no linkage. These LOD scores have known asymptotic distributions and hence can be used to provide a statistical test for linkage. The method has been implemented in a program called QMFLINK. It was applied to data sets simulated using a variety of transmission models and to a measure of monoamine oxidase activity in 105 pedigrees from the Collaborative Study on the Genetics of Alcoholism. With the simulated data, the results showed that the new method could detect linkage well if the true allele frequency for the trait was close to that specified. However, it performed poorly on models in which the true allele frequency was much rarer. For the Collaborative Study on the Genetics of Alcoholism data set only a modest overlap was observed between the results obtained from the new method and those obtained when the same data were analysed previously using regression and variance components analysis. Of interest is that D17S250 produced a maximized LOD score under homogeneity and admixture of 2.6 but did not indicate linkage using the previous methods. However, this region did produce evidence for linkage in a separate data set, suggesting that QMFLINK may have been able to detect a true linkage which was not picked up by the other methods. The application of model-free LOD score analysis to quantitative traits is novel and deserves further evaluation of its merits and disadvantages relative to other methods.

Seedling Emergence and Phenotypic Response of Common Bean Germplasm to Different Temperatures under Controlled Conditions and in Open Field.

PubMed

De Ron, Antonio M; Rodiño, Ana P; Santalla, Marta; González, Ana M; Lema, María J; Martín, Isaura; Kigel, Jaime

2016-01-01

Rapid and uniform seed germination and seedling emergence under diverse environmental conditions is a desirable characteristic for crops. Common bean genotypes (Phaseolus vulgaris L.) differ in their low temperature tolerance regarding growth and yield. Cultivars tolerant to low temperature during the germination and emergence stages and carriers of the grain quality standards demanded by consumers are needed for the success of the bean crop. The objectives of this study were (i) to screen the seedling emergence and the phenotypic response of bean germplasm under a range of temperatures in controlled chamber and field conditions to display stress-tolerant genotypes with good agronomic performances and yield potential, and (ii) to compare the emergence of bean seedlings under controlled environment and in open field conditions to assess the efficiency of genebanks standard germination tests for predicting the performance of the seeds in the field. Three trials were conducted with 28 dry bean genotypes in open field and in growth chamber under low, moderate, and warm temperature. Morpho-agronomic data were used to evaluate the phenotypic performance of the different genotypes. Cool temperatures resulted in a reduction of the rate of emergence in the bean genotypes, however, emergence and early growth of bean could be under different genetic control and these processes need further research to be suitably modeled. Nine groups arose from the Principal Component Analysis (PCA) representing variation in emergence time and proportion of emergence in the controlled chamber and in the open field indicating a trend to lower emergence in large and extra-large seeded genotypes. Screening of seedling emergence and phenotypic response of the bean germplasm under a range of temperatures in controlled growth chambers and under field conditions showed several genotypes, as landraces 272, 501, 593, and the cultivar Borlotto, with stress-tolerance at emergence, and high yield potential that could be valuable genetic material for breeding programs. Additionally, the potential genetic erosion in genebanks was assessed. Regarding bean commercial traits, under low temperature at sowing time seed reached larger size, and crop yield was higher compared to warmer temperatures at the sowing time. Therefore, early sowing of bean is strongly recommended.

Seedling Emergence and Phenotypic Response of Common Bean Germplasm to Different Temperatures under Controlled Conditions and in Open Field

PubMed Central

De Ron, Antonio M.; Rodiño, Ana P.; Santalla, Marta; González, Ana M.; Lema, María J.; Martín, Isaura; Kigel, Jaime

2016-01-01

Rapid and uniform seed germination and seedling emergence under diverse environmental conditions is a desirable characteristic for crops. Common bean genotypes (Phaseolus vulgaris L.) differ in their low temperature tolerance regarding growth and yield. Cultivars tolerant to low temperature during the germination and emergence stages and carriers of the grain quality standards demanded by consumers are needed for the success of the bean crop. The objectives of this study were (i) to screen the seedling emergence and the phenotypic response of bean germplasm under a range of temperatures in controlled chamber and field conditions to display stress-tolerant genotypes with good agronomic performances and yield potential, and (ii) to compare the emergence of bean seedlings under controlled environment and in open field conditions to assess the efficiency of genebanks standard germination tests for predicting the performance of the seeds in the field. Three trials were conducted with 28 dry bean genotypes in open field and in growth chamber under low, moderate, and warm temperature. Morpho-agronomic data were used to evaluate the phenotypic performance of the different genotypes. Cool temperatures resulted in a reduction of the rate of emergence in the bean genotypes, however, emergence and early growth of bean could be under different genetic control and these processes need further research to be suitably modeled. Nine groups arose from the Principal Component Analysis (PCA) representing variation in emergence time and proportion of emergence in the controlled chamber and in the open field indicating a trend to lower emergence in large and extra-large seeded genotypes. Screening of seedling emergence and phenotypic response of the bean germplasm under a range of temperatures in controlled growth chambers and under field conditions showed several genotypes, as landraces 272, 501, 593, and the cultivar Borlotto, with stress-tolerance at emergence, and high yield potential that could be valuable genetic material for breeding programs. Additionally, the potential genetic erosion in genebanks was assessed. Regarding bean commercial traits, under low temperature at sowing time seed reached larger size, and crop yield was higher compared to warmer temperatures at the sowing time. Therefore, early sowing of bean is strongly recommended. PMID:27532005

Molecular Genetics of Supernumerary Tooth Formation

PubMed Central

Wang, Xiu-Ping; Fan, Jiabing

2011-01-01

Summary Despite advances in the knowledge of tooth morphogenesis and differentiation, relatively little is known about the aetiology and molecular mechanisms underlying supernumerary tooth formation. A small number of supernumerary teeth may be a common developmental dental anomaly, while multiple supernumerary teeth usually have a genetic component and they are sometimes thought to represent a partial third dentition in humans. Mice, which are commonly used for studying tooth development, only exhibit one dentition, with very few mouse models exhibiting supernumerary teeth similar to those in humans. Inactivation of Apc or forced activation of Wnt/β(catenin signalling results in multiple supernumerary tooth formation in both humans and in mice, but the key genes in these pathways are not very clear. Analysis of other model systems with continuous tooth replacement or secondary tooth formation, such as fish, snake, lizard, and ferret, is providing insights into the molecular and cellular mechanisms underlying succesional tooth development, and will assist in the studies on supernumerary tooth formation in humans. This information, together with the advances in stem cell biology and tissue engineering, will pave ways for the tooth regeneration and tooth bioengineering. PMID:21309064

Genetics Home Reference: complement component 8 deficiency

MedlinePlus

... in people with Hispanic, Japanese, or African Caribbean heritage, whereas type II primarily occurs in people of Northern European descent. Related Information What information about a genetic condition can statistics provide? Why are some genetic ...

Introgression of genomic components from Chinese Brassica rapa contributes to widening the genetic diversity in rapeseed (B. napus L.), with emphasis on the evolution of Chinese rapeseed.

PubMed

Qian, W; Meng, J; Li, M; Frauen, M; Sass, O; Noack, J; Jung, C

2006-06-01

In spite of its short history of being an oil crop in China, the Chinese semi-winter rapeseed (Brassica napus L., 2n = 38, AACC) has been improved rapidly by intentional introgression of genomic components from Chinese B. rapa (2n = 20, AA). As a result, the Chinese semi-winter rapeseed has diversified genetically from the spring and winter rapeseed grown in the other regions such as Europe and North America. The objectives of this study were to investigate the roles of the introgression of the genomic components from the Chinese B. rapa in widening the genetic diversity of rapeseed and to verify the role of this introgression in the evolution of the Chinese rapeseed. Ten lines of the new type of rapeseed, which were produced by introgression of Chinese B. rapa to Chinese normal rapeseed, were compared for genetic diversity using amplified fragment length polymorphism (AFLP) with three groups of 35 lines of the normal rapeseed, including 9 semi-winter rapeseed lines from China, 9 winter rapeseed lines from Europe and 17 spring rapeseed lines from Northern Europe, Canada and Australia. Analysis of 799 polymorphic fragments revealed that within the groups, the new type rapeseed had the highest genetic diversity, followed by the semi-winter normal rapeseed from China. Spring and winter rapeseed had the lowest genetic diversity. Among the groups, the new type rapeseed group had the largest average genetic distance to the other three groups. Principal component analysis and cluster analysis, however, could not separate the new type rapeseed group from Chinese normal rapeseed group. Our data suggested that the introgression of Chinese B. rapa could significantly diversify the genetic basis of the rapeseed and play an important role in the evolution of Chinese rapeseed. The use of new genetic variation for the exploitation of heterosis in Brassica hybrid breeding is discussed.

The fine-scale genetic structure and evolution of the Japanese population.

PubMed

Takeuchi, Fumihiko; Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Isomura, Minoru; Ohkubo, Takayoshi; Tabara, Yasuharu; Yamamoto, Ken; Yokota, Mitsuhiro; Liu, Xuanyao; Saw, Woei-Yuh; Mamatyusupu, Dolikun; Yang, Wenjun; Xu, Shuhua; Teo, Yik-Ying; Kato, Norihiro

2017-01-01

The contemporary Japanese populations largely consist of three genetically distinct groups-Hondo, Ryukyu and Ainu. By principal-component analysis, while the three groups can be clearly separated, the Hondo people, comprising 99% of the Japanese, form one almost indistinguishable cluster. To understand fine-scale genetic structure, we applied powerful haplotype-based statistical methods to genome-wide single nucleotide polymorphism data from 1600 Japanese individuals, sampled from eight distinct regions in Japan. We then combined the Japanese data with 26 other Asian populations data to analyze the shared ancestry and genetic differentiation. We found that the Japanese could be separated into nine genetic clusters in our dataset, showing a marked concordance with geography; and that major components of ancestry profile of Japanese were from the Korean and Han Chinese clusters. We also detected and dated admixture in the Japanese. While genetic differentiation between Ryukyu and Hondo was suggested to be caused in part by positive selection, genetic differentiation among the Hondo clusters appeared to result principally from genetic drift. Notably, in Asians, we found the possibility that positive selection accentuated genetic differentiation among distant populations but attenuated genetic differentiation among close populations. These findings are significant for studies of human evolution and medical genetics.

Decomposing the Site Frequency Spectrum: The Impact of Tree Topology on Neutrality Tests.

PubMed

Ferretti, Luca; Ledda, Alice; Wiehe, Thomas; Achaz, Guillaume; Ramos-Onsins, Sebastian E

2017-09-01

We investigate the dependence of the site frequency spectrum on the topological structure of genealogical trees. We show that basic population genetic statistics, for instance, estimators of θ or neutrality tests such as Tajima's D , can be decomposed into components of waiting times between coalescent events and of tree topology. Our results clarify the relative impact of the two components on these statistics. We provide a rigorous interpretation of positive or negative values of an important class of neutrality tests in terms of the underlying tree shape. In particular, we show that values of Tajima's D and Fay and Wu's H depend in a direct way on a peculiar measure of tree balance, which is mostly determined by the root balance of the tree. We present a new test for selection in the same class as Fay and Wu's H and discuss its interpretation and power. Finally, we determine the trees corresponding to extreme expected values of these neutrality tests and present formulas for these extreme values as a function of sample size and number of segregating sites. Copyright © 2017 by the Genetics Society of America.

Ambient temperature and genotype differentially affect developmental and phenotypic plasticity in Arabidopsis thaliana.

PubMed

Ibañez, Carla; Poeschl, Yvonne; Peterson, Tom; Bellstädt, Julia; Denk, Kathrin; Gogol-Döring, Andreas; Quint, Marcel; Delker, Carolin

2017-07-06

Global increase in ambient temperatures constitute a significant challenge to wild and cultivated plant species. Forward genetic analyses of individual temperature-responsive traits have resulted in the identification of several signaling and response components. However, a comprehensive knowledge about temperature sensitivity of different developmental stages and the contribution of natural variation is still scarce and fragmented at best. Here, we systematically analyze thermomorphogenesis throughout a complete life cycle in ten natural Arabidopsis thaliana accessions grown under long day conditions in four different temperatures ranging from 16 to 28 °C. We used Q 10 , GxE, phenotypic divergence and correlation analyses to assess temperature sensitivity and genotype effects of more than 30 morphometric and developmental traits representing five phenotype classes. We found that genotype and temperature differentially affected plant growth and development with variing strengths. Furthermore, overall correlations among phenotypic temperature responses was relatively low which seems to be caused by differential capacities for temperature adaptations of individual accessions. Genotype-specific temperature responses may be attractive targets for future forward genetic approaches and accession-specific thermomorphogenesis maps may aid the assessment of functional relevance of known and novel regulatory components.

How powerful are summary-based methods for identifying expression-trait associations under different genetic architectures?

PubMed

Veturi, Yogasudha; Ritchie, Marylyn D

2018-01-01

Transcriptome-wide association studies (TWAS) have recently been employed as an approach that can draw upon the advantages of genome-wide association studies (GWAS) and gene expression studies to identify genes associated with complex traits. Unlike standard GWAS, summary level data suffices for TWAS and offers improved statistical power. Two popular TWAS methods include either (a) imputing the cis genetic component of gene expression from smaller sized studies (using multi-SNP prediction or MP) into much larger effective sample sizes afforded by GWAS - TWAS-MP or (b) using summary-based Mendelian randomization - TWAS-SMR. Although these methods have been effective at detecting functional variants, it remains unclear how extensive variability in the genetic architecture of complex traits and diseases impacts TWAS results. Our goal was to investigate the different scenarios under which these methods yielded enough power to detect significant expression-trait associations. In this study, we conducted extensive simulations based on 6000 randomly chosen, unrelated Caucasian males from Geisinger's MyCode population to compare the power to detect cis expression-trait associations (within 500 kb of a gene) using the above-described approaches. To test TWAS across varying genetic backgrounds we simulated gene expression and phenotype using different quantitative trait loci per gene and cis-expression /trait heritability under genetic models that differentiate the effect of causality from that of pleiotropy. For each gene, on a training set ranging from 100 to 1000 individuals, we either (a) estimated regression coefficients with gene expression as the response using five different methods: LASSO, elastic net, Bayesian LASSO, Bayesian spike-slab, and Bayesian ridge regression or (b) performed eQTL analysis. We then sampled with replacement 50,000, 150,000, and 300,000 individuals respectively from the testing set of the remaining 5000 individuals and conducted GWAS on each set. Subsequently, we integrated the GWAS summary statistics derived from the testing set with the weights (or eQTLs) derived from the training set to identify expression-trait associations using (a) TWAS-MP (b) TWAS-SMR (c) eQTL-based GWAS, or (d) standalone GWAS. Finally, we examined the power to detect functionally relevant genes using the different approaches under the considered simulation scenarios. In general, we observed great similarities among TWAS-MP methods although the Bayesian methods resulted in improved power in comparison to LASSO and elastic net as the trait architecture grew more complex while training sample sizes and expression heritability remained small. Finally, we observed high power under causality but very low to moderate power under pleiotropy.

A strabismus susceptibility locus on chromosome 7p

PubMed Central

Parikh, Vaishali; Shugart, Yin Yao; Doheny, Kimberly F.; Zhang, Jie; Li, Lan; Williams, John; Hayden, David; Craig, Brian; Capo, Hilda; Chamblee, Denise; Chen, Cathy; Collins, Mary; Dankner, Stuart; Fiergang, Dean; Guyton, David; Hunter, David; Hutcheon, Marcia; Keys, Marshall; Morrison, Nancy; Munoz, Michelle; Parks, Marshall; Plotsky, David; Protzko, Eugene; Repka, Michael X.; Sarubbi, Maria; Schnall, Bruce; Siatkowski, R. Michael; Traboulsi, Elias; Waeltermann, Joanne; Nathans, Jeremy

2003-01-01

Strabismus has been known to have a significant genetic component, but the mode of inheritance and the identity of the relevant genes have been enigmatic. This paper reports linkage analysis of nonsyndromic strabismus. The principal results of this study are: (i) the demonstrated feasibility of identifying and recruiting large families in which multiple members have (or had) strabismus; (ii) the linkage in one large family of a presumptive strabismus susceptibility locus to 7p22.1 with a multipoint logarithm of odds score of 4.51 under a model of recessive inheritance; and (iii) the failure to observe significant linkage to 7p in six other multiplex families, consistent with genetic heterogeneity among families. These findings suggest that it will be possible to localize and ultimately identify strabismus susceptibility genes by linkage analysis and mutation screening of candidate genes. PMID:14519848

A three-way parallel ICA approach to analyze links among genetics, brain structure and brain function.

PubMed

Vergara, Victor M; Ulloa, Alvaro; Calhoun, Vince D; Boutte, David; Chen, Jiayu; Liu, Jingyu

2014-09-01

Multi-modal data analysis techniques, such as the Parallel Independent Component Analysis (pICA), are essential in neuroscience, medical imaging and genetic studies. The pICA algorithm allows the simultaneous decomposition of up to two data modalities achieving better performance than separate ICA decompositions and enabling the discovery of links between modalities. However, advances in data acquisition techniques facilitate the collection of more than two data modalities from each subject. Examples of commonly measured modalities include genetic information, structural magnetic resonance imaging (MRI) and functional MRI. In order to take full advantage of the available data, this work extends the pICA approach to incorporate three modalities in one comprehensive analysis. Simulations demonstrate the three-way pICA performance in identifying pairwise links between modalities and estimating independent components which more closely resemble the true sources than components found by pICA or separate ICA analyses. In addition, the three-way pICA algorithm is applied to real experimental data obtained from a study that investigate genetic effects on alcohol dependence. Considered data modalities include functional MRI (contrast images during alcohol exposure paradigm), gray matter concentration images from structural MRI and genetic single nucleotide polymorphism (SNP). The three-way pICA approach identified links between a SNP component (pointing to brain function and mental disorder associated genes, including BDNF, GRIN2B and NRG1), a functional component related to increased activation in the precuneus area, and a gray matter component comprising part of the default mode network and the caudate. Although such findings need further verification, the simulation and in-vivo results validate the three-way pICA algorithm presented here as a useful tool in biomedical data fusion applications. Copyright © 2014 Elsevier Inc. All rights reserved.

On testing an unspecified function through a linear mixed effects model with multiple variance components

PubMed Central

Wang, Yuanjia; Chen, Huaihou

2012-01-01

Summary We examine a generalized F-test of a nonparametric function through penalized splines and a linear mixed effects model representation. With a mixed effects model representation of penalized splines, we imbed the test of an unspecified function into a test of some fixed effects and a variance component in a linear mixed effects model with nuisance variance components under the null. The procedure can be used to test a nonparametric function or varying-coefficient with clustered data, compare two spline functions, test the significance of an unspecified function in an additive model with multiple components, and test a row or a column effect in a two-way analysis of variance model. Through a spectral decomposition of the residual sum of squares, we provide a fast algorithm for computing the null distribution of the test, which significantly improves the computational efficiency over bootstrap. The spectral representation reveals a connection between the likelihood ratio test (LRT) in a multiple variance components model and a single component model. We examine our methods through simulations, where we show that the power of the generalized F-test may be higher than the LRT, depending on the hypothesis of interest and the true model under the alternative. We apply these methods to compute the genome-wide critical value and p-value of a genetic association test in a genome-wide association study (GWAS), where the usual bootstrap is computationally intensive (up to 108 simulations) and asymptotic approximation may be unreliable and conservative. PMID:23020801

On testing an unspecified function through a linear mixed effects model with multiple variance components.

PubMed

Wang, Yuanjia; Chen, Huaihou

2012-12-01

We examine a generalized F-test of a nonparametric function through penalized splines and a linear mixed effects model representation. With a mixed effects model representation of penalized splines, we imbed the test of an unspecified function into a test of some fixed effects and a variance component in a linear mixed effects model with nuisance variance components under the null. The procedure can be used to test a nonparametric function or varying-coefficient with clustered data, compare two spline functions, test the significance of an unspecified function in an additive model with multiple components, and test a row or a column effect in a two-way analysis of variance model. Through a spectral decomposition of the residual sum of squares, we provide a fast algorithm for computing the null distribution of the test, which significantly improves the computational efficiency over bootstrap. The spectral representation reveals a connection between the likelihood ratio test (LRT) in a multiple variance components model and a single component model. We examine our methods through simulations, where we show that the power of the generalized F-test may be higher than the LRT, depending on the hypothesis of interest and the true model under the alternative. We apply these methods to compute the genome-wide critical value and p-value of a genetic association test in a genome-wide association study (GWAS), where the usual bootstrap is computationally intensive (up to 10(8) simulations) and asymptotic approximation may be unreliable and conservative. © 2012, The International Biometric Society.

Genetics of serum carotenoid concentrations and their correlation with obesity-related traits in Mexican American children.

PubMed

Farook, Vidya S; Reddivari, Lavanya; Mummidi, Srinivas; Puppala, Sobha; Arya, Rector; Lopez-Alvarenga, Juan Carlos; Fowler, Sharon P; Chittoor, Geetha; Resendez, Roy G; Kumar, Birunda Mohan; Comuzzie, Anthony G; Curran, Joanne E; Lehman, Donna M; Jenkinson, Christopher P; Lynch, Jane L; DeFronzo, Ralph A; Blangero, John; Hale, Daniel E; Duggirala, Ravindranath; Vanamala, Jairam Kp

2017-07-01

Background: Dietary intake of phytonutrients present in fruits and vegetables, such as carotenoids, is associated with a lower risk of obesity and related traits, but the impact of genetic variation on these associations is poorly understood, especially in children. Objective: We estimated common genetic influences on serum carotenoid concentrations and obesity-related traits in Mexican American (MA) children. Design: Obesity-related data were obtained from 670 nondiabetic MA children, aged 6-17 y. Serum α- and β-carotenoid concentrations were measured in ∼570 (α-carotene in 565 and β-carotene in 572) of these children with the use of an ultraperformance liquid chromatography-photodiode array. We determined heritabilities for both carotenoids and examined their genetic relation with 10 obesity-related traits [body mass index (BMI), waist circumference (WC), high-density lipoprotein (HDL) cholesterol, triglycerides, fat mass (FM), systolic and diastolic blood pressure, fasting insulin and glucose, and homeostasis model assessment of insulin resistance] by using family data and a variance components approach. For these analyses, carotenoid values were inverse normalized, and all traits were adjusted for significant covariate effects of age and sex. Results: Carotenoid concentrations were highly heritable and significant [α-carotene: heritability ( h 2 ) = 0.81, P = 6.7 × 10 -11 ; β-carotene: h 2 = 0.90, P = 3.5 × 10 -15 ]. After adjusting for multiple comparisons, we found significant ( P ≤ 0.05) negative phenotypic correlations between carotenoid concentrations and the following traits: BMI, WC, FM, and triglycerides (range: α-carotene = -0.19 to -0.12; β-carotene = -0.24 to -0.13) and positive correlations with HDL cholesterol (α-carotene = 0.17; β-carotene = 0.24). However, when the phenotypic correlations were partitioned into genetic and environmental correlations, we found marginally significant ( P = 0.051) genetic correlations only between β-carotene and BMI (-0.27), WC (-0.30), and HDL cholesterol (0.31) after accounting for multiple comparisons. None of the environmental correlations were significant. Conclusions: The findings from this study suggest that the serum carotenoid concentrations were under strong additive genetic influences based on variance components analyses, and that the common genetic factors may influence β-carotene and obesity and lipid traits in MA children. © 2017 American Society for Nutrition.

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.

A novel approach to analyzing fMRI and SNP data via parallel independent component analysis

NASA Astrophysics Data System (ADS)

Liu, Jingyu; Pearlson, Godfrey; Calhoun, Vince; Windemuth, Andreas

2007-03-01

There is current interest in understanding genetic influences on brain function in both the healthy and the disordered brain. Parallel independent component analysis, a new method for analyzing multimodal data, is proposed in this paper and applied to functional magnetic resonance imaging (fMRI) and a single nucleotide polymorphism (SNP) array. The method aims to identify the independent components of each modality and the relationship between the two modalities. We analyzed 92 participants, including 29 schizophrenia (SZ) patients, 13 unaffected SZ relatives, and 50 healthy controls. We found a correlation of 0.79 between one fMRI component and one SNP component. The fMRI component consists of activations in cingulate gyrus, multiple frontal gyri, and superior temporal gyrus. The related SNP component is contributed to significantly by 9 SNPs located in sets of genes, including those coding for apolipoprotein A-I, and C-III, malate dehydrogenase 1 and the gamma-aminobutyric acid alpha-2 receptor. A significant difference in the presences of this SNP component is found between the SZ group (SZ patients and their relatives) and the control group. In summary, we constructed a framework to identify the interactions between brain functional and genetic information; our findings provide new insight into understanding genetic influences on brain function in a common mental disorder.

Functional Analysis of the α-1,3-Glucan Synthase Genes agsA and agsB in Aspergillus nidulans: AgsB Is the Major α-1,3-Glucan Synthase in This Fungus

PubMed Central

Yoshimi, Akira; Sano, Motoaki; Inaba, Azusa; Kokubun, Yuko; Fujioka, Tomonori; Mizutani, Osamu; Hagiwara, Daisuke; Fujikawa, Takashi; Nishimura, Marie; Yano, Shigekazu; Kasahara, Shin; Shimizu, Kiminori; Yamaguchi, Masashi; Kawakami, Kazuyoshi; Abe, Keietsu

2013-01-01

Although α-1,3-glucan is one of the major cell wall polysaccharides in filamentous fungi, the physiological roles of α-1,3-glucan remain unclear. The model fungus Aspergillus nidulans possesses two α-1,3-glucan synthase (AGS) genes, agsA and agsB. For functional analysis of these genes, we constructed several mutant strains in A. nidulans: agsA disruption, agsB disruption, and double-disruption strains. We also constructed several CagsB strains in which agsB expression was controlled by the inducible alcA promoter, with or without the agsA-disrupting mutation. The agsA disruption strains did not show markedly different phenotypes from those of the wild-type strain. The agsB disruption strains formed dispersed hyphal cells under liquid culture conditions, regardless of the agsA genetic background. Dispersed hyphal cells were also observed in liquid culture of the CagsB strains when agsB expression was repressed, whereas these strains grew normally in plate culture even under the agsB-repressed conditions. Fractionation of the cell wall based on the alkali solubility of its components, quantification of sugars, and 13C-NMR spectroscopic analysis revealed that α-1,3-glucan was the main component of the alkali-soluble fraction in the wild-type and agsA disruption strains, but almost no α-1,3-glucan was found in the alkali-soluble fraction derived from either the agsB disruption strain or the CagsB strain under the agsB-repressed conditions, regardless of the agsA genetic background. Taken together, our data demonstrate that the two AGS genes are dispensable in A. nidulans, but that AgsB is required for normal growth characteristics under liquid culture conditions and is the major AGS in this species. PMID:23365684

Incorporating a New Bioinformatics Component into Genetics at a Historically Black College: Outcomes and Lessons

ERIC Educational Resources Information Center

Holtzclaw, J. David; Eisen, Arri; Whitney, Erika M.; Penumetcha, Meera; Hoey, J. Joseph; Kimbro, K. Sean

2006-01-01

Many students at minority-serving institutions are underexposed to Internet resources such as the human genome project, PubMed, NCBI databases, and other Web-based technologies because of a lack of financial resources. To change this, we designed and implemented a new bioinformatics component to supplement the undergraduate Genetics course at…

Unnatural reactive amino acid genetic code additions

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

Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Expanding the eukaryotic genetic code

DOEpatents

Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

2013-01-22

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Expanding the eukaryotic genetic code

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

Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Expanding the eukaryotic genetic code

DOEpatents

Chin, Jason W [Cambridge, GB; Cropp, T Ashton [Bethesda, MD; Anderson, J Christopher [San Francisco, CA; Schultz, Peter G [La Jolla, CA

2009-10-27

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Expanding the eukaryotic genetic code

DOEpatents

Chin, Jason W; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G

2015-02-03

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Expanding the eukaryotic genetic code

DOEpatents

Chin, Jason W [Cambridge, GB; Cropp, T Ashton [Bethesda, MD; Anderson, J Christopher [San Francisco, CA; Schultz, Peter G [La Jolla, CA

2009-12-01

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Expanding the eukaryotic genetic code

DOEpatents

Chin, Jason W [Cambridge, GB; Cropp, T Ashton [Bethesda, MD; Anderson, J Christopher [San Francisco, CA; Schultz, Peter G [La Jolla, CA

2012-02-14

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Expanding the eukaryotic genetic code

DOEpatents

Chin, Jason W [Cambridge, GB; Cropp, T Ashton [Bethesda, MD; Anderson, J Christopher [San Francisco, CA; Schultz, Peter G [La Jolla, CA

2009-11-17

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Expanding the eukaryotic genetic code

DOEpatents

Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

2010-09-14

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Unnatural reactive amino acid genetic code additions

DOEpatents

Deiters, Alexander; Cropp, Ashton T; Chin, Jason W; Anderson, Christopher J; Schultz, Peter G

2013-05-21

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Expanding the eukaryotic genetic code

DOEpatents

Chin, Jason W [Cambridge, GB; Cropp, T Ashton [Bethesda, MD; Anderson, J Christopher [San Francisco, CA; Schultz, Peter G [La Jolla, CA

2012-05-08

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Unnatural reactive amino acid genetic code additions

DOEpatents

Deiters, Alexander [La Jolla, CA; Cropp, T Ashton [San Diego, CA; Chin, Jason W [Cambridge, GB; Anderson, J Christopher [San Francisco, CA; Schultz, Peter G [La Jolla, CA

2011-02-15

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Unnatural reactive amino acid genetic code additions

DOEpatents

Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.; Anderson, J. Christopher; Schultz, Peter G.

2014-08-26

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Unnatural reactive amino acid genetic code additions

DOEpatents

Deiters, Alexander [La Jolla, CA; Cropp, T Ashton [Bethesda, MD; Chin, Jason W [Cambridge, GB; Anderson, J Christopher [San Francisco, CA; Schultz, Peter G [La Jolla, CA

2011-08-09

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNAsyn-thetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses.

PubMed

Shaffer, John R; Feingold, Eleanor; Wang, Xiaojing; Tcuenco, Karen T; Weeks, Daniel E; DeSensi, Rebecca S; Polk, Deborah E; Wendell, Steve; Weyant, Robert J; Crout, Richard; McNeil, Daniel W; Marazita, Mary L

2012-03-09

Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries. The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without a priori surface classifications, were applied to our data. The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97), pit and fissure surface caries (r = 0.95), and smooth surface caries (r = 0.89). However, together, these three patterns explained only 37% of the variability in the data, indicating that a priori caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81), but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h(2) = 30-65%, p = 0.043-0.006), whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns. This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding the multifactorial nature of dental caries.

Mixing of Honeybees with Different Genotypes Affects Individual Worker Behavior and Transcription of Genes in the Neuronal Substrate

PubMed Central

Bienefeld, Kaspar; Beye, Martin

2012-01-01

Division of labor in social insects has made the evolution of collective traits possible that cannot be achieved by individuals alone. Differences in behavioral responses produce variation in engagement in behavioral tasks, which as a consequence, generates a division of labor. We still have little understanding of the genetic components influencing these behaviors, although several candidate genomic regions and genes influencing individual behavior have been identified. Here, we report that mixing of worker honeybees with different genotypes influences the expression of individual worker behaviors and the transcription of genes in the neuronal substrate. These indirect genetic effects arise in a colony because numerous interactions between workers produce interacting phenotypes and genotypes across organisms. We studied hygienic behavior of honeybee workers, which involves the cleaning of diseased brood cells in the colony. We mixed ∼500 newly emerged honeybee workers with genotypes of preferred Low (L) and High (H) hygienic behaviors. The L/H genotypic mixing affected the behavioral engagement of L worker bees in a hygienic task, the cooperation among workers in uncapping single brood cells, and switching between hygienic tasks. We found no evidence that recruiting and task-related stimuli are the primary source of the indirect genetic effects on behavior. We suggested that behavioral responsiveness of L bees was affected by genotypic mixing and found evidence for changes in the brain in terms of 943 differently expressed genes. The functional categories of cell adhesion, cellular component organization, anatomical structure development, protein localization, developmental growth and cell morphogenesis were overrepresented in this set of 943 genes, suggesting that indirect genetic effects can play a role in modulating and modifying the neuronal substrate. Our results suggest that genotypes of social partners affect the behavioral responsiveness and the neuronal substrate of individual workers, indicating a complex genetic architecture underlying the expression of behavior. PMID:22348118

Genetic Variants Associated With Quantitative Glucose Homeostasis Traits Translate to Type 2 Diabetes in Mexican Americans: The GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium.

PubMed

Palmer, Nicholette D; Goodarzi, Mark O; Langefeld, Carl D; Wang, Nan; Guo, Xiuqing; Taylor, Kent D; Fingerlin, Tasha E; Norris, Jill M; Buchanan, Thomas A; Xiang, Anny H; Haritunians, Talin; Ziegler, Julie T; Williams, Adrienne H; Stefanovski, Darko; Cui, Jinrui; Mackay, Adrienne W; Henkin, Leora F; Bergman, Richard N; Gao, Xiaoyi; Gauderman, James; Varma, Rohit; Hanis, Craig L; Cox, Nancy J; Highland, Heather M; Below, Jennifer E; Williams, Amy L; Burtt, Noel P; Aguilar-Salinas, Carlos A; Huerta-Chagoya, Alicia; Gonzalez-Villalpando, Clicerio; Orozco, Lorena; Haiman, Christopher A; Tsai, Michael Y; Johnson, W Craig; Yao, Jie; Rasmussen-Torvik, Laura; Pankow, James; Snively, Beverly; Jackson, Rebecca D; Liu, Simin; Nadler, Jerry L; Kandeel, Fouad; Chen, Yii-Der I; Bowden, Donald W; Rich, Stephen S; Raffel, Leslie J; Rotter, Jerome I; Watanabe, Richard M; Wagenknecht, Lynne E

2015-05-01

Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently sampled intravenous glucose tolerance test (four cohorts) or euglycemic clamp (three cohorts), and random-effects models were used to test the association between loci and quantitative traits, adjusting for age, sex, and admixture proportions (Discovery). Analysis revealed a significant (P < 5.00 × 10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P < 0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D case and 9,232 control subjects of Mexican ancestry (Translation). Nonparametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive the risk for T2D. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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.

INHERITED NEUROPATHIES: CLINICAL OVERVIEW AND UPDATE

PubMed Central

KLEIN, CHRISTOPHER J.; DUAN, XIAOHUI; SHY, MICHAEL E.

2014-01-01

Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. PMID:23801417

An Initiative for the Study and Use of Genetic Diversity of Domesticated Plants and Their Wild Relatives.

PubMed

Mastretta-Yanes, Alicia; Acevedo Gasman, Francisca; Burgeff, Caroline; Cano Ramírez, Margarita; Piñero, Daniel; Sarukhán, José

2018-01-01

Domestication has been influenced by formal plant breeding since the onset of intensive agriculture and the Green Revolution. Despite providing food security for some regions, intensive agriculture has had substantial detrimental consequences for the environment and does not fulfill smallholder's needs under most developing countries conditions. Therefore, it is necessary to look for alternative plant production techniques, effective for each environmental, socio-cultural, and economic conditions. This is particularly relevant for countries that are megadiverse and major centers of plant domestication and diversification. In this white paper, a Mexico-centered initiative is proposed, with two main objectives: (1) to study, understand, conserve, and sustainably use the genetic diversity of domesticated plants and their wild relatives, as well as the ongoing evolutionary processes that generate and maintain it; and (2) to strengthen food and forestry production in a socially fair and environmentally friendly way. To fulfill these objectives, the initiative focuses on the source of variability available for domestication ( genetic diversity and functional genomics ), the context in which domestication acts ( breeding and production ) and one of its main challenges ( environmental change ). Research on these components can be framed to target and connect both the theoretical understanding of the evolutionary processes, the practical aspects of conservation, and food and forestry production. The target, main challenges, problems to be faced and key research questions are presented for each component, followed by a roadmap for the consolidation of this proposal as a national initiative.

Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach

PubMed Central

Risso, Davide; Taglioli, Luca; De Iasio, Sergio; Gueresi, Paola; Alfani, Guido; Nelli, Sergio; Rossi, Paolo; Paoli, Giorgio; Tofanelli, Sergio

2015-01-01

This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447–2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8–30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics. PMID:26452043

Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach.

PubMed

Risso, Davide; Taglioli, Luca; De Iasio, Sergio; Gueresi, Paola; Alfani, Guido; Nelli, Sergio; Rossi, Paolo; Paoli, Giorgio; Tofanelli, Sergio

2015-01-01

This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447-2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8-30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics.

Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, and impaired adult social behavior and activity patterns.

PubMed

Wise, Alexandria; Tenezaca, Luis; Fernandez, Robert W; Schatoff, Emma; Flores, Julian; Ueda, Atsushi; Zhong, Xiaotian; Wu, Chun-Fang; Simon, Anne F; Venkatesh, Tadmiri

2015-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions, and hyperactivity. ASD exhibits a strong genetic component with underlying multigene interactions. Candidate gene studies have shown that the neurobeachin (NBEA) gene is disrupted in human patients with idiopathic autism ( Castermans et al., 2003 ). The NBEA gene spans the common fragile site FRA 13A and encodes a signal scaffold protein ( Savelyeva et al., 2006 ). In mice, NBEA has been shown to be involved in the trafficking and function of a specific subset of synaptic vesicles. ( Medrihan et al., 2009 ; Savelyeva et al., 2006 ). Rugose (rg) is the Drosophila homolog of the mammalian and human NBEA. Our previous genetic and molecular analyses have shown that rg encodes an A kinase anchor protein (DAKAP 550), which interacts with components of the epidermal growth factor receptor or EGFR and Notch-mediated signaling pathways, facilitating cross talk between these and other pathways ( Shamloula et al., 2002 ). We now present functional data from studies on the larval neuromuscular junction that reveal abnormal synaptic architecture and physiology. In addition, adult rg loss-of-function mutants exhibit defective social interactions, impaired habituation, aberrant locomotion, and hyperactivity. These results demonstrate that Drosophila NBEA (rg) mutants exhibit phenotypic characteristics reminiscent of human ASD and thus could serve as a genetic model for studying ASDs.

Social reward among juvenile mice

PubMed Central

Panksepp, J B; Lahvis, G P

2007-01-01

Mammalian social relationships, such as mother–offspring attachments and pair bonds, can directly affect reproductive output. However, conspecifics approach one another in a comparatively broad range of contexts, so conceivably there are motivations for social congregation other than those underlying reproduction, parental care or territoriality. Here, we show that reward mediated by social contact is a fundamental aspect of juvenile mouse sociality. Employing a novel social conditioned place preference (SCPP) procedure, we demonstrate that social proximity is rewarding for juvenile mice from three inbred strains (A/J, C57BL/6J and DBA/2J), while mice from a fourth strain (BALB/cJ) are much less responsive to social contact. Importantly, this strain-dependent difference was not related to phenotypic variability in exploratory behavior or contextual learning nor influenced by the genetic background associated with maternal care or social conditioning. Furthermore, the SCPP phenotype was expressed early in development (postnatal day 25) and did not require a specific sex composition within the conditioning group. Finally, SCPP responses resulted from an interaction between two specifiable processes: one component of the interaction facilitated approach toward environments that were associated with social salience, whereas a second component mediated avoidance of environmental cues that predicted social isolation. We have thus identified a genetically prescribed process that can attribute value onto conditions predicting a general form of social contact. To our knowledge, this is the first definitive evidence to show that genetic variation can influence a form of social valuation not directly related to a reproductive behavior. PMID:17212648

Linear score tests for variance components in linear mixed models and applications to genetic association studies.

PubMed

Qu, Long; Guennel, Tobias; Marshall, Scott L

2013-12-01

Following the rapid development of genome-scale genotyping technologies, genetic association mapping has become a popular tool to detect genomic regions responsible for certain (disease) phenotypes, especially in early-phase pharmacogenomic studies with limited sample size. In response to such applications, a good association test needs to be (1) applicable to a wide range of possible genetic models, including, but not limited to, the presence of gene-by-environment or gene-by-gene interactions and non-linearity of a group of marker effects, (2) accurate in small samples, fast to compute on the genomic scale, and amenable to large scale multiple testing corrections, and (3) reasonably powerful to locate causal genomic regions. The kernel machine method represented in linear mixed models provides a viable solution by transforming the problem into testing the nullity of variance components. In this study, we consider score-based tests by choosing a statistic linear in the score function. When the model under the null hypothesis has only one error variance parameter, our test is exact in finite samples. When the null model has more than one variance parameter, we develop a new moment-based approximation that performs well in simulations. Through simulations and analysis of real data, we demonstrate that the new test possesses most of the aforementioned characteristics, especially when compared to existing quadratic score tests or restricted likelihood ratio tests. © 2013, The International Biometric Society.

An Initiative for the Study and Use of Genetic Diversity of Domesticated Plants and Their Wild Relatives

PubMed Central

Mastretta-Yanes, Alicia; Acevedo Gasman, Francisca; Burgeff, Caroline; Cano Ramírez, Margarita; Piñero, Daniel; Sarukhán, José

2018-01-01

Domestication has been influenced by formal plant breeding since the onset of intensive agriculture and the Green Revolution. Despite providing food security for some regions, intensive agriculture has had substantial detrimental consequences for the environment and does not fulfill smallholder’s needs under most developing countries conditions. Therefore, it is necessary to look for alternative plant production techniques, effective for each environmental, socio-cultural, and economic conditions. This is particularly relevant for countries that are megadiverse and major centers of plant domestication and diversification. In this white paper, a Mexico-centered initiative is proposed, with two main objectives: (1) to study, understand, conserve, and sustainably use the genetic diversity of domesticated plants and their wild relatives, as well as the ongoing evolutionary processes that generate and maintain it; and (2) to strengthen food and forestry production in a socially fair and environmentally friendly way. To fulfill these objectives, the initiative focuses on the source of variability available for domestication (genetic diversity and functional genomics), the context in which domestication acts (breeding and production) and one of its main challenges (environmental change). Research on these components can be framed to target and connect both the theoretical understanding of the evolutionary processes, the practical aspects of conservation, and food and forestry production. The target, main challenges, problems to be faced and key research questions are presented for each component, followed by a roadmap for the consolidation of this proposal as a national initiative. PMID:29515612

Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans*

PubMed Central

Andrusiak, Matthew G.; Jin, Yishi

2016-01-01

Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundworm Caenorhabditis elegans was developed as a system to study genes required for development and nervous system function. The powerful genetics of C. elegans in combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components in C. elegans. PMID:26907690

Gene network analysis shows immune-signaling and ERK1/2 as novel genetic markers for multiple addiction phenotypes: alcohol, smoking and opioid addiction.

PubMed

Reyes-Gibby, Cielito C; Yuan, Christine; Wang, Jian; Yeung, Sai-Ching J; Shete, Sanjay

2015-06-05

Addictions to alcohol and tobacco, known risk factors for cancer, are complex heritable disorders. Addictive behaviors have a bidirectional relationship with pain. We hypothesize that the associations between alcohol, smoking, and opioid addiction observed in cancer patients have a genetic basis. Therefore, using bioinformatics tools, we explored the underlying genetic basis and identified new candidate genes and common biological pathways for smoking, alcohol, and opioid addiction. Literature search showed 56 genes associated with alcohol, smoking and opioid addiction. Using Core Analysis function in Ingenuity Pathway Analysis software, we found that ERK1/2 was strongly interconnected across all three addiction networks. Genes involved in immune signaling pathways were shown across all three networks. Connect function from IPA My Pathway toolbox showed that DRD2 is the gene common to both the list of genetic variations associated with all three addiction phenotypes and the components of the brain neuronal signaling network involved in substance addiction. The top canonical pathways associated with the 56 genes were: 1) calcium signaling, 2) GPCR signaling, 3) cAMP-mediated signaling, 4) GABA receptor signaling, and 5) G-alpha i signaling. Cancer patients are often prescribed opioids for cancer pain thus increasing their risk for opioid abuse and addiction. Our findings provide candidate genes and biological pathways underlying addiction phenotypes, which may be future targets for treatment of addiction. Further study of the variations of the candidate genes could allow physicians to make more informed decisions when treating cancer pain with opioid analgesics.

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.

Exploring the Validity of Proposed Transgenic Animal Models of Attention-Deficit Hyperactivity Disorder (ADHD).

PubMed

de la Peña, June Bryan; Dela Peña, Irene Joy; Custodio, Raly James; Botanas, Chrislean Jun; Kim, Hee Jin; Cheong, Jae Hoon

2018-05-01

Attention-deficit/hyperactivity disorder (ADHD) is a common, behavioral, and heterogeneous neurodevelopmental condition characterized by hyperactivity, impulsivity, and inattention. Symptoms of this disorder are managed by treatment with methylphenidate, amphetamine, and/or atomoxetine. The cause of ADHD is unknown, but substantial evidence indicates that this disorder has a significant genetic component. Transgenic animals have become an essential tool in uncovering the genetic factors underlying ADHD. Although they cannot accurately reflect the human condition, they can provide insights into the disorder that cannot be obtained from human studies due to various limitations. An ideal animal model of ADHD must have face (similarity in symptoms), predictive (similarity in response to treatment or medications), and construct (similarity in etiology or underlying pathophysiological mechanism) validity. As the exact etiology of ADHD remains unclear, the construct validity of animal models of ADHD would always be limited. The proposed transgenic animal models of ADHD have substantially increased and diversified over the years. In this paper, we compiled and explored the validity of proposed transgenic animal models of ADHD. Each of the reviewed transgenic animal models has strengths and limitations. Some fulfill most of the validity criteria of an animal model of ADHD and have been extensively used, while there are others that require further validation. Nevertheless, these transgenic animal models of ADHD have provided and will continue to provide valuable insights into the genetic underpinnings of this complex disorder.

Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array.

PubMed

García-Sanz, Ramón; Corchete, Luis Antonio; Alcoceba, Miguel; Chillon, María Carmen; Jiménez, Cristina; Prieto, Isabel; García-Álvarez, María; Puig, Noemi; Rapado, Immaculada; Barrio, Santiago; Oriol, Albert; Blanchard, María Jesús; de la Rubia, Javier; Martínez, Rafael; Lahuerta, Juan José; González Díaz, Marcos; Mateos, María Victoria; San Miguel, Jesús Fernando; Martínez-López, Joaquín; Sarasquete, María Eugenia

2017-12-01

Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Patterns of Population Structure and Environmental Associations to Aridity Across the Range of Loblolly Pine (Pinus taeda L., Pinaceae)

PubMed Central

Eckert, Andrew J.; van Heerwaarden, Joost; Wegrzyn, Jill L.; Nelson, C. Dana; Ross-Ibarra, Jeffrey; González-Martínez, Santíago C.; Neale, David. B.

2010-01-01

Natural populations of forest trees exhibit striking phenotypic adaptations to diverse environmental gradients, thereby making them appealing subjects for the study of genes underlying ecologically relevant phenotypes. Here, we use a genome-wide data set of single nucleotide polymorphisms genotyped across 3059 functional genes to study patterns of population structure and identify loci associated with aridity across the natural range of loblolly pine (Pinus taeda L.). Overall patterns of population structure, as inferred using principal components and Bayesian cluster analyses, were consistent with three genetic clusters likely resulting from expansions out of Pleistocene refugia located in Mexico and Florida. A novel application of association analysis, which removes the confounding effects of shared ancestry on correlations between genetic and environmental variation, identified five loci correlated with aridity. These loci were primarily involved with abiotic stress response to temperature and drought. A unique set of 24 loci was identified as FST outliers on the basis of the genetic clusters identified previously and after accounting for expansions out of Pleistocene refugia. These loci were involved with a diversity of physiological processes. Identification of nonoverlapping sets of loci highlights the fundamental differences implicit in the use of either method and suggests a pluralistic, yet complementary, approach to the identification of genes underlying ecologically relevant phenotypes. PMID:20439779

Fitness variation in response to artificial selection for reduced cell area, cell number and wing area in natural populations of Drosophila melanogaster.

PubMed

Trotta, Vincenzo; Calboli, Federico C F; Ziosi, Marcello; Cavicchi, Sandro

2007-08-16

Genetically based body size differences are naturally occurring in populations of Drosophila melanogaster, with bigger flies in the cold. Despite the cosmopolitan nature of body size clines in more than one Drosophila species, the actual selective mechanisms controlling the genetic basis of body size variation are not fully understood. In particular, it is not clear what the selective value of cell size and cell area variation exactly is. In the present work we determined variation in viability, developmental time and larval competitive ability in response to crowding at two temperatures after artificial selection for reduced cell area, cell number and wing area in four different natural populations of D. melanogaster. No correlated effect of selection on viability or developmental time was observed among all selected populations. An increase in competitive ability in one thermal environment (18 degrees C) under high larval crowding was observed as a correlated response to artificial selection for cell size. Viability and developmental time are not affected by selection for the cellular component of body size, suggesting that these traits only depend on the contingent genetic makeup of a population. The higher larval competitive ability shown by populations selected for reduced cell area seems to confirm the hypothesis that cell area mediated changes have a relationship with fitness, and might be the preferential way to change body size under specific circumstances.

Boosting for detection of gene-environment interactions.

PubMed

Pashova, H; LeBlanc, M; Kooperberg, C

2013-01-30

In genetic association studies, it is typically thought that genetic variants and environmental variables jointly will explain more of the inheritance of a phenotype than either of these two components separately. Traditional methods to identify gene-environment interactions typically consider only one measured environmental variable at a time. However, in practice, multiple environmental factors may each be imprecise surrogates for the underlying physiological process that actually interacts with the genetic factors. In this paper, we develop a variant of L(2) boosting that is specifically designed to identify combinations of environmental variables that jointly modify the effect of a gene on a phenotype. Because the effect modifiers might have a small signal compared with the main effects, working in a space that is orthogonal to the main predictors allows us to focus on the interaction space. In a simulation study that investigates some plausible underlying model assumptions, our method outperforms the least absolute shrinkage and selection and Akaike Information Criterion and Bayesian Information Criterion model selection procedures as having the lowest test error. In an example for the Women's Health Initiative-Population Architecture using Genomics and Epidemiology study, the dedicated boosting method was able to pick out two single-nucleotide polymorphisms for which effect modification appears present. The performance was evaluated on an independent test set, and the results are promising. Copyright © 2012 John Wiley & Sons, Ltd.

Biobanking genetic material for agricultural animal species

USDA-ARS?s Scientific Manuscript database

Biobanking animal germplasm and tissues is a major component of conserving genetic resources. Effectively constructing such gene banks requires an understanding and evaluation of genetic resources, the ability to conserve various tissues through cryopreservation, and a robust information technology ...

Feature selection for neural network based defect classification of ceramic components using high frequency ultrasound.

PubMed

Kesharaju, Manasa; Nagarajah, Romesh

2015-09-01

The motivation for this research stems from a need for providing a non-destructive testing method capable of detecting and locating any defects and microstructural variations within armour ceramic components before issuing them to the soldiers who rely on them for their survival. The development of an automated ultrasonic inspection based classification system would make possible the checking of each ceramic component and immediately alert the operator about the presence of defects. Generally, in many classification problems a choice of features or dimensionality reduction is significant and simultaneously very difficult, as a substantial computational effort is required to evaluate possible feature subsets. In this research, a combination of artificial neural networks and genetic algorithms are used to optimize the feature subset used in classification of various defects in reaction-sintered silicon carbide ceramic components. Initially wavelet based feature extraction is implemented from the region of interest. An Artificial Neural Network classifier is employed to evaluate the performance of these features. Genetic Algorithm based feature selection is performed. Principal Component Analysis is a popular technique used for feature selection and is compared with the genetic algorithm based technique in terms of classification accuracy and selection of optimal number of features. The experimental results confirm that features identified by Principal Component Analysis lead to improved performance in terms of classification percentage with 96% than Genetic algorithm with 94%. Copyright © 2015 Elsevier B.V. All rights reserved.

Variable pleiotropic effects from mutations at the same locus hamper prediction of fitness from a fitness component.

PubMed

Pepin, Kim M; Samuel, Melanie A; Wichman, Holly A

2006-04-01

The relationship of genotype, fitness components, and fitness can be complicated by genetic effects such as pleiotropy and epistasis and by heterogeneous environments. However, because it is often difficult to measure genotype and fitness directly, fitness components are commonly used to estimate fitness without regard to genetic architecture. The small bacteriophage X174 enables direct evaluation of genetic and environmental effects on fitness components and fitness. We used 15 mutants to study mutation effects on attachment rate and fitness in six hosts. The mutants differed from our lab strain of X174 by only one or two amino acids in the major capsid protein (gpF, sites 101 and 102). The sites are variable in natural and experimentally evolved X174 populations and affect phage attachment rate. Within the limits of detection of our assays, all mutations were neutral or deleterious relative to the wild type; 11 mutants had decreased host range. While fitness was predictable from attachment rate in most cases, 3 mutants had rapid attachment but low fitness on most hosts. Thus, some mutations had a pleiotropic effect on a fitness component other than attachment rate. In addition, on one host most mutants had high attachment rate but decreased fitness, suggesting that pleiotropic effects also depended on host. The data highlight that even in this simple, well-characterized system, prediction of fitness from a fitness component depends on genetic architecture and environment.

Climate change in the oceans: evolutionary versus phenotypically plastic responses of marine animals and plants

PubMed Central

Reusch, Thorsten B H

2014-01-01

I summarize marine studies on plastic versus adaptive responses to global change. Due to the lack of time series, this review focuses largely on the potential for adaptive evolution in marine animals and plants. The approaches were mainly synchronic comparisons of phenotypically divergent populations, substituting spatial contrasts in temperature or CO2 environments for temporal changes, or in assessments of adaptive genetic diversity within populations for traits important under global change. The available literature is biased towards gastropods, crustaceans, cnidarians and macroalgae. Focal traits were mostly environmental tolerances, which correspond to phenotypic buffering, a plasticity type that maintains a functional phenotype despite external disturbance. Almost all studies address coastal species that are already today exposed to fluctuations in temperature, pH and oxygen levels. Recommendations for future research include (i) initiation and analyses of observational and experimental temporal studies encompassing diverse phenotypic traits (including diapausing cues, dispersal traits, reproductive timing, morphology) (ii) quantification of nongenetic trans-generational effects along with components of additive genetic variance (iii) adaptive changes in microbe–host associations under the holobiont model in response to global change (iv) evolution of plasticity patterns under increasingly fluctuating environments and extreme conditions and (v) joint consideration of demography and evolutionary adaptation in evolutionary rescue approaches. PMID:24454551

Exploring the use of random regression models with legendre polynomials to analyze measures of volume of ejaculate in Holstein bulls.

PubMed

Carabaño, M J; Díaz, C; Ugarte, C; Serrano, M

2007-02-01

Artificial insemination centers routinely collect records of quantity and quality of semen of bulls throughout the animals' productive period. The goal of this paper was to explore the use of random regression models with orthogonal polynomials to analyze repeated measures of semen production of Spanish Holstein bulls. A total of 8,773 records of volume of first ejaculate (VFE) collected between 12 and 30 mo of age from 213 Spanish Holstein bulls was analyzed under alternative random regression models. Legendre polynomial functions of increasing order (0 to 6) were fitted to the average trajectory, additive genetic and permanent environmental effects. Age at collection and days in production were used as time variables. Heterogeneous and homogeneous residual variances were alternatively assumed. Analyses were carried out within a Bayesian framework. The logarithm of the marginal density and the cross-validation predictive ability of the data were used as model comparison criteria. Based on both criteria, age at collection as a time variable and heterogeneous residuals models are recommended to analyze changes of VFE over time. Both criteria indicated that fitting random curves for genetic and permanent environmental components as well as for the average trajector improved the quality of models. Furthermore, models with a higher order polynomial for the permanent environmental (5 to 6) than for the genetic components (4 to 5) and the average trajectory (2 to 3) tended to perform best. High-order polynomials were needed to accommodate the highly oscillating nature of the phenotypic values. Heritability and repeatability estimates, disregarding the extremes of the studied period, ranged from 0.15 to 0.35 and from 0.20 to 0.50, respectively, indicating that selection for VFE may be effective at any stage. Small differences among models were observed. Apart from the extremes, estimated correlations between ages decreased steadily from 0.9 and 0.4 for measures 1 mo apart to 0.4 and 0.2 for most distant measures for additive genetic and phenotypic components, respectively. Further investigation to account for environmental factors that may be responsible for the oscillating observations of VFE is needed.

Sleep Duration and Area-Level Deprivation in Twins.

PubMed

Watson, Nathaniel F; Horn, Erin; Duncan, Glen E; Buchwald, Dedra; Vitiello, Michael V; Turkheimer, Eric

2016-01-01

We used quantitative genetic models to assess whether area-level deprivation as indicated by the Singh Index predicts shorter sleep duration and modifies its underlying genetic and environmental contributions. Participants were 4,218 adult twin pairs (2,377 monozygotic and 1,841 dizygotic) from the University of Washington Twin Registry. Participants self-reported habitual sleep duration. The Singh Index was determined by linking geocoding addresses to 17 indicators at the census-tract level using data from Census of Washington State and Census Tract Cartographic Boundary Files from 2000 and 2010. Data were analyzed using univariate and bivariate genetic decomposition and quantitative genetic interaction models that assessed A (additive genetics), C (common environment), and E (unique environment) main effects of the Singh Index on sleep duration and allowed the magnitude of residual ACE variance components in sleep duration to vary with the Index. The sample had a mean age of 38.2 y (standard deviation [SD] = 18), and was predominantly female (62%) and Caucasian (91%). Mean sleep duration was 7.38 h (SD = 1.20) and the mean Singh Index score was 0.00 (SD = 0.89). The heritability of sleep duration was 39% and the Singh Index was 12%. The uncontrolled phenotypic regression of sleep duration on the Singh Index showed a significant negative relationship between area-level deprivation and sleep length (b = -0.080, P < 0.001). Every 1 SD in Singh Index was associated with a ∼4.5 min change in sleep duration. For the quasi-causal bivariate model, there was a significant main effect of E (b(0E) = -0.063; standard error [SE] = 0.30; P < 0.05). Residual variance components unique to sleep duration were significant for both A (b(0Au) = 0.734; SE = 0.020; P < 0.001) and E (b(0Eu) = 0.934; SE = 0.013; P < 0.001). Area-level deprivation has a quasi-causal association with sleep duration, with greater deprivation being related to shorter sleep. As area-level deprivation increases, unique genetic and nonshared environmental residual variance in sleep duration increases. © 2016 Associated Professional Sleep Societies, LLC.

Small non-coding RNAs (sncRNA) regulate gene silencing and modify homeostatic status in animals faced with porcine reproductive and respiratory syndrome virus (PRRSV)

USDA-ARS?s Scientific Manuscript database

It has been established that reduced susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) has a genetic component. This genetic component may take the form of small non-coding RNAs (sncRNA), which are molecules that function as regulators of gene expression. Various sncRNAs ...

Dyslipidaemia and coronary heart disease: nature vs nurture.

PubMed

Hegele, R A

In order to enhance health care for patients with coronary heart disease (CHD), genetic markers of susceptibility could be incorporated into a formula for risk evaluation that includes traditional factors. Preventive measures could then be targeted towards 'high-risk' subjects. But can the genetic component be dissected from the environmental component in an intermediate CHD phenotype, such as plasma lipoproteins.

Nutrigenomics and nutrigenetics.

PubMed

Farhud, Dd; Zarif Yeganeh, M; Zarif Yeganeh, M

2010-01-01

The nutrients are able to interact with molecular mechanisms and modulate the physiological functions in the body. The Nutritional Genomics focuses on the interaction between bioactive food components and the genome, which includes Nutrigenetics and Nutrigenomics. The influence of nutrients on f genes expression is called Nutrigenomics, while the heterogeneous response of gene variants to nutrients, dietary components and developing nutraceticals is called Nutrigenetics. Genetic variation is known to affect food tolerances among human subpopulations and may also influence dietary requirements and raising the possibility of individualizing nutritional intake for optimal health and disease prevention on the basis of an individual's genome. Nutrigenomics provides a genetic understanding for how common dietary components affect the balance between health and disease by altering the expression and/or structure of an individual's genetic makeup. Nutrigenetics describes that the genetic profile have impact on the response of body to bioactive food components by influencing their absorption, metabolism, and site of action.In this way, considering different aspects of gene-nutrient interaction and designing appropriate diet for every specific genotype that optimize individual health, diagnosis and nutritional treatment of genome instability, we could prevent and control conversion of healthy phenotype to diseases.

Nutrigenomics and Nutrigenetics

PubMed Central

Farhud, DD; Zarif Yeganeh, M; Zarif Yeganeh, M

2010-01-01

The nutrients are able to interact with molecular mechanisms and modulate the physiological functions in the body. The Nutritional Genomics focuses on the interaction between bioactive food components and the genome, which includes Nutrigenetics and Nutrigenomics. The influence of nutrients on f genes expression is called Nutrigenomics, while the heterogeneous response of gene variants to nutrients, dietary components and developing nutraceticals is called Nutrigenetics. Genetic variation is known to affect food tolerances among human subpopulations and may also influence dietary requirements and raising the possibility of individualizing nutritional intake for optimal health and disease prevention on the basis of an individual’s genome. Nutrigenomics provides a genetic understanding for how common dietary components affect the balance between health and disease by altering the expression and/or structure of an individual’s genetic makeup. Nutrigenetics describes that the genetic profile have impact on the response of body to bioactive food components by influencing their absorption, metabolism, and site of action. In this way, considering different aspects of gene–nutrient interaction and designing appropriate diet for every specific genotype that optimize individual health, diagnosis and nutritional treatment of genome instability, we could prevent and control conversion of healthy phenotype to diseases. PMID:23113033

On some genetic consequences of social structure, mating systems, dispersal, and sampling

PubMed Central

Parreira, Bárbara R.; Chikhi, Lounès

2015-01-01

Many species are spatially and socially organized, with complex social organizations and dispersal patterns that are increasingly documented. Social species typically consist of small age-structured units, where a limited number of individuals monopolize reproduction and exhibit complex mating strategies. Here, we model social groups as age-structured units and investigate the genetic consequences of social structure under distinct mating strategies commonly found in mammals. Our results show that sociality maximizes genotypic diversity, which contradicts the belief that social groups are necessarily subject to strong genetic drift and at high risk of inbreeding depression. Social structure generates an excess of genotypic diversity. This is commonly observed in ecological studies but rarely reported in population genetic studies that ignore social structure. This heterozygosity excess, when detected, is often interpreted as a consequence of inbreeding avoidance mechanisms, but we show that it can occur even in the absence of such mechanisms. Many seemly contradictory results from ecology and population genetics can be reconciled by genetic models that include the complexities of social species. We find that such discrepancies can be explained by the intrinsic properties of social groups and by the sampling strategies of real populations. In particular, the number of social groups and the nature of the individuals that compose samples (e.g., nonreproductive and reproductive individuals) are key factors in generating outbreeding signatures. Sociality is an important component of population structure that needs to be revisited by ecologists and population geneticists alike. PMID:26080393

Chloroplast and nuclear photorelocation movements

PubMed Central

WADA, Masamitsu

2016-01-01

Chloroplasts move toward weak light to increase photosynthetic efficiency, and migrate away from strong light to protect chloroplasts from photodamage and eventual cell death. These chloroplast behaviors were first observed more than 100 years ago, but the underlying mechanism has only recently been identified. Ideal plant materials, such as fern gametophytes for photobiological and cell biological approaches, and Arabidopsis thaliana for genetic analyses, have been used along with sophisticated methods, such as partial cell irradiation and time-lapse video recording under infrared light to study chloroplast movement. These studies have revealed precise chloroplast behavior, and identified photoreceptors, other relevant protein components, and novel actin filament structures required for chloroplast movement. In this review, our findings regarding chloroplast and nuclear movements are described. PMID:27840388

Characterisation of circadian rhythms of various duckweeds.

PubMed

Muranaka, T; Okada, M; Yomo, J; Kubota, S; Oyama, T

2015-01-01

The plant circadian clock controls various physiological phenomena that are important for adaptation to natural day-night cycles. Many components of the circadian clock have been identified in Arabidopsis thaliana, the model plant for molecular genetic studies. Recent studies revealed evolutionary conservation of clock components in green plants. Homologues of clock-related genes have been isolated from Lemna gibba and Lemna aequinoctialis, and it has been demonstrated that these homologues function in the clock system in a manner similar to their functioning in Arabidopsis. While clock components are widely conserved, circadian phenomena display diversity even within the Lemna genus. In order to survey the full extent of diversity in circadian rhythms among duckweed plants, we characterised the circadian rhythms of duckweed by employing a semi-transient bioluminescent reporter system. Using a particle bombardment method, circadian bioluminescent reporters were introduced into nine strains representing five duckweed species: Spirodela polyrhiza, Landoltia punctata, Lemna gibba, L. aequinoctialis and Wolffia columbiana. We then monitored luciferase (luc+) reporter activities driven by AtCCA1, ZmUBQ1 or CaMV35S promoters under entrainment and free-running conditions. Under entrainment, AtCCA1::luc+ showed similar diurnal rhythms in all strains. This suggests that the mechanism of biological timing under day-night cycles is conserved throughout the evolution of duckweeds. Under free-running conditions, we observed circadian rhythms of AtCCA1::luc+, ZmUBQ1::luc+ and CaMV35S::luc+. These circadian rhythms showed diversity in period length and sustainability, suggesting that circadian clock mechanisms are somewhat diversified among duckweeds. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

An integrated overview of spatiotemporal organization and regulation in mitosis in terms of the proteins in the functional supercomplexes.

PubMed

Zheng, Yueyuan; Guo, Junjie; Li, Xu; Xie, Yubin; Hou, Mingming; Fu, Xuyang; Dai, Shengkun; Diao, Rucheng; Miao, Yanyan; Ren, Jian

2014-01-01

Eukaryotic cells may divide via the critical cellular process of cell division/mitosis, resulting in two daughter cells with the same genetic information. A large number of dedicated proteins are involved in this process and spatiotemporally assembled into three distinct super-complex structures/organelles, including the centrosome/spindle pole body, kinetochore/centromere and cleavage furrow/midbody/bud neck, so as to precisely modulate the cell division/mitosis events of chromosome alignment, chromosome segregation and cytokinesis in an orderly fashion. In recent years, many efforts have been made to identify the protein components and architecture of these subcellular organelles, aiming to uncover the organelle assembly pathways, determine the molecular mechanisms underlying the organelle functions, and thereby provide new therapeutic strategies for a variety of diseases. However, the organelles are highly dynamic structures, making it difficult to identify the entire components. Here, we review the current knowledge of the identified protein components governing the organization and functioning of organelles, especially in human and yeast cells, and discuss the multi-localized protein components mediating the communication between organelles during cell division.

The fine-scale genetic structure and evolution of the Japanese population

PubMed Central

Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Isomura, Minoru; Ohkubo, Takayoshi; Tabara, Yasuharu; Yamamoto, Ken; Yokota, Mitsuhiro; Liu, Xuanyao; Saw, Woei-Yuh; Mamatyusupu, Dolikun; Yang, Wenjun; Xu, Shuhua

2017-01-01

The contemporary Japanese populations largely consist of three genetically distinct groups—Hondo, Ryukyu and Ainu. By principal-component analysis, while the three groups can be clearly separated, the Hondo people, comprising 99% of the Japanese, form one almost indistinguishable cluster. To understand fine-scale genetic structure, we applied powerful haplotype-based statistical methods to genome-wide single nucleotide polymorphism data from 1600 Japanese individuals, sampled from eight distinct regions in Japan. We then combined the Japanese data with 26 other Asian populations data to analyze the shared ancestry and genetic differentiation. We found that the Japanese could be separated into nine genetic clusters in our dataset, showing a marked concordance with geography; and that major components of ancestry profile of Japanese were from the Korean and Han Chinese clusters. We also detected and dated admixture in the Japanese. While genetic differentiation between Ryukyu and Hondo was suggested to be caused in part by positive selection, genetic differentiation among the Hondo clusters appeared to result principally from genetic drift. Notably, in Asians, we found the possibility that positive selection accentuated genetic differentiation among distant populations but attenuated genetic differentiation among close populations. These findings are significant for studies of human evolution and medical genetics. PMID:29091727

The potential of genetic engineering of plants for the remediation of soils contaminated with heavy metals.

PubMed

Fasani, Elisa; Manara, Anna; Martini, Flavio; Furini, Antonella; DalCorso, Giovanni

2018-05-01

The genetic engineering of plants to facilitate the reclamation of soils and waters contaminated with inorganic pollutants is a relatively new and evolving field, benefiting from the heterologous expression of genes that increase the capacity of plants to mobilize, stabilize and/or accumulate metals. The efficiency of phytoremediation relies on the mechanisms underlying metal accumulation and tolerance, such as metal uptake, translocation and detoxification. The transfer of genes involved in any of these processes into fast-growing, high-biomass crops may improve their reclamation potential. The successful phytoextraction of metals/metalloids and their accumulation in aerial organs have been achieved by expressing metal ligands or transporters, enzymes involved in sulfur metabolism, enzymes that alter the chemical form or redox state of metals/metalloids and even the components of primary metabolism. This review article considers the potential of genetic engineering as a strategy to improve the phytoremediation capacity of plants in the context of heavy metals and metalloids, using recent case studies to demonstrate the practical application of this approach in the field. © 2017 John Wiley & Sons Ltd.

Computational Analysis of Candidate Disease Genes and Variants for Salt-Sensitive Hypertension in Indigenous Southern Africans

PubMed Central

Tiffin, Nicki; Meintjes, Ayton; Ramesar, Rajkumar; Bajic, Vladimir B.; Rayner, Brian

2010-01-01

Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor (PTH) and type-1angiotensin II receptor (AGTR1). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension. PMID:20886000

The Three Domains of Conservation Genetics: Case Histories from Hawaiian Waters

PubMed Central

2016-01-01

The scientific field of conservation biology is dominated by 3 specialties: phylogenetics, ecology, and evolution. Under this triad, phylogenetics is oriented towards the past history of biodiversity, conserving the divergent branches in the tree of life. The ecological component is rooted in the present, maintaining the contemporary life support systems for biodiversity. Evolutionary conservation (as defined here) is concerned with preserving the raw materials for generating future biodiversity. All 3 domains can be documented with genetic case histories in the waters of the Hawaiian Archipelago, an isolated chain of volcanic islands with 2 types of biodiversity: colonists, and new species that arose from colonists. This review demonstrates that 1) phylogenetic studies have identified previously unknown branches in the tree of life that are endemic to Hawaiian waters; 2) population genetic surveys define isolated marine ecosystems as management units, and 3) phylogeographic analyses illustrate the pathways of colonization that can enhance future biodiversity. Conventional molecular markers have advanced all 3 domains in conservation biology over the last 3 decades, and recent advances in genomics are especially valuable for understanding the foundations of future evolutionary diversity. PMID:27001936

Proceedings from the 2009 Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back

PubMed Central

Rauen, Katherine A.; Schoyer, Lisa; McCormick, Frank; Lin, Angela E.; Allanson, Judith E.; Stevenson, David A.; Gripp, Karen W.; Neri, Giovanni; Carey, John C.; Legius, Eric; Tartaglia, Marco; Schubbert, Suzanne; Roberts, Amy E.; Gelb, Bruce D.; Shannon, Kevin; Gutmann, David H.; McMahon, Martin; Guerra, Carmen; Fagin, James A.; Yu, Benjamin; Aoki, Yoko; Neel, Ben G.; Balmain, Allan; Drake, Richard R.; Nolan, Garry P.; Zenker, Martin; Bollag, Gideon; Sebolt-Leopold, Judith; Gibbs, Jackson B.; Silva, Alcino J.; Patton, E. Elizabeth; Viskochil, David H.; Kieran, Mark W.; Korf, Bruce R.; Hagerman, Randi J.; Packer, Roger J.; Melese, Teri

2012-01-01

The RASopathies are a group of genetic syndromes caused by germline mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Some of these syndromes are neurofibromatosis type 1, Noonan syndrome, Costello syndrome, cardio-facio-cutaneous syndrome, LEOPARD syndrome and Legius syndrome. Their common underlying pathogenetic mechanism brings about significant overlap in phenotypic features and includes craniofacial dysmorphology, cardiac, cutaneous, musculoskeletal, GI and ocular abnormalities, and a predisposition to cancer. The proceedings from the symposium “Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back” chronicle the timely and typical research symposium which brought together clinicians, basic scientists, physician-scientists, advocate leaders, trainees, students and individuals with Ras syndromes and their families. The goals, to discuss basic science and clinical issues, to set forth a solid framework for future research, to direct translational applications towards therapy and to set forth best practices for individuals with RASopathies was successfully meet with a commitment to begin to move towards clinical trials. PMID:20014119

Schizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regions.

PubMed

Viana, Joana; Hannon, Eilis; Dempster, Emma; Pidsley, Ruth; Macdonald, Ruby; Knox, Olivia; Spiers, Helen; Troakes, Claire; Al-Saraj, Safa; Turecki, Gustavo; Schalkwyk, Leonard C; Mill, Jonathan

2017-01-01

Genetic association studies provide evidence for a substantial polygenic component to schizophrenia, although the neurobiological mechanisms underlying the disorder remain largely undefined. Building on recent studies supporting a role for developmentally regulated epigenetic variation in the molecular aetiology of schizophrenia, this study aimed to identify epigenetic variation associated with both a diagnosis of schizophrenia and elevated polygenic risk burden for the disease across multiple brain regions. Genome-wide DNA methylation was quantified in 262 post-mortem brain samples, representing tissue from four brain regions (prefrontal cortex, striatum, hippocampus and cerebellum) from 41 schizophrenia patients and 47 controls. We identified multiple disease-associated and polygenic risk score-associated differentially methylated positions and regions, which are not enriched in genomic regions identified in genetic studies of schizophrenia and do not reflect direct genetic effects on DNA methylation. Our study represents the first analysis of epigenetic variation associated with schizophrenia across multiple brain regions and highlights the utility of polygenic risk scores for identifying molecular pathways associated with aetiological variation in complex disease. © The Author 2016. Published by Oxford University Press.

Enhanced entrainability of genetic oscillators by period mismatch

PubMed Central

Hasegawa, Yoshihiko; Arita, Masanori

2013-01-01

Biological oscillators coordinate individual cellular components so that they function coherently and collectively. They are typically composed of multiple feedback loops, and period mismatch is unavoidable in biological implementations. We investigated the advantageous effect of this period mismatch in terms of a synchronization response to external stimuli. Specifically, we considered two fundamental models of genetic circuits: smooth and relaxation oscillators. Using phase reduction and Floquet multipliers, we numerically analysed their entrainability under different coupling strengths and period ratios. We found that a period mismatch induces better entrainment in both types of oscillator; the enhancement occurs in the vicinity of the bifurcation on their limit cycles. In the smooth oscillator, the optimal period ratio for the enhancement coincides with the experimentally observed ratio, which suggests biological exploitation of the period mismatch. Although the origin of multiple feedback loops is often explained as a passive mechanism to ensure robustness against perturbation, we study the active benefits of the period mismatch, which include increasing the efficiency of the genetic oscillators. Our findings show a qualitatively different perspective for both the inherent advantages of multiple loops and their essentiality. PMID:23389900

Genetics and phylogeny of genus Coilia in China based on AFLP markers

NASA Astrophysics Data System (ADS)

Yang, Qiaoli; Han, Zhiqiang; Sun, Dianrong; Xie, Songguang; Lin, Longshan; Gao, Tianxiang

2010-07-01

The taxonomy of Coilia has been extensively studied in China, and yet phylogenetic relationships among component taxa remain controversial. We used a PCR-based fingerprinting technique, amplified fragment length polymorphism (AFLP) to characterize and identify all four species of Coilia in China. We examined the genetic relationships of the four species of Coilia and a subspecies of Coilia nasus with AFLP. A total of 180 AFLP loci were generated from six primer combinations, of which 76.11% were polymorphic. The mean genetic distance between pairs of taxa ranged from 0.047 to 0.596. The neighbor-joining tree and UPGMA dendrogram resolved the investigated species into three separate lineages: (1) C. mystus, (2) C. grayii and (3) C. brachygnathus, C. nasus, and C. nasus taihuensis. Phylogenetic analysis of the AFLP data is inconsistent with current morphological taxonomic systems. The AFLP data indicated a close relationship among C. brachygnathus, C. nasus taihuensis, and C. nasus. Therefore, the two species described under Coilia ( C. brachygnathus and C. nasus taihuensis) are treated as synonyms of C. nasus.

Genetic control of the alternative pathway of complement in humans and age-related macular degeneration

PubMed Central

Hecker, Laura A.; Edwards, Albert O.; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H.; Brown, William L.; Issa, Peter Charbel; Scholl, Hendrik P.; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E.; Bailey, Kent R.; Oppermann, Martin

2010-01-01

Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues. PMID:19825847

Prevalence, associated factors and heritabilities of metabolic syndrome and its individual components in African Americans: the Jackson Heart Study.

PubMed

Khan, Rumana J; Gebreab, Samson Y; Sims, Mario; Riestra, Pia; Xu, Ruihua; Davis, Sharon K

2015-11-01

Both environmental and genetic factors play important roles in the development of metabolic syndrome (MetS). Studies about its associated factors and genetic contribution in African Americans (AA) are sparse. Our aim was to report the prevalence, associated factors and heritability estimates of MetS and its components in AA men and women. Data of this cross-sectional study come from a large community-based Jackson Heart Study (JHS). We analysed a total of 5227 participants, of whom 1636 from 281 families were part of a family study subset of JHS. Participants were classified as having MetS according to the Adult Treatment Panel III criteria. Multiple logistic regression analysis was performed to isolate independently associated factors of MetS (n=5227). Heritability was estimated from the family study subset using variance component methods (n=1636). About 27% of men and 40% of women had MetS. For men, associated factors with having MetS were older age, lower physical activity, higher body mass index, and higher homocysteine and adiponectin levels (p<0.05 for all). For women, in addition to all these, lower education, current smoking and higher stress were also significant (p<0.05 for all). After adjusting for covariates, the heritability of MetS was 32% (p<0.001). Heritability ranged from 14 to 45% among its individual components. Relatively higher heritability was estimated for waist circumference (45%), high density lipoprotein-cholesterol (43%) and triglycerides (42%). Heritability of systolic blood pressure (BP), diastolic BP and fasting blood glucose was 16%, 15% and 14%, respectively. Stress and low education were associated with having MetS in AA women, but not in men. Higher heritability estimates for lipids and waist circumference support the hypothesis of lipid metabolism playing a central role in the development of MetS and encourage additional efforts to identify the underlying susceptibility genes for this syndrome in AA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Positional cloning in mice and its use for molecular dissection of inflammatory arthritis.

PubMed

Abe, Koichiro; Yu, Philipp

2009-02-01

One of the upcoming next quests in the field of genetics might be molecular dissection of the genetic and environmental components of human complex diseases. In humans, however, there are certain experimental limitations for identification of a single component of the complex interactions by genetic analyses. Experimental animals offer simplified models for genetic and environmental interactions in human complex diseases. In particular, mice are the best mammalian models because of a long history and ample experience for genetic analyses. Forward genetics, which includes genetic screen and subsequent positional cloning of the causative genes, is a powerful strategy to dissect a complex phenomenon without preliminarily molecular knowledge of the process. In this review, first, we describe a general scheme of positional cloning in mice. Next, recent accomplishments on the patho-mechanisms of inflammatory arthritis by forward genetics approaches are introduced; Positional cloning effort for skg, Ali5, Ali18, cmo, and lupo mutants are provided as examples for the application to human complex diseases. As seen in the examples, the identification of genetic factors by positional cloning in the mouse have potential in solving molecular complexity of gene-environment interactions in human complex diseases.

Identification of Causal Genes, Networks, and Transcriptional Regulators of REM Sleep and Wake

PubMed Central

Millstein, Joshua; Winrow, Christopher J.; Kasarskis, Andrew; Owens, Joseph R.; Zhou, Lili; Summa, Keith C.; Fitzpatrick, Karrie; Zhang, Bin; Vitaterna, Martha H.; Schadt, Eric E.; Renger, John J.; Turek, Fred W.

2011-01-01

Study Objective: Sleep-wake traits are well-known to be under substantial genetic control, but the specific genes and gene networks underlying primary sleep-wake traits have largely eluded identification using conventional approaches, especially in mammals. Thus, the aim of this study was to use systems genetics and statistical approaches to uncover the genetic networks underlying 2 primary sleep traits in the mouse: 24-h duration of REM sleep and wake. Design: Genome-wide RNA expression data from 3 tissues (anterior cortex, hypothalamus, thalamus/midbrain) were used in conjunction with high-density genotyping to identify candidate causal genes and networks mediating the effects of 2 QTL regulating the 24-h duration of REM sleep and one regulating the 24-h duration of wake. Setting: Basic sleep research laboratory. Patients or Participants: Male [C57BL/6J × (BALB/cByJ × C57BL/6J*) F1] N2 mice (n = 283). Interventions: None. Measurements and Results: The genetic variation of a mouse N2 mapping cross was leveraged against sleep-state phenotypic variation as well as quantitative gene expression measurement in key brain regions using integrative genomics approaches to uncover multiple causal sleep-state regulatory genes, including several surprising novel candidates, which interact as components of networks that modulate REM sleep and wake. In particular, it was discovered that a core network module, consisting of 20 genes, involved in the regulation of REM sleep duration is conserved across the cortex, hypothalamus, and thalamus. A novel application of a formal causal inference test was also used to identify those genes directly regulating sleep via control of expression. Conclusion: Systems genetics approaches reveal novel candidate genes, complex networks and specific transcriptional regulators of REM sleep and wake duration in mammals. Citation: Millstein J; Winrow CJ; Kasarskis A; Owens JR; Zhou L; Summa KC; Fitzpatrick K; Zhang B; Vitaterna MH; Schadt EE; Renger JJ; Turek FW. Identification of causal genes, networks, and transcriptional regulators of REM sleep and wake. SLEEP 2011;34(11):1469-1477. PMID:22043117

Strains and Stressors: An Analysis of Touchscreen Learning in Genetically Diverse Mouse Strains

PubMed Central

Graybeal, Carolyn; Bachu, Munisa; Mozhui, Khyobeni; Saksida, Lisa M.; Bussey, Timothy J.; Sagalyn, Erica; Williams, Robert W.; Holmes, Andrew

2014-01-01

Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal) in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of “reversal learning,” “motivation-related late reversal learning,” “discrimination learning,” “speed to respond,” and “motivation during discrimination.” Together, these findings provide a valuable reference to inform the choice of strains and genetic backgrounds in future studies using touchscreen-based tasks. PMID:24586288

Aggregate blood pressure responses to serial dietary sodium and potassium intervention: defining responses using independent component analysis.

PubMed

Chen, Gengsheng; de las Fuentes, Lisa; Gu, Chi C; He, Jiang; Gu, Dongfeng; Kelly, Tanika; Hixson, James; Jacquish, Cashell; Rao, D C; Rice, Treva K

2015-06-20

Hypertension is a complex trait that often co-occurs with other conditions such as obesity and is affected by genetic and environmental factors. Aggregate indices such as principal components among these variables and their responses to environmental interventions may represent novel information that is potentially useful for genetic studies. In this study of families participating in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Study, blood pressure (BP) responses to dietary sodium interventions are explored. Independent component analysis (ICA) was applied to 20 variables indexing obesity and BP measured at baseline and during low sodium, high sodium and high sodium plus potassium dietary intervention periods. A "heat map" protocol that classifies subjects based on risk for hypertension is used to interpret the extracted components. ICA and heat map suggest four components best describe the data: (1) systolic hypertension, (2) general hypertension, (3) response to sodium intervention and (4) obesity. The largest heritabilities are for the systolic (64%) and general hypertension (56%) components. There is a pattern of higher heritability for the component response to intervention (40-42%) as compared to those for the traditional intervention responses computed as delta scores (24%-40%). In summary, the present study provides intermediate phenotypes that are heritable. Using these derived components may prove useful in gene discovery applications.

Genetic erosion of Phoenix dactylifera L.: Perceptible, probable or possible?

USDA-ARS?s Scientific Manuscript database

Genetic diversity of date palm (Phoenix dactylefera L.) encompasses genetic differences among and within species, subspecies, populations, cultivars, and individual clones in traditional oases and plantations. Components of this diversity can be estimated, throughout the tree’s ontogeny, at the phen...

Evaluation of water resources system vulnerability based on co-operative co-evolutionary genetic algorithm and projection pursuit model under the DPSIR framework

NASA Astrophysics Data System (ADS)

Zhao, Y.; Su, X. H.; Wang, M. H.; Li, Z. Y.; Li, E. K.; Xu, X.

2017-08-01

Water resources vulnerability control management is essential because it is related to the benign evolution of socio-economic, environmental and water resources system. Research on water resources system vulnerability is helpful to realization of water resources sustainable utilization. In this study, the DPSIR framework of driving forces-pressure-state-impact-response was adopted to construct the evaluation index system of water resources system vulnerability. Then the co-evolutionary genetic algorithm and projection pursuit were used to establish evaluation model of water resources system vulnerability. Tengzhou City in Shandong Province was selected as a study area. The system vulnerability was analyzed in terms of driving forces, pressure, state, impact and response on the basis of the projection value calculated by the model. The results show that the five components all belong to vulnerability Grade II, the vulnerability degree of impact and state were higher than other components due to the fierce imbalance in supply-demand and the unsatisfied condition of water resources utilization. It is indicated that the influence of high speed socio-economic development and the overuse of the pesticides have already disturbed the benign development of water environment to some extents. While the indexes in response represented lower vulnerability degree than the other components. The results of the evaluation model are coincident with the status of water resources system in the study area, which indicates that the model is feasible and effective.

Comparison of factor-analytic and reduced rank models for test-day milk yield in Gyr dairy cattle (Bos indicus).

PubMed

Pereira, R J; Ayres, D R; El Faro, L; Verneque, R S; Vercesi Filho, A E; Albuquerque, L G

2013-09-27

We analyzed 46,161 monthly test-day records of milk production from 7453 first lactations of crossbred dairy Gyr (Bos indicus) x Holstein cows. The following seven models were compared: standard multivariate model (M10), three reduced rank models fitting the first 2, 3, or 4 genetic principal components, and three models considering a 2-, 3-, or 4-factor structure for the genetic covariance matrix. Full rank residual covariance matrices were considered for all models. The model fitting the first two principal components (PC2) was the best according to the model selection criteria. Similar phenotypic, genetic, and residual variances were obtained with models M10 and PC2. The heritability estimates ranged from 0.14 to 0.21 and from 0.13 to 0.21 for models M10 and PC2, respectively. The genetic correlations obtained with model PC2 were slightly higher than those estimated with model M10. PC2 markedly reduced the number of parameters estimated and the time spent to reach convergence. We concluded that two principal components are sufficient to model the structure of genetic covariances between test-day milk yields.

Systems genetic analysis of multivariate response to iron deficiency in mice

PubMed Central

Yin, Lina; Unger, Erica L.; Jellen, Leslie C.; Earley, Christopher J.; Allen, Richard P.; Tomaszewicz, Ann; Fleet, James C.

2012-01-01

The aim of this study was to identify genes that influence iron regulation under varying dietary iron availability. Male and female mice from 20+ BXD recombinant inbred strains were fed iron-poor or iron-adequate diets from weaning until 4 mo of age. At death, the spleen, liver, and blood were harvested for the measurement of hemoglobin, hematocrit, total iron binding capacity, transferrin saturation, and liver, spleen and plasma iron concentration. For each measure and diet, we found large, strain-related variability. A principal-components analysis (PCA) was performed on the strain means for the seven parameters under each dietary condition for each sex, followed by quantitative trait loci (QTL) analysis on the factors. Compared with the iron-adequate diet, iron deficiency altered the factor structure of the principal components. QTL analysis, combined with PosMed (a candidate gene searching system) published gene expression data and literature citations, identified seven candidate genes, Ptprd, Mdm1, Picalm, lip1, Tcerg1, Skp2, and Frzb based on PCA factor, diet, and sex. Expression of each of these is cis-regulated, significantly correlated with the corresponding PCA factor, and previously reported to regulate iron, directly or indirectly. We propose that polymorphisms in multiple genes underlie individual differences in iron regulation, especially in response to dietary iron challenge. This research shows that iron management is a highly complex trait, influenced by multiple genes. Systems genetics analysis of iron homeostasis holds promise for developing new methods for prevention and treatment of iron deficiency anemia and related diseases. PMID:22461179

[Methods of identification and assessment of safety of genetically modified microorganisms in manufacture food production].

PubMed

Khovaev, A A; Nesterenko, L N; Naroditskiĭ, B S

2011-01-01

Methods of identification of genetically modified microorganisms (GMM), used in manufacture food on control probes are presented. Results of microbiological and molecular and genetic analyses of food products and their components important in microbiological and genetic expert examination of GMM in foods are considered. Examination of biosafety of GMM are indicated.

Anthropogenic alterations of genetic diversity within tree populations: Implications for forest ecosystem resilience

Treesearch

Paul G. Schaberg; Donald H. DeHayes; Gary J. Hawley; Samuel E. Nijensohn

2008-01-01

Healthy forests provide many of the essential ecosystem services upon which all life depends. Genetic diversity is an essential component of long-term forest health because it provides a basis for adaptation and resilience to environmental stress and change. In addition to natural processes, numerous anthropogenic factors deplete forest genetic resources. Genetic...

Variability of arginine content and yield components in Valencia peanut germplasm.

PubMed

Aninbon, Chorkaew; Jogloy, Sanun; Vorasoot, Nimitr; Nuchadomrong, Suporn; Holbrook, C Corley; Kvien, Craig; Puppala, Naveen; Patanothai, Aran

2017-06-01

Peanut seeds are rich in arginine, an amino acid that has several positive effects on human health. Establishing the genetic variability of arginine content in peanut will be useful for breeding programs that have high arginine as one of their goals. The objective of this study was to evaluate the variation of arginine content, pods/plant, seeds/pod, seed weight, and yield in Valencia peanut germplasm. One hundred and thirty peanut genotypes were grown under field condition for two years. A randomized complete block design with three replications was used for this study. Arginine content was analyzed in peanut seeds at harvest using spectrophotometry. Yield and yield components were recorded for each genotype. Significant differences in arginine content and yield components were found in the tested Valencia peanut germplasm. Arginine content ranged from 8.68-23.35 μg/g seed. Kremena was the best overall genotype of high arginine content, number of pods/plant, 100 seed weight and pod yield.

A Light Harvesting Complex-Like Protein in Maintenance of Photosynthetic Components in Chlamydomonas1[OPEN

PubMed Central

Zhao, Lei; Cheng, Dongmei; Huang, Xiahe; Chen, Mei; Xing, Jiale; Gao, Liyan; Li, Lingyu; Wang, Yale; Peng, Lianwei; Wang, Yingchun

2017-01-01

Using a genetic approach, we have identified and characterized a novel protein, named Msf1 (Maintenance factor for photosystem I), that is required for the maintenance of specific components of the photosynthetic apparatus in the green alga Chlamydomonas reinhardtii. Msf1 belongs to the superfamily of light-harvesting complex proteins with three transmembrane domains and consensus chlorophyll-binding sites. Loss of Msf1 leads to reduced accumulation of photosystem I and chlorophyll-binding proteins/complexes. Msf1is a component of a thylakoid complex containing key enzymes of the tetrapyrrole biosynthetic pathway, thus revealing a possible link between Msf1 and chlorophyll biosynthesis. Protein interaction assays and greening experiments demonstrate that Msf1 interacts with Copper target homolog1 (CHL27B) and accumulates concomitantly with chlorophyll in Chlamydomonas, implying that chlorophyll stabilizes Msf1. Contrary to other light-harvesting complex-like genes, the expression of Msf1 is not stimulated by high-light stress, but its protein level increases significantly under heat shock, iron and copper limitation, as well as in stationary cells. Based on these results, we propose that Msf1 is required for the maintenance of photosystem I and specific protein-chlorophyll complexes especially under certain stress conditions. PMID:28637830

Assessing Sociability, Social Memory, and Pup Retrieval in Mice.

PubMed

Zimprich, Annemarie; Niessing, Jörn; Cohen, Lior; Garrett, Lillian; Einicke, Jan; Sperling, Bettina; Schmidt, Mathias V; Hölter, Sabine M

2017-12-20

Adaptive social behavior is important in mammals, both for the well-being of the individual and for the thriving of the species. Dysfunctions in social behavior occur in many neurodevelopmental and psychiatric diseases, and research into the genetic components of disease-relevant social deficits can open up new avenues for understanding the underlying biological mechanisms and therapeutic interventions. Genetically modified mouse models are particularly useful in this respect, and robust experimental protocols are needed to reliably assess relevant social behavior phenotypes. Here we describe in detail three protocols to quantitatively measure sociability, one of the most frequently investigated social behavior phenotypes in mice, using a three-chamber sociability test. These protocols can be extended to also assess social memory. In addition, we provide a detailed protocol on pup retrieval, which is a particularly robust maternal behavior amenable to various scientific questions. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Dupuytren's contracture: emerging insight into a Viking disease.

PubMed

Nunn, Adam C; Schreuder, Fred B

2014-01-01

Dupuytren's disease is a fibroproliferative condition of the palm, with a predilection for men, which has affected Northern Europeans since the Viking conquests. Although strongly heritable, clear evidence exists for environmental factors that modify the underlying genetic risk, such as diabetes, heavy drinking, and smoking. Evidence also exists for epilepsy (probably due to treatment with certain anti-epileptic drugs), and Human Immunodeficiency Virus infection. Recent large studies have shown no relationship with manual labour or vibrating tools. Two theories have emerged regarding the pathogenic mechanism: the first attributes the aberrant healing process that characterises Dupuytren's to free radicals, generated as a result of microangiopathy, whereas the second cites a genetic tendency toward apoptosis-resistant myofibroblasts. Despite only one study demonstrating linkage, emerging data from genome-wide association studies highlight a series of single nucleotide polymorphisms near members of the Wnt signalling pathway, and transcriptional profiling studies have consistently identified certain components of the extracellular matrix.

Ethnicity and genetics are more important than diabetes mellitus and hypertension in producing cardiovascular events in patients with the metabolic syndrome: emphasis in the Puerto Rico population.

PubMed

Altieri, Pablo I; Marcial, José M; Banchs, Héctor; Escobales, Nelson; Crespo, María

2013-01-01

Metabolic syndrome is a cluster of risk factors for cardiovascular disease that affects an estimated 50 million Americans. The present article reviews the metabolic syndrome with respect to its definition, epidemiology, pathophysiology and management. A primary focus in research has been to elucidate the processes determined to cause insulin resistance, the fundamental mechanism underlying the metabolic syndrome. Namely, the incidence, component characteristics and complications of the metabolic syndrome in the island of Puerto Rico are described alongside the fact that the metabolic syndrome may be milder in Puerto Rico than in the mainland United States because it is characterized by less aggressive coronary disease and a relatively normal lipid profile. This suggests that the cardiovascular complications are more influenced by genetics and culture than diabetes mellitus and hypertension.

Bifunctional fusion proteins of calmodulin and protein A as affinity ligands in protein purification and in the study of protein-protein interactions.

PubMed

Hentz, N G; Daunert, S

1996-11-15

An affinity chromatography system is described that incorporates a genetically designed bifunctional affinity ligand. The utility of the system in protein purification and in the study of protein-protein interactions is demonstrated by using the interaction between protein A and the heat shock protein DnaK as a model system. The bifunctional affinity ligand was developed by genetically fusing calmodulin (CaM) to protein A (ProtA). The dual functionality of protein A-calmodulin (ProtA-CaM) stems from the molecular recognition properties of the two components of the fusion protein. In particular, CaM serves as the anchoring component by virtue of its binding properties toward phenothiazine. Thus, the ProtA-CaM can be immobilized on a solid support containing phenothiazine from the C-terminal domain of the fusion protein. Protein A is at the N-terminal domain of the fusion protein and serves as the affinity site for DnaK. While DnaK binds specifically to the protein A domain of the bifunctional ligand, it is released upon addition of ATP and under very mild conditions (pH 7.0). In addition to obtaining highly purified DnaK, this system is very rugged in terms of its performance. The proteinaceous bifunctional affinity ligand can be easily removed by addition of EGTA, and fresh ProtA-CaM can be easily reloaded onto the column. This allows for a facile regeneration of the affinity column because the phenothiazine-silica support matrix is stable for long periods of time under a variety of conditions. This study also demonstrates that calmodulin fusions can provide a new approach to study protein-protein interactions. Indeed, the ProtA-CaM fusion protein identified DnaK as a cellular component that interacts with protein A from among the thousands of proteins present in Escherichia coli.

Finding Imaging Patterns of Structural Covariance via Non-Negative Matrix Factorization

PubMed Central

Sotiras, Aristeidis; Resnick, Susan M.; Davatzikos, Christos

2015-01-01

In this paper, we investigate the use of Non-Negative Matrix Factorization (NNMF) for the analysis of structural neuroimaging data. The goal is to identify the brain regions that co-vary across individuals in a consistent way, hence potentially being part of underlying brain networks or otherwise influenced by underlying common mechanisms such as genetics and pathologies. NNMF offers a directly data-driven way of extracting relatively localized co-varying structural regions, thereby transcending limitations of Principal Component Analysis (PCA), Independent Component Analysis (ICA) and other related methods that tend to produce dispersed components of positive and negative loadings. In particular, leveraging upon the well known ability of NNMF to produce parts-based representations of image data, we derive decompositions that partition the brain into regions that vary in consistent ways across individuals. Importantly, these decompositions achieve dimensionality reduction via highly interpretable ways and generalize well to new data as shown via split-sample experiments. We empirically validate NNMF in two data sets: i) a Diffusion Tensor (DT) mouse brain development study, and ii) a structural Magnetic Resonance (sMR) study of human brain aging. We demonstrate the ability of NNMF to produce sparse parts-based representations of the data at various resolutions. These representations seem to follow what we know about the underlying functional organization of the brain and also capture some pathological processes. Moreover, we show that these low dimensional representations favorably compare to descriptions obtained with more commonly used matrix factorization methods like PCA and ICA. PMID:25497684

Transmission, Development, and Plasticity of Synapses

PubMed Central

Harris, Kathryn P.

2015-01-01

Chemical synapses are sites of contact and information transfer between a neuron and its partner cell. Each synapse is a specialized junction, where the presynaptic cell assembles machinery for the release of neurotransmitter, and the postsynaptic cell assembles components to receive and integrate this signal. Synapses also exhibit plasticity, during which synaptic function and/or structure are modified in response to activity. With a robust panel of genetic, imaging, and electrophysiology approaches, and strong evolutionary conservation of molecular components, Drosophila has emerged as an essential model system for investigating the mechanisms underlying synaptic assembly, function, and plasticity. We will discuss techniques for studying synapses in Drosophila, with a focus on the larval neuromuscular junction (NMJ), a well-established model glutamatergic synapse. Vesicle fusion, which underlies synaptic release of neurotransmitters, has been well characterized at this synapse. In addition, studies of synaptic assembly and organization of active zones and postsynaptic densities have revealed pathways that coordinate those events across the synaptic cleft. We will also review modes of synaptic growth and plasticity at the fly NMJ, and discuss how pre- and postsynaptic cells communicate to regulate plasticity in response to activity. PMID:26447126

Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage

PubMed Central

2014-01-01

This article reviews current knowledge of the mechanisms underlying the initial hemorrhage and secondary blood–brain barrier (BBB) dysfunction in primary spontaneous intracerebral hemorrhage (ICH) in adults. Multiple etiologies are associated with ICH, for example, hypertension, Alzheimer’s disease, vascular malformations and coagulopathies (genetic or drug-induced). After the initial bleed, there can be continued bleeding over the first 24 hours, so-called hematoma expansion, which is associated with adverse outcomes. A number of clinical trials are focused on trying to limit such expansion. Significant progress has been made on the causes of BBB dysfunction after ICH at the molecular and cell signaling level. Blood components (e.g. thrombin, hemoglobin, iron) and the inflammatory response to those components play a large role in ICH-induced BBB dysfunction. There are current clinical trials of minimally invasive hematoma removal and iron chelation which may limit such dysfunction. Understanding the mechanisms underlying the initial hemorrhage and secondary BBB dysfunction in ICH is vital for developing methods to prevent and treat this devastating form of stroke. PMID:25120903

Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

PubMed Central

Calaza, Manuel; Witte, Torsten; Papasteriades, Chryssa; Marchini, Maurizio; Migliaresi, Sergio; Kovacs, Attila; Ordi-Ros, Josep; Bijl, Marc; Santos, Maria Jose; Ruzickova, Sarka; Pullmann, Rudolf; Carreira, Patricia; Skopouli, Fotini N.; D'Alfonso, Sandra; Sebastiani, Gian Domenico; Suarez, Ana; Blanco, Francisco J.; Gomez-Reino, Juan J.; Gonzalez, Antonio

2011-01-01

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10−4), oral ulcers (P = 6.9×10−4) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested. PMID:22194982

Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD.

PubMed

Guo, W; Samuels, J F; Wang, Y; Cao, H; Ritter, M; Nestadt, P S; Krasnow, J; Greenberg, B D; Fyer, A J; McCracken, J T; Geller, D A; Murphy, D L; Knowles, J A; Grados, M A; Riddle, M A; Rasmussen, S A; McLaughlin, N C; Nurmi, E L; Askland, K D; Cullen, B A; Piacentini, J; Pauls, D L; Bienvenu, O J; Stewart, S E; Goes, F S; Maher, B; Pulver, A E; Valle, D; Mattheisen, M; Qian, J; Nestadt, G; Shugart, Y Y

2017-07-01

Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10 -7 in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data. Published by Elsevier B.V.

The generation of meaningful information in molecular systems.

PubMed

Wills, Peter R

2016-03-13

The physico-chemical processes occurring inside cells are under the computational control of genetic (DNA) and epigenetic (internal structural) programming. The origin and evolution of genetic information (nucleic acid sequences) is reasonably well understood, but scant attention has been paid to the origin and evolution of the molecular biological interpreters that give phenotypic meaning to the sequence information that is quite faithfully replicated during cellular reproduction. The near universality and age of the mapping from nucleotide triplets to amino acids embedded in the functionality of the protein synthetic machinery speaks to the early development of a system of coding which is still extant in every living organism. We take the origin of genetic coding as a paradigm of the emergence of computation in natural systems, focusing on the requirement that the molecular components of an interpreter be synthesized autocatalytically. Within this context, it is seen that interpreters of increasing complexity are generated by series of transitions through stepped dynamic instabilities (non-equilibrium phase transitions). The early phylogeny of the amino acyl-tRNA synthetase enzymes is discussed in such terms, leading to the conclusion that the observed optimality of the genetic code is a natural outcome of the processes of self-organization that produced it. © 2016 The Author(s).

Bio++: a set of C++ libraries for sequence analysis, phylogenetics, molecular evolution and population genetics.

PubMed

Dutheil, Julien; Gaillard, Sylvain; Bazin, Eric; Glémin, Sylvain; Ranwez, Vincent; Galtier, Nicolas; Belkhir, Khalid

2006-04-04

A large number of bioinformatics applications in the fields of bio-sequence analysis, molecular evolution and population genetics typically share input/output methods, data storage requirements and data analysis algorithms. Such common features may be conveniently bundled into re-usable libraries, which enable the rapid development of new methods and robust applications. We present Bio++, a set of Object Oriented libraries written in C++. Available components include classes for data storage and handling (nucleotide/amino-acid/codon sequences, trees, distance matrices, population genetics datasets), various input/output formats, basic sequence manipulation (concatenation, transcription, translation, etc.), phylogenetic analysis (maximum parsimony, markov models, distance methods, likelihood computation and maximization), population genetics/genomics (diversity statistics, neutrality tests, various multi-locus analyses) and various algorithms for numerical calculus. Implementation of methods aims at being both efficient and user-friendly. A special concern was given to the library design to enable easy extension and new methods development. We defined a general hierarchy of classes that allow the developer to implement its own algorithms while remaining compatible with the rest of the libraries. Bio++ source code is distributed free of charge under the CeCILL general public licence from its website http://kimura.univ-montp2.fr/BioPP.

A novel mutation in SCN9A in a child with congenital insensitivity to pain.

PubMed

Shorer, Zamir; Wajsbrot, Einav; Liran, Tamir-Hostovsky; Levy, Jacov; Parvari, Ruti

2014-01-01

[corrected] Congenital insensitivity to pain (CIP) is a rare condition in which patients have no pain perception and anosmia but are otherwise essentially normal (OMIM 243000). The recent discovery of the genetic defects underlying 3 monogenic pain disorders has provided additional and important insights about some components of human pain. Genetic studies in families demonstrating recessively inherited channelopathy-associated insensitivity to pain have identified nonsense mutations that result in truncation of the voltage-gated sodium channel type IX subunit (SCN9A), a 113.5-kb gene comprising coding 26 exons. Here we describe a patient with CIP with a new mutation in SCN9A not described yet. All exons were sequenced. All 26 coding exons were sequenced and two changes were identified in homozygosity in exon 10: c.1126 A > C causing K376Q and c.1124delG causing p.G375Afs* frame shift. We report a novel, loss-of-function mutation in homozygosity that causes congenital insensitivity to pain and provide a comprehensive clinical description of the patient. This contributes to the clinical and neurophysiological characteristic of the sodium channel Nav1.7 channelopathy and expand our genetic knowledge which might provide more accurate and comprehensive clinical electrophysiological and genetic information. Copyright © 2014 Elsevier Inc. All rights reserved.

Multi-channel acoustic recording and automated analysis of Drosophila courtship songs

PubMed Central

2013-01-01

Background Drosophila melanogaster has served as a powerful model system for genetic studies of courtship songs. To accelerate research on the genetic and neural mechanisms underlying courtship song, we have developed a sensitive recording system to simultaneously capture the acoustic signals from 32 separate pairs of courting flies as well as software for automated segmentation of songs. Results Our novel hardware design enables recording of low amplitude sounds in most laboratory environments. We demonstrate the power of this system by collecting, segmenting and analyzing over 18 hours of courtship song from 75 males from five wild-type strains of Drosophila melanogaster. Our analysis reveals previously undetected modulation of courtship song features and extensive natural genetic variation for most components of courtship song. Despite having a large dataset with sufficient power to detect subtle modulations of song, we were unable to identify previously reported periodic rhythms in the inter-pulse interval of song. We provide detailed instructions for assembling the hardware and for using our open-source segmentation software. Conclusions Analysis of a large dataset of acoustic signals from Drosophila melanogaster provides novel insight into the structure and dynamics of species-specific courtship songs. Our new system for recording and analyzing fly acoustic signals should therefore greatly accelerate future studies of the genetics, neurobiology and evolution of courtship song. PMID:23369160

Associations Between Genetic Ancestries and Nicotine Metabolism Biomarkers in the Multiethnic Cohort Study

PubMed Central

Wang, Hansong; Park, Sungshim L.; Stram, Daniel O.; Haiman, Christopher A.; Wilkens, Lynne R.; Hecht, Stephen S.; Kolonel, Laurence N.; Murphy, Sharon E.; Le Marchand, Loïc

2015-01-01

Differences in internal dose of nicotine and tobacco-derived carcinogens among ethnic/racial groups have been observed. In this study, we explicitly examined the relationships between genetic ancestries (genome-wide average) and 19 tobacco-derived biomarkers in smokers from 3 admixed groups in the Multiethnic Cohort Study (1993–present), namely, African ancestry in African Americans (n = 362), Amerindian ancestry in Latinos (n = 437), and Asian and Native Hawaiian ancestries in Native Hawaiians (n = 300). After multiple comparison adjustment, both African and Asian ancestries were significantly related to a greater level of free cotinine; African ancestry was also significantly related to lower cotinine glucuronidation (P's < 0.00156). The predicted decrease in cotinine glucuronidation was 8.6% (P = 4.5 × 10−6) per a 20% increase in African ancestry. Follow-up admixture mapping revealed that African ancestry in a 12-Mb region on chromosome 4q was related to lower cotinine glucuronidation (P's < 2.7 × 10−7, smallest P = 1.5 × 10−9), although this is the same region reported in our previous genome-wide association study. Our results implicate a genetic ancestral component in the observed ethnic/racial variation in nicotine metabolism. Further studies are needed to identify the underlying genetic variation that could potentially be ethnic/racial specific. PMID:26568573

Gene(s) and individual feeding behavior: Exploring eco-evolutionary dynamics underlying left-right asymmetry in the scale-eating cichlid fish Perissodus microlepis.

PubMed

Raffini, Francesca; Fruciano, Carmelo; Meyer, Axel

2018-06-01

The scale-eating cichlid fish Perissodus microlepis is a textbook example of bilateral asymmetry due to its left or right-bending heads and of negative frequency-dependent selection, which is proposed to maintain this stable polymorphism. The mechanisms that underlie this asymmetry remain elusive. Several studies had initially postulated a simple genetic basis for this trait, but this explanation has been questioned, particularly by reports observing a unimodal distribution of mouth shapes. We hypothesize that this unimodal distribution might be due to a combination of genetic and phenotypically plastic components. Here, we expanded on previous work by investigating a formerly identified candidate SNP associated to mouth laterality, documenting inter-individual variation in feeding preference using stable isotope analyses, and testing their association with mouth asymmetry. Our results suggest that this polymorphism is influenced by both a polygenic basis and inter-individual non-genetic variation, possibly due to feeding experience, individual specialization, and intraspecific competition. We introduce a hypothesis potentially explaining the simultaneous maintenance of left, right, asymmetric and symmetric mouth phenotypes due to the interaction between diverse eco-evolutionary dynamics including niche construction and balancing selection. Future studies will have to further tease apart the relative contribution of genetic and environmental factors and their interactions in an integrated fashion.

Genetic diversity of volatile components in Xinjiang Wild Apple (Malus sieversii).

PubMed

Chen, Xuesen; Feng, Tao; Zhang, Yanmin; He, Tianming; Feng, Jianrong; Zhang, Chunyu

2007-02-01

To evaluate genetic relationships using qualitative and/or quantitative differentiation of volatile components in Xinjiang Wild Apple (Malus sieversii (Lebed.) Roem.) and to acquire basic data for the conservation and utilization of the species, aroma components in ripe fruit of M. sieversii obtained from 30 seedlings at Mohe, Gongliu County, Xinjiang Autonomic Region, China, and in ripe fruit of 4 M. pumila cultivars ('Ralls', 'Delicious', 'Golden Delicious', and 'Fuji') were analyzed using head space-solid phase microextraction and gas chromatography-mass spectrometry. The results indicated that the values of similarity coefficient concerning volatile types between the two species were in accordance with the evolution of M. pumila cultivars (forms), and that M. sieversii seedlings showed considerable genetic variations in these aspects: the total content of volatile components, the classes and contents of each compound classes, the segregation ratio, and content of main components. The results showed significant difference among seedlings and wide genetic diversity within the populations. Comparison of the volatile components in M. sieversii with those in M. pumila cultivars showed that the common compounds whose number were larger than five with the contents over 0.04 mg/L simultaneously between M. sieversii and M. pumila cultivars belonged to esters, alcohols, aldehydes or ketones. This suggests fundamental identity in main volatile components of M. sieversii and M. pumila cultivars. The results above sustained the conclusion "M. sieversii is probably the ancestor of M. pumila". However, there were 48 compounds present in M. pumila that were not detected in M. sieversii, including 6 character impact components (i.e., propyl acetate, (Z)-3-hexenal, 2-methyl-1-butanol acetate, pentyl acetate, 3-furanmethanol, and benzene acetaldehyde). This suggested that in the domestication of M. pumila, introgression of other apple species, except for M. sieversii, by interspecies hybridization was possible. There were 177 compounds in total belonging to 11 classes detected in 30 M. sieversii seedlings, including esters, alcohols, ketones, aldehydes, acids, benzene ramifications, terpenes, heterocycles, hydrocarbon derivates, acetals, and lactones. Among them, acetals and lactones were not detected in M. pumila cultivars, 90 compounds were unique to M. sieversii, and 7 components (1-butanol, ethyl butanoate, 1-hexanol, ethyl hexanoate, 3-octen-1-ol, ethyl octanoate, and damascenone) belonged to character impact odors. Thus, the potential of M. sieversii in "utilization conservation" is enormous as a rare germplasm on genetic improvement of M. pumila cultivars.

Development of a genetic sexing strain in Bactrocera carambolae (Diptera: Tephritidae) by introgression of sex sorting components from B. dorsalis, Salaya1 strain.

PubMed

Isasawin, Siriwan; Aketarawong, Nidchaya; Lertsiri, Sittiwat; Thanaphum, Sujinda

2014-01-01

The carambola fruit fly, Bactrocera carambolae Drew & Hancock is a high profile key pest that is widely distributed in the southwestern ASEAN region. In addition, it has trans-continentally invaded Suriname, where it has been expanding east and southward since 1975. This fruit fly belongs to Bactrocera dorsalis species complex. The development and application of a genetic sexing strain (Salaya1) of B. dorsalis sensu stricto (s.s.) (Hendel) for the sterile insect technique (SIT) has improved the fruit fly control. However, matings between B. dorsalis s.s. and B. carambolae are incompatible, which hinder the application of the Salaya1 strain to control the carambola fruit fly. To solve this problem, we introduced genetic sexing components from the Salaya1 strain into the B. carambolae genome by interspecific hybridization. Morphological characteristics, mating competitiveness, male pheromone profiles, and genetic relationships revealed consistencies that helped to distinguish Salaya1 and B. carambolae strains. A Y-autosome translocation linking the dominant wild-type allele of white pupae gene and a free autosome carrying a recessive white pupae homologue from the Salaya1 strain were introgressed into the gene pool of B. carambolae. A panel of Y-pseudo-linked microsatellite loci of the Salaya1 strain served as markers for the introgression experiments. This resulted in a newly derived genetic sexing strain called Salaya5, with morphological characteristics corresponding to B. carambolae. The rectal gland pheromone profile of Salaya5 males also contained a distinctive component of B. carambolae. Microsatellite DNA analyses confirmed the close genetic relationships between the Salaya5 strain and wild B. carambolae populations. Further experiments showed that the sterile males of Salaya5 can compete with wild males for mating with wild females in field cage conditions. Introgression of sex sorting components from the Salaya1 strain to a closely related B. carambolae strain generated a new genetic sexing strain, Salaya5. Morphology-based taxonomic characteristics, distinctive pheromone components, microsatellite DNA markers, genetic relationships, and mating competitiveness provided parental baseline data and validation tools for the new strain. The Salaya5 strain shows a close similarity with those features in the wild B. carambolae strain. In addition, mating competitiveness tests suggested that Salaya5 has a potential to be used in B. carambolae SIT programs based on male-only releases.

Alimentary regimen in non-alcoholic fatty liver disease: Mediterranean diet

PubMed Central

Abenavoli, Ludovico; Milic, Natasa; Peta, Valentina; Alfieri, Francesco; De Lorenzo, Antonino; Bellentani, Stefano

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The mechanisms of the underlying disease development and progression are awaiting clarification. Insulin resistance and obesity-related inflammation status, among other possible genetic, dietary, and lifestyle factors, are thought to play the key role. There is no consensus concerning the pharmacological treatment. However, the dietary nutritional management to achieve weight loss is an essential component of any treatment strategy. On the basis of its components, the literature reports on the effectiveness of the Mediterranean diet in reducing cardiovascular risk and in preventing major chronic diseases, including obesity and diabetes. New evidence supports the idea that the Mediterranean diet, associated with physical activity and cognitive behaviour therapy, may have an important role in the prevention and the treatment of NAFLD. PMID:25492997

Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans.

PubMed

Andrusiak, Matthew G; Jin, Yishi

2016-04-08

Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundwormCaenorhabditis eleganswas developed as a system to study genes required for development and nervous system function. The powerful genetics ofC. elegansin combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components inC. elegans. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Heritability of somatotype components: a multivariate analysis.

PubMed

Peeters, M W; Thomis, M A; Loos, R J F; Derom, C A; Fagard, R; Claessens, A L; Vlietinck, R F; Beunen, G P

2007-08-01

To study the genetic and environmental determination of variation in Heath-Carter somatotype (ST) components (endomorphy, mesomorphy and ectomorphy). Multivariate path analysis on twin data. Eight hundred and three members of 424 adult Flemish twin pairs (18-34 years of age). The results indicate the significance of sex differences and the significance of the covariation between the three ST components. After age-regression, variation of the population in ST components and their covariation is explained by additive genetic sources of variance (A), shared (familial) environment (C) and unique environment (E). In men, additive genetic sources of variance explain 28.0% (CI 8.7-50.8%), 86.3% (71.6-90.2%) and 66.5% (37.4-85.1%) for endomorphy, mesomorphy and ectomorphy, respectively. For women, corresponding values are 32.3% (8.9-55.6%), 82.0% (67.7-87.7%) and 70.1% (48.9-81.8%). For all components in men and women, more than 70% of the total variation was explained by sources of variance shared between the three components, emphasising the importance of analysing the ST in a multivariate way. The findings suggest that the high heritabilities for mesomorphy and ectomorphy reported in earlier twin studies in adolescence are maintained in adulthood. For endomorphy, which represents a relative measure of subcutaneous adipose tissue, however, the results suggest heritability may be considerably lower than most values reported in earlier studies on adolescent twins. The heritability is also lower than values reported for, for example, body mass index (BMI), which next to the weight of organs and adipose tissue also includes muscle and bone tissue. Considering the differences in heritability between musculoskeletal robustness (mesomorphy) and subcutaneous adipose tissue (endomorphy) it may be questioned whether studying the genetics of BMI will eventually lead to a better understanding of the genetics of fatness, obesity and overweight.

Genetic and environmental influences on Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) maladaptive personality traits and their connections with normative personality traits.

PubMed

Wright, Zara E; Pahlen, Shandell; Krueger, Robert F

2017-05-01

The Diagnostic and Statistical Manual for Mental Disorders-Fifth Edition (DSM-5) proposes an alternative model for personality disorders, which includes maladaptive-level personality traits. These traits can be operationalized by the Personality Inventory for the DSM-5 (PID-5). Although there has been extensive research on genetic and environmental influences on normative level personality, the heritability of the DSM-5 traits remains understudied. The present study addresses this gap in the literature by assessing traits indexed by the PID-5 and the International Personality Item Pool NEO (IPIP-NEO) in adult twins (N = 1,812 individuals). Research aims include (a) replicating past findings of the heritability of normative level personality as measured by the IPIP-NEO as a benchmark for studying maladaptive level traits, (b) ascertaining univariate heritability estimates of maladaptive level traits as measured by the PID-5, (c) establishing how much variation in personality pathology can be attributed to the same genetic components affecting variation in normative level personality, and (d) determining residual variance in personality pathology domains after variance attributable to genetic and environmental components of general personality has been removed. Results revealed that PID-5 traits reflect similar levels of heritability to that of IPIP-NEO traits. Further, maladaptive and normative level traits that correlate at the phenotypic level also correlate at the genotypic level, indicating overlapping genetic components contribute to variance in both. Nevertheless, we also found evidence for genetic and environmental components unique to maladaptive level personality traits, not shared with normative level traits. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

Conserving and managing the trees of the future: genetic resources for Pacific Northwest forests.

Treesearch

Sally Duncan

2003-01-01

Genetic resource management has historically called for altering the genetic structure of plant populations through selection for traits of interest such as rapid growth. Although this is still a principal component of tree breeding programs in the Pacific Northwest, managing genetic resources now also brings a clear focus on retaining a broad diversity within and...

Learning Gene Expression through Modelling and Argumentation: A Case Study Exploring the Connections between the Worlds of Knowledge

ERIC Educational Resources Information Center

Puig, Blanca; Ageitos, Noa; Jiménez-Aleixandre, María Pilar

2017-01-01

There is emerging interest on the interactions between modelling and argumentation in specific contexts, such as genetics learning. It has been suggested that modelling might help students understand and argue on genetics. We propose modelling gene expression as a way to learn molecular genetics and diseases with a genetic component. The study is…

The peopling of Greenland: further insights from the analysis of genetic diversity using autosomal and X-chromosomal markers

PubMed Central

Pereira, Vania; Tomas, Carmen; Sanchez, Juan J; Syndercombe-Court, Denise; Amorim, António; Gusmão, Leonor; Prata, Maria João; Morling, Niels

2015-01-01

The peopling of Greenland has a complex history shaped by population migrations, isolation and genetic drift. The Greenlanders present a genetic heritage with components of European and Inuit groups; previous studies using uniparentally inherited markers in Greenlanders have reported evidence of a sex-biased, admixed genetic background. This work further explores the genetics of the Greenlanders by analysing autosomal and X-chromosomal data to obtain deeper insights into the factors that shaped the genetic diversity in Greenlanders. Fourteen Greenlandic subsamples from multiple geographical settlements were compared to assess the level of genetic substructure in the Greenlandic population. The results showed low levels of genetic diversity in all sets of the genetic markers studied, together with an increased number of X-chromosomal loci in linkage disequilibrium in relation to the Danish population. In the broader context of worldwide populations, Greenlanders are remarkably different from most populations, but they are genetically closer to some Inuit groups from Alaska. Admixture analyses identified an Inuit component in the Greenlandic population of approximately 80%. The sub-populations of Ammassalik and Nanortalik are the least diverse, presenting the lowest levels of European admixture. Isolation-by-distance analyses showed that only 16% of the genetic substructure of Greenlanders is most likely to be explained by geographic barriers. We suggest that genetic drift and a differentiated settlement history around the island explain most of the genetic substructure of the population in Greenland. PMID:24801759

The peopling of Greenland: further insights from the analysis of genetic diversity using autosomal and X-chromosomal markers.

PubMed

Pereira, Vania; Tomas, Carmen; Sanchez, Juan J; Syndercombe-Court, Denise; Amorim, António; Gusmão, Leonor; Prata, Maria João; Morling, Niels

2015-02-01

The peopling of Greenland has a complex history shaped by population migrations, isolation and genetic drift. The Greenlanders present a genetic heritage with components of European and Inuit groups; previous studies using uniparentally inherited markers in Greenlanders have reported evidence of a sex-biased, admixed genetic background. This work further explores the genetics of the Greenlanders by analysing autosomal and X-chromosomal data to obtain deeper insights into the factors that shaped the genetic diversity in Greenlanders. Fourteen Greenlandic subsamples from multiple geographical settlements were compared to assess the level of genetic substructure in the Greenlandic population. The results showed low levels of genetic diversity in all sets of the genetic markers studied, together with an increased number of X-chromosomal loci in linkage disequilibrium in relation to the Danish population. In the broader context of worldwide populations, Greenlanders are remarkably different from most populations, but they are genetically closer to some Inuit groups from Alaska. Admixture analyses identified an Inuit component in the Greenlandic population of approximately 80%. The sub-populations of Ammassalik and Nanortalik are the least diverse, presenting the lowest levels of European admixture. Isolation-by-distance analyses showed that only 16% of the genetic substructure of Greenlanders is most likely to be explained by geographic barriers. We suggest that genetic drift and a differentiated settlement history around the island explain most of the genetic substructure of the population in Greenland.

Nanoscale visualization and characterization of Myxococcus xanthus cells with atomic force microscopy

PubMed Central

Pelling, Andrew E.; Li, Yinuo; Shi, Wenyuan; Gimzewski, James K.

2005-01-01

Multicellular microbial communities are the predominant form of existence for microorganisms in nature. As one of the most primitive social organisms, Myxococcus xanthus has been an ideal model bacterium for studying intercellular interaction and multicellular organization. Through previous genetic and EM studies, various extracellular appendages and matrix components have been found to be involved in the social behavior of M. xanthus, but none of them was directly visualized and analyzed under native conditions. Here, we used atomic force microscopy (AFM) imaging and in vivo force spectroscopy to characterize these cellular structures under native conditions. AFM imaging revealed morphological details on the extracellular ultrastructures at an unprecedented resolution, and in vivo force spectroscopy of live cells in fluid allowed us to nanomechanically characterize extracellular polymeric substances. The findings provide the basis for AFM as a useful tool for investigating microbial-surface ultrastructures and nanomechanical properties under native conditions. PMID:15840722

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.

The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response

PubMed Central

Dedic, Nina; Chen, Alon; Deussing, Jan M.

2018-01-01

Background: Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and conse-quently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2. Objective: Here we review the past and current state of the CRF/CRFR field, ranging from pharmacologi-cal studies to genetic mouse models and virus-mediated manipulations. Results: Although it is well established that CRF/CRFR1 signaling mediates aversive responses, includ-ing anxiety and depression-like behaviors, a number of recent studies have challenged this viewpoint by revealing anxiolytic and appetitive properties of specific CRF/CRFR1 circuits. In contrast, the UCN/CRFR2 system is less well understood and may possibly also exert divergent functions on physiol-ogy and behavior depending on the brain region, underlying circuit, and/or experienced stress conditions. Conclusion: A plethora of available genetic tools, including conventional and conditional mouse mutants targeting CRF system components, has greatly advanced our understanding about the endogenous mecha-nisms underlying HPA system regulation and CRF/UCN-related neuronal circuits involved in stress-related behaviors. Yet, the detailed pathways and molecular mechanisms by which the CRF/UCN-system translates negative or positive stimuli into the final, integrated biological response are not completely un-derstood. The utilization of future complementary methodologies, such as cell-type specific Cre-driver lines, viral and optogenetic tools will help to further dissect the function of genetically defined CRF/UCN neurocircuits in the context of adaptive and maladaptive stress responses. PMID:28260504

PTSD and Gene Variants: New Pathways and New Thinking

PubMed Central

Skelton, Kelly; Ressler, Kerry J.; Norrholm, Seth D.; Jovanovic, Tanja; Bradley-Davino, Bekh

2011-01-01

Posttraumatic Stress Disorder (PTSD) is an anxiety disorder which can develop as a result of exposure to a traumatic event and is associated with significant functional impairment. Family and twin studies have found that risk for PTSD is associated with an underlying genetic vulnerability and that more than 30% of the variance associated with PTSD is related to a heritable component. Using a fear conditioning model to conceptualize the neurobiology of PTSD, three primary neuronal systems have been investigated – the hypothalamic-pituitary-adrenal axis, the locus coeruleus-noradrenegic system, and neurocircuitry interconnecting the limbic system and frontal cortex. The majority of the initial investigations into main effects of candidate genes hypothesized to be associated with PTSD risk have been negative, but studies examining the interaction of genetic polymorphisms with specific environments in predicting PTSD have produced several positive results which have increased our understanding of the determinants of risk and resilience in the aftermath of trauma. Promising avenues of inquiry into the role of epigenetic modification have also been proposed to explain the enduring impact of environmental exposures which occur during key, often early, developmental periods on gene expression. Studies of PTSD endophenotypes, which are heritable biomarkers associated with a circumscribed trait within the more complex psychiatric disorder, may be more directly amenable to analysis of the underlying genetics and neural pathways and have provided promising targets for elucidating the neurobiology of PTSD. Knowledge of the genetic underpinnings and neuronal pathways involved in the etiology and maintenance of PTSD will allow for improved targeting of primary prevention amongst vulnerable individuals or populations, as well as timely, targeted treatment interventions. PMID:21356219

Mitogen activated protein kinase 6 and MAP kinase phosphatase 1 are involved in the response of Arabidopsis roots to L-glutamate.

PubMed

López-Bucio, Jesús Salvador; Raya-González, Javier; Ravelo-Ortega, Gustavo; Ruiz-Herrera, León Francisco; Ramos-Vega, Maricela; León, Patricia; López-Bucio, José; Guevara-García, Ángel Arturo

2018-03-01

The function and components of L-glutamate signaling pathways in plants have just begun to be elucidated. Here, using a combination of genetic and biochemical strategies, we demonstrated that a MAPK module is involved in the control of root developmental responses to this amino acid. Root system architecture plays an essential role in plant adaptation to biotic and abiotic factors via adjusting signal transduction and gene expression. L-Glutamate (L-Glu), an amino acid with neurotransmitter functions in animals, inhibits root growth, but the underlying genetic mechanisms are poorly understood. Through a combination of genetic analysis, in-gel kinase assays, detailed cell elongation and division measurements and confocal analysis of expression of auxin, quiescent center and stem cell niche related genes, the critical roles of L-Glu in primary root growth acting through the mitogen-activated protein kinase 6 (MPK6) and the dual specificity serine-threonine-tyrosine phosphatase MKP1 could be revealed. In-gel phosphorylation assays revealed a rapid and dose-dependent induction of MPK6 and MPK3 activities in wild-type Arabidopsis seedlings in response to L-Glu. Mutations in MPK6 or MKP1 reduced or increased root cell division and elongation in response to L-Glu, possibly modulating auxin transport and/or response, but in a PLETHORA1 and 2 independent manner. Our data highlight MPK6 and MKP1 as components of an L-Glu pathway linking the auxin response, and cell division for primary root growth.

Loads Bias Genetic and Signaling Switches in Synthetic and Natural Systems

PubMed Central

Medford, June; Prasad, Ashok

2014-01-01

Biological protein interactions networks such as signal transduction or gene transcription networks are often treated as modular, allowing motifs to be analyzed in isolation from the rest of the network. Modularity is also a key assumption in synthetic biology, where it is similarly expected that when network motifs are combined together, they do not lose their essential characteristics. However, the interactions that a network module has with downstream elements change the dynamical equations describing the upstream module and thus may change the dynamic and static properties of the upstream circuit even without explicit feedback. In this work we analyze the behavior of a ubiquitous motif in gene transcription and signal transduction circuits: the switch. We show that adding an additional downstream component to the simple genetic toggle switch changes its dynamical properties by changing the underlying potential energy landscape, and skewing it in favor of the unloaded side, and in some situations adding loads to the genetic switch can also abrogate bistable behavior. We find that an additional positive feedback motif found in naturally occurring toggle switches could tune the potential energy landscape in a desirable manner. We also analyze autocatalytic signal transduction switches and show that a ubiquitous positive feedback switch can lose its switch-like properties when connected to a downstream load. Our analysis underscores the necessity of incorporating the effects of downstream components when understanding the physics of biochemical network motifs, and raises the question as to how these effects are managed in real biological systems. This analysis is particularly important when scaling synthetic networks to more complex organisms. PMID:24676102

Altered sleep and affect in the neurotensin receptor 1 knockout mouse.

PubMed

Fitzpatrick, Karrie; Winrow, Christopher J; Gotter, Anthony L; Millstein, Joshua; Arbuzova, Janna; Brunner, Joseph; Kasarskis, Andrew; Vitaterna, Martha H; Renger, John J; Turek, Fred W

2012-07-01

Sleep and mood disorders have long been understood to have strong genetic components, and there is considerable comorbidity of sleep abnormalities and mood disorders, suggesting the involvement of common genetic pathways. Here, we examine a candidate gene implicated in the regulation of both sleep and affective behavior using a knockout mouse model. Previously, we identified a quantitative trait locus (QTL) for REM sleep amount, REM sleep bout number, and wake amount in a genetically segregating population of mice. Here, we show that traits mapping to this QTL correlated with an expression QTL for neurotensin receptor 1 (Ntsr1), a receptor for neurotensin, a ligand known to be involved in several psychiatric disorders. We examined sleep as well as behaviors indicative of anxiety and depression in the NTSR1 knockout mouse. NTSR1 knockouts had a lower percentage of sleep time spent in REM sleep in the dark phase and a larger diurnal variation in REM sleep duration than wild types under baseline conditions. Following sleep deprivation, NTSR1 knockouts exhibited more wake and less NREM rebound sleep. NTSR1 knockouts also showed increased anxious and despair behaviors. Here we illustrate a link between expression of the Ntsr1 gene and sleep traits previously associated with a particular QTL. We also demonstrate a relationship between Ntsr1 and anxiety and despair behaviors. Given the considerable evidence that anxiety and depression are closely linked with abnormalities in sleep, the data presented here provide further evidence that neurotensin and Ntsr1 may be a component of a pathway involved in both sleep and mood disorders.

A Pareto-optimal moving average multigene genetic programming model for daily streamflow prediction

NASA Astrophysics Data System (ADS)

Danandeh Mehr, Ali; Kahya, Ercan

2017-06-01

Genetic programming (GP) is able to systematically explore alternative model structures of different accuracy and complexity from observed input and output data. The effectiveness of GP in hydrological system identification has been recognized in recent studies. However, selecting a parsimonious (accurate and simple) model from such alternatives still remains a question. This paper proposes a Pareto-optimal moving average multigene genetic programming (MA-MGGP) approach to develop a parsimonious model for single-station streamflow prediction. The three main components of the approach that take us from observed data to a validated model are: (1) data pre-processing, (2) system identification and (3) system simplification. The data pre-processing ingredient uses a simple moving average filter to diminish the lagged prediction effect of stand-alone data-driven models. The multigene ingredient of the model tends to identify the underlying nonlinear system with expressions simpler than classical monolithic GP and, eventually simplification component exploits Pareto front plot to select a parsimonious model through an interactive complexity-efficiency trade-off. The approach was tested using the daily streamflow records from a station on Senoz Stream, Turkey. Comparing to the efficiency results of stand-alone GP, MGGP, and conventional multi linear regression prediction models as benchmarks, the proposed Pareto-optimal MA-MGGP model put forward a parsimonious solution, which has a noteworthy importance of being applied in practice. In addition, the approach allows the user to enter human insight into the problem to examine evolved models and pick the best performing programs out for further analysis.

Genetic algorithm applied to the selection of factors in principal component-artificial neural networks: application to QSAR study of calcium channel antagonist activity of 1,4-dihydropyridines (nifedipine analogous).

PubMed

Hemmateenejad, Bahram; Akhond, Morteza; Miri, Ramin; Shamsipur, Mojtaba

2003-01-01

A QSAR algorithm, principal component-genetic algorithm-artificial neural network (PC-GA-ANN), has been applied to a set of newly synthesized calcium channel blockers, which are of special interest because of their role in cardiac diseases. A data set of 124 1,4-dihydropyridines bearing different ester substituents at the C-3 and C-5 positions of the dihydropyridine ring and nitroimidazolyl, phenylimidazolyl, and methylsulfonylimidazolyl groups at the C-4 position with known Ca(2+) channel binding affinities was employed in this study. Ten different sets of descriptors (837 descriptors) were calculated for each molecule. The principal component analysis was used to compress the descriptor groups into principal components. The most significant descriptors of each set were selected and used as input for the ANN. The genetic algorithm (GA) was used for the selection of the best set of extracted principal components. A feed forward artificial neural network with a back-propagation of error algorithm was used to process the nonlinear relationship between the selected principal components and biological activity of the dihydropyridines. A comparison between PC-GA-ANN and routine PC-ANN shows that the first model yields better prediction ability.

Plant response to environmental conditions: assessing potential production, water demand, and negative effects of water deficit

PubMed Central

Tardieu, François

2013-01-01

This paper reviews methods for analyzing plant performance and its genetic variability under a range of environmental conditions. Biomass accumulation is linked every day to available light in the photosynthetically active radiation (PAR) domain, multiplied by the proportion of light intercepted by plants and by the radiation use efficiency. Total biomass is cumulated over the duration of the considered phase (e.g., plant cycle or vegetative phase). These durations are essentially constant for a given genotype provided that time is corrected for temperature (thermal time). Several ways of expressing thermal time are reviewed. Two alternative equations are presented, based either on the effect of transpiration, or on yield components. Their comparative interests and drawbacks are discussed. The genetic variability of each term of considered equations affects yield under water deficit, via mechanisms at different scales of plant organization and time. The effect of any physiological mechanism on yield of stressed plants acts via one of these terms, although the link is not always straightforward. Finally, I propose practical ways to compare the productivity of genotypes in field environments, and a “minimum dataset” of environmental data and traits that should be recorded for that. PMID:23423357

Is life law-like?

PubMed

Weiss, Kenneth M; Buchanan, Anne V

2011-08-01

Genes are generally assumed to be primary biological causes of biological phenotypes and their evolution. In just over a century, a research agenda that has built on Mendel's experiments and on Darwin's theory of natural selection as a law of nature has had unprecedented scientific success in isolating and characterizing many aspects of genetic causation. We revel in these successes, and yet the story is not quite so simple. The complex cooperative nature of genetic architecture and its evolution include teasingly tractable components, but much remains elusive. The proliferation of data generated in our "omics" age raises the question of whether we even have (or need) a unified theory or "law" of life, or even clear standards of inference by which to answer the question. If not, this not only has implications for the widely promulgated belief that we will soon be able to predict phenotypes like disease risk from genes, but also speaks to the limitations in the underlying science itself. Much of life seems to be characterized by ad hoc, ephemeral, contextual probabilism without proper underlying distributions. To the extent that this is true, causal effects are not asymptotically predictable, and new ways of understanding life may be required.

Is Life Law-Like?

PubMed Central

Weiss, Kenneth M.; Buchanan, Anne V.

2011-01-01

Genes are generally assumed to be primary biological causes of biological phenotypes and their evolution. In just over a century, a research agenda that has built on Mendel’s experiments and on Darwin’s theory of natural selection as a law of nature has had unprecedented scientific success in isolating and characterizing many aspects of genetic causation. We revel in these successes, and yet the story is not quite so simple. The complex cooperative nature of genetic architecture and its evolution include teasingly tractable components, but much remains elusive. The proliferation of data generated in our “omics” age raises the question of whether we even have (or need) a unified theory or “law” of life, or even clear standards of inference by which to answer the question. If not, this not only has implications for the widely promulgated belief that we will soon be able to predict phenotypes like disease risk from genes, but also speaks to the limitations in the underlying science itself. Much of life seems to be characterized by ad hoc, ephemeral, contextual probabilism without proper underlying distributions. To the extent that this is true, causal effects are not asymptotically predictable, and new ways of understanding life may be required. PMID:21828277

Inheritance of dermatoglyphic asymmetry and diversity traits in twins based on factor: variance decomposition analysis.

PubMed

Karmakar, Bibha; Malkin, Ida; Kobyliansky, Eugene

2013-06-01

Dermatoglyphic asymmetry and diversity traits from a large number of twins (MZ and DZ) were analyzed based on principal factors to evaluate genetic effects and common familial environmental influences on twin data by the use of maximum likelihood-based Variance decomposition analysis. Sample consists of monozygotic (MZ) twins of two sexes (102 male pairs and 138 female pairs) and 120 pairs of dizygotic (DZ) female twins. All asymmetry (DA and FA) and diversity of dermatoglyphic traits were clearly separated into factors. These are perfectly corroborated with the earlier studies in different ethnic populations, which indicate a common biological validity perhaps exists of the underlying component structures of dermatoglyphic characters. Our heritability result in twins clearly showed that DA_F2 is inherited mostly in dominant type (28.0%) and FA_F1 is additive (60.7%), but no significant difference in sexes was observed for these factors. Inheritance is also very prominent in diversity Factor 1, which is exactly corroborated with our previous findings. The present results are similar with the earlier results of finger ridge count diversity in twin data, which suggested that finger ridge count diversity is under genetic control.

A Buoyancy-Based Screen of Drosophila Larvae for Fat-Storage Mutants Reveals a Role for Sir2 in Coupling Fat Storage to Nutrient Availability

PubMed Central

Reis, Tânia; Van Gilst, Marc R.; Hariharan, Iswar K.

2010-01-01

Obesity has a strong genetic component, but few of the genes that predispose to obesity are known. Genetic screens in invertebrates have the potential to identify genes and pathways that regulate the levels of stored fat, many of which are likely to be conserved in humans. To facilitate such screens, we have developed a simple buoyancy-based screening method for identifying mutant Drosophila larvae with increased levels of stored fat. Using this approach, we have identified 66 genes that when mutated increase organismal fat levels. Among these was a sirtuin family member, Sir2. Sirtuins regulate the storage and metabolism of carbohydrates and lipids by deacetylating key regulatory proteins. However, since mammalian sirtuins function in many tissues in different ways, it has been difficult to define their role in energy homeostasis accurately under normal feeding conditions. We show that knockdown of Sir2 in the larval fat body results in increased fat levels. Moreover, using genetic mosaics, we demonstrate that Sir2 restricts fat accumulation in individual cells of the fat body in a cell-autonomous manner. Consistent with this function, changes in the expression of metabolic enzymes in Sir2 mutants point to a shift away from catabolism. Surprisingly, although Sir2 is typically upregulated under conditions of starvation, Sir2 mutant larvae survive better than wild type under conditions of amino-acid starvation as long as sugars are provided. Our findings point to a Sir2-mediated pathway that activates a catabolic response to amino-acid starvation irrespective of the sugar content of the diet. PMID:21085633

Marker-free transgenic rice expressing the vegetative insecticidal protein (Vip) of Bacillus thuringiensis shows broad insecticidal properties.

PubMed

Pradhan, Subrata; Chakraborty, Anirban; Sikdar, Narattam; Chakraborty, Saikat; Bhattacharyya, Jagannath; Mitra, Joy; Manna, Anulina; Dutta Gupta, Snehasish; Sen, Soumitra Kumar

2016-10-01

Genetically engineered rice lines with broad insecticidal properties against major lepidopteran pests were generated using a synthetic, truncated form of vegetative insecticidal protein (Syn vip3BR) from Bacillus thuringiensis. The selectable marker gene and the redundant transgene(s) were eliminated through Cre/ lox mediated recombination and genetic segregation to make consumer friendly Bt -rice. For sustainable resistance against lepidopteran insect pests, chloroplast targeted synthetic version of bioactive core component of a vegetative insecticidal protein (Syn vip3BR) of Bacillus thuringiensis was expressed in rice under the control of green-tissue specific ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit gene promoter. The transgenic plants (in Oryza sativa indica Swarna cultivar) showed high insect mortality rate in vitro against major rice pests, yellow stem borer (Scirpophaga incertulas), rice leaf folder (Cnaphalocrocis medinalis) and rice horn caterpillar (Melanitis leda ismene) in T1 generation, indicating insecticidal potency of Syn vip3BR. Under field conditions, the T1 plants showed considerable resistance against leaf folders and stem borers. The expression cassette (vip-lox-hpt-lox) as well as another vector with chimeric cre recombinase gene under constitutive rice ubiquitin1 gene promoter was designed for the elimination of selectable marker hygromycin phosphotransferase (hptII) gene. Crossing experiments were performed between T1 plants with single insertion site of vip-lox-hpt-lox T-DNA and one T1 plant with moderate expression of cre recombinase with linked bialaphos resistance (syn bar) gene. Marker gene excision was achieved in hybrids with up to 41.18 % recombination efficiency. Insect resistant transgenic lines, devoid of selectable marker and redundant transgene(s) (hptII + cre-syn bar), were established in subsequent generation through genetic segregation.

Correlation between Relatives given Complete Genotypes: from Identity by Descent to Identity by Function

PubMed Central

Sverdlov, Serge; Thompson, Elizabeth A.

2013-01-01

In classical quantitative genetics, the correlation between the phenotypes of individuals with unknown genotypes and a known pedigree relationship is expressed in terms of probabilities of IBD states. In existing approaches to the inverse problem where genotypes are observed but pedigree relationships are not, dependence between phenotypes is either modeled as Bayesian uncertainty or mapped to an IBD model via inferred relatedness parameters. Neither approach yields a relationship between genotypic similarity and phenotypic similarity with a probabilistic interpretation corresponding to a generative model. We introduce a generative model for diploid allele effect based on the classic infinite allele mutation process. This approach motivates the concept of IBF (Identity by Function). The phenotypic covariance between two individuals given their diploid genotypes is expressed in terms of functional identity states. The IBF parameters define a genetic architecture for a trait without reference to specific alleles or population. Given full genome sequences, we treat a gene-scale functional region, rather than a SNP, as a QTL, modeling patterns of dominance for multiple alleles. Applications demonstrated by simulation include phenotype and effect prediction and association, and estimation of heritability and classical variance components. A simulation case study of the Missing Heritability problem illustrates a decomposition of heritability under the IBF framework into Explained and Unexplained components. PMID:23851163

Detection of Protein Interactions in T3S Systems Using Yeast Two-Hybrid Analysis.

PubMed

Nilles, Matthew L

2017-01-01

Two-hybrid systems, sometimes termed interaction traps, are genetic systems designed to find and analyze interactions between proteins. The most common systems are yeast based (commonly Saccharomyces cerevisae) and rely on the functional reconstitution of the GAL4 transcriptional activator. Reporter genes, such as the lacZ gene of Escherichia coli (encodes β-galactosidase), are placed under GAL4-dependent transcriptional control to provide quick and reliable detection of protein interactions. In this method the use of a yeast-based two-hybrid system is described to study protein interactions between components of type III secretion systems.

Genome wide association studies on yield components using a lentil genetic diversity panel

USDA-ARS?s Scientific Manuscript database

The cool season food legume research community are now at the threshold of deploying the cutting-edge molecular genetics and genomics tools that have led to significant and rapid expansion of gene discovery, knowledge of gene function (including tolerance to biotic and abiotic stresses) and genetic ...

Gene, environment and cognitive function: a Chinese twin ageing study.

PubMed

Xu, Chunsheng; Sun, Jianping; Duan, Haiping; Ji, Fuling; Tian, Xiaocao; Zhai, Yaoming; Wang, Shaojie; Pang, Zengchang; Zhang, Dongfeng; Zhao, Zhongtang; Li, Shuxia; Gue, Matt Mc; Hjelmborg, Jacob V B; Christensen, Kaare; Tan, Qihua

2015-05-01

the genetic and environmental contributions to cognitive function in the old people have been well addressed for the Western populations using twin modelling showing moderate to high heritability. No similar study has been conducted in the world largest and rapidly ageing Chinese population living under distinct environmental condition as the Western populations. this study aims to explore the genetic and environmental impact on normal cognitive ageing in the Chinese twins. cognitive function was measured on 384 complete twin pairs with median age of 50 years for seven cognitive measurements including visuospatial, linguistic skills, naming, memory, attention, abstraction and orientation abilities. Data were analysed by fitting univariate and bivariate twin models to estimate the genetic and environmental components in the variance and co-variance of the cognitive assessments. intra-pair correlation on cognitive measurements was low to moderate in monozygotic twins (0.23-0.41, overall 0.42) and low in dizygotic twins (0.05-0.30, overall 0.31) with the former higher than the latter for each item. Estimate for heritability was moderate for overall cognitive function (0.44, 95% CI: 0.34-0.53) and low to moderate for visuospatial, naming, attention and orientation abilities ranging from 0.28 to 0.38. No genetic contribution was estimated to linguistic skill, abstraction and memory which instead were under low to moderate control by shared environmental factors accounting for 23-33% of the total variances. In contrast, all cognitive performances showed moderate to high influences by the unique environmental factors. genetic factor and common family environment have a limited contribution to cognitive function in the Chinese adults. Individual unique environment is likely to play a major role in determining the levels of cognitive performance. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Robust inference of population structure for ancestry prediction and correction of stratification in the presence of relatedness.

PubMed

Conomos, Matthew P; Miller, Michael B; Thornton, Timothy A

2015-05-01

Population structure inference with genetic data has been motivated by a variety of applications in population genetics and genetic association studies. Several approaches have been proposed for the identification of genetic ancestry differences in samples where study participants are assumed to be unrelated, including principal components analysis (PCA), multidimensional scaling (MDS), and model-based methods for proportional ancestry estimation. Many genetic studies, however, include individuals with some degree of relatedness, and existing methods for inferring genetic ancestry fail in related samples. We present a method, PC-AiR, for robust population structure inference in the presence of known or cryptic relatedness. PC-AiR utilizes genome-screen data and an efficient algorithm to identify a diverse subset of unrelated individuals that is representative of all ancestries in the sample. The PC-AiR method directly performs PCA on the identified ancestry representative subset and then predicts components of variation for all remaining individuals based on genetic similarities. In simulation studies and in applications to real data from Phase III of the HapMap Project, we demonstrate that PC-AiR provides a substantial improvement over existing approaches for population structure inference in related samples. We also demonstrate significant efficiency gains, where a single axis of variation from PC-AiR provides better prediction of ancestry in a variety of structure settings than using 10 (or more) components of variation from widely used PCA and MDS approaches. Finally, we illustrate that PC-AiR can provide improved population stratification correction over existing methods in genetic association studies with population structure and relatedness. © 2015 WILEY PERIODICALS, INC.

Series Hybrid Electric Vehicle Power System Optimization Based on Genetic Algorithm

NASA Astrophysics Data System (ADS)

Zhu, Tianjun; Li, Bin; Zong, Changfu; Wu, Yang

2017-09-01

Hybrid electric vehicles (HEV), compared with conventional vehicles, have complex structures and more component parameters. If variables optimization designs are carried on all these parameters, it will increase the difficulty and the convergence of algorithm program, so this paper chooses the parameters which has a major influence on the vehicle fuel consumption to make it all work at maximum efficiency. First, HEV powertrain components modelling are built. Second, taking a tandem hybrid structure as an example, genetic algorithm is used in this paper to optimize fuel consumption and emissions. Simulation results in ADVISOR verify the feasibility of the proposed genetic optimization algorithm.

Genetic diversity analysis of fruit characteristics of hawthorn germplasm.

PubMed

Su, K; Guo, Y S; Wang, G; Zhao, Y H; Dong, W X

2015-12-07

One hundred and six accessions of hawthorn intraspecific resources, from the National Germplasm Repository at Shenyang, were subjected to genetic diversity and principal component analysis based on evaluation data of 15 fruit traits. Results showed that the genetic diversity of hawthorn fruit traits varied. Among the 15 traits, the fruit shape variable coefficient had the most obvious evaluation, followed by fruit surface state, dot color, taste, weight of single fruit, sepal posture, peduncle form, and metula traits. These are the primary traits by which hawthorn could be classified in the future. The principal component demonstrated that these traits are the most influential factors of hawthorn fruit characteristics.

Genomic diversity and population structure of three autochthonous Greek sheep breeds assessed with genome-wide DNA arrays.

PubMed

Michailidou, S; Tsangaris, G; Fthenakis, G C; Tzora, A; Skoufos, I; Karkabounas, S C; Banos, G; Argiriou, A; Arsenos, G

2018-06-01

In the present study, genome-wide genotyping was applied to characterize the genetic diversity and population structure of three autochthonous Greek breeds: Boutsko, Karagouniko and Chios. Dairy sheep are among the most significant livestock species in Greece numbering approximately 9 million animals which are characterized by large phenotypic variation and reared under various farming systems. A total of 96 animals were genotyped with the Illumina's OvineSNP50K microarray beadchip, to study the population structure of the breeds and develop a specialized panel of single-nucleotide polymorphisms (SNPs), which could distinguish one breed from the others. Quality control on the dataset resulted in 46,125 SNPs, which were used to evaluate the genetic structure of the breeds. Population structure was assessed through principal component analysis (PCA) and admixture analysis, whereas inbreeding was estimated based on runs of homozygosity (ROHs) coefficients, genomic relationship matrix inbreeding coefficients (F GRM ) and patterns of linkage disequilibrium (LD). Associations between SNPs and breeds were analyzed with different inheritance models, to identify SNPs that distinguish among the breeds. Results showed high levels of genetic heterogeneity in the three breeds. Genetic distances among breeds were modest, despite their different ancestries. Chios and Karagouniko breeds were more genetically related to each other compared to Boutsko. Analysis revealed 3802 candidate SNPs that can be used to identify two-breed crosses and purebred animals. The present study provides, for the first time, data on the genetic background of three Greek indigenous dairy sheep breeds as well as a specialized marker panel that can be applied for traceability purposes as well as targeted genetic improvement schemes and conservation programs.

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

Genetic influences on functional connectivity associated with feedback processing and prediction error: Phase coupling of theta-band oscillations in twins.

PubMed

Demiral, Şükrü Barış; Golosheykin, Simon; Anokhin, Andrey P

2017-05-01

Detection and evaluation of the mismatch between the intended and actually obtained result of an action (reward prediction error) is an integral component of adaptive self-regulation of behavior. Extensive human and animal research has shown that evaluation of action outcome is supported by a distributed network of brain regions in which the anterior cingulate cortex (ACC) plays a central role, and the integration of distant brain regions into a unified feedback-processing network is enabled by long-range phase synchronization of cortical oscillations in the theta band. Neural correlates of feedback processing are associated with individual differences in normal and abnormal behavior, however, little is known about the role of genetic factors in the cerebral mechanisms of feedback processing. Here we examined genetic influences on functional cortical connectivity related to prediction error in young adult twins (age 18, n=399) using event-related EEG phase coherence analysis in a monetary gambling task. To identify prediction error-specific connectivity pattern, we compared responses to loss and gain feedback. Monetary loss produced a significant increase of theta-band synchronization between the frontal midline region and widespread areas of the scalp, particularly parietal areas, whereas gain resulted in increased synchrony primarily within the posterior regions. Genetic analyses showed significant heritability of frontoparietal theta phase synchronization (24 to 46%), suggesting that individual differences in large-scale network dynamics are under substantial genetic control. We conclude that theta-band synchronization of brain oscillations related to negative feedback reflects genetically transmitted differences in the neural mechanisms of feedback processing. To our knowledge, this is the first evidence for genetic influences on task-related functional brain connectivity assessed using direct real-time measures of neuronal synchronization. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of induced mutations on quantitative traits in Arabidopsis thaliana: Natural versus artificial conditions.

PubMed

Stearns, Frank W; Fenster, Charles B

2016-12-01

Mutations are the ultimate source of all genetic variations. New mutations are expected to affect quantitative traits differently depending on the extent to which traits contribute to fitness and the environment in which they are tested. The dogma is that the preponderance of mutations affecting fitness will be skewed toward deleterious while their effects on nonfitness traits will be bidirectionally distributed. There are mixed views on the role of stress in modulating these effects. We quantify mutation effects by inducing mutations in Arabidopsis thaliana (Columbia accession) using the chemical ethylmethane sulfonate. We measured the effects of new mutations relative to a premutation founder for fitness components under both natural (field) and artificial (growth room) conditions. Additionally, we measured three other quantitative traits, not expected to contribute directly to fitness, under artificial conditions. We found that induced mutations were equally as likely to increase as decrease a trait when that trait was not closely related to fitness (traits that were neither survivorship nor reproduction). We also found that new mutations were more likely to decrease fitness or fitness-related traits under more stressful field conditions than under relatively benign artificial conditions. In the benign condition, the effect of new mutations on fitness components was similar to traits not as closely related to fitness. These results highlight the importance of measuring the effects of new mutations on fitness and other traits under a range of conditions.

Conservation of a domestic metapopulation structured into related and partly admixed strains.

PubMed

Ramljak, Jelena; Bunevski, Gjoko; Bytyqi, Hysen; Marković, Božidarka; Brka, Muhamed; Ivanković, Ante; Kume, Kristaq; Stojanović, Srđan; Nikolov, Vasil; Simčič, Mojca; Sölkner, Johann; Kunz, Elisabeth; Rothammer, Sophie; Seichter, Doris; Grünenfelder, Hans-Peter; Broxham, Elli T; Kugler, Waltraud; Medugorac, Ivica

2018-04-01

Preservation of genetic diversity is one of the most pressing challenges in the planetary boundaries concept. Within this context, we focused on genetic diversity in a native, unselected and highly admixed domesticated metapopulation. A set of 1,828 individuals from 60 different cattle breeds was analysed using a medium density SNP chip. Among these breeds, 14 Buša strains formed a metapopulation represented by 350 individuals, while the remaining 46 breeds represented the global cattle population. Genetic analyses showed that the scarcely selected and less differentiated Buša metapopulation contributed a substantial proportion (52.6%) of the neutral allelic diversity to this global taurine population. Consequently, there is an urgent need for synchronized maintenance of this highly fragmented domestic metapopulation, which is distributed over several countries without sophisticated infrastructure and highly endangered by continuous replacement crossing as part of the global genetic homogenization process. This study collected and evaluated samples, data and genomewide information and developed genome-assisted cross-border conservation concepts. To detect and maintain genetic integrity of the metapopulation strains, we designed and applied a composite test that combines six metrics based on additive genetic relationships, a nearest neighbour graph and the distribution of semiprivate alleles. Each metric provides distinct information components about past admixture events and offers an objective and powerful tool for the detection of admixed outliers. The here developed conservation methods and presented experiences could easily be adapted to comparable conservation programmes of domesticated or other metapopulations bred and kept in captivity or under some other sort of human control. © 2018 John Wiley & Sons Ltd.

Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways

PubMed Central

2013-01-01

Background Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the most important clinical consequence of T. cruzi infection. The others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Migration of Th1-type T cells play a major role in myocardial damage. Methods Our genetic analysis focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach, defined to catch all the genetic information from each gene. The study was conducted on a large Brazilian population including 315 CCC cases and 118 ASY subjects. Results The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to protection to CCC. These associations were confirmed when we restricted the analysis to severe CCC, characterized by a left ventricular ejection fraction under 40%. Conclusions Our data show that polymorphisms affecting key molecules involved in several immune parameters (innate immunity signal transduction and T cell/monocyte migration) play a role in genetic susceptibility to CCC development. This also points out to the multigenic character of CCC, each polymorphism imparting a small contribution. The identification of genetic markers for CCC will provide information for pathogenesis as well as therapeutic targets. PMID:24330528

Rare disease landscape in Brazil: report of a successful experience in inborn errors of metabolism.

PubMed

Giugliani, Roberto; Vairo, Filippo P; Riegel, Mariluce; de Souza, Carolina F M; Schwartz, Ida V D; Pena, Sérgio D J

2016-06-10

Brazil is a country of continental dimensions, with many social inequalities. The latter are reflected on its health system, which comprises a large public component called SUS, a small paid health insurance component and a third very small private component, in which patients pay personally for medical services. Seventy five percent of the population depends on SUS, which thus far does not provide adequate coverage for genetic medical procedures. In 2014, SUS introduced the "Policy for the Integral Attention to Subjects with Rare Diseases", establishing guidelines for offering diagnosis and treatment. The policy defines the two main axes, genetic and non-genetic rare diseases. In this fashion, public genetic services in SUS will be installed and funded not by themselves, but as part of the more general policy of rare diseases. Unfortunately, up to now this policy is still depending on financial allowances to be effectively launched. In this article, our intention was to describe activities developed in the area of inborn errors of metabolism by a Brazilian reference center. In spite of the lack of support of SUS, thousands of Brazilian families affected by rare genetic metabolic disorders, and many health professionals from all regions of Brazil, already have benefited from the services, training programs and research projects provided by this comprehensive center.

Modeling heat stress effect on Holstein cows under hot and dry conditions: selection tools.

PubMed

Carabaño, M J; Bachagha, K; Ramón, M; Díaz, C

2014-12-01

Data from milk recording of Holstein-Friesian cows together with weather information from 2 regions in Southern Spain were used to define the models that can better describe heat stress response for production traits and somatic cell score (SCS). Two sets of analyses were performed, one aimed at defining the population phenotypic response and the other at studying the genetic components. The first involved 2,514,762 test-day records from up to 5 lactations of 128,112 cows. Two models, one fitting a comfort threshold for temperature and a slope of decay after the threshold, and the other a cubic Legendre polynomial (LP) model were tested. Average (TAVE) and maximum daily temperatures were alternatively considered as covariates. The LP model using TAVE as covariate showed the best goodness of fit for all traits. Estimated rates of decay from this model for production at 25 and 34°C were 36 and 170, 3.8 and 3.0, and 3.9 and 8.2g/d per degree Celsius for milk, fat, and protein yield, respectively. In the second set of analyses, a sample of 280,958 test-day records from first lactations of 29,114 cows was used. Random regression models including quadratic or cubic LP regressions (TEM_) on TAVE or a fixed threshold and an unknown slope (DUMMY), including or not cubic regressions on days in milk (DIM3_), were tested. For milk and SCS, the best models were the DIM3_ models. In contrast, for fat and protein yield, the best model was TEM3. The DIM3DUMMY models showed similar performance to DIM3TEM3. The estimated genetic correlations between the same trait under cold and hot temperatures (ρ) indicated the existence of a large genotype by environment interaction for fat (ρ=0.53 for model TEM3) and protein yield (ρ around 0.6 for DIM3TEM3) and for SCS (ρ=0.64 for model DIM3TEM3), and a small genotype by environment interaction for milk (ρ over 0.8). The eigendecomposition of the additive genetic covariance matrix from model TEM3 showed the existence of a dominant component, a constant term that is not affected by temperature, representing from 64% of the variation for SCS to 91% of the variation for milk. The second component, showing a flat pattern at intermediate temperatures and increasing or decreasing slopes for the extremes, gathered 15, 11, and 24% of the variation for fat and protein yield and SCS, respectively. This component could be further evaluated as a selection criterion for heat tolerance independently of the production level. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Understanding crop genetic diversity under modern plant breeding.

PubMed

Fu, Yong-Bi

2015-11-01

Maximizing crop yield while at the same time minimizing crop failure for sustainable agriculture requires a better understanding of the impacts of plant breeding on crop genetic diversity. This review identifies knowledge gaps and shows the need for more research into genetic diversity changes under plant breeding. Modern plant breeding has made a profound impact on food production and will continue to play a vital role in world food security. For sustainable agriculture, a compromise should be sought between maximizing crop yield under changing climate and minimizing crop failure under unfavorable conditions. Such a compromise requires better understanding of the impacts of plant breeding on crop genetic diversity. Efforts have been made over the last three decades to assess crop genetic diversity using molecular marker technologies. However, these assessments have revealed some temporal diversity patterns that are largely inconsistent with our perception that modern plant breeding reduces crop genetic diversity. An attempt was made in this review to explain such discrepancies by examining empirical assessments of crop genetic diversity and theoretical investigations of genetic diversity changes over time under artificial selection. It was found that many crop genetic diversity assessments were not designed to assess diversity impacts from specific plant breeding programs, while others were experimentally inadequate and contained technical biases from the sampling of cultivars and genomes. Little attention has been paid to theoretical investigations on crop genetic diversity changes from plant breeding. A computer simulation of five simplified breeding schemes showed the substantial effects of plant breeding on the retention of heterozygosity over generations. It is clear that more efforts are needed to investigate crop genetic diversity in space and time under plant breeding to achieve sustainable crop production.

Genetic parameters for milk fatty acids, milk yield and quality traits of a Holstein cattle population reared under tropical conditions

USDA-ARS?s Scientific Manuscript database

Information about genetic parameters is essential for selection decisions and genetic evaluation. Those estimates are population specific, but few studies are available for dairy cattle populations reared under tropical and subtropical conditions. Heritability and genetic correlations for milk yield...

Columbia River White Sturgeon Genetics and Early Life History: Population Segregation and Juvenile Feeding Behavior, 1987 Final Report.

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

Brannon, Ernest L.

1988-06-01

The geographic area of the genetics study broadly covered the distribution range of sturgeon in the Columbia from below Bonneville Dam at Ilwaco at Lake Roosevelt, the Upper Snake River, and the Kootenai River. The two remote river sections provided data important for enhancement considerations. There was little electrophoretic variation seen among individuals from the Kootenai River. Upper Snake river sturgeon showed a higher percentage of polymorphic loci than the Kootenai fish, but lower than the other areas in the Columbia River we sampled. Sample size was increased in both Lake Roosevelt and at Electrophoretic variation was specific to anmore » individual sampling area in several cases and this shaped our conclusions. The 1987 early life history studies concentrated on the feeding behavior of juvenile sturgeon. The chemostimulant components in prey attractive to sturgeon were examined, and the sensory systems utilized by foraging sturgeon were determined under different environmental conditions. These results were discussed with regard to the environmental changes that have occurred in the Columbia River. Under present river conditions, the feeding mechanism of sturgeon is more restricted to certain prey types, and their feeding range may be limited. In these situations, enhancement measures cannot be undertaken without consideration given to the introduction of food resources that will be readily available under present conditions. 89 refs., 7 figs., 11 tabs.« less

Genetic Variability Under the Seedbank Coalescent.

PubMed

Blath, Jochen; González Casanova, Adrián; Eldon, Bjarki; Kurt, Noemi; Wilke-Berenguer, Maite

2015-07-01

We analyze patterns of genetic variability of populations in the presence of a large seedbank with the help of a new coalescent structure called the seedbank coalescent. This ancestral process appears naturally as a scaling limit of the genealogy of large populations that sustain seedbanks, if the seedbank size and individual dormancy times are of the same order as those of the active population. Mutations appear as Poisson processes on the active lineages and potentially at reduced rate also on the dormant lineages. The presence of "dormant" lineages leads to qualitatively altered times to the most recent common ancestor and nonclassical patterns of genetic diversity. To illustrate this we provide a Wright-Fisher model with a seedbank component and mutation, motivated from recent models of microbial dormancy, whose genealogy can be described by the seedbank coalescent. Based on our coalescent model, we derive recursions for the expectation and variance of the time to most recent common ancestor, number of segregating sites, pairwise differences, and singletons. Estimates (obtained by simulations) of the distributions of commonly employed distance statistics, in the presence and absence of a seedbank, are compared. The effect of a seedbank on the expected site-frequency spectrum is also investigated using simulations. Our results indicate that the presence of a large seedbank considerably alters the distribution of some distance statistics, as well as the site-frequency spectrum. Thus, one should be able to detect from genetic data the presence of a large seedbank in natural populations. Copyright © 2015 by the Genetics Society of America.

Quantitative trait loci mapping of the mouse plasma proteome (pQTL).

PubMed

Holdt, Lesca M; von Delft, Annette; Nicolaou, Alexandros; Baumann, Sven; Kostrzewa, Markus; Thiery, Joachim; Teupser, Daniel

2013-02-01

A current challenge in the era of genome-wide studies is to determine the responsible genes and mechanisms underlying newly identified loci. Screening of the plasma proteome by high-throughput mass spectrometry (MALDI-TOF MS) is considered a promising approach for identification of metabolic and disease processes. Therefore, plasma proteome screening might be particularly useful for identifying responsible genes when combined with analysis of variation in the genome. Here, we describe a proteomic quantitative trait locus (pQTL) study of plasma proteome screens in an F(2) intercross of 455 mice mapped with 177 genetic markers across the genome. A total of 69 of 176 peptides revealed significant LOD scores (≥5.35) demonstrating strong genetic regulation of distinct components of the plasma proteome. Analyses were confirmed by mechanistic studies and MALDI-TOF/TOF, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of the two strongest pQTLs: A pQTL for mass-to-charge ratio (m/z) 3494 (LOD 24.9, D11Mit151) was identified as the N-terminal 35 amino acids of hemoglobin subunit A (Hba) and caused by genetic variation in Hba. Another pQTL for m/z 8713 (LOD 36.4; D1Mit111) was caused by variation in apolipoprotein A2 (Apoa2) and cosegregated with HDL cholesterol. Taken together, we show that genome-wide plasma proteome profiling in combination with genome-wide genetic screening aids in the identification of causal genetic variants affecting abundance of plasma proteins.

Quantitative Trait Loci Mapping of the Mouse Plasma Proteome (pQTL)

PubMed Central

Holdt, Lesca M.; von Delft, Annette; Nicolaou, Alexandros; Baumann, Sven; Kostrzewa, Markus; Thiery, Joachim; Teupser, Daniel

2013-01-01

A current challenge in the era of genome-wide studies is to determine the responsible genes and mechanisms underlying newly identified loci. Screening of the plasma proteome by high-throughput mass spectrometry (MALDI-TOF MS) is considered a promising approach for identification of metabolic and disease processes. Therefore, plasma proteome screening might be particularly useful for identifying responsible genes when combined with analysis of variation in the genome. Here, we describe a proteomic quantitative trait locus (pQTL) study of plasma proteome screens in an F2 intercross of 455 mice mapped with 177 genetic markers across the genome. A total of 69 of 176 peptides revealed significant LOD scores (≥5.35) demonstrating strong genetic regulation of distinct components of the plasma proteome. Analyses were confirmed by mechanistic studies and MALDI-TOF/TOF, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of the two strongest pQTLs: A pQTL for mass-to-charge ratio (m/z) 3494 (LOD 24.9, D11Mit151) was identified as the N-terminal 35 amino acids of hemoglobin subunit A (Hba) and caused by genetic variation in Hba. Another pQTL for m/z 8713 (LOD 36.4; D1Mit111) was caused by variation in apolipoprotein A2 (Apoa2) and cosegregated with HDL cholesterol. Taken together, we show that genome-wide plasma proteome profiling in combination with genome-wide genetic screening aids in the identification of causal genetic variants affecting abundance of plasma proteins. PMID:23172855

Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases.

PubMed

Leone, Vanessa; Chang, Eugene B; Devkota, Suzanne

2013-03-01

The incidence of inflammatory bowel diseases (IBD), as well as other inflammatory conditions, has dramatically increased over the past half century. While many studies have shown that IBD exhibits a genetic component via genome-wide association studies, genetic drift alone cannot account for this increase, and other factors, such as those found in the environment must play a role, suggesting a "multiple hit" phenomenon that precipitates disease. One major environmental factor, dietary intake, has shifted to a high fat, high carbohydrate Western-type diet in developing nations, nearly in direct correlation with the increasing incidence of IBD. Recent evidence suggests that specific changes in dietary intake have led to a shift in the composite human gut microbiota, resulting in the emergence of pathobionts that can thrive under specific conditions. In the genetically susceptible host, the emerging pathobionts can lead to increasing incidence and severity of IBD and other inflammatory disorders. Since the gut microbiota is plastic and responds to dietary modulations, the use of probiotics, prebiotics, and/or dietary alterations are all intriguing complementary therapeutic approaches to alleviate IBD symptoms. However, the interactions are complex and it is unlikely that a one-size-fits all approach can be utilized across all populations affected by IBD. Exploration into and thoroughly understanding the interactions between host and microbes, primarily in the genetically susceptible host, will help define strategies that can be tailored to an individual as we move towards an era of personalized medicine to treat IBD.

Advances in the genetic dissection of plant cell walls: tools and resources available in Miscanthus

PubMed Central

Slavov, Gancho; Allison, Gordon; Bosch, Maurice

2013-01-01

Tropical C4 grasses from the genus Miscanthus are believed to have great potential as biomass crops. However, Miscanthus species are essentially undomesticated, and genetic, molecular and bioinformatics tools are in very early stages of development. Furthermore, similar to other crops targeted as lignocellulosic feedstocks, the efficient utilization of biomass is hampered by our limited knowledge of the structural organization of the plant cell wall and the underlying genetic components that control this organization. The Institute of Biological, Environmental and Rural Sciences (IBERS) has assembled an extensive collection of germplasm for several species of Miscanthus. In addition, an integrated, multidisciplinary research programme at IBERS aims to inform accelerated breeding for biomass productivity and composition, while also generating fundamental knowledge. Here we review recent advances with respect to the genetic characterization of the cell wall in Miscanthus. First, we present a summary of recent and on-going biochemical studies, including prospects and limitations for the development of powerful phenotyping approaches. Second, we review current knowledge about genetic variation for cell wall characteristics of Miscanthus and illustrate how phenotypic data, combined with high-density arrays of single-nucleotide polymorphisms, are being used in genome-wide association studies to generate testable hypotheses and guide biological discovery. Finally, we provide an overview of the current knowledge about the molecular biology of cell wall biosynthesis in Miscanthus and closely related grasses, discuss the key conceptual and technological bottlenecks, and outline the short-term prospects for progress in this field. PMID:23847628

Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system.

PubMed

Monzón-Sandoval, Jimena; Castillo-Morales, Atahualpa; Crampton, Sean; McKelvey, Laura; Nolan, Aoife; O'Keeffe, Gerard; Gutierrez, Humberto

2015-01-01

During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune-related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS.

Similar recent selection criteria associated with different behavioural effects in two dog breeds.

PubMed

Sundman, A-S; Johnsson, M; Wright, D; Jensen, P

2016-11-01

Selection during the last decades has split some established dog breeds into morphologically and behaviourally divergent types. These breed splits are interesting models for behaviour genetics since selection has often been for few and well-defined behavioural traits. The aim of this study was to explore behavioural differences between selection lines in golden and Labrador retriever, in both of which a split between a common type (pet and conformation) and a field type (hunting) has occurred. We hypothesized that the behavioural profiles of the types would be similar in both breeds. Pedigree data and results from a standardized behavioural test from 902 goldens (698 common and 204 field) and 1672 Labradors (1023 and 649) were analysed. Principal component analysis revealed six behavioural components: curiosity, play interest, chase proneness, social curiosity, social greeting and threat display. Breed and type affected all components, but interestingly there was an interaction between breed and type for most components. For example, in Labradors the common type had higher curiosity than the field type (F 1,1668 = 18.359; P < 0.001), while the opposite was found in goldens (F 1,897 = 65.201; P < 0.001). Heritability estimates showed considerable genetic contributions to the behavioural variations in both breeds, but different heritabilities between the types within breeds was also found, suggesting different selection pressures. In conclusion, in spite of similar genetic origin and similar recent selection criteria, types behave differently in the breeds. This suggests that the genetic architecture related to behaviour differs between the breeds. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Principles in genetic risk assessment.

PubMed

Baptista, Pedro Viana

2005-03-01

Risk assessment constitutes an essential component of genetic counseling and testing, and the genetic risk should be estimated as accurately as possible for individual and family decision making. All relevant information retrieved from population studies and pedigree and genetic testing enhances the accuracy of the assessment of an individual's genetic risk. This review will focus on the following general aspects implicated in risk assessment: the increasing genetic information regarding disease; complex traits versus Mendelian disorders; and the influence of the environment and disease susceptibility. The influence of these factors on risk assessment will be discussed.

Principles in genetic risk assessment

PubMed Central

Baptista, Pedro Viana

2005-01-01

Risk assessment constitutes an essential component of genetic counseling and testing, and the genetic risk should be estimated as accurately as possible for individual and family decision making. All relevant information retrieved from population studies and pedigree and genetic testing enhances the accuracy of the assessment of an individual's genetic risk. This review will focus on the following general aspects implicated in risk assessment: the increasing genetic information regarding disease; complex traits versus Mendelian disorders; and the influence of the environment and disease susceptibility. The influence of these factors on risk assessment will be discussed. PMID:18360538

Genetic architecture underlying convergent evolution of egg-laying behavior in a seed-feeding beetle.

PubMed

Fox, Charles W; Wagner, James D; Cline, Sara; Thomas, Frances Ann; Messina, Frank J

2009-05-01

Independent populations subjected to similar environments often exhibit convergent evolution. An unresolved question is the frequency with which such convergence reflects parallel genetic mechanisms. We examined the convergent evolution of egg-laying behavior in the seed-feeding beetle Callosobruchus maculatus. Females avoid ovipositing on seeds bearing conspecific eggs, but the degree of host discrimination varies among geographic populations. In a previous experiment, replicate lines switched from a small host to a large one evolved reduced discrimination after 40 generations. We used line crosses to determine the genetic architecture underlying this rapid response. The most parsimonious genetic models included dominance and/or epistasis for all crosses. The genetic architecture underlying reduced discrimination in two lines was not significantly different from the architecture underlying differences between geographic populations, but the architecture underlying the divergence of a third line differed from all others. We conclude that convergence of this complex trait may in some cases involve parallel genetic mechanisms.

Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD.

PubMed

Chen, Hongbo; Kankel, Mark W; Su, Susan C; Han, Steve W S; Ofengeim, Dimitry

2018-03-01

Although amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, was first described in 1874, a flurry of genetic discoveries in the last 10 years has markedly increased our understanding of this disease. These findings have not only enhanced our knowledge of mechanisms leading to ALS, but also have revealed that ALS shares many genetic causes with another neurodegenerative disease, frontotemporal lobar dementia (FTLD). In this review, we survey how recent genetic studies have bridged our mechanistic understanding of these two related diseases and how the genetics behind ALS and FTLD point to complex disorders, implicating non-neuronal cell types in disease pathophysiology. The involvement of non-neuronal cell types is consistent with a non-cell autonomous component in these diseases. This is further supported by studies that identified a critical role of immune-associated genes within ALS/FTLD and other neurodegenerative disorders. The molecular functions of these genes support an emerging concept that various non-autonomous functions are involved in neurodegeneration. Further insights into such a mechanism(s) will ultimately lead to a better understanding of potential routes of therapeutic intervention. Facts ALS and FTLD are severe neurodegenerative disorders on the same disease spectrum. Multiple cellular processes including dysregulation of RNA homeostasis, imbalance of proteostasis, contribute to ALS/FTLD pathogenesis. Aberrant function in non-neuronal cell types, including microglia, contributes to ALS/FTLD. Strong neuroimmune and neuroinflammatory components are associated with ALS/FTLD patients. Open Questions Why can patients with similar mutations have different disease manifestations, i.e., why do C9ORF72 mutations lead to motor neuron loss in some patients while others exhibit loss of neurons in the frontotemporal lobe? Do ALS causal mutations result in microglial dysfunction and contribute to ALS/FTLD pathology? How do microglia normally act to mitigate neurodegeneration in ALS/FTLD? To what extent do cellular signaling pathways mediate non-cell autonomous communications between distinct central nervous system (CNS) cell types during disease? Is it possible to therapeutically target specific cell types in the CNS?

Genetic analysis of feet and leg conformation traits in Nelore cattle.

PubMed

Vargas, G; Neves, H H R; Cardoso, V; Munari, D P; Carvalheiro, R

2017-06-01

Feet and leg conformation scores are important traits in beef cattle because they encompass a wide range of locomotion disorders that can lead to productive and reproductive losses. Thus, the study of feet and legs in beef cattle is essential for evaluating possible responses to selection focusing on minimizing economic losses caused by the occurrence of feet and leg problems. The aim of this study was to estimate variance components for feet and leg conformation traits in Nelore cattle. The data set contained records of approximately 300,000 animals that were born between 2000 and 2013. These animals belonged to the commercial beef cattle breeding program of the CRV Lagoa (). Feet and legs were evaluated by assigning visual scores at 2 different time points: feet and leg evaluated as a binary trait (FL1), measured at yearling (about 550 d of age) to identify whether (or not) an animal has feet and leg defects, and feet and leg score (FL2), ranging from 1 (less desirable) to 5 (more desirable) was assigned to the top 20% of animals according to the selection index adopted by the beef cattle breeding program, which was measured 2 to 5 mo after the yearling evaluation. The FL1 and FL2 traits were analyzed together with yearling weight (YW). The (co)variance components and breeding values were estimated by Bayesian inference using 2-trait animal models. The posterior means (standard errors) of the heritabilities for FL1, FL2, and YW were 0.18 (0.04), 0.39 (0.07), and 0.47 (0.01), respectively. The results indicate that the incidence of feet and leg problems in this population might be reduced by selection. The genetic correlation between FL1 and FL2 (-0.47) was moderate and negative as expected because the classification score that holds up each trait has opposite numerical values. The genetic trends estimated for FL1 and FL2 (-0.042 and 0.021 genetic standard deviations per year, respectively) were favorable and they indicate that the independent culling strategy for feet and leg problems promotes favorable changes and contributes to the genetic progress of these traits in the population under study.

Assessing Attitudes about Genetic Testing as a Component of Continuing Medical Education

ERIC Educational Resources Information Center

Mrazek, Michael; Koenig, Barbara; Skime, Michelle; Snyder, Karen; Hook, Christopher; Black, John, III; Mrazek, David

2007-01-01

Objective: To investigate the attitudes among mental health professionals regarding the use of genetic testing. Methods: Psychiatrists and other mental health professionals (N = 41) who were enrolled in a week-long course in psychiatric genomics completed questionnaires before and after the course designed to assess how diagnostic genetic tests…

76 FR 39812 - Scotts Miracle-Gro Co.; Regulatory Status of Kentucky Bluegrass Genetically Engineered for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

...] Scotts Miracle-Gro Co.; Regulatory Status of Kentucky Bluegrass Genetically Engineered for Herbicide... engineered for herbicide tolerance without the use of plant pest components, does not meet the definition of... has been genetically engineered for herbicide tolerance, does not meet the definition of a regulated...

Loneliness in Adolescence: Gene x Environment Interactions Involving the Serotonin Transporter Gene

ERIC Educational Resources Information Center

van Roekel, Eeske; Scholte, Ron H. J.; Verhagen, Maaike; Goossens, Luc; Engels, Rutger C. M. E.

2010-01-01

Background: Loneliness is assumed to peak in early adolescence and to decrease throughout middle and late adolescence, but longitudinal confirmation of this tendency is lacking. Behavioral genetic studies with twin designs have found a significant genetic component for loneliness in children and adults, but no molecular genetic studies have been…

Exploring Cystic Fibrosis Using Bioinformatics Tools: A Module Designed for the Freshman Biology Course

ERIC Educational Resources Information Center

Zhang, Xiaorong

2011-01-01

We incorporated a bioinformatics component into the freshman biology course that allows students to explore cystic fibrosis (CF), a common genetic disorder, using bioinformatics tools and skills. Students learn about CF through searching genetic databases, analyzing genetic sequences, and observing the three-dimensional structures of proteins…

Genetic anaylsis of a disease resistance gene from loblolly pine

Treesearch

Yinghua Huang; Nili Jin; Alex Diner; Chuck Tauer; Yan Zhang; John Damicone

2003-01-01

Rapid advances in molecular genetics provide great opportunities for studies of host defense mechanisms. Examination of plant responses to disease at the cellular and molecular level permits both discovery of changes in gene expression in the tissues attacked by pathogens, and identification of genetic components involved in the interaction between host and pathogens....

Family Conflict Interacts with Genetic Liability in Predicting Childhood and Adolescent Depression

ERIC Educational Resources Information Center

Rice, Frances; Harold, Gordon T.; Shelton, Katherine H.; Thapar, Anita

2006-01-01

Objective: To test for gene-environment interaction with depressive symptoms and family conflict. Specifically, to first examine whether the influence of family conflict in predicting depressive symptoms is increased in individuals at genetic risk of depression. Second, to test whether the genetic component of variance in depressive symptoms…

Determination of thiamine HCl and pyridoxine HCl in pharmaceutical preparations using UV-visible spectrophotometry and genetic algorithm based multivariate calibration methods.

PubMed

Ozdemir, Durmus; Dinc, Erdal

2004-07-01

Simultaneous determination of binary mixtures pyridoxine hydrochloride and thiamine hydrochloride in a vitamin combination using UV-visible spectrophotometry and classical least squares (CLS) and three newly developed genetic algorithm (GA) based multivariate calibration methods was demonstrated. The three genetic multivariate calibration methods are Genetic Classical Least Squares (GCLS), Genetic Inverse Least Squares (GILS) and Genetic Regression (GR). The sample data set contains the UV-visible spectra of 30 synthetic mixtures (8 to 40 microg/ml) of these vitamins and 10 tablets containing 250 mg from each vitamin. The spectra cover the range from 200 to 330 nm in 0.1 nm intervals. Several calibration models were built with the four methods for the two components. Overall, the standard error of calibration (SEC) and the standard error of prediction (SEP) for the synthetic data were in the range of <0.01 and 0.43 microg/ml for all the four methods. The SEP values for the tablets were in the range of 2.91 and 11.51 mg/tablets. A comparison of genetic algorithm selected wavelengths for each component using GR method was also included.

Genetic support for the dual nature of attention deficit hyperactivity disorder: substantial genetic overlap between the inattentive and hyperactive-impulsive components.

PubMed

McLoughlin, Gráinne; Ronald, Angelica; Kuntsi, Jonna; Asherson, Philip; Plomin, Robert

2007-12-01

Attention deficit hyperactivity disorder (ADHD) is a common, complex and highly heritable disorder, characterised by inattentive, impulsive and overactive behaviour. Evidence for the heritability of ADHD measures in twin population samples has come from the analysis of total scores that combine inattentive and hyperactive-impulsive symptoms subscales. This study investigated, in a community sample, the aetiology of ADHD-like traits and the aetiological overlap between the two dimensions that define the ADHD disorder. Parents of 6,222 approximately 8-year-old twin pairs from the Twins Early Development Study (TEDS) population sample completed the two subscales of the Conners' 18-item DSMIV checklist, a screening instrument for ADHD symptoms. Both subscales were highly heritable (hyperactive-impulsive: 88%; inattentive: 79%). Bivariate genetic modelling indicated substantial genetic overlap between the two components; however, there were significant independent genetic effects. These findings suggest that many genes associated with the hyperactivity-impulsivity dimension will also be associated with the inattentive dimension but that there is significant genetic heterogeneity as well. These results provide genetic support for combining the two behavioural dimensions that define ADHD, but also suggest that some symptom-specific genes will also be identified.

Genetic Augmentation of Syringyl Lignin in Low-lignin Aspen Trees, Final Report

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

Chung-Jui Tsai; Mark F. Davis; Vincent L. Chiang

2004-11-10

As a polysaccharide-encrusting component, lignin is critical to cell wall integrity and plant growth but also hinders recovery of cellulose fibers during the wood pulping process. To improve pulping efficiency, it is highly desirable to genetically modify lignin content and/or structure in pulpwood species to maximize pulp yields with minimal energy consumption and environmental impact. This project aimed to genetically augment the syringyl-to-guaiacyl lignin ratio in low-lignin transgenic aspen in order to produce trees with reduced lignin content, more reactive lignin structures and increased cellulose content. Transgenic aspen trees with reduced lignin content have already been achieved, prior to themore » start of this project, by antisense downregulation of a 4-coumarate:coenzyme A ligase gene (Hu et al., 1999 Nature Biotechnol 17: 808- 812). The primary objective of this study was to genetically augment syringyl lignin biosynthesis in these low-lignin trees in order to enhance lignin reactivity during chemical pulping. To accomplish this, both aspen and sweetgum genes encoding coniferaldehyde 5-hydroxylase (Osakabe et al., 1999 PNAS 96: 8955-8960) were targeted for over-expression in wildtype or low-lignin aspen under control of either a constitutive or a xylem-specific promoter. A second objective for this project was to develop reliable and cost-effective methods, such as pyrolysis Molecular Beam Mass Spectrometry and NMR, for rapid evaluation of cell wall chemical components of transgenic wood samples. With these high-throughput techniques, we observed increased syringyl-to-guaiacyl lignin ratios in the transgenic wood samples, regardless of the promoter used or gene origin. Our results confirmed that the coniferaldehyde 5-hydroxylase gene is key to syringyl lignin biosynthesis. The outcomes of this research should be readily applicable to other pulpwood species, and promise to bring direct economic and environmental benefits to the pulp and paper industry.« less

Using a Genetic Algorithm to Learn Behaviors for Autonomous Vehicles,

DTIC Science & Technology

1992-08-12

Truly autonomous vehicles will require both projective planning and reactive components in order to perform robustly. Projective components are...long time period. This work addresses the problem of creating reactive components for autonomous vehicles . Creating reactive behaviors (stimulus

Genetic parameters of legendre polynomials for first parity lactation curves.

PubMed

Pool, M H; Janss, L L; Meuwissen, T H

2000-11-01

Variance components of the covariance function coefficients in a random regression test-day model were estimated by Legendre polynomials up to a fifth order for first-parity records of Dutch dairy cows using Gibbs sampling. Two Legendre polynomials of equal order were used to model the random part of the lactation curve, one for the genetic component and one for permanent environment. Test-day records from cows registered between 1990 to 1996 and collected by regular milk recording were available. For the data set, 23,700 complete lactations were selected from 475 herds sired by 262 sires. Because the application of a random regression model is limited by computing capacity, we investigated the minimum order needed to fit the variance structure in the data sufficiently. Predictions of genetic and permanent environmental variance structures were compared with bivariate estimates on 30-d intervals. A third-order or higher polynomial modeled the shape of variance curves over DIM with sufficient accuracy for the genetic and permanent environment part. Also, the genetic correlation structure was fitted with sufficient accuracy by a third-order polynomial, but, for the permanent environmental component, a fourth order was needed. Because equal orders are suggested in the literature, a fourth-order Legendre polynomial is recommended in this study. However, a rank of three for the genetic covariance matrix and of four for permanent environment allows a simpler covariance function with a reduced number of parameters based on the eigenvalues and eigenvectors.

Sex-specific genetic variance and the evolution of sexual dimorphism: a systematic review of cross-sex genetic correlations.

PubMed

Poissant, Jocelyn; Wilson, Alastair J; Coltman, David W

2010-01-01

The independent evolution of the sexes may often be constrained if male and female homologous traits share a similar genetic architecture. Thus, cross-sex genetic covariance is assumed to play a key role in the evolution of sexual dimorphism (SD) with consequent impacts on sexual selection, population dynamics, and speciation processes. We compiled cross-sex genetic correlations (r(MF)) estimates from 114 sources to assess the extent to which the evolution of SD is typically constrained and test several specific hypotheses. First, we tested if r(MF) differed among trait types and especially between fitness components and other traits. We also tested the theoretical prediction of a negative relationship between r(MF) and SD based on the expectation that increases in SD should be facilitated by sex-specific genetic variance. We show that r(MF) is usually large and positive but that it is typically smaller for fitness components. This demonstrates that the evolution of SD is typically genetically constrained and that sex-specific selection coefficients may often be opposite in sign due to sub-optimal levels of SD. Most importantly, we confirm that sex-specific genetic variance is an important contributor to the evolution of SD by validating the prediction of a negative correlation between r(MF) and SD.

The complexity of silk under the spotlight of synthetic biology.

PubMed

Vollrath, Fritz

2016-08-15

For centuries silkworm filaments have been the focus of R&D innovation centred on textile manufacture with high added value. Most recently, silk research has focused on more fundamental issues concerning bio-polymer structure-property-function relationships. This essay outlines the complexity and fundamentals of silk spinning, and presents arguments for establishing this substance as an interesting and important subject at the interface of systems biology (discovery) and synthetic biology (translation). It is argued that silk is a generic class of materials where each type of silk presents a different embodiment of emergent properties that combine genetically determined (anticipatory) and environmentally responsive components. In spiders' webs the various silks have evolved to form the interactive components of an intricate fabric that provides an extended phenotype to the spider's body morphology. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Genetic and Genomic Response to Selection for Food Consumption in Drosophila melanogaster.

PubMed

Garlapow, Megan E; Everett, Logan J; Zhou, Shanshan; Gearhart, Alexander W; Fay, Kairsten A; Huang, Wen; Morozova, Tatiana V; Arya, Gunjan H; Turlapati, Lavanya; St Armour, Genevieve; Hussain, Yasmeen N; McAdams, Sarah E; Fochler, Sophia; Mackay, Trudy F C

2017-03-01

Food consumption is an essential component of animal fitness; however, excessive food intake in humans increases risk for many diseases. The roles of neuroendocrine feedback loops, food sensing modalities, and physiological state in regulating food intake are well understood, but not the genetic basis underlying variation in food consumption. Here, we applied ten generations of artificial selection for high and low food consumption in replicate populations of Drosophila melanogaster. The phenotypic response to selection was highly asymmetric, with significant responses only for increased food consumption and minimal correlated responses in body mass and composition. We assessed the molecular correlates of selection responses by DNA and RNA sequencing of the selection lines. The high and low selection lines had variants with significantly divergent allele frequencies within or near 2081 genes and 3526 differentially expressed genes in one or both sexes. A total of 519 genes were both genetically divergent and differentially expressed between the divergent selection lines. We performed functional analyses of the effects of RNAi suppression of gene expression and induced mutations for 27 of these candidate genes that have human orthologs and the strongest statistical support, and confirmed that 25 (93 %) affected the mean and/or variance of food consumption.

Genome-Wide Linkage Analysis to Identify Genetic Modifiers of ALK Mutation Penetrance in Familial Neuroblastoma

PubMed Central

Devoto, Marcella; Specchia, Claudia; Laudenslager, Marci; Longo, Luca; Hakonarson, Hakon; Maris, John; Mossé, Yael

2011-01-01

Background Neuroblastoma (NB) is an important childhood cancer with a strong genetic component related to disease susceptibility. Approximately 1% of NB cases have a positive family history. Following a genome-wide linkage analysis and sequencing of candidate genes in the critical region, we identified ALK as the major familial NB gene. Dominant mutations in ALK are found in more than 50% of familial NB cases. However, in the families used for the linkage study, only about 50% of carriers of ALK mutations are affected by NB. Methods To test whether genetic variation may explain the reduced penetrance of the disease phenotype, we analyzed genome-wide genotype data in ALK mutation-positive families using a model-based linkage approach with different liability classes for carriers and non-carriers of ALK mutations. Results The region with the highest LOD score was located at chromosome 2p23–p24 and included the ALK locus under models of dominant and recessive inheritance. Conclusions This finding suggests that variants in the non-mutated ALK gene or another gene linked to it may affect penetrance of the ALK mutations and risk of developing NB in familial cases. PMID:21734404

Genetic markers for antioxidant capacity in a reef-building coral.

PubMed

Jin, Young K; Lundgren, Petra; Lutz, Adrian; Raina, Jean-Baptiste; Howells, Emily J; Paley, Allison S; Willis, Bette L; van Oppen, Madeleine J H

2016-05-01

The current lack of understanding of the genetic basis underlying environmental stress tolerance in reef-building corals impairs the development of new management approaches to confronting the global demise of coral reefs. On the Great Barrier Reef (GBR), an approximately 51% decline in coral cover occurred over the period 1985-2012. We conducted a gene-by-environment association analysis across 12° latitude on the GBR, as well as both in situ and laboratory genotype-by-phenotype association analyses. These analyses allowed us to identify alleles at two genetic loci that account for differences in environmental stress tolerance and antioxidant capacity in the common coral Acropora millepora. The effect size for antioxidant capacity was considerable and biologically relevant (32.5 and 14.6% for the two loci). Antioxidant capacity is a critical component of stress tolerance because a multitude of environmental stressors cause increased cellular levels of reactive oxygen species. Our findings provide the first step toward the development of novel coral reef management approaches, such as spatial mapping of stress tolerance for use in marine protected area design, identification of stress-tolerant colonies for assisted migration, and marker-assisted selective breeding to create more tolerant genotypes for restoration of denuded reefs.

Genetic analysis of growth traits in Polled Nellore cattle raised on pasture in tropical region using Bayesian approaches.

PubMed

Lopes, Fernando Brito; Magnabosco, Cláudio Ulhôa; Paulini, Fernanda; da Silva, Marcelo Corrêa; Miyagi, Eliane Sayuri; Lôbo, Raysildo Barbosa

2013-01-01

Components of (co)variance and genetic parameters were estimated for adjusted weights at ages 120 (W120), 240 (W240), 365 (W365) and 450 (W450) days of Polled Nellore cattle raised on pasture and born between 1987 and 2010. Analyses were performed using an animal model, considering fixed effects: herd-year-season of birth and calf sex as contemporary groups and the age of cow as a covariate. Gibbs Samplers were used to estimate (co)variance components, genetic parameters and additive genetic effects, which accounted for great proportion of total variation in these traits. High direct heritability estimates for the growth traits were revealed and presented mean 0.43, 0.61, 0.72 and 0.67 for W120, W240, W365 and W450, respectively. Maternal heritabilities were 0.07 and 0.08 for W120 and W240, respectively. Direct additive genetic correlations between the weight at 120, 240, 365 and 450 days old were strong and positive. These estimates ranged from 0.68 to 0.98. Direct-maternal genetic correlations were negative for W120 and W240. The estimates ranged from -0.31 to -0.54. Estimates of maternal heritability ranged from 0.056 to 0.092 for W120 and from 0.064 to 0.096 for W240. This study showed that genetic progress is possible for the growth traits we studied, which is a novel and favorable indicator for an upcoming and promising Polled Zebu breed in Tropical regions. Maternal effects influenced the performance of weight at 120 and 240 days old. These effects should be taken into account in genetic analyses of growth traits by fitting them as a genetic or a permanent environmental effect, or even both. In general, due to a medium-high estimate of environmental (co)variance components, management and feeding conditions for Polled Nellore raised at pasture in tropical regions of Brazil needs improvement and growth performance can be enhanced.

The Sensitivity of Genetic Connectivity Measures to Unsampled and Under-Sampled Sites

PubMed Central

Koen, Erin L.; Bowman, Jeff; Garroway, Colin J.; Wilson, Paul J.

2013-01-01

Landscape genetic analyses assess the influence of landscape structure on genetic differentiation. It is rarely possible to collect genetic samples from all individuals on the landscape and thus it is important to assess the sensitivity of landscape genetic analyses to the effects of unsampled and under-sampled sites. Network-based measures of genetic distance, such as conditional genetic distance (cGD), might be particularly sensitive to sampling intensity because pairwise estimates are relative to the entire network. We addressed this question by subsampling microsatellite data from two empirical datasets. We found that pairwise estimates of cGD were sensitive to both unsampled and under-sampled sites, and FST, Dest, and deucl were more sensitive to under-sampled than unsampled sites. We found that the rank order of cGD was also sensitive to unsampled and under-sampled sites, but not enough to affect the outcome of Mantel tests for isolation by distance. We simulated isolation by resistance and found that although cGD estimates were sensitive to unsampled sites, by increasing the number of sites sampled the accuracy of conclusions drawn from landscape genetic analyses increased, a feature that is not possible with pairwise estimates of genetic differentiation such as FST, Dest, and deucl. We suggest that users of cGD assess the sensitivity of this measure by subsampling within their own network and use caution when making extrapolations beyond their sampled network. PMID:23409155

Development of a genetic sexing strain in Bactrocera carambolae (Diptera: Tephritidae) by introgression of sex sorting components from B. dorsalis, Salaya1 strain

PubMed Central

2014-01-01

Background The carambola fruit fly, Bactrocera carambolae Drew & Hancock is a high profile key pest that is widely distributed in the southwestern ASEAN region. In addition, it has trans-continentally invaded Suriname, where it has been expanding east and southward since 1975. This fruit fly belongs to Bactrocera dorsalis species complex. The development and application of a genetic sexing strain (Salaya1) of B. dorsalis sensu stricto (s.s.) (Hendel) for the sterile insect technique (SIT) has improved the fruit fly control. However, matings between B. dorsalis s.s. and B. carambolae are incompatible, which hinder the application of the Salaya1 strain to control the carambola fruit fly. To solve this problem, we introduced genetic sexing components from the Salaya1 strain into the B. carambolae genome by interspecific hybridization. Results Morphological characteristics, mating competitiveness, male pheromone profiles, and genetic relationships revealed consistencies that helped to distinguish Salaya1 and B. carambolae strains. A Y-autosome translocation linking the dominant wild-type allele of white pupae gene and a free autosome carrying a recessive white pupae homologue from the Salaya1 strain were introgressed into the gene pool of B. carambolae. A panel of Y-pseudo-linked microsatellite loci of the Salaya1 strain served as markers for the introgression experiments. This resulted in a newly derived genetic sexing strain called Salaya5, with morphological characteristics corresponding to B. carambolae. The rectal gland pheromone profile of Salaya5 males also contained a distinctive component of B. carambolae. Microsatellite DNA analyses confirmed the close genetic relationships between the Salaya5 strain and wild B. carambolae populations. Further experiments showed that the sterile males of Salaya5 can compete with wild males for mating with wild females in field cage conditions. Conclusions Introgression of sex sorting components from the Salaya1 strain to a closely related B. carambolae strain generated a new genetic sexing strain, Salaya5. Morphology-based taxonomic characteristics, distinctive pheromone components, microsatellite DNA markers, genetic relationships, and mating competitiveness provided parental baseline data and validation tools for the new strain. The Salaya5 strain shows a close similarity with those features in the wild B. carambolae strain. In addition, mating competitiveness tests suggested that Salaya5 has a potential to be used in B. carambolae SIT programs based on male-only releases. PMID:25471905

Short communication: Principal components and factor analytic models for test-day milk yield in Brazilian Holstein cattle.

PubMed

Bignardi, A B; El Faro, L; Rosa, G J M; Cardoso, V L; Machado, P F; Albuquerque, L G

2012-04-01

A total of 46,089 individual monthly test-day (TD) milk yields (10 test-days), from 7,331 complete first lactations of Holstein cattle were analyzed. A standard multivariate analysis (MV), reduced rank analyses fitting the first 2, 3, and 4 genetic principal components (PC2, PC3, PC4), and analyses that fitted a factor analytic structure considering 2, 3, and 4 factors (FAS2, FAS3, FAS4), were carried out. The models included the random animal genetic effect and fixed effects of the contemporary groups (herd-year-month of test-day), age of cow (linear and quadratic effects), and days in milk (linear effect). The residual covariance matrix was assumed to have full rank. Moreover, 2 random regression models were applied. Variance components were estimated by restricted maximum likelihood method. The heritability estimates ranged from 0.11 to 0.24. The genetic correlation estimates between TD obtained with the PC2 model were higher than those obtained with the MV model, especially on adjacent test-days at the end of lactation close to unity. The results indicate that for the data considered in this study, only 2 principal components are required to summarize the bulk of genetic variation among the 10 traits. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Mouse Models for Unraveling the Importance of Diet in Colon Cancer Prevention

PubMed Central

Tammariello, Alexandra E.; Milner, John A.

2010-01-01

Diet and genetics are both considered important risk determinants for colorectal cancer, a leading cause of death worldwide. Several genetically engineered mouse models have been created, including the ApcMin mouse, to aid in the identification of key cancer related processes and to assist with the characterization of environmental factors, including the diet, which influence risk. Current research using these models provides evidence that several bioactive food components can inhibit genetically predisposed colorectal cancer, while others increase risk. Specifically, calorie restriction or increased exposure to n-3 fatty acids, sulforaphane, chafuroside, curcumin, and dibenzoylmethane were reported protective. Total fat, calories and all-trans retinoic acid are associated with an increased risk. Unraveling the importance of specific dietary components in these models is complicated by the basal diet used, the quantity of test components provided, and interactions among food components. Newer models are increasingly available to evaluate fundamental cellular processes, including DNA mismatch repair, immune function and inflammation as markers for colon cancer risk. Unfortunately, these models have been used infrequently to examine the influence of specific dietary components. The enhanced use of these models can shed mechanistic insights about the involvement of specific bioactive food and components and energy as determinants of colon cancer risk. However, the use of available mouse models to exactly represent processes important to human gastrointestinal cancers will remain a continued scientific challenge. PMID:20122631

Variance component and breeding value estimation for genetic heterogeneity of residual variance in Swedish Holstein dairy cattle.

PubMed

Rönnegård, L; Felleki, M; Fikse, W F; Mulder, H A; Strandberg, E

2013-04-01

Trait uniformity, or micro-environmental sensitivity, may be studied through individual differences in residual variance. These differences appear to be heritable, and the need exists, therefore, to fit models to predict breeding values explaining differences in residual variance. The aim of this paper is to estimate breeding values for micro-environmental sensitivity (vEBV) in milk yield and somatic cell score, and their associated variance components, on a large dairy cattle data set having more than 1.6 million records. Estimation of variance components, ordinary breeding values, and vEBV was performed using standard variance component estimation software (ASReml), applying the methodology for double hierarchical generalized linear models. Estimation using ASReml took less than 7 d on a Linux server. The genetic standard deviations for residual variance were 0.21 and 0.22 for somatic cell score and milk yield, respectively, which indicate moderate genetic variance for residual variance and imply that a standard deviation change in vEBV for one of these traits would alter the residual variance by 20%. This study shows that estimation of variance components, estimated breeding values and vEBV, is feasible for large dairy cattle data sets using standard variance component estimation software. The possibility to select for uniformity in Holstein dairy cattle based on these estimates is discussed. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Sleep Duration and Area-Level Deprivation in Twins

PubMed Central

Watson, Nathaniel F.; Horn, Erin; Duncan, Glen E.; Buchwald, Dedra; Vitiello, Michael V.; Turkheimer, Eric

2016-01-01

Study Objectives: We used quantitative genetic models to assess whether area-level deprivation as indicated by the Singh Index predicts shorter sleep duration and modifies its underlying genetic and environmental contributions. Methods: Participants were 4,218 adult twin pairs (2,377 monozygotic and 1,841 dizygotic) from the University of Washington Twin Registry. Participants self-reported habitual sleep duration. The Singh Index was determined by linking geocoding addresses to 17 indicators at the census-tract level using data from Census of Washington State and Census Tract Cartographic Boundary Files from 2000 and 2010. Data were analyzed using univariate and bivariate genetic decomposition and quantitative genetic interaction models that assessed A (additive genetics), C (common environment), and E (unique environment) main effects of the Singh Index on sleep duration and allowed the magnitude of residual ACE variance components in sleep duration to vary with the Index. Results: The sample had a mean age of 38.2 y (standard deviation [SD] = 18), and was predominantly female (62%) and Caucasian (91%). Mean sleep duration was 7.38 h (SD = 1.20) and the mean Singh Index score was 0.00 (SD = 0.89). The heritability of sleep duration was 39% and the Singh Index was 12%. The uncontrolled phenotypic regression of sleep duration on the Singh Index showed a significant negative relationship between area-level deprivation and sleep length (b = −0.080, P < 0.001). Every 1 SD in Singh Index was associated with a ∼4.5 min change in sleep duration. For the quasi-causal bivariate model, there was a significant main effect of E (b0E = −0.063; standard error [SE] = 0.30; P < 0.05). Residual variance components unique to sleep duration were significant for both A (b0Au = 0.734; SE = 0.020; P < 0.001) and E (b0Eu = 0.934; SE = 0.013; P < 0.001). Conclusions: Area-level deprivation has a quasi-causal association with sleep duration, with greater deprivation being related to shorter sleep. As area-level deprivation increases, unique genetic and nonshared environmental residual variance in sleep duration increases. Citation: Watson NF, Horn E, Duncan GE, Buchwald D, Vitiello MV, Turkheimer E. Sleep duration and area-level deprivation in twins. SLEEP 2016;39(1):67– 77. PMID:26285009

Finding imaging patterns of structural covariance via Non-Negative Matrix Factorization.

PubMed

Sotiras, Aristeidis; Resnick, Susan M; Davatzikos, Christos

2015-03-01

In this paper, we investigate the use of Non-Negative Matrix Factorization (NNMF) for the analysis of structural neuroimaging data. The goal is to identify the brain regions that co-vary across individuals in a consistent way, hence potentially being part of underlying brain networks or otherwise influenced by underlying common mechanisms such as genetics and pathologies. NNMF offers a directly data-driven way of extracting relatively localized co-varying structural regions, thereby transcending limitations of Principal Component Analysis (PCA), Independent Component Analysis (ICA) and other related methods that tend to produce dispersed components of positive and negative loadings. In particular, leveraging upon the well known ability of NNMF to produce parts-based representations of image data, we derive decompositions that partition the brain into regions that vary in consistent ways across individuals. Importantly, these decompositions achieve dimensionality reduction via highly interpretable ways and generalize well to new data as shown via split-sample experiments. We empirically validate NNMF in two data sets: i) a Diffusion Tensor (DT) mouse brain development study, and ii) a structural Magnetic Resonance (sMR) study of human brain aging. We demonstrate the ability of NNMF to produce sparse parts-based representations of the data at various resolutions. These representations seem to follow what we know about the underlying functional organization of the brain and also capture some pathological processes. Moreover, we show that these low dimensional representations favorably compare to descriptions obtained with more commonly used matrix factorization methods like PCA and ICA. Copyright © 2014 Elsevier Inc. All rights reserved.

Estimation of genetic parameters for heat stress, including dominance gene effects, on milk yield in Thai Holstein dairy cattle.

PubMed

Boonkum, Wuttigrai; Duangjinda, Monchai

2015-03-01

Heat stress in tropical regions is a major cause that strongly negatively affects to milk production in dairy cattle. Genetic selection for dairy heat tolerance is powerful technique to improve genetic performance. Therefore, the current study aimed to estimate genetic parameters and investigate the threshold point of heat stress for milk yield. Data included 52 701 test-day milk yield records for the first parity from 6247 Thai Holstein dairy cattle, covering the period 1990 to 2007. The random regression test day model with EM-REML was used to estimate variance components, genetic parameters and milk production loss. A decline in milk production was found when temperature and humidity index (THI) exceeded a threshold of 74, also it was associated with the high percentage of Holstein genetics. All variance component estimates increased with THI. The estimate of heritability of test-day milk yield was 0.231. Dominance variance as a proportion to additive variance (0.035) indicated that non-additive effects might not be of concern for milk genetics studies in Thai Holstein cattle. Correlations between genetic and permanent environmental effects, for regular conditions and due to heat stress, were - 0.223 and - 0.521, respectively. The heritability and genetic correlations from this study show that simultaneous selection for milk production and heat tolerance is possible. © 2014 Japanese Society of Animal Science.

On the use of genetic algorithm to optimize industrial assets lifecycle management under safety and budget constraints

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

Lonchampt, J.; Fessart, K.

2013-07-01

The purpose of this paper is to describe the method and tool dedicated to optimize investments planning for industrial assets. These investments may either be preventive maintenance tasks, asset enhancements or logistic investments such as spare parts purchases. The two methodological points to investigate in such an issue are: 1. The measure of the profitability of a portfolio of investments 2. The selection and planning of an optimal set of investments 3. The measure of the risk of a portfolio of investments The measure of the profitability of a set of investments in the IPOP tool is synthesised in themore » Net Present Value indicator. The NPV is the sum of the differences of discounted cash flows (direct costs, forced outages...) between the situations with and without a given investment. These cash flows are calculated through a pseudo-Markov reliability model representing independently the components of the industrial asset and the spare parts inventories. The component model has been widely discussed over the years but the spare part model is a new one based on some approximations that will be discussed. This model, referred as the NPV function, takes for input an investments portfolio and gives its NPV. The second issue is to optimize the NPV. If all investments were independent, this optimization would be an easy calculation, unfortunately there are two sources of dependency. The first one is introduced by the spare part model, as if components are indeed independent in their reliability model, the fact that several components use the same inventory induces a dependency. The second dependency comes from economic, technical or logistic constraints, such as a global maintenance budget limit or a safety requirement limiting the residual risk of failure of a component or group of component, making the aggregation of individual optimum not necessary feasible. The algorithm used to solve such a difficult optimization problem is a genetic algorithm. After a description of the features of the software a test case is presented showing the influence of the optimization algorithm parameters on its efficiency to find an optimal investments planning. (authors)« less

Guess LOD approach: sufficient conditions for robustness.

PubMed

Williamson, J A; Amos, C I

1995-01-01

Analysis of genetic linkage between a disease and a marker locus requires specifying a genetic model describing both the inheritance pattern and the gene frequencies of the marker and trait loci. Misspecification of the genetic model is likely for etiologically complex diseases. In previous work we have shown through analytic studies that misspecifying the genetic model for disease inheritance does not lead to excess false-positive evidence for genetic linkage provided the genetic marker alleles of all pedigree members are known, or can be inferred without bias from the data. Here, under various selection or ascertainment schemes we extend these previous results to situations in which the genetic model for the marker locus may be incorrect. We provide sufficient conditions for the asymptotic unbiased estimation of the recombination fraction under the null hypothesis of no linkage, and also conditions for the limiting distribution of the likelihood ratio test for no linkage to be chi-squared. Through simulation studies we document some situations under which asymptotic bias can result when the genetic model is misspecified. Among those situations under which an excess of false-positive evidence for genetic linkage can be generated, the most common is failure to provide accurate estimates of the marker allele frequencies. We show that in most cases false-positive evidence for genetic linkage is unlikely to result solely from the misspecification of the genetic model for disease or trait inheritance.

Heritability of somatotype components from early adolescence into young adulthood: a multivariate analysis on a longitudinal twin study.

PubMed

Peeters, M W; Thomis, M A; Claessens, A L; Loos, R J F; Maes, H H M; Lysens, R; Vanden Eynde, B; Vlietinck, R; Beunen, G

2003-01-01

Several studies with different designs have attempted to estimate the heritability of somatotype components. However they often ignore the covariation between the three components as well as possible sex and age effects. Shared environmental factors are not always controlled for. This study explores the pattern of genetic and environmental determination of the variation in Heath-Carter somatotype components from early adolescence into young adulthood. Data from the Leuven Longitudinal Twin Study, a longitudinal sample of Belgian same-aged twins followed from 10 to 18 years (n = 105 pairs, equally divided over five zygosity groups), is entered into a multivariate path analysis. Thus the covariation between the somatotype components is taken into account, gender heterogeneity can be tested, common environmental influences can be distinguished from genetic effects and age effects are controlled for. Heritability estimates from 10 to 18 years range from 0.21 to 0.88, 0.46 to 0.76 and 0.16 to 0.73 for endomorphy, mesomorphy and ectomorphy in boys. In girls, heritability estimates range from 0.76 to 0.89, 0.36 to 0.57 and 0.57 to 0.76 for the respective somatotype components. Sex differences are significant from 14 years onwards. More than half of the variance in all somatotype components for both sexes at all time points is explained by factors the three components have in common. The finding of substantial genetic influence on the variability of somatotype components is further supported. The need to consider somatotype as a whole is stressed as well as the need for sex- and perhaps age-specific analyses. Further multivariate analyses are needed to confirm the present findings.

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.

Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem[OPEN

PubMed Central

Eshbaugh, Robert; Chen, Fang; Atwell, Susana

2017-01-01

To respond to pathogen attack, selection and associated evolution has led to the creation of plant immune system that are a highly effective and inducible defense system. Central to this system are the plant defense hormones jasmonic acid (JA) and salicylic acid (SA) and crosstalk between the two, which may play an important role in defense responses to specific pathogens or even genotypes. Here, we used the Arabidopsis thaliana-Botrytis cinerea pathosystem to test how the host’s defense system functions against genetic variation in a pathogen. We measured defense-related phenotypes and transcriptomic responses in Arabidopsis wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1, individually challenged with 96 diverse B. cinerea isolates. Those data showed genetic variation in the pathogen influences on all components within the plant defense system at the transcriptional level. We identified four gene coexpression networks and two vectors of defense variation triggered by genetic variation in B. cinerea. This showed that the JA and SA signaling pathways functioned to constrain/canalize the range of virulence in the pathogen population, but the underlying transcriptomic response was highly plastic. These data showed that plants utilize major defense hormone pathways to buffer disease resistance, but not the metabolic or transcriptional responses to genetic variation within a pathogen. PMID:29042403

Six quantitative trait loci influence task thresholds for hygienic behaviour in honeybees (Apis mellifera).

PubMed

Oxley, Peter R; Spivak, Marla; Oldroyd, Benjamin P

2010-04-01

Honeybee hygienic behaviour provides colonies with protection from many pathogens and is an important model system of the genetics of a complex behaviour. It is a textbook example of complex behaviour under simple genetic control: hygienic behaviour consists of two components--uncapping a diseased brood cell, followed by removal of the contents--each of which are thought to be modulated independently by a few loci of medium to large effect. A worker's genetic propensity to engage in hygienic tasks affects the intensity of the stimulus required before she initiates the behaviour. Genetic diversity within colonies leads to task specialization among workers, with a minority of workers performing the majority of nest-cleaning tasks. We identify three quantitative trait loci that influence the likelihood that workers will engage in hygienic behaviour and account for up to 30% of the phenotypic variability in hygienic behaviour in our population. Furthermore, we identify two loci that influence the likelihood that a worker will perform uncapping behaviour only, and one locus that influences removal behaviour. We report the first candidate genes associated with engaging in hygienic behaviour, including four genes involved in olfaction, learning and social behaviour, and one gene involved in circadian locomotion. These candidates will allow molecular characterization of this distinctive behavioural mode of disease resistance, as well as providing the opportunity for marker-assisted selection for this commercially significant trait.

Contrasting patterns of variation in weedy traits and unique crop features in divergent populations of US weedy rice (Oryza sativa sp.) in Arkansas and California.

PubMed

Kanapeckas, Kimberly L; Tseng, Te-Ming; Vigueira, Cynthia C; Ortiz, Aida; Bridges, William C; Burgos, Nilda R; Fischer, Albert J; Lawton-Rauh, Amy

2018-06-01

Weed evolution from crops involves changes in key traits, but it is unclear how genetic and phenotypic variation contribute to weed diversification and productivity. Weedy rice is a conspecific weed of rice (Oryza sativa) worldwide. We used principal component analysis and hierarchical clustering to understand how morphologically and evolutionarily distinct US weedy rice populations persist in rice fields in different locations under contrasting management regimes. Further, we used a representative subset of 15 sequence-tagged site fragments of expressed genes from global Oryza to assess genome-wide sequence variation among populations. Crop hull color and crop-overlapping maturity dates plus awns, seed (panicle) shattering (> 50%), pigmented pericarp and stature variation (30.2% of total phenotypic variance) characterize genetically less diverse California weedy rice. By contrast, wild-like hull color, seed shattering (> 50%) and stature differences (55.8% of total phenotypic variance) typify genetically diverse weedy rice ecotypes in Arkansas. Recent de-domestication of weedy species - such as in California weedy rice - can involve trait combinations indistinguishable from the crop. This underscores the need for strict seed certification with genetic monitoring and proactive field inspection to prevent proliferation of weedy plant types. In established populations, tillage practice may affect weed diversity and persistence over time. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Leveraging premalignant biology for immune-based cancer prevention.

PubMed

Spira, Avrum; Disis, Mary L; Schiller, John T; Vilar, Eduardo; Rebbeck, Timothy R; Bejar, Rafael; Ideker, Trey; Arts, Janine; Yurgelun, Matthew B; Mesirov, Jill P; Rao, Anjana; Garber, Judy; Jaffee, Elizabeth M; Lippman, Scott M

2016-09-27

Prevention is an essential component of cancer eradication. Next-generation sequencing of cancer genomes and epigenomes has defined large numbers of driver mutations and molecular subgroups, leading to therapeutic advances. By comparison, there is a relative paucity of such knowledge in premalignant neoplasia, which inherently limits the potential to develop precision prevention strategies. Studies on the interplay between germ-line and somatic events have elucidated genetic processes underlying premalignant progression and preventive targets. Emerging data hint at the immune system's ability to intercept premalignancy and prevent cancer. Genetically engineered mouse models have identified mechanisms by which genetic drivers and other somatic alterations recruit inflammatory cells and induce changes in normal cells to create and interact with the premalignant tumor microenvironment to promote oncogenesis and immune evasion. These studies are currently limited to only a few lesion types and patients. In this Perspective, we advocate a large-scale collaborative effort to systematically map the biology of premalignancy and the surrounding cellular response. By bringing together scientists from diverse disciplines (e.g., biochemistry, omics, and computational biology; microbiology, immunology, and medical genetics; engineering, imaging, and synthetic chemistry; and implementation science), we can drive a concerted effort focused on cancer vaccines to reprogram the immune response to prevent, detect, and reject premalignancy. Lynch syndrome, clonal hematopoiesis, and cervical intraepithelial neoplasia which also serve as models for inherited syndromes, blood, and viral premalignancies, are ideal scenarios in which to launch this initiative.

Genetic Deficiency in Neprilysin or Its Pharmacological Inhibition Initiate Excessive Stress-Induced Alcohol Consumption in Mice

PubMed Central

Gembardt, Florian; Becker, Axel; Schultheiss, Heinz-Peter; Siems, Wolf-Eberhard; Walther, Thomas

2012-01-01

Both acquired and inherited genetic factors contribute to excessive alcohol consumption and the corresponding development of addiction. Here we show that the genetic deficiency in neprilysin [NEP] did not change the kinetics of alcohol degradation but led to an increase in alcohol intake in mice in a 2-bottle-free-choice paradigm after one single stress stimulus (intruder). A repetition of such stress led to an irreversible elevated alcohol consumption. This phenomenon could be also observed in wild-type mice receiving an orally active NEP inhibitor. We therefore elucidated the stress behavior in NEP-deficient mice. In an Elevated Plus Maze, NEP knockouts crossed more often the area between the arms, implicating a significant stronger stress response. Furthermore, such animals showed a decreased locomotor activity under intense light in a locomotor activity test, identifying such mice to be more responsive in aversive situations than their wild-type controls. Since the reduction in NEP activity itself does not lead to significant signs of an altered alcohol preference in mice but requires an environmental stimulus, our findings build a bridge between stress components and genetic factors in the development of alcoholism. Therefore, targeting NEP activity might be a very attractive approach for the treatment of alcohol abuse in a society with increasing social and financial stress. PMID:23185571

Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem.

PubMed

Zhang, Wei; Corwin, Jason A; Copeland, Daniel; Feusier, Julie; Eshbaugh, Robert; Chen, Fang; Atwell, Susana; Kliebenstein, Daniel J

2017-11-01

To respond to pathogen attack, selection and associated evolution has led to the creation of plant immune system that are a highly effective and inducible defense system. Central to this system are the plant defense hormones jasmonic acid (JA) and salicylic acid (SA) and crosstalk between the two, which may play an important role in defense responses to specific pathogens or even genotypes. Here, we used the Arabidopsis thaliana - Botrytis cinerea pathosystem to test how the host's defense system functions against genetic variation in a pathogen. We measured defense-related phenotypes and transcriptomic responses in Arabidopsis wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1 , individually challenged with 96 diverse B. cinerea isolates. Those data showed genetic variation in the pathogen influences on all components within the plant defense system at the transcriptional level. We identified four gene coexpression networks and two vectors of defense variation triggered by genetic variation in B. cinerea This showed that the JA and SA signaling pathways functioned to constrain/canalize the range of virulence in the pathogen population, but the underlying transcriptomic response was highly plastic. These data showed that plants utilize major defense hormone pathways to buffer disease resistance, but not the metabolic or transcriptional responses to genetic variation within a pathogen. © 2017 American Society of Plant Biologists. All rights reserved.

Using parallel factor analysis modeling (PARAFAC) and self-organizing maps to track senescence-induced patterns in leaf litter leachate

NASA Astrophysics Data System (ADS)

Wheeler, K. I.; Levia, D. F., Jr.; Hudson, J. E.

2017-12-01

As trees undergo autumnal processes such as resorption, senescence, and leaf abscission, the dissolved organic matter (DOM) contribution of leaf litter leachate to streams changes. However, little research has investigated how the fluorescent DOM (FDOM) changes throughout the autumn and how this differs inter- and intraspecifically. Two of the major impacts of global climate change on forested ecosystems include altering phenology and causing forest community species and subspecies composition restructuring. We examined changes in FDOM in leachate from American beech (Fagus grandifolia Ehrh.) leaves in Maryland, Rhode Island, Vermont, and North Carolina and yellow poplar (Liriodendron tulipifera L.) leaves from Maryland throughout three different phenophases: green, senescing, and freshly abscissed. Beech leaves from Maryland and Rhode Island have previously been identified as belonging to the same distinct genetic cluster and beech trees from Vermont and the study site in North Carolina from the other. FDOM in samples was characterized using excitation-emission matrices (EEMs) and a six-component parallel factor analysis (PARAFAC) model was created to identify components. Self-organizing maps (SOMs) were used to visualize variation and patterns in the PARAFAC component proportions of the leachate samples. Phenophase and species had the greatest influence on determining where a sample mapped on the SOM when compared to genetic clusters and geographic origin. Throughout senescence, FDOM from all the trees transitioned from more protein-like components to more humic-like ones. Percent greenness of the sampled leaves and the proportion of the tyrosine-like component 1 were found to significantly differ between the two genetic beech clusters. This suggests possible differences in photosynthesis and resorption between the two genetic clusters of beech. The use of SOMs to visualize differences in patterns of senescence between the different species and genetic populations proved to be useful in ways that other multivariate analysis techniques lack.

Recent Historical Migrations Have Shaped the Gene Pool of Arabs and Berbers in North Africa

PubMed Central

Arauna, Lara R.; Mendoza-Revilla, Javier; Mas-Sandoval, Alex; Izaabel, Hassan; Bekada, Asmahan; Benhamamouch, Soraya; Fadhlaoui-Zid, Karima; Zalloua, Pierre; Hellenthal, Garrett

2017-01-01

North Africa is characterized by its diverse cultural and linguistic groups and its genetic heterogeneity. Genomic data has shown an amalgam of components mixed since pre-Holocean times. Though no differences have been found in uniparental and classical markers between Berbers and Arabs, the two main ethnic groups in the region, the scanty genomic data available have highlighted the singularity of Berbers. We characterize the genetic heterogeneity of North African groups, focusing on the putative differences of Berbers and Arabs, and estimate migration dates. We analyze genome-wide autosomal data in five Berber and six Arab groups, and compare them to Middle Easterns, sub-Saharans, and Europeans. Haplotype-based methods show a lack of correlation between geographical and genetic populations, and a high degree of genetic heterogeneity, without strong differences between Berbers and Arabs. Berbers enclose genetically diverse groups, from isolated endogamous groups with high autochthonous component frequencies, large homozygosity runs and low effective population sizes, to admixed groups with high frequencies of sub-Saharan and Middle Eastern components. Admixture time estimates show a complex pattern of recent historical migrations, with a peak around the 7th century C.E. coincident with the Arabization of the region; sub-Saharan migrations since the 1st century B.C. in agreement with Roman slave trade; and a strong migration in the 17th century C.E., coincident with a huge impact of the trans-Atlantic and trans-Saharan trade of sub-Saharan slaves in the Modern Era. The genetic complexity found should be taken into account when selecting reference groups in population genetics and biomedical studies. PMID:27744413

Reflections on changeability versus stability of health-related quality of life: distinguishing between its environmental and genetic components

PubMed Central

Sprangers, Mirjam AG; Schwartz, Carolyn E

2008-01-01

The field of health-related quality of life (HRQOL) could benefit from a broadening of perspectives to include recent advancements in research on adaptation, positive psychology, and genetics. These advances shed new light on the extent to which HRQOL is changeable or fixed. The objective of this paper is to integrate these insights and to discuss their implications for HRQOL research. We describe the Hedonic Treadmill theory, which asserts that positive events only temporarily affect happiness since people quickly return to hedonic neutrality. New empirical evidence suggests important revisions of this theory, providing a more optimistic picture of the possibility for change. Advances in positive psychology show that relatively simple interventions have the power to induce a sustainable increase in levels of happiness. Finally, a small but growing number of studies have found independent genetic influences in well-being, life satisfaction, perceived health, and even HRQOL. Given the increasing empirical evidence that HRQOL can be sustainably enhanced and is in part genetically determined, it may be useful to consider HRQOL as a concept that has state (environmental) and trait (genetic) components. This distinction will allow us to explore new pathways of improving theory, methods, and clinical practice. The overarching novel questions concern the extent to which HRQOL components are environmentally or genetically determined, and which factors lead to lasting improvement. This distinction begs for new research approaches, such as time-sampling techniques and interdisciplinary research investigating the genetic variants of HRQOL. Distinguishing between those aspects that are amenable to change from those that are relatively fixed and stable will help better target specific support interventions. PMID:18976504

Recent Historical Migrations Have Shaped the Gene Pool of Arabs and Berbers in North Africa.

PubMed

Arauna, Lara R; Mendoza-Revilla, Javier; Mas-Sandoval, Alex; Izaabel, Hassan; Bekada, Asmahan; Benhamamouch, Soraya; Fadhlaoui-Zid, Karima; Zalloua, Pierre; Hellenthal, Garrett; Comas, David

2017-02-01

North Africa is characterized by its diverse cultural and linguistic groups and its genetic heterogeneity. Genomic data has shown an amalgam of components mixed since pre-Holocean times. Though no differences have been found in uniparental and classical markers between Berbers and Arabs, the two main ethnic groups in the region, the scanty genomic data available have highlighted the singularity of Berbers. We characterize the genetic heterogeneity of North African groups, focusing on the putative differences of Berbers and Arabs, and estimate migration dates. We analyze genome-wide autosomal data in five Berber and six Arab groups, and compare them to Middle Easterns, sub-Saharans, and Europeans. Haplotype-based methods show a lack of correlation between geographical and genetic populations, and a high degree of genetic heterogeneity, without strong differences between Berbers and Arabs. Berbers enclose genetically diverse groups, from isolated endogamous groups with high autochthonous component frequencies, large homozygosity runs and low effective population sizes, to admixed groups with high frequencies of sub-Saharan and Middle Eastern components. Admixture time estimates show a complex pattern of recent historical migrations, with a peak around the 7th century C.E. coincident with the Arabization of the region; sub-Saharan migrations since the 1st century B.C. in agreement with Roman slave trade; and a strong migration in the 17th century C.E., coincident with a huge impact of the trans-Atlantic and trans-Saharan trade of sub-Saharan slaves in the Modern Era. The genetic complexity found should be taken into account when selecting reference groups in population genetics and biomedical studies. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Are Endophenotypes Based on Measures of Executive Functions Useful for Molecular Genetic Studies of ADHD?

ERIC Educational Resources Information Center

Doyle, Alysa E.; Faraone, Stephen V.; Seidman, Larry J.; Willcutt, Erik G.; Nigg, Joel T.; Waldman, Irwin D.; Pennington, Bruce F.; Peart, Joanne; Biederman, Joseph

2005-01-01

Background: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or…

Genetic and environmental effects on myopia development and progression

PubMed Central

Goldschmidt, E; Jacobsen, N

2014-01-01

This review aims at elucidating the interaction between genetic and environmental factors in the aetiology of primarily low myopia. Genetics greatly influence the growth of the eye, but the fine correlation between the components of refraction for the eye to become emmetrope is affected by environmental factors such as education, metabolism, physical activity, and outdoor activity. PMID:24357837

Genetic Model Fitting in IQ, Assortative Mating & Components of IQ Variance.

ERIC Educational Resources Information Center

Capron, Christiane; Vetta, Adrian R.; Vetta, Atam

1998-01-01

The biometrical school of scientists who fit models to IQ data traces their intellectual ancestry to R. Fisher (1918), but their genetic models have no predictive value. Fisher himself was critical of the concept of heritability, because assortative mating, such as for IQ, introduces complexities into the study of a genetic trait. (SLD)

Achieving World-Class Schools: Mastering School Improvement Using a Genetic Model.

ERIC Educational Resources Information Center

Kimmelman, Paul L.; Kroeze, David J.

In providing its program for education reform, this book uses, as an analogy, the genetic model taken from the Human Genome project. In the first part, "Theoretical Underpinnings," the book explains why a genetic model can be used to improve school systems; describes the critical components of a world-class school system; and details the…

Form Follows Function: A Model for Clinical Supervision of Genetic Counseling Students.

PubMed

Wherley, Colleen; Veach, Patricia McCarthy; Martyr, Meredith A; LeRoy, Bonnie S

2015-10-01

Supervision plays a vital role in genetic counselor training, yet models describing genetic counseling supervision processes and outcomes are lacking. This paper describes a proposed supervision model intended to provide a framework to promote comprehensive and consistent clinical supervision training for genetic counseling students. Based on the principle "form follows function," the model reflects and reinforces McCarthy Veach et al.'s empirically derived model of genetic counseling practice - the "Reciprocal Engagement Model" (REM). The REM consists of mutually interactive educational, relational, and psychosocial components. The Reciprocal Engagement Model of Supervision (REM-S) has similar components and corresponding tenets, goals, and outcomes. The 5 REM-S tenets are: Learning and applying genetic information are key; Relationship is integral to genetic counseling supervision; Student autonomy must be supported; Students are capable; and Student emotions matter. The REM-S outcomes are: Student understands and applies information to independently provide effective services, develop professionally, and engage in self-reflective practice. The 16 REM-S goals are informed by the REM of genetic counseling practice and supported by prior literature. A review of models in medicine and psychology confirms the REM-S contains supervision elements common in healthcare fields, while remaining unique to genetic counseling. The REM-S shows promise for enhancing genetic counselor supervision training and practice and for promoting research on clinical supervision. The REM-S is presented in detail along with specific examples and training and research suggestions.

Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder.

PubMed

Sun, Xiao; Wu, Zhaomin; Cao, Qingjiu; Qian, Ying; Liu, Yong; Yang, Binrang; Chang, Suhua; Yang, Li; Wang, Yufeng

2018-05-16

As a childhood-onset psychiatric disorder, attention deficit hyperactivity disorder (ADHD) is complicated by phenotypic and genetic heterogeneity. Lifelong executive function deficits in ADHD are described in many literatures and have been proposed as endophenotypes of ADHD. However, its genetic basis is still elusive. In this study, we performed a genome-wide association study of executive function, rated with Behavioral Rating Inventory of Executive Function (BRIEF), in ADHD children. We identified one significant variant (rs852004, P = 2.51e-08) for the overall score of BRIEF. The association analyses for each component of executive function found this locus was more associated with inhibit and monitor components. Further principle component analysis and confirmatory factor analysis provided an ADHD-specific executive function pattern including inhibit and monitor factors. SNP rs852004 was mainly associated with the Behavioral Regulation factor. Meanwhile, we found the significant locus was associated with ADHD symptom. The Behavioral Regulation factor mediated its effect on ADHD symptom. Functional magnetic resonance imaging (fMRI) analyses further showed evidence that this variant affected the activity of inhibition control related brain regions. It provided new insights for the genetic basis of executive function in ADHD.

Metabolomic profiling and genomic analysis of wheat aneuploid lines to identify genes controlling biochemical pathways in mature grain.

PubMed

Francki, Michael G; Hayton, Sarah; Gummer, Joel P A; Rawlinson, Catherine; Trengove, Robert D

2016-02-01

Metabolomics is becoming an increasingly important tool in plant genomics to decipher the function of genes controlling biochemical pathways responsible for trait variation. Although theoretical models can integrate genes and metabolites for trait variation, biological networks require validation using appropriate experimental genetic systems. In this study, we applied an untargeted metabolite analysis to mature grain of wheat homoeologous group 3 ditelosomic lines, selected compounds that showed significant variation between wheat lines Chinese Spring and at least one ditelosomic line, tracked the genes encoding enzymes of their biochemical pathway using the wheat genome survey sequence and determined the genetic components underlying metabolite variation. A total of 412 analytes were resolved in the wheat grain metabolome, and principal component analysis indicated significant differences in metabolite profiles between Chinese Spring and each ditelosomic lines. The grain metabolome identified 55 compounds positively matched against a mass spectral library where the majority showed significant differences between Chinese Spring and at least one ditelosomic line. Trehalose and branched-chain amino acids were selected for detailed investigation, and it was expected that if genes encoding enzymes directly related to their biochemical pathways were located on homoeologous group 3 chromosomes, then corresponding ditelosomic lines would have a significant reduction in metabolites compared with Chinese Spring. Although a proportion showed a reduction, some lines showed significant increases in metabolites, indicating that genes directly and indirectly involved in biosynthetic pathways likely regulate the metabolome. Therefore, this study demonstrated that wheat aneuploid lines are suitable experimental genetic system to validate metabolomics-genomics networks. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Mouse genetics and proteomic analyses demonstrate a critical role for complement in a model of DHRD/ML, an inherited macular degeneration

PubMed Central

Garland, Donita L.; Fernandez-Godino, Rosario; Kaur, Inderjeet; Speicher, Kaye D.; Harnly, James M.; Lambris, John D.; Speicher, David W.; Pierce, Eric A.

2014-01-01

Macular degenerations, inherited and age related, are important causes of vision loss. Human genetic studies have suggested perturbation of the complement system is important in the pathogenesis of age-related macular degeneration. The mechanisms underlying the involvement of the complement system are not understood, although complement and inflammation have been implicated in drusen formation. Drusen are an early clinical hallmark of inherited and age-related forms of macular degeneration. We studied one of the earliest stages of macular degeneration which precedes and leads to the formation of drusen, i.e. the formation of basal deposits. The studies were done using a mouse model of the inherited macular dystrophy Doyne Honeycomb Retinal Dystrophy/Malattia Leventinese (DHRD/ML) which is caused by a p.Arg345Trp mutation in EFEMP1. The hallmark of DHRD/ML is the formation of drusen at an early age, and gene targeted Efemp1R345W/R345W mice develop extensive basal deposits. Proteomic analyses of Bruch's membrane/choroid and Bruch's membrane in the Efemp1R345W/R345W mice indicate that the basal deposits comprise normal extracellular matrix (ECM) components present in abnormal amounts. The proteomic analyses also identified significant changes in proteins with immune-related function, including complement components, in the diseased tissue samples. Genetic ablation of the complement response via generation of Efemp1R345W/R345W:C3−/− double-mutant mice inhibited the formation of basal deposits. The results demonstrate a critical role for the complement system in basal deposit formation, and suggest that complement-mediated recognition of abnormal ECM may participate in basal deposit formation in DHRD/ML and perhaps other macular degenerations. PMID:23943789

Survey of the Heritability and Sparse Architecture of Gene Expression Traits across Human Tissues.

PubMed

Wheeler, Heather E; Shah, Kaanan P; Brenner, Jonathon; Garcia, Tzintzuni; Aquino-Michaels, Keston; Cox, Nancy J; Nicolae, Dan L; Im, Hae Kyung

2016-11-01

Understanding the genetic architecture of gene expression traits is key to elucidating the underlying mechanisms of complex traits. Here, for the first time, we perform a systematic survey of the heritability and the distribution of effect sizes across all representative tissues in the human body. We find that local h2 can be relatively well characterized with 59% of expressed genes showing significant h2 (FDR < 0.1) in the DGN whole blood cohort. However, current sample sizes (n ≤ 922) do not allow us to compute distal h2. Bayesian Sparse Linear Mixed Model (BSLMM) analysis provides strong evidence that the genetic contribution to local expression traits is dominated by a handful of genetic variants rather than by the collective contribution of a large number of variants each of modest size. In other words, the local architecture of gene expression traits is sparse rather than polygenic across all 40 tissues (from DGN and GTEx) examined. This result is confirmed by the sparsity of optimal performing gene expression predictors via elastic net modeling. To further explore the tissue context specificity, we decompose the expression traits into cross-tissue and tissue-specific components using a novel Orthogonal Tissue Decomposition (OTD) approach. Through a series of simulations we show that the cross-tissue and tissue-specific components are identifiable via OTD. Heritability and sparsity estimates of these derived expression phenotypes show similar characteristics to the original traits. Consistent properties relative to prior GTEx multi-tissue analysis results suggest that these traits reflect the expected biology. Finally, we apply this knowledge to develop prediction models of gene expression traits for all tissues. The prediction models, heritability, and prediction performance R2 for original and decomposed expression phenotypes are made publicly available (https://github.com/hakyimlab/PrediXcan).

An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice.

PubMed

Metten, Pamela; Schlumbohm, Jason P; Huang, Lawrence C; Greenberg, Gian D; Hack, Wyatt R; Spence, Stephanie E; Crabbe, John C

2018-05-01

Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes. Published by Elsevier Inc.