New genes, more complexity from in-depth study of rat genome

Researchers at the WTCHG have carried out an extensive analysis of the genomes of laboratory rats, combining mapping and sequencing techniques to discover 35 genes that contribute to 31 conditions such as multiple sclerosis, anxiety and cardiovascular disease. The results of the international study by the Rat Genome Sequencing and Mapping Consortium are published in a recent issue of Nature Genetics.

Amelie Baud, Regina Lopez-Aumatell, Richard Mott and Jonathan Flint analysed mapping data from 1500 rats that were cross-bred from a variety of inbred stocks with known characteristics, a population maintained by colleagues at the Autonomous University of Barcelona (UAB). In total they identified 355 short lengths of chromosome, known as quantitative trait loci or QTLs, which significantly influenced the occurrence of disease-related phenotypes.

They further analysed genetic sequences at these loci, looking for variants that might be causing disease. Somewhat to their surprise, they discovered that the relationship between sequence and genetic variation was far from simple: at around 40 per cent of QTLs a single causal variant could not account for a particular phenotype.

Commenting on the additional layer of complexity this study adds to the problem of genetic association, Richard Mott said ‘In this large-scale study in rats we have shown that often a single causal DNA variant in a small genomic region is not enough to explain an association with that region. This means we will have to find out how DNA variants combine to produce their effects on disease, rather than analysing their effects one by one.’

Amelie Baud et al. Combined sequence-based and genetic mapping analysis of complex traits in outbred rats. Nat Gen. 2013. doi:10.1038/ng.2644, published online 26 May 2013