Fine mapping of quantitative trait loci (QTL) for osteochondrosis in Hanoverian warmblood horses

Content Provider	Semantic Scholar
Author	Lampe, Virginie
Copyright Year	2009
Abstract	The objective of this study was to refine quantitative trait loci (QTL) for osteochondrosis (OC) in Hanoverian warmblood horses in order to identify candidate genes with influence on the development of OC. From a high number of QTL identified in a previous whole genome scan, genome-wide significant QTL located on ECA5 and ECA16 and a chromosome-wide significant QTL located on ECA21 were chosen for further fine mapping. The release of the horse genome assembly EquCab2 made it possible to develop new microsatellites which enabled a decrease of the marker distances in QTL regions of less than 1 Mb. Microsatellites were genotyped for 104 progeny of 14 paternal half-sib families of Hanoverian warmblood horses, their dams and eight sires. Data was analysed using non-parametric linkage analysis based on identical by descent (IBD) mapping. Traits used were OC (fetlock and/or hock joints affected), OCD (fetlock and/or hock joints affected), fetlock OC, fetlock OCD, hock OC and hock OCD. On ECA5, a total of 49 new microsatellites were used, which could narrow down the QTL for fetlock OCD to an interval at 76.69 to 92.77 Mb. For fetlock OC, the QTL could be refined to a region from 79.65 to 89.31 Mb. On ECA16, altogether 56 microsatellites and 15 SNPs were genotyped in order to refine the putative QTL. The analysis revealed a delimitation of the QTL for hock OCD to an interval between 17.60 and 45.80 Mb. The QTL for fetlock OC could be narrowed down to a region from 6.55 to 24.26 Mb. Furthermore, the analysis revealed a QTL for OC in fetlock and/or hock joints at 14.38 Mb and in the region from 12.10 to 24.26 Mb for OCD in fetlock and/or hock joints. The refinement of the QTL on ECA21 using 22 microsatellites allowed a verification of the QTL for hock OC and hock OCD at 5.45 to 17.14 Mb. On ECA18, a new QTL for osteochondrosis in fetlock and/or hock joints could be detected between 74.94 and 82.25 Mb after increasing the marker density from seven microsatellites in the whole genome scan to a total of 27 markers. Due to the availability of an equine SNP chip, which assays ~50,000 SNPs simultaneously, a whole genome association analysis was performed with 154 unrelated Hanoverian warmblood horses. Focussing on the refined QTL on ECA5, 16, 18 and 21, single marker and haplotype association was performed for SNPs being located in the QTL and nearby. Haplotype association of SNPs could narrow down the genomic regions to intervals between 76.79 and 81.10 Mb on ECA5, between 17.57 and 20.1 Mb on ECA16 for the QTL for hock OCD, between 79.36 and 80.84 Mb on ECA18 and between 8.97 and 16.18 Mb on ECA21. Furthermore, six QTL on ECA1, 4, 14, 16, 18 and 30 were detected for the trait OC in fetlock and/or hock joints and four QTL for OCD in fetlock and/or hock joints on ECA1, 3, 30 and X. For the trait OC in fetlock joints, five different QTL on ECA2, 16, 26, 30 and X were identified, for the trait OCD in fetlock joints five QTL were observed on ECA2, 3, 13, 22 and 30. For hock OC five QTL were discovered being significant on ECA1, 4, 14, 29 and 30, for hock OCD three QTL were identified on ECA1, 6 and 30. The refinement and identification of QTL was a first step towards the discovery of genes responsible for equine osteochondrosis. It is unlikely that any of the SNP found associated with osteochondrosis represent causal mutations, as most of them are located in intergenic regions. In order to develop a marker test, significant associated SNPs should be verified in a large sample of horses.
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