The mutational spectrum of human autosomal tetranucleotide microsatellites
The mutational spectrum of human autosomal tetranucleotide microsatellites
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DOI：
10.1002/humu.10153
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发表时间：
2003-01-01
期刊：
影响因子：
3.9
通讯作者：
Pena, SDJ
中科院分区：
文献类型：
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作者：
Leopoldino, AM;Pena, SDJ
我们通过多重扩增和单次电泳分析研究了10个微卫星位点，其中包括9个四核苷酸重复序列（D1S1612、D3S2387、D4S2431、D5S2501、D10S1237、D15S657、D16S2622、D18S1270和IFNAR - ALU）以及1个三核苷酸重复序列（D2S1353）。在排除了涉及D1S1612和D5S2501的已证实的无效等位基因事件以及我们怀疑但无法证明确实存在无效等位基因的D3S2387的所有数据后，我们剩下9个位点，涵盖24224次减数分裂和23个突变。其中22个突变（96%）是单步事件。此外，18个突变来自父本，4个来自母本，1个无法确定。突变体中增加和缺失的数量没有显著差异。我们的研究结果与一个简单模型相符，在该模型中，四核苷酸微卫星主要通过DNA滑动在父本生殖细胞中发生突变，因此绝大多数突变是单个重复单元的等概率增加或缺失。通过将我们的四核苷酸位点数据与高突变率和低突变率微卫星的文献信息相结合，我们观察到突变率与最长完美重复区域（LRPR）长度的几何平均值之间存在非常显著的相关性，符合幂律或指数关系。LRPR长度的变化解释了常染色体四核苷酸微卫星突变率方差的多达80%。
We studied by multiplex amplification and single-run electrophoretic analysis 10 microsatellite loci, composed of nine tetranucleotide-repeats (D1S1612, D3S2387, D4S2431, D5S2501, D10S1237, D15S657, D16S2622, D18S1270, and IFNAR-ALU) and one trinucleotide repeat (D2S1353). After elimination of proven null allele events involving D1S1612 and D5S2501 and of all data of D3S2387, in which we suspected but could not prove the occurrence of null alleles, we were left with nine loci, encompassing 24,224 meioses and 23 mutations. Twenty-two of the mutations (96%) were single step events. Moreover, 18 of the mutations were Paternal, four were maternal, and one was indeterminate. There was no significant difference between the number of additions and deletions in the mutants. Our findings are compatible with a simple model in which tetranucleotide microsatellites mutate primarily in paternal germinative cells by DNA slippage, such that the vast majority of mutations are equiprobable additions or deletions of a single-repeat unit. By combining the data from our tetranucleotide loci with literature information of highly and lowly mutable microsatellites, we observed a very highly significant correlation between mutation rate and the geometric mean of the length of the longest perfect repeat region (LRPR), compatible with a power or exponential relationship. The variation of the length of the LRPR explained as much as 80% of the variance of the mutation rate of autosomal tetranucleotide microsatellites.