Portal de Periódicos da CAPES

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

2016; Nature Portfolio; Volume: 48; Issue: 8 Linguagem: Inglês

10.1038/ng.3595

1546-1718

Jérôme Nicod, R. W. Davies, Na Cai, Carl Hassett, Leo Goodstadt, Cormac Cosgrove, Benjamin K. Yee, Vikte Lionikaite, Rebecca E. McIntyre, Carol Ann Remme, Elisabeth M. Lodder, J.S. Gregory, Tertius Hough, Russell Joynson, Hayley Phelps, Barbara Nell, Clare Rowe, Joe Wood, Alison Walling, Nasrin Bopp, Amarjit Bhomra, Polinka Hernandez-Pliego, Jacques Callebert, R.M. Aspden, Nick P. Talbot, Peter A. Robbins, Mark E. Harrison, Martin Fray, Jean‐Marie Launay, Yigal M. Pinto, David A. Blizard, Connie R. Bezzina, David J. Adams, Paul Franken, Tom Weaver, Sara Wells, Steve D. M. Brown, Paul Potter, Paul Klenerman, Arimantas Lionikas, Richard Mott, Jonathan Flint,

Bioinformatics and Genomic Networks

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.