Haplotype Analysis Improved Evidence for Candidate Genes for Intramuscular Fat Percentage from a Genome Wide Association Study of Cattle

Abstract

In genome wide association studies (GWAS), haplotype analyses of SNP data are neglected in favour of single point analysis of associations. In a recent GWAS, we found that none of the known candidate genes for intramuscular fat (IMF) had been identified. In this study, data from the GWAS for these candidate genes were re-analysed as haplotypes. First, we confirmed that the methodology would find evidence for association between haplotypes in candidate genes of the calpain-calpastatin complex and musculus longissimus lumborum peak force (LLPF), because these genes had been confirmed through single point analysis in the GWAS. Then, for intramuscular fat percent (IMF), we found significant partial haplotype substitution effects for the genes ADIPOQ and CXCR4, as well as suggestive associations to the genes CEBPA, FASN, and CAPN1. Haplotypes for these genes explained 80% more of the phenotypic variance compared to the best single SNP. For some genes the analyses suggested that there was more than one causative mutation in some genes, or confirmed that some causative mutations are limited to particular subgroups of a species. Fitting the SNPs and their interactions simultaneously explained a similar amount of the phenotypic variance compared to haplotype analyses. Haplotype analysis is a neglected part of the suite of tools used to analyse GWAS data, would be a useful method to extract more information from these data sets, and may contribute to reducing the missing heritability problem.

Intermuscular and intramuscular adipose tissues: Bad vs. good adipose tissues

“…174 On the contrary, a few other GWA have had limited success in the identification of the genetic drivers of IM percentage which could be due to variations including treatments, genetics etc., resulting in the similar phenotype. 175,176 High throughput genomic technologies using powerful SNP panels will have to be combined with phenomics approach to further understand the complexities of IM.…”

Genome-Wide Association Study Reveals the PLAG1 Gene for Knuckle, Biceps and Shank Weight in Simmental Beef Cattle

“…The huge number of markers genotyped by the BovineSNP50K Bead Chip [3] provide an ample opportunity for us to perform GWAS in beef cattle. In the past few decades, numerous studies were carried out to map quantitative trait loci (QTLs) responsible for milk production, disease resistance [3, 4], reproduction [5], growth [5–8], meat quality [9–12] and carcass traits [12–15] in cattle. For carcass traits, previous studies had mapped several QTLs for carcass weights on BTA 6, 8 and 14, where one QTN was detected on BTA 6 and related to the encoding of NCAPG Ile442Met and the others were identified within gene PLAG1-CHCHD7 in the region on BTA14 [16].…”

Genome-wide association study for backfat thickness in Canchim beef cattle using Random Forest approach

“…One recently developed approach relies on examining how SNPs (single nucleotide polymorphisms) are associated with these qualitative traits [25]. More specifically, this method has been used successfully in studies that examined fat-related traits, such as intramuscular fat percentage, marbling, rib fat, backfat thickness and rump fat depth [26-35]. By the use of high-density SNP panel assays for different breeds and crosses, these studies have collectively found such traits associated with regions on nine bovine chromosomes (6, 15, 17, 20, 21, 24, 25, 26, and 28) [27,28,32,35].…”