Open AccessPresence of recombination hotspots throughout SLC6A3
Author(s) -
Juan Zhao,
Yanhong Zhou,
Nian Xiong,
Hong Qing,
Tao Wang,
Zhicheng Lin
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0218129
Subject(s) - haplotype , genetics , dopamine transporter , biology , gene , allele , 1000 genomes project , genotype , single nucleotide polymorphism , transporter
The human dopamine transporter gene SLC6A3 is involved in substance use disorders (SUDs) among many other common neuropsychiatric illnesses but allelic association results including those with its classic genetic markers 3’VNTR or Int8VNTR remain mixed and unexplainable. To better understand the genetics for reproducible association signals, we report the presence of recombination hotspots based on sequencing of the entire 5’ promoter regions in two small SUDs cohorts, 30 African Americans (AAs) and 30 European Americans (EAs). Recombination rate was the highest near the transcription start site (TSS) in both cohorts. In addition, each cohort carried 57 different promoter haplotypes out of 60 and no haplotypes were shared between the two ethnicities. A quarter of the haplotypes evolved in an ethnicity-specific manner. Finally, analysis of five hundred subjects of European ancestry, from the 1000 Genome Project, confirmed the promoter recombination hotspots and also revealed several additional ones in non-coding regions only. These findings provide an explanation for the mixed results as well as guidance for selection of effective markers to be used in next generation association validation (NGAV), facilitating the delineation of pathogenic variation in this critical neuropsychiatric gene.