A novel hypervariable variable number tandem repeat in the dopamine transporter gene (SLC6A3)

Abner T Apsley; Emma R Domico; Max A Verbiest; Carly A Brogan; Evan R Buck; Andrew J Burich; Kathleen M Cardone; Wesley J Stone; Maria Anisimova; David J Vandenbergh

doi:10.26508/lsa.202201677

A novel hypervariable variable number tandem repeat in the dopamine transporter gene (SLC6A3)

Life Sci Alliance. 2023 Feb 8;6(4):e202201677. doi: 10.26508/lsa.202201677. Print 2023 Apr.

Authors

Abner T Apsley^{1

2}, Emma R Domico¹, Max A Verbiest^{3

4

5}, Carly A Brogan¹, Evan R Buck¹, Andrew J Burich⁶, Kathleen M Cardone¹, Wesley J Stone¹, Maria Anisimova^{3

5}, David J Vandenbergh^{7

2

8

9}

Affiliations

¹ Department of Biobehavioral Health, The Pennsylvania State University, State College, PA, USA.
² The Molecular, Cellular and Integrative Biosciences Program, The Pennsylvania State University, State College, PA, USA.
³ Institute of Computational Life Science, School of Life Sciences and Facility Management, Zürich University of Applied Sciences, Wädenswil, Switzerland.
⁴ Department of Molecular Life Sciences, Faculty of Science, University of Zurich, Zurich, Switzerland.
⁵ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁶ Department of Information Science and Technologies - Applied Data Sciences, The Pennsylvania State University, State College, PA, USA.
⁷ Department of Biobehavioral Health, The Pennsylvania State University, State College, PA, USA djv4@psu.edu.
⁸ Institute of the Neurosciences, The Pennsylvania State University, State College, PA, USA.
⁹ The Bioinformatics and Genomics Program, The Pennsylvania State University, State College, PA, USA.

Abstract

The dopamine transporter gene, SLC6A3, has received substantial attention in genetic association studies of various phenotypes. Although some variable number tandem repeats (VNTRs) present in SLC6A3 have been tested in genetic association studies, results have not been consistent. VNTRs in SLC6A3 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 SLC6A3 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 SLC6A3, 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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Dopamine Plasma Membrane Transport Proteins* / genetics
Haplotypes
Humans
Introns
Minisatellite Repeats* / genetics

Substances

Dopamine Plasma Membrane Transport Proteins
SLC6A3 protein, human

Grants and funding

T32 AG049676/AG/NIA NIH HHS/United States