Mutability of Y-Chromosomal Microsatellites: Rates, Characteristics, Molecular Bases, and Forensic Implications
Mutability of Y-Chromosomal Microsatellites: Rates, Characteristics, Molecular Bases, and Forensic Implications
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DOI：
10.1016/j.ajhg.2010.08.006
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发表时间：
2010-09-10
影响因子：
9.8
通讯作者：
Kayser, Manfred
中科院分区：
文献类型：
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作者：
Ballantyne, Kaye N.;Goedbloed, Miriam;Kayser, Manfred
非重组Y染色体微卫星（Y-STR）被广泛用于推断人口历史，发现家谱关系，并确定刑事司法目的的男性。虽然应用这些技术的一个关键要求是可靠的可变性知识，但迄今为止只有少数Y型可疑交易报告的经验数据。为了纠正这一点，我们分析了近2000个DNA确认的父子对中的大量186个Y-STR标记，覆盖了352，999次减数分裂转移。在通过DNA序列分析确认后，通过贝叶斯方法对检索到的突变数据进行建模，得到突变率为3.78 x 10（-4）（95%可信区间[CI]，1.38 x 10（-5）- 2.02 x 10（-3））至7.44 x 10（-2）（95% CI，6.51 x 10（-2）- 9.09 x 10（-2））。在120个Y-STR标记的924个突变中，观察到重复丢失与获得的非显著性过量（1.16：1），以及单重复与多重复变化的强烈和显著性过量（25.23：1）。虽然总重复数影响Y-STR基因座突变最强烈，重复的复杂性，重复基序的碱基对的长度，和父亲的年龄也有助于Y-STR基因座突变。为了验证如何实际利用这一知识，我们分析了13个最易变的Y-STR在一个独立的样本集，并经验证明其适用于区分密切和远亲男性。这一发现有望彻底改变Y染色体在法医生物学中的应用，从以前的男性谱系分化到未来的男性个体识别。
Nonrecombining Y-chromosomal microsatellites (Y-STRs) are widely used to infer population histories, discover genealogical relationships, and identify males for criminal justice purposes. Although a key requirement for their application is reliable mutability knowledge, empirical data are only available for a small number of Y-STRs thus far. To rectify this, we analyzed a large number of 186 Y-STR markers in nearly 2000 DNA-confirmed father-son pairs, covering an overall number of 352,999 meiotic transfers. Following confirmation by DNA sequence analysis, the retrieved mutation data were modeled via a Bayesian approach, resulting in mutation rates from 3.78 x 10(-4) (95% credible interval [CI], 1.38 x 10(-5) - 2.02 x 10(-3)) to 7.44 x 10(-2) (95% Cl, 6.51 x 10(-2) - 9.09 x 10(-2)) per marker per generation. With the 924 mutations at 120 Y-STR markers, a nonsignificant excess of repeat losses versus gains (1.16:1), as well as a strong and significant excess of single-repeat versus multirepeat changes (25.23:1), was observed. Although the total repeat number influenced Y-STR locus mutability most strongly, repeat complexity, the length in base pairs of the repeated motif, and the father's age also contributed to Y-STR mutability. To exemplify how to practically utilize this knowledge, we analyzed the 13 most mutable Y-STRs in an independent sample set and empirically proved their suitability for distinguishing close and distantly related males. This finding is expected to revolutionize Y-chromosomal applications in forensic biology, from previous male lineage differentiation toward future male individual identification.