Association analysis for feet and legs disorders with whole-genome sequence variants in 3 dairy cattle breeds

Abstract

Identification of genetic variants associated with feet and legs disorders (FLD) will aid in the genetic improvement of these traits by providing knowledge on genes that influence trait variations. In Denmark, FLD in cattle has been recorded since the 1990s. In this report, we used deregressed breeding values as response variables for a genome-wide association study. Bulls (5,334 Danish Holstein, 4,237 Nordic Red Dairy Cattle, and 1,180 Danish Jersey) with deregressed estimated breeding values were genotyped with the Illumina Bovine 54k single nucleotide polymorphism (SNP) genotyping array. Genotypes were imputed to whole-genome sequence variants, and then 22,751,039 SNP on 29 autosomes were used for an association analysis. A modified linear mixed-model approach (efficient mixed-model association eXpedited, EMMAX) and a linear mixed model were used for association analysis. We identified 5 (3,854 SNP), 3 (13,642 SNP), and 0 quantitative trait locus (QTL) regions associated with the FLD index in Danish Holstein, Nordic Red Dairy Cattle, and Danish Jersey populations, respectively. We did not identify any QTL that were common among the 3 breeds. In a meta-analysis of the 3 breeds, 4 QTL regions were significant, but no additional QTL region was identified compared with within-breed analyses. Comparison between top SNP locations within these QTL regions and known genes suggested that RASGRP1, LCORL, MOS, and MITF may be candidate genes for FLD in dairy cattle.

Keywords: feet and legs disorders; genome-wide association; meta-analysis; mixed model.