Detecting genetic signatures of selection is of great interest for many research issues. Common approaches to separate selective from neutral processes focus on the variance of F ST across loci, as does the original Lewontin and Krakauer (LK) test. Modern developments aim to minimize the false positive rate and to increase the power, by accounting for complex demographic structures. Another stimulating goal is to develop straightforward parametric and computationally tractable tests to deal with massive SNP data sets. Here, we propose an extension of the original LK statistic (T LK ), named T F-LK , that uses a phylogenetic estimation of the population's kinship (F ) matrix, thus accounting for historical branching and heterogeneity of genetic drift. Using forward simulations of single-nucleotide polymorphisms (SNPs) data under neutrality and selection, we confirm the relative robustness of the LK statistic (T LK ) to complex demographic history but we show that T F-LK is more powerful in most cases. This new statistic outperforms also a multinomial-Dirichlet-based model [estimation with Markov chain Monte Carlo (MCMC)], when historical branching occurs. Overall, T F-LK detects 15-35% more selected SNPs than T LK for low type I errors (P , 0.001). Also, simulations show that T LK and T F-LK follow a chi-square distribution provided the ancestral allele frequencies are not too extreme, suggesting the possible use of the chi-square distribution for evaluating significance. The empirical distribution of T F-LK can be derived using simulations conditioned on the estimated F matrix. We apply this new test to pig breeds SNP data and pinpoint outliers using T F-LK , otherwise undetected using the less powerful T LK statistic. This new test represents one solution for compromise between advanced SNP genetic data acquisition and outlier analyses.

We herein report new evidence that the QTL effect on chromosome 20 in Finnish Ayrshire can be explained by variation in two distinct genes, growth hormone receptor (GHR) and prolactin receptor (PRLR). In a previous study in Holstein-Friesian dairy cattle an F279Y polymorphism in the transmembrane domain of GHR was found to be associated with an effect on milk yield and composition. The result of our multimarker regression analysis suggests that in Finnish Ayrshire two QTL segregate on the chromosomal region including GHR and PRLR. By sequencing the coding sequences of GHR and PRLR and the sequence of three GHR promoters from the pooled samples of individuals of known QTL genotype, we identified two substitutions that were associated with milk production traits: the previously reported F-to-Y substitution in the transmembrane domain of GHR and an S-to-N substitution in the signal peptide of PRLR. The results provide strong evidence that the effect of PRLR S18N polymorphism is distinct from the GHR F279Y effect. In particular, the GHR F279Y has the highest influence on protein percentage and fat percentage while PRLR S18N markedly influences protein and fat yield. Furthermore, an interaction between the two loci is suggested.

SummaryMany genomic methodologies rely on the presence and extent of linkage disequilibrium (LD) between markers and genetic variants underlying traits of interest, but the extent of LD in the horse has yet to be comprehensively characterized. In this study, we evaluate the extent and decay of LD in a sample of 817 Thoroughbreds. Horses were genotyped for over 50 000 single nucleotide polymorphism (SNP) markers across the genome, with 34 848 autosomal SNPs used in the final analysis. Linkage disequilibrium, as measured by the squared correlation coefficient (r 2 ), was found to be relatively high between closely linked markers (>0.6 at 5 kb) and to extend over long distances, with average r 2 maintained above nonsyntenic levels for single nucleotide polymorphisms (SNPs) up to 20 Mb apart. Using formulae which relate expected LD to effective population size (N e ), and assuming a constant actual population size, N e was estimated to be 100 in our population. Values of historical N e , calculated assuming linear population growth, suggested a decrease in N e since the distant past, reaching a minimum twenty generations ago, followed by a subsequent increase until the present time. The qualitative trends observed in N e can be rationalized by current knowledge of the history of the Thoroughbred breed, and inbreeding statistics obtained from published pedigree analyses are in agreement with observed values of N e . Given the high LD observed and the small estimated N e , genomic methodologies such as genomic selection could feasibly be applied to this population using the existing SNP marker set.

Hip dysplasia is an important and complex genetic disease in dogs with both genetic and environmental influences. Since the osteoarthritis that develops is irreversible the only way to improve welfare, through reducing the prevalence, is through genetic selection. This study aimed to evaluate the progress of selection against hip dysplasia, to quantify potential improvements in the response to selection via use of genetic information and increases in selection intensity, and to prepare for public provision of estimated breeding values (EBV) for hip dysplasia in the UK. Data consisted of 25,243 single records of hip scores of Labrador Retrievers between one and four years old, from radiographs evaluated between 2000 and 2007 as part of the British Veterinary Association (BVA) hip score scheme. A natural logarithm transformation was applied to improve normality and linear mixed models were evaluated using ASREML. Genetic correlations between left and right scores, and total hip scores at one, two and three years of age were found to be close to one, endorsing analysis of total hip score in dogs aged one to three as an appropriate approach. A heritability of 0.35±0.016 and small but significant litter effect (0.07±0.009) were estimated. The observed trends in both mean hip score and mean EBV over year of birth indicate that a small genetic improvement has been taking place, approximately equivalent to avoiding those dogs with the worst 15% of scores. Deterministic analysis supported by simulations showed that a 19% greater response could be achieved using EBV compared to phenotype through increases in accuracy alone. This study establishes that consistent but slow genetic improvement in the hip score of UK Labrador Retrievers has been achieved over the previous decade, and demonstrates that progress may be easily enhanced through the use of EBVs and more intense selection.

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