International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 152 - ACCELERATION OF POSITIONAL CLONING USING A HAPLOTYPE MAP OF THE INBRED LABORATORY MOUSE

Wade C M
Whitehead Institute/MIT Center for Genome Research Cambridge MA 02141 USA

Co-Authors: Kulbokas E J, Kirby A, Karlsson E, Lander E S, Lindblad-Toh K, Daly M J
Institutions: Whitehead Institute/MIT Center for Genome Research Cambridge MA 02141 USA

While decades of phenotyping and detailed analysis of crosses of inbred mice have enabled the initial localization of hundreds of loci involved in complex disease and quantitative phenotypes, very few genes have been conclusively identified from these studies. A clear understanding of the origin and structure of genetic variation in these strains provides a key missing piece of this puzzle.

Recent analysis of polymorphism across the draft mouse genome sequence (Wade et al., 2002) has established that the genomes of commonly used inbred strains are mostly consistent with being mosaics of long segments (~ 2Mb) that are predominantly derived from either western European M. m. domesticus or Asian M. m. musculus ancestry. A critical implication of this observation is that nearly all variation among these strains is comprised of ancestral differences between these highly diverged subspecies and can be easily tracked with a sparse map of SNPs given the observed size of the ancestral segments. To fully realize the power of the genome sequence, we have embarked upon the creation of a “haplotype map” consisting of roughly 50,000 SNPs genotyped in the common inbred laboratory mouse strains.

The proposed map will enable a dramatic acceleration in positional cloning, allowing the entire community of mouse geneticists to rapidly take advantage of decades of phenotyping and linkage mapping studies. Moreover, this effort provides a comprehensive genetic accompaniment to programs such as the Mouse Phenome Project which aims to collect phenotype data for the same commonly used mouse strains.


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