title: High-resolution mapping of the sodium channel modifier Scnm1 on mouse chromosome 3 and identification of a 1.3-kb recombination hot spot.
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.
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D003433:Crosses, Genetic; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009468:Neuromuscular Diseases / Q000235:genetics; D000072260:RNA Splicing Factors; D017422:Sequence Analysis, DNA; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D005819:Genetic Markers; D000072260:RNA Splicing Factors; C486783:SCNM1 protein, human; C476996:Scnm1 protein, mouse; D015222:Sodium Channels