| First Author | Buchner DA | Year | 2003 |
| Journal | Genomics | Volume | 82 |
| Issue | 4 | Pages | 452-9 |
| PubMed ID | 13679025 | Mgi Jnum | J:85319 |
| Mgi Id | MGI:2673887 | Doi | 10.1016/s0888-7543(03)00152-6 |
| Citation | Buchner DA, et al. (2003) High-resolution mapping of the sodium channel modifier Scnm1 on mouse chromosome 3 and identification of a 1.3-kb recombination hot spot. Genomics 82(4):452-9 |
| abstractText | 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. |
