International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 23 - DISSECTION OF OM-MEDIATED EMBRYONIC LETHALITY AND MEIOTIC DRIVE BY COMPARATIVE PHENOTYPE/HAPLOTYPE ANALYSIS IN MOUSE INBRED STRAINS

F. Pardo-Manuel de Villena
University of North Carolina

1) Kim K, 1) Pappalas J, 1) Bell T, 1) Howard I, 2) Thomas S,
1) University of North Carolina, 2) Claflin University

The Om locus is involved for two unusual mouse phenotypes; the early embryonic death known as the DDK syndrome and sperm-mediated meiotic drive during female meiosis.  Two genetic elements, a DDK maternal factor and a paternal gene, are responsible for the lethal phenotype, while another two, the Responder and Shade, are responsible for the drive.  The components of the lethal phenotype and the Responder map to a 400kb interval, while Shade is localized in a 1Mb non-overlapping distal interval.  Identification and validation of candidate genes for each one of the four genetic elements has been challenging because these regions are gene-rich and knockout-based approaches are unlikely to replicate the phenotypes because none of the alleles are predicted be represent null mutations.  To overcome these problems we have defined the functional alleles present in over 10 phylogeneticaly distant inbred strains.  These include laboratory strains of common use as well as wild derived strains from castaneus and molossinus origins.  Our results demonstrate that each element is a separate locus and that different strains carry different combination of functional alleles.  We are also generating SNP-based haplotypes for each strain in these regions.  These data will be used to define regions that share haplotypes between strains carrying functionally equivalent alleles at each of the four loci.  Using this approach we should be able to define the relative positions of each locus within the candidate intervals and ultimately to identify strong candidates for each gene.


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