Effect of heterogeneity in recombination rate on variation in realised relationship.

Individuals of a specified pedigree relationship vary in the proportion of the genome they share identical by descent, i.e. in their realised or actual relationship.

Publisher Correction: Selective effects of heterozygous protein-truncating variants.

In the version of this article initially published, reference 10 incorrectly cited Seplyarskiy, V. B. et al.

One Hundred Years of Linkage Disequilibrium.

One hundred years ago, the first population genetic calculations were made for two loci. They indicated that populations should settle down to a state where the frequency of an allele at one locus is independent of the frequency of an allele at a second locus, even if these loci are linked. Fifty years later it was realized what is obvious in retrospect, that these calculations ignored the effect of chance segregation of linked loci, an effect now widely recognized following the association of closely linked markers (SNPs) with rare genetic diseases.

Oxidative costs of reproduction in mouse strains selected for different levels of food intake and which differ in reproductive performance.

Oxidative damage caused by reactive oxygen species has been hypothesised to underpin the trade-off between reproduction and somatic maintenance, i.e., the life-history-oxidative stress theory.

Is Continued Genetic Improvement of Livestock Sustainable?

Large genetic improvements in the quantitative traits of growth, production, and efficiency of farmed livestock have been made over recent decades, and by introduction of genomic technology these are being enhanced. Such continued improvement requires that there be available variation to utilize. The evidence is that little variation has been lost and such rates are indeed sustainable in the future.

Dominance genetic variation contributes little to the missing heritability for human complex traits.

For human complex traits, non-additive genetic variation has been invoked to explain "missing heritability," but its discovery is often neglected in genome-wide association studies. Here we propose a method of using SNP data to partition and estimate the proportion of phenotypic variance attributed to additive and dominance genetic variation at all SNPs (hSNP(2) and δSNP(2)) in unrelated individuals based on an orthogonal model where the estimate of hSNP(2) is independent of that of δSNP(2). With this method, we analyzed 79 quantitative traits in 6,715 unrelated European Americans.

Heritable environmental variance causes nonlinear relationships between traits: application to birth weight and stillbirth of pigs.

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.

Limits to sustained energy intake. XXII. Reproductive performance of two selected mouse lines with different thermal conductance.

Maximal sustained energy intake (SusEI) appears limited, but the factors imposing the limit are disputed. We studied reproductive performance in two lines of mice selected for high and low food intake (MH and ML, respectively), and known to have large differences in thermal conductance (29% higher in the MH line at 21°C). When these mice raised their natural litters, their metabolisable energy intake significantly increased over the first 13 days of lactation and then reached a plateau.

Influence of gene interaction on complex trait variation with multilocus models.

Although research effort is being expended into determining the importance of epistasis and epistatic variance for complex traits, there is considerable controversy about their importance. Here we undertake an analysis for quantitative traits utilizing a range of multilocus quantitative genetic models and gene frequency distributions, focusing on the potential magnitude of the epistatic variance. All the epistatic terms involving a particular locus appear in its average effect, with the number of two-locus interaction terms increasing in proportion to the square of the number of loci and that of third order as the cube and so on.

The action of stabilizing selection, mutation, and drift on epistatic quantitative traits.

For a quantitative trait under stabilizing selection, the effect of epistasis on its genetic architecture and on the changes of genetic variance caused by bottlenecking were investigated using theory and simulation. Assuming empirical estimates of the rate and effects of mutations and the intensity of selection, we assessed the impact of two-locus epistasis (synergistic/antagonistic) among linked or unlinked loci on the distribution of effects and frequencies of segregating loci in populations at the mutation-selection-drift balance. Strong pervasive epistasis did not modify substantially the genetic properties of the trait and, therefore, the most likely explanation for the low amount of variation usually accounted by the loci detected in genome-wide association analyses is that many causal loci will pass undetected.

Applications of population genetics to animal breeding, from wright, fisher and lush to genomic prediction.

Although animal breeding was practiced long before the science of genetics and the relevant disciplines of population and quantitative genetics were known, breeding programs have mainly relied on simply selecting and mating the best individuals on their own or relatives' performance. This is based on sound quantitative genetic principles, developed and expounded by Lush, who attributed much of his understanding to Wright, and formalized in Fisher's infinitesimal model. Analysis at the level of individual loci and gene frequency distributions has had relatively little impact.

On estimation of genetic variance within families using genome-wide identity-by-descent sharing.

Background: Traditionally, heritability and other genetic parameters are estimated from between-family variation. With the advent of dense genotyping, it is now possible to compute the proportion of the genome that is shared by pairs of sibs and thus undertake the estimation within families, thereby avoiding environmental covariances of family members. Formulae for the sampling variance of estimates have been derived previously for families with two sibs, which are relevant for humans, but sampling errors are large.

Assumptions and properties of limiting pathway models for analysis of epistasis in complex traits.

For most complex traits, results from genome-wide association studies show that the proportion of the phenotypic variance attributable to the additive effects of individual SNPs, that is, the heritability explained by the SNPs, is substantially less than the estimate of heritability obtained by standard methods using correlations between relatives. This difference has been called the "missing heritability". One explanation is that heritability estimates from family (including twin) studies are biased upwards.

Identification of pedigree relationship from genome sharing.

Determination of degree of relationship traditionally has been undertaken using genotypic data on individual loci, typically assumed to be independent. With dense marker data as now available, it is possible to identify the regions of the genome shared identical by descent (ibd). This information can be used to determine pedigree relationship (R), e.

Quantitative genetics in the genomics era.

The genetic analysis of quantitative or complex traits has been based mainly on statistical quantities such as genetic variances and heritability. These analyses continue to be developed, for example in studies of natural populations. Genomic methods are having an impact on progress and prospects.

FTO genotype is associated with phenotypic variability of body mass index.

There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ∼170,000 samples on height and body mass index (BMI) in human populations.

On the pleiotropic structure of the genotype-phenotype map and the evolvability of complex organisms.

Analyses of effects of mutants on many traits have enabled estimates to be obtained of the magnitude of pleiotropy, and in reviews of such data others have concluded that the degree of pleiotropy is highly restricted, with implications on the evolvability of complex organisms. We show that these conclusions are highly dependent on statistical assumptions, for example significance levels. We analyze models with pleiotropic effects on all traits at all loci but by variable amounts, considering distributions of numbers of traits declared significant, overall pleiotropic effects, and extent of apparent modularity of effects.

Genome partitioning of genetic variation for complex traits using common SNPs.

We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ∼45%, ∼17%, ∼25% and ∼21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ∼0.5-1% can be explained by X chromosome SNPs.

Genetic analysis of environmental variation.

Environmental variation (VE) in a quantitative trait - variation in phenotype that cannot be explained by genetic variation or identifiable genetic differences - can be regarded as being under some degree of genetic control. Such variation may be either between repeated expressions of the same trait within individuals (e.g.

The population genetics of mutations: good, bad and indifferent.

Population genetics is fundamental to our understanding of evolution, and mutations are essential raw materials for evolution. In this introduction to more detailed papers that follow, we aim to provide an oversight of the field. We review current knowledge on mutation rates and their harmful and beneficial effects on fitness and then consider theories that predict the fate of individual mutations or the consequences of mutation accumulation for quantitative traits.

Understanding and using quantitative genetic variation.

Quantitative genetics, or the genetics of complex traits, is the study of those characters which are not affected by the action of just a few major genes. Its basis is in statistical models and methodology, albeit based on many strong assumptions. While these are formally unrealistic, methods work.