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Originally published as Genetics Published Articles Ahead of Print on August 5, 2005.
Genetics, Vol. 171, 673-681, October 2005, Copyright © 2005
doi:10.1534/genetics.104.028902
Using Progenitor Strain Information to Identify Quantitative Trait Nucleotides in Outbred Mice
B. Yalcin, J. Flint and R. Mott1
Wellcome Trust Centre for Human Genetics, Oxford University, Oxford OX3 7BN, United Kingdom
1 Corresponding author: Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Dr., Oxford OX3 7BN, United Kingdom.
E-mail: rmott{at}well.ox.ac.uk
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.
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