Development and application of a nonbinary SNP-based microhaplotype panel for paternity testing involving close relatives
Development and application of a nonbinary SNP-based microhaplotype panel for paternity testing involving close relatives
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基于非二元 SNP 的微单倍型面板的开发和应用，用于涉及近亲的亲子鉴定
DOI：
10.1016/j.fsigen.2020.102255
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发表时间：
2020-05-01
影响因子：
3.1
通讯作者：
Zha, Lagabaiyila
中科院分区：
文献类型：
--
作者：
Sun, Shule;Liu, Ying;Zha, Lagabaiyila
涉及近亲的亲子鉴定在法医遗传学领域面临着挑战。微单倍型因其低突变率和高分辨能力而成为一种很有前途的遗传标记。在这项研究中，我们从1000个基因组计划中选择了30个微单倍型，其中包括一个非二元SNP，以及从仅包含二元SNP的已发表研究中选择的另外6个微单倍型，建立了一个用于亲子鉴定的微单倍型面板。大多数微单倍型产生的有效等位基因数（a (e)）较高，其谐波平均值为3.91，杂合度的算术平均值为0.74。我们从6个大家庭中收集了54个不相关的个体和53个样本。值得注意的是，来自6个大家庭的13个样本是不相关的，因此它们也被纳入了不相关的个体。基于6个大家庭的53个样本，构建了38对亲子、55对伯父/伯母/孙辈（非亲生亲子）和29对全兄弟姐妹的家系。基因型和单倍型分析结果表明，该品种的组合辨别力（CPD）达到0.9999999999999999999999999999799，累积排除概率（CPE）达到0.99999999999999548。排除亲属（叔叔/阿姨/祖父母）的联合概率（CPER）为0.999999993(> 0.9999)，表明我们的小组在防止近亲为亲生父母的误解方面有很好的效果。对于38对亲子组合，使用微单倍型面板的CPI高于使用Goldeneye 20A试剂盒的CPI，因为我们的面板多态性更高，位点更多。对于55对非生理性亲子对，使用STR基因座的CPI无法帮助确定9对非生理性亲子对“排除”父系关系，而使用微单倍型基因座的CPI无法帮助排除4对非生理性亲子对（CPI > 0.0001）。使用来自str和微单倍型数据集的CPI，所有非生物学的亲子二人组都可以被视为排除在外。通过对2000对模拟配对的参数分析，评价该面板排除近亲属的效率，在t(1) = 4和t(2) = - 4的阈值下，有效性为0.988。此外，考虑物理联系后，29对全同胞指数（CFSI）的平均对数（10）约为7.55。这些数据表明，这种基于非二元snp的微单倍型面板在亲子鉴定中具有优势，特别是在STR突变或近亲涉及的病例中。
Paternity testing involving close relatives is facing challenges in the field of forensic genetics. Microhaplotype has been proposed as a promising genetic marker for their low mutation rates and high discrimination power recently. In this study, we selected 30 microhaplotypes from 1000 genome projects, including one non-binary SNP, and other six microhaplotypes from published studies containing only binary SNPs to established a panel of microhaplotypes for paternity testing. Most microhaplotypes generated a high effective number of alleles (A(e)) with the harmonic mean value of A(e) of 3.91 and the arithmetic mean value of heterozygosity of 0.74, respectively. We collected 54 unrelated individuals and 53 samples from six extended families. It was noting that 13 samples from six extended families were unrelated so they were also included in unrelated individuals. The pedigrees of 38 parent-child duos, 55 uncle/aunt/grandparent-child duos (non-biological parent-child duos) and 29 full sibling pairs were constructed based on 53 samples from six extended families. The genotype and haplotype results demonstrated that the combined power of discrimination (CPD) reached 0.99999999999999999999999999999999799 and the cumulative probability of exclusion (CPE) reached 0.999999999999548. The combined probability of excluding relatives (uncle/aunt/grandparent) (CPER) was 0.999999993 ( > 0.9999), indicating that our panel had good effectiveness in preventing the misinterpretation of close relatives being biological parents. For 38 parent-child duos, the CPI by using the microhaplotypes panel was higher than the one by using Goldeneye 20A kit due to higher polymorphism and more loci in our panel. For 55 non-biological parent-child duos, the CPIs by using STR loci could not help determine 9 non-biological parent-child duos as "exclusions" of paternity while the CPIs by using microhaplotype loci could not help exclude the parenthood of 4 non-biological parent-child duos (CPI > 0.0001). Using the CPI derived from both datasets of STRs and microhaplotypes, all the non-biological parent-child duos could be considered as exclusions. The efficiency of excluding close relatives for this panel was evaluated by analyzing the parameters of 2000 simulated pairs, and the effectiveness was 0.988 at the threshold of t(1) = 4 and t(2) = - 4. Moreover, the average Log(10), combined full sibling index (CFSI) for all 29 full sibling pairs was about 7.55 after physical linkage taken account. These data demonstrated that this nonbinary SNPs-based microhaplotype panel has advantages in paternity testing, especially in STR mutated or close relatives involved cases.