Department of Biobehavioral Health, The Pennsylvania State University, State College, PA, USA.
The Molecular, Cellular and Integrative Biosciences Program, The Pennsylvania State University, State College, PA, USA.
Life Sci Alliance. 2023 Feb 8;6(4). doi: 10.26508/lsa.202201677. Print 2023 Apr.
The dopamine transporter gene, , has received substantial attention in genetic association studies of various phenotypes. Although some variable number tandem repeats (VNTRs) present in have been tested in genetic association studies, results have not been consistent. VNTRs in that have not been examined genetically were characterized. The Tandem Repeat Annotation Library was used to characterize the VNTRs of 64 unrelated long-read haplotype-phased sequences. Sequence similarity of each repeat unit of the five VNTRs is reported, along with the correlations of SNP-SNP, SNP-VNTR, and VNTR-VNTR alleles across the gene. One of these VNTRs is a novel hyper-VNTR (hyVNTR) in intron 8 of , which contains a range of 3.4-133.4 repeat copies and has a consensus sequence length of 38 bp, with 82% G+C content. The 38-base repeat was predicted to form G-quadruplexes in silico and was confirmed by circular dichroism spectroscopy. In addition, this hyVNTR contains multiple putative binding sites for PRDM9, which, in combination with low levels of linkage disequilibrium around the hyVNTR, suggests it might be a recombination hotspot.
多巴胺转运体基因 ，在各种表型的遗传关联研究中受到了广泛关注。虽然 中存在的一些可变数串联重复序列（VNTRs）已经在遗传关联研究中进行了测试，但结果并不一致。本研究对 中尚未进行遗传检测的 VNTRs 进行了特征描述。使用串联重复序列注释库对 64 个无关的长读长单体型相位 序列的 VNTRs 进行了特征描述。报告了这 5 个 VNTRs 的每个重复单元的序列相似性，以及基因内 SNP-SNP、SNP-VNTR 和 VNTR-VNTR 等位基因的相关性。其中一个 VNTR 是 8 号内含子中的一个新的超 VNTR（hyVNTR），包含 3.4-133.4 个重复拷贝，其一致序列长度为 38bp，G+C 含量为 82%。预测 38 个碱基的重复序列在体内形成 G-四链体，并通过圆二色性光谱得到证实。此外，该 hyVNTR 包含多个 PRDM9 的可能结合位点，与 hyVNTR 周围低水平的连锁不平衡相结合，表明其可能是一个重组热点。
