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PubMed 13679025


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Title: High-resolution mapping of the sodium channel modifier Scnm1 on mouse chromosome 3 and identification of a 1.3-kb recombination hot spot.

Authors: David A Buchner, Michelle Trudeau, Alfred L George, Leslie K Sprunger, Miriam H Meisler

Journal, date & volume: Genomics, 2003 Oct , 82, 452-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/13679025


Abstract
Variation between inbred strains of mice can be used to identify modifier genes affecting the susceptibility to inherited disease. The medJ allele of the sodium channel Scn8a contains a splice site mutation that results in sodium channel deficiency. The severity of the neurological disorder is determined by the modifier locus Scnm1. The wild-type allele of the modifier results in correct splicing of 10% of Scn8amedJ pre-mRNA and a dystonic phenotype. The susceptible allele of the modifier in strain C57BL/6J results in 5% correctly spliced transcripts and a lethal phenotype. A mapping cross with C3H using 26 new markers and 2304 affected F2 animals localized the modifier gene to a 950-kb interval on mouse chromosome 3. Fine mapping of recombination breakpoints revealed a recombination hot spot of 1.3 kb. The ratio of genetic to physical distance in the hot spot is 85 cM/Mb, two orders of magnitude higher than the mouse genome average of 0.5 cM/Mb. The role of the modifier in other disorders in human and mouse can be tested with linked markers described here.