title: A genomic portrait of haplotype diversity and signatures of selection in indigenous southern African populations.
abstract: We report a study of genome-wide, dense SNP (∼ 900K) and copy number polymorphism data of indigenous southern Africans. We demonstrate the genetic contribution to southern and eastern African populations, which involved admixture between indigenous San, Niger-Congo-speaking and populations of Eurasian ancestry. This finding illustrates the need to account for stratification in genome-wide association studies, and that admixture mapping would likely be a successful approach in these populations. We developed a strategy to detect the signature of selection prior to and following putative admixture events. Several genomic regions show an unusual excess of Niger-Kordofanian, and unusual deficiency of both San and Eurasian ancestry, which were considered the footprints of selection after population admixture. Several SNPs with strong allele frequency differences were observed predominantly between the admixed indigenous southern African populations, and their ancestral Eurasian populations. Interestingly, many candidate genes, which were identified within the genomic regions showing signals for selection, were associated with southern African-specific high-risk, mostly communicable diseases, such as malaria, influenza, tuberculosis, and human immunodeficiency virus/AIDs. This observation suggests a potentially important role that these genes might have played in adapting to the environment. Additionally, our analyses of haplotype structure, linkage disequilibrium, recombination, copy number variation and genome-wide admixture highlight, and support the unique position of San relative to both African and non-African populations. This study contributes to a better understanding of population ancestry and selection in south-eastern African populations; and the data and results obtained will support research into the genetic contributions to infectious as well as non-communicable diseases in the region.
authors: Computational Biology Group, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Centre for Proteomic and Genomic Research, Cape Town, South Africa.
authors: Emile R
authors: ER
authors: Chimusa
authors: Computational Biology Group, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors: Ayton
authors: A
authors: Meintjies
authors: Computational Biology Group, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors: Milaine
authors: M
authors: Tchanga
authors: Computational Biology Group, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors: Nicola
authors: N
authors: Mulder
authors: Cathal
authors: C
authors: Seoighe
authors: School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland.
authors: Cathal
authors: C
authors: Seioghe
authors: Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of Witwatersrand and the National Health Laboratory Service, Johannesburg, South Africa.
authors: Himla
authors: H
authors: Soodyall
authors: MRC Human Genetics Research Unit, Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors: Rajkumar
authors: R
authors: Ramesar
mesh_terms: D000353:Africa, Southern; D056915:DNA Copy Number Variations / Q000235:genetics; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011995:Recombination, Genetic; D012641:Selection, Genetic