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Genetics. 2005 Oct;171(2):673-81. Epub 2005 Aug 5.

Using progenitor strain information to identify quantitative trait nucleotides in outbred mice.

Author information

1
Wellcome Trust Centre for Human Genetics, Oxford University, UK.

Abstract

We have developed a fast and economical strategy for dissecting the genetic architecture of quantitative trait loci at a molecular level. The method uses two pieces of information: mapping data from crosses that involve more than two inbred strains and sequence variants in the progenitor strains within the interval containing a quantitative trait locus (QTL). By testing whether the strain distribution pattern in the progenitor strains is consistent with the observed genetic effect of the QTL we can assign a probability that any sequence variant is a quantitative trait nucleotide (QTN). It is not necessary to genotype the animals except at a skeleton of markers; the genotypes at all other polymorphisms are estimated by a multipoint analysis. We apply the method to a 4.8-Mb region on mouse chromosome 1 that contains a QTL influencing anxiety segregating in a heterogeneous stock and show that, under the assumption that a single QTN is present and lies in a region conserved between the human and mouse genomes, it is possible to reduce the number of variants likely to be the quantitative trait nucleotide from many thousands to <20.

PMID:
16085706
PMCID:
PMC1456780
DOI:
10.1534/genetics.104.028902
[Indexed for MEDLINE]
Free PMC Article

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