Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Austria.
Forensic Sci Int Genet. 2012 May;6(3):381-6. doi: 10.1016/j.fsigen.2011.07.015. Epub 2011 Aug 27.
Well defined estimates of mutation rates are a prerequisite for the use of short tandem repeat (STR-) loci in relationship testing. We investigated 65 isolated genetic inconsistencies, which were observed within 50,796 allelic transfers at 23 STR-loci (ACTBP2 (SE33), CD4, CSF1PO, F13A1, F13B, FES, FGA, vWA, TH01, TPOX, D2S1338, D3S1358, D5S818, D7S820, D8S1132, D8S1179, D12S391, D13S317, D16S539, D17S976, D18S51, D19S433, D21S11) in Caucasoid families residing in Austria and Switzerland. Sequencing data of repeat and flanking regions and the median of all theoretically possible mutational steps showed valuable information to characterise the mutational events with regard to parental origin, change of repeat number (mutational step size) and direction of mutation (losses and gains of repeats). Apart from predominant single-step mutations including one case with a double genetic inconsistency, two double-step and two apparent four-step mutations could be identified. More losses than gains of repeats and more mutations originating from the paternal than the maternal lineage were observed (31 losses, 22 gains, 12 losses or gains and 47 paternal, 11 maternal mutations and 7 unclear of parental origin). The mutation in the paternal germline was 3.3 times higher than in the maternal germline. The results of our study show, that apart from the vast majority of single-step mutations rare multi-step mutations can be observed. Therefore, the interpretation of mutational events should not rigidly be restricted to the shortest possible mutational step, because rare but true multi-step mutations can easily be overlooked, if haplotype analysis is not possible.
明确的突变率估计是在关系测试中使用短串联重复（STR）基因座的前提条件。我们研究了 65 个孤立的遗传不一致性，这些不一致性是在 23 个 STR 基因座（ACTBP2（SE33）、CD4、CSF1PO、F13A1、F13B、FES、FGA、vWA、TH01、TPOX、D2S1338、D3S1358、D5S818、D7S820、D8S1132、D8S1179、D12S391、D13S317、D16S539、D17S976、D18S51、D19S433、D21S11）的等位基因转移中观察到的 50796 个等位基因转移中，这些转移发生在居住在奥地利和瑞士的高加索人群体的家族中。重复和侧翼区域的测序数据以及所有理论上可能的突变步骤中位数为描述突变事件提供了有价值的信息，这些信息涉及亲本来源、重复数（突变步骤大小）的变化和突变方向（重复的丢失和获得）。除了主要的单步突变外，还包括一个具有双重遗传不一致性的案例，我们可以识别出两个双步突变和两个明显的四步突变。观察到的重复丢失多于获得，且来自父系的突变多于来自母系的突变（31 个丢失、22 个获得、12 个丢失或获得，以及 47 个来自父系、11 个来自母系和 7 个来源不明的突变）。父系生殖细胞中的突变是母系生殖细胞中的突变的 3.3 倍。我们的研究结果表明，除了绝大多数单步突变外，还可以观察到罕见的多步突变。因此，如果不能进行单体型分析，对突变事件的解释不应严格限制在最短的可能突变步骤，因为如果不注意，很容易忽略罕见但真实的多步突变。
