A deep population reference panel of tandem repeat variation

Helyaneh Ziaei Jam; Yang Li; Ross DeVito; Nima Mousavi; Nichole Ma; Ibra Lujumba; Yagoub Adam; Mikhail Maksimov; Bonnie Huang; Egor Dolzhenko; Yunjiang Qiu; Fredrick Elishama Kakembo; Habi Joseph; Blessing Onyido; Jumoke Adeyemi; Mehrdad Bakhtiari; Jonghun Park; Sara Javadzadeh; Daudi Jjingo; Ezekiel Adebiyi; Vineet Bafna; Melissa Gymrek

doi:10.1038/s41467-023-42278-3

A deep population reference panel of tandem repeat variation

Nat Commun. 2023 Oct 23;14(1):6711. doi: 10.1038/s41467-023-42278-3.

Authors

Helyaneh Ziaei Jam¹, Yang Li², Ross DeVito¹, Nima Mousavi³, Nichole Ma², Ibra Lujumba⁴, Yagoub Adam⁵, Mikhail Maksimov¹, Bonnie Huang⁶, Egor Dolzhenko⁷, Yunjiang Qiu⁷, Fredrick Elishama Kakembo⁴, Habi Joseph⁴, Blessing Onyido^{8

9}, Jumoke Adeyemi^{8

9}, Mehrdad Bakhtiari¹, Jonghun Park¹, Sara Javadzadeh¹, Daudi Jjingo^{4

10}, Ezekiel Adebiyi^{5

8

9

11}, Vineet Bafna¹, Melissa Gymrek^{12

13}

Affiliations

¹ Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.
² Department of Medicine, University of California San Diego, La Jolla, CA, USA.
³ Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA.
⁴ The African Center of Excellence in Bioinformatics and Data Intensive Sciences, the Infectious Diseases Institute, Makerere University, Kampala, Uganda.
⁵ Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun, 112233, Nigeria.
⁶ Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
⁷ Illumina Incorporated, San Diego, CA, 92122, USA.
⁸ Department of Computer & Information Sciences, Covenant University, Ota, Ogun, 112233, Nigeria.
⁹ Covenant Applied Informatics and Communication Africa Centre of Excellence (CApIC-ACE), Covenant University, Ota, Ogun, 112233, Nigeria.
¹⁰ Department of Computer Science, Makerere University, Kampala, Uganda.
¹¹ Applied Bioinformatics Division, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, 69120, Germany.
¹² Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA. [email protected].
¹³ Department of Medicine, University of California San Diego, La Jolla, CA, USA. [email protected].

Abstract

Tandem repeats (TRs) represent one of the largest sources of genetic variation in humans and are implicated in a range of phenotypes. Here we present a deep characterization of TR variation based on high coverage whole genome sequencing from 3550 diverse individuals from the 1000 Genomes Project and H3Africa cohorts. We develop a method, EnsembleTR, to integrate genotypes from four separate methods resulting in high-quality genotypes at more than 1.7 million TR loci. Our catalog reveals novel sequence features influencing TR heterozygosity, identifies population-specific trinucleotide expansions, and finds hundreds of novel eQTL signals. Finally, we generate a phased haplotype panel which can be used to impute most TRs from nearby single nucleotide polymorphisms (SNPs) with high accuracy. Overall, the TR genotypes and reference haplotype panel generated here will serve as valuable resources for future genome-wide and population-wide studies of TRs and their role in human phenotypes.

Publication types

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

MeSH terms

Genotype
Humans
Polymorphism, Single Nucleotide*
Tandem Repeat Sequences*
Whole Genome Sequencing

Abstract

Publication types

MeSH terms

Grants and funding