Genetic prediction of complex traits: integrating infinitesimal and marked genetic effects

Genetic prediction for complex traits is usually based on models including individual (infinitesimal) or marker effects. Here, we concentrate on models including both the individual and the marker effects. In particular, we develop a ''Mendelian segregation'' model combining infinitesimal effects for base individuals and realized Mendelian sampling in descendants described by the available DNA data. The model is illustrated with an example and the analyses of a public simulated data file. Further, the potential contribution of such models is assessed by simulation. Accuracy, measured as the correlation between true (simulated) and predicted genetic values, was similar for all models compared under different genetic backgrounds. As expected, the segregation model is worthwhile when markers capture a low fraction of total genetic variance. (Résumé d'auteur

Alpha-Relaxation Processes in Binary Hard-Sphere Mixtures

Molecular-dynamics simulations are presented for two correlation functions formed with the partial density fluctuations of binary hard-sphere mixtures in order to explore the effects of mixing on the evolution of glassy dynamics upon compressing the liquid into high-density states. Partial-density-fluctuation correlation functions for the two species are reported. Results for the alpha-relaxation process are quantified by parameters for the strength, the stretching, and the time scale, where the latter varies over almost four orders of magnitude upon compression. The parameters exhibit an appreciable dependence on the wave vector; and this dependence is different for the correlation function referring to the smaller and that for the larger species. These features are shown to be in semi-quantitative agreement with those calculated within the mode-coupling theory for ideal liquid-glass transitions.Comment: 14 pages, 20 figures, RevTe

Peak effect and its evolution with defect structure in YBa2Cu3O7-d thin films at microwave frequencies

The vortex dynamics in YBa2Cu3O7-d thin films have been studied at microwave frequencies. A pronounced peak in the surface resistance, Rs, is observed in these films at frequencies of 4.88 and 9.55 GHz for magnetic fields varying from 0.2 to 0.8 T. The peak is associated with an order-disorder transformation of the flux line lattice as the temperature or field is increased. The occurrence of the peak in Rs is crucially dependent on the depinning frequency, wp and on the nature and concentration of growth defects present in these films. Introduction of artificial defects by swift heavy ion irradiation with 200 MeV Ag ion at a fluence of 4x1010 ions/cm2 enhances wp and suppresses the peak at 4.88 GHz but the peak at 9.55 GHz remains unaffected. A second peak at lower temperature has also been observed at 9.55 GHz. This is related to twin boundaries from angular dependence studies of Rs. Based on the temperature variation of Rs, vortex phase diagrams have been constructed at 9.55 GHz.Comment: 8 pages, 4 figures Submitted to Physical Review

Fission Hindrance in hot 216Th: Evaporation Residue Measurements

The fusion evaporation-residue cross section for 32S+184W has been measured at beam energies of E_beam = 165, 174, 185, 196, 205, 215, 225, 236, 246,and 257 MeV using the ATLAS Fragment Mass Analyzer. The data are compared with Statistical Model calculations and it is found that a nuclear dissipation strength, which increases with excitation energy, is required to reproduce the excitation function. A comparison with previously published data show that the dissipation strength depends strongly on the shell structure of the nuclear system.Comment: 15 pages 9 figure

Higher order glass-transition singularities in colloidal systems with attractive interactions

The transition from a liquid to a glass in colloidal suspensions of particles interacting through a hard core plus an attractive square-well potential is studied within the mode-coupling-theory framework. When the width of the attractive potential is much shorter than the hard-core diameter, a reentrant behavior of the liquid-glass line, and a glass-glass-transition line are found in the temperature-density plane of the model. For small well-width values, the glass-glass-transition line terminates in a third order bifurcation point, i.e. in a A_3 (cusp) singularity. On increasing the square-well width, the glass-glass line disappears, giving rise to a fourth order A_4 (swallow-tail) singularity at a critical well width. Close to the A_3 and A_4 singularities the decay of the density correlators shows stretching of huge dynamical windows, in particular logarithmic time dependence.Comment: 19 pages, 12 figures, Phys. Rev. E, in prin

Studies on changes of estimated breeding values of U.S. Holstein bulls for final score from the first to second crop of daughters

The purpose of this study was to find ways of reducing changes of sire predicted transmitting ability for type’s final scores (PTATs) from the first to second crop of daughters. The PTATs were estimated from two datasets: D01 (scores recorded up to 2001) and D05 (scores recorded up to 2005). The PTAT changes were calculated as the difference between the evaluations based on D01 and D05. The PTATs were adjusted to a common genetic base of all evaluated cows born in 1995. The single-trait (ST) animal model included the fixed effects of the herd–year–season–classifier, age by year group at classification, stage of lactation at classification, registry status of animals, and additive genetic and permanent environment random effects. Unknown parent groups (UPGs) were defined based on every other birth year starting from 1972. Modifications to the ST model included the usage of a single record per cow, separate UPGs for first and second crop daughters, separate UPGs for sires and dams, and deepened pedigrees for dams with missing phenotypic records. Also, the multiple-trait (MT) model treated records of registered and grade cows as correlated traits. The mean PTAT change, for all of the sires, was close to zero in all of the models analyzed. The estimated mean PTAT change for 145 sires with 40 to 100 first crop and ≥200 second crop daughters was −0.33, −0.20, −0.13, −0.28, and −0.12 with ST, only first records, only last records, updated pedigrees, and allowing separate parent groups (PGs) for sires and dams after updating the pedigrees, respectively. The percentages of sires showing PTAT decline were reduced from 74.5 (with ST) to 57.3 by using only the last records of cows, and to 56.4 by allowing separate UPGs for sires and dams after updating the pedigrees. Though updating of the pedigrees alone was not effective, separate UPGs for sires together with additional pedigree was helpful in reducing the bias

Phenotypic covariance of longevity, immunity and stress resistance in the Caenorhabditis nematodes

Background \ud Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin– like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four \ud Caenorhabditis species. \ud \ud Methodology/Principal Findings \ud We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged \ud significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions \ud The gonochoristic species display a significantly longer lifespan (p < 0.0001)and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Phenotypic covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. \ud \ud Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Introgression of a major QTL from an inferior into a superior population using genomic selection

<p>Abstract</p> <p>Background</p> <p>Selection schemes aiming at introgressing genetic material from a donor into a recipient line may be performed by backcross-breeding programs combined with selection to preserve the favourable characteristics of the donor population. This stochastic simulation study investigated whether genomic selection can be effective in preserving a major quantitative trait locus (QTL) allele from a donor line during the backcrossing phase.</p> <p>Methods</p> <p>In a simulation study, two fish populations were generated: a recipient line selected for a production trait and a donor line characterized by an enhanced level of disease resistance. Both traits were polygenic, but one major QTL affecting disease resistance was segregating only within the donor line. Backcrossing was combined with three types of selection (for total merit index) among the crossbred individuals: classical selection, genomic selection using genome-wide dense marker maps, and gene-assisted genomic selection. It was assumed that production could be observed directly on the selection candidates, while disease resistance had to be inferred from tested sibs of the selection candidates.</p> <p>Results</p> <p>Classical selection was inefficient in preserving the target QTL through the backcrossing phase. In contrast, genomic selection (without specific knowledge of the target QTL) was usually effective in preserving the target QTL, and had higher genetic response to selection, especially for disease resistance. Compared with pure genomic selection, gene-assisted selection had an advantage with respect to disease resistance (28–40% increase in genetic gain) and acted as an extra precaution against loss of the target QTL. However, for total merit index the advantage of gene-assisted genomic selection over genomic selection was lower (4–5% increase in genetic gain).</p> <p>Conclusion</p> <p>Substantial differences between introgression programs using classical and genomic selection were observed, and the former was generally inferior with respect to both genetic gain and the ability to preserve the target QTL. Combining genomic selection with gene-assisted selection for the target QTL acted as an extra precaution against loss of the target QTL and gave additional genetic gain for disease resistance. However, the effect on total merit index was limited.</p

Using the Pareto principle in genome-wide breeding value estimation

Genome-wide breeding value (GWEBV) estimation methods can be classified based on the prior distribution assumptions of marker effects. Genome-wide BLUP methods assume a normal prior distribution for all markers with a constant variance, and are computationally fast. In Bayesian methods, more flexible prior distributions of SNP effects are applied that allow for very large SNP effects although most are small or even zero, but these prior distributions are often also computationally demanding as they rely on Monte Carlo Markov chain sampling. In this study, we adopted the Pareto principle to weight available marker loci, i.e., we consider that x% of the loci explain (100 - x)% of the total genetic variance. Assuming this principle, it is also possible to define the variances of the prior distribution of the 'big' and 'small' SNP. The relatively few large SNP explain a large proportion of the genetic variance and the majority of the SNP show small effects and explain a minor proportion of the genetic variance. We name this method MixP, where the prior distribution is a mixture of two normal distributions, i.e. one with a big variance and one with a small variance. Simulation results, using a real Norwegian Red cattle pedigree, show that MixP is at least as accurate as the other methods in all studied cases. This method also reduces the hyper-parameters of the prior distribution from 2 (proportion and variance of SNP with big effects) to 1 (proportion of SNP with big effects), assuming the overall genetic variance is known. The mixture of normal distribution prior made it possible to solve the equations iteratively, which greatly reduced computation loads by two orders of magnitude. In the era of marker density reaching million(s) and whole-genome sequence data, MixP provides a computationally feasible Bayesian method of analysis