Whole Genome Sequencing Reveals Population Diversity and Variation in HIV-1 Specific Host Genes

Overview

Journal Front Genet

Date 2024 Jan 5

PMID 38179408

Authors

Prisca K Thami

Wonderful T Choga

Collet Dandara

Stephen J OBrien

Myron Essex

Simani Gaseitsiwe

Emile R Chimusa

Affiliations

Soon will be listed here.

Abstract

HIV infection continues to be a major global public health issue. The population heterogeneity in susceptibility or resistance to HIV-1 and progression upon infection is attributable to, among other factors, host genetic variation. Therefore, identifying population-specific variation and genetic modifiers of HIV infectivity can catapult the invention of effective strategies against HIV-1 in African populations. Here, we investigated whole genome sequences of 390 unrelated HIV-positive and -negative individuals from Botswana. We report 27.7 million single nucleotide variations (SNVs) in the complete genomes of Botswana nationals, of which 2.8 million were missing in public databases. Our population structure analysis revealed a largely homogenous structure in the Botswana population. Admixture analysis showed elevated components shared between the Botswana population and the Niger-Congo (65.9%), Khoe-San (32.9%), and Europeans (1.1%) ancestries in the population of Botswana. Statistical significance of the mutational burden of deleterious and loss-of-function variants per gene against a null model was estimated. The most deleterious variants were enriched in five genes: (the Actin Related Protein T2), (homeobox D12), (ATP binding cassette subfamily B member 5), (ATPase phospholipid transporting 8B4) and (ATP Binding Cassette Subfamily C Member 12). These genes are enriched in the glycolysis and gluconeogenesis ( < 2.84e-6) pathways and therefore, may contribute to the emerging field of immunometabolism in which therapy against HIV-1 infection is being evaluated. Published transcriptomic evidence supports the role of the glycolysis/gluconeogenesis pathways in the regulation of susceptibility to HIV, and that cumulative effects of genetic modifiers in glycolysis/gluconeogenesis pathways may potentially have effects on the expression and clinical variability of HIV-1. Identified genes and pathways provide novel avenues for other interventions, with the potential for informing the design of new therapeutics.

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