1)贵州医科大学毒性检测中心,法医学院,贵阳 561113;2)公安部鉴定中心,法医遗传学公安部重点实验室,北京市现场物证检验工程技术研究中心, 现场物证溯源技术国家工程实验室,北京 100038;3)中国人民公安大学侦查学院,北京 100038;4)山西医科大学法医学院,晋中 030600;5)江苏师范大学生命科学学院,江苏省系统发育与比较基因组学重点实验室,徐州 221116
国家重点研发计划(2022YFC3341004),国家自然科学基金(81772027)和公安部科技计划(2023JSZ02)资助项目。
1)Toxicity Testing Center, Department of Forensic Medicine, Guizhou Medical University, Guiyang 561113, China;2)Institute of Forensic Science, Key Laboratory of Forensic Genetics, Beijing Engineering Research Center of Crime Scene Evidence Examination, National Engineering Laboratory for Forensic Science, Beijing 100038, China;3)School of Investigation, People’s Public Security University of China, Beijing 100038, China;4)School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, China;5)Jiangsu Key Laboratory of Phylogenomics and Comparative Genomics, School of Life Sciences, Jiangsu Normal University, Xuzhou 221116, China
This work was supported by grants from the National Key Research and Development Program of China (2022YFC3341004), The National Natural Science Foundation of China (81772027), and the Science and Technology Program of the Ministry of Public Security (2023JSZ02).
目的 Y染色体单倍群分配的准确性在男性样本的父系祖先溯源中至关重要。随着高通量测序技术的发展,目前研究常基于全基因组或芯片数据中高密度Y染色体单核苷酸多态性(Y-SNP)的分型来判别个体的Y染色体单倍群。本研究系统评估了4种常见的高密度单核苷酸多态性(SNP)分型检测体系,包括全球筛查芯片(Global Screening Array,GSA)、中国基因分型芯片(Chinese Genotyping Array,CGA)、Affymetrix芯片及1240K捕获体系的单倍群判别效能,为不同体系的数据比对提供参考依据。方法 基于千人基因组计划1 590例男性样本的30×全基因组测序(whole genome sequencing,WGS)数据提取了上述4种Y-SNP位点集的分型结果,收集了109个中国汉族家系的384对1~12级亲缘样本的GSA芯片分型数据,利用Y-LineageTracker v1.3.0软件进行单倍群判别。评估4种Y-SNP位点集与全基因组分型数据获取的单倍群一致性、分辨率。评估千人基因组计划及本研究收集的109份家系样本的单倍群一致性、分辨率。评估不同量级Y-SNP对单倍群判别结果的影响。结果 GSA和CGA位点集在判别单倍群亚群和分辨率上优于其他两种位点集;GSA、CGA和1240K位点集的单倍群判定与全基因组分型数据一致性均超过88.70%,而Affymetrix平台的一致性显著降低至61.89%。所有家系样本中4组位点集均未出现单倍群不匹配亲缘关系对。在1 000~10 000个Y-SNP范围内,Y-SNP位点组合数量与分类一致性呈正相关,但当Y-SNP数量超过10 000时,其分类一致性趋于平缓。结论 GSA和CGA位点集兼具高分辨率与高一致性,能够在法医实践中为Y单倍群判定提供可靠依据。
Objective The accuracy of Y-chromosome haplogroup assignment is crucial for tracing paternal lineage in male samples. With the advancement of high-throughput sequencing technologies, high-density Y-SNP genotyping from whole-genome or array-based data has become a standard method for determining Y-chromosome haplogroups. This study systematically evaluated the performance of 4 commonly used high-density SNP genotyping systems—namely, the Global Screening Array (GSA), Chinese Genotyping Array (CGA), Affymetrix array, and the 1240K capture panel—for haplogroup assignment. This work provides a reference for data comparison across different systems.Methods We extracted genotype data for the 4 Y-SNP panels from 30× whole-genome sequencing (WGS) data of 1 590 male samples from the 1000 Genomes Project. Additionally, GSA array genotype data from 384 relative pairs (spanning 1st- to 12th-degree relationships) from 109 Chinese Han families were collected. Haplogroup assignment was performed using Y-LineageTracker v1.3.0 software. We assessed the concordance and resolution of haplogroup assignments between the four Y-SNP panels and the WGS data. The consistency and resolution of haplogroup assignments were also evaluated for both the 1000 Genomes Project samples and the 109 family samples collected in this study. Furthermore, the impact of varying numbers of Y-SNPs on haplogroup assignment was examined.Results The GSA and CGA panels demonstrated superior resolution and discrimination of haplogroup subclades compared with the other two panels. The haplogroup assignments from the GSA, CGA, and 1240K panels showed high concordance with WGS data, with consistency rates exceeding 88.70%, whereas the Affymetrix platform exhibited a significantly lower consistency rate of 61.89%. Specifically, the GSA and CGA panels consistently demonstrated superior performance compared with the other two panels in the assignment of haplogroups O-M175 and H-L901, achieving complete concordance (100%) for both haplogroups. In contrast, the Affymetrix panel erroneously assigned all individuals belonging to haplogroup O-M175 to haplogroup K2-M526. Furthermore, its accuracy for haplogroup H-L901 was exceedingly low, at merely 1.41%. This poor performance was characterized by the misassignment of 98.59% of H-L901 samples—specifically, 1.41% to J-M304 and a predominant 97.18% to F-M89. For haplogroup R-M207, all four panels exhibited uniformly high levels of consistency, with concordance values exceeding 94.00%. Notably, for haplogroup E-M96, the 1240K and Affymetrix panels outperformed the GSA and CGA panels in terms of concordance, representing the first instance in which these two panels surpassed the latter. Conversely, for haplogroups J-M304, Q-M242, and I-M170, all 4 panels showed relatively elevated misclassification rates, with the Affymetrix array demonstrating the poorest overall performance. None of the four panels showed any discordant haplogroup assignments among the familial relative pairs analyzed. A positive correlation was observed between the number of Y-SNPs (ranging from 1 000 to 10 000) and classification consistency; however, classification consistency plateaued when the number of Y-SNPs exceeded 10 000. Furthermore, a random sampling analysis conducted on the GSA and CGA panels demonstrated that the haplogroup misclassification rate exhibited negligible fluctuation across the Y-SNP range of 500 to 1 000. Conversely, a marked enhancement in classification consistency was observed as the number of markers increased from 1 000 to 5 000, ultimately reaching a plateau within the interval of 5 000 to 8 000 markers.Conclusion These findings indicate that the GSA and CGA panels provide high resolution and concordance, delivering reliable Y-haplogroup assignment for forensic investigations.
张德琴,王春年,娄琳琳,倪萌,高静,黄江,江丽.高密度Y-SNP分型体系用于法医实践中Y单倍群推断的效能评估[J].生物化学与生物物理进展,2026,53(2):458-469 ZHANG De-Qin, WANG Chun-Nian, LOU Lin-Lin, NI Meng, GAO Jing, HUANG Jiang, JIANG Li. Assessing High-density Y-SNP Panels for Paternal Haplogroup Assignment in Forensic Practice[J]. Progress in Biochemistry and Biophysics,2026,53(2):458-469
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