Biochemistry and Molecular Biology

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Browsing Biochemistry and Molecular Biology by Subject "African populations"

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    African evolutionary history inferred from whole genome sequence data of 44 indigenous African populations.
    (Genome Biology, 2019-04-26) Nyambo, Thomas B.
    Background: Africa is the origin of modern humans within the past 300 thousand years. To infer the complex demographic history of African populations and adaptation to diverse environments, we sequenced the genomes of 92 individuals from 44 indigenous African populations. Results: Genetic structure analyses indicate that among Africans, genetic ancestry is largely partitioned by geography and language, though we observe mixed ancestry in many individuals, consistent with both short- and long-range migration events followed by admixture. Phylogenetic analysis indicates that the San genetic lineage is basal to all modern human lineages. The San and Niger-Congo, Afroasiatic, and Nilo-Saharan lineages were substantially diverged by 160 kya (thousand years ago). In contrast, the San and Central African rainforest hunter-gatherer (CRHG), Hadza hunter-gatherer, and Sandawe hunter-gatherer lineages were diverged by ~ 120–100 kya. Niger-Congo, Nilo-Saharan, and Afroasiatic lineages diverged more recently by ~ 54–16 kya. Eastern and western CRHG lineages diverged by ~ 50– 31 kya, and the western CRHG lineages diverged by ~ 18–12 kya. The San and CRHG populations maintained the largest effective population size compared to other populations prior to 60 kya. Further, we observed signatures of positive selection at genes involved in muscle development, bone synthesis, reproduction, immune function, energy metabolism, and cell signaling, which may contribute to local adaptation of African populations. Conclusions: We observe high levels of genomic variation between ethnically diverse Africans which is largely correlated with geography and language. Our study indicates ancient population substructure and local adaptation of Africans. Keywords: African populations, Genomic variation, Human evolution, Local adaptation, Demographic history, Effective population size, Whole genome sequencing
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    Haplotype variation and genotype imputation in African populations.
    (Genetic epidemiology, 2011-11-28) Nyambo, Thomas B.
    Sub-Saharan Africa has been identified as the part of the world with the greatest human genetic diversity. This high level of diversity causes difficulties for genome-wide association (GWA) studies in African populations—for example, by reducing the accuracy of genotype imputation in African populations compared to non-African populations. Here, we investigate haplotype variation and imputation in Africa, using 253 unrelated individuals from 15 Sub-Saharan African populations. We identify the populations that provide the greatest potential for serving as reference panels for imputing genotypes in the remaining groups. Considering reference panels comprising samples of recent African descent in Phase 3 of the HapMap Project, we identify mixtures of reference groups that produce the maximal imputation accuracy in each of the sampled populations. We find that optimal HapMap mixtures and maximal imputation accuracies identified in detailed tests of imputation procedures can instead be predicted by using simple summary statistics that measure relationships between the pattern of genetic variation in a target population and the patterns in potential reference panels. Our results provide an empirical basis for facilitating the selection of reference panels in GWA studies of diverse human populations, especially those of African ancestry.
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    Identifying Darwinian selection acting on different human APOL1 variants among diverse African populations.
    (The American Journal of Human Genetics, 2013-07-11) Nyambo, Thomas B.
    Disease susceptibility can arise as a consequence of adaptation to infectious disease. Recent findings have suggested that higher rates of chronic kidney disease (CKD) in individuals with recent African ancestry might be attributed to two risk alleles (G1 and G2) at the serum- resistance-associated (SRA)-interacting-domain-encoding region of APOL1. These two alleles appear to have arisen adaptively, possibly as a result of their protective effects against human African trypanosomiasis (HAT), or African sleeping sickness. In order to explore the distribution of potential functional variation at APOL1, we studied nucleotide variation in 187 individuals across ten geographically and genetically diverse African ethnic groups with exposure to two Trypanosoma brucei subspecies that cause HAT. We observed unusually high levels of nonsynonymous polymorphism in the regions encoding the functional domains that are required for lysing parasites. Whereas allele frequencies of G2 were similar across all populations (3%–8%), the G1 allele was only common in the Yoruba (39%). Addi- tionally, we identified a haplotype (termed G3) that contains a nonsynonymous change at the membrane-addressing-domain-encoding region of APOL1 and is present in all populations except for the Yoruba. Analyses of long-range patterns of linkage disequilibrium indi- cate evidence of recent selection acting on the G3 haplotype in Fulani from Cameroon. Our results indicate that the G1 and G2 variants in APOL1 are geographically restricted and that there might be other functional variants that could play a role in HAT resistance and CKD risk in African populations.
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    P072 HLA types in ethnically diverse sub-saharan african populations
    (Human Immunology, 2019-07) Nyambo, Thomas B.
    Aim: A comprehensive characterization of the HLA allelic diversity of ethnically diverse populations of African ancestry from sub-Saharan Africa (SSA) has been attempted. Methods: DNA was isolated from whole blood of 520 volunteers from 12 ethnically diverse populations in Botswana, Cameroon, Ethiopia and Tanzania. All individuals were sampled from rural communities and known to practice traditional subsistence lifestyles (hunter-gathering, agro-pastoralism or pastoralism). Current analysis is part of a larger study (N = 3000) aimed to document genomic variation, population history, natural selection and genetic/environmental risk factors associated with diabetes, hypertension and infec- tious disease in African descent populations. In this preliminary study, 231 unrelated individuals were fully characterized at 11 HLA loci by next generation sequencing-based (Holotype, OMIXON) third-field resolution HLA typing. Results: Among the 231 individuals, 291 HLA alleles were identified: 42 HLA-A, 52 HLA-B, 36 HLA-C, 22 HLA-DPA1, 47 HLA-DPB1, 20 HLA-DQA1, 26 HLA-DQB1, 31 HLA-DRB1, 7 HLA-DRB3, 5 HLA-DRB4 and 3 HLA-DRB5. These 291 alleles included 31 (11%) novel alleles (6 synonymous and 25 non-synonymous) and 260 (89%) previously described alleles. The populations from Eastern Africa carried the highest number of new alleles (n = 16) compared to Southern (n = 10) and Central (n = 8) Africa. Conclusions: This study has identified 260 known and 31 previously unknown HLA allele sequences in just 231 unrelated individuals from 12 distinct populations in SSA. These 31 previously uncharacterized alleles were quite frequent in these populations. These data provide critical information potentially enriching our understanding of the evolution of HLA polymorphisms in Africa and the role they may play in health and disease. Disclosures: J.L. Duke:7. Other (Identify); Company/Organization; Royal Fees from OMIXON.D. Ferriola:7. Other (Identify); Company/Organization; Royal Fees from OMIXON.D.S. Monos:2. Consultant; Company/Organiz ation; OMIXON. 4. Scientific/Medical Advisor; Company/Organization; OMIXON. 7. Other (Identify); Company/Organization; Royal Fees from OMIXON.