Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing.
Jérôme NicodRobert W DaviesNa CaiCarl HassettLeo GoodstadtCormac CosgroveBenjamin K YeeVikte LionikaiteRebecca E McIntyreCarol Ann RemmeElisabeth M LodderJennifer S GregoryTertius HoughRussell JoynsonHayley PhelpsBarbara NellClare RoweJoe WoodAlison WallingNasrin BoppAmarjit BhomraPolinka Hernandez-PliegoJacques CallebertRichard M AspdenNick P TalbotPeter A RobbinsMark HarrisonMartin FrayJean-Marie LaunayYigal M PintoDavid A BlizardConnie R BezzinaDavid J AdamsPaul FrankenTom WeaverSara WellsSteve D M BrownPaul K PotterPaul KlenermanArimantas LionikasRichard F MottJonathan FlintPublished in: Nature genetics (2016)
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.
Keyphrases
- genetic diversity
- genome wide association
- genome wide
- high resolution
- dna methylation
- copy number
- high density
- single cell
- affordable care act
- wound healing
- high fat diet induced
- healthcare
- skeletal muscle
- type diabetes
- single molecule
- small molecule
- high throughput
- genome wide identification
- mesenchymal stem cells
- wild type
- soft tissue
- cell free