Immunology and Histocompatibility Department, Evangelismos General Hospital, 10676 Athens, Greece.
School of Electrical and Computer Engineering, National Technical University of Athens (ECE-NTUA), 15772 Zografou, Greece.
Genes (Basel). 2024 Jan 24;15(2):150. doi: 10.3390/genes15020150.
In the realm of DNA testing with legal implications, the reliability and precision of genetic markers play a pivotal role in confirming or negating paternity claims. This study aimed to assess the potential utility of human leukocyte antigen (HLA) gene polymorphism through massively parallel sequencing (MPS) technology as robust forensic markers for parentage testing involving genetic deficiencies. It sought to redefine the significance of HLA genes in this context. Data on autosomal short tandem repeat (aSTR) mutational events across 18 paternity cases involving 16 commonly employed microsatellite loci were presented. In instances where traditional aSTR analysis failed to establish statistical certainty, kinship determination was pursued via HLA genotyping, encompassing the amplification of 17 linked HLA loci. Within the framework of this investigation, phase-resolved genotypes for HLA genes were meticulously generated, resulting in the definition of 34 inherited HLA haplotypes. An impressive total of 274 unique HLA alleles, which were classified at either the field 3 or 4 level, were identified, including the discovery of four novel HLA alleles. Likelihood ratio (LR) values, which indicated the likelihood of the observed data under a true biological relationship versus no relationship, were subsequently calculated. The analysis of the LR values demonstrated that the HLA genes significantly enhanced kinship determination compared with the aSTR analysis. Combining LR values from aSTR markers and HLA loci yielded conclusive outcomes in duo paternity cases, showcasing the potential of HLA genes and MPS technology for deeper insights and diversity in genetic testing. Comprehensive reference databases and high-resolution HLA typing across diverse populations are essential. Reintegrating HLA alleles into forensic identification complements existing markers, creating a potent method for future forensic analysis.
在具有法律影响的 DNA 检测领域，遗传标记的可靠性和精确性在确认或否定亲子关系主张方面起着关键作用。本研究旨在评估人类白细胞抗原 (HLA) 基因多态性通过大规模平行测序 (MPS) 技术作为涉及遗传缺陷的亲子关系检测的强大法医标记的潜力。它旨在重新定义 HLA 基因在这方面的意义。本研究提供了涉及 16 个常用微卫星位点的 18 个亲子案例中常染色体短串联重复 (aSTR) 突变事件的数据。在传统的 aSTR 分析未能确定统计确定性的情况下，通过 HLA 基因分型（涵盖 17 个连锁 HLA 基因座的扩增）进行了亲属关系确定。在该研究的框架内，精心生成了 HLA 基因的相位分辨基因型，从而定义了 34 个遗传 HLA 单倍型。总共鉴定出 274 个独特的 HLA 等位基因，其中包括在字段 3 或 4 水平分类的 HLA 等位基因，包括发现了四个新的 HLA 等位基因。随后计算了表明观察到的数据在真实生物学关系下的可能性与无关系下的可能性的似然比 (LR) 值。LR 值的分析表明，与 aSTR 分析相比，HLA 基因显著增强了亲属关系的确定。将 aSTR 标记和 HLA 基因座的 LR 值结合起来，在双重父子关系案例中得出了结论性的结果，展示了 HLA 基因和 MPS 技术在遗传检测中更深层次的见解和多样性的潜力。全面的参考数据库和跨多种人群的高分辨率 HLA 分型至关重要。将 HLA 等位基因重新整合到法医鉴定中补充了现有的标记，为未来的法医分析创造了一种强大的方法。
