Neumann P E, Collins R L
Department of Neurology, Children's Hospital, Boston, MA.
Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5408-12. doi: 10.1073/pnas.88.12.5408.
Mice of some inbred strains, such as 21-day-old DBA/2J mice, have generalized convulsions when exposed to intense auditory stimulation. Analysis of susceptibility to audiogenic seizures in BXD recombinant inbred strains has demonstrated the influence of at least three loci. One locus, Asp-1, is located on chromosome 12 between Ah and D12Nyu1; another locus, Asp-2, is on chromosome 4, tightly linked to b. Here we report evidence that Asp-2 is located within an 8-centimorgan segment distal to b and that Asp-3 is linked to Mtv-1 on chromosome 7. We also present evidence that these three loci account for most of the heritable variation in susceptibility to audiogenic seizures in crosses of DBA/2J and C57BL/6J mice and that susceptibility to audiogenic seizures is influenced by genomic imprinting. Thus, genomic imprinting may complicate linkage and mapping studies and should be considered in analyses of complex modes of inheritance.
一些近交系小鼠，如21日龄的DBA/2J小鼠，在受到强烈听觉刺激时会发生全身性惊厥。对BXD重组近交系小鼠听源性癫痫易感性的分析表明，至少有三个基因座起作用。一个基因座Asp-1位于12号染色体上Ah和D12Nyu1之间；另一个基因座Asp-2位于4号染色体上，与b紧密连锁。在此我们报告证据表明，Asp-2位于b远端的一个8厘摩区域内，且Asp-3与7号染色体上的Mtv-1连锁。我们还提供证据表明，在DBA/2J和C57BL/6J小鼠杂交中，这三个基因座解释了听源性癫痫易感性的大部分遗传变异，且听源性癫痫易感性受基因组印记影响。因此，基因组印记可能会使连锁和定位研究复杂化，在复杂遗传模式分析中应予以考虑。
