The mouse is an important model for the study of quantitative traits, particularly those important for human diseases, as 80% of its genes have a human orthologue. Many Quantitative trait loci (QTLs) have been mapped in mice and other organisms, but fine-mapping remains a difficulty.
Valdar et al have overcome this issue by using heterogeneous mice for fine-scale analysis of multiple phenotypes (Valdar, 2006). The group was able to map 843 QTLs at high resolution across the whole mouse genome using a bootstrap aggregation analysis, used previously in plant genetics. They found that the phenotypes had complex genetic architectures, as the genetic components of most of the phenotypes arose from many small effect loci and the QTLs were likely to fractionate further.
The mapped QTLs contributed to variation in 97 traits including models of human disease, immunological and biochemical phenotypes. Single-gene resolution was not achieved in all cases, but over 300 QTLs were found to contain fewer than three genes. Some large-effect QTLs were also identified, including HDL cholesterol, serum alkaline phosphatase, ratio of CD4 to CD8 cells and startle response. Molecular characterization of small-effect QTLs remains a challenge, however this work has paved the way for future research.
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References:
primary
Valdar, W et al. (2006) ‘Genome-wide genetic association of complex traits in heterogeneous stock mice’, Nature Genetics, 38: 879-886.
secondary
Holland, J.B. (2007) ‘Genetic architecture of complex traits in plants’, Current Opinion in Plant Biology, 10: 156-161.
Mackay, T. F. C. (2004) ‘Complementing Complexity’, Nature Genetics, 36: 1145-1147.
Willis-Owen, S.A.G. and Flint, J. (2006) ‘The genetic basis of emotional behaviour in mice’, European Journal of Human Genetics, 14: 721-728.
