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QTL Mapping of Complex Phenotypes in Rodents

The quantitative trait locus (QTL) approach, which uses the continuous values of phenotypic variables in each individual of a population, is particularly appropriate in genetic studies of complex phenotypes, including hypertension, Type 1 and Type 2 diabetes mellitus, atopy, arthritis and behavioral traits. The analysis of the genetic basis of complex traits is in theory simplified in inbred models. The rat represents an essential model organism for the analysis of distinct subphenotypes that participate in the pathophysiological process involved in a multifactorial disorder. Over the past 10 years, approximately 150 QTLs have been identified in rat models of human diseases. Most of rat QTL studies have applied standard genetic strategies based on genetic and phenotypic analyses in a segregating population (F2 or first backcross), often supported by a comprehensive pathophysiological screening of the hybrids.

For most of the rat QTLs, the production and both genetic and phenotypic characterization of congenic lines currently provide the most reliable way of progressing from mapping of a QTL to identification of the susceptibility genes. With significant progress in the number of rat polymorphic markers and the construction of dense linkage maps, a marker assisted protocol ("speed congenics") can now be applied in order to increase transfer efficiency of a targeted locus from a donor strain onto the genetic background of a recipient strain.

Relevant publications