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

被引:12
作者
Buchner, DA
Trudeau, M
George, AL
Sprunger, LK
Meisler, MH
机构
[1] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA
[2] Vanderbilt Univ, Div Med Genet, Nashville, TN 37232 USA
关键词
modifier gene; neuromuscular disease; pre-mRNA splicing; Scn8a; Nav1.6; SNP;
D O I
10.1016/S0888-7543(03)00152-6
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Variation between inbred strains of mice can be used to identify modifier genes affecting the susceptibility to inherited disease. The med(J) 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 Scn8a(medj) 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. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:452 / 459
页数:8
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