Science.gov

Sample records for addition genetic analysis

  1. Product versus additive threshold models for analysis of reproduction outcomes in animal genetics.

    PubMed

    David, I; Bodin, L; Gianola, D; Legarra, A; Manfredi, E; Robert-Granié, C

    2009-08-01

    The phenotypic observation of some reproduction traits (e.g., insemination success, interval from lambing to insemination) is the result of environmental and genetic factors acting on 2 individuals: the male and female involved in a mating couple. In animal genetics, the main approach (called additive model) proposed for studying such traits assumes that the phenotype is linked to a purely additive combination, either on the observed scale for continuous traits or on some underlying scale for discrete traits, of environmental and genetic effects affecting the 2 individuals. Statistical models proposed for studying human fecundability generally consider reproduction outcomes as the product of hypothetical unobservable variables. Taking inspiration from these works, we propose a model (product threshold model) for studying a binary reproduction trait that supposes that the observed phenotype is the product of 2 unobserved phenotypes, 1 for each individual. We developed a Gibbs sampling algorithm for fitting a Bayesian product threshold model including additive genetic effects and showed by simulation that it is feasible and that it provides good estimates of the parameters. We showed that fitting an additive threshold model to data that are simulated under a product threshold model provides biased estimates, especially for individuals with high breeding values. A main advantage of the product threshold model is that, in contrast to the additive model, it provides distinct estimates of fixed effects affecting each of the 2 unobserved phenotypes.

  2. Association analysis of historical bread wheat germplasm using additive genetic covariance of relatives and population structure.

    PubMed

    Crossa, José; Burgueño, Juan; Dreisigacker, Susanne; Vargas, Mateo; Herrera-Foessel, Sybil A; Lillemo, Morten; Singh, Ravi P; Trethowan, Richard; Warburton, Marilyn; Franco, Jorge; Reynolds, Matthew; Crouch, Jonathan H; Ortiz, Rodomiro

    2007-11-01

    Linkage disequilibrium can be used for identifying associations between traits of interest and genetic markers. This study used mapped diversity array technology (DArT) markers to find associations with resistance to stem rust, leaf rust, yellow rust, and powdery mildew, plus grain yield in five historical wheat international multienvironment trials from the International Maize and Wheat Improvement Center (CIMMYT). Two linear mixed models were used to assess marker-trait associations incorporating information on population structure and covariance between relatives. An integrated map containing 813 DArT markers and 831 other markers was constructed. Several linkage disequilibrium clusters bearing multiple host plant resistance genes were found. Most of the associated markers were found in genomic regions where previous reports had found genes or quantitative trait loci (QTL) influencing the same traits, providing an independent validation of this approach. In addition, many new chromosome regions for disease resistance and grain yield were identified in the wheat genome. Phenotyping across up to 60 environments and years allowed modeling of genotype x environment interaction, thereby making possible the identification of markers contributing to both additive and additive x additive interaction effects of traits.

  3. A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease.

    PubMed

    Holmans, Peter; Moskvina, Valentina; Jones, Lesley; Sharma, Manu; Vedernikov, Alexey; Buchel, Finja; Saad, Mohamad; Sadd, Mohamad; Bras, Jose M; Bettella, Francesco; Nicolaou, Nayia; Simón-Sánchez, Javier; Mittag, Florian; Gibbs, J Raphael; Schulte, Claudia; Durr, Alexandra; Guerreiro, Rita; Hernandez, Dena; Brice, Alexis; Stefánsson, Hreinn; Majamaa, Kari; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W; Martinez, Maria; Singleton, Andrew B; Nalls, Michael A; Hardy, John; Morris, Huw R; Williams, Nigel M

    2013-03-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1-2% in people >60 and 3-4% in people >80. Genome-wide association (GWA) studies have now implicated significant evidence for association in at least 18 genomic regions. We have studied a large PD-meta analysis and identified a significant excess of SNPs (P < 1 × 10(-16)) that are associated with PD but fall short of the genome-wide significance threshold. This result was independent of variants at the 18 previously implicated regions and implies the presence of additional polygenic risk alleles. To understand how these loci increase risk of PD, we applied a pathway-based analysis, testing for biological functions that were significantly enriched for genes containing variants associated with PD. Analysing two independent GWA studies, we identified that both had a significant excess in the number of functional categories enriched for PD-associated genes (minimum P = 0.014 and P = 0.006, respectively). Moreover, 58 categories were significantly enriched for associated genes in both GWA studies (P < 0.001), implicating genes involved in the 'regulation of leucocyte/lymphocyte activity' and also 'cytokine-mediated signalling' as conferring an increased susceptibility to PD. These results were unaltered by the exclusion of all 178 genes that were present at the 18 genomic regions previously reported to be strongly associated with PD (including the HLA locus). Our findings, therefore, provide independent support to the strong association signal at the HLA locus and imply that the immune-related genetic susceptibility to PD is likely to be more widespread in the genome than previously appreciated.

  4. Additive and nonadditive genetic variation in avian personality traits.

    PubMed

    van Oers, K; Drent, P J; de Jong, G; van Noordwijk, A J

    2004-11-01

    Individuals of all vertebrate species differ consistently in their reactions to mildly stressful challenges. These typical reactions, described as personalities or coping strategies, have a clear genetic basis, but the structure of their inheritance in natural populations is almost unknown. We carried out a quantitative genetic analysis of two personality traits (exploration and boldness) and the combination of these two traits (early exploratory behaviour). This study was carried out on the lines resulting from a two-directional artificial selection experiment on early exploratory behaviour (EEB) of great tits (Parus major) originating from a wild population. In analyses using the original lines, reciprocal F(1) and reciprocal first backcross generations, additive, dominance, maternal effects ands sex-dependent expression of exploration, boldness and EEB were estimated. Both additive and dominant genetic effects were important determinants of phenotypic variation in exploratory behaviour and boldness. However, no sex-dependent expression was observed in either of these personality traits. These results are discussed with respect to the maintenance of genetic variation in personality traits, and the expected genetic structure of other behavioural and life history traits in general.

  5. Explaining additional genetic variation in complex traits

    PubMed Central

    Robinson, Matthew R.; Wray, Naomi R.; Visscher, Peter M.

    2015-01-01

    Genome-wide association studies (GWAS) have provided valuable insights into the genetic basis of complex traits, discovering >6000 variants associated with >500 quantitative traits and common complex diseases in humans. The associations identified so far represent only a fraction of those which influence phenotype, as there are likely to be very many variants across the entire frequency spectrum, each of which influences multiple traits, with only a small average contribution to the phenotypic variance. This presents a considerable challenge to further dissection of the remaining unexplained genetic variance within populations, which limits our ability to predict disease risk, identify new drug targets, improve and maintain food sources, and understand natural diversity. This challenge will be met within the current framework through larger sample size, better phenotyping including recording of non-genetic risk factors, focused study designs, and an integration of multiple sources of phenotypic and genetic information. The current evidence supports the application of quantitative genetic approaches, and we argue that one should retain simpler theories until simplicity can be traded for greater explanatory power. PMID:24629526

  6. Unnatural reactive amino acid genetic code additions

    SciTech Connect

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

    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.

  7. Unnatural reactive amino acid genetic code additions

    SciTech Connect

    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.

  8. Unnatural reactive amino acid genetic code additions

    SciTech Connect

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

    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.

  9. Unnatural reactive amino acid genetic code additions

    SciTech Connect

    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.

  10. Efficient Improvement of Silage Additives by Using Genetic Algorithms

    PubMed Central

    Davies, Zoe S.; Gilbert, Richard J.; Merry, Roger J.; Kell, Douglas B.; Theodorou, Michael K.; Griffith, Gareth W.

    2000-01-01

    The enormous variety of substances which may be added to forage in order to manipulate and improve the ensilage process presents an empirical, combinatorial optimization problem of great complexity. To investigate the utility of genetic algorithms for designing effective silage additive combinations, a series of small-scale proof of principle silage experiments were performed with fresh ryegrass. Having established that significant biochemical changes occur over an ensilage period as short as 2 days, we performed a series of experiments in which we used 50 silage additive combinations (prepared by using eight bacterial and other additives, each of which was added at six different levels, including zero [i.e., no additive]). The decrease in pH, the increase in lactate concentration, and the free amino acid concentration were measured after 2 days and used to calculate a “fitness” value that indicated the quality of the silage (compared to a control silage made without additives). This analysis also included a “cost” element to account for different total additive levels. In the initial experiment additive levels were selected randomly, but subsequently a genetic algorithm program was used to suggest new additive combinations based on the fitness values determined in the preceding experiments. The result was very efficient selection for silages in which large decreases in pH and high levels of lactate occurred along with low levels of free amino acids. During the series of five experiments, each of which comprised 50 treatments, there was a steady increase in the amount of lactate that accumulated; the best treatment combination was that used in the last experiment, which produced 4.6 times more lactate than the untreated silage. The additive combinations that were found to yield the highest fitness values in the final (fifth) experiment were assessed to determine a range of biochemical and microbiological quality parameters during full-term silage

  11. Efficient improvement of silage additives by using genetic algorithms.

    PubMed

    Davies, Z S; Gilbert, R J; Merry, R J; Kell, D B; Theodorou, M K; Griffith, G W

    2000-04-01

    The enormous variety of substances which may be added to forage in order to manipulate and improve the ensilage process presents an empirical, combinatorial optimization problem of great complexity. To investigate the utility of genetic algorithms for designing effective silage additive combinations, a series of small-scale proof of principle silage experiments were performed with fresh ryegrass. Having established that significant biochemical changes occur over an ensilage period as short as 2 days, we performed a series of experiments in which we used 50 silage additive combinations (prepared by using eight bacterial and other additives, each of which was added at six different levels, including zero [i.e. , no additive]). The decrease in pH, the increase in lactate concentration, and the free amino acid concentration were measured after 2 days and used to calculate a "fitness" value that indicated the quality of the silage (compared to a control silage made without additives). This analysis also included a "cost" element to account for different total additive levels. In the initial experiment additive levels were selected randomly, but subsequently a genetic algorithm program was used to suggest new additive combinations based on the fitness values determined in the preceding experiments. The result was very efficient selection for silages in which large decreases in pH and high levels of lactate occurred along with low levels of free amino acids. During the series of five experiments, each of which comprised 50 treatments, there was a steady increase in the amount of lactate that accumulated; the best treatment combination was that used in the last experiment, which produced 4.6 times more lactate than the untreated silage. The additive combinations that were found to yield the highest fitness values in the final (fifth) experiment were assessed to determine a range of biochemical and microbiological quality parameters during full-term silage fermentation. We

  12. Genetic Analysis of Xenopus tropicalis

    PubMed Central

    Geach, Timothy J.; Stemple, Derek L.; Zimmerman, Lyle B.

    2014-01-01

    The pipid frog Xenopus tropicalis has emerged as a powerful new model system for combining genetic and genomic analysis of tetrapod development with robust embryological, molecular and biochemical assays. Its early development closely resembles that of its well-understood relative X. laevis, from which techniques and reagents can be readily transferred. In contrast to the tetraploid X. laevis, X. tropicalis has a compact diploid genome with strong synteny to those of amniotes. Recently, advances in high-throughput sequencing together with solution-hybridization whole-exome enrichment technology offer powerful strategies for cloning novel mutations as well as reverse genetic identification of sequence lesions in specific genes of interest. Further advantages include the wide range of functional and molecular assays available, the large number of embryos/meioses produced, and the ease of haploid genetics and gynogenesis. The addition of these genetic tools to X. tropicalis provides a uniquely flexible platform for analysis of gene function in vertebrate development. PMID:22956083

  13. Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course.

    PubMed

    Graff, Mariaelisa; Ngwa, Julius S; Workalemahu, Tsegaselassie; Homuth, Georg; Schipf, Sabine; Teumer, Alexander; Völzke, Henry; Wallaschofski, Henri; Abecasis, Goncalo R; Edward, Lakatta; Francesco, Cucca; Sanna, Serena; Scheet, Paul; Schlessinger, David; Sidore, Carlo; Xiao, Xiangjun; Wang, Zhaoming; Chanock, Stephen J; Jacobs, Kevin B; Hayes, Richard B; Hu, Frank; Van Dam, Rob M; Crout, Richard J; Marazita, Mary L; Shaffer, John R; Atwood, Larry D; Fox, Caroline S; Heard-Costa, Nancy L; White, Charles; Choh, Audrey C; Czerwinski, Stefan A; Demerath, Ellen W; Dyer, Thomas D; Towne, Bradford; Amin, Najaf; Oostra, Ben A; Van Duijn, Cornelia M; Zillikens, M Carola; Esko, Tõnu; Nelis, Mari; Nikopensius, Tit; Metspalu, Andres; Strachan, David P; Monda, Keri; Qi, Lu; North, Kari E; Cupples, L Adrienne; Gordon-Larsen, Penny; Berndt, Sonja I

    2013-09-01

    Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10⁻⁸) near FTO (P = 3.72 × 10⁻²³), TMEM18 (P = 3.24 × 10⁻¹⁷), MC4R (P = 4.41 × 10⁻¹⁷), TNNI3K (P = 4.32 × 10⁻¹¹), SEC16B (P = 6.24 × 10⁻⁹), GNPDA2 (P = 1.11 × 10⁻⁸) and POMC (P = 4.94 × 10⁻⁸) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10⁻⁵ after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18-90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different ages.

  14. Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course

    PubMed Central

    Graff, Mariaelisa; Ngwa, Julius S.; Workalemahu, Tsegaselassie; Homuth, Georg; Schipf, Sabine; Teumer, Alexander; Völzke, Henry; Wallaschofski, Henri; Abecasis, Goncalo R.; Edward, Lakatta; Francesco, Cucca; Sanna, Serena; Scheet, Paul; Schlessinger, David; Sidore, Carlo; Xiao, Xiangjun; Wang, Zhaoming; Chanock, Stephen J.; Jacobs, Kevin B.; Hayes, Richard B.; Hu, Frank; Van Dam, Rob M.; Crout, Richard J.; Marazita, Mary L.; Shaffer, John R; Atwood, Larry D.; Fox, Caroline S.; Heard-Costa, Nancy L.; White, Charles; Choh, Audrey C.; Czerwinski, Stefan A.; Demerath, Ellen W.; Dyer, Thomas D.; Towne, Bradford; Amin, Najaf; Oostra, Ben A.; Van Duijn, Cornelia M.; Zillikens, M. Carola; Esko, Tõnu; Nelis, Mari; Nikopensius, Tit; Metspalu, Andres; Strachan, David P.; Monda, Keri; Qi, Lu; North, Kari E.; Cupples, L. Adrienne; Gordon-Larsen, Penny; Berndt, Sonja I.

    2013-01-01

    Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10−8) near FTO (P = 3.72 × 10−23), TMEM18 (P = 3.24 × 10−17), MC4R (P = 4.41 × 10−17), TNNI3K (P = 4.32 × 10−11), SEC16B (P = 6.24 × 10−9), GNPDA2 (P = 1.11 × 10−8) and POMC (P = 4.94 × 10−8) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10−5 after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18–90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different ages. PMID:23669352

  15. The Expression of Additive and Nonadditive Genetic Variation under Stress

    PubMed Central

    Blows, M. W.; Sokolowski, M. B.

    1995-01-01

    Experimental lines of Drosophila melanogaster derived from a natural population, which had been isolated in the laboratory for ~70 generations, were crossed to determine if the expression of additive, dominance and epistatic genetic variation in development time and viability was associated with the environment. No association was found between the level of additive genetic effects and environmental value for either trait, but nonadditive genetic effects increased at both extremes of the environmental range for development time. The expression of high levels of dominance and epistatic genetic variation at environmental extremes may be a general expectation for some traits. The disruption of the epistatic gene complexes in the parental lines resulted in hybrid breakdown toward faster development and there was some indication of hybrid breakdown toward higher viability. A combination of genetic drift and natural selection had therefore resulted in different epistatic gene complexes being selected after ~70 generations from a common genetic base. After crossing, the hybrid populations were observed for 10 generations. Epistasis contributed on average 12 hr in development time. Fluctuating asymmetry in sternopleural bristle number also evolved in the hybrid populations, decreasing by >18% in the first seven generations after hybridization. PMID:7672585

  16. Additional mechanisms conferring genetic susceptibility to Alzheimer’s disease

    PubMed Central

    Calero, Miguel; Gómez-Ramos, Alberto; Calero, Olga; Soriano, Eduardo; Avila, Jesús; Medina, Miguel

    2015-01-01

    Familial Alzheimer’s disease (AD), mostly associated with early onset, is caused by mutations in three genes (APP, PSEN1, and PSEN2) involved in the production of the amyloid β peptide. In contrast, the molecular mechanisms that trigger the most common late onset sporadic AD remain largely unknown. With the implementation of an increasing number of case-control studies and the upcoming of large-scale genome-wide association studies there is a mounting list of genetic risk factors associated with common genetic variants that have been associated with sporadic AD. Besides apolipoprotein E, that presents a strong association with the disease (OR∼4), the rest of these genes have moderate or low degrees of association, with OR ranging from 0.88 to 1.23. Taking together, these genes may account only for a fraction of the attributable AD risk and therefore, rare variants and epistastic gene interactions should be taken into account in order to get the full picture of the genetic risks associated with AD. Here, we review recent whole-exome studies looking for rare variants, somatic brain mutations with a strong association to the disease, and several studies dealing with epistasis as additional mechanisms conferring genetic susceptibility to AD. Altogether, recent evidence underlines the importance of defining molecular and genetic pathways, and networks rather than the contribution of specific genes. PMID:25914626

  17. Additive genetic contribution to symptom dimensions in major depressive disorder.

    PubMed

    Pearson, Rahel; Palmer, Rohan H C; Brick, Leslie A; McGeary, John E; Knopik, Valerie S; Beevers, Christopher G

    2016-05-01

    Major depressive disorder (MDD) is a phenotypically heterogeneous disorder with a complex genetic architecture. In this study, genomic-relatedness-matrix restricted maximum-likelihood analysis (GREML) was used to investigate the extent to which variance in depression symptoms/symptom dimensions can be explained by variation in common single nucleotide polymorphisms (SNPs) in a sample of individuals with MDD (N = 1,558) who participated in the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. A principal components analysis of items from the Hamilton Rating Scale for Depression (HRSD) obtained prior to treatment revealed 4 depression symptom components: (a) appetite, (b) core depression symptoms (e.g., depressed mood, anhedonia), (c) insomnia, and (d) anxiety. These symptom dimensions were associated with SNP-based heritability (hSNP2) estimates of 30%, 14%, 30%, and 5%, respectively. Results indicated that the genetic contribution of common SNPs to depression symptom dimensions were not uniform. Appetite and insomnia symptoms in MDD had a relatively strong genetic contribution whereas the genetic contribution was relatively small for core depression and anxiety symptoms. While in need of replication, these results suggest that future gene discovery efforts may strongly benefit from parsing depression into its constituent parts. (PsycINFO Database Record

  18. Ontogeny of additive and maternal genetic effects: lessons from domestic mammals.

    PubMed

    Wilson, Alastair J; Reale, Denis

    2006-01-01

    Evolution of size and growth depends on heritable variation arising from additive and maternal genetic effects. Levels of heritable (and nonheritable) variation might change over ontogeny, increasing through "variance compounding" or decreasing through "compensatory growth." We test for these processes using a meta-analysis of age-specific weight traits in domestic ungulates. Generally, mean standardized variance components decrease with age, consistent with compensatory growth. Phenotypic convergence among adult sheep occurs through decreasing environmental and maternal genetic variation. Maternal variation similarly declines in cattle. Maternal genetic effects are thus reduced with age (both in absolute and relative terms). Significant trends in heritability (decreasing in cattle, increasing in sheep) result from declining maternal and environmental components rather than from changing additive variation. There was no evidence for increasing standardized variance components. Any compounding must therefore be masked by more important compensatory processes. While extrapolation of these patterns to processes in natural population is difficult, our results highlight the inadequacy of assuming constancy in genetic parameters over ontogeny. Negative covariance between direct and maternal genetic effects was common. Negative correlations with additive and maternal genetic variances indicate that antagonistic pleiotropy (between additive and maternal genetic effects) may maintain genetic variance and limit responses to selection.

  19. Non-additive and additive genetic effects on extraversion in 3314 Dutch adolescent twins and their parents.

    PubMed

    Rettew, David C; Rebollo-Mesa, Irene; Hudziak, James J; Willemsen, Gonneke; Boomsma, Dorret I

    2008-05-01

    The influence of non-additive genetic influences on personality traits has been increasingly reported in adult populations. Less is known, however, with respect to younger samples. In this study, we examine additive and non-additive genetic contributions to the personality trait of extraversion in 1,689 Dutch twin pairs, 1,505 mothers and 1,637 fathers of the twins. The twins were on average 15.5 years (range 12-18 years). To increase statistical power to detect non-additive genetic influences, data on extraversion were also collected in parents and simultaneously analyzed. Genetic modeling procedures incorporating age as a potential modifier of heritability showed significant influences of additive (20-23%) and non-additive genetic factors (31-33%) in addition to unshared environment (46-48%) for adolescents and for their parents. The additive genetic component was slightly and positively related to age. No significant sex differences were found for either extraversion means or for the magnitude of the genetic and environmental influences. There was no evidence of non-random mating for extraversion in the parental generation. Results show that in addition to additive genetic influences, extraversion in adolescents is influenced by non-additive genetic factors.

  20. Comparing GWAS Results of Complex Traits Using Full Genetic Model and Additive Models for Revealing Genetic Architecture

    PubMed Central

    Monir, Md. Mamun; Zhu, Jun

    2017-01-01

    Most of the genome-wide association studies (GWASs) for human complex diseases have ignored dominance, epistasis and ethnic interactions. We conducted comparative GWASs for total cholesterol using full model and additive models, which illustrate the impacts of the ignoring genetic variants on analysis results and demonstrate how genetic effects of multiple loci could differ across different ethnic groups. There were 15 quantitative trait loci with 13 individual loci and 3 pairs of epistasis loci identified by full model, whereas only 14 loci (9 common loci and 5 different loci) identified by multi-loci additive model. Again, 4 full model detected loci were not detected using multi-loci additive model. PLINK-analysis identified two loci and GCTA-analysis detected only one locus with genome-wide significance. Full model identified three previously reported genes as well as several new genes. Bioinformatics analysis showed some new genes are related with cholesterol related chemicals and/or diseases. Analyses of cholesterol data and simulation studies revealed that the full model performs were better than the additive-model performs in terms of detecting power and unbiased estimations of genetic variants of complex traits. PMID:28079101

  1. Genetic Association Analysis of Drusen Progression

    PubMed Central

    Hoffman, Joshua D.; van Grinsven, Mark J. J. P.; Li, Chun; Brantley, Milam; McGrath, Josephine; Agarwal, Anita; Scott, William K.; Schwartz, Stephen G.; Kovach, Jaclyn; Pericak-Vance, Margaret; Sanchez, Clara I.; Haines, Jonathan L.

    2016-01-01

    Purpose Age-related macular degeneration is a common form of vision loss affecting older adults. The etiology of AMD is multifactorial and is influenced by environmental and genetic risk factors. In this study, we examine how 19 common risk variants contribute to drusen progression, a hallmark of AMD pathogenesis. Methods Exome chip data was made available through the International AMD Genomics Consortium (IAMDGC). Drusen quantification was carried out with color fundus photographs using an automated drusen detection and quantification algorithm. A genetic risk score (GRS) was calculated per subject by summing risk allele counts at 19 common genetic risk variants weighted by their respective effect sizes. Pathway analysis of drusen progression was carried out with the software package Pathway Analysis by Randomization Incorporating Structure. Results We observed significant correlation with drusen baseline area and the GRS in the age-related eye disease study (AREDS) dataset (ρ = 0.175, P = 0.006). Measures of association were not statistically significant between drusen progression and the GRS (P = 0.54). Pathway analysis revealed the cell adhesion molecules pathway as the most highly significant pathway associated with drusen progression (corrected P = 0.02). Conclusions In this study, we explored the potential influence of known common AMD genetic risk factors on drusen progression. Our results from the GRS analysis showed association of increasing genetic burden (from 19 AMD associated loci) to baseline drusen load but not drusen progression in the AREDS dataset while pathway analysis suggests additional genetic contributors to AMD risk. PMID:27116550

  2. TOPICAL REVIEW: Integrated genetic analysis microsystems

    NASA Astrophysics Data System (ADS)

    Lagally, Eric T.; Mathies, Richard A.

    2004-12-01

    With the completion of the Human Genome Project and the ongoing DNA sequencing of the genomes of other animals, bacteria, plants and others, a wealth of new information about the genetic composition of organisms has become available. However, as the demand for sequence information grows, so does the workload required both to generate this sequence and to use it for targeted genetic analysis. Microfabricated genetic analysis systems are well poised to assist in the collection and use of these data through increased analysis speed, lower analysis cost and higher parallelism leading to increased assay throughput. In addition, such integrated microsystems may point the way to targeted genetic experiments on single cells and in other areas that are otherwise very difficult. Concomitant with these advantages, such systems, when fully integrated, should be capable of forming portable systems for high-speed in situ analyses, enabling a new standard in disciplines such as clinical chemistry, forensics, biowarfare detection and epidemiology. This review will discuss the various technologies available for genetic analysis on the microscale, and efforts to integrate them to form fully functional robust analysis devices.

  3. Genetic Assessment of Additional Endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study

    PubMed Central

    Greenwood, Tiffany A.; Lazzeroni, Laura C.; Calkins, Monica E.; Freedman, Robert; Green, Michael F.; Gur, Raquel E.; Gur, Ruben C.; Light, Gregory A.; Nuechterlein, Keith H.; Olincy, Ann; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Stone, William S.; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

    2015-01-01

    The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes. Genotyping via a custom array of 1536 SNPs from 94 candidate genes identified associations for CTNNA2, ERBB4, GRID1, GRID2, GRIK3, GRIK4, GRIN2B, NOS1AP, NRG1, and RELN across multiple endophenotypes. An experiment-wide p value of 0.003 suggested that the associations across all SNPs and endophenotypes collectively exceeded chance. Linkage analyses performed using a genome-wide SNP array further identified significant or suggestive linkage for six of the candidate endophenotypes, with several genes of interest located beneath the linkage peaks (e.g., CSMD1, DISC1, DLGAP2, GRIK2, GRIN3A, and SLC6A3). While the partial convergence of the association and linkage likely reflects differences in density of gene coverage provided by the distinct genotyping platforms, it is also likely an indication of the differential contribution of rare and common variants for some genes and methodological differences in detection ability. Still, many of the genes implicated by COGS through endophenotypes have been identified by independent studies of common, rare, and de novo variation in schizophrenia, all converging on a functional genetic network related to glutamatergic neurotransmission that warrants further investigation. PMID:26597662

  4. Genetic Prediction in the Genetic Analysis Workshop 18 Sequencing Data

    PubMed Central

    Ziegler, Andreas; Bohossian, Nora; Diego, Vincent P.; Yao, Chen

    2015-01-01

    High-throughput sequencing data can be used to predict phenotypes from genotypes, and this corresponds to establishing a prognostic model. In extended pedigrees the relatedness of subjects provides additional information so that genetic values, fixed or random genetic components, and heritability can be estimated. At the Genetic Analysis Workshop 18 the working group on genetic prediction dealt with both establishing a prognostic model and, in one contribution, comparing standard logistic regression with robust logistic regression in a sample of unrelated affected or unaffected individuals. Results of both logistic regression approaches were similar. All other contributions to this group used extended family data, in general using the quantitative trait blood pressure. The individual contributions varied in several important aspects, such as the estimation of the kinship matrix and the estimation method. Contributors chose various approaches for model validation, including different versions of cross-validation or within-family validation. Within-family validation included model building in the upper generations and validation in later generations. The choice of the statistical model and the computational algorithm had substantial effects on computation time. If decorrelation approaches were applied, the computational burden was substantially reduced. Some software packages estimated negative eigenvalues, although eigenvalues of correlation matrices should be nonnegative. Most statistical models and software packages have been developed for experimental crosses and planned breeding programs. With their specialized pedigree structures, they are not sufficiently flexible to accommodate the variability of human pedigrees in general, and improved implementations are required. PMID:25112190

  5. Microfluidics for single-cell genetic analysis.

    PubMed

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

    2014-09-07

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

  6. Additive and non-additive genetic components of the jack male life history in Chinook salmon (Oncorhynchus tshawytscha).

    PubMed

    Forest, Adriana R; Semeniuk, Christina A D; Heath, Daniel D; Pitcher, Trevor E

    2016-08-01

    Chinook salmon, Oncorhynchus tshawytscha, exhibit alternative reproductive tactics (ARTs) where males exist in two phenotypes: large "hooknose" males and smaller "jacks" that reach sexual maturity after only 1 year in seawater. The mechanisms that determine "jacking rate"-the rate at which males precociously sexually mature-are known to involve both genetics and differential growth rates, where individuals that become jacks exhibit higher growth earlier in life. The additive genetic components have been studied and it is known that jack sires produce significantly more jack offspring than hooknose sires, and vice versa. The current study was the first to investigate both additive and non-additive genetic components underlying jacking through the use of a full-factorial breeding design using all hooknose sires. The effect of dams and sires descendant from a marker-assisted broodstock program that identified "high performance" and "low performance" lines using growth- and survival-related gene markers was also studied. Finally, the relative growth of jack, hooknose, and female offspring was examined. No significant dam, sire, or interaction effects were observed in this study, and the maternal, additive, and non-additive components underlying jacking were small. Differences in jacking rates in this study were determined by dam performance line, where dams that originated from the low performance line produced significantly more jacks. Jack offspring in this study had a significantly larger body size than both hooknose males and females starting 1 year post-fertilization. This study provides novel information regarding the genetic architecture underlying ARTs in Chinook salmon that could have implications for the aquaculture industry, where jacks are not favoured due to their small body size and poor flesh quality.

  7. Additional EIPC Study Analysis. Final Report

    SciTech Connect

    Hadley, Stanton W; Gotham, Douglas J.; Luciani, Ralph L.

    2014-12-01

    Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations were developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 14 topics was developed for further analysis. This paper brings together the earlier interim reports of the first 13 topics plus one additional topic into a single final report.

  8. Arthritis Genetics Analysis Aids Drug Discovery

    MedlinePlus

    ... Matters NIH Research Matters January 13, 2014 Arthritis Genetics Analysis Aids Drug Discovery An international research team ... may play a role in triggering the disease. Genetic factors are also thought to play a role. ...

  9. The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

    ERIC Educational Resources Information Center

    Miller, Geoffrey F.; Penke, Lars

    2007-01-01

    Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

  10. Microsatellite data analysis for population genetics.

    PubMed

    Kim, Kyung Seok; Sappington, Thomas W

    2013-01-01

    Theories and analytical tools of population genetics have been widely applied for addressing various questions in the fields of ecological genetics, conservation biology, and any context where the role of dispersal or gene flow is important. Underlying much of population genetics is the analysis of variation at selectively neutral marker loci, and microsatellites continue to be a popular choice of marker. In recent decades, software programs to estimate population genetics parameters have been developed at an increasing pace as computational science and theoretical knowledge advance. Numerous population genetics software programs are presently available to analyze microsatellite genotype data, but only a handful are commonly employed for calculating parameters such as genetic variation, genetic structure, patterns of spatial and temporal gene flow, population demography, individual population assignment, and genetic relationships within and between populations. In this chapter, we introduce statistical analyses and relevant population genetic software programs that are commonly employed in the field of population genetics and molecular ecology.

  11. Accounting for additive genetic mutations on litter size in Ripollesa sheep.

    PubMed

    Casellas, J; Caja, G; Piedrafita, J

    2010-04-01

    Little is known about mutational variability in livestock, among which only a few mutations with relatively large effects have been reported. In this manuscript, mutational variability was analyzed in 1,765 litter size records from 404 Ripollesa ewes to characterize the magnitude of this genetic source of variation and check the suitability of including mutational effects in genetic evaluations of this breed. Threshold animal models accounting for additive genetic mutations were preferred to models without mutational contributions, with an average difference in the deviance information criterion of more than 5 units. Moreover, the statistical relevance of the additive genetic mutation term was checked through a Bayes factor approach, which showed that the models with mutational variability were 8.5 to 22.7 times more probable than the others. The mutational heritability (percentage of the phenotypic variance accounted for by mutational variance) was 0.6 or 0.9%, depending on whether genetic dominance effects were accounted for by the analytical model. The inclusion of mutational effects in the genetic model for evaluating litter size in Ripollesa ewes called for some minor modifications in the genetic merit order of the individuals evaluated, which suggested that the continuous uploading of new additive mutations could be taken into account to optimize the selection scheme. This study is the first attempt to estimate mutational variances in a livestock species and thereby contribute to better characterization of the genetic background of productive traits of interest.

  12. [Questions safety and tendency of using genetically modified microorganisms in food, food additives and food derived].

    PubMed

    Khovaev, A A

    2008-01-01

    In this article analysis questions of using genetically modified microorganisms in manufacture food production, present new GMM used in manufacture -food ferments; results of medical biological appraisal/ microbiological and genetic expert examination/ of food, getting by use microorganisms or there producents with indication modern of control methods.

  13. Microsatellite data analysis for population genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Theories and analytical tools of population genetics have been widely applied for addressing various questions in the fields of ecological genetics, conservation biology, and any context where the role of dispersal or gene flow is important. Underlying much of population genetics is the analysis of ...

  14. Estimation of Additive, Dominance, and Imprinting Genetic Variance Using Genomic Data

    PubMed Central

    Lopes, Marcos S.; Bastiaansen, John W. M.; Janss, Luc; Knol, Egbert F.; Bovenhuis, Henk

    2015-01-01

    Traditionally, exploration of genetic variance in humans, plants, and livestock species has been limited mostly to the use of additive effects estimated using pedigree data. However, with the development of dense panels of single-nucleotide polymorphisms (SNPs), the exploration of genetic variation of complex traits is moving from quantifying the resemblance between family members to the dissection of genetic variation at individual loci. With SNPs, we were able to quantify the contribution of additive, dominance, and imprinting variance to the total genetic variance by using a SNP regression method. The method was validated in simulated data and applied to three traits (number of teats, backfat, and lifetime daily gain) in three purebred pig populations. In simulated data, the estimates of additive, dominance, and imprinting variance were very close to the simulated values. In real data, dominance effects account for a substantial proportion of the total genetic variance (up to 44%) for these traits in these populations. The contribution of imprinting to the total phenotypic variance of the evaluated traits was relatively small (1–3%). Our results indicate a strong relationship between additive variance explained per chromosome and chromosome length, which has been described previously for other traits in other species. We also show that a similar linear relationship exists for dominance and imprinting variance. These novel results improve our understanding of the genetic architecture of the evaluated traits and shows promise to apply the SNP regression method to other traits and species, including human diseases. PMID:26438289

  15. The contribution of additive genetic variation to personality variation: heritability of personality.

    PubMed

    Dochtermann, Ned A; Schwab, Tori; Sih, Andrew

    2015-01-07

    Individual animals frequently exhibit repeatable differences from other members of their population, differences now commonly referred to as 'animal personality'. Personality differences can arise, for example, from differences in permanent environmental effects--including parental and epigenetic contributors--and the effect of additive genetic variation. Although several studies have evaluated the heritability of behaviour, less is known about general patterns of heritability and additive genetic variation in animal personality. As overall variation in behaviour includes both the among-individual differences that reflect different personalities and temporary environmental effects, it is possible for personality to be largely genetically influenced even when heritability of behaviour per se is quite low. The relative contribution of additive genetic variation to personality variation can be estimated whenever both repeatability and heritability are estimated for the same data. Using published estimates to address this issue, we found that approximately 52% of animal personality variation was attributable to additive genetic variation. Thus, while the heritability of behaviour is often moderate or low, the heritability of personality is much higher. Our results therefore (i) demonstrate that genetic differences are likely to be a major contributor to variation in animal personality and (ii) support the phenotypic gambit: that evolutionary inferences drawn from repeatability estimates may often be justified.

  16. Genetic algorithm-guided discovery of additive combinations that direct quantum dot assembly.

    PubMed

    Bawazer, Lukmaan A; Ihli, Johannes; Comyn, Timothy P; Critchley, Kevin; Empson, Christopher J; Meldrum, Fiona C

    2015-01-14

    The use of combinations of organic additives to control crystallization, as occurs in biomineralization, is rarely investigated due to the vast potential reaction space. It is demonstrated here that combinatorial approaches led by genetic algorithm heuristics can enable identification of active additive combinations, and four key organic molecules are rapidly identified, which generate highly fluorescent CdS quantum dot superstructures.

  17. GISH analysis of disomic Brassica napus-Crambe abyssinica chromosome addition lines produced by microspore culture from monosomic addition lines.

    PubMed

    Wang, Youping; Sonntag, Karin; Rudloff, Eicke; Wehling, Peter; Snowdon, Rod J

    2006-02-01

    Two Brassica napus-Crambe abyssinica monosomic addition lines (2n=39, AACC plus a single chromosome from C. abyssinca) were obtained from the F(2) progeny of the asymmetric somatic hybrid. The alien chromosome from C. abyssinca in the addition line was clearly distinguished by genomic in situ hybridization (GISH). Twenty-seven microspore-derived plants from the addition lines were obtained. Fourteen seedlings were determined to be diploid plants (2n=38) arising from spontaneous chromosome doubling, while 13 seedlings were confirmed as haploid plants. Doubled haploid plants produced after treatment with colchicine and two disomic chromosome addition lines (2n=40, AACC plus a single pair of homologous chromosomes from C. abyssinca) could again be identified by GISH analysis. The lines are potentially useful for molecular genetic analysis of novel C. abyssinica genes or alleles contributing to traits relevant for oilseed rape (B. napus) breeding.

  18. A Genetic Analysis of Mortality in Pigs

    PubMed Central

    Varona, Luis; Sorensen, Daniel

    2010-01-01

    An analysis of mortality is undertaken in two breeds of pigs: Danish Landrace and Yorkshire. Zero-inflated and standard versions of hierarchical Poisson, binomial, and negative binomial Bayesian models were fitted using Markov chain Monte Carlo (MCMC). The objectives of the study were to investigate whether there is support for genetic variation for mortality and to study the quality of fit and predictive properties of the various models. In both breeds, the model that provided the best fit to the data was the standard binomial hierarchical model. The model that performed best in terms of the ability to predict the distribution of stillbirths was the hierarchical zero-inflated negative binomial model. The best fit of the binomial hierarchical model and of the zero-inflated hierarchical negative binomial model was obtained when genetic variation was included as a parameter. For the hierarchical binomial model, the estimate of the posterior mean of the additive genetic variance (posterior standard deviation in brackets) at the level of the logit of the probability of a stillbirth was 0.173(0.039) in Landrace and 0.202(0.048) in Yorkshire. The implications of these results from a breeding perspective are briefly discussed. PMID:19901070

  19. [Total analysis of organic rubber additives].

    PubMed

    He, Wen-Xuan; Robert, Shanks; You, Ye-Ming

    2010-03-01

    In the present paper, after middle pressure chromatograph separation using both positive phase and reversed-phase conditions, the organic additives in ethylene-propylene rubber were identified by infrared spectrometer. At the same time, by using solid phase extraction column to maintain the main component-fuel oil in organic additves to avoid its interfering with minor compounds, other organic additves were separated and analysed by GC/Ms. In addition, the remaining active compound such as benzoyl peroxide was identified by CC/Ms, through analyzing acetone extract directly. Using the above mentioned techniques, soften agents (fuel oil, plant oil and phthalte), curing agent (benzoylperoxide), vulcanizing accelerators (2-mercaptobenzothiazole, ethyl thiuram and butyl thiuram), and antiagers (2, 6-Di-tert-butyl-4-methyl phenol and styrenated phenol) in ethylene-propylene rubber were identified. Although the technique was established in ethylene-propylene rubber system, it can be used in other rubber system.

  20. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  1. Common genetic variants, acting additively, are a major source of risk for autism

    PubMed Central

    2012-01-01

    Background Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. Methods By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. Results By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Conclusions Our results, when viewed in the context of results from genome

  2. Do Health Professionals Need Additional Competencies for Stratified Cancer Prevention Based on Genetic Risk Profiling?

    PubMed Central

    Chowdhury, Susmita; Henneman, Lidewij; Dent, Tom; Hall, Alison; Burton, Alice; Pharoah, Paul; Pashayan, Nora; Burton, Hilary

    2015-01-01

    There is growing evidence that inclusion of genetic information about known common susceptibility variants may enable population risk-stratification and personalized prevention for common diseases including cancer. This would require the inclusion of genetic testing as an integral part of individual risk assessment of an asymptomatic individual. Front line health professionals would be expected to interact with and assist asymptomatic individuals through the risk stratification process. In that case, additional knowledge and skills may be needed. Current guidelines and frameworks for genetic competencies of non-specialist health professionals place an emphasis on rare inherited genetic diseases. For common diseases, health professionals do use risk assessment tools but such tools currently do not assess genetic susceptibility of individuals. In this article, we compare the skills and knowledge needed by non-genetic health professionals, if risk-stratified prevention is implemented, with existing competence recommendations from the UK, USA and Europe, in order to assess the gaps in current competences. We found that health professionals would benefit from understanding the contribution of common genetic variations in disease risk, the rationale for a risk-stratified prevention pathway, and the implications of using genomic information in risk-assessment and risk management of asymptomatic individuals for common disease prevention. PMID:26068647

  3. Do Health Professionals Need Additional Competencies for Stratified Cancer Prevention Based on Genetic Risk Profiling?

    PubMed

    Chowdhury, Susmita; Henneman, Lidewij; Dent, Tom; Hall, Alison; Burton, Alice; Pharoah, Paul; Pashayan, Nora; Burton, Hilary

    2015-06-09

    There is growing evidence that inclusion of genetic information about known common susceptibility variants may enable population risk-stratification and personalized prevention for common diseases including cancer. This would require the inclusion of genetic testing as an integral part of individual risk assessment of an asymptomatic individual. Front line health professionals would be expected to interact with and assist asymptomatic individuals through the risk stratification process. In that case, additional knowledge and skills may be needed. Current guidelines and frameworks for genetic competencies of non-specialist health professionals place an emphasis on rare inherited genetic diseases. For common diseases, health professionals do use risk assessment tools but such tools currently do not assess genetic susceptibility of individuals. In this article, we compare the skills and knowledge needed by non-genetic health professionals, if risk-stratified prevention is implemented, with existing competence recommendations from the UK, USA and Europe, in order to assess the gaps in current competences. We found that health professionals would benefit from understanding the contribution of common genetic variations in disease risk, the rationale for a risk-stratified prevention pathway, and the implications of using genomic information in risk-assessment and risk management of asymptomatic individuals for common disease prevention.

  4. Additive genetic breeding values correlate with the load of partially deleterious mutations.

    PubMed

    Tomkins, Joseph L; Penrose, Marissa A; Greeff, Johan; LeBas, Natasha R

    2010-05-14

    The mutation-selection-balance model predicts most additive genetic variation to arise from numerous mildly deleterious mutations of small effect. Correspondingly, "good genes" models of sexual selection and recent models for the evolution of sex are built on the assumption that mutational loads and breeding values for fitness-related traits are correlated. In support of this concept, inbreeding depression was negatively genetically correlated with breeding values for traits under natural and sexual selection in the weevil Callosobruchus maculatus. The correlations were stronger in males and strongest for condition. These results confirm the role of existing, partially recessive mutations in maintaining additive genetic variation in outbred populations, reveal the nature of good genes under sexual selection, and show how sexual selection can offset the cost of sex.

  5. Genetic Analysis of Plant Mixtures

    PubMed Central

    Griffing, B.

    1989-01-01

    Plant mixtures are difficult to analyze genetically because of possible interactions between neighboring plants (i.e., between plants in the same biological group). However, a genetic modeling scheme has been devised which, theoretically, can accommodate such interactions. This study was an attempt to put the theoretical modeling procedure to an experimental test. To this end an experimental procedure was devised that generated biological groups from a well defined base population. A cultural system was used which permitted growing plant mixtures in controlled environmental facilities. This allowed the experiment to be conducted over a wide range of temperature and nutrient conditions. Application of the theoretical gene model to the experimental data permitted identification of those classes of gene effects that were responsible for genetic variation exhibited by the mixtures. Adequacy of the genetic modeling description was corroborated by precise prediction of an independent genetic response. The genetic analyses also identified statistically significant temperature-and nutrient-dependent forms of heterosis. It was concluded that the study demonstrated the suitability of the theoretical group gene model for describing complexities inherent in plant mixtures. PMID:17246509

  6. Genetic epidemiology. Approaches to the genetic analysis of rheumatoid arthritis.

    PubMed

    John, S; Worthington, J

    2001-01-01

    The basis of susceptibility to rheumatoid arthritis (RA) is complex, comprising genetic and environmental susceptibility factors. We have reviewed the available approaches to the investigation of the genetic basis of complex diseases and how these are being applied to RA. Affected-sibling-pair methods for nonparametric linkage analysis, linkage-disequilibrium-based approaches, transmission disequilibrium testing, and disease-association studies are discussed. The pros, cons, and limitations of the approaches are considered and are illustrated by examples from the literature about rheumatoid arthritis.

  7. Genetic Analysis of Hyperthermophilic Archaebacterial Phenomena

    DTIC Science & Technology

    1994-02-28

    Sulfolobus acidocaldarius . Prior studies with these organisms were limited to those that could be done in liquid culture. This was a serious limitation...techniques for the study of the extremely hypertherthophiiic archaebacteriwn, Sulfolcbus acidocaldarius . APPROACH: Develop, refine and use genetic...resulted in several major advances in the development and analysis of genetics systems in the extreme thermophilic archaebacterium, Sulfolobus a

  8. Genetic analysis of mechanisms of aging.

    PubMed

    Rose, M R; Archer, M A

    1996-06-01

    A wide range of genetic models with postponed aging are now available, from selected mice and Drosophilia to mutant Caenorhabditis elegans and Saccharomyces cerevisiae. These systems allow efficient testing of alternative mechanistic hypotheses for aging. Genetic analysis is forging stronger connections between particular alleles and susceptibility to particular 'diseases of aging'; for example, two different genes for Alzheimer disease have been identified.

  9. [Chromosome analysis and genetic testing].

    PubMed

    Isobe, Yasushi; Miura, Ikuo

    2014-03-01

    Chromosomal and genetic tests are essential to establish correct diagnoses of the lymphoma. When the tissue examination is planned, these should be done simultaneously with the morphological and immunophenotypic evaluations. Chromosome analyses can identify the genomic alterations of tumor cells. Some chromosome abnormalities define disease subtypes. For example, recurrent 14q32 translocations involving the immunoglobulin heavy chain locus support the diagnosis of B-cell lymphoma, and their translocation partners identify the types. In contrast, genetic testings are performed to confirm the presence of certain abnormalities including gene rearrangements, mutations, amplifications and deletions in each case. These results provide us detailed information for diagnosis, prognosis, and choice of therapy.

  10. Simultaneous Estimation of Additive and Mutational Genetic Variance in an Outbred Population of Drosophila serrata

    PubMed Central

    McGuigan, Katrina; Aguirre, J. David; Blows, Mark W.

    2015-01-01

    How new mutations contribute to genetic variation is a key question in biology. Although the evolutionary fate of an allele is largely determined by its heterozygous effect, most estimates of mutational variance and mutational effects derive from highly inbred lines, where new mutations are present in homozygous form. In an attempt to overcome this limitation, middle-class neighborhood (MCN) experiments have been used to assess the fitness effect of new mutations in heterozygous form. However, because MCN populations harbor substantial standing genetic variance, estimates of mutational variance have not typically been available from such experiments. Here we employ a modification of the animal model to analyze data from 22 generations of Drosophila serrata bred in an MCN design. Mutational heritability, measured for eight cuticular hydrocarbons, 10 wing-shape traits, and wing size in this outbred genetic background, ranged from 0.0006 to 0.006 (with one exception), a similar range to that reported from studies employing inbred lines. Simultaneously partitioning the additive and mutational variance in the same outbred population allowed us to quantitatively test the ability of mutation-selection balance models to explain the observed levels of additive and mutational genetic variance. The Gaussian allelic approximation and house-of-cards models, which assume real stabilizing selection on single traits, both overestimated the genetic variance maintained at equilibrium, but the house-of-cards model was a closer fit to the data. This analytical approach has the potential to be broadly applied, expanding our understanding of the dynamics of genetic variance in natural populations. PMID:26384357

  11. High volume molecular genetic identification of single nucleotide polymorphisms using Genetic Bit Analysis Application to human genetic diagnosis

    SciTech Connect

    Boyce-Jacino, M.T.; Reynolds, J.; Nikiforov, T.

    1994-09-01

    The most common type of genetic disease-associated mutation is the single nucleotide polymorphism (SNP). Because most genetic diseases can be caused by multiple SNPs in the same gene, effective routine diagnosis of complex genetic diseases is dependent on a simple and reliable method of interrogating SNP sites. Molecular Tool`s solid phase assay capable of direct genotyping (single base sequencing) of SNP sites, Genetic Bit Analysis (GBA), involves hybridization-capture of a single-stranded PCR product to a sequence-specific, microtiter plate-bound oligonucleotide primer. The captured PCR product then acts as template for single-base extension of the capture primer across the polymorphic site, enabling direct determination of the base composition of the polymorphism through a simple colormetric assay. Genotyping in a high volume, semi-automated, processing system with a current capacity of 100 SNP interrogations per technician per day enables the screening of candidate mutations rapidly and cost-effectively, critically important to comprehensive genetic diagnosis. Using this gel-free technology, we have developed prototype diagnostic tests for CFTR and ApoE polymorphisms which enable direct sequencing of the polymorphic base at each site of interest. Routine clinical diagnosis of genetically complex diseases such as cystic fibrosis is dependent on this combination of robust biochemistry and simple format. Additionally, the ability to transfer the format and biochemistry to any disease gene of interest enables the broad application of this technology to clinical diagnostics, especially for genetically complex diseases.

  12. Pattern of inbreeding depression, condition dependence, and additive genetic variance in Trinidadian guppy ejaculate traits

    PubMed Central

    Gasparini, Clelia; Devigili, Alessandro; Dosselli, Ryan; Pilastro, Andrea

    2013-01-01

    In polyandrous species, a male's reproductive success depends on his fertilization capability and traits enhancing competitive fertilization success will be under strong, directional selection. This leads to the prediction that these traits should show stronger condition dependence and larger genetic variance than other traits subject to weaker or stabilizing selection. While empirical evidence of condition dependence in postcopulatory traits is increasing, the comparison between sexually selected and ‘control’ traits is often based on untested assumption concerning the different strength of selection acting on these traits. Furthermore, information on selection in the past is essential, as both condition dependence and genetic variance of a trait are likely to be influenced by the pattern of selection acting historically on it. Using the guppy (Poecilia reticulata), a livebearing fish with high levels of multiple paternity, we performed three independent experiments on three ejaculate quality traits, sperm number, velocity, and size, which have been previously shown to be subject to strong, intermediate, and weak directional postcopulatory selection, respectively. First, we conducted an inbreeding experiment to determine the pattern of selection in the past. Second, we used a diet restriction experiment to estimate their level of condition dependence. Third, we used a half-sib/full-sib mating design to estimate the coefficients of additive genetic variance (CVA) underlying these traits. Additionally, using a simulated predator evasion test, we showed that both inbreeding and diet restriction significantly reduced condition. According to predictions, sperm number showed higher inbreeding depression, stronger condition dependence, and larger CVA than sperm velocity and sperm size. The lack of significant genetic correlation between sperm number and velocity suggests that the former may respond to selection independently one from other ejaculate quality traits

  13. Genetic analysis of Vibrio parahaemolyticus intestinal colonization

    PubMed Central

    Hubbard, Troy P.; Chao, Michael C.; Abel, Sören; Blondel, Carlos J.; Abel zur Wiesch, Pia; Zhou, Xiaohui; Davis, Brigid M.; Waldor, Matthew K.

    2016-01-01

    Vibrio parahaemolyticus is the most common cause of seafood-borne gastroenteritis worldwide and a blight on global aquaculture. This organism requires a horizontally acquired type III secretion system (T3SS2) to infect the small intestine, but knowledge of additional factors that underlie V. parahaemolyticus pathogenicity is limited. We used transposon-insertion sequencing to screen for genes that contribute to viability of V. parahaemolyticus in vitro and in the mammalian intestine. Our analysis enumerated and controlled for the host infection bottleneck, enabling robust assessment of genetic contributions to in vivo fitness. We identified genes that contribute to V. parahaemolyticus colonization of the intestine independent of known virulence mechanisms in addition to uncharacterized components of T3SS2. Our study revealed that toxR, an ancestral locus in Vibrio species, is required for V. parahaemolyticus fitness in vivo and for induction of T3SS2 gene expression. The regulatory mechanism by which V. parahaemolyticus ToxR activates expression of T3SS2 resembles Vibrio cholerae ToxR regulation of distinct virulence elements acquired via lateral gene transfer. Thus, disparate horizontally acquired virulence systems have been placed under the control of this ancestral transcription factor across independently evolved human pathogens. PMID:27185914

  14. Analysis of Genetically Complex Epilepsies

    PubMed Central

    Ottman, Ruth

    2006-01-01

    During the last decade, great progress has been made in the discovery of genes that influence risk for epilepsy. However, these gene discoveries have been in epilepsies with Mendelian modes of inheritance, which comprise only a tiny fraction of all epilepsy. Most people with epilepsy have no affected relatives, suggesting that the great majority of all epilepsies are genetically complex: multiple genes contribute to their etiology, none of which has a major effect on disease risk. Gene discovery in the genetically complex epilepsies is a formidable task. It is unclear which epilepsy phenotypes are most advantageous to study, and chromosomal localization and mutation detection are much more difficult than in Mendelian epilepsies. Association studies are very promising for the identification of complex epilepsy genes, but we are still in the earliest stages of their application in the epilepsies. Future studies should employ very large sample sizes to ensure adequate statistical power, clinical phenotyping methods of the highest quality, designs and analytic techniques that control for population stratification, and state-of-the-art molecular methods. Collaborative studies are essential to achieve these goals. PMID:16359464

  15. Additive genetic variation in schizophrenia risk is shared by populations of African and European descent.

    PubMed

    de Candia, Teresa R; Lee, S Hong; Yang, Jian; Browning, Brian L; Gejman, Pablo V; Levinson, Douglas F; Mowry, Bryan J; Hewitt, John K; Goddard, Michael E; O'Donovan, Michael C; Purcell, Shaun M; Posthuma, Danielle; Visscher, Peter M; Wray, Naomi R; Keller, Matthew C

    2013-09-05

    To investigate the extent to which the proportion of schizophrenia's additive genetic variation tagged by SNPs is shared by populations of European and African descent, we analyzed the largest combined African descent (AD [n = 2,142]) and European descent (ED [n = 4,990]) schizophrenia case-control genome-wide association study (GWAS) data set available, the Molecular Genetics of Schizophrenia (MGS) data set. We show how a method that uses genomic similarities at measured SNPs to estimate the additive genetic correlation (SNP correlation [SNP-rg]) between traits can be extended to estimate SNP-rg for the same trait between ethnicities. We estimated SNP-rg for schizophrenia between the MGS ED and MGS AD samples to be 0.66 (SE = 0.23), which is significantly different from 0 (p(SNP-rg = 0) = 0.0003), but not 1 (p(SNP-rg = 1) = 0.26). We re-estimated SNP-rg between an independent ED data set (n = 6,665) and the MGS AD sample to be 0.61 (SE = 0.21, p(SNP-rg = 0) = 0.0003, p(SNP-rg = 1) = 0.16). These results suggest that many schizophrenia risk alleles are shared across ethnic groups and predate African-European divergence.

  16. Monte Carlo methods in genetic analysis

    SciTech Connect

    Lin, Shili

    1996-12-31

    Many genetic analyses require computation of probabilities and likelihoods of pedigree data. With more and more genetic marker data deriving from new DNA technologies becoming available to researchers, exact computations are often formidable with standard statistical methods and computational algorithms. The desire to utilize as much available data as possible, coupled with complexities of realistic genetic models, push traditional approaches to their limits. These methods encounter severe methodological and computational challenges, even with the aid of advanced computing technology. Monte Carlo methods are therefore increasingly being explored as practical techniques for estimating these probabilities and likelihoods. This paper reviews the basic elements of the Markov chain Monte Carlo method and the method of sequential imputation, with an emphasis upon their applicability to genetic analysis. Three areas of applications are presented to demonstrate the versatility of Markov chain Monte Carlo for different types of genetic problems. A multilocus linkage analysis example is also presented to illustrate the sequential imputation method. Finally, important statistical issues of Markov chain Monte Carlo and sequential imputation, some of which are unique to genetic data, are discussed, and current solutions are outlined. 72 refs.

  17. Quantitative genetic analysis of injury liability in infants and toddlers

    SciTech Connect

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

    1995-02-27

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

  18. Genetic analysis of embryo dormancy. Final report

    SciTech Connect

    Galau, G.

    1998-09-01

    Primary dormancy is the inability of mature seed to immediately germinate until specific environmental stimuli are perceived that predict that future conditions will support plant growth and seed set. The analysis of abscisic acid deficient and insensitive mutants, in particular in Arabidopsis, suggests that embryo abscisic acid may be directly involved in the development of primary dormancy. Other studies implicate the continued accumulation of LEA proteins as inhibiting germination in dormant embryos. The results of these physiological, molecular and genetic approaches are complex and equivocal. There is a real need for approaches that test the separate nature of vivipary inhibition and primary dormancy and deliberately seed to decouple and dissect them. These approaches should be of help in understanding both late embryo development and primary dormancy. The approach taken here is to directly isolate mutants of Arabidopsis that appear to be deficient only in primary dormancy, that is fresh seed that germinate rapidly without the normally-required cold-stratification. The authors have isolated at least 8 independent, rapidly germinating RGM mutants of Arabidopsis. All others aspects of plant growth and development appear normal in these lines, suggesting that the rgm mutants are defective only in the establishment or maintenance of primary dormancy. At least one of these may be tagged with T-DNA. In addition, about 50 RGM isolates have been recovered from EMS-treated seed.

  19. Female and male genetic effects on offspring paternity: additive genetic (co)variances in female extra-pair reproduction and male paternity success in song sparrows (Melospiza melodia).

    PubMed

    Reid, Jane M; Arcese, Peter; Keller, Lukas F; Losdat, Sylvain

    2014-08-01

    Ongoing evolution of polyandry, and consequent extra-pair reproduction in socially monogamous systems, is hypothesized to be facilitated by indirect selection stemming from cross-sex genetic covariances with components of male fitness. Specifically, polyandry is hypothesized to create positive genetic covariance with male paternity success due to inevitable assortative reproduction, driving ongoing coevolution. However, it remains unclear whether such covariances could or do emerge within complex polyandrous systems. First, we illustrate that genetic covariances between female extra-pair reproduction and male within-pair paternity success might be constrained in socially monogamous systems where female and male additive genetic effects can have opposing impacts on the paternity of jointly reared offspring. Second, we demonstrate nonzero additive genetic variance in female liability for extra-pair reproduction and male liability for within-pair paternity success, modeled as direct and associative genetic effects on offspring paternity, respectively, in free-living song sparrows (Melospiza melodia). The posterior mean additive genetic covariance between these liabilities was slightly positive, but the credible interval was wide and overlapped zero. Therefore, although substantial total additive genetic variance exists, the hypothesis that ongoing evolution of female extra-pair reproduction is facilitated by genetic covariance with male within-pair paternity success cannot yet be definitively supported or rejected either conceptually or empirically.

  20. An integrated system for genetic analysis

    PubMed Central

    Fiddy, Simon; Cattermole, David; Xie, Dong; Duan, Xiao Yuan; Mott, Richard

    2006-01-01

    Background Large-scale genetic mapping projects require data management systems that can handle complex phenotypes and detect and correct high-throughput genotyping errors, yet are easy to use. Description We have developed an Integrated Genotyping System (IGS) to meet this need. IGS securely stores, edits and analyses genotype and phenotype data. It stores information about DNA samples, plates, primers, markers and genotypes generated by a genotyping laboratory. Data are structured so that statistical genetic analysis of both case-control and pedigree data is straightforward. Conclusion IGS can model complex phenotypes and contain genotypes from whole genome association studies. The database makes it possible to integrate genetic analysis with data curation. The IGS web site contains further information. PMID:16623936

  1. Additive genetic variance and developmental plasticity in growth trajectories in a wild cooperative mammal.

    PubMed

    Huchard, E; Charmantier, A; English, S; Bateman, A; Nielsen, J F; Clutton-Brock, T

    2014-09-01

    Individual variation in growth is high in cooperative breeders and may reflect plastic divergence in developmental trajectories leading to breeding vs. helping phenotypes. However, the relative importance of additive genetic variance and developmental plasticity in shaping growth trajectories is largely unknown in cooperative vertebrates. This study exploits weekly sequences of body mass from birth to adulthood to investigate sources of variance in, and covariance between, early and later growth in wild meerkats (Suricata suricatta), a cooperative mongoose. Our results indicate that (i) the correlation between early growth (prior to nutritional independence) and adult mass is positive but weak, and there are frequent changes (compensatory growth) in post-independence growth trajectories; (ii) among parameters describing growth trajectories, those describing growth rate (prior to and at nutritional independence) show undetectable heritability while associated size parameters (mass at nutritional independence and asymptotic mass) are moderately heritable (0.09 ≤ h(2) < 0.3); and (iii) additive genetic effects, rather than early environmental effects, mediate the covariance between early growth and adult mass. These results reveal that meerkat growth trajectories remain plastic throughout development, rather than showing early and irreversible divergence, and that the weak effects of early growth on adult mass, an important determinant of breeding success, are partly genetic. In contrast to most cooperative invertebrates, the acquisition of breeding status is often determined after sexual maturity and strongly impacted by chance in many cooperative vertebrates, who may therefore retain the ability to adjust their morphology to environmental changes and social opportunities arising throughout their development, rather than specializing early.

  2. Molecular genetic analysis of archival gliomas using diagnostic smears.

    PubMed

    Walker, C; Joyce, K; Du Plessis, D; MacHell, Y; Sibson, D R; Broome, J

    2000-10-01

    Investigation of the clinical significance of genetic alterations in gliomas requires molecular genetic analysis using samples from retrospective or prospective clinical studies. However, diagnostic tissue is often severely limited and because of fixation, paraffin-embedded tissues (PET) contain degraded DNA. Intra-operative cytological preparations (smears) archived after diagnosis may represent an additional source of clinical material for genetic analysis. In this study, tissue samples were obtained by precision microdissection of archived diagnostic smears from 20 cases (1961-1999). All samples produced polymerase chain reaction (PCR) products for the beta globin gene, but the most recent samples amplified best and gave longer amplimers. For six cases, direct comparison was made between samples microdissected from smears and the corresponding PET. Samples from smears showed improved PCR performance and similar alleles on microsatellite marker analysis. One case, with smears of uninvolved cortex and tumour tissue available for microdissection, showed allelic imbalance at 10q23 on the basis of the smear results alone. PCR products from smears were shown to be suitable for direct sequence analysis (p53 gene). A PTEN mutation, found previously in an anaplastic astrocytoma by analysis of PET, was detected in the corresponding diagnostic smear. The results of this study indicate that tissue samples microdissected from diagnostic intra-operative cytological preparations may be suitable for molecular genetic analysis of gliomas.

  3. Widespread evidence for non-additive genetic variation in Cloninger's and Eysenck's personality dimensions using a twin plus sibling design.

    PubMed

    Keller, Matthew C; Coventry, William L; Heath, Andrew C; Martin, Nicholas G

    2005-11-01

    Studies using the classical twin design often conclude that most genetic variation underlying personality is additive in nature. However, studies analyzing only twins are very limited in their ability to detect non-additive genetic variation and are unable to detect sources of variation unique to twins, which can mask non-additive genetic variation. The current study assessed 9672 MZ and DZ twin individuals and 3241 of their siblings to investigate the environmental and genetic architecture underlying eight dimensions of personality: four from Eysenck's Personality Questionnaire and four from Cloninger's Temperament and Character Inventory. Broad-sense heritability estimates from best-fitting models were two to three times greater than the narrow-sense heritability estimates for Harm Avoidance, Novelty Seeking, Reward Dependence, Persistence, Extraversion, and Neuroticism. This genetic non-additivity could be due to dominance, additive-by-additive epistasis, or to additive genetic effects combined with higher-order epistasis. Environmental effects unique to twins were detected for both Lie and Psychoticism but accounted for little overall variation. Our results illustrate the increased sensitivity afforded by extending the classical twin design to include siblings, and may provide clues to the evolutionary origins of genetic variation underlying personality.

  4. A brief history of genetic variation analysis.

    PubMed

    Ahmadian, Afshin; Lundeberg, Joakim

    2002-05-01

    As the human genome sequence is determined, there is an emerging need for the analysis of human sequence variations as genetic markers in diagnosis, linkage and association studies, cancer research, and pharmacogenomics. There are several different techniques and approaches for detecting these genetic variations, and here we review some of these techniques and their application fields. However, all the techniques have advantages and disadvantages, andfactors such as laboratory instrumentation, personnel experience, required accuracy, required throughput, and cost often have to be taken into account before selecting a method.

  5. Survival analysis with incomplete genetic data.

    PubMed

    Lin, D Y

    2014-01-01

    Genetic data are now collected frequently in clinical studies and epidemiological cohort studies. For a large study, it may be prohibitively expensive to genotype all study subjects, especially with the next-generation sequencing technology. Two-phase sampling, such as case-cohort and nested case-control sampling, is cost-effective in such settings but entails considerable analysis challenges, especially if efficient estimators are desired. Another type of missing data arises when the investigators are interested in the haplotypes or the genetic markers that are not on the genotyping platform used for the current study. Valid and efficient analysis of such missing data is also interesting and challenging. This article provides an overview of these issues and outlines some directions for future research.

  6. Analysis of Mlsc genetics. A novel instance of genetic redundancy

    PubMed Central

    1989-01-01

    The identity of the self determinants involved in the selection of the T cell repertoire has been a matter of considerable interest. In addition to the apparent critical role of MHC gene products, accumulated experimental results indicate the importance of non-MHC gene products in T cell repertoire selection. In particular, murine Mlsa and Mlsc determinants have been shown to be highly stimulatory to allogeneic T cells and to be involved in the negative selection (elimination) of self-reactive T cells expressing selected TCR V beta segments. In this work, a unique phenomenon of genetic redundancy is described in the control of Mlsc expression: Mlsc appears to be controlled by at least two unlinked loci, and the product of either one of these loci is sufficient to evoke Mlsc-specific T cell response and to act as a ligand in the deletion of self Mlsc-reactive V beta 3+ T cells. Based on these findings, we propose a possible explanation for the fact that Mls-like genes or gene products have not been identified in other species such as man. PMID:2477483

  7. Surface analysis and evaluation of progressive addition lens

    NASA Astrophysics Data System (ADS)

    Li, Zhiying; Li, Dan

    2016-10-01

    The Progressive addition lens is used increasingly extensive with its advantages of meeting the requirements of distant and near vision at the same time. Started from the surface equations of progressive addition lens, combined with evaluation method of spherical power and cylinder power, the relationship equations between the surface sag and optical power distribution are derived. According to the requirements on difference of actual and nominal optical power from Chinese National Standard, the tolerance analysis and evaluation of prototype progressive addition surface with addition of 2.5m-1 ( 7.5m-1 10m-1 ) is given in detail. The tolerance analysis method provides theoretical proof for lens processing control accuracy, and the processing feasibility of lens is evaluated much more reasonably.

  8. Computed Tomography Inspection and Analysis for Additive Manufacturing Components

    NASA Technical Reports Server (NTRS)

    Beshears, Ronald D.

    2016-01-01

    Computed tomography (CT) inspection was performed on test articles additively manufactured from metallic materials. Metallic AM and machined wrought alloy test articles with programmed flaws were inspected using a 2MeV linear accelerator based CT system. Performance of CT inspection on identically configured wrought and AM components and programmed flaws was assessed using standard image analysis techniques to determine the impact of additive manufacturing on inspectability of objects with complex geometries.

  9. Very low levels of direct additive genetic variance in fitness and fitness components in a red squirrel population

    PubMed Central

    McFarlane, S Eryn; Gorrell, Jamieson C; Coltman, David W; Humphries, Murray M; Boutin, Stan; McAdam, Andrew G

    2014-01-01

    A trait must genetically correlate with fitness in order to evolve in response to natural selection, but theory suggests that strong directional selection should erode additive genetic variance in fitness and limit future evolutionary potential. Balancing selection has been proposed as a mechanism that could maintain genetic variance if fitness components trade off with one another and has been invoked to account for empirical observations of higher levels of additive genetic variance in fitness components than would be expected from mutation–selection balance. Here, we used a long-term study of an individually marked population of North American red squirrels (Tamiasciurus hudsonicus) to look for evidence of (1) additive genetic variance in lifetime reproductive success and (2) fitness trade-offs between fitness components, such as male and female fitness or fitness in high- and low-resource environments. “Animal model” analyses of a multigenerational pedigree revealed modest maternal effects on fitness, but very low levels of additive genetic variance in lifetime reproductive success overall as well as fitness measures within each sex and environment. It therefore appears that there are very low levels of direct genetic variance in fitness and fitness components in red squirrels to facilitate contemporary adaptation in this population. PMID:24963372

  10. Molecular genetics of obsessive-compulsive disorder: a comprehensive meta-analysis of genetic association studies.

    PubMed

    Taylor, S

    2013-07-01

    Twin studies indicate that obsessive-compulsive disorder (OCD) is strongly influenced by additive genetic factors. Yet, molecular genetic association studies have yielded inconsistent results, possibly because of differences across studies in statistical power. Meta-analysis can yield greater power. This study reports the first comprehensive meta-analysis of the relationship between OCD and all previously examined polymorphisms for which there was sufficient information in the source studies to compute odds ratios (ORs). A total of 230 polymorphisms from 113 genetic association studies were identified. A full meta-analysis was conducted for 20 polymorphisms that were examined in 5 or more data sets, and a secondary meta-analysis (limited to the computation of mean effect sizes) was conducted for 210 polymorphisms that were examined in fewer than 5 data sets. In the main meta-analysis, OCD was associated with serotonin-related polymorphisms (5-HTTLPR and HTR2A) and, in males only, with polymorphisms involved in catecholamine modulation (COMT and MAOA). Nonsignificant trends were identified for two dopamine-related polymorphisms (DAT1 and DRD3) and a glutamate-related polymorphism (rs3087879). The secondary meta-analysis identified another 18 polymorphisms with significant ORs that merit further investigation. This study demonstrates that OCD is associated with multiple genes, with most having a modest association with OCD. This suggests a polygenic model of OCD, consistent with twin studies, in which multiple genes make small, incremental contributions to the risk of developing the disorder. Future studies, with sufficient power to detect small effects, are needed to investigate the genetic basis of OCD subtypes, such as early vs late onset OCD.

  11. Multilocus Genetic Analysis of Brain Images

    PubMed Central

    Hibar, Derrek P.; Kohannim, Omid; Stein, Jason L.; Chiang, Ming-Chang; Thompson, Paul M.

    2011-01-01

    The quest to identify genes that influence disease is now being extended to find genes that affect biological markers of disease, or endophenotypes. Brain images, in particular, provide exquisitely detailed measures of anatomy, function, and connectivity in the living brain, and have identified characteristic features for many neurological and psychiatric disorders. The emerging field of imaging genomics is discovering important genetic variants associated with brain structure and function, which in turn influence disease risk and fundamental cognitive processes. Statistical approaches for testing genetic associations are not straightforward to apply to brain images because the data in brain images is spatially complex and generally high dimensional. Neuroimaging phenotypes typically include 3D maps across many points in the brain, fiber tracts, shape-based analyses, and connectivity matrices, or networks. These complex data types require new methods for data reduction and joint consideration of the image and the genome. Image-wide, genome-wide searches are now feasible, but they can be greatly empowered by sparse regression or hierarchical clustering methods that isolate promising features, boosting statistical power. Here we review the evolution of statistical approaches to assess genetic influences on the brain. We outline the current state of multivariate statistics in imaging genomics, and future directions, including meta-analysis. We emphasize the power of novel multivariate approaches to discover reliable genetic influences with small effect sizes. PMID:22303368

  12. Optimal Multicomponent Analysis Using the Generalized Standard Addition Method.

    ERIC Educational Resources Information Center

    Raymond, Margaret; And Others

    1983-01-01

    Describes an experiment on the simultaneous determination of chromium and magnesium by spectophotometry modified to include the Generalized Standard Addition Method computer program, a multivariate calibration method that provides optimal multicomponent analysis in the presence of interference and matrix effects. Provides instructions for…

  13. Toxicological safety assessment of genetically modified Bacillus thuringiensis with additional N-acyl homoserine lactonase gene.

    PubMed

    Peng, Donghai; Zhou, Chenfei; Chen, Shouwen; Ruan, Lifang; Yu, Ziniu; Sun, Ming

    2008-01-01

    The aim of the present study is to evaluate the toxicology safety to mammals of a genetically modified (GM) Bacillus thuringiensis with an additional N-acyl homoserine lactones gene (aiiA), which possesses insecticidal activity together with restraint of bacterial pathogenicity and is intended for use as a multifunctional biopesticide. Safety assessments included an acute oral toxicity test and 28-d animal feeding study in Wistar rats, primary eye and dermal irritation in Zealand White rabbits, and delayed contact hypersensitivity in guinea pigs. Tests were conducted using spray-dried powder preparation. This GM product showed toxicity neither in oral acute toxicity test nor in 28-d animal feeding test at a dose of 5,000 mg/kg body weight. During the animal feeding test, there were no significant differences in growth, food and water consumption, hematology, blood biochemical indices, organ weights, and histopathology finding between rats in controls and tested groups. Tested animals in primary eye and dermal irritation and delayed contact hypersensitivity test were also devoid of any toxicity compared to controls. All the above results demonstrated that the GM based multifunctional B. thuringiensis has low toxicity and low eye and dermal irritation and would not cause hypersensitivity to laboratory mammals and therefore could be regarded as safe for use as a pesticide.

  14. A global analysis of soil acidification caused by nitrogen addition

    NASA Astrophysics Data System (ADS)

    Tian, Dashuan; Niu, Shuli

    2015-02-01

    Nitrogen (N) deposition-induced soil acidification has become a global problem. However, the response patterns of soil acidification to N addition and the underlying mechanisms remain far from clear. Here, we conducted a meta-analysis of 106 studies to reveal global patterns of soil acidification in responses to N addition. We found that N addition significantly reduced soil pH by 0.26 on average globally. However, the responses of soil pH varied with ecosystem types, N addition rate, N fertilization forms, and experimental durations. Soil pH decreased most in grassland, whereas boreal forest was not observed a decrease to N addition in soil acidification. Soil pH decreased linearly with N addition rates. Addition of urea and NH4NO3 contributed more to soil acidification than NH4-form fertilizer. When experimental duration was longer than 20 years, N addition effects on soil acidification diminished. Environmental factors such as initial soil pH, soil carbon and nitrogen content, precipitation, and temperature all influenced the responses of soil pH. Base cations of Ca2+, Mg2+ and K+ were critical important in buffering against N-induced soil acidification at the early stage. However, N addition has shifted global soils into the Al3+ buffering phase. Overall, this study indicates that acidification in global soils is very sensitive to N deposition, which is greatly modified by biotic and abiotic factors. Global soils are now at a buffering transition from base cations (Ca2+, Mg2+ and K+) to non-base cations (Mn2+ and Al3+). This calls our attention to care about the limitation of base cations and the toxic impact of non-base cations for terrestrial ecosystems with N deposition.

  15. [Kinetic analysis of additive effect on desulfurization activity].

    PubMed

    Han, Kui-hua; Zhao, Jian-li; Lu, Chun-mei; Wang, Yong-zheng; Zhao, Gai-ju; Cheng, Shi-qing

    2006-02-01

    The additive effects of A12O3, Fe2O3 and MnCO3 on CaO sulfation kinetics were investigated by thermogravimetic analysis method and modified grain model. The activation energy (Ea) and the pre-exponential factor (k0) of surface reaction, the activation energy (Ep) and the pre-exponential factor (D0) of product layer diffusion reaction were calculated according to the model. Additions of MnCO3 can enhance the initial reaction rate, product layer diffusion and the final CaO conversion of sorbents, the effect mechanism of which is similar to that of Fe2O3. The method based isokinetic temperature Ts and activation energy can not estimate the contribution of additive to the sulfation reactivity, the rate constant of the surface reaction (k), and the effective diffusivity of reactant in the product layer (Ds) under certain experimental conditions can reflect the effect of additives on the activation. Unstoichiometric metal oxide may catalyze the surface reaction and promote the diffusivity of reactant in the product layer by the crystal defect and distinct diffusion of cation and anion. According to the mechanism and effect of additive on the sulfation, the effective temperature and the stoichiometric relation of reaction, it is possible to improve the utilization of sorbent by compounding more additives to the calcium-based sorbent.

  16. Planning additional drilling campaign using two-space genetic algorithm: A game theoretical approach

    NASA Astrophysics Data System (ADS)

    Kumral, Mustafa; Ozer, Umit

    2013-03-01

    Grade and tonnage are the most important technical uncertainties in mining ventures because of the use of estimations/simulations, which are mostly generated from drill data. Open pit mines are planned and designed on the basis of the blocks representing the entire orebody. Each block has different estimation/simulation variance reflecting uncertainty to some extent. The estimation/simulation realizations are submitted to mine production scheduling process. However, the use of a block model with varying estimation/simulation variances will lead to serious risk in the scheduling. In the medium of multiple simulations, the dispersion variances of blocks can be thought to regard technical uncertainties. However, the dispersion variance cannot handle uncertainty associated with varying estimation/simulation variances of blocks. This paper proposes an approach that generates the configuration of the best additional drilling campaign to generate more homogenous estimation/simulation variances of blocks. In other words, the objective is to find the best drilling configuration in such a way as to minimize grade uncertainty under budget constraint. Uncertainty measure of the optimization process in this paper is interpolation variance, which considers data locations and grades. The problem is expressed as a minmax problem, which focuses on finding the best worst-case performance i.e., minimizing interpolation variance of the block generating maximum interpolation variance. Since the optimization model requires computing the interpolation variances of blocks being simulated/estimated in each iteration, the problem cannot be solved by standard optimization tools. This motivates to use two-space genetic algorithm (GA) approach to solve the problem. The technique has two spaces: feasible drill hole configuration with minimization of interpolation variance and drill hole simulations with maximization of interpolation variance. Two-space interacts to find a minmax solution

  17. Traditional Approaches to Molecular Genetic Analysis.

    PubMed

    Walker, Christopher J; Goodfellow, Paul J

    2017-01-01

    Molecular studies of endometrial cancer have evolved with the tools available to researchers: the methods for measuring nucleic acids, protein expression, and combinations thereof. Today "molecular genetic analysis" implies a broad range of indirect and direct tests that yield molecular phenotypes or genotypes, immunotypes, or signatures that were not conceived of when the histologic and biologic heterogeneity was first fully acknowledged.We will provide a historical perspective on molecular genetic studies of endometrial cancers focusing on candidate genes and how early foundational research shaped both our understanding of the disease and current research directions. Examples of direct tests (mutation, DNA methylation, and/or protein expression) will be provided along with examples of indirect tests that have been and continue to be central to endometrial cancer molecular biology, such as DNA content or microsatellite instability analysis. We will highlight clinically relevant examples of molecular phenotyping and direct evaluation of candidate genes that integrate direct and indirect testing as part of routine patient care. This is not intended to be an exhaustive review but rather an overview of the progress that has been made and how early work is shaping current molecular, clinical, and biologic studies of endometrial cancer.

  18. ANALYSIS OF MPC ACCESS REQUIREMENTS FOR ADDITION OF FILLER MATERIALS

    SciTech Connect

    W. Wallin

    1996-09-03

    This analysis is prepared by the Mined Geologic Disposal System (MGDS) Waste Package Development Department (WPDD) in response to a request received via a QAP-3-12 Design Input Data Request (Ref. 5.1) from WAST Design (formerly MRSMPC Design). The request is to provide: Specific MPC access requirements for the addition of filler materials at the MGDS (i.e., location and size of access required). The objective of this analysis is to provide a response to the foregoing request. The purpose of this analysis is to provide a documented record of the basis for the response. The response is stated in Section 8 herein. The response is based upon requirements from an MGDS perspective.

  19. A strategy analysis for genetic association studies with known inbreeding

    PubMed Central

    2011-01-01

    Background Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the beta-thalassemia, which is a well known Mendelian

  20. Genetic predisposition to coronary heart disease and stroke using an additive genetic risk score: a population-based study in Greece

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To determine the extent to which the risk for incident coronary heart disease (CHD) increases in relation to a genetic risk score (GRS) that additively integrates the influence of high-risk alleles in nine documented single nucleotide polymorphisms (SNPs) for CHD, and to examine whether t...

  1. Spectral Envelopes and Additive + Residual Analysis/Synthesis

    NASA Astrophysics Data System (ADS)

    Rodet, Xavier; Schwarz, Diemo

    The subject of this chapter is the estimation, representation, modification, and use of spectral envelopes in the context of sinusoidal-additive-plus-residual analysis/synthesis. A spectral envelope is an amplitude-vs-frequency function, which may be obtained from the envelope of a short-time spectrum (Rodet et al., 1987; Schwarz, 1998). [Precise definitions of such an envelope and short-time spectrum (STS) are given in Section 2.] The additive-plus-residual analysis/synthesis method is based on a representation of signals in terms of a sum of time-varying sinusoids and of a non-sinusoidal residual signal [e.g., see Serra (1989), Laroche et al. (1993), McAulay and Quatieri (1995), and Ding and Qian (1997)]. Many musical sound signals may be described as a combination of a nearly periodic waveform and colored noise. The nearly periodic part of the signal can be viewed as a sum of sinusoidal components, called partials, with time-varying frequency and amplitude. Such sinusoidal components are easily observed on a spectral analysis display (Fig. 5.1) as obtained, for instance, from a discrete Fourier transform.

  2. Genome-Enabled Estimates of Additive and Nonadditive Genetic Variances and Prediction of Apple Phenotypes Across Environments

    PubMed Central

    Kumar, Satish; Molloy, Claire; Muñoz, Patricio; Daetwyler, Hans; Chagné, David; Volz, Richard

    2015-01-01

    The nonadditive genetic effects may have an important contribution to total genetic variation of phenotypes, so estimates of both the additive and nonadditive effects are desirable for breeding and selection purposes. Our main objectives were to: estimate additive, dominance and epistatic variances of apple (Malus × domestica Borkh.) phenotypes using relationship matrices constructed from genome-wide dense single nucleotide polymorphism (SNP) markers; and compare the accuracy of genomic predictions using genomic best linear unbiased prediction models with or without including nonadditive genetic effects. A set of 247 clonally replicated individuals was assessed for six fruit quality traits at two sites, and also genotyped using an Illumina 8K SNP array. Across several fruit quality traits, the additive, dominance, and epistatic effects contributed about 30%, 16%, and 19%, respectively, to the total phenotypic variance. Models ignoring nonadditive components yielded upwardly biased estimates of additive variance (heritability) for all traits in this study. The accuracy of genomic predicted genetic values (GEGV) varied from about 0.15 to 0.35 for various traits, and these were almost identical for models with or without including nonadditive effects. However, models including nonadditive genetic effects further reduced the bias of GEGV. Between-site genotypic correlations were high (>0.85) for all traits, and genotype-site interaction accounted for <10% of the phenotypic variability. The accuracy of prediction, when the validation set was present only at one site, was generally similar for both sites, and varied from about 0.50 to 0.85. The prediction accuracies were strongly influenced by trait heritability, and genetic relatedness between the training and validation families. PMID:26497141

  3. The Multi-allelic Genetic Architecture of a Variance-Heterogeneity Locus for Molybdenum Concentration in Leaves Acts as a Source of Unexplained Additive Genetic Variance

    PubMed Central

    Forsberg, Simon K. G.; Andreatta, Matthew E.; Huang, Xin-Yuan; Danku, John; Salt, David E.; Carlborg, Örjan

    2015-01-01

    Genome-wide association (GWA) analyses have generally been used to detect individual loci contributing to the phenotypic diversity in a population by the effects of these loci on the trait mean. More rarely, loci have also been detected based on variance differences between genotypes. Several hypotheses have been proposed to explain the possible genetic mechanisms leading to such variance signals. However, little is known about what causes these signals, or whether this genetic variance-heterogeneity reflects mechanisms of importance in natural populations. Previously, we identified a variance-heterogeneity GWA (vGWA) signal for leaf molybdenum concentrations in Arabidopsis thaliana. Here, fine-mapping of this association reveals that the vGWA emerges from the effects of three independent genetic polymorphisms that all are in strong LD with the markers displaying the genetic variance-heterogeneity. By revealing the genetic architecture underlying this vGWA signal, we uncovered the molecular source of a significant amount of hidden additive genetic variation or “missing heritability”. Two of the three polymorphisms underlying the genetic variance-heterogeneity are promoter variants for Molybdate transporter 1 (MOT1), and the third a variant located ~25 kb downstream of this gene. A fourth independent association was also detected ~600 kb upstream of MOT1. Use of a T-DNA knockout allele highlights Copper Transporter 6; COPT6 (AT2G26975) as a strong candidate gene for this association. Our results show that an extended LD across a complex locus including multiple functional alleles can lead to a variance-heterogeneity between genotypes in natural populations. Further, they provide novel insights into the genetic regulation of ion homeostasis in A. thaliana, and empirically confirm that variance-heterogeneity based GWA methods are a valuable tool to detect novel associations of biological importance in natural populations. PMID:26599497

  4. Genetic analysis of glutamatergic function in Drosophila

    SciTech Connect

    Chase, B.A.; Kankel, D.R.

    1987-01-01

    Neurotransmitters are essential for communication between neurons and hence are vital in the overall integrative functioning of the nervous system. Previous work on acetylcholine metabolism in the fruit fly, Drosophila melanogaster, has also raised the possibility that transmitter metabolism may play a prominent role in either the achievement or maintenance of the normal structure of the central nervous system in this species. Unfortunately, acetylcholine is rather poorly characterized as a neurotransmitter in Drosophila; consequently, we have begun an analysis of the role of glutamate (probably the best characterized transmitter in this organism) in the formation and/or maintenance of nervous system structure. We present here the results of a series of preliminary analyses. To suggest where glutamatergic function may be localized, an examination of the spatial distribution of high affinity (/sup 3/H)-glutamate binding sites are presented. We present the results of an analysis of the spatial and temporal distribution of enzymatic activities thought to be important in the regulation of transmitter-glutamate pools (i.e., glutamate oxaloacetic transaminase, glutaminase, and glutamate dehydrogenase). To begin to examine whether mutations in any of these functions are capable of affecting glutamatergic activity, we present the results of an initial genetic analysis of one enzymatic function, glutamate oxaloacetic transaminase (GOT), chosen because of its differential distribution within the adult central nervous system and musculature.

  5. 29 CFR 2590.702-1 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... diabetes. A begins to experience excessive sweating, thirst, and fatigue. A's physician examines A and... adult onset diabetes mellitus (Type 2 diabetes). (ii) Conclusion. In this Example 1, A has been... involved. The diagnosis is not based principally on genetic information. Thus, Type 2 diabetes...

  6. 45 CFR 146.122 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... diabetes. A begins to experience excessive sweating, thirst, and fatigue. A's physician examines A and... adult onset diabetes mellitus (Type 2 diabetes). (ii) Conclusion. In this Example 1, A has been... involved. The diagnosis is not based principally on genetic information. Thus, Type 2 diabetes...

  7. Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes.

    PubMed

    de Jong, Simone; van Eijk, Kristel R; Zeegers, Dave W L H; Strengman, Eric; Janson, Esther; Veldink, Jan H; van den Berg, Leonard H; Cahn, Wiepke; Kahn, René S; Boks, Marco P M; Ophoff, Roel A

    2012-09-01

    There is genetic evidence that schizophrenia is a polygenic disorder with a large number of loci of small effect on disease susceptibility. Genome-wide association studies (GWASs) of schizophrenia have had limited success, with the best finding at the MHC locus at chromosome 6p. A recent effort of the Psychiatric GWAS consortium (PGC) yielded five novel loci for schizophrenia. In this study, we aim to highlight additional schizophrenia susceptibility loci from the PGC study by combining the top association findings from the discovery stage (9394 schizophrenia cases and 12 462 controls) with expression QTLs (eQTLs) and differential gene expression in whole blood of schizophrenia patients and controls. We examined the 6192 single-nucleotide polymorphisms (SNPs) with significance threshold at P<0.001. eQTLs were calculated for these SNPs in a sample of healthy controls (n=437). The transcripts significantly regulated by the top SNPs from the GWAS meta-analysis were subsequently tested for differential expression in an independent set of schizophrenia cases and controls (n=202). After correction for multiple testing, the eQTL analysis yielded 40 significant cis-acting effects of the SNPs. Seven of these transcripts show differential expression between cases and controls. Of these, the effect of three genes (RNF5, TRIM26 and HLA-DRB3) coincided with the direction expected from meta-analysis findings and were all located within the MHC region. Our results identify new genes of interest and highlight again the involvement of the MHC region in schizophrenia susceptibility.

  8. GENETIC ANALYSIS OF ABSCISIC ACID BIOSYNTHESIS

    SciTech Connect

    MCCARTY D R

    2012-01-10

    The carotenoid cleavage dioxygenases (CCD) catalyze synthesis of a variety of apo-carotenoid secondary metabolites in plants, animals and bacteria. In plants, the reaction catalyzed by the 11, 12, 9-cis-epoxy carotenoid dioxygenase (NCED) is the first committed and key regulated step in synthesis of the plant hormone, abscisic acid (ABA). ABA is a key regulator of plant stress responses and has critical functions in normal root and seed development. The molecular mechanisms responsible for developmental control of ABA synthesis in plant tissues are poorly understood. Five of the nine CCD genes present in the Arabidopsis genome encode NCED's involved in control of ABA synthesis in the plant. This project is focused on functional analysis of these five AtNCED genes as a key to understanding developmental regulation of ABA synthesis and dissecting the role of ABA in plant development. For this purpose, the project developed a comprehensive set of gene knockouts in the AtNCED genes that facilitate genetic dissection of ABA synthesis. These mutants were used in combination with key molecular tools to address the following specific objectives: (1) the role of ABA synthesis in root development; (2) developmental control of ABA synthesis in seeds; (3) analysis of ATNCED over-expressers; (4) preliminary crystallography of the maize VP14 protein.

  9. Quantitative Analysis of Triple Mutant Genetic Interactions

    PubMed Central

    Braberg, Hannes; Alexander, Richard; Shales, Michael; Xu, Jiewei; Franks-Skiba, Kathleen E.; Wu, Qiuqin; Haber, James E.; Krogan, Nevan J.

    2014-01-01

    The quantitative analysis of genetic interactions between pairs of gene mutations has proven effective for characterizing cellular functions but can miss important interactions for functionally redundant genes. To address this limitation, we have developed an approach termed Triple Mutant Analysis (TMA). The procedure relies on a query strain that contains two deletions in a pair of redundant or otherwise related genes, that is crossed against a panel of candidate deletion strains to isolate triple mutants and measure their growth. A central feature of TMA is to interrogate mutants that are synthetically sick when two other genes are deleted but interact minimally with either single deletion. This approach has been valuable for discovering genes that restore critical functions when the principle actors are deleted. TMA has also uncovered double mutant combinations that produce severe defects because a third protein becomes deregulated and acts in a deleterious fashion, and it has revealed functional differences between proteins presumed to act together. The protocol is optimized for Singer ROTOR pinning robots, takes 3 weeks to complete, and measures interactions for up to 30 double mutants against a library of 1536 single mutants. PMID:25010907

  10. Worldwide Genetic Analysis of the CFTR Region

    PubMed Central

    Mateu, Eva; Calafell, Francesc; Lao, Oscar; Bonné-Tamir, Batsheva; Kidd, Judith R.; Pakstis, Andrew; Kidd, Kenneth K.; Bertranpetit, Jaume

    2001-01-01

    Mutations at the cystic fibrosis transmembrane conductance regulator gene (CFTR) cause cystic fibrosis, the most prevalent severe genetic disorder in individuals of European descent. We have analyzed normal allele and haplotype variation at four short tandem repeat polymorphisms (STRPs) and two single-nucleotide polymorphisms (SNPs) in CFTR in 18 worldwide population samples, comprising a total of 1,944 chromosomes. The rooted phylogeny of the SNP haplotypes was established by typing ape samples. STRP variation within SNP haplotype backgrounds was highest in most ancestral haplotypes—although, when STRP allele sizes were taken into account, differences among haplotypes became smaller. Haplotype background determines STRP diversity to a greater extent than populations do, which indicates that haplotype backgrounds are older than populations. Heterogeneity among STRPs can be understood as the outcome of differences in mutation rate and pattern. STRP sites had higher heterozygosities in Africans, although, when whole haplotypes were considered, no significant differences remained. Linkage disequilibrium (LD) shows a complex pattern not easily related to physical distance. The analysis of the fraction of possible different haplotypes not found may circumvent some of the methodological difficulties of LD measure. LD analysis showed a positive correlation with locus polymorphism, which could partly explain the unusual pattern of similar LD between Africans and non-Africans. The low values found in non-Africans may imply that the size of the modern human population that emerged “Out of Africa” may be larger than what previous LD studies suggested. PMID:11104661

  11. Decreasing Cloudiness Over China: An Updated Analysis Examining Additional Variables

    SciTech Connect

    Kaiser, D.P.

    2000-01-14

    As preparation of the IPCC's Third Assessment Report takes place, one of the many observed climate variables of key interest is cloud amount. For several nations of the world, there exist records of surface-observed cloud amount dating back to the middle of the 20th Century or earlier, offering valuable information on variations and trends. Studies using such databases include Sun and Groisman (1999) and Kaiser and Razuvaev (1995) for the former Soviet Union, Angel1 et al. (1984) for the United States, Henderson-Sellers (1986) for Europe, Jones and Henderson-Sellers (1992) for Australia, and Kaiser (1998) for China. The findings of Kaiser (1998) differ from the other studies in that much of China appears to have experienced decreased cloudiness over recent decades (1954-1994), whereas the other land regions for the most part show evidence of increasing cloud cover. This paper expands on Kaiser (1998) by analyzing trends in additional meteorological variables for Chi na [station pressure (p), water vapor pressure (e), and relative humidity (rh)] and extending the total cloud amount (N) analysis an additional two years (through 1996).

  12. Sensitivity analysis of geometric errors in additive manufacturing medical models.

    PubMed

    Pinto, Jose Miguel; Arrieta, Cristobal; Andia, Marcelo E; Uribe, Sergio; Ramos-Grez, Jorge; Vargas, Alex; Irarrazaval, Pablo; Tejos, Cristian

    2015-03-01

    Additive manufacturing (AM) models are used in medical applications for surgical planning, prosthesis design and teaching. For these applications, the accuracy of the AM models is essential. Unfortunately, this accuracy is compromised due to errors introduced by each of the building steps: image acquisition, segmentation, triangulation, printing and infiltration. However, the contribution of each step to the final error remains unclear. We performed a sensitivity analysis comparing errors obtained from a reference with those obtained modifying parameters of each building step. Our analysis considered global indexes to evaluate the overall error, and local indexes to show how this error is distributed along the surface of the AM models. Our results show that the standard building process tends to overestimate the AM models, i.e. models are larger than the original structures. They also show that the triangulation resolution and the segmentation threshold are critical factors, and that the errors are concentrated at regions with high curvatures. Errors could be reduced choosing better triangulation and printing resolutions, but there is an important need for modifying some of the standard building processes, particularly the segmentation algorithms.

  13. Genetic and environmental influences on impulsivity: A meta-analysis of twin, family and adoption studies

    PubMed Central

    Bezdjian, Serena; Baker, Laura A.; Tuvblad, Catherine

    2011-01-01

    A meta-analysis of twin, family and adoption studies was conducted to estimate the magnitude of genetic and environmental influences on impulsivity. The best fitting model for 41 key studies (58 independent samples from 14 month old infants to adults; N = 27,147) included equal proportions of variance due to genetic (0.50) and non-shared environmental (0.50) influences, with genetic effects being both additive (0.38) and non-additive (0.12). Shared environmental effects were unimportant in explaining individual differences in impulsivity. Age, sex, and study design (twin vs. adoption) were all significant moderators of the magnitude of genetic and environmental influences on impulsivity. The relative contribution of genetic effects (broad sense heritability) and unique environmental effects were also found to be important throughout development from childhood to adulthood. Total genetic effects were found to be important for all ages, but appeared to be strongest in children. Analyses also demonstrated that genetic effects appeared to be stronger in males than in females. Method of assessment (laboratory tasks vs. questionnaires), however, was not a significant moderator of the genetic and environmental influences on impulsivity. These results provide a structured synthesis of existing behavior genetic studies on impulsivity by providing a clearer understanding of the relative genetic and environmental contributions in impulsive traits through various stages of development. PMID:21889436

  14. Genetic analysis of captive proboscis monkeys.

    PubMed

    Ogata, Mitsuaki; Seino, Satoru

    2015-01-01

    Information on the genetic relationships of captive founders is important for captive population management. In this study, we investigated DNA polymorphisms of four microsatellite loci and the mitochondrial control region sequence of five proboscis monkeys residing in a Japanese zoo as captive founders, to clarify their genetic relationship. We found that two of the five monkeys appeared to be genetically related. Furthermore, the haplotypes of the mitochondrial control region of the five monkeys were well differentiated from the haplotypes previously reported from wild populations from the northern area of Borneo, indicating a greater amount of genetic diversity in proboscis monkeys than previously reported.

  15. Methods for genetic linkage analysis using trisomies

    SciTech Connect

    Feingold, E.; Lamb, N.E.; Sherman, S.L.

    1994-09-01

    Certain genetic disorders (e.g. congenital cataracts, duodenal atresia) are rare in the general population, but more common in people with Down`s syndrome. We present a method for using individuals with trisomy 21 to map genes for such traits. Our methods are analogous to methods for mapping autosomal dominant traits using affected relative pairs by looking for markers with greater than expected identity-by-descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected reduction to homozygosity in the chromosomes inherited form the non-disjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the gene, a confidence interval for that distance, and methods for computing power and sample sizes. The methods are described in the context of gene-dosage model for the etiology of the disorder, but can be extended to other models. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers, how to test candidate genes, and how to handle the effect of reduced recombination associated with maternal meiosis I non-disjunction.

  16. Longitudinal Genetic Analysis of Anxiety Sensitivity

    ERIC Educational Resources Information Center

    Zavos, Helena M. S.; Gregory, Alice M.; Eley, Thalia C.

    2012-01-01

    Anxiety sensitivity is associated with both anxiety and depression and has been shown to be heritable. Little, however, is known about the role of genetic influence on continuity and change of symptoms over time. The authors' aim was to examine the stability of anxiety sensitivity during adolescence. By using a genetically sensitive design, the…

  17. Genetic variation at the TPH2 gene influences impulsivity in addition to eating disorders.

    PubMed

    Slof-Op't Landt, Margarita C T; Bartels, Meike; Middeldorp, Christel M; van Beijsterveldt, Catherina E M; Slagboom, P Eline; Boomsma, Dorret I; van Furth, Eric F; Meulenbelt, Ingrid

    2013-01-01

    Genes are involved in eating disorders (EDs) and self-induced vomiting (SV), a key symptom of different types of EDs. Perfectionism and impulsivity are potential risk factors for EDs. TPH2 (tryptophan hydroxylase 2) SNP rs1473473 was previously associated with anorexia nervosa and EDs characterized by SV. Could perfectionism or impulsivity be underlying the association between rs1473473 and EDs? Genetic association between TPH2 SNP rs1473473 and perfectionism or impulsivity was first evaluated in a random control group (N = 512). The associations obtained in this control group were subsequently tested in a group of patients with an ED (N = 267). The minor allele of rs1473473 (OR = 1.49) was more frequent in impulsive controls, but also in impulsive patients with an ED (OR = 1.83). The largest effect was found in the patients with an ED characterized by SV (OR = 2.51, p = 0.02). Genetic variation at the TPH2 gene appeared to affect impulsivity which, in turn, might predispose to the SV phenotype.

  18. Additive genetic variation for tolerance to estrogen pollution in natural populations of Alpine whitefish (Coregonus sp., Salmonidae).

    PubMed

    Brazzola, Gregory; Chèvre, Nathalie; Wedekind, Claus

    2014-11-01

    The evolutionary potential of natural populations to adapt to anthropogenic threats critically depends on whether there exists additive genetic variation for tolerance to the threat. A major problem for water-dwelling organisms is chemical pollution, and among the most common pollutants is 17α-ethinylestradiol (EE2), the synthetic estrogen that is used in oral contraceptives and that can affect fish at various developmental stages, including embryogenesis. We tested whether there is variation in the tolerance to EE2 within Alpine whitefish. We sampled spawners from two species of different lakes, bred them in vitro in a full-factorial design each, and studied growth and mortality of embryos. Exposure to EE2 turned out to be toxic in all concentrations we tested (≥1 ng/L). It reduced embryo viability and slowed down embryogenesis. We found significant additive genetic variation in EE2-induced mortality in both species, that is, genotypes differed in their tolerance to estrogen pollution. We also found maternal effects on embryo development to be influenced by EE2, that is, some maternal sib groups were more susceptible to EE2 than others. In conclusion, the toxic effects of EE2 were strong, but both species demonstrated the kind of additive genetic variation that is necessary for an evolutionary response to this type of pollution.

  19. Additive genetic variation for tolerance to estrogen pollution in natural populations of Alpine whitefish (Coregonus sp., Salmonidae)

    PubMed Central

    Brazzola, Gregory; Chèvre, Nathalie; Wedekind, Claus

    2014-01-01

    The evolutionary potential of natural populations to adapt to anthropogenic threats critically depends on whether there exists additive genetic variation for tolerance to the threat. A major problem for water-dwelling organisms is chemical pollution, and among the most common pollutants is 17α-ethinylestradiol (EE2), the synthetic estrogen that is used in oral contraceptives and that can affect fish at various developmental stages, including embryogenesis. We tested whether there is variation in the tolerance to EE2 within Alpine whitefish. We sampled spawners from two species of different lakes, bred them in vitro in a full-factorial design each, and studied growth and mortality of embryos. Exposure to EE2 turned out to be toxic in all concentrations we tested (≥1 ng/L). It reduced embryo viability and slowed down embryogenesis. We found significant additive genetic variation in EE2-induced mortality in both species, that is, genotypes differed in their tolerance to estrogen pollution. We also found maternal effects on embryo development to be influenced by EE2, that is, some maternal sib groups were more susceptible to EE2 than others. In conclusion, the toxic effects of EE2 were strong, but both species demonstrated the kind of additive genetic variation that is necessary for an evolutionary response to this type of pollution. PMID:25553069

  20. Genetic manipulation of Aspergillus nidulans: meiotic progeny for genetic analysis and strain construction.

    PubMed

    Todd, Richard B; Davis, Meryl A; Hynes, Michael J

    2007-01-01

    The multicellular microbial eukaryote Aspergillus nidulans is an excellent model for the study of a wide array of biological processes. Studies in this system contribute significantly to understanding fundamental biological principles and are relevant for biotechnology and industrial applications, as well as human, animal and plant fungal pathogenesis. A. nidulans is easily manipulated using classical and molecular genetics. Here, we describe the storage and handling of A. nidulans and procedures for genetic crossing, progeny analysis and growth testing. These procedures are used for Mendelian analysis of segregation of alleles to show whether a mutant phenotype segregates as a single gene and independent assortment of genes to determine the linkage relationship between genes. Meiotic crossing is used for construction of multiple mutant strains for genetic analysis. Genetic crossing and analysis of progeny can be undertaken in 2-3 weeks and growth testing takes 2-3 days.

  1. Four Additional Cases of Diphyllobothrium nihonkaiense Infection Confirmed by Analysis of COX1 Gene in Korea

    PubMed Central

    Park, Sang Hyun; Jeon, Hyeong Kyu; Kim, Jin Bong

    2015-01-01

    Most of the diphyllobothriid tapeworms isolated from human samples in the Republic of Korea (= Korea) have been identified as Diphyllobothrium nihonkaiense by genetic analysis. This paper reports confirmation of D. nihonkaiense infections in 4 additional human samples obtained between 1995 and 2014, which were analyzed at the Department of Parasitology, Hallym University College of Medicine, Korea. Analysis of the mitochondrial cytochrome c oxidase 1 (cox1) gene revealed a 98.5-99.5% similarity with a reference D. nihonkaiense sequence in GenBank. The present report adds 4 cases of D. nihonkaiense infections to the literature, indicating that the dominant diphyllobothriid tapeworm species in Korea is D. nihonkaiense but not D. latum. PMID:25748716

  2. Integrative Lifecourse and Genetic Analysis of Military Working Dogs

    DTIC Science & Technology

    2012-10-01

    September 2012 4. TITLE AND SUBTITLE Integrative Lifecourse and Genetic Analysis of Military Working Dogs 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...methodology has been critical. I was able to acquire genetic material and appropriately identify dogs that were ideal for our new methodology. My direct...AD_________________ Award Number: W81XWH-11-2-0225 TITLE: Integrative Lifecourse and Genetic

  3. Navy Additive Manufacturing: Policy Analysis for Future DLA Material Support

    DTIC Science & Technology

    2014-12-01

    support programs. 14. SUBJECT TERMS additive manufacturing, 3D printing, technology adoption 15. NUMBER OF PAGES 69 16...LEFT BLANK xii LIST OF ACRONYMS AND ABBREVIATIONS 3D Three Dimensions or Three Dimensional 3DP 3D Printing AM Additive Manufacturing AMDO...this is about to change. Additive manufacturing (AM) systems (commonly known as “ 3D printing”) could bring the organic parts manufacturing capability

  4. Additional studies of sheep haemopexin: genetic control, frequencies and postnatal development.

    PubMed

    Stratil, A; Bobák, P; Margetín, M; Glasnák, V

    1989-01-01

    This study presents evidence that sheep haemopexin phenotypes are genetically controlled by three alleles, HpxA, HpxB1 and HpxB2, of a single autosomal locus. Frequencies of two alleles, HpxA and HpxB (HpxB encompasses two isoalleles, HpxB1 and HpxB2), were studied in eight sheep breeds in Czechoslovakia. The frequency of the HpxA allele was highest (ranging from 0.81 in Merino to 1.0 in East Friesian sheep). Qualitative and quantitative changes in haemopexin during postnatal development were studied by starch gel electrophoresis and rocket immunoelectrophoresis respectively. In electrophoresis, 1- or 2-day-old lambs had two very weak zones corresponding in mobility to two slower zones of adult animals. Later, the third more anodic zone appeared and gradually increased in intensity. In 1-month-old lambs the patterns were practically identical with those of adult animals. Using rocket immunoelectrophoresis, the level of haemopexin shortly after birth was practically zero. It rose sharply till the sixth day of life; then the level continued to rise slowly till about 1 month of age. The mean haemopexin level in adult sheep was 64.5 +/- 18.26 (SD) mg/100ml serum, ranging from 30.5 to 116.5 mg/100ml.

  5. Hybrid Additive Manufacturing Technologies - An Analysis Regarding Potentials and Applications

    NASA Astrophysics Data System (ADS)

    Merklein, Marion; Junker, Daniel; Schaub, Adam; Neubauer, Franziska

    Imposing the trend of mass customization of lightweight construction in industry, conventional manufacturing processes like forming technology and chipping production are pushed to their limits for economical manufacturing. More flexible processes are needed which were developed by the additive manufacturing technology. This toolless production principle offers a high geometrical freedom and an optimized utilization of the used material. Thus load adjusted lightweight components can be produced in small lot sizes in an economical way. To compensate disadvantages like inadequate accuracy and surface roughness hybrid machines combining additive and subtractive manufacturing are developed. Within this paper the principles of mainly used additive manufacturing processes of metals and their possibility to be integrated into a hybrid production machine are summarized. It is pointed out that in particular the integration of deposition processes into a CNC milling center supposes high potential for manufacturing larger parts with high accuracy. Furthermore the combination of additive and subtractive manufacturing allows the production of ready to use products within one single machine. Additionally actual research for the integration of additive manufacturing processes into the production chain will be analyzed. For the long manufacturing time of additive production processes the combination with conventional manufacturing processes like sheet or bulk metal forming seems an effective solution. Especially large volumes can be produced by conventional processes. In an additional production step active elements can be applied by additive manufacturing. This principle is also investigated for tool production to reduce chipping of the high strength material used for forming tools. The aim is the addition of active elements onto a geometrical simple basis by using Laser Metal Deposition. That process allows the utilization of several powder materials during one process what

  6. Integrative Lifecourse and Genetic Analysis of Military Working Dogs

    DTIC Science & Technology

    2014-12-01

    Award Number: W81XWH-11-2-0226 TITLE: Integrative Lifecourse and Genetic Analysis of Military Working Dogs PRINCIPAL INVESTIGATOR: Kun Huang...Integrative Lifecourse and Genetic Analysis of Military Working Dogs 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-2-0226 5c. PROGRAM ELEMENT NUMBER...of the military working dog population. There are several critical aspects to meeting the aims of this proposal. 1) development of data driven

  7. Genetic evidence for an additional function of phage T4 gene 32 protein: interaction with ligase.

    PubMed

    Mosig, G; Breschkin, A M

    1975-04-01

    Gene 32 of bacteriophage T4 is essential for DNA replication, recombination, and repair. In an attempt to clarify the role of the corresponding gene product, we have looked for mutations that specifically inactivate one but not all of its functions and for compensating suppressor mutations in other genes. Here we describe a gene 32 ts mutant that does not produce progeny, but in contrast to an am mutant investigated by others, is capable of some primary and secondary DNA replication and of forming "joint" recombinational intermediates after infection of Escherichia coli B at the restrictive temperature. However, parental and progeny DNA strands are not ligated to covalently linked "recombinant" molecules, and single strands of vegetative DNA do not exceed unit length. Progeny production as well as capacity for covalent linkage in this gene 32 ts mutant are partially restored by additional rII mutations. Suppression by rII depends on functioning host ligase [EC 6.5.1.2; poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming, NMN-forming)]. This gene 32 ts mutation (unlike some others) in turn suppresses the characteristic plaque morphology of rII mutants. We conclude that gene 32 protein, in addition to its role in DNA replication and in the formation of "joint" recombinational intermediates, interacts with T4 ligase [EC 6.5.1.1; poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming)] when recombining DNA strands are covalently linked. The protein of the mutant that we describe here is mainly defective in this interaction, thus inactivating T4 ligase in recombination. Suppressing rII mutations facilitate substitution of host ligase. There is suggestive evidence that these interactions occur at the membrane.

  8. Molecular genetic analysis of giant cell glioblastomas.

    PubMed Central

    Meyer-Puttlitz, B.; Hayashi, Y.; Waha, A.; Rollbrocker, B.; Boström, J.; Wiestler, O. D.; Louis, D. N.; Reifenberger, G.; von Deimling, A.

    1997-01-01

    Glioblastomas (GBMs) are a heterogeneous group of tumors. Recently, distinct molecular genetic alterations have been linked to subgroups of patients with GBM. Giant cell (gc)GBMs are a rare variant of GBM characterized by a marked preponderance of multinucleated giant cells. Several reports have associated this entity with a more favorable prognosis than the majority of GBMs. To evaluate whether gcGBM may also represent a genetically defined subgroup of GBM, we analyzed a series of 19 gcGBMs for mutations in the TP53 gene for amplification of the EGFR and CDK4 genes and for homozygous deletions in the CDKN2A (p16/MTS1) gene. Seventeen of nineteen gcGBMs carried TP53 mutations whereas EGFR and CDK4 gene amplification was seen in only one tumor each and homozygous deletion of CDKN2A was not observed at all. The strikingly high incidence of TP53 mutations and the relative absence of other genetic alterations groups gcGBM together with a previously recognized molecular genetic variant of GBM (type 1 GBM). It is tempting to speculate that the better prognosis of gcGBM patients may result from the low incidence of EGFR amplification and CDKN2A deletion, changes known for their growth-promoting potential. Images Figure 1 PMID:9284834

  9. Global Population Genetic Analysis of Aspergillus fumigatus

    PubMed Central

    Ashu, Eta Ebasi; Hagen, Ferry; Chowdhary, Anuradha

    2017-01-01

    ABSTRACT Aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen capable of causing invasive aspergillosis, a globally distributed disease with a mortality rate of up to 90% in high-risk populations. Effective control and prevention of this disease require a thorough understanding of its epidemiology. However, despite significant efforts, the global molecular epidemiology of A. fumigatus remains poorly understood. In this study, we analyzed 2,026 A. fumigatus isolates from 13 countries in four continents using nine highly polymorphic microsatellite markers. Genetic cluster analyses suggest that our global sample of A. fumigatus isolates belonged to eight genetic clusters, with seven of the eight clusters showing broad geographic distributions. We found common signatures of sexual recombination within individual genetic clusters and clear evidence of hybridization between several clusters. Limited but statistically significant genetic differentiations were found among geographic and ecological populations. However, there was abundant evidence for gene flow at the local, regional, and global scales. Interestingly, the triazole-susceptible and triazole-resistant populations showed different population structures, consistent with antifungal drug pressure playing a significant role in local adaptation. Our results suggest that global populations of A. fumigatus are shaped by historical differentiation, contemporary gene flow, sexual reproduction, and the localized antifungal drug selection that is driving clonal expansion of genotypes resistant to multiple triazole drugs. IMPORTANCE The genetic diversity and geographic structure of the human fungal pathogen A. fumigatus have been the subject of many studies. However, most previous studies had relatively limited sample ranges and sizes and/or used genetic markers with low-level polymorphisms. In this paper, we characterize a global collection of strains of A. fumigatus using a panel of 9 highly

  10. Molecular genetic analysis of plant gravitropism

    NASA Technical Reports Server (NTRS)

    Lomax, T. L.

    1997-01-01

    The analysis of mutants is a powerful approach for elucidating the components of complex biological processes. A growing number of mutants have been isolated which affect plant gravitropism and the classes of mutants found thus far provide important information about the gravity response mechanism. The wide variety of mutants isolated, especially in Arabidopsis, indicates that gravitropism is a complex, multi-step process. The existence of mutants altered in either root gravitropism alone, shoot gravitropism alone, or both indicates that the root and shoot gravitropic mechanisms have both separate and common steps. Reduced starch mutants have confirmed the role of amyloplasts in sensing the gravity signal. The hormone auxin is thought to act as the transducing signal between the sites of gravity perception (the starch parenchyma cells surrounding the vascular tissue in shoots and the columella cells of root caps) and asymmetric growth (the epidermal cells of the elongation zone(s) of each organ). To date, all mutants that are resistant to high concentrations of auxin have also been found to exhibit a reduced gravitropic response, thus supporting the role of auxin. Not all gravitropic mutants are auxin-resistant, however, indicating that there are additional steps which do not involve auxin. Studies with mutants of tomato which exhibit either reduced or reversed gravitropic responses further support the role of auxin redistribution in gravitropism and suggest that both red light and cytokinin interact with gravitropism through controlling lateral auxin transport. Plant responses to gravity thus likely involve changes in both auxin transport and sensitivity.

  11. Molecular genetic analysis of plant gravitropism.

    PubMed

    Lomax, T L

    1997-06-01

    The analysis of mutants is a powerful approach for elucidating the components of complex biological processes. A growing number of mutants have been isolated which affect plant gravitropism and the classes of mutants found thus far provide important information about the gravity response mechanism. The wide variety of mutants isolated, especially in Arabidopsis, indicates that gravitropism is a complex, multi-step process. The existence of mutants altered in either root gravitropism alone, shoot gravitropism alone, or both indicates that the root and shoot gravitropic mechanisms have both separate and common steps. Reduced starch mutants have confirmed the role of amyloplasts in sensing the gravity signal. The hormone auxin is thought to act as the transducing signal between the sites of gravity perception (the starch parenchyma cells surrounding the vascular tissue in shoots and the columella cells of root caps) and asymmetric growth (the epidermal cells of the elongation zone(s) of each organ). To date, all mutants that are resistant to high concentrations of auxin have also been found to exhibit a reduced gravitropic response, thus supporting the role of auxin. Not all gravitropic mutants are auxin-resistant, however, indicating that there are additional steps which do not involve auxin. Studies with mutants of tomato which exhibit either reduced or reversed gravitropic responses further support the role of auxin redistribution in gravitropism and suggest that both red light and cytokinin interact with gravitropism through controlling lateral auxin transport. Plant responses to gravity thus likely involve changes in both auxin transport and sensitivity.

  12. Population genetic analysis of Giardia duodenalis: genetic diversity and haplotype sharing between clinical and environmental sources.

    PubMed

    Durigan, Mauricio; Ciampi-Guillardi, Maisa; Rodrigues, Ricardo C A; Greinert-Goulart, Juliane A; Siqueira-Castro, Isabel C V; Leal, Diego A G; Yamashiro, Sandra; Bonatti, Taís R; Zucchi, Maria I; Franco, Regina M B; de Souza, Anete P

    2017-01-11

    Giardia duodenalis is a flagellated intestinal protozoan responsible for infections in various hosts including humans and several wild and domestic animals. Few studies have correlated environmental contamination and clinical infections in the same region. The aim of this study was to compare groups of Giardia duodenalis from clinical and environmental sources through population genetic analyses to verify haplotype sharing and the degree of genetic similarity among populations from clinical and environmental sources in the metropolitan region of Campinas. The results showed high diversity of haplotypes and substantial genetic similarity between clinical and environmental groups of G. duodenalis. We demonstrated sharing of Giardia genotypes among the different populations studied. The comparison between veterinary and human sequences led us to identify new zoonotic genotypes, including human isolates from genetic assemblage C. The application of a population genetic analysis in epidemiological studies allows quantification of the degree of genetic similarity among populations of Giardia duodenalis from different sources of contamination. The genetic similarity of Giardia isolates among human, veterinary, and environmental groups reinforced the correlation between clinical and environmental isolates in this region, which is of great importance for public health.

  13. Collection of pedigree data for genetic analysis in isolate populations.

    PubMed

    Williams-Blangero, Sarah; Blangero, John

    2006-02-01

    Pedigree data are useful for a wealth of research purposes in human population biology and genetics. The collection of extended pedigrees represents the most powerful sampling design for quantitative genetic and linkage studies of both normal and disease-related quantitative traits. In this paper we outline an approach for collecting pedigree data in stable isolate populations. As an example, the pedigree for the Jirel population, which was obtained using the methods presented, is described. The Jirel pedigree contains 2,000 study participants and more than 62,000 pairwise relationships that are informative for genetic analysis. Once such pedigrees are genetically characterized by a genome scan for a given trait, they become an invaluable resource for future genetic studies of any quantitative trait.

  14. Additional analysis of dendrochemical data of Fallon, Nevada.

    PubMed

    Sheppard, Paul R; Helsel, Dennis R; Speakman, Robert J; Ridenour, Gary; Witten, Mark L

    2012-04-05

    Previously reported dendrochemical data showed temporal variability in concentration of tungsten (W) and cobalt (Co) in tree rings of Fallon, Nevada, US. Criticism of this work questioned the use of the Mann-Whitney test for determining change in element concentrations. Here, we demonstrate that Mann-Whitney is appropriate for comparing background element concentrations to possibly elevated concentrations in environmental media. Given that Mann-Whitney tests for differences in shapes of distributions, inter-tree variability (e.g., "coefficient of median variation") was calculated for each measured element across trees within subsites and time periods. For W and Co, the metals of highest interest in Fallon, inter-tree variability was always higher within versus outside of Fallon. For calibration purposes, this entire analysis was repeated at a different town, Sweet Home, Oregon, which has a known tungsten-powder facility, and inter-tree variability of W in tree rings confirmed the establishment date of that facility. Mann-Whitney testing of simulated data also confirmed its appropriateness for analysis of data affected by point-source contamination. This research adds important new dimensions to dendrochemistry of point-source contamination by adding analysis of inter-tree variability to analysis of central tendency. Fallon remains distinctive by a temporal increase in W beginning by the mid 1990s and by elevated Co since at least the early 1990s, as well as by high inter-tree variability for W and Co relative to comparison towns.

  15. Analysis of fluorine addition to the vanguard first stage

    NASA Technical Reports Server (NTRS)

    Tomazic, William A; Schmidt, Harold W; Tischler, Adelbert O

    1957-01-01

    The effect of adding fluorine to the Vanguard first-stage oxidant was anlyzed. An increase in specific impulse of 5.74 percent may be obtained with 30 percent fluorine. This increase, coupled with increased mass ratio due to greater oxidant density, gave up to 24.6-percent increase in first-stage burnout energy with 30 percent fluorine added. However, a change in tank configuration is required to accommodate the higher oxidant-fuel ratio necessary for peak specific impulse with fluorine addition.

  16. Adaptive divergence despite strong genetic drift: genomic analysis of the evolutionary mechanisms causing genetic differentiation in the island fox (Urocyon littoralis).

    PubMed

    Funk, W Chris; Lovich, Robert E; Hohenlohe, Paul A; Hofman, Courtney A; Morrison, Scott A; Sillett, T Scott; Ghalambor, Cameron K; Maldonado, Jesus E; Rick, Torben C; Day, Mitch D; Polato, Nicholas R; Fitzpatrick, Sarah W; Coonan, Timothy J; Crooks, Kevin R; Dillon, Adam; Garcelon, David K; King, Julie L; Boser, Christina L; Gould, Nicholas; Andelt, William F

    2016-05-01

    The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are predicted to be strong on islands and both could drive population divergence and speciation. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of six subspecies, each of which occupies a different California Channel Island. Analysis of 5293 SNP loci generated using Restriction-site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mechanism driving population divergence among island fox populations. In particular, populations had exceptionally low genetic variation, small Ne (range = 2.1-89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland grey foxes, and vice versa, indicating genetic drift drives genome-wide divergence. Nonetheless, outlier tests identified 3.6-6.6% of loci as high FST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high FST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small Ne in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness and reduced adaptive potential.

  17. Implementation of the Realized Genomic Relationship Matrix to Open-Pollinated White Spruce Family Testing for Disentangling Additive from Nonadditive Genetic Effects

    PubMed Central

    Gamal El-Dien, Omnia; Ratcliffe, Blaise; Klápště, Jaroslav; Porth, Ilga; Chen, Charles; El-Kassaby, Yousry A.

    2016-01-01

    The open-pollinated (OP) family testing combines the simplest known progeny evaluation and quantitative genetics analyses as candidates’ offspring are assumed to represent independent half-sib families. The accuracy of genetic parameter estimates is often questioned as the assumption of “half-sibling” in OP families may often be violated. We compared the pedigree- vs. marker-based genetic models by analysing 22-yr height and 30-yr wood density for 214 white spruce [Picea glauca (Moench) Voss] OP families represented by 1694 individuals growing on one site in Quebec, Canada. Assuming half-sibling, the pedigree-based model was limited to estimating the additive genetic variances which, in turn, were grossly overestimated as they were confounded by very minor dominance and major additive-by-additive epistatic genetic variances. In contrast, the implemented genomic pairwise realized relationship models allowed the disentanglement of additive from all nonadditive factors through genetic variance decomposition. The marker-based models produced more realistic narrow-sense heritability estimates and, for the first time, allowed estimating the dominance and epistatic genetic variances from OP testing. In addition, the genomic models showed better prediction accuracies compared to pedigree models and were able to predict individual breeding values for new individuals from untested families, which was not possible using the pedigree-based model. Clearly, the use of marker-based relationship approach is effective in estimating the quantitative genetic parameters of complex traits even under simple and shallow pedigree structure. PMID:26801647

  18. Implementation of the Realized Genomic Relationship Matrix to Open-Pollinated White Spruce Family Testing for Disentangling Additive from Nonadditive Genetic Effects.

    PubMed

    Gamal El-Dien, Omnia; Ratcliffe, Blaise; Klápště, Jaroslav; Porth, Ilga; Chen, Charles; El-Kassaby, Yousry A

    2016-01-22

    The open-pollinated (OP) family testing combines the simplest known progeny evaluation and quantitative genetics analyses as candidates' offspring are assumed to represent independent half-sib families. The accuracy of genetic parameter estimates is often questioned as the assumption of "half-sibling" in OP families may often be violated. We compared the pedigree- vs. marker-based genetic models by analysing 22-yr height and 30-yr wood density for 214 white spruce [Picea glauca (Moench) Voss] OP families represented by 1694 individuals growing on one site in Quebec, Canada. Assuming half-sibling, the pedigree-based model was limited to estimating the additive genetic variances which, in turn, were grossly overestimated as they were confounded by very minor dominance and major additive-by-additive epistatic genetic variances. In contrast, the implemented genomic pairwise realized relationship models allowed the disentanglement of additive from all nonadditive factors through genetic variance decomposition. The marker-based models produced more realistic narrow-sense heritability estimates and, for the first time, allowed estimating the dominance and epistatic genetic variances from OP testing. In addition, the genomic models showed better prediction accuracies compared to pedigree models and were able to predict individual breeding values for new individuals from untested families, which was not possible using the pedigree-based model. Clearly, the use of marker-based relationship approach is effective in estimating the quantitative genetic parameters of complex traits even under simple and shallow pedigree structure.

  19. Porosity Measurements and Analysis for Metal Additive Manufacturing Process Control

    PubMed Central

    Slotwinski, John A; Garboczi, Edward J; Hebenstreit, Keith M

    2014-01-01

    Additive manufacturing techniques can produce complex, high-value metal parts, with potential applications as critical metal components such as those found in aerospace engines and as customized biomedical implants. Material porosity in these parts is undesirable for aerospace parts - since porosity could lead to premature failure - and desirable for some biomedical implants - since surface-breaking pores allows for better integration with biological tissue. Changes in a part’s porosity during an additive manufacturing build may also be an indication of an undesired change in the build process. Here, we present efforts to develop an ultrasonic sensor for monitoring changes in the porosity in metal parts during fabrication on a metal powder bed fusion system. The development of well-characterized reference samples, measurements of the porosity of these samples with multiple techniques, and correlation of ultrasonic measurements with the degree of porosity are presented. A proposed sensor design, measurement strategy, and future experimental plans on a metal powder bed fusion system are also presented. PMID:26601041

  20. Porosity Measurements and Analysis for Metal Additive Manufacturing Process Control.

    PubMed

    Slotwinski, John A; Garboczi, Edward J; Hebenstreit, Keith M

    2014-01-01

    Additive manufacturing techniques can produce complex, high-value metal parts, with potential applications as critical metal components such as those found in aerospace engines and as customized biomedical implants. Material porosity in these parts is undesirable for aerospace parts - since porosity could lead to premature failure - and desirable for some biomedical implants - since surface-breaking pores allows for better integration with biological tissue. Changes in a part's porosity during an additive manufacturing build may also be an indication of an undesired change in the build process. Here, we present efforts to develop an ultrasonic sensor for monitoring changes in the porosity in metal parts during fabrication on a metal powder bed fusion system. The development of well-characterized reference samples, measurements of the porosity of these samples with multiple techniques, and correlation of ultrasonic measurements with the degree of porosity are presented. A proposed sensor design, measurement strategy, and future experimental plans on a metal powder bed fusion system are also presented.

  1. Analysis of Saccharides by the Addition of Amino Acids

    NASA Astrophysics Data System (ADS)

    Ozdemir, Abdil; Lin, Jung-Lee; Gillig, Kent J.; Gulfen, Mustafa; Chen, Chung-Hsuan

    2016-06-01

    In this work, we present the detection sensitivity improvement of electrospray ionization (ESI) mass spectrometry of neutral saccharides in a positive ion mode by the addition of various amino acids. Saccharides of a broad molecular weight range were chosen as the model compounds in the present study. Saccharides provide strong noncovalent interactions with amino acids, and the complex formation enhances the signal intensity and simplifies the mass spectra of saccharides. Polysaccharides provide a polymer-like ESI spectrum with a basic subunit difference between multiply charged chains. The protonated spectra of saccharides are not well identified because of different charge state distributions produced by the same molecules. Depending on the solvent used and other ions or molecules present in the solution, noncovalent interactions with saccharides may occur. These interactions are affected by the addition of amino acids. Amino acids with polar side groups show a strong tendency to interact with saccharides. In particular, serine shows a high tendency to interact with saccharides and significantly improves the detection sensitivity of saccharide compounds.

  2. Additional EIPC Study Analysis: Interim Report on High Priority Topics

    SciTech Connect

    Hadley, Stanton W

    2013-11-01

    Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations were developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 13 topics was developed for further analysis; this paper discusses the first five.

  3. Risk analysis of sulfites used as food additives in China.

    PubMed

    Zhang, Jian Bo; Zhang, Hong; Wang, Hua Li; Zhang, Ji Yue; Luo, Peng Jie; Zhu, Lei; Wang, Zhu Tian

    2014-02-01

    This study was to analyze the risk of sulfites in food consumed by the Chinese people and assess the health protection capability of maximum-permitted level (MPL) of sulfites in GB 2760-2011. Sulfites as food additives are overused or abused in many food categories. When the MPL in GB 2760-2011 was used as sulfites content in food, the intake of sulfites in most surveyed populations was lower than the acceptable daily intake (ADI). Excess intake of sulfites was found in all the surveyed groups when a high percentile of sulfites in food was in taken. Moreover, children aged 1-6 years are at a high risk to intake excess sulfites. The primary cause for the excess intake of sulfites in Chinese people is the overuse and abuse of sulfites by the food industry. The current MPL of sulfites in GB 2760-2011 protects the health of most populations.

  4. Disclosure of hydraulic fracturing fluid chemical additives: analysis of regulations.

    PubMed

    Maule, Alexis L; Makey, Colleen M; Benson, Eugene B; Burrows, Isaac J; Scammell, Madeleine K

    2013-01-01

    Hydraulic fracturing is used to extract natural gas from shale formations. The process involves injecting into the ground fracturing fluids that contain thousands of gallons of chemical additives. Companies are not mandated by federal regulations to disclose the identities or quantities of chemicals used during hydraulic fracturing operations on private or public lands. States have begun to regulate hydraulic fracturing fluids by mandating chemical disclosure. These laws have shortcomings including nondisclosure of proprietary or "trade secret" mixtures, insufficient penalties for reporting inaccurate or incomplete information, and timelines that allow for after-the-fact reporting. These limitations leave lawmakers, regulators, public safety officers, and the public uninformed and ill-prepared to anticipate and respond to possible environmental and human health hazards associated with hydraulic fracturing fluids. We explore hydraulic fracturing exemptions from federal regulations, as well as current and future efforts to mandate chemical disclosure at the federal and state level.

  5. Genetic Analysis of Mice Skin Exposed by Hyper-Gravity

    NASA Astrophysics Data System (ADS)

    Takahashi, Rika; Terada, Masahiro; Seki, Masaya; Higashibata, Akira; Majima, Hideyuki J.; Ohira, Yoshinobu; Mukai, Chiaki; Ishioka, Noriaki

    2013-02-01

    In the space environment, physiological alterations, such as low bone density, muscle weakness and decreased immunity, are caused by microgravity and cosmic radiation. On the other hand, it is known that the leg muscles are hypertrophy by 2G-gravity. An understanding of the effects on human body from microgravity to hyper-gravity is very important. Recently, the Japan Aerospace Exploration Agency (JAXA) has started a project to detect the changes on gene expression and mineral metabolism caused by microgravity by analyzing the hair of astronauts who stay in the international Space Station (ISS) for a long time. From these results of human hair’s research, the genetic effects of human hair roots by microgravity will become clear. However, it is unclear how the gene expression of hair roots was effected by hypergravity. Therefore, in this experiment, we analyzed the effect on mice skin contained hair roots by comparing microgravity or hypergravity exposed mice. The purpose of this experiment is to evaluate the genetic effects on mice skin by microgravity or 2G-gravity. The samples were taken from mice exposed to space flight (FL) or hypergravity environment (2G) for 3-months, respectively. The extracted and amplified RNA from these mice skin was used to DNA microarray analysis. in this experiment, we analyzed the effect of gravity by using mice skin contained hair roots, which exposed space (FL) and hyper-gravity (2G) for 3 months and each control. By DNA microarray analysis, we found the common 98 genes changed in both FL and 2G. Among these 98 genes, the functions and pathways were identified by Gene Ontology (GO) analysis and Ingenuity Pathways Analysis (IPA) software. Next, we focused the one of the identified pathways and compared the effects on each molecules in this pathways by the different environments, such as FL and 2G. As the results, we could detect some interesting molecules, which might be depended on the gravity levels. In addition, to investigate

  6. Polyglot programming in applications used for genetic data analysis.

    PubMed

    Nowak, Robert M

    2014-01-01

    Applications used for the analysis of genetic data process large volumes of data with complex algorithms. High performance, flexibility, and a user interface with a web browser are required by these solutions, which can be achieved by using multiple programming languages. In this study, I developed a freely available framework for building software to analyze genetic data, which uses C++, Python, JavaScript, and several libraries. This system was used to build a number of genetic data processing applications and it reduced the time and costs of development.

  7. Polyglot Programming in Applications Used for Genetic Data Analysis

    PubMed Central

    Nowak, Robert M.

    2014-01-01

    Applications used for the analysis of genetic data process large volumes of data with complex algorithms. High performance, flexibility, and a user interface with a web browser are required by these solutions, which can be achieved by using multiple programming languages. In this study, I developed a freely available framework for building software to analyze genetic data, which uses C++, Python, JavaScript, and several libraries. This system was used to build a number of genetic data processing applications and it reduced the time and costs of development. PMID:25197633

  8. Rice artificial hybridization for genetic analysis.

    PubMed

    Sha, Xueyan

    2013-01-01

    Artificial hybridization has probably been practiced since ancient time; however, the science of genetics did not initiate until Gregor Mendel conducted a series of crosses between different pure lines of garden pea and made careful observations and systematical analyses of their offspring. Artificial hybridization or crossing between carefully chosen parents has been and still is the primary way to transfer genes from different germplasm for self-pollinated rice. Through gene recombination, novel genetic variation is created by different arrangements of genes existing in parental lines. Procedures of artificial hybridization involve the selection of appropriate panicles from representative plants of the female parents, the emasculation of female parents, and the pollination of emasculated panicles with abundant pollens of selected male parents. Of the numerous proposed methods, hot water and vacuum emasculation have proven to be the most robust and reliable ones. A successful and efficient hybridization program also relies on the knowledge of parental lines or germplasm, the reproductive biology and development of rice, the conditions needed to promote flowering and seed development, and the techniques to synchronize flowering of diverse parents.

  9. The Genetic Analysis of an Acinetobacter johnsonii Clinical Strain Evidenced the Presence of Horizontal Genetic Transfer.

    PubMed

    Montaña, Sabrina; Schramm, Sareda T J; Traglia, German Matías; Chiem, Kevin; Parmeciano Di Noto, Gisela; Almuzara, Marisa; Barberis, Claudia; Vay, Carlos; Quiroga, Cecilia; Tolmasky, Marcelo E; Iriarte, Andrés; Ramírez, María Soledad

    2016-01-01

    Acinetobacter johnsonii rarely causes human infections. While most A. johnsonii isolates are susceptible to virtually all antibiotics, strains harboring a variety of β-lactamases have recently been described. An A. johnsonii Aj2199 clinical strain recovered from a hospital in Buenos Aires produces PER-2 and OXA-58. We decided to delve into its genome by obtaining the whole genome sequence of the Aj2199 strain. Genome comparison studies on Aj2199 revealed 240 unique genes and a close relation to strain WJ10621, isolated from the urine of a patient in China. Genomic analysis showed evidence of horizontal genetic transfer (HGT) events. Forty-five insertion sequences and two intact prophages were found in addition to several resistance determinants such as blaPER-2, blaOXA-58, blaTEM-1, strA, strB, ereA, sul1, aacC2 and a new variant of blaOXA-211, called blaOXA-498. In particular, blaPER-2 and blaTEM-1 are present within the typical contexts previously described in the Enterobacteriaceae family. These results suggest that A. johnsonii actively acquires exogenous DNA from other bacterial species and concomitantly becomes a reservoir of resistance genes.

  10. The Genetic Analysis of an Acinetobacter johnsonii Clinical Strain Evidenced the Presence of Horizontal Genetic Transfer

    PubMed Central

    Montaña, Sabrina; Schramm, Sareda T. J.; Traglia, German Matías; Chiem, Kevin; Parmeciano Di Noto, Gisela; Almuzara, Marisa; Barberis, Claudia; Vay, Carlos; Quiroga, Cecilia; Tolmasky, Marcelo E.; Iriarte, Andrés; Ramírez, María Soledad

    2016-01-01

    Acinetobacter johnsonii rarely causes human infections. While most A. johnsonii isolates are susceptible to virtually all antibiotics, strains harboring a variety of β-lactamases have recently been described. An A. johnsonii Aj2199 clinical strain recovered from a hospital in Buenos Aires produces PER-2 and OXA-58. We decided to delve into its genome by obtaining the whole genome sequence of the Aj2199 strain. Genome comparison studies on Aj2199 revealed 240 unique genes and a close relation to strain WJ10621, isolated from the urine of a patient in China. Genomic analysis showed evidence of horizontal genetic transfer (HGT) events. Forty-five insertion sequences and two intact prophages were found in addition to several resistance determinants such as blaPER-2, blaOXA-58, blaTEM-1, strA, strB, ereA, sul1, aacC2 and a new variant of blaOXA-211, called blaOXA-498. In particular, blaPER-2 and blaTEM-1 are present within the typical contexts previously described in the Enterobacteriaceae family. These results suggest that A. johnsonii actively acquires exogenous DNA from other bacterial species and concomitantly becomes a reservoir of resistance genes. PMID:27548264

  11. Polygenic mutation in Droosophila melanogaster: Genetic analysis of selection lines

    SciTech Connect

    Fry, J.D.; deRonde, K.A.; Mackay, T.F.C.

    1995-03-01

    The authors have conducted genetic analyses of 12 long-term selection lines of Drosophila melanogaster derived from a highly inbred base population, containing new mutations affecting abdominal and sternopleural bristle number. Biometric analysis of the number of effective factors differentiating the selected lines from the base inbred indicated that with the exception of the three lines selected for increased number of abdominal bristles, three or more mutations contributed to the responses of the selection lines. Analysis of the chromosomal distribution of effects revealed that mutations affecting abdominal bristle number occurred on all three major chromosomes. In addition, Y-linked mutations with effects ranging from one to three bristles occurred in all three lines selected for decreased number of abdominal bristles, as well as in one line selected for increased abdominal bristle number. Mutations affecting sternopleural bristle number were mainly on the X and third chromosomes. One abdominal and one sternopleural selection line showed evidence of a segregating lethal with large effects on bristle number. As an indirect test for allelism of mutations occurring in different selection lines, the three lines selected in the same direction for the same trait were crossed in all possible combinations, and selection continued from the F{sub 2} hybrides. Responses of the hybrid lines usually did not exceed those of the most extreme parental lines, indicating that the responses of the parental lines may have been partly due to mutations at the same loci, although other interpretations are possible.

  12. Evolution of the additive genetic variance–covariance matrix under continuous directional selection on a complex behavioural phenotype

    PubMed Central

    Careau, Vincent; Wolak, Matthew E.; Carter, Patrick A.; Garland, Theodore

    2015-01-01

    Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance–covariance matrix (G). Yet knowledge of G in a population experiencing new or altered selection is not sufficient to predict selection response because G itself evolves in ways that are poorly understood. We experimentally evaluated changes in G when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change. PMID:26582016

  13. Selection for increased desiccation resistance in Drosophila melanogaster: Additive genetic control and correlated responses for other stresses

    SciTech Connect

    Hoffmann, A.A.; Parsons, P.A. )

    1989-08-01

    Previously we found that Drosophila melanogaster lines selected for increased desiccation resistance have lowered metabolic rate and behavioral activity levels, and show correlated responses for resistance to starvation and a toxic ethanol level. These results were consistent with a prediction that increased resistance to many environmental stresses may be genetically correlated because of a reduction in metabolic energy expenditure. Here we present experiments on the genetic basis of the selection response and extend the study of correlated responses to other stresses. The response to selection was not sex-specific and involved X-linked and autosomal genes acting additively. Activity differences contributed little to differences in desiccation resistance between selected and control lines. Selected lines had lower metabolic rates than controls in darkness when activity was inhibited. Adults from selected lines showed increased resistance to a heat shock, {sup 60}Co-gamma-radiation, and acute ethanol and acetic acid stress. The desiccation, ethanol and starvation resistance of isofemale lines set up from the F2s of a cross between one of the selected and one of the control lines were correlated. Selected and control lines did not differ in ether-extractable lipid content or in resistance to acetone, ether or a cold shock.

  14. Evolution of the additive genetic variance-covariance matrix under continuous directional selection on a complex behavioural phenotype.

    PubMed

    Careau, Vincent; Wolak, Matthew E; Carter, Patrick A; Garland, Theodore

    2015-11-22

    Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance-covariance matrix ( G: ). Yet knowledge of G: in a population experiencing new or altered selection is not sufficient to predict selection response because G: itself evolves in ways that are poorly understood. We experimentally evaluated changes in G: when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G: induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G: induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G: and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change.

  15. A MULTI-LOCUS, MULTI-TAXA PHYLOGEOGRAPHICAL ANALYSIS OF GENETIC DIVERSITY

    EPA Science Inventory

    In addition to measuring spatial patterns of genetic diversity, population genetic measures of biological resources should include temporal data that indicate whether the observed patterns are the result of historical or contemporary processes. In general, genetic measures focus...

  16. Integrative Bayesian Analysis of Neuroimaging-Genetic Data with Application to Cocaine Dependence

    PubMed Central

    Azadeh, Shabnam; Hobbs, Brian P.; Ma, Liangsuo; Nielsen, David A.; Moeller, F. Gerard; Baladandayuthapani, Veerabhadran

    2016-01-01

    Neuroimaging and genetic studies provide distinct and complementary information about the structural and biological aspects of a disease. Integrating the two sources of data facilitates the investigation of the links between genetic variability and brain mechanisms among different individuals for various medical disorders. This article presents a general statistical framework for integrative Bayesian analysis of neuroimaging-genetic (iBANG) data, which is motivated by a neuroimaging-genetic study in cocaine dependence. Statistical inference necessitated the integration of spatially dependent voxel-level measurements with various patient-level genetic and demographic characteristics under an appropriate probability model to account for the multiple inherent sources of variation. Our framework uses Bayesian model averaging to integrate genetic information into the analysis of voxel-wise neuroimaging data, accounting for spatial correlations in the voxels. Using multiplicity controls based on the false discovery rate, we delineate voxels associated with genetic and demographic features that may impact diffusion as measured by fractional anisotropy (FA) obtained from DTI images. We demonstrate the benefits of accounting for model uncertainties in both model fit and prediction. Our results suggest that cocaine consumption is associated with FA reduction in most white matter regions of interest in the brain. Additionally, gene polymorphisms associated with GABAergic, serotonergic and dopaminergic neurotransmitters and receptors were associated with FA. PMID:26484829

  17. Replication of a gene-environment interaction Via Multimodel inference: additive-genetic variance in adolescents' general cognitive ability increases with family-of-origin socioeconomic status.

    PubMed

    Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

    2015-03-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES-an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research.

  18. Replication of a Gene-Environment Interaction via Multimodel Inference: Additive-Genetic Variance in Adolescents’ General Cognitive Ability Increases with Family-of-Origin Socioeconomic Status

    PubMed Central

    Kirkpatrick, Robert M.; McGue, Matt; Iacono, William G.

    2015-01-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES—an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research. PMID:25539975

  19. Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders.

    PubMed

    Ligthart, Lannie; Hottenga, Jouke-Jan; Lewis, Cathryn M; Farmer, Anne E; Craig, Ian W; Breen, Gerome; Willemsen, Gonneke; Vink, Jacqueline M; Middeldorp, Christel M; Byrne, Enda M; Heath, Andrew C; Madden, Pamela A F; Pergadia, Michele L; Montgomery, Grant W; Martin, Nicholas G; Penninx, Brenda W J H; McGuffin, Peter; Boomsma, Dorret I; Nyholt, Dale R

    2014-02-01

    Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR-NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the 'pure' forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD.

  20. Molecular basis of inherited antithrombin deficiency in Portuguese families: identification of genetic alterations and screening for additional thrombotic risk factors.

    PubMed

    David, Dezsö; Ribeiro, Sofia; Ferrão, Lénia; Gago, Teresa; Crespo, Francisco

    2004-06-01

    Antithrombin (AT), the most important coagulation serine proteases inhibitor, plays an important role in maintaining the hemostatic balance. Inherited AT deficiency, mainly characterized by predisposition to recurrent venous thromboembolism, is transmitted in an autosomal dominant manner. In this study, we analyzed the underlying genetic alterations in 12 unrelated Portuguese thrombophilic families with AT deficiency. At the same time, the modulating effect of the FV Leiden mutation, PT 20210A, PAI-1 4G, and MTHFR 677T allelic variants, on the thrombotic risk of AT deficient patients was also evaluated. Three novel frameshift alterations, a 4-bp deletion in exon 4 and two 1-bp insertions in exon 6, were identified in six unrelated type I AT deficient families. A novel missense mutation in exon 3a, which changes the highly conserved F147 residue, and a novel splice site mutation in the invariant acceptor AG dinucleotide of intron 2 were also identified in unrelated type I AT deficient families. In addition to these, two previously reported missense mutations changing the AT reactive site bond (R393-S394) and leading to type II-RS deficiency, and a previously reported cryptic splice site mutation (IVS4-14G-->A), were also identified. In these families, increased thrombotic risk associated with co-inheritance of the FV Leiden mutation and of the PAI-1 4G variant was also observed. In conclusion, we present the first data regarding the underlying genetic alterations in Portuguese thrombophilic families with AT deficiency, and confirm that the FV Leiden mutation and probably the PAI-1 4G variant represent additional thrombotic risk factors in these families.

  1. Molecular genetic analysis of activation-tagged transcription factors thought to be involved in photomorphogenesis

    SciTech Connect

    Neff, Michael M.

    2011-06-23

    This is a final report for Department of Energy Grant No. DE-FG02-08ER15927 entitled “Molecular Genetic Analysis of Activation-Tagged Transcription Factors Thought to be Involved in Photomorphogenesis”. Based on our preliminary photobiological and genetic analysis of the sob1-D mutant, we hypothesized that OBP3 is a transcription factor involved in both phytochrome and cryptochrome-mediated signal transduction. In addition, we hypothesized that OBP3 is involved in auxin signaling and root development. Based on our preliminary photobiological and genetic analysis of the sob2-D mutant, we also hypothesized that a related gene, LEP, is involved in hormone signaling and seedling development.

  2. Promoting utilization of Saccharum spp. genetic resources through genetic diversity analysis and core collection construction.

    PubMed

    Nayak, Spurthi N; Song, Jian; Villa, Andrea; Pathak, Bhuvan; Ayala-Silva, Tomas; Yang, Xiping; Todd, James; Glynn, Neil C; Kuhn, David N; Glaz, Barry; Gilbert, Robert A; Comstock, Jack C; Wang, Jianping

    2014-01-01

    Sugarcane (Saccharum spp.) and other members of Saccharum spp. are attractive biofuel feedstocks. One of the two World Collections of Sugarcane and Related Grasses (WCSRG) is in Miami, FL. This WCSRG has 1002 accessions, presumably with valuable alleles for biomass, other important agronomic traits, and stress resistance. However, the WCSRG has not been fully exploited by breeders due to its lack of characterization and unmanageable population. In order to optimize the use of this genetic resource, we aim to 1) genotypically evaluate all the 1002 accessions to understand its genetic diversity and population structure and 2) form a core collection, which captures most of the genetic diversity in the WCSRG. We screened 36 microsatellite markers on 1002 genotypes and recorded 209 alleles. Genetic diversity of the WCSRG ranged from 0 to 0.5 with an average of 0.304. The population structure analysis and principal coordinate analysis revealed three clusters with all S. spontaneum in one cluster, S. officinarum and S. hybrids in the second cluster and mostly non-Saccharum spp. in the third cluster. A core collection of 300 accessions was identified which captured the maximum genetic diversity of the entire WCSRG which can be further exploited for sugarcane and energy cane breeding. Sugarcane and energy cane breeders can effectively utilize this core collection for cultivar improvement. Further, the core collection can provide resources for forming an association panel to evaluate the traits of agronomic and commercial importance.

  3. Promoting Utilization of Saccharum spp. Genetic Resources through Genetic Diversity Analysis and Core Collection Construction

    PubMed Central

    Pathak, Bhuvan; Ayala-Silva, Tomas; Yang, Xiping; Todd, James; Glynn, Neil C.; Kuhn, David N.; Glaz, Barry; Gilbert, Robert A.; Comstock, Jack C.; Wang, Jianping

    2014-01-01

    Sugarcane (Saccharum spp.) and other members of Saccharum spp. are attractive biofuel feedstocks. One of the two World Collections of Sugarcane and Related Grasses (WCSRG) is in Miami, FL. This WCSRG has 1002 accessions, presumably with valuable alleles for biomass, other important agronomic traits, and stress resistance. However, the WCSRG has not been fully exploited by breeders due to its lack of characterization and unmanageable population. In order to optimize the use of this genetic resource, we aim to 1) genotypically evaluate all the 1002 accessions to understand its genetic diversity and population structure and 2) form a core collection, which captures most of the genetic diversity in the WCSRG. We screened 36 microsatellite markers on 1002 genotypes and recorded 209 alleles. Genetic diversity of the WCSRG ranged from 0 to 0.5 with an average of 0.304. The population structure analysis and principal coordinate analysis revealed three clusters with all S. spontaneum in one cluster, S. officinarum and S. hybrids in the second cluster and mostly non-Saccharum spp. in the third cluster. A core collection of 300 accessions was identified which captured the maximum genetic diversity of the entire WCSRG which can be further exploited for sugarcane and energy cane breeding. Sugarcane and energy cane breeders can effectively utilize this core collection for cultivar improvement. Further, the core collection can provide resources for forming an association panel to evaluate the traits of agronomic and commercial importance. PMID:25333358

  4. Additional challenges for uncertainty analysis in river engineering

    NASA Astrophysics Data System (ADS)

    Berends, Koen; Warmink, Jord; Hulscher, Suzanne

    2016-04-01

    the proposed intervention. The implicit assumption underlying such analysis is that both models are commensurable. We hypothesize that they are commensurable only to a certain extent. In an idealised study we have demonstrated that prediction performance loss should be expected with increasingly large engineering works. When accounting for parametric uncertainty of floodplain roughness in model identification, we see uncertainty bounds for predicted effects of interventions increase with increasing intervention scale. Calibration of these types of models therefore seems to have a shelf-life, beyond which calibration does not longer improves prediction. Therefore a qualification scheme for model use is required that can be linked to model validity. In this study, we characterize model use along three dimensions: extrapolation (using the model with different external drivers), extension (using the model for different output or indicators) and modification (using modified models). Such use of models is expected to have implications for the applicability of surrogating modelling for efficient uncertainty analysis as well, which is recommended for future research. Warmink, J. J.; Straatsma, M. W.; Huthoff, F.; Booij, M. J. & Hulscher, S. J. M. H. 2013. Uncertainty of design water levels due to combined bed form and vegetation roughness in the Dutch river Waal. Journal of Flood Risk Management 6, 302-318 . DOI: 10.1111/jfr3.12014

  5. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

    PubMed Central

    Sadovnick, A. Dessa; Traboulsee, Anthony L.; Bernales, Cecily Q.; Ross, Jay P.; Forwell, Amanda L.; Yee, Irene M.; Guillot-Noel, Lena; Fontaine, Bertrand; Cournu-Rebeix, Isabelle; Alcina, Antonio; Fedetz, Maria; Izquierdo, Guillermo; Matesanz, Fuencisla; Hilven, Kelly; Dubois, Bénédicte; Goris, An; Astobiza, Ianire; Alloza, Iraide; Antigüedad, Alfredo; Vandenbroeck, Koen; Akkad, Denis A.; Aktas, Orhan; Blaschke, Paul; Buttmann, Mathias; Chan, Andrew; Epplen, Joerg T.; Gerdes, Lisa-Ann; Kroner, Antje; Kubisch, Christian; Kümpfel, Tania; Lohse, Peter; Rieckmann, Peter; Zettl, Uwe K.; Zipp, Frauke; Bertram, Lars; Lill, Christina M; Fernandez, Oscar; Urbaneja, Patricia; Leyva, Laura; Alvarez-Cermeño, Jose Carlos; Arroyo, Rafael; Garagorri, Aroa M.; García-Martínez, Angel; Villar, Luisa M.; Urcelay, Elena; Malhotra, Sunny; Montalban, Xavier; Comabella, Manuel; Berger, Thomas; Fazekas, Franz; Reindl, Markus; Schmied, Mascha C.; Zimprich, Alexander; Vilariño-Güell, Carles

    2016-01-01

    Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility. PMID:27194806

  6. Analysis of Variance Components for Genetic Markers with Unphased Genotypes.

    PubMed

    Wang, Tao

    2016-01-01

    An ANOVA type general multi-allele (GMA) model was proposed in Wang (2014) on analysis of variance components for quantitative trait loci or genetic markers with phased or unphased genotypes. In this study, by applying the GMA model, we further examine estimation of the genetic variance components for genetic markers with unphased genotypes based on a random sample from a study population. In one locus and two loci cases, we first derive the least square estimates (LSE) of model parameters in fitting the GMA model. Then we construct estimators of the genetic variance components for one marker locus in a Hardy-Weinberg disequilibrium population and two marker loci in an equilibrium population. Meanwhile, we explore the difference between the classical general linear model (GLM) and GMA based approaches in association analysis of genetic markers with quantitative traits. We show that the GMA model can retain the same partition on the genetic variance components as the traditional Fisher's ANOVA model, while the GLM cannot. We clarify that the standard F-statistics based on the partial reductions in sums of squares from GLM for testing the fixed allelic effects could be inadequate for testing the existence of the variance component when allelic interactions are present. We point out that the GMA model can reduce the confounding between the allelic effects and allelic interactions at least for independent alleles. As a result, the GMA model could be more beneficial than GLM for detecting allelic interactions.

  7. Kinetic analysis of microbial respiratory response to substrate addition

    NASA Astrophysics Data System (ADS)

    Blagodatskaya, Evgenia; Blagodatsky, Sergey; Yuyukina, Tatayna; Kuzyakov, Yakov

    2010-05-01

    Heterotrophic component of CO2 emitted from soil is mainly due to the respiratory activity of soil microorganisms. Field measurements of microbial respiration can be used for estimation of C-budget in soil, while laboratory estimation of respiration kinetics allows the elucidation of mechanisms of soil C sequestration. Physiological approaches based on 1) time-dependent or 2) substrate-dependent respiratory response of soil microorganisms decomposing the organic substrates allow to relate the functional properties of soil microbial community with decomposition rates of soil organic matter. We used a novel methodology combining (i) microbial growth kinetics and (ii) enzymes affinity to the substrate to show the shift in functional properties of the soil microbial community after amendments with substrates of contrasting availability. We combined the application of 14C labeled glucose as easily available C source to soil with natural isotope labeling of old and young soil SOM. The possible contribution of two processes: isotopic fractionation and preferential substrate utilization to the shifts in δ13C during SOM decomposition in soil after C3-C4 vegetation change was evaluated. Specific growth rate (µ) of soil microorganisms was estimated by fitting the parameters of the equation v(t) = A + B * exp(µ*t), to the measured CO2 evolution rate (v(t)) after glucose addition, and where A is the initial rate of non-growth respiration, B - initial rate of the growing fraction of total respiration. Maximal mineralization rate (Vmax), substrate affinity of microbial enzymes (Ks) and substrate availability (Sn) were determined by Michaelis-Menten kinetics. To study the effect of plant originated C on δ13C signature of SOM we compared the changes in isotopic composition of different C pools in C3 soil under grassland with C3-C4 soil where C4 plant Miscanthus giganteus was grown for 12 years on the plot after grassland. The shift in 13δ C caused by planting of M. giganteus

  8. Rate of evolutionary change in cranial morphology of the marsupial genus Monodelphis is constrained by the availability of additive genetic variation.

    PubMed

    Porto, A; Sebastião, H; Pavan, S E; VandeBerg, J L; Marroig, G; Cheverud, J M

    2015-04-01

    We tested the hypothesis that the rate of marsupial cranial evolution is dependent on the distribution of genetic variation in multivariate space. To do so, we carried out a genetic analysis of cranial morphological variation in laboratory strains of Monodelphis domestica and used estimates of genetic covariation to analyse the morphological diversification of the Monodelphis brevicaudata species group. We found that within-species genetic variation is concentrated in only a few axes of the morphospace and that this strong genetic covariation influenced the rate of morphological diversification of the brevicaudata group, with between-species divergence occurring fastest when occurring along the genetic line of least resistance. Accounting for the geometric distribution of genetic variation also increased our ability to detect the selective regimen underlying species diversification, with several instances of selection only being detected when genetic covariances were taken into account. Therefore, this work directly links patterns of genetic covariation among traits to macroevolutionary patterns of morphological divergence. Our findings also suggest that the limited distribution of Monodelphis species in morphospace is the result of a complex interplay between the limited dimensionality of available genetic variation and strong stabilizing selection along two major axes of genetic variation.

  9. Efficient set tests for the genetic analysis of correlated traits.

    PubMed

    Casale, Francesco Paolo; Rakitsch, Barbara; Lippert, Christoph; Stegle, Oliver

    2015-08-01

    Set tests are a powerful approach for genome-wide association testing between groups of genetic variants and quantitative traits. We describe mtSet (http://github.com/PMBio/limix), a mixed-model approach that enables joint analysis across multiple correlated traits while accounting for population structure and relatedness. mtSet effectively combines the benefits of set tests with multi-trait modeling and is computationally efficient, enabling genetic analysis of large cohorts (up to 500,000 individuals) and multiple traits.

  10. A roadmap for the genetic analysis of renal aging

    PubMed Central

    Noordmans, Gerda A; Hillebrands, Jan-Luuk; van Goor, Harry; Korstanje, Ron

    2015-01-01

    Several studies show evidence for the genetic basis of renal disease, which renders some individuals more prone than others to accelerated renal aging. Studying the genetics of renal aging can help us to identify genes involved in this process and to unravel the underlying pathways. First, this opinion article will give an overview of the phenotypes that can be observed in age-related kidney disease. Accurate phenotyping is essential in performing genetic analysis. For kidney aging, this could include both functional and structural changes. Subsequently, this article reviews the studies that report on candidate genes associated with renal aging in humans and mice. Several loci or candidate genes have been found associated with kidney disease, but identification of the specific genetic variants involved has proven to be difficult. CUBN, UMOD, and SHROOM3 were identified by human GWAS as being associated with albuminuria, kidney function, and chronic kidney disease (CKD). These are promising examples of genes that could be involved in renal aging, and were further mechanistically evaluated in animal models. Eventually, we will provide approaches for performing genetic analysis. We should leverage the power of mouse models, as testing in humans is limited. Mouse and other animal models can be used to explain the underlying biological mechanisms of genes and loci identified by human GWAS. Furthermore, mouse models can be used to identify genetic variants associated with age-associated histological changes, of which Far2, Wisp2, and Esrrg are examples. A new outbred mouse population with high genetic diversity will facilitate the identification of genes associated with renal aging by enabling high-resolution genetic mapping while also allowing the control of environmental factors, and by enabling access to renal tissues at specific time points for histology, proteomics, and gene expression. PMID:26219736

  11. A roadmap for the genetic analysis of renal aging.

    PubMed

    Noordmans, Gerda A; Hillebrands, Jan-Luuk; van Goor, Harry; Korstanje, Ron

    2015-10-01

    Several studies show evidence for the genetic basis of renal disease, which renders some individuals more prone than others to accelerated renal aging. Studying the genetics of renal aging can help us to identify genes involved in this process and to unravel the underlying pathways. First, this opinion article will give an overview of the phenotypes that can be observed in age-related kidney disease. Accurate phenotyping is essential in performing genetic analysis. For kidney aging, this could include both functional and structural changes. Subsequently, this article reviews the studies that report on candidate genes associated with renal aging in humans and mice. Several loci or candidate genes have been found associated with kidney disease, but identification of the specific genetic variants involved has proven to be difficult. CUBN, UMOD, and SHROOM3 were identified by human GWAS as being associated with albuminuria, kidney function, and chronic kidney disease (CKD). These are promising examples of genes that could be involved in renal aging, and were further mechanistically evaluated in animal models. Eventually, we will provide approaches for performing genetic analysis. We should leverage the power of mouse models, as testing in humans is limited. Mouse and other animal models can be used to explain the underlying biological mechanisms of genes and loci identified by human GWAS. Furthermore, mouse models can be used to identify genetic variants associated with age-associated histological changes, of which Far2, Wisp2, and Esrrg are examples. A new outbred mouse population with high genetic diversity will facilitate the identification of genes associated with renal aging by enabling high-resolution genetic mapping while also allowing the control of environmental factors, and by enabling access to renal tissues at specific time points for histology, proteomics, and gene expression.

  12. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  13. A genetic analysis of Adh1 regulation

    SciTech Connect

    Freeling, M.

    1992-01-01

    The overall goal of our research proposal is to understand the meaning of the various cis-acting sites responsible for AdH1 expression in the entire maize plant. Progress is reported in the following areas: Studies on the TATA box and analysis of revertants of the Adh1-3F1124 allele; screening for more different mutants that affect Adh1 expression differentially; studies on cis-acting sequences required for root-specific Adh1 expression; refinement of the use of the particle gun; and functional analysis of a non- glycolytic anaerobic protein.

  14. Genetics of murine craniofacial morphology: Diallel analysis of the eight founders of the Collaborative Cross

    PubMed Central

    Percival, Christopher J.; Liberton, Denise K.; de Villena, Fernando Pardo-Manuel; Spritz, Richard; Marcucio, Ralph

    2016-01-01

    Summary Using eight inbred founder strains of the mouse Collaborative Cross (CC) project and their reciprocal F1 hybrids, we quantified variation in craniofacial morphology across mouse strains, explored genetic contributions to craniofacial variation that distinguish the founder strains, and tested whether specific or summary measures of craniofacial shape display stronger additive genetic contributions. This study thus provides critical information about phenotypic diversity among CC founder strains and about the genetic contributions to this phenotypic diversity, which is relevant to understanding the basis of variation in standard laboratory strains and natural populations. Craniofacial shape was quantified as a series of size-adjusted linear dimensions (RDs) and by principal components (PC) analysis of morphological landmarks captured from computed tomography images from 62 out of the 64 reciprocal crosses of the CC founder strains. We first identified aspects of skull morphology that vary between these phenotypically ‘normal’ founder strains and that are defining characteristics of these strains. We estimated the contributions of additive and various non-additive genetic factors to phenotypic variation using diallel analyses of a subset of these strongly differing RDs and the first 8 PCs of skull shape variation. We find little difference in the genetic contributions to RD measures and PC scores, suggesting fundamental similarities in the magnitude of genetic contributions to both specific and summary measures of craniofacial phenotypes. Our results indicate that there are stronger additive genetic effects associated with defining phenotypic characteristics of specific founder strains, suggesting these distinguishing measures are good candidates for use in genotype-phenotype association studies of CC mice. Our results add significantly to understanding of genotype-phenotype associations in the skull, which serve as a foundation for modeling the origins of

  15. Genetic variation analysis of the Bali street dog using microsatellites

    PubMed Central

    Irion, Dawn N; Schaffer, Alison L; Grant, Sherry; Wilton, Alan N; Pedersen, Niels C

    2005-01-01

    Background Approximately 800,000 primarily feral dogs live on the small island of Bali. To analyze the genetic diversity in this population, forty samples were collected at random from dogs in the Denpasar, Bali region and tested using 31 polymorphic microsatellites. Australian dingoes and 28 American Kennel Club breeds were compared to the Bali Street Dog (BSD) for allelic diversity, heterozygosities, F-statistics, GST estimates, Nei's DA distance and phylogenetic relationships. Results The BSD proved to be the most heterogeneous, exhibiting 239 of the 366 total alleles observed across all groups and breeds and had an observed heterozygosity of 0.692. Thirteen private alleles were observed in the BSD with an additional three alleles observed only in the BSD and the Australian dingo. The BSD was related most closely to the Chow Chow with a FST of 0.088 and also with high bootstrap support to the Australian dingo and Akita in the phylogenetic analysis. Conclusions This preliminary study into the diversity and relationship of the BSD to other domestic and feral dog populations shows the BSD to be highly heterogeneous and related to populations of East Asian origin. These results indicate that a viable and diverse population of dogs existed on the island of Bali prior to its geographic isolation approximately 12,000 years ago and has been little influenced by domesticated European dogs since that time. PMID:15701179

  16. Network-centric Analysis of Genetic Predisposition in Diabetic Nephropathy

    PubMed Central

    Ntemka, A; Iliadis, F; Papanikolaou, NA; Grekas, D

    2011-01-01

    Diabetic nephropathy is a serious, long-term complication of diabetes and the leading cause of end-stage renal disease throughout the world. Although this disease is progressively imposing a heavier burden on the health care system, in many aspects it remains poorly understood. In addition to environmental influences, there is abundant evidence in support of genetic susceptibility to microvascular complications of nephropathy in diabetic patients. Familial clustering of phenotypes such as end-stage renal disease, albuminuria and kidney disease have been reported in large scale population studies throughout the world demonstrating strong contribution of inherited factors. Recent genome-wide linkage scans identified several chromosomal regions that are likely to contain diabetic nephropathy susceptibility genes, and association analyses have evaluated positional candidate genes under linkage peaks. In this review we have extracted from the literature the most promising candidate genes thought to confer susceptibility to diabetic nephropathy and mapped them to affected pathways by using network-centric analysis. Several of the top susceptibility genes have been identified as network hubs and bottlenecks suggesting that they might be important agents in the onset of diabetic nephropathy. PMID:22435020

  17. Genetic analysis of albuminuria in collaborative cross and multiple mouse intercross populations

    PubMed Central

    Thaisz, Jill; Tsaih, Shirng-Wern; Feng, Minjie; Philip, Vivek M.; Zhang, Yunyu; Yanas, Liane; Sheehan, Susan; Xu, Lingfei; Miller, Darla R.; Paigen, Beverly; Chesler, Elissa J.; Churchill, Gary A.

    2012-01-01

    Albuminuria is an important marker of nephropathy that increases the risk of progressive renal and chronic cardiovascular diseases. The genetic basis of kidney disease is well-established in humans and rodent models, but the causal genes remain to be identified. We applied several genetic strategies to map and refine genetic loci affecting albuminuria in mice and translated the findings to human kidney disease. First, we measured albuminuria in mice from 33 inbred strains, used the data for haplotype association mapping (HAM), and detected 10 genomic regions associated with albuminuria. Second, we performed eight F2 intercrosses between genetically diverse strains to identify six loci underlying albuminuria, each of which was concordant to kidney disease loci in humans. Third, we used the Oak Ridge National Laboratory incipient Collaborative Cross subpopulation to detect an additional novel quantitative trait loci (QTL) underlying albuminuria. We also performed a ninth intercross, between genetically similar strains, that substantially narrowed an albuminuria QTL on Chromosome 17 to a region containing four known genes. Finally, we measured renal gene expression in inbred mice to detect pathways highly correlated with albuminuria. Expression analysis also identified Glcci1, a gene known to affect podocyte structure and function in zebrafish, as a strong candidate gene for the albuminuria QTL on Chromosome 6. Overall, these findings greatly enhance our understanding of the genetic basis of albuminuria in mice and may guide future studies into the genetic basis of kidney disease in humans. PMID:22859403

  18. Genetic analysis in the Collaborative Cross breeding population

    PubMed Central

    Philip, Vivek M.; Sokoloff, Greta; Ackert-Bicknell, Cheryl L.; Striz, Martin; Branstetter, Lisa; Beckmann, Melissa A.; Spence, Jason S.; Jackson, Barbara L.; Galloway, Leslie D.; Barker, Paul; Wymore, Ann M.; Hunsicker, Patricia R.; Durtschi, David C.; Shaw, Ginger S.; Shinpock, Sarah; Manly, Kenneth F.; Miller, Darla R.; Donohue, Kevin D.; Culiat, Cymbeline T.; Churchill, Gary A.; Lariviere, William R.; Palmer, Abraham A.; O'Hara, Bruce F.; Voy, Brynn H.; Chesler, Elissa J.

    2011-01-01

    Genetic reference populations in model organisms are critical resources for systems genetic analysis of disease related phenotypes. The breeding history of these inbred panels may influence detectable allelic and phenotypic diversity. The existing panel of common inbred strains reflects historical selection biases, and existing recombinant inbred panels have low allelic diversity. All such populations may be subject to consequences of inbreeding depression. The Collaborative Cross (CC) is a mouse reference population with high allelic diversity that is being constructed using a randomized breeding design that systematically outcrosses eight founder strains, followed by inbreeding to obtain new recombinant inbred strains. Five of the eight founders are common laboratory strains, and three are wild-derived. Since its inception, the partially inbred CC has been characterized for physiological, morphological, and behavioral traits. The construction of this population provided a unique opportunity to observe phenotypic variation as new allelic combinations arose through intercrossing and inbreeding to create new stable genetic combinations. Processes including inbreeding depression and its impact on allelic and phenotypic diversity were assessed. Phenotypic variation in the CC breeding population exceeds that of existing mouse genetic reference populations due to both high founder genetic diversity and novel epistatic combinations. However, some focal evidence of allele purging was detected including a suggestive QTL for litter size in a location of changing allele frequency. Despite these inescapable pressures, high diversity and precision for genetic mapping remain. These results demonstrate the potential of the CC population once completed and highlight implications for development of related populations. PMID:21734011

  19. Autosomal and X-Linked Additive Genetic Variation for Lifespan and Aging: Comparisons Within and Between the Sexes in Drosophila melanogaster.

    PubMed

    Griffin, Robert M; Schielzeth, Holger; Friberg, Urban

    2016-12-07

    Theory makes several predictions concerning differences in genetic variation between the X chromosome and the autosomes due to male X hemizygosity. The X chromosome should: (i) typically show relatively less standing genetic variation than the autosomes, (ii) exhibit more variation in males compared to females because of dosage compensation, and (iii) potentially be enriched with sex-specific genetic variation. Here, we address each of these predictions for lifespan and aging in Drosophila melanogaster To achieve unbiased estimates of X and autosomal additive genetic variance, we use 80 chromosome substitution lines; 40 for the X chromosome and 40 combining the two major autosomes, which we assay for sex-specific and cross-sex genetic (co)variation. We find significant X and autosomal additive genetic variance for both traits in both sexes (with reservation for X-linked variation of aging in females), but no conclusive evidence for depletion of X-linked variation (measured through females). Males display more X-linked variation for lifespan than females, but it is unclear if this is due to dosage compensation since also autosomal variation is larger in males. Finally, our results suggest that the X chromosome is enriched for sex-specific genetic variation in lifespan but results were less conclusive for aging overall. Collectively, these results suggest that the X chromosome has reduced capacity to respond to sexually concordant selection on lifespan from standing genetic variation, while its ability to respond to sexually antagonistic selection may be augmented.

  20. Autosomal and X-Linked Additive Genetic Variation for Lifespan and Aging: Comparisons Within and Between the Sexes in Drosophila melanogaster

    PubMed Central

    Griffin, Robert M.; Schielzeth, Holger; Friberg, Urban

    2016-01-01

    Theory makes several predictions concerning differences in genetic variation between the X chromosome and the autosomes due to male X hemizygosity. The X chromosome should: (i) typically show relatively less standing genetic variation than the autosomes, (ii) exhibit more variation in males compared to females because of dosage compensation, and (iii) potentially be enriched with sex-specific genetic variation. Here, we address each of these predictions for lifespan and aging in Drosophila melanogaster. To achieve unbiased estimates of X and autosomal additive genetic variance, we use 80 chromosome substitution lines; 40 for the X chromosome and 40 combining the two major autosomes, which we assay for sex-specific and cross-sex genetic (co)variation. We find significant X and autosomal additive genetic variance for both traits in both sexes (with reservation for X-linked variation of aging in females), but no conclusive evidence for depletion of X-linked variation (measured through females). Males display more X-linked variation for lifespan than females, but it is unclear if this is due to dosage compensation since also autosomal variation is larger in males. Finally, our results suggest that the X chromosome is enriched for sex-specific genetic variation in lifespan but results were less conclusive for aging overall. Collectively, these results suggest that the X chromosome has reduced capacity to respond to sexually concordant selection on lifespan from standing genetic variation, while its ability to respond to sexually antagonistic selection may be augmented. PMID:27678519

  1. Genetic Analysis of Nitroaromatic Degradation by Clostridium

    DTIC Science & Technology

    2013-07-30

    Phenazine , a molecule produced by some soil bacteria was found to have a significant effect on metabolite pattern in two clostridium test strains...potential Effect on butyrate levels Methylene blue +0.011 no phenazine -1-carboxylic acid -0.116 More butyrate TNT -0.253 More butyrate Neutral red -0.325...interesting in light of the analysis of natural mobile soluble electron carriers in natural soil ecosystems where molecules such as quinones, and phenazines

  2. Multivariate Genetic Analysis of Learning and Early Reading Development

    ERIC Educational Resources Information Center

    Byrne, Brian; Wadsworth, Sally; Boehme, Kristi; Talk, Andrew C.; Coventry, William L.; Olson, Richard K.; Samuelsson, Stefan; Corley, Robin

    2013-01-01

    The genetic factor structure of a range of learning measures was explored in twin children, recruited in preschool and followed to Grade 2 ("N"?=?2,084). Measures of orthographic learning and word reading were included in the analyses to determine how these patterned with the learning processes. An exploratory factor analysis of the…

  3. The complex genetics of gait speed: genome-wide meta-analysis approach

    PubMed Central

    Lunetta, Kathryn L.; Smith, Jennifer A.; Eicher, John D.; Vered, Rotem; Deelen, Joris; Arnold, Alice M.; Buchman, Aron S.; Tanaka, Toshiko; Faul, Jessica D.; Nethander, Maria; Fornage, Myriam; Adams, Hieab H.; Matteini, Amy M.; Callisaya, Michele L.; Smith, Albert V.; Yu, Lei; De Jager, Philip L.; Evans, Denis A.; Gudnason, Vilmundur; Hofman, Albert; Pattie, Alison; Corley, Janie; Launer, Lenore J.; Knopman, Davis S.; Parimi, Neeta; Turner, Stephen T.; Bandinelli, Stefania; Beekman, Marian; Gutman, Danielle; Sharvit, Lital; Mooijaart, Simon P.; Liewald, David C.; Houwing-Duistermaat, Jeanine J.; Ohlsson, Claes; Moed, Matthijs; Verlinden, Vincent J.; Mellström, Dan; van der Geest, Jos N.; Karlsson, Magnus; Hernandez, Dena; McWhirter, Rebekah; Liu, Yongmei; Thomson, Russell; Tranah, Gregory J.; Uitterlinden, Andre G.; Weir, David R.; Zhao, Wei; Starr, John M.; Johnson, Andrew D.; Ikram, M. Arfan; Bennett, David A.; Cummings, Steven R.; Deary, Ian J.; Harris, Tamara B.; Kardia, Sharon L. R.; Mosley, Thomas H.; Srikanth, Velandai K.; Windham, Beverly G.; Newman, Ann B.; Walston, Jeremy D.; Davies, Gail; Evans, Daniel S.; Slagboom, Eline P.; Ferrucci, Luigi; Kiel, Douglas P.; Murabito, Joanne M.; Atzmon, Gil

    2017-01-01

    Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging. PMID:28077804

  4. Genetic diversity of popcorn genotypes using molecular analysis.

    PubMed

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

    2015-08-19

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

  5. Castor bean organelle genome sequencing and worldwide genetic diversity analysis.

    PubMed

    Rivarola, Maximo; Foster, Jeffrey T; Chan, Agnes P; Williams, Amber L; Rice, Danny W; Liu, Xinyue; Melake-Berhan, Admasu; Huot Creasy, Heather; Puiu, Daniela; Rosovitz, M J; Khouri, Hoda M; Beckstrom-Sternberg, Stephen M; Allan, Gerard J; Keim, Paul; Ravel, Jacques; Rabinowicz, Pablo D

    2011-01-01

    Castor bean is an important oil-producing plant in the Euphorbiaceae family. Its high-quality oil contains up to 90% of the unusual fatty acid ricinoleate, which has many industrial and medical applications. Castor bean seeds also contain ricin, a highly toxic Type 2 ribosome-inactivating protein, which has gained relevance in recent years due to biosafety concerns. In order to gain knowledge on global genetic diversity in castor bean and to ultimately help the development of breeding and forensic tools, we carried out an extensive chloroplast sequence diversity analysis. Taking advantage of the recently published genome sequence of castor bean, we assembled the chloroplast and mitochondrion genomes extracting selected reads from the available whole genome shotgun reads. Using the chloroplast reference genome we used the methylation filtration technique to readily obtain draft genome sequences of 7 geographically and genetically diverse castor bean accessions. These sequence data were used to identify single nucleotide polymorphism markers and phylogenetic analysis resulted in the identification of two major clades that were not apparent in previous population genetic studies using genetic markers derived from nuclear DNA. Two distinct sub-clades could be defined within each major clade and large-scale genotyping of castor bean populations worldwide confirmed previously observed low levels of genetic diversity and showed a broad geographic distribution of each sub-clade.

  6. Castor Bean Organelle Genome Sequencing and Worldwide Genetic Diversity Analysis

    PubMed Central

    Chan, Agnes P.; Williams, Amber L.; Rice, Danny W.; Liu, Xinyue; Melake-Berhan, Admasu; Huot Creasy, Heather; Puiu, Daniela; Rosovitz, M. J.; Khouri, Hoda M.; Beckstrom-Sternberg, Stephen M.; Allan, Gerard J.; Keim, Paul; Ravel, Jacques; Rabinowicz, Pablo D.

    2011-01-01

    Castor bean is an important oil-producing plant in the Euphorbiaceae family. Its high-quality oil contains up to 90% of the unusual fatty acid ricinoleate, which has many industrial and medical applications. Castor bean seeds also contain ricin, a highly toxic Type 2 ribosome-inactivating protein, which has gained relevance in recent years due to biosafety concerns. In order to gain knowledge on global genetic diversity in castor bean and to ultimately help the development of breeding and forensic tools, we carried out an extensive chloroplast sequence diversity analysis. Taking advantage of the recently published genome sequence of castor bean, we assembled the chloroplast and mitochondrion genomes extracting selected reads from the available whole genome shotgun reads. Using the chloroplast reference genome we used the methylation filtration technique to readily obtain draft genome sequences of 7 geographically and genetically diverse castor bean accessions. These sequence data were used to identify single nucleotide polymorphism markers and phylogenetic analysis resulted in the identification of two major clades that were not apparent in previous population genetic studies using genetic markers derived from nuclear DNA. Two distinct sub-clades could be defined within each major clade and large-scale genotyping of castor bean populations worldwide confirmed previously observed low levels of genetic diversity and showed a broad geographic distribution of each sub-clade. PMID:21750729

  7. Understanding genetics: Analysis of secondary students' conceptual status

    NASA Astrophysics Data System (ADS)

    Tsui, Chi-Yan; Treagust, David F.

    2007-02-01

    This article explores the conceptual change of students in Grades 10 and 12 in three Australian senior high schools when the teachers included computer multimedia to a greater or lesser extent in their teaching of a genetics course. The study, underpinned by a multidimensional conceptual-change framework, used an interpretive approach and a case-based design with multiple data collection methods. Over 4-8 weeks, the students learned genetics in classroom lessons that included BioLogica activities, which feature multiple representations. Results of the online tests and interview tasks revealed that most students improved their understanding of genetics as evidenced in the development of genetics reasoning. However, using Thorley's (1990) status analysis categories, a cross-case analysis of the gene conceptions of 9 of the 26 students interviewed indicated that only 4 students' postinstructional conceptions were intelligible-plausible-fruitful. Students' conceptual change was consistent with classroom teaching and learning. Findings suggested that multiple representations supported conceptual understanding of genetics but not in all students. It was also shown that status can be a viable hallmark enabling researchers to identify students' conceptual change that would otherwise be less accessible. Thorley's method for analyzing conceptual status is discussed.

  8. A genetic analysis of Adhl regulation

    SciTech Connect

    Freeling, M.

    1992-01-01

    Several separate but related studies are reported on the mechanism of alcohol dehydrogenase (Adh-1) are reported. A study of a deletion mutation in the TATA box region which resulted in an increase from 6--60% of wildtype Adh-1 expression in the revertant has led to a focus on trans-acting protein factors that bind the TATA box. Analysis of another revertant has led to study of cis-acting sequences in Adh-1 expression. Screening efforts aimed at defining different mutants affecting Adh-1 expression are reported.

  9. Whole-Genome sequencing and genetic variant analysis of a quarter Horse mare

    PubMed Central

    2012-01-01

    Background The catalog of genetic variants in the horse genome originates from a few select animals, the majority originating from the Thoroughbred mare used for the equine genome sequencing project. The purpose of this study was to identify genetic variants, including single nucleotide polymorphisms (SNPs), insertion/deletion polymorphisms (INDELs), and copy number variants (CNVs) in the genome of an individual Quarter Horse mare sequenced by next-generation sequencing. Results Using massively parallel paired-end sequencing, we generated 59.6 Gb of DNA sequence from a Quarter Horse mare resulting in an average of 24.7X sequence coverage. Reads were mapped to approximately 97% of the reference Thoroughbred genome. Unmapped reads were de novo assembled resulting in 19.1 Mb of new genomic sequence in the horse. Using a stringent filtering method, we identified 3.1 million SNPs, 193 thousand INDELs, and 282 CNVs. Genetic variants were annotated to determine their impact on gene structure and function. Additionally, we genotyped this Quarter Horse for mutations of known diseases and for variants associated with particular traits. Functional clustering analysis of genetic variants revealed that most of the genetic variation in the horse's genome was enriched in sensory perception, signal transduction, and immunity and defense pathways. Conclusions This is the first sequencing of a horse genome by next-generation sequencing and the first genomic sequence of an individual Quarter Horse mare. We have increased the catalog of genetic variants for use in equine genomics by the addition of novel SNPs, INDELs, and CNVs. The genetic variants described here will be a useful resource for future studies of genetic variation regulating performance traits and diseases in equids. PMID:22340285

  10. 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.

  11. Methods for the survey and genetic analysis of populations

    DOEpatents

    Ashby, Matthew

    2003-09-02

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

  12. Distribution and genetic analysis of TTV and TTMV major phylogenetic groups in French blood donors.

    PubMed

    Biagini, Philippe; Gallian, Pierre; Cantaloube, Jean-François; Attoui, Houssam; de Micco, Philippe; de Lamballerie, Xavier

    2006-02-01

    TTV and TTMV (recently assigned to the floating genus Anellovirus) infect human populations (including healthy individuals) at high prevalence (>80%). They display notably high levels of genetic diversity, but very little is known regarding the distribution of Anellovirus genetic groups in human populations. We analyzed the distribution of the major genetic groups of TTV and TTMV in healthy voluntary blood donors using group-independent and group-specific PCR amplifications systems, combined with sequence determination and phylogenetic analysis. Analysis of Anellovirus groups revealed a non-random pattern of group distribution with a predominant prevalence of TTV phylogenetic groups 1, 3, and 5, and of TTMV group 1. Multiple co-infections were observed. In addition, TTMV sequences exhibiting a high genetic divergence with reference sequences were identified. This study provided the first picture of the genetic distribution of the major phylogenetic groups of members of the genus Anellovirus in a cohort of French voluntary blood donors. Obtaining such data from a reference population comprising healthy individuals was an essential step that will allow the subsequent comparative analysis of cohorts including patients with well-characterized diseases, in order to identify any possible relationship between Anellovirus infection and human diseases.

  13. A genetic analysis of nitrosative stress.

    PubMed

    Foster, Matthew W; Liu, Limin; Zeng, Ming; Hess, Douglas T; Stamler, Jonathan S

    2009-02-03

    Nitrosative stress is induced by pathophysiological levels of nitric oxide (NO) and S-nitrosothiols (e.g., S-nitrosoglutathione, GSNO) and arises, at least in significant part, from the nitrosylation of critical protein Cys thiols (S-nitrosylation) and metallocofactors. However, the mechanisms by which NO and GSNO mediate nitrosative stress are not well understood. Using yeast Saccharomyces cerevisiae strains lacking NO- and/or GSNO-consuming enzymes (flavohemoglobin and GSNO reductase, respectively), we measured the individual and combined effects of NO and GSNO on both cell growth and the formation of protein-bound NO species. Our results suggest an intracellular equilibrium between NO and GSNO, dependent in part on cell-catalyzed release of NO from GSNO (i.e., "SNO-lyase" activity). However, whereas NO induces multiple types of protein-based modifications, levels of which correlate with inhibition of cell growth, GSNO mainly affects protein S-nitrosylation, and the relationship between S-nitrosylation and nitrosative stress is more complex. These data support the idea of multiple classes of protein-SNO, likely reflected in divergent routes of synthesis and degradation. Indeed, a significant fraction of protein S-nitrosylation by NO occurs in the absence of O(2), which is commonly assumed to drive this reaction but instead is apparently dependent in substantial part upon protein-bound transition metals. Additionally, our findings suggest that nitrosative stress is mediated principally via the S-nitrosylation of a subset of protein targets, which include protein SNOs that are stable to cellular glutathione (and thus are not metabolized by GSNO reductase). Collectively, these results provide new evidence for the mechanisms through which NO and GSNO mediate nitrosative stress as well as the cellular pathways of protein S-nitrosylation and denitrosylation involving metalloproteins, SNO lyase(s) and GSNO reductase.

  14. Quantitative analysis of soil calcium by laser-induced breakdown spectroscopy using addition and addition-internal standardizations

    NASA Astrophysics Data System (ADS)

    Shirvani-Mahdavi, Hamidreza; Shafiee, Parisa

    2016-12-01

    Matrix mismatching in the quantitative analysis of materials through calibration-based laser-induced breakdown spectroscopy (LIBS) is a serious problem. In this paper, to overcome the matrix mismatching, two distinct approaches named addition standardization (AS) and addition-internal combinatorial standardization (A-ICS) are demonstrated for LIBS experiments. Furthermore, in order to examine the efficiency of these methods, the concentration of calcium in ordinary garden soil without any fertilizer is individually measured by each of the two procedures. To achieve this purpose, ten standard samples with different concentrations of calcium (as the analyte) and copper (as the internal standard) are prepared in the form of cylindrical tablets, so that the soil plays the role of the matrix in all of them. The measurements indicate that the relative error of concentration compared to a certified value derived by induced coupled plasma optical emission spectroscopy is 3.97% and 2.23% for AS and A-ICS methods, respectively. Furthermore, calculations related to standard deviation indicates that A-ICS method may be more accurate than AS one.

  15. [Genetical analysis on cross incubation of Beauveria bassiana].

    PubMed

    Wang, C; Ding, D; Wang, S; Li, Z

    2000-10-01

    Heterokaryon of Beauveria bassiana was formed during the cross incubation of two vegetative compatible strains with genetic markers of actidione resistance and 34 degrees C tolerance. The chromosome(s) or its fragment successive losses, recombination and segreation led to haploidization during the conidia formation period. After at least 4 generations of parasexual cycle, the genetic character of heterokayon could get to relative stable. Genetic marker and RAPD analysis indicated that the combinants showed the phenomenon of preferential selection of one parental type by unrandom chromosome lossing and the gene of the other parental strain was suppressed or lost completely. Different culture medium, in vivo or in vitro, and different mixture ratio of original strain spores could affect parasexual process and then the preferential selection. The results also demonstrated the heterosis effect of cross culture.

  16. Genetic diversity analysis in Piper species (Piperaceae) using RAPD markers.

    PubMed

    Sen, Sandeep; Skaria, Reby; Abdul Muneer, P M

    2010-09-01

    The genetic diversity of eight species of Piper (Piperaceae) viz., P. nigrum, P. longum, P. betle, P. chaba, P. argyrophyllum, P. trichostachyon, P. galeatum, and P. hymenophyllum from Kerala state, India were analyzed by Random amplified polymorphic DNA (RAPD). Out of 22 10-mer RAPD primers screened, 11 were selected for comparative analysis of different species of Piper. High genetic variations were found among different Piper species studied. Among the total of 149 RAPD fragments amplified, 12 bands (8.05%) were found monomorphic in eight species. The remaining 137 fragments were found polymorphic (91.95%). Species-specific bands were found in all eight species studied. The average gene diversity or heterozygosity (H) was 0.33 across all the species, genetic distances ranged from 0.21 to 0.69. The results of this study will facilitate germplasm identification, management, and conservation.

  17. [Screening of peafowl microsatellite primers and analysis of genetic diversity].

    PubMed

    Bao, Wen-Bin; Chen, Guo-Hong; Shu, Jing-Ting; Xu, Qi; Li, Hui-Fang

    2006-10-01

    The applicability of chicken microsatellite primers to peafowl population was analyzed in the present paper, and the results showed 14 of 29 pairs of microsatellite primers from chicken could amplify peafowl DNA and produce specific allele patterns. A mean of 1.71 alleles was found for each locus. Seven pairs were highly polymorphic, and MCW0080 and MCW0098 were ideal markers for peafowl. Genetic diversity analysis within and between the green peafowl and the blue peafowl populations demonstrated that the expected heterozygosity of two peafowl populations were 0.2482 and 0.2744, respectively. The inbreeding index (FST), Reynolds' genetic distance and gene flow between the two populations were 0.078, 0.0603 and 3.896 respectively. These results indicate that the heterozygosity and the genetic diversity of these two peafowl populations were very low, and suggest a tendency towards intermixing.

  18. Molecular population genetic analysis of emerged bacterial pathogens: selected insights.

    PubMed Central

    Musser, J. M.

    1996-01-01

    Research in bacterial population genetics has increased in the last 10 years. Population genetic theory and tools and related strategies have been used to investigate bacterial pathogens that have contributed to recent episodes of temporal variation in disease frequency and severity. A common theme demonstrated by these analyses is that distinct bacterial clones are responsible for disease outbreaks and increases in infection frequency. Many of these clones are characterized by unique combinations of virulence genes or alleles of virulence genes. Because substantial interclonal variance exists in relative virulence, molecular population genetic studies have led to the concept that the unit of bacterial pathogenicity is the clone or cell line. Continued new insights into host parasite interactions at the molecular level will be achieved by combining clonal analysis of bacterial pathogens with large-scale comparative sequencing of virulence genes. PMID:8903193

  19. Genome-wide transcript analysis of maize hybrids: allelic additive gene expression and yield heterosis.

    PubMed

    Guo, Mei; Rupe, Mary A; Yang, Xiaofeng; Crasta, Oswald; Zinselmeier, Christopher; Smith, Oscar S; Bowen, Ben

    2006-09-01

    Heterosis, or hybrid vigor, has been widely exploited in plant breeding for many decades, but the molecular mechanisms underlying the phenomenon remain unknown. In this study, we applied genome-wide transcript profiling to gain a global picture of the ways in which a large proportion of genes are expressed in the immature ear tissues of a series of 16 maize hybrids that vary in their degree of heterosis. Key observations include: (1) the proportion of allelic additively expressed genes is positively associated with hybrid yield and heterosis; (2) the proportion of genes that exhibit a bias towards the expression level of the paternal parent is negatively correlated with hybrid yield and heterosis; and (3) there is no correlation between the over- or under-expression of specific genes in maize hybrids with either yield or heterosis. The relationship of the expression patterns with hybrid performance is substantiated by analysis of a genetically improved modern hybrid (Pioneer hybrid 3394) versus a less improved older hybrid (Pioneer hybrid 3306) grown at different levels of plant density stress. The proportion of allelic additively expressed genes is positively associated with the modern high yielding hybrid, heterosis and high yielding environments, whereas the converse is true for the paternally biased gene expression. The dynamic changes of gene expression in hybrids responding to genotype and environment may result from differential regulation of the two parental alleles. Our findings suggest that differential allele regulation may play an important role in hybrid yield or heterosis, and provide a new insight to the molecular understanding of the underlying mechanisms of heterosis.

  20. Analysis of genetic diversity in Bolivian llama populations using microsatellites.

    PubMed

    Barreta, J; Gutiérrez-Gil, B; Iñiguez, V; Romero, F; Saavedra, V; Chiri, R; Rodríguez, T; Arranz, J J

    2013-08-01

    South American camelids (SACs) have a major role in the maintenance and potential future of rural Andean human populations. More than 60% of the 3.7 million llamas living worldwide are found in Bolivia. Due to the lack of studies focusing on genetic diversity in Bolivian llamas, this analysis investigates both the genetic diversity and structure of 12 regional groups of llamas that span the greater part of the range of distribution for this species in Bolivia. The analysis of 42 microsatellite markers in the considered regional groups showed that, in general, there were high levels of polymorphism (a total of 506 detected alleles; average PIC across per marker: 0.66), which are comparable with those reported for other populations of domestic SACs. The estimated diversity parameters indicated that there was high intrapopulational genetic variation (average number of alleles and average expected heterozygosity per marker: 12.04 and 0.68, respectively) and weak genetic differentiation among populations (FST range: 0.003-0.052). In agreement with these estimates, Bolivian llamas showed a weak genetic structure and an intense gene flow between all the studied regional groups, which is due to the exchange of reproductive males between the different flocks. Interestingly, the groups for which the largest pairwise FST estimates were observed, Sud Lípez and Nor Lípez, showed a certain level of genetic differentiation that is probably due to the pattern of geographic isolation and limited communication infrastructures of these southern localities. Overall, the population parameters reported here may serve as a reference when establishing conservation policies that address Bolivian llama populations.

  1. Genetic analysis of Streptococcus suis isolates from wild rabbits.

    PubMed

    Sánchez del Rey, V; Fernández-Garayzábal, J F; Briones, V; Iriso, A; Domínguez, L; Gottschalk, M; Vela, A I

    2013-08-30

    This work aims to investigate the presence of Streptococcus suis in wild rabbits. A total of 65 S. suis isolates were recovered from 33.3% of the wild rabbits examined. Most isolates (86.2%) belong to genotype cps9. These isolates were further characterized by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and virulence genotyping. Overall, S. suis exhibited a low genetic diversity. Only 5 genetic profiles were obtained by PFGE and most isolates (71.4%) were included in two pulsotypes that were also widely distributed among the wild rabbit population. MLST analysis assigned all cps9 isolates into three new singlestones (ST216, ST217 and ST284), which were not genetically related to the European ST87 and Spanish ST61 widespread swine clones, indicating a different genetic background for the S. suis isolates from wild rabbits and pigs. Wild rabbit isolates exhibited the genotype mrp-/epf-/sly-, different from those showed by most of the swine S. suis isolates of the ST87 and ST61 clones. None of the S. suis isolated from wild rabbits exhibited the genotype cps2/mrp+/epf+/sly+ associated with human infections. These results indicate that S. suis isolates from wild rabbits are not genetically related with prevalent clones usually associated with infections in pigs or humans in Europe and do not exhibit either their virulence genotypes. Therefore, although wild rabbits could represent an unknown reservoir of this pathogen, they could not represent a potential risk for pigs or humans.

  2. Population genetic analysis and sub-structuring in Babesia bovis.

    PubMed

    Simuunza, Martin; Bilgic, Huseyin; Karagenc, Tulin; Syakalima, Michelo; Shiels, Brian; Tait, Andy; Weir, William

    2011-06-01

    The tick-borne protozoan parasite, Babesia bovis is one of the causes of bovine babesiosis, an economically important disease of cattle in tropical and sub-tropical countries. Using the recently published genome sequence of the parasite, we developed a panel of eight mini- and micro-satellite markers and used these to investigate the role of genetic exchange in the population structure and diversity of the parasite using isolates from Zambia and Turkey. This population genetic analysis showed that genetic exchange occurs and that there are high levels of genetic diversity, with geographical sub-structuring quantified using Wright's F Index. Linkage disequilibrium was observed when isolates from both countries were treated as one population, but when isolates from Zambia were analysed separately linkage equilibrium was observed. The Turkish isolates were sub-structured, containing two genetically distinct sub-groups, both of which appeared to be in linkage equilibrium. The results of the Zambian study suggest that a sub-set of the parasite population is responsible for the westward spread of babesiosis into the previously disease-free central region of the country. The Zambian isolates had a significantly higher number of genotypes per sample than those from Turkey and age was found to be a significant predictor of the multiplicity of infection. The high levels of diversity seen in the Zambian and Turkish B. bovis populations have implications in the development of subunit vaccines against the disease and the spread of drug resistance.

  3. Two-phase analysis in consensus genetic mapping.

    PubMed

    Ronin, Y; Mester, D; Minkov, D; Belotserkovski, R; Jackson, B N; Schnable, P S; Aluru, S; Korol, A

    2012-05-01

    Numerous mapping projects conducted on different species have generated an abundance of mapping data. Consequently, many multilocus maps have been constructed using diverse mapping populations and marker sets for the same organism. The quality of maps varies broadly among populations, marker sets, and software used, necessitating efforts to integrate the mapping information and generate consensus maps. The problem of consensus genetic mapping (MCGM) is by far more challenging compared with genetic mapping based on a single dataset, which by itself is also cumbersome. The additional complications introduced by consensus analysis include inter-population differences in recombination rate and exchange distribution along chromosomes; variations in dominance of the employed markers; and use of different subsets of markers in different labs. Hence, it is necessary to handle arbitrary patterns of shared sets of markers and different level of mapping data quality. In this article, we introduce a two-phase approach for solving MCGM. In phase 1, for each dataset, multilocus ordering is performed combined with iterative jackknife resampling to evaluate the stability of marker orders. In this phase, the ordering problem is reduced to the well-known traveling salesperson problem (TSP). Namely, for each dataset, we look for order that gives minimum sum of recombination distances between adjacent markers. In phase 2, the optimal consensus order of shared markers is selected from the set of allowed orders and gives the minimal sum of total lengths of nonconflicting maps of the chromosome. This criterion may be used in different modifications to take into account the variation in quality of the original data (population size, marker quality, etc.). In the foregoing formulation, consensus mapping is considered as a specific version of TSP that can be referred to as "synchronized TSP." The conflicts detected after phase 1 are resolved using either a heuristic algorithm over the

  4. Analysis of mitochondrial genetic diversity of Ustilago maydis in Mexico.

    PubMed

    Jiménez-Becerril, María F; Hernández-Delgado, Sanjuana; Solís-Oba, Myrna; González Prieto, Juan M

    2016-10-11

    The current understanding of the genetic diversity of the phytopathogenic fungus Ustilago maydis is limited. To determine the genetic diversity and structure of U. maydis, 48 fungal isolates were analyzed using mitochondrial simple sequence repeats (SSRs). Tumours (corn smut or 'huitlacoche') were collected from different Mexican states with diverse environmental conditions. Using bioinformatic tools, five microsatellites were identified within intergenic regions of the U. maydis mitochondrial genome. SSRMUM4 was the most polymorphic marker. The most common repeats were hexanucleotides. A total of 12 allelic variants were identified, with a mean of 2.4 alleles per locus. An estimate of the genetic diversity using analysis of molecular variance (AMOVA) revealed that the highest variance component is within states (84%), with moderate genetic differentiation between states (16%) (FST = 0.158). A dendrogram generated using the unweighted paired-grouping method with arithmetic averages (UPGMA) and the Bayesian analysis of population structure grouped the U. maydis isolates into two subgroups (K = 2) based on their shared SSRs.

  5. Additive genetic variation in resistance of Nile tilapia (Oreochromis niloticus) to Streptococcus iniae and S. agalactiae capsular type Ib: is genetic resistance correlated?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus (S.) iniae and S. agalactiae are both economically important Gram positive bacterial pathogens affecting the globally farmed tilapia (Oreochromis spp.). Historically control of these bacteria in tilapia culture has included biosecurity, therapeutants and vaccination strategies. Genet...

  6. Random amplified polymorphic DNA analysis of genetically modified organisms.

    PubMed

    Yoke-Kqueen, Cheah; Radu, Son

    2006-12-15

    Randomly amplified polymorphic DNA (RAPD) was used to analyzed 78 samples comprises of certified reference materials (soya and maize powder), raw seeds (soybean and maize), processed food and animal feed. Combination assay of two arbitrary primers in the RAPD analysis enable to distinguish genetically modified organism (GMO) reference materials from the samples tested. Dendrogram analysis revealed 13 clusters at 45% similarity from the RAPD. RAPD analysis showed that the maize and soybean samples were clustered differently besides the GMO and non-GMO products.

  7. Evidence of Shared Genome-Wide Additive Genetic Effects on Interpersonal Trauma Exposure and Generalized Vulnerability to Drug Dependence in a Population of Substance Users.

    PubMed

    Palmer, Rohan H C; Nugent, Nicole R; Brick, Leslie A; Bidwell, Cinnamon L; McGeary, John E; Keller, Matthew C; Knopik, Valerie S

    2016-06-01

    Exposure to traumatic experiences is associated with an increased risk for drug dependence and poorer response to substance abuse treatment (Claus & Kindleberger, 2002; Jaycox, Ebener, Damesek, & Becker, 2004). Despite this evidence, the reasons for the observed associations of trauma and the general tendency to be dependent upon drugs of abuse remain unclear. Data (N = 2,596) from the Study of Addiction: Genetics and Environment were used to analyze (a) the degree to which commonly occurring single nucleotide polymorphisms (SNPs; minor allele frequency > 1%) in the human genome explains exposure to interpersonal traumatic experiences, and (b) the extent to which additive genetic effects on trauma are shared with additive genetic effects on drug dependence. Our results suggested moderate additive genetic influences on interpersonal trauma, h(2) SNP-Interpersonal = .47, 95% confidence interval (CI) [.10, .85], that are partially shared with additive genetic effects on generalized vulnerability to drug dependence, h(2) SNP-DD = .36, 95% CI [.11, .61]; rG-SNP = .49, 95% CI [.02, .96]. Although the design/technique does not exclude the possibility that substance abuse causally increases risk for traumatic experiences (or vice versa), these findings raise the possibility that commonly occurring SNPs influence both the general tendency towards drug dependence and interpersonal trauma.

  8. Metabolic engineering: techniques for analysis of targets for genetic manipulations.

    PubMed

    Nielsen, J

    Metabolic engineering has been defined as the purposeful modification of intermediary metabolism using recombinant DNA techniques. With this definition metabolic engineering includes: (1) inserting new pathways in microorganisms with the aim of producing novel metabolites, e.g., production of polyketides by Streptomyces; (2) production of heterologous peptides, e.g., production of human insulin, erythropoitin, and tPA; and (3) improvement of both new and existing processes, e.g., production of antibiotics and industrial enzymes. Metabolic engineering is a multidisciplinary approach, which involves input from chemical engineers, molecular biologists, biochemists, physiologists, and analytical chemists. Obviously, molecular biology is central in the production of novel products, as well as in the improvement of existing processes. However, in the latter case, input from other disciplines is pivotal in order to target the genetic modifications; with the rapid developments in molecular biology, progress in the field is likely to be limited by procedures to identify the optimal genetic changes. Identification of the optimal genetic changes often requires a meticulous mapping of the cellular metabolism at different operating conditions, and the application of metabolic engineering to process optimization is, therefore, expected mainly to have an impact on the improvement of processes where yield, productivity, and titer are important design factors, i.e., in the production of metabolites and industrial enzymes. Despite the prospect of obtaining major improvement through metabolic engineering, this approach is, however, not expected to completely replace the classical approach to strain improvement-random mutagenesis followed by screening. Identification of the optimal genetic changes for improvement of a given process requires analysis of the underlying mechanisms, at best, at the molecular level. To reveal these mechanisms a number of different techniques may be applied

  9. Genetic relationships among twelve Chinese indigenous goat populations based on microsatellite analysis

    PubMed Central

    Li, Meng-Hua; Zhao, Shu-Hong; Bian, Ci; Wang, Hai-Sheng; Wei, Hong; Liu, Bang; Yu, Mei; Fan, Bin; Chen, Shi-Lin; Zhu, Meng-Jin; Li, Shi-Jun; Xiong, Tong-An; Li, Kui

    2002-01-01

    Twelve Chinese indigenous goat populations were genotyped for twenty-six microsatellite markers recommended by the EU Sheep and Goat Biodiversity Project. A total of 452 goats were tested. Seventeen of the 26 microsatellite markers used in this analysis had four or more alleles. The mean expected heterozygosity and the mean observed heterozygosity for the population varied from 0.611 to 0.784 and 0.602 to 0.783 respectively. The mean FST (0.105) demonstrated that about 89.5% of the total genetic variation was due to the genetic differentiation within each population. A phylogenetic tree based on the Nei (1978) standard genetic distance displayed a remarkable degree of consistency with their different geographical origins and their presumed migration throughout China. The correspondence analysis did not only distinguish population groups, but also confirmed the above results, classifying the important populations contributing to diversity. Additionally, some specific alleles were shown to be important in the construction of the population structure. The study analyzed the recent origins of these populations and contributed to the knowledge and genetic characterization of Chinese indigenous goat populations. In addition, the seventeen microsatellites recommended by the EU Sheep and Goat Biodiversity Project proved to be useful for the biodiversity studies in goat breeds. PMID:12473236

  10. Genetic analysis in the Collaborative Cross breeding population

    SciTech Connect

    Philip, Vivek; Sokoloff, Greta; Ackert-Bicknell, Cheryl; Striz, Martin; Branstetter, Lisa R; Beckmann, Melissa; Spence, Jason S; Jackson, Barbara L; Galloway, Leslie D; Barker, Gene; Wymore, Ann M; Hunsicker, Patricia R; Durtschi, David W; Shaw, Ginger S; Shinpock, Sarah G; Manly, Kenneth F; Miller, Darla R; Donahue, Kevin; Culiat, Cymbeline T; Churchill, Gary A; Lariviere, William R; Palmer, Abraham; O'Hara, Bruce; Voy, Brynn H; Chesler, Elissa J

    2011-01-01

    Genetic reference populations in model organisms are critical resources for systems genetic analysis of disease related phenotypes. The breeding history of these inbred panels may influence detectable allelic and phenotypic diversity. The existing panel of common inbred strains reflects historical selection biases, and existing recombinant inbred panels have low allelic diversity. All such populations may be subject to consequences of inbreeding depression. The Collaborative Cross (CC) is a mouse reference population with high allelic diversity that is being constructed using a randomized breeding design that systematically outcrosses eight founder strains, followed by inbreeding to obtain new recombinant inbred strains. Five of the eight founders are common laboratory strains, and three are wild-derived. Since its inception, the partially inbred CC has been characterized for physiological, morphological, and behavioral traits. The construction of this population provided a unique opportunity to observe phenotypic variation as new allelic combinations arose through intercrossing and inbreeding to create new stable genetic combinations. Processes including inbreeding depression and its impact on allelic and phenotypic diversity were assessed. Phenotypic variation in the CC breeding population exceeds that of existing mouse genetic reference populations due to both high founder genetic diversity and novel epistatic combinations. However, some focal evidence of allele purging was detected including a suggestive QTL for litter size in a location of changing allele frequency. Despite these inescapable pressures, high diversity and precision for genetic mapping remain. These results demonstrate the potential of the CC population once completed and highlight implications for development of related populations. Supplementary material consists of Supplementary Table 1 Phenotypic means, variances, ranges and heritabilities for all traits and generations, Supplementary Table

  11. Genetic Analysis of Haploids from Industrial Strains of Baker's Yeast.

    PubMed

    Oda, Y; Ouchi, K

    1989-07-01

    Strains of baker's yeast conventionally used by the baking industry in Japan were tested for the ability to sporulate and produce viable haploid spores. Three isolates which possessed the properties of baker's yeasts were obtained from single spores. Each strain was a haploid, and one of these strains, YOY34, was characterized. YOY34 fermented maltose and sucrose, but did not utilize galactose, unlike its parental strain. Genetic analysis showed that YOY34 carried two MAL genes, one functional and one cryptic; two SUC genes; and one defective gal gene. The genotype of YOY34 was identified as MATalpha MAL1 MAL3g SUC2 SUC4 gall. The MAL1 gene from this haploid was constitutively expressed, was dominant over other wild-type MAL tester genes, and gave a weak sucrose fermentation. YOY34 was suitable for both bakery products, like conventional baker's yeasts, and for genetic analysis, like laboratory strains.

  12. Genetic linkage analysis of manic depression in Iceland.

    PubMed Central

    Curtis, D; Sherrington, R; Brett, P; Holmes, D S; Kalsi, G; Brynjolfsson, J; Petursson, H; Rifkin, L; Murphy, P; Moloney, E

    1993-01-01

    Genetic linkage analysis has been used to study five Icelandic pedigrees multiply affected with manic depression. Genetic markers were chosen from regions which had been implicated by other studies or to which candidate genes had been localized. The transmission model used was of a dominant gene with incomplete penetrance and allowing for a large number of phenocopies, especially for unipolar rather than bipolar cases. Multipoint analysis with linked markers enabled information to be gained from regions spanning large distances. Using this approach we have excluded regions of chromosome 11p, 11q, 8q, 5q, 9q and Xq. Candidate genes excluded include those for tyrosine hydroxylase, the dopamine type 2 receptor, proenkephalin, the 5HT1A receptor and dopamine beta hydroxylase. Nevertheless, we remain optimistic that this approach will eventually identify at least some of the genes predisposing to manic depression. PMID:8105081

  13. The S-leut anthropometric traits: genetic analysis.

    PubMed

    Paganini-Hill, A; Martin, A O; Spence, M A

    1981-05-01

    Genetic analyses were conducted on 51 anthropometric measurements and on four factors derived from them by factor analysis. These variables were obtained on 784 members of a religious isolate, the S-leut. Correlations were computed between relatives, and heritabilities were estimates using information on extended families. Longitudinal measurements generally exhibited the highest heritabilities. The test for fit of a major gene model was significant for 13 of the 55 variables, the circumferential and breadth measurements giving the strongest evidence for major gene control. In another approach to establishment of genetic control, linkage analysis was performed between the anthropometric variables and blood group and serum protein polymorphisms. Several traits showed some evidence for linkage but none achieved statistical significance.

  14. Describing the genetic architecture of epilepsy through heritability analysis.

    PubMed

    Speed, Doug; O'Brien, Terence J; Palotie, Aarno; Shkura, Kirill; Marson, Anthony G; Balding, David J; Johnson, Michael R

    2014-10-01

    Epilepsy is a disease with substantial missing heritability; despite its high genetic component, genetic association studies have had limited success detecting common variants which influence susceptibility. In this paper, we reassess the role of common variants on epilepsy using extensions of heritability analysis. Our data set consists of 1258 UK patients with epilepsy, of which 958 have focal epilepsy, and 5129 population control subjects, with genotypes recorded for over 4 million common single nucleotide polymorphisms. Firstly, we show that on the liability scale, common variants collectively explain at least 26% (standard deviation 5%) of phenotypic variation for all epilepsy and 27% (standard deviation 5%) for focal epilepsy. Secondly we provide a new method for estimating the number of causal variants for complex traits; when applied to epilepsy, our most optimistic estimate suggests that at least 400 variants influence disease susceptibility, with potentially many thousands. Thirdly, we use bivariate analysis to assess how similar the genetic architecture of focal epilepsy is to that of non-focal epilepsy; we demonstrate both significant differences (P = 0.004) and significant similarities (P = 0.01) between the two subtypes, indicating that although the clinical definition of focal epilepsy does identify a genetically distinct epilepsy subtype, there is also scope to improve the classification of epilepsy by incorporating genotypic information. Lastly, we investigate the potential value in using genetic data to diagnose epilepsy following a single epileptic seizure; we find that a prediction model explaining 10% of phenotypic variation could have clinical utility for deciding which single-seizure individuals are likely to benefit from immediate anti-epileptic drug therapy.

  15. Describing the genetic architecture of epilepsy through heritability analysis

    PubMed Central

    O’Brien, Terence J.; Palotie, Aarno; Shkura, Kirill; Marson, Anthony G.; Balding, David J.

    2014-01-01

    Epilepsy is a disease with substantial missing heritability; despite its high genetic component, genetic association studies have had limited success detecting common variants which influence susceptibility. In this paper, we reassess the role of common variants on epilepsy using extensions of heritability analysis. Our data set consists of 1258 UK patients with epilepsy, of which 958 have focal epilepsy, and 5129 population control subjects, with genotypes recorded for over 4 million common single nucleotide polymorphisms. Firstly, we show that on the liability scale, common variants collectively explain at least 26% (standard deviation 5%) of phenotypic variation for all epilepsy and 27% (standard deviation 5%) for focal epilepsy. Secondly we provide a new method for estimating the number of causal variants for complex traits; when applied to epilepsy, our most optimistic estimate suggests that at least 400 variants influence disease susceptibility, with potentially many thousands. Thirdly, we use bivariate analysis to assess how similar the genetic architecture of focal epilepsy is to that of non-focal epilepsy; we demonstrate both significant differences (P = 0.004) and significant similarities (P = 0.01) between the two subtypes, indicating that although the clinical definition of focal epilepsy does identify a genetically distinct epilepsy subtype, there is also scope to improve the classification of epilepsy by incorporating genotypic information. Lastly, we investigate the potential value in using genetic data to diagnose epilepsy following a single epileptic seizure; we find that a prediction model explaining 10% of phenotypic variation could have clinical utility for deciding which single-seizure individuals are likely to benefit from immediate anti-epileptic drug therapy. PMID:25063994

  16. Targeted Analysis of Whole Genome Sequence Data to Diagnose Genetic Cardiomyopathy

    DOE PAGES

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

    2014-09-01

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

  17. Targeted Analysis of Whole Genome Sequence Data to Diagnose Genetic Cardiomyopathy

    SciTech Connect

    Golbus, Jessica R.; Puckelwartz, Megan J.; Dellefave-Castillo, Lisa; Fahrenbach, John P.; Nelakuditi, Viswateja; Pesce, Lorenzo L.; Pytel, Peter; McNally, Elizabeth M.

    2014-09-01

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

  18. Population and genomic lessons from genetic analysis of two Indian populations.

    PubMed

    Juyal, Garima; Mondal, Mayukh; Luisi, Pierre; Laayouni, Hafid; Sood, Ajit; Midha, Vandana; Heutink, Peter; Bertranpetit, Jaume; Thelma, B K; Casals, Ferran

    2014-10-01

    Indian demographic history includes special features such as founder effects, interpopulation segregation, complex social structure with a caste system and elevated frequency of consanguineous marriages. It also presents a higher frequency for some rare mendelian disorders and in the last two decades increased prevalence of some complex disorders. Despite the fact that India represents about one-sixth of the human population, deep genetic studies from this terrain have been scarce. In this study, we analyzed high-density genotyping and whole-exome sequencing data of a North and a South Indian population. Indian populations show higher differentiation levels than those reported between populations of other continents. In this work, we have analyzed its consequences, by specifically assessing the transferability of genetic markers from or to Indian populations. We show that there is limited genetic marker portability from available genetic resources such as HapMap or the 1,000 Genomes Project to Indian populations, which also present an excess of private rare variants. Conversely, tagSNPs show a high level of portability between the two Indian populations, in contrast to the common belief that North and South Indian populations are genetically very different. By estimating kinship from mates and consanguinity in our data from trios, we also describe different patterns of assortative mating and inbreeding in the two populations, in agreement with distinct mating preferences and social structures. In addition, this analysis has allowed us to describe genomic regions under recent adaptive selection, indicating differential adaptive histories for North and South Indian populations. Our findings highlight the importance of considering demography for design and analysis of genetic studies, as well as the need for extending human genetic variation catalogs to new populations and particularly to those with particular demographic histories.

  19. Differential Network Analysis Reveals Genetic Effects on Catalepsy Modules

    PubMed Central

    Iancu, Ovidiu D.; Oberbeck, Denesa; Darakjian, Priscila; Kawane, Sunita; Erk, Jason; McWeeney, Shannon; Hitzemann, Robert

    2013-01-01

    We performed short-term bi-directional selective breeding for haloperidol-induced catalepsy, starting from three mouse populations of increasingly complex genetic structure: an F2 intercross, a heterogeneous stock (HS) formed by crossing four inbred strains (HS4) and a heterogeneous stock (HS-CC) formed from the inbred strain founders of the Collaborative Cross (CC). All three selections were successful, with large differences in haloperidol response emerging within three generations. Using a custom differential network analysis procedure, we found that gene coexpression patterns changed significantly; importantly, a number of these changes were concordant across genetic backgrounds. In contrast, absolute gene-expression changes were modest and not concordant across genetic backgrounds, in spite of the large and similar phenotypic differences. By inferring strain contributions from the parental lines, we are able to identify significant differences in allelic content between the selected lines concurrent with large changes in transcript connectivity. Importantly, this observation implies that genetic polymorphisms can affect transcript and module connectivity without large changes in absolute expression levels. We conclude that, in this case, selective breeding acts at the subnetwork level, with the same modules but not the same transcripts affected across the three selections. PMID:23555609

  20. Maternal genetic effect in DNA analysis: egg on your traits.

    PubMed

    Wilson, Golder N

    2012-07-01

    A dilemma of penetrance parallels the uncertainty principle as array analyses uncover a disturbing continuity of human molecular variation. Among mechanisms for altered penetrance is maternal genetic effect, hypothesized to explain mother-offspring discordance from 12/13 translocation [Wilson et al., 1991] and important to consider when confronting identical genetic changes in normal mothers and their abnormal children. A boy with developmental delays, autistic features, minimal dysmorphology, and maternally inherited 17p13.3 microduplication could exemplify maternal genetic effect, as could a boy with altered brain pattern and maternally inherited Sonic Hedgehog mutation reported by Schell-Apacik et al. [2009]. Maternal genetic effects, characterized in fly, fish, and mouse, are important to consider in human DNA analysis so that identical findings in mother and child are not routinely dismissed as benign variations. Suspect families can define relevant maternal-zygote transition (MZT) genes, provide assays for oocyte function and disruption, and shift anomaly emphasis from pattern recognition to pattern restoration.

  1. Genetic analysis of hispanic individuals with cystic fibrosis

    SciTech Connect

    Grebe, T.A.; Doane, W.W.; Norman, R.A.; Rhodes, S.N. ); Seltzer, W.K. ); DeMarchi, J.; Silva, D.K.; Gozal, D.; Bowman, C.M.; Accurso, F.J.; Jain, K.D. )

    1994-03-01

    The authors have performed molecular genetic analysis of Hispanic individuals with cystic fibrosis (CF) in the southwestern United States. Of 129 CF chromosomes analyzed, oly 46% (59/129) carry [Delta]F508. The G542X mutation was found on 5% (7/129) of CF chromosomes. The 3849+10kbC[yields]T mutation, detected primarily in Ashkenazi Jews, was present on 2% (3/129). R1162X and R334W, mutations identified in Spain and Italy, each occurred on 1.6% (2/129) of CF chromosomes. W1282X and R553X were each detected once. G551D and N1303K were not found. Overall, screening for 22 or more mutations resulted in detection of only 58% of CF transmembrane conductance regulator gene mutations among Hispanic individuals. Analysis of KM19/XV2c haplotypes revealed an unusual distribution. Although the majority of [Delta]508 mutations are on chromosomes of B haplotypes, the other CF mutations are on A and C haplotypes at higher-than-expected frequencies. These genetic analysis demonstrate significant differences between Hispanic individuals with CF and those of the general North American population. Assessment of carrier/affected risk in Hispanic CF individuals cannot, therefore, be based on the mutation frequencies found through studies of the general population but must be adjusted to better reflect the genetic makeup of this ethnic group. Further studies are necessary to identify the causative mutation(s) in this population and to better delineate genotype/phenotype correlations. These will enable counselors to provide more accurate genetic counseling. 22 refs., 2 tabs.

  2. Monitoring Impact of a Pesticide Treatment on Bacterial Soil Communities by Metabolic and Genetic Fingerprinting in Addition to Conventional Testing Procedures

    PubMed Central

    Engelen, Bert; Meinken, Kristin; von Wintzingerode, Friedrich; Heuer, Holger; Malkomes, Hans-Peter; Backhaus, Horst

    1998-01-01

    community patterns, or genetic fingerprints, resulting from application of the different herbicides were obtained by the sequence-specific separation of partial 16S rDNA amplification products in temperature gradient gel electrophoresis. Significant pattern variations were quantified. For detailed analysis, application-responsive bands from the Herbogil and Oleo treatments were sequenced and their tentative phylogenetic positions were identified. Data interpretation and the potentials and biases of the additional observation windows on microbial communities are discussed. PMID:9687435

  3. Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-‘environment’ joint actions on CHD for severa...

  4. Genetic analysis of modern and historical burned human remains.

    PubMed

    von Wurmb-Schwark, Nicole; Ringleb, Arne; Gebühr, Michael; Simeoni, Eva

    2005-03-01

    Burning of corpses is a well-known funeral procedure that has been performed for a long time in many cultures. Nowadays more and more corpses are burned in crematories and buried in urns, often for practical and financial reasons. In some scientific, criminal or civil cases even after cremation there is the need of genetic investigations for identification or paternity testing. Furthermore, burned remains are the only remains left in North Europe from 1200 BC to 500 AD. This makes genetic investigation of those materials interesting for anthropological reasons. We present on one hand a systematic investigation of 10 corpses before and after the cremation and on the other hand the analysis of seven historical remains representing the bronze age. We chose the ground bone powder and the less destroyed bone parts respectively and employed a slightly modified commercially available DNA extraction method. The presence of human nuclear and mitochondrial DNA was tested by a simple but highly sensitive Duplex-PCR. DNA quantification was done using real time PCR, and genetic typing was tried out using the AmpFISTR Identifiler Multiplex Kit, followed by an automatic analysis on an AbiPrism310.

  5. Genetic heterogeneity and HOMOG analysis in British malignant hyperthermia families.

    PubMed Central

    Robinson, R; Curran, J L; Hall, W J; Halsall, P J; Hopkins, P M; Markham, A F; Stewart, A D; West, S P; Ellis, F R

    1998-01-01

    Malignant hyperthermia (MH) is an autosomal dominant genetic condition that presents in susceptible people undergoing general anaesthesia. The clinical disorder is a major cause of anaesthetic morbidity and mortality. The UK Malignant Hyperthermia Group has performed genetic linkage analysis on 20 large, well defined malignant hyperthermia families, using hypervariable markers on chromosome 19q13.1, including the candidate MH gene RYR1, the gene coding for the skeletal muscle ryanodine receptor protein. The results were analysed using LINKAGE to perform two point and multipoint lod scores, then HOMOG to calculate levels of heterogeneity. The results clearly showed genetic heterogeneity between MH families; nine of the families gave results entirely consistent with linkage to the region around RYR1 while the same region was clearly excluded in three families. In the remaining eight MHS families there were single recombinant events between RYR1 and MH susceptibility. HOMOG analysis was of little added benefit in determining the likelihood of linkage to RYR1 in these families. This confirmation of the presence of heterogeneity in the UK MH population, along with the possibility of the presence of two MH genes in some pedigrees, indicates that it would be premature and potentially dangerous to offer diagnosis of MH by DNA based methods at this time. PMID:9541102

  6. Molecular genetic analysis of two families with keratosis follicularis spinulosa decalvans: refinement of gene localization and evidence for genetic heterogeneity.

    PubMed

    Oosterwijk, J C; Richard, G; van der Wielen, M J; van de Vosse, E; Harth, W; Sandkuijl, L A; Bakker, E; van Ommen, G J

    1997-10-01

    X-linked keratosis follicularis spinulosa decalvans (KFSD) is a rare disorder affecting both skin and eyes. In the two extended KFSD families analysed to date, the gene was mapped to Xp22.13-p22.2. By analyzing several new markers in this region, we were able to narrow the candidate region to a 1-Mb interval between DXS7161 and (DXS7593, DXS7105) in the large Dutch pedigree. In addition, we analyzed 23 markers in Xp21.2-p22.2 in a German family with KFSD. Haplotype and recombination analysis positioned the KFSD gene in this family most likely outside the candidate region on Xp22.13-p22.2. This finding is suggestive for genetic heterogeneity: in this pedigree there is either another locus on the X-chromosome, or KFSD is transmitted here as an autosomal dominant trait with variable expression.

  7. The Genetic Architecture of Quantitative Traits Cannot Be Inferred from Variance Component Analysis

    PubMed Central

    Huang, Wen; Mackay, Trudy F. C.

    2016-01-01

    Classical quantitative genetic analyses estimate additive and non-additive genetic and environmental components of variance from phenotypes of related individuals without knowing the identities of quantitative trait loci (QTLs). Many studies have found a large proportion of quantitative trait variation can be attributed to the additive genetic variance (VA), providing the basis for claims that non-additive gene actions are unimportant. In this study, we show that arbitrarily defined parameterizations of genetic effects seemingly consistent with non-additive gene actions can also capture the majority of genetic variation. This reveals a logical flaw in using the relative magnitudes of variance components to indicate the relative importance of additive and non-additive gene actions. We discuss the implications and propose that variance component analyses should not be used to infer the genetic architecture of quantitative traits. PMID:27812106

  8. Integrated microfluidic systems for high-performance genetic analysis.

    PubMed

    Liu, Peng; Mathies, Richard A

    2009-10-01

    Driven by the ambitious goals of genome-related research, fully integrated microfluidic systems have developed rapidly to advance biomolecular and, in particular, genetic analysis. To produce a microsystem with high performance, several key elements must be strategically chosen, including device materials, temperature control, microfluidic control, and sample/product transport integration. We review several significant examples of microfluidic integration in DNA sequencing, gene expression analysis, pathogen detection, and forensic short tandem repeat typing. The advantages of high speed, increased sensitivity, and enhanced reliability enable these integrated microsystems to address bioanalytical challenges such as single-copy DNA sequencing, single-cell gene expression analysis, pathogen detection, and forensic identification of humans in formats that enable large-scale and point-of-analysis applications.

  9. Rabbit MSTN gene polymorphisms and genetic effect analysis.

    PubMed

    Qiao, X B; Xu, K Y; Li, B; Luan, X; Xia, T; Fan, X Z

    2014-04-08

    We analyzed meat samples of nine pure lines of rabbit and its 37 hybrid combinations by sequencing and single-strand conformation polymorphism techniques to explore genetic polymorphisms of all the three exon regions and part of the 5'-regulatory region of the myostatin (MSTN) gene. Thus, we detected a single nucleotide mutation (T→C) on the 476 locus of the 5'-regulatory region, but no mutation sites were detected in the exon areas. The correlation analysis showed that the mutation had some favorable genetic effects, and it resulted in increased liver weight, carcass weight, forelegs weight, back and waist weight, ham weight, and tare weight, whereas it decreased muscle drip loss and cooking loss (P < 0.05). These results suggest that the mutations in the upstream regulatory region of the MSTN gene are beneficial to the rabbit soma development, and the mutations can be used as molecular markers for the selection of the meat quality of rabbits.

  10. Genetic-basis analysis of heterotic loci in Dongxiang common wild rice (Oryza rufipogon Griff.).

    PubMed

    Luo, Xiao-Jin; Xin, Xiao-Yun; Yang, Jin-Shui

    2012-04-01

    Heterosis is widely used in genetic crop improvement; however, the genetic basis of heterosis is incompletely understood. The use of whole-genome segregating populations poses a problem for establishing the genetic basis of heterosis, in that interactions often mask the effects of individual loci. However, introgression line (IL) populations permit the partitioning of heterosis into defined genomic regions, eliminating a major part of the genome-wide epistasis. In our previous study, based on mid-parental heterosis (HMP) value with single-point analysis, 42 heterotic loci (HLs) associated with six yield-related traits were detected in wild and cultivated rice using a set of 265 ILs of Dongxiang common wild rice (Oryza rufipogon Griff.). In this study, the genetic effects of HLs were determined as the combined effects of both additive and dominant gene actions, estimated from the performance values of testcross F1s and the dominance effects estimated from the HMP values of testcross F1s. We characterized the gene action type at each HL. Thirty-eight of the 42 HLs were over-dominant, and in the absence of epistasis, four HLs were dominant. Therefore, we favour that over-dominance is a major genetic basis of 'wild-cultivar' crosses at the single functional Mendelian locus level.

  11. DNA degradation and genetic analysis of empty puparia: genetic identification limits in forensic entomology.

    PubMed

    Mazzanti, Morena; Alessandrini, Federica; Tagliabracci, Adriano; Wells, Jeffrey D; Campobasso, Carlo P

    2010-02-25

    Puparial cases are common remnants of necrophagous flies in crime investigations. They usually represent the longest developmental time and, therefore, they can be very useful for the estimation of the post-mortem interval (PMI). However, before any PMI estimate, it is crucial to identify the species of fly eclosed from each puparium associated with the corpse. Morphological characteristics of the puparium are often distinctive enough to permit a species identification. But, even an accurate morphological analysis of empty puparia cannot discriminate among different species of closely related flies. Furthermore, morphological identification may be impossible if the fly puparia are poorly preserved or in fragments. This study explores the applicability of biomolecular techniques on empty puparia and their fragments for identification purposes. A total of 63 empty puparia of necrophagous Diptera resulting from forensic casework were examined. Samples were divided into three groups according to size, type and time of eclosion in order to verify whether the physical characteristics and puparia weathering can influence the amount of DNA extraction. The results suggest that a reliable genetic identification of forensically important flies may also be performed from empty puparia and/or their fragments. However, DNA degradation can deeply compromise the genetic analysis since the older the fly puparia, the smaller are the amplified fragments.

  12. Genetic Geostatistical Framework for Spatial Analysis of Fine-Scale Genetic Heterogeneity in Modern Populations: Results from the KORA Study.

    PubMed

    Diaz-Lacava, A N; Walier, M; Holler, D; Steffens, M; Gieger, C; Furlanello, C; Lamina, C; Wichmann, H E; Becker, T

    2015-01-01

    Aiming to investigate fine-scale patterns of genetic heterogeneity in modern humans from a geographic perspective, a genetic geostatistical approach framed within a geographic information system is presented. A sample collected for prospective studies in a small area of southern Germany was analyzed. None indication of genetic heterogeneity was detected in previous analysis. Socio-demographic and genotypic data of German citizens were analyzed (212 SNPs; n = 728). Genetic heterogeneity was evaluated with observed heterozygosity (H O ). Best-fitting spatial autoregressive models were identified, using socio-demographic variables as covariates. Spatial analysis included surface interpolation and geostatistics of observed and predicted patterns. Prediction accuracy was quantified. Spatial autocorrelation was detected for both socio-demographic and genetic variables. Augsburg City and eastern suburban areas showed higher H O values. The selected model gave best predictions in suburban areas. Fine-scale patterns of genetic heterogeneity were observed. In accordance to literature, more urbanized areas showed higher levels of admixture. This approach showed efficacy for detecting and analyzing subtle patterns of genetic heterogeneity within small areas. It is scalable in number of loci, even up to whole-genome analysis. It may be suggested that this approach may be applicable to investigate the underlying genetic history that is, at least partially, embedded in geographic data.

  13. Genome-Wide Pathway Analysis Identifies Genetic Pathways Associated with Psoriasis.

    PubMed

    Aterido, Adrià; Julià, Antonio; Ferrándiz, Carlos; Puig, Lluís; Fonseca, Eduardo; Fernández-López, Emilia; Dauden, Esteban; Sánchez-Carazo, José Luís; López-Estebaranz, José Luís; Moreno-Ramírez, David; Vanaclocha, Francisco; Herrera, Enrique; de la Cueva, Pablo; Dand, Nick; Palau, Núria; Alonso, Arnald; López-Lasanta, María; Tortosa, Raül; García-Montero, Andrés; Codó, Laia; Gelpí, Josep Lluís; Bertranpetit, Jaume; Absher, Devin; Capon, Francesca; Myers, Richard M; Barker, Jonathan N; Marsal, Sara

    2016-03-01

    Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To date, the psoriasis heritability is only partially explained. However, there is increasing evidence that the missing heritability in psoriasis could be explained by multiple genetic variants of low effect size from common genetic pathways. The objective of this study was to identify new genetic variation associated with psoriasis risk at the pathway level. We genotyped 598,258 single nucleotide polymorphisms in a discovery cohort of 2,281 case-control individuals from Spain. We performed a genome-wide pathway analysis using 1,053 reference biological pathways. A total of 14 genetic pathways (PFDR ≤ 2.55 × 10(-2)) were found to be significantly associated with psoriasis risk. Using an independent validation cohort of 7,353 individuals from the UK, a total of 6 genetic pathways were significantly replicated (PFDR ≤ 3.46 × 10(-2)). We found genetic pathways that had not been previously associated with psoriasis risk such as retinol metabolism (Pcombined = 1.84 × 10(-4)), the transport of inorganic ions and amino acids (Pcombined = 1.57 × 10(-7)), and post-translational protein modification (Pcombined = 1.57 × 10(-7)). In the latter pathway, MGAT5 showed a strong network centrality, and its association with psoriasis risk was further validated in an additional case-control cohort of 3,429 individuals (P < 0.05). These findings provide insights into the biological mechanisms associated with psoriasis susceptibility.

  14. Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations.

    PubMed

    Santure, Anna W; Poissant, Jocelyn; De Cauwer, Isabelle; van Oers, Kees; Robinson, Matthew R; Quinn, John L; Groenen, Martien A M; Visser, Marcel E; Sheldon, Ben C; Slate, Jon

    2015-12-01

    Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar phenotypic variation in different populations? Great tits (Parus major) have been studied extensively in long-term studies across Europe and consequently are considered an ecological 'model organism'. Recently, genomic resources have been developed for the great tit, including a custom SNP chip and genetic linkage map. In this study, we used a suite of approaches to investigate the genetic architecture of eight quantitative traits in two long-term study populations of great tits--one in the Netherlands and the other in the United Kingdom. Overall, we found little evidence for the presence of genes of large effects in either population. Instead, traits appeared to be influenced by many genes of small effect, with conservative estimates of the number of contributing loci ranging from 31 to 310. Despite concordance between population-specific heritabilities, we found no evidence for the presence of loci having similar effects in both populations. While population-specific genetic architectures are possible, an undetected shared architecture cannot be rejected because of limited power to map loci of small and moderate effects. This study is one of few examples of genetic architecture analysis in replicated wild populations and highlights some of the challenges and limitations researchers will face when attempting similar molecular quantitative genetic studies in free-living populations.

  15. Genetic analysis of 12 unrelated CADASIL families: Demonstration of genetic homogeneity: Physical mapping of the gene

    SciTech Connect

    Tournier-Lasserve, E.; Nibbio, A.; Vahedi, K.

    1994-09-01

    CADASIL is the acronym (Cerebral Autosomal Dominant Arteriopathy with Subcortical Ischemic Strokes and Leukoencephalopathy) designating a recently identified mendelian cerebral arteriopathy characterized by the recurrence of ischemic sensory and motor deficits leading to a progressive subcortical dementia. Magnetic resonance imaging of the brain shows extensive areas of increased signal in the hemispheric white matter. We recently mapped the CADASIL locus in 2 large families on chromosome 19 in a 14 cM interval bracketed by D19S221 and D19S215{sup *}. Forty additional families have been collected. Twelve of them including more than 200 members have already been genotyped with a set of 10 highly polymorphic markers located between D19S221 and D19S215. All families are significantly linked to chromosome 19 demonstrating genetic homogeneity. Combined lod scores for several of these markers are above 30. The size of the mapping interval has been reduced to 2 cM. Genetic testing for presymptomatic individuals is now possible with respect to all ethical rules in this severe condition. Lastly, physical mapping of the affected gene has been started and data will be presented at the meeting.

  16. Genetic Analysis of Oncorhynchus Nerka : Life History and Genetic Analysis of Redfish Lake Oncorhynchus Nerka, 1993-1994 Completion Report.

    SciTech Connect

    Brannon, E.L.; Thorgaard, G.H.; Cummings, S.A.

    1994-10-01

    The study has shown through life history examination and DNA analysis that three forms of O. nerka are present in Redfish Lake. The three forms are closely related, but may be sufficiently different to be considered three separate stocks. Fishhook Creek kokanee are temporally isolated from the beach spawners, and may represent the gene pool most similar to the historic sockeye population that once spawned there. Fishhook Creek offers the best spawning area available in the lake system, and should be considered for use in reestablishing an anadromous Fishhook Creek sockeye swain. The resident beach spawning strain of O. nerka is likewise the most similar genetic form of the companion anadromous beach spawning O. nerka, and needs to be considered the most appropriate genetic source to help minimize reduced fitness of the sockeye from inbreeding.

  17. Analysis methods for the determination of anthropogenic additions of P to agricultural soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phosphorus additions and measurement in soil is of concern on lands where biosolids have been applied. Colorimetric analysis for plant-available P may be inadequate for the accurate assessment of soil P. Phosphate additions in a regulatory environment need to be accurately assessed as the reported...

  18. Genetic Analysis Workshop 16: Introduction to Workshop Summaries

    PubMed Central

    MacCluer, Jean W; Amos, Christopher I; Gregersen, Peter K; Heard-Costa, Nancy; Lee, Monica; Kraja, Aldi T; Borecki, Ingrid B; Cupples, L Adrienne; Almasy, Laura

    2010-01-01

    Genetic Analysis Workshop 16 GAW16) was held September 17-20, 2008 in St. Louis, Missouri. The focus of GAW16 was on methods and challenges in analysis of single-nucleotide polymorphism (SNP) data from genome-wide scans. GAW16 attracted 221 participants from 12 countries. The 168 contributions were organized into 17 discussion groups of 6 to 17 papers each. Three data sets were available for analysis. Two of these were data from ongoing studies, generously provided by the investigators. The North American Rheumatoid Arthritis Consortium provided case-control data on rheumatoid arthritis, and the Framingham Heart Study made available information on cardiovascular risk factors for participants in three generations of pedigree data. The third data set included simulated phenotypes for participants in the Framingham Heart Study, using actual pedigree structures and genotypes. This volume includes a paper for each of the 17 discussion groups, summarizing their main findings. PMID:19924709

  19. Overview of genetic analysis of human opioid receptors.

    PubMed

    Spampinato, Santi M

    2015-01-01

    The human μ-opioid receptor gene (OPRM1), due to its genetic and structural variation, has been a target of interest in several pharmacogenetic studies. The μ-opioid receptor (MOR), encoded by OPRM1, contributes to regulate the analgesic response to pain and also controls the rewarding effects of many drugs of abuse, including opioids, nicotine, and alcohol. Genetic polymorphisms of opioid receptors are candidates for the variability of clinical opioid effects. The non-synonymous polymorphism A118G of the OPRM1 has been repeatedly associated with the efficacy of opioid treatments for pain and various types of dependence. Genetic analysis of human opioid receptors has evidenced the presence of numerous polymorphisms either in exonic or in intronic sequences as well as the presence of synonymous coding variants that may have important effects on transcription, mRNA stability, and splicing, thus affecting gene function despite not directly disrupting any specific residue. Genotyping of opioid receptors is still in its infancy and a relevant progress in this field can be achieved by using advanced gene sequencing techniques described in this review that allow the researchers to obtain vast quantities of data on human genomes and transcriptomes in a brief period of time and with affordable costs.

  20. Molecular diversity analysis of eggplant (Solanum melongena) genetic resources.

    PubMed

    Ali, Z; Xu, Z L; Zhang, D Y; He, X L; Bahadur, S; Yi, J X

    2011-06-14

    Eggplant (Solanum melongena), a vegetable that is cultivated worldwide, is of considerable importance to agriculture in China. We analyzed the diversity of this plant using inter-simple sequence repeat (ISSR) and RAPD procedures to subdivide 143 Chinese-cultivated eggplants based on coefficient of parentage, genetic diversity index (GDI) and canonical discriminant analysis. ISSR markers were more effective than RAPD markers for detecting genetic diversity, which ranged from 0.10-0.51, slightly lower than what is known from other crops. Our ISSR/RAPD data provide molecular evidence that coincides with morphological-based classification into three varieties and further subdivision into eight groups, except for two groups. Intensive use of elite parents and extensive crossing within groups have resulted in increased coefficient of parentage and proportional contribution but decreased GDI during the past decades. The mean coefficient of parentage and proportional contribution increased from 0.05 to 0.10% and from 3.22 to 6.46% during 1980-1991 and 1992-2003, respectively. The GDI of landraces was 0.21, higher than the 0.09 and 0.08 calculated for the hybrid cultivars released during the two periods. The recent introduction of alien genotypes into eggplant breeding programs may broaden the genetic base.

  1. Genetic aspect of Alzheimer disease: Results of complex segregation analysis

    SciTech Connect

    Sadonvick, A.D.; Lee, I.M.L.; Bailey-Wilson, J.E.

    1994-09-01

    The study was designed to evaluate the possibility that a single major locus will explain the segregation of Alzheimer disease (AD). The data were from the population-based AD Genetic Database and consisted of 402 consecutive, unrelated probands, diagnosed to have either `probable` or `autopsy confirmed` AD and their 2,245 first-degree relatives. In this analysis, a relative was considered affected with AD only when there were sufficient medical/autopsy data to support diagnosis of AD being the most likely cause of the dementia. Transmission probability models allowing for a genotype-dependent and logistically distributed age-of-onset were used. The program REGTL in the S.A.G.E. computer program package was used for a complex segregation analysis. The models included correction for single ascertainment. Regressive familial effects were not estimated. The data were analyzed to test for single major locus (SML), random transmission and no transmission (environmental) hypotheses. The results of the complex segregation analysis showed that (1) the SML was the best fit, and (2) the non-genetic models could be rejected.

  2. Genetic Analysis of Reduced γ-Tocopherol Content in Ethiopian Mustard Seeds

    PubMed Central

    García-Navarro, Elena; Fernández-Martínez, José M.; Pérez-Vich, Begoña

    2016-01-01

    Ethiopian mustard (Brassica carinata A. Braun) line BCT-6, with reduced γ-tocopherol content in the seeds, has been previously developed. The objective of this research was to conduct a genetic analysis of seed tocopherols in this line. BCT-6 was crossed with the conventional line C-101 and the F1, F2, and BC plant generations were analyzed. Generation mean analysis using individual scaling tests indicated that reduced γ-tocopherol content fitted an additive-dominant genetic model with predominance of additive effects and absence of epistatic interactions. This was confirmed through a joint scaling test and additional testing of the goodness of fit of the model. Conversely, epistatic interactions were identified for total tocopherol content. Estimation of the minimum number of genes suggested that both γ- and total tocopherol content may be controlled by two genes. A positive correlation between total tocopherol content and the proportion of γ-tocopherol was identified in the F2 generation. Additional research on the feasibility of developing germplasm with high tocopherol content and reduced concentration of γ-tocopherol is required. PMID:27275005

  3. Genetic Analysis of Reduced γ-Tocopherol Content in Ethiopian Mustard Seeds.

    PubMed

    García-Navarro, Elena; Fernández-Martínez, José M; Pérez-Vich, Begoña; Velasco, Leonardo

    2016-01-01

    Ethiopian mustard (Brassica carinata A. Braun) line BCT-6, with reduced γ-tocopherol content in the seeds, has been previously developed. The objective of this research was to conduct a genetic analysis of seed tocopherols in this line. BCT-6 was crossed with the conventional line C-101 and the F1, F2, and BC plant generations were analyzed. Generation mean analysis using individual scaling tests indicated that reduced γ-tocopherol content fitted an additive-dominant genetic model with predominance of additive effects and absence of epistatic interactions. This was confirmed through a joint scaling test and additional testing of the goodness of fit of the model. Conversely, epistatic interactions were identified for total tocopherol content. Estimation of the minimum number of genes suggested that both γ- and total tocopherol content may be controlled by two genes. A positive correlation between total tocopherol content and the proportion of γ-tocopherol was identified in the F2 generation. Additional research on the feasibility of developing germplasm with high tocopherol content and reduced concentration of γ-tocopherol is required.

  4. Genetic analysis of Apuleia leiocarpa as revealed by random amplified polymorphic DNA markers: prospects for population genetic studies.

    PubMed

    Lencina, K H; Konzen, E R; Tsai, S M; Bisognin, D A

    2016-12-19

    Apuleia leiocarpa (Vogel) J.F. MacBride is a hardwood species native to South America, which is at serious risk of extinction. Therefore, it is of prime importance to examine the genetic diversity of this species, information required for developing conservation, sustainable management, and breeding strategies. Although scarcely used in recent years, random amplified polymorphic DNA markers are useful resources for the analysis of genetic diversity and structure of tree species. This study represents the first genetic analysis based on DNA markers in A. leiocarpa that aimed to investigate the levels of polymorphism and to select markers for the precise characterization of its genetic structure. We adapted the original DNA extraction protocol based on cetyltrimethyl ammonium bromide, and describe a simple procedure that can be used to obtain high-quality samples from leaf tissues of this tree. Eighteen primers were selected, revealing 92 bands, from which 75 were polymorphic and 61 were sufficient to represent the overall genetic structure of the population without compromising the precision of the analysis. Some fragments were conserved among individuals, which can be sequenced and used to analyze nucleotide diversity parameters through a wider set of A. leiocarpa individuals and populations. The individuals were separated into 11 distinct groups with variable levels of genetic diversity, which is important for selecting desirable genotypes and for the development of a conservation and sustainable management program. Our results are of prime importance for further investigations concerning the genetic characterization of this important, but vulnerable species.

  5. Genomic Analysis Reveals Novel Diversity among the 1976 Philadelphia Legionnaires’ Disease Outbreak Isolates and Additional ST36 Strains

    PubMed Central

    Mercante, Jeffrey W.; Morrison, Shatavia S.; Desai, Heta P.; Raphael, Brian H.; Winchell, Jonas M.

    2016-01-01

    Legionella pneumophila was first recognized as a cause of severe and potentially fatal pneumonia during a large-scale outbreak of Legionnaires’ disease (LD) at a Pennsylvania veterans’ convention in Philadelphia, 1976. The ensuing investigation and recovery of four clinical isolates launched the fields of Legionella epidemiology and scientific research. Only one of the original isolates, “Philadelphia-1”, has been widely distributed or extensively studied. Here we describe the whole-genome sequencing (WGS), complete assembly, and comparative analysis of all Philadelphia LD strains recovered from that investigation, along with L. pneumophila isolates sharing the Philadelphia sequence type (ST36). Analyses revealed that the 1976 outbreak was due to multiple serogroup 1 strains within the same genetic lineage, differentiated by an actively mobilized, self-replicating episome that is shared with L. pneumophila str. Paris, and two large, horizontally-transferred genomic loci, among other polymorphisms. We also found a completely unassociated ST36 strain that displayed remarkable genetic similarity to the historical Philadelphia isolates. This similar strain implies the presence of a potential clonal population, and suggests important implications may exist for considering epidemiological context when interpreting phylogenetic relationships among outbreak-associated isolates. Additional extensive archival research identified the Philadelphia isolate associated with a non-Legionnaire case of “Broad Street pneumonia”, and provided new historical and genetic insights into the 1976 epidemic. This retrospective analysis has underscored the utility of fully-assembled WGS data for Legionella outbreak investigations, highlighting the increased resolution that comes from long-read sequencing and a sequence type-matched genomic data set. PMID:27684472

  6. Genetic analysis and attribution of microbial forensics evidence.

    PubMed

    Budowle, Bruce; Johnson, Martin D; Fraser, Claire M; Leighton, Terrance J; Murch, Randall S; Chakraborty, Ranajit

    2005-01-01

    Because of the availability of pathogenic microorganisms and the relatively low cost of preparing and disseminating bioweapons, there is a continuing threat of biocrime and bioterrorism. Thus, enhanced capabilities are needed that enable the full and robust forensic exploitation and interpretation of microbial evidence from acts of bioterrorism or biocrimes. To respond to the need, greater resources and efforts are being applied to the burgeoning field of microbial forensics. Microbial forensics focuses on the characterization, analysis and interpretation of evidence for attributional purposes from a bioterrorism act, biocrime, hoax or inadvertent agent release. To enhance attribution capabilities, a major component of microbial forensics is the analysis of nucleic acids to associate or eliminate putative samples. The degree that attribution can be addressed depends on the context of the case, the available knowledge of the genetics, phylogeny, and ecology of the target microorganism, and technologies applied. The types of genetic markers and features that can impact statistical inferences of microbial forensic evidence include: single nucleotide polymorphisms, repetitive sequences, insertions and deletions, mobile elements, pathogenicity islands, virulence and resistance genes, house keeping genes, structural genes, whole genome sequences, asexual and sexual reproduction, horizontal gene transfer, conjugation, transduction, lysogeny, gene conversion, recombination, gene duplication, rearrangements, and mutational hotspots. Nucleic acid based typing technologies include: PCR, real-time PCR, MLST, MLVA, whole genome sequencing, and microarrays.

  7. Genetic analysis of growth traits in Harnali sheep

    PubMed Central

    Lalit; Malik, Z. S.; Dalal, D. S.; Dahiya, S. P.; Patil, C. S.; Dahiya, Ravinder

    2016-01-01

    Aim: The present investigation was to study genetic characteristics of Harnali sheep with respect to growth performance and to estimate genetic parameters. Materials and Methods: The 22 years (1992-2013) data of growth traits of a 1603 synthetic population of Harnali sheep maintained at Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, was utilized for this study. A mixed methodology with regression on their dam's weight was used to study the effect of non-genetic factors on growth traits. Heritability, genetic and phenotypic correlations were estimated using paternal half-sib analysis for body weight at various ages and average daily gain (ADG) for different growth periods. Result: The overall least squares mean of body weights recorded for birth weight (BW), weaning weight (WW), six months body weight (SMW), one yearling body weight (YBW), average daily gain from birth to 3 months (ADG1) and average daily gain from 3 to 12 months (ADG2) were 3.35±0.05 kg, 12.41±0.08 kg, 16.30±0.12 kg, 21.88±0.08 kg, 100.66±0.86 g/day and 35.07±0.39 g/day, respectively. The effects of year of birth significantly (p<0.01) influenced the BW, WW, SMW, YWB, ADG1 and ADG2. The effects of sex of lamb significantly (p<0.01) influenced the BW, WW SMW, YWB, ADG1 and ADG2. The effects of dam's weight at lambing significantly (p<0.01) influenced BW, WW, SMW, YWB, ADG1 and ADG2. No definite trend was observed over the years for the averages of body weight and gain. The heritability estimates of BW, WW, SMW, YBW, ADG1 and ADG2 were 0.40±0.05, 0.38±0.05, 0.45±0.06, 0.29±0.05, 0.40±0.06 and 0.33±0.02, respectively. The male lambs were significantly heavier than females at all stages of growth. The heritability estimates were moderate for all the growth traits and high genetic correlations of BW and WW with SMW were found. Conclusion: Due to high heritability and positive correlations of SMW with other body weights and daily gain, it was concluded that selection on

  8. Analysis of membrane lipid biogenesis pathways using yeast genetics.

    PubMed

    Gsell, Martina; Daum, Günther

    2013-01-01

    The yeast Saccharomyces cerevisiae has become a valuable eukaryotic model organism to study biochemical and cellular processes at a molecular basis. A common strategy for such studies is the use of single and multiple mutants constructed by genetic manipulation which are compromised in individual enzymatic steps or certain metabolic pathways. Here, we describe selected examples of yeast research on phospholipid metabolism with emphasis on our own work dealing with investigations of phosphatidylethanolamine synthesis. Such studies start with the selection and construction of appropriate mutants and lead to phenotype analysis, lipid profiling, enzymatic analysis, and in vivo experiments. Comparing results obtained with wild-type and mutant strains allows us to understand the role of gene products and metabolic processes in more detail. Such studies are valuable not only for contributing to our knowledge of the complex network of lipid metabolism, but also of effects of lipids on structure and function of cellular membranes.

  9. An entropy test for single-locus genetic association analysis

    PubMed Central

    2010-01-01

    Background The etiology of complex diseases is due to the combination of genetic and environmental factors, usually many of them, and each with a small effect. The identification of these small-effect contributing factors is still a demanding task. Clearly, there is a need for more powerful tests of genetic association, and especially for the identification of rare effects Results We introduce a new genetic association test based on symbolic dynamics and symbolic entropy. Using a freely available software, we have applied this entropy test, and a conventional test, to simulated and real datasets, to illustrate the method and estimate type I error and power. We have also compared this new entropy test to the Fisher exact test for assessment of association with low-frequency SNPs. The entropy test is generally more powerful than the conventional test, and can be significantly more powerful when the genotypic test is applied to low allele-frequency markers. We have also shown that both the Fisher and Entropy methods are optimal to test for association with low-frequency SNPs (MAF around 1-5%), and both are conservative for very rare SNPs (MAF<1%) Conclusions We have developed a new, simple, consistent and powerful test to detect genetic association of biallelic/SNP markers in case-control data, by using symbolic dynamics and symbolic entropy as a measure of gene dependence. We also provide a standard asymptotic distribution of this test statistic. Given that the test is based on entropy measures, it avoids smoothed nonparametric estimation. The entropy test is generally as good or even more powerful than the conventional and Fisher tests. Furthermore, the entropy test is more computationally efficient than the Fisher's Exact test, especially for large number of markers. Therefore, this entropy-based test has the advantage of being optimal for most SNPs, regardless of their allele frequency (Minor Allele Frequency (MAF) between 1-50%). This property is quite beneficial

  10. Genetic improvement of laying hens viability using survival analysis

    PubMed Central

    Ducrocq, Vincent; Besbes, Badi; Protais, Michel

    2000-01-01

    The survival of about eight generations of a large strain of laying hens was analysed separating the rearing period (RP) from the production period (PP), after hens were housed. For RP (respectively PP), 97.8% (resp., 94.1% ) of the 109 160 (resp., 100 665) female records were censored after 106 days (resp., 313 days) on the average. A Cox proportional hazards model stratified by flock (= season) and including a hatch-within-flock (HWF) fixed effect seemed to reasonably fit the RP data. For PP, this model could be further simplified to a non-stratified Weibull model. The extension of these models to sire-dam frailty (mixed) models permitted the estimation of the sire genetic variances at 0.261 ± 0.026 and 0.088 ± 0.010 for RP and PP, respectively. Heritabilities on the log scale were equal to 0.48 and 0.19. Non-additive genetic effects could not be detected. Selection was simulated by evaluating all sires and dams, after excluding all records from the last generation. Then, actual parents of this last generation were distributed into four groups according to their own pedigree index. Raw survivor curves of the progeny of extreme parental groups substantially differed (e.g., by 1.7% at 300 days for PP), suggesting that selection based on solutions from the frailty models could be efficient, despite the very large proportion of censored records. PMID:14736405

  11. Endogenous allergens and compositional analysis in the allergenicity assessment of genetically modified plants.

    PubMed

    Fernandez, A; Mills, E N C; Lovik, M; Spoek, A; Germini, A; Mikalsen, A; Wal, J M

    2013-12-01

    Allergenicity assessment of genetically modified (GM) plants is one of the key pillars in the safety assessment process of these products. As part of this evaluation, one of the concerns is to assess that unintended effects (e.g. over-expression of endogenous allergens) relevant for the food safety have not occurred due to the genetic modification. Novel technologies are now available and could be used as complementary and/or alternative methods to those based on human sera for the assessment of endogenous allergenicity. In view of these developments and as a step forward in the allergenicity assessment of GM plants, it is recommended that known endogenous allergens are included in the compositional analysis as additional parameters to be measured.

  12. Genetic admixture history of Eastern Indonesia as revealed by Y-chromosome and mitochondrial DNA analysis.

    PubMed

    Mona, Stefano; Grunz, Katharina E; Brauer, Silke; Pakendorf, Brigitte; Castrì, Loredana; Sudoyo, Herawati; Marzuki, Sangkot; Barnes, Robert H; Schmidtke, Jörg; Stoneking, Mark; Kayser, Manfred

    2009-08-01

    Eastern Indonesia possesses more linguistic diversity than any other region in Southeast Asia, with both Austronesian (AN) languages that are of East Asian origin, as well as non-Austronesian (NAN) languages of likely Melanesian origin. Here, we investigated the genetic history of human populations from seven eastern Indonesian islands, including AN and NAN speakers, as well as the relationship between languages and genes, by means of nonrecombining Y-chromosomal (NRY) and mitochondrial DNA (mtDNA) analysis. We found that the eastern Indonesian gene pool consists of East Asian as well as Melanesian components, as might be expected based on linguistic evidence, but also harbors putative indigenous eastern Indonesian signatures that perhaps reflect the initial occupation of the Wallacea by aboriginal hunter-gatherers already in Palaeolithic times. Furthermore, both NRY and mtDNA data showed a complete lack of correlation between linguistic and genetic relationships, most likely reflecting genetic admixture and/or language shift. In addition, we noted a small fraction of the NRY and mtDNA data shared between eastern Indonesians and Australian Aborigines likely reflecting an ancient link between Asia and Australia. Our data thus provide insights into the complex genetic ancestry history of eastern Indonesian islanders characterized by several admixture episodes and demonstrate a clear example of the lack of the often-assumed correlation between the genes and languages of human populations.

  13. Genetic analysis of photoreceptor action pathways in Arabidopsis thaliana

    SciTech Connect

    Not Available

    1991-01-01

    The specific strategies and long-term goals of this proposal remain intact relative to the original proposal. We continue to isolate and characterize photomorphogenic mutants of Arabidopsis thaliana. The molecular and biochemical characterization of one of these mutants, det1, has led to one publication of original data and to one Society for Experimental Biology Symposium paper (see below). The phenotype of a second mutant, det2, has also been studied during this funding period. In addition, we have continued work on a general strategy to isolate mutations in trans-acting regulatory factors that mediate light-regulated gene expression, and have identified several potentially interesting regulatory mutants. In the third funding period, we will concentrate on the genetical, biochemical, and molecular characterization of these new mutants. Construction of double mutants between the new mutants and the previously characterized morphological mutants should allow us to construct a pathway for light-regulated seedling development in Arabidopsis.

  14. Genetic analysis and QTL mapping of seed coat color in sesame (Sesamum indicum L.).

    PubMed

    Zhang, Haiyang; Miao, Hongmei; Wei, Libin; Li, Chun; Zhao, Ruihong; Wang, Cuiying

    2013-01-01

    Seed coat color is an important agronomic trait in sesame, as it is associated with seed biochemical properties, antioxidant content and activity and even disease resistance of sesame. Here, using a high-density linkage map, we analyzed genetic segregation and quantitative trait loci (QTL) for sesame seed coat color in six generations (P1, P2, F1, BC1, BC2 and F2). Results showed that two major genes with additive-dominant-epistatic effects and polygenes with additive-dominant-epistatic effects were responsible for controlling the seed coat color trait. Average heritability of the major genes in the BC1, BC2 and F2 populations was 89.30%, 24.00%, and 91.11% respectively, while the heritability of polygenes was low in the BC1 (5.43%), in BC2 (0.00%) and in F2 (0.89%) populations. A high-density map was constructed using 724 polymorphic markers. 653 SSR, AFLP and RSAMPL loci were anchored in 14 linkage groups (LG) spanning a total of 1,216.00 cM. The average length of each LG was 86.86 cM and the marker density was 1.86 cM per marker interval. Four QTLs for seed coat color, QTL1-1, QTL11-1, QTL11-2 and QTL13-1, whose heritability ranged from 59.33%-69.89%, were detected in F3 populations using CIM and MCIM methods. Alleles at all QTLs from the black-seeded parent tended to increase the seed coat color. Results from QTLs mapping and classical genetic analysis among the P1, P2, F1, BC1, BC2 and F2 populations were comparatively consistent. This first QTL analysis and high-density genetic linkage map for sesame provided a good foundation for further research on sesame genetics and molecular marker-assisted selection (MAS).

  15. Genetic analysis of plasmid determinants for microcin J25 production and immunity.

    PubMed Central

    Solbiati, J O; Ciaccio, M; Farías, R N; Salomón, R A

    1996-01-01

    Microcin J25 (MccJ25) is a small peptide antibiotic produced by an Escherichia coli strain isolated from human feces. The genetic determinants for MccJ25 synthesis and immunity have been cloned from the low-copy-number wild-type plasmid pTUC1OO into the compatible vectors pBR322 and pACYC184. Physical and phenotypical analysis of insertion mutations and complementation tests defined three contiguous genes involved in MccJ25 production which span a region of about 2.2 kb. Immunity to the antibiotic is provided by an additional gene adjacent to the production region. PMID:8655570

  16. A genetic analysis of mancozeb resistance in Typhlodromus pyri (Acari: Phytoseiidae).

    PubMed

    Auger, Philippe; Bonafos, Romain; Kreiter, Serge; Delorme, Robert

    2005-01-01

    A field population of Typhlodromus pyri (Acari: Phytoseiidae) tolerant to mancozeb was selected in the laboratory. After 10 mancozeb selections the LC50 value for mancozeb was 73 times higher in the selected-10 strain compared to the standard susceptible strain. A genetic analysis using reciprocal crosses and backcrosses of female F1 progeny found no maternal effect. Resistance in the selected-10 strain was codominant in expression, dominance value was about -0.1. Backcrosses between F1 females and the susceptible strain indicate that the resistance to mancozeb could be principally conferred by a predominant gene, but additional factors would also be involved.

  17. Genetic analysis of human parainfluenza viruses circulating in Korea, 2006.

    PubMed

    Park, Kwang Sook; Yang, Mi Hwa; Lee, Chang Kyu; Song, Ki-Joon

    2014-06-01

    Human parainfluenza viruses (HPIV) are important causes of respiratory tract infections in young children. To characterize the molecular epidemiology of an HPIV outbreak occurring in Korea during 2006, genetic analysis of 269 cell culture isolates from HPIV-infected children, was conducted using nested reverse transcription-PCR (RT-PCR). HPIV-1 was detected in 70.3% of tested samples (189/269). The detection rate of HPIV-2 and HPIV-3 was 1.5% (4/269) and 9.3% (25/269), respectively. Mixed HPIV-1, -2 and -3 infections were detected in 19.0% (51/269): HPIV-1 and HPIV-2 in 15, HPIV-1 and HPIV-3 in 26, HPIV-2 and HPIV-3 in 6, and HPIV-1, -2 and -3 in 4. Of these positive samples for three different types HIPV-1, -2, and -3, two each representative strains were selected, the full length of hemagglutinin-neuraminidase (HN) gene for HPIV was amplified by RT-PCR, and sequenced. Multiple alignment analysis, based on reference sequence of HPIV-1, -2, and -3 strains available in GenBank, showed that the identity of nucleotide and deduced amino acid sequences was 92.4-97.6% and 92.7-97.9%, respectively, for HPIV-1, 88.5-99.8% and 88.6-100% for HPIV-2, and 96.3-99.5% and 95.0-99.3% for HPIV-3, respectively. Phylogenetic analysis showed that HPIV-1, -2, and -3 strains identified in this study were closely related among the strains in the same type with no significant genetic variability. These results show that HPIV of multiple imported sources was circulating in Korea.

  18. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  19. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  20. Genetics of acheiropodia (the handless and footless families of Brazil). VI. Formal genetic analysis.

    PubMed Central

    Freire-Maia, A; Freire-Maia, N; Morton, N E; Azevêdo, E S; Quelce-Salgado, A

    1975-01-01

    A genetic analysis is presented of data from 22 Brazilian sibships with cases of acheiropodia (the handless and footless families of Brazil). Segregation analysis performed using a 16K CDC 3100 computer showed a segregation frequency of .245 +/- .040, which is close to the expected value of .25. No sporadic cases were detected. The ascertainment of the probands was through multiple incomplete selection (pi = .55 +/- .07). The data are consistent with the hypothesis of an extremely rare autosomal recessive gene as the etiological factor in acheiropodia. Prevalence is estimated as 29 +/- 4, which is the same as the number of high risk cases; gene frequency equals .0009 +/- .0005, and the incidence at birth is 4 times 10(-6) by the indirect method or 7 times 10(-6) by the direct method. The frequency of heterozygotes at birth is assumed to be 0.18% (450 times the frequency of affected). Population size is approximately 10 million, and the number of founders on a unique-mutation hypothesis is estimated as about 500. All these estimates are first approximations and must be accepted with caution. Images Fig. 1 PMID:1155460

  1. Power analysis of principal components regression in genetic association studies.

    PubMed

    Shen, Yan-feng; Zhu, Jun

    2009-10-01

    Association analysis provides an opportunity to find genetic variants underlying complex traits. A principal components regression (PCR)-based approach was shown to outperform some competing approaches. However, a limitation of this method is that the principal components (PCs) selected from single nucleotide polymorphisms (SNPs) may be unrelated to the phenotype. In this article, we investigate the theoretical properties of such a method in more detail. We first derive the exact power function of the test based on PCR, and hence clarify the relationship between the test power and the degrees of freedom (DF). Next, we extend the PCR test to a general weighted PCs test, which provides a unified framework for understanding the properties of some related statistics. We then compare the performance of these tests. We also introduce several data-driven adaptive alternatives to overcome difficulties in the PCR approach. Finally, we illustrate our results using simulations based on real genotype data. Simulation study shows the risk of using the unsupervised rule to determine the number of PCs, and demonstrates that there is no single uniformly powerful method for detecting genetic variants.

  2. Genetic analysis of peste des petits ruminants virus from Pakistan

    PubMed Central

    2013-01-01

    Background Peste des petits ruminants (PPR) is an endemic and highly contagious disease in small ruminants of Pakistan. Despite the fact that an effective vaccine is available, outbreaks are regularly occurring in the country. Thus so far, the diagnosis has primarily been made based on clinical outcome or serology. This study was carried out to characterize PPRV from an emerging wave of outbreaks from Punjab, Pakistan. Results A total of 32 blood samples from five different flocks were tested with real-time PCR for the presence of PPRV genome. The samples detected positive in real-time PCR (n = 17) were subjected to conventional PCR for the amplification of the nucleoprotein (N) gene. Phylogenetic analysis of the sequenced N genes (n = 8) indicated the grouping of all the sequences in lineage IV along with PPRV strains from Asian and Middle East. However, interestingly sequences were divided into two groups. One group of viruses (n = 7) clustered with previously characterized Pakistani isolates whereas one strain of PPRV was distinct and clustered with Saudi Arabian and Iranian strains of PPRV. Conclusions Results demonstrated in this study expanded the information on the genetic nature of different PPRV population circulating in small ruminants. Such information is essential to understand genetic nature of PPRV strains throughout the country. Proper understanding of these viruses will help to devise control strategies in PPRV endemic countries such as Pakistan. PMID:23537146

  3. Genetic analysis of arsenic accumulation in maize using QTL mapping

    NASA Astrophysics Data System (ADS)

    Fu, Zhongjun; Li, Weihua; Xing, Xiaolong; Xu, Mengmeng; Liu, Xiaoyang; Li, Haochuan; Xue, Yadong; Liu, Zonghua; Tang, Jihua

    2016-02-01

    Arsenic (As) is a toxic heavy metal that can accumulate in crops and poses a threat to human health. The genetic mechanism of As accumulation is unclear. Herein, we used quantitative trait locus (QTL) mapping to unravel the genetic basis of As accumulation in a maize recombinant inbred line population derived from the Chinese crossbred variety Yuyu22. The kernels had the lowest As content among the different maize tissues, followed by the axes, stems, bracts and leaves. Fourteen QTLs were identified at each location. Some of these QTLs were identified in different environments and were also detected by joint analysis. Compared with the B73 RefGen v2 reference genome, the distributions and effects of some QTLs were closely linked to those of QTLs detected in a previous study; the QTLs were likely in strong linkage disequilibrium. Our findings could be used to help maintain maize production to satisfy the demand for edible corn and to decrease the As content in As-contaminated soil through the selection and breeding of As pollution-safe cultivars.

  4. Genetic analysis of arsenic accumulation in maize using QTL mapping

    PubMed Central

    Fu, Zhongjun; Li, Weihua; Xing, Xiaolong; Xu, Mengmeng; Liu, Xiaoyang; Li, Haochuan; Xue, Yadong; Liu, Zonghua; Tang, Jihua

    2016-01-01

    Arsenic (As) is a toxic heavy metal that can accumulate in crops and poses a threat to human health. The genetic mechanism of As accumulation is unclear. Herein, we used quantitative trait locus (QTL) mapping to unravel the genetic basis of As accumulation in a maize recombinant inbred line population derived from the Chinese crossbred variety Yuyu22. The kernels had the lowest As content among the different maize tissues, followed by the axes, stems, bracts and leaves. Fourteen QTLs were identified at each location. Some of these QTLs were identified in different environments and were also detected by joint analysis. Compared with the B73 RefGen v2 reference genome, the distributions and effects of some QTLs were closely linked to those of QTLs detected in a previous study; the QTLs were likely in strong linkage disequilibrium. Our findings could be used to help maintain maize production to satisfy the demand for edible corn and to decrease the As content in As-contaminated soil through the selection and breeding of As pollution-safe cultivars. PMID:26880701

  5. Genetic therapy in gliomas: historical analysis and future perspectives.

    PubMed

    Mattei, Tobias Alécio; Ramina, Ricardo; Miura, Flavio Key; Aguiar, Paulo Henrique; Valiengo, Leandro da Costa

    2005-03-01

    High-grade gliomas are relatively frequent in adults, and consist of the most malignant kind of primary brain tumor. Being resistant to standard treatment modalities such as surgery, radiation, and chemotherapy, it is fatal within 1 to 2 years of onset of symptoms. Although several gene therapy systems proved to be efficient in controlling or eradicating these tumors in animal models, the clinical studies performed so far were not equally successful. Most clinical studies showed that methodologies that increase tumor infection/transduction and, consequently confer more permanent activity against the tumor, will lead to enhanced therapeutic results. Due to the promising practical clinical benefits that can be expected for the near future, an exposition to the practicing neurosurgeon about the basic issues in genetic therapy of gliomas seems convenient. Among the main topics, we shall discuss anti-tumoral mechanisms of various genes that can be transfected, the advantages and drawbacks of the different vectors utilized, the possibilities of tumor targeting by modifications in the native tropism of virus vectors, as well as the different physical methods for vector delivery to the tumors. Along with the exposition we will also review of the history of the genetic therapy for gliomas, with special focus on the main problems found during the advancement of scientific discoveries in this area. A general analysis is also made of the present state of this promising therapeutic modality, with reference to the problems that still must be solved and the new paradigms for future research in this area.

  6. Genetic Analysis of Southwestern Iranian Patients with Familial Mediterranean Fever

    PubMed Central

    Haghighat, Mahmoud; Moghtaderi, Mozhgan; Farjadian, Shirin

    2017-01-01

    Background: Familial Mediterranean fever (FMF) is an autosomal recessive genetic disorder characterized by recurrent episodes of self-limited fever and serosal tissues inflammation. Methods: To evaluate clinical symptoms and common genetic mutations in southwestern Iranian patients with FMF, 20 unrelated patients were enrolled in this study based on clinical criteria. A panel of 12 common MEFV gene mutations was tested Results: The most frequent clinical presentations of the patients were fever, colicky abdominal pain and arthritis. Eighteen patients responded completely to colchicine therapy. MEFV gene mutations were detected in only 40% of the patients. The most common mutation was E148Q, detected in five patients (25%). The V726A, M694V and P369S mutations were each observed in one patient. Conclusions: Although none of the 12 mutations we included in our test panel was detected in 60% of our patients, all of them had FMF symptoms and responded well to colchicine. MEFV full gene sequencing analysis in these patients may lead to finding new mutations in southwestern Iranian FMF patients which would be helpful in designing a local diagnostic kit. PMID:28367474

  7. Genetic analysis of arsenic accumulation in maize using QTL mapping.

    PubMed

    Fu, Zhongjun; Li, Weihua; Xing, Xiaolong; Xu, Mengmeng; Liu, Xiaoyang; Li, Haochuan; Xue, Yadong; Liu, Zonghua; Tang, Jihua

    2016-02-16

    Arsenic (As) is a toxic heavy metal that can accumulate in crops and poses a threat to human health. The genetic mechanism of As accumulation is unclear. Herein, we used quantitative trait locus (QTL) mapping to unravel the genetic basis of As accumulation in a maize recombinant inbred line population derived from the Chinese crossbred variety Yuyu22. The kernels had the lowest As content among the different maize tissues, followed by the axes, stems, bracts and leaves. Fourteen QTLs were identified at each location. Some of these QTLs were identified in different environments and were also detected by joint analysis. Compared with the B73 RefGen v2 reference genome, the distributions and effects of some QTLs were closely linked to those of QTLs detected in a previous study; the QTLs were likely in strong linkage disequilibrium. Our findings could be used to help maintain maize production to satisfy the demand for edible corn and to decrease the As content in As-contaminated soil through the selection and breeding of As pollution-safe cultivars.

  8. Plants with genetically modified events combined by conventional breeding: an assessment of the need for additional regulatory data.

    PubMed

    Pilacinski, W; Crawford, A; Downey, R; Harvey, B; Huber, S; Hunst, P; Lahman, L K; MacIntosh, S; Pohl, M; Rickard, C; Tagliani, L; Weber, N

    2011-01-01

    Crop varieties with multiple GM events combined by conventional breeding have become important in global agriculture. The regulatory requirements in different countries for such products vary considerably, placing an additional burden on regulatory agencies in countries where the submission of additional data is required and delaying the introduction of innovative products to meet agricultural needs. The process of conventional plant breeding has predictably provided safe food and feed products both historically and in the modern era of plant breeding. Thus, previously approved GM events that have been combined by conventional plant breeding and contain GM traits that are not likely to interact in a manner affecting safety should be considered to be as safe as their conventional counterparts. Such combined GM event crop varieties should require little, if any, additional regulatory data to meet regulatory requirements.

  9. Genome-wide Comparative Analysis of Atopic Dermatitis and Psoriasis Gives Insight into Opposing Genetic Mechanisms

    PubMed Central

    Baurecht, Hansjörg; Hotze, Melanie; Brand, Stephan; Büning, Carsten; Cormican, Paul; Corvin, Aiden; Ellinghaus, David; Ellinghaus, Eva; Esparza-Gordillo, Jorge; Fölster-Holst, Regina; Franke, Andre; Gieger, Christian; Hubner, Norbert; Illig, Thomas; Irvine, Alan D.; Kabesch, Michael; Lee, Young A.E.; Lieb, Wolfgang; Marenholz, Ingo; McLean, W.H. Irwin; Morris, Derek W.; Mrowietz, Ulrich; Nair, Rajan; Nöthen, Markus M.; Novak, Natalija; O’Regan, Grainne M.; Schreiber, Stefan; Smith, Catherine; Strauch, Konstantin; Stuart, Philip E.; Trembath, Richard; Tsoi, Lam C.; Weichenthal, Michael; Barker, Jonathan; Elder, James T.; Weidinger, Stephan; Cordell, Heather J.; Brown, Sara J.

    2015-01-01

    Atopic dermatitis and psoriasis are the two most common immune-mediated inflammatory disorders affecting the skin. Genome-wide studies demonstrate a high degree of genetic overlap, but these diseases have mutually exclusive clinical phenotypes and opposing immune mechanisms. Despite their prevalence, atopic dermatitis and psoriasis very rarely co-occur within one individual. By utilizing genome-wide association study and ImmunoChip data from >19,000 individuals and methodologies developed from meta-analysis, we have identified opposing risk alleles at shared loci as well as independent disease-specific loci within the epidermal differentiation complex (chromosome 1q21.3), the Th2 locus control region (chromosome 5q31.1), and the major histocompatibility complex (chromosome 6p21–22). We further identified previously unreported pleiotropic alleles with opposing effects on atopic dermatitis and psoriasis risk in PRKRA and ANXA6/TNIP1. In contrast, there was no evidence for shared loci with effects operating in the same direction on both diseases. Our results show that atopic dermatitis and psoriasis have distinct genetic mechanisms with opposing effects in shared pathways influencing epidermal differentiation and immune response. The statistical analysis methods developed in the conduct of this study have produced additional insight from previously published data sets. The approach is likely to be applicable to the investigation of the genetic basis of other complex traits with overlapping and distinct clinical features. PMID:25574825

  10. Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.

    PubMed

    Baurecht, Hansjörg; Hotze, Melanie; Brand, Stephan; Büning, Carsten; Cormican, Paul; Corvin, Aiden; Ellinghaus, David; Ellinghaus, Eva; Esparza-Gordillo, Jorge; Fölster-Holst, Regina; Franke, Andre; Gieger, Christian; Hubner, Norbert; Illig, Thomas; Irvine, Alan D; Kabesch, Michael; Lee, Young A E; Lieb, Wolfgang; Marenholz, Ingo; McLean, W H Irwin; Morris, Derek W; Mrowietz, Ulrich; Nair, Rajan; Nöthen, Markus M; Novak, Natalija; O'Regan, Grainne M; Schreiber, Stefan; Smith, Catherine; Strauch, Konstantin; Stuart, Philip E; Trembath, Richard; Tsoi, Lam C; Weichenthal, Michael; Barker, Jonathan; Elder, James T; Weidinger, Stephan; Cordell, Heather J; Brown, Sara J

    2015-01-08

    Atopic dermatitis and psoriasis are the two most common immune-mediated inflammatory disorders affecting the skin. Genome-wide studies demonstrate a high degree of genetic overlap, but these diseases have mutually exclusive clinical phenotypes and opposing immune mechanisms. Despite their prevalence, atopic dermatitis and psoriasis very rarely co-occur within one individual. By utilizing genome-wide association study and ImmunoChip data from >19,000 individuals and methodologies developed from meta-analysis, we have identified opposing risk alleles at shared loci as well as independent disease-specific loci within the epidermal differentiation complex (chromosome 1q21.3), the Th2 locus control region (chromosome 5q31.1), and the major histocompatibility complex (chromosome 6p21-22). We further identified previously unreported pleiotropic alleles with opposing effects on atopic dermatitis and psoriasis risk in PRKRA and ANXA6/TNIP1. In contrast, there was no evidence for shared loci with effects operating in the same direction on both diseases. Our results show that atopic dermatitis and psoriasis have distinct genetic mechanisms with opposing effects in shared pathways influencing epidermal differentiation and immune response. The statistical analysis methods developed in the conduct of this study have produced additional insight from previously published data sets. The approach is likely to be applicable to the investigation of the genetic basis of other complex traits with overlapping and distinct clinical features.

  11. Genetic polymorphism and evolutionary differentiation of Eastern Chinese Han: a comprehensive and comparative analysis on KIRs

    PubMed Central

    Yin, Caiyong; Hu, Li; Huang, Huijie; Yu, Yanfang; Li, Zheng; Ji, Qiang; Kong, Xiaochao; Wang, Zhongqun; Yan, Jinchuan; Yan, Jiangwei; Zhu, Bofeng; Chen, Feng

    2017-01-01

    Killer cell immunoglobulin-like receptor genes, namely KIRs, cluster together within the 160 kb genomic DNA region. In this study, we used PCR-SSP approach and successfully identified the genotype of 17 KIR genes in 123 independent healthy donors residing in the Jiangsu province, China. All individuals were positive at the 7 genes. The observed carrier gene frequencies (OFs) of remaining 10 KIRs ranged from 14.63% (KIR2DS3) to 95.93% (KIR3DL1). We found 27 distinct genotypes excluding KIR1D. The most frequent occurred in 63 individuals (51.22%). The linkage disequilibrium analysis signified 29 positive and 6 negative relations in 45 pairwise comparisons. To study population differentiation, we drew a Heatmap based on the data of KIRs from 59 populations and conducted Hierarchical Clustering by Euclidean distances. We next validated our results by estimating pairwise DA distances and illustrating a Neighbor-Joining tree, as well as a MDS plot covering 3 additional Chinese Han groups. The phylogenetic reconstruction and cluster analysis strongly indicated a genetically close relationship between Eastern and Jilin Hans. In conclusion, the present study provided a meritorious resource of KIR genotyping for population genetics, and could be helpful to uncover the genetic mechanism of KIRs in immune disease in the future. PMID:28205529

  12. Genetic polymorphism and evolutionary differentiation of Eastern Chinese Han: a comprehensive and comparative analysis on KIRs.

    PubMed

    Yin, Caiyong; Hu, Li; Huang, Huijie; Yu, Yanfang; Li, Zheng; Ji, Qiang; Kong, Xiaochao; Wang, Zhongqun; Yan, Jinchuan; Yan, Jiangwei; Zhu, Bofeng; Chen, Feng

    2017-02-16

    Killer cell immunoglobulin-like receptor genes, namely KIRs, cluster together within the 160 kb genomic DNA region. In this study, we used PCR-SSP approach and successfully identified the genotype of 17 KIR genes in 123 independent healthy donors residing in the Jiangsu province, China. All individuals were positive at the 7 genes. The observed carrier gene frequencies (OFs) of remaining 10 KIRs ranged from 14.63% (KIR2DS3) to 95.93% (KIR3DL1). We found 27 distinct genotypes excluding KIR1D. The most frequent occurred in 63 individuals (51.22%). The linkage disequilibrium analysis signified 29 positive and 6 negative relations in 45 pairwise comparisons. To study population differentiation, we drew a Heatmap based on the data of KIRs from 59 populations and conducted Hierarchical Clustering by Euclidean distances. We next validated our results by estimating pairwise DA distances and illustrating a Neighbor-Joining tree, as well as a MDS plot covering 3 additional Chinese Han groups. The phylogenetic reconstruction and cluster analysis strongly indicated a genetically close relationship between Eastern and Jilin Hans. In conclusion, the present study provided a meritorious resource of KIR genotyping for population genetics, and could be helpful to uncover the genetic mechanism of KIRs in immune disease in the future.

  13. Analysis of Genetic Code Ambiguity Arising from Nematode-Specific Misacylated tRNAs

    PubMed Central

    Hamashima, Kiyofumi; Mori, Masaru; Andachi, Yoshiki; Tomita, Masaru; Kohara, Yuji; Kanai, Akio

    2015-01-01

    The faithful translation of the genetic code requires the highly accurate aminoacylation of transfer RNAs (tRNAs). However, it has been shown that nematode-specific V-arm-containing tRNAs (nev-tRNAs) are misacylated with leucine in vitro in a manner that transgresses the genetic code. nev-tRNAGly (CCC) and nev-tRNAIle (UAU), which are the major nev-tRNA isotypes, could theoretically decode the glycine (GGG) codon and isoleucine (AUA) codon as leucine, causing GGG and AUA codon ambiguity in nematode cells. To test this hypothesis, we investigated the functionality of nev-tRNAs and their impact on the proteome of Caenorhabditis elegans. Analysis of the nucleotide sequences in the 3’ end regions of the nev-tRNAs showed that they had matured correctly, with the addition of CCA, which is a crucial posttranscriptional modification required for tRNA aminoacylation. The nuclear export of nev-tRNAs was confirmed with an analysis of their subcellular localization. These results show that nev-tRNAs are processed to their mature forms like common tRNAs and are available for translation. However, a whole-cell proteome analysis found no detectable level of nev-tRNA-induced mistranslation in C. elegans cells, suggesting that the genetic code is not ambiguous, at least under normal growth conditions. Our findings indicate that the translational fidelity of the nematode genetic code is strictly maintained, contrary to our expectations, although deviant tRNAs with misacylation properties are highly conserved in the nematode genome. PMID:25602944

  14. A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population

    PubMed Central

    Zhao, Shan-Chao; Ren, Guoping; Yu, Yongwei; Wu, Yudong; Wu, Ji; Xue, Yao; Zhou, Bo; Zhang, Yanling; Xu, Xingxing; Li, Jie; He, Weiyang; Benlloch, Sara; Ross-Adams, Helen; Chen, Li; Li, Jucong; Hong, Yingqia; Kote-Jarai, Zsofia; Cui, Xingang; Hou, Jianguo; Guo, Jianming; Xu, Lei; Yin, Changjun; Zhou, Yuanping; Neal, David E.; Oliver, Tim; Cao, Guangwen; Zhang, Zhengdong; Easton, Douglas F.; Chelala, Claude; Olama, Ali Amin Al; Eeles, Rosalind A.; Zhang, Hongwei; Lu, Yong-Jie

    2016-01-01

    Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer. PMID:26881390

  15. Genetic Analysis of the Cytoplasmic Dynein Subunit Families

    PubMed Central

    Pfister, K. Kevin; Shah, Paresh R; Hummerich, Holger; Russ, Andreas; Cotton, James; Annuar, Azlina Ahmad; King, Stephen M; Fisher, Elizabeth M. C

    2006-01-01

    Cytoplasmic dyneins, the principal microtubule minus-end-directed motor proteins of the cell, are involved in many essential cellular processes. The major form of this enzyme is a complex of at least six protein subunits, and in mammals all but one of the subunits are encoded by at least two genes. Here we review current knowledge concerning the subunits, their interactions, and their functional roles as derived from biochemical and genetic analyses. We also carried out extensive database searches to look for new genes and to clarify anomalies in the databases. Our analysis documents evolutionary relationships among the dynein subunits of mammals and other model organisms, and sheds new light on the role of this diverse group of proteins, highlighting the existence of two cytoplasmic dynein complexes with distinct cellular roles. PMID:16440056

  16. Comparison of variants of canonical correlation analysis and partial least squares for combined analysis of MRI and genetic data.

    PubMed

    Grellmann, Claudia; Bitzer, Sebastian; Neumann, Jane; Westlye, Lars T; Andreassen, Ole A; Villringer, Arno; Horstmann, Annette

    2015-02-15

    The standard analysis approach in neuroimaging genetics studies is the mass-univariate linear modeling (MULM) approach. From a statistical view, however, this approach is disadvantageous, as it is computationally intensive, cannot account for complex multivariate relationships, and has to be corrected for multiple testing. In contrast, multivariate methods offer the opportunity to include combined information from multiple variants to discover meaningful associations between genetic and brain imaging data. We assessed three multivariate techniques, partial least squares correlation (PLSC), sparse canonical correlation analysis (sparse CCA) and Bayesian inter-battery factor analysis (Bayesian IBFA), with respect to their ability to detect multivariate genotype-phenotype associations. Our goal was to systematically compare these three approaches with respect to their performance and to assess their suitability for high-dimensional and multi-collinearly dependent data as is the case in neuroimaging genetics studies. In a series of simulations using both linearly independent and multi-collinear data, we show that sparse CCA and PLSC are suitable even for very high-dimensional collinear imaging data sets. Among those two, the predictive power was higher for sparse CCA when voxel numbers were below 400 times sample size and candidate SNPs were considered. Accordingly, we recommend Sparse CCA for candidate phenotype, candidate SNP studies. When voxel numbers exceeded 500 times sample size, the predictive power was the highest for PLSC. Therefore, PLSC can be considered a promising technique for multivariate modeling of high-dimensional brain-SNP-associations. In contrast, Bayesian IBFA cannot be recommended, since additional post-processing steps were necessary to detect causal relations. To verify the applicability of sparse CCA and PLSC, we applied them to an experimental imaging genetics data set provided for us. Most importantly, application of both methods replicated

  17. Analysis of Genetic Mosaics of the Nematode CAENORHABDITIS ELEGANS

    PubMed Central

    Herman, Robert K.

    1984-01-01

    A new method for producing genetic mosaics, which involves the spontaneous somatic loss of free chromosome fragments, is demonstrated. Four genes that affect the behavior of C. elegans were studied in mosaic animals. The analysis was greatly aided by the fact that the complete cell lineage of wild-type animals is known. Two of the mutant genes affect certain sensory responses and prevent uptake of fluorescein isothiocyanate (FITC) by certain sensory neurons. Mosaic analysis indicated that one of these mutant genes is cell autonomous with respect to its effect on FITC uptake and the other is cell nonautonomous. In the latter case, the genotype of a non-neuronal supporting cell that surrounds the processes of the neurons that normally take up FITC probably is critical. The other two mutant genes affect animal movement. Mosaic analysis indicated that the expression of one of these genes is specific to certain neurons (motor neurons of the ventral and dorsal nerve cords are prime candidates) and the expression of the other gene is specific to muscle cells. PMID:6434374

  18. [Genetic diversity and genetic differentiation of Rhododendron concinnum wild populations in Qinling Mountains of Northwest China: an AFLP analysis].

    PubMed

    Zhao, Bing; Xu, Man; Si, Guo-Chen; Li, Hou-Hua; Zhang, Yan-Long

    2012-11-01

    By using amplified fragment length polymorphism (AFLP) technique, an investigation was made on the genetic diversity and genetic differentiation of seven wild populations of Rhododendron concinnum in Qinling Mountains of Northwest China. A total of 182 amplification products were generated from three AFLP selective primer combinations, of which, 151 were polymorphic. The percentage of polymorphism was 83.1%. The change trends showed by the percentage of polymorphic loci (PPL), Nei's gene diversity (h), and Shannon's information index (I) were uniform, and the order of the populations was Meixian > Zhashui > Zhen' an > Huxian > Ningqiang > Nanzheng > Zhouzhi. The POPGENE analysis showed that the R. concinnum had higher genetic diversity at both species level (PPL = 91.22%, I = 0.7217, h = 0.5095) and population level (PPL = 77.56%, I = 0.6409, h = 0.4725). The coefficient of gene differentiation among the populations (Gst) was 0.0726, indicating that 92.74% of genetic variation occurred within the populations. The analysis of molecular variance (AMOVA) showed that 85.3% of the genetic variation was within the populations, and 14.7% of it was among the populations. The unweighted pair group method with arithmeticmean (UPGMA) indicated that there was no significant correlation between the genetic distance and the geographic distance among the R. concinnum populations. The conservation strategies for R. concinnum germplasm resources were put forward.

  19. Multivariate qualitative analysis of banned additives in food safety using surface enhanced Raman scattering spectroscopy

    NASA Astrophysics Data System (ADS)

    He, Shixuan; Xie, Wanyi; Zhang, Wei; Zhang, Liqun; Wang, Yunxia; Liu, Xiaoling; Liu, Yulong; Du, Chunlei

    2015-02-01

    A novel strategy which combines iteratively cubic spline fitting baseline correction method with discriminant partial least squares qualitative analysis is employed to analyze the surface enhanced Raman scattering (SERS) spectroscopy of banned food additives, such as Sudan I dye and Rhodamine B in food, Malachite green residues in aquaculture fish. Multivariate qualitative analysis methods, using the combination of spectra preprocessing iteratively cubic spline fitting (ICSF) baseline correction with principal component analysis (PCA) and discriminant partial least squares (DPLS) classification respectively, are applied to investigate the effectiveness of SERS spectroscopy for predicting the class assignments of unknown banned food additives. PCA cannot be used to predict the class assignments of unknown samples. However, the DPLS classification can discriminate the class assignment of unknown banned additives using the information of differences in relative intensities. The results demonstrate that SERS spectroscopy combined with ICSF baseline correction method and exploratory analysis methodology DPLS classification can be potentially used for distinguishing the banned food additives in field of food safety.

  20. 7 CFR 91.38 - Additional fees for appeal of analysis.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Additional fees for appeal of analysis. 91.38 Section 91.38 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED)...

  1. 7 CFR 91.38 - Additional fees for appeal of analysis.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Additional fees for appeal of analysis. 91.38 Section 91.38 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED)...

  2. Multivariate qualitative analysis of banned additives in food safety using surface enhanced Raman scattering spectroscopy.

    PubMed

    He, Shixuan; Xie, Wanyi; Zhang, Wei; Zhang, Liqun; Wang, Yunxia; Liu, Xiaoling; Liu, Yulong; Du, Chunlei

    2015-02-25

    A novel strategy which combines iteratively cubic spline fitting baseline correction method with discriminant partial least squares qualitative analysis is employed to analyze the surface enhanced Raman scattering (SERS) spectroscopy of banned food additives, such as Sudan I dye and Rhodamine B in food, Malachite green residues in aquaculture fish. Multivariate qualitative analysis methods, using the combination of spectra preprocessing iteratively cubic spline fitting (ICSF) baseline correction with principal component analysis (PCA) and discriminant partial least squares (DPLS) classification respectively, are applied to investigate the effectiveness of SERS spectroscopy for predicting the class assignments of unknown banned food additives. PCA cannot be used to predict the class assignments of unknown samples. However, the DPLS classification can discriminate the class assignment of unknown banned additives using the information of differences in relative intensities. The results demonstrate that SERS spectroscopy combined with ICSF baseline correction method and exploratory analysis methodology DPLS classification can be potentially used for distinguishing the banned food additives in field of food safety.

  3. Stimulation of terrestrial ecosystem carbon storage by nitrogen addition: a meta-analysis

    PubMed Central

    Yue, Kai; Peng, Yan; Peng, Changhui; Yang, Wanqin; Peng, Xin; Wu, Fuzhong

    2016-01-01

    Elevated nitrogen (N) deposition alters the terrestrial carbon (C) cycle, which is likely to feed back to further climate change. However, how the overall terrestrial ecosystem C pools and fluxes respond to N addition remains unclear. By synthesizing data from multiple terrestrial ecosystems, we quantified the response of C pools and fluxes to experimental N addition using a comprehensive meta-analysis method. Our results showed that N addition significantly stimulated soil total C storage by 5.82% ([2.47%, 9.27%], 95% CI, the same below) and increased the C contents of the above- and below-ground parts of plants by 25.65% [11.07%, 42.12%] and 15.93% [6.80%, 25.85%], respectively. Furthermore, N addition significantly increased aboveground net primary production by 52.38% [40.58%, 65.19%] and litterfall by 14.67% [9.24%, 20.38%] at a global scale. However, the C influx from the plant litter to the soil through litter decomposition and the efflux from the soil due to microbial respiration and soil respiration showed insignificant responses to N addition. Overall, our meta-analysis suggested that N addition will increase soil C storage and plant C in both above- and below-ground parts, indicating that terrestrial ecosystems might act to strengthen as a C sink under increasing N deposition. PMID:26813078

  4. Stimulation of terrestrial ecosystem carbon storage by nitrogen addition: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Yue, Kai; Peng, Yan; Peng, Changhui; Yang, Wanqin; Peng, Xin; Wu, Fuzhong

    2016-01-01

    Elevated nitrogen (N) deposition alters the terrestrial carbon (C) cycle, which is likely to feed back to further climate change. However, how the overall terrestrial ecosystem C pools and fluxes respond to N addition remains unclear. By synthesizing data from multiple terrestrial ecosystems, we quantified the response of C pools and fluxes to experimental N addition using a comprehensive meta-analysis method. Our results showed that N addition significantly stimulated soil total C storage by 5.82% ([2.47%, 9.27%], 95% CI, the same below) and increased the C contents of the above- and below-ground parts of plants by 25.65% [11.07%, 42.12%] and 15.93% [6.80%, 25.85%], respectively. Furthermore, N addition significantly increased aboveground net primary production by 52.38% [40.58%, 65.19%] and litterfall by 14.67% [9.24%, 20.38%] at a global scale. However, the C influx from the plant litter to the soil through litter decomposition and the efflux from the soil due to microbial respiration and soil respiration showed insignificant responses to N addition. Overall, our meta-analysis suggested that N addition will increase soil C storage and plant C in both above- and below-ground parts, indicating that terrestrial ecosystems might act to strengthen as a C sink under increasing N deposition.

  5. Additive genetic variation in resistance traits of an exotic pine species: little evidence for constraints on evolution of resistance against native herbivores.

    PubMed

    Moreira, X; Zas, R; Sampedro, L

    2013-05-01

    The apparent failure of invasions by alien pines in Europe has been explained by the co-occurrence of native pine congeners supporting herbivores that might easily recognize the new plants as hosts. Previous studies have reported that exotic pines show reduced tolerance and capacity to induce resistance to those native herbivores. We hypothesize that limited genetic variation in resistance to native herbivores and the existence of evolutionary trade-offs between growth and resistance could represent additional potential constraints on the evolution of invasiveness of exotic pines outside their natural range. In this paper, we examined genetic variation for constitutive and induced chemical defences (measured as non-volatile resin in the stem and total phenolics in the needles) and resistance to two major native generalist herbivores of pines in cafeteria bioassays (the phloem-feeder Hylobius abietis and the defoliator Thaumetopoea pityocampa) using half-sib families drawn from a sample of the population of Pinus radiata introduced to Spain in the mid-19th century. We found (i) significant genetic variation, with moderate-to-high narrow-sense heritabilities for both the production of constitutive non-volatile resin and induced total phenolics, and for constitutive resistance against T. pityocampa in bioassays, (ii) no evolutionary trade-offs between plant resistance and growth traits or between the production of different quantitative chemical defences and (iii) a positive genetic correlation between constitutive resistance to the two studied herbivores. Overall, results of our study indicate that the exotic pine P. radiata has limited genetic constraints on the evolution of resistance against herbivores in its introduced range, suggesting that, at least in terms of interactions with these enemies, this pine species has potential to become invasive in the future.

  6. Extended genetic analysis of Brazilian isolates of Bacillus cereus and Bacillus thuringiensis

    PubMed Central

    Zahner, Viviane; Silva, Ana Carolina Telles de Carvalho e; de Moraes, Gabriela Pinhel; McIntosh, Douglas; de Filippis, Ivano

    2013-01-01

    Multiple locus sequence typing (MLST) was undertaken to extend the genetic characterization of 29 isolates of Bacillus cereus and Bacillus thuringiensis previously characterized in terms of presence/absence of sequences encoding virulence factors and via variable number tandem repeat (VNTR). Additional analysis involved polymerase chain reaction for the presence of sequences (be, cytK, inA, pag, lef, cya and cap), encoding putative virulence factors, not investigated in the earlier study. MLST analysis ascribed novel and unique sequence types to each of the isolates. A phylogenetic tree was constructed from a single sequence of 2,838 bp of concatenated loci sequences. The strains were not monophyletic by analysis of any specific housekeeping gene or virulence characteristic. No clear association in relation to source of isolation or to genotypic profile based on the presence or absence of putative virulence genes could be identified. Comparison of VNTR profiling with MLST data suggested a correlation between these two methods of genetic analysis. In common with the majority of previous studies, MLST was unable to provide clarification of the basis for pathogenicity among members of the B. cereus complex. Nevertheless, our application of MLST served to reinforce the notion that B. cereus and B. thuringiensis should be considered as the same species. PMID:23440117

  7. Reducing the matrix effects in chemical analysis: fusion of isotope dilution and standard addition methods

    NASA Astrophysics Data System (ADS)

    Pagliano, Enea; Meija, Juris

    2016-04-01

    The combination of isotope dilution and mass spectrometry has become an ubiquitous tool of chemical analysis. Often perceived as one of the most accurate methods of chemical analysis, it is not without shortcomings. Current isotope dilution equations are not capable of fully addressing one of the key problems encountered in chemical analysis: the possible effect of sample matrix on measured isotope ratios. The method of standard addition does compensate for the effect of sample matrix by making sure that all measured solutions have identical composition. While it is impossible to attain such condition in traditional isotope dilution, we present equations which allow for matrix-matching between all measured solutions by fusion of isotope dilution and standard addition methods.

  8. Analysis of occupational accidents: prevention through the use of additional technical safety measures for machinery

    PubMed Central

    Dźwiarek, Marek; Latała, Agata

    2016-01-01

    This article presents an analysis of results of 1035 serious and 341 minor accidents recorded by Poland's National Labour Inspectorate (PIP) in 2005–2011, in view of their prevention by means of additional safety measures applied by machinery users. Since the analysis aimed at formulating principles for the application of technical safety measures, the analysed accidents should bear additional attributes: the type of machine operation, technical safety measures and the type of events causing injuries. The analysis proved that the executed tasks and injury-causing events were closely connected and there was a relation between casualty events and technical safety measures. In the case of tasks consisting of manual feeding and collecting materials, the injuries usually occur because of the rotating motion of tools or crushing due to a closing motion. Numerous accidents also happened in the course of supporting actions, like removing pollutants, correcting material position, cleaning, etc. PMID:26652689

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

    PubMed Central

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

    2015-01-01

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

  10. Viability of in-house datamarting approaches for population genetics analysis of SNP genotypes

    PubMed Central

    Amigo, Jorge; Phillips, Christopher; Salas, Antonio; Carracedo, Ángel

    2009-01-01

    Background Databases containing very large amounts of SNP (Single Nucleotide Polymorphism) data are now freely available for researchers interested in medical and/or population genetics applications. While many of these SNP repositories have implemented data retrieval tools for general-purpose mining, these alone cannot cover the broad spectrum of needs of most medical and population genetics studies. Results To address this limitation, we have built in-house customized data marts from the raw data provided by the largest public databases. In particular, for population genetics analysis based on genotypes we have built a set of data processing scripts that deal with raw data coming from the major SNP variation databases (e.g. HapMap, Perlegen), stripping them into single genotypes and then grouping them into populations, then merged with additional complementary descriptive information extracted from dbSNP. This allows not only in-house standardization and normalization of the genotyping data retrieved from different repositories, but also the calculation of statistical indices from simple allele frequency estimates to more elaborate genetic differentiation tests within populations, together with the ability to combine population samples from different databases. Conclusion The present study demonstrates the viability of implementing scripts for handling extensive datasets of SNP genotypes with low computational costs, dealing with certain complex issues that arise from the divergent nature and configuration of the most popular SNP repositories. The information contained in these databases can also be enriched with additional information obtained from other complementary databases, in order to build a dedicated data mart. Updating the data structure is straightforward, as well as permitting easy implementation of new external data and the computation of supplementary statistical indices of interest. PMID:19344481

  11. Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

    PubMed Central

    2010-01-01

    Background Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. Methods A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. Results We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-ε4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR

  12. Feature selection using genetic algorithms for fetal heart rate analysis.

    PubMed

    Xu, Liang; Redman, Christopher W G; Payne, Stephen J; Georgieva, Antoniya

    2014-07-01

    The fetal heart rate (FHR) is monitored on a paper strip (cardiotocogram) during labour to assess fetal health. If necessary, clinicians can intervene and assist with a prompt delivery of the baby. Data-driven computerized FHR analysis could help clinicians in the decision-making process. However, selecting the best computerized FHR features that relate to labour outcome is a pressing research problem. The objective of this study is to apply genetic algorithms (GA) as a feature selection method to select the best feature subset from 64 FHR features and to integrate these best features to recognize unfavourable FHR patterns. The GA was trained on 404 cases and tested on 106 cases (both balanced datasets) using three classifiers, respectively. Regularization methods and backward selection were used to optimize the GA. Reasonable classification performance is shown on the testing set for the best feature subset (Cohen's kappa values of 0.45 to 0.49 using different classifiers). This is, to our knowledge, the first time that a feature selection method for FHR analysis has been developed on a database of this size. This study indicates that different FHR features, when integrated, can show good performance in predicting labour outcome. It also gives the importance of each feature, which will be a valuable reference point for further studies.

  13. Genetic analysis of the chitinase system of Serratia marcescens 2170.

    PubMed Central

    Watanabe, T; Kimura, K; Sumiya, T; Nikaidou, N; Suzuki, K; Suzuki, M; Taiyoji, M; Ferrer, S; Regue, M

    1997-01-01

    To carry out a genetic analysis of the degradation and utilization of chitin by Serratia marcescens 2170, various Tn5 insertion mutants with characteristic defects in chitinase production were isolated and partially characterized. Prior to the isolation of the mutants, proteins secreted into culture medium in the presence of chitin were analyzed. Four chitinases, A, B, C1, and C2, among other proteins, were detected in the culture supernatant of S. marcescens 2170. All four chitinases and a 21-kDa protein (CBP21) lacking chitinase activity showed chitin binding activity. Cloning and sequencing analysis of the genes encoding chitinases A and B of strain 2170 revealed extensive similarities to those of other strains of S. marcescens described previously. Tn5 insertion mutagenesis of strain 2170 was carried out, and mutants which formed altered clearing zones of colloidal chitin were selected. The obtained mutants were divided into five classes as follows: mutants with (i) no clearing zones, (ii) fuzzy clearing zones, (iii) large clearing zones, (iv) delayed clearing zones, and (v) small clearing zones. Preliminary characterization suggested that some of these mutants have defects in chitinase excretion, a negatively regulating mechanism of chitinase gene expression, an essential factor for chitinase gene expression, and a structural gene for a particular chitinase. These mutants could allow researchers to identify the genes involved in the degradation and utilization of chitin by S. marcescens 2170. PMID:9371460

  14. Genetic and Biochemical Analysis of High Iron Toxicity in Yeast

    PubMed Central

    Lin, Huilan; Li, Liangtao; Jia, Xuan; Ward, Diane McVey; Kaplan, Jerry

    2011-01-01

    Iron storage in yeast requires the activity of the vacuolar iron transporter Ccc1. Yeast with an intact CCC1 are resistant to iron toxicity, but deletion of CCC1 renders yeast susceptible to iron toxicity. We used genetic and biochemical analysis to identify suppressors of high iron toxicity in Δccc1 cells to probe the mechanism of high iron toxicity. All genes identified as suppressors of high iron toxicity in aerobically grown Δccc1 cells encode organelle iron transporters including mitochondrial iron transporters MRS3, MRS4, and RIM2. Overexpression of MRS3 suppressed high iron toxicity by decreasing cytosolic iron through mitochondrial iron accumulation. Under anaerobic conditions, Δccc1 cells were still sensitive to high iron toxicity, but overexpression of MRS3 did not suppress iron toxicity and did not result in mitochondrial iron accumulation. We conclude that Mrs3/Mrs4 can sequester iron within mitochondria under aerobic conditions but not anaerobic conditions. We show that iron toxicity in Δccc1 cells occurred under both aerobic and anaerobic conditions. Microarray analysis showed no evidence of oxidative damage under anaerobic conditions, suggesting that iron toxicity may not be solely due to oxidative damage. Deletion of TSA1, which encodes a peroxiredoxin, exacerbated iron toxicity in Δccc1 cells under both aerobic and anaerobic conditions, suggesting a unique role for Tsa1 in iron toxicity. PMID:21115478

  15. Quantitative analysis of triple-mutant genetic interactions.

    PubMed

    Braberg, Hannes; Alexander, Richard; Shales, Michael; Xu, Jiewei; Franks-Skiba, Kathleen E; Wu, Qiuqin; Haber, James E; Krogan, Nevan J

    2014-08-01

    The quantitative analysis of genetic interactions between pairs of gene mutations has proven to be effective for characterizing cellular functions, but it can miss important interactions for functionally redundant genes. To address this limitation, we have developed an approach termed triple-mutant analysis (TMA). The procedure relies on a query strain that contains two deletions in a pair of redundant or otherwise related genes, which is crossed against a panel of candidate deletion strains to isolate triple mutants and measure their growth. A central feature of TMA is to interrogate mutants that are synthetically sick when two other genes are deleted but interact minimally with either single deletion. This approach has been valuable for discovering genes that restore critical functions when the principal actors are deleted. TMA has also uncovered double-mutant combinations that produce severe defects because a third protein becomes deregulated and acts in a deleterious fashion, and it has revealed functional differences between proteins presumed to act together. The protocol is optimized for Singer ROTOR pinning robots, takes 3 weeks to complete and measures interactions for up to 30 double mutants against a library of 1,536 single mutants.

  16. Genetic analysis of organogenesis in the cotyledons of zygotic embryos of sunflower (Helianthus annuus L.).

    PubMed

    Sarrafi, A; Roustan, J P; Fallot, J; Alibert, G

    1996-02-01

    Crosses were made between five cytoplasmic male-sterile and five restorer sunflower inbred lines. Twenty-five F1 hybrids and their parents were studied for their organogenesis ability in a randomized block design with four replications. Each replication per genotype consisted of ten petri dishes with four expiants. Regeneration medium consisted of full MS medium modified by the addition of hormones and solidified with 6 g/l agar. Statistical analysis showed that both general and specific combining abilities were significant for all of the organogenesis parameters studied, and both showed several significant positive or negative values. General combining ability values were usually higher than those of specific combining ability, indicating the importance of additive genetic control for organogenesis parameters in sunflower. Narrow-sense heritability for the number of explants producing shoots and roots was 65.8%, which suggests that organogenesis of currently inferior inbred lines in sunflower should be improved in a crossing program.

  17. Analysis of genetic diversity in red clover (Trifolium pratense L.) breeding populations as revealed by RAPD genetic markers.

    PubMed

    Ulloa, Odeth; Ortega, Fernando; Campos, Hugo

    2003-08-01

    Red clover is an important forage legume species for temperate regions and very little is known about the genetic organization of its breeding populations. We used random amplified polymorphic DNA (RAPD) genetic markers to address the genetic diversity and the distribution of variation in 20 breeding populations and cultivars from Chile, Argentina, Uruguay, and Switzerland. Genetic distances were calculated for all possible pairwise combinations. A high level of polymorphism was found and the proportion of polymorphic loci across populations was 74.2%. A population derived from a non-certified seedlot displayed a higher proportion of polymorphic loci than its respective certified seedlot. Gene diversity values and population genetics parameters suggest that the populations analyzed are diverse. An analysis of molecular variance (AMOVA) revealed that the largest proportion of variation (80.4%) resides at the within population level. RAPD markers are a useful tool for red clover breeding programs. A dendrogram based on genetic distances divided the breeding populations analyzed into three distinct groups. The amount and partition of diversity observed can be of value in identifying the populations that parents of synthetic cultivars are derived from and to exploit the variation available in the populations analyzed.

  18. AFLP analysis reveals high genetic diversity but low population structure in Coccidioides posadasii isolates from Mexico and Argentina

    PubMed Central

    2013-01-01

    Background Coccidioides immitis and C. posadasii cause coccidioidomycosis, a disease that is endemic to North and South America, but for Central America, the incidence of coccidioidomycosis has not been clearly established. Several studies suggest genetic variability in these fungi; however, little definitive information has been discovered about the variability of Coccidioides fungi in Mexico (MX) and Argentina (AR). Thus, the goals for this work were to study 32 Coccidioides spp. isolates from MX and AR, identify the species of these Coccidioides spp. isolates, analyse their phenotypic variability, examine their genetic variability and investigate the Coccidioides reproductive system and its level of genetic differentiation. Methods Coccidioides spp. isolates from MX and AR were taxonomically identified by phylogenetic inference analysis using partial sequences of the Ag2/PRA gene and their phenotypic characteristics analysed. The genetic variability, reproductive system and level of differentiation were estimated using AFLP markers. The level of genetic variability was assessed measuring the percentage of polymorphic loci, number of effective allele, expected heterocygosity and Index of Association (IA). The degree of genetic differentiation was determined by AMOVA. Genetic similarities among isolates were estimated using Jaccard index. The UPGMA was used to contsruct the corresponding dendrogram. Finally, a network of haplotypes was built to evaluate the genealogical relationships among AFLP haplotypes. Results All isolates of Coccidioides spp. from MX and AR were identified as C. posadasii. No phenotypic variability was observed among the C. posadasii isolates from MX and AR. Analyses of genetic diversity and population structure were conducted using AFLP markers. Different estimators of genetic variability indicated that the C. posadasii isolates from MX and AR had high genetic variability. Furthermore, AMOVA, dendrogram and haplotype network showed a small

  19. [The construction of the genetic map and QTL locating analysis on chromosome 2 in swine].

    PubMed

    Qu, Yan-Chun; Deng, Chang-Yan; Xiong, Yuan-Zhu; Zheng, Rong; Yu, Li; Su, Yu-Hong; Liu, Gui-Lan

    2002-01-01

    The study constructed the genetic linkage map of porcine chromosome 2 and further analysis of quantitative trait loci was conducted. The results of the study demonstrated that all 7 microsatellite loci we chose were with relatively high polymorphism, and its polymorphic information content was from 0.40182 to 0.58477. The genetic map we constructed for resource family was 152.9 cM in length, with the order of all loci highly consistent with the USDA map. All marker intervals were longer than USDA map with the interval between marker Sw2516 and Sw1201 as an exception. Furthermore, we conducted QTLs locating analysis by combining the genetic map with the phenotypic data. QTLs affecting lively estimated traits such as lean meat percentage, were located at 60-65 cM on chromosome 2, while QTLs for the height and marbling of Longissmus dorsi muscle were located at 20 cM and 55 cM, respectively Among them, QTL for estimated lean meat percentage was significant at chromosome-wise level (P < 0.01) and was responsible for 21.55% of the phenotypic variance. QTLs for the height and marbling of Longissmus dorsi muscle were responsible for 10.12% and 10.97% of the phenotypic variance, respectively. The additive and dominance effect of lively estimated traits were in the inverse tendency, while the QTL for the height of Longissmus dorsi muscle had its additive and dominance effect in the same tendency and was with advantageous allele in Large White. The QTLs we detected had relatively large effect on phenotype and built a basis for molecular marker assisted selection and breeding.

  20. Genetic Analysis of Teosinte Alleles for Kernel Composition Traits in Maize.

    PubMed

    Karn, Avinash; Gillman, Jason D; Flint-Garcia, Sherry A

    2017-02-10

    Teosinte (Zea mays ssp. parviglumis) is the wild ancestor of modern maize (Zea mays ssp. mays). Teosinte contains greater genetic diversity compared to maize inbreds and landraces, but its use is limited by insufficient genetic resources to evaluate its value. A population of teosinte near isogenic lines (teosinte NILs) was previously developed to broaden the resources for genetic diversity of maize, and to discover novel alleles for agronomic and domestication traits. The 961 teosinte NILs were developed by backcrossing ten geographically diverse parviglumis accessions into the B73 (reference genome inbred) background. The NILs were grown in two replications in 2009 and 2010 in Columbia, Missouri and Aurora, New York, respectively, and Near Infrared Reflectance (NIR) spectroscopy and Nuclear Magnetic Resonance (NMR) calibrations were developed and used to rapidly predict total kernel starch, protein and oil content on a dry matter basis in bulk whole grains of teosinte NILs. Our joint-linkage quantitative trait locus (QTL) mapping analysis identified two starch, three protein and six oil QTLs, which collectively explained 18%, 23% and 45% of the total variation, respectively. A range of strong additive allelic effects for kernel starch, protein and oil content were identified relative to the B73 allele. Our results support our hypothesis that teosinte harbors stronger alleles for kernel composition traits than maize, and that teosinte can be exploited for the improvement of kernel composition traits in modern maize germplasm.

  1. Genetic Analysis of Teosinte Alleles for Kernel Composition Traits in Maize

    PubMed Central

    Karn, Avinash; Gillman, Jason D.; Flint-Garcia, Sherry A.

    2017-01-01

    Teosinte (Zea mays ssp. parviglumis) is the wild ancestor of modern maize (Zea mays ssp. mays). Teosinte contains greater genetic diversity compared with maize inbreds and landraces, but its use is limited by insufficient genetic resources to evaluate its value. A population of teosinte near isogenic lines (NILs) was previously developed to broaden the resources for genetic diversity of maize, and to discover novel alleles for agronomic and domestication traits. The 961 teosinte NILs were developed by backcrossing 10 geographically diverse parviglumis accessions into the B73 (reference genome inbred) background. The NILs were grown in two replications in 2009 and 2010 in Columbia, MO and Aurora, NY, respectively, and near infrared reflectance spectroscopy and nuclear magnetic resonance calibrations were developed and used to rapidly predict total kernel starch, protein, and oil content on a dry matter basis in bulk whole grains of teosinte NILs. Our joint-linkage quantitative trait locus (QTL) mapping analysis identified two starch, three protein, and six oil QTL, which collectively explained 18, 23, and 45% of the total variation, respectively. A range of strong additive allelic effects for kernel starch, protein, and oil content were identified relative to the B73 allele. Our results support our hypothesis that teosinte harbors stronger alleles for kernel composition traits than maize, and that teosinte can be exploited for the improvement of kernel composition traits in modern maize germplasm. PMID:28188181

  2. Molecular genetic analysis and evolution of begomoviruses and betasatellites causing yellow mosaic disease of bhendi.

    PubMed

    Kumar, R Vinoth; Prasanna, H C; Singh, A K; Ragunathan, D; Garg, G K; Chakraborty, S

    2017-04-01

    In India, Bhendi yellow vein mosaic disease (BYVMD) is one of the most economically important diseases of bhendi/okra and is caused by a complex of monopartite begomovirus (Bhendi yellow vein mosaic virus-BYVMV) and betasatellite (Bhendi yellow vein betasatellite-BYVB). In this study, we have analyzed the role of possible evolutionary factors involved in the evolution of BYVMV and BYVB isolates. Evidence of inter-species and inter-strain recombination events was detected among the viral isolates, and majority of these recombinant isolates possess microsatellites in their genome. Recombination analysis suggests that cotton-infecting and bhendi-infecting begomoviruses probably share a recent common ancestor. In addition to genetic differentiation and gene flow, high degree of genetic variability was detected among the viral population. A strong purifying selection seems to be acting on the viral coding regions. The nucleotide substitution rate of V1 gene (for BYVMV) and βC1 gene (for BYVB) was estimated to be 7.55 × 10(-4) and 2.25 × 10(-3) nucleotide substitutions/site/year, respectively. The present study underlines that the evolution of BYVMD-associated viral components is driven by selection acting on the genetic variation generated by recombination and mutation.

  3. Comprehensive Primer Design for Analysis of Population Genetics in Non-Sequenced Organisms

    PubMed Central

    Tezuka, Ayumi; Matsushima, Noe; Nemoto, Yoriko; Akashi, Hiroshi D.; Kawata, Masakado; Makino, Takashi

    2012-01-01

    Nuclear sequence markers are useful tool for the study of the history of populations and adaptation. However, it is not easy to obtain multiple nuclear primers for organisms with poor or no genomic sequence information. Here we used the genomes of organisms that have been fully sequenced to design comprehensive sets of primers to amplify polymorphic genomic fragments of multiple nuclear genes in non-sequenced organisms. First, we identified a large number of candidate polymorphic regions that were flanked on each side by conserved regions in the reference genomes. We then designed primers based on these conserved sequences and examined whether the primers could be used to amplify sequences in target species, montane brown frog (Rana ornativentris), anole lizard (Anolis sagrei), guppy (Poecilia reticulata), and fruit fly (Drosophila melanogaster), for population genetic analysis. We successfully obtained polymorphic markers for all target species studied. In addition, we found that sequence identities of the regions between the primer sites in the reference genomes affected the experimental success of DNA amplification and identification of polymorphic loci in the target genomes, and that exonic primers had a higher success rate than intronic primers in amplifying readable sequences. We conclude that this comparative genomic approach is a time- and cost-effective way to obtain polymorphic markers for non-sequenced organisms, and that it will contribute to the further development of evolutionary ecology and population genetics for non-sequenced organisms, aiding in the understanding of the genetic basis of adaptation. PMID:22393396

  4. DHLAS: A web-based information system for statistical genetic analysis of HLA population data.

    PubMed

    Thriskos, P; Zintzaras, E; Germenis, A

    2007-03-01

    DHLAS (database HLA system) is a user-friendly, web-based information system for the analysis of human leukocyte antigens (HLA) data from population studies. DHLAS has been developed using JAVA and the R system, it runs on a Java Virtual Machine and its user-interface is web-based powered by the servlet engine TOMCAT. It utilizes STRUTS, a Model-View-Controller framework and uses several GNU packages to perform several of its tasks. The database engine it relies upon for fast access is MySQL, but others can be used a well. The system estimates metrics, performs statistical testing and produces graphs required for HLA population studies: (i) Hardy-Weinberg equilibrium (calculated using both asymptotic and exact tests), (ii) genetics distances (Euclidian or Nei), (iii) phylogenetic trees using the unweighted pair group method with averages and neigbor-joining method, (iv) linkage disequilibrium (pairwise and overall, including variance estimations), (v) haplotype frequencies (estimate using the expectation-maximization algorithm) and (vi) discriminant analysis. The main merit of DHLAS is the incorporation of a database, thus, the data can be stored and manipulated along with integrated genetic data analysis procedures. In addition, it has an open architecture allowing the inclusion of other functions and procedures.

  5. Genetic programming:  a novel method for the quantitative analysis of pyrolysis mass spectral data.

    PubMed

    Gilbert, R J; Goodacre, R; Woodward, A M; Kell, D B

    1997-11-01

    A technique for the analysis of multivariate data by genetic programming (GP) is described, with particular reference to the quantitative analysis of orange juice adulteration data collected by pyrolysis mass spectrometry (PyMS). The dimensionality of the input space was reduced by ranking variables according to product moment correlation or mutual information with the outputs. The GP technique as described gives predictive errors equivalent to, if not better than, more widespread methods such as partial least squares and artificial neural networks but additionally can provide a means for easing the interpretation of the correlation between input and output variables. The described application demonstrates that by using the GP method for analyzing PyMS data the adulteration of orange juice with 10% sucrose solution can be quantified reliably over a 0-20% range with an RMS error in the estimate of ∼1%.

  6. Falcon: Visual analysis of large, irregularly sampled, and multivariate time series data in additive manufacturing

    DOE PAGES

    Steed, Chad A.; Halsey, William; Dehoff, Ryan; ...

    2017-02-16

    Flexible visual analysis of long, high-resolution, and irregularly sampled time series data from multiple sensor streams is a challenge in several domains. In the field of additive manufacturing, this capability is critical for realizing the full potential of large-scale 3D printers. Here, we propose a visual analytics approach that helps additive manufacturing researchers acquire a deep understanding of patterns in log and imagery data collected by 3D printers. Our specific goals include discovering patterns related to defects and system performance issues, optimizing build configurations to avoid defects, and increasing production efficiency. We introduce Falcon, a new visual analytics system thatmore » allows users to interactively explore large, time-oriented data sets from multiple linked perspectives. Falcon provides overviews, detailed views, and unique segmented time series visualizations, all with adjustable scale options. To illustrate the effectiveness of Falcon at providing thorough and efficient knowledge discovery, we present a practical case study involving experts in additive manufacturing and data from a large-scale 3D printer. The techniques described are applicable to the analysis of any quantitative time series, though the focus of this paper is on additive manufacturing.« less

  7. Dental indications for the instrumental functional analysis in additional consideration of health-economic aspects

    PubMed Central

    Tinnemann, Peter; Stöber, Yvonne; Roll, Stephanie; Vauth, Christoph; Willich, Stefan N.; Greiner, Wolfgang

    2010-01-01

    Background Besides clinical and radiological examination instrumental functional analyses are performed as diagnostic procedures for craniomandibular dysfunctions. Instrumental functional analyses cause substantial costs and shows a considerable variability between individual dentist practices. Objectives On the basis of published scientific evidence the validity of the instrumental functional analysis for the diagnosis of craniomandibular dysfunctions compared to clinical diagnostic procedures; the difference of the various forms of the instrumental functional analysis; the existence of a dependency on additional other factors and the need for further research are determined in this report. In addition, the cost effectiveness of the instrumental functional analysis is analysed in a health-policy context, and social, legal and ethical aspects are considered. Methods A literature search is performed in over 27 databases and by hand. Relevant companies and institutions are contacted concerning unpublished studies. The inclusion criteria for publications are (i) diagnostic studies with the indication “craniomandibular malfunction”, (ii) a comparison between clinical and instrumental functional analysis, (iii) publications since 1990, (iv) publications in English or German. The identified literature is evaluated by two scientists regarding the relevance of content and methodical quality. Results The systematic database search resulted in 962 hits. 187 medical and economic complete publications are evaluated. Since the evaluated studies are not relevant enough to answer the medical or health economic questions no study is included. Discussion The inconsistent terminology concerning craniomandibular dysfunctions and instrumental functional analyses results in a broad literature search in databases and an extensive search by hand. Since no relevant results concerning the validity of the instrumental functional analysis in comparison to the clinical functional analysis

  8. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains

    PubMed Central

    Bennett, Brian J.; Davis, Richard C.; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R. Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C.; Hazen, Stanley L.; Gargalovic, Peter S.; Lusis, Aldons J.

    2015-01-01

    Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression

  9. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains.

    PubMed

    Bennett, Brian J; Davis, Richard C; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C; Hazen, Stanley L; Gargalovic, Peter S; Lusis, Aldons J

    2015-12-01

    Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression

  10. Physiological basis of tolerance to complete submergence in rice involves genetic factors in addition to the SUB1 gene

    PubMed Central

    Singh, Sudhanshu; Mackill, David J.; Ismail, Abdelbagi M.

    2014-01-01

    1 lines. This suggests the possibility of further improvements in submergence tolerance by incorporating additional traits present in FR13A or other similar landraces. PMID:25281725

  11. Physiological basis of tolerance to complete submergence in rice involves genetic factors in addition to the SUB1 gene.

    PubMed

    Singh, Sudhanshu; Mackill, David J; Ismail, Abdelbagi M

    2014-10-03

    1 lines. This suggests the possibility of further improvements in submergence tolerance by incorporating additional traits present in FR13A or other similar landraces.

  12. An improved Agrobacterium-mediated transformation system for the functional genetic analysis of Penicillium marneffei.

    PubMed

    Kummasook, Aksarakorn; Cooper, Chester R; Vanittanakom, Nongnuch

    2010-12-01

    We have developed an improved Agrobacterium-mediated transformation (AMT) system for the functional genetic analysis of Penicillium marneffei, a thermally dimorphic, human pathogenic fungus. Our AMT protocol included the use of conidia or pre-germinated conidia of P. marneffei as the host recipient for T-DNA from Agrobacterium tumefaciens and co-cultivation at 28°C for 36 hours. Bleomycin-resistant transformants were selected as yeast-like colonies following incubation at 37°C. The efficiency of transformation was approximately 123 ± 3.27 and 239 ± 13.12 transformants per plate when using 5 × 10(4) conidia and pre-germinated conidia as starting materials, respectively. Southern blot analysis demonstrated that 95% of transformants contained single copies of T-DNA. Inverse PCR was employed for identifying flanking sequences at the T-DNA insertion sites. Analysis of these sequences indicated that integration occurred as random recombination events. Among the mutants isolated were previously described stuA and gasC defective strains. These AMT-derived mutants possessed single T-DNA integrations within their particular coding sequences. In addition, other morphological and pigmentation mutants possessing a variety of gene-specific defects were isolated, including two mutants having T-DNA integrations within putative promoter regions. One of the latter integration events was accompanied by the deletion of the entire corresponding gene. Collectively, these results indicated that AMT could be used for large-scale, functional genetic analyses in P. marneffei. Such analyses can potentially facilitate the identification of those genetic elements related to morphogenesis, as well as pathogenesis in this medically important fungus.

  13. Genome-wide meta-analysis of maize heterosis reveals the potential role of additive gene expression at pericentromeric loci

    PubMed Central

    2014-01-01

    Background The identification of QTL involved in heterosis formation is one approach to unravel the not yet fully understood genetic basis of heterosis - the improved agronomic performance of hybrid F1 plants compared to their inbred parents. The identification of candidate genes underlying a QTL is important both for developing markers and determining the molecular genetic basis of a trait, but remains difficult owing to the large number of genes often contained within individual QTL. To address this problem in heterosis analysis, we applied a meta-analysis strategy for grain yield (GY) of Zea mays L. as example, incorporating QTL-, hybrid field-, and parental gene expression data. Results For the identification of genes underlying known heterotic QTL, we made use of tight associations between gene expression pattern and the trait of interest, identified by correlation analyses. Using this approach genes strongly associated with heterosis for GY were discovered to be clustered in pericentromeric regions of the complex maize genome. This suggests that expression differences of sequences in recombination-suppressed regions are important in the establishment of heterosis for GY in F1 hybrids and also in the conservation of heterosis for GY across genotypes. Importantly functional analysis of heterosis-associated genes from these genomic regions revealed over-representation of a number of functional classes, identifying key processes contributing to heterosis for GY. Based on the finding that the majority of the analyzed heterosis-associated genes were addtitively expressed, we propose a model referring to the influence of cis-regulatory variation on heterosis for GY by the compensation of fixed detrimental expression levels in parents. Conclusions The study highlights the utility of a meta-analysis approach that integrates phenotypic and multi-level molecular data to unravel complex traits in plants. It provides prospects for the identification of genes relevant for

  14. Genetic analysis of ewe stayability and its association with lamb growth and adult production.

    PubMed

    Borg, R C; Notter, D R; Kott, R W

    2009-11-01

    Records from 2,525 adult Targhee ewes and 10,099 lambs were used to estimate genetic parameters in an animal model for ewe stayability (STAY), productive life (PL), adult BW (AW) and BCS, fleece characteristics, and number of lambs born (NLB) and for lamb BW at birth and approximately 45 d, 120 d (120W; weaning), 12 mo, and 18 mo of age. Stayabilities were analyzed as overall stayability (STAYn|2), which indicated presence or absence of a ewe at n yr of age, given that she was present at 2 yr of age, or marginal stayability (STAYn|n-1) recording the presence of a ewe at n yr of age, given that she was present in the previous year. Productive life was measured as the age of ewe in years at her last lambing. Lamb BW were corrected for age at weighing; BW taken at or before weaning were adjusted for effects of type of birth and rearing, age of dam, and sex using National Sheep Improvement Program methods. The NLB was likewise adjusted for effects of ewe age before analysis. Birth year was included as a fixed effect for all traits. Year of record and, for AW and CS, the number of lambs born or born and reared were also included in models for adult traits. Models for all traits included random additive genetic and residual effects. Random maternal genetic and dam permanent environmental effects were also included in the model for lamb (pre)weaning BW, and random permanent environmental effects of the ewe were included in models for adult traits. The heritability estimate for PL was 0.05 (P < 0.10). Additive variance in STAY was only present after 5 yr of age (P < 0.05), with estimated heritabilities ranging from 0.04 to 0.10. Phenotypic correlations between STAY and other traits were near zero, ranging from -0.07 to 0.14. Estimates of genetic correlations of STAY5|4 and STAY6|2 with maternal genetic effects on 120W were positive (both 0.46; P < 0.05), suggesting that STAY and maternal effects on 120W both reflect genetic variation in ewe fitness characteristics. Genetic

  15. Fine structure genetic analysis of a beta-globin promoter.

    PubMed

    Myers, R M; Tilly, K; Maniatis, T

    1986-05-02

    A novel procedure for saturation mutagenesis of cloned DNA was used to obtain more than 100 single base substitutions within the promoter of the mouse beta-major globin gene. The effects of these promoter substitutions on transcription were determined by transfecting the cloned mutant genes into HeLa cells on plasmids containing an SV40 transcription enhancer, and measuring the levels of correctly initiated beta-globin transcripts after 2 days. Mutations in three regions of the promoter resulted in a significant decrease in the level of transcription: (i) the CACCC box, located between -87 and -95, (ii) the CCAAT box, located between -72 and -77, and (iii) the TATA box, located between -26 and -30 relative to the start site of transcription. In contrast, two different mutations in nucleotides immediately upstream from the CCAAT box resulted in a 3- to 3.5-fold increase in transcription. With two minor exceptions, single base substitutions in all other regions of the promoter had no effect on transcription. These results precisely delineate the cis-acting sequences required for accurate and efficient initiation of beta-globin transcription, and they establish a general approach for the fine structure genetic analysis of eukaryotic regulatory sequences.

  16. Genetic analysis of teosinte for kernel composition traits in maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Teosinte (Zea mays ssp. parviglumis) is the wild ancestor of modern maize (Zea mays ssp. mays). Teosinte contains greater genetic diversity compared to maize inbreds and landraces, but its use is limited by insufficient genetic resources to evaluate its value. A population of teosinte near isogenic ...

  17. Analysis of Errors Made by Students Solving Genetics Problems.

    ERIC Educational Resources Information Center

    Costello, Sandra Judith

    The purpose of this study was to analyze the errors made by students solving genetics problems. A sample of 10 non-science undergraduate students was obtained from a private college in Northern New Jersey. The results support prior research in the area of genetics education and show that a weak understanding of the relationship of meiosis to…

  18. Analysis of Molecular Genetics Content in Spanish Secondary School Textbooks

    ERIC Educational Resources Information Center

    Martinez-Gracia, M. V.; Gil-Quilez, M. J.; Osada, J.

    2006-01-01

    The treatment of molecular biology in thirty-four Spanish high school biology textbooks has been analysed using a check-list made up of twenty-three items. The study showed a tendency to confuse the genetic code with genetic information. The treatment of DNA transcription, regulation of gene expression and translation were presented as masses of…

  19. Genetic analysis of gravity signal transduction in roots

    NASA Astrophysics Data System (ADS)

    Masson, Patrick; Strohm, Allison; Baldwin, Katherine

    gravitropism, we sought genetic enhancers of arg1 as a way to identify new gravity signal transducers. Two of these modifiers, named mar1 and mar2, were found to affect genes that encode two subunits of the plastidic outer-membrane protein import complex, TOC75 and TOC132, respectively. mar2 did not affect the ultrastructure of amyloplasts in the statocytes nor did it alter their ability to sediment in response to gravistimulation, suggesting a role for the outer membrane of the amyloplasts in gravity signal transduction (reviewed in Stanga et al., 2009, Plant Signal Behavior 4(10): 1-9). The contribution of TOC132 in gravity signal transduction is being investigated by analyzing the regions of this protein that are needed for the pathway, and investigating the contribution of a putative TOC132-interacting protein in gravity signal transduction. We have also isolated additional putative enhancers of arg1-2 in the hope of identifying new plastid-associated gravity signal transducers, and have initiated a screen for genetic enhancers of mar2 to seek new transducers in the ARG1 branch of the pathway.

  20. Hierarchical linear modeling of longitudinal pedigree data for genetic association analysis.

    PubMed

    Tan, Qihua; B Hjelmborg, Jacob V; Thomassen, Mads; Jensen, Andreas Kryger; Christiansen, Lene; Christensen, Kaare; Zhao, Jing Hua; Kruse, Torben A

    2014-01-01

    Genetic association analysis on complex phenotypes under a longitudinal design involving pedigrees encounters the problem of correlation within pedigrees, which could affect statistical assessment of the genetic effects. Approaches have been proposed to integrate kinship correlation into the mixed-effect models to explicitly model the genetic relationship. These have proved to be an efficient way of dealing with sample clustering in pedigree data. Although current algorithms implemented in popular statistical packages are useful for adjusting relatedness in the mixed modeling of genetic effects on the mean level of a phenotype, they are not sufficiently straightforward to handle the kinship correlation on the time-dependent trajectories of a phenotype. We introduce a 2-level hierarchical linear model to separately assess the genetic associations with the mean level and the rate of change of a phenotype, integrating kinship correlation in the analysis. We apply our method to the Genetic Analysis Workshop 18 genome-wide association studies data on chromosome 3 to estimate the genetic effects on systolic blood pressure measured over time in large pedigrees. Our method identifies genetic variants associated with blood pressure with estimated inflation factors of 0.99, suggesting that our modeling of random effects efficiently handles the genetic relatedness in pedigrees. Application to simulated data captures important variants specified in the simulation. Our results show that the method is useful for genetic association studies in related samples using longitudinal design.

  1. Simulation Approach for Timing Analysis of Genetic Logic Circuits.

    PubMed

    Baig, Hasan; Madsen, Jan

    2017-02-01

    Constructing genetic logic circuits is an application of synthetic biology in which parts of the DNA of a living cell are engineered to perform a dedicated Boolean function triggered by an appropriate concentration of certain proteins or by different genetic components. These logic circuits work in a manner similar to electronic logic circuits, but they are much more stochastic and hence much harder to characterize. In this article, we introduce an approach to analyze the threshold value and timing of genetic logic circuits. We show how this approach can be used to analyze the timing behavior of single and cascaded genetic logic circuits. We further analyze the timing sensitivity of circuits by varying the degradation rates and concentrations. Our approach can be used not only to characterize the timing behavior but also to analyze the timing constraints of cascaded genetic logic circuits, a capability that we believe will be important for design automation in synthetic biology.

  2. Genetic and Epidemiological Analysis of Influenza Virus Epidemics in Taiwan during 2003 to 2006▿ †

    PubMed Central

    Jian, Jhih-Wei; Chen, Guang-Wu; Lai, Cheng-Tsung; Hsu, Li-Ching; Chen, Pei-Jer; Kuo, Steve Hsu-Sung; Wu, Ho-Sheng; Shih, Shin-Ru

    2008-01-01

    The genetic characterization of Taiwanese influenza A and B viruses on the basis of analyses of pairwise amino acid variations, genetic clustering, and phylogenetics was performed. A total of 548, 2,123, and 1,336 sequences of the HA1 genes of influenza A virus subtypes H1 and H3 and influenza B virus, respectively, collected during 2003 to 2006 from an island-wide surveillance network were determined. Influenza A virus H3 showed activity during all periods, although it was dominant only in the winters of 2002-2003 and 2003-2004. Instead, influenza B virus and influenza A virus H1 were dominant in the winters of 2004-2005 and 2005-2006, respectively. Additionally, two influenza A virus H3 peaks were found in the summers of 2004 and 2005. From clustering analysis, similar characteristics of high sequence diversity and short life spans for the influenza A virus H1 and H3 clusters were observed, despite their distinct seasonal patterns. In contrast, clusters with longer life spans and fewer but larger clusters were found among the influenza B viruses. We also noticed that more amino acid changes at antigenic sites, especially at sites B and D in the H3 viruses, were found in 2003 and 2004 than in the following 2 years. The only epidemic of the H1 viruses, which occurred in the winter of 2005-2006, was caused by two genetically distinct lineages, and neither of them showed apparent antigenic changes compared with the antigens of the vaccine strain. For the influenza B viruses, the multiple dominant lineages of Yamagata-like strains with large genetic variations observed reflected the evolutionary pressure caused by the Yamagata-like vaccine strain. On the other hand, only one dominant lineage of Victoria-like strains circulated from 2004 to 2006. PMID:18256223

  3. Genetic analysis of vertebral regionalization and number in medaka (Oryzias latipes) inbred lines.

    PubMed

    Kimura, Tetsuaki; Shinya, Minori; Naruse, Kiyosi

    2012-11-01

    Vertebral number is the most variable trait among vertebrates. In addition to the vertebral number, the ratio of abdominal to caudal vertebrae is a variable trait. The vertebral number and the ratio of abdominal to caudal vertebrae contribute to vertebrate diversity. It is very interesting to know how to determine the vertebral number and the ratio of abdominal to caudal vertebrae. In this study, we identify differences in the vertebral number and the ratio of abdominal vertebrae to vertebral number between two inbred lines of medaka, namely, Hd-rRII1 and Kaga. To identify the genetic factor of those differences, we performed quantitative trait locus (QTL) analysis for vertebral number and the ratio of abdominal vertebrae to vertebral number using 200 F(2) fish. Our results show a suggestive QTL of the ratio of abdominal vertebrae to vertebral number on chromosome 15, and five QTL of vertebral number on chromosomes 1, 10, 11, 17, and 23. The QTL on chromosome 15 contains hoxDb cluster genes. The QTL of vertebral number include some genes related to the segmentation clock and axial elongation. In addition, we show that the difference in vertebral number between two inbred lines is derived from differences in the anteroposterior length of somites. Our results emphasize that the developmental process should be considered in genetic analyses for vertebral number.

  4. Genetic and evolutionary analysis of the Drosophila larval neuromuscular junction

    NASA Astrophysics Data System (ADS)

    Campbell, Megan

    Although evolution of brains and behaviors is of fundamental biological importance, we lack comprehensive understanding of the general principles governing these processes or the specific mechanisms and molecules through which the evolutionary changes are effected. Because synapses are the basic structural and functional units of nervous systems, one way to address these problems is to dissect the genetic and molecular pathways responsible for morphological evolution of a defined synapse. I have undertaken such an analysis by examining morphology of the larval neuromuscular junction (NMJ) in wild caught D. melanogaster as well as in over 20 other species of Drosophila. Whereas variation in NMJ morphology within a species is limited, I discovered a surprisingly extensive variation among different species. Compared with evolution of other morphological traits, NMJ morphology appears to be evolving very rapidly. Moreover, my data indicate that natural selection rather than genetic drift is primarily responsible for evolution of NMJ morphology. To dissect underlying molecular mechanisms that may govern NMJ growth and evolutionary divergence, I focused on a naturally occurring variant in D. melanogaster that causes NMJ overgrowth. I discovered that the variant mapped to Mob2, a gene encoding a kinase adapter protein originally described in yeast as a member of the Mitotic Exit Network (MEN). I have subsequently examined mutations in the Drosophila orthologs of all the core components of the yeast MEN and found that all of them function as part of a common pathway that acts presynaptically to negatively regulate NMJ growth. As in the regulation of yeast cytokinesis, these components of the MEN appear to act ultimately by regulating actin dynamics during the process of bouton growth and division. These studies have thus led to the discovery of an entirely new role for the MEN---regulation of synaptic growth---that is separate from its function in cell division. This work

  5. Toward genetics-based virus taxonomy: comparative analysis of a genetics-based classification and the taxonomy of picornaviruses.

    PubMed

    Lauber, Chris; Gorbalenya, Alexander E

    2012-04-01

    Virus taxonomy has received little attention from the research community despite its broad relevance. In an accompanying paper (C. Lauber and A. E. Gorbalenya, J. Virol. 86:3890-3904, 2012), we have introduced a quantitative approach to hierarchically classify viruses of a family using pairwise evolutionary distances (PEDs) as a measure of genetic divergence. When applied to the six most conserved proteins of the Picornaviridae, it clustered 1,234 genome sequences in groups at three hierarchical levels (to which we refer as the "GENETIC classification"). In this study, we compare the GENETIC classification with the expert-based picornavirus taxonomy and outline differences in the underlying frameworks regarding the relation of virus groups and genetic diversity that represent, respectively, the structure and content of a classification. To facilitate the analysis, we introduce two novel diagrams. The first connects the genetic diversity of taxa to both the PED distribution and the phylogeny of picornaviruses. The second depicts a classification and the accommodated genetic diversity in a standardized manner. Generally, we found striking agreement between the two classifications on species and genus taxa. A few disagreements concern the species Human rhinovirus A and Human rhinovirus C and the genus Aphthovirus, which were split in the GENETIC classification. Furthermore, we propose a new supergenus level and universal, level-specific PED thresholds, not reached yet by many taxa. Since the species threshold is approached mostly by taxa with large sampling sizes and those infecting multiple hosts, it may represent an upper limit on divergence, beyond which homologous recombination in the six most conserved genes between two picornaviruses might not give viable progeny.

  6. Marker-Based Estimates Reveal Significant Non-additive Effects in Clonally Propagated Cassava (Manihot esculenta): Implications for the Prediction of Total Genetic Value and the Selection of Varieties.

    PubMed

    Wolfe, Marnin D; Kulakow, Peter; Rabbi, Ismail Y; Jannink, Jean-Luc

    2016-08-31

    In clonally propagated crops, non-additive genetic effects can be effectively exploited by the identification of superior genetic individuals as varieties. Cassava (Manihot esculenta Crantz) is a clonally propagated staple food crop that feeds hundreds of millions. We quantified the amount and nature of non-additive genetic variation for three key traits in a breeding population of cassava from sub-Saharan Africa using additive and non-additive genome-wide marker-based relationship matrices. We then assessed the accuracy of genomic prediction for total (additive plus non-additive) genetic value. We confirmed previous findings based on diallel populations, that non-additive genetic variation is significant for key cassava traits. Specifically, we found that dominance is particularly important for root yield and epistasis contributes strongly to variation in CMD resistance. Further, we showed that total genetic value predicted observed phenotypes more accurately than additive only models for root yield but not for dry matter content, which is mostly additive or for CMD resistance, which has high narrow-sense heritability. We address the implication of these results for cassava breeding and put our work in the context of previous results in cassava, and other plant and animal species.

  7. Genetic Markers and Quantitative Genetic Variation in Medicago Truncatula (Leguminosae): A Comparative Analysis of Population Structure

    PubMed Central

    Bonnin, I.; Prosperi, J. M.; Olivieri, I.

    1996-01-01

    Two populations of the selfing annual Medicago truncatula Gaertn. (Leguminoseae), each subdivided into three subpopulations, were studied for both metric traits (quantitative characters) and genetic markers (random amplified polymorphic DNA and one morphological, single-locus marker). Hierarchical analyses of variance components show that (1) populations are more differentiated for quantitative characters than for marker loci, (2) the contribution of both within and among subpopulations components of variance to overall genetic variance of these characters is reduced as compared to markers, and (3) at the population level, within population structure is slightly but not significantly larger for markers than for quantitative traits. Under the hypothesis that most markers are neutral, such comparisons may be used to make hypotheses about the strength and heterogeneity of natural selection in the face of genetic drift and gene flow. We thus suggest that in these populations, quantitative characters are under strong divergent selection among populations, and that gene flow is restricted among populations and subpopulations. PMID:8844165

  8. Genetic analysis of Eclosion hormone action during Drosophila larval ecdysis.

    PubMed

    Krüger, Eileen; Mena, Wilson; Lahr, Eleanor C; Johnson, Erik C; Ewer, John

    2015-12-15

    Insect growth is punctuated by molts, during which the animal produces a new exoskeleton. The molt culminates in ecdysis, an ordered sequence of behaviors that causes the old cuticle to be shed. This sequence is activated by Ecdysis triggering hormone (ETH), which acts on the CNS to activate neurons that produce neuropeptides implicated in ecdysis, including Eclosion hormone (EH), Crustacean cardioactive peptide (CCAP) and Bursicon. Despite more than 40 years of research on ecdysis, our understanding of the precise roles of these neurohormones remains rudimentary. Of particular interest is EH; although it is known to upregulate ETH release, other roles for EH have remained elusive. We isolated an Eh null mutant in Drosophila and used it to investigate the role of EH in larval ecdysis. We found that null mutant animals invariably died at around the time of ecdysis, revealing an essential role in its control. Further analyses showed that these animals failed to express the preparatory behavior of pre-ecdysis while directly expressing the motor program of ecdysis. Although ETH release could not be detected, the lack of pre-ecdysis could not be rescued by injections of ETH, suggesting that EH is required within the CNS for ETH to trigger the normal ecdysial sequence. Using a genetically encoded calcium probe, we showed that EH configured the response of the CNS to ETH. These findings show that EH plays an essential role in the Drosophila CNS in the control of ecdysis, in addition to its known role in the periphery of triggering ETH release.

  9. ANALYSIS OF DISTRIBUTION FEEDER LOSSES DUE TO ADDITION OF DISTRIBUTED PHOTOVOLTAIC GENERATORS

    SciTech Connect

    Tuffner, Francis K.; Singh, Ruchi

    2011-08-09

    Distributed generators (DG) are small scale power supplying sources owned by customers or utilities and scattered throughout the power system distribution network. Distributed generation can be both renewable and non-renewable. Addition of distributed generation is primarily to increase feeder capacity and to provide peak load reduction. However, this addition comes with several impacts on the distribution feeder. Several studies have shown that addition of DG leads to reduction of feeder loss. However, most of these studies have considered lumped load and distributed load models to analyze the effects on system losses, where the dynamic variation of load due to seasonal changes is ignored. It is very important for utilities to minimize the losses under all scenarios to decrease revenue losses, promote efficient asset utilization, and therefore, increase feeder capacity. This paper will investigate an IEEE 13-node feeder populated with photovoltaic generators on detailed residential houses with water heater, Heating Ventilation and Air conditioning (HVAC) units, lights, and other plug and convenience loads. An analysis of losses for different power system components, such as transformers, underground and overhead lines, and triplex lines, will be performed. The analysis will utilize different seasons and different solar penetration levels (15%, 30%).

  10. Analysis of redox additive-based overcharge protection for rechargeable lithium batteries

    NASA Technical Reports Server (NTRS)

    Narayanan, S. R.; Surampudi, S.; Attia, A. I.; Bankston, C. P.

    1991-01-01

    The overcharge condition in secondary lithium batteries employing redox additives for overcharge protection, has been theoretically analyzed in terms of a finite linear diffusion model. The analysis leads to expressions relating the steady-state overcharge current density and cell voltage to the concentration, diffusion coefficient, standard reduction potential of the redox couple, and interelectrode distance. The model permits the estimation of the maximum permissible overcharge rate for any chosen set of system conditions. Digital simulation of the overcharge experiment leads to numerical representation of the potential transients, and estimate of the influence of diffusion coefficient and interelectrode distance on the transient attainment of the steady state during overcharge. The model has been experimentally verified using 1,1-prime-dimethyl ferrocene as a redox additive. The analysis of the experimental results in terms of the theory allows the calculation of the diffusion coefficient and the formal potential of the redox couple. The model and the theoretical results may be exploited in the design and optimization of overcharge protection by the redox additive approach.

  11. About DNA databasing and investigative genetic analysis of externally visible characteristics: A public survey.

    PubMed

    Zieger, Martin; Utz, Silvia

    2015-07-01

    During the last decade, DNA profiling and the use of DNA databases have become two of the most employed instruments of police investigations. This very rapid establishment of forensic genetics is yet far from being complete. In the last few years novel types of analyses have been presented to describe phenotypically a possible perpetrator. We conducted the present study among German speaking Swiss residents for two main reasons: firstly, we aimed at getting an impression of the public awareness and acceptance of the Swiss DNA database and the perception of a hypothetical DNA database containing all Swiss residents. Secondly, we wanted to get a broader picture of how people that are not working in the field of forensic genetics think about legal permission to establish phenotypic descriptions of alleged criminals by genetic means. Even though a significant number of study participants did not even know about the existence of the Swiss DNA database, its acceptance appears to be very high. Generally our results suggest that the current forensic use of DNA profiling is considered highly trustworthy. However, the acceptance of a hypothetical universal database would be only as low as about 30% among the 284 respondents to our study, mostly because people are concerned about the security of their genetic data, their privacy or a possible risk of abuse of such a database. Concerning the genetic analysis of externally visible characteristics and biogeographical ancestry, we discover a high degree of acceptance. The acceptance decreases slightly when precise characteristics are presented to the participants in detail. About half of the respondents would be in favor of the moderate use of physical traits analyses only for serious crimes threatening life, health or sexual integrity. The possible risk of discrimination and reinforcement of racism, as discussed by scholars from anthropology, bioethics, law, philosophy and sociology, is mentioned less frequently by the study

  12. Quantitative analysis of fitness and genetic interactions in yeast on a genome scale.

    PubMed

    Baryshnikova, Anastasia; Costanzo, Michael; Kim, Yungil; Ding, Huiming; Koh, Judice; Toufighi, Kiana; Youn, Ji-Young; Ou, Jiongwen; San Luis, Bryan-Joseph; Bandyopadhyay, Sunayan; Hibbs, Matthew; Hess, David; Gingras, Anne-Claude; Bader, Gary D; Troyanskaya, Olga G; Brown, Grant W; Andrews, Brenda; Boone, Charles; Myers, Chad L

    2010-12-01

    Global quantitative analysis of genetic interactions is a powerful approach for deciphering the roles of genes and mapping functional relationships among pathways. Using colony size as a proxy for fitness, we developed a method for measuring fitness-based genetic interactions from high-density arrays of yeast double mutants generated by synthetic genetic array (SGA) analysis. We identified several experimental sources of systematic variation and developed normalization strategies to obtain accurate single- and double-mutant fitness measurements, which rival the accuracy of other high-resolution studies. We applied the SGA score to examine the relationship between physical and genetic interaction networks, and we found that positive genetic interactions connect across functionally distinct protein complexes revealing a network of genetic suppression among loss-of-function alleles.

  13. Accelerating epistasis analysis in human genetics with consumer graphics hardware

    PubMed Central

    2009-01-01

    available for other tasks. The GPU workstation containing three GPUs costs $2000 while obtaining similar performance on a Beowulf cluster requires 150 CPU cores which, including the added infrastructure and support cost of the cluster system, cost approximately $82,500. Conclusion Graphics hardware based computing provides a cost effective means to perform genetic analysis of epistasis using MDR on large datasets without the infrastructure of a computing cluster. PMID:19630950

  14. Analysis of error-prone survival data under additive hazards models: measurement error effects and adjustments.

    PubMed

    Yan, Ying; Yi, Grace Y

    2016-07-01

    Covariate measurement error occurs commonly in survival analysis. Under the proportional hazards model, measurement error effects have been well studied, and various inference methods have been developed to correct for error effects under such a model. In contrast, error-contaminated survival data under the additive hazards model have received relatively less attention. In this paper, we investigate this problem by exploring measurement error effects on parameter estimation and the change of the hazard function. New insights of measurement error effects are revealed, as opposed to well-documented results for the Cox proportional hazards model. We propose a class of bias correction estimators that embraces certain existing estimators as special cases. In addition, we exploit the regression calibration method to reduce measurement error effects. Theoretical results for the developed methods are established, and numerical assessments are conducted to illustrate the finite sample performance of our methods.

  15. Application of liquid chromatography in polymer non-ionic antistatic additives analysis.

    PubMed

    González-Rodríguez, M Victoria; Dopico-García, M Sonia; Noguerol-Cal, Rosalía; Carballeira-Amarelo, Tania; López-Vilariño, José M; Fernández-Martínez, Gerado

    2010-11-01

    This article investigates the applicability of HPLC-UV, ultra performance LC-evaporative light-scattering detection (UPLC-ELSD), HPLC-ESI(+)-MS and HPLC-hybrid linear ion trap (LTQ) Orbitrap MS for the analysis of different non-ionic antistatic additives, Span 20, Span 60, Span 65, Span 80, Span 85 (sorbitan fatty acid esters), Atmer 129 (glycerol fatty acid ester) and Atmer 163 (ethoxylated alkylamine). Several alkyl chain length or different degrees of esterification of polyol derivatives can be present in commercial mixtures of these polymer additives. Therefore, their identification and quantification is complicated. Qualitative composition of the studied compounds was analysed by MS. HPLC-UV, UPLC-ELSD and HPLC-LTQ Orbitrap MS methods were applied to the quantitative determination of the different Spans, Atmer 129 and Atmer 163, respectively. Quality parameters of these methods were established and no derivatization was necessary.

  16. Enhanced genetic analysis of single human bioparticles recovered by simplified micromanipulation from forensic 'touch DNA' evidence.

    PubMed

    Farash, Katherine; Hanson, Erin K; Ballantyne, Jack

    2015-03-09

    DNA profiles can be obtained from 'touch DNA' evidence, which comprises microscopic traces of human biological material. Current methods for the recovery of trace DNA employ cotton swabs or adhesive tape to sample an area of interest. However, such a 'blind-swabbing' approach will co-sample cellular material from the different individuals, even if the individuals' cells are located in geographically distinct locations on the item. Thus, some of the DNA mixtures encountered in touch DNA samples are artificially created by the swabbing itself. In some instances, a victim's DNA may be found in significant excess thus masking any potential perpetrator's DNA. In order to circumvent the challenges with standard recovery and analysis methods, we have developed a lower cost, 'smart analysis' method that results in enhanced genetic analysis of touch DNA evidence. We describe an optimized and efficient micromanipulation recovery strategy for the collection of bio-particles present in touch DNA samples, as well as an enhanced amplification strategy involving a one-step 5 µl microvolume lysis/STR amplification to permit the recovery of STR profiles from the bio-particle donor(s). The use of individual or few (i.e., "clumps") bioparticles results in the ability to obtain single source profiles. These procedures represent alternative enhanced techniques for the isolation and analysis of single bioparticles from forensic touch DNA evidence. While not necessary in every forensic investigation, the method could be highly beneficial for the recovery of a single source perpetrator DNA profile in cases involving physical assault (e.g., strangulation) that may not be possible using standard analysis techniques. Additionally, the strategies developed here offer an opportunity to obtain genetic information at the single cell level from a variety of other non-forensic trace biological material.

  17. Addition of three-dimensional isoparametric elements to NASA structural analysis program (NASTRAN)

    NASA Technical Reports Server (NTRS)

    Field, E. I.; Johnson, S. E.

    1973-01-01

    Implementation is made of the three-dimensional family of linear, quadratic and cubic isoparametric solid elements into the NASA Structural Analysis program, NASTRAN. This work included program development, installation, testing, and documentation. The addition of these elements to NASTRAN provides a significant increase in modeling capability particularly for structures requiring specification of temperatures, material properties, displacements, and stresses which vary throughout each individual element. Complete program documentation is presented in the form of new sections and updates for direct insertion to the three NASTRAN manuals. The results of demonstration test problems are summarized. Excellent results are obtained with the isoparametric elements for static, normal mode, and buckling analyses.

  18. Results of investigations of Ethernet network fault-tolerance parameters by using additional analysis subsystem

    NASA Astrophysics Data System (ADS)

    Sultanov, Albert H.; Gayfulin, Renat R.; Vinogradova, Irina L.

    2008-04-01

    Fiber optic telecommunication systems with duplex data transmitting over single fiber require reflection minimization. Moreover reflections may be so high that causes system deactivating by misoperation of conventional alarm, and system can not automatically adjudge the collision, so operator manual control is required. In this paper we proposed technical solution of mentioned problem based on additional analysis subsystem, realized on the installed Ufa-city fiber optic CTV system "Crystal". Experience of it's maintenance and results of investigations of the fault tolerance parameters are represented

  19. Genetic analysis of a Drosophila microtubule-associated protein

    PubMed Central

    1992-01-01

    The 205-kD microtubule-associated protein (205K MAP) is one of the principal MAPs in Drosophila. 205K MAP is similar to the HeLa 210K/MAP4 family of MAPs since it shares the following biochemical properties: it is present in several isoforms, has a molecular mass of approximately 200 kD, and is thermostable. Furthermore, immuno-crossreactivity has been observed between mouse MAP4, HeLa 210K, and Drosophila 205K MAP. Currently, there is little information concerning the biological function of this group of nonmotor MAPs. We have used a classical genetic approach to try to identify the role of the 205K MAP in Drosophila by isolating mutations in the 205K MAP gene. An F2 lethal screen was used to acquire deficiencies of 100EF, the chromosomal location of the 205K MAP gene. Drosophila bearing a homozygous deficiency for the 205K MAP region are fully viable and show no obvious phenotype. A recently developed polymerase chain reaction screen was also used to recover five P-element insertions upstream from the 205K MAP gene. Western blot analysis has shown that these insertions result in hypomorphic mutations of the 205K MAP gene. As was seen with animals that have no 205K MAP, these mutations appear to have no phenotype. These data unambiguously demonstrate that the 205K MAP gene is inessential for development. These results also suggest that there may exist protein(s) with redundant function that can substitute for 205K MAP. PMID:1309812

  20. Genetic and genomic analysis of RNases in model cyanobacteria.

    PubMed

    Cameron, Jeffrey C; Gordon, Gina C; Pfleger, Brian F

    2015-10-01

    Cyanobacteria are diverse photosynthetic microbes with the ability to convert CO2 into useful products. However, metabolic engineering of cyanobacteria remains challenging because of the limited resources for modifying the expression of endogenous and exogenous biochemical pathways. Fine-tuned control of protein production will be critical to optimize the biological conversion of CO2 into desirable molecules. Messenger RNAs (mRNAs) are labile intermediates that play critical roles in determining the translation rate and steady-state protein concentrations in the cell. The majority of studies on mRNA turnover have focused on the model heterotrophic bacteria Escherichia coli and Bacillus subtilis. These studies have elucidated many RNA modifying and processing enzymes and have highlighted the differences between these Gram-negative and Gram-positive bacteria, respectively. In contrast, much less is known about mRNA turnover in cyanobacteria. We generated a compendium of the major ribonucleases (RNases) and provide an in-depth analysis of RNase III-like enzymes in commonly studied and diverse cyanobacteria. Furthermore, using targeted gene deletion, we genetically dissected the RNases in Synechococcus sp. PCC 7002, one of the fastest growing and industrially attractive cyanobacterial strains. We found that all three cyanobacterial homologs of RNase III and a member of the RNase II/R family are not essential under standard laboratory conditions, while homologs of RNase E/G, RNase J1/J2, PNPase, and a different member of the RNase II/R family appear to be essential for growth. This work will enhance our understanding of native control of gene expression and will facilitate the development of an RNA-based toolkit for metabolic engineering in cyanobacteria.

  1. Internal quantum efficiency analysis of solar cell by genetic algorithm

    SciTech Connect

    Xiong, Kanglin; Yang, Hui; Lu, Shulong; Zhou, Taofei; Wang, Rongxin; Qiu, Kai; Dong, Jianrong; Jiang, Desheng

    2010-11-15

    To investigate factors limiting the performance of a GaAs solar cell, genetic algorithm is employed to fit the experimentally measured internal quantum efficiency (IQE) in the full spectra range. The device parameters such as diffusion lengths and surface recombination velocities are extracted. Electron beam induced current (EBIC) is performed in the base region of the cell with obtained diffusion length agreeing with the fit result. The advantage of genetic algorithm is illustrated. (author)

  2. Genetic and Dyanmic Analysis of Murine Peak Bone Density

    DTIC Science & Technology

    1997-10-01

    Animal Care and Use, Human Subjects, civil Rights, Handicapped Individuals, Sex Discrimination, Scientific Fraud (Misconduct) Assurance, Delinquent ...B6CASTF2 cross served its purposes fully and will not be pursued further at this time. Biological stimulus tests show that genetic differences ...and endosteal surfaces of tibias. These data primarily reflect changes in cortical bone compartment. Genetic differences discriminating C57BL/6J from

  3. A multiple additive regression tree analysis of three exposure measures during Hurricane Katrina.

    PubMed

    Curtis, Andrew; Li, Bin; Marx, Brian D; Mills, Jacqueline W; Pine, John

    2011-01-01

    This paper analyses structural and personal exposure to Hurricane Katrina. Structural exposure is measured by flood height and building damage; personal exposure is measured by the locations of 911 calls made during the response. Using these variables, this paper characterises the geography of exposure and also demonstrates the utility of a robust analytical approach in understanding health-related challenges to disadvantaged populations during recovery. Analysis is conducted using a contemporary statistical approach, a multiple additive regression tree (MART), which displays considerable improvement over traditional regression analysis. By using MART, the percentage of improvement in R-squares over standard multiple linear regression ranges from about 62 to more than 100 per cent. The most revealing finding is the modelled verification that African Americans experienced disproportionate exposure in both structural and personal contexts. Given the impact of exposure to health outcomes, this finding has implications for understanding the long-term health challenges facing this population.

  4. Basic principles and laboratory analysis of genetic variation.

    PubMed

    Gonzalez-Bosquet, Jesus; Chanock, Stephen J

    2011-01-01

    With the draft of the human genome and advances in technology, the approach toward mapping complex diseases and traits has changed. Human genetics has evolved into the study of the genome as a complex structure harbouring clues for multifaceted disease risk with the majority still unknown. The discovery of new candidate regions by genome-wide association studies (GWAS) has changed strategies for the study of genetic predisposition. More genome-wide, "agnostic" approaches, with increasing numbers of participants from high-quality epidemiological studies are for the first time replicating results in different settings. However, new-found regions (which become the new candidate "genes") require extensive follow-up and investigation of their functional significance. Understanding the true effect of genetic variability on the risk of complex diseases is paramount. The importance of designing high-quality studies to assess environmental contributions, as well as the interactions between genes and exposures, cannot be stressed enough. This chapter will address the basic issues of genetic variation, including population genetics, as well as analytical platforms and tools needed to investigate the contribution of genetics to human diseases and traits.

  5. Multivariate analysis in a genetic divergence study of Psidium guajava.

    PubMed

    Nogueira, A M; Ferreira, M F S; Guilhen, J H S; Ferreira, A

    2014-12-18

    The family Myrtaceae is widespread in the Atlantic Forest and is well-represented in the Espírito Santo State in Brazil. In the genus Psidium of this family, guava (Psidium guajava L.) is the most economically important species. Guava is widely cultivated in tropical and subtropical countries; however, the widespread cultivation of only a small number of guava tree cultivars may cause the genetic vulnerability of this crop, making the search for promising genotypes in natural populations important for breeding programs and conservation. In this study, the genetic diversity of 66 guava trees sampled in the southern region of Espírito Santo and in Caparaó, MG, Brazil were evaluated. A total of 28 morphological descriptors (11 quantitative and 17 multicategorical) and 18 microsatellite markers were used. Principal component, discriminant and cluster analyses, descriptive analyses, and genetic diversity analyses using simple sequence repeats were performed. Discrimination of accessions using molecular markers resulted in clustering of genotypes of the same origin, which was not observed using morphological data. Genetic diversity was detected between and within the localities evaluated, regardless of the methodology used. Genetic differentiation among the populations using morphological and molecular data indicated the importance of the study area for species conservation, genetic erosion estimation, and exploitation in breeding programs.

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

    PubMed

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

    2016-09-01

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

  7. Female mate choice predicts paternity success in the absence of additive genetic variance for other female paternity bias mechanisms in Drosophila serrata.

    PubMed

    Collet, J M; Blows, M W

    2014-11-01

    After choosing a first mate, polyandrous females have access to a range of opportunities to bias paternity, such as repeating matings with the preferred male, facilitating fertilization from the best sperm or differentially investing in offspring according to their sire. Female ability to bias paternity after a first mating has been demonstrated in a few species, but unambiguous evidence remains limited by the access to complex behaviours, sperm storage organs and fertilization processes within females. Even when found at the phenotypic level, the potential evolution of any mechanism allowing females to bias paternity other than mate choice remains little explored. Using a large population of pedigreed females, we developed a simple test to determine whether there is additive genetic variation in female ability to bias paternity after a first, chosen, mating. We applied this method in the highly polyandrous Drosophila serrata, giving females the opportunity to successively mate with two males ad libitum. We found that despite high levels of polyandry (females mated more than once per day), the first mate choice was a significant predictor of male total reproductive success. Importantly, there was no detectable genetic variance in female ability to bias paternity beyond mate choice. Therefore, whether or not females can bias paternity before or after copulation, their role on the evolution of sexual male traits is likely to be limited to their first mate choice in D. serrata.

  8. Statins Have No Additional Benefit for Pulmonary Hypertension: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Wang, Lin; Qu, Moying; Chen, Yao; Zhou, Yaxiong; Wan, Zhi

    2016-01-01

    Objectives We performed a meta-analysis to explore the effects of adding statins to standard treatment on adult patients of pulmonary hypertension (PH). Methods A systematic search up to December, 2015 of Medline, EMBASE, Cochrane Database of Systematic reviews and Cochrane Central Register of Controlled Trials was performed to identify randomized controlled trials with PH patients treated with statins. Results Five studies involving 425 patients were included into this meta-analysis. The results of our analysis showed that the statins can’t significantly increase 6-minute walking distance (6MWD, mean difference [MD] = -0.33 [CI: -18.25 to 17.59]), decrease the BORG dyspnea score (MD = -0.72 [CI: -2.28 to 0.85]), the clinical worsening risk (11% in statins vs. 10.1% in controls, Risk ratio = 1.06 [CI: 0.61, 1.83]), or the systolic pulmonary arterial pressure (SPAP) (MD = -0.72 [CI: -2.28 to 0.85]). Subgroup analysis for PH due to COPD or non-COPD also showed no significance. Conclusions Statins have no additional beneficial effect on standard therapy for PH, but the results from subgroup of PH due to COPD seem intriguing and further study with larger sample size and longer follow-up is suggested. PMID:27992469

  9. Regression analysis of mixed recurrent-event and panel-count data with additive rate models.

    PubMed

    Zhu, Liang; Zhao, Hui; Sun, Jianguo; Leisenring, Wendy; Robison, Leslie L

    2015-03-01

    Event-history studies of recurrent events are often conducted in fields such as demography, epidemiology, medicine, and social sciences (Cook and Lawless, 2007, The Statistical Analysis of Recurrent Events. New York: Springer-Verlag; Zhao et al., 2011, Test 20, 1-42). For such analysis, two types of data have been extensively investigated: recurrent-event data and panel-count data. However, in practice, one may face a third type of data, mixed recurrent-event and panel-count data or mixed event-history data. Such data occur if some study subjects are monitored or observed continuously and thus provide recurrent-event data, while the others are observed only at discrete times and hence give only panel-count data. A more general situation is that each subject is observed continuously over certain time periods but only at discrete times over other time periods. There exists little literature on the analysis of such mixed data except that published by Zhu et al. (2013, Statistics in Medicine 32, 1954-1963). In this article, we consider the regression analysis of mixed data using the additive rate model and develop some estimating equation-based approaches to estimate the regression parameters of interest. Both finite sample and asymptotic properties of the resulting estimators are established, and the numerical studies suggest that the proposed methodology works well for practical situations. The approach is applied to a Childhood Cancer Survivor Study that motivated this study.

  10. Additive-dominance genetic model analyses for late-maturity alpha-amylase activity in a bread wheat factorial crossing population.

    PubMed

    Rasul, Golam; Glover, Karl D; Krishnan, Padmanaban G; Wu, Jixiang; Berzonsky, William A; Ibrahim, Amir M H

    2015-12-01

    Elevated level of late maturity α-amylase activity (LMAA) can result in low falling number scores, reduced grain quality, and downgrade of wheat (Triticum aestivum L.) class. A mating population was developed by crossing parents with different levels of LMAA. The F2 and F3 hybrids and their parents were evaluated for LMAA, and data were analyzed using the R software package 'qgtools' integrated with an additive-dominance genetic model and a mixed linear model approach. Simulated results showed high testing powers for additive and additive × environment variances, and comparatively low powers for dominance and dominance × environment variances. All variance components and their proportions to the phenotypic variance for the parents and hybrids were significant except for the dominance × environment variance. The estimated narrow-sense heritability and broad-sense heritability for LMAA were 14 and 54%, respectively. High significant negative additive effects for parents suggest that spring wheat cultivars 'Lancer' and 'Chester' can serve as good general combiners, and that 'Kinsman' and 'Seri-82' had negative specific combining ability in some hybrids despite of their own significant positive additive effects, suggesting they can be used as parents to reduce LMAA levels. Seri-82 showed very good general combining ability effect when used as a male parent, indicating the importance of reciprocal effects. High significant negative dominance effects and high-parent heterosis for hybrids demonstrated that the specific hybrid combinations; Chester × Kinsman, 'Lerma52' × Lancer, Lerma52 × 'LoSprout' and 'Janz' × Seri-82 could be generated to produce cultivars with significantly reduced LMAA level.

  11. Development of a Fluidigm SNP panel for genetic analysis in rainbow trout

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although microsatellite markers have been widely used in aquaculture species for genetic analysis such as parentage assignment and genetic mapping, SNPs (single nucleotide polymorphism) are the marker of choice as they are highly abundant and are amenable for high throughput genotyping. Recently we ...

  12. A Behaviour-Genetic Analysis of Orthographic Learning, Spelling and Decoding

    ERIC Educational Resources Information Center

    Byrne, Brian; Coventry, William L.; Olson, Richard K.; Hulslander, Jacqueline; Wadsworth, Sally; DeFries, John C.; Corley, Robin; Willcutt, Erik G.; Samuelsson, Stefan

    2008-01-01

    As part of a longitudinal twin study of literacy and language, we conducted a behaviour-genetic analysis of orthographic learning, spelling and decoding in Grade 2 children (225 identical and 214 fraternal twin pairs) in the United States and Australia. Each variable showed significant genetic and unique environment influences. Multivariate…

  13. Genetic Analysis of Recombinant Inbred Lines For Sorghum Bicolor x Perennial S. Propinquum.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    From an annual S. bicolor x perennial S. propinquum F2 population used in early-generation genetic analysis, we have produced and describe here a recombinant inbred line (RIL) population of 161 F5 genotypes that segregates for rhizomatousness and many other traits. The genetic map of the recombinant...

  14. A Fully Non-Metallic Gas Turbine Engine Enabled by Additive Manufacturing Part I: System Analysis, Component Identification, Additive Manufacturing, and Testing of Polymer Composites

    NASA Technical Reports Server (NTRS)

    Grady, Joseph E.; Haller, William J.; Poinsatte, Philip E.; Halbig, Michael C.; Schnulo, Sydney L.; Singh, Mrityunjay; Weir, Don; Wali, Natalie; Vinup, Michael; Jones, Michael G.; Patterson, Clark; Santelle, Tom; Mehl, Jeremy

    2015-01-01

    The research and development activities reported in this publication were carried out under NASA Aeronautics Research Institute (NARI) funded project entitled "A Fully Nonmetallic Gas Turbine Engine Enabled by Additive Manufacturing." The objective of the project was to conduct evaluation of emerging materials and manufacturing technologies that will enable fully nonmetallic gas turbine engines. The results of the activities are described in three part report. The first part of the report contains the data and analysis of engine system trade studies, which were carried out to estimate reduction in engine emissions and fuel burn enabled due to advanced materials and manufacturing processes. A number of key engine components were identified in which advanced materials and additive manufacturing processes would provide the most significant benefits to engine operation. The technical scope of activities included an assessment of the feasibility of using additive manufacturing technologies to fabricate gas turbine engine components from polymer and ceramic matrix composites, which were accomplished by fabricating prototype engine components and testing them in simulated engine operating conditions. The manufacturing process parameters were developed and optimized for polymer and ceramic composites (described in detail in the second and third part of the report). A number of prototype components (inlet guide vane (IGV), acoustic liners, engine access door) were additively manufactured using high temperature polymer materials. Ceramic matrix composite components included turbine nozzle components. In addition, IGVs and acoustic liners were tested in simulated engine conditions in test rigs. The test results are reported and discussed in detail.

  15. Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy.

    PubMed

    Carmona, F David; Coit, Patrick; Saruhan-Direskeneli, Güher; Hernández-Rodríguez, José; Cid, María C; Solans, Roser; Castañeda, Santos; Vaglio, Augusto; Direskeneli, Haner; Merkel, Peter A; Boiardi, Luigi; Salvarani, Carlo; González-Gay, Miguel A; Martín, Javier; Sawalha, Amr H

    2017-03-09

    Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.

  16. Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy

    PubMed Central

    Carmona, F. David; Coit, Patrick; Saruhan-Direskeneli, Güher; Hernández-Rodríguez, José; Cid, María C.; Solans, Roser; Castañeda, Santos; Vaglio, Augusto; Direskeneli, Haner; Merkel, Peter A.; Boiardi, Luigi; Salvarani, Carlo; González-Gay, Miguel A.; Martín, Javier; Sawalha, Amr H.; Martínez-Berriochoa, Agustín; Unzurrunzaga, Ainhoa; Hidalgo-Conde, Ana; Vuelta, Ana Belén Madroñero; Fernández-Nebro, Antonio; Ordóñez-Cañizares, M. Carmen; Fernández-Gutiérrez, Benjamín; Rodríguez-Rodríguez, Luis; Escalante, Begoña; Marí-Alfonso, Begoña; Sopeña, Bernardo; Gómez-Vaquero, Carmen; Raya, Enrique; Grau, Elena; Román, José A.; Vicente, Esther F.; de Miguel, Eugenio; López-Longo, Francisco J.; Martínez, Lina; Morado, Inmaculada C.; Díaz-López, J. Bernardino; Caminal-Montero, Luis; Martínez-Zapico, Aleida; Narváez, Javier; Monfort, Jordi; Tío, Laura; Miranda-Filloy, José A.; Sánchez-Martín, Julio; Alegre-Sancho, Juan J.; Sáez-Comet, Luis; Pérez-Conesa, Mercedes; Corbera-Bellalta, Marc; Ramentol-Sintas, Marc; García-Villanueva, María Jesús; Guijarro Rojas, Mercedes; Ortego-Centeno, Norberto; Ríos Fernández, Raquel; Callejas, José Luis; Sanchez Pernaute, Olga; Fanlo Mateo, Patricia; Blanco, Ricardo; Prieto-González, Sergio; Martínez-Taboada, Víctor Manuel; Soriano, Alessandra; Lunardi, Claudio; Gianfreda, Davide; Santilli, Daniele; Bonatti, Francesco; Muratore, Francesco; Pazzola, Giulia; Addimanda, Olga; Emmi, Giacomo; Ramirez, Giuseppe A.; Beretta, Lorenzo; Govoni, Marcello; Cimmino, Marco A.; Mesut Onat, Ahmet; Cefle, Ayse; Yazici, Ayten; Kısacık, Bünyamin; Dalkilic, Ediz; Seyahi, Emire; Fresko, Izzet; Tunc, Ercan; Erken, Eren; TE Ozer, Hüseyin; Aksu, Kenan; Keser, Gokhan; Ozturk, Mehmet A.; Bıcakcıgil, Muge; Duzgun, Nurşen; Karadag, Omer; Kiraz, Sedat; Pamuk, Ömer N.; Akar, Servet; Onen, Fatos; Akkoc, Nurullah; Kamali, Sevil; Inanc, Murat; Yentür, Sibel P.; Aydin, Sibel Z.; Alibaz-Oner, Fatma; Kaşifoğlu, Timuçin; Cobankara, Veli; Ozbalkan, Zeynep; Ates, Askin; Karaaslan, Yasar; Carette, Simon; Chung, Sharon A.; Cuthbertson, David; Forbess, Lindsay J.; Hoffman, Gary S.; Khalidi, Nader A.; Koening, Curry L.; Langford, Carol A.; McAlear, Carol A.; McKinnon-Maksimowicz, Kathleen; Monach, Paul A.; Moreland, Larry; Pagnoux, Christian; Seo, Philip; Spiera, Robert; Sreih, Antoine G.; Warrington, Kenneth J.; Ytterberg, Steven R.

    2017-01-01

    Giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus. PMID:28277489

  17. Genetic analysis on growth and carcass traits in Nelore cattle.

    PubMed

    Zuin, R G; Buzanskas, M E; Caetano, S L; Venturini, G C; Guidolin, D G F; Grossi, D A; Chud, T C S; Paz, C C P; Lôbo, R B; Munari, D P

    2012-07-01

    In this study, the objective was to estimate genetic parameters of body weight at 210 (BW210) and 365 (BW365) days of age in relation to rib eye area (REA), subcutaneous back fat thickness (BF) and rump fat (RF), and their respective genetic trends, in Nelore beef cattle. Estimates of genetic parameters and breeding values for the studied traits were obtained using the REML method. The direct and maternal heritability estimates were respectively: 0.25±0.02 and 0.21±0.01, for BW210, and 0.29±0.02 and 0.09±0.01, for BW365. The heritability estimates for transformed REA, BF and RF were 0.29±0.03, 0.21±0.02 and 0.23±0.03, respectively. There were genetic associations between BW210 and REA, BW365 and REA, and BF and RF, while the other correlations were low. The selection process that was conducted at the farms participating in the breeding program, taking the proposed selection index into consideration, caused genetic changes to these traits.

  18. Genetic Analysis of High Bone Mass Cases from the BARCOS Cohort of Spanish Postmenopausal Women

    PubMed Central

    Urreizti, Roser; Civit, Sergi; Cols, Neus; García-Giralt, Natàlia; Yoskovitz, Guy; Aranguren, Alvaro; Malouf, Jorge; Di Gregorio, Silvana; Río, Luís Del; Güerri, Roberto; Nogués, Xavier; Díez-Pérez, Adolfo; Grinberg, Daniel; Balcells, Susana

    2014-01-01

    The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM. PMID:24736728

  19. Genetic analysis of a novel nidovirus from fathead minnows

    USGS Publications Warehouse

    Batts, William N.; Goodwin, Andrew E.; Winton, James R.

    2012-01-01

    A bacilliform virus was isolated from diseased fathead minnows (Pimephales promelas). Analysis of the complete genome coding for the polyprotein (pp1ab), spike (S), membrane (M) and nucleocapsid (N) proteins revealed that the virus was most like white bream virus (WBV), another bacilliform virus isolated from white bream (Blicca bjoerkna L.) and the type species of the genus Bafinivirus within the order Nidovirales. In addition to similar gene order and size, alignment of deduced amino acid sequences of the pp1ab, M, N and S proteins of the fathead minnow nidovirus (FHMNV) with those of WBV showed 46, 44, 39 and 15 % identities, respectively. Phylogenetic analysis using the conserved helicase domain of the replicase showed FHMNV was distinct from WBV, yet the closest relative identified to date. Thus, FHMNV appears to represent a second species in the genus Bafinivirus. A PCR assay was developed for the identification of future FHMNV-like isolates.

  20. Genetic analysis of calving traits by the multi-trait individual animal model.

    PubMed

    Weller, J I; Ezra, E

    2016-01-01

    Five alternative models were applied for analysis of dystocia and stillbirth in first and second parities. Models 1 and 2 were included only to estimate the parameters required for model 4, and models 3 and 5 are included only as comparisons to the model 4 estimates. Variance components were estimated by multi-trait REML, including cows with valid calving records for both parities. For the effects of sire of calf on first and second parities, variance components were estimated including only calvings with the same sire of calf for both parities. All heritabilities for the cow effect were quite low, but higher for dystocia than for stillbirth and higher in first parity. The sire-of-calf heritabilities were higher than the cow effect heritabilities, except for stillbirth in parity 2. Unlike the effect of cow correlations, all sire of calf correlations were >0.6, and the correlations for the same trait in parities 1 and 2 were >0.9. Thus, a multi-trait analysis should yield a significant gain in accuracy with respect to the sire of calf effects for bulls not mated to virgin heifers. A multi-trait individual animal model algorithm was developed for joint analysis of dystocia and stillbirth in first and second parities. Relationships matrices were included both for the effects of cow and sire of calf. In addition, random herd-year-season and fixed sex of calf effects were included in the model. Records were preadjusted for calving month and age. A total of 899,223 Israeli Holstein cows with first calvings since 1985 were included in the complete analysis. Approximate reliabilities were computed for both sire of cow and sire of calf effects. Correlations between these reliabilities and reliabilities obtained by direct inversion of the coefficient matrix for a sire of cow-sire of calf model were all close to 0.99. Phenotypic trends for cows born from 1983 through 2007 were economically unfavorable for dystocia and favorable for stillbirth in both parities. Genetic trends

  1. Variogram Analysis of the Spatial Genetic Structure of Continuous Populations Using Multilocus Microsatellite Data

    PubMed Central

    Wagner, Helene H.; Holderegger, Rolf; Werth, Silke; Gugerli, Felix; Hoebee, Susan E.; Scheidegger, Christoph

    2005-01-01

    A geostatistical perspective on spatial genetic structure may explain methodological issues of quantifying spatial genetic structure and suggest new approaches to addressing them. We use a variogram approach to (i) derive a spatial partitioning of molecular variance, gene diversity, and genotypic diversity for microsatellite data under the infinite allele model (IAM) and the stepwise mutation model (SMM), (ii) develop a weighting of sampling units to reflect ploidy levels or multiple sampling of genets, and (iii) show how variograms summarize the spatial genetic structure within a population under isolation-by-distance. The methods are illustrated with data from a population of the epiphytic lichen Lobaria pulmonaria, using six microsatellite markers. Variogram-based analysis not only avoids bias due to the underestimation of population variance in the presence of spatial autocorrelation, but also provides estimates of population genetic diversity and the degree and extent of spatial genetic structure accounting for autocorrelation. PMID:15654102

  2. Informed consent, participation in, and withdrawal from a population based cohort study involving genetic analysis

    PubMed Central

    Matsui, K; Kita, Y; Ueshima, H

    2005-01-01

    Design: Descriptive analyses. Setting and participants: The study evaluated two non-genetic subcohorts comprising 3166 people attending for a health checkup during 2002, and two genetic subcohorts comprising 2195 people who underwent a checkup during 2003. Main outcome measurements: Analysis endpoints were differences in participation rates between the non-genetic and genetic subcohorts, differences between providing non-extensive and extensive preliminary information, and changes in participation status between baseline and at 6 months. Results: Participation rates in the genetic subcohorts were 4·7–9·3% lower than those in the non-genetic subcohorts. The odds ratios (OR) of participation in genetic research were between 0·60 and 0·77, and the OR for withdrawal from the research was over 7·70; providing preliminary extensive information about genetic research reduced the withdrawal risks (OR 0·15 for all dependent variables) but worsened participation rates (OR 0·63–0·74). Conclusions: The general population responded sceptically towards genetic research. It is crucial that genetic researchers utilise an informative and educational consent process worthy of public trust. PMID:15994356

  3. A multivariate analysis of genetic variation in the advertisement call of the gray treefrog, Hyla versicolor.

    PubMed

    Welch, Allison M; Smith, Michael J; Gerhardt, H Carl

    2014-06-01

    Genetic variation in sexual displays is crucial for an evolutionary response to sexual selection, but can be eroded by strong selection. Identifying the magnitude and sources of additive genetic variance underlying sexually selected traits is thus an important issue in evolutionary biology. We conducted a quantitative genetics experiment with gray treefrogs (Hyla versicolor) to investigate genetic variances and covariances among features of the male advertisement call. Two energetically expensive traits showed significant genetic variation: call duration, expressed as number of pulses per call, and call rate, represented by its inverse, call period. These two properties also showed significant genetic covariance, consistent with an energetic constraint to call production. Combining the genetic variance-covariance matrix with previous estimates of directional sexual selection imposed by female preferences predicts a limited increase in call duration but no change in call rate despite significant selection on both traits. In addition to constraints imposed by the genetic covariance structure, an evolutionary response to sexual selection may also be limited by high energetic costs of long-duration calls and by preferences that act most strongly against very short-duration calls. Meanwhile, the persistence of these preferences could be explained by costs of mating with males with especially unattractive calls.

  4. Genetically encoded optical indicators for the analysis of neuronal circuits.

    PubMed

    Knöpfel, Thomas

    2012-10-01

    In a departure from previous top-down or bottom-up strategies used to understand neuronal circuits, many forward-looking research programs now place the circuit itself at their centre. This has led to an emphasis on the dissection and elucidation of neuronal circuit elements and mechanisms, and on studies that ask how these circuits generate behavioural outputs. This movement towards circuit-centric strategies is progressing rapidly as a result of technological advances that combine genetic manipulation with light-based methods. The core tools of these new approaches are genetically encoded optical indicators and actuators that enable non-destructive interrogation and manipulation of neuronal circuits in behaving animals with cellular-level precision. This Review examines genetically encoded reporters of neuronal function and assesses their value for circuit-oriented neuroscientific investigations.

  5. The genetic analysis of tolerance to infections: a review

    PubMed Central

    Kause, Antti; Ødegård, Jørgen

    2012-01-01

    Tolerance to infections is defined as the ability of a host to limit the impact of a given pathogen burden on host performance. Uncoupling resistance and tolerance is a challenge, and there is a need to be able to separate them using specific trait recording or statistical methods. We present three statistical methods that can be used to investigate genetics of tolerance-related traits. Firstly, using random regressions, tolerance can be analyzed as a reaction norm slope in which host performance (y-axis) is regressed against an increasing pathogen burden (x-axis). Genetic variance in tolerance slopes is the genetic variance for tolerance. Variation in tolerance can induce genotype re-ranking and changes in genetic and phenotypic variation in host performance along the pathogen burden trajectory, contributing to environment-dependent genetic responses to selection. Such genotype-by-environment interactions can be quantified by combining random regressions and covariance functions. To apply random regressions, pathogen burden of individuals needs to be recorded. Secondly, when pathogen burden is not recorded, the cure model for time-until-death data allows separating two traits, susceptibility and endurance. Susceptibility is whether or not an individual was susceptible to an infection, whereas endurance denotes how long time it took until the infection killed a susceptible animal (influenced by tolerance). Thirdly, the normal mixture model can be used to classify continuously distributed host performance, such as growth rate, into different sub-classes (e.g., non-infected and infected), which allows estimation of host performance reduction specific to infected individuals. Moreover, genetics of host performance can be analyzed separately in healthy and affected animals, even in the absence of pathogen burden and survival data. These methods provide novel tools to increase our understanding on the impact of parasites, pathogens, and production diseases on host

  6. Genome-wide genetic diversity, population structure and admixture analysis in African and Asian cattle breeds.

    PubMed

    Edea, Z; Bhuiyan, M S A; Dessie, T; Rothschild, M F; Dadi, H; Kim, K S

    2015-02-01

    Knowledge about genetic diversity and population structure is useful for designing effective strategies to improve the production, management and conservation of farm animal genetic resources. Here, we present a comprehensive genome-wide analysis of genetic diversity, population structure and admixture based on 244 animals sampled from 10 cattle populations in Asia and Africa and genotyped for 69,903 autosomal single-nucleotide polymorphisms (SNPs) mainly derived from the indicine breed. Principal component analysis, STRUCTURE and distance analysis from high-density SNP data clearly revealed that the largest genetic difference occurred between the two domestic lineages (taurine and indicine), whereas Ethiopian cattle populations represent a mosaic of the humped zebu and taurine. Estimation of the genetic influence of zebu and taurine revealed that Ethiopian cattle were characterized by considerable levels of introgression from South Asian zebu, whereas Bangladeshi populations shared very low taurine ancestry. The relationships among Ethiopian cattle populations reflect their history of origin and admixture rather than phenotype-based distinctions. The high within-individual genetic variability observed in Ethiopian cattle represents an untapped opportunity for adaptation to changing environments and for implementation of within-breed genetic improvement schemes. Our results provide a basis for future applications of genome-wide SNP data to exploit the unique genetic makeup of indigenous cattle breeds and to facilitate their improvement and conservation.

  7. Genetic relatedness analysis: modern data and new challenges.

    PubMed

    Weir, Bruce S; Anderson, Amy D; Hepler, Amanda B

    2006-10-01

    Individuals who belong to the same family or the same population are related because of their shared ancestry. Population and quantitative genetics theory is built with parameters that describe relatedness, and the estimation of these parameters from genetic markers enables progress in fields as disparate as plant breeding, human disease gene mapping and forensic science. The large number of multiallelic microsatellite loci and biallelic SNPs that are now available have markedly increased the precision with which relationships can be estimated, although they have also revealed unexpected levels of genomic heterogeneity of relationship measures.

  8. Genetic Polymorphisms Involved in Folate Metabolism and Maternal Risk for Down Syndrome: A Meta-Analysis

    PubMed Central

    Balduino Victorino, Daniella; de Godoy, Moacir Fernandes; Goloni-Bertollo, Eny Maria; Pavarino, Érika Cristina

    2014-01-01

    Inconclusive results of the association between genetic polymorphisms involved in folate metabolism and maternal risk for Down syndrome (DS) have been reported. Therefore, this meta-analysis was conducted. We searched electronic databases through May, 2014, for eligible studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association, which was estimated by fixed or random effects models. Heterogeneity among studies was evaluated using Q-test and I2 statistic. Subgroup and sensitivity analyses were also conducted. Publication bias was estimated using Begg's and Egger's tests. A total of 17 case-controls studies were included. There was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS. In the subgroup analysis, increased maternal risk for DS was found in Caucasians. Additionally, the polymorphic heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.844ins68, no significant associations have been found, neither in the overall analyses nor in the stratified analyses by ethnicity. In conclusion, our meta-analysis suggested that the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS. PMID:25544792

  9. Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination.

    PubMed

    Woodman, Andrew; Arnold, Jamie J; Cameron, Craig E; Evans, David J

    2016-08-19

    Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3' non-coding region we have further developed a cell-based assay (the 3'CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process.

  10. Analysis to Estimate Genetic Variations in the Idarubicin-Resistant Derivative MOLT-3

    PubMed Central

    Komiyama, Tomoyoshi; Ogura, Atsushi; Hirokawa, Takatsugu; Zhijing, Miao; Kamiguchi, Hiroshi; Asai, Satomi; Miyachi, Hayato; Kobayashi, Hiroyuki

    2016-01-01

    Gene alterations are a well-established mechanism leading to drug resistance in acute leukemia cells. A full understanding of the mechanisms of drug resistance in these cells will facilitate more effective chemotherapy. In this study, we investigated the mechanism(s) of drug resistance in the human acute leukemia cell line MOLT-3 and its idarubicin-resistant derivative MOLT-3/IDR through complete mitochondrial and nuclear DNA analyses. We identified genetic differences between these two cell lines. The ND3 mutation site (p.Thr61Ile) in the mitochondrial DNA sequence was unique to MOLT-3/IDR cells. Moreover, we identified five candidate genes harboring genetic alterations, including GALNT2, via CGH array analysis. Sequencing of the GALNT2 exon revealed a G1716K mutation present within the stop codon in MOLT-3/IDR cells but absent from MOLT-3 cells. This mutation led to an additional 18 amino acids in the protein encoded by GALNT2. Using real-time PCR, we determined an expression value for this gene of 0.35. Protein structure predictions confirmed a structural change in GALNT2 in MOLT-3/IDR cells that corresponded to the site of the mutation. We speculate that this mutation may be related to idarubicin resistance. PMID:28025493

  11. Meta-analysis and genome-wide interpretation of genetic susceptibility to drug addiction

    PubMed Central

    2011-01-01

    Background Classical genetic studies provide strong evidence for heritable contributions to susceptibility to developing dependence on addictive substances. Candidate gene and genome-wide association studies (GWAS) have sought genes, chromosomal regions and allelic variants likely to contribute to susceptibility to drug addiction. Results Here, we performed a meta-analysis of addiction candidate gene association studies and GWAS to investigate possible functional mechanisms associated with addiction susceptibility. From meta-data retrieved from 212 publications on candidate gene association studies and 5 GWAS reports, we linked a total of 843 haplotypes to addiction susceptibility. We mapped the SNPs in these haplotypes to functional and regulatory elements in the genome and estimated the magnitude of the contributions of different molecular mechanisms to their effects on addiction susceptibility. In addition to SNPs in coding regions, these data suggest that haplotypes in gene regulatory regions may also contribute to addiction susceptibility. When we compared the lists of genes identified by association studies and those identified by molecular biological studies of drug-regulated genes, we observed significantly higher participation in the same gene interaction networks than expected by chance, despite little overlap between the two gene lists. Conclusions These results appear to offer new insights into the genetic factors underlying drug addiction. PMID:21999673

  12. K-mer natural vector and its application to the phylogenetic analysis of genetic sequences

    PubMed Central

    Wen, Jia; Chan, Raymond H.; Yau, Shek-Chung; He, Rong L.; Yau, Stephen S. T.

    2014-01-01

    Based on the well-known k-mer model, we propose a k-mer natural vector model for representing a genetic sequence based on the numbers and distributions of k-mers in the sequence. We show that there exists a one-to-one correspondence between a genetic sequence and its associated k-mer natural vector. The k-mer natural vector method can be easily and quickly used to perform phylogenetic analysis of genetic sequences without requiring evolutionary models or human intervention. Whole or partial genomes can be handled more effective with our proposed method. It is applied to the phylogenetic analysis of genetic sequences, and the obtaining results fully demonstrate that the k-mer natural vector method is a very powerful tool for analysing and annotating genetic sequences and determining evolutionary relationships both in terms of accuracy and efficiency. PMID:24858075

  13. Molecular marker-based genetic diversity analysis of scantly studied Brazilian accessions of a medicinal plant, Morinda citrifolia L. (noni).

    PubMed

    Bordallo, P N; Monteiro, A M R; Sousa, J A; Aragão, F A S

    2017-02-23

    Morinda citrifolia L., commonly known as noni, has been used for the treatment of various diseases for over two centuries. It was introduced and widely disseminated in Brazil because of its high market value and ease of adaptation to the soil and climatic conditions of the country. The aim of this study was to estimate the genetic variability of noni accessions from the collection of Embrapa Agroindústria Tropical in Brazil. We evaluated 36 plants of the 13 accessions of noni from the germplasm collection of M. citrifolia. Several methods of DNA extraction were tested. After definition of the method, the DNA of each sample was subjected to polymerase chain reactions using 20 random amplified polymorphic DNA primers. The band patterns on agarose gel were converted into a binary data matrix, which was used to estimate the genetic distances between the plants and to perform the cluster analyses. Of the total number of markers used in this study, 125 (81.1%) were polymorphic. The genetic distances between the genotypes ranged from 0.04 to 0.49. Regardless of the high number of polymorphic bands, the genetic variability of the noni plants evaluated was low since most of the genotypes belonged to the same cluster as shown by the dendrogram and Tocher's cluster analysis. The low genetic diversity among the studied noni individuals indicates that additional variability should be introduced in the germplasm collection of noni by gathering new individuals and/or by hybridizing contrasting individuals.

  14. Analysis of Genetic Diversity and Population Structure of Sesame Accessions from Africa and Asia as Major Centers of Its Cultivation

    PubMed Central

    Dossa, Komivi; Wei, Xin; Zhang, Yanxin; Fonceka, Daniel; Yang, Wenjuan; Diouf, Diaga; Liao, Boshou; Cissé, Ndiaga; Zhang, Xiurong

    2016-01-01

    Sesame is an important oil crop widely cultivated in Africa and Asia. Understanding the genetic diversity of accessions from these continents is critical to designing breeding methods and for additional collection of sesame germplasm. To determine the genetic diversity in relation to geographical regions, 96 sesame accessions collected from 22 countries distributed over six geographic regions in Africa and Asia were genotyped using 33 polymorphic SSR markers. Large genetic variability was found within the germplasm collection. The total number of alleles was 137, averaging 4.15 alleles per locus. The accessions from Asia displayed more diversity than those from Africa. Accessions from Southern Asia (SAs), Eastern Asia (EAs), and Western Africa (WAf) were highly diversified, while those from Western Asia (WAs), Northern Africa (NAf), and Southeastern Africa (SAf) had the lowest diversity. The analysis of molecular variance revealed that more than 44% of the genetic variance was due to diversity among geographic regions. Five subpopulations, including three in Asia and two in Africa, were cross-identified through phylogenetic, PCA, and STRUCTURE analyses. Most accessions clustered in the same population based on their geographical origins. Our results provide technical guidance for efficient management of sesame genetic resources in breeding programs and further collection of sesame germplasm from these different regions. PMID:27077887

  15. Analysis of Genetic Diversity and Population Structure of Sesame Accessions from Africa and Asia as Major Centers of Its Cultivation.

    PubMed

    Dossa, Komivi; Wei, Xin; Zhang, Yanxin; Fonceka, Daniel; Yang, Wenjuan; Diouf, Diaga; Liao, Boshou; Cissé, Ndiaga; Zhang, Xiurong

    2016-04-12

    Sesame is an important oil crop widely cultivated in Africa and Asia. Understanding the genetic diversity of accessions from these continents is critical to designing breeding methods and for additional collection of sesame germplasm. To determine the genetic diversity in relation to geographical regions, 96 sesame accessions collected from 22 countries distributed over six geographic regions in Africa and Asia were genotyped using 33 polymorphic SSR markers. Large genetic variability was found within the germplasm collection. The total number of alleles was 137, averaging 4.15 alleles per locus. The accessions from Asia displayed more diversity than those from Africa. Accessions from Southern Asia (SAs), Eastern Asia (EAs), and Western Africa (WAf) were highly diversified, while those from Western Asia (WAs), Northern Africa (NAf), and Southeastern Africa (SAf) had the lowest diversity. The analysis of molecular variance revealed that more than 44% of the genetic variance was due to diversity among geographic regions. Five subpopulations, including three in Asia and two in Africa, were cross-identified through phylogenetic, PCA, and STRUCTURE analyses. Most accessions clustered in the same population based on their geographical origins. Our results provide technical guidance for efficient management of sesame genetic resources in breeding programs and further collection of sesame germplasm from these different regions.

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

    PubMed

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

    2017-03-01

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

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

    PubMed Central

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

    2017-01-01

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

  18. fullfact: an R package for the analysis of genetic and maternal variance components from full factorial mating designs.

    PubMed

    Houde, Aimee Lee S; Pitcher, Trevor E

    2016-03-01

    Full factorial breeding designs are useful for quantifying the amount of additive genetic, nonadditive genetic, and maternal variance that explain phenotypic traits. Such variance estimates are important for examining evolutionary potential. Traditionally, full factorial mating designs have been analyzed using a two-way analysis of variance, which may produce negative variance values and is not suited for unbalanced designs. Mixed-effects models do not produce negative variance values and are suited for unbalanced designs. However, extracting the variance components, calculating significance values, and estimating confidence intervals and/or power values for the components are not straightforward using traditional analytic methods. We introduce fullfact - an R package that addresses these issues and facilitates the analysis of full factorial mating designs with mixed-effects models. Here, we summarize the functions of the fullfact package. The observed data functions extract the variance explained by random and fixed effects and provide their significance. We then calculate the additive genetic, nonadditive genetic, and maternal variance components explaining the phenotype. In particular, we integrate nonnormal error structures for estimating these components for nonnormal data types. The resampled data functions are used to produce bootstrap-t confidence intervals, which can then be plotted using a simple function. We explore the fullfact package through a worked example. This package will facilitate the analyses of full factorial mating designs in R, especially for the analysis of binary, proportion, and/or count data types and for the ability to incorporate additional random and fixed effects and power analyses.

  19. Genetic characterization and phylogenic analysis of H5N1 avian influenza virus detected in peafowl in Kirkuk province, Iraq.

    PubMed

    Rashid, Peshnyar M A; Saeed, Nahla M; Dyary, Hiewa Othman

    2016-12-30

    A highly pathogenic avian influenza (HPAI), H5N1, was detected for the first time in peafowls in Kirkuk province, Iraq in 2015. Genetic analysis of the Kirkuk H5N1 indicated molecular markers for avian-type receptors. The Kirkuk H5N1 hemagglutinin gene had an infrequent amino acid cleavage site (SPQREKRRKRGLF), and neuraminidase genes showed sensitive molecular markers for antiviral drugs. Additionally, the phylogenetic analysis found that the Kirkuk H5N1 belonged to subclade 2.3.2.1c. Our results showed that the 2015 H5N1 from the Iraqi city of Kirkuk exhibited new genetic characterization and was different from the 2006 H5N1 isolate from Iraq.

  20. Genetic variation frequencies in Wilms' tumor: A meta-analysis and systematic review.

    PubMed

    Deng, Changkai; Dai, Rong; Li, Xuliang; Liu, Feng

    2016-05-01

    Over the last few decades, numerous biomarkers in Wilms' tumor have been confirmed and shown variations in prevalence. Most of these studies were based on small sample sizes. We carried out a meta-analysis of the research published from 1992 to 2015 to obtain more precise and comprehensive outcomes for genetic tests. In the present study, 70 out of 5175 published reports were eligible for the meta-analysis, which was carried out using Stata 12.0 software. Pooled prevalence for gene mutations WT1, WTX, CTNNB1, TP53, MYCN, DROSHA, and DGCR8 was 0.141 (0.104, 0.178), 0.147 (0.110, 0.184), 0.140 (0.100, 0.190), 0.410 (0.214, 0.605), 0.071 (0.041, 0.100), 0.082 (0.048, 0.116), and 0.036 (0.026, 0.046), respectively. Pooled prevalence of loss of heterozygosity at 1p, 11p, 11q, 16q, and 22q was 0.109 (0.084, 0.133), 0.334 (0.295, 0.373), 0.199 (0.146, 0.252), 0.151 (0.129, 0.172), and 0.148 (0.108, 0.189), respectively. Pooled prevalence of 1q and chromosome 12 gain was 0.218 (0.161, 0.275) and 0.273 (0.195, 0.350), respectively. The limited prevalence of currently known genetic alterations in Wilms' tumors indicates that significant drivers of initiation and progression remain to be discovered. Subgroup analyses indicated that ethnicity may be one of the sources of heterogeneity. However, in meta-regression analyses, no study-level characteristics of indicators were found to be significant. In addition, the findings of our sensitivity analysis and possible publication bias remind us to interpret results with caution.

  1. Genetic analysis of Trichinella populations by 'cold' single-strand conformation polymorphism analysis.

    PubMed

    Gasser, Robin B; Hu, Min; El-Osta, Youssef Abs; Zarlenga, Dante S; Pozio, Edoardo

    2005-09-05

    A non-isotopic single-strand conformation polymorphism ('cold' SSCP) technique has been assessed for the analysis of sequence variability in the expansion segment 5 (ES5) of domain IV and the D3 domain of nuclear ribosomal DNA within and/or among isolates and individual muscle (first-stage) larvae representing all currently recognized species/genotypes of Trichinella. Data are consistent with the ability of cold SSCP to identify intra-specific as well as inter-specific variability among Trichinella genotypes. The cold SSCP approach should be applicable to a range of other genetic markers for comparative studies of Trichinella populations globally.

  2. Genetic and biochemical analysis of solvent formation in Clostridium acetobutylicum

    SciTech Connect

    Bennett, G.N.; Rudolph, F.B.

    1998-05-01

    The anaerobic organism Clostridium acetobutylicum has been used for commercial production of important organic solvents due to its ability to convert a wide variety of crude substrates to acids and alcohols. Current knowledge concerning the molecular genetics, cell regulation and metabolic engineering of this organism is still rather limited. The objectives are to improve the knowledge of the molecular genetics and enzymology of Clostridia in order to make genetic alterations which will more effectively channel cell metabolism toward production of desired products. Two factors that limit butanol production in continuous cultures are: (1) The degeneration of the culture, with an increase in the proportion of cells which are incapable of solvent production. Currently isolated degenerate strains are being evaluated to analyze the molecular mechanism of degeneration to determine if it is due to a genetic loss of solvent related genes, loss of a regulatory element, or an increase in general mutagenesis. Recent studies show two general types of degenerates, one which seems to have lost essential solvent pathway genes and another which has not completely lost all solvent production capability and retains the DNA bearing solvent pathway genes. (2) The production of hydrogen which uses up reducing equivalents in the cell. If the reducing power were more fully directed to the reduction reactions involved in butanol production, the process would be more efficient. The authors have studied oxidation reduction systems related to this process. These studies focus on ferredoxin and rubredoxin and their oxidoreductases.

  3. Understanding Genetics: Analysis of Secondary Students' Conceptual Status

    ERIC Educational Resources Information Center

    Tsui, Chi-Yan; Treagust, David F.

    2007-01-01

    This article explores the conceptual change of students in Grades 10 and 12 in three Australian senior high schools when the teachers included computer multimedia to a greater or lesser extent in their teaching of a genetics course. The study, underpinned by a multidimensional conceptual-change framework, used an interpretive approach and a…

  4. Antioxidant value addition in human diets: genetic transformation of Brassica juncea with gamma-TMT gene for increased alpha-tocopherol content.

    PubMed

    Yusuf, Mohd Aslam; Sarin, Neera Bhalla

    2007-02-01

    Alpha-tocopherol, the most biologically active form of vitamin E, is implicated in decreasing the risk of several types of cancers, coronary heart disease and a number of degenerative human conditions, when taken in excess of the recommended daily allowance. Natural alpha-tocopherol has twice the bioavailability of the synthetic isomer. This study describes a successful attempt at fortifying human diets with natural alpha-tocopherol by taking recourse to genetic engineering of an important oilseed crop, Brassica juncea. Gamma-tocopherol methyl transferase cDNA from Arabidopsis thaliana, coding for the enzyme catalysing the conversion of the large gamma-tocopherol pool to alpha-tocopherol, was overexpressed in B. juncea plants. The successful integration of the transgene was confirmed by PCR and Southern blot analysis, while the enhanced transcript level was evident in the northern blot analysis. HPLC analysis of the seeds of the T1 transgenic lines showed a shift in tocopherol profile with the highest over-expressors having alpha-tocopherol levels as high as sixfold over the non-transgenic controls. This study discusses the production of a transgenic oilseed crop with high alpha-tocopherol levels, which can provide a feasible, innocuous, and inexpensive way of taking the beneficial effects of high alpha-tocopherol intake to the masses.

  5. Additional Keplerian Signals in the HARPS data for Gliese 667C: Further Analysis

    NASA Astrophysics Data System (ADS)

    Gregory, Philip C.; Lawler, Samantha M.; Gladman, Brett

    2014-01-01

    A re-analysis of Gliese 667C HARPS precision radial velocity data was carried out with a Bayesian multi-planet Kepler periodogram (from 0 to 7 planets) based on a fusion Markov chain Monte Carlo algorithm. The most probable number of signals detected is six with a Bayesian false alarm probability of 0.012. The residuals were shown to be consistent with white noise. The six signals detected include two previously reported with periods of 7.198 (b) and 28.14 (c) days, plus additional periods of 30.82, 38.82, 53.22, and 91.3 days. The existence of these Keplerian-like signals suggest the possibility of additional planets in the habitable zone of Gl 667C although some of the signals could be artifacts arising from the sampling or stellar surface activity. N-body orbital integrations are being undertaken to determine which of these signals are consistent with a stable planetary system. Preliminary results demonstrate that four of the signals, with periods of 7.2, 28.1, 38.8, & 91 d, are consistent with a stable 4 planet system on time scales of 107 yr. The M sin i values are ~5.5, 4.4, 1.9, and 4.7 M⊕, respectively.

  6. An analysis of candidates for addition to the Clean Air Act list of hazardous air pollutants.

    PubMed

    Lunder, Sonya; Woodruff, Tracey J; Axelrad, Daniel A

    2004-02-01

    There are 188 air toxics listed as hazardous air pollutants (HAPs) in the Clean Air Act (CAA), based on their potential to adversely impact public health. This paper presents several analyses performed to screen potential candidates for addition to the HAPs list. We analyzed 1086 HAPs and potential HAPs, including chemicals regulated by the state of California or with emissions reported to the Toxics Release Inventory (TRI). HAPs and potential HAPs were ranked by their emissions to air, and by toxicity-weighted (tox-wtd) emissions for cancer and noncancer, using emissions information from the TRI and toxicity information from state and federal agencies. Separate consideration was given for persistent, bioaccumulative toxins (PBTs), reproductive or developmental toxins, and chemicals under evaluation for regulation as toxic air contaminants in California. Forty-four pollutants were identified as candidate HAPs based on three ranking analyses and whether they were a PBT or a reproductive or developmental toxin. Of these, nine qualified in two or three different rankings (ammonia [NH3], copper [Cu], Cu compounds, nitric acid [HNO3], N-methyl-2-pyrrolidone, sulfuric acid [H2SO4], vanadium [V] compounds, zinc [Zn], and Zn compounds). This analysis suggests further evaluation of several pollutants for possible addition to the CAA list of HAPs.

  7. The genetic impact of demographic decline and reintroduction in the wild boar (Sus scrofa): a microsatellite analysis.

    PubMed

    Vernesi, C; Crestanello, B; Pecchioli, E; Tartari, D; Caramelli, D; Hauffe, H; Bertorelle, G

    2003-03-01

    The reintroduction of wild boar from central Europe after World War II has contributed substantially to the range expansion of this species in Italy, where indiscriminate hunting in earlier times resulted in extreme demographic reduction. However, the genetic impact of such processes is not well-understood. In this study, 105 individuals from Italian and Hungarian wild boar populations were characterized for nine autosomal microsatellite loci. The Hungarian samples, and two central Italian samples from protected areas (parks) where reintroduction is not documented, were assumed to be representative of the genetic composition of the source and the target populations in the reintroduction process, respectively. Animals hunted in the wild in the Florence area of Tuscany (Italy) were then studied to identify the effects of reintroduction. The results we obtained can be summarized as follows: (i) none of the populations analysed shows genetic evidence of demographic decline; (ii) the three parental populations from Italy and Hungary are genetically distinct; however, the low level of divergence appears in conflict with the naming of the Italian and the European subspecies (Sus scrofa majori and Sus scrofa scrofa, respectively); in addition, the Italian groups appear to be as divergent from each other as they are from the Hungarian population; (iii) most of the individuals hunted near Florence are genetically intermediate between the parental groups, suggesting that hybridization has occurred in this area, the average introgression of Hungarian genotypes is 13%, but approximately 45% of the genetic pool of these individuals can not be directly attributed to any of the parental populations we analysed; (iv) analysis of microsatellite loci, though in a limited number, is an important tool for estimating the genetic effect of reintroduction in the wild boar, and therefore for the development of conservation and management strategies for this species.

  8. Genome-wide analysis highlights genetic dilution in Algerian sheep.

    PubMed

    Gaouar, S B S; Lafri, M; Djaout, A; El-Bouyahiaoui, R; Bouri, A; Bouchatal, A; Maftah, A; Ciani, E; Da Silva, A B

    2017-03-01

    Algeria represents a reservoir of genetic diversity with local sheep breeds adapted to a large range of environments and showing specific features necessary to deal with harsh conditions. This remarkable diversity results from the traditional management of dryland by pastoralists over centuries. Most of these breeds are poorly productive, and the economic pressure leads farmers to realize anarchic cross-breeding (that is, not carried out in the framework of selection plans) with the hope to increase animal's conformation. In this study, eight of the nine local Algerian sheep breeds (D'men, Hamra, Ouled-Djellal, Rembi, Sidaoun, Tazegzawt, Berber and Barbarine) were investigated for the first time by genome-wide single-nucleotide polymorphism genotyping. At an international scale, Algerian sheep occupied an original position shaped by relations with African and European (particularly Italian) breeds. The strong genetic proximity with Caribbean and Brazilian breeds confirmed that the genetic make-up of these American breeds was largely influenced by the Atlantic slave trade. At a national scale, an alarming genetic dilution of the Berber (a primitive breed) and the Rembi was observed, as a consequence of uncontrolled mating practices with Ouled-Djellal. A similar, though less pronounced, phenomenon was also detected for the Barbarine, another ancestral breed. Genetic originality appeared to be better preserved in Tazegzawt, Hamra, D'men and Sidaoun. These breeds should be given high priority in the establishment of conservation plans to halt their progressive loss. For Berber and Barbarine that also occur in the bordering neighbor countries, urgent concerted transnational actions are needed.

  9. Large, Prospective Analysis of the Reasons Patients Do Not Pursue BRCA Genetic Testing Following Genetic Counseling.

    PubMed

    Hayden, Sommer; Mange, Sarah; Duquette, Debra; Petrucelli, Nancie; Raymond, Victoria M

    2017-01-16

    Genetic counseling (GC) and genetic testing (GT) identifies high-risk individuals who benefit from enhanced medical management. Not all individuals undergo GT following GC and understanding the reasons why can impact clinical efficiency, reduce GT costs through appropriate identification of high-risk individuals, and demonstrate the value of pre-GT GC. A collaborative project sponsored by the Michigan Department of Health and Human Services prospectively collects anonymous data on BRCA-related GC visits performed by providers in Michigan, including demographics, patient/family cancer history, GT results, and reasons for declining GT. From 2008 to 2012, 10,726 patients underwent GC; 3476 (32.4%) did not pursue GT. Primary reasons included: not the best test candidate (28.1%), not clinically indicated (23.3%), and insurance/out of pocket cost concerns (13.6%). Patient disinterest was the primary reason for declining in 17.1%. Insurance/out of pocket cost concerns were the primary reason for not testing in 13.4% of untested individuals with private insurance. Among untested individuals with breast and/or ovarian cancer, 22.5% reported insurance/out of pocket cost concerns as the primary reason for not testing and 6.6% failed to meet Medicare criteria. In a five-year time period, nearly one-third of patients who underwent BRCA GC did not pursue GT. GT was not indicated in almost half of patients. Insurance/out of pocket cost concerns continue to be barriers.

  10. Genetic Analysis and QTL Mapping of Fruit Peduncle Length in Cucumber (Cucumis sativus L.)

    PubMed Central

    Zhang, Song; Wang, Ye; Zhang, Sheng-Ping; Gu, Xing-Fang

    2016-01-01

    Mechanized harvesting of cucumbers offers significant advantages compared to manual labor as both shortages and costs of labor increase. However the efficient use of machines depends on breeding plants with longer peduncles, but the genetic and molecular basis of fruit peduncle development in cucumber is not well understood. In this study, F2 populations were developed from a cross between two inbred lines, 1101 with a long peduncle and 1694 with a short peduncle. These were grown at two field sites, Hainan, with a tropical marine climate, in December 2014, and Beijing, with a warm temperate climate, in May 2015. Electron microscope examination of the pith cells in the peduncles of the two parental lines showed that line 1101 had significantly greater numbers of smaller cells compared to line 1694. The inheritance of cucumber fruit peduncle length (FPL) was investigated by the mixed major gene and polygene inheritance model. Genetic analysis indicated that FPL in cucumber is quantitatively inherited and controlled by one additive major gene and additive-dominant polygenes (D-2 model). A total of 1460 pairs of SSR (simple sequence repeat) primers were analyzed to identify quantitative trait loci (QTLs). Two similar genetic maps with 78 SSR markers which covered 720.6 cM in seven linkage groups were constructed based on two F2 populations. QTL analysis from the data collected at the two field sites showed that there are two minor QTLs on chromosome 1, named qfpl1.1 and qfpl1.2, and one major QTL on chromosome 6, named qfpl6.1. The marker UW021226, which was the closest one to qfpl6.1, had an accuracy rate of 79.0% when tested against plants selected from populations of the two parents. The results from this study provide insights into the inheritance and molecular mechanism of the variation of FPL in cucumber, and further research will be carried out to fine map qfpl6.1 to develop more accurate markers for MAS breeding. PMID:27936210

  11. Population structure and genetic variability in the Murrah dairy breed of water buffalo in Brazil accessed via pedigree analysis.

    PubMed

    Malhado, Carlos Henrique Mendes; Malhado, Ana Claudia Mendes; Carneiro, Paulo Luiz Souza; Ramos, Alcides Amorim; Ambrosini, Diego Pagung; Pala, Akin

    2012-12-01

    The objective of this study was to use pedigree analysis to evaluate the population structure and genetic variability in the Murrah dairy breed of water buffalo (Bubalus bubalis) in Brazil. Pedigree analysis was performed on 5,061 animals born between 1972 and 2002. The effective number of founders (fe) was 60, representing 6.32 % of the potential number of founders. The effective number of ancestors (fa) was 36 and the genetic contribution of the 17 most influent ancestors explained 50 % of the genetic variability in the population. The ratio fe/fa (effective number of founders/effective number of ancestors), which expresses the effect of population bottlenecks, was 1.66. Completeness level for the whole pedigree was 76.8, 49.2, 27.7, and 12.8 % for, respectively, the first, second, third, and fourth known parental generations. The average inbreeding values for the whole analyzed pedigree and for inbreed animals were, respectively, 1.28 and 7.64 %. The average relatedness coefficient between individuals of the population was estimated to be 2.05 %-the highest individual coefficient was 10.31 %. The actual inbreeding and average relatedness coefficient are probably higher than estimated due to low levels of pedigree completeness. Moreover, the inbreeding coefficient increased with the addition of each generation to the pedigree, indicating that incomplete pedigrees tend to underestimate the level of inbreeding. Introduction of new sires with the lowest possible average relatedness coefficient and the use of appropriate mating strategies are recommended to keep inbreeding at acceptable levels and increase the genetic variability in this economically important species, which has relatively low numbers compared to other commercial cattle breeds. The inclusion of additional parameters, such as effective number of founders, effective number of ancestors, and fe/fa ratio, provides better resolution as compared to the inclusion of inbreeding coefficient and may help

  12. Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome

    PubMed Central

    Forero-Castro, Maribel; Robledo, Cristina; Benito, Rocío; Abáigar, María; África Martín, Ana; Arefi, Maryam; Fuster, José Luis; de las Heras, Natalia; Rodríguez, Juan N.; Quintero, Jonathan; Riesco, Susana; Hermosín, Lourdes; de la Fuente, Ignacio; Recio, Isabel; Ribera, Jordi; Labrador, Jorge; Alonso, José M.; Olivier, Carmen; Sierra, Magdalena; Megido, Marta; Corchete-Sánchez, Luis A.; Ciudad Pizarro, Juana; García, Juan Luis; Ribera, José M.; Hernández-Rivas, Jesús M.

    2016-01-01

    Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge. Aims: To characterize the presence of additional DNA copy number alterations (CNAs) in children and adults with ALL by whole-genome oligonucleotide array (aCGH) analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults). The NimbleGen CGH 12x135K array (Roche) was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q). CNAs were associated with age, phenotype, genetic subtype and overall survival (OS). In the whole cohort of children, the losses on 14q32.33 (p = 0.019) and 15q13.2 (p = 0.04) were related to shorter OS. In the group of children without good- or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001) and Xp21.1 (p = 0.029), and the loss of 17p (p = 0.014) were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL. PMID:26872047

  13. An analysis of genetic variation in Astragalus cremnophylax var. cremnophylax, a critically endangered plant, using AFLP markers.

    PubMed

    Travis, S E; Maschinski, J; Keim, P

    1996-12-01

    A recently developed molecular technique (amplified fragment length polymorphisms, AFLP) was used for characterizing genetic heterogeneity within and among populations of a critically endangered species of plant, Astragalus cremnophylax var. cremnophylax. Using AFLP, up to 50 polymorphic genetic markers per AFLP-PCR amplification were generated, and a total of 220 variable markers overall. This information was used first to assess genetic diversity within each of the three known populations of Astragalus cremnophylax var. cremnophylax from Grand Canyon National Park in Arizona, USA: North Rim (NR; n = 970), South Rim Site 1 (SR1; n = 500), and South Rim Site 2 (SR2; n = 2). Diversity in the form of average heterozygosity [symbol: see text] H [symbol: see text] and the proportion of polymorphic genes [symbol: see text] P [symbol: see text] was greatest in the NR population ([symbol: see text] H [symbol: see text] = 0.13 and [symbol: see text] P [symbol: see text] = 0.38) and least in the SR2 population ([symbol: see text] H [symbol: see text] = 0.02 and [symbol: see text] P [symbol: see text] = 0.04). Diversity was also quite low for the SR1 population ([symbol: see text] H [symbol: see text] = 0.04 and [symbol: see text] P [symbol: see text] = 0.10). In addition, substantial genetic differentiation among populations was indicated by both phenetic (AMOVA) and genetic analyses (overall corrected FST = 0.41). This finding was corroborated by the results of several multivariate analyses which utilized the genetic data, including a UPGMA cluster analysis and a principal coordinate analysis which revealed the existence of discrete groups corresponding to the populations. Population structure was further revealed within the NR population which was known to consist of four spatially separated groups of plants. Several recommendations for the future management of the species are discussed.

  14. Genetic interest assessment

    NASA Astrophysics Data System (ADS)

    Doughney, Erin

    Genetics is becoming increasingly integrated into peoples' lives. Different measures have been taken to try and better genetics education. This thesis examined undergraduate students at the University of North Texas not majoring in the life sciences interest in genetic concepts through the means of a Likert style survey. ANOVA analysis showed there was variation amongst the interest level in different genetic concepts. In addition age and lecture were also analyzed as contributing factors to students' interest. Both age and lecture were evaluated to see if they contributed to the interest of students in genetic concepts and neither showed statistical significance. The Genetic Interest Assessment (GIA) serves to help mediate the gap between genetic curriculum and students' interest.

  15. Genetic analysis of experimental allergic encephalomyelitis in mice

    SciTech Connect

    Baker, D.; Rosenwasser, O.A.; O`Neill, J.K.; Turk, J.L.

    1995-10-15

    Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that exhibits many pathologic similarities with multiple sclerosis. While products of the MHC are known to control the development of EAE, it is clear that non-MHC products also influence susceptibility. The chromosomal locations of these were investigated in selective crosses between MHC class II-compatible, EAE-susceptible Biozzi ABH, and low responder nonobese diabetic (NOD) mice. The disease was dominant and highly influenced by gender in the backcross one (BC{sub 1}) generation. Female mice were significantly more susceptible than male mice. Segregation of disease frequency of female animals in this cross suggested that EAE was controlled by a major locus. Although microsatellite-based exclusion mapping indicated that a number of regions on chromosomes 5, 6, 7, 8, 9, 10, 11, 12, 13, and 18 showed evidence of linkage (p<0.05) compared with expected random distributions of alleles, disease susceptibility was most strongly linked (p<0.05) to chromosome 7. However, by selectively analyzing animals that were either severely affected or almost normal, additional susceptibility loci were mapped on chromosomes 18 and 11 that were linked (p<0.001) to resistance and the development of severe disease, respectively. The data indicate a major locus on chromosome 7, affecting initiation and severity of EAE that is probably modified by several other unlinked loci. These localizations may provide candidate loci for the analysis of human autoimmune-demyelinating disease. 30 refs., 5 tabs.

  16. Developmental Genetic Analysis of Contrabithorax Mutations in Drosophila Melanogaster

    PubMed Central

    Gonzalez-Gaitan, M. A.; Micol, J. L.; Garcia-Bellido, A.

    1990-01-01

    A developmental analysis of the Contrabithorax (Cbx) alleles offers the opportunity to examine the role of the Ultrabithorax (Ubx) gene in controlling haltere, as alternative to wing, morphogenesis in Drosophila. Several Cbx alleles are known with different spatial specificity in their wing toward haltere homeotic transformation. The molecular data on these mutations, however, does not readily explain differences among mutant phenotypes. In this work, we have analyzed the ``apogenetic'' mosaic spots of transformation in their adult phenotype, in mitotic recombination clones and in the spatial distribution of Ubx proteins in imaginal discs. The results suggest that the phenotypes emerge from early clonality in some Cbx alleles, and from cell-cell interactions leading to recruitment of cells to Ubx gene expression in others. We have found, in addition, mutual interactions between haltere and wing territories in pattern and dorsoventral symmetries, suggesting short distance influences, ``accommodation,'' during cell proliferation of the anlage. These findings are considered in an attempt to explain allele specificity in molecular and developmental terms. PMID:1977655

  17. Great bustard population structure in central Spain: concordant results from genetic analysis and dispersal study.

    PubMed

    Martín, Carlos A; Alonso, Juan C; Alonso, Javier; Pitra, Christian; Lieckfeldt, Dietmar

    2002-01-22

    We found significant sex differences in the mtDNA genetic structure and dispersal patterns of great bustards in a population of 11 breeding groups, "leks", in central Spain. The analysis of genetic distances showed that the female population was divided into three groups of leks separated by ca. 50 km, whereas male haplotypes were randomly distributed among leks. Genetic distances among pairs of leks were positively correlated with geographical distances in females but not in males. While female haplotype distributions were homogeneous among leks at close distances, differences in male genetic structure were highly variable even between two close leks. These results from genetic analyses were concordant with those from a radiotracking study on natal dispersal. Natal dispersal distances were higher in males than in females. Also, the frequency of movement of a female between two leks was positively correlated with their genetic affinity and geographical proximity. In males, the frequency of movement was correlated with geographical proximity but not with genetic affinity. Males dispersed among genetically unrelated leks, contributing to keep nuclear genetic diversity in the population, whereas females tended to be philopatric. These results suggest that isolation-by-distance influences the distribution of maternal lineages at a regional level.

  18. Engineering and Functional Analysis of Mitotic Kinases Through Chemical Genetics.

    PubMed

    Jones, Mathew J K; Jallepalli, Prasad V

    2016-01-01

    During mitosis, multiple protein kinases transform the cytoskeleton and chromosomes into new and highly dynamic structures that mediate the faithful transmission of genetic information and cell division. However, the large number and strong conservation of mammalian kinases in general pose significant obstacles to interrogating them with small molecules, due to the difficulty in identifying and validating those which are truly selective. To overcome this problem, a steric complementation strategy has been developed, in which a bulky "gatekeeper" residue within the active site of the kinase of interest is replaced with a smaller amino acid, such as glycine or alanine. The enlarged catalytic pocket can then be targeted in an allele-specific manner with bulky purine analogs. This strategy provides a general framework for dissecting kinase function with high selectivity, rapid kinetics, and reversibility. In this chapter we discuss the principles and techniques needed to implement this chemical genetic approach in mammalian cells.

  19. Initial genetic analysis of Xylella fastidiosa in Texas.

    PubMed

    Morano, Lisa D; Bextine, Blake R; Garcia, Dennis A; Maddox, Shermel V; Gunawan, Stanley; Vitovsky, Natalie J; Black, Mark C

    2008-04-01

    Xylella fastidiosa is the causative agent of Pierce's Disease of grape. No published record of X. fastidiosa genetics in Texas exists despite growing financial risk to the U.S. grape industry, a Texas population of the glassy-winged sharpshooter insect vector (Homalodisca vitripennis) now spreading in California, and evidence that the bacterium is ubiquitous to southern states. Using sequences of conserved gyrB and mopB genes, we have established at least two strains in Texas, grape strain and ragweed strain, corresponding genetically with subsp. piercei and multiplex, respectively. The grape strain in Texas is found in Vitis vinifera varieties, hybrid vines, and wild Vitis near vineyards, whereas the ragweed strain in Texas is found in annuals, shrubs, and trees near vineyards or other areas. RFLP and QRT PCR techniques were used to differentiate grape and ragweed strains with greater efficiency than sequencing and are practical for screening numerous X. fastidiosa isolates for clade identity.

  20. Genetic variability of Lizard canary breed inferred from pedigree analysis.

    PubMed

    Cecchi, Francesca; Ciampolini, Roberta; Giacalone, Gianluca; Paci, Gisella

    2014-09-01

    The genealogical data of 471 (whole population: WP) Lizard canaries of an Italian breeder were analyzed to evaluate the genetic variability of the breed. The reference population (RP) comprised 346 living reproductive birds. Average generation interval was 1.61 ± 0.718 for males and 1.72 ± 0.863 for females. The average value of inbreeding (F) and relatedness (AR) in the RP were 15.83% and 22.63%, while the average increase in inbreeding was estimated to be 6.71% per generation (effective population size = 7.49). The results showed the need to reduce the level of inbreeding which would result in significant loss of genetic variation and in significant inbreeding depression.

  1. Genetic information analysis of bacteriophage phiX 174.

    PubMed

    Figueroa, R; Sepúleda, A; Soto, M A; Tohá, J

    1977-01-01

    The genetic information of phix 174 genome (genes and intermediate segments) is analyzed in terms of its independent (D1 index) and dependent information (D2 and D3 Markovian indexes), as well as of its ability to generate secondary structure. Genes B and E, enclosed in A and D respectively, have: 1) values of D1 and D3 indexes closer to the theoretical random distribution curves than those of (A-B) and (D-E) gene fractions, and 2) in the ability for secondary structure generation minor differences with genes A and D. F leads to G and mRNA start leads to A intermediate segments differ from randomness in their D1 and D2 indexes, but not so much in the D3 values. All these data point out the use of code degeneracy for increasing the genetic information density of the virus.

  2. Genetic analysis in neurology: the next 10 years.

    PubMed

    Pittman, Alan; Hardy, John

    2013-06-01

    In recent years, neurogenetics research had made some remarkable advances owing to the advent of genotyping arrays and next-generation sequencing. These improvements to the technology have allowed us to determine the whole-genome structure and its variation and to examine its effect on phenotype in an unprecedented manner. The identification of rare disease-causing mutations has led to the identification of new biochemical pathways and has facilitated a greater understanding of the etiology of many neurological diseases. Furthermore, genome-wide association studies have provided information on how common genetic variability impacts on the risk for the development of various complex neurological diseases. Herein, we review how these technological advances have changed the approaches being used to study the genetic basis of neurological disease and how the research findings will be translated into clinical utility.

  3. [Genetic analysis of life-style related diseases].

    PubMed

    Nagai, Tokihisa; Miki, Tetsuro

    2005-03-01

    In our country to which the aging society was invited, life-style related diseases, such as cancer, ischemic cardiac disease, apoplexy, and diabetes, are increasing. These life-style related diseases are multi-factor diseases. And genetic factors, environmental factors, and aging factors are concerned. This genetic factors are prescribed by gene polymorphism between individuals. The method of identifying these gene polymorphism has two kinds, microsatellite and single nucleotide polymorphism (SNP). If the relation of life-style related diseases and gene polymorphism will be solved from now on, realization of patient-tailored treatment according to the individual, extension of healthy life expectancy, improvement in quality of life, and decrease of medical expenses are expected.

  4. Microsatellite analysis of genetic relationships between wild and cultivated melons in Northwest and Central China.

    PubMed

    Hu, Jianbin; Wang, Panqiao; Li, Qiong; Su, Yan

    2014-12-01

    The genetic relationships between the wild and cultivated melon accessions from Northwest and Central China were dissected using 22 microsatellite markers. A total of 153 alleles, a high level of expected heterozygosity (0.669), and a low observed heterozygosity (0.156) were detected in the total panel. Differences on the allelic composition and heterozygosity levels were found between the two accession types and the wild accessions revealed a higher level of genetic diversity. The UPGMA analysis of the total panel showed that (a) most wild accessions from Northwest China were clustered independently from the cultivated accessions, and (b) the wild and cultivated accessions from Central China presented a high genetic closeness and showed a divergence from those of Northwest China. Similar positioning of the most accessions was observed with the principal coordinate analysis and STRUCTURE analysis. Pairwise FST and Nei's genetic distance quantified the genetic differentiation among the different accession types and further verified our findings. We concluded that the wild melons from Northwest China have a distinctive genetic background and could be the true wild forms, while the wild melons from Central China showed a close relationship to the local cultivars and could be a return from the cultivated melons in the same region. Our results offer an insight into the genetic resources of the main melon producing regions in China, which is essential for maximizing utilization of the traits of interest in wild melons.

  5. Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep

    PubMed Central

    Oikonomou, Grigorios

    2017-01-01

    Abstract Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain. Similar to rodent genetic studies, we found that zebrafish that lack histamine due to mutation of histidine decarboxylase (hdc) exhibit largely normal sleep/wake behaviors. Zebrafish containing predicted null mutations in several histamine receptors also lack robust sleep/wake phenotypes, although we are unable to verify that these mutants are completely nonfunctional. Consistent with some rodent studies, we found that arousal induced by overexpression of the neuropeptide hypocretin (Hcrt) or by stimulation of hcrt-expressing neurons is not blocked in hdc or hrh1 mutants. We also found that the number of hcrt-expressing or histaminergic neurons is unaffected in animals that lack histamine or Hcrt signaling, respectively. Thus, while acute pharmacological manipulation of histamine signaling has been shown to have profound effects on zebrafish and mammalian sleep, our results suggest that chronic loss of histamine signaling due to genetic mutations has only subtle effects on sleep in zebrafish, similar to rodents. PMID:28275716

  6. Genetic Analysis of Daily Activity in Humans and Mice

    DTIC Science & Technology

    2007-11-02

    of the technical developments that have made such genetic dissections a productive force in the mouse , have, when combined with innovations in...and Mice AFOSR grant F49620-97-1-0321 Joseph S. Takahashi Dept. of Neurobiology & Physiology Northwestern University 2153 North Campus Dr. Evanston...Activity in Humans and Mice Unclassified 5c. PROGRAM ELEMENT NUMBER 5d. PROJECT NUMBER 5e. TASK NUMBER 6. AUTHOR(S) Takahashi, Joseph S. ; 5f. WORK

  7. Bioinformatics analysis and genetic diversity of the poliovirus.

    PubMed

    Liu, Yanhan; Ma, Tengfei; Liu, Jianzhu; Zhao, Xiaona; Cheng, Ziqiang; Guo, Huijun; Wang, Shujing; Xu, Ruixue

    2014-12-01

    Poliomyelitis, a disease which can manifest as muscle paralysis, is caused by the poliovirus, which is a human enterovirus and member of the family Picornaviridae that usually transmits by the faecal-oral route. The viruses of the OPV (oral poliovirus attenuated-live vaccine) strains can mutate in the human intestine during replication and some of these mutations can lead to the recovery of serious neurovirulence. Informatics research of the poliovirus genome can be used to explain further the characteristics of this virus. In this study, sequences from 100 poliovirus isolates were acquired from GenBank. To determine the evolutionary relationship between the strains, we compared and analysed the sequences of the complete poliovirus genome and the VP1 region. The reconstructed phylogenetic trees for the complete sequences and the VP1 sequences were both divided into two branches, indicating that the genetic relationships of the whole poliovirus genome and the VP1 sequences are very similar. This branching indicates that the virulence and pathogenicity of poliomyelitis may be associated with the VP1 region. Sequence alignment of the VP1 region revealed numerous mutation sites in which mutation rates of >30 % were detected. In a group of strains recorded in the USA, mutation sites and mutation types were the same and this may be associated with their distribution in the evolutionary tree and their genetic relationship. In conclusion, the genetic evolutionary relationships of poliovirus isolate sequences are determined to a great extent by the VP1 protein, and poliovirus strains located on the same branch of the phylogenetic tree contain the same mutation spots and mutation types. Hence, the genetic characteristics of the VP1 region in the poliovirus genome should be analysed to identify the transmission route of poliovirus and provide the basis of viral immunity development.

  8. Integrative Lifecourse and Genetic Analysis of Military Working Dogs

    DTIC Science & Technology

    2013-10-01

    not only the presence or absence of the binary A or B alleles at each marker , but also the signal intensity of the marker and the ratio of the two...put through the IUT compound hypothesis: i) for each subset of an IUT group, which genetic markers have statistically significant frequency...differences in cases and controls, ii) keep only the markers that are significant in all subsets of an IUT (thus not requiring multiple testing correction

  9. Analysis of additive metals in fuel and emission aerosols of diesel vehicles with and without particle traps.

    PubMed

    Ulrich, Andrea; Wichser, Adrian

    2003-09-01

    Fuel additives used in particle traps have to comply with environmental directives and should not support the formation of additional toxic substances. The emission of metal additives from diesel engines with downstream particle traps has been studied. Aspects of the optimisation of sampling procedure, sample preparation and analysis are described. Exemplary results in form of a mass balance calculation are presented. The results demonstrate the high retention rate of the studied filter system but also possible deposition of additive metals in the engine.

  10. Genetic analysis of wheat domestication and evolution under domestication.

    PubMed

    Peleg, Zvi; Fahima, Tzion; Korol, Abraham B; Abbo, Shahal; Saranga, Yehoshua

    2011-10-01

    Wheat is undoubtedly one of the world's major food sources since the dawn of Near Eastern agriculture and up to the present day. Morphological, physiological, and genetic modifications involved in domestication and subsequent evolution under domestication were investigated in a tetraploid recombinant inbred line population, derived from a cross between durum wheat and its immediate progenitor wild emmer wheat. Experimental data were used to test previous assumptions regarding a protracted domestication process. The brittle rachis (Br) spike, thought to be a primary characteristic of domestication, was mapped to chromosome 2A as a single gene, suggesting, in light of previously reported Br loci (homoeologous group 3), a complex genetic model involved in spike brittleness. Twenty-seven quantitative trait loci (QTLs) conferring threshability and yield components (kernel size and number of kernels per spike) were mapped. The large number of QTLs detected in this and other studies suggests that following domestication, wheat evolutionary processes involved many genomic changes. The Br gene did not show either genetic (co-localization with QTLs) or phenotypic association with threshability or yield components, suggesting independence of the respective loci. It is argued here that changes in spike threshability and agronomic traits (e.g. yield and its components) are the outcome of plant evolution under domestication, rather than the result of a protracted domestication process. Revealing the genomic basis of wheat domestication and evolution under domestication, and clarifying their inter-relationships, will improve our understanding of wheat biology and contribute to further crop improvement.

  11. Genetic Analysis of the Henry Mountains Bison Herd.

    PubMed

    Ranglack, Dustin H; Dobson, Lauren K; du Toit, Johan T; Derr, James

    2015-01-01

    Wild American plains bison (Bison bison) populations virtually disappeared in the late 1800s, with some remnant animals retained in what would become Yellowstone National Park and on private ranches. Some of these private bison were intentionally crossbred with cattle for commercial purposes. This forced hybridization resulted in both mitochondrial and nuclear introgression of cattle genes into some of the extant bison genome. As the private populations grew, excess animals, along with their history of cattle genetics, provided founders for newly established public bison populations. Of the US public bison herds, only those in Yellowstone and Wind Cave National Parks (YNP and WCNP) appear to be free of detectable levels of cattle introgression. However, a small free-ranging population (~350 animals) exists on public land, along with domestic cattle, in the Henry Mountains (HM) of southern Utah. This isolated bison herd originated from a founder group translocated from YNP in the 1940s. Using genetic samples from 129 individuals, we examined the genetic status of the HM population and found no evidence of mitochondrial or nuclear introgression of cattle genes. This new information confirms it is highly unlikely for free-living bison to crossbreed with cattle, and this disease-free HM bison herd is valuable for the long-term conservation of the species. This bison herd is a subpopulation of the YNP/WCNP/HM metapopulation, within which it can contribute significantly to national efforts to restore the American plains bison to more of its native range.

  12. Genetic analysis of female gametophyte development and function.

    PubMed Central

    Drews, G N; Lee, D; Christensen, C A

    1998-01-01

    The female gametophyte is an absolutely essential structure for angiosperm reproduction. It produces the egg cell and central cell (which give rise to the embryo and endosperm, respectively) and mediates several reproductive processes including pollen tube guidance, fertilization, the induction of seed development, and perhaps also maternal control of embryo development. Although much has been learned about these processes at the cytological level, specific molecules mediating and controlling megagametogenesis and female gametophyte function have not been identified. A genetic approach to the identification of such molecules has been initiated in Arabidopsis and maize. Although genetic analyses are still in their infancy, mutations affecting female gametophyte function and specific steps of megagametogenesis have already been identified. Large-scale genetic screens aimed at identifying mutants affecting every step of megagametogenesis and female gametophyte function are in progress; the characterization of genes identified in these screens should go a long way toward defining the molecules that are required for female gametophyte development and function. PMID:9477569

  13. Functional and genetic analysis of choroid plexus development in zebrafish

    PubMed Central

    Henson, Hannah E.; Parupalli, Chaithanyarani; Ju, Bensheng; Taylor, Michael R.

    2014-01-01

    The choroid plexus, an epithelial-based structure localized in the brain ventricle, is the major component of the blood-cerebrospinal fluid barrier. The choroid plexus produces the cerebrospinal fluid and regulates the components of the cerebrospinal fluid. Abnormal choroid plexus function is associated with neurodegenerative diseases, tumor formation in the choroid plexus epithelium, and hydrocephaly. In this study, we used zebrafish (Danio rerio) as a model system to understand the genetic components of choroid plexus development. We generated an enhancer trap line, Et(cp:EGFP)sj2, that expresses enhanced green fluorescent protein (EGFP) in the choroid plexus epithelium. Using immunohistochemistry and fluorescent tracers, we demonstrated that the zebrafish choroid plexus possesses brain barrier properties such as tight junctions and transporter activity. Thus, we have established zebrafish as a functionally relevant model to study choroid plexus development. Using an unbiased approach, we performed a forward genetic dissection of the choroid plexus to identify genes essential for its formation and function. Using Et(cp:EGFP)sj2, we isolated 10 recessive mutant lines with choroid plexus abnormalities, which were grouped into five classes based on GFP intensity, epithelial localization, and overall choroid plexus morphology. We also mapped the mutation for two mutant lines to chromosomes 4 and 21, respectively. The mutants generated in this study can be used to elucidate specific genes and signaling pathways essential for choroid plexus development, function, and/or maintenance and will provide important insights into how these genetic mutations contribute to disease. PMID:25426018

  14. A comparative analysis of British and Taiwanese students' conceptual and procedural knowledge of fraction addition

    NASA Astrophysics Data System (ADS)

    Li, Hui-Chuan

    2014-10-01

    This study examines students' procedural and conceptual achievement in fraction addition in England and Taiwan. A total of 1209 participants (561 British students and 648 Taiwanese students) at ages 12 and 13 were recruited from England and Taiwan to take part in the study. A quantitative design by means of a self-designed written test is adopted as central to the methodological considerations. The test has two major parts: the concept part and the skill part. The former is concerned with students' conceptual knowledge of fraction addition and the latter is interested in students' procedural competence when adding fractions. There were statistically significant differences both in concept and skill parts between the British and Taiwanese groups with the latter having a higher score. The analysis of the students' responses to the skill section indicates that the superiority of Taiwanese students' procedural achievements over those of their British peers is because most of the former are able to apply algorithms to adding fractions far more successfully than the latter. Earlier, Hart [1] reported that around 30% of the British students in their study used an erroneous strategy (adding tops and bottoms, for example, 2/3 + 1/7 = 3/10) while adding fractions. This study also finds that nearly the same percentage of the British group remained using this erroneous strategy to add fractions as Hart found in 1981. The study also provides evidence to show that students' understanding of fractions is confused and incomplete, even those who are successfully able to perform operations. More research is needed to be done to help students make sense of the operations and eventually attain computational competence with meaningful grounding in the domain of fractions.

  15. Analysis of Time to Event Outcomes in Randomized Controlled Trials by Generalized Additive Models

    PubMed Central

    Argyropoulos, Christos; Unruh, Mark L.

    2015-01-01

    Background Randomized Controlled Trials almost invariably utilize the hazard ratio calculated with a Cox proportional hazard model as a treatment efficacy measure. Despite the widespread adoption of HRs, these provide a limited understanding of the treatment effect and may even provide a biased estimate when the assumption of proportional hazards in the Cox model is not verified by the trial data. Additional treatment effect measures on the survival probability or the time scale may be used to supplement HRs but a framework for the simultaneous generation of these measures is lacking. Methods By splitting follow-up time at the nodes of a Gauss Lobatto numerical quadrature rule, techniques for Poisson Generalized Additive Models (PGAM) can be adopted for flexible hazard modeling. Straightforward simulation post-estimation transforms PGAM estimates for the log hazard into estimates of the survival function. These in turn were used to calculate relative and absolute risks or even differences in restricted mean survival time between treatment arms. We illustrate our approach with extensive simulations and in two trials: IPASS (in which the proportionality of hazards was violated) and HEMO a long duration study conducted under evolving standards of care on a heterogeneous patient population. Findings PGAM can generate estimates of the survival function and the hazard ratio that are essentially identical to those obtained by Kaplan Meier curve analysis and the Cox model. PGAMs can simultaneously provide multiple measures of treatment efficacy after a single data pass. Furthermore, supported unadjusted (overall treatment effect) but also subgroup and adjusted analyses, while incorporating multiple time scales and accounting for non-proportional hazards in survival data. Conclusions By augmenting the HR conventionally reported, PGAMs have the potential to support the inferential goals of multiple stakeholders involved in the evaluation and appraisal of clinical trial

  16. Comparative proteomic analysis of drug sodium iron chlorophyllin addition to Hep 3B cell line.

    PubMed

    Zhang, Jun; Wang, Wenhai; Yang, Fengying; Zhou, Xinwen; Jin, Hong; Yang, Peng-yuan

    2012-09-21

    The human hepatoma 3B cell line was chosen as an experimental model for in vitro test of drug screening. The drugs included chlorophyllin and its derivatives such as fluo-chlorophyllin, sodium copper chlorophyllin, and sodium iron chlorophyllin. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) method was used in this study to obtain the primary screening results. The results showed that sodium iron chlorophyllin had the best LC(50) value. Proteomic analysis was then performed for further investigation of the effect of sodium iron chlorophyllin addition to the Hep 3B cell line. The proteins identified from a total protein extract of Hep 3B before and after the drug addition were compared by two-dimensional-gel-electrophoresis. Then 32 three-fold differentially expressed proteins were successfully identified by MALDI-TOF-TOF-MS. There are 29 unique proteins among those identified proteins. These proteins include proliferating cell nuclear antigen (PCNA), T-complex protein, heterogeneous nuclear protein, nucleophosmin, heat shock protein A5 (HspA5) and peroxiredoxin. HspA5 is one of the proteins which are involved in protecting cancer cells against stress-induced apoptosis in cultured cells, protecting them against apoptosis through various mechanisms. Peroxiredoxin has anti-oxidant function and is related to cell proliferation, and signal transduction. It can protect the oxidation of other proteins. Peroxiredoxin has a close relationship with cancer and can eventually become a disease biomarker. This might help to develop a novel treatment method for carcinoma cancer.

  17. A Genetic Relationship between Phosphorus Efficiency and Photosynthetic Traits in Soybean As Revealed by QTL Analysis Using a High-Density Genetic Map

    PubMed Central

    Li, Hongyan; Yang, Yuming; Zhang, Hengyou; Chu, Shanshan; Zhang, Xingguo; Yin, Dongmei; Yu, Deyue; Zhang, Dan

    2016-01-01

    Plant productivity relies on photosynthesis, and the photosynthetic process relies on phosphorus (P). The genetic basis of photosynthesis and P efficiency (PE) affecting yield has been separately characterized in various crop plants. However, the genetic relationship between PE and photosynthesis remains to be elucidated. In this study, we used a combined analysis of phenotypic correlation, linkage mapping, and expression analysis to dissect the relationship between PE and photosynthesis. We found significant phenotypic correlations between PE and photosynthetic related traits, particularly under low P stress. A total of 172 QTLs for both traits were detected and classified into 29 genomic regions. 12 (41.4%) of 29 regions were detected to be associated with both PE and photosynthetic related traits. Three major QTLs, q14-2, q15-2, and q19-2, were found to be associated with both traits and explained 6.6–58.9% of phenotypic variation. A photosynthetic-specific QTL cluster, q12-1, was detected under both normal and low P conditions, suggesting that genes responsible for this region were less effected by low P stress, and could be used in high photosynthetic efficiency breeding programs. In addition, several candidate genes with significantly differential expression upon low P stress, such as a purple acid phosphatase gene (Glyma.19G193900) within q19-2 region, were considered as promising candidates involved in regulating both soybean PE and photosynthetic capacity. Our results reveal a significant genetic relationship between PE and photosynthetic traits, and uncover several major genomic regions specific or common to these traits. The markers linked closely to these major QTLs may be used for selection of soybean varieties with improved P efficiency and photosynthetic capacity. PMID:27446154

  18. A Genetic Relationship between Phosphorus Efficiency and Photosynthetic Traits in Soybean As Revealed by QTL Analysis Using a High-Density Genetic Map.

    PubMed

    Li, Hongyan; Yang, Yuming; Zhang, Hengyou; Chu, Shanshan; Zhang, Xingguo; Yin, Dongmei; Yu, Deyue; Zhang, Dan

    2016-01-01

    Plant productivity relies on photosynthesis, and the photosynthetic process relies on phosphorus (P). The genetic basis of photosynthesis and P efficiency (PE) affecting yield has been separately characterized in various crop plants. However, the genetic relationship between PE and photosynthesis remains to be elucidated. In this study, we used a combined analysis of phenotypic correlation, linkage mapping, and expression analysis to dissect the relationship between PE and photosynthesis. We found significant phenotypic correlations between PE and photosynthetic related traits, particularly under low P stress. A total of 172 QTLs for both traits were detected and classified into 29 genomic regions. 12 (41.4%) of 29 regions were detected to be associated with both PE and photosynthetic related traits. Three major QTLs, q14-2, q15-2, and q19-2, were found to be associated with both traits and explained 6.6-58.9% of phenotypic variation. A photosynthetic-specific QTL cluster, q12-1, was detected under both normal and low P conditions, suggesting that genes responsible for this region were less effected by low P stress, and could be used in high photosynthetic efficiency breeding programs. In addition, several candidate genes with significantly differential expression upon low P stress, such as a purple acid phosphatase gene (Glyma.19G193900) within q19-2 region, were considered as promising candidates involved in regulating both soybean PE and photosynthetic capacity. Our results reveal a significant genetic relationship between PE and photosynthetic traits, and uncover several major genomic regions specific or common to these traits. The markers linked closely to these major QTLs may be used for selection of soybean varieties with improved P efficiency and photosynthetic capacity.

  19. Proteomic analysis of pemphigus autoantibodies indicates a larger, more diverse, and more dynamic repertoire than determined by B-cell genetics

    PubMed Central

    Chen, Jing; Zheng, Qi; Hammers, Christoph M.; Ellebrecht, Christoph T.; Mukherjee, Eric M.; Tang, Hsin-Yao; Lin, Chenyan; Yuan, Huijie; Pan, Meng; Langenhan, Jana; Komorowski, Lars; Siegel, Don L.; Payne, Aimee S.; Stanley, John R.

    2016-01-01

    Summary In autoantibody-mediated diseases such as pemphigus serum antibodies lead to disease. Genetic analysis of B cells has allowed characterization of antibody repertoires in such diseases but would be complemented by proteomic analysis of serum autoantibodies. Here we show using proteomic analysis that the serum autoantibody repertoire in pemphigus is much more polyclonal than found by genetic studies of B cells. In addition many B cells encode pemphigus autoantibodies that are not secreted into the serum. Heavy chain variable gene usage of serum autoantibodies is not shared among patients, implying targeting of the coded proteins will not be a useful therapeutic strategy. Analysis of autoantibodies over years in individual patients indicates that many antibody clones persist but the proportion of each changes. These studies indicate a dynamic and diverse autoantibody response not revealed by genetic studies, and explain why similar overall autoantibody titers may give variable disease activity. PMID:28052253

  20. Haplotype sharing analysis with SNPs in candidate genes: the Genetic Analysis Workshop 12 example.

    PubMed

    Fischer, Christine; Beckmann, Lars; Majoram, Paul; te Meerman, Gerard; Chang-Claude, Jenny

    2003-01-01

    Haplotype sharing analysis was used to investigate the association of affection status with single nucleotide polymorphism (SNP) haplotypes within candidate gene 1 in one sample each from the isolated and the general population of Genetic Analysis Workshop (GAW) 12 simulated data. Gene 1 has direct influence on affection and harbors more than 70 SNPs. Haplotype sharing analysis depends heavily on previous haplotype estimation. Using GENEHUNTER haplotypes, strong evidence was found for most SNPs in the isolated population sample, thus providing evidence for an involvement of this gene, but the maximum -log(10)(p) values for the haplotype sharing statistics (HSS) test statistic did not correspond to the location of the true variant in either population. In comparison, transmission disequilibrium test (TDT) analysis showed the strongest results at the disease-causing variant in both populations, and these were outstanding in the general population. In this example, TDT analysis appears to perform better than HSS in identifying the disease-causing variant, using SNPs within a candidate gene in an outbred population. Simulations showed that the performance of HSS is hampered by closely spaced SNPs in strong linkage disequilibrium with the functional variant and by ambiguous haplotypes.

  1. Analysis of the genetic diversity of Candida isolates obtained from diabetic patients and kidney transplant recipients

    PubMed Central

    Benedetti, Volmir Pitt; Savi, Daiani Cristina; Aluizio, Rodrigo; Adamoski, Douglas; Kava-Cordeiro, Vanessa; Galli-Terasawa, Lygia V; Glienke, Chirlei

    2016-01-01

    Yeasts of the genus Candida have high genetic variability and are the most common opportunistic pathogenic fungi in humans. In this study, we evaluated the genetic diversity among 120 isolates of Candida spp. obtained from diabetic patients, kidney transplant recipients and patients without any immune deficiencies from Paraná state, Brazil. The analysis was performed using the ITS1-5.8S-ITS2 region and a partial sequence of 28S rDNA. In the phylogenetic analysis, we observed a consistent separation of the species C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, C. parapsilosis, C. metapsilosis and C. orthopsilosis, however with low intraspecific variability. In the analysis of the C. albicans species, two clades were formed. Clade A included the largest number of isolates (91.2%) and the majority of isolates from GenBank (71.4%). The phylogenetic analysis showed low intraspecific genetic diversity, and the genetic polymorphisms between C. albicans isolates were similar to genetic divergence found in other studies performed with isolates from Brazil. This low genetic diversity of isolates can be explained by the geographic proximity of the patients evaluated. It was observed that yeast colonisation was highest in renal transplant recipients and diabetic patients and that C. albicans was the species most frequently isolated. PMID:27276363

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

    PubMed

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

    2016-03-11

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

  3. Analysis of the genetic diversity of Candida isolates obtained from diabetic patients and kidney transplant recipients.

    PubMed

    Benedetti, Volmir Pitt; Savi, Daiani Cristina; Aluizio, Rodrigo; Adamoski, Douglas; Kava-Cordeiro, Vanessa; Galli-Terasawa, Lygia V; Glienke, Chirlei

    2016-06-07

    Yeasts of the genus Candida have high genetic variability and are the most common opportunistic pathogenic fungi in humans. In this study, we evaluated the genetic diversity among 120 isolates of Candida spp. obtained from diabetic patients, kidney transplant recipients and patients without any immune deficiencies from Paraná state, Brazil. The analysis was performed using the ITS1-5.8S-ITS2 region and a partial sequence of 28S rDNA. In the phylogenetic analysis, we observed a consistent separation of the species C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, C. parapsilosis, C. metapsilosis and C. orthopsilosis, however with low intraspecific variability. In the analysis of the C. albicans species, two clades were formed. Clade A included the largest number of isolates (91.2%) and the majority of isolates from GenBank (71.4%). The phylogenetic analysis showed low intraspecific genetic diversity, and the genetic polymorphisms between C. albicans isolates were similar to genetic divergence found in other studies performed with isolates from Brazil. This low genetic diversity of isolates can be explained by the geographic proximity of the patients evaluated. It was observed that yeast colonisation was highest in renal transplant recipients and diabetic patients and that C. albicans was the species most frequently isolated.

  4. Two-dimensional enrichment analysis for mining high-level imaging genetic associations.

    PubMed

    Yao, Xiaohui; Yan, Jingwen; Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L; Inlow, Mark; Moore, Jason H; Saykin, Andrew J; Shen, Li

    2017-03-01

    Enrichment analysis has been widely applied in the genome-wide association studies, where gene sets corresponding to biological pathways are examined for significant associations with a phenotype to help increase statistical power and improve biological interpretation. In this work, we expand the scope of enrichment analysis into brain imaging genetics, an emerging field that studies how genetic variation influences brain structure and function measured by neuroimaging quantitative traits (QT). Given the high dimensionality of both imaging and genetic data, we propose to study Imaging Genetic Enrichment Analysis (IGEA), a new enrichment analysis paradigm that jointly considers meaningful gene sets (GS) and brain circuits (BC) and examines whether any given GS-BC pair is enriched in a list of gene-QT findings. Using gene expression data from Allen Human Brain Atlas and imaging genetics data from Alzheimer's Disease Neuroimaging Initiative as test beds, we present an IGEA framework and conduct a proof-of-concept study. This empirical study identifies 25 significant high-level two-dimensional imaging genetics modules. Many of these modules are relevant to a variety of neurobiological pathways or neurodegenerative diseases, showing the promise of the proposal framework for providing insight into the mechanism of complex diseases.

  5. Loophole-free Bell test using electron spins in diamond: second experiment and additional analysis

    PubMed Central

    Hensen, B.; Kalb, N.; Blok, M. S.; Dréau, A. E.; Reiserer, A.; Vermeulen, R. F. L.; Schouten, R. N.; Markham, M.; Twitchen, D. J.; Goodenough, K.; Elkouss, D.; Wehner, S.; Taminiau, T. H.; Hanson, R.

    2016-01-01

    The recently reported violation of a Bell inequality using entangled electronic spins in diamonds (Hensen et al., Nature 526, 682–686) provided the first loophole-free evidence against local-realist theories of nature. Here we report on data from a second Bell experiment using the same experimental setup with minor modifications. We find a violation of the CHSH-Bell inequality of 2.35 ± 0.18, in agreement with the first run, yielding an overall value of S = 2.38 ± 0.14. We calculate the resulting P-values of the second experiment and of the combined Bell tests. We provide an additional analysis of the distribution of settings choices recorded during the two tests, finding that the observed distributions are consistent with uniform settings for both tests. Finally, we analytically study the effect of particular models of random number generator (RNG) imperfection on our hypothesis test. We find that the winning probability per trial in the CHSH game can be bounded knowing only the mean of the RNG bias. This implies that our experimental result is robust for any model underlying the estimated average RNG bias, for random bits produced up to 690 ns too early by the random number generator. PMID:27509823

  6. Characterization and analysis of surface notches on Ti-alloy plates fabricated by additive manufacturing techniques

    NASA Astrophysics Data System (ADS)

    Chan, Kwai S.

    2015-12-01

    Rectangular plates of Ti-6Al-4V with extra low interstitial (ELI) were fabricated by layer-by-layer deposition techniques that included electron beam melting (EBM) and laser beam melting (LBM). The surface conditions of these plates were characterized using x-ray micro-computed tomography. The depth and radius of surface notch-like features on the LBM and EBM plates were measured from sectional images of individual virtual slices of the rectangular plates. The stress concentration factors of individual surface notches were computed and analyzed statistically to determine the appropriate distributions for the notch depth, notch radius, and stress concentration factor. These results were correlated with the fatigue life of the Ti-6Al-4V ELI alloys from an earlier investigation. A surface notch analysis was performed to assess the debit in the fatigue strength due to the surface notches. The assessment revealed that the fatigue lives of the additively manufactured plates with rough surface topographies and notch-like features are dominated by the fatigue crack growth of large cracks for both the LBM and EBM materials. The fatigue strength reduction due to the surface notches can be as large as 60%-75%. It is concluded that for better fatigue performance, the surface notches on EBM and LBM materials need to be removed by machining and the surface roughness be improved to a surface finish of about 1 μm.

  7. Failure location prediction by finite element analysis for an additive manufactured mandible implant.

    PubMed

    Huo, Jinxing; Dérand, Per; Rännar, Lars-Erik; Hirsch, Jan-Michaél; Gamstedt, E Kristofer

    2015-09-01

    In order to reconstruct a patient with a bone defect in the mandible, a porous scaffold attached to a plate, both in a titanium alloy, was designed and manufactured using additive manufacturing. Regrettably, the implant fractured in vivo several months after surgery. The aim of this study was to investigate the failure of the implant and show a way of predicting the mechanical properties of the implant before surgery. All computed tomography data of the patient were preprocessed to remove metallic artefacts with metal deletion technique before mandible geometry reconstruction. The three-dimensional geometry of the patient's mandible was also reconstructed, and the implant was fixed to the bone model with screws in Mimics medical imaging software. A finite element model was established from the assembly of the mandible and the implant to study stresses developed during mastication. The stress distribution in the load-bearing plate was computed, and the location of main stress concentration in the plate was determined. Comparison between the fracture region and the location of the stress concentration shows that finite element analysis could serve as a tool for optimizing the design of mandible implants.

  8. Loophole-free Bell test using electron spins in diamond: second experiment and additional analysis

    NASA Astrophysics Data System (ADS)

    Hensen, B.; Kalb, N.; Blok, M. S.; Dréau, A. E.; Reiserer, A.; Vermeulen, R. F. L.; Schouten, R. N.; Markham, M.; Twitchen, D. J.; Goodenough, K.; Elkouss, D.; Wehner, S.; Taminiau, T. H.; Hanson, R.

    2016-08-01

    The recently reported violation of a Bell inequality using entangled electronic spins in diamonds (Hensen et al., Nature 526, 682–686) provided the first loophole-free evidence against local-realist theories of nature. Here we report on data from a second Bell experiment using the same experimental setup with minor modifications. We find a violation of the CHSH-Bell inequality of 2.35 ± 0.18, in agreement with the first run, yielding an overall value of S = 2.38 ± 0.14. We calculate the resulting P-values of the second experiment and of the combined Bell tests. We provide an additional analysis of the distribution of settings choices recorded during the two tests, finding that the observed distributions are consistent with uniform settings for both tests. Finally, we analytically study the effect of particular models of random number generator (RNG) imperfection on our hypothesis test. We find that the winning probability per trial in the CHSH game can be bounded knowing only the mean of the RNG bias. This implies that our experimental result is robust for any model underlying the estimated average RNG bias, for random bits produced up to 690 ns too early by the random number generator.

  9. Analysis of Dengue Virus Genetic Diversity during Human and Mosquito Infection Reveals Genetic Constraints.

    PubMed

    Sessions, October M; Wilm, Andreas; Kamaraj, Uma Sangumathi; Choy, Milly M; Chow, Angelia; Chong, Yuwen; Ong, Xin Mei; Nagarajan, Niranjan; Cook, Alex R; Ooi, Eng Eong

    2015-01-01

    Dengue viruses (DENV) cause debilitating and potentially life-threatening acute disease throughout the tropical world. While drug development efforts are underway, there are concerns that resistant strains will emerge rapidly. Indeed, antiviral drugs that target even conserved regions in other RNA viruses lose efficacy over time as the virus mutates. Here, we sought to determine if there are regions in the DENV genome that are not only evolutionarily conserved but genetically constrained in their ability to mutate and could hence serve as better antiviral targets. High-throughput sequencing of DENV-1 genome directly from twelve, paired dengue patients' sera and then passaging these sera into the two primary mosquito vectors showed consistent and distinct sequence changes during infection. In particular, two residues in the NS5 protein coding sequence appear to be specifically acquired during infection in Ae. aegypti but not Ae. albopictus. Importantly, we identified a region within the NS3 protein coding sequence that is refractory to mutation during human and mosquito infection. Collectively, these findings provide fresh insights into antiviral targets and could serve as an approach to defining evolutionarily constrained regions for therapeutic targeting in other RNA viruses.

  10. Analysis of Dengue Virus Genetic Diversity during Human and Mosquito Infection Reveals Genetic Constraints

    PubMed Central

    Sessions, October M.; Wilm, Andreas; Kamaraj, Uma Sangumathi; Choy, Milly M.; Chow, Angelia; Chong, Yuwen; Ong, Xin Mei; Nagarajan, Niranjan; Cook, Alex R.; Ooi, Eng Eong

    2015-01-01

    Dengue viruses (DENV) cause debilitating and potentially life-threatening acute disease throughout the tropical world. While drug development efforts are underway, there are concerns that resistant strains will emerge rapidly. Indeed, antiviral drugs that target even conserved regions in other RNA viruses lose efficacy over time as the virus mutates. Here, we sought to determine if there are regions in the DENV genome that are not only evolutionarily conserved but genetically constrained in their ability to mutate and could hence serve as better antiviral targets. High-throughput sequencing of DENV-1 genome directly from twelve, paired dengue patients’ sera and then passaging these sera into the two primary mosquito vectors showed consistent and distinct sequence changes during infection. In particular, two residues in the NS5 protein coding sequence appear to be specifically acquired during infection in Ae. aegypti but not Ae. albopictus. Importantly, we identified a region within the NS3 protein coding sequence that is refractory to mutation during human and mosquito infection. Collectively, these findings provide fresh insights into antiviral targets and could serve as an approach to defining evolutionarily constrained regions for therapeutic targeting in other RNA viruses. PMID:26327586

  11. Molecular genetic analysis of heterosis in interspecific hybrids of Argopecten purpuratus x A. irradians irradians.

    PubMed

    Hu, L P; Huang, X T; Sun, Y; Mao, J X; Wang, S; Wang, C D; Bao, Z M

    2015-09-09

    Argopecten purpuratus and Argopecten irradians irradians hybridization was successfully performed and the hybrid offspring displayed apparent heterosis in growth traits. To better understand the genetic basis of heterosis, the genomic composition and genetic variation of the hybrids were analyzed with amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers. Seven of eight universal SSR primers displayed polymorphism in the hybrids and their parental groups, and hybrids inherited both parental geno-types at each locus. Using five primer combinations in AFLP analysis, 433 loci were amplified in the hybrids and their parental groups. The frequency of polymorphisms was 88.22%. F1 hybrids inherited 88.11 and 92.88% of AFLP bands from their parents. Some loci did not follow Mendelian Law, including 48 loci in parents that were lost, and 11 new loci that were amplified in the hybrids. The parameters of Nei's gene diversity, Shannon's Information index, genetic distance, and molecular variance between groups were calculated. The genetic differentiation between two hybrid groups (0.253) was smaller than that between hybrids and their parents (0.554 to 0.645), and was especially smaller than that between two parental groups (0.769). The high genetic similarity (0.9347) and low genetic differentiation (0.2531) between two hybrid groups suggests that these hybrid groups were genetically very close. Heterozygosities of hybrid groups were higher than those of parental groups, indicating that the hybrids had increased genetic diversity.

  12. The multi-niche crowding genetic algorithm: Analysis and applications

    SciTech Connect

    Cedeno, Walter

    1995-09-01

    The ability of organisms to evolve and adapt to the environment has provided mother nature with a rich and diverse set of species. Only organisms well adapted to their environment can survive from one generation to the next, transferring on the traits, that made them successful, to their offspring. Competition for resources and the ever changing environment drives some species to extinction and at the same time others evolve to maintain the delicate balance in nature. In this disertation we present the multi-niche crowding genetic algorithm, a computational metaphor to the survival of species in ecological niches in the face of competition. The multi-niche crowding genetic algorithm maintains stable subpopulations of solutions in multiple niches in multimodal landscapes. The algorithm introduces the concept of crowding selection to promote mating among members with qirnilar traits while allowing many members of the population to participate in mating. The algorithm uses worst among most similar replacement policy to promote competition among members with similar traits while allowing competition among members of different niches as well. We present empirical and theoretical results for the success of the multiniche crowding genetic algorithm for multimodal function optimization. The properties of the algorithm using different parameters are examined. We test the performance of the algorithm on problems of DNA Mapping, Aquifer Management, and the File Design Problem. Applications that combine the use of heuristics and special operators to solve problems in the areas of combinatorial optimization, grouping, and multi-objective optimization. We conclude by presenting the advantages and disadvantages of the algorithm and describing avenues for future investigation to answer other questions raised by this study.

  13. Genetic analysis of 24 French families with multiple endocrine neoplasia type 2A

    SciTech Connect

    Narod, S.A.; Morgan, K. ); Lavoue, M.F.; Lenoir, G.M.; Sobol, H. ); Calmettes, C. ); Goodfellow, P.J. )

    1992-09-01

    The gene for multiple endocrine neoplasia type 2A (MEN2A) has been mapped to the pericentromeric region of chromosome 10 by linkage analysis. Thirty-four families with multiple cases of medullary carcinoma of the thyroid (MTC), including 24 families with origins in France, have been typed with nine polymorphic markers spanning the centromere of chromosome 10. No recombination was observed between the MEN2A locus and either of the four loci D10Z1 (lod score 12.79), D10S102 (lod score 6.38), D10S94 (lod score 7.76), and D10S34 (lod score 5.94). There was no evidence for genetic linkage heterogeneity in the panel of 34 families. Haplotypes were constructed for a total of 11 polymorphisms in the MEN2A region, for mutation bearing chromosomes in 24 French families and for 100 spouse controls. One haplotype was present in four MEN2A families but was not observed in any control (P<0.1). Two additional families share a core segment of this haplotype near the MEN2A gene. It is likely that these six families have a common affected ancestor. Because the incidence of pheochromocytoma among carriers varies from 0% to 74% within these six families, it is probable that additional factors modify the expression of the MEN2A gene. 39 refs., 5 figs., 4 tabs.

  14. Functional Analysis of the Human Genome:. Study of Genetic Disease

    NASA Astrophysics Data System (ADS)

    Tsui, Lap-Chee

    2003-04-01

    I will divide my remarks into 3 parts. First, I will give a brief summary of the Human Genome Project. Second, I will describe our work on human chromosome 7 to illustrate how we could contribute to the Project and disease research. Third, I would like to bring across the argument that study of genetic disease is an integral component of the Human Genome Project. In particular, I will use cystic fibrosis as an example to elaborate why I consider disease study is a part of functional genomics.

  15. Genetic Analysis of Gravity Signal Transduction in Arabidopsis thaliana Seedlings

    NASA Astrophysics Data System (ADS)

    Boonsirichai, K.; Harrison, B.; Stanga, J.; Young, L.-S.; Neal, C.; Sabat, G.; Murthy, N.; Harms, A.; Sedbrook, J.; Masson, P.

    The primary roots of Arabidopsis thaliana seedlings respond to gravity stimulation by developing a tip curvature that results from differential cellular elongation on opposite flanks of the elongation zone. This curvature appears modulated by a lateral gradient of auxin that originates in the gravity-perceiving cells (statocytes) of the root cap through an apparent lateral repositioning of a component the auxin efflux carrier complex within these cells (Friml et al, 2002, Nature 415: 806-809). Unfortunately, little is known about the molecular mechanisms that govern early phases of gravity perception and signal transduction within the root-cap statocytes. We have used a molecular genetic approach to uncover some of these mechanisms. Mutations in the Arabidopsis ARG1 and ARL2 genes, which encode J-domain proteins, resulted in specific alterations in root and hypocotyl gravitropism, without pleiotropic phenotypes. Interestingly, ARG1 and ARL2 appear to function in the same genetic pathway. A combination of molecular genetic, biochemical and cell-biological approaches were used to demonstrate that ARG1 functions in early phases of gravity signal transduction within the root and hypocotyl statocytes, and is needed for efficient lateral auxin transport within the cap. The ARG1 protein is associated with components of the secretory and/or endosomal pathways, suggesting its role in the recycling of components of the auxin efflux carrier complex between plasma membrane and endosome (Boonsirichai et al, 2003, Plant Cell 15:2612-2625). Genetic modifiers of arg1-2 were isolated and shown to enhance the gravitropic defect of arg1-2, while resulting in little or no gravitropic defects in a wild type ARG1 background. A slight tendency for arg1-2;mar1-1 and arg1-2;mar2-1 double-mutant organs to display an opposite gravitropic response compared to wild type suggests that all three genes contribute to the interpretation of the gravity-vector information by seedling organs. The

  16. Economic methods for valuing the outcomes of genetic testing: beyond cost-effectiveness analysis.

    PubMed

    Grosse, Scott D; Wordsworth, Sarah; Payne, Katherine

    2008-09-01

    Genetic testing in health care can provide information to help with disease prediction, diagnosis, prognosis, and treatment. Assessing the clinical utility of genetic testing requires a process to value and weight different outcomes. This article discusses the relative merits of different economic measures and methods to inform recommendations relative to genetic testing for risk of disease, including cost-effectiveness analysis and cost-benefit analysis. Cost-effectiveness analyses refer to analyses that calculate the incremental cost per unit of health outcomes, such as deaths prevented or life-years saved because of some intervention. Cost-effectiveness analyses that use preference-based measures of health state utility such as quality-adjusted life-years to define outcomes are referred to as cost-utility analyses. Cost-effectiveness analyses presume that health policy decision makers seek to maximize health subject to resource constraints. Cost-benefit analyses can incorporate monetary estimates of willingness-to-pay for genetic testing, including the perceived value of information independent of health outcomes. These estimates can be derived from contingent valuation or discrete choice experiments. Because important outcomes of genetic testing do not fit easily within traditional measures of health, cost-effectiveness analyses do not necessarily capture the full range of outcomes of genetic testing that are important to decision makers and consumers. We recommend that health policy decision makers consider the value to consumers of information and other nonhealth attributes of genetic testing strategies.

  17. 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

  18. Current genetic methodologies in the identification of disaster victims and in forensic analysis.

    PubMed

    Ziętkiewicz, Ewa; Witt, Magdalena; Daca, Patrycja; Zebracka-Gala, Jadwiga; Goniewicz, Mariusz; Jarząb, Barbara; Witt, Michał

    2012-02-01

    This review presents the basic problems and currently available molecular techniques used for genetic profiling in disaster victim identification (DVI). The environmental conditions of a mass disaster often result in severe fragmentation, decomposition and intermixing of the remains of victims. In such cases, traditional identification based on the anthropological and physical characteristics of the victims is frequently inconclusive. This is the reason why DNA profiling became the gold standard for victim identification in mass-casualty incidents (MCIs) or any forensic cases where human remains are highly fragmented and/or degraded beyond recognition. The review provides general information about the sources of genetic material for DNA profiling, the genetic markers routinely used during genetic profiling (STR markers, mtDNA and single-nucleotide polymorphisms [SNP]) and the basic statistical approaches used in DNA-based disaster victim identification. Automated technological platforms that allow the simultaneous analysis of a multitude of genetic markers used in genetic identification (oligonucleotide microarray techniques and next-generation sequencing) are also presented. Forensic and population databases containing information on human variability, routinely used for statistical analyses, are discussed. The final part of this review is focused on recent developments, which offer particularly promising tools for forensic applications (mRNA analysis, transcriptome variation in individuals/populations and genetic profiling of specific cells separated from mixtures).

  19. Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA-DTI working group.

    PubMed

    Jahanshad, Neda; Kochunov, Peter V; Sprooten, Emma; Mandl, René C; Nichols, Thomas E; Almasy, Laura; Blangero, John; Brouwer, Rachel M; Curran, Joanne E; de Zubicaray, Greig I; Duggirala, Ravi; Fox, Peter T; Hong, L Elliot; Landman, Bennett A; Martin, Nicholas G; McMahon, Katie L; Medland, Sarah E; Mitchell, Braxton D; Olvera, Rene L; Peterson, Charles P; Starr, John M; Sussmann, Jessika E; Toga, Arthur W; Wardlaw, Joanna M; Wright, Margaret J; Hulshoff Pol, Hilleke E; Bastin, Mark E; McIntosh, Andrew M; Deary, Ian J; Thompson, Paul M; Glahn, David C

    2013-11-01

    The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA-DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18-85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/).

  20. Comparative proteomic analysis of apomictic monosomic addition line of Beta corolliflora and Beta vulgaris L. in sugar beet.

    PubMed

    Zhu, Hong; Bi, Ying-Dong; Yu, Li-Jie; Guo, De-Dong; Wang, Bai-Chen

    2009-11-01

    Apomixis refers to a process in which plants produce seed without fertilization through female syngamy that produces embryos genetically identical to the maternal parent. In sugar beet, interspecific hybrids between diploid Beta vulgaris and tetraploid Beta corolliflora were established and monosomic addition line M14 was selected because of the apomictic phenotype. By using two-dimensional electrophoresis gels we identified the proteins which were differently expressed between the M14 and B. vulgaris. A total of 27 protein spots which varied expressed between lines were isolated and successfully identified with MALDI-TOF MS. Among them five protein spots were found to be only presented in M14 and two protein spots only expressed in Beta. According to their functional annotations described in Swissprot database, these proteins were, respectively, involved in important biological pathways, such as cell division, functionally classified using the KEGG functional classification system. The result may be useful for us to better understand the genetic mechanism of apomixes.

  1. Pedigree analysis of the Turkish Arab horse population: structure, inbreeding and genetic variability.

    PubMed

    Duru, S

    2017-02-13

    The aim of this study was to evaluate genetic variability in the Turkish Arab horse population using pedigree information. This study is the first detailed pedigree analysis of the breed in Turkey. Pedigree data were collected from the National Studbook. The pedigree data for 23 668 horses, born between 1904 and 2014, were used in the analysis. From this data set, a reference population (RP) of 14 838 animals symbolising the last generation was defined. Demographic parameters, the inbreeding level (F), the average relatedness (AR), the effective population size (N e), the effective number of founders (f e), the effective number of ancestors (f a) and the number of founder genome equivalents (f g) were calculated for the population. The average generation interval for the RP was 12.2±4.6 years, whereas the calculated pedigree completeness levels were 98.2%, 96.6% and 95.0% for the first, second and third known generations. The mean equivalent generations (t), the average complete generations and the mean maximum generations for the RP were 7.8, 5.4 and 12.2, respectively, whereas the mean F and AR were 4.6% and 9.5% for the RP. The rate of inbred animals was 94.2% for the RP, whereas the number of founders, the number of ancestors and the f e, f a and f g were 342, 223, 40, 22 and 9.6 for the RP. The large differences observed between f e, and the number of founders demonstrates that genetic diversity decreased between the founder and the RP. Contribution of the 14 most influential founder to the RP was 50.0%, whereas just eight ancestral horses can account for 50% of the genetic variability. N e estimated via an individual increase in inbreeding per generation ( $$ \\hskip3pt{\\bar{\\hskip-2ptN}_{{\\rm e}} } $$ ), and paired increase in coancestry $$\\left(\\! \\hskip3pt{\\bar{\\hskip-2ptN}_{{ eC}} } \\right)$$ , were 74.4±3.9 and 73.5±0.58, respectively. The inbreeding increases with the pedigree knowledge. In addition, the decrease in inbreeding in last years

  2. Genetic analysis of 7 medieval skeletons from Aragonese Pyrenees

    PubMed Central

    Núńez, Carolina; Sosa, Cecilia; Baeta, Miriam; Geppert, Maria; Turnbough, Meredith; Phillips, Nicole; Casalod, Yolanda; Bolea, Miguel; Roby, Rhonda; Budowle, Bruce; Martínez-Jarreta, Begońa

    2011-01-01

    Aim To perform a genetic characterization of 7 skeletons from medieval age found in a burial site in the Aragonese Pyrenees. Methods Allele frequencies of autosomal short tandem repeats (STR) loci were determined by 3 different STR systems. Mitochondrial DNA (mtDNA) and Y-chromosome haplogroups were determined by sequencing of the hypervariable segment 1 of mtDNA and typing of phylogenetic Y chromosome single nucleotide polymorphisms (Y-SNP) markers, respectively. Possible familial relationships were also investigated. Results Complete or partial STR profiles were obtained in 3 of the 7 samples. Mitochondrial DNA haplogroup was determined in 6 samples, with 5 of them corresponding to the haplogroup H and 1 to the haplogroup U5a. Y-chromosome haplogroup was determined in 2 samples, corresponding to the haplogroup R. In one of them, the sub-branch R1b1b2 was determined. mtDNA sequences indicated that some of the individuals could be maternally related, while STR profiles indicated no direct family relationships. Conclusions Despite the antiquity of the samples and great difficulty that genetic analyses entail, the combined use of autosomal STR markers, Y-chromosome informative SNPs, and mtDNA sequences allowed us to genotype a group of skeletons from the medieval age. PMID:21674829

  3. Genetic Analysis of Stellate Elements of Drosophila Melanogaster

    PubMed Central

    Palumbo, G.; Bonaccorsi, S.; Robbins, L. G.; Pimpinelli, S.

    1994-01-01

    Repeated elements are remarkably important for male meiosis and spermiogenesis in Drosophila melanogaster. Pairing of the X and Y chromosomes is mediated by the ribosomal RNA genes of the Y chromosome and X chromosome heterochromatin, spermiogenesis depends on the fertility factors of the Y chromosome. Intriguingly, a peculiar genetic system of interaction between the Y-linked crystal locus and the X-linked Stellate elements seem to be also involved in male meiosis and spermiogenesis. Deletion of the crystal element of the Y, via an interaction with the Stellate elements of the X, causes meiotic abnormalities, gamete-genotype dependent failure of sperm development (meiotic drive), and deposition of protein crystals in spermatocytes. The current hypothesis is that the meiotic abnormalities observed in cry(-) males is due to an induced overexpression of the normally repressed Ste elements. An implication of this hypothesis is that the strength of the abnormalities would depend on the amount of the Ste copies. To test this point we have genetically and cytologically examined the relationship of Ste copy number and organization to meiotic behavior in cry(-) males. We found that heterochromatic as well as euchromatic Ste repeats are functional and that the abnormality in chromosome condensation and the frequency of nondisjunction are related to Ste copy number. Moreover, we found that meiosis is disrupted after synapsis and that cry-induced meiotic drive is probably not mediated by Ste. PMID:7896100

  4. Poppr: an R package for genetic analysis of populations with mixed (clonal/sexual) reproduction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Poppr is an R package for analysis of population genetic data. It extends the adegenet package and provides several novel tools, particularly with regard to analysis of data from admixed, clonal, and/or sexual populations. Currently, poppr can be used for dominant/codominant and haploid/diploid gene...

  5. A genome-wide analysis of populations from European Russia reveals a new pole of genetic diversity in northern Europe.

    PubMed

    Khrunin, Andrey V; Khokhrin, Denis V; Filippova, Irina N; Esko, Tõnu; Nelis, Mari; Bebyakova, Natalia A; Bolotova, Natalia L; Klovins, Janis; Nikitina-Zake, Liene; Rehnström, Karola; Ripatti, Samuli; Schreiber, Stefan; Franke, Andre; Macek, Milan; Krulišová, Veronika; Lubinski, Jan; Metspalu, Andres; Limborska, Svetlana A

    2013-01-01

    Several studies examined the fine-scale structure of human genetic variation in Europe. However, the European sets analyzed represent mainly northern, western, central, and southern Europe. Here, we report an analysis of approximately 166,000 single nucleotide polymorphisms in populations from eastern (northeastern) Europe: four Russian populations from European Russia, and three populations from the northernmost Finno-Ugric ethnicities (Veps and two contrast groups of Komi people). These were compared with several reference European samples, including Finns, Estonians, Latvians, Poles, Czechs, Germans, and Italians. The results obtained demonstrated genetic heterogeneity of populations living in the region studied. Russians from the central part of European Russia (Tver, Murom, and Kursk) exhibited similarities with populations from central-eastern Europe, and were distant from Russian sample from the northern Russia (Mezen district, Archangelsk region). Komi samples, especially Izhemski Komi, were significantly different from all other populations studied. These can be considered as a second pole of genetic diversity in northern Europe (in addition to the pole, occupied by Finns), as they had a distinct ancestry component. Russians from Mezen and the Finnic-speaking Veps were positioned between the two poles, but differed from each other in the proportions of Komi and Finnic ancestries. In general, our data provides a more complete genetic map of Europe accounting for the diversity in its most eastern (northeastern) populations.

  6. Genetic analysis across different spatial scales reveals multiple dispersal mechanisms for the invasive hydrozoan Cordylophora in the Great Lakes.

    PubMed

    Darling, John A; Folino-Rorem, Nadine C

    2009-12-01

    Discerning patterns of post-establishment spread by invasive species is critically important for the design of effective management strategies and the development of appropriate theoretical models predicting spatial expansion of introduced populations. The globally invasive colonial hydrozoan Cordylophora produces propagules both sexually and vegetatively and is associated with multiple potential dispersal mechanisms, making it a promising system to investigate complex patterns of population structure generated throughout the course of rapid range expansion. Here, we explore genetic patterns associated with the spread of this taxon within the North American Great Lakes basin. We collected intensively from eight harbours in the Chicago area in order to conduct detailed investigation of local population expansion. In addition, we collected from Lakes Michigan, Erie, and Ontario, as well as Lake Cayuga in the Finger Lakes of upstate New York in order to assess genetic structure on a regional scale. Based on data from eight highly polymorphic microsatellite loci we examined the spatial extent of clonal genotypes, assessed levels of neutral genetic diversity, and explored patterns of migration and dispersal at multiple spatial scales through assessment of population level genetic differentiation (pairwise F(ST) and factorial correspondence analysis), Bayesian inference of population structure, and assignment tests on individual genotypes. Results of these analyses indicate that Cordylophora populations in this region spread predominantly through sexually produced propagules, and that while limited natural larval dispersal can drive expansion locally, regional expansion likely relies on anthropogenic dispersal vectors.

  7. Clonal analysis of delayed karyotypic abnormalities and gene mutations in radiation-induced genetic instability.

    PubMed Central

    Grosovsky, A J; Parks, K K; Giver, C R; Nelson, S L

    1996-01-01

    Many tumors exhibit extensive chromosomal instability, but karyotypic alterations will be significant in carcinogenesis only by influencing specific oncogenes or tumor suppressor loci within the affected chromosomal segments. In this investigation, the specificity of chromosomal rearrangements attributable to radiation-induced genomic instability is detailed, and a qualitative and quantitative correspondence with mutagenesis is demonstrated. Chromosomal abnormalities preferentially occurred near the site of prior rearrangements, resulting in complex abnormalities, or near the centromere, resulting in deletion or translocation of the entire chromosome arm, but no case of an interstitial chromosomal deletion was observed. Evidence for chromosomal instability in the progeny of irradiated cells also included clonal karyotypic heterogeneity. The persistence of instability was demonstrated for at least 80 generations by elevated mutation rates at the heterozygous, autosomal marker locus tk. Among those TK- mutants that showed a loss of heterozygosity, a statistically significant increase in mutation rate was observed only for those in which the loss of heterozygosity encompasses the telomeric region. This mutational specificity corresponds with the prevalence of terminal deletions, additions, and translocations, and the absence of interstitial deletions, in karyotypic analysis. Surprisingly, the elevated rate of TK- mutations is also partially attributable to intragenic base substitutions and small deletions, and DNA sequence analysis of some of these mutations is presented. Complex chromosomal abnormalities appear to be the most significant indicators of a high rate of persistent genetic instability which correlates with increased rates of both intragenic and chromosomal-scale mutations at tk. PMID:8887655

  8. Genetic modifier loci of mouse Mfrp(rd6) identified by quantitative trait locus analysis.

    PubMed

    Won, Jungyeon; Charette, Jeremy R; Philip, Vivek M; Stearns, Timothy M; Zhang, Weidong; Naggert, Jürgen K; Krebs, Mark P; Nishina, Patsy M

    2014-01-01

    The identification of genes that modify pathological ocular phenotypes in mouse models may improve our understanding of disease mechanisms and lead to new treatment strategies. Here, we identify modifier loci affecting photoreceptor cell loss in homozygous Mfrp(rd6) mice, which exhibit a slowly progressive photoreceptor degeneration. A cohort of 63 F2 homozygous Mfrp(rd6) mice from a (B6.C3Ga-Mfrp(rd6)/J × CAST/EiJ) F1 intercross exhibited a variable number of cell bodies in the retinal outer nuclear layer at 20 weeks of age. Mice were genotyped with a panel of single nucleotide polymorphism markers, and genotypes were correlated with phenotype by quantitative trait locus (QTL) analysis to map modifier loci. A genome-wide scan revealed a statistically significant, protective candidate locus on CAST/EiJ Chromosome 1 and suggestive modifier loci on Chromosomes 6 and 11. Multiple regression analysis of a three-QTL model indicated that the modifier loci on Chromosomes 1 and 6 together account for 26% of the observed phenotypic variation, while the modifier locus on Chromosome 11 explains only an additional 4%. Our findings indicate that the severity of the Mfrp(rd6) retinal degenerative phenotype in mice depends on the strain genetic background and that a significant modifier locus on CAST/EiJ Chromosome 1 protects against Mfrp(rd6)-associated photoreceptor loss.

  9. Genetic analysis of seed yield, oil content and their components in safflower (Carthamus tinctorius L.).

    PubMed

    Ramachandram, M; Goud, J V

    1981-05-01

    The genetic architecture of seed yield, oil content and their components was studied in a diallel cross of F1 and F2: eleven parents, representing an adequate diversity for all considered characters in safflower were used. Combining ability analysis revealed the predominance of gca variance for plant height, total capitula, seed weight, seed number and seed yield in F1 and F2 generations and for days to flowering and oil content in F1. The analysis of components of variance indicated that the non-additive factor was the major influence on total capitula and seed yield in F1s, and F2s, and on plant height, seed weight and seed number in the F2 alone. The heterogeneity of the dominance component over generations has been attributed to coupling phase linkage. All four Indian parents, namely S 144, A1, MS 49 and 6 spl, together with G 1157 and US 104 in the exotic group, were the best combiners for seed yield and/or for one of its components while the remainder of the exotic parents were characterized by high gca effects for oil content. VFstp 1 and Frio were the only parents approximating both properties of oil content and seed yield. Breeding methods, such as biparental mating followed by reciprocal recurrent selection, were suggested for the simultaneous improvement of seed yield and oil content.

  10. Genetic variability analysis of Zymomonas mobilis strains from the UFPEDA microorganisms collection.

    PubMed

    Silva, L C N; Araújo, J M; Azevedo, J L; Padilha, R J S A; Yara, R

    2015-02-02

    Zymomonas mobilis is a Gram-negative bacterium that has drawn attention in the bioethanol industry. Besides bioethanol, this bacterium also produces other biotechnological products such as levans, which show antitumor activity. Molecular studies involving Z. mobilis have advanced to the point that allows us to characterize interspecies genetic diversity and understand their metabolism, and these data are essential for better utilization of this species. In this study, the genetic diversity of 24 strains from the Microorganisms Collection of Departamento de Antibióticos (UFPEDA) from Universidade Federal de Pernambuco were characterized. The methods used were amplified ribosomal DNA restriction analysis and diversity analysis of the internally transcribed 16S-23S rDNA spacer region (ISR). These analyses revealed low genetic variability of the 16S rDNA gene. These data confirm that these isolates are, or are closely related to, Z. mobilis. Moreover, the analysis of the ISR confirmed the genetic variability of strains deposited in the UFPEDA collection of microorganisms and grouped these strains into ten ribotypes, which can be used in the future for breeding programs and for the preservation of biodiversity. Furthermore, this study characterized the genetic variability between the UFPEDA 205/ ZAP, UFPEDA 98/AG11, and ZAG strains, which were obtained by spheroplast fusion among them. The data also indicate that there is genetic variability among the UFPEDA 202/CP4 and UFPEDA 633/ ZM4 strains, demonstrating that these important Z. mobilis strains are distinct, as suggested in previous studies.

  11. How scary! An analysis of visual communication concerning genetically modified organisms in Italy.

    PubMed

    Ventura, Vera; Frisio, Dario G; Ferrazzi, Giovanni; Siletti, Elena

    2016-04-01

    Several studies provide evidence of the role of written communication in influencing public perception towards genetically modified organisms, whereas visual communication has been sparsely investigated. This article aims to evaluate the exposure of the Italian population to scary genetically modified organism-related images. A set of 517 images collected through Google are classified considering fearful attributes, and an index that accounts for the scary impact of these images is built. Then, through an ordinary least-squares regression, we estimate the relationship between the Scary Impact Index and a set of variables that describes the context in which the images appear. The results reveal that the first (and most viewed) Google result images contain the most frightful contents. In addition, the agri-food sector in Italy is strongly oriented towards offering a negative representation of genetically modified organisms. Exposure to scary images could be a factor that affects the negative perception of genetically modified organisms in Italy.

  12. Quantitative Genetic Analysis of Temperature Regulation in MUS MUSCULUS. I. Partitioning of Variance

    PubMed Central

    Lacy, Robert C.; Lynch, Carol Becker

    1979-01-01

    Heritabilities (from parent-offspring regression) and intraclass correlations of full sibs for a variety of traits were estimated from 225 litters of a heterogeneous stock (HS/Ibg) of laboratory mice. Initial variance partitioning suggested different adaptive functions for physiological, morphological and behavioral adjustments with respect to their thermoregulatory significance. Metabolic heat-production mechanisms appear to have reached their genetic limits, with little additive genetic variance remaining. This study provided no genetic evidence that body size has a close directional association with fitness in cold environments, since heritability estimates for weight gain and adult weight were similar and high, whether or not the animals were exposed to cold. Behavioral heat conservation mechanisms also displayed considerable amounts of genetic variability. However, due to strong evidence from numerous other studies that behavior serves an important adaptive role for temperature regulation in small mammals, we suggest that fluctuating selection pressures may have acted to maintain heritable variation in these traits. PMID:17248909

  13. An information-theoretic approach to estimating the composite genetic effects contributing to variation among generation means: Moving beyond the joint-scaling test for line cross analysis.

    PubMed

    Blackmon, Heath; Demuth, Jeffery P

    2016-02-01

    The pace and direction of evolution in response to selection, drift, and mutation are governed by the genetic architecture that underlies trait variation. Consequently, much of evolutionary theory is predicated on assumptions about whether genes can be considered to act in isolation, or in the context of their genetic background. Evolutionary biologists have disagreed, sometimes heatedly, over which assumptions best describe evolution in nature. Methods for estimating genetic architectures that favor simpler (i.e., additive) models contribute to this debate. Here we address one important source of bias, model selection in line cross analysis (LCA). LCA estimates genetic parameters conditional on the best model chosen from a vast model space using relatively few line means. Current LCA approaches often favor simple models and ignore uncertainty in model choice. To address these issues we introduce Software for Analysis of Genetic Architecture (SAGA), which comprehensively assesses the potential model space, quantifies model selection uncertainty, and uses model weighted averaging to accurately estimate composite genetic effects. Using simulated data and previously published LCA studies, we demonstrate the utility of SAGA to more accurately define the components of complex genetic architectures, and show that traditional approaches have underestimated the importance of epistasis.

  14. Molecular Genetic Analysis of Survival Motor Neuron Gene in 460 Turkish Cases with Suspicious Spinal Muscular Atrophy Disease

    PubMed Central

    RASHNONEJAD, Afrooz; ONAY, Huseyin; ATIK, Tahir; ATAN SAHIN, Ozlem; GOKBEN, Sarenur; TEKGUL, Hasan; OZKINAY, Ferda

    2016-01-01

    Objective To describe 12 yr experience of molecular genetic diagnosis of Spinal Muscular Atrophy (SMA) in 460 cases of Turkish patients. Materials & Methods A retrospective analysis was performed on data from 460 cases, referred to Medical Genetics Laboratory, Ege University’s Hospital, Izmir, Turkey, prediagnosed as SMA or with family history of SMA between 2003 and 2014. The PCR-restriction fragment length polymorphism (RFLP) and the Multiplex ligation–dependent probe amplification (MLPA) analysis were performed to detect the survival motor neuron (SMN)1 deletions and to estimate SMN1 and SMN2 gene copy numbers. Results Using PCR-RFLP test, 159 of 324 postnatal and 18 of 77 prenatal cases were detected to have SMN1 deletions. From positive samples, 88.13% had a homozygous deletion in both exon 7 and exon 8 of SMN1. Using MLPA, 54.5% of families revealed heterozygous deletions of SMN1, and 2 or 3 copies of SMN2, suggesting a healthy SMA carrier. Among patients referred for SMA testing, the annual percentage of patients diagnosed as SMA has decreased gradually from 90.62% (2003) down to 20.83% (2014). Conclusion Although PCR-RFLP method is a reliable test for SMA screening, MLPA is a necessary additional test and provide relevant data for genetic counseling of families having previously affected child. The gradual decrease in the percentage of patients molecularly diagnosed as SMA shows that clinicians have begun to use genetic tests in the differential diagnosis of muscular atrophies. Cost and availability of these genetic tests has greatly attributed to their use. PMID:27843464

  15. Performance of the Tariff Method: validation of a simple additive algorithm for analysis of verbal autopsies

    PubMed Central

    2011-01-01

    Background Verbal autopsies provide valuable information for studying mortality patterns in populations that lack reliable vital registration data. Methods for transforming verbal autopsy results into meaningful information for health workers and policymakers, however, are often costly or complicated to use. We present a simple additive algorithm, the Tariff Method (termed Tariff), which can be used for assigning individual cause of death and for determining cause-specific mortality fractions (CSMFs) from verbal autopsy data. Methods Tariff calculates a score, or "tariff," for each cause, for each sign/symptom, across a pool of validated verbal autopsy data. The tariffs are summed for a given response pattern in a verbal autopsy, and this sum (score) provides the basis for predicting the cause of death in a dataset. We implemented this algorithm and evaluated the method's predictive ability, both in terms of chance-corrected concordance at the individual cause assignment level and in terms of CSMF accuracy at the population level. The analysis was conducted separately for adult, child, and neonatal verbal autopsies across 500 pairs of train-test validation verbal autopsy data. Results Tariff is capable of outperforming physician-certified verbal autopsy in most cases. In terms of chance-corrected concordance, the method achieves 44.5% in adults, 39% in children, and 23.9% in neonates. CSMF accuracy was 0.745 in adults, 0.709 in children, and 0.679 in neonates. Conclusions Verbal autopsies can be an efficient means of obtaining cause of death data, and Tariff provides an intuitive, reliable method for generating individual cause assignment and CSMFs. The method is transparent and flexible and can be readily implemented by users without training in statistics or computer science. PMID:21816107

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

    PubMed

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

    2016-01-01

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

  17. Analysis of synthetic motor oils for additive elements by ICP-AES

    SciTech Connect

    Williams, M.C.; Salmon, S.G.

    1995-12-31

    Standard motor oils are made by blending paraffinic or naphthenic mineral oil base stocks with additive packages containing anti-wear agents, dispersants, corrosion inhibitors, and viscosity index improvers. The blender can monitor the correct addition of the additives by determining the additive elements in samples dissolved in a solvent by ICP-AES. Internal standardization is required to control sample transport interferences due to differences in viscosity between samples and standards. Synthetic motor oils, made with poly-alpha-olefins and trimethylol propane esters, instead of mineral oils, pose an additional challenge since these compounds affect the plasma as well as having sample transport interference considerations. The synthetic lubricant base stocks add significant oxygen to the sample matrix, which makes the samples behave differently than standards prepared in mineral oil. Determination of additive elements in synthetic motor oils will be discussed.

  18. Genetic analysis of CHCHD2 in a southern Spanish population.

    PubMed

    Tejera-Parrado, Cristina; Jesús, Silvia; Huertas-Fernández, Ismael; Bernal-Bernal, Inmaculada; Bonilla-Toribio, Marta; Córdoba-Tevar, Isabel; Abreu-Rodríguez, Irene; Carrillo, Fátima; Bernal-Escudero, Maravilla; Vargas-González, Laura; Carballo, Manuel; Gómez-Garre, Pilar; Mir, Pablo

    2017-02-01

    Researching genetic factors involved in Parkinson's disease (PD) is crucial to increase our knowledge about the pathophysiology of the disorder. A missense mutation has recently been reported within CHCHD2, a gene newly associated with autosomal dominant PD. Subsequent studies in different ethnic populations have not reached any conclusive result about the role of CHCHD2 in PD. Therefore, the aim of this study was to investigate the implication of this gene for a PD population from southern Spain (including 536 PD patients and 518 unrelated control subjects). We studied all 4 exons of CHCHD2 and their exon-intron boundary regions. Four variants were observed in non-coding regions. No significant differences were observed in the allele frequencies of these variants between patients and controls. Thus, our study suggests that CHCHD2 is probably not involved in the etiopathogenesis of PD in our population.

  19. Historical analysis of Newfoundland dog fur colour genetics

    PubMed Central

    Bondeson, J.

    2015-01-01

    This article makes use of digitized historic newspapers to analyze Newfoundland dog fur colour genetics, and fur colour variations over time. The results indicate that contrary to the accepted view, the ‘Solid’ gene was introduced into the British population of Newfoundland dogs in the 1840s. Prior to that time, the dogs were white and black (Landseer) or white and brown, and thus spotted/spotted homozygotes. Due to ‘Solid’ being dominant over ‘spotted’, and selective breeding, today the majority of Newfoundland dogs are solid black. Whereas small white marks on the chest and/or paw appears to be a random event, the historical data supports the existence of an ‘Irish spotted’ fur colour pattern, with white head blaze, breast, paws and tail tip, in spotted/spotted homozygotes. PMID:26623371

  20. Pathway analysis supports association of nonsyndromic cryptorchidism with genetic loci linked to cytoskeleton-dependent functions

    PubMed Central

    Barthold, Julia Spencer; Wang, Yanping; Kolon, Thomas F.; Kollin, Claude; Nordenskjöld, Agneta; Olivant Fisher, Alicia; Figueroa, T. Ernesto; BaniHani, Ahmad H.; Hagerty, Jennifer A.; Gonzaléz, Ricardo; Noh, Paul H.; Chiavacci, Rosetta M.; Harden, Kisha R.; Abrams, Debra J.; Kim, Cecilia E.; Li, Jin; Hakonarson, Hakon; Devoto, Marcella

    2015-01-01

    top loci, none reaching genome-wide significance, but one passing this threshold in a subphenotype analysis of proximal testis position (rs55867206, near SH3PXD2B, odds ratio = 2.2 (95% confidence interval 1.7, 2.9), P = 2 × 10−9). An additional 127 top loci emerged in at least one secondary analysis, particularly of more severe phenotypes. Cytoskeleton-dependent molecular and cellular functions were prevalent in pathway analysis of suggestive signals, and may implicate loci encoding cytoskeletal proteins that participate in androgen receptor signaling. Genes linked to human syndromic cryptorchidism, including hypogonadotropic hypogonadism, and to hormone-responsive and/or differentially expressed genes in normal and cryptorchid rat gubernaculum, were also significantly overrepresented. No tested marker showed significant replication in an independent population. The results suggest heterogeneous, multilocus and potentially multifactorial susceptibility to nonsyndromic cryptorchidism. LIMITATIONS, REASONS FOR CAUTION The present study failed to identify genome-wide significant markers associated with cryptorchidism that could be replicated in an independent population, so further studies are required to define true positive signals among suggestive loci. WIDER IMPLICATIONS OF THE FINDINGS As the only GWAS to date of nonsyndromic cryptorchidism, these data will provide a basis for future efforts to understand genetic susceptibility to this common reproductive anomaly and the potential for additive risk from environmental exposures. STUDY FUNDING/COMPETING INTERESTS This work was supported by R01HD060769 (the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD)), P20RR20173 (the National Center for Research Resources (NCRR), currently P20GM103464 from the National Institute of General Medical Sciences (NIGMS)), an Institute Development Fund to the Center for Applied Genomics at The Children's Hospital of Philadelphia, and Nemours

  1. Genetic analysis of molecular markers for propamocarb residue in Cucumis sativus using quantitative trait locus mapping.

    PubMed

    Xin, M; Wang, L; Ma, B H; Qin, Z W; Zhou, X Y

    2016-11-03

    The use of pesticides to protect plants against harmful organisms, such as pathogenic microorganisms, is one of the most effective ways to improve agricultural production. However, the continuous use of pesticides might present a risk to human health, animals, and the environment. In this study, two cucumber (Cucumis sativus) varieties containing different levels of pesticide residues, D9320 and D0351, were selected to establish an F2 population. A genetic model and genetic linkage map were constructed. The results showed that the heredity of pesticide residues was dominated by an additive effect and was significantly influenced by non-additive factors in cucumber. QCp1 was detected as a quantitative trait locus (QTL) that might be involved in regulating the levels of pesticide residue in cucumber. Moreover, the cucumber genetic map was compared with the LG6 map, and the results indicated that this QTL was closely related to the level of pesticide residue in cucumber.

  2. Genetic analysis of 17 Y-STRs in a Mestizo population from the Central Valley of Mexico.

    PubMed

    Santana, Carla; Noris, Gino; Meraz-Ríos, Marco Antonio; Magaña, Jonathan J; Calderon-Aranda, Emma S; Muñoz, Maria de Lourdes; Gómez, Rocío

    2014-01-01

    This study aims to portray the complex diversity of the Mexican Mestizo population, which represents 98.8% of the entire population of Mexico. We compiled extended haplotype data of the Y chromosome from populations in the Central Valley of Mexico (CVM), which we compared with other Mestizo and parental (Amerindian, European, and African) populations. A complex ancestral relationship was found in the CVM population, suggesting cosmopolitan origins. Nevertheless, the most preeminent lineages point toward a European ancestry, where the R1b lineage was most frequent. In addition, important frequencies of Amerindian lineages were also found in the Mestizo sample studied. Interestingly, the Amerindian ancestry showed a remarkable substructure, which was represented by the two main founding lineages: QL54 (× M3) and M3. However, even within each lineage a high diversity was found despite the small number of sample bearers of these lineages. Further, we detected important genetic differences between the CVM populations and the Mexican Mestizo populations from the north and south. This result points to the fact that Mestizo populations present different ancestral proportions, which are related to the demographic events that gave origin to each population. Finally, we provide additional forensic statistical parameters that are useful in the interpretation of genetic analysis where autosomal loci are limited. Our findings illustrate the complex genetic background of the Mexican Mestizo population and reinforce the need to encompass more geographic regions to generate more robust data for forensic applications.

  3. Heritability of personality: A meta-analysis of behavior genetic studies.

    PubMed

    Vukasović, Tena; Bratko, Denis

    2015-07-01

    The aim of this meta-analysis was to systematize available findings in the field of personality heritability and test for possible moderator effects of study design, type of personality model, and gender on heritability estimates. Study eligibility criteria were: personality model, behavior genetic study design, self-reported data, essential statistical indicators, and independent samples. A total of 134 primary studies with 190 potentially independent effect sizes were identified. After exclusion of studies that did not meet inclusion criteria and/or met 1 of the exclusion criteria, the final sample included 62 independent effect sizes, representing more than 100,000 participants of both genders and all ages. Data analyses were performed using the random-effects model, software program R package metafor. The average effect size was .40, indicating that 40% of individual differences in personality were due to genetic, while 60% are due to environmental influences. After correction for possible publication bias the conclusion was unaltered. Additional analyses showed that personality model and gender were not significant moderators of personality heritability estimate, while study design was a significant moderator with twin studies showing higher estimates, .47, compared to family and adoption studies, .22. Personality model also was not a significant moderator of heritability estimates for neuroticism or extraversion, 2 personality traits contained in most personality trait theories and/or models. This study is the first to empirically test and confirm moderator effect of study design on heritability estimates in the field of personality. Limitations of the study, as well as suggestion for future studies, are discussed. (PsycINFO Database Record

  4. Evidence of Allopolyploidy in Urochloa humidicola Based on Cytological Analysis and Genetic Linkage Mapping.

    PubMed

    Vigna, Bianca B Z; Santos, Jean C S; Jungmann, Leticia; do Valle, Cacilda B; Mollinari, Marcelo; Pastina, Maria M; Pagliarini, Maria Suely; Garcia, Antonio A F; Souza, Anete P

    2016-01-01

    The African species Urochloa humidicola (Rendle) Morrone & Zuloaga (syn. Brachiaria humidicola (Rendle) Schweick.) is an important perennial forage grass found throughout the tropics. This species is polyploid, ranging from tetra to nonaploid, and apomictic, which makes genetic studies challenging; therefore, the number of currently available genetic resources is limited. The genomic architecture and evolution of U. humidicola and the molecular markers linked to apomixis were investigated in a full-sib F1 population obtained by crossing the sexual accession H031 and the apomictic cultivar U. humidicola cv. BRS Tupi, both of which are hexaploid. A simple sequence repeat (SSR)-based linkage map was constructed for the species from 102 polymorphic and specific SSR markers based on simplex and double-simplex markers. The map consisted of 49 linkage groups (LGs) and had a total length of 1702.82 cM, with 89 microsatellite loci and an average map density of 10.6 cM. Eight homology groups (HGs) were formed, comprising 22 LGs, and the other LGs remained ungrouped. The locus that controls apospory (apo-locus) was mapped in LG02 and was located 19.4 cM from the locus Bh027.c.D2. In the cytological analyses of some hybrids, bi- to hexavalents at diakinesis were observed, as well as two nucleoli in some meiocytes, smaller chromosomes with preferential allocation within the first metaphase plate and asynchronous chromosome migration to the poles during anaphase. The linkage map and the meiocyte analyses confirm previous reports of hybridization and suggest an allopolyploid origin of the hexaploid U. humidicola. This is the first linkage map of an Urochloa species, and it will be useful for future quantitative trait locus (QTL) analysis after saturation of the map and for genome assembly and evolutionary studies in Urochloa spp. Moreover, the results of the apomixis mapping are consistent with previous reports and confirm the need for additional studies to search for a co

  5. Whole genome sequence and analysis of the Marwari horse breed and its genetic origin

    PubMed Central

    2014-01-01

    Background The horse (Equus ferus caballus) is one of the earliest domesticated species and has played an important role in the development of human societies over the past 5,000 years. In this study, we characterized the genome of the Marwari horse, a rare breed with unique phenotypic characteristics, including inwardly turned ear tips. It is thought to have originated from the crossbreeding of local Indian ponies with Arabian horses beginning in the 12th century. Results We generated 101 Gb (~30 × coverage) of whole genome sequences from a Marwari horse using the Illumina HiSeq2000 sequencer. The sequences were mapped to the horse reference genome at a mapping rate of ~98% and with ~95% of the genome having at least 10 × coverage. A total of 5.9 million single nucleotide variations, 0.6 million small insertions or deletions, and 2,569 copy number variation blocks were identified. We confirmed a strong Arabian and Mongolian component in the Marwari genome. Novel variants from the Marwari sequences were annotated, and were found to be enriched in olfactory functions. Additionally, we suggest a potential functional genetic variant in the TSHZ1 gene (p.Ala344>Val) associated with the inward-turning ear tip shape of the Marwari horses. Conclusions Here, we present an analysis of the Marwari horse genome. This is the first genomic data for an Asian breed, and is an invaluable resource for future studies of genetic variation associated with phenotypes and diseases in horses. PMID:25521865

  6. A Genetic and Molecular Analysis of the 46c Chromosomal Region Surrounding the Fmrfamide Neuropeptide Gene in Drosophila Melanogaster

    PubMed Central

    O'Brien, M. A.; Roberts, M. S.; Taghert, P. H.

    1994-01-01

    We have analyzed the FMRFamide neuropeptide gene region of Drosophila melanogaster. This gene maps to the 46C region of chromosome 2R; this interval previously was not well characterized. For this genetic and molecular analysis, we have used X-ray mutagenesis, EMS mutagenesis, and the recently reported local P element transposition method. We identified four overlapping deletions, two of which have proximal breakpoints that define a 50-60-kb region surrounding the FMRFamide gene in 46C. To this small region, we mapped three lethal complementation groups; 10 additional lethal complementation groups were mapped to more distal regions of 46CD. One of these groups corresponds to even-skipped, the other 12 are previously unidentified. Using various lines of evidence we excluded the possibility that FMRFamide corresponds to any of the three lethal complementation groups mapping to its immediate 50-60-kb vicinity. The positions of two of the three lethal complementation groups were identified with P elements using a local transposition scheme. The third lethal complementation group was excluded as being FMRFamide mutants by sequence analysis and by immunocytochemistry with proFMRFamide precursor-specific antibodies. This analysis has (1) provided a genetic map of the 46CD chromosomal region and a detailed molecular map of a portion of the 46C region and (2) provided additional evidence of the utility of local transposition for targeting nearby genes. PMID:8056304

  7. The effect of close relatives on unsupervised Bayesian clustering algorithms in population genetic structure analysis.

    PubMed

    Rodríguez-Ramilo, Silvia T; Wang, Jinliang

    2012-09-01

    The inference of population genetic structures is essential in many research areas in population genetics, conservation biology and evolutionary biology. Recently, unsupervised Bayesian clustering algorithms have been developed to detect a hidden population structure from genotypic data, assuming among others that individuals taken from the population are unrelated. Under this assumption, markers in a sample taken from a subpopulation can be considered to be in Hardy-Weinberg and linkage equilibrium. However, close relatives might be sampled from the same subpopulation, and consequently, might cause Hardy-Weinberg and linkage disequilibrium and thus bias a population genetic structure analysis. In this study, we used simulated and real data to investigate the impact of close relatives in a sample on Bayesian population structure analysis. We also showed that, when close relatives were identified by a pedigree reconstruction approach and removed, the accuracy of a population genetic structure analysis can be greatly improved. The results indicate that unsupervised Bayesian clustering algorithms cannot be used blindly to detect genetic structure in a sample with closely related individuals. Rather, when closely related individuals are suspected to be frequent in a sample, these individuals should be first identified and removed before conducting a population structure analysis.

  8. Analysis of genetic diversity and differentiation of seven stocks of Litopenaeus vannamei using microsatellite markers

    NASA Astrophysics Data System (ADS)

    Zhang, Kai; Wang, Weiji; Li, Weiya; Zhang, Quanqi; Kong, Jie

    2014-08-01

    Seven microsatellite markers were used to evaluate the genetic diversity and differentiation of seven stocks of Litopenaeus vannamei, which were introduced from Central and South America to China. All seven microsatellite loci were polymorphic, with polymorphism information content ( PIC) values ranging from 0.593 to 0.952. Totally 92 alleles were identified, and the number of alleles ( Na) and effective alleles ( Ne) varied between 4 and 21 and 2.7 and 14.6, respectively. Observed heterozygosity ( H o) values were lower than the expected heterozygosity ( H e) values (0.526-0.754), which indicated that the seven stocks possessed a rich genetic diversity. Thirty-seven tests were detected for reasonable significant deviation from Hardy-Weinberg equilibrium. F is values were positive at five loci, suggesting that there was a relatively high degree of inbreeding within stocks. Pairwise F st values ranged from 0.0225 to 0.151, and most of the stock pairs were moderately differentiated. Genetic distance and cluster analysis using UPGMA revealed a close genetic relationship of L. vannamei between Pop2 and Pop3. AMOVA indicated that the genetic variation among stocks (11.3%) was much lower than that within stocks (88.7%). Although the seven stocks had a certain degree of genetic differentiation and a rich genetic diversity, there is an increasing risk of decreased performance due to inbreeding in subsequent generations.

  9. Genetic diversity in cultivated carioca common beans based on molecular marker analysis

    PubMed Central

    Küpper Cardoso Perseguini, Juliana Morini; Chioratto, Alisson Fernando; Zucchi, Maria Imaculada; Colombo, Carlos Augusto; Carbonell, Sérgio Augusto Moraes; Costa Mondego, Jorge Mauricio; Gazaffi, Rodrigo; Franco Garcia, Antonio Augusto; de Campos, Tatiana; de Souza, Anete Pereira; Rubiano, Luciana Benchimol

    2011-01-01

    A wide array of molecular markers has been used to investigate the genetic diversity among common bean species. However, the best combination of markers for studying such diversity among common bean cultivars has yet to be determined. Few reports have examined the genetic diversity of the carioca bean, commercially one of the most important common beans in Brazil. In this study, we examined the usefulness of two molecular marker systems (simple sequence repeats – SSRs and amplified fragment length polymorphisms – AFLPs) for assessing the genetic diversity of carioca beans. The amount of information provided by Roger’s modified genetic distance was used to analyze SSR data and Jaccards similarity coefficient was used for AFLP data. Seventy SSRs were polymorphic and 20 AFLP primer combinations produced 635 polymorphic bands. Molecular analysis showed that carioca genotypes were quite diverse. AFLPs revealed greater genetic differentiation and variation within the carioca genotypes (Gst = 98% and Fst = 0.83, respectively) than SSRs and provided better resolution for clustering the carioca genotypes. SSRs and AFLPs were both suitable for assessing the genetic diversity of Brazilian carioca genotypes since the number of markers used in each system provided a low coefficient of variation. However, fingerprint profiles were generated faster with AFLPs, making them a better choice for assessing genetic diversity in the carioca germplasm. PMID:21637550

  10. A theoretical analysis of population genetics of plants on restored habitats

    SciTech Connect

    Bogoliubov, A.G.; Loehle, C.

    1997-07-01

    Seed and propagules used for habitat restoration are not likely to be closely adapted to local site conditions. Rapid changes of genotypes frequencies on local microsites and/or microevolution would allow plants to become better adapted to a site. These same factors would help to maintain genetic diversity and ensure the survival of small endangered populations. The authors used population genetics models to examine the selection of genotypes during establishment on restored sites. Vegetative spread was shown to affect selection and significantly reduce genetic diversity. To study general microevolution, the authors linked a model of resource usage with a genetics model and analyzed competition between genotypes. A complex suite of feasible ecogenetic states was shown to result. The state actually resulting would depend strongly on initial conditions. This analysis indicated that genetic structure can vary locally and can produce overall genetic variability that is not simply the result of microsite adaptations. For restoration activities, the implication is that small differences in seed source could lead to large differences in local genetic structure after selection.

  11. A theoretical analysis of population genetics of plants on restored habitats

    SciTech Connect

    Bogoliubov, A.G.; Loehle, C.

    1995-02-01

    Seed and propagules used for habitat restoration are not likely to be closely adapted to local site conditions. Rapid changes of genotypes frequencies on local microsites and/or microevolution would allow plants to become better adapted to a site. These same factors would help to maintain genetic diversity and ensure the survival of small endangered populations. We used population genetics models to examine the selection of genotypes during establishment on restored sites. Vegetative spread was shown to affect selection and significantly reduce genetic diversity. To study general microevolution, we linked a model of resource usage with a genetics model and analyzed competition between genotypes. A complex suite of feasible ecogenetic states was shown to result. The state actually resulting would depend strongly on initial conditions. This analysis indicated that genetic structure can vary locally and can produce overall genetic variability that is not simply the result of microsite adaptations. For restoration activities, the implication is that small differences in seed source could lead to large differences in local genetic structure after selection.

  12. The Importance of Source: A Mixed Methods Analysis of Undergraduate Students' Attitudes toward Genetically Modified Food

    ERIC Educational Resources Information Center

    Ruth, Taylor K.; Rumble, Joy N.; Gay, Keegan D.; Rodriguez, Mary T.

    2016-01-01

    Even though science says genetically modified (GM) foods are safe, many consumers remain skeptical of the technology. Additionally, the scientific community has trouble communicating to the public, causing consumers to make uninformed decisions. The Millennial Generation will have more buying power than any other generation before them, and more…

  13. Rule based classifier for the analysis of gene-gene and gene-environment interactions in genetic association studies

    PubMed Central

    2011-01-01

    Background Several methods have been presented for the analysis of complex interactions between genetic polymorphisms and/or environmental factors. Despite the available methods, there is still a need for alternative methods, because no single method will perform well in all scenarios. The aim of this work was to evaluate the performance of three selected rule based classifier algorithms, RIPPER, RIDOR and PART, for the analysis of genetic association studies. Methods Overall, 42 datasets were simulated with three different case-control models, a varying number of subjects (300, 600), SNPs (500, 1500, 3000) and noise (5%, 10%, 20%). The algorithms were applied to each of the datasets with a set of algorithm-specific settings. Results were further investigated with respect to a) the Model, b) the Rules, and c) the Attribute level. Data analysis was performed using WEKA, SAS and PERL. Results The RIPPER algorithm discovered the true case-control model at least once in >33% of the datasets. The RIDOR and PART algorithm performed poorly for model detection. The RIPPER, RIDOR and PART algorithm discovered the true case-control rules in more than 83%, 83% and 44% of the datasets, respectively. All three algorithms were able to detect the attributes utilized in the respective case-control models in most datasets. Conclusions The current analyses substantiate the utility of rule based classifiers such as RIPPER, RIDOR and PART for the detection of gene-gene/gene-environment interactions in genetic association studies. These classifiers could provide a valuable new method, complementing existing approaches, in the analysis of genetic association studies. The methods provide an advantage in being able to handle both categorical and continuous variable types. Further, because the outputs of the analyses are easy to interpret, the rule based classifier approach could quickly generate testable hypotheses for additional evaluation. Since the algorithms are computationally

  14. Comparative analysis of patterns of localization of mobile genetic elements in selection-genetic experiments on Drosophila melanogaster

    SciTech Connect

    Vasil`eva, L.A.; Ratner, V.A. |; Zabanov, S.A.

    1995-07-01

    A comparative selection-genetic analysis of three heterogeneous lines of Drosophila melanogaster with an interrupted longitudinal wing vein was performed. In the control line, riC, and two selection lines, riSP and riSN, overall patterns of localization of six families mobile genetic elements (MGE) (MDG1, MDG2, MDG3, MDG4, copia, and 297) were compared. In all, the lines contained 220 sites (copies) in 153 segments of the Bridges` map. According to response to selection, six classes of sites were identified: strong positive (P), weak positive (p), neutral (0), weak negative (n), strong negative (N), and abnormal (A). More than 50% of the sites (P + N + p + n) were shown to respond to selection; the contrasting classes (P and N and p and n) counterbalanced each other. These sites are assumed to mark actual parts of the genome, where polygenes are located. In other words, more than 50% of the total number of the genome sites act as polygenes controlling this quantitative character and respond to selection. Pleiotropy of polygenes in such a system must be very high. 22.2% of sites are neutral (class 0); apparently, they do not mark polygenes. The remaining 21.8% of sites (class A) show an anomalous response to selection. They are assumed to mark the polygenes of another genetic system, which participated in the maintenance of homeostasis in the original line riC. On the basis of this evidence, the concept of oligogenes and polygenes is developed. Oligogenes and polygenes are genes that occupy respectively limiting and nonlimiting positions in systems of expression. Adaptive properties of oligogenes are evaluated first and evolve rapidly. Adaptive properties of polygenes are evaluated only with regard to their total set and are limited by oligogenes. Variation of polygenic systems is generated by polygenic combination and spontaneous transpositions and excisions of MGE. 26 refs., 5 tabs.

  15. [Genetic analysis of microsatellite polymorphism in the Elliot's Pheasant (Syrmaticus ellioti) in China].

    PubMed

    Lin, Fang-Jun; Jiang, Ping-Ping; Ding, Ping

    2010-10-01

    In this study, we reported the population genetic analyses in the Elliot's Pheasant(Syrnaticus ellioti) using seven polymorphism microsatellite loci based on 105 individuals from 4 geographical populations. Departures from Hardy-Weinberg equilibrium were found in four geographical populations. The average number of alleles was 8.86, with a total of 62 alleles across 7 loci; observed heterozygosity (HO) was generally low and the average number was 0.504. For the seven microsatellite loci, the polymorphism information content ranged from 0.549 to 0.860, with an average number 0.712. Population bottlenecks of the four geographical populations were tested by infinite allele mutation model, step-wise mutation model and two-phase mutation model, which found that each population had experienced bottleneck effect during the recent period. Fst analysis across all geographical populations indicated that the genetic differentiaton between the Guizhou geographical population and the Hunan geographical population was highly significant (P<0.001), a finding supported by the far genetic relationship showed by the neighbor-joining tree of four geographical populations based on Nei's unbiased genetic distances. Using hierarchical analysis of molecular variance (Guizhou geographical population relative to all others pooled), we found a low level of the genetic variation among geographical populations and that between groups. However, differences among populations relative to the total sample explained most of the genetic variance (92.84%), which was significant.

  16. Delineation of genetic relatedness and population structure of oral and enteric Campylobacter concisus strains by analysis of housekeeping genes.

    PubMed

    Mahendran, Vikneswari; Octavia, Sophie; Demirbas, Omer Faruk; Sabrina, Sheryl; Ma, Rena; Lan, Ruiting; Riordan, Stephen M; Grimm, Michael C; Zhang, Li

    2015-08-01

    Campylobacter concisus is an oral bacterium that has been shown to be associated with inflammatory bowel disease (IBD). In this study we examined clusters of oral C. concisus strains isolated from patients with IBD and healthy controls by analysing six housekeeping genes. In addition, we investigated the population structure of C. concisus strains. Whether oral and enteric strains form distinct clusters based on the sequences of these housekeeping genes was also investigated. The oral C. concisus strains were found to contain two genomospecies, which belong to the two genomospecies previously found in enteric C. concisus strains. C. concisus clusters formed based on the sequences of a single aspA gene were the same as that formed by using previously reported MLST schemes. The analysis of combined oral and enteric C. concisus strains found that enteric C. concisus strains did not form distinct clusters. Genetic structure analysis identified five subpopulations of C. concisus and showed that genetic recombination between C. concisus strains was common. However, genetic recombination was significantly less in oral strains isolated from patients with IBD than from healthy individuals. Previously reported oral and enteric intestinal epithelial invasive C. concisus strains were in cluster II and subpopulation III. Furthermore, this study shows that there are no distinct enteric C. concisus strain clusters or subpopulations.

  17. Assessing genetic diversity in a sugarcane germplasm collection using an automated AFLP analysis.

    PubMed

    Besse, P; Taylor, G; Carroll, B; Berding, N; Burner, D; McIntyre, C L

    1998-10-01

    An assessment of genetic diversity within and between Saccharum, Old World Erianthus sect. Ripidium, and North American E.giganteus (S.giganteum) was conducted using Amplified Fragment Length Polymorphism (AFLP(TM)) markers. An automated gel scoring system (GelCompar(TM)) was successfully used to analyse the complex AFLP patterns obtained in sugarcane and its relatives. Similarity coefficient calculations and clustering revealed a genetic structure for Saccharum and Erianthus sect. Ripidium that was identical to the one previously obtained using other molecular marker types, showing the appropriateness of AFLP markers and the associated automated analysis in assessing genetic diversity in sugarcane. A genetic structure that correlated with cytotype (2n=30, 60, 90) was revealed within the North American species, E. giganteus (S.giganteum). Complex relationships among Saccharum, Erianthus sect. Ripidium, and North American E.giganteus were revealed and are discussed in the light of a similar study which involved RAPD markers.

  18. Combined sequence-based and genetic mapping analysis of complex traits in outbred rats.

    PubMed

    Baud, Amelie; Hermsen, Roel; Guryev, Victor; Stridh, Pernilla; Graham, Delyth; McBride, Martin W; Foroud, Tatiana; Calderari, Sophie; Diez, Margarita; Ockinger, Johan; Beyeen, Amennai D; Gillett, Alan; Abdelmagid, Nada; Guerreiro-Cacais, Andre Ortlieb; Jagodic, Maja; Tuncel, Jonatan; Norin, Ulrika; Beattie, Elisabeth; Huynh, Ngan; Miller, William H; Koller, Daniel L; Alam, Imranul; Falak, Samreen; Osborne-Pellegrin, Mary; Martinez-Membrives, Esther; Canete, Toni; Blazquez, Gloria; Vicens-Costa, Elia; Mont-Cardona, Carme; Diaz-Moran, Sira; Tobena, Adolf; Hummel, Oliver; Zelenika, Diana; Saar, Kathrin; Patone, Giannino; Bauerfeind, Anja; Bihoreau, Marie-Therese; Heinig, Matthias; Lee, Young-Ae; Rintisch, Carola; Schulz, Herbert; Wheeler, David A; Worley, Kim C; Muzny, Donna M; Gibbs, Richard A; Lathrop, Mark; Lansu, Nico; Toonen, Pim; Ruzius, Frans Paul; de Bruijn, Ewart; Hauser, Heidi; Adams, David J; Keane, Thomas; Atanur, Santosh S; Aitman, Tim J; Flicek, Paul; Malinauskas, Tomas; Jones, E Yvonne; Ekman, Diana; Lopez-Aumatell, Regina; Dominiczak, Anna F; Johannesson, Martina; Holmdahl, Rikard; Olsson, Tomas; Gauguier, Dominique; Hubner, Norbert; Fernandez-Teruel, Alberto; Cuppen, Edwin; Mott, Richard; Flint, Jonathan

    2013-07-01

    Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.

  19. Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

    PubMed Central

    Baud, Amelie; Hermsen, Roel; Guryev, Victor; Stridh, Pernilla; Graham, Delyth; McBride, Martin W.; Foroud, Tatiana; Calderari, Sophie; Diez, Margarita; Ockinger, Johan; Beyeen, Amennai D.; Gillett, Alan; Abdelmagid, Nada; Guerreiro-Cacais, Andre Ortlieb; Jagodic, Maja; Tuncel, Jonatan; Norin, Ulrika; Beattie, Elisabeth; Huynh, Ngan; Miller, William H.; Koller, Daniel L.; Alam, Imranul; Falak, Samreen; Osborne-Pellegrin, Mary; Martinez-Membrives, Esther; Canete, Toni; Blazquez, Gloria; Vicens-Costa, Elia; Mont-Cardona, Carme; Diaz-Moran, Sira; Tobena, Adolf; Hummel, Oliver; Zelenika, Diana; Saar, Kathrin; Patone, Giannino; Bauerfeind, Anja; Bihoreau, Marie-Therese; Heinig, Matthias; Lee, Young-Ae; Rintisch, Carola; Schulz, Herbert; Wheeler, David A.; Worley, Kim C.; Muzny, Donna M.; Gibbs, Richard A.; Lathrop, Mark; Lansu, Nico; Toonen, Pim; Ruzius, Frans Paul; de Bruijn, Ewart; Hauser, Heidi; Adams, David J.; Keane, Thomas; Atanur, Santosh S.; Aitman, Tim J.; Flicek, Paul; Malinauskas, Tomas; Jones, E. Yvonne; Ekman, Diana; Lopez-Aumatell, Regina; Dominiczak, Anna F; Johannesson, Martina; Holmdahl, Rikard; Olsson, Tomas; Gauguier, Dominique; Hubner, Norbert; Fernandez-Teruel, Alberto; Cuppen, Edwin; Mott, Richard; Flint, Jonathan

    2013-01-01

    Genetic mapping on fully sequenced individuals is transforming our understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating novel genes in models of anxiety, heart disease and multiple sclerosis. The relation between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show the extent and spatial pattern of variation in inbred rats differ significantly from those of inbred mice, and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species. PMID:23708188

  20. Moving toward System Genetics through Multiple Trait Analysis in Genome-Wide Association Studies

    PubMed Central

    Shriner, Daniel

    2011-01-01

    Association studies are a staple of genotype–phenotype mapping studies, whether they are based on single markers, haplotypes, candidate genes, genome-wide genotypes, or whole genome sequences. Although genetic epidemiological studies typically contain data collected on multiple traits which themselves are often correlated, most analyses have been performed on single traits. Here, I review several methods that have been developed to perform multiple trait analysis. These methods range from traditional multivariate models for systems of equations to recently developed graphical approaches based on network theory. The application of network theory to genetics is termed systems genetics and has the potential to address long-standing questions in genetics about complex processes such as coordinate regulation, homeostasis, and pleiotropy. PMID:22303408