International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 154 - RAPID EFFICIENT PLACEMENT OF NEW MUTANT PHENOTYPES ON THE MOUSE GENETIC MAP

Rowe LB, Barter ME

The Jackson Laboratory, Bar Harbor, ME, United States

Major mutagenesis programs are underway at several institutions, providing mice for screening for diverse phenotypes to develop new models for human disease and to help dissect biological pathways. At The Jackson Laboratory, ENU-mutagenized C57BL/6J mice are being screened by three major project groups, Neuromuscular Function (NMF), Heart, Lung, Blood and Sleep Disorders (HLBS), and Reproductive Genomics (ReproGenomics), as well as many smaller project interests (eg. eye defects, hearing defects, obesity, and others). Rapid localization of these new mutations on the mouse genetic map is essential to define remutations at previously known loci or identify newly affected genes. We have developed a high throughput genome scanning system that regularly allows defining chromosomal localization within two days of the availability of animals segregating the phenotype. From as few as 6 affected and a few unaffected N2 or F2 animals (or, less optimally, G3 or G4 sibships), genome scanning by haplotype analysis (Neuhaus and Beier, 1998 Mammalian Genome 9: 150-154) rapidly identifies the candidate region. If more than ten affected and a similar number of unaffected N2, F2 or G3 are available for the mapping, genome scans by pooling (Taylor et al. 1994 Genomics 21: 626-632) are the most efficient method. Using these two scanning methodologies, we have been able to successfully map an average of two new mutations a week. Our lab also provides rapid DNA preparation for genotyping, and genotyping services for other in-house mapping projects including congenic line breeder selection ("speed congenics") and major modifier locus mapping.

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