Recent developments in genetic analysis of complex traits.

Michael FW Festing
MRC Toxicology Unit, Hodgkin Building, University of Leicester, PO Box 138, Lancaster Road, Leicester LE1 9HN, UK.

Many characters such as diabetes, cancer, heart disease and susceptibility to infectious organisms have both a genetic and an environmental component. In many cases, the genetic component involves many different genetic loci. Until recently, genetic analysis of such characters has been virtually impossible. However, the development of sets of recombinant inbred mouse strains and a wide range of polymorphic microsatellite genetic markers has now made it possible to map susceptibility genes to chromosomal regions where there may be some candidate loci. This has important implications for the diagnosis and prevention of human disease. A useful model system is susceptibility to mouse lung adenomas induced by urethane. Strain A/J is highly susceptible and C67BL/6 is resistant. A gene linked to Kras2 on chromosome 6 was identified using RI strains. Subsequent genetic analysis has involved F2 or backcross hybrids between susceptible and resistant strains. A total of about 7-8 loci have now been mapped. The challenge now is to obtain positive identification of these susceptibility loci, and to see whether there are similar loci in the human genome controlling susceptibility to lung cancer.
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