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Open Access

Fine-mapping of fearfulness

  • William Wells
Genome Biology20001:spotlight-20001030-02

Published: 30 October 2000


Quantitative Trait LocusFine MappingPlague60th GenerationInbred Mouse

Geneticists cut their teeth on conditions controlled by single loci. The harder task is to find the many loci that work together to control a single trait. In the 7 November Proceedings of the National Academy of Sciences Mott et al. demonstrate a new method for mapping these quantitative trait loci (QTL; Proc Natl Acad Sci USA 2000, published online before print). Previous methods all have their limits: family-based studies tend to be small and so can only do coarse mapping; population-based association studies give greater numbers (and thus potentially greater resolution) but are complicated by variable and unknown inheritance histories; and breeding studies in mice are plagued by a possible lack of segregating loci when two inbred mouse populations are used as founders. Mott et al. get around this last problem by using the progeny from an eight-way cross that was started 30 years ago and is now in its 60th generation. They use dynamic programming to calculate the probability that a given allele is descended from one of the eight progenitors. Use of single-marker association often fails because different QTL alleles occur on similar haplotypes, but multipoint analysis allows the authors to fine-map all five of the previously identified loci for fearfulness in mice. The authors propose that whole-genome fine mapping with this method would be cost-effective if 20 or more traits were mapped in parallel on the same set of mice.


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© BioMed Central Ltd 2000