Identifying genetic variants and pathways influencing daughter averages for twinning in North American Holstein cattle and evaluating the potential for genomic selection

Abstract

Multiple birth in dairy cattle is a detrimental trait both economically for producers and for animal health. Genetics of twinning is complex and has led to several quantitative trait loci regions being associated with increased twinning. To identify variants associated with this trait, calving records from 2 time periods were used to estimate daughter averages for twinning for Holstein bulls. Multiple analyses were conducted and compared including GWAS, genomic prediction, and gene set enrichment analysis for pathway detection. Although pathway analysis did not yield many congruent pathways of interest between data sets, it did indicate two of interest. Both pathways have ties to the strong candidate region on BTA11 from the genomewide association analysis across data sets. This region does not overlap with previously identified quantitative trait loci regions for twinning or ovulation rate in cattle. The strongest associated SNPs were upstream from 2 candidate genes LHCGR and FSHR, which are involved in folliculogenesis. Genomic prediction showed a moderate correlation accuracy (0.43) when predicting genomic breeding values for bulls with estimates from calving records from 2010 to 2016. Future analysis of the region on BTA11 and the relation of the candidate genes could improve this accuracy.

Associated regions for multiple birth in Brown Swiss and Original Braunvieh cattle on chromosomes 15 and 11

“…There is little evidence in the literature of a major QTL for the multiple birth trait in cattle. In an own study, a major QTL on chr 11 at 31 Mb was detected with a candidate causal variant in the 5′ regulatory region of the LHCGR gene in Swiss Holstein (Widmer et al, 2021) and recently confirmed in the North American Holstein population (Lett & Kirkpatrick, 2022). In two older studies with data from Norwegian cattle and North American Holsteins, a candidate gene with a possible major effect on the trait, IGF1 , was observed (Kim et al, 2009; Lien et al, 2000).…”

“…So far, a study has analysed the Holstein population using large-scale data and identified a major QTL for multiple births on chr 11 with a possible effect on the genes LHCGR and FSHR (Widmer et al, 2021). This QTL region was confirmed in a recent study in the North American Holstein population using whole-genome sequencing (WGS) data (Lett & Kirkpatrick, 2022). It is therefore very likely that multiple births are a polygenic trait where almost no QTL have been identified yet.…”