Department of Forensic Molecular Biology, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam The Netherlands.
Int J Legal Med. 2009 Nov;123(6):471-82. doi: 10.1007/s00414-009-0342-y. Epub 2009 Mar 26.
The Y-chromosomal short tandem repeat (Y-STR) polymorphisms included in the AmpFlSTR Yfiler polymerase chain reaction amplification kit have become widely used for forensic and evolutionary applications where a reliable knowledge on mutation properties is necessary for correct data interpretation. Therefore, we investigated the 17 Yfiler Y-STRs in 1,730-1,764 DNA-confirmed father-son pairs per locus and found 84 sequence-confirmed mutations among the 29,792 meiotic transfers covered. Of the 84 mutations, 83 (98.8%) were single-repeat changes and one (1.2%) was a double-repeat change (ratio, 1:0.01), as well as 43 (51.2%) were repeat gains and 41 (48.8%) repeat losses (ratio, 1:0.95). Medians from Bayesian estimation of locus-specific mutation rates ranged from 0.0003 for DYS448 to 0.0074 for DYS458, with a median rate across all 17 Y-STRs of 0.0025. The mean age (at the time of son's birth) of fathers with mutations was with 34.40 (+/-11.63) years higher than that of fathers without ones at 30.32 (+/-10.22) years, a difference that is highly statistically significant (p < 0.001). A Poisson-based modeling revealed that the Y-STR mutation rate increased with increasing father's age on a statistically significant level (alpha = 0.0294, 2.5% quantile = 0.0001). From combining our data with those previously published, considering all together 135,212 meiotic events and 331 mutations, we conclude for the Yfiler Y-STRs that (1) none had a mutation rate of >1%, 12 had mutation rates of >0.1% and four of <0.1%, (2) single-repeat changes were strongly favored over multiple-repeat ones for all loci but 1 and (3) considerable variation existed among loci in the ratio of repeat gains versus losses. Our finding of three Y-STR mutations in one father-son pair (and two pairs with two mutations each) has consequences for determining the threshold of allelic differences to conclude exclusion constellations in future applications of Y-STRs in paternity testing and pedigree analyses.
Y 染色体短串联重复序列（Y-STR）多态性已被广泛应用于法医和进化研究领域，在这些领域中，正确的数据解释需要可靠的突变特性知识。因此，我们调查了每个位点的 17 个 Yfiler Y-STR 在 1730-1764 对 DNA 确认的父子对中的情况，并在覆盖的 29792 次减数分裂转移中发现了 84 个序列确认的突变。在 84 个突变中，83 个（98.8%）是单重复变化，1 个（1.2%）是双重复变化（比例为 1:0.01），43 个（51.2%）是重复增益，41 个（48.8%）是重复损失（比例为 1:0.95）。贝叶斯估计的每个位点特异性突变率中位数从 DYS448 的 0.0003 到 DYS458 的 0.0074 不等，所有 17 个 Y-STR 的中位数为 0.0025。有突变的父亲的平均年龄（在儿子出生时）为 34.40（+/-11.63）岁，高于没有突变的父亲的 30.32（+/-10.22）岁，差异具有统计学意义（p<0.001）。基于泊松模型的分析表明，Y-STR 突变率随着父亲年龄的增加呈统计学显著增加（alpha=0.0294，2.5%分位数=0.0001）。将我们的数据与以前发表的数据结合起来，考虑到总共 135212 次减数分裂事件和 331 个突变，我们得出结论，对于 Yfiler Y-STR 而言：（1）没有一个突变率大于 1%，12 个突变率大于 0.1%，4 个小于 0.1%；（2）除了 1 个位点之外，所有位点的单重复变化都明显优于多重复变化；（3）各位点的重复增益与损失比值存在较大差异。在一个父子对中发现了三个 Y-STR 突变（还有两对每个都有两个突变），这对确定等位基因差异的阈值以在未来的 Y-STR 父子关系鉴定和系谱分析中有意义。
