Identification of a Nonsense Mutation in CWC15 Associated with Decreased Reproductive Efficiency in Jersey Cattle

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 recessiv...

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Main Authors:	Sonstegard, Tad S., Cole, John B., VanRaden, Paul M., Van Tassell, Curtis P., Null, Daniel J., Schroeder, Steven G., Bickhart, Derek, McClure, Matthew C.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551820/

id	pubmed-3551820
recordtype	oai_dc
spelling	pubmed-35518202013-01-24 Identification of a Nonsense Mutation in CWC15 Associated with Decreased Reproductive Efficiency in Jersey Cattle Sonstegard, Tad S. Cole, John B. VanRaden, Paul M. Van Tassell, Curtis P. Null, Daniel J. Schroeder, Steven G. Bickhart, Derek McClure, Matthew C. Research Article 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. Public Library of Science 2013-01-22 /pmc/articles/PMC3551820/ /pubmed/23349982 http://dx.doi.org/10.1371/journal.pone.0054872 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sonstegard, Tad S. Cole, John B. VanRaden, Paul M. Van Tassell, Curtis P. Null, Daniel J. Schroeder, Steven G. Bickhart, Derek McClure, Matthew C.
spellingShingle	Sonstegard, Tad S. Cole, John B. VanRaden, Paul M. Van Tassell, Curtis P. Null, Daniel J. Schroeder, Steven G. Bickhart, Derek McClure, Matthew C. Identification of a Nonsense Mutation in CWC15 Associated with Decreased Reproductive Efficiency in Jersey Cattle
author_facet	Sonstegard, Tad S. Cole, John B. VanRaden, Paul M. Van Tassell, Curtis P. Null, Daniel J. Schroeder, Steven G. Bickhart, Derek McClure, Matthew C.
author_sort	Sonstegard, Tad S.
title	Identification of a Nonsense Mutation in CWC15 Associated with Decreased Reproductive Efficiency in Jersey Cattle
title_short	Identification of a Nonsense Mutation in CWC15 Associated with Decreased Reproductive Efficiency in Jersey Cattle
title_full	Identification of a Nonsense Mutation in CWC15 Associated with Decreased Reproductive Efficiency in Jersey Cattle
title_fullStr	Identification of a Nonsense Mutation in CWC15 Associated with Decreased Reproductive Efficiency in Jersey Cattle
title_full_unstemmed	Identification of a Nonsense Mutation in CWC15 Associated with Decreased Reproductive Efficiency in Jersey Cattle
title_sort	identification of a nonsense mutation in cwc15 associated with decreased reproductive efficiency in jersey cattle
description	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.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551820/
_version_	1611948725355151360

Identification of a Nonsense Mutation in CWC15 Associated with Decreased Reproductive Efficiency in Jersey Cattle

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