Genetic Variants in REC8, RNF212, and PRDM9 Influence Male Recombination in Cattle

Abstract

We use >250,000 cross-over events identified in >10,000 bovine sperm cells to perform an extensive characterization of meiotic recombination in male cattle. We map Quantitative Trait Loci (QTL) influencing genome-wide recombination rate, genome-wide hotspot usage, and locus-specific recombination rate. We fine-map three QTL and present strong evidence that genetic variants in REC8 and RNF212 influence genome-wide recombination rate, while genetic variants in PRDM9 influence genome-wide hotspot usage.

Author Summary

Homologous recombination is an essential cellular process that determines proper chromosome segregation during meiosis, affects fertility, and influences evolvability. Nevertheless, the components of the recombination apparatus remain incompletely characterized in mammals. One approach to identify such components is to identify the genes that underlie inherited variation in recombination phenotypes. In addition to providing mechanistic insights, this would allow the study of the evolutionary forces that shape the recombination process. In this paper, we take advantage of genotypes for 50,000 genome-wide SNP markers to measure four recombination phenotypes (genome-wide recombination rate, genome-wide hotspot usage, locus-specific recombination rate, genome-wide cross-over interference) for >750 bulls on the basis of >250,000 cross-overs detected in sperm cells transmitted to >10,000 sons. We quantify the heritability and scan the genome for Quantitative Trait Loci (QTL) influencing each one of these recombination phenotypes. We perform a detailed genetic analysis of three such QTL, thereby providing evidence that genetic variants in REC8 and RNF212 influence genome-wide recombination rate, while genetic variants in an X-linked PRDM9 paralogue influence genome-wide hotspot usage.