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

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.   We took 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 quantified the heritability and scan the genome for Quantitative Trait Loci (QTL) influencing each one of these recombination phenotypes.  We performed 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.