Jessica L. Petersen 1 , * , James R. Mickelson 1 , Aaron K. Rendahl 2 , Stephanie J. Valberg 1 , Lisa S. Andersson 3 , Jeanette Axelsson 3 , Ernie Bailey 4 , Danika Bannasch 5 , Matthew M. Binns 6 , Alexandre S. Borges 7 , Pieter Brama 8 , Artur da Câmara Machado 9 , Stefano Capomaccio 10 , Katia Cappelli 10 , E. Gus Cothran 11 , Ottmar Distl 12 , Laura Fox-Clipsham 13 , Kathryn T. Graves 4 , Gérard Guérin 14 , Bianca Haase 15 , Telhisa Hasegawa 16 , Karin Hemmann 17 , Emmeline W. Hill 18 , Tosso Leeb 19 , Gabriella Lindgren 3 , Hannes Lohi 17 , Maria Susana Lopes 9 , Beatrice A. McGivney 18 , Sofia Mikko 3 , Nicholas Orr 20 , M. Cecilia T. Penedo 5 , Richard J. Piercy 21 , Marja Raekallio 17 , Stefan Rieder 22 , Knut H. Røed 23 , June Swinburne 13 , 24 , Teruaki Tozaki 25 , Mark Vaudin 13 , Claire M. Wade 15 , Molly E. McCue 1
17 January 2013
Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F ST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes ( DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse.
A breed of the horse typically consists of individuals sharing very similar aesthetic and performance traits. However, a great deal of variation in traits exists between breeds. The range of variation observed among breeds can be illustrated by the size difference between the Miniature horse (0.74 m and 100 kg) and draft horse (1.8 m and 900 kg), or by comparing the optimum racing distance of the Quarter Horse (1/4 mile) to that of the Arabian (100 miles or more). In this study, we exploited the breed structure of the horse to identify regions of the genome that are significantly different between breeds and therefore may harbor genes and genetic variants targeted by selective breeding. This work resulted in the identification of variants in the Paint and Quarter Horse significantly associated with altered muscle fiber type proportions favorable for increased sprinting ability. A strong signature of selection was also identified in breeds that perform alternative gaits, and several genomic regions identified are hypothesized to be involved in the determination of size. This study has demonstrated the utility of this approach for studying the equine genome and is the first to show a functional consequence of selective breeding in the horse.