Abstract
With the recent advent of genomic tools for cattle, several recessive conditions affecting fertility have been identified and selected against, such as deficiency of uridine monophosphate synthase, complex vertebral malformation, and brachyspina. The current report refines the location of a recessive haplotype affecting fertility in Jersey cattle using crossover haplotypes, discovers the causative mutation using whole genome sequencing, and examines the gene’s role in embryo loss. In an attempt to identify unknown recessive lethal alleles in the current dairy population, a search using deep Mendelian sampling of 5,288 Jersey cattle was conducted for high-frequency haplotypes that have a deficit of homozygotes at the population level. This search led to the discovery of a putative recessive lethal in Jersey cattle on Bos taurus autosome 15. The haplotype, denoted JH1, was associated with reduced fertility, and further investigation identified one highly-influential Jersey bull as the putative source ancestor. By combining SNP analysis of whole-genome sequences aligned to the JH1 interval and subsequent SNP validation a nonsense mutation in CWC15 was identified as the likely causative mutation underlying the fertility phenotype. No homozygous recessive individuals were found in 749 genotyped animals, whereas all known carriers and carrier haplotypes possessed one copy of the mutant allele. This newly identified lethal has been responsible for a substantial number of spontaneous abortions in Jersey dairy cattle throughout the past half-century. With the mutation identified, selection against the deleterious allele in breeding schemes will aid in reducing the incidence of this defect in the population. These results also show that carrier status can be imputed with high accuracy. Whole-genome resequencing proved to be a powerful strategy to rapidly identify a previously mapped deleterious mutation in a known carrier of a recessive lethal allele.
Highlights
400 Mendelian disorders have been identified in cattle species [1], and new conditions are periodically identified [e.g., 2–4]
The initial JH1 interval spanning about 5 Mb on BTA15 from 11,439,502 to 16,147,383 on the UMD 3.1 map [13] was narrowed to a 15-marker window (15,162,470 to 15,949,175) through analysis of additional SNP50 genotypes submitted to the National Dairy Database [24]
34 haplotypes containing the suspect region from the 75-SNP haplotypes were identified in the fine-mapped region, and animals possessing these haplotypes were labeled as carriers
Summary
400 Mendelian disorders have been identified in cattle species [1], and new conditions are periodically identified [e.g., 2–4]. Mutations underlying recessive disorders in cattle have successfully been identified using DNA sequencing [10], and the cost of DNA sequencing has decreased dramatically, dropping from an average of $500.00 per Mb in October 2007 to $0.09 per Mb in October 2011 [11]. SNP genotypes are used to identify animals that are carriers of the haplotype of interest. Carrier animals are selected for full genome sequencing based on such factors as their relationship to the breed and the frequency of their haplotypes in the population. Sequences from these animal are aligned to the target interval of the genome to identify potential sequence variants underlying the phenotype
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
