Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing
| Autor: | Jérôme Nicod, Joseph Wood, Jean-Marie Launay, Benjamin K Yee, Arimantas Lionikas, Connie R. Bezzina, Amarjit Bhomra, Jacques Callebert, Robert W. Davies, Martin Fray, Tertius Hough, Cormac Cosgrove, Barbara Nell, Leo Goodstadt, Elisabeth M. Lodder, Richard Mott, Hayley Phelps, Jonathan Flint, Paul Klenerman, Vikte Lionikaite, Paul Franken, Steve D. M. Brown, Paul Potter, Carl Hassett, Yigal M. Pinto, Sara Wells, Alison Walling, Richard M. Aspden, Nasrin Bopp, Russell Joynson, David J. Adams, Jennifer S. Gregory, Rebecca E. McIntyre, Nick P. Talbot, Tom Weaver, Na Cai, David A. Blizard, Mark Harrison, Polinka Hernandez-Pliego, Carol Ann Remme, Peter A. Robbins, Clare Rowe |
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| Přispěvatelé: | ACS - Amsterdam Cardiovascular Sciences, Cardiology |
| Rok vydání: | 2016 |
| Předmět: |
Genetic Markers
0301 basic medicine False discovery rate Multifactorial Inheritance Genotype Quantitative Trait Loci Genome-wide association study Computational biology Biology Quantitative trait locus Polymorphism Single Nucleotide Genetic analysis Article Mice 03 medical and health sciences Animals Outbred Strains Genetics Animals Genotyping Genetic association Haplotype Chromosome Mapping Phenotype 030104 developmental biology Haplotypes Genetic marker Genome-Wide Association Study |
| Zdroj: | Nature genetics, 48(8), 912-918. Nature Publishing Group Nature genetics Nature Genetics Nature Genetics, vol. 48, no. 8, pp. 912-918 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.3595 |
| Popis: | Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15×) sequencing with a new method to impute the ancestral haplotype space in 1,887 commercially available outbred mice. We mapped 156 unique quantitative trait loci for 92 phenotypes at a 5% false discovery rate. Gene-level mapping resolution was achieved at about one-fifth of the loci, implicating Unc13c and Pgc1a at loci for the quality of sleep, Adarb2 for home cage activity, Rtkn2 for intensity of reaction to startle, Bmp2 for wound healing, Il15 and Id2 for several T cell measures and Prkca for bone mineral content. These findings have implications for diverse areas of mammalian biology and demonstrate how genome-wide association studies can be extended via low-coverage sequencing to species with highly recombinant outbred populations. |
| Databáze: | OpenAIRE |
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