An 85-kb tandem triplication in the slow Wallerian degeneration (Wlds) mouse
An 85-kb tandem triplication in the slow Wallerian degeneration (Wlds) mouse
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DOI：
10.1073/pnas.95.17.9985
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发表时间：
1998-08-18
影响因子：
11.1
通讯作者：
Perry, VH
中科院分区：
文献类型：
--
作者：
Coleman, MP;Conforti, L;Perry, VH
沃勒氏变性是受损轴突远端残端变性。它通常发生在大约24小时的时间过程中，但在缓慢的沃勒氏变性突变小鼠（C57BL/Wld(s)）中延迟长达3周。该基因可以防止快速的沃勒氏变性（Wld），之前已经被定位到4号染色体的远端。本文报道了Wld位点的精细遗传定位，产生了1.4 mb的细菌人工染色体和P1人工染色体组，并在候选区域内鉴定了85 kb的串联三倍定位。该突变是C57BL/Wld(s)在36个测试菌株中所特有的，因此是导致延迟性沃勒氏变性的突变的强有力候选。在脊椎动物中很少有串联三胞胎的报道，也没有证据表明突变机制，所以这种不寻常的突变被更详细地描述了。对该重复单元的边界进行序列分析，发现其远端边界有一个小卫星阵列，近端边界有一个匹配的8bp序列。这一发现表明，短同源序列之间的重组（“非法”或“非同源”重组）参与了重排。此外，在两只Wld(s)小鼠中发现了一个重复等位基因，这表明重复拷贝数存在一定的不稳定性，表明三倍复制是由不均匀杂交引起的。
Wallerian degeneration is the degeneration of the distal stump of an injured axon. It normally occurs over a time course of around 24 hr but it is delayed in the slow Wallerian degeneration mutant mouse (C57BL/Wld(s)) for up to 3 weeks. The gene, which protects from rapid Wallerian degeneration, Wld, previously has been mapped to distal chromosome 4. This paper reports the fine genetic mapping of the Wld locus, the generation of a 1.4-Mb bacterial artificial chromosome and P1 artificial chromosome contig, and the identification of an 85-kb tandem triplication mapping within the candidate region. The mutation is unique to C57BL/Wld(s) among 36 strains tested and therefore is a strong candidate for the mutation that leads to delayed Wallerian degeneration. There are very few reports of tandem triplications in a vertebrate and no evidence for a mutation mechanism so this unusual mutation was characterized in more detail. Sequence analysis of the boundaries of the repeat unit revealed a minisatellite array at the distal boundary and a matching 8-bp sequence at the proximal boundary. This finding suggests that recombination between short homologous sequences ("illegitimate" or "nonhomologous" recombination) was involved in the rearrangement. In addition, a duplication allele was identified in two Wld(s) mice, indicating some instability in the repeat copy number and suggesting that the triplication arose from a duplication by unequal crossing over.