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.

Exploring the potential genetic heterogeneity in the incidence of hoof and leg disorders in Austrian Fleckvieh and Braunvieh cattle

“…Although the number of published studies related to GWAS for hoof and leg disorders is very limited, their common feature is the lack of overlap in significant results both, between and even within the studies. Similarly, to our study, Wu et al [9] applied the same GWAS model to feet and leg disorders in three breeds and depending on breed identified different significant regions between Danish Red and Danish Holstein, while no significance was observed in Jersey. In addition, earlier van der Spek et al [10] found a very low overlap in significance while analysing a cow data set and a bull data set ascertained from the same population of Holstein-Friesian cattle, with only three SNPs in bulls overlapped with 94 SNPs significant for claw disorders in cows.…”

Integrating Sequence-based GWAS and RNA-Seq Provides Novel Insights into the Genetic Basis of Mastitis and Milk Production in Dairy Cattle

“…The average reliabilities of the de-regressed proofs for milk, fat, and protein yields and mastitis resistance were 0.95, 0.95, 0.95, and 0.85, respectively, in HOL; 0.95, 0.95, 0.95, and 0.83, respectively, in RDC; and 0.92, 0.92, 0.92, and 0.76, respectively, in JER. The details of the imputation from 50 K and High-Density (HD, 700 K) genotypes of these cattle to whole-genome sequence data have been described previously54. Briefly, a multi-breed reference of 3,383 individuals (1,222 HOL, 1,326 RDC, and 835 JER) with HD genotypes was used to impute individuals with 50 K genotypes to the HD level.…”

“…Briefly, a multi-breed reference of 3,383 individuals (1,222 HOL, 1,326 RDC, and 835 JER) with HD genotypes was used to impute individuals with 50 K genotypes to the HD level. Individuals with the imputed HD genotypes were then imputed to the whole-sequence level using a multi-breed reference of 1,222 individuals from run4 of the 1,000 Bull Genome project (288 HOL, 56 RDC, 61 JER and 743 individuals from different breeds)55 and private sequence data from Aarhus University (23 HOL, 30 RDC and 27 JER)54. IMPUTE2 v2.3.156 was applied to impute 50 K to the HD level, and Minimac257 was used to impute HD to the whole-sequence level.…”

Exploring the genetic architecture and improving genomic prediction accuracy for mastitis and milk production traits in dairy cattle by mapping variants to hepatic transcriptomic regions responsive to intra-mammary infection

“…Imputation from Illumina BovineSNP50 BeadChip (50 K) to Illumina BovineHD BeadChip (high-density, HD) genotypes for these individuals and further to whole-genome sequence variants was described previously [36, 37]. Briefly, genotypes from the 50 K SNP chip for each individual were first imputed to HD genotypes using a multi-breed reference of 3383 animals (1222 HOL, 1326 Nordic Red, and 835 JER).…”

“…The accuracy of imputation was above 0.85 for the across-breed imputation of 19,498,365 SNPs. Detailed information about imputation accuracy was previously reported in [37]. For each breed, SNPs with a large deviation from Hardy–Weinberg proportions ( P  < 10 −6 ) or with minor allele frequency (MAF) <0.01 were further excluded.…”