Combined sequence-based and genetic mapping analysis of complex traits in outbred rats
Author:
- Rat Genome Sequencing and Mapping ConsortiumRCRat Genome Sequencing and Mapping Consortium
- 26 May 2013
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 45 (7) , 767-775
Abstract
The Rat Genome Sequencing and Mapping Consortium reports a combined sequence-based and genetic mapping analysis of 160 phenotypes in an outbred rat heterogeneous stock. They identify 31 genes involved in 27 different phenotypes. Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.Keywords
This publication has 48 references indexed in Scilit:
- DNase I sensitivity QTLs are a major determinant of human expression variationNature, 2012
- Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac diseaseNature Genetics, 2011
- Mouse genomic variation and its effect on phenotypes and gene regulationNature, 2011
- Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosisNature, 2011
- Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred linesNature, 2010
- Quantitative Trait Loci for CD4:CD8 Lymphocyte Ratio Are Associated with Risk of Type 1 Diabetes and HIV-1 Immune ControlThe American Journal of Human Genetics, 2010
- The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammationNature Immunology, 2009
- Genome-wide genetic association of complex traits in heterogeneous stock miceNature Genetics, 2006
- Genome sequence of the Brown Norway rat yields insights into mammalian evolutionNature, 2004
- BLAT—The BLAST-Like Alignment ToolGenome Research, 2002