McIntyre, RE;
Nicod, J;
Daniela Robles-Espinoza, C;
Maciejowski, J;
Cai, N;
Hill, J;
Verstraten, R;
... Adams, DJ; + view all
(2016)
A Genome-Wide Association Study for Regulators of Micronucleus Formation in Mice.
G3
, 6
(8)
pp. 2343-2354.
10.1534/g3.116.030767.
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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 tumor 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 extranuclear 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 sexual dimorphism in micronucleus formation, with a locus on chromosome 11 being specific to males.
| Type: | Article |
|---|---|
| Title: | A Genome-Wide Association Study for Regulators of Micronucleus Formation in Mice |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1534/g3.116.030767 |
| Publisher version: | http://doi.org/10.1534/g3.116.030767 |
| Language: | English |
| Additional information: | Copyright © 2016 McIntyre 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. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, Micronuclei, genomic instability, genome-wide association study (GWAS), Outbred mice, genetic mapping, AICARDI-GOUTIERES-SYNDROME, VARIANT ANNOTATION, PERIPHERAL-BLOOD, SEX DISPARITIES, CANCER, GENES, MOUSE, GENERATION, PROTEIN, CHROMOTHRIPSIS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1503765 |
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