CHARACTERIZATION OF GENETIC RECOMBINATION AND ITS INFLUENCING FACTORS IN CATTLE

Abstract

Meiotic recombination is a fundamental biological process in which parental genetic materials are exchanged during egg or sperm development. Recombination is necessary for proper chromosomal disjunction during meiosis. Aberrations in this process have been confirmed as the cause of aneuploidy, leading to a potentially deleterious outcome. Along with mutation, recombination is a major force to promote genetic diversity and drive the evolution of genomes. Despite the importance of recombination, the frequency and location of recombination vary wildly within and between individuals, populations, and species. In this thesis, I characterized patterns of recombination in the cattle genome and conducted a comprehensive study of the effect of genetics, sex and age on recombination and its evolution using a uniquely large cattle database hosted at the USDA, where over a million animals with full pedigree information have been genotyped and new data are being generated at an increasing speed. First, we characterized five PRDM9 alleles and generated allele-specific recombination maps using data derived from over 239,000 meioses in Holstein. We found one allele of PRDM9 to be very different from others in both protein composition and recombination landscape. By comparing recombination maps from sperm and pedigree data, we validated the quality of pedigree-based results. Second, we extended our analysis in recombination patterns to four major U.S. dairy cattle breeds, Holstein, Jersey, Ayrshire, and Brown Swiss. We identified over 8.9 million crossover events and constructed eight genome-wide recombination maps for the two sexes in four cattle breeds. We confirmed a longer male genetic map in bovine and found breed-specific recombination hotspots. Our GWAS analyses confirmed seven loci associated with genome-wide recombination rate and the association of the PRDM9 gene with hotspot usage in two sexes and multiple cattle breeds. Third, we explored the plastic nature of recombination in cattle by examining the effect of maternal age and temperature using data derived from 36,999 three-generation families in Holstein for which temperature data were available. We presented a quadratic relationship between recombination frequency and maternal age and a positive correlation between temperature and recombination rate. By analyzing large genomic datasets with pedigree information in cattle, these studies advanced our understanding of meiotic recombination in a domestic livestock species.