Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing

Jonathan Flint, Richard Mott and colleagues employ low-coverage (0.15×) sequencing and their new imputation method STITCH to perform genome-wide association analysis for complex traits in an outbred mouse population. They find >250 QTLs for 92 phenotypes and obtain gene-level mapping resolution f...

Full description

Saved in:

Bibliographic Details
Published in:	Nature genetics Vol. 48; no. 8; pp. 912 - 918
Main Authors:	Nicod, Jérôme, Davies, Robert W, Cai, Na, Hassett, Carl, Goodstadt, Leo, Cosgrove, Cormac, Yee, Benjamin K, Lionikaite, Vikte, McIntyre, Rebecca E, Remme, Carol Ann, Lodder, Elisabeth M, Gregory, Jennifer S, Hough, Tertius, Joynson, Russell, Phelps, Hayley, Nell, Barbara, Rowe, Clare, Wood, Joe, Walling, Alison, Bopp, Nasrin, Bhomra, Amarjit, Hernandez-Pliego, Polinka, Callebert, Jacques, Aspden, Richard M, Talbot, Nick P, Robbins, Peter A, Harrison, Mark, Fray, Martin, Launay, Jean-Marie, Pinto, Yigal M, Blizard, David A, Bezzina, Connie R, Adams, David J, Franken, Paul, Weaver, Tom, Wells, Sara, Brown, Steve D M, Potter, Paul K, Klenerman, Paul, Lionikas, Arimantas, Mott, Richard, Flint, Jonathan
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-08-2016 Nature Publishing Group
Subjects:	631/114/2163 631/208/205/2138 Agriculture Animal Genetics and Genomics Animals Animals, Outbred Strains - genetics Biomedicine Cancer Research Chromosome Mapping Chromosomes Gene Function Gene mapping Genetic Markers - genetics Genome-wide association studies Genome-Wide Association Study Genomes Genotype Haplotypes Haplotypes - genetics Human Genetics Identification and classification Laboratories Medical research Methods Mice Multifactorial Inheritance - genetics Phenotype Physiology Polymorphism, Single Nucleotide - genetics Quality control Quantitative trait loci Quantitative Trait Loci - genetics R&D Research & development
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Jonathan Flint, Richard Mott and colleagues employ low-coverage (0.15×) sequencing and their new imputation method STITCH to perform genome-wide association analysis for complex traits in an outbred mouse population. They find >250 QTLs for 92 phenotypes and obtain gene-level mapping resolution for around 20% of the loci. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1061-4036 1546-1718
DOI:	10.1038/ng.3595