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Sample records for dominance genetic variance

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

    PubMed

    Sztepanacz, Jacqueline L; Blows, Mark W

    2015-05-01

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

  2. Dominance Genetic Variance for Traits Under Directional Selection in Drosophila serrata

    PubMed Central

    Sztepanacz, Jacqueline L.; Blows, Mark W.

    2015-01-01

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

  3. 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

  4. Hierarchical spatial modeling of additive and dominance genetic variance for large spatial trial datasets.

    PubMed

    Finley, Andrew O; Banerjee, Sudipto; Waldmann, Patrik; Ericsson, Tore

    2009-06-01

    This article expands upon recent interest in Bayesian hierarchical models in quantitative genetics by developing spatial process models for inference on additive and dominance genetic variance within the context of large spatially referenced trial datasets. Direct application of such models to large spatial datasets are, however, computationally infeasible because of cubic-order matrix algorithms involved in estimation. The situation is even worse in Markov chain Monte Carlo (MCMC) contexts where such computations are performed for several iterations. Here, we discuss approaches that help obviate these hurdles without sacrificing the richness in modeling. For genetic effects, we demonstrate how an initial spectral decomposition of the relationship matrices negate the expensive matrix inversions required in previously proposed MCMC methods. For spatial effects, we outline two approaches for circumventing the prohibitively expensive matrix decompositions: the first leverages analytical results from Ornstein-Uhlenbeck processes that yield computationally efficient tridiagonal structures, whereas the second derives a modified predictive process model from the original model by projecting its realizations to a lower-dimensional subspace, thereby reducing the computational burden. We illustrate the proposed methods using a synthetic dataset with additive, dominance, genetic effects and anisotropic spatial residuals, and a large dataset from a Scots pine (Pinus sylvestris L.) progeny study conducted in northern Sweden. Our approaches enable us to provide a comprehensive analysis of this large trial, which amply demonstrates that, in addition to violating basic assumptions of the linear model, ignoring spatial effects can result in downwardly biased measures of heritability.

  5. On the Additive and Dominant Variance and Covariance of Individuals Within the Genomic Selection Scope

    PubMed Central

    Vitezica, Zulma G.; Varona, Luis; Legarra, Andres

    2013-01-01

    Genomic evaluation models can fit additive and dominant SNP effects. Under quantitative genetics theory, additive or “breeding” values of individuals are generated by substitution effects, which involve both “biological” additive and dominant effects of the markers. Dominance deviations include only a portion of the biological dominant effects of the markers. Additive variance includes variation due to the additive and dominant effects of the markers. We describe a matrix of dominant genomic relationships across individuals, D, which is similar to the G matrix used in genomic best linear unbiased prediction. This matrix can be used in a mixed-model context for genomic evaluations or to estimate dominant and additive variances in the population. From the “genotypic” value of individuals, an alternative parameterization defines additive and dominance as the parts attributable to the additive and dominant effect of the markers. This approach underestimates the additive genetic variance and overestimates the dominance variance. Transforming the variances from one model into the other is trivial if the distribution of allelic frequencies is known. We illustrate these results with mouse data (four traits, 1884 mice, and 10,946 markers) and simulated data (2100 individuals and 10,000 markers). Variance components were estimated correctly in the model, considering breeding values and dominance deviations. For the model considering genotypic values, the inclusion of dominant effects biased the estimate of additive variance. Genomic models were more accurate for the estimation of variance components than their pedigree-based counterparts. PMID:24121775

  6. On the additive and dominant variance and covariance of individuals within the genomic selection scope.

    PubMed

    Vitezica, Zulma G; Varona, Luis; Legarra, Andres

    2013-12-01

    Genomic evaluation models can fit additive and dominant SNP effects. Under quantitative genetics theory, additive or "breeding" values of individuals are generated by substitution effects, which involve both "biological" additive and dominant effects of the markers. Dominance deviations include only a portion of the biological dominant effects of the markers. Additive variance includes variation due to the additive and dominant effects of the markers. We describe a matrix of dominant genomic relationships across individuals, D, which is similar to the G matrix used in genomic best linear unbiased prediction. This matrix can be used in a mixed-model context for genomic evaluations or to estimate dominant and additive variances in the population. From the "genotypic" value of individuals, an alternative parameterization defines additive and dominance as the parts attributable to the additive and dominant effect of the markers. This approach underestimates the additive genetic variance and overestimates the dominance variance. Transforming the variances from one model into the other is trivial if the distribution of allelic frequencies is known. We illustrate these results with mouse data (four traits, 1884 mice, and 10,946 markers) and simulated data (2100 individuals and 10,000 markers). Variance components were estimated correctly in the model, considering breeding values and dominance deviations. For the model considering genotypic values, the inclusion of dominant effects biased the estimate of additive variance. Genomic models were more accurate for the estimation of variance components than their pedigree-based counterparts.

  7. Genetic Dominance & Cellular Processes

    ERIC Educational Resources Information Center

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  8. Genetic Dominance & Cellular Processes

    ERIC Educational Resources Information Center

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  9. Dominance, Information, and Hierarchical Scaling of Variance Space.

    ERIC Educational Resources Information Center

    Ceurvorst, Robert W.; Krus, David J.

    1979-01-01

    A method for computation of dominance relations and for construction of their corresponding hierarchical structures is presented. The link between dominance and variance allows integration of the mathematical theory of information with least squares statistical procedures without recourse to logarithmic transformations of the data. (Author/CTM)

  10. Dominance, Information, and Hierarchical Scaling of Variance Space.

    ERIC Educational Resources Information Center

    Ceurvorst, Robert W.; Krus, David J.

    1979-01-01

    A method for computation of dominance relations and for construction of their corresponding hierarchical structures is presented. The link between dominance and variance allows integration of the mathematical theory of information with least squares statistical procedures without recourse to logarithmic transformations of the data. (Author/CTM)

  11. Estimation of dominance variance in purebred Yorkshire swine.

    PubMed

    Culbertson, M S; Mabry, J W; Misztal, I; Gengler, N; Bertrand, J K; Varona, L

    1998-02-01

    We used 179,485 Yorkshire reproductive and 239,354 Yorkshire growth records to estimate additive and dominance variances by Method Fraktur R. Estimates were obtained for number born alive (NBA), 21-d litter weight (LWT), days to 104.5 kg (DAYS), and backfat at 104.5 kg (BF). The single-trait models for NBA and LWT included the fixed effects of contemporary group and regression on inbreeding percentage and the random effects mate within contemporary group, animal permanent environment, animal additive, and parental dominance. The single-trait models for DAYS and BF included the fixed effects of contemporary group, sex, and regression on inbreeding percentage and the random effects litter of birth, dam permanent environment, animal additive, and parental dominance. Final estimates were obtained from six samples for each trait. Regression coefficients for 10% inbreeding were found to be -.23 for NBA, -.52 kg for LWT, 2.1 d for DAYS, and 0 mm for BF. Estimates of additive and dominance variances expressed as a percentage of phenotypic variances were, respectively, 8.8 +/- .5 and 2.2 +/- .7 for NBA, 8.1 +/- 1.1 and 6.3 +/- .9 for LWT, 33.2 +/- .4 and 10.3 +/- 1.5 for DAYS, and 43.6 +/- .9 and 4.8 +/- .7 for BF. The ratio of dominance to additive variances ranged from .78 to .11.

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

    PubMed

    Zhu, J

    1995-12-01

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

  13. Analysis of Conditional Genetic Effects and Variance Components in Developmental Genetics

    PubMed Central

    Zhu, J.

    1995-01-01

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

  14. Characterizing the evolution of genetic variance using genetic covariance tensors.

    PubMed

    Hine, Emma; Chenoweth, Stephen F; Rundle, Howard D; Blows, Mark W

    2009-06-12

    Determining how genetic variance changes under selection in natural populations has proved to be a very resilient problem in evolutionary genetics. In the same way that understanding the availability of genetic variance within populations requires the simultaneous consideration of genetic variance in sets of functionally related traits, determining how genetic variance changes under selection in natural populations will require ascertaining how genetic variance-covariance (G) matrices evolve. Here, we develop a geometric framework using higher-order tensors, which enables the empirical characterization of how G matrices have diverged among populations. We then show how divergence among populations in genetic covariance structure can then be associated with divergence in selection acting on those traits using key equations from evolutionary theory. Using estimates of G matrices of eight male sexually selected traits from nine geographical populations of Drosophila serrata, we show that much of the divergence in genetic variance occurred in a single trait combination, a conclusion that could not have been reached by examining variation among the individual elements of the nine G matrices. Divergence in G was primarily in the direction of the major axes of genetic variance within populations, suggesting that genetic drift may be a major cause of divergence in genetic variance among these populations.

  15. Variance in the reproductive success of dominant male mountain gorillas.

    PubMed

    Robbins, Andrew M; Gray, Maryke; Uwingeli, Prosper; Mburanumwe, Innocent; Kagoda, Edwin; Robbins, Martha M

    2014-10-01

    Using 30 years of demographic data from 15 groups, this study estimates how harem size, female fertility, and offspring survival may contribute to variance in the siring rates of dominant male mountain gorillas throughout the Virunga Volcano Region. As predicted for polygynous species, differences in harem size were the greatest source of variance in the siring rate, whereas differences in female fertility and offspring survival were relatively minor. Harem size was positively correlated with offspring survival, even after removing all known and suspected cases of infanticide, so the correlation does not seem to reflect differences in the ability of males to protect their offspring. Harem size was not significantly correlated with female fertility, which is consistent with the hypothesis that mountain gorillas have minimal feeding competition. Harem size, offspring survival, and siring rates were not significantly correlated with the proportion of dominant tenures that occurred in multimale groups versus one-male groups; even though infanticide is less likely when those tenures end in multimale groups than one-male groups. In contrast with the relatively small contribution of offspring survival to variance in the siring rates of this study, offspring survival is a major source of variance in the male reproductive success of western gorillas, which have greater predation risks and significantly higher rates of infanticide. If differences in offspring protection are less important among male mountain gorillas than western gorillas, then the relative importance of other factors may be greater for mountain gorillas. Thus, our study illustrates how variance in male reproductive success and its components can differ between closely related species.

  16. Bottleneck Effects on Genetic Variance for Courtship Repertoire

    PubMed Central

    Meffert, L. M.

    1995-01-01

    Bottleneck effects on evolutionary potential in mating behavior were addressed through assays of additive genetic variances and resulting phenotypic responses to drift in the courtship repertoires of six two-pair founder-flush lines and two control populations of the housefly. A simulation addressed the complication that an estimate of the genetic variance for a courtship trait (e.g., male performance vigor or the female requirement for copulation) must involve assays against the background behavior of the mating partners. The additive ``environmental'' effect of the mating partner's phenotype simply dilutes the net parent-offspring covariance for a trait. However, if there is an interaction with this ``environmental'' component, negative parent-offspring covariances can result under conditions of high incompatibility between the population's distributions for male performance and female choice requirements, despite high levels of genetic variance. All six bottlenecked lines exhibited significant differentiation from the controls in at least one measure of the parent-offspring covariance for male performance or female choice (estimated by 50 parent-son and 50 parent-daughter covariances for 10 courtship traits per line) which translated to significant phenotypic drift. However, the average effect across traits or across lines did not yield a significant net increase in genetic variance due to bottlenecks. Concerted phenotypic differentiation due to the founder-flush event provided indirect evidence of directional dominance in a subset of traits. Furthermore, indirect evidence of genotype-environment interactions (potentially producing genotype-genotype effects) was found in the negative parent-offspring covariances predicted by the male-female interaction simulation and by the association of the magnitude of phenotypic drift with the absolute value of the parent-offspring covariance. Hence, nonadditive genetic effects on mating behavior may be important in

  17. Variance in Dominant Grain Size Across the Mississippi River Delta

    NASA Astrophysics Data System (ADS)

    Miller, K. L.; Chamberlain, E. L.; Esposito, C. R.; Wagner, R. W.; Mohrig, D. C.

    2016-02-01

    Proposals to restore coastal Louisiana often center on Mississippi River diversion projects wherein water and sediment are routed into wetlands and shallow waters in an effort to build land. Successful design and implementation of diversions will include consideration of behavior and characteristics of sediment, both in the river and in the receiving basin. The Mississippi River sediment load is primarily mud (roughly 75%), with the remainder being very-fine to medium sand or organic detritus. The dominance of muds leads many to suggest that diversions should focus on capturing the mud fraction despite the smaller size and longer settling times required for these particles compared to sand; others believe that sand should be the focus. We present a systemic analysis of the texture of land-building sediment in the Mississippi Delta using borehole data from various depositional environments representing a range of spatial scales, system ages, and fluvial and basin characteristics. We include subdelta-scale data from the incipient Wax Lake Delta and from the distal plain of the abandoned Lafourche subdelta, as well as crevasse-scale data from modern Cubit's Gap and the Attakapas splay, an inland Lafourche crevasse. Comparison of these sites demonstrates a large variance in the volumetric mud to sand ratios across the system. We consider the differences to be emblematic of the various forcings on each lobe as it formed and suggest that the most efficient building block for a diversion is a function of the receiving basin and is not uniform across the entire delta.

  18. Orthogonal Estimates of Variances for Additive, Dominance, and Epistatic Effects in Populations.

    PubMed

    Vitezica, Zulma G; Legarra, Andrés; Toro, Miguel A; Varona, Luis

    2017-07-01

    Genomic prediction methods based on multiple markers have potential to include nonadditive effects in prediction and analysis of complex traits. However, most developments assume a Hardy-Weinberg equilibrium (HWE). Statistical approaches for genomic selection that account for dominance and epistasis in a general context, without assuming HWE (e.g., crosses or homozygous lines), are therefore needed. Our method expands the natural and orthogonal interactions (NOIA) approach, which builds incidence matrices based on genotypic (not allelic) frequencies, to include genome-wide epistasis for an arbitrary number of interacting loci in a genomic evaluation context. This results in an orthogonal partition of the variances, which is not warranted otherwise. We also present the partition of variance as a function of genotypic values and frequencies following Cockerham's orthogonal contrast approach. Then we prove for the first time that, even not in HWE, the multiple-loci NOIA method is equivalent to construct epistatic genomic relationship matrices for higher-order interactions using Hadamard products of additive and dominant genomic orthogonal relationships. A standardization based on the trace of the relationship matrices is, however, needed. We illustrate these results with two simulated F1 (not in HWE) populations, either in linkage equilibrium (LE), or in linkage disequilibrium (LD) and divergent selection, and pure biological dominant pairwise epistasis. In the LE case, correct and orthogonal estimates of variances were obtained using NOIA genomic relationships but not if relationships were constructed assuming HWE. For the LD simulation, differences were smaller, due to the smaller deviation of the F1 from HWE. Wrongly assuming HWE to build genomic relationships and estimate variance components yields biased estimates, inflates the total genetic variance, and the estimates are not empirically orthogonal. The NOIA method to build genomic relationships, coupled with

  19. The depletion of genetic variance by sexual selection.

    PubMed

    Van Homrigh, Anna; Higgie, Megan; McGuigan, Katrina; Blows, Mark W

    2007-03-20

    Sexually selected traits display substantial genetic variance [1, 2], in conflict with the expectation that sexual selection will deplete it [3-5]. Condition dependence is thought to resolve this paradox [5-7], but experimental tests that relate the direction of sexual selection to the availability of genetic variance are lacking. Here, we show that condition-dependent expression is not sufficient to maintain genetic variance available to sexual selection in multiple male sexually selected traits. We employed an experimental design that simultaneously determined the quantitative genetic basis of nine male cuticular hydrocarbons (CHCs) of Drosophila bunnanda, the extent of condition dependence of these traits, and the strength and direction of sexual selection acting upon them. The CHCs of D. bunnanda are condition dependent, with 18% of the genetic variance in male body size explained by genetic variance in CHCs. Despite the presence of genetic variance in individual male traits, 98% of the genetic variance in CHCs was found to be orientated more than 88 degrees away from the direction of sexual selection and therefore unavailable to selection. A lack of genetic variance in male traits in the direction of sexual selection may represent a general feature of sexually selected systems, even in the presence of condition-dependent trait expression.

  20. The phenome-wide distribution of genetic variance.

    PubMed

    Blows, Mark W; Allen, Scott L; Collet, Julie M; Chenoweth, Stephen F; McGuigan, Katrina

    2015-07-01

    A general observation emerging from estimates of additive genetic variance in sets of functionally or developmentally related traits is that much of the genetic variance is restricted to few trait combinations as a consequence of genetic covariance among traits. While this biased distribution of genetic variance among functionally related traits is now well documented, how it translates to the broader phenome and therefore any trait combination under selection in a given environment is unknown. We show that 8,750 gene expression traits measured in adult male Drosophila serrata exhibit widespread genetic covariance among random sets of five traits, implying that pleiotropy is common. Ultimately, to understand the phenome-wide distribution of genetic variance, very large additive genetic variance-covariance matrices (G) are required to be estimated. We draw upon recent advances in matrix theory for completing high-dimensional matrices to estimate the 8,750-trait G and show that large numbers of gene expression traits genetically covary as a consequence of a single genetic factor. Using gene ontology term enrichment analysis, we show that the major axis of genetic variance among expression traits successfully identified genetic covariance among genes involved in multiple modes of transcriptional regulation. Our approach provides a practical empirical framework for the genetic analysis of high-dimensional phenome-wide trait sets and for the investigation of the extent of high-dimensional genetic constraint.

  1. Comparing estimates of genetic variance across different relationship models.

    PubMed

    Legarra, Andres

    2016-02-01

    Use of relationships between individuals to estimate genetic variances and heritabilities via mixed models is standard practice in human, plant and livestock genetics. Different models or information for relationships may give different estimates of genetic variances. However, comparing these estimates across different relationship models is not straightforward as the implied base populations differ between relationship models. In this work, I present a method to compare estimates of variance components across different relationship models. I suggest referring genetic variances obtained using different relationship models to the same reference population, usually a set of individuals in the population. Expected genetic variance of this population is the estimated variance component from the mixed model times a statistic, Dk, which is the average self-relationship minus the average (self- and across-) relationship. For most typical models of relationships, Dk is close to 1. However, this is not true for very deep pedigrees, for identity-by-state relationships, or for non-parametric kernels, which tend to overestimate the genetic variance and the heritability. Using mice data, I show that heritabilities from identity-by-state and kernel-based relationships are overestimated. Weighting these estimates by Dk scales them to a base comparable to genomic or pedigree relationships, avoiding wrong comparisons, for instance, "missing heritabilities".

  2. Prediction error variances for interbreed genetic evaluations.

    PubMed

    Van Vleck, L D; Cundiff, L V

    1994-08-01

    A table for adjusting expected progeny differences (EPD) to a base year and breed basis depends on analyses of records of progeny of bulls of different breeds in a common environment and requires that those reference bulls also have other progeny to provide within-breed EPD. Currently, the germ plasm evaluation project at the Meat Animal Research Center (MARC) provides such a common environment for reference bulls of several breeds for estimation of breed differences for the reference sires. Reference sire estimates of breed differences are adjusted by the difference between average EPD of reference bulls and average EPD for the base year for that breed. Two related questions are as follows: 1) What are confidence ranges for the adjustments and 2) What are accuracies of interbreed EPD? Application of statistical principles and algebra shows that 1) apparent confidence ranges for breed adjustments are small, 2) apparent confidence ranges are substantially underestimated when random sire effects within breed are ignored, 3) correct confidence ranges also are small, 4) usual measures of accuracy cannot be applied to interbreed comparisons, and 5) standard errors of prediction used in calculating confidence ranges for interbreed comparisons are much less affected by variance of the adjustment factors than by within-breed accuracies for two bulls being compared except for bulls with accuracies of near unity. Alternatives of predicting differences between bulls of the same or different breeds or between a bull of any breed and an average bull of a base breed are discussed in terms of confidence ranges.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. 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.

  4. Genetic Variance in the SES-IQ Correlation.

    ERIC Educational Resources Information Center

    Eckland, Bruce K.

    1979-01-01

    Discusses questions dealing with genetic aspects of the correlation between IQ and socioeconomic status (SES). Questions include: How does assortative mating affect the genetic variance of IQ? Is the relationship between an individual's IQ and adult SES a causal one? And how can IQ research improve schools and schooling? (Author/DB)

  5. Selection and genetic (co)variance in bighorn sheep.

    PubMed

    Coltman, David W; O'Donoghue, Paul; Hogg, John T; Festa-Bianchet, Marco

    2005-06-01

    Genetic theory predicts that directional selection should deplete additive genetic variance for traits closely related to fitness, and may favor the maintenance of alleles with antagonistically pleiotropic effects on fitness-related traits. Trait heritability is therefore expected to decline with the degree of association with fitness, and some genetic correlations between selected traits are expected to be negative. Here we demonstrate a negative relationship between trait heritability and association with lifetime reproductive success in a wild population of bighorn sheep (Ovis canadensis) at Ram Mountain, Alberta, Canada. Lower heritability for fitness-related traits, however, was not wholly a consequence of declining genetic variance, because those traits showed high levels of residual variance. Genetic correlations estimated between pairs of traits with significant heritability were positive. Principal component analyses suggest that positive relationships between morphometric traits constitute the main axis of genetic variation. Trade-offs in the form of negative genetic or phenotypic correlations among the traits we have measured do not appear to constrain the potential for evolution in this population.

  6. Quantitative genetics in soybean: Is dominance important?

    USDA-ARS?s Scientific Manuscript database

    In soybeans, dominance is generally considered to be non-existent or of little importance. Because genetic variation due to dominance dissipates rapidly with inbreeding, dominance would presumably not be useful in breeding soybean cultivars which are highly inbred. Yet, there is evidence for hetero...

  7. The genetic and environmental roots of variance in negativity toward foreign nationals.

    PubMed

    Kandler, Christian; Lewis, Gary J; Feldhaus, Lea Henrike; Riemann, Rainer

    2015-03-01

    This study quantified genetic and environmental roots of variance in prejudice and discriminatory intent toward foreign nationals and examined potential mediators of these genetic influences: right-wing authoritarianism (RWA), social dominance orientation (SDO), and narrow-sense xenophobia (NSX). In line with the dual process motivational (DPM) model, we predicted that the two basic attitudinal and motivational orientations-RWA and SDO-would account for variance in out-group prejudice and discrimination. In line with other theories, we expected that NSX as an affective component would explain additional variance in out-group prejudice and discriminatory intent. Data from 1,397 individuals (incl. twins as well as their spouses) were analyzed. Univariate analyses of twins' and spouses' data yielded genetic (incl. contributions of assortative mating) and multiple environmental sources (i.e., social homogamy, spouse-specific, and individual-specific effects) of variance in negativity toward strangers. Multivariate analyses suggested an extension to the DPM model by including NSX in addition to RWA and SDO as predictor of prejudice and discrimination. RWA and NSX primarily mediated the genetic influences on the variance in prejudice and discriminatory intent toward foreign nationals. In sum, the findings provide the basis of a behavioral genetic framework integrating different scientific disciplines for the study of negativity toward out-groups.

  8. Estimates of genetic variance and variance of predicted genetic merits using pedigree or genomic relationship matrices in six Brown Swiss cattle populations for different traits.

    PubMed

    Loberg, A; Dürr, J W; Fikse, W F; Jorjani, H; Crooks, L

    2015-10-01

    The amount of variance captured in genetic estimations may depend on whether a pedigree-based or genomic relationship matrix is used. The purpose of this study was to investigate the genetic variance as well as the variance of predicted genetic merits (PGM) using pedigree-based or genomic relationship matrices in Brown Swiss cattle. We examined a range of traits in six populations amounting to 173 population-trait combinations. A main aim was to determine how using different relationship matrices affect variance estimation. We calculated ratios between different types of estimates and analysed the impact of trait heritability and population size. The genetic variances estimated by REML using a genomic relationship matrix were always smaller than the variances that were similarly estimated using a pedigree-based relationship matrix. The variances from the genomic relationship matrix became closer to estimates from a pedigree relationship matrix as heritability and population size increased. In contrast, variances of predicted genetic merits obtained using a genomic relationship matrix were mostly larger than variances of genetic merit predicted using pedigree-based relationship matrix. The ratio of the genomic to pedigree-based PGM variances decreased as heritability and population size rose. The increased variance among predicted genetic merits is important for animal breeding because this is one of the factors influencing genetic progress.

  9. Escape from predators and genetic variance in birds.

    PubMed

    Jiang, Y; Møller, A P

    2017-09-12

    Predation is a common cause of death in numerous organisms, and a host of antipredator defences have evolved. Such defences often have a genetic background as shown by significant heritability and microevolutionary responses towards weaker defences in the absence of predators. Flight initiation distance (FID) is the distance at which an individual animal takes flight when approached by a human, and hence, it reflects the life-history compromise between risk of predation and the benefits of foraging. Here, we analysed FID in 128 species of birds in relation to three measures of genetic variation, band sharing coefficient for minisatellites, observed heterozygosity and inbreeding coefficient for microsatellites in order to test whether FID was positively correlated with genetic variation. We found consistently shorter FID for a given body size in the presence of high band sharing coefficients, low heterozygosity and high inbreeding coefficients in phylogenetic analyses after controlling statistically for potentially confounding variables. These findings imply that antipredator behaviour is related to genetic variance. We predict that many threatened species with low genetic variability will show reduced antipredator behaviour and that subsequent predator-induced reductions in abundance may contribute to unfavourable population trends for such species. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  10. Response to selection while maximizing genetic variance in small populations.

    PubMed

    Cervantes, Isabel; Gutiérrez, Juan Pablo; Meuwissen, Theo H E

    2016-09-20

    Rare breeds represent a valuable resource for future market demands. These populations are usually well-adapted, but their low census compromises the genetic diversity and future of these breeds. Since improvement of a breed for commercial traits may also confer higher probabilities of survival for the breed, it is important to achieve good responses to artificial selection. Therefore, efficient genetic management of these populations is essential to ensure that they respond adequately to genetic selection in possible future artificial selection scenarios. Scenarios that maximize the maximum genetic variance in a unique population could be a valuable option. The aim of this work was to study the effect of the maximization of genetic variance to increase selection response and improve the capacity of a population to adapt to a new environment/production system. We simulated a random scenario (A), a full-sib scenario (B), a scenario applying the maximum variance total (MVT) method (C), a MVT scenario with a restriction on increases in average inbreeding (D), a MVT scenario with a restriction on average individual increases in inbreeding (E), and a minimum coancestry scenario (F). Twenty replicates of each scenario were simulated for 100 generations, followed by 10 generations of selection. Effective population size was used to monitor the outcomes of these scenarios. Although the best response to selection was achieved in scenarios B and C, they were discarded because they are unpractical. Scenario A was also discarded because of its low response to selection. Scenario D yielded less response to selection and a smaller effective population size than scenario E, for which response to selection was higher during early generations because of the moderately structured population. In scenario F, response to selection was slightly higher than in Scenario E in the last generations. Application of MVT with a restriction on individual increases in inbreeding resulted in the

  11. Argentine Population Genetic Structure: Large Variance in Amerindian Contribution

    PubMed Central

    Seldin, Michael F.; Tian, Chao; Shigeta, Russell; Scherbarth, Hugo R.; Silva, Gabriel; Belmont, John W.; Kittles, Rick; Gamron, Susana; Allevi, Alberto; Palatnik, Simon A.; Alvarellos, Alejandro; Paira, Sergio; Caprarulo, Cesar; Guillerón, Carolina; Catoggio, Luis J.; Prigione, Cristina; Berbotto, Guillermo A.; García, Mercedes A.; Perandones, Carlos E.; Pons-Estel, Bernardo A.; Alarcon-Riquelme, Marta E.

    2011-01-01

    Argentine population genetic structure was examined using a set of 78 ancestry informative markers (AIMs) to assess the contributions of European, Amerindian, and African ancestry in 94 individuals members of this population. Using the Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%, the Amerindian contribution was 19.4%, and the African contribution was 2.5%. Similar results were found using weighted least mean square method: European, 80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the current results showed very few individuals (four of 94) with greater than 10% African admixture. Notably, when individual admixture was examined, the Amerindian and European admixture showed a very large variance and individual Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine subjects. These results indicate that admixture must be considered when clinical epidemiology or case control genetic analyses are studied in this population. Moreover, the current study provides a set of informative SNPs that can be used to ascertain or control for this potentially hidden stratification. In addition, the large variance in admixture proportions in individual Argentine subjects shown by this study suggests that this population is appropriate for future admixture mapping studies. PMID:17177183

  12. Assessment of the genetic variance of late-onset Alzheimer’s disease

    PubMed Central

    Ridge, Perry G.; Hoyt, Kaitlyn B.; Boehme, Kevin; Mukherjee, Shubhabrata; Crane, Paul K.; Haines, Jonathan L.; Mayeux, Richard; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Kauwe, John S.K.

    2016-01-01

    Alzheimer’s disease (AD) is a complex genetic disorder with no effective treatments. More than 20 common markers have been identified, which are associated with AD. Recently, several rare variants have been identified in APP, TREM2, and UNC5C that affect risk for AD. Despite the many successes, the genetic architecture of AD remains unsolved. We used Genome-wide Complex Trait Analysis to 1) estimate phenotypic variance explained by genetics, 2) calculate genetic variance explained by known AD SNPs, and 3) identify the genomic locations of variation that explain the remaining unexplained genetic variance. In total, 53.24% of phenotypic variance is explained by genetics, but known AD SNPs only explain 30.62% of the genetic variance. Of the unexplained genetic variance, approximately 41% is explained by unknown SNPs in regions adjacent to known AD SNPs, and the remaining unexplained genetic variance outside these regions. PMID:27036079

  13. The molecular basis of genetic dominance.

    PubMed Central

    Wilkie, A O

    1994-01-01

    Studies of mutagenesis in many organisms indicate that the majority (over 90%) of mutations are recessive to wild type. If recessiveness represents the 'default' state, what are the distinguishing features that make a minority of mutations give rise to dominant or semidominant characters? This review draws on the rapid expansion in knowledge of molecular and cellular biology to classify the molecular mechanisms of dominant mutation. The categories discussed include (1) reduced gene dosage, expression, or protein activity (haploinsufficiency); (2) increased gene dosage; (3) ectopic or temporally altered mRNA expression; (4) increased or constitutive protein activity; (5) dominant negative effects; (6) altered structural proteins; (7) toxic protein alterations; and (8) new protein functions. This provides a framework for understanding the basis of dominant genetic phenomena in humans and other organisms. Images PMID:8182727

  14. Quantitative genetic divergence and standing genetic (co)variance in thermal reaction norms along latitude.

    PubMed

    Berger, David; Postma, Erik; Blanckenhorn, Wolf U; Walters, Richard J

    2013-08-01

    Although the potential to adapt to warmer climate is constrained by genetic trade-offs, our understanding of how selection and mutation shape genetic (co)variances in thermal reaction norms is poor. Using 71 isofemale lines of the fly Sepsis punctum, originating from northern, central, and southern European climates, we tested for divergence in juvenile development rate across latitude at five experimental temperatures. To investigate effects of evolutionary history in different climates on standing genetic variation in reaction norms, we further compared genetic (co)variances between regions. Flies were reared on either high or low food resources to explore the role of energy acquisition in determining genetic trade-offs between different temperatures. Although the latter had only weak effects on the strength and sign of genetic correlations, genetic architecture differed significantly between climatic regions, implying that evolution of reaction norms proceeds via different trajectories at high latitude versus low latitude in this system. Accordingly, regional genetic architecture was correlated to region-specific differentiation. Moreover, hot development temperatures were associated with low genetic variance and stronger genetic correlations compared to cooler temperatures. We discuss the evolutionary potential of thermal reaction norms in light of their underlying genetic architectures, evolutionary histories, and the materialization of trade-offs in natural environments.

  15. Inbreeding and the genetic variance in floral traits of Mimulus guttatus.

    PubMed

    Kelly, J K; Arathi, H S

    2003-01-01

    The additive genetic variance, V(A), is frequently used as a measure of evolutionary potential in natural plant populations. Many plants inbreed to some extent; a notable observation given that random mating is essential to the model that predicts evolutionary change from V(A). With inbreeding, V(A) is not the only relevant component of genetic variation. Several nonadditive components emerge from the combined effects of inbreeding and genetic dominance. An important empirical question is whether these components are quantitatively significant. We use maximum likelihood estimation to extract estimates for V(A) and the nonadditive 'inbreeding components' from an experimental study of the wildflower Mimulus guttatus. The inbreeding components contribute significantly to four of five floral traits, including several measures of flower size and stigma-anther separation. These results indicate that inbreeding will substantially alter the evolutionary response to natural selection on floral characters.

  16. Dominant takeover regimes for genetic algorithms

    NASA Technical Reports Server (NTRS)

    Noever, David; Baskaran, Subbiah

    1995-01-01

    The genetic algorithm (GA) is a machine-based optimization routine which connects evolutionary learning to natural genetic laws. The present work addresses the problem of obtaining the dominant takeover regimes in the GA dynamics. Estimated GA run times are computed for slow and fast convergence in the limits of high and low fitness ratios. Using Euler's device for obtaining partial sums in closed forms, the result relaxes the previously held requirements for long time limits. Analytical solution reveal that appropriately accelerated regimes can mark the ascendancy of the most fit solution. In virtually all cases, the weak (logarithmic) dependence of convergence time on problem size demonstrates the potential for the GA to solve large N-P complete problems.

  17. Genetic variance of Trichomonas vaginalis isolates by Southern hybridization.

    PubMed

    Ryu, J S; Min, D Y; Shin, M H; Cho, Y H

    1998-09-01

    In the present study, genomic DNAs were purified from Korean isolates (KT8, KT6, KT-Kim and KT-Lee) and foreign strains (CDC85, IR78 and NYH 286) of Trichomonas vaginalis, and hybridized with a probe based on the repetitive sequence cloned from T. vaginalis to observe the genetic differences. By Southern hybridization, all isolates of T. vaginalis except the NYH286 strain had 11 bands. Therefore all isolates examined were distinguishable into 3 groups according to their banding patterns; i) KT8, KT6 and KT-Kim isolates had 11 identical bands such as 1 kb, 1.2 kb, 1.6 kb, 1.9 kb, 2.3 kb, 2.7 kb, 3.2 kb, 3.4 kb, 3.8 kb, 4.9 kb and 6.0 kb. ii) The metronidazole-resistant IR78 strain had the same bands as KT-Lee isolate at bands of 1 kb, 1.2 kb, 1.6 kb, 1.8 kb, 2.1 kb, 2.5 kb, 2.7 kb, 2.9 kb, 3.4 kb, 5.0 kb and 6.0 kb. Bands of CDC85, metronidazole-resistant strain, were similar to those of IR78 and KT-Lee, except that 3.2 kb replaced 2.9 kb. iii) NYH286 particularly had 12 bands and band patterns were similar to IR78 with a few exceptions as follows: i) 6.2 kb in place of 6.0 kb, ii) 2.0 kb and 2.2 kb instead of 2.1 kb. Through the results obtained, genetic variance of T. vaginalis isolates was demonstrated by Southern hybridization.

  18. 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

  19. Environmental stress, inbreeding, and the nature of phenotypic and genetic variance in Drosophila melanogaster.

    PubMed Central

    Fowler, Kevin; Whitlock, Michael C

    2002-01-01

    Fifty-two lines of Drosophila melanogaster founded by single-pair population bottlenecks were used to study the effects of inbreeding and environmental stress on phenotypic variance, genetic variance and survivorship. Cold temperature and high density cause reduced survivorship, but these stresses do not cause repeatable changes in the phenotypic variance of most wing morphological traits. Wing area, however, does show increased phenotypic variance under both types of environmental stress. This increase is no greater in inbred than in outbred lines, showing that inbreeding does not increase the developmental effects of stress. Conversely, environmental stress does not increase the extent of inbreeding depression. Genetic variance is not correlated with environmental stress, although the amount of genetic variation varies significantly among environments and lines vary significantly in their response to environmental change. Drastic changes in the environment can cause changes in phenotypic and genetic variance, but not in a way reliably predicted by the notion of 'stress'. PMID:11934358

  20. Assessment of the genetic variance of late-onset Alzheimer's disease.

    PubMed

    Ridge, Perry G; Hoyt, Kaitlyn B; Boehme, Kevin; Mukherjee, Shubhabrata; Crane, Paul K; Haines, Jonathan L; Mayeux, Richard; Farrer, Lindsay A; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Kauwe, John S K

    2016-05-01

    Alzheimer's disease (AD) is a complex genetic disorder with no effective treatments. More than 20 common markers have been identified, which are associated with AD. Recently, several rare variants have been identified in Amyloid Precursor Protein (APP), Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) and Unc-5 Netrin Receptor C (UNC5C) that affect risk for AD. Despite the many successes, the genetic architecture of AD remains unsolved. We used Genome-wide Complex Trait Analysis to (1) estimate phenotypic variance explained by genetics; (2) calculate genetic variance explained by known AD single nucleotide polymorphisms (SNPs); and (3) identify the genomic locations of variation that explain the remaining unexplained genetic variance. In total, 53.24% of phenotypic variance is explained by genetics, but known AD SNPs only explain 30.62% of the genetic variance. Of the unexplained genetic variance, approximately 41% is explained by unknown SNPs in regions adjacent to known AD SNPs, and the remaining unexplained genetic variance outside these regions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Age at menarche as a fitness trait: nonadditive genetic variance detected in a large twin sample.

    PubMed Central

    Treloar, S A; Martin, N G

    1990-01-01

    The etiological role of genotype and environment in recalled age at menarche was examined using an unselected sample of 1,177 MZ and 711 DZ twin pairs aged 18 years and older. The correlation for onset of menarche between MZ twins was .65 +/- .03, and that for DZ pairs was .18 +/- .04, although these differed somewhat between four birth cohorts. Environmental factors were more important in the older cohorts (perhaps because of less reliable recall). Total genotypic variance (additive plus nonadditive) ranged from 61% in the oldest cohort to 68% in the youngest cohort. In the oldest birth cohort (born before 1939), there was evidence of greater influence of environmental factors on age at menarche in the second-born twin, although there was no other evidence in the data that birth trauma affected timing. The greater part of the genetic variance was nonadditive (dominance or epistasis), and this is typical of a fitness trait. It appears that genetic nonadditivity is in the decreasing direction, and this is consistent with selection for early menarche during human evolution. Breakdown of inbreeding depression as a possible explanation for the secular decline in age at menarche is discussed. PMID:2349942

  2. 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

  3. Genetic Variance for Body Size in a Natural Population of Drosophila Buzzatii

    PubMed Central

    Ruiz, A.; Santos, M.; Barbadilla, A.; Quezada-Diaz, J. E.; Hasson, E.; Fontdevila, A.

    1991-01-01

    Previous work has shown thorax length to be under directional selection in the Drosophila buzzatii population of Carboneras. In order to predict the genetic consequences of natural selection, genetic variation for this trait was investigated in two ways. First, narrow sense heritability was estimated in the laboratory F(2) generation of a sample of wild flies by means of the offspring-parent regression. A relatively high value, 0.59, was obtained. Because the phenotypic variance of wild flies was 7-9 times that of the flies raised in the laboratory, ``natural'' heritability may be estimated as one-seventh to one-ninth that value. Second, the contribution of the second and fourth chromosomes, which are polymorphic for paracentric inversions, to the genetic variance of thorax length was estimated in the field and in the laboratory. This was done with the assistance of a simple genetic model which shows that the variance among chromosome arrangements and the variance among karyotypes provide minimum estimates of the chromosome's contribution to the additive and genetic variances of the triat, respectively. In males raised under optimal conditions in the laboratory, the variance among second-chromosome karyotypes accounted for 11.43% of the total phenotypic variance and most of this variance was additive; by contrast, the contribution of the fourth chromosome was nonsignificant. The variance among second-chromosome karyotypes accounted for 1.56-1.78% of the total phenotypic variance in wild males and was nonsignificant in wild females. The variance among fourth chromosome karyotypes accounted for 0.14-3.48% of the total phenotypic variance in wild flies. At both chromosomes, the proportion of additive variance was higher in mating flies than in nonmating flies. PMID:1916242

  4. Genetics Home Reference: autosomal dominant partial epilepsy with auditory features

    MedlinePlus

    ... Genetics Home Health Conditions ADPEAF autosomal dominant partial epilepsy with auditory features Enable Javascript to view the ... Open All Close All Description Autosomal dominant partial epilepsy with auditory features ( ADPEAF ) is an uncommon form ...

  5. Genetic and environmental heterogeneity of residual variance of weight traits in Nellore beef cattle

    PubMed Central

    2012-01-01

    Background Many studies have provided evidence of the existence of genetic heterogeneity of environmental variance, suggesting that it could be exploited to improve robustness and uniformity of livestock by selection. However, little is known about the perspectives of such a selection strategy in beef cattle. Methods A two-step approach was applied to study the genetic heterogeneity of residual variance of weight gain from birth to weaning and long-yearling weight in a Nellore beef cattle population. First, an animal model was fitted to the data and second, the influence of additive and environmental effects on the residual variance of these traits was investigated with different models, in which the log squared estimated residuals for each phenotypic record were analyzed using the restricted maximum likelihood method. Monte Carlo simulation was performed to assess the reliability of variance component estimates from the second step and the accuracy of estimated breeding values for residual variation. Results The results suggest that both genetic and environmental factors have an effect on the residual variance of weight gain from birth to weaning and long-yearling in Nellore beef cattle and that uniformity of these traits could be improved by selecting for lower residual variance, when considering a large amount of information to predict genetic merit for this criterion. Simulations suggested that using the two-step approach would lead to biased estimates of variance components, such that more adequate methods are needed to study the genetic heterogeneity of residual variance in beef cattle. PMID:22672564

  6. A Paradox of Genetic Variance in Epigamic Traits: Beyond "Good Genes" View of Sexual Selection.

    PubMed

    Radwan, Jacek; Engqvist, Leif; Reinhold, Klaus

    Maintenance of genetic variance in secondary sexual traits, including bizarre ornaments and elaborated courtship displays, is a central problem of sexual selection theory. Despite theoretical arguments predicting that strong sexual selection leads to a depletion of additive genetic variance, traits associated with mating success show relatively high heritability. Here we argue that because of trade-offs associated with the production of costly epigamic traits, sexual selection is likely to lead to an increase, rather than a depletion, of genetic variance in those traits. Such trade-offs can also be expected to contribute to the maintenance of genetic variation in ecologically relevant traits with important implications for evolutionary processes, e.g. adaptation to novel environments or ecological speciation. However, if trade-offs are an important source of genetic variation in sexual traits, the magnitude of genetic variation may have little relevance for the possible genetic benefits of mate choice.

  7. Epistasis Is a Major Determinant of the Additive Genetic Variance in Mimulus guttatus.

    PubMed

    Monnahan, Patrick J; Kelly, John K

    2015-05-01

    The influence of genetic interactions (epistasis) on the genetic variance of quantitative traits is a major unresolved problem relevant to medical, agricultural, and evolutionary genetics. The additive genetic component is typically a high proportion of the total genetic variance in quantitative traits, despite that underlying genes must interact to determine phenotype. This study estimates direct and interaction effects for 11 pairs of Quantitative Trait Loci (QTLs) affecting floral traits within a single population of Mimulus guttatus. With estimates of all 9 genotypes for each QTL pair, we are able to map from QTL effects to variance components as a function of population allele frequencies, and thus predict changes in variance components as allele frequencies change. This mapping requires an analytical framework that properly accounts for bias introduced by estimation errors. We find that even with abundant interactions between QTLs, most of the genetic variance is likely to be additive. However, the strong dependency of allelic average effects on genetic background implies that epistasis is a major determinant of the additive genetic variance, and thus, the population's ability to respond to selection.

  8. Epistasis Is a Major Determinant of the Additive Genetic Variance in Mimulus guttatus

    PubMed Central

    Monnahan, Patrick J.; Kelly, John K.

    2015-01-01

    The influence of genetic interactions (epistasis) on the genetic variance of quantitative traits is a major unresolved problem relevant to medical, agricultural, and evolutionary genetics. The additive genetic component is typically a high proportion of the total genetic variance in quantitative traits, despite that underlying genes must interact to determine phenotype. This study estimates direct and interaction effects for 11 pairs of Quantitative Trait Loci (QTLs) affecting floral traits within a single population of Mimulus guttatus. With estimates of all 9 genotypes for each QTL pair, we are able to map from QTL effects to variance components as a function of population allele frequencies, and thus predict changes in variance components as allele frequencies change. This mapping requires an analytical framework that properly accounts for bias introduced by estimation errors. We find that even with abundant interactions between QTLs, most of the genetic variance is likely to be additive. However, the strong dependency of allelic average effects on genetic background implies that epistasis is a major determinant of the additive genetic variance, and thus, the population’s ability to respond to selection. PMID:25946702

  9. Genetics Home Reference: autosomal dominant hyper-IgE syndrome

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions autosomal dominant hyper-IgE syndrome ...

  10. Age-dependent genetic variance in a life-history trait in the mute swan

    PubMed Central

    Charmantier, Anne; Perrins, Christopher; McCleery, Robin H; Sheldon, Ben C

    2005-01-01

    Genetic variance in characters under natural selection in natural populations determines the way those populations respond to that selection. Whether populations show temporal and/or spatial constancy in patterns of genetic variance and covariance is regularly considered, as this will determine whether selection responses are constant over space and time. Much less often considered is whether characters show differing amounts of genetic variance over the life-history of individuals. Such age-specific variation, if present, has important potential consequences for the force of natural selection and for understanding the causes of variation in quantitative characters. Using data from a long-term study of the mute swan Cygnus olor, we report the partitioning of phenotypic variance in timing of breeding (subject to strong natural selection) into component parts over 12 different age classes. We show that the additive genetic variance and heritability of this trait are strongly age-dependent, with higher additive genetic variance present in young and, particularly, old birds, but little evidence of any genetic variance for birds of intermediate ages. These results demonstrate that age can have a very important influence on the components of variation of characters in natural populations, and consequently that separate age classes cannot be assumed to be equivalent, either with respect to their evolutionary potential or response. PMID:16555791

  11. Age-dependent genetic variance in a life-history trait in the mute swan.

    PubMed

    Charmantier, Anne; Perrins, Christopher; McCleery, Robin H; Sheldon, Ben C

    2006-01-22

    Genetic variance in characters under natural selection in natural populations determines the way those populations respond to that selection. Whether populations show temporal and/or spatial constancy in patterns of genetic variance and covariance is regularly considered, as this will determine whether selection responses are constant over space and time. Much less often considered is whether characters show differing amounts of genetic variance over the life-history of individuals. Such age-specific variation, if present, has important potential consequences for the force of natural selection and for understanding the causes of variation in quantitative characters. Using data from a long-term study of the mute swan Cygnus olor, we report the partitioning of phenotypic variance in timing of breeding (subject to strong natural selection) into component parts over 12 different age classes. We show that the additive genetic variance and heritability of this trait are strongly age-dependent, with higher additive genetic variance present in young and, particularly, old birds, but little evidence of any genetic variance for birds of intermediate ages. These results demonstrate that age can have a very important influence on the components of variation of characters in natural populations, and consequently that separate age classes cannot be assumed to be equivalent, either with respect to their evolutionary potential or response.

  12. Genetic control of residual variance of yearling weight in Nellore beef cattle.

    PubMed

    Iung, L H S; Neves, H H R; Mulder, H A; Carvalheiro, R

    2017-04-01

    There is evidence for genetic variability in residual variance of livestock traits, which offers the potential for selection for increased uniformity of production. Different statistical approaches have been employed to study this topic; however, little is known about the concordance between them. The aim of our study was to investigate the genetic heterogeneity of residual variance on yearling weight (YW; 291.15 ± 46.67) in a Nellore beef cattle population; to compare the results of the statistical approaches, the two-step approach and the double hierarchical generalized linear model (DHGLM); and to evaluate the effectiveness of power transformation to accommodate scale differences. The comparison was based on genetic parameters, accuracy of EBV for residual variance, and cross-validation to assess predictive performance of both approaches. A total of 194,628 yearling weight records from 625 sires were used in the analysis. The results supported the hypothesis of genetic heterogeneity of residual variance on YW in Nellore beef cattle and the opportunity of selection, measured through the genetic coefficient of variation of residual variance (0.10 to 0.12 for the two-step approach and 0.17 for DHGLM, using an untransformed data set). However, low estimates of genetic variance associated with positive genetic correlations between mean and residual variance (about 0.20 for two-step and 0.76 for DHGLM for an untransformed data set) limit the genetic response to selection for uniformity of production while simultaneously increasing YW itself. Moreover, large sire families are needed to obtain accurate estimates of genetic merit for residual variance, as indicated by the low heritability estimates (<0.007). Box-Cox transformation was able to decrease the dependence of the variance on the mean and decreased the estimates of genetic parameters for residual variance. The transformation reduced but did not eliminate all the genetic heterogeneity of residual variance

  13. Genetic Variance in the F2 Generation of Divergently Selected Parents

    Treesearch

    M.P. Koshy; G. Namkoong; J.H. Roberds

    1998-01-01

    Either by selective breeding for population divergence or by using natural population differences, F2 and advanced generation hybrids can be developed with high variances. We relate the size of the genetic variance to the population divergence based on a forward and backward mutation model at a locus with two alleles with additive gene action....

  14. Genetic variance in micro-environmental sensitivity for milk and milk quality in Walloon Holstein cattle.

    PubMed

    Vandenplas, J; Bastin, C; Gengler, N; Mulder, H A

    2013-09-01

    Animals that are robust to environmental changes are desirable in the current dairy industry. Genetic differences in micro-environmental sensitivity can be studied through heterogeneity of residual variance between animals. However, residual variance between animals is usually assumed to be homogeneous in traditional genetic evaluations. The aim of this study was to investigate genetic heterogeneity of residual variance by estimating variance components in residual variance for milk yield, somatic cell score, contents in milk (g/dL) of 2 groups of milk fatty acids (i.e., saturated and unsaturated fatty acids), and the content in milk of one individual fatty acid (i.e., oleic acid, C18:1 cis-9), for first-parity Holstein cows in the Walloon Region of Belgium. A total of 146,027 test-day records from 26,887 cows in 747 herds were available. All cows had at least 3 records and a known sire. These sires had at least 10 cows with records and each herd × test-day had at least 5 cows. The 5 traits were analyzed separately based on fixed lactation curve and random regression test-day models for the mean. Estimation of variance components was performed by running iteratively expectation maximization-REML algorithm by the implementation of double hierarchical generalized linear models. Based on fixed lactation curve test-day mean models, heritability for residual variances ranged between 1.01×10(-3) and 4.17×10(-3) for all traits. The genetic standard deviation in residual variance (i.e., approximately the genetic coefficient of variation of residual variance) ranged between 0.12 and 0.17. Therefore, some genetic variance in micro-environmental sensitivity existed in the Walloon Holstein dairy cattle for the 5 studied traits. The standard deviations due to herd × test-day and permanent environment in residual variance ranged between 0.36 and 0.45 for herd × test-day effect and between 0.55 and 0.97 for permanent environmental effect. Therefore, nongenetic effects also

  15. Estimates for genetic variance components in reciprocal recurrent selection in populations derived from maize single-cross hybrids.

    PubMed

    dos Reis, Matheus Costa; Pádua, José Maria Villela; Abreu, Guilherme Barbosa; Guedes, Fernando Lisboa; Balbi, Rodrigo Vieira; de Souza, João Cândido

    2014-01-01

    This study was carried out to obtain the estimates of genetic variance and covariance components related to intra- and interpopulation in the original populations (C0) and in the third cycle (C3) of reciprocal recurrent selection (RRS) which allows breeders to define the best breeding strategy. For that purpose, the half-sib progenies of intrapopulation (P11 and P22) and interpopulation (P12 and P21) from populations 1 and 2 derived from single-cross hybrids in the 0 and 3 cycles of the reciprocal recurrent selection program were used. The intra- and interpopulation progenies were evaluated in a 10 × 10 triple lattice design in two separate locations. The data for unhusked ear weight (ear weight without husk) and plant height were collected. All genetic variance and covariance components were estimated from the expected mean squares. The breakdown of additive variance into intrapopulation and interpopulation additive deviations (σ τ (2)) and the covariance between these and their intrapopulation additive effects (Cov Aτ) found predominance of the dominance effect for unhusked ear weight. Plant height for these components shows that the intrapopulation additive effect explains most of the variation. Estimates for intrapopulation and interpopulation additive genetic variances confirm that populations derived from single-cross hybrids have potential for recurrent selection programs.

  16. Estimates for Genetic Variance Components in Reciprocal Recurrent Selection in Populations Derived from Maize Single-Cross Hybrids

    PubMed Central

    dos Reis, Matheus Costa; Pádua, José Maria Villela; Abreu, Guilherme Barbosa; Guedes, Fernando Lisboa; Balbi, Rodrigo Vieira; de Souza, João Cândido

    2014-01-01

    This study was carried out to obtain the estimates of genetic variance and covariance components related to intra- and interpopulation in the original populations (C0) and in the third cycle (C3) of reciprocal recurrent selection (RRS) which allows breeders to define the best breeding strategy. For that purpose, the half-sib progenies of intrapopulation (P11 and P22) and interpopulation (P12 and P21) from populations 1 and 2 derived from single-cross hybrids in the 0 and 3 cycles of the reciprocal recurrent selection program were used. The intra- and interpopulation progenies were evaluated in a 10 × 10 triple lattice design in two separate locations. The data for unhusked ear weight (ear weight without husk) and plant height were collected. All genetic variance and covariance components were estimated from the expected mean squares. The breakdown of additive variance into intrapopulation and interpopulation additive deviations (σ τ 2) and the covariance between these and their intrapopulation additive effects (CovAτ) found predominance of the dominance effect for unhusked ear weight. Plant height for these components shows that the intrapopulation additive effect explains most of the variation. Estimates for intrapopulation and interpopulation additive genetic variances confirm that populations derived from single-cross hybrids have potential for recurrent selection programs. PMID:25009831

  17. Genetic heterogeneity of within-family variance of body weight in Atlantic salmon (Salmo salar)

    PubMed Central

    2013-01-01

    Background Canalization is defined as the stability of a genotype against minor variations in both environment and genetics. Genetic variation in degree of canalization causes heterogeneity of within-family variance. The aims of this study are twofold: (1) quantify genetic heterogeneity of (within-family) residual variance in Atlantic salmon and (2) test whether the observed heterogeneity of (within-family) residual variance can be explained by simple scaling effects. Results Analysis of body weight in Atlantic salmon using a double hierarchical generalized linear model (DHGLM) revealed substantial heterogeneity of within-family variance. The 95% prediction interval for within-family variance ranged from ~0.4 to 1.2 kg2, implying that the within-family variance of the most extreme high families is expected to be approximately three times larger than the extreme low families. For cross-sectional data, DHGLM with an animal mean sub-model resulted in severe bias, while a corresponding sire-dam model was appropriate. Heterogeneity of variance was not sensitive to Box-Cox transformations of phenotypes, which implies that heterogeneity of variance exists beyond what would be expected from simple scaling effects. Conclusions Substantial heterogeneity of within-family variance was found for body weight in Atlantic salmon. A tendency towards higher variance with higher means (scaling effects) was observed, but heterogeneity of within-family variance existed beyond what could be explained by simple scaling effects. For cross-sectional data, using the animal mean sub-model in the DHGLM resulted in biased estimates of variance components, which differed substantially both from a standard linear mean animal model and a sire-dam DHGLM model. Although genetic differences in canalization were observed, selection for increased canalization is difficult, because there is limited individual information for the variance sub-model, especially when based on cross-sectional data

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

    PubMed

    Blows, Mark W; McGuigan, Katrina

    2015-05-01

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

  19. 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

  20. A new explained-variance based genetic risk score for predictive modeling of disease risk.

    PubMed

    Che, Ronglin; Motsinger-Reif, Alison A

    2012-09-25

    The goal of association mapping is to identify genetic variants that predict disease, and as the field of human genetics matures, the number of successful association studies is increasing. Many such studies have shown that for many diseases, risk is explained by a reasonably large number of variants that each explains a very small amount of disease risk. This is prompting the use of genetic risk scores in building predictive models, where information across several variants is combined for predictive modeling. In the current study, we compare the performance of four previously proposed genetic risk score methods and present a new method for constructing genetic risk score that incorporates explained variance information. The methods compared include: a simple count Genetic Risk Score, an odds ratio weighted Genetic Risk Score, a direct logistic regression Genetic Risk Score, a polygenic Genetic Risk Score, and the new explained variance weighted Genetic Risk Score. We compare the methods using a wide range of simulations in two steps, with a range of the number of deleterious single nucleotide polymorphisms (SNPs) explaining disease risk, genetic modes, baseline penetrances, sample sizes, relative risks (RR) and minor allele frequencies (MAF). Several measures of model performance were compared including overall power, C-statistic and Akaike's Information Criterion. Our results show the relative performance of methods differs significantly, with the new explained variance weighted GRS (EV-GRS) generally performing favorably to the other methods.

  1. Maintenance of Quantitative Genetic Variance Under Partial Self-Fertilization, with Implications for Evolution of Selfing

    PubMed Central

    Lande, Russell; Porcher, Emmanuelle

    2015-01-01

    We analyze two models of the maintenance of quantitative genetic variance in a mixed-mating system of self-fertilization and outcrossing. In both models purely additive genetic variance is maintained by mutation and recombination under stabilizing selection on the phenotype of one or more quantitative characters. The Gaussian allele model (GAM) involves a finite number of unlinked loci in an infinitely large population, with a normal distribution of allelic effects at each locus within lineages selfed for τ consecutive generations since their last outcross. The infinitesimal model for partial selfing (IMS) involves an infinite number of loci in a large but finite population, with a normal distribution of breeding values in lineages of selfing age τ. In both models a stable equilibrium genetic variance exists, the outcrossed equilibrium, nearly equal to that under random mating, for all selfing rates, r, up to critical value, r^, the purging threshold, which approximately equals the mean fitness under random mating relative to that under complete selfing. In the GAM a second stable equilibrium, the purged equilibrium, exists for any positive selfing rate, with genetic variance less than or equal to that under pure selfing; as r increases above r^ the outcrossed equilibrium collapses sharply to the purged equilibrium genetic variance. In the IMS a single stable equilibrium genetic variance exists at each selfing rate; as r increases above r^ the equilibrium genetic variance drops sharply and then declines gradually to that maintained under complete selfing. The implications for evolution of selfing rates, and for adaptive evolution and persistence of predominantly selfing species, provide a theoretical basis for the classical view of Stebbins that predominant selfing constitutes an “evolutionary dead end.” PMID:25969460

  2. Maintenance of Quantitative Genetic Variance Under Partial Self-Fertilization, with Implications for Evolution of Selfing.

    PubMed

    Lande, Russell; Porcher, Emmanuelle

    2015-07-01

    We analyze two models of the maintenance of quantitative genetic variance in a mixed-mating system of self-fertilization and outcrossing. In both models purely additive genetic variance is maintained by mutation and recombination under stabilizing selection on the phenotype of one or more quantitative characters. The Gaussian allele model (GAM) involves a finite number of unlinked loci in an infinitely large population, with a normal distribution of allelic effects at each locus within lineages selfed for τ consecutive generations since their last outcross. The infinitesimal model for partial selfing (IMS) involves an infinite number of loci in a large but finite population, with a normal distribution of breeding values in lineages of selfing age τ. In both models a stable equilibrium genetic variance exists, the outcrossed equilibrium, nearly equal to that under random mating, for all selfing rates, r, up to critical value, [Formula: see text], the purging threshold, which approximately equals the mean fitness under random mating relative to that under complete selfing. In the GAM a second stable equilibrium, the purged equilibrium, exists for any positive selfing rate, with genetic variance less than or equal to that under pure selfing; as r increases above [Formula: see text] the outcrossed equilibrium collapses sharply to the purged equilibrium genetic variance. In the IMS a single stable equilibrium genetic variance exists at each selfing rate; as r increases above [Formula: see text] the equilibrium genetic variance drops sharply and then declines gradually to that maintained under complete selfing. The implications for evolution of selfing rates, and for adaptive evolution and persistence of predominantly selfing species, provide a theoretical basis for the classical view of Stebbins that predominant selfing constitutes an "evolutionary dead end."

  3. The contribution of dominance and inbreeding depression in estimating variance components for litter size in Pannon White rabbits.

    PubMed

    Nagy, I; Gorjanc, G; Curik, I; Farkas, J; Kiszlinger, H; Szendrő, Zs

    2013-08-01

    In a synthetic closed population of Pannon White rabbits, additive (VA ), dominance (VD ) and permanent environmental (VPe ) variance components as well as doe (bF d ) and litter (bF l ) inbreeding depression were estimated for the number of kits born alive (NBA), number of kits born dead (NBD) and total number of kits born (TNB). The data set consisted of 18,398 kindling records of 3883 does collected from 1992 to 2009. Six models were used to estimate dominance and inbreeding effects. The most complete model estimated VA and VD to contribute 5.5 ± 1.1% and 4.8 ± 2.4%, respectively, to total phenotypic variance (VP ) for NBA; the corresponding values for NBD were 1.9 ± 0.6% and 5.3 ± 2.4%, for TNB, 6.2 ± 1.0% and 8.1 ± 3.2% respectively. These results indicate the presence of considerable VD . Including dominance in the model generally reduced VA and VPe estimates, and had only a very small effect on inbreeding depression estimates. Including inbreeding covariates did not affect estimates of any variance component. A 10% increase in doe inbreeding significantly increased NBD (bF d  = 0.18 ± 0.07), while a 10% increase in litter inbreeding significantly reduced NBA (bF l  = -0.41 ± 0.11) and TNB (bF l  = -0.34 ± 0.10). These findings argue for including dominance effects in models of litter size traits in populations that exhibit significant dominance relationships. © 2012 Blackwell Verlag GmbH.

  4. 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…

  5. 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…

  6. Analysis of Quantitative Traits in Two Long-Term Randomly Mated Soybean Populations I. Genetic Variances

    USDA-ARS?s Scientific Manuscript database

    The genetic effects of long term random mating and natural selection aided by genetic male sterility were evaluated in two soybean [Glycine max (L.) Merr.] populations: RSII and RSIII. Population means, variances, and heritabilities were estimated to determine the effects of 26 generations of random...

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

    PubMed

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

    2015-11-01

    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.

  8. 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

  9. Complex sources of variance in female dominance rank in a nepotistic society

    PubMed Central

    Lea, Amanda J.; Learn, Niki H.; Theus, Marcus J.; Altmann, Jeanne; Alberts, Susan C.

    2016-01-01

    Many mammalian societies are structured by dominance hierarchies, and an individual’s position within this hierarchy can influence reproduction, behaviour, physiology and health. In nepotistic hierarchies, which are common in cercopithecine primates and also seen in spotted hyaenas, Crocuta crocuta, adult daughters are expected to rank immediately below their mother, and in reverse age order (a phenomenon known as ‘youngest ascendancy’). This pattern is well described, but few studies have systematically examined the frequency or causes of departures from the expected pattern. Using a longitudinal data set from a natural population of yellow baboons, Papio cynocephalus, we measured the influence of maternal kin, paternal kin and group size on female rank positions at two life history milestones, menarche and first live birth. At menarche, most females (73%) ranked adjacent to their family members (i.e. the female held an ordinal rank in consecutive order with other members of her maternal family); however, only 33% of females showed youngest ascendancy within their matriline at menarche. By the time they experienced their first live birth, many females had improved their dominance rank: 78% ranked adjacent to their family members and 49% showed youngest ascendancy within their matriline. The presence of mothers and maternal sisters exerted a powerful influence on rank outcomes. However, the presence of fathers, brothers and paternal siblings did not produce a clear effect on female dominance rank in our analyses, perhaps because females in our data set co-resided with variable numbers and types of paternal and male relatives. Our results also raise the possibility that female body size or competitive ability may influence dominance rank, even in this classically nepotistic species. In total, our analyses reveal that the predictors of dominance rank in nepotistic rank systems are much more complex than previously thought. PMID:26997663

  10. Ontogenetic changes in genetic variances of age-dependent plasticity along a latitudinal gradient

    PubMed Central

    Nilsson-Örtman, V; Rogell, B; Stoks, R; Johansson, F

    2015-01-01

    The expression of phenotypic plasticity may differ among life stages of the same organism. Age-dependent plasticity can be important for adaptation to heterogeneous environments, but this has only recently been recognized. Whether age-dependent plasticity is a common outcome of local adaptation and whether populations harbor genetic variation in this respect remains largely unknown. To answer these questions, we estimated levels of additive genetic variation in age-dependent plasticity in six species of damselflies sampled from 18 populations along a latitudinal gradient spanning 3600 km. We reared full sib larvae at three temperatures and estimated genetic variances in the height and slope of thermal reaction norms of body size at three points in time during ontogeny using random regression. Our data show that most populations harbor genetic variation in growth rate (reaction norm height) in all ontogenetic stages, but only some populations and ontogenetic stages were found to harbor genetic variation in thermal plasticity (reaction norm slope). Genetic variances in reaction norm height differed among species, while genetic variances in reaction norm slope differed among populations. The slope of the ontogenetic trend in genetic variances of both reaction norm height and slope increased with latitude. We propose that differences in genetic variances reflect temporal and spatial variation in the strength and direction of natural selection on growth trajectories and age-dependent plasticity. Selection on age-dependent plasticity may depend on the interaction between temperature seasonality and time constraints associated with variation in life history traits such as generation length. PMID:25649500

  11. Genetic basis of between-individual and within-individual variance of docility.

    PubMed

    Martin, J G A; Pirotta, E; Petelle, M B; Blumstein, D T

    2017-04-01

    Between-individual variation in phenotypes within a population is the basis of evolution. However, evolutionary and behavioural ecologists have mainly focused on estimating between-individual variance in mean trait and neglected variation in within-individual variance, or predictability of a trait. In fact, an important assumption of mixed-effects models used to estimate between-individual variance in mean traits is that within-individual residual variance (predictability) is identical across individuals. Individual heterogeneity in the predictability of behaviours is a potentially important effect but rarely estimated and accounted for. We used 11 389 measures of docility behaviour from 1576 yellow-bellied marmots (Marmota flaviventris) to estimate between-individual variation in both mean docility and its predictability. We then implemented a double hierarchical animal model to decompose the variances of both mean trait and predictability into their environmental and genetic components. We found that individuals differed both in their docility and in their predictability of docility with a negative phenotypic covariance. We also found significant genetic variance for both mean docility and its predictability but no genetic covariance between the two. This analysis is one of the first to estimate the genetic basis of both mean trait and within-individual variance in a wild population. Our results indicate that equal within-individual variance should not be assumed. We demonstrate the evolutionary importance of the variation in the predictability of docility and illustrate potential bias in models ignoring variation in predictability. We conclude that the variability in the predictability of a trait should not be ignored, and present a coherent approach for its quantification. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  12. Estimating Modifying Effect of Age on Genetic and Environmental Variance Components in Twin Models.

    PubMed

    He, Liang; Sillanpää, Mikko J; Silventoinen, Karri; Kaprio, Jaakko; Pitkäniemi, Janne

    2016-04-01

    Twin studies have been adopted for decades to disentangle the relative genetic and environmental contributions for a wide range of traits. However, heritability estimation based on the classical twin models does not take into account dynamic behavior of the variance components over age. Varying variance of the genetic component over age can imply the existence of gene-environment (G×E) interactions that general genome-wide association studies (GWAS) fail to capture, which may lead to the inconsistency of heritability estimates between twin design and GWAS. Existing parametricG×Einteraction models for twin studies are limited by assuming a linear or quadratic form of the variance curves with respect to a moderator that can, however, be overly restricted in reality. Here we propose spline-based approaches to explore the variance curves of the genetic and environmental components. We choose the additive genetic, common, and unique environmental variance components (ACE) model as the starting point. We treat the component variances as variance functions with respect to age modeled by B-splines or P-splines. We develop an empirical Bayes method to estimate the variance curves together with their confidence bands and provide an R package for public use. Our simulations demonstrate that the proposed methods accurately capture dynamic behavior of the component variances in terms of mean square errors with a data set of >10,000 twin pairs. Using the proposed methods as an alternative and major extension to the classical twin models, our analyses with a large-scale Finnish twin data set (19,510 MZ twins and 27,312 DZ same-sex twins) discover that the variances of the A, C, and E components for body mass index (BMI) change substantially across life span in different patterns and the heritability of BMI drops to ∼50% after middle age. The results further indicate that the decline of heritability is due to increasing unique environmental variance, which provides more

  13. Quantitative genetic variance and multivariate clines in the Ivyleaf morning glory, Ipomoea hederacea.

    PubMed

    Stock, Amanda J; Campitelli, Brandon E; Stinchcombe, John R

    2014-08-19

    Clinal variation is commonly interpreted as evidence of adaptive differentiation, although clines can also be produced by stochastic forces. Understanding whether clines are adaptive therefore requires comparing clinal variation to background patterns of genetic differentiation at presumably neutral markers. Although this approach has frequently been applied to single traits at a time, we have comparatively fewer examples of how multiple correlated traits vary clinally. Here, we characterize multivariate clines in the Ivyleaf morning glory, examining how suites of traits vary with latitude, with the goal of testing for divergence in trait means that would indicate past evolutionary responses. We couple this with analysis of genetic variance in clinally varying traits in 20 populations to test whether past evolutionary responses have depleted genetic variance, or whether genetic variance declines approaching the range margin. We find evidence of clinal differentiation in five quantitative traits, with little evidence of isolation by distance at neutral loci that would suggest non-adaptive or stochastic mechanisms. Within and across populations, the traits that contribute most to population differentiation and clinal trends in the multivariate phenotype are genetically variable as well, suggesting that a lack of genetic variance will not cause absolute evolutionary constraints. Our data are broadly consistent theoretical predictions of polygenic clines in response to shallow environmental gradients. Ecologically, our results are consistent with past findings of natural selection on flowering phenology, presumably due to season-length variation across the range.

  14. Estimating Modifying Effect of Age on Genetic and Environmental Variance Components in Twin Models

    PubMed Central

    He, Liang; Sillanpää, Mikko J.; Silventoinen, Karri; Kaprio, Jaakko; Pitkäniemi, Janne

    2016-01-01

    Twin studies have been adopted for decades to disentangle the relative genetic and environmental contributions for a wide range of traits. However, heritability estimation based on the classical twin models does not take into account dynamic behavior of the variance components over age. Varying variance of the genetic component over age can imply the existence of gene–environment (G × E) interactions that general genome-wide association studies (GWAS) fail to capture, which may lead to the inconsistency of heritability estimates between twin design and GWAS. Existing parametric G × E interaction models for twin studies are limited by assuming a linear or quadratic form of the variance curves with respect to a moderator that can, however, be overly restricted in reality. Here we propose spline-based approaches to explore the variance curves of the genetic and environmental components. We choose the additive genetic, common, and unique environmental variance components (ACE) model as the starting point. We treat the component variances as variance functions with respect to age modeled by B-splines or P-splines. We develop an empirical Bayes method to estimate the variance curves together with their confidence bands and provide an R package for public use. Our simulations demonstrate that the proposed methods accurately capture dynamic behavior of the component variances in terms of mean square errors with a data set of >10,000 twin pairs. Using the proposed methods as an alternative and major extension to the classical twin models, our analyses with a large-scale Finnish twin data set (19,510 MZ twins and 27,312 DZ same-sex twins) discover that the variances of the A, C, and E components for body mass index (BMI) change substantially across life span in different patterns and the heritability of BMI drops to ∼50% after middle age. The results further indicate that the decline of heritability is due to increasing unique environmental variance, which provides

  15. Genetic factors explain half of all variance in serum eosinophil cationic protein.

    PubMed

    Elmose, C; Sverrild, A; van der Sluis, S; Kyvik, K O; Backer, V; Thomsen, S F

    2014-12-01

    Eosinophil cationic protein (ECP) is one of four basic proteins of the secretory granules of eosinophils. It has a variety of functions associated with inflammatory responses. Little is known about the causes for variation in serum ECP levels. To identify factors associated with variation in serum ECP and to determine the relative proportion of the variation in ECP due to genetic and non-genetic factors, in an adult twin sample. A sample of 575 twins, selected through a proband with self-reported asthma, had serum ECP, lung function, airway responsiveness to methacholine, exhaled nitric oxide, and skin test reactivity, measured. Linear regression analysis and variance component models were used to study factors associated with variation in ECP and the relative genetic influence on ECP levels. Sex (regression coefficient = -0.107, P < 0.001), body mass index (BMI) (0.007, P = 0.028), and airway responsiveness to methacholine (0.074, P = 0.001) were significantly associated with ECP. Adjusted for these factors, ECP correlated 0.53 (P < 0.001) and 0.27 (P = 0.001) in monozygotic and dizygotic twins, respectively (P-value for difference = 0.05). According to the most parsimonious variance component model, genetic factors accounted for 57% (CI: 42-72%, P < 0.001) of the variance in ECP levels, whereas the remainder (43%) was ascribable to non-shared environmental factors. The genetic correlation between ECP and airway responsiveness to methacholine was statistically non-significant (r = -0.11, P = 0.50). Around half of all variance in serum ECP is explained by genetic factors. Serum ECP is influenced by sex, BMI, and airway responsiveness. Serum ECP and airway responsiveness seem not to share genetic variance. © 2014 John Wiley & Sons Ltd.

  16. Two-Variance-Component Model Improves Genetic Prediction in Family Datasets.

    PubMed

    Tucker, George; Loh, Po-Ru; MacLeod, Iona M; Hayes, Ben J; Goddard, Michael E; Berger, Bonnie; Price, Alkes L

    2015-11-05

    Genetic prediction based on either identity by state (IBS) sharing or pedigree information has been investigated extensively with best linear unbiased prediction (BLUP) methods. Such methods were pioneered in plant and animal-breeding literature and have since been applied to predict human traits, with the aim of eventual clinical utility. However, methods to combine IBS sharing and pedigree information for genetic prediction in humans have not been explored. We introduce a two-variance-component model for genetic prediction: one component for IBS sharing and one for approximate pedigree structure, both estimated with genetic markers. In simulations using real genotypes from the Candidate-gene Association Resource (CARe) and Framingham Heart Study (FHS) family cohorts, we demonstrate that the two-variance-component model achieves gains in prediction r(2) over standard BLUP at current sample sizes, and we project, based on simulations, that these gains will continue to hold at larger sample sizes. Accordingly, in analyses of four quantitative phenotypes from CARe and two quantitative phenotypes from FHS, the two-variance-component model significantly improves prediction r(2) in each case, with up to a 20% relative improvement. We also find that standard mixed-model association tests can produce inflated test statistics in datasets with related individuals, whereas the two-variance-component model corrects for inflation. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  17. The Moderating Effect of Religiosity on the Genetic Variance of Problem Alcohol Use

    PubMed Central

    Button, Tanya M. M.; Hewitt, John K.; Rhee, Soo Hyun; Corley, Robin P.; Stallings, Michael C.

    2010-01-01

    Background Previous studies have demonstrated that the heritability of alcohol related phenotypes depends upon the social background in which it is measured (e.g., urbanicity, marital status, and religiosity). The aim of the current study was to identify whether religiosity moderated the genetic variance of problem alcohol use in males and females at two time points: adolescence and early adulthood. Method Participants were 312 male MZ pairs, 379 female MZ pairs, 231 male DZ pairs, 235 female DZ pairs, and 275 opposite sex DZ pairs participating in the University of Colorado Center on Antisocial Drug Dependence. Religiosity was measured using the Value on Religion Scale (Jessor and Jessor 1977), and problem alcohol use was measured using the Composite International Diagnostic Interview-Substance Abuse Module (Cottler et al. 1989). Data were analyzed using a model-fitting approach to the twin data. Results In adolescence, genetic variance of problem alcohol use decreased significantly with increasing levels of religiosity in both males and females whereas in early adulthood, religiosity did not moderate the genetic variance of problem alcohol use in either males or females. Conclusion Religiosity appears to moderate the genetic effects on problem alcohol use during adolescence, but not during early adulthood. The reduced genetic variance for problem alcohol use in adolescence may be the consequence of greater social control in adolescence than in young adulthood. PMID:20569244

  18. Genetic interactions affecting human gene expression identified by variance association mapping

    PubMed Central

    Brown, Andrew Anand; Buil, Alfonso; Viñuela, Ana; Lappalainen, Tuuli; Zheng, Hou-Feng; Richards, J Brent; Small, Kerrin S; Spector, Timothy D; Dermitzakis, Emmanouil T; Durbin, Richard

    2014-01-01

    Non-additive interaction between genetic variants, or epistasis, is a possible explanation for the gap between heritability of complex traits and the variation explained by identified genetic loci. Interactions give rise to genotype dependent variance, and therefore the identification of variance quantitative trait loci can be an intermediate step to discover both epistasis and gene by environment effects (GxE). Using RNA-sequence data from lymphoblastoid cell lines (LCLs) from the TwinsUK cohort, we identify a candidate set of 508 variance associated SNPs. Exploiting the twin design we show that GxE plays a role in ∼70% of these associations. Further investigation of these loci reveals 57 epistatic interactions that replicated in a smaller dataset, explaining on average 4.3% of phenotypic variance. In 24 cases, more variance is explained by the interaction than their additive contributions. Using molecular phenotypes in this way may provide a route to uncovering genetic interactions underlying more complex traits. DOI: http://dx.doi.org/10.7554/eLife.01381.001 PMID:24771767

  19. 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

  20. Two-Variance-Component Model Improves Genetic Prediction in Family Datasets

    PubMed Central

    Tucker, George; Loh, Po-Ru; MacLeod, Iona M.; Hayes, Ben J.; Goddard, Michael E.; Berger, Bonnie; Price, Alkes L.

    2015-01-01

    Genetic prediction based on either identity by state (IBS) sharing or pedigree information has been investigated extensively with best linear unbiased prediction (BLUP) methods. Such methods were pioneered in plant and animal-breeding literature and have since been applied to predict human traits, with the aim of eventual clinical utility. However, methods to combine IBS sharing and pedigree information for genetic prediction in humans have not been explored. We introduce a two-variance-component model for genetic prediction: one component for IBS sharing and one for approximate pedigree structure, both estimated with genetic markers. In simulations using real genotypes from the Candidate-gene Association Resource (CARe) and Framingham Heart Study (FHS) family cohorts, we demonstrate that the two-variance-component model achieves gains in prediction r2 over standard BLUP at current sample sizes, and we project, based on simulations, that these gains will continue to hold at larger sample sizes. Accordingly, in analyses of four quantitative phenotypes from CARe and two quantitative phenotypes from FHS, the two-variance-component model significantly improves prediction r2 in each case, with up to a 20% relative improvement. We also find that standard mixed-model association tests can produce inflated test statistics in datasets with related individuals, whereas the two-variance-component model corrects for inflation. PMID:26544803

  1. Genetic factors account for half of the phenotypic variance in liability to sleep-related bruxism in young adults: a nationwide Finnish twin cohort study.

    PubMed

    Rintakoski, Katariina; Hublin, Christer; Lobbezoo, Frank; Rose, Richard J; Kaprio, Jaakko

    2012-12-01

    The aim of the present study was to examine the role of genetic and environmental factors in the phenotypic variance of bruxism in a large population-based cohort of young adult twins in Finland. The material of the present study derives from the FinnTwin16 cohort study consisting of five birth cohorts of twin pairs born in 1975-1979 who completed a questionnaire (at mean age 24, range 23-27 years) with data on frequency of sleep-related bruxism in 2000-2002. We used quantitative genetic modeling, based on the genetic similarity of monozygotic and dizygotic twins, to estimate the most probable genetic model for bruxism, based on decomposition of phenotypic variance into components:additive genetic effects (A), dominant genetic effects (D), and non-shared environmental effects (E). On average, 8.7% experienced bruxism weekly, 23.4% rarely, and 67.9% never, with no significant gender difference (p = .052). The best fitting genetic model for bruxism was the AE-model. Additive genetic effects accounted for 52% (95% Cl 0.41--0.62) of the total phenotypic variance. Sex-limitation model revealed no gender differences. Genetic factors account for a substantial proportion of the phenotypic variation of the liability to sleep-related bruxism, with no gender difference in its genetic architecture.

  2. Fertilization success and the estimation of genetic variance in sperm competitiveness.

    PubMed

    Garcia-Gonzalez, Francisco; Evans, Jonathan P

    2011-03-01

    A key question in sexual selection is whether the ability of males to fertilize eggs under sperm competition exhibits heritable genetic variation. Addressing this question poses a significant problem, however, because a male's ability to win fertilizations ultimately depends on the competitive ability of rival males. Attempts to partition genetic variance in sperm competitiveness, as estimated from measures of fertilization success, must therefore account for stochastic effects due to the random sampling of rival sperm competitors. In this contribution, we suggest a practical solution to this problem. We advocate the use of simple cross-classified breeding designs for partitioning sources of genetic variance in sperm competitiveness and fertilization success and show how these designs can be used to avoid stochastic effects due to the random sampling of rival sperm competitors. We illustrate the utility of these approaches by simulating various scenarios for estimating genetic parameters in sperm competitiveness, and show that the probability of detecting additive genetic variance in this trait is restored when stochastic effects due to the random sampling of rival sperm competitors are controlled. Our findings have important implications for the study of the evolutionary maintenance of polyandry. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

  3. Indirect genetics effects and evolutionary constraint: an analysis of social dominance in red deer, Cervus elaphus.

    PubMed

    Wilson, A J; Morrissey, M B; Adams, M J; Walling, C A; Guinness, F E; Pemberton, J M; Clutton-Brock, T H; Kruuk, L E B

    2011-04-01

    By determining access to limited resources, social dominance is often an important determinant of fitness. Thus, if heritable, standard theory predicts mean dominance should evolve. However, dominance is usually inferred from the tendency to win contests, and given one winner and one loser in any dyadic contest, the mean proportion won will always equal 0.5. Here, we argue that the apparent conflict between quantitative genetic theory and common sense is resolved by recognition of indirect genetic effects (IGEs). We estimate selection on, and genetic (co)variance structures for, social dominance, in a wild population of red deer Cervus elaphus, on the Scottish island of Rum. While dominance is heritable and positively correlated with lifetime fitness, contest outcomes depend as much on the genes carried by an opponent as on the genotype of a focal individual. We show how this dependency imposes an absolute evolutionary constraint on the phenotypic mean, thus reconciling theoretical predictions with common sense. More generally, we argue that IGEs likely provide a widespread but poorly recognized source of evolutionary constraint for traits influenced by competition.

  4. Genetic regulatory network motifs constrain adaptation through curvature in the landscape of mutational (co)variance

    PubMed Central

    Hether, Tyler D.; Hohenlohe, Paul A.

    2013-01-01

    Systems biology is accumulating a wealth of understanding about the structure of genetic regulatory networks, leading to a more complete picture of the complex genotype-phenotype relationship. However, models of multivariate phenotypic evolution based on quantitative genetics have largely not incorporated a network-based view of genetic variation. Here we model a set of two-node, two-phenotype genetic network motifs, covering a full range of regulatory interactions. We find that network interactions result in different patterns of mutational (co)variance at the phenotypic level (the M-matrix), not only across network motifs but also across phenotypic space within single motifs. This effect is due almost entirely to mutational input of additive genetic (co)variance. Variation in M has the effect of stretching and bending phenotypic space with respect to evolvability, analogous to the curvature of space-time under general relativity, and similar mathematical tools may apply in each case. We explored the consequences of curvature in mutational variation by simulating adaptation under divergent selection with gene flow. Both standing genetic variation (the G-matrix) and rate of adaptation are constrained by M, so that G and adaptive trajectories are curved across phenotypic space. Under weak selection the phenotypic mean at migration-selection balance also depends on M. PMID:24219635

  5. Estimation of genetic parameters and their sampling variances of quantitative traits in the type 2 modified augmented design

    USDA-ARS?s Scientific Manuscript database

    We proposed a method to estimate the error variance among non-replicated genotypes, thus to estimate the genetic parameters by using replicated controls. We derived formulas to estimate sampling variances of the genetic parameters. Computer simulation indicated that the proposed methods of estimatin...

  6. Variance decomposition of MRI-based covariance maps using genetically informative samples and structural equation modeling.

    PubMed

    Schmitt, J Eric; Lenroot, Rhoshel K; Ordaz, Sarah E; Wallace, Gregory L; Lerch, Jason P; Evans, Alan C; Prom, Elizabeth C; Kendler, Kenneth S; Neale, Michael C; Giedd, Jay N

    2009-08-01

    The role of genetics in driving intracortical relationships is an important question that has rarely been studied in humans. In particular, there are no extant high-resolution imaging studies on genetic covariance. In this article, we describe a novel method that combines classical quantitative genetic methodologies for variance decomposition with recently developed semi-multivariate algorithms for high-resolution measurement of phenotypic covariance. Using these tools, we produced correlational maps of genetic and environmental (i.e. nongenetic) relationships between several regions of interest and the cortical surface in a large pediatric sample of 600 twins, siblings, and singletons. These analyses demonstrated high, fairly uniform, statistically significant genetic correlations between the entire cortex and global mean cortical thickness. In agreement with prior reports on phenotypic covariance using similar methods, we found that mean cortical thickness was most strongly correlated with association cortices. However, the present study suggests that genetics plays a large role in global brain patterning of cortical thickness in this manner. Further, using specific gyri with known high heritabilities as seed regions, we found a consistent pattern of high bilateral genetic correlations between structural homologues, with environmental correlations more restricted to the same hemisphere as the seed region, suggesting that interhemispheric covariance is largely genetically mediated. These findings are consistent with the limited existing knowledge on the genetics of cortical variability as well as our prior multivariate studies on cortical gyri.

  7. Estimation of genetic parameters for heat stress, including dominance gene effects, on milk yield in Thai Holstein dairy cattle.

    PubMed

    Boonkum, Wuttigrai; Duangjinda, Monchai

    2015-03-01

    Heat stress in tropical regions is a major cause that strongly negatively affects to milk production in dairy cattle. Genetic selection for dairy heat tolerance is powerful technique to improve genetic performance. Therefore, the current study aimed to estimate genetic parameters and investigate the threshold point of heat stress for milk yield. Data included 52 701 test-day milk yield records for the first parity from 6247 Thai Holstein dairy cattle, covering the period 1990 to 2007. The random regression test day model with EM-REML was used to estimate variance components, genetic parameters and milk production loss. A decline in milk production was found when temperature and humidity index (THI) exceeded a threshold of 74, also it was associated with the high percentage of Holstein genetics. All variance component estimates increased with THI. The estimate of heritability of test-day milk yield was 0.231. Dominance variance as a proportion to additive variance (0.035) indicated that non-additive effects might not be of concern for milk genetics studies in Thai Holstein cattle. Correlations between genetic and permanent environmental effects, for regular conditions and due to heat stress, were - 0.223 and - 0.521, respectively. The heritability and genetic correlations from this study show that simultaneous selection for milk production and heat tolerance is possible. © 2014 Japanese Society of Animal Science.

  8. Age-specific patterns of genetic variance in Drosophila melanogaster. I. Mortality

    SciTech Connect

    Promislow, D.E.L.; Tatar, M.; Curtsinger, J.W.

    1996-06-01

    Peter Medawar proposed that senescence arises from an age-related decline in the force of selection, which allows late-acting deleterious mutations to accumulate. Subsequent workers have suggested that mutation accumulation could produce an age-related increase in additive genetic variance (V{sub A}) for fitness traits, as recently found in Drosophila melanogaster. Here we report results from a genetic analysis of mortality in 65,134 D. melanogaster. Additive genetic variance for female mortality rates increases from 0.007 in the first week of life to 0.325 by the third week, and then declines to 0.002 by the seventh week. Males show a similar pattern, though total variance is lower than in females. In contrast to a predicted divergence in mortality curves, mortality curves of different genotypes are roughly parallel. Using a three-parameter model, we find significant V{sub A} for the slope and constant term of the curve describing age-specific mortality rates, and also for the rate at which mortality decelerates late in life. These results fail to support a prediction derived from Medawar`s {open_quotes}mutation accumulation{close_quotes} theory for the evolution of senescence. However, our results could be consistent with alternative interpretations of evolutionary models of aging. 65 refs., 2 figs., 2 tabs.

  9. Editing genomic DNA in cancer cells with high genetic variance: benefit or risk?

    PubMed

    Wang, Lin; Wang, Yixiang; Guo, Chuanbin

    2014-05-01

    The generation of stably-transfected cell lines is a common and very important technology in cancer science. Considerable knowledge in the field of life sciences has been gained through the modification of the genetic code. However, there is a risk in evaluating exogenous gene function through editing genomic DNA in a cancer cell with high genetic variance. In the present study, we showed that genomic DNA status should be considered when evaluating the exogenous gene function in a cancer cell line with high variant genome through stable transfection technology, immunostaining, wound healing assay, transwell invasion assay, real-time PCR, western blot and karyotyping analysis. Our results showed that the S100P expression level was not related to the migration and invasion abilities in these stably transfected cell lines derived from a human salivary adenoid cystic carcinoma cell line SACC-83. The MMP expression pattern was detected by western blot analysis which matched the biological behaviors in these cells. The genomic analysis showed that SACC-83 presented hypotetraploid karyotyping with high variance. Our data indicated that establishment of stable transgenic cancer cell lines should consider the status of genetic variance in a cancer cell to avoid any biased conclusion.

  10. Colour ornamentation in the blue tit: quantitative genetic (co)variances across sexes.

    PubMed

    Charmantier, A; Wolak, M E; Grégoire, A; Fargevieille, A; Doutrelant, C

    2017-02-01

    Although secondary sexual traits are commonly more developed in males than females, in many animal species females also display elaborate ornaments or weaponry. Indirect selection on correlated traits in males and/or direct sexual or social selection in females are hypothesized to drive the evolution and maintenance of female ornaments. Yet, the relative roles of these evolutionary processes remain unidentified, because little is known about the genetic correlation that might exist between the ornaments of both sexes, and few estimates of sex-specific autosomal or sex-linked genetic variances are available. In this study, we used two wild blue tit populations with 9 years of measurements on two colour ornaments: one structurally based (blue crown) and one carotenoid based (yellow chest). We found significant autosomal heritability for the chromatic part of the structurally based colouration in both sexes, whereas carotenoid chroma was heritable only in males, and the achromatic part of both colour patches was mostly non heritable. Power limitations, which are probably common among most data sets collected so far in wild populations, prevented estimation of sex-linked genetic variance. Bivariate analyses revealed very strong cross-sex genetic correlations in all heritable traits, although the strength of these correlations was not related to the level of sexual dimorphism. In total, our results suggest that males and females share a majority of their genetic variation underlying colour ornamentation, and hence the evolution of these sex-specific traits may depend greatly on correlated responses to selection in the opposite sex.

  11. 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

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

    PubMed

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

    2013-12-01

    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. Evidence for further genetic heterogeneity in autosomal dominant retinitis pigmentosa

    SciTech Connect

    Kumar-Singh, R.; Kenna, P.F.; Farrar, G.J.; Humphries, P. )

    1993-01-01

    We have investigated the possible involvement of further genetic heterogeneity in autosomal dominant retinitis pigmentosa using a previously unreported large Irish family with the disease. We have utilized polymorphic microsatellite markers to exclude the disease gene segregating in this family from 3q, 6p, and the pericentric region of 8, that is, each of the three chromosomal regions to which adRP loci are known to map. Hence, we provide definitive evidence for the involvement of a fourth locus in autosomal dominant retinitis pigmentosa. 25 refs., 2 figs.

  14. Sex-specific genetic variance and the evolution of sexual dimorphism: a systematic review of cross-sex genetic correlations.

    PubMed

    Poissant, Jocelyn; Wilson, Alastair J; Coltman, David W

    2010-01-01

    The independent evolution of the sexes may often be constrained if male and female homologous traits share a similar genetic architecture. Thus, cross-sex genetic covariance is assumed to play a key role in the evolution of sexual dimorphism (SD) with consequent impacts on sexual selection, population dynamics, and speciation processes. We compiled cross-sex genetic correlations (r(MF)) estimates from 114 sources to assess the extent to which the evolution of SD is typically constrained and test several specific hypotheses. First, we tested if r(MF) differed among trait types and especially between fitness components and other traits. We also tested the theoretical prediction of a negative relationship between r(MF) and SD based on the expectation that increases in SD should be facilitated by sex-specific genetic variance. We show that r(MF) is usually large and positive but that it is typically smaller for fitness components. This demonstrates that the evolution of SD is typically genetically constrained and that sex-specific selection coefficients may often be opposite in sign due to sub-optimal levels of SD. Most importantly, we confirm that sex-specific genetic variance is an important contributor to the evolution of SD by validating the prediction of a negative correlation between r(MF) and SD.

  15. Genetically Determined Variation in Lysis Time Variance in the Bacteriophage φX174.

    PubMed

    Baker, Christopher W; Miller, Craig R; Thaweethai, Tanayott; Yuan, Jeffrey; Baker, Meghan Hollibaugh; Joyce, Paul; Weinreich, Daniel M

    2016-04-07

    Researchers in evolutionary genetics recently have recognized an exciting opportunity in decomposing beneficial mutations into their proximal, mechanistic determinants. The application of methods and concepts from molecular biology and life history theory to studies of lytic bacteriophages (phages) has allowed them to understand how natural selection sees mutations influencing life history. This work motivated the research presented here, in which we explored whether, under consistent experimental conditions, small differences in the genome of bacteriophage φX174 could lead to altered life history phenotypes among a panel of eight genetically distinct clones. We assessed the clones' phenotypes by applying a novel statistical framework to the results of a serially sampled parallel infection assay, in which we simultaneously inoculated each of a large number of replicate host volumes with ∼1 phage particle. We sequentially plated the volumes over the course of infection and counted the plaques that formed after incubation. These counts served as a proxy for the number of phage particles in a single volume as a function of time. From repeated assays, we inferred significant, genetically determined heterogeneity in lysis time and burst size, including lysis time variance. These findings are interesting in light of the genetic and phenotypic constraints on the single-protein lysis mechanism of φX174. We speculate briefly on the mechanisms underlying our results, and we discuss the potential importance of lysis time variance in viral evolution.

  16. Genetically Determined Variation in Lysis Time Variance in the Bacteriophage φX174

    PubMed Central

    Baker, Christopher W.; Miller, Craig R.; Thaweethai, Tanayott; Yuan, Jeffrey; Baker, Meghan Hollibaugh; Joyce, Paul; Weinreich, Daniel M.

    2016-01-01

    Researchers in evolutionary genetics recently have recognized an exciting opportunity in decomposing beneficial mutations into their proximal, mechanistic determinants. The application of methods and concepts from molecular biology and life history theory to studies of lytic bacteriophages (phages) has allowed them to understand how natural selection sees mutations influencing life history. This work motivated the research presented here, in which we explored whether, under consistent experimental conditions, small differences in the genome of bacteriophage φX174 could lead to altered life history phenotypes among a panel of eight genetically distinct clones. We assessed the clones’ phenotypes by applying a novel statistical framework to the results of a serially sampled parallel infection assay, in which we simultaneously inoculated each of a large number of replicate host volumes with ∼1 phage particle. We sequentially plated the volumes over the course of infection and counted the plaques that formed after incubation. These counts served as a proxy for the number of phage particles in a single volume as a function of time. From repeated assays, we inferred significant, genetically determined heterogeneity in lysis time and burst size, including lysis time variance. These findings are interesting in light of the genetic and phenotypic constraints on the single-protein lysis mechanism of φX174. We speculate briefly on the mechanisms underlying our results, and we discuss the potential importance of lysis time variance in viral evolution. PMID:26921293

  17. The apportionment of total genetic variation by categorical analysis of variance.

    PubMed

    Khang, Tsung Fei; Yap, Von Bing

    2010-01-01

    We wish to suggest the categorical analysis of variance as a means of quantifying the proportion of total genetic variation attributed to different sources of variation. This method potentially challenges researchers to rethink conclusions derived from a well-known method known as the analysis of molecular variance (AMOVA). The CATANOVA framework allows explicit definition, and estimation, of two measures of genetic differentiation. These parameters form the subject of interest in many research programmes, but are often confused with the correlation measures defined in AMOVA, which cannot be interpreted as relative contributions of particular sources of variation. Through a simulation approach, we show that under certain conditions, researchers who use AMOVA to estimate these measures of genetic differentiation may attribute more than justified amounts of total variation to population labels. Moreover, the two measures can also lead to incongruent conclusions regarding the genetic structure of the populations of interest. Fortunately, one of the two measures seems robust to variations in relative sample sizes used. Its merits are illustrated in this paper using mitochondrial haplotype and amplified fragment length polymorphism (AFLP) data.

  18. Estimation of genetic (co)variances of Gompertz growth function parameters in pigs.

    PubMed

    Coyne, J M; Matilainen, K; Berry, D P; Sevon-Aimonen, M-L; Mäntysaari, E A; Juga, J; Serenius, T; McHugh, N

    2017-04-01

    The objective of this study was to estimate genetic (co)variances for the Gompertz growth function parameters, asymptotic mature weight (A), the ratio of mature weight to birthweight (B) and rate of maturation (k), using alternative modelling approaches. The data set consisted of 51 893 live weight records from 10 201 growing pigs. The growth of each pig was modelled using the Gompertz model employing either a two-step fixed effect or mixed model approach or a one-step mixed model approach using restricted maximum likelihood for the estimation of genetic (co)variance. Heritability estimates for the Gompertz growth function parameters, A (0.40), B (0.69) and k (0.45), were greatest for the one-step approach, compared with the two-step fixed effects approach, A (0.10), B (0.33) and k (0.13), and the two-step mixed model approach, A (0.17), B (0.32) and k (0.18). Inferred genetic correlations (i.e. correlations of estimated breeding values) between growth function parameters within models ranged from -0.78 to 0.76, and across models ranged from 0.28 to 0.73 for parameter A, 0.75 to 0.88 for parameter B and 0.09 to 0.37 for parameter k. Correlations between predicted daily sire live weights based on the Gompertz growth curve parameters' estimated breeding values from 60 to 200 days of age between all three modelled approaches were moderately to strongly correlated (0.75 to 0.95). Results from this study provide heritability estimates for biologically interpretable parameters of pig growth through the quantification of genetic (co)variances, thereby facilitating the estimation of breeding values for inclusion in breeding objectives to aid in breeding and selection decisions.

  19. Age and sex affect quantitative genetic parameters for dominance rank and aggression in free-living greylag geese.

    PubMed

    Weiß, B M; Foerster, K

    2013-02-01

    Knowledge of the genetic and environmental influences on a character is pivotal for understanding evolutionary changes in quantitative traits in natural populations. Dominance and aggression are ubiquitous traits that are selectively advantageous in many animal societies and have the potential to impact the evolutionary trajectory of animal populations. Here we provide age- and sex-specific estimates of additive genetic and environmental components of variance for dominance rank and aggression rate in a free-living, human-habituated bird population subject to natural selection. We use a long-term data set on individually marked greylag geese (Anser anser) and show that phenotypic variation in dominance-related behaviours contains significant additive genetic variance, parental effects and permanent environment effects. The relative importance of these variance components varied between age and sex classes, whereby the most pronounced differences concerned nongenetic components. In particular, parental effects were larger in juveniles of both sexes than in adults. In paired adults, the partner's identity had a larger influence on male dominance rank and aggression rate than in females. In sex- and age-specific estimates, heritabilities did not differ significantly between age and sex classes. Adult dominance rank was only weakly genetically correlated between the sexes, leading to considerably higher heritabilities in sex-specific estimates than across sexes. We discuss these patterns in relation to selection acting on dominance rank and aggression in different life history stages and sexes and suggest that different adaptive optima could be a mechanism for maintaining genetic variation in dominance-related traits in free-living animal populations. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

  20. Additive genetic variance in polyandry enables its evolution, but polyandry is unlikely to evolve through sexy or good sperm processes.

    PubMed

    Travers, L M; Simmons, L W; Garcia-Gonzalez, F

    2016-05-01

    Polyandry is widespread despite its costs. The sexually selected sperm hypotheses ('sexy' and 'good' sperm) posit that sperm competition plays a role in the evolution of polyandry. Two poorly studied assumptions of these hypotheses are the presence of additive genetic variance in polyandry and sperm competitiveness. Using a quantitative genetic breeding design in a natural population of Drosophila melanogaster, we first established the potential for polyandry to respond to selection. We then investigated whether polyandry can evolve through sexually selected sperm processes. We measured lifetime polyandry and offensive sperm competitiveness (P2 ) while controlling for sampling variance due to male × male × female interactions. We also measured additive genetic variance in egg-to-adult viability and controlled for its effect on P2 estimates. Female lifetime polyandry showed significant and substantial additive genetic variance and evolvability. In contrast, we found little genetic variance or evolvability in P2 or egg-to-adult viability. Additive genetic variance in polyandry highlights its potential to respond to selection. However, the low levels of genetic variance in sperm competitiveness suggest that the evolution of polyandry may not be driven by sexy sperm or good sperm processes. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  1. Genetic selection for increased mean and reduced variance of twinning rate in Belclare ewes.

    PubMed

    Cottle, D J; Gilmour, A R; Pabiou, T; Amer, P R; Fahey, A G

    2016-04-01

    It is sometimes possible to breed for more uniform individuals by selecting animals with a greater tendency to be less variable, that is, those with a smaller environmental variance. This approach has been applied to reproduction traits in various animal species. We have evaluated fecundity in the Irish Belclare sheep breed by analyses of flocks with differing average litter size (number of lambs per ewe per year, NLB) and have estimated the genetic variance in environmental variance of lambing traits using double hierarchical generalized linear models (DHGLM). The data set comprised of 9470 litter size records from 4407 ewes collected in 56 flocks. The percentage of pedigreed lambing ewes with singles, twins and triplets was 30, 54 and 14%, respectively, in 2013 and has been relatively constant for the last 15 years. The variance of NLB increases with the mean in this data; the correlation of mean and standard deviation across sires is 0.50. The breeding goal is to increase the mean NLB without unduly increasing the incidence of triplets and higher litter sizes. The heritability estimates for lambing traits were NLB, 0.09; triplet occurrence (TRI) 0.07; and twin occurrence (TWN), 0.02. The highest and lowest twinning flocks differed by 23% (75% versus 52%) in the proportion of ewes lambing twins. Fitting bivariate sire models to NLB and the residual from the NLB model using a double hierarchical generalized linear model (DHGLM) model found a strong genetic correlation (0.88 ± 0.07) between the sire effect for the magnitude of the residual (VE ) and sire effects for NLB, confirming the general observation that increased average litter size is associated with increased variability in litter size. We propose a threshold model that may help breeders with low litter size increase the percentage of twin bearers without unduly increasing the percentage of ewes bearing triplets in Belclare sheep.

  2. Sex chromosome linked genetic variance and the evolution of sexual dimorphism of quantitative traits.

    PubMed

    Husby, Arild; Schielzeth, Holger; Forstmeier, Wolfgang; Gustafsson, Lars; Qvarnström, Anna

    2013-03-01

    Theory predicts that sex chromsome linkage should reduce intersexual genetic correlations thereby allowing the evolution of sexual dimorphism. Empirical evidence for sex linkage has come largely from crosses and few studies have examined how sexual dimorphism and sex linkage are related within outbred populations. Here, we use data on an array of different traits measured on over 10,000 individuals from two pedigreed populations of birds (collared flycatcher and zebra finch) to estimate the amount of sex-linked genetic variance (h(2)z ). Of 17 traits examined, eight showed a nonzero h(2)Z estimate but only four were significantly different from zero (wing patch size and tarsus length in collared flycatchers, wing length and beak color in zebra finches). We further tested how sexual dimorphism and the mode of selection operating on the trait relate to the proportion of sex-linked genetic variance. Sexually selected traits did not show higher h(2)Z than morphological traits and there was only a weak positive relationship between h(2)Z and sexual dimorphism. However, given the relative scarcity of empirical studies, it is premature to make conclusions about the role of sex chromosome linkage in the evolution of sexual dimorphism.

  3. Estimation of (co)variance components and genetic parameters of greasy fleece weights in Muzaffarnagari sheep.

    PubMed

    Mandal, A; Neser, F W C; Roy, R; Rout, P K; Notter, D R

    2009-02-01

    Variance components and genetic parameters for greasy fleece weights of Muzaffarnagari sheep maintained at the Central Institute for Research on Goats, Makhdoom, Mathura, India, over a period of 29 years (1976 to 2004) were estimated by restricted maximum likelihood (REML), fitting six animal models including various combinations of maternal effects. Data on body weights at 6 (W6) and 12 months (W12) of age were also included in the study. Records of 2807 lambs descended from 160 rams and 1202 ewes were used for the study. Direct heritability estimates for fleece weight at 6 (FW6) and 12 months of age (FW12), and total fleece weights up to 1 year of age (TFW) were 0.14, 0.16 and 0.25, respectively. Maternal genetic and permanent environmental effects did not significantly influence any of the traits under study. Genetic correlations among fleece weights and body weights were obtained from multivariate analyses. Direct genetic correlations of FW6 with W6 and W12 were relatively large, ranging from 0.61 to 0.67, but only moderate genetic correlations existed between FW12 and W6 (0.39) and between FW12 and W12 (0.49). The genetic correlation between FW6 and FW12 was very high (0.95), but the corresponding phenotypic correlation was much lower (0.28). Heritability estimates for all traits were at least 0.15, indicating that there is potential for their improvement by selection. The moderate to high positive genetic correlations between fleece weights and body weights at 6 and 12 months of age suggest that some of the genetic factors that influence animal growth also influence wool growth. Thus selection to improve the body weights or fleece weights at 6 months of age will also result in genetic improvement of fleece weights at subsequent stages of growth.

  4. Genetics of Dominant Gibberellin-Insensitive Dwarfism in Maize

    PubMed Central

    Harberd, N. P.; Freeling, M.

    1989-01-01

    D8 and Mpl1 are two dominant dwarfing mutations of maize. Although they differ in severity of dwarfism, both D8 and Mpl1 mutants are unresponsive to gibberellin (GA). Because of their close phenotypic resemblance to the recessive GA-sensitive dwarf mutants these dominant mutations may identify a gene whose product is involved in the reception of GA. With this possibility in mind we have studied the genetic properties of D8 and Mpl1. Both mutations map close to Adh1 on chromosome 1L. By marking normal and translocated 1L arms with different Adh1 electrophoretic mobility alleles, we investigated the effect of gene dosage on dominant dwarf phenotype. The results suggest that D8 and Mpl1 encode novel product functions and that these functions are relatively insensitive to the presence of the (presumed) wild-type product. Using X-ray induced chromosome breakage we created sectors of wild-type cells within D8 or Mpl1 tissue; these sectors were marked by the linked recessive lw mutation. The phenotypes of these sectors demonstrated that, at least in certain plant organs and tissues, dominant dwarfism can be an autonomous phenotype. These results are consistent with the hypothesis that the wild-type gene product acts as a GA receptor. The potential utility of dominant dwarf phenotype in plant developmental analysis is discussed, and possible mechanisms for the action of the D8 and Mpl1 mutations are considered. PMID:17246493

  5. Effect of captivity on genetic variance for five traits in the large milkweed bug (Oncopeltus fasciatus).

    PubMed

    Rodríguez-Clark, K M

    2004-07-01

    Understanding the changes in genetic variance which may occur as populations move from nature into captivity has been considered important when populations in captivity are used as models of wild ones. However, the inherent significance of these changes has not previously been appreciated in a conservation context: are the methods aimed at founding captive populations with gene diversity representative of natural populations likely also to capture representative quantitative genetic variation? Here, I investigate changes in heritability and a less traditional measure, evolvability, between nature and captivity for the large milkweed bug, Oncopeltus fasciatus, to address this question. Founders were collected from a 100-km transect across the north-eastern US, and five traits (wing colour, pronotum colour, wing length, early fecundity and later fecundity) were recorded for founders and for their offspring during two generations in captivity. Analyses reveal significant heritable variation for some life history and morphological traits in both environments, with comparable absolute levels of evolvability across all traits (0-30%). Randomization tests show that while changes in heritability and total phenotypic variance were highly variable, additive genetic variance and evolvability remained stable across the environmental transition in the three morphological traits (changing 1-2% or less), while they declined significantly in the two life-history traits (5-8%). Although it is unclear whether the declines were due to selection or gene-by-environment interactions (or both), such declines do not appear inevitable: captive populations with small numbers of founders may contain substantial amounts of the evolvability found in nature, at least for some traits.

  6. Colour ornamentation in the blue tit: quantitative genetic (co)variances across sexes

    PubMed Central

    Charmantier, A; Wolak, M E; Grégoire, A; Fargevieille, A; Doutrelant, C

    2017-01-01

    Although secondary sexual traits are commonly more developed in males than females, in many animal species females also display elaborate ornaments or weaponry. Indirect selection on correlated traits in males and/or direct sexual or social selection in females are hypothesized to drive the evolution and maintenance of female ornaments. Yet, the relative roles of these evolutionary processes remain unidentified, because little is known about the genetic correlation that might exist between the ornaments of both sexes, and few estimates of sex-specific autosomal or sex-linked genetic variances are available. In this study, we used two wild blue tit populations with 9 years of measurements on two colour ornaments: one structurally based (blue crown) and one carotenoid based (yellow chest). We found significant autosomal heritability for the chromatic part of the structurally based colouration in both sexes, whereas carotenoid chroma was heritable only in males, and the achromatic part of both colour patches was mostly non heritable. Power limitations, which are probably common among most data sets collected so far in wild populations, prevented estimation of sex-linked genetic variance. Bivariate analyses revealed very strong cross-sex genetic correlations in all heritable traits, although the strength of these correlations was not related to the level of sexual dimorphism. In total, our results suggest that males and females share a majority of their genetic variation underlying colour ornamentation, and hence the evolution of these sex-specific traits may depend greatly on correlated responses to selection in the opposite sex. PMID:27577691

  7. Determining the effective dimensionality of the genetic variance-covariance matrix.

    PubMed

    Hine, Emma; Blows, Mark W

    2006-06-01

    Determining the dimensionality of G provides an important perspective on the genetic basis of a multivariate suite of traits. Since the introduction of Fisher's geometric model, the number of genetically independent traits underlying a set of functionally related phenotypic traits has been recognized as an important factor influencing the response to selection. Here, we show how the effective dimensionality of G can be established, using a method for the determination of the dimensionality of the effect space from a multivariate general linear model introduced by Amemiya (1985). We compare this approach with two other available methods, factor-analytic modeling and bootstrapping, using a half-sib experiment that estimated G for eight cuticular hydrocarbons of Drosophila serrata. In our example, eight pheromone traits were shown to be adequately represented by only two underlying genetic dimensions by Amemiya's approach and factor-analytic modeling of the covariance structure at the sire level. In contrast, bootstrapping identified four dimensions with significant genetic variance. A simulation study indicated that while the performance of Amemiya's method was more sensitive to power constraints, it performed as well or better than factor-analytic modeling in correctly identifying the original genetic dimensions at moderate to high levels of heritability. The bootstrap approach consistently overestimated the number of dimensions in all cases and performed less well than Amemiya's method at subspace recovery.

  8. The Dominance Concept Inventory: A Tool for Assessing Undergraduate Student Alternative Conceptions about Dominance in Mendelian and Population Genetics

    ERIC Educational Resources Information Center

    Abraham, Joel K.; Perez, Kathryn E.; Price, Rebecca M.

    2014-01-01

    Despite the impact of genetics on daily life, biology undergraduates understand some key genetics concepts poorly. One concept requiring attention is dominance, which many students understand as a fixed property of an allele or trait and regularly conflate with frequency in a population or selective advantage. We present the Dominance Concept…

  9. The Dominance Concept Inventory: A Tool for Assessing Undergraduate Student Alternative Conceptions about Dominance in Mendelian and Population Genetics

    ERIC Educational Resources Information Center

    Abraham, Joel K.; Perez, Kathryn E.; Price, Rebecca M.

    2014-01-01

    Despite the impact of genetics on daily life, biology undergraduates understand some key genetics concepts poorly. One concept requiring attention is dominance, which many students understand as a fixed property of an allele or trait and regularly conflate with frequency in a population or selective advantage. We present the Dominance Concept…

  10. Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy.

    PubMed Central

    Votruba, M; Moore, A T; Bhattacharya, S S

    1998-01-01

    Inherited optic neuropathies are a significant cause of childhood and adult blindness and dominant optic atrophy (DOA) is the most common form of autosomally inherited (non-glaucomatous) optic neuropathy. Patients with DOA present with an insidious onset of bilateral visual loss and they characteristically have temporal optic nerve pallor, centrocaecal visual field scotoma, and a colour vision deficit, which is frequently blue-yellow. Evidence from histological and electrophysiological studies suggests that the pathology is confined to the retinal ganglion cell. A gene for dominant optic atrophy (OPA1) has been mapped to chromosome 3q28-qter, and studies are under way to refine the genetic interval in which the gene lies, to map the region physically, and hence to clone the gene. A second locus for dominant optic atrophy has recently been shown to map to chromosome 18q12.2-12.3 near the Kidd blood group locus. The cloning of genes for dominant optic atrophy will provide important insights into the pathophysiology of the retinal ganglion cell in health and disease. These insights may prove to be of great value in the understanding of other primary ganglion cell diseases, such as the mitochondrially inherited Leber's hereditary optic neuropathy and other diseases associated with ganglion cell loss, such as glaucoma. Images PMID:9783700

  11. The effect of a population bottleneck on the evolution of genetic variance/covariance structure.

    PubMed

    Jarvis, J P; Cropp, S N; Vaughn, T T; Pletscher, L S; King-Ellison, K; Adams-Hunt, E; Erickson, C; Cheverud, J M

    2011-10-01

    It is well known that standard population genetic theory predicts decreased additive genetic variance (V(a) ) following a population bottleneck and that theoretical models including interallelic and intergenic interactions indicate such loss may be avoided. However, few empirical data from multicellular model systems are available, especially regarding variance/covariance (V/CV) relationships. Here, we compare the V/CV structure of seventeen traits related to body size and composition between control (60 mating pairs/generation) and bottlenecked (2 mating pairs/generation; average F = 0.39) strains of mice. Although results for individual traits vary considerably, multivariate analysis indicates that V(a) in the bottlenecked populations is greater than expected. Traits with patterns and amounts of epistasis predictive of enhanced V(a) also show the largest deviations from additive expectations. Finally, the correlation structure of weekly weights is not significantly different between control and experimental lines but correlations between necropsy traits do differ, especially those involving the heart, kidney and tail length. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  12. Comparing sensory experience in bitter taste perception of phenylthiocarbamide within and between human twins and singletons: intrapair differences in thresholds and genetic variance estimates.

    PubMed

    Sharma, Krishan

    2008-06-01

    Quantitative genetic studies revealed that not all of the phenotypic variance in PTC taste perception is heritable. To study quantitative variations in PTC tasting ability in twins and to estimate heritability of PTC taste perception on the taste of twin data on males and females sexes separately. The data for PTC taste sensitivity following the classic method of Harris & Kalmus (1949) were collected on a sample of 141 twin pairs (66 MZ and 75 DZ) and 275 singletons (128 males and 147 females) from Chandigarh, India. Genetic analyses were performed following Christian (1979), Donner (1986) and Sham (1998). Frequency of non-tasters was similar in twins (33 %) and singletons (32 %), but significant sex differences were observed. No differences were found between zygosities for mean thresholds. Similarly, no evidence of variance heterogeneity and environmental covariance was seen between zygosities. Since no basic assumption of the twin method was found violated, within-pair estimates of genetic variance would be unbiased. These estimates were highly significant in both males and females. However, dominance and additive components of genetic variance were found to differ between sexes. PTC thresholds do not seem to be significantly affected by environmental factors as no variance inequality was observed between twin zygosities. Intensity of bitterness (scalar dimensions) of PTC is a separate trait having no commonality with the genetic basis of recognition threshold for PTC tasting ability. The receptors recognizing bitter taste are different from the receptors determining intensity of taste. The absolute difference between co-twins in PTC thresholds can be used as a simple tool in the twin zygosity diagnosis. The results show that none of the MZ co-twins had manifested difference of more than 3 in their PTC threshold.

  13. No evidence of genetic heterogeneity in dominant optic atrophy.

    PubMed Central

    Bonneau, D; Souied, E; Gerber, S; Rozet, J M; D'Haens, E; Journel, H; Plessis, G; Weissenbach, J; Munnich, A; Kaplan, J

    1995-01-01

    Autosomal dominant optic atrophy (OPA, MIM 165500) is an eye disease causing a variable reduction of visual acuity with an insidious onset in the first six years of life. It is associated with a central scotoma and an acquired blue-yellow dyschromatopsia. A gene for dominant optic atrophy (OPA1) has recently been mapped to chromosome 3q in three large Danish pedigrees. Here, we confirm the mapping of OPA1 to chromosome 3q28-qter by showing close linkage of the disease locus to three recently reported microsatellite DNA markers in the interval defined by loci D3S1314 and D3S1265 in four French families (Zmax = 5.13 at theta = 0 for probe AFM 308yf1 at locus D3S1601). Multipoint analysis supports the mapping of the disease gene to the genetic interval defined by loci D3S1314 and D3S1265. The present study provides three new markers closely linked to the disease gene for future genetic studies in OPA. PMID:8825922

  14. 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.

  15. Estimation of genetic variance for macro- and micro-environmental sensitivity using double hierarchical generalized linear models.

    PubMed

    Mulder, Han A; Rönnegård, Lars; Fikse, W Freddy; Veerkamp, Roel F; Strandberg, Erling

    2013-07-04

    Genetic variation for environmental sensitivity indicates that animals are genetically different in their response to environmental factors. Environmental factors are either identifiable (e.g. temperature) and called macro-environmental or unknown and called micro-environmental. The objectives of this study were to develop a statistical method to estimate genetic parameters for macro- and micro-environmental sensitivities simultaneously, to investigate bias and precision of resulting estimates of genetic parameters and to develop and evaluate use of Akaike's information criterion using h-likelihood to select the best fitting model. We assumed that genetic variation in macro- and micro-environmental sensitivities is expressed as genetic variance in the slope of a linear reaction norm and environmental variance, respectively. A reaction norm model to estimate genetic variance for macro-environmental sensitivity was combined with a structural model for residual variance to estimate genetic variance for micro-environmental sensitivity using a double hierarchical generalized linear model in ASReml. Akaike's information criterion was constructed as model selection criterion using approximated h-likelihood. Populations of sires with large half-sib offspring groups were simulated to investigate bias and precision of estimated genetic parameters. Designs with 100 sires, each with at least 100 offspring, are required to have standard deviations of estimated variances lower than 50% of the true value. When the number of offspring increased, standard deviations of estimates across replicates decreased substantially, especially for genetic variances of macro- and micro-environmental sensitivities. Standard deviations of estimated genetic correlations across replicates were quite large (between 0.1 and 0.4), especially when sires had few offspring. Practically, no bias was observed for estimates of any of the parameters. Using Akaike's information criterion the true genetic

  16. Estimation of genetic variance for macro- and micro-environmental sensitivity using double hierarchical generalized linear models

    PubMed Central

    2013-01-01

    Background Genetic variation for environmental sensitivity indicates that animals are genetically different in their response to environmental factors. Environmental factors are either identifiable (e.g. temperature) and called macro-environmental or unknown and called micro-environmental. The objectives of this study were to develop a statistical method to estimate genetic parameters for macro- and micro-environmental sensitivities simultaneously, to investigate bias and precision of resulting estimates of genetic parameters and to develop and evaluate use of Akaike’s information criterion using h-likelihood to select the best fitting model. Methods We assumed that genetic variation in macro- and micro-environmental sensitivities is expressed as genetic variance in the slope of a linear reaction norm and environmental variance, respectively. A reaction norm model to estimate genetic variance for macro-environmental sensitivity was combined with a structural model for residual variance to estimate genetic variance for micro-environmental sensitivity using a double hierarchical generalized linear model in ASReml. Akaike’s information criterion was constructed as model selection criterion using approximated h-likelihood. Populations of sires with large half-sib offspring groups were simulated to investigate bias and precision of estimated genetic parameters. Results Designs with 100 sires, each with at least 100 offspring, are required to have standard deviations of estimated variances lower than 50% of the true value. When the number of offspring increased, standard deviations of estimates across replicates decreased substantially, especially for genetic variances of macro- and micro-environmental sensitivities. Standard deviations of estimated genetic correlations across replicates were quite large (between 0.1 and 0.4), especially when sires had few offspring. Practically, no bias was observed for estimates of any of the parameters. Using Akaike

  17. Estimation of genetic connectedness diagnostics based on prediction errors without the prediction error variance-covariance matrix.

    PubMed

    Holmes, John B; Dodds, Ken G; Lee, Michael A

    2017-03-02

    An important issue in genetic evaluation is the comparability of random effects (breeding values), particularly between pairs of animals in different contemporary groups. This is usually referred to as genetic connectedness. While various measures of connectedness have been proposed in the literature, there is general agreement that the most appropriate measure is some function of the prediction error variance-covariance matrix. However, obtaining the prediction error variance-covariance matrix is computationally demanding for large-scale genetic evaluations. Many alternative statistics have been proposed that avoid the computational cost of obtaining the prediction error variance-covariance matrix, such as counts of genetic links between contemporary groups, gene flow matrices, and functions of the variance-covariance matrix of estimated contemporary group fixed effects. In this paper, we show that a correction to the variance-covariance matrix of estimated contemporary group fixed effects will produce the exact prediction error variance-covariance matrix averaged by contemporary group for univariate models in the presence of single or multiple fixed effects and one random effect. We demonstrate the correction for a series of models and show that approximations to the prediction error matrix based solely on the variance-covariance matrix of estimated contemporary group fixed effects are inappropriate in certain circumstances. Our method allows for the calculation of a connectedness measure based on the prediction error variance-covariance matrix by calculating only the variance-covariance matrix of estimated fixed effects. Since the number of fixed effects in genetic evaluation is usually orders of magnitudes smaller than the number of random effect levels, the computational requirements for our method should be reduced.

  18. Estimates of (co)variance components and genetic parameters for growth traits of Avikalin sheep.

    PubMed

    Prince, Leslie Leo L; Gowane, Gopal R; Chopra, Ashish; Arora, Amrit L

    2010-08-01

    (Co)variance components and genetic parameters for various growth traits of Avikalin sheep maintained at Central Sheep and Wool Research Institute, Avikanagar, Rajasthan, India, were estimated by Restricted Maximum Likelihood, fitting six animal models with various combinations of direct and maternal effects. Records of 3,840 animals descended from 257 sires and 1,194 dams were taken for this study over a period of 32 years (1977-2008). Direct heritability estimates (from best model as per likelihood ratio test) for weight at birth, weaning, 6 and 12 months of age, and average daily gain from birth to weaning, weaning to 6 months, and 6 to 12 months were 0.28 +/- 0.03, 0.20 +/- 0.03, 0.28 +/- 0.07, 0.15 +/- 0.04, 0.21 +/- 0.03, 0.16 and 0.03 +/- 0.03, respectively. Maternal heritability for traits declined as animal grows older and it was not at all evident at adult age and for post-weaning daily gain. Maternal permanent environmental effect (c(2)) declined significantly with advancement of age of animal. A small effect of c(2) on post-weaning weights was probably a carryover effect of pre-weaning maternal influence. A significant large negative genetic correlation was observed between direct and maternal genetic effects for all the traits, indicating antagonistic pleiotropy, which needs special care while formulating breeding plans. A fair rate of genetic progress seems possible in the flock by selection for all traits, but direct and maternal genetic correlation needs to be taken in to consideration.

  19. Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis.

    PubMed

    Loh, Po-Ru; Bhatia, Gaurav; Gusev, Alexander; Finucane, Hilary K; Bulik-Sullivan, Brendan K; Pollack, Samuela J; de Candia, Teresa R; Lee, Sang Hong; Wray, Naomi R; Kendler, Kenneth S; O'Donovan, Michael C; Neale, Benjamin M; Patterson, Nick; Price, Alkes L

    2015-12-01

    Heritability analyses of genome-wide association study (GWAS) cohorts have yielded important insights into complex disease architecture, and increasing sample sizes hold the promise of further discoveries. Here we analyze the genetic architectures of schizophrenia in 49,806 samples from the PGC and nine complex diseases in 54,734 samples from the GERA cohort. For schizophrenia, we infer an overwhelmingly polygenic disease architecture in which ≥71% of 1-Mb genomic regions harbor ≥1 variant influencing schizophrenia risk. We also observe significant enrichment of heritability in GC-rich regions and in higher-frequency SNPs for both schizophrenia and GERA diseases. In bivariate analyses, we observe significant genetic correlations (ranging from 0.18 to 0.85) for several pairs of GERA diseases; genetic correlations were on average 1.3 tunes stronger than the correlations of overall disease liabilities. To accomplish these analyses, we developed a fast algorithm for multicomponent, multi-trait variance-components analysis that overcomes prior computational barriers that made such analyses intractable at this scale.

  20. Evolvability of individual traits in a multivariate context: partitioning the additive genetic variance into common and specific components.

    PubMed

    McGuigan, Katrina; Blows, Mark W

    2010-07-01

    Genetic covariation among multiple traits will bias the direction of evolution. Although a trait's phenotypic context is crucial for understanding evolutionary constraints, the evolutionary potential of one (focal) trait, rather than the whole phenotype, is often of interest. The extent to which a focal trait can evolve independently depends on how much of the genetic variance in that trait is unique. Here, we present a hypothesis-testing framework for estimating the genetic variance in a focal trait that is independent of variance in other traits. We illustrate our analytical approach using two Drosophila bunnanda trait sets: a contact pheromone system comprised of cuticular hydrocarbons (CHCs), and wing shape, characterized by relative warps of vein position coordinates. Only 9% of the additive genetic variation in CHCs was trait specific, suggesting individual traits are unlikely to evolve independently. In contrast, most (72%) of the additive genetic variance in wing shape was trait specific, suggesting relative warp representations of wing shape could evolve independently. The identification of genetic variance in focal traits that is independent of other traits provides a way of studying the evolvability of individual traits within the broader context of the multivariate phenotype.

  1. Population divergence along lines of genetic variance and covariance in the invasive plant Lythrum salicaria in eastern North America.

    PubMed

    Colautti, Robert I; Barrett, Spencer C H

    2011-09-01

    Evolution during biological invasion may occur over contemporary timescales, but the rate of evolutionary change may be inhibited by a lack of standing genetic variation for ecologically relevant traits and by fitness trade-offs among them. The extent to which these genetic constraints limit the evolution of local adaptation during biological invasion has rarely been examined. To investigate genetic constraints on life-history traits, we measured standing genetic variance and covariance in 20 populations of the invasive plant purple loosestrife (Lythrum salicaria) sampled along a latitudinal climatic gradient in eastern North America and grown under uniform conditions in a glasshouse. Genetic variances within and among populations were significant for all traits; however, strong intercorrelations among measurements of seedling growth rate, time to reproductive maturity and adult size suggested that fitness trade-offs have constrained population divergence. Evidence to support this hypothesis was obtained from the genetic variance-covariance matrix (G) and the matrix of (co)variance among population means (D), which were 79.8% (95% C.I. 77.7-82.9%) similar. These results suggest that population divergence during invasive spread of L. salicaria in eastern North America has been constrained by strong genetic correlations among life-history traits, despite large amounts of standing genetic variation for individual traits. © 2011 The Author(s).

  2. The ARMC5 gene shows extensive genetic variance in primary macronodular adrenocortical hyperplasia

    PubMed Central

    Correa, Ricardo; Zilbermint, Mihail; Berthon, Annabel; Espiard, Stephanie; Batsis, Maria; Papadakis, Georgios Z.; Xekouki, Paraskevi; Lodish, Maya B.; Bertherat, Jerome; Faucz, Fabio R.; Stratakis, Constantine A.

    2015-01-01

    Objective Primary macronodular adrenal hyperplasia (PMAH) is a rare type of Cushing’s syndrome (CS) that results in increased cortisol production and bilateral enlargement of the adrenal glands. Recent work showed that the disease may be caused by germline and somatic mutations in the ARMC5 gene, a likely tumor-suppressor gene (TSG). We investigated 20 different adrenal nodules from one patient with PMAH for ARMC5 somatic sequence changes. Design All of the nodules where obtained from a single patient who underwent bilateral adrenalectomy. DNA was extracted by standard protocols and the ARMC5 sequence was determined by the Sanger method. Results Sixteen of 20 adrenocortical nodules harbored, in addition to what appeared to be the germline mutation, a second somatic variant. The p.Trp476* sequence change was present in all 20 nodules, as well as in normal tissue from the adrenal capsule, identifying it as the germline defect; each of the 16 other variants were found in different nodules: 6 were frame shift, 4 were missense, 3 were nonsense, and 1 was a splice site variation. Allelic losses were confirmed in 2 of the nodules. Conclusion This is the most genetic variance of the ARMC5 gene ever described in a single patient with PMAH: each of 16 adrenocortical nodules had a second new, “private”, and -in most cases- completely inactivating ARMC5 defect, in addition to the germline mutation. The data support the notion that ARMC5 is a TSG that needs a second, somatic hit, to mediate tumorigenesis leading to polyclonal nodularity; however, the driver of this extensive genetic variance of the second ARMC5 allele in adrenocortical tissue in the context of a germline defect and PMAH remains a mystery. PMID:26162405

  3. Genetic vasopressin 1b receptor variance in overweight and diabetes mellitus

    PubMed Central

    Enhörning, Sofia; Sjögren, Marketa; Hedblad, Bo; Nilsson, Peter M; Struck, Joachim; Melander, Olle

    2016-01-01

    Objective Recently, imbalance in the vasopressin (AVP) system, measured as elevated levels of copeptin (the C-terminal part of the AVP pro-hormone) in plasma, was linked to the development of abdominal obesity and diabetes mellitus (DM). Here, we aim to investigate if the genetic variation of the human AVP receptor 1b gene (AVPR1B) is associated with measures of obesity and DM. Design Malmö Diet and Cancer study (MDC) is a population-based prospective cohort examined 1991–1996. Methods Four tag single nucleotide polymorphisms (SNPs: rs35810727, rs28373064, rs35439639, rs35608965) of AVPR1B were genotyped in the cardiovascular cohort (n=6103) of MDC (MDC-CC) and associated with measures of obesity and DM. Significant SNPs were replicated in another 24 344 MDC individuals (MDC replication cohort). Results In MDC-CC, the major allele of rs35810727 was associated with elevated BMI (β-coefficient±s.e.m.; 0.30±0.14, P=0.03) and waist (0.78±0.36, P=0.03) after age and gender adjustment. The association with BMI was replicated in the MDC replication cohort (0.21±0.07, P=0.003), whereas that with waist was not significant. In MDC-CC there was no association between the major allele of rs35810727 and DM, but in the complete MDC cohort (n=30 447) the major allele of rs35810727 was associated with DM (OR (95% CI); 1.10 (1.00–1.20), P=0.04). Conclusions Genetic variance of AVPR1B contributes to overweight. Furthermore, our data indicate a link between AVPR1B variance and DM development. Our data point at a relationship between the disturbance of the pharmacologically modifiable AVP system and the body weight regulation. PMID:26503846

  4. Genetic heterogeneity of autosomal dominant polycystic kidney disease in Argentina.

    PubMed Central

    Iglesias, D M; Martín, R S; Fraga, A; Virginillo, M; Kornblihtt, A R; Arrizurieta, E; Viribay, M; San Millán, J L; Herrera, M; Bernath, V

    1997-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder with genetic heterogeneity. Up to three loci are involved in this disease, PKD1 on chromosome 16p13.3, PKD2 on 4q21, and a third locus of unknown location. Here we report the existence of locus heterogeneity for this disease in the Argentinian population by performing linkage analysis on 12 families of Caucasian origin. Eleven families showed linkage to PKD 1 and one family showed linkage to PKD2. Two recombinants in the latter family placed the locus PKD2 proximal to D4S1563, in agreement with data recently published on the cloning of this gene. Analysis of clinical data suggests a milder ADPKD phenotype for the PKD2 family. PMID:9350815

  5. Condition-dependent traits and the capture of genetic variance in male advertisement song.

    PubMed

    Brandt, L S E; Greenfield, M D

    2004-07-01

    The occurrence of additive genetic variance (VA) for male sexual traits remains a major problem in evolutionary biology. Directional selection normally imposed by female choice is expected to reduce VA greatly, yet recent surveys indicate that a substantial amount remains in many species. We addressed this problem, also known as the 'lek paradox', in Achroia grisella (Lepidoptera: Pyralidae), an acoustic moth in which males advertise to females with a pulsed ultrasonic song. Using a standard half-sib/full-sib breeding design, we generated F1 progeny from whom we determined VA and genetic covariance (COVA) among seven traits: three song characters, an overall index of song attractiveness, nightly singing period, adult lifespan, and body mass at adult eclosion. Because A. grisella neither feed nor drink as adults, the last trait, eclosion body mass, is considered a measure of 'condition'. We found significant levels of VA and narrow-sense heritabilities (h2) for all seven traits and significant genetic correlations (= COVAi,j / radical (VA i x VA j)) between most pairs of traits (i, j). Male attractiveness was positively correlated with body mass (condition), adult lifespan, and nightly singing period, which we interpret as an energy constraint preventing males in poor condition from singing attractively, from singing many hours per night, and from surviving an extended lifespan. The positive genetic correlation (r = 0.79) between condition and attractiveness, combined with significant levels of VA for both traits, indicates that much of the variation in male song can be explained by VA for condition. Finally, we discuss the morphological and physiological links between condition and song attractiveness, and the ultimate factors that may maintain VA for condition. Copyright 2004 Blackwell Publishing Ltd

  6. Autosomal dominant cyclic hematopoiesis: Genetics, phenotype, and natural history

    SciTech Connect

    Palmer, S.E.; Stephens, K.; Dale, D.C.

    1994-09-01

    Autosomal dominant cyclic hematopoiesis (ADCH; cyclic neutropenia) is a rare disorder manifested by transient neutropenia that recurs every three weeks. To facilitate mapping the ADCH gene by genetic linkage analysis, we studied 9 ADCH families with 42 affected individuals. Pedigrees revealed AD inheritance with no evidence for decreased penetrance. Similar intra- and interfamilial variable expression was observed, with no evidence to support heterogeneity. At least 3 families displayed apparent new mutations. Many adults developed chronic neutropenia, while offspring always cycled during childhood. Children displayed recurrent oral ulcers, gingivitis, lymphadenopathy, fever, and skin and other infections with additional symptoms. Interestingly, there were no cases of neonatal infection. Some children required multiple hospitalizations for treatment. Four males under age 18 died of Clostridium sepsis following necrotizing enterocolitis; all had affected mothers. No other deaths due to ADCH were found; most had improvement of symptoms and infections as adults. Adults experienced increased tooth loss prior to age 30 (16 out of 27 adults, with 9 edentulous). No increase in myelodysplasia, malignancy, or congenital anomalies was observed. Recombinant G-CSF treatment resulted in dramatic improvement of symptoms and infections. The results suggest that ADCH is not a benign disorder, especially in childhood, and abdominal pain requires immediate evaluation. Diagnosis of ADCH requires serial blood counts in the proband and at least one CBC in relatives to exclude similar disorders. Genetic counseling requires specific histories as well as CBCs of each family member at risk to determine status regardless of symptom history, especially to assess apparent new mutations.

  7. Dominant Genetic Variation and Missing Heritability for Human Complex Traits: Insights from Twin versus Genome-wide Common SNP Models.

    PubMed

    Chen, Xu; Kuja-Halkola, Ralf; Rahman, Iffat; Arpegård, Johannes; Viktorin, Alexander; Karlsson, Robert; Hägg, Sara; Svensson, Per; Pedersen, Nancy L; Magnusson, Patrik K E

    2015-11-05

    In order to further illuminate the potential role of dominant genetic variation in the "missing heritability" debate, we investigated the additive (narrow-sense heritability, h(2)) and dominant (δ(2)) genetic variance for 18 human complex traits. Within the same study base (10,682 Swedish twins), we calculated and compared the estimates from classic twin-based structural equation model with SNP-based genomic-relatedness-matrix restricted maximum likelihood [GREML(d)] method. Contributions of δ(2) were evident for 14 traits in twin models (average δ(2)twin = 0.25, range 0.14-0.49), two of which also displayed significant δ(2) in the GREMLd analyses (triglycerides δ(2)SNP = 0.28 and waist circumference δ(2)SNP = 0.19). On average, the proportion of h(2)SNP/h(2)twin was 70% for ADE-fitted traits (for which the best-fitting model included additive and dominant genetic and unique environmental components) and 31% for AE-fitted traits (for which the best-fitting model included additive genetic and unique environmental components). Independent evidence for contribution from shared environment, also in ADE-fitted traits, was obtained from self-reported within-pair contact frequency and age at separation. We conclude that despite the fact that additive genetics appear to constitute the bulk of genetic influences for most complex traits, dominant genetic variation might often be masked by shared environment in twin and family studies and might therefore have a more prominent role than what family-based estimates often suggest. The risk of erroneously attributing all inherited genetic influences (additive and dominant) to the h(2) in too-small twin studies might also lead to exaggerated "missing heritability" (the proportion of h(2) that remains unexplained by SNPs). Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Genetic and phenotypic variance and covariance components for methane emission and postweaning traits in Angus cattle.

    PubMed

    Donoghue, K A; Bird-Gardiner, T; Arthur, P F; Herd, R M; Hegarty, R F

    2016-04-01

    Ruminants contribute 80% of the global livestock greenhouse gas (GHG) emissions mainly through the production of methane, a byproduct of enteric microbial fermentation primarily in the rumen. Hence, reducing enteric methane production is essential in any GHG emissions reduction strategy in livestock. Data on 1,046 young bulls and heifers from 2 performance-recording research herds of Angus cattle were analyzed to provide genetic and phenotypic variance and covariance estimates for methane emissions and production traits and to examine the interrelationships among these traits. The cattle were fed a roughage diet at 1.2 times their estimated maintenance energy requirements and measured for methane production rate (MPR) in open circuit respiration chambers for 48 h. Traits studied included DMI during the methane measurement period, MPR, and methane yield (MY; MPR/DMI), with means of 6.1 kg/d (SD 1.3), 132 g/d (SD 25), and 22.0 g/kg (SD 2.3) DMI, respectively. Four forms of residual methane production (RMP), which is a measure of actual minus predicted MPR, were evaluated. For the first 3 forms, predicted MPR was calculated using published equations. For the fourth (RMP), predicted MPR was obtained by regression of MPR on DMI. Growth and body composition traits evaluated were birth weight (BWT), weaning weight (WWT), yearling weight (YWT), final weight (FWT), and ultrasound measures of eye muscle area, rump fat depth, rib fat depth, and intramuscular fat. Heritability estimates were moderate for MPR (0.27 [SE 0.07]), MY (0.22 [SE 0.06]), and the RMP traits (0.19 [SE 0.06] for each), indicating that genetic improvement to reduce methane emissions is possible. The RMP traits and MY were strongly genetically correlated with each other (0.99 ± 0.01). The genetic correlation of MPR with MY as well as with the RMP traits was moderate (0.32 to 0.63). The genetic correlation between MPR and the growth traits (except BWT) was strong (0.79 to 0.86). These results indicate that

  10. The effect of genetic drift on the variance/covariance components generated by multilocus additive x additive epistatic systems.

    PubMed

    López-Fanjul, Carlos; Fernández, Almudena; Toro, Miguel A

    2006-03-21

    The effect of population bottlenecks on the components of the genetic variance/covariance generated by n neutral independent additive x additive loci has been studied theoretically. In its simplest version, this situation can be modelled by specifying the allele frequencies and homozygous effects at each locus, and an additional factor measuring the strength of the n-th order epistatic interaction. The variance/covariance components in an infinitely large panmictic population (ancestral components) were compared with their expected values at equilibrium over replicates randomly derived from the base population, after t bottlenecks of size N (derived components). Formulae were obtained giving the derived components (and the between-line variance) as functions of the ancestral ones (alternatively, in terms of allele frequencies and effects) and the corresponding inbreeding coefficient F(t). The n-th order derived component of the genetic variance/covariance is continuously eroded by inbreeding, but the remaining components may increase initially until a critical F(t) value is attained, which is inversely related to the order of the pertinent component, and subsequently decline to zero. These changes can be assigned to the between-line variances/covariances of gene substitution and epistatic effects induced by drift. Numerical examples indicate that: (1) the derived additive variance/covariance component will generally exceed its ancestral value unless epistasis is weak; (2) the derived epistatic variance/covariance components will generally exceed their ancestral values unless allele frequencies are extreme; (3) for systems showing equal ancestral additive and total non-additive variance/covariance components, those including a smaller number of epistatic loci may generate a larger excess in additive variance/covariance after bottlenecks than others involving a larger number of loci, provided that F(t) is low. Our results indicate that it is unlikely that the rate of

  11. Effects of strains, strain crosses and environments on additive genetic and phenotypic variances in Drosophila melanogaster.

    PubMed

    Noor, R R; Barker, J S; Kinghorn, B P

    1993-01-12

    The stability of phenotypic, additive genetic and environmental variances of thorax length of Drosophila melanogaster in pure and synthetic strains was examined in two different environments. Two pure strains from different geographic locations (Melbourne and Townsville) were used, together with three synthetic populations formed from them. The existence of differences in thorax length between the Melbourne and Townsville populations, genotype by environment interaction, and heterosis in crosses between these populations indicate that they are genetically different. Thus geographic separation can cause differences in mean thorax length of flies from different populations. Both the difference in selection histories between the two localities and drift could lead to these differences. Up to the thirty fifth generation there was no evidence of any reduction in the difference between the Melbourne and Townsville populations, in either laboratory environment. The genetic differentiation of strains therefore may be maintained over many generations under new environmental conditions. The fluctuation over generations of heterosis of thorax length is possibly caused by the fluctuation of the rate of loss of favourable epistatic interaction in crossbred genotypes in combination with natural selection effects. V(p) was significantly higher in poor than in the good environment. This higher V(p) in the poor environment is most likly due to higher non additive genetic variance. V(p) was also significantly influenced by strain. In general, V(p) values of synthetic strains were higher than those of pure strains in both environments. Finally, the additive and environmental variances of thorax length were relatively stable across strains, generations and environments. ZUSAMMENFASSUNG: Wirkung von Herkünften, Kreuzungen und Umwelten auf additiv-genetische und phänotypische Varianzen in Drosophila melanogaster Die Stabilität phänotypischer, additiv-genetischer und umweltbedingter

  12. Estimation of variance components and genetic trends for twinning rate in Holstein dairy cattle of Iran.

    PubMed

    Ghavi Hossein-Zadeh, N; Nejati-Javaremi, A; Miraei-Ashtiani, S R; Kohram, H

    2009-07-01

    Calving records from the Animal Breeding Center of Iran, collected from January 1991 to December 2007 and comprising 1,163,594 Holstein calving events from 2,552 herds, were analyzed using a linear animal model, linear sire model, threshold animal model, and threshold sire model to estimate variance components, heritabilities, genetic correlations, and genetic trends for twinning rate in the first, second, and third parities. The overall twinning rate was 3.01%. Mean incidence of twins increased from first to fourth and later parities: 1.10, 3.20, 4.22, and 4.50%, respectively. For first-parity cows, a maximum frequency of twinning was observed from January through April (1.36%), and second- and third-parity cows showed peaks from July to September (at 3.35 and 4.55%, respectively). The phenotypic rate of twinning decreased from 1991 to 2007 for the first, second, and third parities. Sire predicted transmitting abilities were estimated using linear sire model and threshold sire model analyses. Sire transmitting abilities for twinning rate in the first, second, and third parities ranged from -0.30 to 0.42, -0.32 to 0.31, and -0.27 to 0.30, respectively. Heritability estimates of twinning rate for parities 1, 2, and 3 ranged from 1.66 to 10.6%, 1.35 to 9.0%, and 1.10 to 7.3%, respectively, using different models for analysis. Heritability estimates for twinning rate, obtained from the analysis of threshold models, were greater than the estimates of linear models. Solutions for age at calving for the first, second, and third parities demonstrated that cows older at calving were more likely to have twins. Genetic correlations for twinning rate between parities 2 and 3 were greater than correlations between parities 1 and 2 and between parities 1 and 3. There was a slightly increasing trend for twinning rate in parities 1, 2, and 3 over time with the analysis of linear animal and linear sire models, but the trend for twinning rate in parities 1, 2, and 3 with threshold

  13. Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis

    SciTech Connect

    Palmer, S.E. |; Dale, D.C.

    1996-12-30

    Cyclic hematopoiesis (CH, or cyclic neutropenia) is a rare disease manifested by transient severe neutropenia that recurs approximately every 21 days. The hematologic profile of families with the autosomal dominant form (ADCH) has not been well characterized, and it is unknown if the phenotype is distinct from the more common sporadic congenital or acquired forms of CH. We studied nine ADCH families whose children displayed typical CH blood patterns. Pedigrees confirmed dominant inheritance without evidence of heterogeneity or decreased penetrance; three pedigrees suggested new mutations. Families were Caucasian with exception of one with a Cherokee Native American founder. A wide spectrum of symptom severity, ranging from asymptomatic to life-threatening illness, was observed within families. The phenotype changed with age. Children displayed typical neutrophil cycles with symptoms of mucosal ulceration, lymphadenopathy, and infections. Adults often had fewer and milder symptoms, sometimes accompanied by mild chronic neutropenia without distinct cycles. While CH is commonly described as {open_quotes}benign{close_quotes}, four children in three of the nine families died of Clostridium or E. coli colitis, documenting the need for urgent evaluation of abdominal pain. Misdiagnosis with other neutropenias was common but can be avoided by serial blood counts in index cases. Genetic counseling requires specific histories and complete blood counts in relatives at risk to assess status regardless of symptoms, especially to determine individuals with new mutations. We propose diagnostic criteria for ADCH in affected children and adults. Recombinant human granulocyte colony-stimulating factor treatment resulted in dramatic improvement of neutropenia and morbidity. The differential diagnosis from other forms of familial neutropenia is reviewed. 45 refs., 4 figs., 1 tab.

  14. High-dimensional variance partitioning reveals the modular genetic basis of adaptive divergence in gene expression during reproductive character displacement.

    PubMed

    McGraw, Elizabeth A; Ye, Yixin H; Foley, Brad; Chenoweth, Stephen F; Higgie, Megan; Hine, Emma; Blows, Mark W

    2011-11-01

    Although adaptive change is usually associated with complex changes in phenotype, few genetic investigations have been conducted on adaptations that involve sets of high-dimensional traits. Microarrays have supplied high-dimensional descriptions of gene expression, and phenotypic change resulting from adaptation often results in large-scale changes in gene expression. We demonstrate how genetic analysis of large-scale changes in gene expression generated during adaptation can be accomplished by determining high-dimensional variance partitioning within classical genetic experimental designs. A microarray experiment conducted on a panel of recombinant inbred lines (RILs) generated from two populations of Drosophila serrata that have diverged in response to natural selection, revealed genetic divergence in 10.6% of 3762 gene products examined. Over 97% of the genetic divergence in transcript abundance was explained by only 12 genetic modules. The two most important modules, explaining 50% of the genetic variance in transcript abundance, were genetically correlated with the morphological traits that are known to be under selection. The expression of three candidate genes from these two important genetic modules was assessed in an independent experiment using qRT-PCR on 430 individuals from the panel of RILs, and confirmed the genetic association between transcript abundance and morphological traits under selection.

  15. Genetics Home Reference: autosomal dominant congenital stationary night blindness

    MedlinePlus

    ... stationary night blindness autosomal dominant congenital stationary night blindness Printable PDF Open All Close All Enable Javascript ... collapse boxes. Description Autosomal dominant congenital stationary night blindness is a disorder of the retina , which is ...

  16. Autosomal dominant polycystic kidney disease: clinical and genetic aspects.

    PubMed

    Sessa, A; Ghiggeri, G M; Turco, A E

    1997-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease caused by at least three different genes. The renal and extrarenal clinical manifestations, and the systemic complications due to cystic and non-cystic abnormalities in ADPKD patients have been widely investigated. Cellular and molecular aspects of cystogenetic mechanisms concern epithelial tubular cell proliferation, remodelling of extracellular matrix, fluid secretion and accumulation, and relations between cell proliferation and apoptosis. In vitro studies on cystogenesis suggest a key role of cell-to-cell or cell-to-matrix interactions. Surface proteins mediating cell-to-cell contact, such as E-cadherin (polycystin?), integrin interactions, growth factors, receptor expression, are involved in the process of differentiation of the cellular condition and of the extracellular matrix. Blocking any one of these complex mechanisms should influence the orientation and polarization of epithelial tubular cells and should mediate the inversion of fluid secretion which ends in renal cystogenesis. ADPKD comprises at least three phenotypically indistinguishable but genetically distinct entities, caused by mutations in three autosomal genes: PKD1 (chromosome 16p13.3) is present in about 85% of patients; PKD2 (chromosome 4q13q23) in 10%; PKD3 (unknown chromosome) in a few families. PCR-based mutation detection methods, automated DNA sequencing, and other "functional" methods are used to screen and analyse ADPKD patients. It is not yet known whether the mutations identified so far in PKD1 and PKD2 inactivate the genes or generate an aberrant product. The products of PKD1 and PKD2 genes have been called polycystin 1 and 2. Polycystins are members of a family of interactive proteins involved in complex adhesive cell-cell, cell-matrix, protein-protein, and protein-carbohydrate interactions in the extracellular compartment, and are involved in the same pathway (ion channel regulator? ion channel

  17. Late-acting dominant lethal genetic systems and mosquito control

    PubMed Central

    Phuc, Hoang Kim; Andreasen, Morten H; Burton, Rosemary S; Vass, Céline; Epton, Matthew J; Pape, Gavin; Fu, Guoliang; Condon, Kirsty C; Scaife, Sarah; Donnelly, Christl A; Coleman, Paul G; White-Cooper, Helen; Alphey, Luke

    2007-01-01

    Background Reduction or elimination of vector populations will tend to reduce or eliminate transmission of vector-borne diseases. One potential method for environmentally-friendly, species-specific population control is the Sterile Insect Technique (SIT). SIT has not been widely used against insect disease vectors such as mosquitoes, in part because of various practical difficulties in rearing, sterilization and distribution. Additionally, vector populations with strong density-dependent effects will tend to be resistant to SIT-based control as the population-reducing effect of induced sterility will tend to be offset by reduced density-dependent mortality. Results We investigated by mathematical modeling the effect of manipulating the stage of development at which death occurs (lethal phase) in an SIT program against a density-dependence-limited insect population. We found late-acting lethality to be considerably more effective than early-acting lethality. No such strains of a vector insect have been described, so as a proof-of-principle we constructed a strain of the principal vector of the dengue and yellow fever viruses, Aedes (Stegomyia) aegypti, with the necessary properties of dominant, repressible, highly penetrant, late-acting lethality. Conclusion Conventional SIT induces early-acting (embryonic) lethality, but genetic methods potentially allow the lethal phase to be tailored to the program. For insects with strong density-dependence, we show that lethality after the density-dependent phase would be a considerable improvement over conventional methods. For density-dependent parameters estimated from field data for Aedes aegypti, the critical release ratio for population elimination is modeled to be 27% to 540% greater for early-acting rather than late-acting lethality. Our success in developing a mosquito strain with the key features that the modeling indicated were desirable demonstrates the feasibility of this approach for improved SIT for disease

  18. Late-acting dominant lethal genetic systems and mosquito control.

    PubMed

    Phuc, Hoang Kim; Andreasen, Morten H; Burton, Rosemary S; Vass, Céline; Epton, Matthew J; Pape, Gavin; Fu, Guoliang; Condon, Kirsty C; Scaife, Sarah; Donnelly, Christl A; Coleman, Paul G; White-Cooper, Helen; Alphey, Luke

    2007-03-20

    Reduction or elimination of vector populations will tend to reduce or eliminate transmission of vector-borne diseases. One potential method for environmentally-friendly, species-specific population control is the Sterile Insect Technique (SIT). SIT has not been widely used against insect disease vectors such as mosquitoes, in part because of various practical difficulties in rearing, sterilization and distribution. Additionally, vector populations with strong density-dependent effects will tend to be resistant to SIT-based control as the population-reducing effect of induced sterility will tend to be offset by reduced density-dependent mortality. We investigated by mathematical modeling the effect of manipulating the stage of development at which death occurs (lethal phase) in an SIT program against a density-dependence-limited insect population. We found late-acting lethality to be considerably more effective than early-acting lethality. No such strains of a vector insect have been described, so as a proof-of-principle we constructed a strain of the principal vector of the dengue and yellow fever viruses, Aedes (Stegomyia) aegypti, with the necessary properties of dominant, repressible, highly penetrant, late-acting lethality. Conventional SIT induces early-acting (embryonic) lethality, but genetic methods potentially allow the lethal phase to be tailored to the program. For insects with strong density-dependence, we show that lethality after the density-dependent phase would be a considerable improvement over conventional methods. For density-dependent parameters estimated from field data for Aedes aegypti, the critical release ratio for population elimination is modeled to be 27% to 540% greater for early-acting rather than late-acting lethality. Our success in developing a mosquito strain with the key features that the modeling indicated were desirable demonstrates the feasibility of this approach for improved SIT for disease control.

  19. Small Variance in Growth Rate in Annual Plants has Large Effects on Genetic Drift

    USDA-ARS?s Scientific Manuscript database

    When plant size is strongly correlated with plant reproduction, variance in growth rates results in a lognormal distribution of seed production within a population. Fecundity variance affects effective population size (Ne), which reflects the ability of a population to maintain beneficial mutations ...

  20. Genetics Home Reference: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions CADASIL cerebral autosomal dominant arteriopathy ...

  1. Knowledge extraction algorithm for variances handling of CP using integrated hybrid genetic double multi-group cooperative PSO and DPSO.

    PubMed

    Du, Gang; Jiang, Zhibin; Diao, Xiaodi; Yao, Yang

    2012-04-01

    Although the clinical pathway (CP) predefines predictable standardized care process for a particular diagnosis or procedure, many variances may still unavoidably occur. Some key index parameters have strong relationship with variances handling measures of CP. In real world, these problems are highly nonlinear in nature so that it's hard to develop a comprehensive mathematic model. In this paper, a rule extraction approach based on combing hybrid genetic double multi-group cooperative particle swarm optimization algorithm (PSO) and discrete PSO algorithm (named HGDMCPSO/DPSO) is developed to discovery the previously unknown and potentially complicated nonlinear relationship between key parameters and variances handling measures of CP. Then these extracted rules can provide abnormal variances handling warning for medical professionals. Three numerical experiments on Iris of UCI data sets, Wisconsin breast cancer data sets and CP variances data sets of osteosarcoma preoperative chemotherapy are used to validate the proposed method. When compared with the previous researches, the proposed rule extraction algorithm can obtain the high prediction accuracy, less computing time, more stability and easily comprehended by users, thus it is an effective knowledge extraction tool for CP variances handling.

  2. Estimates of (co)variance components and genetic parameters for growth traits in Sirohi goat.

    PubMed

    Gowane, Gopal R; Chopra, Ashish; Prakash, Ved; Arora, A L

    2011-01-01

    Data were collected over a period of 21 years (1988-2008) to estimate (co)variance components for birth weight (BWT), weaning weight (WWT), 6-month weight (6WT), 9-month weight (9WT), 12-month weight (12WT), average daily gain from birth to weaning (ADG1), weaning to 6WT (ADG2), and from 6WT to 12WT (ADG3) in Sirohi goats maintained at the Central Sheep and Wool Research Institute, Avikanagar, Rajasthan, India. Analyses were carried out by restricted maximum likelihood, fitting six animal models with various combinations of direct and maternal effects. The best model was chosen after testing the improvement of the log-likelihood values. Heritability estimates for BWT, WWT, 6WT, 9WT, 12WT, ADG1, ADG2, and ADG3 were 0.39 ± 0.05, 0.09 ± 0.03, 0.06 ± 0.02, 0.09 ± 0.03, 0.11 ± 0.03, 0.10 ± 0.3, 0.04 ± 0.02, and 0.01 ± 0.01, respectively. For BWT and ADG1, only direct effects were significant. Estimate of maternal permanent environmental effect were important for body weights from weaning to 12WT and also for ADG2 and ADG3. However, direct maternal effects were not significant throughout. Estimate of c (2) were 0.06 ± 0.02, 0.03 ± 0.02, 0.06 ± 0.02, 0.05 ± 0.02, 0.02 ± 0.02, and 0.02 ± 0.02 for 3WT, 6WT, 9WT, 12WT, ADG2, and ADG3, respectively. The estimated repeatabilities across years of ewe effects on kid body weights were 0.10, 0.08, 0.05, 0.08, and 0.08 at birth, weaning, 6, 9, and 12 months of age, respectively. Results suggest possibility of modest rate of genetic progress for body weight traits and ADG1 through selection, whereas only slow progress will be possible for post-weaning gain. Genetic and phenotypic correlations between body weight traits were high and positive. High genetic correlation between 6WT and 9WT suggests that selection of animals at 6 months can be carried out instead of present practice of selection at 9 months.

  3. Age-specific patterns of genetic variance in Drosophila melanogaster. II. Fecundity and its genetic covariance with age-specific mortality

    SciTech Connect

    Tatar, M.; Promislow, D.E.L.; Khazaeli, A.A.; Curtsinger, J.W.

    1996-06-01

    Under the mutation accumulation model of senescence, it was predicted that the additive genetic variance (V{sub A}) for fitness traits will increase with age. We measured age-specific mortality and fecundity from 65,134 Drosophila melanogaster and estimated genetic variance components, based on reciprocal crosses of extracted second chromosome lines. Elsewhere we report the results for mortality. Here, for fecundity, we report a biomodal pattern for V{sub A} with peaks at 3 days and at 17-31 days. Under the antagonistic pleiotropy model of senescence, it was predicted that negative correlations will exist between early and late life history traits. For fecundity itself we find positive genetic correlations among age classes >3 days but negative nonsignificant correlations between fecundity at 3 days and at older age classes. For fecundity vs. age-specific mortality, we find positive fitness correlations (negative genetic correlations) among the traits at all ages >3 days but a negative fitness correlation between fecundity at 3 days and mortality at the oldest ages (positive genetic correlations). For age-specific mortality itself we find overwhelmingly positive genetic correlations among all age classes. The data suggest that mutation accumulation may be a major source of standing genetic variance for senescence. 75 refs., 4 figs., 1 tab.

  4. Role of inbreeding depression, non-inbred dominance deviations and random year-season effect in genetic trends for prolificacy in closed rabbit lines.

    PubMed

    Fernández, E N; Sánchez, J P; Martínez, R; Legarra, A; Baselga, M

    2017-07-06

    In closed rabbit lines selected for prolificacy at the Polytechnic University of Valencia, genetic responses are predicted using BLUP. With a standard additive BLUP model and year-season (YS) effects fitted as fixed, genetic trends were overestimated compared to responses estimated using control populations obtained from frozen embryos. In these lines, there is a confounding between genetic trend, YS effects and inbreeding, and the role of dominance is uncertain. This is a common situation in data from reproductively closed selection lines. This paper fits different genetic evaluation models to data of these lines, aiming to identify the source of these biases: dominance, inbreeding depression and/or an ill-conditioned model due to the strong collinearity between YS, inbreeding and genetic trend. The study involved three maternal lines (A, V and H) and analysed two traits, total born (TB) and the number of kits at weaning (NW). Models fitting YS effect as fixed or random were implemented, in addition to additive genetic, permanent environment effects and non-inbred dominance deviations effects. When YS was fitted as a fixed effect, the genetic trends were overestimated compared to control populations, inbreeding had an apparent positive effect on litter size and the environmental trends were negative. When YS was fitted as random, the genetic trends were compatible with control populations results, inbreeding had a negative effect (lower prolificacy) and environmental trends were flat. The model fitting random YS, inbreeding and non-inbred dominance deviations yielded the following ratios of additive and dominance variances to total variance for NW: 0.06 and 0.01 for line A, 0.06 and 0.00 for line V and 0.01 and 0.08 for line H. Except for line H, dominance deviations seem to be of low relevance. When it is confounded with inbreeding as in these lines, fitting YS effect as random allows correct estimation of genetic trends. © 2017 Blackwell Verlag GmbH.

  5. Genetics Home Reference: autosomal dominant leukodystrophy with autonomic disease

    MedlinePlus

    ... need a cane, walker, or wheelchair for assistance. Intelligence is usually unaffected; however, people who have had ... Hobson G, Brusco A, Brussino A, Padiath QS. Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides ...

  6. Genetic (co)variance of rainbow trout (Oncorhynchus mykiss) body weight and its uniformity across production environments.

    PubMed

    Sae-Lim, Panya; Kause, Antti; Janhunen, Matti; Vehviläinen, Harri; Koskinen, Heikki; Gjerde, Bjarne; Lillehammer, Marie; Mulder, Han A

    2015-05-19

    When rainbow trout from a single breeding program are introduced into various production environments, genotype-by-environment (GxE) interaction may occur. Although growth and its uniformity are two of the most important traits for trout producers worldwide, GxE interaction on uniformity of growth has not been studied. Our objectives were to quantify the genetic variance in body weight (BW) and its uniformity and the genetic correlation (rg) between these traits, and to investigate the degree of GxE interaction on uniformity of BW in breeding (BE) and production (PE) environments using double hierarchical generalized linear models. Log-transformed data were also used to investigate whether the genetic variance in uniformity of BW, GxE interaction on uniformity of BW, and rg between BW and its uniformity were influenced by a scale effect. Although heritability estimates for uniformity of BW were low and of similar magnitude in BE (0.014) and PE (0.012), the corresponding coefficients of genetic variation reached 19 and 21%, which indicated a high potential for response to selection. The genetic re-ranking for uniformity of BW (rg = 0.56) between BE and PE was moderate but greater after log-transformation, as expressed by the low rg (-0.08) between uniformity in BE and PE, which indicated independent genetic rankings for uniformity in the two environments when the scale effect was accounted for. The rg between BW and its uniformity were 0.30 for BE and 0.79 for PE but with log-transformed BW, these values switched to -0.83 and -0.62, respectively. Genetic variance exists for uniformity of BW in both environments but its low heritability implies that a large number of relatives are needed to reach even moderate accuracy of selection. GxE interaction on uniformity is present for both environments and sib-testing in PE is recommended when the aim is to improve uniformity across environments. Positive and negative rg between BW and its uniformity estimated with original

  7. 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.

  8. 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 Central

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

    2014-01-01

    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. PMID:24724612

  9. The Dominance Concept Inventory: A Tool for Assessing Undergraduate Student Alternative Conceptions about Dominance in Mendelian and Population Genetics

    PubMed Central

    Perez, Kathryn E.; Price, Rebecca M.

    2014-01-01

    Despite the impact of genetics on daily life, biology undergraduates understand some key genetics concepts poorly. One concept requiring attention is dominance, which many students understand as a fixed property of an allele or trait and regularly conflate with frequency in a population or selective advantage. We present the Dominance Concept Inventory (DCI), an instrument to gather data on selected alternative conceptions about dominance. During development of the 16-item test, we used expert surveys (n = 12), student interviews (n = 42), and field tests (n = 1763) from introductory and advanced biology undergraduates at public and private, majority- and minority-serving, 2- and 4-yr institutions in the United States. In the final field test across all subject populations (n = 709), item difficulty ranged from 0.08 to 0.84 (0.51 ± 0.049 SEM), while item discrimination ranged from 0.11 to 0.82 (0.50 ± 0.048 SEM). Internal reliability (Cronbach's alpha) was 0.77, while test–retest reliability values were 0.74 (product moment correlation) and 0.77 (intraclass correlation). The prevalence of alternative conceptions in the field tests shows that introductory and advanced students retain confusion about dominance after instruction. All measures support the DCI as a useful instrument for measuring undergraduate biology student understanding and alternative conceptions about dominance. PMID:26086665

  10. The Dominance Concept Inventory: A Tool for Assessing Undergraduate Student Alternative Conceptions about Dominance in Mendelian and Population Genetics.

    PubMed

    Abraham, Joel K; Perez, Kathryn E; Price, Rebecca M

    2014-01-01

    Despite the impact of genetics on daily life, biology undergraduates understand some key genetics concepts poorly. One concept requiring attention is dominance, which many students understand as a fixed property of an allele or trait and regularly conflate with frequency in a population or selective advantage. We present the Dominance Concept Inventory (DCI), an instrument to gather data on selected alternative conceptions about dominance. During development of the 16-item test, we used expert surveys (n = 12), student interviews (n = 42), and field tests (n = 1763) from introductory and advanced biology undergraduates at public and private, majority- and minority-serving, 2- and 4-yr institutions in the United States. In the final field test across all subject populations (n = 709), item difficulty ranged from 0.08 to 0.84 (0.51 ± 0.049 SEM), while item discrimination ranged from 0.11 to 0.82 (0.50 ± 0.048 SEM). Internal reliability (Cronbach's alpha) was 0.77, while test-retest reliability values were 0.74 (product moment correlation) and 0.77 (intraclass correlation). The prevalence of alternative conceptions in the field tests shows that introductory and advanced students retain confusion about dominance after instruction. All measures support the DCI as a useful instrument for measuring undergraduate biology student understanding and alternative conceptions about dominance.

  11. Speeding Up Microevolution: The Effects of Increasing Temperature on Selection and Genetic Variance in a Wild Bird Population

    PubMed Central

    Husby, Arild; Visser, Marcel E.; Kruuk, Loeske E. B.

    2011-01-01

    The amount of genetic variance underlying a phenotypic trait and the strength of selection acting on that trait are two key parameters that determine any evolutionary response to selection. Despite substantial evidence that, in natural populations, both parameters may vary across environmental conditions, very little is known about the extent to which they may covary in response to environmental heterogeneity. Here we show that, in a wild population of great tits (Parus major), the strength of the directional selection gradients on timing of breeding increased with increasing spring temperatures, and that genotype-by-environment interactions also predicted an increase in additive genetic variance, and heritability, of timing of breeding with increasing spring temperature. Consequently, we therefore tested for an association between the annual selection gradients and levels of additive genetic variance expressed each year; this association was positive, but non-significant. However, there was a significant positive association between the annual selection differentials and the corresponding heritability. Such associations could potentially speed up the rate of micro-evolution and offer a largely ignored mechanism by which natural populations may adapt to environmental changes. PMID:21408101

  12. Good Genes and Sexual Selection in Dung Beetles (Onthophagus taurus): Genetic Variance in Egg-to-Adult and Adult Viability

    PubMed Central

    Garcia-Gonzalez, Francisco; Simmons, Leigh W.

    2011-01-01

    Whether species exhibit significant heritable variation in fitness is central for sexual selection. According to good genes models there must be genetic variation in males leading to variation in offspring fitness if females are to obtain genetic benefits from exercising mate preferences, or by mating multiply. However, sexual selection based on genetic benefits is controversial, and there is limited unambiguous support for the notion that choosy or polyandrous females can increase the chances of producing offspring with high viability. Here we examine the levels of additive genetic variance in two fitness components in the dung beetle Onthophagus taurus. We found significant sire effects on egg-to-adult viability and on son, but not daughter, survival to sexual maturity, as well as moderate coefficients of additive variance in these traits. Moreover, we do not find evidence for sexual antagonism influencing genetic variation for fitness. Our results are consistent with good genes sexual selection, and suggest that both pre- and postcopulatory mate choice, and male competition could provide indirect benefits to females. PMID:21267411

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

    PubMed Central

    Hallsson, Lára R; Björklund, Mats

    2012-01-01

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

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

    PubMed

    Hallsson, Lára R; Björklund, Mats

    2012-01-01

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

  15. Power graph compression reveals dominant relationships in genetic transcription networks.

    PubMed

    Ahnert, Sebastian E

    2013-11-01

    We introduce a framework for the discovery of dominant relationship patterns in transcription networks, by compressing the network into a power graph with overlapping power nodes. Our application of this approach to the transcription networks of S. cerevisiae and E. coli, paired with GO term enrichment analysis, provides a highly informative overview of the most prominent relationships in the gene regulatory networks of these two organisms.

  16. Stability of genetic variance and covariance for reproductive characters in the face of climate change in a wild bird population.

    PubMed

    Garant, Dany; Hadfield, Jarrod D; Kruuk, Loeske E B; Sheldon, Ben C

    2008-01-01

    Global warming has had numerous effects on populations of animals and plants, with many species in temperate regions experiencing environmental change at unprecedented rates. Populations with low potential for adaptive evolutionary change and plasticity will have little chance of persistence in the face of environmental change. Assessment of the potential for adaptive evolution requires the estimation of quantitative genetic parameters, but it is as yet unclear what impact, if any, global warming will have on the expression of genetic variances and covariances. Here we assess the impact of a changing climate on the genetic architecture underlying three reproductive traits in a wild bird population. We use a large, long-term, data set collected on great tits (Parus major) in Wytham Woods, Oxford, and an 'animal model' approach to quantify the heritability of, and genetic correlations among, laying date, clutch size and egg mass during two periods with contrasting temperature conditions over a 40-year period (1965-1988 [cooler] vs. 1989-2004 [warmer]). We found significant additive genetic variance and heritability for all traits under both temperature regimes. We also found significant negative genetic covariances and correlations between clutch size and egg weight during both periods, and among laying date and clutch size in the colder years only. The overall G matrix comparison among periods, however, showed only a minor difference among periods, thus suggesting that genotype by environment interactions are negligible in this context. Our results therefore suggest that despite substantial changes in temperature and in mean laying date phenotype over the last decades, and despite the large sample sizes available, we are unable to detect any significant change in the genetic architecture of the reproductive traits studied.

  17. Additive genetic variance of quantitative traits in natural and pond-bred populations of the Lake Tanganyika cichlid Tropheus moorii.

    PubMed

    Koch, Martin; Wilson, Alastair J; Kerschbaumer, Michaela; Wiedl, Thomas; Sturmbauer, Christian

    Quantitative genetic studies in natural populations are of growing interest to speciation research since divergence is often believed to arise through micro-evolutionary change, caused by natural selection on functional morphological traits. The species flock of cichlid fishes in Africa's oldest lake, Lake Tanganyika, offers a rare opportunity to study this process. Using the cichlid species Tropheus moorii, we assessed the potential for microevolution in a set of morphological traits by estimating their quantitative genetic basis of variation. Two approaches were employed: (1) estimation of trait heritabilities (h(2)) in situ from a sample of wild caught fish, and (2) estimation of h(2) from first generation offspring produced in a semi-natural breeding experiment. In both cases, microsatellite data were used to infer pedigree structure among the sampled individuals and estimates of h(2) were made using an animal model approach. Although power was limited by the pedigree structures estimated (particularly in the wild caught sample), we nonetheless demonstrate the presence of significant additive genetic variance for aspects of morphology that, in the cichlid species Tropheus moorii, are expected to be functionally and ecologically important, and therefore likely targets of natural selection. We hypothesize that traits showing significant additive genetic variance, such as the mouth position have most likely played a key role in the adaptive evolution of the cichlid fish Tropheus moorii.

  18. Pedigree-based estimation of covariance between dominance deviations and additive genetic effects in closed rabbit lines considering inbreeding and using a computationally simpler equivalent model.

    PubMed

    Fernández, E N; Legarra, A; Martínez, R; Sánchez, J P; Baselga, M

    2017-06-01

    Inbreeding generates covariances between additive and dominance effects (breeding values and dominance deviations). In this work, we developed and applied models for estimation of dominance and additive genetic variances and their covariance, a model that we call "full dominance," from pedigree and phenotypic data. Estimates with this model such as presented here are very scarce both in livestock and in wild genetics. First, we estimated pedigree-based condensed probabilities of identity using recursion. Second, we developed an equivalent linear model in which variance components can be estimated using closed-form algorithms such as REML or Gibbs sampling and existing software. Third, we present a new method to refer the estimated variance components to meaningful parameters in a particular population, i.e., final partially inbred generations as opposed to outbred base populations. We applied these developments to three closed rabbit lines (A, V and H) selected for number of weaned at the Polytechnic University of Valencia. Pedigree and phenotypes are complete and span 43, 39 and 14 generations, respectively. Estimates of broad-sense heritability are 0.07, 0.07 and 0.05 at the base versus 0.07, 0.07 and 0.09 in the final generations. Narrow-sense heritability estimates are 0.06, 0.06 and 0.02 at the base versus 0.04, 0.04 and 0.01 at the final generations. There is also a reduction in the genotypic variance due to the negative additive-dominance correlation. Thus, the contribution of dominance variation is fairly large and increases with inbreeding and (over)compensates for the loss in additive variation. In addition, estimates of the additive-dominance correlation are -0.37, -0.31 and 0.00, in agreement with the few published estimates and theoretical considerations. © 2017 Blackwell Verlag GmbH.

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  20. Who’s Afraid of Math? Two Sources of Genetic Variance for Mathematical Anxiety

    PubMed Central

    Wang, Zhe; Hart, Sara Ann; Kovas, Yulia; Lukowski, Sarah; Soden, Brooke; Thompson, Lee A.; Plomin, Robert; McLoughlin, Grainne; Bartlett, Christopher W.; Lyons, Ian M.; Petrill, Stephen A.

    2015-01-01

    Background Emerging work suggests that academic achievement may be influenced by the management of affect as well as through efficient information processing of task demands. In particular, mathematical anxiety has attracted recent attention because of its damaging psychological effects and potential associations with mathematical problem-solving and achievement. The present study investigated the genetic and environmental factors contributing to the observed differences in the anxiety people feel when confronted with mathematical tasks. In addition, the genetic and environmental mechanisms that link mathematical anxiety with math cognition and general anxiety were also explored. Methods Univariate and multivariate quantitative genetic models were conducted in a sample of 514 12-year-old twin siblings. Results Genetic factors accounted for roughly 40% of the variation in mathematical anxiety, with the remaining being accounted for by child-specific environmental factors. Multivariate genetic analyses suggested that mathematical anxiety was influenced by the genetic and non-familial environmental risk factors associated with general anxiety and additional independent genetic influences associated with math-based problem solving. Conclusions The development of mathematical anxiety may involve not only exposure to negative experiences with mathematics, but also likely involves genetic risks related to both anxiety and math cognition. These results suggest that integrating cognitive and affective domains may be particularly important for mathematics, and may extend to other areas of academic achievement. PMID:24611799

  1. Who is afraid of math? Two sources of genetic variance for mathematical anxiety.

    PubMed

    Wang, Zhe; Hart, Sara Ann; Kovas, Yulia; Lukowski, Sarah; Soden, Brooke; Thompson, Lee A; Plomin, Robert; McLoughlin, Grainne; Bartlett, Christopher W; Lyons, Ian M; Petrill, Stephen A

    2014-09-01

    Emerging work suggests that academic achievement may be influenced by the management of affect as well as through efficient information processing of task demands. In particular, mathematical anxiety has attracted recent attention because of its damaging psychological effects and potential associations with mathematical problem solving and achievement. This study investigated the genetic and environmental factors contributing to the observed differences in the anxiety people feel when confronted with mathematical tasks. In addition, the genetic and environmental mechanisms that link mathematical anxiety with math cognition and general anxiety were also explored. Univariate and multivariate quantitative genetic models were conducted in a sample of 514 12-year-old twin siblings. Genetic factors accounted for roughly 40% of the variation in mathematical anxiety, with the remaining being accounted for by child-specific environmental factors. Multivariate genetic analyses suggested that mathematical anxiety was influenced by the genetic and nonfamilial environmental risk factors associated with general anxiety and additional independent genetic influences associated with math-based problem solving. The development of mathematical anxiety may involve not only exposure to negative experiences with mathematics, but also likely involves genetic risks related to both anxiety and math cognition. These results suggest that integrating cognitive and affective domains may be particularly important for mathematics and may extend to other areas of academic achievement. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

  2. Genetic Model Fitting in IQ, Assortative Mating & Components of IQ Variance.

    ERIC Educational Resources Information Center

    Capron, Christiane; Vetta, Adrian R.; Vetta, Atam

    1998-01-01

    The biometrical school of scientists who fit models to IQ data traces their intellectual ancestry to R. Fisher (1918), but their genetic models have no predictive value. Fisher himself was critical of the concept of heritability, because assortative mating, such as for IQ, introduces complexities into the study of a genetic trait. (SLD)

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  4. Accuracy of whole-genome prediction using a genetic architecture-enhanced variance-covariance matrix.

    PubMed

    Zhang, Zhe; Erbe, Malena; He, Jinlong; Ober, Ulrike; Gao, Ning; Zhang, Hao; Simianer, Henner; Li, Jiaqi

    2015-02-09

    Obtaining accurate predictions of unobserved genetic or phenotypic values for complex traits in animal, plant, and human populations is possible through whole-genome prediction (WGP), a combined analysis of genotypic and phenotypic data. Because the underlying genetic architecture of the trait of interest is an important factor affecting model selection, we propose a new strategy, termed BLUP|GA (BLUP-given genetic architecture), which can use genetic architecture information within the dataset at hand rather than from public sources. This is achieved by using a trait-specific covariance matrix ( T: ), which is a weighted sum of a genetic architecture part ( S: matrix) and the realized relationship matrix ( G: ). The algorithm of BLUP|GA (BLUP-given genetic architecture) is provided and illustrated with real and simulated datasets. Predictive ability of BLUP|GA was validated with three model traits in a dairy cattle dataset and 11 traits in three public datasets with a variety of genetic architectures and compared with GBLUP and other approaches. Results show that BLUP|GA outperformed GBLUP in 20 of 21 scenarios in the dairy cattle dataset and outperformed GBLUP, BayesA, and BayesB in 12 of 13 traits in the analyzed public datasets. Further analyses showed that the difference of accuracies for BLUP|GA and GBLUP significantly correlate with the distance between the T: and G: matrices. The new strategy applied in BLUP|GA is a favorable and flexible alternative to the standard GBLUP model, allowing to account for the genetic architecture of the quantitative trait under consideration when necessary. This feature is mainly due to the increased similarity between the trait-specific relationship matrix ( T: matrix) and the genetic relationship matrix at unobserved causal loci. Applying BLUP|GA in WGP would ease the burden of model selection. Copyright © 2015 Zhang et al.

  5. Direct and maternal (co)variance components, genetic parameters, and annual trends for growth traits of Makooei sheep in Iran.

    PubMed

    Mohammadi, Hossein; Shahrebabak, Mohammad Moradi; Vatankhah, Mahmood; Shahrebabak, Hossein Moradi

    2013-01-01

    Genetic parameters and genetic trends for birth weight (BW), weaning weight (WW), 6-month weight (6MW), and yearling weight (YW) traits were estimated by using records of 5,634 Makooei lambs, descendants of 289 sires and 1,726 dams, born between 1996 and 2009 at the Makooei sheep breeding station, West Azerbaijan, Iran. The (co)variance components were estimated with different animal models using a restricted maximum likelihood procedure and the most appropriate model for each trait was determined by Akaike's Information Criterion. Breeding values of animals were predicted with best linear unbiased prediction methodology under multi-trait animal models and genetic trends were estimated by regression mean breeding values on birth year. The most appropriate model for BW was a model including direct and maternal genetic effects, regardless of their covariance. The model for WW and 6MW included direct additive genetic effects. The model for YW included direct genetic effects only. Direct heritabilities based on the best model were estimated 0.15 ± 0.04, 0.16 ± 0.03, 0.21 ± 0.04, and 0.22 ± 0.06 for BW, WW, 6MW, and YW, respectively, and maternal heritability obtained 0.08 ± 0.02 for BW. Genetic correlations among the traits were positive and varied from 0.28 for BW-YW to 0.66 for BW-WW and phenotypic correlations were generally lower than the genetic correlations. Genetic trends were 8.1 ± 2, 67.4 ± 5, 38.7 ± 4, and 47.6 ± 6 g per year for BW, WW, 6MW, and YW, respectively.

  6. Variance in estimated pairwise genetic distance under high versus low coverage sequencing: The contribution of linkage disequilibrium.

    PubMed

    Shpak, Max; Ni, Yang; Lu, Jie; Müller, Peter

    2017-10-01

    The mean pairwise genetic distance among haplotypes is an estimator of the population mutation rate θ and a standard measure of variation in a population. With the advent of next-generation sequencing (NGS) methods, this and other population parameters can be estimated under different modes of sampling. One approach is to sequence individual genomes with high coverage, and to calculate genetic distance over all sample pairs. The second approach, typically used for microbial samples or for tumor cells, is sequencing a large number of pooled genomes with very low individual coverage. With low coverage, pairwise genetic distances are calculated across independently sampled sites rather than across individual genomes. In this study, we show that the variance in genetic distance estimates is reduced with low coverage sampling if the mean pairwise linkage disequilibrium weighted by allele frequencies is positive. Practically, this means that if on average the most frequent alleles over pairs of loci are in positive linkage disequilibrium, low coverage sequencing results in improved estimates of θ, assuming similar per-site read depths. We show that this result holds under the expected distribution of allele frequencies and linkage disequilibria for an infinite sites model at mutation-drift equilibrium. From simulations, we find that the conditions for reduced variance only fail to hold in cases where variant alleles are few and at very low frequency. These results are applied to haplotype frequencies from a lung cancer tumor to compute the weighted linkage disequilibria and the expected error in estimated genetic distance using high versus low coverage. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. (Co)variance components, genetic parameters and annual trends for calf weights in a Brahman herd kept on floodable savanna.

    PubMed

    Plasse, Dieter; Verde, Omar; Arango, Jesús; Camaripano, Luis; Fossi, Hugo; Romero, Rafael; Rodriguez, Carlos M; Rumbos, José L

    2002-12-31

    (Co)variance components and genetic parameters were estimated for body weights of an elite Brahman herd under a designed, supervised management and genetic program, including strategic artificial insemination (AI). Restricted maximum likelihood methods were used with a univariate animal model for birth weight (BW) and a bivariate model for weaning weight (205-day weight, 205W) and 18-month weight (548-day weight, 548W). Models included random animal direct and maternal genetic effects, maternal permanent environmental effect (c2), and sex-year-month of birth-age of dam and genetic group (identified and unidentified paternity), as fixed effects. Analysis A1 included all calves and analysis A2 included only those with identified sires. Of the 8,066 calves born, 36% were progeny of AI, 11% from single sire and 53% from multi-sire herds. They were born from 1985 to 1998, from 2559 dams and 146 sires (78 identified). Estimates of direct, maternal and total heritabilities from A1 for BW, 205W and 548W were: 0.23, 0.07 and 0.30; 0.08, 0.14 and 0.16; 0.16, 0.04 and 0.28, respectively. Corresponding estimates of direct maternal genetic correlations were 0.22, 0.07 and 0.86, and c2 estimates were 0.04, 0.14 and 0.04, respectively. Estimates of direct and maternal genetic, and permanent environmental correlations between 205W and 548W were: 0.66, 0.70 and 1.00. Variances and genetic parameters from A1 and A2 were, in general, very similar. Estimates of phenotypic, and direct and maternal genetic trends per year from A1 were: 0.393, 0.004 and 0.003 kg (BW), 3.367, 0.142 and 0.115 kg (205W), 1.813, 0.263 and 0.095 kg (548W). Estimates of direct and maternal genetic trends from A2 were: 0.033 and -0.002 kg (BW); 0.186 and 0.276 kg (205W); 0.471 and 0.136 kg (548W). The modern selection methods that have been used recently should be continued, with emphasis on the improvement of cow efficiency for sustainable beef production on floodable savanna combined with improved pasture.

  8. Artificial selection and maintenance of genetic variance in the global dairy cow population

    PubMed Central

    Brotherstone, S; Goddard, M

    2005-01-01

    Genetic improvement of dairy cows, which has increased the milk yield of cows in the UK by 1200 kg per lactation in 12 years, is an excellent example of the application of quantitative genetics to agriculture. The most important traits of dairy cattle are expressed only in females, but the main opportunity for selection is in males. Despite this, genetic improvement was achieved by the invention of a new statistical methodology, called ‘best linear unbiased prediction’ to estimate the breeding value of bulls. Intense selection of the best bulls, combined with the worldwide use of these bulls through artificial insemination and frozen semen, has created a global population and caused concern that the genetic variation available in the future will be reduced. Maintenance of genetic variation and long-term genetic gains would be aided by rational payment systems, use of crossbreeding where profitable, inclusion of all economically important traits in the breeding objective, recognition of genotype by environment interactions and the use of selection algorithms that balance estimated breeding value against the average relationship among the selected animals. Fortunately, all of these things are happening to some degree. PMID:16048790

  9. Artificial selection and maintenance of genetic variance in the global dairy cow population.

    PubMed

    Brotherstone, S; Goddard, M

    2005-07-29

    Genetic improvement of dairy cows, which has increased the milk yield of cows in the UK by 1200 kg per lactation in 12 years, is an excellent example of the application of quantitative genetics to agriculture. The most important traits of dairy cattle are expressed only in females, but the main opportunity for selection is in males. Despite this, genetic improvement was achieved by the invention of a new statistical methodology, called 'best linear unbiased prediction' to estimate the breeding value of bulls. Intense selection of the best bulls, combined with the worldwide use of these bulls through artificial insemination and frozen semen, has created a global population and caused concern that the genetic variation available in the future will be reduced. Maintenance of genetic variation and long-term genetic gains would be aided by rational payment systems, use of crossbreeding where profitable, inclusion of all economically important traits in the breeding objective, recognition of genotype by environment interactions and the use of selection algorithms that balance estimated breeding value against the average relationship among the selected animals. Fortunately, all of these things are happening to some degree.

  10. A variance components factor model for genetic association studies: a Bayesian analysis.

    PubMed

    Nonyane, B A S; Whittaker, J C

    2010-09-01

    Studies of gene-trait associations for complex diseases often involve multiple traits that may vary by genotype groups or patterns. Such traits are usually manifestations of lower-dimensional latent factors or disease syndromes. We illustrate the use of a variance components factor (VCF) model to model the association between multiple traits and genotype groups as well as any other existing patient-level covariates. This model characterizes the correlations between traits as underlying latent factors that can be used in clinical decision-making. We apply it within the Bayesian framework and provide a straightforward implementation using the WinBUGS software. The VCF model is illustrated with simulated data and an example that comprises changes in plasma lipid measurements of patients who were treated with statins to lower low-density lipoprotein cholesterol, and polymorphisms from the apolipoprotein-E gene. The simulation shows that this model clearly characterizes existing multiple trait manifestations across genotype groups where individuals' group assignments are fully observed or can be deduced from the observed data. It also allows one to investigate covariate by genotype group interactions that may explain the variability in the traits. The flexibility to characterize such multiple trait manifestations makes the VCF model more desirable than the univariate variance components model, which is applied to each trait separately. The Bayesian framework offers a flexible approach that allows one to incorporate prior information. (c) 2010 Wiley-Liss, Inc.

  11. Dominance, epistasis and the genetics of postzygotic isolation.

    PubMed Central

    Turelli, M; Orr, H A

    2000-01-01

    The sterility and inviability of species hybrids can be explained by between-locus "Dobzhansky-Muller" incompatibilities: alleles that are fit on their "normal" genetic backgrounds sometimes lower fitness when brought together in hybrids. We present a model of two-locus incompatibilities that distinguishes among three types of hybrid interactions: those between heterozygous loci (H(0)), those between a heterozygous and a homozygous (or hemizygous) locus (H(1)), and those between homozygous loci (H(2)). We predict the relative fitnesses of hybrid genotypes by calculating the expected numbers of each type of incompatibility. We use this model to study Haldane's rule and the large effect of X chromosomes on postzygotic isolation. We show that the severity of H(0) vs. H(1) incompatibilities is key to understanding Haldane's rule, while the severity of H(1) vs. H(2) incompatibilities must also be considered to explain large X effects. Large X effects are not inevitable in backcross analyses but rather-like Haldane's rule-may often reflect the recessivity of alleles causing postzygotic isolation. We also consider incompatibilities involving the Y (or W) chromosome and maternal effects. Such incompatibilities are common in Drosophila species crosses, and their consequences in male- vs. female-heterogametic taxa may explain the pattern of exceptions to Haldane's rule. PMID:10747061

  12. Estimation of the Proportion of Variation Accounted for by DNA Tests. I: Genetic Variance

    USDA-ARS?s Scientific Manuscript database

    The proportion of genetic variation accounted for (Rg2) is an important characteristic of a DNA test. For each of 3 levels of narrow sense heritability of the observed trait (h2gy) and 4 levels of Rg2, 500 independent replicates of an observed trait and a molecular breeding value (MBV) for 1000 offs...

  13. Deleterious mutations and the genetic variance of male fitness components in Mimulus guttatus.

    PubMed

    Kelly, John K

    2003-07-01

    Deleterious mutations are relevant to a broad range of questions in genetics and evolutionary biology. I present an application of the "biometric method" for estimating mutational parameters for male fitness characters of the yellow monkeyflower, Mimulus guttatus. The biometric method rests on two critical assumptions. The first is that experimental inbreeding changes genotype frequencies without changing allele frequencies; i.e., there is no genetic purging during the experiment. I satisfy this condition by employing a breeding design in which the parents are randomly extracted, fully homozygous inbred lines. The second is that all genetic variation is attributable to deleterious mutations maintained in mutation-selection balance. I explicitly test this hypothesis using likelihood ratios. Of the three deleterious mutation models tested, the first two are rejected for all characters. The failure of these models is due to an excess of additive genetic variation relative to the expectation under mutation-selection balance. The third model is not rejected for either of two log-transformed male fitness traits. However, this model imposes only "weak conditions" and is not sufficiently detailed to provide estimates for mutational parameters. The implication is that, if biometric methods are going to yield useful parameter estimates, they will need to consider mutational models more complicated than those typically employed in experimental studies.

  14. Reasoning over genetic variance information in cause-and-effect models of neurodegenerative diseases.

    PubMed

    Naz, Mufassra; Kodamullil, Alpha Tom; Hofmann-Apitius, Martin

    2016-05-01

    The work we present here is based on the recent extension of the syntax of the Biological Expression Language (BEL), which now allows for the representation of genetic variation information in cause-and-effect models. In our article, we describe, how genetic variation information can be used to identify candidate disease mechanisms in diseases with complex aetiology such as Alzheimer's disease and Parkinson's disease. In those diseases, we have to assume that many genetic variants contribute moderately to the overall dysregulation that in the case of neurodegenerative diseases has such a long incubation time until the first clinical symptoms are detectable. Owing to the multilevel nature of dysregulation events, systems biomedicine modelling approaches need to combine mechanistic information from various levels, including gene expression, microRNA (miRNA) expression, protein-protein interaction, genetic variation and pathway. OpenBEL, the open source version of BEL, has recently been extended to match this requirement, and we demonstrate in our article, how candidate mechanisms for early dysregulation events in Alzheimer's disease can be identified based on an integrative mining approach that identifies 'chains of causation' that include single nucleotide polymorphism information in BEL models.

  15. Reasoning over genetic variance information in cause-and-effect models of neurodegenerative diseases

    PubMed Central

    Naz, Mufassra; Kodamullil, Alpha Tom

    2016-01-01

    The work we present here is based on the recent extension of the syntax of the Biological Expression Language (BEL), which now allows for the representation of genetic variation information in cause-and-effect models. In our article, we describe, how genetic variation information can be used to identify candidate disease mechanisms in diseases with complex aetiology such as Alzheimer’s disease and Parkinson’s disease. In those diseases, we have to assume that many genetic variants contribute moderately to the overall dysregulation that in the case of neurodegenerative diseases has such a long incubation time until the first clinical symptoms are detectable. Owing to the multilevel nature of dysregulation events, systems biomedicine modelling approaches need to combine mechanistic information from various levels, including gene expression, microRNA (miRNA) expression, protein–protein interaction, genetic variation and pathway. OpenBEL, the open source version of BEL, has recently been extended to match this requirement, and we demonstrate in our article, how candidate mechanisms for early dysregulation events in Alzheimer’s disease can be identified based on an integrative mining approach that identifies ‘chains of causation’ that include single nucleotide polymorphism information in BEL models. PMID:26249223

  16. Understanding the cellular and molecular mechanisms of dominant and recessive inheritance in genetics course.

    PubMed

    Wanjin, Xing; Morigen, Morigen

    2015-01-01

    In Mendellian genetics, the dominance and recessiveness are used to describe the functional relationship between two alleles of one gene in a heterozygote. The allele which constitutes a phenotypical character over the other is named dominant and the one functionally masked is called recessive. The definitions thereby led to the creation of Mendel's laws on segregation and independent assortment and subsequent classic genetics. The discrimination of dominance and recessiveness originally is a requirement for Mendel's logical reasoning, but now it should be explained by cellular and molecular principles in the modern genetics. To answer the question raised by students of how the dominance and recessiveness are controlled, we reviewed the recent articles and tried to summarize the cellular and molecular basis of dominant and recessive inheritance. Clearly, understanding the essences of dominant and recessive inheritance requires us to know the dissimilarity of the alleles and their products (RNA and/or proteins), and the way of their function in cells. The alleles spatio-temporally play different roles on offering cells, tissues or organs with discernible phenotypes, namely dominant or recessive. Here, we discuss the changes of allele dominance and recessiveness at the cellular and molecular levels based on the variation of gene structure, gene regulation, function and types of gene products, in order to make students understand gene mutation and function more comprehensively and concretely.

  17. 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.

  18. Molecular-genetic variance of RH blood group system within human population of Bosnia and Herzegovina.

    PubMed

    Lasić, Lejla; Lojo-Kadrić, Naida; Silajdžić, Elma; Pojskić, Lejla; Hadžiselimović, Rifat; Pojskić, Naris

    2013-02-01

    There are two major theories for inheritance of Rh blood group system: Fisher - Race theory and Wiener theory. Aim of this study was identifying frequency of RHDCE alleles in Bosnian - Herzegovinian population and introduction of this method in screening for Rh phenotype in B&H since this type of analysis was not used for blood typing in B&H before. Rh blood group was typed by Polymerase Chain Reaction, using the protocols and primers previously established by other authors, then carrying out electrophoresis in 2-3% agarose gel. Percentage of Rh positive individuals in our sample is 84.48%, while the percentage of Rh negative individuals is 15.52%. Inter-rater agreement statistic showed perfect agreement (K=1) between the results of Rh blood system detection based on serological and molecular-genetics methods. In conclusion, molecular - genetic methods are suitable for prenatal genotyping and specific cases while standard serological method is suitable for high-throughput of samples.

  19. Genetic diversity within a dominant plant outweighs plant species diversity in structuring an arthropod community.

    PubMed

    Crawford, Kerri M; Rudgers, Jennifer A

    2013-05-01

    Plant biodiversity is being lost at a rapid rate. This has spurred much interest in elucidating the consequences of this loss for higher trophic levels. Experimental tests have shown that both plant species diversity and genetic diversity within a plant species can influence arthropod community structure. However, the majority of these studies have been conducted in separate systems, so their relative importance is currently unresolved. Furthermore, potential interactions between the two levels of diversity, which likely occur in natural systems, have not been investigated. To clarify these issues, we conducted three experiments in a freshwater sand dune ecosystem. We (1) independently manipulated plant species diversity, (2) independently manipulated genetic diversity within the dominant plant species, Ammophila breviligulata, and (3) jointly manipulated genetic diversity within the dominant plant and species diversity. We found that genetic diversity within the dominant plant species, Ammophila breviligulata, more strongly influenced arthropod communities than plant species diversity, but this effect was dependent on the presence of other species. In species mixtures, A. breviligulata genetic diversity altered overall arthropod community composition, and arthropod richness and abundance peaked at the highest level of genetic diversity. Positive nonadditive effects of diversity were detected, suggesting that arthropods respond to emergent properties of diverse plant communities. However, in the independent manipulations where A. breviligulata was alone, effects of genetic diversity were weaker, with only arthropod richness responding. In contrast, plant species diversity only influenced arthropods when A. breviligulata was absent, and then only influenced herbivore abundance. In addition to showing that genetic diversity within a dominant plant species can have large effects on arthropod community composition, these results suggest that understanding how species

  20. Previous estimates of mitochondrial DNA mutation level variance did not account for sampling error: comparing the mtDNA genetic bottleneck in mice and humans.

    PubMed

    Wonnapinij, Passorn; Chinnery, Patrick F; Samuels, David C

    2010-04-09

    In cases of inherited pathogenic mitochondrial DNA (mtDNA) mutations, a mother and her offspring generally have large and seemingly random differences in the amount of mutated mtDNA that they carry. Comparisons of measured mtDNA mutation level variance values have become an important issue in determining the mechanisms that cause these large random shifts in mutation level. These variance measurements have been made with samples of quite modest size, which should be a source of concern because higher-order statistics, such as variance, are poorly estimated from small sample sizes. We have developed an analysis of the standard error of variance from a sample of size n, and we have defined error bars for variance measurements based on this standard error. We calculate variance error bars for several published sets of measurements of mtDNA mutation level variance and show how the addition of the error bars alters the interpretation of these experimental results. We compare variance measurements from human clinical data and from mouse models and show that the mutation level variance is clearly higher in the human data than it is in the mouse models at both the primary oocyte and offspring stages of inheritance. We discuss how the standard error of variance can be used in the design of experiments measuring mtDNA mutation level variance. Our results show that variance measurements based on fewer than 20 measurements are generally unreliable and ideally more than 50 measurements are required to reliably compare variances with less than a 2-fold difference. (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  1. The evolution of interacting phenotypes: genetics and evolution of social dominance.

    PubMed

    Moore, Allen J; Haynes, Kenneth F; Preziosi, Richard F; Moore, Patricia J

    2002-12-01

    Although the argument over genetic influences on social dominance is contentious, genetic models of interacting phenotypes provide a theoretical framework for heritable effects on, and therefore evolution of, social behavior. Here we adapt the interacting phenotype model to show how social dominance can evolve. Our model makes a number of predictions: rapid evolution of behavior, strong correlated responses in associated traits (such as a badge of status), and, because context is important for social dominance, integrated evolution of both dominant and subordinate behavior reflecting direct and indirect genetic effects and social selection. We also describe the results of empirical work, artificial selection based on social status within a hierarchy in the cockroach Nauphoeta cinerea, that we used to test the predictions of our model. There was little change within selection lines in the expression of agonistic behavior, but by just generation 7 of selection, in comparisons between lines, high-line males consistently dominated low and control males, while low-line males were consistently subordinate to high-line and control males. There was a strong correlated response to selection in the pheromonal badge of status. Some correlated responses to selection differed among replicate lines, with the compound that makes males subordinate changed in one replicate, while the compound that confers dominance was altered in the other. Overall, our results are consistent with predictions from models of interacting phenotypes: social dominance is influenced by additive genetic variation, can evolve as a result of social selection, and evolution of social interactions appears to be rapid. Finally, different responses in the replicates allowed us to test very specific predictions regarding the role of the social pheromone in N. cinerea, highlighting the value of artificial selection experiments as a tool in evolutionary behavioral genetic studies.

  2. Temporal Genetic Variance and Propagule-Driven Genetic Structure Characterize Naturalized Rainbow Trout (Oncorhynchus mykiss) from a Patagonian Lake Impacted by Trout Farming

    PubMed Central

    Seeb, Lisa W.; Seeb, James E.; Arismendi, Ivan; Hernández, Cristián E.; Gajardo, Gonzalo; Galleguillos, Ricardo; Cádiz, Maria I.; Musleh, Selim S.

    2015-01-01

    Knowledge about the genetic underpinnings of invasions—a theme addressed by invasion genetics as a discipline—is still scarce amid well documented ecological impacts of non-native species on ecosystems of Patagonia in South America. One of the most invasive species in Patagonia’s freshwater systems and elsewhere is rainbow trout (Oncorhynchus mykiss). This species was introduced to Chile during the early twentieth century for stocking and promoting recreational fishing; during the late twentieth century was reintroduced for farming purposes and is now naturalized. We used population- and individual-based inference from single nucleotide polymorphisms (SNPs) to illuminate three objectives related to the establishment and naturalization of Rainbow Trout in Lake Llanquihue. This lake has been intensively used for trout farming during the last three decades. Our results emanate from samples collected from five inlet streams over two seasons, winter and spring. First, we found that significant intra- population (temporal) genetic variance was greater than inter-population (spatial) genetic variance, downplaying the importance of spatial divergence during the process of naturalization. Allele frequency differences between cohorts, consistent with variation in fish length between spring and winter collections, might explain temporal genetic differences. Second, individual-based Bayesian clustering suggested that genetic structure within Lake Llanquihue was largely driven by putative farm propagules found at one single stream during spring, but not in winter. This suggests that farm broodstock might migrate upstream to breed during spring at that particular stream. It is unclear whether interbreeding has occurred between “pure” naturalized and farm trout in this and other streams. Third, estimates of the annual number of breeders (Nb) were below 73 in half of the collections, suggestive of genetically small and recently founded populations that might experience

  3. Temporal Genetic Variance and Propagule-Driven Genetic Structure Characterize Naturalized Rainbow Trout (Oncorhynchus mykiss) from a Patagonian Lake Impacted by Trout Farming.

    PubMed

    Benavente, Javiera N; Seeb, Lisa W; Seeb, James E; Arismendi, Ivan; Hernández, Cristián E; Gajardo, Gonzalo; Galleguillos, Ricardo; Cádiz, Maria I; Musleh, Selim S; Gomez-Uchida, Daniel

    2015-01-01

    Knowledge about the genetic underpinnings of invasions-a theme addressed by invasion genetics as a discipline-is still scarce amid well documented ecological impacts of non-native species on ecosystems of Patagonia in South America. One of the most invasive species in Patagonia's freshwater systems and elsewhere is rainbow trout (Oncorhynchus mykiss). This species was introduced to Chile during the early twentieth century for stocking and promoting recreational fishing; during the late twentieth century was reintroduced for farming purposes and is now naturalized. We used population- and individual-based inference from single nucleotide polymorphisms (SNPs) to illuminate three objectives related to the establishment and naturalization of Rainbow Trout in Lake Llanquihue. This lake has been intensively used for trout farming during the last three decades. Our results emanate from samples collected from five inlet streams over two seasons, winter and spring. First, we found that significant intra- population (temporal) genetic variance was greater than inter-population (spatial) genetic variance, downplaying the importance of spatial divergence during the process of naturalization. Allele frequency differences between cohorts, consistent with variation in fish length between spring and winter collections, might explain temporal genetic differences. Second, individual-based Bayesian clustering suggested that genetic structure within Lake Llanquihue was largely driven by putative farm propagules found at one single stream during spring, but not in winter. This suggests that farm broodstock might migrate upstream to breed during spring at that particular stream. It is unclear whether interbreeding has occurred between "pure" naturalized and farm trout in this and other streams. Third, estimates of the annual number of breeders (Nb) were below 73 in half of the collections, suggestive of genetically small and recently founded populations that might experience substantial

  4. Common genetic heterogeneity of human interleukin-37 leads to functional variance.

    PubMed

    Yan, Jingjing; Zhang, Yuling; Cheng, Shimeng; Kang, Bin; Peng, Jinbiao; Zhang, Xiaodan; Yuan, Meichun; Chu, Wenqi; Zhang, Wen; Shen, Jiayin; Zhang, Shuye

    2017-09-01

    Interleukin-37 (IL-37) is an inhibitory member of the IL-1 family of cytokines. We previously found that balanced selection maintains common variations of the human IL37 gene. However, the functional consequences of this selection have yet to be validated. Here, using cells expressing exogenous IL-37 variants, including IL-37 Ref and IL-37 Var1 and Var2, we found that the three variants of IL-37 exhibited different immunoregulatory potencies in response to immune stimulation. The protein level of IL-37 Var2 was found to be significantly less than that of IL-37 Ref or Var1, despite the comparable mRNA levels of all three variants. Further study showed that IL-37 Var2 was rapidly degraded by a proteasome-dependent mechanism mediated by enhanced polyubiquitination, leading to a transient upregulation of IL-37 Var2 after immune stimulation. Finally, when ectopically expressed in cells, human IL-37 Var2 exerted less inhibition on proinflammatory cytokine production than did other IL-37 variants. Conversely, purified extracellular IL-37 variant proteins demonstrated comparable inhibitory abilities in vitro. In conclusion, our study reveals that common genetic variants of IL37 lead to different immune-inhibitory potencies, primarily as a result of differences in IL-37 protein stability, suggesting the possible involvement of these variants in various human diseases.

  5. 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.

  6. Development of new source diagnostic methods and variance reduction techniques for Monte Carlo eigenvalue problems with a focus on high dominance ratio problems

    NASA Astrophysics Data System (ADS)

    Wenner, Michael T.

    Obtaining the solution to the linear Boltzmann equation is often is often a daunting task. The time-independent form is an equation of six independent variables which cannot be solved analytically in all but some special problems. Instead, numerical approaches have been devised. This work focuses on improving Monte Carlo methods for its solution in eigenvalue form. First, a statistical method of stationarity detection called the KPSS test adapted as a Monte Carlo eigenvalue source convergence test. The KPSS test analyzes the source center of mass series which was chosen since it should be indicative of overall source behavior, and is physically easy to understand. A source center of mass plot alone serves as a good visual source convergence diagnostic. The KPSS test and three different information theoretic diagnostics were implemented into the well known KENOV.a code inside of the SCALE (version 5) code package from Oak Ridge National Laboratory and compared through analysis of a simple problem and several difficult source convergence benchmarks. Results showed that the KPSS test can add to the overall confidence by identifying more problematic simulations than without its usage. Not only this, the source center of mass information on hand visually aids in the understanding of the problem physics. The second major focus of this dissertation concerned variance reduction methodologies for Monte Carlo eigenvalue problems. The CADIS methodology, based on importance sampling, was adapted to the eigenvalue problems. It was shown that the straight adaption of importance sampling can provide a significant variance reduction in determination of keff (in cases studied up to 30%?). A modified version of this methodology was developed which utilizes independent deterministic importance simulations. In this new methodology, each particle is simulated multiple times, once to every other discretized source region utilizing the importance for that region only. Since each particle

  7. Genetics advances in autosomal dominant focal epilepsies: focus on DEPDC5.

    PubMed

    Baulac, Stéphanie

    2014-01-01

    Rare multiplex families with autosomal dominant focal epilepsies have been described with specific age-related and electroclinical syndromes: autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), familial temporal lobe epilepsy (FTLE), and familial focal epilepsy with variable foci (FFEVF). Molecular genetic advances in inherited focal epilepsies have pinpointed their genetic heterogeneity and the fact that they are mediated by different biological pathways: ion channel subunit genes have been linked to ADNFLE (CHRNA4, CHRNA2, CHRNB2, and KCNT1, encoding, respectively, the α4, α2, and β2 subunits of the neuronal nicotinic acetylcholine receptor, and a potassium channel subunit); neuronal secreted protein (LGI1-encoding epitempin) has been linked to autosomal dominant epilepsy with auditory features; and mTORC1-repressor DEPDC5 (DEP domain-containing protein 5) gene has recently been reported in a broad spectrum of inherited focal epilepsies (ADNFLE, FTLE, FFEVF). This chapter focuses on DEPDC5, a newly identified gene.

  8. A survey of attitudes toward clinical trials and genetic disclosure in autosomal dominant Alzheimer's disease.

    PubMed

    Grill, Joshua D; Bateman, Randall J; Buckles, Virginia; Oliver, Angela; Morris, John C; Masters, Colin L; Klunk, William E; Ringman, John M

    2015-01-01

    Because of its genetic underpinnings and consistent age of onset within families, autosomal dominant Alzheimer's disease (ADAD) provides a unique opportunity to conduct clinical trials of investigational agents as preventative or symptom-delaying treatments. The design of such trials may be complicated by low rates of genetic testing and disclosure among persons at risk of inheriting disease-causing mutations. To better understand the attitudes toward genetic testing and clinical trials of persons at risk for ADAD, we surveyed participants in the Dominantly Inherited Alzheimer's Network (DIAN), a multisite longitudinal study of clinical and biomarker outcomes in ADAD that does not require learning genetic status to participate. Eighty participants completed a brief anonymous survey by mail or on-line; 40 % reported knowing if they carried a gene mutation, 15 % did not know but expressed a desire to learn their genetic status, and 45 % did not know and did not desire to know their genetic status. Among participants who knew or wished to know their genetic status, 86 % were interested in participating in a clinical trial. Seventy-two percent of participants who did not wish to learn their genetic status reported that they would change their mind, if learning that they carried a mutation gave them the opportunity to participate in a clinical trial. Nearly all participants responded that they would be interested if an open-label extension were offered. These results suggest that the availability of clinical trials to prevent ADAD can affect persons' desire to undergo genetic testing and that consideration can be given to performing studies in which such testing is required.

  9. Variance components and genetic parameters for milk production and lactation pattern in an ethiopian multibreed dairy cattle population.

    PubMed

    Gebreyohannes, Gebregziabher; Koonawootrittriron, Skorn; Elzo, Mauricio A; Suwanasopee, Thanathip

    2013-09-01

    The objective of this study was to estimate variance components and genetic parameters for lactation milk yield (LY), lactation length (LL), average milk yield per day (YD), initial milk yield (IY), peak milk yield (PY), days to peak (DP) and parameters (ln(a) and c) of the modified incomplete gamma function (MIG) in an Ethiopian multibreed dairy cattle population. The dataset was composed of 5,507 lactation records collected from 1,639 cows in three locations (Bako, Debre Zeit and Holetta) in Ethiopia from 1977 to 2010. Parameters for MIG were obtained from regression analysis of monthly test-day milk data on days in milk. The cows were purebred (Bos indicus) Boran (B) and Horro (H) and their crosses with different fractions of Friesian (F), Jersey (J) and Simmental (S). There were 23 breed groups (B, H, and their crossbreds with F, J, and S) in the population. Fixed and mixed models were used to analyse the data. The fixed model considered herd-year-season, parity and breed group as fixed effects, and residual as random. The single and two-traits mixed animal repeatability models, considered the fixed effects of herd-year-season and parity subclasses, breed as a function of cow H, F, J, and S breed fractions and general heterosis as a function of heterozygosity, and the random additive animal, permanent environment, and residual effects. For the analysis of LY, LL was added as a fixed covariate to all models. Variance components and genetic parameters were estimated using average information restricted maximum likelihood procedures. The results indicated that all traits were affected (p<0.001) by the considered fixed effects. High grade B×F cows (3/16B 13/16F) had the highest least squares means (LSM) for LY (2,490±178.9 kg), IY (10.5±0.8 kg), PY (12.7±0.9 kg), YD (7.6±0.55 kg) and LL (361.4±31.2 d), while B cows had the lowest LSM values for these traits. The LSM of LY, IY, YD, and PY tended to increase from the first to the fifth parity. Single

  10. Indirect genetic effects and the lek paradox: inter-genotypic competition may strengthen genotype x environment interactions and conserve genetic variance.

    PubMed

    Danielson-François, Anne M; Zhou, Yihong; Greenfield, Michael D

    2009-05-01

    Understanding the evolutionary mechanisms that maintain genetic variation in natural populations is one of the fundamental goals of evolutionary biology. There is growing evidence that genotype-by-environment interaction (G x E) can maintain additive genetic variance (V (A)), but we lack information on the relative performance of genotypes under the competitive situations encountered in the field. Competing genotypes may influence each other, and this interaction is also subject to selection through indirect genetic effects (IGE). Here, we explore how genotypes perform when interacting and evaluate IGE in order to understand its influence on V (A) for sexually-selected traits in the lesser waxmoth, Achroia grisella. We found that inter-genotype differences and crossover interactions under joint rearing are equal to or greater than values when reared separately. A focal genotype exhibited different performances when jointly reared with various genotypes-suggesting that IGE may be responsible for the increased levels of crossover and differences in performance observed. We suggest that some genotypes are superior competitors for food acquisition in the larval stage, and that these differences influence the development and evolution of other genotypes through IGE. We reaffirm the role of G x E in maintaining V (A) and note the general importance of IGE in studies of evolutionary mechanisms.

  11. Genetic (co)variances and breeding value estimation of Gompertz growth curve parameters in Finnish Yorkshire boars, gilts and barrows.

    PubMed

    Koivula, M; Sevón-Aimonen, M-L; Strandén, I; Matilainen, K; Serenius, T; Stalder, K J; Mäntysaari, E A

    2008-06-01

    This paper's objectives were to estimate the genetic (co)variance components of the Gompertz growth curve parameters and to evaluate the relationship of estimated breeding values (EBV) based on average daily gain (ADG) and Gompertz growth curves. Finnish Yorkshire central test station performance data was obtained from the Faba Breeding (Vantaa, Finland). The final data set included 121,488 weight records from 10,111 pigs. Heritability estimates for the Gompertz growth parameters mature weight (alpha), logarithm of mature weight to birth weight ratio (beta) and maturation rate (kappa) were 0.44, 0.55 and 0.31, respectively. Genotypic and phenotypic correlations between the growth curve parameters were high and mainly negative. The only positive relationship was found between alpha and beta. Pearson and Spearman rank correlation coefficients between EBV for ADG and daily gain calculated from Gompertz growth curves were 0.79. The Spearman rank correlation between the sire EBV for ADG and Gompertz growth curve parameter-based ADG for all sires with at least 15 progeny was 0.86. Growth curves differ significantly between individuals and this information could be utilized for selection purposes when improving growth rate in pigs.

  12. Diversity and population structure of a dominant deciduous tree based on morphological and genetic data

    PubMed Central

    Zhang, Qin-di; Jia, Rui-Zhi; Meng, Chao; Ti, Chao-Wen; Wang, Yi-Ling

    2015-01-01

    Knowledge of the genetic diversity and structure of tree species across their geographic ranges is essential for sustainable use and management of forest ecosystems. Acer grosseri Pax., an economically and ecologically important maple species, is mainly distributed in North China. In this study, the genetic diversity and population differentiation of 24 natural populations of this species were evaluated using sequence-related amplified polymorphism markers and morphological characters. The results show that highly significant differences occurred in 32 morphological traits. The coefficient of variation of 34 characters was 18.19 %. Principal component analysis indicated that 18 of 34 traits explained 60.20 % of the total variance. The phenotypic differentiation coefficient (VST) was 36.06 % for all morphological traits. The Shannon–Wiener index of 34 morphological characters was 6.09, while at the population level, it was 1.77. The percentage of polymorphic bands of all studied A. grosseri populations was 82.14 %. Nei's gene diversity (He) and Shannon's information index (I) were 0.35 and 0.50, respectively. Less genetic differentiation was detected among the natural populations (GST = 0.20, ΦST = 0.10). Twenty-four populations of A. grosseri formed two main clusters, which is consistent with morphological cluster analysis. Principal coordinates analysis and STRUCTURE analysis supported the UPGMA-cluster dendrogram. There was no significant correlation between genetic and geographical distances among populations. Both molecular and morphological data suggested that A. grosseri is rich in genetic diversity. The high level of genetic variation within populations could be affected by the biological characters, mating system and lifespan of A. grosseri, whereas the lower genetic diversity among populations could be caused by effective gene exchange, selective pressure from environmental heterogeneity and the species' geographical range. PMID:26311734

  13. Chemical Variation in a Dominant Tree Species: Population Divergence, Selection and Genetic Stability across Environments

    PubMed Central

    O’Reilly-Wapstra, Julianne M.; Miller, Alison M.; Hamilton, Matthew G.; Williams, Dean; Glancy-Dean, Naomi; Potts, Brad M.

    2013-01-01

    Understanding among and within population genetic variation of ecologically important plant traits provides insight into the potential evolutionary processes affecting those traits. The strength and consistency of selection driving variability in traits would be affected by plasticity in differences among genotypes across environments (G×E). We investigated population divergence, selection and environmental plasticity of foliar plant secondary metabolites (PSMs) in a dominant tree species, Eucalyptus globulus. Using two common garden trials we examined variation in PSMs at multiple genetic scales; among 12 populations covering the full geographic range of the species and among up to 60 families within populations. Significant genetic variation in the expression of many PSMs resides both among and within populations of E. globulus with moderate (e.g., sideroxylonal A h2op = 0.24) to high (e.g., macrocarpal G h2op = 0.48) narrow sense heritabilities and high coefficients of additive genetic variation estimated for some compounds. A comparison of Qst and Fst estimates suggest that variability in some of these traits may be due to selection. Importantly, there was no genetic by environment interaction in the expression of any of the quantitative chemical traits despite often significant site effects. These results provide evidence that natural selection has contributed to population divergence in PSMs in E. globulus, and identifies the formylated phloroglucinol compounds (particularly sideroxylonal) and a dominant oil, 1,8-cineole, as candidates for traits whose genetic architecture has been shaped by divergent selection. Additionally, as the genetic differences in these PSMs that influence community phenotypes is stable across environments, the role of plant genotype in structuring communities is strengthened and these genotypic differences may be relatively stable under global environmental changes. PMID:23526981

  14. Chemical variation in a dominant tree species: population divergence, selection and genetic stability across environments.

    PubMed

    O'Reilly-Wapstra, Julianne M; Miller, Alison M; Hamilton, Matthew G; Williams, Dean; Glancy-Dean, Naomi; Potts, Brad M

    2013-01-01

    Understanding among and within population genetic variation of ecologically important plant traits provides insight into the potential evolutionary processes affecting those traits. The strength and consistency of selection driving variability in traits would be affected by plasticity in differences among genotypes across environments (G×E). We investigated population divergence, selection and environmental plasticity of foliar plant secondary metabolites (PSMs) in a dominant tree species, Eucalyptus globulus. Using two common garden trials we examined variation in PSMs at multiple genetic scales; among 12 populations covering the full geographic range of the species and among up to 60 families within populations. Significant genetic variation in the expression of many PSMs resides both among and within populations of E. globulus with moderate (e.g., sideroxylonal A h(2)op = 0.24) to high (e.g., macrocarpal G h(2)op = 0.48) narrow sense heritabilities and high coefficients of additive genetic variation estimated for some compounds. A comparison of Qst and Fst estimates suggest that variability in some of these traits may be due to selection. Importantly, there was no genetic by environment interaction in the expression of any of the quantitative chemical traits despite often significant site effects. These results provide evidence that natural selection has contributed to population divergence in PSMs in E. globulus, and identifies the formylated phloroglucinol compounds (particularly sideroxylonal) and a dominant oil, 1,8-cineole, as candidates for traits whose genetic architecture has been shaped by divergent selection. Additionally, as the genetic differences in these PSMs that influence community phenotypes is stable across environments, the role of plant genotype in structuring communities is strengthened and these genotypic differences may be relatively stable under global environmental changes.

  15. No Evidence for Genetic Contribution of Ocular Dominance: The Guangzhou Twin Eye Study.

    PubMed

    Yan, Xixi; Congdon, Nathan; Zhang, Jian; Chen, Qianyun; Guo, Xinxing; He, Mingguang

    2014-01-01

    The purpose of this study was to explore the heritability of ocular dominance in a classic twin study. A classical twin study. Twins aged 7 to 19 years enrolled from the Guangzhou Twin Registry received comprehensive eye examinations. Ocular dominance was assessed by the "hole-in-the-card test" by trained optometrists. Zygosity of the participants was confirmed by genotyping in all same-sex twin pairs. The pairwise concordance rate was calculated as the main outcome. After excluding 110 children with anisometropia of 2.0 diopters or greater and 24 children with alternating ocular dominance, a total of 941 twin pairs were identified in the analysis, including 596 monozygotic and 345 dizygotic pairs. Right-eye dominance was present in 59.3% of twins with available data. The pairwise concordance rate was 0.529 and 0.530 in monozygotic and dizygotic twin pairs, respectively (P > 0.5). The tetrachoric correlation was 0.043 and 0.035, respectively. When comparing the young twins and their parents, no significant difference in the percentage of offspring with left-eye dominance was found between right × right parent mating group and non-right × right parent mating groups. Genetic factors may not be involved in ocular dominance in Chinese teens and children.

  16. Detecting dominant resonant modes of rolling bearing faults using the niching genetic algorithm

    NASA Astrophysics Data System (ADS)

    Docekal, Adam; Smid, Radislav; Kreidl, Marcel; Krpata, Pavel

    2011-10-01

    In this paper we propose an improvement of methods for adaptive selection of frequency bands containing transients which indicate the presence of the dominant resonant modes of rolling bearing faults using niching genetic algorithm optimization. The main aim of this approach is to diagnose the condition of the bearings and to be able to recognize faults on various parts of bearings and possible combinations of faults. Because the vibration signals corresponding to faults on bearings are typically transients with a wide frequency range occurring around the excited mechanical resonant modes and drowned in the acquired vibration signals, it is necessary to emphasize these excited transients using a matched bank of filters. The dominant resonant modes of a bearing and the system modes produced from fault source are usually unknown, and so there is a need for robust global search methods able to deal with non-linear problems with multiple optima. Instead of applying an optimization method repeatedly for every optimum, non-dominated extensions of the genetic algorithm can be applied only one time to find and maintain multiple optimal solutions. The efficiency of the proposed approach - niching genetic algorithm with fitness sharing - was evaluated using vibration signals acquired on four tapered roller bearings with defined combinations of seeded faults.

  17. Solving multi-objective job shop scheduling problems using a non-dominated sorting genetic algorithm

    NASA Astrophysics Data System (ADS)

    Piroozfard, Hamed; Wong, Kuan Yew

    2015-05-01

    The efforts of finding optimal schedules for the job shop scheduling problems are highly important for many real-world industrial applications. In this paper, a multi-objective based job shop scheduling problem by simultaneously minimizing makespan and tardiness is taken into account. The problem is considered to be more complex due to the multiple business criteria that must be satisfied. To solve the problem more efficiently and to obtain a set of non-dominated solutions, a meta-heuristic based non-dominated sorting genetic algorithm is presented. In addition, task based representation is used for solution encoding, and tournament selection that is based on rank and crowding distance is applied for offspring selection. Swapping and insertion mutations are employed to increase diversity of population and to perform intensive search. To evaluate the modified non-dominated sorting genetic algorithm, a set of modified benchmarking job shop problems obtained from the OR-Library is used, and the results are considered based on the number of non-dominated solutions and quality of schedules obtained by the algorithm.

  18. Variance components of aggressive behavior in genetically highly connected Pietrain populations kept under two different housing conditions.

    PubMed

    Appel, Anne K; Voß, Barbara; Tönepöhl, Björn; König von Borstel, Uta; Gauly, Matthias

    2013-12-01

    Mixing of unfamiliar pigs is a standard management procedure in commercial pig production and is often associated with a period of intense and physically damaging aggression. Aggression is considered a problem for animal welfare and production. The objective of the present paper was to investigate the genetic background of aggressive behavior traits at mixing of unfamiliar gilts under 2 different housing conditions. Therefore, a total of 543 purebred Pietrain gilts, from 2 nucleus farms (farm A: n = 302; farm B: n = 241) of 1 breeding company, were tested at an average age of 214 d (SD 12.2 d) for aggressive behavior by 1 observer. Observations included the frequencies of aggressive attack and reciprocal fighting during mixing with unfamiliar gilts. On farm A 41% of the gilts were purebred Pietrains, whereas 59% were purebred Landrace or Duroc gilts. On the farm B 42% of the gilts were purebred Pietrains, and 58% purebred Large White gilts. The average size of the newly mixed groups of gilts was 28 animals on farm A and 18 animals on farm B. The Pietrain gilts from the 2 herds were genetically closely linked. They were the offspring of 96 sires, with 64% of these sires having tested progeny in both farms. There were clear differences in the housing of the animals between the 2 farms. The test pen on farm A had a solid concrete floor littered with wooden shavings and was equipped with a dry feeder. On farm B there was a partly slatted floor, and the gilts were fed by an electronic sow feeder. Mean space allowance was 2.6 m(2)/gilt on farm A and 3.9 m(2)/gilt on farm B. Although large interindividual differences existed, gilts from farm B performed numerically more aggressive attack (mean 1.12, SD 1.42 vs. mean 0.71, SD 1.20) and reciprocal fighting (mean 0.78, SD 0.98 vs. mean 0.44, SD 0.82) when compared with gilts from farm A. The heritabilities and additive genetic variances for behavioral traits were estimated with a linear animal model and were on a low level

  19. A comparison of identity-by-descent and identity-by-state matrices that are used for genetic evaluation and estimation of variance components.

    PubMed

    Fernando, R L; Cheng, H; Sun, X; Garrick, D J

    2017-06-01

    The genetic covariance matrix conditional on pedigree is proportional to the pedigree-based additive relationship matrix (PARM), which is twice the matrix of identity-by-descent (IBD) probabilities. In genomic prediction, IBD probabilities in the PARM, which are expected genetic similarities between relatives that are derived from the pedigree, are substituted by realized similarities that are derived from genotypes to obtain a genomic additive relationship matrix (GARM). Different definitions of similarity lead to different GARMs, and two commonly used GARMS are the matrix G, which is based on an allele substitution effect model, and the matrix T, which is based on an allele effect model. We show that although the two matrices T and G are not proportional, they give identical predictions of differences between breeding values. When genomic information is used for variance component estimation, the GARM Gx is computed from genotype covariates that have been standardized to have unit variance. That approach is equivalent to fitting a random regression model using the same standardized covariates. We show that under Hardy-Weinberg and linkage equilibria (LE) that the genetic variance is kσγ2, where σγ2 is the variance of a randomly sampled element from the vector of k substitution effects. However, if linkage disequilibrium (LD) has been generated through selection, covariances between genotypes at different loci will be negative, and therefore, the additive genetic variance will be lower than kσγ2. When the GARM Gx is assumed to be proportional to the genetic covariance matrix, the parameter being estimated is kσγ2. We have demonstrated by simulation that kσγ2 overestimates the additive genetic variance when LD is generated by selection. We argue that unlike the PARM, GARMs are not proportional to a genetic covariance matrix conditional on the observed causal genotypes. The objective here is to recognize the difference between these covariance matrices and

  20. Bimodal expressivity in dominant retinitis pigmentosa genetically linked to chromosome 19q.

    PubMed Central

    Evans, K; al-Maghtheh, M; Fitzke, F W; Moore, A T; Jay, M; Inglehearn, C F; Arden, G B; Bird, A C

    1995-01-01

    A clinical, psychophysical, and electrophysiologic study was undertaken of two autosomal dominant retinitis pigmentosa pedigrees with a genetic mutation assigned to chromosome 19q by linkage analysis. Members with the abnormal haplotype were either symptomatic with adolescent onset nyctalopia, restricted visual fields, and non-detectable electroretinographic responses by 30 years of age, or asymptomatic with normal fundus appearance and minimal or no psychophysical or electroretinographic abnormalities. There was no correlation in the severity in parents and their offspring. Pedigree analysis suggested that although the offspring of parents with the genetic mutation were at 50% risk of having the genetic defect, the risk of being symptomatic during a working lifetime was only 31%. Such bimodal phenotypic expressivity in these particular pedigrees may be explained by a second, allelic genetic influence and may be a phenomenon unique to this genetic locus. Genetic counselling in families expressing this phenotype can only be based on haplotype analysis since clinical investigations, even in the most elderly, would not preclude the presence of the mutant gene. PMID:7488604

  1. Negative-dominance phenomenon with genetic variants of the cardiac sodium channel Nav1.5.

    PubMed

    Sottas, Valentin; Abriel, Hugues

    2016-07-01

    During the past two decades, many pathological genetic variants in SCN5A, the gene encoding the pore-forming subunit of the cardiac (monomeric) sodium channel Na(v)1.5, have been described. Negative dominance is a classical genetic concept involving a "poison" mutant peptide that negatively interferes with the co-expressed wild-type protein, thus reducing its cellular function. This phenomenon has been described for genetic variants of multimeric K(+) channels, which mechanisms are well understood. Unexpectedly, several pathologic SCN5A variants that are linked to Brugada syndrome also demonstrate such a dominant-negative (DN) effect. The molecular determinants of these observations, however, are not yet elucidated. This review article summarizes recent findings that describe the mechanisms underlying the DN phenomenon of genetic variants of K(+), Ca(2+), Cl(-) and Na(+) channels, and in particular Brugada syndrome variants of Na(v)1.5. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  2. High variance in reproductive success generates a false signature of a genetic bottleneck in populations of constant size: a simulation study

    PubMed Central

    2013-01-01

    Background Demographic bottlenecks can severely reduce the genetic variation of a population or a species. Establishing whether low genetic variation is caused by a bottleneck or a constantly low effective number of individuals is important to understand a species’ ecology and evolution, and it has implications for conservation management. Recent studies have evaluated the power of several statistical methods developed to identify bottlenecks. However, the false positive rate, i.e. the rate with which a bottleneck signal is misidentified in demographically stable populations, has received little attention. We analyse this type of error (type I) in forward computer simulations of stable populations having greater than Poisson variance in reproductive success (i.e., variance in family sizes). The assumption of Poisson variance underlies bottleneck tests, yet it is commonly violated in species with high fecundity. Results With large variance in reproductive success (Vk ≥ 40, corresponding to a ratio between effective and census size smaller than 0.1), tests based on allele frequencies, allelic sizes, and DNA sequence polymorphisms (heterozygosity excess, M-ratio, and Tajima’s D test) tend to show erroneous signals of a bottleneck. Similarly, strong evidence of population decline is erroneously detected when ancestral and current population sizes are estimated with the model based method MSVAR. Conclusions Our results suggest caution when interpreting the results of bottleneck tests in species showing high variance in reproductive success. Particularly in species with high fecundity, computer simulations are recommended to confirm the occurrence of a population bottleneck. PMID:24131797

  3. Genetic variation within a dominant shrub species determines plant species colonization in a coastal dune ecosystem.

    PubMed

    Crutsinger, Gregory M; Strauss, Sharon Y; Rudgers, Jennifer A

    2010-04-01

    The diversity and structure of plant communities is often determined by the presence and identity of competitively dominant species. Recent studies suggest that intraspecific variation within dominants may also have important community-level consequences. In a coastal dunes ecosystem of northern California, we use a decade-old common garden experiment to test the effects of a genetically based architectural dimorphism within a dominant native shrub, Baccharis pilularis, on plant colonization success and understory plant diversity. We found that erect Baccharis morphs had higher richness and cover of colonizing plant species (both native and exotic species) compared to prostrate morphs, as well as higher biomass of a dominant exotic dune grass (Ammophila arenaria). Trait differences between architectural morphs influenced the abiotic understory environment (light availability, soil surface temperature, and litter depth) and were associated with species colonization success. Taken together, our results demonstrate that incorporating within-species variation, particularly within dominant species, into community ecological research can increase the ability to predict patterns of species diversity and assembly within communities.

  4. Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita.

    PubMed

    Leachman, Sancy A; Hickerson, Robyn P; Hull, Peter R; Smith, Frances J D; Milstone, Leonard M; Lane, E Birgitte; Bale, Sherri J; Roop, Dennis R; McLean, W H Irwin; Kaspar, Roger L

    2008-09-01

    The field of science and medicine has experienced a flood of data and technology associated with the human genome project. Over 10,000 human diseases have been genetically defined, but little progress has been made with respect to the clinical application of this knowledge. A notable exception to this exists for pachyonychia congenita (PC), a rare, dominant-negative keratin disorder. The establishment of a non-profit organization, PC Project, has led to an unprecedented coalescence of patients, scientists, and physicians with a unified vision of developing novel therapeutics for PC. Utilizing the technological by-products of the human genome project, such as RNA interference (RNAi) and quantitative RT-PCR (qRT-PCR), physicians and scientists have collaborated to create a candidate siRNA therapeutic that selectively inhibits a mutant allele of KRT6A, the most commonly affected PC keratin. In vitro investigation of this siRNA demonstrates potent inhibition of the mutant allele and reversal of the cellular aggregation phenotype. In parallel, an allele-specific quantitative real-time RT-PCR assay has been developed and validated on patient callus samples in preparation for clinical trials. If clinical efficacy is ultimately demonstrated, this "first-in-skin" siRNA may herald a paradigm shift in the treatment of dominant-negative genetic disorders.

  5. Gene Loss Dominates As a Source of Genetic Variation within Clonal Pathogenic Bacterial Species.

    PubMed

    Bolotin, Evgeni; Hershberg, Ruth

    2015-07-10

    Some of the most dangerous pathogens such as Mycobacterium tuberculosis and Yersinia pestis evolve clonally. This means that little or no recombination occurs between strains belonging to these species. Paradoxically, although different members of these species show extreme sequence similarity of orthologous genes, some show considerable intraspecies phenotypic variation, the source of which remains elusive. To examine the possible sources of phenotypic variation within clonal pathogenic bacterial species, we carried out an extensive genomic and pan-genomic analysis of the sources of genetic variation available to a large collection of clonal and nonclonal pathogenic bacterial species. We show that while nonclonal species diversify through a combination of changes to gene sequences, gene loss and gene gain, gene loss completely dominates as a source of genetic variation within clonal species. Indeed, gene loss is so prevalent within clonal species as to lead to levels of gene content variation comparable to those found in some nonclonal species that are much more diverged in their gene sequences and that acquire a substantial number of genes horizontally. Gene loss therefore needs to be taken into account as a potential dominant source of phenotypic variation within clonal bacterial species.

  6. Comprehensive Genetic Analysis of Japanese Autosomal Dominant Sensorineural Hearing Loss Patients

    PubMed Central

    Iwasa, Yoh-ichiro; Nishio, Shin-ya; Usami, Shin-ichi

    2016-01-01

    Background In general, autosomal dominant inherited hearing loss does not have a founder mutation, with the causative mutation different in each family. For this reason, there has been a strong need for efficient diagnosis methods for autosomal dominant sensorineural hearing loss (ADSNHL) patients. This study sought to verify the effectiveness of our analysis algorithm for the screening of ADSNHL patients as well as the usefulness of the massively parallel DNA sequencing (MPS). Subjects and Methods Seventy-five Japanese ADSNHL patients from 53 ENT departments nationwide participated in this study. We conducted genetic analysis of 75 ADSNHL patients using the Invader assay, TaqMan genotyping assay and MPS-based genetic screening. Results A total of 46 (61.3%) ADSNHL patients were found to have at least one candidate gene variant. Conclusion We were able to achieve a high mutation detection rate through the combination of the Invader assay, TaqMan genotyping assay and MPS. MPS could be used to successfully identify mutations in rare deafness genes. PMID:27911912

  7. Heritable Micro-environmental Variance Covaries with Fitness in an Outbred Population of Drosophila serrata.

    PubMed

    Sztepanacz, Jacqueline L; McGuigan, Katrina; Blows, Mark W

    2017-08-01

    The genetic basis of stochastic variation within a defined environment, and the consequences of such micro-environmental variance for fitness are poorly understood . Using a multigenerational breeding design in Drosophila serrata, we demonstrated that the micro-environmental variance in a set of morphological wing traits in a randomly mating population had significant additive genetic variance in most single wing traits. Although heritability was generally low (<1%), coefficients of additive genetic variance were of a magnitude typical of other morphological traits, indicating that the micro-environmental variance is an evolvable trait. Multivariate analyses demonstrated that the micro-environmental variance in wings was genetically correlated among single traits, indicating that common mechanisms of environmental buffering exist for this functionally related set of traits. In addition, through the dominance genetic covariance between the major axes of micro-environmental variance and fitness, we demonstrated that micro-environmental variance shares a genetic basis with fitness, and that the pattern of selection is suggestive of variance-reducing selection acting on micro-environmental variance. Copyright © 2017 by the Genetics Society of America.

  8. Prediction of testcross means and variances among F3 progenies of F1 crosses from testcross means and genetic distances of their parents in maize.

    PubMed

    Melchinger, A E; Gumber, R K; Leipert, R B; Vuylsteke, M; Kuiper, M

    1998-03-01

    Prediction of the means and genetic variances in segregating generations could help to assess the breeding potential of base populations. In this study, we investigated whether the testcross (TC) means and variances of F3 progenies from F1 crosses in European maize can be predicted from the TC means of their parents and F1 crosses and four measures of parental genetic divergence: genetic distance (GD) determined by 194 RFLP or 691 AFLP(TM) (1) markers, mid-parent heterosis (MPH), and absolute difference between the TC means of parents (∣P1-P2∣). The experimental materials comprised six sets of crosses; each set consisted of four elite inbreds from the flint or dent germplasm and the six possible F1 crosses between them, which were evaluated for mid-parent heterosis. Testcross progenies of these materials and 20 random F3 plants per F1 cross were produced with a single-cross tester from the opposite heterotic group and evaluated in two environments. The characters studied were plant height, dry matter content and grain yield. The genetic distance between parent lines ranged between 0.17 and 0.70 for RFLPs and between 0.14 and 0.57 for AFLPs in the six sets. Testcross-means of parents, F1 crosses, and F3 populations averaged across the six crosses in a particular set generally agreed well for all three traits. Bartlett's test revealed heterogeneous TC variances among the six crosses in all sets for plant height, in four sets for grain yield and in five sets for dry matter content. Correlations among the TC means of the parents, F1 crosses, and F3 populations were highly significant and positive for all traits. Estimates of the TC variance among F3 progenies for the 36 crosses showed only low correlations with the four measures of parental genetic divergence for all traits. The results demonstrated that for our material, the TC means of the parents or the parental F1 cross can be used as predictors for the TC means of F3 populations. However, the prediction of the

  9. Autosomal dominant ataxia: Genetic evidence for locus heterogeneity from a cuban founder-effect population

    PubMed Central

    Auburger, Georg; Diaz, Guillermo Orozco; Capote, Raul Ferreira; Sanchez, Suzana Gispert; Perez, Marta Paradoa; del Cueto, Marianela Estrada; Meneses, Mirna Garcia; Farrall, Martin; Williamson, Robert; Chamberlain, Susan; Baute, Luis Heredero

    1990-01-01

    The locus for autosomal dominant ataxia with a diagnosis of olivo-ponto-cerebellar atrophy at autopsy has been previously assigned to chromosome 6p. However, evidence for two alternative locations has been reported. We have recently described a large potential founder-effect population of such patients in the Holguin province of Cuba. With an estimated 1,000 patients available for analysis, this extensive cluster of families provides a unique opportunity for the definitive localization of the genetic mutation. Linkage analysis between the disease locus in this population and markers within and flanking the HLA region on chromosome 6 were undertaken in 12 families comprising over 100 affected individuals. Despite similarity in the clinical phenotype between those families where the disease locus has been reported to be linked to the HLA locus and the Cuban patients, no evidence of linkage to this region could be demonstrated in the latter. The disease locus was excluded from a 96-cM genetic interval of the short arm of chromosome 6, encompassing the F13A1–HLA–GLO1–MUT/D6S4 loci. These data strongly support the existence of genetic heterogeneity for the disease. PMID:1971152

  10. 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

  11. 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.

  12. Autosomal dominant retinitis pigmentosa with apparent incomplete penetrance: a clinical, electrophysiological, psychophysical, and molecular genetic study.

    PubMed Central

    Moore, A T; Fitzke, F; Jay, M; Arden, G B; Inglehearn, C F; Keen, T J; Bhattacharya, S S; Bird, A C

    1993-01-01

    Twenty five symptomatic individuals and six asymptomatic obligate gene carriers from four families with autosomal dominant retinitis pigmentosa (adRP) showing apparent incomplete penetrance have been studied. Symptomatic individuals from three families showed early onset of night blindness, non-recordable rod electroretinograms, and marked elevation of both rod and cone thresholds in all subjects tested. In the fourth family, there was more variation in the age of onset of night blindness and some symptomatic individuals showed well preserved rod and cone function in some retinal areas. All asymptomatic individuals tested had evidence of mild abnormalities of rod and cone function, indicating that these families show marked variation in expressivity rather than true non-penetrance of the adRP gene. No mutations of the rhodopsin or RDS genes were found in these families and the precise genetic mutation(s) remain to be identified. PMID:8025041

  13. Permutation-based variance component test in generalized linear mixed model with application to multilocus genetic association study.

    PubMed

    Zeng, Ping; Zhao, Yang; Li, Hongliang; Wang, Ting; Chen, Feng

    2015-04-22

    In many medical studies the likelihood ratio test (LRT) has been widely applied to examine whether the random effects variance component is zero within the mixed effects models framework; whereas little work about likelihood-ratio based variance component test has been done in the generalized linear mixed models (GLMM), where the response is discrete and the log-likelihood cannot be computed exactly. Before applying the LRT for variance component in GLMM, several difficulties need to be overcome, including the computation of the log-likelihood, the parameter estimation and the derivation of the null distribution for the LRT statistic. To overcome these problems, in this paper we make use of the penalized quasi-likelihood algorithm and calculate the LRT statistic based on the resulting working response and the quasi-likelihood. The permutation procedure is used to obtain the null distribution of the LRT statistic. We evaluate the permutation-based LRT via simulations and compare it with the score-based variance component test and the tests based on the mixture of chi-square distributions. Finally we apply the permutation-based LRT to multilocus association analysis in the case-control study, where the problem can be investigated under the framework of logistic mixed effects model. The simulations show that the permutation-based LRT can effectively control the type I error rate, while the score test is sometimes slightly conservative and the tests based on mixtures cannot maintain the type I error rate. Our studies also show that the permutation-based LRT has higher power than these existing tests and still maintains a reasonably high power even when the random effects do not follow a normal distribution. The application to GAW17 data also demonstrates that the proposed LRT has a higher probability to identify the association signals than the score test and the tests based on mixtures. In the present paper the permutation-based LRT was developed for variance

  14. Fitness of Transgenic Mosquito Aedes aegypti Males Carrying a Dominant Lethal Genetic System

    PubMed Central

    Massonnet-Bruneel, Blandine; Corre-Catelin, Nicole; Lacroix, Renaud; Lees, Rosemary S.; Hoang, Kim Phuc; Nimmo, Derric; Alphey, Luke; Reiter, Paul

    2013-01-01

    OX513A is a transgenic strain of Aedes aegypti engineered to carry a dominant, non-sex-specific, late-acting lethal genetic system that is repressed in the presence of tetracycline. It was designed for use in a sterile-insect (SIT) pest control system called RIDL® (Release of Insects carrying a Dominant Lethal gene) by which transgenic males are released in the field to mate with wild females; in the absence of tetracycline, the progeny from such matings will not survive. We investigated the mating fitness of OX513A in the laboratory. Male OX513A were as effective as Rockefeller (ROCK) males at inducing refractoriness to further mating in wild type females and there was no reduction in their ability to inseminate multiple females. They had a lower mating success but yielded more progeny than the wild-type comparator strain (ROCK) when one male of each strain was caged with a ROCK female. Mating success and fertility of groups of 10 males—with different ratios of RIDL to ROCK—competing for five ROCK females was similar, but the median longevity of RIDL males was somewhat (18%) lower. We conclude that the fitness under laboratory conditions of OX513A males carrying a tetracycline repressible lethal gene is comparable to that of males of the wild-type comparator strain. PMID:23690948

  15. Fitness of transgenic mosquito Aedes aegypti males carrying a dominant lethal genetic system.

    PubMed

    Massonnet-Bruneel, Blandine; Corre-Catelin, Nicole; Lacroix, Renaud; Lees, Rosemary S; Hoang, Kim Phuc; Nimmo, Derric; Alphey, Luke; Reiter, Paul

    2013-01-01

    OX513A is a transgenic strain of Aedes aegypti engineered to carry a dominant, non-sex-specific, late-acting lethal genetic system that is repressed in the presence of tetracycline. It was designed for use in a sterile-insect (SIT) pest control system called RIDL® (Release of Insects carrying a Dominant Lethal gene) by which transgenic males are released in the field to mate with wild females; in the absence of tetracycline, the progeny from such matings will not survive. We investigated the mating fitness of OX513A in the laboratory. Male OX513A were as effective as Rockefeller (ROCK) males at inducing refractoriness to further mating in wild type females and there was no reduction in their ability to inseminate multiple females. They had a lower mating success but yielded more progeny than the wild-type comparator strain (ROCK) when one male of each strain was caged with a ROCK female. Mating success and fertility of groups of 10 males-with different ratios of RIDL to ROCK-competing for five ROCK females was similar, but the median longevity of RIDL males was somewhat (18%) lower. We conclude that the fitness under laboratory conditions of OX513A males carrying a tetracycline repressible lethal gene is comparable to that of males of the wild-type comparator strain.

  16. Genetic transformation of Nannochloropsis oculata with a bacterial phleomycin resistance gene as dominant selective marker

    NASA Astrophysics Data System (ADS)

    Ma, Xiaolei; Pan, Kehou; Zhang, Lin; Zhu, Baohua; Yang, Guanpin; Zhang, Xiangyang

    2016-04-01

    The gene ble from Streptoalloteichus hindustanus is widely used as a selective antibiotic marker. It can control the phleomycin resistance, and significantly increase the tolerance of hosts to zeocin. The unicellular marine microalga Nannochloropsis oculata is extremely sensitive to zeocin. We selected ble as the selective marker for the genetic transformation of N. oculata. After the algal cells at a density of 2×107 cells mL-1 was digested with 4% hemicellulase and 2% driselase for 1 h, the protoplasts accounted for 90% of the total. The ble was placed at the downstream of promoter HSP70A-RUBS2 isolated from Chlamydomonas reinhardtii, yielding a recombinant expression construct pMS188. The construct was transferred into the protoplasts through electroporation (1 kV, 15 μS). The transformed protoplasts were cultured in fresh f/2 liquid medium, and selected on solid f/2 medium supplemented with 500 ng mL-1 zeocin. The PCR result proved that ble existed in the transformants. Three transformants had been cultured for at least 5 generations without losing ble. Southern blotting analysis showed that the ble has been integrated into the genome of N. oculata. The ble will serve as a new dominant selective marker in genetic engineering N. oculata.

  17. FADS2 Genetic Variance in Combination with Fatty Acid Intake Might Alter Composition of the Fatty Acids in Brain

    PubMed Central

    Rizzi, Thais S.; van der Sluis, Sophie; Derom, Catherine; Thiery, Evert; van Kesteren, Ronald E.; Jacobs, Nele; Van Gestel, Sofie; Vlietinck, Robert; Verhage, Matthijs; Heutink, Peter; Posthuma, Danielle

    2013-01-01

    Multiple lines of evidence suggest that fatty acids (FA) play an important role in cognitive function. However, little is known about the functional genetic pathways involved in cognition. The main goals of this study were to replicate previously reported interaction effects between breast feeding (BF) and FA desaturase (FADS) genetic variation on IQ and to investigate the possible mechanisms by which these variants might moderate BF effect, focusing on brain expression. Using a sample of 534 twins, we observed a trend in the moderation of BF effects on IQ by FADS2 variation. In addition, we made use of publicly available gene expression databases from both humans (193) and mice (93) and showed that FADS2 variants also correlate with FADS1 brain expression (P-value<1.1E-03). Our results provide novel clues for the understanding of the genetic mechanisms regulating FA brain expression and improve the current knowledge of the FADS moderation effect on cognition. PMID:23826354

  18. Beyond mean allelic effects: A locus at the major color gene MC1R associates also with differing levels of phenotypic and genetic (co)variance for coloration in barn owls.

    PubMed

    San-Jose, Luis M; Ducret, Valérie; Ducrest, Anne-Lyse; Simon, Céline; Roulin, Alexandre

    2017-09-01

    The mean phenotypic effects of a discovered variant help to predict major aspects of the evolution and inheritance of a phenotype. However, differences in the phenotypic variance associated to distinct genotypes are often overlooked despite being suggestive of processes that largely influence phenotypic evolution, such as interactions between the genotypes with the environment or the genetic background. We present empirical evidence for a mutation at the melanocortin-1-receptor gene, a major vertebrate coloration gene, affecting phenotypic variance in the barn owl, Tyto alba. The white MC1R allele, which associates with whiter plumage coloration, also associates with a pronounced phenotypic and additive genetic variance for distinct color traits. Contrarily, the rufous allele, associated with a rufous coloration, relates to a lower phenotypic and additive genetic variance, suggesting that this allele may be epistatic over other color loci. Variance differences between genotypes entailed differences in the strength of phenotypic and genetic associations between color traits, suggesting that differences in variance also alter the level of integration between traits. This study highlights that addressing variance differences of genotypes in wild populations provides interesting new insights into the evolutionary mechanisms and the genetic architecture underlying the phenotype. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. The Genetics of Vascular Complications in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

    PubMed Central

    Rossetti, Sandro; Harris, Peter C.

    2014-01-01

    The most important extra-renal manifestation of autosomal dominant polycystic kidney disease (ADPKD) in terms of debilitating injury and premature death is the development of intracranial aneurysms (IAs) and other vascular complications, resulting in subarachnoid hemorrhage (SAH). IAs are found at a rate approximately five times higher in ADPKD patients than in the general population and in patients with a family history of SAH/IAs the frequency is elevated further three to five times, indicating the importance of genetic factors in its etiology. Expression of the ADPKD gene products, polycystin-1 (PKD1) and polycystin-2 (PKD2), in vascular smooth muscle and the endothelium, and evidence that reduced levels of these proteins leads to IA development in mouse models, suggests a direct role of these proteins in the vascular disease. PKD1 and PKD2 patients seem equally likely to develop IAs, while patients with mutations to the 5’ half of PKD1 may more likely have vascular complications. Genome wide association and candidate studies of multiplex families with IAs without ADPKD have identified a number of genes/proteins that may be risk factors for the development of IAs. These candidate proteins largely have roles in the maintenance and remodeling of the arterial wall of small brain arteries. The development of the genetic methodologies of massively parallel sequencing mean it is now possible to test these and other candidates in ADPKD families with multiplex and singleton IA cases. Identifying strong modifiers of this phenotype will be important for prioritizing patients for presymptomatic screening and interventions. PMID:23971643

  20. Variance Components and Genetic Parameters Estimated for Fat and Protein Content in Individual Months of Lactation: The Case of Tsigai Sheep.

    PubMed

    Oravcová, Marta

    2016-02-01

    The objective of this study was to assess variance components and genetic parameters for fat and protein content in Tsigai sheep using multivariate animal models in which fat and protein content in individual months of lactation were treated as different traits, and univariate models in which fat and protein content were treated as repeated measures of the same traits. Test day measurements were taken between the second and the seventh month of lactation. The fixed effects were lactation number, litter size and days in milk. The random effects were animal genetic effect and permanent environmental effect of ewe. The effect of flock-year-month of test day measurement was fitted either as a fixed (FYM) or random (fym) effect. Heritabilities for fat content were estimated between 0.06 and 0.17 (FYM fitted) and between 0.06 and 0.11 (fym fitted). Heritabilities for protein content were estimated between 0.15 and 0.23 (FYM fitted) and between 0.10 and 0.18 (fym fitted). For fat content, variance ratios of permanent environmental effect of ewe were estimated between 0.04 and 0.11 (FYM fitted) and between 0.02 and 0.06 (fym fitted). For protein content, variance ratios of permanent environmental effect of ewe were estimated between 0.13 and 0.20 (FYM fitted) and between 0.08 and 0.12 (fym fitted). The proportion of phenotypic variance explained by fym effect ranged from 0.39 to 0.43 for fat content and from 0.25 to 0.36 for protein content. Genetic correlations between individual months of lactation ranged from 0.74 to 0.99 (fat content) and from 0.64 to 0.99 (protein content). Fat content heritabilities estimated with univariate animal models roughly corresponded with heritability estimates from multivariate models: 0.13 (FYM fitted) and 0.07 (fym fitted). Protein content heritabilities estimated with univariate animal models also corresponded with heritability estimates from multivariate models: 0.18 (FYM fitted) and 0.13 (fym fitted).

  1. Genetic control of the environmental variance for birth weight in seven generations of a divergent selection experiment in mice.

    PubMed

    Formoso-Rafferty, N; Cervantes, I; Ibáñez-Escriche, N; Gutiérrez, J P

    2016-06-01

    Data from seven generations of a divergent selection experiment designed for environmental variability of birth weight were analysed to estimate genetic parameters and to explore signs of selection response. A total of 10 783 birth weight records from 638 females and 1127 litters in combination with 10 007 pedigree records were used. Each record of birth weight was assigned to the mother of the pup in a heteroscedastic model, and after seven generations of selection, evidence of success in the selection process was shown. A Bayesian analysis showed that success of the selection process started from the first generation for birth weight and from the second generation for its environmental variability. Genetic parameters were estimated across generations. However, only from the third generation onwards were the records useful to consider the results to be reliable. The results showed a consistent positive and low genetic correlation between the birth weight trait and its environmental variability, which could allow an independent selection process. This study has demonstrated that the genetic control of the birth weight environmental variability is possible in mice. Nevertheless, before the results are applied directly in farm animals, it would be worth confirming any other implications on other important traits, such as robustness, longevity and welfare.

  2. School Performance and Genetic and Environmental Variance in Antisocial Behavior at the Transition from Adolescence to Adulthood

    PubMed Central

    Johnson, Wendy; McGue, Matthew K.; Iacono, William G.

    2009-01-01

    Antisocial behavior increases in adolescence, particularly among those who perform poorly in school. As adolescents move into adulthood, both educational attainment and the extent to which antisocial behavior continues have implications for their abilities to take on constructive social roles. We used a population-representative longitudinal twin study to explore how links between genetic and environmental influences at ages 17 and 24 may be implicated in the developmental processes involved. At age 17, expression of both genetic and nonshared environmental vulnerabilities unique to antisocial behavior was greater among those with low GPA than among those with higher GPA. This suggested that maintenance of high GPA buffered the impact of both genetic and environmental influences encouraging antisocial behavior. When GPA was high, both genetic and environmental influences involved in both traits encouraged good school performance and restrained antisocial behavior. At age 24, however, correlated family environmental influences drove the association between educational attainment and antisocial behavior. Antisocial characteristics involving school performance and educational attainment that transcend generations may slot individuals into social categories that restrict opportunities and reinforce antisocial characteristics. PMID:19586174

  3. μ-Calpain, calpastatin, and growth hormone receptor genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in Angus cattle selected to increase minor haplotype and allele frequencies.

    PubMed

    Tait, R G; Shackelford, S D; Wheeler, T L; King, D A; Casas, E; Thallman, R M; Smith, T P L; Bennett, G L

    2014-02-01

    Genetic marker effects and interactions are estimated with poor precision when minor marker allele frequencies are low. An Angus population was subjected to marker assisted selection for multiple years to increase divergent haplotype and minor marker allele frequencies to 1) estimate effect size and mode of inheritance for previously reported SNP on targeted beef carcass quality traits; 2) estimate effects of previously reported SNP on nontarget performance traits; and 3) evaluate tenderness SNP specific residual variance models compared to a single residual variance model for tenderness. Divergent haplotypes within µ-calpain (CAPN1), and SNP within calpastatin (CAST) and growth hormone receptor (GHR) were successfully selected to increase their frequencies. Traits evaluated were birth BW, weaning BW, final BW, fat thickness, LM area, USDA marbling score, yield grade, slice shear force (SSF), and visible and near infrared predicted slice shear force. Both CAPN1 and CAST exhibited additive (P < 0.001) modes of inheritance for SSF and neither exhibited dominance (P ≥ 0.19). Furthermore, the interaction between CAPN1 and CAST for SSF was not significant (P = 0.55). Estimated additive effects of CAPN1 (1.049 kg) and CAST (1.257 kg) on SSF were large in this study. Animals homozygous for tender alleles at both CAPN1 and CAST would have 4.61 kg lower SSF (38.6% of the mean) than animals homozygous tough for both markers. There was also an effect of CAST on yield grade (P < 0.02). The tender CAST allele was associated with more red meat yield and less trimmable fat. There were no significant effects (P ≥ 0.23) for GHR on any of the traits evaluated in this study. Furthermore, CAST specific residual variance models were found to fit significantly better (P < 0.001) than single residual variance models for SSF, with the tougher genotypes having larger residual variance. Thus, the risk of a tough steak from the undesired CAST genotype is increased through both an

  4. Genetic variation within a dominant shrub structures green and brown community assemblages.

    PubMed

    Crutsinger, Gregory M; Rodriguez-Cabal, Mariano A; Roddy, Adam B; Peay, Kabir G; Bastow, Justin L; Kidder, Allison G; Dawson, Todd E; Fine, Paul V A; Rudgers, Jennifer A

    2014-02-01

    Two rising challenges in ecology are understanding the linkages between above- and belowground components of terrestrial ecosystems and connecting genes to their ecological consequences. Here, we blend these emerging perspectives using a long-term common-garden experiment in a coastal dune ecosystem, whose dominant shrub species, Baccharis pilularis, exists as erect or prostrate architectural morphotypes. We explored variation in green (foliage-based) and brown (detritus-based) community assemblages, local ecosystem processes, and understory microclimate between the two morphs. Prostrate morphs supported more individuals, species, and different compositions of foliage arthropods, litter microarthropods, and soil bacteria than erect morphs. The magnitude of community compositional differences was maintained from crown to litter to soil. Despite showing strikingly similar responses, green and brown assemblages were associated with different underlying mechanisms. Differences in estimated shrub biomass best explained variation in the green assemblage, while understory abiotic conditions accounted for variation in the brown assemblage. Prostrate morphs produced more biomass and litter, which corresponded with their strong lateral growth in a windy environment. Compared to erect morphs, the denser canopy and thicker litter layer of prostrate morphs helped create more humid understory conditions. As a result, decomposition rates were higher under prostrate shrubs, despite prostrate litter being of poorer quality. Together, our results support the hypothesis that intraspecific genetic variation in primary producers is a key mediator of above- and belowground linkages, and that integrating the two perspectives can lead to new insights into how terrestrial communities are linked with ecosystem pools and processes.

  5. Clinical and genetic identification of a large chinese family with autosomal dominant retinitis pigmentosa.

    PubMed

    Yang, Yezhen; Tian, Di; Lee, Janet; Zeng, Jing; Zhang, Huiming; Chen, Siying; Guo, Hui; Xiong, Zhiming; Xia, Kun; Hu, Zhengmao; Luo, Jing

    2015-03-01

    Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by night blindness, progressive peripheral visual field loss, and loss of central vision. Fifty-three RP pathogenic genes are responsible for RP. Pre-mRNA processing factor 31(PRPF31) gene is the third most common cause of autosomal dominant retinitis pigmentosa (adRP), and so far more than 40 mutations in PRPF31 have been detected. To identify the underlying genetic defect in a five-generation Chinese family affected with adRP and to study the genotype-phenotype relationship of this family. Detailed clinical investigations were undertaken and peripheral blood samples were collected from 25 individuals. Microsatellite (STR) markers tightly linked to genes known to be responsible for adRP were selected for linkage analysis. Exons and adjacent splice junctions of the candidate gene were amplified and sequenced. This adRP family exhibited an incomplete penetrance of the RP phenotype. In affected individuals, age of disease onset was from infancy to 4 years of age. Typical RP features were associated with this mutation. Linkage analysis identified a maximum two-point LOD score of 3.20 with D19S418, which is close to PRPF31. A mutation PRPF31: (c.358-359 del AA) was identified by linkage analysis. A PRPF31 mutation was identified to be responsible for adRP in a large Chinese family. Our findings expand the mutation spectrum of RP in the Chinese population.

  6. (Co)variance components and genetic parameters for growth traits in Arabi sheep using different animal models.

    PubMed

    Shokrollahi, B; Baneh, H

    2012-02-08

    The objective of the present study was to estimate genetic parameters for body weight at different ages in Arabi sheep using data collected from 1999 to 2009. Investigated traits consisted of birth weight (N = 2776), weaning weight (N = 2002) and weight at six months of age (N = 1885). The data were analyzed using restricted maximum likelihood analysis, by fitting univariate and multivariate animal models. All three weight traits were significantly influenced by birth year, sex and birth type. Age of dam only significantly affected birth weight. Log-likelihood ratio tests were conducted to determine the most suitable model for each growth trait in univariate analyses. Direct and total heritability estimates for birth weight, weaning weight and weight at six months of age (based on the best model) were 0.42 and 0.16 (model 4), 0.38 and 0.13 (model 4) and 0.14 and 0.14 (model 1), respectively. Estimation of maternal heritability for birth weight and weaning weight was 0.22 and 0.18, respectively. Genetic and phenotypic correlations among these traits were positive. Phenotypic correlations among traits were low to moderate. Genetic correlations among traits were positive and higher than the corresponding phenotypic correlations. Weaning weight had a strong and significant correlation with weight at six months of age (0.99). We conclude that selection can be made in animals based on weaning weight instead of the present practice of selection based on weight at six months.

  7. Why is genetic screening for autosomal dominant disorders underutilized in families? The case of hereditary hemorrhagic telangiectasia (HHT)

    PubMed Central

    Bernhardt, Barbara A.; Zayac, Cara; Pyeritz, Reed E.

    2011-01-01

    Purpose Appropriate management of autosomal dominant disorders reduces morbidity and mortality, but relies on identifying which family members are affected. Genetic testing may identify relatives needing follow-up, but is underutilized. We conducted this study to identify barriers to genetic testing for one disorder, hereditary hemorrhagic telangiectasia (HHT). Methods Surveys and on-line discussion groups with people from HHT families. Results Multiple barriers to HHT genetic testing were identified including lack of knowledge about genetic testing, problems with access, and emotional barriers. Many participants: did not understand the rationale for HHT testing or benefits of early detection; believed that genetic testing is expensive and not covered by insurance; believed that primary care providers don’t know how to order genetic testing. Access to HHT testing is limited by distance from an HHT Center or a genetics clinic. Emotional barriers include fear of insurance discrimination; denial of having HHT or being at risk; guilt and stigma. Conclusion Voluntary disease organizations should develop and disseminate brief educational materials that describe the rationale for genetic testing, and emphasize the benefits of early detection and treatment. In addition, laboratories offering genetic testing should provide support for primary care physicians to order and interpret genetic tests. PMID:21637104

  8. Effective population size of steelhead trout: influence of variance in reproductive success, hatchery programs, and genetic compensation between life-history forms.

    PubMed

    Araki, Hitoshi; Waples, Robin S; Ardren, William R; Cooper, Becky; Blouin, Michael S

    2007-03-01

    The effective population size is influenced by many biological factors in natural populations. To evaluate their relative importance, we estimated the effective number of breeders per year (Nb) and effective population size per generation (Ne) in anadromous steelhead trout (Oncorhynchus mykiss) in the Hood River, Oregon (USA). Using demographic data and genetic parentage analysis on an almost complete sample of all adults that returned to the river over 15 years (>15,000 individuals), we estimated Nb for 13 run years and Ne for three entire generations. The results are as follows: (i) the ratio of Ne to the estimated census population size (N) was 0.17-0.40, with large variance in reproductive success among individuals being the primary cause of the reduction in Ne/N; (ii) fish from a traditional hatchery program (Htrad: nonlocal, multiple generations in a hatchery) had negative effects on Nb, not only by reducing mean reproductive success but also by increasing variance in reproductive success among breeding parents, whereas no sign of such effects was found in fish from supplementation hatchery programs (Hsupp: local, single generation in a hatchery); and (iii) Nb was relatively stable among run years, despite the widely fluctuating annual run sizes of anadromous adults. We found high levels of reproductive contribution of nonanadromous parents to anadromous offspring when anadromous run size is small, suggesting a genetic compensation between life-history forms (anadromous and nonanadromous). This is the first study showing that reproductive interaction between different life-history forms can buffer the genetic impact of fluctuating census size on Ne.

  9. Attitudes in Patients with Autosomal Dominant Polycystic Kidney Disease Toward Prenatal Diagnosis and Preimplantation Genetic Diagnosis.

    PubMed

    Swift, Oscar; Vilar, Enric; Rahman, Belinda; Side, Lucy; Gale, Daniel P

    2016-12-01

    No recommendations currently exist regarding implementation of both prenatal diagnosis and preimplantation genetic diagnosis (PGD) for autosomal dominant polycystic kidney disease (ADPKD). This study evaluated attitudes in ADPKD patients with either chronic kidney disease (CKD) stages I-IV or end-stage renal failure (ESRF) toward prenatal diagnosis and PGD. Ninety-six ADPKD patients were recruited from an outpatient clinic, wards, and dialysis units. Thirty-eight patients had ESRF and 58 had CKD stages I-IV. Participants were given an information sheet on prenatal diagnosis and PGD and subsequently completed a questionnaire. The median age of participants was 51.5 years. Seventeen percent of ADPKD patients with CKD and 18% of ADPKD patients with ESRF would consider prenatal diagnosis and termination of pregnancy for ADPKD. Fifty percent with CKD would have opted for PGD (or might consider it in the future) were it available and funded by the UK National Health Service, compared to 63% in the ESRF group (p = 0.33). Sixty-nine percent in the CKD group and 68% in the ESRF group believed that PGD should be offered to other patients. There was a spectrum of attitudes among this cohort. A proportion of patients believe that PGD should be made available to prospective parents with this disease. The discrepancy between the low proportion (17% CKD, 18% ESRF) who would consider prenatal diagnosis and termination of pregnancy and the higher number who hypothetically express an intention or wish to access PGD (50% CKD and 63% ESRF) indicates far greater acceptability for diagnostic methods that occur before embryo implantation. It is not known how the development of methods to identify patients whose renal function is likely to decline rapidly and treatments altering the natural history of ADPKD will affect these attitudes.

  10. Genetic variance contributes to ingestive processes: a survey of eleven inbred mouse strains for fat (Intralipid) intake.

    PubMed

    Lewis, Sarah R; Dym, Cheryl; Chai, Christina; Singh, Amreeta; Kest, Benjamin; Bodnar, Richard J

    2007-01-30

    Genetic variation across inbred and outbred mouse strains have been observed for intake of sweet solutions, salts, bitter tastants and a high-fat diet. Our laboratory recently reported marked strain differences in the amounts and/or percentages of kilocalories of sucrose consumed among 11 inbred and one outbred mouse strains exposed to a wide range of nine sucrose concentrations (0.0001-5%) in two-bottle 24-h preference tests. To assess whether differences in fat intake were similarly associated with genetic variation, the present study examined intake of chow, water and an emulsified fat source (Intralipid) across nine different concentrations (0.00001-5%) in the same 11 inbred and 1 outbred mouse strains using two-bottle 24-h preference tests, which controlled for Intralipid concentration presentation effects, Intralipid and water bottle positions, and measurement of kilocalorie intake consumed as Intralipid or chow. Strains displayed differential increases in Intralipid intake relative to corresponding water with significant effects observed at the seven (BALB/cJ: 0.001% threshold sensitivity), four (AKR/J, C57BL/6J, DBA/2J, SWR/J: 0.5% threshold sensitivity), three (CD-1, C57BL/10J, SJL/J: 1% threshold sensitivity) and two (A/J, CBA/J, C3H/HeJ, 129P3/J: 2% threshold sensitivity) highest concentrations. In assessing the percentage of kilocalories consumed as Intralipid, SWR/J mice consumed significantly more at the three highest concentrations to a greater degree than BALB/cJ, C57BL/6J, CD-1, C3H/HeJ, DBA/J and 129P3/J strains which in turn consumed more than A/J, AKR/J, CBA/J, C57BL/10J and SJL/J mice. Relatively strong (h2 = 0.73-0.79) heritability estimates were obtained for weight-adjusted Intralipid intake at those concentrations (0.001-1%) that displayed the largest strain-specific effects in sensitivity to Intralipid. The identification of strains with diverging abilities to regulate kilocalorie intake when presented with high Intralipid concentrations

  11. CAPN1, CAST, and DGAT1 genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in a beef cattle population selected for haplotype and allele equalization.

    PubMed

    Tait, R G; Shackelford, S D; Wheeler, T L; King, D A; Keele, J W; Casas, E; Smith, T P L; Bennett, G L

    2014-12-01

    Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC III) was subjected to marker-assisted selection for multiple years to equalize specific marker frequencies to 1) estimate effect size and mode of inheritance for previously reported SNP on targeted beef carcass quality traits (n=254), 2) estimate pleiotropic effects of previously reported SNP on nontarget performance traits (n=542 or 254), and 3) evaluate tenderness SNP specific residual variance for LM tenderness. Three haplotypes within μ-calpain (CAPN1), a SNP in calpastatin (CAST), and a dinucleotide substitution in diacylglycerol O-acyltransferase 1 (DGAT1) were successfully selected to equalize their frequencies. Traits evaluated were birth BW, weaning BW, yearling BW, final BW, dressing percent, HCW, fat thickness, LM area, USDA marbling score, yield grade, LM slice shear force (SSF), and visible and near-infrared (VISNIR)-predicted SSF. While the CAPN1 genotype effect on SSF was not significant (P=0.12), the direction and size of CAPN1 contrasts were consistent with previous research. Effects on SSF between divergent CAPN1 haplotypes (1.153 kg) and the additive effect of CAST (0.902 kg) were large, and animals homozygous for tender alleles at both CAPN1 and CAST would have 4.11 kg lower SSF (27.5% of the mean) than animals homozygous tough for both markers. Furthermore, the interaction between CAPN1 and CAST for SSF was not significant (P=0.40). There were significant effects for DGAT1 on adjusted fat thickness (P=0.02) and VISNIR-predicted SSF (P<0.001) with additive and dominance modes of inheritance (P<0.05) for both traits. Furthermore, CAST genotype specific residual variance models fit significantly better (P<0.001) than single residual variance models for SSF, with the tougher genotypes having progressively larger residual (and hence phenotypic) variances. Therefore, risk of a tough steak

  12. Crossing the threshold: gene flow, dominance and the critical level of standing genetic variation required for adaptation to novel environments.

    PubMed

    Nuismer, S L; MacPherson, A; Rosenblum, E B

    2012-12-01

    Genetic architecture plays an important role in the process of adaptation to novel environments. One example is the role of allelic dominance, where advantageous recessive mutations have a lower probability of fixation than advantageous dominant mutations. This classic observation, termed 'Haldane's sieve', has been well explored theoretically for single isolated populations adapting to new selective regimes. However, the role of dominance is less well understood for peripheral populations adapting to novel environments in the face of recurrent and maladaptive gene flow. Here, we use a combination of analytical approximations and individual-based simulations to explore how dominance influences the likelihood of adaptation to novel peripheral environments. We demonstrate that in the face of recurrent maladaptive gene flow, recessive alleles can fuel adaptation only when their frequency exceeds a critical threshold within the ancestral range.

  13. Estimates of (co)variance components and genetic parameters for body weights and first greasy fleece weight in Bharat Merino sheep.

    PubMed

    Gowane, G R; Chopra, A; Prince, L L L; Paswan, C; Arora, A L

    2010-03-01

    (Co)variance components and genetic parameters of weight at birth (BWT), weaning (3WT), 6, 9 and 12 months of age (6WT, 9WT and 12WT, respectively) and first greasy fleece weight (GFW) of Bharat Merino sheep, maintained at Central Sheep and Wool Research Institute, Avikanagar, Rajasthan, India, were estimated by restricted maximum likelihood, fitting six animal models with various combinations of direct and maternal effects. Data were collected over a period of 10 years (1998 to 2007). A log-likelihood ratio test was used to select the most appropriate univariate model for each trait, which was subsequently used in bivariate analysis. Heritability estimates for BWT, 3WT, 6WT, 9WT and 12WT and first GFW were 0.05 ± 0.03, 0.04 ± 0.02, 0.00, 0.03 ± 0.03, 0.09 ± 0.05 and 0.05 ± 0.03, respectively. There was no evidence for the maternal genetic effect on the traits under study. Maternal permanent environmental effect contributed 19% for BWT and 6% to 11% from 3WT to 9WT and 11% for first GFW. Maternal permanent environmental effect on the post-3WT was a carryover effect of maternal influences during pre-weaning age. A low rate of genetic progress seems possible in the flock through selection. Direct genetic correlations between body weight traits were positive and ranged from 0.36 between BWT and 6WT to 0.94 between 3WT and 6WT and between 6WT and 12WT. Genetic correlations of 3WT with 6WT, 9WT and 12WT were high and positive (0.94, 0.93 and 0.93, respectively), suggesting that genetic gain in post-3WT will be maintained if selection age is reduced to 3 months. The genetic correlations of GFW with live weights were 0.01, 0.16, 0.18, 0.40 and 0.32 for BWT, 3WT, 6WT, 9WT and 12WT, respectively. Correlations of permanent environmental effects of the dam across different traits were high and positive for all the traits (0.45 to 0.98).

  14. The genetic structure of Asian corn borer, Ostrinia furnacalis, populations in China: haplotype variance in northern populations and potential impact on management of resistance to transgenic maize.

    PubMed

    Li, Jing; Coates, Brad S; Kim, Kyung Seok; Bourguet, Denis; Ponsard, Sergine; He, Kanglai; Wang, Zhenying

    2014-01-01

    Asian corn borer, Ostrinia furnacalis (Guenée), is a severe pest that infests cultivated maize in the major production regions of China. Populations show genotype-by-environment variation in voltinism, such that populations with a single generation (univoltine) are fixed in Northern China where growing seasons are short. Low genetic differentiation was found among samples from 33 collection sites across China and one site from North Korea (n=1673) using variation at 6 nuclear microsatellite loci (ENA corrected global FST=0.020; P value<0.05). Analysis of molecular variance indicated that geographic region, number of generations or voltinism accounted for <0.38% of the total genetic variation at nuclear loci and was corroborated by clustering of co-ancestries among genotypes using the program STRUCTURE. In contrast, a mitochondrial haplotype network identified 4 distinct clusters, where 70.5% of samples from univoltine populations were within a single group. Univoltine populations were also placed into a unique cluster using Population Graph and Principal component analyses, which showed significant differentiation with multivoltine populations (φST=0.400; P value<0.01). This study suggests that gene flow among O. furnacalis in China may be high among regions, with the exception of northeastern localities. Haplotype variation may be due to random genetic drift resulting from partial reproductive isolation between univoltine and multivoltine O. furnacalis populations. Such reproductive isolation might impact the potential spread of alleles that confer resistance to transgenic maize in China. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. 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.

  16. Effects of single nucleotide polymorphism marker density on degree of genetic variance explained and genomic evaluation for carcass traits in Japanese Black beef cattle

    PubMed Central

    2014-01-01

    Background Japanese Black cattle are a beef breed whose meat is well known to excel in meat quality, especially in marbling, and whose effective population size is relatively low in Japan. Unlike dairy cattle, the accuracy of genomic evaluation (GE) for carcass traits in beef cattle, including this breed, has been poorly studied. For carcass weight and marbling score in the breed, as well as the extent of whole genome linkage disequilibrium (LD), the effects of equally-spaced single nucleotide polymorphisms (SNPs) density on genomic relationship matrix (G matrix), genetic variance explained and GE were investigated using the genotype data of about 40,000 SNPs and two statistical models. Results Using all pairs of two adjacent SNPs in the whole SNP set, the means of LD (r 2 ) at ranges 0–0.1, 0.1–0.2, 0.2–0.5 and 0.5–1 Mb were 0.22, 0.13, 0.10 and 0.08, respectively, and 25.7, 13.9, 10.4 and 6.4% of the r 2 values exceeded 0.3, respectively. While about 90% of the genetic variance for carcass weight estimated using all available SNPs was explained using 4,000–6,000 SNPs, the corresponding percentage for marbling score was consistently lower. With the conventional linear model incorporating the G matrix, correlation between the genomic estimated breeding values (GEBVs) obtained using 4,000 SNPs and all available SNPs was 0.99 for carcass weight and 0.98 for marbling score, with an underestimation of the former GEBVs, especially for marbling score. Conclusions The Japanese Black is likely to be in a breed group with a relatively high extent of whole genome LD. The results indicated that the degree of marbling is controlled by only QTLs with relatively small effects, compared with carcass weight, and that using at least 4,000 equally-spaced SNPs, there is a possibility of ranking animals genetically for these carcass traits in this breed. PMID:24491120

  17. Genetic correlations and little genetic variance for reaction norms may limit potential for adaptation to pollution by ionic and nanoparticulate silver in a whitefish (Salmonidae).

    PubMed

    Clark, Emily S; Pompini, Manuel; Uppal, Anshu; Wedekind, Claus

    2016-05-01

    For natural populations to adapt to anthropogenic threats, heritable variation must persist in tolerance traits. Silver nanoparticles, the most widely used engineered nanoparticles, are expected to increase in concentrations in freshwaters. Little is known about how these particles affect wild populations, and whether genetic variation persists in tolerance to permit rapid evolutionary responses. We sampled wild adult whitefish and crossed them in vitro full factorially. In total, 2896 singly raised embryos of 48 families were exposed to two concentrations (0.5 μg/L; 100 μg/L) of differently sized silver nanoparticles or ions (silver nitrate). These doses were not lethal; yet higher concentrations prompted embryos to hatch earlier and at a smaller size. The induced hatching did not vary with nanoparticle size and was stronger in the silver nitrate group. Additive genetic variation for hatching time was significant across all treatments, with no apparent environmental dependencies. No genetic variation was found for hatching plasticity. We found some treatment-dependent heritable variation for larval length and yolk volume, and one instance of additive genetic variation for the reaction norm on length at hatching. Our assessment suggests that the effects of silver exposure on additive genetic variation vary according to trait and silver source. While the long-term fitness consequences of low-level silver exposure on whitefish embryos must be further investigated to determine whether it is, in fact, detrimental, our results suggest that the evolutionary potential for adaptation to these types of pollutants may be low.

  18. Mating strategies in dominant meerkats: evidence for extra-pair paternity in relation to genetic relatedness between pair mates.

    PubMed

    Leclaire, S; Nielsen, J F; Sharp, S P; Clutton-Brock, T H

    2013-07-01

    Rates of extra-pair paternity (EPP) have frequently been associated with genetic relatedness between social mates in socially monogamous birds. However, evidence is limited in mammals. Here, we investigate whether dominant females use divorce or extra-pair paternity as a strategy to avoid the negative effects of inbreeding when paired with a related male in meerkats Suricata suricatta, a species where inbreeding depression is evident for several traits. We show that dominant breeding pairs seldom divorce, but that rates of EPP are associated with genetic similarity between mates. Although extra-pair males are no more distantly related to the female than social males, they are more heterozygous. Nevertheless, extra-pair pups are not more heterozygous than within-pair pups. Whether females benefit from EPP in terms of increased fitness of the offspring, such as enhanced survival or growth, requires further investigations.

  19. Extending GelJ for interoperability: Filling the gap in the bioinformatics resources for population genetics analysis with dominant markers.

    PubMed

    Domínguez, César; Heras, Jónathan; Mata, Eloy; Pascual, Vico; Vázquez-Garcidueñas, Maria Soledad; Vázquez-Marrufo, Gerardo

    2017-03-01

    The manual transformation of DNA fingerprints of dominant markers into the input of tools for population genetics analysis is a time-consuming and error-prone task; especially when the researcher deals with a large number of samples. In addition, when the researcher needs to use several tools for population genetics analysis, the situation worsens due to the incompatibility of data-formats across tools. The goal of this work consists in automating, from banding patterns of gel images, the input-generation for the great diversity of tools devoted to population genetics analysis. After a thorough analysis of tools for population genetics analysis with dominant markers, and tools for working with phylogenetic trees; we have detected the input requirements of those systems. In the case of programs devoted to phylogenetic trees, the Newick and Nexus formats are widely employed; whereas, each population genetics analysis tool uses its own specific format. In order to handle such a diversity of formats in the latter case, we have developed a new XML format, called PopXML, that takes into account the variety of information required by each population genetics analysis tool. Moreover, the acquired knowledge has been incorporated into the pipeline of the GelJ system - a tool for analysing DNA fingerprint gel images - to reach our automatisation goal. We have implemented, in the GelJ system, a pipeline that automatically generates, from gel banding patterns, the input of tools for population genetics analysis and phylogenetic trees. Such a pipeline has been employed to successfully generate, from thousands of banding patterns, the input of 29 population genetics analysis tools and 32 tools for managing phylogenetic trees. GelJ has become the first tool that fills the gap between gel image processing software and population genetics analysis with dominant markers, phylogenetic reconstruction, and tree editing software. This has been achieved by automating the process of

  20. Geographic Variation in Genetic Dominance of the Color Morphs of the Red-Backed Salamander, PLETHODON CINEREUS.

    PubMed

    Highton, R

    1975-06-01

    Female parent-offspring phenotypic data on color morph frequencies in the red-backed salamander, Plethodon cinereus, were obtained from two Virginia localities (164 broods from Greene County and 97 broods from Giles County). The color morph data indicate that the striped morph is genetically dominant in Giles County and recessive in Greene County. It is suggested that epistatic interaction of two or more loci is responsible for the difference between the localities.

  1. Geographic Variation in Genetic Dominance of the Color Morphs of the Red-Backed Salamander, PLETHODON CINEREUS

    PubMed Central

    Highton, Richard

    1975-01-01

    Female parent-offspring phenotypic data on color morph frequencies in the red-backed salamander, Plethodon cinereus, were obtained from two Virginia localities (164 broods from Greene County and 97 broods from Giles County). The color morph data indicate that the striped morph is genetically dominant in Giles County and recessive in Greene County. It is suggested that epistatic interaction of two or more loci is responsible for the difference between the localities. PMID:17248684

  2. Genomic analysis of dominance effects on milk production and conformation traits in Fleckvieh cattle

    PubMed Central

    2014-01-01

    Background Estimates of dominance variance in dairy cattle based on pedigree data vary considerably across traits and amount to up to 50% of the total genetic variance for conformation traits and up to 43% for milk production traits. Using bovine SNP (single nucleotide polymorphism) genotypes, dominance variance can be estimated both at the marker level and at the animal level using genomic dominance effect relationship matrices. Yield deviations of high-density genotyped Fleckvieh cows were used to assess cross-validation accuracy of genomic predictions with additive and dominance models. The potential use of dominance variance in planned matings was also investigated. Results Variance components of nine milk production and conformation traits were estimated with additive and dominance models using yield deviations of 1996 Fleckvieh cows and ranged from 3.3% to 50.5% of the total genetic variance. REML and Gibbs sampling estimates showed good concordance. Although standard errors of estimates of dominance variance were rather large, estimates of dominance variance for milk, fat and protein yields, somatic cell score and milkability were significantly different from 0. Cross-validation accuracy of predicted breeding values was higher with genomic models than with the pedigree model. Inclusion of dominance effects did not increase the accuracy of the predicted breeding and total genetic values. Additive and dominance SNP effects for milk yield and protein yield were estimated with a BLUP (best linear unbiased prediction) model and used to calculate expectations of breeding values and total genetic values for putative offspring. Selection on total genetic value instead of breeding value would result in a larger expected total genetic superiority in progeny, i.e. 14.8% for milk yield and 27.8% for protein yield and reduce the expected additive genetic gain only by 4.5% for milk yield and 2.6% for protein yield. Conclusions Estimated dominance variance was substantial

  3. Locus BoLA-DRB3 is just an ordinary site of the polygene when explaining genetic variance of somatic cell count and milk yield.

    PubMed

    Oprzadek, Jolanta; Sender, Grazyna; Pawlik, Adrianna; Lukaszewicz, Marek

    2015-11-01

    The study aimed at clarifying the problem of the hitherto contradictory results regarding usefulness of BoLA-DRB3 locus as a marker in selection against mastitis and for milk yield. Treating the BoLA-DRB3 locus effect as random was proposed in place of considering it fixed. Somatic cell counts and milk yields recorded monthly on a test day (22,424) of 619 Polish Holstein cows genotyped for BoLA-DRB3 were analysed with an animal model including a random effect for genotype at this locus. The BoLA-DRB3 alleles were defined as restriction patterns obtained with three endonucleases. Two alternative BoLA-DRB3 additive genotype (co)variance structures were constructed for 161 genotypes recorded. One was based on the allelic similarity of the genotypes resulting in element values of 0 (no common allele), 0.5 (one allele in common), and 1 (diagonal). The other considered restriction site similarity (up to 3 in 1 allele) giving element values of 0 (no common restriction sites) and then increasingly in steps of 1/6 up to 6/6 (diagonal), where the numerator represents the number of common sites between genotypes. The DRB3 variance component for the natural logarithm of somatic cell count did not exceed 0.006 of the polygenic additive component or 0.003 for milk yield. Hence, unless we fail to detect the causative site or to properly define traits being the projection of a site, the effect of the genotype at the BoLA-DRB3 locus does not explain variation in somatic cell count and milk yield at a degree expected of a genetic marker.

  4. Partial Dominance, Overdominance and Epistasis as the Genetic Basis of Heterosis in Upland Cotton (Gossypium hirsutum L.).

    PubMed

    Liang, Qingzhi; Shang, Lianguang; Wang, Yumei; Hua, Jinping

    2015-01-01

    Determination of genetic basis of heterosis may promote hybrid production in Upland cotton (Gossypium hirsutum L.). This study was designed to explore the genetic mechanism of heterosis for yield and yield components in F2: 3 and F2: 4 populations derived from a hybrid 'Xinza No. 1'. Replicated yield field trials of the progenies were conducted in 2008 and 2009. Phenotypic data analyses indicated overdominance in F1 for yield and yield components. Additive and dominance effects at single-locus level and digenic epistatic interactions at two-locus level were analyzed by 421 marker loci spanning 3814 cM of the genome. A total of 38 and 49 QTLs controlling yield and yield components were identified in F2: 3 and F2: 4 populations, respectively. Analyses of these QTLs indicated that the effects of partial dominance and overdominance contributed to heterosis in Upland cotton simultaneously. Most of the QTLs showed partial dominance whereas 13 QTLs showing overdominance in F2:3 population, and 19 QTLs showed overdominance in F2:4. Among them, 21 QTLs were common in both F2: 3 and F2: 4 populations. A large number of two-locus interactions for yield and yield components were detected in both generations. AA (additive × additive) epistasis accounted for majority portion of epistatic effects. Thirty three complementary two-locus homozygotes (11/22 and 22/11) were the best genotypes for AA interactions in terms of bolls per plant. Genotypes of double homozygotes, 11/22, 22/11 and 22/22, performed best for AD/DA interactions, while genotype of 11/12 performed best for DD interactions. These results indicated that (1) partial dominance and overdominance effects at single-locus level and (2) epistasis at two-locus level elucidated the genetic basis of heterosis in Upland cotton.

  5. Partial Dominance, Overdominance and Epistasis as the Genetic Basis of Heterosis in Upland Cotton (Gossypium hirsutum L.)

    PubMed Central

    Wang, Yumei; Hua, Jinping

    2015-01-01

    Determination of genetic basis of heterosis may promote hybrid production in Upland cotton (Gossypium hirsutum L.). This study was designed to explore the genetic mechanism of heterosis for yield and yield components in F2: 3 and F2: 4 populations derived from a hybrid ‘Xinza No. 1’. Replicated yield field trials of the progenies were conducted in 2008 and 2009. Phenotypic data analyses indicated overdominance in F1 for yield and yield components. Additive and dominance effects at single-locus level and digenic epistatic interactions at two-locus level were analyzed by 421 marker loci spanning 3814 cM of the genome. A total of 38 and 49 QTLs controlling yield and yield components were identified in F2: 3 and F2: 4 populations, respectively. Analyses of these QTLs indicated that the effects of partial dominance and overdominance contributed to heterosis in Upland cotton simultaneously. Most of the QTLs showed partial dominance whereas 13 QTLs showing overdominance in F2:3 population, and 19 QTLs showed overdominance in F2:4. Among them, 21 QTLs were common in both F2: 3 and F2: 4 populations. A large number of two-locus interactions for yield and yield components were detected in both generations. AA (additive × additive) epistasis accounted for majority portion of epistatic effects. Thirty three complementary two-locus homozygotes (11/22 and 22/11) were the best genotypes for AA interactions in terms of bolls per plant. Genotypes of double homozygotes, 11/22, 22/11 and 22/22, performed best for AD/DA interactions, while genotype of 11/12 performed best for DD interactions. These results indicated that (1) partial dominance and overdominance effects at single-locus level and (2) epistasis at two-locus level elucidated the genetic basis of heterosis in Upland cotton. PMID:26618635

  6. Variance, Genetic Control, and Spatial Phenotypic Plasticity of Morphological and Phenological Traits in Prunus spinosa and Its Large Fruited Forms (P. x fruticans)

    PubMed Central

    Vander Mijnsbrugge, Kristine; Turcsán, Arion; Depypere, Leander; Steenackers, Marijke

    2016-01-01

    growth site with the shortest growing season while interestingly, the leaf width was enlarged. Leaf size traits appeared more plastic on the long shoots compared to the short shoots, although partitioning of variance did not display a lesser genetic control. PMID:27857718

  7. Variance in age-specific sex composition of Pacific halibut catches, and comparison of statistical and genetic methods for reconstructing sex ratios

    NASA Astrophysics Data System (ADS)

    Loher, Timothy; Woods, Monica A.; Jimenez-Hidalgo, Isadora; Hauser, Lorenz

    2016-01-01

    Declines in size at age of Pacific halibut Hippoglossus stenolepis, in concert with sexually-dimorphic growth and a constant minimum commercial size limit, have led to the expectation that the sex composition of commercial catches should be increasingly female-biased. Sensitivity analyses suggest that variance in sex composition of landings may be the most influential source of uncertainty affecting current understanding of spawning stock biomass. However, there is no reliable way to determine sex at landing because all halibut are eviscerated at sea. In 2014, a statistical method based on survey data was developed to estimate the probability that fish of any given length at age (LAA) would be female, derived from the fundamental observation that large, young fish are likely female whereas small, old fish have a high probability of being male. Here, we examine variability in age-specific sex composition using at-sea commercial and closed-season survey catches, and compare the accuracy of the survey-based LAA technique to genetic markers for reconstructing the sex composition of catches. Sexing by LAA performed best for summer-collected samples, consistent with the hypothesis that the ability to characterize catches can be influenced by seasonal demographic shifts. Additionally, differences between survey and commercial selectivity that allow fishers to harvest larger fish within cohorts may generate important mismatch between survey and commercial datasets. Length-at-age-based estimates ranged from 4.7% underestimation of female proportion to 12.0% overestimation, with mean error of 5.8 ± 1.5%. Ratios determined by genetics were closer to true sample proportions and displayed less variability; estimation to within < 1% of true ratios was limited to genetics. Genetic estimation of female proportions ranged from 4.9% underestimation to 2.5% overestimation, with a mean absolute error of 1.2 ± 1.2%. Males were generally more difficult to assign than females: 6.7% of

  8. Two pedigrees segregating Duane’s retraction syndrome as a dominant trait map to the DURS2 genetic locus

    PubMed Central

    Engle, Elizabeth C.; Andrews, Caroline; Law, Krystal; Demer, Joseph L.

    2010-01-01

    PURPOSE To determine the molecular etiologies of Duane’s retraction syndrome (DRS), we are investigating its genetic bases. We have previously identified the transcription factors SALL4 and HOXA1 as the genes mutated in DRS with radial anomalies, and in DRS with deafness, vascular anomalies, and cognitive deficits, respectively. We know less, however, about the genetic etiology of DRS when it occurs in isolation, and only one genetic locus for isolated DRS, the DURS2 locus on chromosome 2, has been mapped to date. Toward the goal of identifying the DURS2 gene, we have ascertained and studied two pedigrees that segregate DRS as a dominant trait. METHODS We enrolled members of two large dominant DRS pedigrees into our ongoing study of the genetic basis of the congenital cranial dysinnervation disorders, and conducted linkage analysis to determine if their DRS phenotype maps to the DURS2 locus. RESULTS By haplotype analysis, the DRS phenotype in each family co-segregates with markers spanning the DURS2 region, and linkage analysis reveals maximum lod scores of >2, establishing that the DRS phenotype in these two pedigrees maps to the DURS2 locus. CONCLUSIONS These two pedigrees double the published pedigrees known to map to the DURS2 locus, and can thus contribute toward the search for the DURS2 gene. The affected members represent a genetically defined population of DURS2-linked DRS individuals, and hence studies of their clinical and structural features can enhance our understanding of the DURS2 phenotype, as described in the companion paper. PMID:17197532

  9. Confirmation of QTL effects and evidence of genetic dominance of honeybee defensive behavior: results of colony and individual behavioral assays.

    PubMed

    Guzmán-Novoa, Ernesto; Hunt, Greg J; Uribe, José L; Smith, Christine; Arechavaleta-Velasco, Miguel E

    2002-03-01

    The stinging and guarding components of the defensive behavior of European, Africanized, hybrid, and backcross honeybees (Apis mellifera L.) were compared and analyzed at both colony and individual levels. Hybrid and Africanized backcross colonies stung as many times as Africanized ones. European backcross colonies stung more than European bees but not as many times as Africanized or Africanized backcross colonies. The degree of dominance for the number of times that worker bees stung a leather patch was estimated to be 84.3%, 200.8%, and 145.8% for hybrid, backcross European, and backcross Africanized colonies, respectively. Additionally, both guards at the colony entrance and fast-stinging workers of one European backcross colony had a significantly higher frequency of an Africanized DNA marker allele, located near "sting1," a QTL previously implicated in stinging behavior at the colony level. However, guards and fast-stinging bees from a backcross to the Africanized parental colony did not differ from control bees in their frequency for the Africanized and European markers, as would be expected if large genetic dominance effects for sting1 exist. These results support the hypothesis that genetic dominance influences the defensive behavior of honeybees and confirm the effect of sting1 on the defensiveness of individual worker bees.

  10. Dominant feature selection for the fault diagnosis of rotary machines using modified genetic algorithm and empirical mode decomposition

    NASA Astrophysics Data System (ADS)

    Lu, Lei; Yan, Jihong; de Silva, Clarence W.

    2015-05-01

    This paper develops a novel dominant feature selection method using a genetic algorithm with a dynamic searching strategy. It is applied in the search for the most representative features in rotary mechanical fault diagnosis, and is shown to improve the classification performance with fewer features. First, empirical mode decomposition (EMD) is employed to decompose a vibration signal into intrinsic mode functions (IMFs) which represent the signal characteristic with sample oscillatory modes. Then, a modified genetic algorithm with variable-range encoding and dynamic searching strategy is used to establish relationships between optimized feature subsets and the classification performance. Next, a statistical model that uses receiver operating characteristic (ROC) is developed to select dominant features. Finally, support vector machine (SVM) is used to classify different fault patterns. Two real-world problems, rotor-unbalance vibration and bearing corrosion, are employed to evaluate the proposed feature selection scheme and fault diagnosis system. Statistical results obtained by analyzing the two problems, and comparative studies with five well-known feature selection techniques, demonstrate that the method developed in this paper can achieve improvements in identification accuracy with lower feature dimensionality. In addition, the results indicate that the proposed method is a promising tool to select dominant features in rotary machinery fault diagnosis.

  11. Previous Estimates of Mitochondrial DNA Mutation Level Variance Did Not Account for Sampling Error: Comparing the mtDNA Genetic Bottleneck in Mice and Humans

    PubMed Central

    Wonnapinij, Passorn; Chinnery, Patrick F.; Samuels, David C.

    2010-01-01

    In cases of inherited pathogenic mitochondrial DNA (mtDNA) mutations, a mother and her offspring generally have large and seemingly random differences in the amount of mutated mtDNA that they carry. Comparisons of measured mtDNA mutation level variance values have become an important issue in determining the mechanisms that cause these large random shifts in mutation level. These variance measurements have been made with samples of quite modest size, which should be a source of concern because higher-order statistics, such as variance, are poorly estimated from small sample sizes. We have developed an analysis of the standard error of variance from a sample of size n, and we have defined error bars for variance measurements based on this standard error. We calculate variance error bars for several published sets of measurements of mtDNA mutation level variance and show how the addition of the error bars alters the interpretation of these experimental results. We compare variance measurements from human clinical data and from mouse models and show that the mutation level variance is clearly higher in the human data than it is in the mouse models at both the primary oocyte and offspring stages of inheritance. We discuss how the standard error of variance can be used in the design of experiments measuring mtDNA mutation level variance. Our results show that variance measurements based on fewer than 20 measurements are generally unreliable and ideally more than 50 measurements are required to reliably compare variances with less than a 2-fold difference. PMID:20362273

  12. Genetic vasectomy-overexpression of Prm1-EGFP fusion protein in elongating spermatids causes dominant male sterility in mice.

    PubMed

    Haueter, Sabine; Kawasumi, Miyuri; Asner, Igor; Brykczynska, Urszula; Cinelli, Paolo; Moisyadi, Stefan; Bürki, Kurt; Peters, Antoine H F M; Pelczar, Pawel

    2010-03-01

    Transgenic mice are vital tools in both basic and applied research. Unfortunately, the transgenesis process as well as many other assisted reproductive techniques involving embryo transfer rely on vasectomized males to induce pseudopregnancy in surrogate mothers. Vasectomy is a surgical procedure associated with moderate pain and must be carried out under full anaesthesia by qualified personnel. Eliminating the need for vasectomy would be beneficial from the economic and animal welfare point of view. Our aim was to develop a transgene-based alternative to the surgical vasectomy procedure. We generated several transgenic mouse lines expressing a Protamine-1 (Prm1) EGFP fusion protein under the transcriptional and translational regulatory control of Prm1. Male mice from lines showing moderate transgene expression were fully fertile whereas strong overexpression of the Prm1-EGFP fusion protein resulted in complete and dominant male sterility without affecting the ability to mate and to produce copulatory plugs. Sterility was due to impaired spermatid maturation affecting sperm viability and motility. Furthermore, sperm having high Prm1-EGFP levels failed to support preimplantation embryonic development following Intracytoplasmic Sperm Injection (ICSI). The "genetic vasectomy system" was further improved by genetically linking the dominant male sterility to ubiquitous EGFP expression in the soma as an easy phenotypic marker enabling rapid genotyping of transgenic males and females. This double transgenic approach represents a reliable and cost-effective "genetic vasectomy" procedure making the conventional surgical vasectomy methodology obsolete. (c) 2010 Wiley-Liss, Inc.

  13. Within Host Evolution Selects for a Dominant Genotype of Mycobacterium tuberculosis while T Cells Increase Pathogen Genetic Diversity

    PubMed Central

    Copin, Richard; Louie, Eddie; Escuyer, Vincent; Gagneux, Sebastien; Palmer, Guy H.

    2016-01-01

    Molecular epidemiological assessments, drug treatment optimization, and development of immunological interventions all depend on understanding pathogen adaptation and genetic variation, which differ for specific pathogens. Mycobacterium tuberculosis is an exceptionally successful human pathogen, yet beyond knowledge that this bacterium has low overall genomic variation but acquires drug resistance mutations, little is known of the factors that drive its population genomic characteristics. Here, we compared the genetic diversity of the bacteria that established infection to the bacterial populations obtained from infected tissues during murine M. tuberculosis pulmonary infection and human disseminated M. bovis BCG infection. We found that new mutations accumulate during in vitro culture, but that in vivo, purifying selection against new mutations dominates, indicating that M. tuberculosis follows a dominant lineage model of evolution. Comparing bacterial populations passaged in T cell-deficient and immunocompetent mice, we found that the presence of T cells is associated with an increase in the diversity of the M. tuberculosis genome. Together, our findings put M. tuberculosis genetic evolution in a new perspective and clarify the impact of T cells on sequence diversity of M. tuberculosis. PMID:27973588

  14. Molecular analysis and genetic mapping of the rhodopsin gene in families with autosomal dominant retinitis pigmentosa

    SciTech Connect

    Bunge, S.; Wedemann, H.; Samanns, C.; Horn, M.; Schwinger, E.; Gal, A. ); David, D. ); Terwilliger, D.J.; Ott, J. ); Born, L.I. van den )

    1993-07-01

    Eighty-eight patients/families with autosomal dominant retinitis pigmentosa (RP) were screened for rhodopsin mutations. Direct sequencing revealed 13 different mutations in a total of 14 (i.e., 16%) unrelated patients. Five of these mutations (T4K, Q28H, R135G, F220C, and C222R) have not been reported so far. In addition, multipoint linkage analysis was performed on two large families with autosomal dominant RP due to rhodopsin mutations by using five DNA probes from 3q21-q24. No tight linkage was found between the rhodopsin locus (RHO) and D3S47 ([theta][sub max] = 0.08). By six-point analysis, RHO was localized in the region between D3S21 and D3S47, with a maximum lod score of 13.447 directly at D3S20. 13 refs., 1 fig., 2 tabs.

  15. The heat-shock response and the molecular basis of genetic dominance.

    PubMed

    Forsdyke, D R

    1994-03-07

    Wild-type alleles are usually dominant over deleterious mutant alleles. For a particular pair of such alleles possible populations include a wild-type homozygote population, a heterozygote population, and a mutant homozygote population. Fisher's theory that dominance would evolve by selection acting on the heterozygote subpopulation has lost ground in favour of the "dose-response" theory under which dominance is an incidental consequence of selection acting on the wild-type homozygote population. This postulates a "margin of safety" in the quantity of wild-type gene product so that heterozygotes with only one copy of a wild-type allele still have sufficient product for normal function. The selective force postulated to lead to the evolution of this margin of safety is some unspecified "extreme environment disturbance". The author has proposed elsewhere that the heat-shock response evolved very early as part of an intracellular system for self/not-self discrimination. This paper proposes that the rapid decrease in quantity of most normal proteins occurring in the heat-shock response would have provided a sufficient selective force for the margin of safety to have evolved.

  16. Genetic Mapping and Dominance of the Amber Suppressor, Su1 (supD), in Escherichia coli K-121

    PubMed Central

    Hoffman, Edwin P.; Wilhelm, Robert C.

    1970-01-01

    In this report Su1 (supD), which is known to suppress “amber” mutations by means of a specific transfer ribonucleic acid, has been mapped relative to his and uvrC and has been found to be located at about 37.5 min on the Taylor and Trotter genetic map of the Escherichia coli K-12 chromosome. In addition, Su1+ has been shown to be dominant over Su1−, which supports the idea that Su1 is the structural gene for the suppressing transfer ribonucleic acid. PMID:4912529

  17. Genetic differentiation and genetic diversity of Castanopsis (Fagaceae), the dominant tree species in Japanese broadleaved evergreen forests, revealed by analysis of EST-associated microsatellites.

    PubMed

    Aoki, Kyoko; Ueno, Saneyoshi; Kamijo, Takashi; Setoguchi, Hiroaki; Murakami, Noriaki; Kato, Makoto; Tsumura, Yoshihiko

    2014-01-01

    The broadleaved evergreen forests of the East Asian warm temperate zone are characterised by their high biodiversity and endemism, and there is therefore a need to extend our understanding of its genetic diversity and phylogeographic patterns. Castanopsis (Fagaceae) is one of the dominant tree species in the broadleaved evergreen forests of Japan. In this study we investigate the genetic diversity, genetic structure and leaf epidermal morphology of 63 natural populations of C. sieboldii and C. cuspidata, using 32 Expressed Sequence Tag associated microsatellites. The overall genetic differentiation between populations was low (GST = 0.069 in C. sieboldii and GST = 0.057 in C. cuspidata). Neighbor-joining tree and Bayesian clustering analyses revealed that the populations of C. sieboldii and C. cuspidata were genetically clearly differentiated, a result which is consistent with the morphology of their epidermal cell layers. This suggests that C. sieboldii and C. cuspidata should be treated as independent species, although intermediate morphologies are often observed, especially at sites where the two species coexist. The higher level of genetic diversity observed in the Kyushu region (for both species) and the Ryukyu Islands (for C. sieboldii) is consistent with the available fossil pollen data for Castanopsis-type broadleaved evergreen trees during the Last Glacial Maximum and suggests the existence of refugia for Castanopsis forests in southern Japan. Within the C. sieboldii populations, Bayesian clustering analyses detected three clusters, in the western and eastern parts of the main islands and in the Ryukyu Islands. The west-east genetic differentiation observed for this species in the main islands, a pattern which is also found in several plant and animal species inhabiting Castanopsis forests in Japan, suggests that they have been isolated from each other in the western and eastern populations for an extended period of time, and may imply the

  18. Genetic Differentiation and Genetic Diversity of Castanopsis (Fagaceae), the Dominant Tree Species in Japanese Broadleaved Evergreen Forests, Revealed by Analysis of EST-Associated Microsatellites

    PubMed Central

    Aoki, Kyoko; Ueno, Saneyoshi; Kamijo, Takashi; Setoguchi, Hiroaki; Murakami, Noriaki; Kato, Makoto; Tsumura, Yoshihiko

    2014-01-01

    The broadleaved evergreen forests of the East Asian warm temperate zone are characterised by their high biodiversity and endemism, and there is therefore a need to extend our understanding of its genetic diversity and phylogeographic patterns. Castanopsis (Fagaceae) is one of the dominant tree species in the broadleaved evergreen forests of Japan. In this study we investigate the genetic diversity, genetic structure and leaf epidermal morphology of 63 natural populations of C. sieboldii and C. cuspidata, using 32 Expressed Sequence Tag associated microsatellites. The overall genetic differentiation between populations was low (GST = 0.069 in C. sieboldii and GST = 0.057 in C. cuspidata). Neighbor-joining tree and Bayesian clustering analyses revealed that the populations of C. sieboldii and C. cuspidata were genetically clearly differentiated, a result which is consistent with the morphology of their epidermal cell layers. This suggests that C. sieboldii and C. cuspidata should be treated as independent species, although intermediate morphologies are often observed, especially at sites where the two species coexist. The higher level of genetic diversity observed in the Kyushu region (for both species) and the Ryukyu Islands (for C. sieboldii) is consistent with the available fossil pollen data for Castanopsis-type broadleaved evergreen trees during the Last Glacial Maximum and suggests the existence of refugia for Castanopsis forests in southern Japan. Within the C. sieboldii populations, Bayesian clustering analyses detected three clusters, in the western and eastern parts of the main islands and in the Ryukyu Islands. The west-east genetic differentiation observed for this species in the main islands, a pattern which is also found in several plant and animal species inhabiting Castanopsis forests in Japan, suggests that they have been isolated from each other in the western and eastern populations for an extended period of time, and may imply the

  19. Dominant Enhancers of Egfr in Drosophila Melanogaster: Genetic Links between the Notch and Egfr Signaling Pathways

    PubMed Central

    Price, J. V.; Savenye, E. D.; Lum, D.; Breitkreutz, A.

    1997-01-01

    The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed an F(1) screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context. PMID:9383058

  20. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum.

    PubMed Central

    Campion, D; Dumanchin, C; Hannequin, D; Dubois, B; Belliard, S; Puel, M; Thomas-Anterion, C; Michon, A; Martin, C; Charbonnier, F; Raux, G; Camuzat, A; Penet, C; Mesnage, V; Martinez, M; Clerget-Darpoux, F; Brice, A; Frebourg, T

    1999-01-01

    To determine the prevalence of early-onset Alzheimer disease (EOAD) and of autosomal dominant forms of EOAD (ADEOAD), we performed a population-based study in the city of Rouen (426,710 residents). EOAD was defined as onset of disease at age <61 years, and ADEOAD was defined as the occurrence of at least three EOAD cases in three generations. Using these stringent criteria, we calculated that the EOAD and ADEOAD prevalences per 100,000 persons at risk were 41.2 and 5.3, respectively. We then performed a mutational analysis of the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) in 34 families with ADEOAD ascertained in France. In 19 (56%) of these families, we identified 16 distinct PSEN1 missense mutations, including 4 (Thr147Ile, Trp165Cys, Leu173Trp, and Ser390Ile) not reported elsewhere. APP mutations, including a novel mutation located at codon 715, were identified in 5 (15%) of the families. In the 10 remaining ADEOAD families and in 9 additional autosomal dominant Alzheimer disease families that did not fulfill the strict criteria for ADEOAD, no PSEN1, PSEN2, or APP mutation was identified. These results show that (1) PSEN1 and APP mutations account for 71% of ADEOAD families and (2) nonpenetrance at age <61 years is probably infrequent for PSEN1 or APP mutations. PMID:10441572

  1. Peptide-dominated membranes preceding the genetic takeover by RNA: latest thinking on a classic controversy.

    PubMed

    Egel, Richard

    2009-10-01

    It is commonly presumed that abiotic membranes were colonized by proteins later on. Yet, hydrophobic peptides could have formed primordial protein-dominated membranes on their own. In a metabolism-first context, "autocatalytically closed" sets of statistical peptides could organize a self-maintaining protometabolism, assisted by an unfolding set of ribotide-related cofactors. Pairwise complementary ribotide cofactors may have formed docking guides for stochastic peptide formation, before replicating RNA emerged from this subset. Tidally recurring wet-drying cycles and an early onset of photosynthetic activities are considered most likely to meet the thermodynamic requirements. Conceivably, the earliest peptide-dominated vesicles were engaged in light harvesting, together with isoprenoid-tethered pigments, rather than providing an external boundary. Early on, the bulk of prebiotic organic matter can have formed a contiguous layer covering the mineral sediment, held in place by colloidal coherence of a hydrogel matrix. This unconventional scenario assumes a late onset of cellular individualization - perhaps from within, resembling endosporogenesis.

  2. Further evidence for a locus for autosomal dominant juvenile glaucoma on chromosome 1q and evidence for genetic heterogeneity

    SciTech Connect

    Wiggs, J.; Paglinauan, C.; Stawski, S.

    1994-09-01

    Glaucoma is a term used to describe a group of disorders which have in common a characteristic degeneration of the optic nerve associated with typical visual field defects and usually associated with elevated intraocular pressure. Two percent of white Americans and 6-10% of black Americans are affected by the disease. Compelling data indicate that susceptibility to many types of glaucoma is inherited. Hereditary juvenile glaucoma is one form of glaucoma that develops in children and is inherited as an autosomal dominant trait with high penetrance. Using a single large Caucasian pedigree affected with autosomal dominant juvenile glaucoma, Sheffield discovered positive linkage to a group of markers that map to a 30 cM region on the long arm of chromosome 1 (1q21-q31). We have subsequently identified three unrelated Caucasian pedigrees affected with autosomal dominant juvenile glaucoma that also demonstrate linkage to this region on chromosome 1, with the highest combined lod score of 5.12 at theta = .05 for marker D1S218. The identification of critical recombinant individuals in our three pedigrees has allowed us to further localize the disease gene to a 12 cM region between markers D1S242 and D1S431. In addition, we have identified several pedigrees which do not demonstrate linkage to chromosome 1q, including a black family affected with autosomal dominant juvenile glaucoma that is indistinguishable clinically from the disorder affecting the caucasian pedigrees and three pedigrees affected with pigmentary dispersion syndrome, a form of glaucoma that also affects the juvenile population and is also inherited as an autosomal dominant trait. These findings provide evidence for genetic heterogeneity in juvenile glaucoma.

  3. Structure and stability of genetic variance-covariance matrices: A Bayesian sparse factor analysis of transcriptional variation in the three-spined stickleback.

    PubMed

    Siren, J; Ovaskainen, O; Merilä, J

    2017-07-26

    The genetic variance-covariance matrix (G) is a quantity of central importance in evolutionary biology due to its influence on the rate and direction of multivariate evolution. However, the predictive power of empirically estimated G-matrices is limited for two reasons. First, phenotypes are high-dimensional, whereas traditional statistical methods are tuned to estimate and analyse low-dimensional matrices. Second, the stability of G to environmental effects and over time remains poorly understood. Using Bayesian sparse factor analysis (BSFG) designed to estimate high-dimensional G-matrices, we analysed levels variation and covariation in 10,527 expressed genes in a large (n = 563) half-sib breeding design of three-spined sticklebacks subject to two temperature treatments. We found significant differences in the structure of G between the treatments: heritabilities and evolvabilities were higher in the warm than in the low-temperature treatment, suggesting more and faster opportunity to evolve in warm (stressful) conditions. Furthermore, comparison of G and its phenotypic equivalent P revealed the latter is a poor substitute of the former. Most strikingly, the results suggest that the expected impact of G on evolvability-as well as the similarity among G-matrices-may depend strongly on the number of traits included into analyses. In our results, the inclusion of only few traits in the analyses leads to underestimation in the differences between the G-matrices and their predicted impacts on evolution. While the results highlight the challenges involved in estimating G, they also illustrate that by enabling the estimation of large G-matrices, the BSFG method can improve predicted evolutionary responses to selection. © 2017 John Wiley & Sons Ltd.

  4. Estimation of epistatic variance components and heritability in founder populations and crosses.

    PubMed

    Young, Alexander I; Durbin, Richard

    2014-12-01

    Genetic association studies have explained only a small proportion of the estimated heritability of complex traits, leaving the remaining heritability "missing." Genetic interactions have been proposed as an explanation for this, because they lead to overestimates of the heritability and are hard to detect. Whether this explanation is true depends on the proportion of variance attributable to genetic interactions, which is difficult to measure in outbred populations. Founder populations exhibit a greater range of kinship than outbred populations, which helps in fitting the epistatic variance. We extend classic theory to founder populations, giving the covariance between individuals due to epistasis of any order. We recover the classic theory as a limit, and we derive a recently proposed estimator of the narrow sense heritability as a corollary. We extend the variance decomposition to include dominance. We show in simulations that it would be possible to estimate the variance from pairwise interactions with samples of a few thousand from strongly bottlenecked human founder populations, and we provide an analytical approximation of the standard error. Applying these methods to 46 traits measured in a yeast (Saccharomyces cerevisiae) cross, we estimate that pairwise interactions explain 10% of the phenotypic variance on average and that third- and higher-order interactions explain 14% of the phenotypic variance on average. We search for third-order interactions, discovering an interaction that is shared between two traits. Our methods will be relevant to future studies of epistatic variance in founder populations and crosses. Copyright © 2014 by the Genetics Society of America.

  5. Genetic differentiation in spite of high gene flow in the dominant rainforest tree of southeastern Australia, Nothofagus cunninghamii.

    PubMed

    Duncan, C J; Worth, J R P; Jordan, G J; Jones, R C; Vaillancourt, R E

    2016-01-01

    Nothofagus cunninghamii is a long-lived, wind-pollinated tree species that dominates the cool temperate rainforests of southeastern Australia. The species' distribution is more or less continuous in western Tasmania but is fragmented elsewhere. However, it is unknown whether this fragmentation has affected the species' genetic architecture. Thus, we examined N. cunninghamii using 12 nuclear microsatellites and 633 individuals from 18 populations spanning the species' natural range. Typical of wind-pollinated trees, there was low range-wide genetic structure (FST=0.04) consistent with significant gene flow across most of the species' range. However, gene flow was not high enough to overcome the effects of drift across some disjunctions. Victorian populations (separated from Tasmania by the 240 km wide Bass Strait) formed a genetic group distinct from Tasmanian populations, had lower diversity (mean allelic richness (Ar)=5.4 in Victoria versus 6.9 in Tasmania) and were significantly more differentiated from one another than those in Tasmania (FST=0.045 in Victoria versus 0.012 in Tasmania). Evidence for bottlenecking was found in small populations that were at least 20 km from other populations. Interestingly, we found little divergence in microsatellite markers between the extremes of genetically based morphological and physiological altitudinal clines suggesting adaptive differentiation is strongly driven by selection because it is likely to be occurring in the presence of gene flow. Even though the cool temperate rainforests of Australia are highly relictual, the species is relatively robust to population fragmentation due to high levels of genetic diversity and gene flow, especially in Tasmania.

  6. Genetic differentiation in spite of high gene flow in the dominant rainforest tree of southeastern Australia, Nothofagus cunninghamii

    PubMed Central

    Duncan, C J; Worth, J R P; Jordan, G J; Jones, R C; Vaillancourt, R E

    2016-01-01

    Nothofagus cunninghamii is a long-lived, wind-pollinated tree species that dominates the cool temperate rainforests of southeastern Australia. The species' distribution is more or less continuous in western Tasmania but is fragmented elsewhere. However, it is unknown whether this fragmentation has affected the species' genetic architecture. Thus, we examined N. cunninghamii using 12 nuclear microsatellites and 633 individuals from 18 populations spanning the species' natural range. Typical of wind-pollinated trees, there was low range-wide genetic structure (FST=0.04) consistent with significant gene flow across most of the species' range. However, gene flow was not high enough to overcome the effects of drift across some disjunctions. Victorian populations (separated from Tasmania by the 240 km wide Bass Strait) formed a genetic group distinct from Tasmanian populations, had lower diversity (mean allelic richness (Ar)=5.4 in Victoria versus 6.9 in Tasmania) and were significantly more differentiated from one another than those in Tasmania (FST=0.045 in Victoria versus 0.012 in Tasmania). Evidence for bottlenecking was found in small populations that were at least 20 km from other populations. Interestingly, we found little divergence in microsatellite markers between the extremes of genetically based morphological and physiological altitudinal clines suggesting adaptive differentiation is strongly driven by selection because it is likely to be occurring in the presence of gene flow. Even though the cool temperate rainforests of Australia are highly relictual, the species is relatively robust to population fragmentation due to high levels of genetic diversity and gene flow, especially in Tasmania. PMID:26350630

  7. The effects of locus number, genetic divergence, and genotyping error on the utility of dominant markers for hybrid identification

    PubMed Central

    Sovic, Michael G; Kubatko, Laura S; Fuerst, Paul A

    2014-01-01

    In surveys of hybrid zones, dominant genetic markers are often used to identify individuals of hybrid origin and assign these individuals to one of several potential hybrid classes. Quantitative analyses that address the statistical power of dominant markers in such inference are scarce. In this study, dominant genotype data were simulated to evaluate the effects of, first, the number of loci analyzed, second, the magnitude of differentiation between the markers scored in the groups that are hybridizing, and third, the level of genotyping error associated with the data when assigning individuals to various parental and hybrid categories. The overall performance of the assignment methods was relatively modest at the lowest level of divergence examined (Fst ˜ 0.4), but improved substantially at higher levels of differentiation (Fst ˜ 0.67 or 0.8). The effect of genotyping error was dependent on the level of divergence between parental taxa, with larger divergences tempering the effects of genotyping error. These results highlight the importance of considering the effects of each of the variables when assigning individuals to various parental and hybrid categories, and can help guide decisions regarding the number of loci employed in future hybridization studies to achieve the power and level of resolution desired. PMID:24634730

  8. Statistics of Scientific Procedures on Living Animals 2012: another increase in experimentation - genetically-altered animals dominate again.

    PubMed

    Hudson-Shore, Michelle

    2013-09-01

    The Annual Statistics of Scientific Procedures on Living Animals Great Britain 2012 reveal that the level of animal experimentation in Great Britain continues to rise, with just over 4.1 million procedures being started in that year. Despite the previous year's indication that the dominance of the production and use of genetically-altered (GA, i.e. genetically-modified animals plus animals with harmful genetic defects) animal might be abating, it returned with a vengeance in 2012. Breeding increased from 43% to 48% of all procedures, and GA animals were involved in 59% of all the procedures. Indeed, if the breeding of these animals were removed from the statistics, the total number of procedures would actually decline by 2%. In order to honour their pledge to reduce animal use in science, the Coalition Government will have to address this issue. The general trends in the species used, and the numbers and types of procedures, are also reviewed. Finally, forthcoming changes to the statistics are discussed.

  9. Autosomal dominant retinitis pigmentosa: no evidence for nonallelic genetic heterogeneity on 3q.

    PubMed Central

    Kumar-Singh, R; Wang, H; Humphries, P; Farrar, G J

    1993-01-01

    Since the initial report of linkage of autosomal dominant retinitis pigmentosa (adRP) to the long arm of chromosome 3, several mutations in the gene encoding rhodopsin, which also maps to 3q, have been reported in adRP pedigrees. However, there has been some discussion as to the possibility of a second adRP locus on 3q. This suggestion has important diagnostic and research implications and must raise doubts about the usefulness of linked markers for reliable diagnosis of RP patients. In order to address this issue we have performed an admixture test (A-test) on 10 D3S47-linked adRP pedigrees and have found a likelihood ratio of heterogeneity versus homogeneity of 4.90. We performed a second A-test, combining the data from all families with known rhodopsin mutations. In this test we obtained a reduced likelihood ratio of heterogeneity versus homogeneity, of 1.0. On the basis of these statistical analyses we have found no significant support for two adRP loci on chromosome 3q. Furthermore, using 40 CEPH families, we have localized the rhodopsin gene to the D3S47-D3S20 interval, with a maximum lod score (Zm) of 20 and have found that the order qter-D3S47-rhodopsin-D3S20-cen is significantly more likely than any other order. In addition, we have mapped (Zm = 30) the microsatellite marker D3S621 relative to other loci in this region of the genome. PMID:8430695

  10. Autosomal dominant retinitis pigmentosa: No evidence for nonallelic genetic heterogeneity on 3q

    SciTech Connect

    Kumar-Singh, R.; He Wang; Humphries, P.; Farrar, G.J. )

    1993-02-01

    Since the initial report of linkage of autosomal dominant retinitis pigmentosa (adRP) to the long arm of chromosome 3, several mutations in the gene encoding rhodopsin, which also maps to 3q, have been reported in adRP pedigrees. However, there has been some discussion as to the possibility of a second adRP locus on 3q. This suggestion has important diagnostic and research implications and must raise doubts about the usefulness of linked markers for reliable diagnosis of RP patients. In order to address this issue the authors have performed an admixture test (A-test) on 10 D3S47-linked adRP pedigrees and have found a likelihood ratio of heterogeneity versus homogeneity of 4.90. They performed a second A-test, combining the data from all families with known rhodopsin mutations. In this test they obtained a reduced likelihood ratio of heterogeneity versus homogeneity, of 1.0. On the basis of these statistical analyses they have found no significant support for two adRP loci on chromosome 3q. Furthermore, using 40 CEPH families, they have localized the rhodopsin gene to the D3S47-D3S20 interval, with a maximum lod score (Z[sub m]) of 20 and have found that the order qter-D3S47-rhodopsin-D3S20-cen is significantly more likely than any other order. In addition, they have mapped (Z[sub m] = 30) the microsatellite marker D3S621 relative to other loci in this region of the genome. 27 refs., 3 figs., 3 tabs.

  11. Evolutionary Dynamics Analysis of Human Metapneumovirus Subtype A2: Genetic Evidence for Its Dominant Epidemic

    PubMed Central

    Li, Jianguo; Ren, Lili; Guo, Li; Xiang, Zichun; Paranhos-Baccalà, Gláucia; Vernet, Guy; Wang, Jianwei

    2012-01-01

    Human metapneumovirus (hMPV) is a respiratory viral pathogen in children worldwide. hMPV is divided into four subtypes: hMPV_A1, hMPV_A2, hMPV_B1, and hMPV_B2. hMPV_A2 can be further divided into hMPV_A2a and A2b based on phylogenetic analysis. The typical prevalence pattern of hMPV involves a shift of the predominant subtype within one or two years. However, hMPV_A2, in particular hMPV_A2b, has circulated worldwide with a several years long term high epidemic. To study this distinct epidemic behavior of hMPV_A2, we analyzed 294 sequences of partial G genes of the virus from different countries. Molecular evolutionary data indicates that hMPV_A2 evolved toward heterogeneity faster than the other subtypes. Specifically, a Bayesian skyline plot analysis revealed that hMPV_A2 has undergone a generally upward fluctuation since 1997, whereas the other subtypes experienced only one upward fluctuation. Although hMPV_A2 showed a lower value of mean dN/dS than the other subtypes, it had the largest number of positive selection sites. Meanwhile, various styles of mutation were observed in the mutation hotspots of hMPV_A2b. Bayesian phylogeography analysis also revealed two fusions of diffusion routes of hMPV_A2b in India (June 2006) and Beijing, China (June 2008). Sequences of hMPV_A2b retrieved from GenBank boosted simultaneously with the two fusions respectively, indicating that fusion of genetic transmission routes from different regions improved survival of hMPV_A2. Epidemic and evolutionary dynamics of hMPV_A2b were similar to those of hMPV_A2. Overall, our findings provide important molecular insights into hMPV epidemics and viral variation, and explain the occurrence of an atypical epidemic of hMPV_A2, particularly hMPV_A2b. PMID:22479641

  12. The first Indian-origin family with genetically proven cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

    PubMed

    Yadav, Sunaina; Bentley, Paul; Srivastava, Padma; Prasad, Kameshwar; Sharma, Pankaj

    2013-01-01

    We report the first family of Indian origin known to be affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Seventeen members of the family spanning 3 generations had neurologic syndromes compatible with CADASIL, of whom 5 were genetically confirmed carriers of the Notch3 gene R141C mutation in exon 4 (421(C→T) and 141(Cys→Arg)). Our report highlights that CADASIL not only occurs sporadically in South Asians, but also may account for stroke in South Asians with a strong family history. Furthermore, the similarity of clinical presentations described here to those typical for Caucasian case series suggests that the CADASIL phenotype is preserved across racial groups.

  13. Genetic linkage of autosomal dominant juvenile glaucoma to 1q21-q31 in three affected pedigrees

    SciTech Connect

    Wiggs, J.L.; Paglinauan, C.; Fine, A.; Sporn, C.; Lou, D. ); Haines, J.L. )

    1994-05-15

    Glaucoma is a common disorder that results in irreversible damage to the optic nerve, causing absolute blindness. In most cases, the optic nerve is damaged by an elevation of the intraocular pressure that is the result of an abnormality in the normal drainage function of the trabecular meshwork. A family history of glaucoma is an important risk factor for the disease, suggesting that genetic defects predisposing to this condition are likely. Three pedigrees segregating an autosomal dominant juvenile glaucoma demonstrated significant linkage to a group of closely spaced markers on chromosome 1. These results confirm the initial mapping of this disease and suggest that this region on chromosome 1 contains an important locus for juvenile glaucoma. The authors describe recombination events that improve the localization of the responsible gene, reducing the size of the candidate region from 30 to 12 cM. 27 refs., 2 figs., 1 tab.

  14. A non-dominated sorting genetic algorithm for a bi-objective pick-up and delivery problem

    NASA Astrophysics Data System (ADS)

    Velasco, N.; Dejax, P.; Guéret, C.; Prins, C.

    2012-03-01

    Some companies must transport their personnel within facilities. This is especially the case for oil companies that use helicopters to transport engineers, technicians and assistant personnel from platform to platform. This operation has the potential to become expensive if the transportation routes are not correctly planned and provide a bad quality of service. Here this issue is modelled as a pick-up and delivery problem where a set of transportation requests should be scheduled in routes, minimizing the total transportation cost while the most urgent requests are satisfied by priority. To solve the problem, a method based on a Non-dominated Sorting Genetic Algorithm (NSGA-II) is proposed. This algorithm is tested on both randomly generated and real instances provided by a petroleum company. The results show that the proposed algorithm improves the best-known solutions.

  15. A Nonsyndromic Autosomal Dominant Oligodontia with A Novel Mutation of PAX9-A Clinical and Genetic Report

    PubMed Central

    Prasanna, Praveen; Athimuthu, Anantharaj; Bhat, Prasanna Kumar; Puttashamachari, Yogish

    2015-01-01

    Oligodontia is congenital absence of one or more teeth which has familial abnormality and attributable to various mutations or polymorphisms of genes often associated with malformative syndromes. The present case reports a rare case of non syndromic oligodontia in an 8-year-old girl with missing 14 permanent teeth excluding third molars in mixed dentition. It is a rare finding which has not been frequently documented in Indian children. Mutations in MSX1 and PAX9 have been described in families in which inherited oligodontia characteristically involves permanent incisors, lateral incisors, premolars and molars. Our study analysed one large family with dominantly inherited oligodontia clinically and genetically. This phonotype is distinct from oligodontia phenotypes associated with mutations in PAX9. Sequencing of the PAX9 revealed a novel mutation in the paired domain of the molecule. The multiple sequence alignment and SNP analysis of the PAX9 exon 2 revealed two mutations. PMID:26266225

  16. BRAIN ABNORMALITIES IN YOUNG ADULTS AT GENETIC RISK FOR AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE: A CROSS-SECTIONAL STUDY

    PubMed Central

    Reiman, Eric M.; Quiroz, Yakeel T.; Fleisher, Adam S.; Chen, Kewei; Velez-Pardo, Carlos; Jimenez-Del-Rio, Marlene; Fagan, Anne M.; Shah, Aarti R.; Alvarez, Sergio; Arbelaez, Andrés; Giraldo, Margarita; Acosta-Baena, Natalia; Sperling, Reisa A.; Dickerson, Brad; Stern, Chantal E.; Tirado, Victoria; Munoz, Claudia; Reiman, Rebecca A.; Huentelman, Matthew J.; Alexander, Gene E.; Langbaum, Jessica B.S.; Kosik, Kenneth S.; Tariot, Pierre N.; Lopera, Francisco

    2013-01-01

    Summary Background We previously detected functional brain imaging abnormalities in young adults at genetic risk for late-onset Alzheimer’s disease (AD). Here, we sought to characterize structural and functional magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and plasma biomarker abnormalities in young adults at risk for autosomal dominant early-onset AD. Biomarker measurements were characterized and compared in presenilin 1 (PSEN1) E280A mutation carriers and non-carriers from the world’s largest known autosomal dominant early-onset AD kindred, more than two decades before the carriers’ estimated median age of 44 at the onset of mild cognitive impairment (MCI) and before their estimated age of 28 at the onset of amyloid-β (Aβ) plaque deposition. Methods Biomarker data for this cross-sectional study were acquired in Antioquia, Colombia between July and August, 2010. Forty-four participants from the Colombian Alzheimer’s Prevention Initiative (API) Registry had structural MRIs, functional MRIs during associative memory encoding/novel viewing and control tasks, and cognitive assessments. They included 20 mutation carriers and 24 non-carriers, who were cognitively normal, 18-26 years old and matched for their gender, age, and educational level. Twenty of the participants, including 10 mutation carriers and 10 non-carriers, had lumbar punctures and venipunctures. Primary outcome measures included task-dependent hippocampal/parahippocampal activations and precuneus/posterior cingulate deactivations, regional gray matter reductions, CSF Aβ1-42, total tau and phospho-tau181 levels, and plasma Aβ1-42 levels and Aβ1-42/Aβ1-40 ratios. Structural and functional MRI data were compared using automated brain mapping algorithms and AD-related search regions. Cognitive and fluid biomarkers were compared using Mann-Whitney tests. Findings The mutation carrier and non-carrier groups did not differ significantly in their dementia ratings, neuropsychological

  17. Multi-objective optimal design of magnetorheological engine mount based on an improved non-dominated sorting genetic algorithm

    NASA Astrophysics Data System (ADS)

    Zheng, Ling; Duan, Xuwei; Deng, Zhaoxue; Li, Yinong

    2014-03-01

    A novel flow-mode magneto-rheological (MR) engine mount integrated a diaphragm de-coupler and the spoiler plate is designed and developed to isolate engine and the transmission from the chassis in a wide frequency range and overcome the stiffness in high frequency. A lumped parameter model of the MR engine mount in single degree of freedom system is further developed based on bond graph method to predict the performance of the MR engine mount accurately. The optimization mathematical model is established to minimize the total of force transmissibility over several frequency ranges addressed. In this mathematical model, the lumped parameters are considered as design variables. The maximum of force transmissibility and the corresponding frequency in low frequency range as well as individual lumped parameter are limited as constraints. The multiple interval sensitivity analysis method is developed to select the optimized variables and improve the efficiency of optimization process. An improved non-dominated sorting genetic algorithm (NSGA-II) is used to solve the multi-objective optimization problem. The synthesized distance between the individual in Pareto set and the individual in possible set in engineering is defined and calculated. A set of real design parameters is thus obtained by the internal relationship between the optimal lumped parameters and practical design parameters for the MR engine mount. The program flowchart for the improved non-dominated sorting genetic algorithm (NSGA-II) is given. The obtained results demonstrate the effectiveness of the proposed optimization approach in minimizing the total of force transmissibility over several frequency ranges addressed.

  18. Characterization of macular structure and function in two Swedish families with genetically identified autosomal dominant retinitis pigmentosa

    PubMed Central

    Abdulridha-Aboud, Wissam; Kjellström, Ulrika; Andréasson, Sten

    2016-01-01

    Purpose To study the phenotype in two families with genetically identified autosomal dominant retinitis pigmentosa (adRP) focusing on macular structure and function. Methods Clinical data were collected at the Department of Ophthalmology, Lund University, Sweden, for affected and unaffected family members from two pedigrees with adRP. Examinations included optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Molecular genetic screening was performed for known mutations associated with adRP. Results The mode of inheritance was autosomal dominant in both families. The members of the family with a mutation in the PRPF31 (p.IVS6+1G>T) gene had clinical features characteristic of RP, with severely reduced retinal rod and cone function. The degree of deterioration correlated well with increasing age. The mfERG showed only centrally preserved macular function that correlated well with retinal thinning on OCT. The family with a mutation in the RHO (p.R135W) gene had an extreme intrafamilial variability of the phenotype, with more severe disease in the younger generations. OCT showed pathology, but the degree of morphological changes was not correlated with age or with the mfERG results. The mother, with a de novo mutation in the RHO (p.R135W) gene, had a normal ffERG, and her retinal degeneration was detected merely with the reduced mfERG. Conclusions These two families demonstrate the extreme inter- and intrafamilial variability in the clinical phenotype of adRP. This is the first Swedish report of the clinical phenotype associated with a mutation in the PRPF31 (p.IVS6+1G>T) gene. Our results indicate that methods for assessment of the central retinal structure and function may improve the detection and characterization of the RP phenotype. PMID:27212874

  19. Estimation of Epistatic Variance Components and Heritability in Founder Populations and Crosses

    PubMed Central

    Young, Alexander I.; Durbin, Richard

    2014-01-01

    Genetic association studies have explained only a small proportion of the estimated heritability of complex traits, leaving the remaining heritability “missing.” Genetic interactions have been proposed as an explanation for this, because they lead to overestimates of the heritability and are hard to detect. Whether this explanation is true depends on the proportion of variance attributable to genetic interactions, which is difficult to measure in outbred populations. Founder populations exhibit a greater range of kinship than outbred populations, which helps in fitting the epistatic variance. We extend classic theory to founder populations, giving the covariance between individuals due to epistasis of any order. We recover the classic theory as a limit, and we derive a recently proposed estimator of the narrow sense heritability as a corollary. We extend the variance decomposition to include dominance. We show in simulations that it would be possible to estimate the variance from pairwise interactions with samples of a few thousand from strongly bottlenecked human founder populations, and we provide an analytical approximation of the standard error. Applying these methods to 46 traits measured in a yeast (Saccharomyces cerevisiae) cross, we estimate that pairwise interactions explain 10% of the phenotypic variance on average and that third- and higher-order interactions explain 14% of the phenotypic variance on average. We search for third-order interactions, discovering an interaction that is shared between two traits. Our methods will be relevant to future studies of epistatic variance in founder populations and crosses. PMID:25326236

  20. Eco-geographical diversity of cowpea bradyrhizobia in Senegal is marked by dominance of two genetic types.

    PubMed

    Wade, Tatiana Krasova; Le Quéré, Antoine; Laguerre, Gisèle; N'zoué, Angèle; Ndione, Jacques-André; Dorego, Francis; Sadio, Omar; Ndoye, Ibrahima; Neyra, Marc

    2014-03-01

    The genetic diversity of native cowpea rhizobia originating from 60 sites across four eco-geographic zones in Senegal was studied. More than 300 cowpea nodules were analyzed by PCR-RFLP of the 16S-23S rDNA InterGenic Spacer region (IGS). Alignments of IGS sequences indicated that all genotypes were grouping within the Bradyrhizobium genus. The geographical distribution showed that apart from five IGS types, the others were specifically found in only one region. The diversity was significantly higher in the Senegal River valley zone, which presents lower mean annual rainfalls and slightly alkaline soils. Interestingly, two IGS types dominated the Senegalese rhizobial collection, one IGS type (VI) was found on more than half of the nodules collected in the northern Senegal River valley while another IGS type (I) was recovered from the great majority of nodules in the three other regions sampled. Two representative strains from each of these two dominant types were isolated and further analyzed. Multi Locus Sequence Analyses using 6 housekeeping genes indicate that they belong to a new Bradyrhizobium species closely related to B. yuanmingense. Phylogenetic analyses of 2 symbiotic genes nodC and nifH show that they are clustered with B. arachidis. Physiological tests on these strains have shown that under laboratory conditions, the growth of the IGS type VI strains was slightly less affected by a higher osmotic strength in the medium and to alkaline pH, which corroborates the soil physico-chemical parameters.

  1. Immunological loss-of-function due to genetic gain-of-function in humans: autosomal dominance of the third kind

    PubMed Central

    Quartier, Pierre

    2015-01-01

    All the human primary immunodeficiencies (PIDs) recognized as such in the 1950s were Mendelian traits and, whether autosomal or X-linked, displayed recessive inheritance. The first autosomal dominant (AD) PID, hereditary angioedema, was recognized in 1963. However, since the first identification of autosomal recessive (AR), X-linked recessive (XR) and AD PID-causing genes in 1985 (ADA; severe combined immunodeficiency), 1986 (CYBB, chronic granulomatous disease) and 1989 (SERPING1; hereditary angioedema), respectively, the number of genetically defined AD PIDs has increased more rapidly than that of any other type of PID. AD PIDs now account for 61 of the 260 known conditions (23%). All known AR PIDs are caused by alleles with some loss-of-function (LOF). A single XR PID is caused by gain-of-function (GOF) mutations (WASP-related neutropenia, 2001). In contrast, only 44 of 61 AD defects are caused by LOF alleles, which exert dominance by haploinsufficiency or negative dominance. Since 2003, up to 17 AD disorders of the third kind, due to GOF alleles, have been described. Remarkably, six of the 17 genes concerned also harbor monoallelic (STAT3), biallelic (C3, CFB, CARD11, PIK3R1) or both monoallelic and biallelic (STAT1) LOF alleles in patients with other clinical phenotypes. Most heterozygous GOF alleles result in auto-inflammation, auto-immunity, or both, with a wide range of immunological and clinical forms. Some also underlie infections and, fewer, allergies, by impairing or enhancing immunity to non-self. Malignancies are also rare. The enormous diversity of immunological and clinical phenotypes is thought provoking and mirrors the diversity and pleiotropy of the underlying genotypes. These experiments of nature provide a unique insight into the quantitative regulation of human immunity. PMID:25645939

  2. Horka, a dominant mutation of Drosophila, induces nondisjunction and, through paternal effect, chromosome loss and genetic mosaics

    SciTech Connect

    Szabad, J.; Mathe, E.; Puro, J.

    1995-04-01

    Fs(3) Horka (Horka) was described as a dominant female-sterile mutation of Drosophila melanogaster. Genetic and cytological data show that Horka induces mostly equational nondisjunction during spermatogenesis but not chromosome loss and possesses a predominant paternal effect: the X, second, third and the fourth chromosomes, but not the Y, are rendered unstable while undergoing spermatogenesis and may be lost in the descending zygotes. The frequency of Horka-induced chromosome loss is usually 2-4% but varies with the genetic background and can be over 20%. The X chromosome loss occurs during the gonomeric and the initial cleavage divisions. Loss of the X and fourth chromosomes shows no correlation. We propose, based on similarities in the mutant phenotypes with the chromosome destabilizing mutations nonclaret disjunctional and paternal loss, that the normal Horka{sup +} product is required for function of the centromeres and/or nearby regions. Horka is a convenient tool for the generation of gynandromorphs, autosome mosaics and for the study of gene expression in mosaics. 55 refs., 6 figs., 8 tabs.

  3. Nonlinear Epigenetic Variance: Review and Simulations

    ERIC Educational Resources Information Center

    Kan, Kees-Jan; Ploeger, Annemie; Raijmakers, Maartje E. J.; Dolan, Conor V.; van Der Maas, Han L. J.

    2010-01-01

    We present a review of empirical evidence that suggests that a substantial portion of phenotypic variance is due to nonlinear (epigenetic) processes during ontogenesis. The role of such processes as a source of phenotypic variance in human behaviour genetic studies is not fully appreciated. In addition to our review, we present simulation studies…

  4. Nonlinear Epigenetic Variance: Review and Simulations

    ERIC Educational Resources Information Center

    Kan, Kees-Jan; Ploeger, Annemie; Raijmakers, Maartje E. J.; Dolan, Conor V.; van Der Maas, Han L. J.

    2010-01-01

    We present a review of empirical evidence that suggests that a substantial portion of phenotypic variance is due to nonlinear (epigenetic) processes during ontogenesis. The role of such processes as a source of phenotypic variance in human behaviour genetic studies is not fully appreciated. In addition to our review, we present simulation studies…

  5. Does variance in drinking motives explain the genetic overlap between personality and alcohol use disorder symptoms? A twin study of young women

    PubMed Central

    Littlefield, Andrew K.; Agrawal, Arpana; Ellingson, Jarrod M.; Kristjansson, Sean; Madden, Pamela A. F.; Bucholz, Kathleen K.; Slutske, Wendy S.; Heath, Andrew C.; Sher, Kenneth J.

    2011-01-01

    Background Genetic risk for alcohol dependence has been shown to overlap with genetic factors contributing to variation in dimensions of personality. Though drinking motives have been posited as important mediators of the alcohol-personality relation, the extent to which the genetic covariance between alcohol use disorder (AUD) symptoms (i.e. abuse and dependence criteria) and personality is explained by genetic factors contributing to variation in drinking motives remains unclear. Methods Using data from 2,904 young adult female twins, the phenotypic and genetic associations among personality dimensions (constraint [measured by the Multidimensional Personality Questionnaire; Tellegen, 1982], conscientiousness, neuroticism, and agreeableness [measured by the NEO-PI; Costa & McCrae, 1985]), internal drinking motives (enhancement and coping motives [measured by the Drinking Motive Questionnaire; Cooper, 1994]), and AUD symptoms were tested. Results Significant genetic associations were found between all personality measures and AUD symptoms. Coping motives showed significant genetic overlap with AUD symptoms and most personality measures, whereas enhancement motives were not significantly heritable. Adjusting for coping motives, genetic correlations between AUD symptoms and traits of neuroticism and agreeableness were no longer statistically significant. Conclusions Findings suggest that genetic variation in drinking to cope might account for a considerable proportion of the genetic covariance between specific personality dimensions and AUD symptoms. PMID:21790670

  6. Genetic Isolation, Cloning, and Analysis of a Mutator-Induced, Dominant Antimorph of the Maize amylose extender1 Locus.

    PubMed Central

    Stinard, PS; Robertson, DS; Schnable, PS

    1993-01-01

    We report the genetic identification, molecular cloning, and characterization of a dominant mutant at the amylose extender1 locus, Ae1-5180. The identities of our clones are corroborated by their ability to reveal DNA polymorphisms between seven wild-type revertants from Ae1-5180 relative to the Ae1-5180 mutant allele and between four of five independently derived, Mutator (Mu)-induced recessive ae1 alleles relative to their respective wild-type progenitor alleles. The Ae1-5180 mutation is associated with two Mu1 insertions flanked by complex rearrangements of ae1-related sequences. One of the Mu1 elements is flanked by inverted repeats of ae1-related DNA of at least 5.0 kb in length. This Mu1 element and at least some of this flanking inverted repeat DNA are absent or hypermethylated in six of seven wild-type revertants of Ae1-5180 that were analyzed. The second Mu1 element is flanked on one side by the 5.0-kb ae1-specific repeat and on the other side by a sequence that does not hybridize to the ae1-related repeat sequence. This second Mu1 element is present in revertants to the wild type and does not, therefore, appear to affect ae1 gene function. A 2.7-kb ae1 transcript can be detected in wild-type and homozygous ae1-Ref endosperms 20 days after pollination. This transcript is absent in endosperms containing one, two, or three doses of Ae1-5180. This result is consistent with a suppression model to explain the dominant gene action of Ae1-5180 and establishes Ae1-5180 as an antimorphic allele. Homozygous wild-type seedlings produce no detectable transcript, indicating some degree of tissue specificity for ae1 expression. Sequence analyses establish that ae1 encodes starch branching enzyme II. PMID:12271046

  7. Pervasive effects of a dominant foliar endophytic fungus on host genetic and phenotypic expression in a tropical tree

    PubMed Central

    Mejía, Luis C.; Herre, Edward A.; Sparks, Jed P.; Winter, Klaus; García, Milton N.; Van Bael, Sunshine A.; Stitt, Joseph; Shi, Zi; Zhang, Yufan; Guiltinan, Mark J.; Maximova, Siela N.

    2014-01-01

    It is increasingly recognized that macro-organisms (corals, insects, plants, vertebrates) consist of both host tissues and multiple microbial symbionts that play essential roles in their host's ecological and evolutionary success. Consequently, identifying benefits and costs of symbioses, as well as mechanisms underlying them are research priorities. All plants surveyed under natural conditions harbor foliar endophytic fungi (FEF) in their leaf tissues, often at high densities. Despite producing no visible effects on their hosts, experiments have nonetheless shown that FEF reduce pathogen and herbivore damage. Here, combining results from three genomic, and two physiological experiments, we demonstrate pervasive genetic and phenotypic effects of the apparently asymptomatic endophytes on their hosts. Specifically, inoculation of endophyte-free (E−) Theobroma cacao leaves with Colletotrichum tropicale (E+), the dominant FEF species in healthy T. cacao, induces consistent changes in the expression of hundreds of host genes, including many with known defensive functions. Further, E+ plants exhibited increased lignin and cellulose content, reduced maximum rates of photosynthesis (Amax), and enrichment of nitrogen-15 and carbon-13 isotopes. These phenotypic changes observed in E+ plants correspond to changes in expression of specific functional genes in related pathways. Moreover, a cacao gene (Tc00g04254) highly up-regulated by C. tropicale also confers resistance to pathogen damage in the absence of endophytes or their products in host tissues. Thus, the benefits of increased pathogen resistance in E+ plants are derived in part from up-regulation of intrinsic host defense responses, and appear to be offset by potential costs including reduced photosynthesis, altered host nitrogen metabolism, and endophyte heterotrophy of host tissues. Similar effects are likely in most plant-endophyte interactions, and should be recognized in the design and interpretation of genetic

  8. Increased wheel-running activity in the genetically skeletal muscle fast-twitch fiber-dominant rats.

    PubMed

    Suwa, Masataka; Nakano, Hiroshi; Higaki, Yasuki; Nakamura, Tomohiro; Katsuta, Shigeru; Kumagai, Shuzo

    2003-01-01

    The purpose of the present study was to investigate whether genetic differences in muscle histochemical characteristics were related to the voluntary wheel-running activity level by using genetically fast-twitch fiber-dominant rats (FFDR) and control rats (CR). The rats were divided into four groups; sedentary CR (Sed-CR), wheel-running CR (WR-CR), sedentary FFDR (Sed-FFDR), and wheel-running FFDR (WR-FFDR). Wheel access was started at age 9 wk and lasted for 7 days. The FFDR showed a lower percentage of type I fibers of the deep portion of gastrocnemius and soleus muscles and a higher percentage of both type IIX fibers of the gastrocnemius muscle and type IIA fibers of the soleus muscle compared with CR. A higher capillary density and smaller fiber cross-sectional area were also observed in FFDR. The daily running distance in WR-FFDR was higher than in WR-CR for each 7 days. The total running distance for 7 days in WR-FFDR was 3.2-fold higher than in WR-CR. On day 7 of the 7-day test, the total number of active 1-min intervals for 24 h, the average rpm when they were active, and the maximum rpm for any single 1-min period in the WR-FFDR were significantly higher than in the WR-CR (1.5-, 2.9-, and 2.0-fold, respectively). These results suggest that mechanical or physiological muscle characteristics may thus affect the wheel-running activity level.

  9. Evidence that BMI and type 2 diabetes share only a minor fraction of genetic variance: a follow-up study of 23,585 monozygotic and dizygotic twins from the Finnish Twin Cohort Study.

    PubMed

    Lehtovirta, M; Pietiläinen, K H; Levälahti, E; Heikkilä, K; Groop, L; Silventoinen, K; Koskenvuo, M; Kaprio, J

    2010-07-01

    We investigated whether BMI predicts type 2 diabetes in twins and to what extent that is explained by common genetic factors. This was a population-based twin cohort study. Monozygotic (n = 4,076) and dizygotic (n = 9,109) non-diabetic twin pairs born before 1958 answered a questionnaire in 1975, from which BMI was obtained. Information on incident cases of diabetes was obtained by linkage to nationwide registers until 2005. Altogether, 1,332 twins (6.3% of men, 5.1% of women) developed type 2 diabetes. The HR for type 2 diabetes increased monotonically with a mean of 1.22 (95% CI 1.20-1.24) per BMI unit and of 1.97 (95% CI 1.87-2.08) per SD of BMI. The HRs for lean, overweight, obese and morbidly obese participants were 0.59, 2.96, 6.80 and 13.64 as compared with normal weight participants. Model heritability estimates for bivariate variance due to an additive genetic component and non-shared environmental component were 75% (men) and 71% (women) for BMI, and 73% and 64%, respectively for type 2 diabetes. The correlations between genetic variance components (r (g)) indicated that one fifth of the covariance of BMI and type 2 diabetes was due to shared genetic influences. Although the mean monozygotic concordance for type 2 diabetes was approximately twice the dizygotic one, age of onset of diabetes within twin pair members varied greatly, irrespective of zygosity. A 28-year follow-up of adult Finnish twins showed that despite high trait heritability estimates, only a fraction of covariation in BMI and incident type 2 diabetes was of genetic origin.

  10. Resonance Assignment of the NMR Spectra of Disordered Proteins Using a Multi-Objective Non-Dominated Sorting Genetic Algorithm

    PubMed Central

    Yang, Yu; Fritzsching, Keith J.

    2014-01-01

    A multi-objective genetic algorithm is introduced to predict the assignment of protein solid-state NMR spectra with partial resonance overlap and missing peaks due to broad linewidths, molecular motion, and low sensitivity. This non-dominated sorting genetic algorithm II (NSGA-II) aims to identify all possible assignments that are consistent with the spectra and to compare the relative merit of these assignments. Our approach is modeled after the recently introduced Monte Carlo simulated annealing (MC/SA) protocol, with the key difference that NSGA-II simultaneously optimizes multiple assignment objectives instead of searching for possible assignments based on a single composite score. The multiple objectives include maximizing the number of consistently assigned peaks between multiple spectra (“good connections”), maximizing the number of used peaks, minimizing the number of inconsistently assigned peaks between spectra (“bad connections”), and minimizing the number of assigned peaks that have no matching peaks in the other spectra (“edges”). Using six solid-state NMR protein chemical shift datasets with varying levels of imperfection that was introduced by peak deletion, random chemical shift changes, and manual peak picking of spectra with moderately broad linewidths, we show that the NSGA-II algorithm produces a large number of valid and good assignments rapidly. For high-quality chemical shift peak lists, NSGA-II and MC/SA perform similarly well. However, when the peak lists contain many missing peaks that are uncorrelated between different spectra and have chemical shift deviations between spectra, the modified NSGA-II produces a larger number of valid solutions than MC/SA, and is more effective at distinguishing good from mediocre assignments by avoiding the hazard of suboptimal weighting factors for the various objectives. These two advantages, namely diversity and better evaluation, lead to a higher probability of predicting the correct

  11. Genetic Analysis of the Rhodopsin Gene Identifies a Mosaic Dominant Retinitis Pigmentosa Mutation in a Healthy Individual

    PubMed Central

    Beryozkin, Avigail; Levy, Gal; Blumenfeld, Anat; Meyer, Segev; Namburi, Prasanthi; Morad, Yair; Gradstein, Libe; Swaroop, Anand; Banin, Eyal; Sharon, Dror

    2016-01-01

    Purpose Retinitis pigmentosa (RP) is a group of clinically and genetically heterogeneous hereditary retinal diseases that result in blindness due to photoreceptor degeneration. Mutations in the rhodopsin (RHO) gene are the most common cause of autosomal dominant RP (adRP) and are responsible for 16% to 35% of adRP cases in the Western population. Our purpose was to investigate the contribution of RHO to adRP in the Israeli and Palestinian populations. Methods Thirty-two adRP families participated in the study. Mutation detection was performed by whole exome sequencing (WES) and Sanger sequencing of RHO exons. Fluorescence PCR reactions of serially diluted samples were used to predict the percentage of mosaic cells in blood samples. Results Eight RHO disease-causing mutations were identified in nine families, with only one novel mutation, c.548-638dup91bp, identified in a family where WES failed to detect any causal variant. Segregation analysis revealed that the origin of the mutation is in a mosaic healthy individual carrying the mutation in approximately 13% of blood cells. Conclusions This is the first report of the mutation spectrum of a known adRP gene in the Israeli and Palestinian populations, leading to the identification of seven previously reported mutations and one novel mutation. Our study shows that RHO mutations are a major cause of adRP in this cohort and are responsible for 28% of adRP families. The novel mutation exhibits a unique phenomenon in which an unaffected individual is mosaic for an adRP-causing mutation. PMID:26962691

  12. Genetic suppression of atrial fibrillation using a dominant-negative ether-a-go-go-related gene mutant.

    PubMed

    Soucek, Radim; Thomas, Dierk; Kelemen, Kamilla; Bikou, Olympia; Seyler, Claudia; Voss, Frederik; Becker, Rüdiger; Koenen, Michael; Katus, Hugo A; Bauer, Alexander

    2012-02-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Gene therapy-dependent modulation of atrial electrophysiology may provide a more specific alternative to pharmacological and ablative treatment strategies. We hypothesized that genetic inactivation of atrial repolarizing ether-a-go-go-related gene (ERG) K(+) currents using a dominant-negative mutant would provide rhythm control in AF. Ten domestic swine underwent pacemaker implantation and were subjected to atrial burst pacing to induce persistent AF. Animals were then randomized to receive either AdCERG-G627S to suppress ERG/I(Kr) currents or green fluorescent protein (AdGFP) as control. Adenoviruses were applied using a novel hybrid technique combining atrial virus injection and epicardial electroporation to increase transgene expression. In pigs treated with AdCERG-G627S, the onset of persistent AF was prevented (n = 2) or significantly delayed compared with AdGFP controls (12 ± 2.1 vs. 6.2 ± 1.3 days; P < .001) during 14-day follow-up. Effective refractory periods were prolonged in the AdCERG-G627S group compared with AdGFP animals (221.5 ± 4.7 ms vs. 197.0 ± 4.7 ms; P < .006). Impairment of left ventricular ejection fraction (LVEF) during AF was prevented by AdCERG-G627S application (LVEF(CERG-G627S) = 62.1% ± 4.0% vs. LVEF(GFP) = 30.3% ± 9.1%; P < .001). Inhibition of ERG function using atrial AdCERG-G627S gene transfer suppresses or delays the onset of persistent AF by prolongation of atrial refractoriness in a porcine model. Targeted gene therapy represents an alternative to pharmacological or ablative treatment of AF. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  13. Generalized Analysis of Molecular Variance

    PubMed Central

    Nievergelt, Caroline M; Libiger, Ondrej; Schork, Nicholas J

    2007-01-01

    Many studies in the fields of genetic epidemiology and applied population genetics are predicated on, or require, an assessment of the genetic background diversity of the individuals chosen for study. A number of strategies have been developed for assessing genetic background diversity. These strategies typically focus on genotype data collected on the individuals in the study, based on a panel of DNA markers. However, many of these strategies are either rooted in cluster analysis techniques, and hence suffer from problems inherent to the assignment of the biological and statistical meaning to resulting clusters, or have formulations that do not permit easy and intuitive extensions. We describe a very general approach to the problem of assessing genetic background diversity that extends the analysis of molecular variance (AMOVA) strategy introduced by Excoffier and colleagues some time ago. As in the original AMOVA strategy, the proposed approach, termed generalized AMOVA (GAMOVA), requires a genetic similarity matrix constructed from the allelic profiles of individuals under study and/or allele frequency summaries of the populations from which the individuals have been sampled. The proposed strategy can be used to either estimate the fraction of genetic variation explained by grouping factors such as country of origin, race, or ethnicity, or to quantify the strength of the relationship of the observed genetic background variation to quantitative measures collected on the subjects, such as blood pressure levels or anthropometric measures. Since the formulation of our test statistic is rooted in multivariate linear models, sets of variables can be related to genetic background in multiple regression-like contexts. GAMOVA can also be used to complement graphical representations of genetic diversity such as tree diagrams (dendrograms) or heatmaps. We examine features, advantages, and power of the proposed procedure and showcase its flexibility by using it to analyze a

  14. Generalized analysis of molecular variance.

    PubMed

    Nievergelt, Caroline M; Libiger, Ondrej; Schork, Nicholas J

    2007-04-06

    Many studies in the fields of genetic epidemiology and applied population genetics are predicated on, or require, an assessment of the genetic background diversity of the individuals chosen for study. A number of strategies have been developed for assessing genetic background diversity. These strategies typically focus on genotype data collected on the individuals in the study, based on a panel of DNA markers. However, many of these strategies are either rooted in cluster analysis techniques, and hence suffer from problems inherent to the assignment of the biological and statistical meaning to resulting clusters, or have formulations that do not permit easy and intuitive extensions. We describe a very general approach to the problem of assessing genetic background diversity that extends the analysis of molecular variance (AMOVA) strategy introduced by Excoffier and colleagues some time ago. As in the original AMOVA strategy, the proposed approach, termed generalized AMOVA (GAMOVA), requires a genetic similarity matrix constructed from the allelic profiles of individuals under study and/or allele frequency summaries of the populations from which the individuals have been sampled. The proposed strategy can be used to either estimate the fraction of genetic variation explained by grouping factors such as country of origin, race, or ethnicity, or to quantify the strength of the relationship of the observed genetic background variation to quantitative measures collected on the subjects, such as blood pressure levels or anthropometric measures. Since the formulation of our test statistic is rooted in multivariate linear models, sets of variables can be related to genetic background in multiple regression-like contexts. GAMOVA can also be used to complement graphical representations of genetic diversity such as tree diagrams (dendrograms) or heatmaps. We examine features, advantages, and power of the proposed procedure and showcase its flexibility by using it to analyze a

  15. The majority of genetic variation in orangutan personality and subjective well-being is nonadditive.

    PubMed

    Adams, Mark James; King, James E; Weiss, Alexander

    2012-07-01

    The heritability of human personality is well-established. Recent research indicates that nonadditive genetic effects, such as dominance and epistasis, play a large role in personality variation. One possible explanation for the latter finding is that there has been recent selection on human personality. To test this possibility, we estimated additive and nonadditive genetic variance in personality and subjective well-being of zoo-housed orangutans. More than half of the genetic variance in these traits could be attributed to nonadditive genetic effects, modeled as dominance. Subjective well-being had genetic overlap with personality, though less so than has been found in humans or chimpanzees. Since a large portion of nonadditive genetic variance in personality is not unique to humans, the nonadditivity of human personality is not sufficient evidence for recent selection of personality in humans. Nonadditive genetic variance may be a general feature of the genetic structure of personality in primates and other animals.

  16. A Cosmic Variance Cookbook

    NASA Astrophysics Data System (ADS)

    Moster, Benjamin P.; Somerville, Rachel S.; Newman, Jeffrey A.; Rix, Hans-Walter

    2011-04-01

    Deep pencil beam surveys (<1 deg2) are of fundamental importance for studying the high-redshift universe. However, inferences about galaxy population properties (e.g., the abundance of objects) are in practice limited by "cosmic variance." This is the uncertainty in observational estimates of the number density of galaxies arising from the underlying large-scale density fluctuations. This source of uncertainty can be significant, especially for surveys which cover only small areas and for massive high-redshift galaxies. Cosmic variance for a given galaxy population can be determined using predictions from cold dark matter theory and the galaxy bias. In this paper, we provide tools for experiment design and interpretation. For a given survey geometry, we present the cosmic variance of dark matter as a function of mean redshift \\bar{z} and redshift bin size Δz. Using a halo occupation model to predict galaxy clustering, we derive the galaxy bias as a function of mean redshift for galaxy samples of a given stellar mass range. In the linear regime, the cosmic variance of these galaxy samples is the product of the galaxy bias and the dark matter cosmic variance. We present a simple recipe using a fitting function to compute cosmic variance as a function of the angular dimensions of the field, \\bar{z}, Δz, and stellar mass m *. We also provide tabulated values and a software tool. The accuracy of the resulting cosmic variance estimates (δσ v /σ v ) is shown to be better than 20%. We find that for GOODS at \\bar{z}=2 and with Δz = 0.5, the relative cosmic variance of galaxies with m *>1011 M sun is ~38%, while it is ~27% for GEMS and ~12% for COSMOS. For galaxies of m * ~ 1010 M sun, the relative cosmic variance is ~19% for GOODS, ~13% for GEMS, and ~6% for COSMOS. This implies that cosmic variance is a significant source of uncertainty at \\bar{z}=2 for small fields and massive galaxies, while for larger fields and intermediate mass galaxies, cosmic variance is

  17. A COSMIC VARIANCE COOKBOOK

    SciTech Connect

    Moster, Benjamin P.; Rix, Hans-Walter; Somerville, Rachel S.; Newman, Jeffrey A. E-mail: rix@mpia.de E-mail: janewman@pitt.edu

    2011-04-20

    Deep pencil beam surveys (<1 deg{sup 2}) are of fundamental importance for studying the high-redshift universe. However, inferences about galaxy population properties (e.g., the abundance of objects) are in practice limited by 'cosmic variance'. This is the uncertainty in observational estimates of the number density of galaxies arising from the underlying large-scale density fluctuations. This source of uncertainty can be significant, especially for surveys which cover only small areas and for massive high-redshift galaxies. Cosmic variance for a given galaxy population can be determined using predictions from cold dark matter theory and the galaxy bias. In this paper, we provide tools for experiment design and interpretation. For a given survey geometry, we present the cosmic variance of dark matter as a function of mean redshift z-bar and redshift bin size {Delta}z. Using a halo occupation model to predict galaxy clustering, we derive the galaxy bias as a function of mean redshift for galaxy samples of a given stellar mass range. In the linear regime, the cosmic variance of these galaxy samples is the product of the galaxy bias and the dark matter cosmic variance. We present a simple recipe using a fitting function to compute cosmic variance as a function of the angular dimensions of the field, z-bar , {Delta}z, and stellar mass m{sub *}. We also provide tabulated values and a software tool. The accuracy of the resulting cosmic variance estimates ({delta}{sigma}{sub v}/{sigma}{sub v}) is shown to be better than 20%. We find that for GOODS at z-bar =2 and with {Delta}z = 0.5, the relative cosmic variance of galaxies with m{sub *}>10{sup 11} M{sub sun} is {approx}38%, while it is {approx}27% for GEMS and {approx}12% for COSMOS. For galaxies of m{sub *} {approx} 10{sup 10} M{sub sun}, the relative cosmic variance is {approx}19% for GOODS, {approx}13% for GEMS, and {approx}6% for COSMOS. This implies that cosmic variance is a significant source of uncertainty at z

  18. Direct and maternal (co)variance components, genetic parameters and annual trends for growth traits of Dorper sheep in semi-arid Kenya.

    PubMed

    Kariuki, C M; Ilatsia, Evans D; Kosgey, Isaac S; Kahi, Alexander K

    2010-03-01

    Genetic and phenotypic parameters were estimated for lamb growth traits for the Dorper sheep in semi-arid Kenya using an animal model. Data on lamb growth performance were extracted from available performance records at the Sheep and Goats Station in Naivasha, Kenya. Growth traits considered were body weights at birth (BW0, kg), at 1 month (BW1, kg), at 2 months (BW2, kg), at weaning (WW, kg), at 6 months (BW6, kg), at 9 months (BW9, kg) and at yearling (YW, kg), average daily gain from birth to 6 months (ADG(0-6), gm) and from 6 months to 1 year (ADG(6-12), gm). Direct heritability estimates were, correspondingly, 0.18, 0.36, 0.32, 0.28, 0.21, 0.14, 0.29, 0.12 and 0.30 for BW0, BW1, BW2, WW, BW6, BW9, YW, ADG(0-6) and ADG(6-12). The corresponding maternal genetic heritability estimates for body weights up to 9 months were 0.16, 0.10, 0.10, 0.19, 0.21 and 0.18. Direct-maternal genetic correlations were negative and high ranging between -0.47 to -0.94. Negative genetic correlations were observed for ADG(0-6)-ADG(6-12), BW2-ADG(6-12), WW-ADG(6-12) and BW6-ADG(6-12). Phenotypic correlations ranged from 0.15 to 0.96. Maternal effects are important in the growth performance of the Dorper sheep though a negative correlation exists between direct and maternal genetic effects. The current study has provided important information on the extent of additive genetic variation in the existing flocks that could now be used in determining the merit of breeding rams and ewes for sale to the commercial flocks. The estimates provided would form the basis of designing breeding schemes for the Dorper sheep in Kenya. Implications of the study to future Dorper sheep breeding programmes are also discussed.

  19. A novel homologous dominant selection marker for genetic transformation of Penicillium chrysogenum: overexpression of squalene epoxidase-encoding ergA.

    PubMed

    Sigl, Claudia; Handler, Monika; Sprenger, Georg; Kürnsteiner, Hubert; Zadra, Ivo

    2010-11-01

    Genetic engineering requires genetic selection markers. For generation of biosafe strains in industrial applications, homologous dominant selection markers allowing "self-cloning" are best suited but scarce. Here we describe a novel homologous dominant genetic selection system for the filamentous fungus Penicillium chrysogenum based on overexpression of the P. chrysogenum squalene epoxidase-encoding ergA gene, which confers resistance against terbinafine. Terbinafine (TRB) is a potent antifungal drug used in therapy of fungal infections. Overexpression of ergA was driven by the P. chrysogenum endoxylanase xylP promoter that is highly inducible by xylose. The suitability of the novel selection marker cassette for genetic manipulation was proven by its use for targeted deletion of the transcription factor nosA in P. chrysogenum. NosA-deficiency did not affect growth rates on solid or in liquid media, conidiation in light or darkness, and resistance to hydrogen peroxide. However, NosA-deficiency significantly decreased penicillin productivity. As TRB inhibits the growth of a variety of fungal species, this novel selection marker is expected to be suitable for genetic engineering of diverse fungal species.

  20. Variational bayesian method of estimating variance components.

    PubMed

    Arakawa, Aisaku; Taniguchi, Masaaki; Hayashi, Takeshi; Mikawa, Satoshi

    2016-07-01

    We developed a Bayesian analysis approach by using a variational inference method, a so-called variational Bayesian method, to determine the posterior distributions of variance components. This variational Bayesian method and an alternative Bayesian method using Gibbs sampling were compared in estimating genetic and residual variance components from both simulated data and publically available real pig data. In the simulated data set, we observed strong bias toward overestimation of genetic variance for the variational Bayesian method in the case of low heritability and low population size, and less bias was detected with larger population sizes in both methods examined. The differences in the estimates of variance components between the variational Bayesian and the Gibbs sampling were not found in the real pig data. However, the posterior distributions of the variance components obtained with the variational Bayesian method had shorter tails than those obtained with the Gibbs sampling. Consequently, the posterior standard deviations of the genetic and residual variances of the variational Bayesian method were lower than those of the method using Gibbs sampling. The computing time required was much shorter with the variational Bayesian method than with the method using Gibbs sampling. © 2016 Japanese Society of Animal Science.

  1. Genetic variances, heritabilities and maternal effects on body weight, breast meat yield, meat quality traits and the shape of the growth curve in turkey birds

    PubMed Central

    2011-01-01

    Background Turkey is an important agricultural species and is largely used as a meat bird. In 2004, turkey represented 6.5% of the world poultry meat production. The world-wide turkey population has rapidly grown due to increased commercial farming. Due to the high demand for turkey meat from both consumers and industry global turkey stocks increased from 100 million in 1970 to over 276 million in 2004. This rapidly increasing importance of turkeys was a reason to design this study for the estimation of genetic parameters that control body weight, body composition, meat quality traits and parameters that shape the growth curve in turkey birds. Results The average heritability estimate for body weight traits was 0.38, except for early weights that were strongly affected by maternal effects. This study showed that body weight traits, upper asymptote (a growth curve trait), percent breast meat and redness of meat had high heritability whereas heritabilities of breast length, breast width, percent drip loss, ultimate pH, lightness and yellowness of meat were medium to low. We found high positive genetic and phenotypic correlations between body weight, upper asymptote, most breast meat yield traits and percent drip loss but percent drip loss was found strongly negatively correlated with ultimate pH. Percent breast meat, however, showed genetic correlations close to zero with body weight traits and upper asymptote. Conclusion The results of this analysis and the growth curve from the studied population of turkey birds suggest that the turkey birds could be selected for breeding between 60 and 80 days of age in order to improve overall production and the production of desirable cuts of meat. The continuous selection of birds within this age range could promote high growth rates but specific attention to meat quality would be needed to avoid a negative impact on the quality of meat. PMID:21266032

  2. Genetic variance and covariance and breed differences for feed intake and average daily gain to improve feed efficiency in growing cattle.

    PubMed

    Retallick, K J; Bormann, J M; Weaber, R L; MacNeil, M D; Bradford, H L; Freetly, H C; Hales, K E; Moser, D W; Snelling, W M; Thallman, R M; Kuehn, L A

    2017-04-01

    Feed costs are a major economic expense in finishing and developing cattle; however, collection of feed intake data is costly. Examining relationships among measures of growth and intake, including breed differences, could facilitate selection for efficient cattle. Objectives of this study were to estimate genetic parameters for growth and intake traits and compare indices for feed efficiency to accelerate selection response. On-test ADFI and on-test ADG (TESTADG) and postweaning ADG (PWADG) records for 5,606 finishing steers and growing heifers were collected at the U.S. Meat Animal Research Center in Clay Center, NE. On-test ADFI and ADG data were recorded over testing periods that ranged from 62 to 148 d. Individual quadratic regressions were fitted for BW on time, and TESTADG was predicted from the resulting equations. We included PWADG in the model to improve estimates of growth and intake parameters; PWADG was derived by dividing gain from weaning weight to yearling weight by the number of days between the weights. Genetic parameters were estimated using multiple-trait REML animal models with TESTADG, ADFI, and PWADG for both sexes as dependent variables. Fixed contemporary groups were cohorts of calves simultaneously tested, and covariates included age on test, age of dam, direct and maternal heterosis, and breed composition. Genetic correlations (SE) between steer TESTADG and ADFI, PWADG and ADFI, and TESTADG and PWADG were 0.33 (0.10), 0.59 (0.06), and 0.50 (0.09), respectively, and corresponding estimates for heifers were 0.66 (0.073), 0.77 (0.05), and 0.88 (0.05), respectively. Indices combining EBV for ADFI with EBV for ADG were developed and evaluated. Greater improvement in feed efficiency can be expected using an unrestricted index versus a restricted index. Heterosis significantly affected each trait contributing to greater ADFI and TESTADG. Breed additive effects were estimated for ADFI, TESTADG, and the efficiency indices.

  3. Significant variance in genetic diversity among populations of Schistosoma haematobium detected using microsatellite DNA loci from a genome-wide database

    PubMed Central

    2013-01-01

    Background Urogenital schistosomiasis caused by Schistosoma haematobium is widely distributed across Africa and is increasingly being targeted for control. Genome sequences and population genetic parameters can give insight into the potential for population- or species-level drug resistance. Microsatellite DNA loci are genetic markers in wide use by Schistosoma researchers, but there are few primers available for S. haematobium. Methods We sequenced 1,058,114 random DNA fragments from clonal cercariae collected from a snail infected with a single Schistosoma haematobium miracidium. We assembled and aligned the S. haematobium sequences to the genomes of S. mansoni and S. japonicum, identifying microsatellite DNA loci across all three species and designing primers to amplify the loci in S. haematobium. To validate our primers, we screened 32 randomly selected primer pairs with population samples of S. haematobium. Results We designed >13,790 primer pairs to amplify unique microsatellite loci in S. haematobium, (available at http://www.cebio.org/projetos/schistosoma-haematobium-genome). The three Schistosoma genomes contained similar overall frequencies of microsatellites, but the frequency and length distributions of specific motifs differed among species. We identified 15 primer pairs that amplified consistently and were easily scored. We genotyped these 15 loci in S. haematobium individuals from six locations: Zanzibar had the highest levels of diversity; Malawi, Mauritius, Nigeria, and Senegal were nearly as diverse; but the sample from South Africa was much less diverse. Conclusions About half of the primers in the database of Schistosoma haematobium microsatellite DNA loci should yield amplifiable and easily scored polymorphic markers, thus providing thousands of potential markers. Sequence conservation among S. haematobium, S. japonicum, and S. mansoni is relatively high, thus it should now be possible to identify markers that are universal among Schistosoma

  4. The quantum Allan variance

    NASA Astrophysics Data System (ADS)

    Chabuda, Krzysztof; Leroux, Ian D.; Demkowicz-Dobrzański, Rafał

    2016-08-01

    The instability of an atomic clock is characterized by the Allan variance, a measure widely used to describe the noise of frequency standards. We provide an explicit method to find the ultimate bound on the Allan variance of an atomic clock in the most general scenario where N atoms are prepared in an arbitrarily entangled state and arbitrary measurement and feedback are allowed, including those exploiting coherences between succeeding interrogation steps. While the method is rigorous and general, it becomes numerically challenging for large N and long averaging times.

  5. Isolation by Elevation: Genetic Structure at Neutral and Putatively Non-Neutral Loci in a Dominant Tree of Subtropical Forests, Castanopsis eyrei

    PubMed Central

    Shi, Miao-Miao; Michalski, Stefan G.; Chen, Xiao-Yong; Durka, Walter

    2011-01-01

    Background The distribution of genetic diversity among plant populations growing along elevational gradients can be affected by neutral as well as selective processes. Molecular markers used to study these patterns usually target neutral processes only, but may also be affected by selection. In this study, the effects of elevation and successional stage on genetic diversity of a dominant tree species were investigated controlling for neutrality of the microsatellite loci used. Methodology/Principal Findings Diversity and differentiation among 24 populations of Castanopsis eyrei from different elevations (251–920 m) and successional stages were analysed by eight microsatellite loci. We found that one of the loci (Ccu97H18) strongly deviated from a neutral model of differentiation among populations due to either divergent selection or hitchhiking with an unknown selected locus. The analysis showed that C. eyrei populations had a high level of genetic diversity within populations (AR = 7.6, HE = 0.82). Genetic variation increased with elevation for both the putatively selected locus Ccu97H18 and the neutral loci. At locus Ccu97H18 one allele was dominant at low elevations, which was replaced at higher elevations by an increasing number of other alleles. The level of genetic differentiation at neutral loci was similar to that of other Fagaceae species (FST = 0.032,  = 0.15). Population differentiation followed a model of isolation by distance but additionally, strongly significant isolation by elevation was found, both for neutral loci and the putatively selected locus. Conclusions/Significance The results indicate higher gene flow among similar elevational levels than across different elevational levels and suggest a selective influence of elevation on the distribution of genetic diversity in C. eyrei. The study underlines the importance to check the selective neutrality of marker loci in analyses of population structure. PMID:21701584

  6. Isolation by elevation: genetic structure at neutral and putatively non-neutral loci in a dominant tree of subtropical forests, Castanopsis eyrei.

    PubMed

    Shi, Miao-Miao; Michalski, Stefan G; Chen, Xiao-Yong; Durka, Walter

    2011-01-01

    The distribution of genetic diversity among plant populations growing along elevational gradients can be affected by neutral as well as selective processes. Molecular markers used to study these patterns usually target neutral processes only, but may also be affected by selection. In this study, the effects of elevation and successional stage on genetic diversity of a dominant tree species were investigated controlling for neutrality of the microsatellite loci used. Diversity and differentiation among 24 populations of Castanopsis eyrei from different elevations (251-920 m) and successional stages were analysed by eight microsatellite loci. We found that one of the loci (Ccu97H18) strongly deviated from a neutral model of differentiation among populations due to either divergent selection or hitchhiking with an unknown selected locus. The analysis showed that C. eyrei populations had a high level of genetic diversity within populations (A(R) = 7.6, H(E) = 0.82). Genetic variation increased with elevation for both the putatively selected locus Ccu97H18 and the neutral loci. At locus Ccu97H18 one allele was dominant at low elevations, which was replaced at higher elevations by an increasing number of other alleles. The level of genetic differentiation at neutral loci was similar to that of other Fagaceae species (F(ST) = 0.032,  = 0.15). Population differentiation followed a model of isolation by distance but additionally, strongly significant isolation by elevation was found, both for neutral loci and the putatively selected locus. The results indicate higher gene flow among similar elevational levels than across different elevational levels and suggest a selective influence of elevation on the distribution of genetic diversity in C. eyrei. The study underlines the importance to check the selective neutrality of marker loci in analyses of population structure.

  7. Ecotypes of an ecologically dominant prairie grass (Andropogon gerardii) exhibit genetic divergence across the U.S. Midwest grasslands' environmental gradient.

    PubMed

    Gray, Miranda M; St Amand, Paul; Bello, Nora M; Galliart, Matthew B; Knapp, Mary; Garrett, Karen A; Morgan, Theodore J; Baer, Sara G; Maricle, Brian R; Akhunov, Eduard D; Johnson, Loretta C

    2014-12-01

    Big bluestem (Andropogon gerardii) is an ecologically dominant grass with wide distribution across the environmental gradient of U.S. Midwest grasslands. This system offers an ideal natural laboratory to study population divergence and adaptation in spatially varying climates. Objectives were to: (i) characterize neutral genetic diversity and structure within and among three regional ecotypes derived from 11 prairies across the U.S. Midwest environmental gradient, (ii) distinguish between the relative roles of isolation by distance (IBD) vs. isolation by environment (IBE) on ecotype divergence, (iii) identify outlier loci under selection and (iv) assess the association between outlier loci and climate. Using two primer sets, we genotyped 378 plants at 384 polymorphic AFLP loci across regional ecotypes from central and eastern Kansas and Illinois. Neighbour-joining tree and PCoA revealed strong genetic differentiation between Kansas and Illinois ecotypes, which was better explained by IBE than IBD. We found high genetic variability within prairies (80%) and even fragmented Illinois prairies, surprisingly, contained high within-prairie genetic diversity (92%). Using Bayenv2, 14 top-ranked outlier loci among ecotypes were associated with temperature and precipitation variables. Six of seven BayeScanFST outliers were in common with Bayenv2 outliers. High genetic diversity may enable big bluestem populations to better withstand changing climates; however, population divergence supports the use of local ecotypes in grassland restoration. Knowledge of genetic variation in this ecological dominant and other grassland species will be critical to understanding grassland response and restoration challenges in the face of a changing climate.

  8. Genetic variance contributes to dopamine and opioid receptor antagonist-induced inhibition of intralipid (fat) intake in inbred and outbred mouse strains.

    PubMed

    Dym, Cheryl T; Bae, Veronica S; Kraft, Tamar; Yakubov, Yakov; Winn, Amanda; Sclafani, Anthony; Bodnar, Richard J

    2010-02-26

    Preference for and intake of solid and emulsified fat (intralipid) solutions vary across different mouse strains. Fat intake in rodents is inhibited by dopamine and opioid receptor antagonists, but any variation in these responses as a function of genetic background is unknown. Therefore, the present study compared the ability of dopamine D1-like (SCH23390) and general opioid (naltrexone) receptor antagonism to alter intake of fat emulsions (intralipid) in mice. Two-hour intakes of 5% intralipid were measured (5-120 min) in seven inbred (BALB/c, C57BL/6, C57BL/10, DBA/2, SJL, SWR, 129P3) and one outbred (CD-1) mouse strains following treatment with vehicle, SCH23390 (50-1600 nmol/kg, ip) and naltrexone (0.001-5 mg/kg, sc). SCH23390 significantly, dose-dependently and differentially reduced intralipid intake at all five (DBA/2, SWR, CD-1), four (SJL, C57BL/6), three (129P3) and one (C57BL/10) of the doses tested, but failed to affect intralipid intake in BALB/c mice. Naltrexone significantly, dose-dependently and differentially reduced intralipid intake at all four (DBA/2), three (SWR, SJL), two (CD-1, C57BL/10) and one (C57BL/6, 129P3) of the doses tested, and also failed to affect intralipid intake in BALB/cJ mice. SCH23390 and naltrexone were respectively 13.3-fold and 9.3-fold more potent in inhibiting intralipid intake in the most sensitive (DBA/2) relative to the least sensitive (BALB/c) mouse strains. A strong positive relationship (r=0.91) was observed for the abilities of SCH23390 and naltrexone to inhibit intralipid intake across strains. These findings indicate that dopaminergic and opioid signaling mechanisms differentially control intralipid intake across different mouse strains, suggesting important genetic and pharmacological interactions in the short-term control of rewarding and post-ingestive consequences of fat intake.

  9. Conversations across Meaning Variance

    ERIC Educational Resources Information Center

    Cordero, Alberto

    2013-01-01

    Progressive interpretations of scientific theories have long been denounced as naive, because of the inescapability of meaning variance. The charge reportedly applies to recent realist moves that focus on theory-parts rather than whole theories. This paper considers the question of what "theory-parts" of epistemic significance (if any) relevantly…

  10. Conversations across Meaning Variance

    ERIC Educational Resources Information Center

    Cordero, Alberto

    2013-01-01

    Progressive interpretations of scientific theories have long been denounced as naive, because of the inescapability of meaning variance. The charge reportedly applies to recent realist moves that focus on theory-parts rather than whole theories. This paper considers the question of what "theory-parts" of epistemic significance (if any) relevantly…

  11. Naive Analysis of Variance

    ERIC Educational Resources Information Center

    Braun, W. John

    2012-01-01

    The Analysis of Variance is often taught in introductory statistics courses, but it is not clear that students really understand the method. This is because the derivation of the test statistic and p-value requires a relatively sophisticated mathematical background which may not be well-remembered or understood. Thus, the essential concept behind…

  12. Minimum variance geographic sampling

    NASA Technical Reports Server (NTRS)

    Terrell, G. R. (Principal Investigator)

    1980-01-01

    Resource inventories require samples with geographical scatter, sometimes not as widely spaced as would be hoped. A simple model of correlation over distances is used to create a minimum variance unbiased estimate population means. The fitting procedure is illustrated from data used to estimate Missouri corn acreage.

  13. Genetic variance in the HIV-1 founder virus Vpr affects its ability to induce cell cycle G₂arrest and cell apoptosis.

    PubMed

    Jianyuan, Zhao; Jiwei, Ding; Zeyun, Mi; Jinming, Zhou; Tao, Wei; Shan, Cen

    2015-05-01

    In the event of acute infection, only a few HIV-1 viral variants can establish the initial productive clinical infection, and these viral variants are known as transmitted/founder viruses (T/F viruses). As one of the accessory proteins of HIV-1, viral protein R (Vpr) plays an important role in viral replication. Therefore, the characterization of T/F virus Vpr is beneficial to understand how virus replicates in a new host. In this study, flow cytometry was used to analyze the effect of G₂arrest and cell apoptosis induced by the T/F virus Vpr and the chronic strain MJ4 Vpr. The results showed that the ability of T/F virus ZM246 Vpr and ZM247 Vpr inducing G₂arrest and cell apoptosis are more potent than the MJ4 Vpr. The comparison of protein sequences indicated that the amino acids of 77, 85 and 94 contain high freqency mutations, suggesting that these sites may be involved in inducing G₂arrest and cell apoptosis. Taken together, our work suggests that in acute infections, T/F viruses increase the capacity of G₂arrest and cell apoptosis and promote viral replication and transmission in a new host by Vpr genetic mutation.

  14. The Rules of Aggression: How Genetic, Chemical and Spatial Factors Affect Intercolony Fights in a Dominant Species, the Mediterranean Acrobat Ant Crematogaster scutellaris

    PubMed Central

    Frizzi, Filippo; Ciofi, Claudio; Dapporto, Leonardo; Natali, Chiara; Chelazzi, Guido; Turillazzi, Stefano; Santini, Giacomo

    2015-01-01

    Nest-mate recognition plays a key role in the biology of ants. Although individuals coming from a foreign nest are, in most cases, promptly rejected, the degree of aggressiveness towards non nest-mates may be highly variable among species and relies on genetic, chemical and environmental factors. We analyzed intraspecific relationships among neighboring colonies of the dominant Mediterranean acrobat ant Crematogaster scutellaris integrating genetic, chemical and behavioral analyses. Colony structure, parental relationships between nests, cuticular hydrocarbons profiles (CHCs) and aggressive behavior against non nest-mates were studied in 34 nests located in olive tree trunks. Bayesian clustering analysis of allelic variation at nine species-specific microsatellite DNA markers pooled nests into 14 distinct clusters, each representing a single colony, confirming a polydomous arrangement of nests in this species. A marked genetic separation among colonies was also detected, probably due to long distance dispersion of queens and males during nuptial flights. CHCs profiles varied significantly among colonies and between nests of the same colony. No relationship between CHCs profiles and genetic distances was detected. The level of aggressiveness between colonies was inversely related to chemical and spatial distance, suggesting a ‘nasty neighbor’ effect. Our findings also suggest that CHCs profiles in C. scutellaris may be linked to external environmental factors rather than genetic relationships. PMID:26445245

  15. The Rules of Aggression: How Genetic, Chemical and Spatial Factors Affect Intercolony Fights in a Dominant Species, the Mediterranean Acrobat Ant Crematogaster scutellaris.

    PubMed

    Frizzi, Filippo; Ciofi, Claudio; Dapporto, Leonardo; Natali, Chiara; Chelazzi, Guido; Turillazzi, Stefano; Santini, Giacomo

    2015-01-01

    Nest-mate recognition plays a key role in the biology of ants. Although individuals coming from a foreign nest are, in most cases, promptly rejected, the degree of aggressiveness towards non nest-mates may be highly variable among species and relies on genetic, chemical and environmental factors. We analyzed intraspecific relationships among neighboring colonies of the dominant Mediterranean acrobat ant Crematogaster scutellaris integrating genetic, chemical and behavioral analyses. Colony structure, parental relationships between nests, cuticular hydrocarbons profiles (CHCs) and aggressive behavior against non nest-mates were studied in 34 nests located in olive tree trunks. Bayesian clustering analysis of allelic variation at nine species-specific microsatellite DNA markers pooled nests into 14 distinct clusters, each representing a single colony, confirming a polydomous arrangement of nests in this species. A marked genetic separation among colonies was also detected, probably due to long distance dispersion of queens and males during nuptial flights. CHCs profiles varied significantly among colonies and between nests of the same colony. No relationship between CHCs profiles and genetic distances was detected. The level of aggressiveness between colonies was inversely related to chemical and spatial distance, suggesting a 'nasty neighbor' effect. Our findings also suggest that CHCs profiles in C. scutellaris may be linked to external environmental factors rather than genetic relationships.

  16. Genetic variance contributes to ingestive processes: a survey of 2-deoxy-D-glucose-induced feeding in eleven inbred mouse strains.

    PubMed

    Lewis, Sarah R; Ahmed, Sabrina; Khaimova, Eleonora; Israel, Yuriy; Singh, Amreeta; Kandov, Yakov; Kest, Benjamin; Bodnar, Richard J

    2006-03-30

    The feeding response following administration of the anti-metabolic glucose analogue, 2-deoxy-d-glucose (2DG), is conceptualized as an experimental model of glucoprivation, which may contribute to the understanding of inter-individual differences in glucose and carbohydrate intake and, ultimately, obesity. Although variation in the intake of several nutrients as well as food and water are known to be associated with genetic variation, it is not known whether 2DG-induced feeding is similarly genotype dependent. The present study therefore examined 2DG-induced feeding in mice of 11 inbred (A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL6/J, C57BL10/J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1) strains across a wide range of previously determined effective 2-DG doses (200, 400, 600, 800 mg/kg) and test times (1-4 h). Orderly dose-dependent increases in 2DG-induced feeding occurred after all four doses in outbred CD-1 and inbred DBA/2J mice, across the three highest doses for BALB/cJ, SJL/J and 129P3/J mice, and across the two highest doses for CBA/J and AKR/J mice. Limited instances of 2DG-induced feeding were noted only at the highest dose in A/J and C3H/HeJ mice, or at a moderate dose in C57BL/6J mice. Further, the full 2DG dose range failed to alter food intake in C57BL/10J mice, and produced significant reductions in food intake in SWR/J mice. Food intake after 2DG doses of 200-600 mg/kg, but not 800 mg/kg, displayed significant cross-correlation, suggesting that large 2DG doses may recruit non-specific effects upon food intake. There was no correlation between food intake in the absence (vehicle baseline) of and presence of 2DG, suggesting that the regulation of glucose intake in non-challenged mice does not predict subsequent responses to glucoprivic challenge. The data demonstrate genotype-dependent variability in this glucoprivic response, and may provide the basis for the subsequent identification of trait-relevant genes.

  17. Cosmic Strings and Cosmic Variance

    NASA Astrophysics Data System (ADS)

    Gangui, Alejandro; Perivolaropoulos, Leandros

    1995-07-01

    By using a simple analytical model based on counting random multiple impulses inflicted on photons by a network of cosmic strings we show how to construct the general q-point temperature correlation function of the cosmic microwave background radiation. Our analysis is especially sensible for large angular scales where the Kaiser-Stebbins effect is dominant. Then we concentrate on the four-point function and, in particular, on its zero-lag limit, namely, the excess kurtosis parameter, for which we obtain a predicted value of ˜10-2. In addition, we estimate the cosmic variance for the kurtosis due to a Gaussian fluctuation field, showing its dependence on the primordial spectral index of density fluctuations n and finding agreement with previous published results for the particular case of a flat Harrison-Zel'dovich spectrum. Our value for the kurtosis compares well with previous analyses but falls below the threshold imposed by the cosmic variance when commonly accepted parameters from string simulations are considered. In particular the non-Gaussian signal is found to be inversely proportional to the scaling number of defects, as could be expected by the central limit theorem.

  18. Spectral Ambiguity of Allan Variance

    NASA Technical Reports Server (NTRS)

    Greenhall, C. A.

    1996-01-01

    We study the extent to which knowledge of Allan variance and other finite-difference variances determines the spectrum of a random process. The variance of first differences is known to determine the spectrum. We show that, in general, the Allan variance does not. A complete description of the ambiguity is given.

  19. Factors affecting the reproductive success of dominant male meerkats.

    PubMed

    Spong, Göran F; Hodge, Sarah J; Young, Andrew J; Clutton-Brock, Tim H

    2008-05-01

    Identifying traits that affect the reproductive success of individuals is fundamental for our understanding of evolutionary processes. In cooperative breeders, a dominant male typically restricts mating access to the dominant female for extended periods, resulting in pronounced variation in reproductive success among males. This may result in strong selection for traits that increase the likelihood of dominance acquisition, dominance retention and reproductive rates while dominant. However, despite considerable research on reproductive skew, few studies have explored the factors that influence these three processes among males in cooperative species. Here we use genetic, behavioural and demographic data to investigate the factors affecting reproductive success in dominant male meerkats (Suricata suricatta). Our data show that dominant males sire the majority of all offspring surviving to 1 year. A male's likelihood of becoming dominant is strongly influenced by age, but not by weight. Tenure length and reproductive rate, both important components of dominant male reproductive success, are largely affected by group size and composition, rather than individual traits. Dominant males in large groups have longer tenures, but after this effect is controlled, male tenure length also correlates negatively to the number of adult females in the group. Male reproductive rate also declines as the number of intra- and extra-group competitors increases. As the time spent in the dominant position and reproductive rate while dominant explain > 80% of the total variance in reproductive success, group composition thus has major implications for male reproductive success.

  20. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM interval

    SciTech Connect

    Ducros, A.; Alamowitch, S.; Nagy, T.

    1996-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently identified autosomal dominant cerebral arteriopathy characterized by the recurrence of subcortical infarcts leading to dementia. A genetic linkage analysis conducted in two large families recently allowed us to map the affected gene on chromosome 19 in a 12-cM interval bracketed by D19S221 and D19S215. In the present study, these first 2 families and 13 additional ones, including a total of 199 potentially informative meiosis, have been genotyped with eight polymorphic markers located between D19S221 and D19S215. All families were linked to chromosome 19. The highest combined lod score (Z{sub max} = 37.24 at {theta} = .01) was obtained with marker D19S841, a new CA{sub n} microsatellite marker that we isolated from chromosome 19 cosmids. The recombinant events observed within these families were used to refine the genetic mapping of CADASIL within a 2-cM interval that is now bracketed by D19S226 and D19S199 on 19p13.1. These data strongly suggest the genetic homogeneity of this recently identified condition and establish the value of its clinical and neuroimaging diagnostic criteria. Besides their importance for the ongoing positional cloning of the CADASIL gene, these data help to refine the genetic mapping of CADASIL relative to familial hemiplegic migraine and hereditary paroxysmal cerebellar ataxia, conditions that we both mapped within the same chromosome 19 region. 35 refs., 5 figs., 2 tabs.

  1. Dominant ER Stress-Inducing WFS1 Mutations Underlie a Genetic Syndrome of Neonatal/Infancy-Onset Diabetes, Congenital Sensorineural Deafness, and Congenital Cataracts.

    PubMed

    De Franco, Elisa; Flanagan, Sarah E; Yagi, Takuya; Abreu, Damien; Mahadevan, Jana; Johnson, Matthew B; Jones, Garan; Acosta, Fernanda; Mulaudzi, Mphele; Lek, Ngee; Oh, Vera; Petz, Oliver; Caswell, Richard; Ellard, Sian; Urano, Fumihiko; Hattersley, Andrew T

    2017-07-01

    Neonatal diabetes is frequently part of a complex syndrome with extrapancreatic features: 18 genes causing syndromic neonatal diabetes have been identified to date. There are still patients with neonatal diabetes who have novel genetic syndromes. We performed exome sequencing in a patient and his unrelated, unaffected parents to identify the genetic etiology of a syndrome characterized by neonatal diabetes, sensorineural deafness, and congenital cataracts. Further testing was performed in 311 patients with diabetes diagnosed before 1 year of age in whom all known genetic causes had been excluded. We identified 5 patients, including the initial case, with three heterozygous missense mutations in WFS1 (4/5 confirmed de novo). They had diabetes diagnosed before 12 months (2 before 6 months) (5/5), sensorineural deafness diagnosed soon after birth (5/5), congenital cataracts (4/5), and hypotonia (4/5). In vitro studies showed that these WFS1 mutations are functionally different from the known recessive Wolfram syndrome-causing mutations, as they tend to aggregate and induce robust endoplasmic reticulum stress. Our results establish specific dominant WFS1 mutations as a cause of a novel syndrome including neonatal/infancy-onset diabetes, congenital cataracts, and sensorineural deafness. This syndrome has a discrete pathophysiology and differs genetically and clinically from recessive Wolfram syndrome. © 2017 by the American Diabetes Association.

  2. Multi-objective parametric optimization of Inertance type pulse tube refrigerator using response surface methodology and non-dominated sorting genetic algorithm

    NASA Astrophysics Data System (ADS)

    Rout, Sachindra K.; Choudhury, Balaji K.; Sahoo, Ranjit K.; Sarangi, Sunil K.

    2014-07-01

    The modeling and optimization of a Pulse Tube Refrigerator is a complicated task, due to its complexity of geometry and nature. The aim of the present work is to optimize the dimensions of pulse tube and regenerator for an Inertance-Type Pulse Tube Refrigerator (ITPTR) by using Response Surface Methodology (RSM) and Non-Sorted Genetic Algorithm II (NSGA II). The Box-Behnken design of the response surface methodology is used in an experimental matrix, with four factors and two levels. The diameter and length of the pulse tube and regenerator are chosen as the design variables where the rest of the dimensions and operating conditions of the ITPTR are constant. The required output responses are the cold head temperature (Tcold) and compressor input power (Wcomp). Computational fluid dynamics (CFD) have been used to model and solve the ITPTR. The CFD results agreed well with those of the previously published paper. Also using the results from the 1-D simulation, RSM is conducted to analyse the effect of the independent variables on the responses. To check the accuracy of the model, the analysis of variance (ANOVA) method has been used. Based on the proposed mathematical RSM models a multi-objective optimization study, using the Non-sorted genetic algorithm II (NSGA-II) has been performed to optimize the responses.

  3. Variance Decomposition Using an IRT Measurement Model

    PubMed Central

    Glas, Cees A. W.; Boomsma, Dorret I.

    2007-01-01

    Large scale research projects in behaviour genetics and genetic epidemiology are often based on questionnaire or interview data. Typically, a number of items is presented to a number of subjects, the subjects’ sum scores on the items are computed, and the variance of sum scores is decomposed into a number of variance components. This paper discusses several disadvantages of the approach of analysing sum scores, such as the attenuation of correlations amongst sum scores due to their unreliability. It is shown that the framework of Item Response Theory (IRT) offers a solution to most of these problems. We argue that an IRT approach in combination with Markov chain Monte Carlo (MCMC) estimation provides a flexible and efficient framework for modelling behavioural phenotypes. Next, we use data simulation to illustrate the potentially huge bias in estimating variance components on the basis of sum scores. We then apply the IRT approach with an analysis of attention problems in young adult twins where the variance decomposition model is extended with an IRT measurement model. We show that when estimating an IRT measurement model and a variance decomposition model simultaneously, the estimate for the heritability of attention problems increases from 40% (based on sum scores) to 73%. PMID:17534709

  4. Genetic mutation, linkage and heterogeneity analysis in Spanish pedigrees and isolated cases of autosomal dominant spinocerebellar ataxia (SCA)

    SciTech Connect

    Volpini, V.; Matilla, T.; Genis, D.

    1994-09-01

    We report a genetic study of 14 Spanish kindreds and 11 isolated cases with SCA. The diagnosis was ascertained in 60 members, but clinical data were only obtained for 35 of them. One defective gene responsible for the disease was localized to 6p22-p23 (SCA1) and the mutation consists of an expansion of an intragenic (CAG){sub n} repeat (REP). We studied all of our genealogical and isolated affected individuals in order to know their 6p mutational status. Thus we detected a large pedigree which has the pathological expansion with {open_quotes}n{close_quotes} in the range of 41 to 57 repeats. The expansion increases through generations and correlates with anticipation. In the Spanish population, the non-pathological range of {open_quotes}n{close_quotes} is from 6 to 39 repeats. These sequences are {open_quotes}protected{close_quotes} having an interrupted repeat configuration, studied by restriction and sequencing analysis. This mutation was not present in the genealogical or isolated affected individuals studied. We also tested our families with the recently reported CAG expansion in 12p-12ter (DRPLA) and obtained negative results. Linkage analysis in non-SCA1, DRPLA families using markers from others chromosomal regions, 12q23-24.1 (SCA2) and 14q24.3-q32 (SCA3), results in negative lod scores and shows genetic heterogeneity in our population.

  5. Demerelate: calculating inter-individual relatedness for kinship analysis based on co-dominant diploid genetic markers using R.

    PubMed

    Kraemer, Philipp; Gerlach, Gabriele

    2017-03-09

    The Demerelate package offers algorithms to calculate different inter-individual relatedness measurements. Three different allele sharing indices, five pairwise weighted estimates of relatedness and four pairwise weighted estimates with sample size correction are implemented to analyze kinship structures within populations. Statistics are based on randomization tests; modeling relatedness coefficients by logistic regression, modeling relatedness with geographic distance by mantel correlation and comparing mean relatedness between populations using pairwise t-tests. Demerelate provides an advance on previous software packages by including some estimators not available in R to date, along with FIS , as well as combining analysis of relatedness and spatial structuring. An UPGMA tree visualizes genetic relatedness among individuals. Additionally, Demerelate summarizes information on datasets (allele vs. genotype frequencies; heterozygosity; FIS -values). Demerelate is - to our knowledge - the first R-package implementing basic allele sharing indices such as Blouin's Mxy relatedness, the estimator of Wang corrected for sample size (wangxy ), estimators based on Morans I adapted to genetic relatedness as well as combining all estimators with geographic information. The R environment enables users to better understand relatedness within populations due to the flexibility of Demerelate of accepting different datasets as empirical data, reference data, geographical data and by providing intermediate results. Each statistic and tool can be used separately, which helps to understand the suitability of the data for relatedness analysis, and can be easily implemented in custom pipelines. This article is protected by copyright. All rights reserved.

  6. Nominal analysis of "variance".

    PubMed

    Weiss, David J

    2009-08-01

    Nominal responses are the natural way for people to report actions or opinions. Because nominal responses do not generate numerical data, they have been underutilized in behavioral research. On those occasions in which nominal responses are elicited, the responses are customarily aggregated over people or trials so that large-sample statistics can be employed. A new analysis is proposed that directly associates differences among responses with particular sources in factorial designs. A pair of nominal responses either matches or does not; when responses do not match, they vary. That analogue to variance is incorporated in the nominal analysis of "variance" (NANOVA) procedure, wherein the proportions of matches associated with sources play the same role as do sums of squares in an ANOVA. The NANOVA table is structured like an ANOVA table. The significance levels of the N ratios formed by comparing proportions are determined by resampling. Fictitious behavioral examples featuring independent groups and repeated measures designs are presented. A Windows program for the analysis is available.

  7. Testing the genetic predictions of a biogeographical model in a dominant endemic Eastern Pacific coral (Porites panamensis) using a genetic seascape approach

    PubMed Central

    Saavedra-Sotelo, Nancy C; Calderon-Aguilera, Luis E; Reyes-Bonilla, Héctor; Paz-García, David A; López-Pérez, Ramón A; Cupul-Magaña, Amilcar; Cruz-Barraza, José A; Rocha-Olivares, Axayácatl

    2013-01-01

    The coral fauna of the Eastern Tropical Pacific (ETP) is depauperate and peripheral; hence, it has drawn attention to the factors allowing its survival. Here, we use a genetic seascape approach and ecological niche modeling to unravel the environmental factors correlating with the genetic variation of Porites panamensis, a hermatypic coral endemic to the ETP. Specifically, we test if levels of diversity and connectivity are higher among abundant than among depauperate populations, as expected by a geographically relaxed version of the Abundant Center Hypothesis (rel-ACH). Unlike the original ACH, referring to a geographical center of distribution of maximal abundance, the rel-ACH refers only to a center of maximum abundance, irrespective of its geographic position. The patterns of relative abundance of P. panamensis in the Mexican Pacific revealed that northern populations from Baja California represent its center of abundance; and southern depauperate populations along the continental margin are peripheral relative to it. Genetic patterns of diversity and structure of nuclear DNA sequences (ribosomal DNA and a single copy open reading frame) and five alloenzymatic loci partially agreed with rel-ACH predictions. We found higher diversity levels in peninsular populations and significant differentiation between peninsular and continental colonies. In addition, continental populations showed higher levels of differentiation and lower connectivity than peninsular populations in the absence of isolation by distance in each region. Some discrepancies with model expectations may relate to the influence of significant habitat discontinuities in the face of limited dispersal potential. Environmental data analyses and niche modeling allowed us to identify temperature, water clarity, and substrate availability as the main factors correlating with patterns of abundance, genetic diversity, and structure, which may hold the key to the survival of P. panamensis in the face of

  8. Genotypic-specific variance in Caenorhabditis elegans lifetime fecundity

    PubMed Central

    Diaz, S Anaid; Viney, Mark

    2014-01-01

    Organisms live in heterogeneous environments, so strategies that maximze fitness in such environments will evolve. Variation in traits is important because it is the raw material on which natural selection acts during evolution. Phenotypic variation is usually thought to be due to genetic variation and/or environmentally induced effects. Therefore, genetically identical individuals in a constant environment should have invariant traits. Clearly, genetically identical individuals do differ phenotypically, usually thought to be due to stochastic processes. It is now becoming clear, especially from studies of unicellular species, that phenotypic variance among genetically identical individuals in a constant environment can be genetically controlled and that therefore, in principle, this can be subject to selection. However, there has been little investigation of these phenomena in multicellular species. Here, we have studied the mean lifetime fecundity (thus a trait likely to be relevant to reproductive success), and variance in lifetime fecundity, in recently-wild isolates of the model nematode Caenorhabditis elegans. We found that these genotypes differed in their variance in lifetime fecundity: some had high variance in fecundity, others very low variance. We find that this variance in lifetime fecundity was negatively related to the mean lifetime fecundity of the lines, and that the variance of the lines was positively correlated between environments. We suggest that the variance in lifetime fecundity may be a bet-hedging strategy used by this species. PMID:25360248

  9. Transcriptomic evidence for the evolution of shoot meristem function in sporophyte-dominant land plants through concerted selection of ancestral gametophytic and sporophytic genetic programs.

    PubMed

    Frank, Margaret H; Scanlon, Michael J

    2015-02-01

    Alternation of generations, in which the haploid and diploid stages of the life cycle are each represented by multicellular forms that differ in their morphology, is a defining feature of the land plants (embryophytes). Anciently derived lineages of embryophytes grow predominately in the haploid gametophytic generation from apical cells that give rise to the photosynthetic body of the plant. More recently evolved plant lineages have multicellular shoot apical meristems (SAMs), and photosynthetic shoot development is restricted to the sporophyte generation. The molecular genetic basis for this evolutionary shift from gametophyte-dominant to sporophyte-dominant life cycles remains a major question in the study of land plant evolution. We used laser microdissection and next generation RNA sequencing to address whether angiosperm meristem patterning genes expressed in the sporophytic SAM of Zea mays are expressed in the gametophytic apical cells, or in the determinate sporophytes, of the model bryophytes Marchantia polymorpha and Physcomitrella patens. A wealth of upregulated genes involved in stem cell maintenance and organogenesis are identified in the maize SAM and in both the gametophytic apical cell and sporophyte of moss, but not in Marchantia. Significantly, meiosis-specific genetic programs are expressed in bryophyte sporophytes, long before the onset of sporogenesis. Our data suggest that this upregulated accumulation of meiotic gene transcripts suppresses indeterminate cell fate in the Physcomitrella sporophyte, and overrides the observed accumulation of meristem patterning genes. A model for the evolution of indeterminate growth in the sporophytic generation through the concerted selection of ancestral meristem gene programs from gametophyte-dominant lineages is proposed.

  10. Genetic analysis of wild-isolated Neurospora crassa strains identified as dominant suppressors of repeat-induced point mutation.

    PubMed Central

    Bhat, Ashwin; Noubissi, Felicite K; Vyas, Meenal; Kasbekar, Durgadas P

    2003-01-01

    Repeat-induced point mutation (RIP) in Neurospora results in inactivation of duplicated DNA sequences. RIP is thought to provide protection against foreign elements such as retrotransposons, only one of which has been found in N. crassa. To examine the role of RIP in nature, we have examined seven N. crassa strains, identified among 446 wild isolates scored for dominant suppression of RIP. The test system involved a small duplication that targets RIP to the easily scorable gene erg-3. We previously showed that RIP in a small duplication is suppressed if another, larger duplication is present in the cross, as expected if the large duplication competes for the RIP machinery. In two of the strains, RIP suppression was associated with a barren phenotype--a characteristic of Neurospora duplications that is thought to result in part from a gene-silencing process called meiotic silencing by unpaired DNA (MSUD). A suppressor of MSUD (Sad-1) was shown not to prevent known large duplications from impairing RIP. Single-gene duplications also can be barren but are too short to suppress RIP. RIP suppression in strains that were not barren showed inheritance that was either simple Mendelian or complex. Adding copies of the LINE-like retrotransposon Tad did not affect RIP efficiency. PMID:12871906

  11. Autosomal dominant polycystic kidney disease in University Clinic of Nephrology and Haemodialysis of Cotonou: clinical and genetical findings.

    PubMed

    Laleye, A; Awede, B; Agboton, B; Azonbakin, S; Biaou, O; Sagbo, G; Adjagba, M; Audrezet, M P; Ferec, C; Darboux, R

    2012-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, but poorly studied in Africa. Its frequency in the University Clinic of Nephrology and Hemodialysis of Cotonou during the ten last years was 7 cases per year with a hospital prevalence estimated at 18 per 1000. The mean age of patients was 47.2 years extending from 29 to 70 years. Males were predominant with a sex ratio of 1.13. Family history was found in 47% of patients. The most common manifestations were lumbar pain (62%), high blood pressure (59%) urinary tract infections (53%), hematuria (46%), and abdominal masses (43%). Hepatic cysts were the most extra renal manifestations, found in 34% of cases. Renal failure was observed in 72% of patients of our series, six of them were under dialysis. Direct sequencing of polycystin 1 gene enabled us to identify some new mutations: 4 nonsense mutations (p.Q2824X exon 23, p.Q1651X exon 15, p.W1666X exon 15, p.R966W exon 12), a duplication (c_1761.1745 dup exon 9), a deletion (c.9397 + 1_9397 + 8del intron 26) and a deletion-insertion (c.7290_7291delins CTGCA exon 18).

  12. Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant).

    PubMed

    Bichet, Daniel G; Bockenhauer, Detlef

    2016-03-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Population genetic patterns among social groups of the endangered Central American spider monkey (Ateles geoffroyi) in a human-dominated landscape.

    PubMed

    Hagell, Suzanne; Whipple, Amy V; Chambers, Carol L

    2013-05-01

    SPIDER MONKEYS (GENUS: Ateles) are a widespread Neotropical primate with a highly plastic socioecological strategy. However, the Central American species, Ateles geoffroyi, was recently re-listed as endangered due to the accelerated loss of forest across the subcontinent. There is inconsistent evidence that spider monkey populations could persist when actively protected, but their long-term viability in unprotected, human-dominated landscapes is not known. We analyzed noninvasive genetic samples from 185 individuals in 14 putative social groups on the Rivas Isthmus in southwestern Nicaragua. We found evidence of weak but significant genetic structure in the mitochondrial control region and in eight nuclear microsatellite loci plus negative spatial autocorrelation in Fst and kinship. The overall pattern suggests strong localized mating and at least historical female-biased dispersal, as is expected for this species. Heterozygosity was significantly lower than expected under random mating and lower than that found in other spider monkey populations, possibly reflecting a recent decline in genetic diversity and a threat from inbreeding. We conclude that despite a long history of human disturbance on this landscape, spider monkeys were until recently successful at maintaining gene flow. We consider the recent decline to be further indication of accelerated anthropogenic disturbance, but also of an opportunity to conserve native biodiversity. Spider monkeys are one of many wildlife species in Central America that is threatened by land cover change, and an apt example of how landscape-scale conservation planning could be used to ensure long-term persistence.

  14. Novel crystallin gamma B mutations in a Kuwaiti family with autosomal dominant congenital cataracts reveal genetic and clinical heterogeneity

    PubMed Central

    Abdelmoaty, Sidky; Al-Hajeri, Amal; Behbehani, Abdulmutalib; Alkuraya, Fowzan

    2012-01-01

    Purpose To explore the disease locus and causative mutation for autosomal dominant congenital cataracts (ADCC) in a Kuwaiti family. There were seven affected and three unaffected subjects in the family. Methods Whole-genome linkage analysis was performed using Gene Chip Human Mapping 250 K Arrays to identify regions of linkage. Potential genes within this region were cloned and sequenced to identify the disease-causing mutation. Results The highest logarithm of odds score (1.5) region 2q34–36.1, spanning the crystallin beta A2 (CRYBA2) gene, showed no sequence changes. Thus, the second highest logarithm of odds score (1.49) region, 2q33–37, spanning the gamma crystalline gene cluster (CRYG), was considered. Sequencing of the CRYGA, B, C, and D genes revealed two novel heterozygous deletions and one trinucleotide polymorphism in the CRYGB gene. These mutations included a heterozygous g.67delG, intron 1 deletion in four of the affected family members with lamellar cataracts and a heterozygous g.167delC, exon 2 deletion inherited from the Egyptian grandmother by her granddaughter, resulting in anterior polar cataracts. Another patient with complete cataracts was a compound heterozygote with both of the above-mentioned mutations. In addition, the novel trinucleotide polymorphism g.20–22 GGT>AAA was detected in three of the family members. Conclusions We report the linkage of ADCC to chromosome 2q33–37, which spans the CRYGB gene. This study is the first to report complex heterogeneous mutations in the CRYGB gene resulting in ADCC with three distinct phenotypes (lamellar, anterior polar, and complete cataracts) in the same family. PMID:23288985

  15. Autosomal dominant

    MedlinePlus

    ... whether the trait is dominant or recessive. A single abnormal gene on one of the first 22 nonsex ( autosomal ) chromosomes from either parent can cause an autosomal disorder. Dominant inheritance means ...

  16. Cosmology without cosmic variance

    SciTech Connect

    Bernstein, Gary M.; Cai, Yan -Chuan

    2011-10-01

    The growth of structures in the Universe is described by a function G that is predicted by the combination of the expansion history of the Universe and the laws of gravity within it. We examine the improvements in constraints on G that are available from the combination of a large-scale galaxy redshift survey with a weak gravitational lensing survey of background sources. We describe a new combination of such observations that in principle this yields a measure of the growth rate that is free of sample variance, i.e. the uncertainty in G can be reduced without bound by increasing the number of redshifts obtained within a finite survey volume. The addition of background weak lensing data to a redshift survey increases information on G by an amount equivalent to a 10-fold increase in the volume of a standard redshift-space distortion measurement - if the lensing signal can be measured to sub-per cent accuracy. This argues that a combined lensing and redshift survey over a common low-redshift volume of the Universe is a more powerful test of general relativity than an isolated redshift survey over larger volume at high redshift, especially as surveys begin to cover most of the available sky.

  17. Cosmology without cosmic variance

    DOE PAGES

    Bernstein, Gary M.; Cai, Yan -Chuan

    2011-10-01

    The growth of structures in the Universe is described by a function G that is predicted by the combination of the expansion history of the Universe and the laws of gravity within it. We examine the improvements in constraints on G that are available from the combination of a large-scale galaxy redshift survey with a weak gravitational lensing survey of background sources. We describe a new combination of such observations that in principle this yields a measure of the growth rate that is free of sample variance, i.e. the uncertainty in G can be reduced without bound by increasing themore » number of redshifts obtained within a finite survey volume. The addition of background weak lensing data to a redshift survey increases information on G by an amount equivalent to a 10-fold increase in the volume of a standard redshift-space distortion measurement - if the lensing signal can be measured to sub-per cent accuracy. This argues that a combined lensing and redshift survey over a common low-redshift volume of the Universe is a more powerful test of general relativity than an isolated redshift survey over larger volume at high redshift, especially as surveys begin to cover most of the available sky.« less

  18. Optimization of an ammonia-cooled rectangular microchannel heat sink using multi-objective non-dominated sorting genetic algorithm (NSGA2)

    NASA Astrophysics Data System (ADS)

    Adham, Ahmed Mohammed; Mohd-Ghazali, Normah; Ahmad, Robiah

    2012-10-01

    The ever decreasing size of modern electronic packaging has induced researchers to search for an effective and efficient heat removal system to handle the continuously increasing power density. Investigations have involved different geometry, material and coolant to address the thermal management issues. This paper reports the potential improvement in the overall performance of a rectangular microchannel heat sink using a new gaseous coolant namely ammonia gas. Using a multi-objective general optimization scheme with the thermal resistance model as an analysis method in combination with a non-dominated sorting genetic algorithm as an optimization technique, it was found that significant reduction in the total thermal resistance up to 34 % for ammonia-cooled compared to air-cooled microchannel heat sink under the same operating conditions is achievable. In addition, a considerable decrease in the microchannel heat sink's mass up to 30 % was achieved due to the different heat sink's material used.

  19. PABPN1 (GCN)11 as a Dominant Allele in Oculopharyngeal Muscular Dystrophy –Consequences in Clinical Diagnosis and Genetic Counselling

    PubMed Central

    Richard, Pascale; Trollet, Capucine; Gidaro, Teresa; Demay, Laurence; Brochier, Guy; Malfatti, Edoardo; Tom, Fernando MS; Fardeau, Michel; Lafor, Pascal; Romero, Norma; Martin-N, Marie-Laure; Sol, Guilhem; Ferrer-Monasterio, Xavier; Saint-Guily, Jean Lacau; Eymard, Bruno

    2015-01-01

    Abstract Oculopharyngeal muscular dystrophy (OPMD) is mainly characterized by ptosis and dysphagia. The genetic cause is a short expansion of a (GCN)10 repeat encoding for polyalanine in the poly(A) binding protein nuclear 1 (PABPN1) gene to (GCN)12–17 repeats. The (GCN)11/Ala11 allele has so far been described to be either a polymorphism or a recessive allele with no effect on the phenotype in the heterozygous state. Here we report the clinical and histopathological phenotype of a patient carrying a single (GCN)11/Ala11 heterozygous allele and presenting an atypical form of OPMD with dysphagia and late and mild oculomotor symptoms. Intranuclear inclusions were observed in his muscle biopsy. This suggests a dominant mode of expression of the (GCN)11/Ala11 allele associated with a partial penetrance of OPMD. PMID:27858728

  20. Identification, genetic characterization, GA response and molecular mapping of Sdt97: a dominant mutant gene conferring semi-dwarfism in rice (Oryza sativa L.).

    PubMed

    Tong, Ji-Ping; Liu, Xue-Jun; Zhang, Shi-Yong; Li, Shao-Qing; Peng, Xiao-Jue; Yang, Jing; Zhu, Ying-Guo

    2007-08-01

    Semi-dwarfism is an important agronomic trait in rice breeding programmes. sd-1, termed the 'Green Revolution gene', confers semi-dwarf stature, increases harvest index, improves lodging resistance, and is associated with increased responsiveness to nitrogen fertilizer. It has contributed substantially to the significant increase in rice production. In this paper, a novel semi-dwarf mutant in rice is reported. Genetic analysis revealed that only a single dominant gene locus non-allelic to sd-1, temporarily designated Sdt97, is involved in the control of semi-dwarfism of the mutant. The semi-dwarfism of the mutant could be partly restored to the tall wild-type by application of exogenous GA3, suggesting that the mutant gene Sdt97 may be involved in the gibberellin (GA) synthesis pathway and not the GA response pathway in rice. A residual heterozygous line (RHL) population derived from a recombinant inbred line (RIL) was developed. Simple sequence repeat (SSR) and bulked segregation analysis (BSA) combined with recessive class analysis (RCA) techniques were used to map Sdt97 to the long arm of chromosome 6 at the interval between two STS markers, N6 and TX5, with a genetic distance of 0.2 cM and 0.8 cM, respectively. A contig map was constructed based on the reference sequence aligned by the Sdt97 linked markers. The physical map of the Sdt97 locus was defined to a 118 kb interval, and 19 candidate genes were detected in the target region. This is the first time that a dominant semi-dwarf gene has been reported in rice. Cloning and functional analysis of gene Sdt97 will help us to learn more about molecular mechanism of rice semi-dwarfism.

  1. A healthy delivery of twins by assisted reproduction followed by preimplantation genetic screening in a woman with X-linked dominant incontinentia pigmenti.

    PubMed

    Kim, Myung Joo; Lyu, Sang Woo; Seok, Hyun Ha; Park, Ji Eun; Shim, Sung Han; Yoon, Tae Ki

    2014-12-01

    The purpose of this study is to report a successful twin pregnancy and delivery in a female patient with X-linked dominant incontinentia pigmenti (IP) who underwent assisted reproductive technology followed by preimplantation genetic screening (PGS). A 29-year-old female with IP had a previous history of recurrent spontaneous abortion. A molecular analysis revealed the patient had a de novo mutation, 1308_1309insCCCCTTG(p.Ala438ProfsTer26), in the inhibitor of the kappa B kinase gamma gene located in the Xq28 region. IVF/ICSI and PGS was performed, in which male embryos were sexed using array-based comparative genomic hybridization (aCGH). After IVF/ICSI and PGS using aCGH on seven embryos, two euploid male blastocysts were transferred with a 50% probability of a viable male pregnancy. The dizygotic twin pregnancy was confirmed and the amniocentesis results of each twin were normal with regard to the mutation found in the mother. The patient delivered healthy twin babies during the 37th week of gestation. This case shows the beneficial role of PGS in achieving a successful pregnancy through euploid male embryo gender selection in a woman with X-linked dominant IP with a history of multiple male miscarriages.

  2. A healthy delivery of twins by assisted reproduction followed by preimplantation genetic screening in a woman with X-linked dominant incontinentia pigmenti

    PubMed Central

    Kim, Myung Joo; Lyu, Sang Woo; Seok, Hyun Ha; Park, Ji Eun

    2014-01-01

    The purpose of this study is to report a successful twin pregnancy and delivery in a female patient with X-linked dominant incontinentia pigmenti (IP) who underwent assisted reproductive technology followed by preimplantation genetic screening (PGS). A 29-year-old female with IP had a previous history of recurrent spontaneous abortion. A molecular analysis revealed the patient had a de novo mutation, 1308_1309insCCCCTTG(p.Ala438ProfsTer26), in the inhibitor of the kappa B kinase gamma gene located in the Xq28 region. IVF/ICSI and PGS was performed, in which male embryos were sexed using array-based comparative genomic hybridization (aCGH). After IVF/ICSI and PGS using aCGH on seven embryos, two euploid male blastocysts were transferred with a 50% probability of a viable male pregnancy. The dizygotic twin pregnancy was confirmed and the amniocentesis results of each twin were normal with regard to the mutation found in the mother. The patient delivered healthy twin babies during the 37th week of gestation. This case shows the beneficial role of PGS in achieving a successful pregnancy through euploid male embryo gender selection in a woman with X-linked dominant IP with a history of multiple male miscarriages. PMID:25599040

  3. The genetic architecture of fitness in a seed beetle: assessing the potential for indirect genetic benefits of female choice.

    PubMed

    Bilde, T; Friberg, U; Maklakov, A A; Fry, J D; Arnqvist, G

    2008-10-26

    Quantifying the amount of standing genetic variation in fitness represents an empirical challenge. Unfortunately, the shortage of detailed studies of the genetic architecture of fitness has hampered progress in several domains of evolutionary biology. One such area is the study of sexual selection. In particular, the evolution of adaptive female choice by indirect genetic benefits relies on the presence of genetic variation for fitness. Female choice by genetic benefits fall broadly into good genes (additive) models and compatibility (non-additive) models where the strength of selection is dictated by the genetic architecture of fitness. To characterize the genetic architecture of fitness, we employed a quantitative genetic design (the diallel cross) in a population of the seed beetle Callosobruchus maculatus, which is known to exhibit post-copulatory female choice. From reciprocal crosses of inbred lines, we assayed egg production, egg-to-adult survival, and lifetime offspring production of the outbred F1 daughters (F1 productivity). We used the bio model to estimate six components of genetic and environmental variance in fitness. We found sizeable additive and non-additive genetic variance in F1 productivity, but lower genetic variance in egg-to-adult survival, which was strongly influenced by maternal and paternal effects. Our results show that, in order to gain a relevant understanding of the genetic architecture of fitness, measures of offspring fitness should be inclusive and should include quantifications of offspring reproductive success. We note that our estimate of additive genetic variance in F1 productivity (CVA=14%) is sufficient to generate indirect selection on female choice. However, our results also show that the major determinant of offspring fitness is the genetic interaction between parental genomes, as indicated by large amounts of non-additive genetic variance (dominance and/or epistasis) for F1 productivity. We discuss the processes that may

  4. The genetic architecture of fitness in a seed beetle: assessing the potential for indirect genetic benefits of female choice

    PubMed Central

    2008-01-01

    Background Quantifying the amount of standing genetic variation in fitness represents an empirical challenge. Unfortunately, the shortage of detailed studies of the genetic architecture of fitness has hampered progress in several domains of evolutionary biology. One such area is the study of sexual selection. In particular, the evolution of adaptive female choice by indirect genetic benefits relies on the presence of genetic variation for fitness. Female choice by genetic benefits fall broadly into good genes (additive) models and compatibility (non-additive) models where the strength of selection is dictated by the genetic architecture of fitness. To characterize the genetic architecture of fitness, we employed a quantitative genetic design (the diallel cross) in a population of the seed beetle Callosobruchus maculatus, which is known to exhibit post-copulatory female choice. From reciprocal crosses of inbred lines, we assayed egg production, egg-to-adult survival, and lifetime offspring production of the outbred F1 daughters (F1 productivity). Results We used the bio model to estimate six components of genetic and environmental variance in fitness. We found sizeable additive and non-additive genetic variance in F1 productivity, but lower genetic variance in egg-to-adult survival, which was strongly influenced by maternal and paternal effects. Conclusion Our results show that, in order to gain a relevant understanding of the genetic architecture of fitness, measures of offspring fitness should be inclusive and should include quantifications of offspring reproductive success. We note that our estimate of additive genetic variance in F1 productivity (CVA = 14%) is sufficient to generate indirect selection on female choice. However, our results also show that the major determinant of offspring fitness is the genetic interaction between parental genomes, as indicated by large amounts of non-additive genetic variance (dominance and/or epistasis) for F1 productivity. We

  5. Estimating the encounter rate variance in distance sampling

    USGS Publications Warehouse

    Fewster, R.M.; Buckland, S.T.; Burnham, K.P.; Borchers, D.L.; Jupp, P.E.; Laake, J.L.; Thomas, L.

    2009-01-01

    The dominant source of variance in line transect sampling is usually the encounter rate variance. Systematic survey designs are often used to reduce the true variability among different realizations of the design, but estimating the variance is difficult and estimators typically approximate the variance by treating the design as a simple random sample of lines. We explore the properties of different encounter rate variance estimators under random and systematic designs. We show that a design-based variance estimator improves upon the model-based estimator of Buckland et al. (2001, Introduction to Distance Sampling. Oxford: Oxford University Press, p. 79) when transects are positioned at random. However, if populations exhibit strong spatial trends, both estimators can have substantial positive bias under systematic designs. We show that poststratification is effective in reducing this bias. ?? 2008, The International Biometric Society.

  6. Information Dominance

    DTIC Science & Technology

    1997-11-01

    Information dominance may be defined as superiority in the generation, manipulation, and use of information sufficient to afford its possessors... information dominance at the strategic level: knowing oneself and one’s enemy; and, at best, inducing them to see things as one does.

  7. Sampling Errors of Variance Components.

    ERIC Educational Resources Information Center

    Sanders, Piet F.

    A study on sampling errors of variance components was conducted within the framework of generalizability theory by P. L. Smith (1978). The study used an intuitive approach for solving the problem of how to allocate the number of conditions to different facets in order to produce the most stable estimate of the universe score variance. Optimization…

  8. Identifying Source Populations and Genetic Structure for Savannah Elephants in Human-Dominated Landscapes and Protected Areas in the Kenya-Tanzania Borderlands

    PubMed Central

    Ahlering, Marissa A.; Eggert, Lori S.; Western, David; Estes, Anna; Munishi, Linus; Fleischer, Robert; Roberts, Melissa; Maldonado, Jesus E.

    2012-01-01

    We investigated the genetic metapopulation structure of elephants across the trans Rift Valley region of Kenya and Tanzania, one of the remaining strongholds for savannah elephants (Loxodonata africana) in East Africa, using microsatellite and mitochondrial DNA (mtDNA) markers. We then examined this population structure to determine the source population for a recent colonization event of savannah elephants on community-owned land within the trans rift valley region. Four of the five sampled populations showed significant genetic differentiation (p<0.05) as measured with both mtDNA haplotypes and microsatellites. Only the samples from the adjacent Maasai Mara and Serengeti ecosystems showed no significant differentiation. A phylogenetic neighbour-joining tree constructed from mtDNA haplotypes detected four clades. Clade four corresponds to the F clade of previous mtDNA studies that reported to have originated in forest elephants (Loxodonta cyclotis) but to also be present in some savannah elephant populations. The split between clade four and the other three clades corresponded strongly to the geographic distribution of mtDNA haplotypes across the rift valley in the study area. Clade four was the dominant clade detected on the west side of the rift valley with rare occurrences on the east side. Finally, the strong patterns of population differentiation clearly indicated that the recent colonists to the community-owned land in Kenya came from the west side of the rift valley. Our results indicate strong female philopatry within the isolated populations of the trans rift valley region, with gene flow primarily mediated via male movements. The recent colonization event from Maasai Mara or Serengeti suggests there is hope for maintaining connectivity and population viability outside formal protected areas in the region. PMID:23300634

  9. Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity

    SciTech Connect

    Othmane, K.B.; Loprest, L.J.; Wilkinson, K.M. ); Middleton, L.T. )

    1993-08-01

    Charcot-Marie-Tooth (CMT) disease type 2 (CMT2) is an inherited peripheral neuropathy characterized by variable age of onset and normal or slightly diminished nerve conduction velocity. CMT2 is pathologically and genetically distinct from CMT type 1 (CMT1). While CMT1 has been shown to be genetically heterogeneous, no chromosomal localization has been established for CMT2. The authors have performed pedigree linkage analysis in six large autosomal dominant CMT2 families and have demonstrated linkage and heterogeneity to a series of microsatellites (D1S160, D1S170, D1S244, D1S228 and D1S199) in the distal region of the short arm of chromosome 1. Significant evidence for heterogeneity was found using admixture analyses and the two-point lod scores. Admixture analyses using the multipoint results for the markers D1S244, D1S228, and D1S199 supported the two-point findings. Three families, DUK662, DUK1241, and 1523 gave posterior probabilities of 1.0, 0.98, and 0.88 of being of the linked type. Multipoint analysis examining the [open quotes]linked[close quotes] families showed that the most favored location for the CMT2A gene is within the interval flanked by D1S244 and D1S228 (odds approximately 70:1 of lying within versus outside that interval). These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrate further heterogeneity in the CMT phenotype.

  10. Identifying source populations and genetic structure for savannah elephants in human-dominated landscapes and protected areas in the Kenya-Tanzania borderlands.

    PubMed

    Ahlering, Marissa A; Eggert, Lori S; Western, David; Estes, Anna; Munishi, Linus; Fleischer, Robert; Roberts, Melissa; Maldonado, Jesus E

    2012-01-01

    We investigated the genetic metapopulation structure of elephants across the trans Rift Valley region of Kenya and Tanzania, one of the remaining strongholds for savannah elephants (Loxodonata africana) in East Africa, using microsatellite and mitochondrial DNA (mtDNA) markers. We then examined this population structure to determine the source population for a recent colonization event of savannah elephants on community-owned land within the trans rift valley region. Four of the five sampled populations showed significant genetic differentiation (p<0.05) as measured with both mtDNA haplotypes and microsatellites. Only the samples from the adjacent Maasai Mara and Serengeti ecosystems showed no significant differentiation. A phylogenetic neighbour-joining tree constructed from mtDNA haplotypes detected four clades. Clade four corresponds to the F clade of previous mtDNA studies that reported to have originated in forest elephants (Loxodonta cyclotis) but to also be present in some savannah elephant populations. The split between clade four and the other three clades corresponded strongly to the geographic distribution of mtDNA haplotypes across the rift valley in the study area. Clade four was the dominant clade detected on the west side of the rift valley with rare occurrences on the east side. Finally, the strong patterns of population differentiation clearly indicated that the recent colonists to the community-owned land in Kenya came from the west side of the rift valley. Our results indicate strong female philopatry within the isolated populations of the trans rift valley region, with gene flow primarily mediated via male movements. The recent colonization event from Maasai Mara or Serengeti suggests there is hope for maintaining connectivity and population viability outside formal protected areas in the region.

  11. Compound Heterozygosity of Dominant and Recessive COL7A Alleles in a Severely Affected Patient with a Family History of Dystrophic Epidermolysis Bullosa: Clinical Findings, Genetic Testing, and Treatment Implications.

    PubMed

    Watson, Kendra D; Schoch, Jennifer J; Beek, Geoffrey J; Hand, Jennifer L

    2017-03-01

    An 8-year-old girl born to a family with more than three generations of dominant dystrophic epidermolysis bullosa (DDEB) presented with life-threatening confluent skin erosions, mitten hand deformity, and failure to thrive. Reassessment of her family history and genetic testing showed compound heterozygous COL7A mutations, one inherited from her DDEB-affected mother and one from her unaffected, healthy father. This family illustrates the risk of unexpected, severe, autosomal recessive epidermolysis bullosa (EB) in a family with milder, multigenerational autosomal dominant EB. Clinicians should recognize the clinical spectrum of dystrophic EB and recommend genetic consultation when the phenotype conflicts with family history.

  12. A Pkd1-Fbn1 genetic interaction implicates TGF-β signaling in the pathogenesis of vascular complications in autosomal dominant polycystic kidney disease.

    PubMed

    Liu, Dongyan; Wang, Connie J; Judge, Daniel P; Halushka, Marc K; Ni, Jie; Habashi, Jennifer P; Moslehi, Javid; Bedja, Djahida; Gabrielson, Kathleen L; Xu, Hangxue; Qian, Feng; Huso, David; Dietz, Harry C; Germino, Gregory G; Watnick, Terry

    2014-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of renal failure that is due to mutations in two genes, PKD1 and PKD2. Vascular complications, including aneurysms, are a well recognized feature of ADPKD, and a subgroup of families exhibits traits reminiscent of Marfan syndrome (MFS). MFS is caused by mutations in fibrillin-1 (FBN1), which encodes an extracellular matrix protein with homology to latent TGF-β binding proteins. It was recently demonstrated that fibrillin-1 deficiency is associated with upregulation of TGF-β signaling. We investigated the overlap between ADPKD and MFS by breeding mice with targeted mutations in Pkd1 and Fbn1. Double heterozygotes displayed an exacerbation of the typical Fbn1 heterozygous aortic phenotype. We show that the basis of this genetic interaction results from further upregulation of TGF-β signaling caused by Pkd1 haploinsufficiency. In addition, we demonstrate that loss of PKD1 alone is sufficient to induce a heightened responsiveness to TGF-β. Our data link the interaction of two important diseases to a fundamental signaling pathway.

  13. Small Drinking Water System Variances

    EPA Pesticide Factsheets

    Small system variances allow a small system to install and maintain technology that can remove a contaminant to the maximum extent that is affordable and protective of public health in lieu of technology that can achieve compliance with the regulation.

  14. The genetic basis of political sophistication.

    PubMed

    Arceneaux, Kevin; Johnson, Martine; Maes, Hermine H

    2012-02-01

    Political sophistication is a concept that encompasses political reasoning, the coherence of people's issue attitudes, and their knowledge of political processes. To what extent is political sophistication affected by genes and environments? Do these distinct but related measures of sophistication share a common genetic structure? We analyze survey data collected from participants in the Minnesota Twin Registry to estimate influences of genes and environments on variables used to measure political sophistication. Additive genetic factors explain 48-76% of the variation in educational attainment, political interest, and political knowledge, while dominance genetics influence 28% of the variance of ideological consistency. Multivariate analyses show that, although these measures share common genetic and unique environmental factors to a modest extent, much of the variance is explained by specific genetic and unique environmental factors. Ideological consistency appears to be mostly distinct from the other measures, as it is strongly accounted for by unique environmental influences.

  15. veqtl-mapper: variance association mapping for molecular phenotypes.

    PubMed

    Brown, Andrew Anand

    2017-09-01

    Genetic loci associated with the variance of phenotypic traits have been of recent interest as they can be signatures of genetic interactions, gene by environment interactions, parent of origin effects and canalization. We present a fast efficient tool to map loci affecting variance of gene expression and other molecular phenotypes in cis. Results: Applied to the publicly available Geuvadis gene expression dataset, we identify 816 loci associated with variance of gene expression using an additive model, and 32 showing differences in variance between homozygous and heterozygous alleles, signatures of parent of origin effects. Documentation and links to source code and binaries for linux can be found at https://funpopgen.github.io/veqm/ . andrew.brown@unige.ch. Supplementary data are available at Bioinformatics online.

  16. Selection enhanced estimates of µ-calpain, calpastatin, and dacylglycerol O-acyltransferase 1 genetic effects on pre-weaning performance, carcass quality traits, and residual variance of tenderness in composite ... cattle

    USDA-ARS?s Scientific Manuscript database

    Selection of the composite MARC III population for markers allowed better estimates of effects and inheritance of markers for targeted carcass quality traits (n=254) and nontargeted traits and an evaluation of SNP specific residual variance models for tenderness. Genotypic effects of CAPN1 haplotyp...

  17. Analysis of variance components of testcross progenies in an autotetraploid species and consequences for recurrent selection with a tester.

    PubMed

    Gallais, A

    1992-01-01

    For autotetraploid species the development of the concept of test value (value in testcross) leads to a simple description of the variance among testcross progenies. When defining directly genetic effects at the level of the value of the progenies, there is no contribution of triand tetragenic interactions. To estimate additive and dominance variances it is only necessary to have the population of progenies structured in half-sib or full-sib families; it is then possible to determine the presence of epistasis using a two-way mating design. When the theory of recurrent selection is applied dominance variance can be neglected for the prediction of genetic advance in one cycle as well for the development of combined selection when progenies are structured in families. The results are similar to those for diploids with two-locus epistasis. The more efficient scheme consists of the development of pair-crossing in off-season generations (for intercrossing) and simultaneous crossing of each plant to the tester. In comparison to the classical scheme, the relative efficiency of such a scheme is 41%. The use of combined selection will further increase this superiority.

  18. 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 ...

  19. Variance in male lifetime reproductive success and estimation of the degree of polygyny in a primate.

    PubMed

    Dubuc, Constance; Ruiz-Lambides, Angelina; Widdig, Anja

    2014-07-01

    The degree of polygyny is predicted to influence the strength of direct male-male competition, leading to a high variance in male lifetime reproductive success and to reproduction limited to the prime period of adulthood. Here, we explore the variance in male lifetime reproductive success and reproductive time in an anthropoid primate forming multimale-multifemale groups. Males of this species form dominance hierarchies, which are expected to skew reproduction toward few high-ranking males. At the same time, however, females mate with multiple males (polygynandry), which should limit the degree of polygyny. Using 20 years of genetic and demographic data, we calculated lifetime reproductive success for the free-ranging rhesus macaque (Macaca mulatta) population of Cayo Santiago for subjects that died naturally or reached senescence. Our results show that 1) male lifetime reproductive success was significantly skewed (range: 0-47 offspring; males reproducing below average: 62.8%; nonbreeders: 17.4%), 2) variance in male lifetime reproductive success was 5 times larger than in females, and 3) male lifetime reproductive success was more influenced by variation in fecundity (60%) than longevity (25%), suggesting that some direct male-male competition takes place. However, the opportunity for selection (i.e., standardized variance in male lifetime reproductive success) is low compared with that in other large mammal species characterized by a high degree of polygyny. Moreover, male reproductive life extended much beyond the prime period, showing that physical strength was not required to acquire mates. We conclude that rhesus macaques exhibit a moderate degree of polygyny and, therefore, low levels of direct male-male competition for fertile females, despite the fact that males form linear dominance hierarchies.

  20. Multicomponent, multi-azimuth pre-stack seismic waveform inversion for azimuthally anisotropic media using a parallel and computationally efficient non-dominated sorting genetic algorithm

    NASA Astrophysics Data System (ADS)

    Li, Tao; Mallick, Subhashis

    2015-02-01

    Consideration of azimuthal anisotropy, at least to an orthorhombic symmetry is important in exploring the naturally fractured and unconventional hydrocarbon reservoirs. Full waveform inversion of multicomponent seismic data can, in principle, provide more robust estimates of subsurface elastic parameters and density than the inversion of single component (P wave) seismic data. In addition, azimuthally dependent anisotropy can only be resolved by carefully studying the multicomponent seismic displacement data acquired and processed along different azimuths. Such an analysis needs an inversion algorithm capable of simultaneously optimizing multiple objectives, one for each data component along each azimuth. These multicomponent and multi-azimuthal seismic inversions are non-linear with non-unique solutions; it is therefore appropriate to treat the objectives as a vector and simultaneously optimize each of its components such that the optimal set of solutions could be obtained. The fast non-dominated sorting genetic algorithm (NSGA II) is a robust stochastic global search method capable of handling multiple objectives, but its computational expense increases with increasing number of objectives and the number of model parameters to be inverted for. In addition, an accurate extraction of subsurface azimuthal anisotropy requires multicomponent seismic data acquired at a fine spatial resolution along many source-to-receiver azimuths. Because routine acquisition of such data is prohibitively expensive, they are typically available along two or at most three azimuthal orientations at a spatial resolution where such an inversion could be applied. This paper proposes a novel multi-objective methodology using a parallelized version of NSGA II for waveform inversion of multicomponent seismic displacement data along two azimuths. By scaling the objectives prior to ranking, redefining the crowding distance as functions of the scaled objective and the model spaces, and varying

  1. Analysis of Variance: Variably Complex

    ERIC Educational Resources Information Center

    Drummond, Gordon B.; Vowler, Sarah L.

    2012-01-01

    These authors have previously described how to use the "t" test to compare two groups. In this article, they describe the use of a different test, analysis of variance (ANOVA) to compare more than two groups. ANOVA is a test of group differences: do at least two of the means differ from each other? ANOVA assumes (1) normal distribution…

  2. VPSim: Variance propagation by simulation

    SciTech Connect

    Burr, T.; Coulter, C.A.; Prommel, J.

    1997-12-01

    One of the fundamental concepts in a materials control and accountability system for nuclear safeguards is the materials balance (MB). All transfers into and out of a material balance area are measured, as are the beginning and ending inventories. The resulting MB measures the material loss, MB = T{sub in} + I{sub B} {minus} T{sub out} {minus} I{sub E}. To interpret the MB, the authors must estimate its measurement error standard deviation, {sigma}{sub MB}. When feasible, they use a method usually known as propagation of variance (POV) to estimate {sigma}{sub MB}. The application of POV for estimating the measurement error variance of an MB is straightforward but tedious. By applying POV to individual measurement error standard deviations they can estimate {sigma}{sub MB} (or more generally, they can estimate the variance-covariance matrix, {Sigma}, of a sequence of MBs). This report describes a new computer program (VPSim) that uses simulation to estimate the {Sigma} matrix of a sequence of MBs. Given the proper input data, VPSim calculates the MB and {sigma}{sub MB}, or calculates a sequence of n MBs and the associated n-by-n covariance matrix, {Sigma}. The covariance matrix, {Sigma}, contains the variance of each MB in the diagonal entries and the covariance between pairs of MBs in the off-diagonal entries.

  3. Hybrid biasing approaches for global variance reduction.

    PubMed

    Wu, Zeyun; Abdel-Khalik, Hany S

    2013-02-01

    A new variant of Monte Carlo-deterministic (DT) hybrid variance reduction approach based on Gaussian process theory is presented for accelerating convergence of Monte Carlo simulation and compared with Forward-Weighted Consistent Adjoint Driven Importance Sampling (FW-CADIS) approach implemented in the SCALE package from Oak Ridge National Laboratory. The new approach, denoted the Gaussian process approach, treats the responses of interest as normally distributed random processes. The Gaussian process approach improves the selection of the weight windows of simulated particles by identifying a subspace that captures the dominant sources of statistical response variations. Like the FW-CADIS approach, the Gaussian process approach utilizes particle importance maps obtained from deterministic adjoint models to derive weight window biasing. In contrast to the FW-CADIS approach, the Gaussian process approach identifies the response correlations (via a covariance matrix) and employs them to reduce the computational overhead required for global variance reduction (GVR) purpose. The effective rank of the covariance matrix identifies the minimum number of uncorrelated pseudo responses, which are employed to bias simulated particles. Numerical experiments, serving as a proof of principle, are presented to compare the Gaussian process and FW-CADIS approaches in terms of the global reduction in standard deviation of the estimated responses.

  4. Functional analysis of variance for association studies.

    PubMed

    Vsevolozhskaya, Olga A; Zaykin, Dmitri V; Greenwood, Mark C; Wei, Changshuai; Lu, Qing

    2014-01-01

    While progress has been made in identifying common genetic variants associated with human diseases, for most of common complex diseases, the identified genetic variants only account for a small proportion of heritability. Challenges remain in finding additional unknown genetic variants predisposing to complex diseases. With the advance in next-generation sequencing technologies, sequencing studies have become commonplace in genetic research. The ongoing exome-sequencing and whole-genome-sequencing studies generate a massive amount of sequencing variants and allow researchers to comprehensively investigate their role in human diseases. The discovery of new disease-associated variants can be enhanced by utilizing powerful and computationally efficient statistical methods. In this paper, we propose a functional analysis of variance (FANOVA) method for testing an association of sequence variants in a genomic region with a qualitative trait. The FANOVA has a number of advantages: (1) it tests for a joint effect of gene variants, including both common and rare; (2) it fully utilizes linkage disequilibrium and genetic position information; and (3) allows for either protective or risk-increasing causal variants. Through simulations, we show that FANOVA outperform two popularly used methods - SKAT and a previously proposed method based on functional linear models (FLM), - especially if a sample size of a study is small and/or sequence variants have low to moderate effects. We conduct an empirical study by applying three methods (FANOVA, SKAT and FLM) to sequencing data from Dallas Heart Study. While SKAT and FLM respectively detected ANGPTL 4 and ANGPTL 3 associated with obesity, FANOVA was able to identify both genes associated with obesity.

  5. Variance decomposition in stochastic simulators

    SciTech Connect

    Le Maître, O. P.; Knio, O. M.; Moraes, A.

    2015-06-28

    This work aims at the development of a mathematical and computational approach that enables quantification of the inherent sources of stochasticity and of the corresponding sensitivities in stochastic simulations of chemical reaction networks. The approach is based on reformulating the system dynamics as being generated by independent standardized Poisson processes. This reformulation affords a straightforward identification of individual realizations for the stochastic dynamics of each reaction channel, and consequently a quantitative characterization of the inherent sources of stochasticity in the system. By relying on the Sobol-Hoeffding decomposition, the reformulation enables us to perform an orthogonal decomposition of the solution variance. Thus, by judiciously exploiting the inherent stochasticity of the system, one is able to quantify the variance-based sensitivities associated with individual reaction channels, as well as the importance of channel interactions. Implementation of the algorithms is illustrated in light of simulations of simplified systems, including the birth-death, Schlögl, and Michaelis-Menten models.

  6. Estimating the Modified Allan Variance

    NASA Technical Reports Server (NTRS)

    Greenhall, Charles

    1995-01-01

    The third-difference approach to modified Allan variance (MVAR) leads to a tractable formula for a measure of MVAR estimator confidence, the equivalent degrees of freedom (edf), in the presence of power-law phase noise. The effect of estimation stride on edf is tabulated. A simple approximation for edf is given, and its errors are tabulated. A theorem allowing conservative estimates of edf in the presence of compound noise processes is given.

  7. Comparison of imputation variance estimators.

    PubMed

    Hughes, R A; Sterne, Jac; Tilling, K

    2016-12-01

    Appropriate imputation inference requires both an unbiased imputation estimator and an unbiased variance estimator. The commonly used variance estimator, proposed by Rubin, can be biased when the imputation and analysis models are misspecified and/or incompatible. Robins and Wang proposed an alternative approach, which allows for such misspecification and incompatibility, but it is considerably more complex. It is unknown whether in practice Robins and Wang's multiple imputation procedure is an improvement over Rubin's multiple imputation. We conducted a critical review of these two multiple imputation approaches, a re-sampling method called full mechanism bootstrapping and our modified Rubin's multiple imputation procedure via simulations and an application to data. We explored four common scenarios of misspecification and incompatibility. In general, for a moderate sample size (n = 1000), Robins and Wang's multiple imputation produced the narrowest confidence intervals, with acceptable coverage. For a small sample size (n = 100) Rubin's multiple imputation, overall, outperformed the other methods. Full mechanism bootstrapping was inefficient relative to the other methods and required modelling of the missing data mechanism under the missing at random assumption. Our proposed modification showed an improvement over Rubin's multiple imputation in the presence of misspecification. Overall, Rubin's multiple imputation variance estimator can fail in the presence of incompatibility and/or misspecification. For unavoidable incompatibility and/or misspecification, Robins and Wang's multiple imputation could provide more robust inferences. © The Author(s) 2014.

  8. µ-Calpain, calpastatin, and growth hormone receptor genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in Angus cattle selected to increase minor haplotype ... frequencies

    USDA-ARS?s Scientific Manuscript database

    Genetic marker effects and interactions are estimated with poor precision when minor marker allele frequencies are low. An Angus population was subjected to marker assisted selection for multiple years to increase divergent haplotype and minor marker allele frequencies to 1) estimate effect size an...

  9. CAPN1, CAST, and DGAT1 genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in a beef cattle population selected for haplotype and allele equalization

    USDA-ARS?s Scientific Manuscript database

    Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC III) was subjected to marker assisted selection for multiple years to equalize specific marker frequencies to 1) estimate effect size an...

  10. Fine-scale population genetic structure of the Bengal tiger (Panthera tigris tigris) in a human-dominated western Terai Arc Landscape, India.

    PubMed

    Singh, Sujeet Kumar; Aspi, Jouni; Kvist, Laura; Sharma, Reeta; Pandey, Puneet; Mishra, Sudhanshu; Singh, Randeep; Agrawal, Manoj; Goyal, Surendra Prakash

    2017-01-01

    Despite massive global conservation strategies, tiger populations continued to decline until recently, mainly due to habitat loss, human-animal conflicts, and poaching. These factors are known to affect the genetic characteristics of tiger populations and decrease local effective population sizes. The Terai Arc Landscape (TAL) at the foothills of the Himalaya is one of the 42 source sites of tigers around the globe. Therefore, information on how landscape features and anthropogenic factors affect the fine-scale spatial genetic structure and variation of tigers in TAL is needed to develop proper management strategies for achieving long-term conservation goals. We document, for the first time, the genetic characteristics of this tiger population by genotyping 71 tiger samples using 13 microsatellite markers from the western region of TAL (WTAL) of 1800 km2. Specifically, we aimed to estimate the genetic variability, population structure, and gene flow. The microsatellite markers indicated that the levels of allelic diversity (MNA = 6.6) and genetic variation (Ho = 0.50, HE = 0.64) were slightly lower than those reported previously in other Bengal tiger populations. We observed moderate gene flow and significant genetic differentiation (FST= 0.060) and identified the presence of cryptic genetic structure using Bayesian and non-Bayesian approaches. There was low and significantly asymmetric migration between the two main subpopulations of the Rajaji Tiger Reserve and the Corbett Tiger Reserve in WTAL. Sibship relationships indicated that the functionality of the corridor between these subpopulations may be retained if the quality of the habitat does not deteriorate. However, we found that gene flow is not adequate in view of changing land use matrices. We discuss the need to maintain connectivity by implementing the measures that have been suggested previously to minimize the level of human disturbance, including relocation of villages and industries, prevention of

  11. Fine-scale population genetic structure of the Bengal tiger (Panthera tigris tigris) in a human-dominated western Terai Arc Landscape, India

    PubMed Central

    Singh, Sujeet Kumar; Aspi, Jouni; Kvist, Laura; Sharma, Reeta; Pandey, Puneet; Mishra, Sudhanshu; Singh, Randeep; Agrawal, Manoj; Goyal, Surendra Prakash

    2017-01-01

    Despite massive global conservation strategies, tiger populations continued to decline until recently, mainly due to habitat loss, human-animal conflicts, and poaching. These factors are known to affect the genetic characteristics of tiger populations and decrease local effective population sizes. The Terai Arc Landscape (TAL) at the foothills of the Himalaya is one of the 42 source sites of tigers around the globe. Therefore, information on how landscape features and anthropogenic factors affect the fine-scale spatial genetic structure and variation of tigers in TAL is needed to develop proper management strategies for achieving long-term conservation goals. We document, for the first time, the genetic characteristics of this tiger population by genotyping 71 tiger samples using 13 microsatellite markers from the western region of TAL (WTAL) of 1800 km2. Specifically, we aimed to estimate the genetic variability, population structure, and gene flow. The microsatellite markers indicated that the levels of allelic diversity (MNA = 6.6) and genetic variation (Ho = 0.50, HE = 0.64) were slightly lower than those reported previously in other Bengal tiger populations. We observed moderate gene flow and significant genetic differentiation (FST= 0.060) and identified the presence of cryptic genetic structure using Bayesian and non-Bayesian approaches. There was low and significantly asymmetric migration between the two main subpopulations of the Rajaji Tiger Reserve and the Corbett Tiger Reserve in WTAL. Sibship relationships indicated that the functionality of the corridor between these subpopulations may be retained if the quality of the habitat does not deteriorate. However, we found that gene flow is not adequate in view of changing land use matrices. We discuss the need to maintain connectivity by implementing the measures that have been suggested previously to minimize the level of human disturbance, including relocation of villages and industries, prevention of

  12. Familial resemblance of borderline personality disorder features: genetic or cultural transmission?

    PubMed

    Distel, Marijn A; Rebollo-Mesa, Irene; Willemsen, Gonneke; Derom, Catherine A; Trull, Timothy J; Martin, Nicholas G; Boomsma, Dorret I

    2009-01-01

    Borderline personality disorder is a severe personality disorder for which genetic research has been limited to family studies and classical twin studies. These studies indicate that genetic effects explain 35 to 45% of the variance in borderline personality disorder and borderline personality features. However, effects of non-additive (dominance) genetic factors, non-random mating and cultural transmission have generally not been explored. In the present study an extended twin-family design was applied to self-report data of twins (N = 5,017) and their siblings (N = 1,266), parents (N = 3,064) and spouses (N = 939) from 4,015 families, to estimate the effects of additive and non-additive genetic and environmental factors, cultural transmission and non-random mating on individual differences in borderline personality features. Results showed that resemblance among biological relatives could completely be attributed to genetic effects. Variation in borderline personality features was explained by additive genetic (21%; 95% CI 17-26%) and dominant genetic (24%; 95% CI 17-31%) factors. Environmental influences (55%; 95% CI 51-60%) explained the remaining variance. Significant resemblance between spouses was observed, which was best explained by phenotypic assortative mating, but it had only a small effect on the genetic variance (1% of the total variance). There was no effect of cultural transmission from parents to offspring.

  13. Variance propagation by simulation (VPSim)

    SciTech Connect

    Burr, T.L.; Coulter, C.A.; Prommel, J.M.

    1997-07-01

    The application of propagation of variance (POV) for estimating the variance of a material balance is straightforward but tedious. Several computer codes exist today to help perform POV. Examples include MAWST (`materials accounting with sequential testing,` used by some Department of Energy sites) and VP (`variance propagation,` used for training). Also, some sites have such simple error models that custom `spreadsheet like` calculations are adequate. Any software to perform POV will have its strengths and weaknesses. A main disadvantage of MAWST is probably its limited form of error models. This limited form forces the user to use cryptic pseudo measurements to effectively extend the allowed error models. A common example is to include sampling error in the total random error by dividing the actual measurement into two pseudo measurements. Because POV can be tedious and input files can be presented in multiple ways to MAWST, it is valuable to have an alternative method to compare results. This paper describes a new code, VPSim, that uses Monte Carlo simulation to do POV. VPSim does not need to rely on pseudo measurements. It is written in C++, runs under Windows NT, and has a user friendly interface. VPSim has been tested on several example problems, and in this paper we compare its results to results from MAWST. We also describe its error models and indicate the structure of its input files. A main disadvantage of VPSim is its long run times. If many simulations are required (20,000 or more, repeated two or more times) and if each balance period has many (10,000 or more) measurements, then run times can be one-half hour or more. For small and modest sized problems, run times are a few minutes. The main advantage of VPSim is that its input files are simple to construct, and therefore also are relatively easy to inspect.

  14. Estimating the Modified Allan Variance

    NASA Technical Reports Server (NTRS)

    Greenhall, Charles

    1995-01-01

    A paper at the 1992 FCS showed how to express the modified Allan variance (mvar) in terms of the third difference of the cumulative sum of time residuals. Although this reformulated definition was presented merely as a computational trick for simplifying the calculation of mvar estimates, it has since turned out to be a powerful theoretical tool for deriving the statistical quality of those estimates in terms of their equivalent degrees of freedom (edf), defined for an estimator V by edf V = 2(EV)2/(var V). Confidence intervals for mvar can then be constructed from levels of the appropriate 2 distribution.

  15. Mitral disc-valve variance

    PubMed Central

    Berroya, Renato B.; Escano, Fernando B.

    1972-01-01

    This report deals with a rare complication of disc-valve prosthesis in the mitral area. A significant disc poppet and struts destruction of mitral Beall valve prostheses occurred 20 and 17 months after implantation. The resulting valve incompetence in the first case contributed to the death of the patient. The durability of Teflon prosthetic valves appears to be in question and this type of valve probably will be unacceptable if there is an increasing number of disc-valve variance in the future. Images PMID:5017573

  16. The evolution and consequences of sex-specific reproductive variance.

    PubMed

    Mullon, Charles; Reuter, Max; Lehmann, Laurent

    2014-01-01

    Natural selection favors alleles that increase the number of offspring produced by their carriers. But in a world that is inherently uncertain within generations, selection also favors alleles that reduce the variance in the number of offspring produced. If previous studies have established this principle, they have largely ignored fundamental aspects of sexual reproduction and therefore how selection on sex-specific reproductive variance operates. To study the evolution and consequences of sex-specific reproductive variance, we present a population-genetic model of phenotypic evolution in a dioecious population that incorporates previously neglected components of reproductive variance. First, we derive the probability of fixation for mutations that affect male and/or female reproductive phenotypes under sex-specific selection. We find that even in the simplest scenarios, the direction of selection is altered when reproductive variance is taken into account. In particular, previously unaccounted for covariances between the reproductive outputs of different individuals are expected to play a significant role in determining the direction of selection. Then, the probability of fixation is used to develop a stochastic model of joint male and female phenotypic evolution. We find that sex-specific reproductive variance can be responsible for changes in the course of long-term evolution. Finally, the model is applied to an example of parental-care evolution. Overall, our model allows for the evolutionary analysis of social traits in finite and dioecious populations, where interactions can occur within and between sexes under a realistic scenario of reproduction.

  17. The Evolution and Consequences of Sex-Specific Reproductive Variance

    PubMed Central

    Mullon, Charles; Reuter, Max; Lehmann, Laurent

    2014-01-01

    Natural selection favors alleles that increase the number of offspring produced by their carriers. But in a world that is inherently uncertain within generations, selection also favors alleles that reduce the variance in the number of offspring produced. If previous studies have established this principle, they have largely ignored fundamental aspects of sexual reproduction and therefore how selection on sex-specific reproductive variance operates. To study the evolution and consequences of sex-specific reproductive variance, we present a population-genetic model of phenotypic evolution in a dioecious population that incorporates previously neglected components of reproductive variance. First, we derive the probability of fixation for mutations that affect male and/or female reproductive phenotypes under sex-specific selection. We find that even in the simplest scenarios, the direction of selection is altered when reproductive variance is taken into account. In particular, previously unaccounted for covariances between the reproductive outputs of different individuals are expected to play a significant role in determining the direction of selection. Then, the probability of fixation is used to develop a stochastic model of joint male and female phenotypic evolution. We find that sex-specific reproductive variance can be responsible for changes in the course of long-term evolution. Finally, the model is applied to an example of parental-care evolution. Overall, our model allows for the evolutionary analysis of social traits in finite and dioecious populations, where interactions can occur within and between sexes under a realistic scenario of reproduction. PMID:24172130

  18. A Wavelet Perspective on the Allan Variance.

    PubMed

    Percival, Donald B

    2016-04-01

    The origins of the Allan variance trace back 50 years ago to two seminal papers, one by Allan (1966) and the other by Barnes (1966). Since then, the Allan variance has played a leading role in the characterization of high-performance time and frequency standards. Wavelets first arose in the early 1980s in the geophysical literature, and the discrete wavelet transform (DWT) became prominent in the late 1980s in the signal processing literature. Flandrin (1992) briefly documented a connection between the Allan variance and a wavelet transform based upon the Haar wavelet. Percival and Guttorp (1994) noted that one popular estimator of the Allan variance-the maximal overlap estimator-can be interpreted in terms of a version of the DWT now widely referred to as the maximal overlap DWT (MODWT). In particular, when the MODWT is based on the Haar wavelet, the variance of the resulting wavelet coefficients-the wavelet variance-is identical to the Allan variance when the latter is multiplied by one-half. The theory behind the wavelet variance can thus deepen our understanding of the Allan variance. In this paper, we review basic wavelet variance theory with an emphasis on the Haar-based wavelet variance and its connection to the Allan variance. We then note that estimation theory for the wavelet variance offers a means of constructing asymptotically correct confidence intervals (CIs) for the Allan variance without reverting to the common practice of specifying a power-law noise type a priori. We also review recent work on specialized estimators of the wavelet variance that are of interest when some observations are missing (gappy data) or in the presence of contamination (rogue observations or outliers). It is a simple matter to adapt these estimators to become estimators of the Allan variance. Finally we note that wavelet variances based upon wavelets other than the Haar offer interesting generalizations of the Allan variance.

  19. The ethics of contacting family members of a subject in a genetic research study to return results for an autosomal dominant syndrome.

    PubMed

    Taylor, Holly A; Wilfond, Benjamin S

    2013-01-01

    This case explores the ethical landscape around recontacting a subject's relatives to return genetic research results when the informed consent form signed by the original cohort of subjects is silent on whether investigators may share new information with the research subject's family. As a result of rapid advances in genetic technology, methods to identify genetic markers can mature during the life course of a study. In this case, the investigators identified the genetic mutation responsible for the disorder after a number of their original subjects had died. The researchers now have the ability to inform relatives of the subject about their risk of developing the same disease. Mark Rothstein, JD, from the University of Louisville School of Medicine, provides an overview of the medical/scientific, legal, and ethical issues underlying this case. Lauren Milner, PhD, and colleagues at Stanford University explore how the relationship between researcher and subject affect this debate. Seema Shah, JD, and colleagues at the National Institutes of Health and University of California, Los Angeles (UCLA) discuss whether and how requirements of the duty to warn are applicable in this case.

  20. The contribution of dominance to phenotype prediction in a pine breeding and simulated population

    PubMed Central

    de Almeida Filho, J E; Guimarães, J F R; e Silva, F F; de Resende, M D V; Muñoz, P; Kirst, M; Resende, M F R

    2016-01-01

    Pedigrees and dense marker panels have been used to predict the genetic merit of individuals in plant and animal breeding, accounting primarily for the contribution of additive effects. However, nonadditive effects may also affect trait variation in many breeding systems, particularly when specific combining ability is explored. Here we used models with different priors, and including additive-only and additive plus dominance effects, to predict polygenic (height) and oligogenic (fusiform rust resistance) traits in a structured breeding population of loblolly pine (Pinus taeda L.). Models were largely similar in predictive ability, and the inclusion of dominance only improved modestly the predictions for tree height. Next, we simulated a genetically similar population to assess the ability of predicting polygenic and oligogenic traits controlled by different levels of dominance. The simulation showed an overall decrease in the accuracy of total genomic predictions as dominance increases, regardless of the method used for prediction. Thus, dominance effects may not be accounted for as effectively in prediction models compared with traits controlled by additive alleles only. When the ratio of dominance to total phenotypic variance reached 0.2, the additive–dominance prediction models were significantly better than the additive-only models. However, in the prediction of the subsequent progeny population, this accuracy increase was only observed for the oligogenic trait. PMID:27118156

  1. Heritable environmental variance causes nonlinear relationships between traits: application to birth weight and stillbirth of pigs.

    PubMed

    Mulder, Herman A; Hill, William G; Knol, Egbert F

    2015-04-01

    There is recent evidence from laboratory experiments and analysis of livestock populations that not only the phenotype itself, but also its environmental variance, is under genetic control. Little is known about the relationships between the environmental variance of one trait and mean levels of other traits, however. A genetic covariance between these is expected to lead to nonlinearity between them, for example between birth weight and survival of piglets, where animals of extreme weights have lower survival. The objectives were to derive this nonlinear relationship analytically using multiple regression and apply it to data on piglet birth weight and survival. This study provides a framework to study such nonlinear relationships caused by genetic covariance of environmental variance of one trait and the mean of the other. It is shown that positions of phenotypic and genetic optima may differ and that genetic relationships are likely to be more curvilinear than phenotypic relationships, dependent mainly on the environmental correlation between these traits. Genetic correlations may change if the population means change relative to the optimal phenotypes. Data of piglet birth weight and survival show that the presence of nonlinearity can be partly explained by the genetic covariance between environmental variance of birth weight and survival. The framework developed can be used to assess effects of artificial and natural selection on means and variances of traits and the statistical method presented can be used to estimate trade-offs between environmental variance of one trait and mean levels of others. Copyright © 2015 by the Genetics Society of America.

  2. Warped functional analysis of variance.

    PubMed

    Gervini, Daniel; Carter, Patrick A

    2014-09-01

    This article presents an Analysis of Variance model for functional data that explicitly incorporates phase variability through a time-warping component, allowing for a unified approach to estimation and inference in presence of amplitude and time variability. The focus is on single-random-factor models but the approach can be easily generalized to more complex ANOVA models. The behavior of the estimators is studied by simulation, and an application to the analysis of growth curves of flour beetles is presented. Although the model assumes a smooth latent process behind the observed trajectories, smootheness of the observed data is not required; the method can be applied to irregular time grids, which are common in longitudinal studies.

  3. Inheritance Beyond Plain Heritability: Variance-Controlling Genes in Arabidopsis thaliana

    PubMed Central

    Shen, Xia; Pettersson, Mats; Rönnegård, Lars; Carlborg, Örjan

    2012-01-01

    The phenotypic effect of a gene is normally described by the mean-difference between alternative genotypes. A gene may, however, also influence the phenotype by causing a difference in variance between genotypes. Here, we reanalyze a publicly available Arabidopsis thaliana dataset [1] and show that genetic variance heterogeneity appears to be as common as normal additive effects on a genomewide scale. The study also develops theory to estimate the contributions of variance differences between genotypes to the phenotypic variance, and this is used to show that individual loci can explain more than 20% of the phenotypic variance. Two well-studied systems, cellular control of molybdenum level by the ion-transporter MOT1 and flowering-time regulation by the FRI-FLC expression network, and a novel association for Leaf serration are used to illustrate the contribution of major individual loci, expression pathways, and gene-by-environment interactions to the genetic variance heterogeneity. PMID:22876191

  4. 40 CFR 52.2183 - Variance provision.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Dakota § 52.2183 Variance provision. The revisions to the variance provisions in Chapter 74:26:01:31.01 of the South Dakota Air Pollution...

  5. 40 CFR 52.2183 - Variance provision.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Dakota § 52.2183 Variance provision. The revisions to the variance provisions in Chapter 74:26:01:31.01 of the South Dakota Air Pollution...

  6. 40 CFR 52.2183 - Variance provision.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Dakota § 52.2183 Variance provision. The revisions to the variance provisions in Chapter 74:26:01:31.01 of the South Dakota Air Pollution...

  7. 40 CFR 52.2183 - Variance provision.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Dakota § 52.2183 Variance provision. The revisions to the variance provisions in Chapter 74:26:01:31.01 of the South Dakota Air Pollution...

  8. 40 CFR 52.2183 - Variance provision.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Dakota § 52.2183 Variance provision. The revisions to the variance provisions in Chapter 74:26:01:31.01 of the South Dakota Air Pollution...

  9. Population Genetic Structure, Abundance, and Health Status of Two Dominant Benthic Species in the Saba Bank National Park, Caribbean Netherlands: Montastraea cavernosa and Xestospongia muta

    PubMed Central

    de Bakker, Didier M.; Meesters, Erik H. W. G.; van Bleijswijk, Judith D. L.; Luttikhuizen, Pieternella C.; Breeuwer, Hans J. A. J.; Becking, Leontine E.

    2016-01-01

    Saba Bank, a submerged atoll in the Caribbean Sea with an area of 2,200 km2, has attained international conservation status due to the rich diversity of species that reside on the bank. In order to assess the role of Saba Bank as a potential reservoir of diversity for the surrounding reefs, we examined the population genetic structure, abundance and health status of two prominent benthic species, the coral Montastraea cavernosa and the sponge Xestospongia muta. Sequence data were collected from 34 colonies of M. cavernosa (nDNA ITS1-5.8S-ITS2; 892 bp) and 68 X. muta sponges (mtDNA I3-M11 partition of COI; 544 bp) on Saba Bank and around Saba Island, and compared with published data across the wider Caribbean. Our data indicate that there is genetic connectivity between populations on Saba Bank and the nearby Saba Island as well as multiple locations in the wider Caribbean, ranging in distance from 100s–1000s km. The genetic diversity of Saba Bank populations of M. cavernosa (π = 0.055) and X. muta (π = 0.0010) was comparable to those in other regions in the western Atlantic. Densities and health status were determined along 11 transects of 50 m2 along the south-eastern rim of Saba Bank. The densities of M. cavernosa (0.27 ind. m-2, 95% CI: 0.12–0.52) were average, while the densities of X. muta (0.09 ind. m-2, 95% CI: 0.02–0.32) were generally higher with respect to other Caribbean locations. No disease or bleaching was present in any of the specimens of the coral M. cavernosa, however, we did observe partial tissue loss (77.9% of samples) as well as overgrowth (48.1%), predominantly by cyanobacteria. In contrast, the majority of observed X. muta (83.5%) showed signs of presumed bleaching. The combined results of apparent gene flow among populations on Saba Bank and surrounding reefs, the high abundance and unique genetic diversity, indicate that Saba Bank could function as an important buffer for the region. Either as a natural source of larvae to

  10. Population Genetic Structure, Abundance, and Health Status of Two Dominant Benthic Species in the Saba Bank National Park, Caribbean Netherlands: Montastraea cavernosa and Xestospongia muta.

    PubMed

    de Bakker, Didier M; Meesters, Erik H W G; van Bleijswijk, Judith D L; Luttikhuizen, Pieternella C; Breeuwer, Hans J A J; Becking, Leontine E

    2016-01-01

    Saba Bank, a submerged atoll in the Caribbean Sea with an area of 2,200 km2, has attained international conservation status due to the rich diversity of species that reside on the bank. In order to assess the role of Saba Bank as a potential reservoir of diversity for the surrounding reefs, we examined the population genetic structure, abundance and health status of two prominent benthic species, the coral Montastraea cavernosa and the sponge Xestospongia muta. Sequence data were collected from 34 colonies of M. cavernosa (nDNA ITS1-5.8S-ITS2; 892 bp) and 68 X. muta sponges (mtDNA I3-M11 partition of COI; 544 bp) on Saba Bank and around Saba Island, and compared with published data across the wider Caribbean. Our data indicate that there is genetic connectivity between populations on Saba Bank and the nearby Saba Island as well as multiple locations in the wider Caribbean, ranging in distance from 100s-1000s km. The genetic diversity of Saba Bank populations of M. cavernosa (π = 0.055) and X. muta (π = 0.0010) was comparable to those in other regions in the western Atlantic. Densities and health status were determined along 11 transects of 50 m2 along the south-eastern rim of Saba Bank. The densities of M. cavernosa (0.27 ind. m-2, 95% CI: 0.12-0.52) were average, while the densities of X. muta (0.09 ind. m-2, 95% CI: 0.02-0.32) were generally higher with respect to other Caribbean locations. No disease or bleaching was present in any of the specimens of the coral M. cavernosa, however, we did observe partial tissue loss (77.9% of samples) as well as overgrowth (48.1%), predominantly by cyanobacteria. In contrast, the majority of observed X. muta (83.5%) showed signs of presumed bleaching. The combined results of apparent gene flow among populations on Saba Bank and surrounding reefs, the high abundance and unique genetic diversity, indicate that Saba Bank could function as an important buffer for the region. Either as a natural source of larvae to replenish

  11. Imaging structural co-variance between human brain regions

    PubMed Central

    Alexander-Bloch, Aaron; Giedd, Jay N.; Bullmore, Ed

    2014-01-01

    Brain structure varies between people in a markedly organized fashion. Communities of brain regions co-vary in their morphological properties. For example, cortical thickness in one region influences the thickness of structurally and functionally connected regions. Such networks of structural co-variance partially recapitulate the functional networks of healthy individuals and the foci of grey matter loss in neurodegenerative disease. This architecture is genetically heritable, is associated with behavioural and cognitive abilities and is changed systematically across the lifespan. The biological meaning of this structural co-variance remains controversial, but it appears to reflect developmental coordination or synchronized maturation between areas of the brain. This Review discusses the state of current research into brain structural co-variance, its underlying mechanisms and its potential value in the understanding of various neurological and psychiatric conditions. PMID:23531697

  12. Wildlife identified as major source of Escherichia coli in agriculturally dominated watersheds by BOX A1R-derived genetic fingerprints.

    PubMed

    Somarelli, J A; Makarewicz, J C; Sia, R; Simon, R

    2007-01-01

    The presence of Escherichia coli in recreational and potable waters is a major concern to the general public as elevated levels of E. coli suggest the presence of pathogenic bacteria and viruses. Unfortunately, traditional microbial techniques do not allow specific identification of the source of E. coli. This reduces the ability to target management practices that reduce bacterial contamination. In the Finger Lakes region of western New York, USA, wildlife resides in relatively high densities on watersheds dominated by people and dairy farms, and as a result, the sources of fecal degradation of potable and recreational waters are often unknown. In the Conesus Lake watershed, the sources of microbial contamination were assessed using Rep-PCR molecular tools, a method of amplifying repetitive DNA sequences found throughout the E. coli genome to produce distinct fingerprints for a given ecotype. Molecular fingerprints of E. coli isolated from regional populations of cattle, humans, geese and deer were compared to E. coli isolated from stream water samples. Canonical discriminant function analysis indicated that the DNA fingerprints of the original source group isolates were correctly predicted 90.2% of the time. Since land use in the sub-watersheds was dominated by dairy and cash crop farms, it was expected that the majority of E. coli isolated would be identified as cows; however, an unexpectedly high percentage of isolates were identified as wildlife (geese and deer). Geese were the dominant source of E. coli (44.7-73.7% of the total sources) in four sub-watersheds followed by cows (10.5-21.1%), deer (10.5-18.4%), humans (5.3-12.9%) and unidentifiable sources (0.0-11.8%). Management practices intended to decrease the number of cattle or the amount of manure spread in a sub-watershed were reflected in a decrease of E. coli ecotypes associated with dairy cows.

  13. VARAN: A Linear Model Variance Analysis Program.

    ERIC Educational Resources Information Center

    Hall, Charles E.; And Others

    This memorandum is the manual for the VARAN (VARiance ANalysis) program, which is the latest addition to a series of computer programs for multivariate analysis of variance. As with earlier programs, analysis of variance, univariate and multivariate, is the main target of the program. Correlation analysis of all types is available with printout in…

  14. Speed Variance and Its Influence on Accidents.

    ERIC Educational Resources Information Center

    Garber, Nicholas J.; Gadirau, Ravi

    A study was conducted to investigate the traffic engineering factors that influence speed variance and to determine to what extent speed variance affects accident rates. Detailed analyses were carried out to relate speed variance with posted speed limit, design speeds, and other traffic variables. The major factor identified was the difference…

  15. The Effect of an Experimental Bottleneck upon Quantitative Genetic Variation in the Housefly

    PubMed Central

    Bryant, Edwin H.; McCommas, Steven A.; Combs, Lisa M.

    1986-01-01

    Effects of a population bottleneck (founder-flush cycle) upon quantitative genetic variation of morphometric traits were examined in replicated experimental lines of the housefly founded with one, four or 16 pairs of flies. Heritability and additive genetic variances for eight morphometric traits generally increased as a result of the bottleneck, but the pattern of increase among bottleneck sizes differed among traits. Principal axes of the additive genetic correlation matrix for the control line yielded two suites of traits, one associated with general body size and another set largely independent of body size. In the former set containing five of the traits, additive genetic variance was greatest in the bottleneck size of four pairs, whereas in the latter set of two traits the largest additive genetic variance occurred in the smallest bottleneck size of one pair. One trait exhibited changes in additive genetic variance intermediate between these two major responses. These results were inconsistent with models of additive effects of alleles within loci or of additive effects among loci. An observed decline in viability measures and body size in the bottleneck lines also indicated that there was nonadditivity of allelic effects for these traits. Several possible nonadditive models were explored that increased additive genetic variance as a result of a bottleneck. These included a model with complete dominance, a model with overdominance and a model incorporating multiplicative epistasis. PMID:17246359

  16. Genetic architecture of nonadditive inheritance in Arabidopsis thaliana hybrids

    PubMed Central

    Seymour, Danelle K.; Chae, Eunyoung; Grimm, Dominik G.; Martín Pizarro, Carmen; Habring-Müller, Anette; Vasseur, François; Rakitsch, Barbara; Borgwardt, Karsten M.

    2016-01-01

    The ubiquity of nonparental hybrid phenotypes, such as hybrid vigor and hybrid inferiority, has interested biologists for over a century and is of considerable agricultural importance. Although examples of both phenomena have been subject to intense investigation, no general model for the molecular basis of nonadditive genetic variance has emerged, and prediction of hybrid phenotypes from parental information continues to be a challenge. Here we explore the genetics of hybrid phenotype in 435 Arabidopsis thaliana individuals derived from intercrosses of 30 parents in a half diallel mating scheme. We find that nonadditive genetic effects are a major component of genetic variation in this population and that the genetic basis of hybrid phenotype can be mapped using genome-wide association (GWA) techniques. Significant loci together can explain as much as 20% of phenotypic variation in the surveyed population and include examples that have both classical dominant and overdominant effects. One candidate region inherited dominantly in the half diallel contains the gene for the MADS-box transcription factor AGAMOUS-LIKE 50 (AGL50), which we show directly to alter flowering time in the predicted manner. Our study not only illustrates the promise of GWA approaches to dissect the genetic architecture underpinning hybrid performance but also demonstrates the contribution of classical dominance to genetic variance. PMID:27803326

  17. Genetic architecture of nonadditive inheritance in Arabidopsis thaliana hybrids.

    PubMed

    Seymour, Danelle K; Chae, Eunyoung; Grimm, Dominik G; Martín Pizarro, Carmen; Habring-Müller, Anette; Vasseur, François; Rakitsch, Barbara; Borgwardt, Karsten M; Koenig, Daniel; Weigel, Detlef

    2016-11-15

    The ubiquity of nonparental hybrid phenotypes, such as hybrid vigor and hybrid inferiority, has interested biologists for over a century and is of considerable agricultural importance. Although examples of both phenomena have been subject to intense investigation, no general model for the molecular basis of nonadditive genetic variance has emerged, and prediction of hybrid phenotypes from parental information continues to be a challenge. Here we explore the genetics of hybrid phenotype in 435 Arabidopsis thaliana individuals derived from intercrosses of 30 parents in a half diallel mating scheme. We find that nonadditive genetic effects are a major component of genetic variation in this population and that the genetic basis of hybrid phenotype can be mapped using genome-wide association (GWA) techniques. Significant loci together can explain as much as 20% of phenotypic variation in the surveyed population and include examples that have both classical dominant and overdominant effects. One candidate region inherited dominantly in the half diallel contains the gene for the MADS-box transcription factor AGAMOUS-LIKE 50 (AGL50), which we show directly to alter flowering time in the predicted manner. Our study not only illustrates the promise of GWA approaches to dissect the genetic architecture underpinning hybrid performance but also demonstrates the contribution of classical dominance to genetic variance.

  18. Medical genetics

    SciTech Connect

    Jorde, L.B.; Carey, J.C.; White, R.L.

    1995-10-01

    This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

  19. Accounting for dominance to improve genomic evaluations of dairy cows for fertility and milk production traits.

    PubMed

    Aliloo, Hassan; Pryce, Jennie E; González-Recio, Oscar; Cocks, Benjamin G; Hayes, Ben J

    2016-02-01

    Dominance effects may contribute to genetic variation of complex traits in dairy cattle, especially for traits closely related to fitness such as fertility. However, traditional genetic evaluations generally ignore dominance effects and consider additive genetic effects only. Availability of dense single nucleotide polymorphisms (SNPs) panels provides the opportunity to investigate the role of dominance in quantitative variation of complex traits at both the SNP and animal levels. Including dominance effects in the genomic evaluation of animals could also help to increase the accuracy of prediction of future phenotypes. In this study, we estimated additive and dominance variance components for fertility and milk production traits of genotyped Holstein and Jersey cows in Australia. The predictive abilities of a model that accounts for additive effects only (additive), and a model that accounts for both additive and dominance effects (additive + dominance) were compared in a fivefold cross-validation. Estimates of the proportion of dominance variation relative to phenotypic variation that is captured by SNPs, for production traits, were up to 3.8 and 7.1 % in Holstein and Jersey cows, respectively, whereas, for fertility, they were equal to 1.2 % in Holstein and very close to zero in Jersey cows. We found that including dominance in the model was not consistently advantageous. Based on maximum likelihood ratio tests, the additive + dominance model fitted the data better than the additive model, for milk, fat and protein yields in both breeds. However, regarding the prediction of phenotypes assessed with fivefold cross-validation, including dominance effects in the model improved accuracy only for fat yield in Holstein cows. Regression coefficients of phenotypes on genetic values and mean squared errors of predictions showed that the predictive ability of the additive + dominance model was superior to that of the additive model for some of the traits. In both breeds

  20. Heritable Environmental Variance Causes Nonlinear Relationships Between Traits: Application to Birth Weight and Stillbirth of Pigs

    PubMed Central

    Mulder, Herman A.; Hill, William G.; Knol, Egbert F.

    2015-01-01

    There is recent evidence from laboratory experiments and analysis of livestock populations that not only the phenotype itself, but also its environmental variance, is under genetic control. Little is known about the relationships between the environmental variance of one trait and mean levels of other traits, however. A genetic covariance between these is expected to lead to nonlinearity between them, for example between birth weight and survival of piglets, where animals of extreme weights have lower survival. The objectives were to derive this nonlinear relationship analytically using multiple regression and apply it to data on piglet birth weight and survival. This study provides a framework to study such nonlinear relationships caused by genetic covariance of environmental variance of one trait and the mean of the other. It is shown that positions of phenotypic and genetic optima may differ and that genetic relationships are likely to be more curvilinear than phenotypic relationships, dependent mainly on the environmental correlation between these traits. Genetic correlations may change if the population means change relative to the optimal phenotypes. Data of piglet birth weight and survival show that the presence of nonlinearity can be partly explained by the genetic covariance between environmental variance of birth weight and survival. The framework developed can be used to assess effects of artificial and natural selection on means and variances of traits and the statistical method presented can be used to estimate trade-offs between environmental variance of one trait and mean levels of others. PMID:25631318

  1. Pathogenic Potential, Genetic Diversity, and Population Structure of Escherichia coli Strains Isolated from a Forest-Dominated Watershed (Comox Lake) in British Columbia, Canada

    PubMed Central

    Mazumder, Asit

    2014-01-01

    Escherichia coli isolates (n = 658) obtained from drinking water intakes of Comox Lake (2011 to 2013) were screened for the following virulence genes (VGs): stx1 and stx2 (Shiga toxin-producing E. coli [STEC]), eae and the adherence factor (EAF) gene (enteropathogenic E. coli [EPEC]), heat-stable (ST) enterotoxin (variants STh and STp) and heat-labile enterotoxin (LT) genes (enterotoxigenic E. coli [ETEC]), and ipaH (enteroinvasive E. coli [EIEC]). The only genes detected were eae and stx2, which were carried by 37.69% (n = 248) of the isolates. Only eae was harbored by 26.74% (n = 176) of the isolates, representing potential atypical EPEC strains, while only stx2 was detected in 10.33% (n = 68) of the isolates, indicating potential STEC strains. Moreover, four isolates were positive for both the stx2 and eae genes, representing potential EHEC strains. The prevalence of VGs (eae or stx2) was significantly (P < 0.0001) higher in the fall season, and multiple genes (eae plus stx2) were detected only in fall. Repetitive element palindromic PCR (rep-PCR) fingerprint analysis of 658 E. coli isolates identified 335 unique fingerprints, with an overall Shannon diversity (H′) index of 3.653. Diversity varied among seasons over the years, with relatively higher diversity during fall. Multivariate analysis of variance (MANOVA) revealed that the majority of the fingerprints showed a tendency to cluster according to year, season, and month. Taken together, the results indicated that the diversity and population structure of E. coli fluctuate on a temporal scale, reflecting the presence of diverse host sources and their behavior over time in the watershed. Furthermore, the occurrence of potentially pathogenic E. coli strains in the drinking water intakes highlights the risk to human health associated with direct and indirect consumption of untreated surface water. PMID:25548059

  2. Pathogenic potential, genetic diversity, and population structure of Escherichia coli strains isolated from a forest-dominated watershed (Comox Lake) in British Columbia, Canada.

    PubMed

    Chandran, Abhirosh; Mazumder, Asit

    2015-03-01

    Escherichia coli isolates (n = 658) obtained from drinking water intakes of Comox Lake (2011 to 2013) were screened for the following virulence genes (VGs): stx1 and stx2 (Shiga toxin-producing E. coli [STEC]), eae and the adherence factor (EAF) gene (enteropathogenic E. coli [EPEC]), heat-stable (ST) enterotoxin (variants STh and STp) and heat-labile enterotoxin (LT) genes (enterotoxigenic E. coli [ETEC]), and ipaH (enteroinvasive E. coli [EIEC]). The only genes detected were eae and stx2, which were carried by 37.69% (n = 248) of the isolates. Only eae was harbored by 26.74% (n = 176) of the isolates, representing potential atypical EPEC strains, while only stx2 was detected in 10.33% (n = 68) of the isolates, indicating potential STEC strains. Moreover, four isolates were positive for both the stx2 and eae genes, representing potential EHEC strains. The prevalence of VGs (eae or stx2) was significantly (P < 0.0001) higher in the fall season, and multiple genes (eae plus stx2) were detected only in fall. Repetitive element palindromic PCR (rep-PCR) fingerprint analysis of 658 E. coli isolates identified 335 unique fingerprints, with an overall Shannon diversity (H') index of 3.653. Diversity varied among seasons over the years, with relatively higher diversity during fall. Multivariate analysis of variance (MANOVA) revealed that the majority of the fingerprints showed a tendency to cluster according to year, season, and month. Taken together, the results indicated that the diversity and population structure of E. coli fluctuate on a temporal scale, reflecting the presence of diverse host sources and their behavior over time in the watershed. Furthermore, the occurrence of potentially pathogenic E. coli strains in the drinking water intakes highlights the risk to human health associated with direct and indirect consumption of untreated surface water.

  3. Restricted sample variance reduces generalizability.

    PubMed

    Lakes, Kimberley D

    2013-06-01

    One factor that affects the reliability of observed scores is restriction of range on the construct measured for a particular group of study participants. This study illustrates how researchers can use generalizability theory to evaluate the impact of restriction of range in particular sample characteristics on the generalizability of test scores and to estimate how changes in measurement design could improve the generalizability of the test scores. An observer-rated measure of child self-regulation (Response to Challenge Scale; Lakes, 2011) is used to examine scores for 198 children (Grades K through 5) within the generalizability theory (GT) framework. The generalizability of ratings within relatively developmentally homogeneous samples is examined and illustrates the effect of reduced variance among ratees on generalizability. Forecasts for g coefficients of various D study designs demonstrate how higher generalizability could be achieved by increasing the number of raters or items. In summary, the research presented illustrates the importance of and procedures for evaluating the generalizability of a set of scores in a particular research context.

  4. VARIANCE OF MICROSOMAL PROTEIN AND ...

    EPA Pesticide Factsheets

    Differences in the pharmacokinetics of xenobiotics among humans makes them differentially susceptible to risk. Differences in enzyme content can mediate pharmacokinetic differences. Microsomal protein is often isolated fromliver to characterize enzyme content and activity, but no measures exist to extrapolate these data to the intact liver. Measures were developed from up to 60 samples of adult human liver to characterize the content of microsomal protein and cytochrome P450 (CYP) enzymes. Statistical evaluations are necessary to estimate values far from the mean value. Adult human liver contains 52.9 - 1.476 mg microsomal protein per g; 2587 - 1.84 pmoles CYP2E1 per g; and 5237 - 2.214 pmols CYP3A per g (geometric mean - geometric standard deviation). These values are useful for identifying and testing susceptibility as a function of enzyme content when used to extrapolate in vitro rates of chemical metabolism for input to physiologically based pharmacokinetic models which can then be exercised to quantify the effect of variance in enzyme expression on risk-relevant pharmacokinetic outcomes.

  5. Molecular genetic diagnosis of autosomal dominant polycystic kidney disease in a newborn with bilateral cystic kidneys detected prenatally and multiple skeletal malformations.

    PubMed

    Turco, A E; Padovani, E M; Chiaffoni, G P; Peissel, B; Rossetti, S; Marcolongo, A; Gammaro, L; Maschio, G; Pignatti, P F

    1993-05-01

    We report a case of an unusual prenatal presentation of polycystic kidneys associated with multiple skeletal limb defects, including polydactyly, syndactyly, bilateral agenesis of the tibia, and club foot. The ultrasonographic picture was consistent with a diagnosis of polycystic kidney disease, either the adult onset autosomal dominant type (ADPKD) or the early onset autosomal recessive form (ARPKD). However, there was a positive family history for ADPKD. Linkage analysis was performed in 10 family members, of whom four were affected, using six flanking DNA markers tightly linked to the PKD1 locus on chromosome 16p, and one marker linked to the putative PKD2 locus on chromosome 2p. Lod score determinations indicated that the affected gene in the family is most likely PKD1. The patient inherited the disease linked haplotype from his affected mother.

  6. Molecular genetic diagnosis of autosomal dominant polycystic kidney disease in a newborn with bilateral cystic kidneys detected prenatally and multiple skeletal malformations.

    PubMed Central

    Turco, A E; Padovani, E M; Chiaffoni, G P; Peissel, B; Rossetti, S; Marcolongo, A; Gammaro, L; Maschio, G; Pignatti, P F

    1993-01-01

    We report a case of an unusual prenatal presentation of polycystic kidneys associated with multiple skeletal limb defects, including polydactyly, syndactyly, bilateral agenesis of the tibia, and club foot. The ultrasonographic picture was consistent with a diagnosis of polycystic kidney disease, either the adult onset autosomal dominant type (ADPKD) or the early onset autosomal recessive form (ARPKD). However, there was a positive family history for ADPKD. Linkage analysis was performed in 10 family members, of whom four were affected, using six flanking DNA markers tightly linked to the PKD1 locus on chromosome 16p, and one marker linked to the putative PKD2 locus on chromosome 2p. Lod score determinations indicated that the affected gene in the family is most likely PKD1. The patient inherited the disease linked haplotype from his affected mother. Images PMID:8320707

  7. Genetic mapping of the human amphiphysin gene (AMPH) at 7p14-p13 excludes its involvement in retinitis pigmentosa 9 or dominant cystoid macular dystrophy

    SciTech Connect

    Yamamoto, R.; Kilimann, M.W.; Li, X.

    1995-10-01

    Amphiphysin is a protein concentrated in neuronal synapses and peripherally associated with synaptic vesicles. It is expressed in many neurons of the central and peripheral nervous systems and also in the adrenal medulla, the anterior and posterior pituitary, cell lines of the endocrine pancreas, and male germ cells. Its subcellular localization and tissue distribution indicate a potential involvement in mechanisms of regulated exocytosis. A role in the dynamic organization of the membrane-associated cytoskeleton is suggested by sequence similarity to the products of two yeast genes, RVS161 and RVS167. Mutation of either of these results in an abnormal actin distribution, disturbs budding morphology, and impairs cell entry into stationary phase. Amphiphysin is the dominant autoantigen in paraneoplastic Stiff-Man syndrome, a neurological autoimmune disorder characterized by progressive rigidity of the body musculature with superimposed painful spasms. 9 refs., 1 fig., 1 tab.

  8. Autosomal dominant familial Mediterranean fever in Northern European Caucasians associated with deletion of p.M694 residue-a case series and genetic exploration.

    PubMed

    Rowczenio, Dorota M; Iancu, Daniela S; Trojer, Hadija; Gilbertson, Janet A; Gillmore, Julian D; Wechalekar, Ashutosh D; Tekman, Mehmet; Stanescu, Horia C; Kleta, Robert; Lane, Thirusha; Hawkins, Philip N; Lachmann, Helen J

    2017-02-01

    This study was undertaken to characterize the phenotype and response to treatment in patients with autosomal dominant FMF caused by MEFV p.M694del mutation and to use haplotype reconstruction to investigate the possibility of common ancestry. MEFV gene was analysed in 3500 subjects with suspected FMF referred to a single UK centre between 2002 and 2014. Patients with p.M694del underwent additional screening of the SAA1 gene as well as haplotype reconstruction of the MEFV locus. The p.M694del variant was identified in 21 patients, sharing an identical disease haplotype that appears to have arisen about 550 years ago. The SAA1.1 allele was found in four patients, including two with AA amyloidosis. The clinical features comprised typical FMF symptoms with median age at onset of 18 years; three patients presented with AA amyloidosis, of whom two had had symptoms of FMF in retrospect. Fifteen patients had received colchicine treatment, all with excellent responses. The p.M694del variant is associated with autosomal dominantly inherited FMF in Northern European Caucasians. Symptoms may develop later in life than in classical recessive FMF but are otherwise similar, as is the response to colchicine treatment. The 14% incidence of AA amyloidosis may reflect delay in diagnosis associated with extreme rarity of FMF in this population. The common haplotype suggests a single founder living in about 1460. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Transcript co-variance with Nestin in two mouse genetic reference populations identifies Lef1 as a novel candidate regulator of neural precursor cell proliferation in the adult hippocampus

    PubMed Central

    Ashbrook, David G.; Delprato, Anna; Grellmann, Claudia; Klein, Marieke; Wetzel, Richard; Overall, Rupert W.; Badea, Alexandra

    2014-01-01

    Adult neurogenesis, the lifelong production of new neurons in the adult brain, is under complex genetic control but many of the genes involved remain to be identified. In this study, we have integrated publicly available gene expression data from the BXD and CXB recombinant inbred mouse lines to discover genes co-expressed in the adult hippocampus with Nestin, a common marker of the neural precursor cell population. In addition, we incorporated spatial expression information to restrict candidates to genes with high differential gene expression in the hippocampal dentate gyrus. Incorporating data from curated protein-protein interaction databases revealed interactions between our candidate genes and those already known to be involved in adult neurogenesis. Enrichment analysis suggested a link to the Wnt/β-catenin pathway, known to be involved in adult neurogenesis. In particular, our candidates were enriched in targets of Lef1, a modulator of the Wnt pathway. In conclusion, our combination of bioinformatics approaches identified six novel candidate genes involved in adult neurogenesis; Amer3, Eya3, Mtdh, Nr4a3, Polr2a, and Tbkbp1. Further, we propose a role for Lef1 transcriptional control in the regulation of adult hippocampal precursor cell proliferation. PMID:25565948

  10. Genetics

    USDA-ARS?s Scientific Manuscript database

    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 ...

  11. Genetics

    USDA-ARS?s Scientific Manuscript database

    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...

  12. Meta-analysis of SNPs involved in variance heterogeneity using Levene's test for equal variances.

    PubMed

    Deng, Wei Q; Asma, Senay; Paré, Guillaume

    2014-03-01

    Meta-analysis is a commonly used approach to increase the sample size for genome-wide association searches when individual studies are otherwise underpowered. Here, we present a meta-analysis procedure to estimate the heterogeneity of the quantitative trait variance attributable to genetic variants using Levene's test without needing to exchange individual-level data. The meta-analysis of Levene's test offers the opportunity to combine the considerable sample size of a genome-wide meta-analysis to identify the genetic basis of phenotypic variability and to prioritize single-nucleotide polymorphisms (SNPs) for gene-gene and gene-environment interactions. The use of Levene's test has several advantages, including robustness to departure from the normality assumption, freedom from the influence of the main effects of SNPs, and no assumption of an additive genetic model. We conducted a meta-analysis of the log-transformed body mass index of 5892 individuals and identified a variant with a highly suggestive Levene's test P-value of 4.28E-06 near the NEGR1 locus known to be associated with extreme obesity.

  13. Meta-analysis of SNPs involved in variance heterogeneity using Levene's test for equal variances

    PubMed Central

    Deng, Wei Q; Asma, Senay; Paré, Guillaume

    2014-01-01

    Meta-analysis is a commonly used approach to increase the sample size for genome-wide association searches when individual studies are otherwise underpowered. Here, we present a meta-analysis procedure to estimate the heterogeneity of the quantitative trait variance attributable to genetic variants using Levene's test without needing to exchange individual-level data. The meta-analysis of Levene's test offers the opportunity to combine the considerable sample size of a genome-wide meta-analysis to identify the genetic basis of phenotypic variability and to prioritize single-nucleotide polymorphisms (SNPs) for gene–gene and gene–environment interactions. The use of Levene's test has several advantages, including robustness to departure from the normality assumption, freedom from the influence of the main effects of SNPs, and no assumption of an additive genetic model. We conducted a meta-analysis of the log-transformed body mass index of 5892 individuals and identified a variant with a highly suggestive Levene's test P-value of 4.28E-06 near the NEGR1 locus known to be associated with extreme obesity. PMID:23921533

  14. Increasing selection response by Bayesian modeling of heterogeneous environmental variances

    USDA-ARS?s Scientific Manuscript database

    Heterogeneity of environmental variance among genotypes reduces selection response because genotypes with higher variance are more likely to be selected than low-variance genotypes. Modeling heterogeneous variances to obtain weighted means corrected for heterogeneous variances is difficult in likel...

  15. Multi-objective optimization of discrete time-cost tradeoff problem in project networks using non-dominated sorting genetic algorithm

    NASA Astrophysics Data System (ADS)

    Shahriari, Mohammadreza

    2016-03-01

    The time-cost tradeoff problem is one of the most important and applicable problems in project scheduling area. There are many factors that force the mangers to crash the time. This factor could be early utilization, early commissioning and operation, improving the project cash flow, avoiding unfavorable weather conditions, compensating the delays, and so on. Since there is a need to allocate extra resources to short the finishing time of project and the project managers are intended to spend the lowest possible amount of money and achieve the maximum crashing time, as a result, both direct and indirect costs will be influenced in the project, and here, we are facing into the time value of money. It means that when we crash the starting activities in a project, the extra investment will be tied in until the end date of the project; however, when we crash the final activities, the extra investment will be tied in for a much shorter period. This study is presenting a two-objective mathematical model for balancing compressing the project time with activities delay to prepare a suitable tool for decision makers caught in available facilities and due to the time of projects. Also drawing the scheduling problem to real world conditions by considering nonlinear objective function and the time value of money are considered. The presented problem was solved using NSGA-II, and the effect of time compressing reports on the non-dominant set.

  16. Multi-objective optimization of combustion, performance and emission parameters in a jatropha biodiesel engine using Non-dominated sorting genetic algorithm-II

    NASA Astrophysics Data System (ADS)

    Dhingra, Sunil; Bhushan, Gian; Dubey, Kashyap Kumar

    2014-03-01

    The present work studies and identifies the different variables that affect the output parameters involved in a single cylinder direct injection compression ignition (CI) engine using jatropha biodiesel. Response surface methodology based on Central composite design (CCD) is used to design the experiments. Mathematical models are developed for combustion parameters (Brake specific fuel consumption (BSFC) and peak cylinder pressure (Pmax)), performance parameter brake thermal efficiency (BTE) and emission parameters (CO, NO x , unburnt HC and smoke) using regression techniques. These regression equations are further utilized for simultaneous optimization of combustion (BSFC, Pmax), performance (BTE) and emission (CO, NO x , HC, smoke) parameters. As the objective is to maximize BTE and minimize BSFC, Pmax, CO, NO x , HC, smoke, a multiobjective optimization problem is formulated. Nondominated sorting genetic algorithm-II is used in predicting the Pareto optimal sets of solution. Experiments are performed at suitable optimal solutions for predicting the combustion, performance and emission parameters to check the adequacy of the proposed model. The Pareto optimal sets of solution can be used as guidelines for the end users to select optimal combination of engine output and emission parameters depending upon their own requirements.

  17. Coupling Genetic and Chemical Microbiome Profiling Reveals Heterogeneity of Archaeome and Bacteriome in Subsurface Biofilms That Are Dominated by the Same Archaeal Species

    PubMed Central

    Holman, Hoi-Ying N.; DeSantis, Todd Z.; Wanner, Gerhard; Andersen, Gary L.; Perras, Alexandra K.; Meck, Sandra; Völkel, Jörg; Bechtel, Hans A.; Wirth, Reinhard; Moissl-Eichinger, Christine

    2014-01-01

    Earth harbors an enormous portion of subsurface microbial life, whose microbiome flux across geographical locations remains mainly unexplored due to difficult access to samples. Here, we investigated the microbiome relatedness of subsurface biofilms of two sulfidic springs in southeast Germany that have similar physical and chemical parameters and are fed by one deep groundwater current. Due to their unique hydrogeological setting these springs provide accessible windows to subsurface biofilms dominated by the same uncultivated archaeal species, called SM1 Euryarchaeon. Comparative analysis of infrared imaging spectra demonstrated great variations in archaeal membrane composition between biofilms of the two springs, suggesting different SM1 euryarchaeal strains of the same species at both aquifer outlets. This strain variation was supported by ultrastructural and metagenomic analyses of the archaeal biofilms, which included intergenic spacer region sequencing of the rRNA gene operon. At 16S rRNA gene level, PhyloChip G3 DNA microarray detected similar biofilm communities for archaea, but site-specific communities for bacteria. Both biofilms showed an enrichment of different deltaproteobacterial operational taxonomic units, whose families were, however, congruent as were their lipid spectra. Consequently, the function of the major proportion of the bacteriome appeared to be conserved across the geographic locations studied, which was confirmed by dsrB-directed quantitative PCR. Consequently, microbiome differences of these subsurface biofilms exist at subtle nuances for archaea (strain level variation) and at higher taxonomic levels for predominant bacteria without a substantial perturbation in bacteriome function. The results of this communication provide deep insight into the dynamics of subsurface microbial life and warrant its future investigation with regard to metabolic and genomic analyses. PMID:24971452

  18. A model for the initiation and progression of non-chromaffin paragangliomas: An autosomal dominant disorder with genetic heterogeneity and genomic imprinting

    SciTech Connect

    Mariman, E.C.M.; Beersum, S.E.C. van; Ropers, H.H.

    1994-09-01

    Non-chromaffin paragangliomas are autosomal dominantly inherited tumors of the head and neck region (frequency: 1:30,000). Genomic imprinting influences the expression of the disorder. Tumor development is restricted to offspring of male disease gene carriers. By linkage analysis and haplotyping of a single family, in which the pattern of inheritance is consistent with genomic imprinting, we have mapped the gene to a 5 cM region of chromosome 11q13.1 between D11S956 and PYGM. A maximum lod score of 7.62 at {theta}=0.0 was obtained for D11S480. This interval does not overlap with the segment 11q22.3-q23.3, to which a locus for glomus tumors has been assigned in other families. Moreover, the 5cM interval was excluded as the location of the disease gene in a second family showing the imprinting phenomenon, whereas an indication for linkage was obtained (Z=+2.65) with markers from the distal locus. These observations argue for the presence of two distinct imprinted genes for paragangliomas on 11q. Clinical findings suggest that at least one, but probably both genes code for tumor suppressor required for tumor initiation. According to this model, imprinting would account for the silencing of the two maternal copies, whereas a paternal copy would be inactive due to an inherited mutation. Tumors would then result from somatic inactivation of the other paternal gene copy in individual cells. In tumors, relaxation of imprinting seems to be a frequent feature. Here, it would necessitate subsequent inactivation of maternal gene copies to allow tumor progression. Indeed, selective loss of maternal alleles in paragangliomas has been observed with markers from 11 q. Definite proof for this model should come from the isolation and expression studies of the involved genes.

  19. Genetic and Environmental Stability of Neuroticism From Adolescence to Adulthood.

    PubMed

    Nivard, Michel G; Middeldorp, Christel M; Dolan, Conor V; Boomsma, Dorret I

    2015-12-01

    Longitudinal studies of neuroticism have shown that, on average, neuroticism scores decrease from adolescence to adulthood. The heritability of neuroticism is estimated between 0.30 and 0.60 and does not seem to vary greatly as a function of age. Shared environmental effects are rarely reported. Less is known about the role of genetic and environmental influences on the rank order stability of neuroticism in the period from adolescence to adulthood. We studied the stability of neuroticism in a cohort sequential (classical) twin design, from adolescence (age 14 years) to young adulthood (age 32 years). A genetic simplex model that was fitted to the longitudinal neuroticism data showed that the genetic stability of neuroticism was relatively high (genetic correlations between adjacent age bins >0.9), and increased from adolescence to adulthood. Environmental stability was appreciably lower (environmental correlations between adjacent age bins were between 0.3 and 0.6). This low stability was largely due to age-specific environmental variance, which was dominated by measurement error. This attenuated the age-to-age environmental correlations. We constructed an environmental covariance matrix corrected for this error, under the strong assumption that all age-specific environmental variance is error variance. The environmental (co)variance matrix corrected for attenuation revealed highly stable environmental influences on neuroticism (correlations between adjacent age bins were between 0.7 and 0.9). Our results indicate that both genetic and environmental influences have enduring effects on individual differences in neuroticism.

  20. Variance components for direct and maternal effects on body weights of Katahdin lambs.

    PubMed

    Ngere, L; Burke, J M; Notter, D R; Morgan, J L M

    2017-08-01

    The aim of this study was to estimate genetic parameters for BW in Katahdin lambs. Six animal models were used to study direct and maternal effects on birth weight (BWT), weaning weight (WWT), and postweaning weight (PWWT) using 41,066 BWT, 33,980 WWT, and 22,793 PWWT records collected over 17 yr in 100 flocks. Models included fixed effects of management group, dam age, type of birth (for BWT) or birth and rearing (for WWT and PWWT), and lamb age at weighing (fitted as a covariate for WWT and PWWT; all < 0.05). Variance components for random effects were estimated in sequentially more complex models and tested for significance with likelihood-ratio tests. A model that fitted only an additive animal effect overestimated additive variance for all BW, resulting in larger estimates of direct heritability than models that included maternal effects. Maternal effects explained variation ( < 0.05) in all BW. Heritability estimates for optimal models were 0.15 ± 0.01 for BWT, 0.18 ± 0.02 for WWT, and 0.20 ± 0.02 for PWWT. Estimates of maternal heritabilities were 0.14 for BWT, 0.10 for WWT, and 0.06 for PWWT, with SE = 0.01. Permanent environmental maternal effects explained 4 to 6% (±1%) of total phenotypic variances for these BW. Litter effects included temporary environmental effects common to littermates and a proportion of the dominance genetic variance and accounted for 16 to 19% (±1%) of phenotypic variance. Correlations between additive direct and maternal genetic effects were -0.14 for BWT, -0.23 for WWT, and -0.04 for PWWT but differed from 0 ( < 0.05) only for WWT. The total heritability predicted the total response in direct and maternal genetic effects from mass selection and was 0.23 for BWT, 0.20 for WWT, and 0.23 for PWWT. Direct and maternal additive, maternal permanent environmental, residual, and phenotypic correlations between BWT and WWT were 0.53 ± 0.05, 0.58 ± 0.06, 0.51 ± 0.06, 0.39 ± 0.01, and 0.44 ± 0.01, respectively; those between BWT

  1. 40 CFR 59.106 - Variance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.106 Variance. (a) Any regulated...

  2. 40 CFR 59.106 - Variance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.106 Variance. (a) Any regulated...

  3. 40 CFR 59.106 - Variance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.106 Variance. (a) Any regulated...

  4. 40 CFR 59.106 - Variance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.106 Variance. (a) Any regulated...

  5. 40 CFR 59.106 - Variance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.106 Variance. (a) Any regulated...

  6. The phenotypic variance gradient - a novel concept.

    PubMed

    Pertoldi, Cino; Bundgaard, Jørgen; Loeschcke, Volker; Barker, James Stuart Flinton

    2014-11-01

    Evolutionary ecologists commonly use reaction norms, which show the range of phenotypes produced by a set of genotypes exposed to different environments, to quantify the degree of phenotypic variance and the magnitude of plasticity of morphometric and life-history traits. Significant differences among the values of the slopes of the reaction norms are interpreted as significant differences in phenotypic plasticity, whereas significant differences among phenotypic variances (variance or coefficient of variation) are interpreted as differences in the degree of developmental instability or canalization. We highlight some potential problems with this approach to quantifying phenotypic variance and suggest a novel and more informative way to plot reaction norms: namely "a plot of log (variance) on the y-axis versus log (mean) on the x-axis, with a reference line added". This approach gives an immediate impression of how the degree of phenotypic variance varies across an environmental gradient, taking into account the consequences of the scaling effect of the variance with the mean. The evolutionary implications of the variation in the degree of phenotypic variance, which we call a "phenotypic variance gradient", are discussed together with its potential interactions with variation in the degree of phenotypic plasticity and canalization.

  7. Morphological and Genetic Variation along a North-to-South Transect in Stipa purpurea, a Dominant Grass on the Qinghai-Tibetan Plateau: Implications for Response to Climate Change

    PubMed Central

    You, Jianling; Qi, Danhui; Zhou, Yin; Chen, Jiakuan; Song, Zhiping

    2016-01-01

    Estimating the potential of species to cope with rapid environmental climatic modifications is of vital importance for determining their future viability and conservation. The variation between existing populations along a climatic gradient may predict how a species will respond to future climate change. Stipa purpurea is a dominant grass species in the alpine steppe and meadow of the Qinghai-Tibetan Plateau (QTP). Ecological niche modelling was applied to S. purpurea, and its distribution was found to be most strongly correlated with the annual precipitation and the mean temperature of the warmest quarter. We established a north-to-south transect over 2000 km long on the QTP reflecting the gradients of temperature and precipitation, and then we estimated the morphological by sampling fruited tussocks and genetic divergence by using 11 microsatellite markers between 20 populations along the transect. Reproductive traits (the number of seeds and reproductive shoots), the reproductive-vegetative growth ratio and the length of roots in the S. purpurea populations varied significantly with climate variables. S. purpurea has high genetic diversity (He = 0.585), a large effective population size (Ne >1,000), and a considerable level of gene flow between populations. The S. purpurea populations have a mosaic genetic structure: some distant populations (over 1000 km apart) clustered genetically, whereas closer populations (< 100 km apart) had diverged significantly, suggesting local adaptation. Asymmetrical long-distance inter-population gene flow occurs along the sampling transect and might be mediated by seed dispersal via migratory herbivores, such as the chiru (Pantholops hodgsonii). These findings suggest that population performance variation and gene flow both facilitate the response of S. purpurea to climate change. PMID:27580056

  8. Combining Study Outcome Measures Using Dominance Adjusted Weights

    ERIC Educational Resources Information Center

    Makambi, Kepher H.; Lu, Wenxin

    2013-01-01

    Weighting of studies in meta-analysis is usually implemented by using the estimated inverse variances of treatment effect estimates. However, there is a possibility of one study dominating other studies in the estimation process by taking on a weight that is above some upper limit. We implement an estimator of the heterogeneity variance that takes…

  9. Combining Study Outcome Measures Using Dominance Adjusted Weights

    ERIC Educational Resources Information Center

    Makambi, Kepher H.; Lu, Wenxin

    2013-01-01

    Weighting of studies in meta-analysis is usually implemented by using the estimated inverse variances of treatment effect estimates. However, there is a possibility of one study dominating other studies in the estimation process by taking on a weight that is above some upper limit. We implement an estimator of the heterogeneity variance that takes…

  10. 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

  11. 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.

  12. 40 CFR 142.41 - Variance request.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....41 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Variances Issued by the Administrator Under Section 1415(a) of the Act § 142.41 Variance request. A supplier of water may request the granting of...

  13. 40 CFR 142.41 - Variance request.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....41 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Variances Issued by the Administrator Under Section 1415(a) of the Act § 142.41 Variance request. A supplier of water may request the granting of...

  14. Variance Design and Air Pollution Control

    ERIC Educational Resources Information Center

    Ferrar, Terry A.; Brownstein, Alan B.

    1975-01-01

    Air pollution control authorities were forced to relax air quality standards during the winter of 1972 by granting variances. This paper examines the institutional characteristics of these variance policies from an economic incentive standpoint, sets up desirable structural criteria for institutional design and arrives at policy guidelines for…

  15. 20 CFR 654.402 - Variances.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... EMPLOYMENT SERVICE SYSTEM Housing for Agricultural Workers Purpose and Applicability § 654.402 Variances. (a... which the employer has taken to protect the health and safety of workers and adequately show that such... the health and safety of the workers. The RA shall send the approved variance to the employer and...

  16. 20 CFR 654.402 - Variances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... EMPLOYMENT SERVICE SYSTEM Housing for Agricultural Workers Purpose and Applicability § 654.402 Variances. (a... which the employer has taken to protect the health and safety of workers and adequately show that such... the health and safety of the workers. The RA shall send the approved variance to the employer and...

  17. 20 CFR 654.402 - Variances.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... EMPLOYMENT SERVICE SYSTEM Housing for Agricultural Workers Purpose and Applicability § 654.402 Variances. (a... which the employer has taken to protect the health and safety of workers and adequately show that such... the health and safety of the workers. The RA shall send the approved variance to the employer and...

  18. 20 CFR 654.402 - Variances.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... EMPLOYMENT SERVICE SYSTEM Housing for Agricultural Workers Purpose and Applicability § 654.402 Variances. (a... which the employer has taken to protect the health and safety of workers and adequately show that such... the health and safety of the workers. The RA shall send the approved variance to the employer and...

  19. 20 CFR 654.402 - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... EMPLOYMENT SERVICE SYSTEM Housing for Agricultural Workers Purpose and Applicability § 654.402 Variances. (a... which the employer has taken to protect the health and safety of workers and adequately show that such... the health and safety of the workers. The RA shall send the approved variance to the employer and...

  20. 10 CFR 851.31 - Variance process.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... and health standard and, in addition to the content required by paragraph (c) of this section, must.... Contractors desiring a variance from a safety and health standard, or portion thereof, may submit a written... standard, or portion thereof, from which the contractor seeks a variance; (4) A description of the steps...

  1. 10 CFR 851.31 - Variance process.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and health standard and, in addition to the content required by paragraph (c) of this section, must.... Contractors desiring a variance from a safety and health standard, or portion thereof, may submit a written... standard, or portion thereof, from which the contractor seeks a variance; (4) A description of the steps...

  2. 10 CFR 851.31 - Variance process.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and health standard and, in addition to the content required by paragraph (c) of this section, must.... Contractors desiring a variance from a safety and health standard, or portion thereof, may submit a written... standard, or portion thereof, from which the contractor seeks a variance; (4) A description of the steps...

  3. 10 CFR 1022.16 - Variances.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Variances. 1022.16 Section 1022.16 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) COMPLIANCE WITH FLOODPLAIN AND WETLAND ENVIRONMENTAL REVIEW REQUIREMENTS Procedures for Floodplain and Wetland Reviews § 1022.16 Variances. (a) Emergency actions. DOE may...

  4. 10 CFR 1022.16 - Variances.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Variances. 1022.16 Section 1022.16 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) COMPLIANCE WITH FLOODPLAIN AND WETLAND ENVIRONMENTAL REVIEW REQUIREMENTS Procedures for Floodplain and Wetland Reviews § 1022.16 Variances. (a) Emergency actions. DOE may...

  5. 10 CFR 1022.16 - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Variances. 1022.16 Section 1022.16 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) COMPLIANCE WITH FLOODPLAIN AND WETLAND ENVIRONMENTAL REVIEW REQUIREMENTS Procedures for Floodplain and Wetland Reviews § 1022.16 Variances. (a) Emergency actions. DOE may...

  6. 10 CFR 1022.16 - Variances.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Variances. 1022.16 Section 1022.16 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) COMPLIANCE WITH FLOODPLAIN AND WETLAND ENVIRONMENTAL REVIEW REQUIREMENTS Procedures for Floodplain and Wetland Reviews § 1022.16 Variances. (a) Emergency actions. DOE may...

  7. 10 CFR 1022.16 - Variances.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Variances. 1022.16 Section 1022.16 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) COMPLIANCE WITH FLOODPLAIN AND WETLAND ENVIRONMENTAL REVIEW REQUIREMENTS Procedures for Floodplain and Wetland Reviews § 1022.16 Variances. (a) Emergency actions. DOE may...

  8. Variance Design and Air Pollution Control

    ERIC Educational Resources Information Center

    Ferrar, Terry A.; Brownstein, Alan B.

    1975-01-01

    Air pollution control authorities were forced to relax air quality standards during the winter of 1972 by granting variances. This paper examines the institutional characteristics of these variance policies from an economic incentive standpoint, sets up desirable structural criteria for institutional design and arrives at policy guidelines for…

  9. Genetic studies: dominant lethal study, sex linked recessive lethal, ames mutagenicity, and heritable translocation test of thermal processed, frozen, electron irradiated, and gamma irradiated chicken. Final report Jun 76-Aug 83

    SciTech Connect

    Sullivan, D.; Lusskin, R.M.; Thomson, G.M.; Kuzdas, C.D.; Ronning, D.C.

    1983-01-01

    Four samples of chicken meat identified as the frozen control, thermally processed, gamma sterilized (5.9 Mrad), and electron sterilized (5.9 MeV), along with negative and positive controls, were evaluated for genetic activity. The samples were evaluated for ability to induce dominant lethal mutations in spermatid and spermatozoan stages of spermatogenesis in mice fed 35 percent chicken meat. The test meat samples were not observed to have an effect on the incidence of the dominant lethal mutations. However, the positive control failed to give a positive response. The meat samples were investigated for mutagenic activity employing Drosophila melanogaster in the sex linked recessive lethal test. The samples were determined to be nonmutagenic in this test and the positive control gave a significant response. Reduced production of offspring in cultures of Drosophila reared on gamma irradiated chicken which could not be overcome by the addition of vitamins was observed. Pre-incubation tests with and without added mutagens revealed that in no case was a positive result observed in the Ames test from chicken meat without an added mutagen. The manner in which chicken meat was processed had no effect upon the response to the Ames test. A heritable translocation test in mice failed to reveal any cytological evidence of translocation heterozygosity in any of the chicken-containing diets.

  10. Portfolio optimization with mean-variance model

    NASA Astrophysics Data System (ADS)

    Hoe, Lam Weng; Siew, Lam Weng

    2016-06-01

    Investors wish to achieve the target rate of return at the minimum level of risk in their investment. Portfolio optimization is an investment strategy that can be used to minimize the portfolio risk and can achieve the target rate of return. The mean-variance model has been proposed in portfolio optimization. The mean-variance model is an optimization model that aims to minimize the portfolio risk which is the portfolio variance. The objective of this study is to construct the optimal portfolio using the mean-variance model. The data of this study consists of weekly returns of 20 component stocks of FTSE Bursa Malaysia Kuala Lumpur Composite Index (FBMKLCI). The results of this study show that the portfolio composition of the stocks is different. Moreover, investors can get the return at minimum level of risk with the constructed optimal mean-variance portfolio.

  11. Variance Assistance Document: Land Disposal Restrictions Treatability Variances and Determinations of Equivalent Treatment

    EPA Pesticide Factsheets

    This document provides assistance to those seeking to submit a variance request for LDR treatability variances and determinations of equivalent treatment regarding the hazardous waste land disposal restrictions program.

  12. Gravity Wave Variances and Propagation Derived from AIRS Radiances

    NASA Technical Reports Server (NTRS)

    Gong, Jie; Wu, Dong L.; Eckermann, S. D.

    2012-01-01

    As the first gravity wave (GW) climatology study using nadir-viewing infrared sounders, 50 Atmospheric Infrared Sounder (AIRS) radiance channels are selected to estimate GW variances at pressure levels between 2-100 hPa. The GW variance for each scan in the cross-track direction is derived from radiance perturbations in the scan, independently of adjacent scans along the orbit. Since the scanning swaths are perpendicular to the satellite orbits, which are inclined meridionally at most latitudes, the zonal component of GW propagation can be inferred by differencing the variances derived between the westmost and the eastmost viewing angles. Consistent with previous GW studies using various satellite instruments, monthly mean AIRS variance shows large enhancements over meridionally oriented mountain ranges as well as some islands at winter hemisphere high latitudes. Enhanced wave activities are also found above tropical deep convective regions. GWs prefer to propagate westward above mountain ranges, and eastward above deep convection. AIRS 90 field-of-views (FOVs), ranging from +48 deg. to -48 deg. off nadir, can detect large-amplitude GWs with a phase velocity propagating preferentially at steep angles (e.g., those from orographic and convective sources). The annual cycle dominates the GW variances and the preferred propagation directions for all latitudes. Indication of a weak two-year variation in the tropics is found, which is presumably related to the Quasi-biennial oscillation (QBO). AIRS geometry makes its out-tracks capable of detecting GWs with vertical wavelengths substantially shorter than the thickness of instrument weighting functions. The novel discovery of AIRS capability of observing shallow inertia GWs will expand the potential of satellite GW remote sensing and provide further constraints on the GW drag parameterization schemes in the general circulation models (GCMs).

  13. [Genetics and genetic counseling].

    PubMed

    Izzi, Claudia; Liut, Francesca; Dallera, Nadia; Mazza, Cinzia; Magistroni, Riccardo; Savoldi, Gianfranco; Scolari, Francesco

    2016-01-01

    Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic disease, characterized by progressive development of bilateral renal cysts. Two causative genes have been identified: PKD1 and PKD2. ADPKD phenotype is highly variable. Typically, ADPKD is an adult onset disease. However, occasionally, ADPKD manifests as very early onset disease. The phenotypic variability of ADPKD can be explained at three genetic levels: genic, allelic and gene modifier effects. Recent advances in molecular screening for PKD gene mutations and the introduction of the new next generation sequencing (NGS)- based genotyping approach have generated considerable improvement regarding the knowledge of genetic basis of ADPKD. The purpose of this article is to provide a comprehensive review of the genetics of ADPKD, focusing on new insights in genotype-phenotype correlation and exploring novel clinical approach to genetic testing. Evaluation of these new genetic information requires a multidisciplinary approach involving a nephrologist and a clinical geneticist.

  14. Portfolio optimization using median-variance approach

    NASA Astrophysics Data System (ADS)

    Wan Mohd, Wan Rosanisah; Mohamad, Daud; Mohamed, Zulkifli

    2013-04-01

    Optimization models have been applied in many decision-making problems particularly in portfolio selection. Since the introduction of Markowitz's theory of portfolio selection, various approaches based on mathematical programming have been introduced such as mean-variance, mean-absolute deviation, mean-variance-skewness and conditional value-at-risk (CVaR) mainly to maximize return and minimize risk. However most of the approaches assume that the distribution of data is normal and this is not generally true. As an alternative, in this paper, we employ the median-variance approach to improve the portfolio optimization. This approach has successfully catered both types of normal and non-normal distribution of data. With this actual representation, we analyze and compare the rate of return and risk between the mean-variance and the median-variance based portfolio which consist of 30 stocks from Bursa Malaysia. The results in this study show that the median-variance approach is capable to produce a lower risk for each return earning as compared to the mean-variance approach.

  15. Variance estimation for stratified propensity score estimators.

    PubMed

    Williamson, E J; Morley, R; Lucas, A; Carpenter, J R

    2012-07-10

    Propensity score methods are increasingly used to estimate the effect of a treatment or exposure on an outcome in non-randomised studies. We focus on one such method, stratification on the propensity score, comparing it with the method of inverse-probability weighting by the propensity score. The propensity score--the conditional probability of receiving the treatment given observed covariates--is usually an unknown probability estimated from the data. Estimators for the variance of treatment effect estimates typically used in practice, however, do not take into account that the propensity score itself has been estimated from the data. By deriving the asymptotic marginal variance of the stratified estimate of treatment effect, correctly taking into account the estimation of the propensity score, we show that routinely used variance estimators are likely to produce confidence intervals that are too conservative when the propensity score model includes variables that predict (cause) the outcome, but only weakly predict the treatment. In contrast, a comparison with the analogous marginal variance for the inverse probability weighted (IPW) estimator shows that routinely used variance estimators for the IPW estimator are likely to produce confidence intervals that are almost always too conservative. Because exact calculation of the asymptotic marginal variance is likely to be complex, particularly for the stratified estimator, we suggest that bootstrap estimates of variance should be used in practice.

  16. Neural field theory with variance dynamics.

    PubMed

    Robinson, P A

    2013-06-01

    Previous neural field models have mostly been concerned with prediction of mean neural activity and with second order quantities such as its