Rat Genome Sequencing and Mapping Consortium Nat. Genet. 45, 767–775 (2013).

The Rat Genome Sequencing and Mapping Consortium has tackled the challenge of finding genetic variants that contribute to complex phenotypes by using a combination of genome sequencing and genetic mapping. They used over 1,000 outbred rats, descended from eight inbred progenitors, that were amenable to genetic mapping because their quantitative trait loci (QTL) could be resolved to high resolution, their genomes could be imputed from those of the founders and they had well-defined haplotypes. The researchers genotyped the outbred rats on a high-density single-nucleotide polymorphism array and measured 160 phenotypes for common disease models such as anxiety, diabetes and osteoporosis. They identified 355 QTLs for 122 phenotypes, and for 31 phenotypes they found the causal genes. Surprisingly, they also found that about half of all QTLs could not be attributed to a single variant; these QTLs may instead result from multiple alleles at closely linked loci.