Copy number variation in human genomes from three major ethno-linguistic groups in Africa

Abstract

Background: Copy number variation is an important class of genomic variation that has been reported in 75% of the human genome. However, it is underreported in African populations. Copy number variants (CNVs) could have important impacts on disease susceptibility and environmental adaptation. To describe CNVs and their possible impacts in Africans, we sequenced genomes of 232 individuals from three major African ethno-linguistic groups: (1) Niger Congo A from Guinea and Côte d'Ivoire, (2) Niger Congo B from Uganda and the Democratic Republic of Congo and (3) Nilo-Saharans from Uganda. We used GenomeSTRiP and cn.MOPS to identify copy number variant regions (CNVRs). Results: We detected 7608 CNVRs, of which 2172 were only deletions, 2384 were only insertions and 3052 had both. We detected 224 previously un-described CNVRs. The majority of novel CNVRs were present at low frequency and were not shared between populations. We tested for evidence of selection associated with CNVs and also for population structure. Signatures of selection identified previously, using SNPs from the same populations, were overrepresented in CNVRs. When CNVs were tagged with SNP haplotypes to identify SNPs that could predict the presence of CNVs, we identified haplotypes tagging 3096 CNVRs, 372 CNVRs had SNPs with evidence of selection (iHS > 3) and 222 CNVRs had both. This was more than expected (p < 0.0001) and included loci where CNVs have previously been associated with HIV, Rhesus D and preeclampsia. When integrated with 1000 Genomes CNV data, we replicated their observation of population stratification by continent but no clustering by populations within Africa, despite inclusion of Nilo-Saharans and Niger-Congo populations within our dataset. Conclusions: Novel CNVRs in the current study increase representation of African diversity in the database of genomic variants. Over-representation of CNVRs in SNP signatures of selection and an excess of SNPs that both tag CNVs and are subject to selection show that CNVs may be the actual targets of selection at some loci. However, unlike SNPs, CNVs alone do not resolve African ethno-linguistic groups. Tag haplotypes for CNVs identified may be useful in predicting African CNVs in future studies where only SNP data is available.

High Levels of Genetic Diversity within Nilo-Saharan Populations: Implications for Human Adaptation

“…24 An analysis of copy number variation has been published separately. 25 From the 1000 Genomes project 16 we obtained variant call files of 50 samples from each of the Esan and Yoruba from Nigeria; Mende from Sierra Leone; Gambian from Western Division of The Gambia; Luhya from Western Kenya; five samples from each of five populations of West Eurasian origin: Utah residents with northern and western European ancestry, Finnish from Finland, British in England and Scotland, Iberian from Spain, Toscani from Italy.…”

Genome-wide copy number variations in a large cohort of bantu African children

“…Over the years, additional studies of individuals from diverse populations, including of African descent as part of 1000 Genomes Project, reported an increasing number of CNVs (> 50,000) [ 20 – 23 ]. Most recently, CNVs and other structural variants (> 400,000) in 4937 individuals of African and African American ancestry were reported as part of the Genome Aggregation Database (gnomAD) [ 29 , 43 ], and novel CNVRs were identified by Nyangiri and colleagues [ 44 ]. In our study, we identified 48 CNVRs which may represent CNVRs that are either specific to the Bantu African population or that may be very rare in populations currently represented in existing CNV datasets.…”

“…We compared Bantu CNVRs to variants obtained from DGV (release date 2020-02-15) [41], the Genome Aggregation Database (gnomAD v2.1) [29,43], African CNVR [44] and CNVs identified in low-mappability regions [45]. DGV CNVs dataset were downloaded from DGV website [46].…”

Genome-wide Copy Number Variations in a Large Cohort of Bantu African Children

“…We compared Bantu CNVRs to variants obtained from DGV (release date 2020-02-15) (23), the Genome Aggregation Database (gnomAD v2.1) (21,24), African CNVR (25) and CNVs identified in low-mappability regions (26). DGV CNVs dataset were downloaded from DGV website (61).…”

“…Over the years, additional studies of individuals from diverse populations, including of African descent as part of 1000 Genomes Project, reported an increasing number of CNVs (>50000)(37)(38)(39)(40). Most recently, CNVs and other structural variants (> 400000) in 4937 individuals of African and African-American ancestry were reported as part of the Genome Aggregation Database (gnomAD)(21,24), and novel CNVRs were identified by Nyangiri and colleagues(25).…”