Kim Soon Hee, Lee Jin Myeong, Hyun Young Se, Choi Dong Ho
Seoul Institute, National Forensic Service, 139, Jiyang-ro, Yangcheon-gu, Seoul 08036, Republic of Korea.
Seoul Institute, National Forensic Service, 139, Jiyang-ro, Yangcheon-gu, Seoul 08036, Republic of Korea.
Leg Med (Tokyo). 2019 Mar;37:95-102. doi: 10.1016/j.legalmed.2019.02.002. Epub 2019 Feb 11.
The unknown origin of DNA samples derived from crime scenes generates a considerable amount of uncertainty, as do unexpected short tandem repeat (STR) results caused by sample mix-ups, contamination, medical interventions, and transgender individuals (broad meaning). Genetic abnormalities such as somatic/germline mutations, mosaicism or chimerism, sex reversal cases, aneuploidies, and chromosomal structural rearrangements are also possible causes of such results. The evidence offered by the present study suggested that additional DYS385 alleles, as seen in mixed stain samples and in the potentially single-source DNA profile of a female, originated from the female DNA source only. For the case reported here, we propose an interchromosomal insertion hypothesis, in which a 768-kb segment including the P4 palindrome of the azoospermia factor (AZFb) region was deleted from the Y chromosome and inserted into the X chromosome or an autosome during male meiosis. Y-SNP data points from the AccuID platform and in-house PCR assays narrowed down the expected length of the target region. Bioinformatics analysis followed by whole genome amplification and whole genome sequencing showed that a 529-kb segment including the P4 palindrome (HSFY/DYS385)/DYS460 region from the female sample mapped to the Y reference sequence (GRCh37). To our knowledge, the interchromosomal insertional translocation event was identified as an unknown type of genomic rearrangement in the forensic genetic field.
来自犯罪现场的DNA样本来源不明会产生相当大的不确定性,样本混淆、污染、医疗干预以及跨性别者(广义)导致的意外短串联重复序列(STR)结果也会如此。体细胞/生殖系突变、嵌合体或奇美拉现象、性反转病例、非整倍体以及染色体结构重排等基因异常也是造成此类结果的可能原因。本研究提供的证据表明,混合染色样本以及一名女性潜在单源DNA图谱中出现的额外DYS385等位基因仅源自女性DNA来源。对于此处报告的案例,我们提出一种染色体间插入假说,即在男性减数分裂过程中,一个包含无精子症因子(AZFb)区域P4回文序列的768 kb片段从Y染色体上缺失,并插入到X染色体或常染色体中。AccuID平台的Y-SNP数据点和内部PCR检测缩小了目标区域的预期长度。随后通过全基因组扩增和全基因组测序进行的生物信息学分析表明,女性样本中一个包含P4回文序列(HSFY/DYS385)/DYS460区域的529 kb片段与Y参考序列(GRCh37)匹配。据我们所知,染色体间插入易位事件在法医遗传学领域被确定为一种未知类型的基因组重排。