THE INBRED-OUTBRED CROSS

This page describes a new use of Heterogeneous Stocks, to simulataneously detect and fine-map QTL. Ta new version of HAPPY that can analyse such data will be available shortly. Full details of the method are available from Mott R and Flint J (2002) Simultaneous Detection and Fine-mapping of Quantitative Trait Loci in Mice using Heterogenous Stocks Genetics 160:1609-1618

Abstract

We describe a method to simultaneously detect and fine map quantitative trait loci (QTL) that is especially suited to the mapping of modifier loci in mouse mutant models. The method exploits the high level of historical recombination present in a heterogeneous stock (HS), an outbred population of mice derived from known founder strains. The experimental design is an F2 cross between the HS and a genetically distinct line, such as one carrying a knockout or transgene. QTL detection is performed by a standard genome scan with � 100 markers and fine mapping by typing the same animals using densely spaced markers over those candidate regions detected by the scan. The analysis uses an extension of the dynamic-programming technique employed previously to fine map QTL in HS mice. We show by simulation that a QTL accounting for 5% of the total variance can be detected and fine mapped with � 50% probability to within 3 cM by genotyping � 1500 animals.