Using progenitor strain information to identify quantitative trait nucleotides in outbred mice.
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.
Yalcin
B
B
Wellcome Trust Centre for Human Genetics, Oxford University, UK.
Flint
J
J
Mott
R
R
D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D003433:Crosses, Genetic; D014644:Genetic Variation; D005838:Genotype; D051379:Mice / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics / Q000302:isolation & purification*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D017422:Sequence Analysis, DNA
D009711:Nucleotides