Abstract
The molecular analysis of genes influencing human height has been notoriously difficult. Genome-wide association studies (GWAS) for height in humans based on tens of thousands to hundreds of thousands of samples so far revealed ∼200 loci for human height explaining only 20% of the heritability. In domestic animals isolated populations with a greatly reduced genetic heterogeneity facilitate a more efficient analysis of complex traits. We performed a genome-wide association study on 1,077 Franches-Montagnes (FM) horses using ∼40,000 SNPs. Our study revealed two QTL for height at withers on chromosomes 3 and 9. The association signal on chromosome 3 is close to the LCORL/NCAPG genes. The association signal on chromosome 9 is close to the ZFAT gene. Both loci have already been shown to influence height in humans. Interestingly, there are very large intergenic regions at the association signals. The two detected QTL together explain ∼18.2% of the heritable variation of height in horses. However, another large fraction of the variance for height in horses results from ECA 1 (11.0%), although the association analysis did not reveal significantly associated SNPs on this chromosome. The QTL region on ECA 3 associated with height at withers was also significantly associated with wither height, conformation of legs, ventral border of mandible, correctness of gaits, and expression of the head. The region on ECA 9 associated with height at withers was also associated with wither height, length of croup and length of back. In addition to these two QTL regions on ECA 3 and ECA 9 we detected another QTL on ECA 6 for correctness of gaits. Our study highlights the value of domestic animal populations for the genetic analysis of complex traits.
Highlights
Horse genomics [1] made a tremendous step, when the whole genome sequence of the domestic horse was made publicly available in 2007 [2]
We analyzed the association of these data with respect to deregressed estimated breeding values instead of direct phenotypic measurements for 28 conformation traits including height at withers, which varied between 145 cm and 165 cm on the phenotypic level (Figure 1)
We analyzed the data using a mixed-model considering the genomic relationships in order to account for population stratification, which resulted in a genomic inflation factor of 1.04 after the correction
Summary
Horse genomics [1] made a tremendous step, when the whole genome sequence of the domestic horse was made publicly available in 2007 [2]. Information from that sequence served as the primary resource for the development of a commercial horse SNP array, and high-throughput genotyping. As a result genome-wide association studies (GWAS) became feasible in a so far unprecedented manner. A brief overview on the present state of horse genome research, trait mapping, and breed diversity studies, is given in a special supplementary issue of Animal Genetics from December 2010. That some of the most spectacular findings from GWAS until today were the detection of SNPs on horse chromosome 18 within and proximal to the myostatin gene (MSTN), associated with racing performance in Thoroughbred horses [3,4,5].
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