International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Doherty H
Co-Authors: Kim K, Bell T, Ideraabdullah F, Pardo-Manuel de Villena F

In mammals, meiotic drive is achieved by preferential segregation of one chromosome over another to the functional product of female meiosis. Although meiotic drive is a well-known exception to Mendel's law of segregation, the molecular mechanisms are not understood. Two components are required in all meiotic drive systems, the Responder and the Distorter. The Distorter is the effector in the system, and “drives” alleles at the Responder. The goal of this project is molecular identification of the Distorter in the Om (Ovum mutant) meiotic drive system. Using recombination mapping we have defined a 300kb candidate interval for the Distorter locus on mouse chromosome 11. This locus was named Shade (for Sperm haploid distorter element). We have compiled the phenotypes and haplotypes for this region in four classical strains (C57BL/6J, A/J, DBA2/J, and 129X1/SvJ). Within the candidate interval there is a 200kb region, containing four genes, where there is complete haplotype/phenotype concordance. Interestingly, within the region of concordance there are two missense mutations and three UTR mutations. We also characterized the drive phenotype for 11 additional classical and wild-derived strains. We are currently completing the haplotypes in the candidate interval for these additional strains. Based on the level of haplotype-sharing for these strains observed in other genomic regions, we expect the reduced size of the candidate interval to approach one gene and possibly to a single mutation. Identification of Shade should permit the characterization of the molecular mechanism behind meiotic drive, an important evolutionary force in shaping the mammalian genome.

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