Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
Forensic Sci Int Genet. 2013 Sep;7(5):475-81. doi: 10.1016/j.fsigen.2013.05.008. Epub 2013 Jun 28.
Short tandem repeat (STR) loci are commonly used in forensic casework, familial analysis for human identification, and for monitoring hematopoietic cell engraftment after bone marrow transplant. Unexpected genetic variation leading to sequence and length differences in STR loci can complicate STR typing, and presents challenges in casework interpretation. Copy number variation (CNV) is a relatively recently identified form of genetic variation consisting of genomic regions present at variable copy numbers within an individual compared to a reference genome. Large scale population studies have demonstrated that likely all individuals carry multiple regions with CNV of 1kb in size or greater in their genome. To date, no study correlating genomic regions containing STR loci with CNV has been conducted. In this study, we analyzed results from 32,850 samples sent for clinical array comparative genomic hybridization (CGH) analysis for the presence of CNV at regions containing the 13 CODIS (Combined DNA Index System) STR, and the Amelogenin X (AMELX) and Amelogenin Y (AMELY) loci. Thirty-two individuals with CNV involving STR loci on chromosomes 2, 4, 7, 11, 12, 13, 16, and 21, and twelve with CNV involving the AMELX/AMELY loci were identified. These results were correlated with data from publicly available databases housing information on CNV identified in normal populations and additional clinical cases. These collective results demonstrate the presence of CNV in regions containing 9 of the 13 CODIS STR and AMELX/Y loci. Further characterization of STR profiles within regions of CNV, additional cataloging of these variants in multiple populations, and contributing such examples to the public domain will provide valuable information for reliable use of these loci.
短串联重复 (STR) 基因座通常用于法医案件、人类鉴定的家族分析，以及监测骨髓移植后造血细胞植入。导致 STR 基因座序列和长度差异的意外遗传变异会使 STR 分型复杂化，并在案例解释方面带来挑战。拷贝数变异 (CNV) 是一种相对较新发现的遗传变异形式，由个体基因组中存在的与参考基因组相比存在可变拷贝数的基因组区域组成。大规模的人群研究表明，几乎所有个体的基因组中都携带多个大小为 1kb 或更大的 CNV 区域。迄今为止，尚未有研究将包含 STR 基因座的基因组区域与 CNV 相关联。在这项研究中，我们分析了 32850 个样本的结果，这些样本是为了检测包含 13 个 CODIS（联合 DNA 索引系统）STR 以及 amelogenin X（AMELX）和 amelogenin Y（AMELY）基因座的区域中是否存在 CNV 而进行的临床阵列比较基因组杂交 (CGH) 分析。鉴定出 32 名个体的染色体 2、4、7、11、12、13、16 和 21 上的 STR 基因座涉及 CNV，12 名个体的 AMELX/AMELY 基因座涉及 CNV。这些结果与来自正常人群和其他临床病例中 CNV 信息的公共数据库中的数据相关联。这些综合结果表明，在包含 13 个 CODIS STR 和 AMELX/Y 基因座的 9 个基因座的区域中存在 CNV。进一步表征 CNV 区域内的 STR 谱，在多个群体中对这些变体进行额外的编目，并将这些变体示例贡献到公共领域，将为可靠使用这些基因座提供有价值的信息。
