Review: Genetic mutations affecting bull fertility

Abstract

Cattle are a well-suited "model organism" to study the genetic underpinnings of variation in male reproductive performance. The adoption of artificial insemination and genomic prediction in many cattle breeds provide access to microarray-derived genotypes and repeated measurements for semen quality and insemination success in several thousand bulls. Similar-sized mapping cohorts with phenotypes for male fertility are not available for most other species precluding powerful association testing. The repeated measurements of the artificial insemination bulls' semen quality enable the differentiation between transient and biologically relevant trait fluctuations, and thus, are an ideal source of phenotypes for variance components estimation and genome-wide association testing. Genome-wide case-control association testing involving bulls with either aberrant sperm quality or low insemination success revealed several causal recessive loss-of-function alleles underpinning monogenic reproductive disorders. These variants are routinely monitored with customised genotyping arrays in the male selection candidates to avoid the use of subfertile or infertile bulls for artificial insemination and natural service. Genome-wide association studies with quantitative measurements of semen quality and insemination success revealed quantitative trait loci for male fertility, but the underlying causal variants remain largely unknown. Moreover, these loci explain only a small part of the heritability of male fertility. Integrating genome-wide association studies with gene expression and other omics data from male reproductive tissues is required for the fine-mapping of candidate causal variants underlying variation in male reproductive performance in cattle.

Keywords: Association testing; Cattle; Causal variants; Insemination success; Semen quality.