Novel polymorphic and copy number diversity in the antibody IGH locus of South African individuals.

The heavy chain of an antibody is crucial for mediating antigen binding. IGHV genes, which partially encode the heavy chain of antibodies, exhibit vast genetic diversity largely through polymorphism and copy number variation (CNV). These genetic variations impact population-level expression levels. In this study, we analyzed expressed antibody transcriptomes and matched germline IGHV genes from donors from KwaZulu-Natal, South Africa. Amplicon NGS targeting germline IGHV sequences was performed on genomic DNA from 70 participants, eight of whom had matched datasets of expressed antibody transcriptomes. Germline IGHV sequencing identified 161 unique IGHV alleles, of which 32 were novel. A further 21 novel IGHV alleles were detected in the expressed transcriptomes of these donors. We also examined the datasets for CNV, uncovering gene duplications of 10 IGHV genes from germline sequencing and 33 genes in the expressed transcriptomes. Many of the IGHV gene duplications have not been described in other populations. This study expands our understanding of genetic differences in distinct populations and suggests the potential impact of genetic diversity on immune responses.