DNA methylation profiles unique to Kalahari KhoeSan individuals

Alexander Goncearenco; Brenna A LaBarre; Hanna M Petrykowska; Weerachai Jaratlerdsiri; M S Riana Bornman; Stephen D Turner; Vanessa M Hayes; Laura Elnitski

doi:10.1080/15592294.2020.1809852

DNA methylation profiles unique to Kalahari KhoeSan individuals

Epigenetics. 2021 May;16(5):537-553. doi: 10.1080/15592294.2020.1809852. Epub 2020 Sep 6.

Authors

Affiliations

¹ Genomic Functional Analysis Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
² Graduate Program in Bioinformatics, Boston University, Boston, MA, USA.
³ Laboratory for Human Comparative & Prostate Cancer Genomics, Garvan Institute of Medical Research, Darlinghurst, Australia.
⁴ School of Health Systems and Public Health, University of Pretoria, Pretoria, South Africa.
⁵ Division of Biomedical Informatics, University of Virginia School of Medicine, Charlottesville, VA, USA.
⁶ Faculty of Health Sciences, University of Limpopo, Sovenga, South Africa.
⁷ Sydney Medical School, University of Sydney, Camperdown, Australia.

Abstract

Genomes of KhoeSan individuals of the Kalahari Desert provide the greatest understanding of single nucleotide diversity in the human genome. Compared with individuals in industrialized environments, the KhoeSan have a unique foraging and hunting lifestyle. Given these dramatic environmental differences, and the responsiveness of the methylome to environmental exposures of many types, we hypothesized that DNA methylation patterns would differ between KhoeSan and neighbouring agropastoral and/or industrial Bantu. We analysed Illumina HumanMethylation 450 k array data generated from blood samples from 38 KhoeSan and 42 Bantu, and 6 Europeans. After removing CpG positions associated with annotated and novel polymorphisms and controlling for white blood cell composition, sex, age and technical variation we identified 816 differentially methylated CpG loci, out of which 133 had an absolute beta-value difference of at least 0.05. Notably SLC39A4/ZIP4, which plays a role in zinc transport, was one of the most differentially methylated loci. Although the chronological ages of the KhoeSan are not formally recorded, we compared historically estimated ages to methylation-based calculations. This study demonstrates that the epigenetic profile of KhoeSan individuals reveals differences from other populations, and along with extensive genetic diversity, this community brings increased accessibility and understanding to the diversity of the human genome.

Keywords: Illumina methylation array; Khoesan; Methylation; epigenome; methylation probes; single nucleotide variants.

Publication types

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

MeSH terms

Black People / genetics*
Botswana
Cation Transport Proteins*
CpG Islands*
DNA Methylation*
Epigenesis, Genetic*
Ethnicity
Genome, Human
Humans
White People

Substances

Cation Transport Proteins
SLC39A4 protein, human

Grants and funding

Intramural Program of the National Human Genome Research Institute to L.E. This work was also supported by an Australian Research Council Discovery Project grant awarded to V.M.H. (DP170103071) and sampling contributed by the Cancer Association of South Africa to M.S.R.B. and V.M.H. V.M.H. is supported by the University of Sydney Foundation in a Petre Foundation chair position.