A genome-wide association study for regulators of micronucleus formation in mice
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
In mammals the regulation of genomic instability plays a key role in tumor suppression and also controls genome plasticity, which is important for recombination during the processes of immunity and meiosis. Most studies to identify regulators of genomic instability have been performed in cells in culture or in systems that report on gross rearrangements of the genome, yet subtle differences in the level of genomic instability can contribute to whole organism phenotypes such as tumour predisposition. Here we performed a genome-wide association study in a population of 1379 outbred Crl:CFW(SW)-US_P08 mice to dissect the genetic landscape of micronucleus formation, a biomarker of chromosomal breaks, whole chromosome loss, and extra-nuclear DNA. Variation in micronucleus levels is a complex trait with a genome-wide heritability of 53.1%. We identify seven loci influencing micronucleus formation (false discovery rate<5%), and define candidate genes at each locus. Intriguingly at several loci we find evidence for sex-specific genetic effects in micronucleus formation, with a locus on chromosome 11 being specific to males.
Date Issued
2016-05-27
Date Acceptance
2016-05-24
Citation
G3-Genes Genomes Genetics, 2016, 6 (8), pp.2343-2354
ISSN
2160-1836
Publisher
Genetics Society of America: G3
Start Page
2343
End Page
2354
Journal / Book Title
G3-Genes Genomes Genetics
Volume
6
Issue
8
Copyright Statement
Copyright © 2016 Author et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/27233670
PII: g3.116.030767
Subjects
Micronuclei
Outbred mice
genetic mapping
genome-wide association study (GWAS)
genomic instability
Publication Status
Published