Dataset Information

Evidence for selection at HIV host susceptibility genes in a West Central African human population.

ABSTRACT: BACKGROUND:HIV-1 derives from multiple independent transfers of simian immunodeficiency virus (SIV) strains from chimpanzees to human populations. We hypothesized that human populations in west central Africa may have been exposed to SIV prior to the pandemic, and that previous outbreaks may have selected for genetic resistance to immunodeficiency viruses. To test this hypothesis, we examined the genomes of Biaka Western Pygmies, who historically resided in communities within the geographic range of the central African chimpanzee subspecies (Pan troglodytes troglodytes) that carries strains of SIV ancestral to HIV-1. RESULTS:SNP genotypes of the Biaka were compared to those of African human populations who historically resided outside the range of P. t. troglodytes, including the Mbuti Eastern Pygmies. Genomic regions showing signatures of selection were compared to the genomic locations of genes reported to be associated with HIV infection or pathogenesis. In the Biaka, a strong signal of selection was detected at CUL5, which codes for a component of the vif-mediated APOBEC3 degradation pathway. A CUL5 allele protective against AIDS progression was fixed in the Biaka. A signal of selection was detected at TRIM5, which codes for an HIV post-entry restriction factor. A protective mis-sense mutation in TRIM5 had the highest frequency in Biaka compared to other African populations, as did a protective allele for APOBEC3G, which codes for an anti-HIV-1 restriction factor. Alleles protective against HIV-1 for APOBEC3H, CXCR6 and HLA-C were at higher frequencies in the Biaka than in the Mbuti. Biaka genomes showed a strong signal of selection at TSG101, an inhibitor of HIV-1 viral budding. CONCLUSIONS:We found protective alleles or evidence for selection in the Biaka at a number of genes associated with HIV-1 infection or progression. Pygmies have also been reported to carry genotypes protective against HIV-1 for the genes CCR5 and CCL3L1. Our hypothesis that HIV-1 may have shaped the genomes of some human populations in West Central Africa appears to merit further investigation.

SUBMITTER: Zhao K

PROVIDER: S-EPMC3537702 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evidence for selection at HIV host susceptibility genes in a West Central African human population.

Zhao Kai K Ishida Yasuko Y Oleksyk Taras K TK Winkler Cheryl A CA Roca Alfred L AL

BMC evolutionary biology 20121206

<h4>Background</h4>HIV-1 derives from multiple independent transfers of simian immunodeficiency virus (SIV) strains from chimpanzees to human populations. We hypothesized that human populations in west central Africa may have been exposed to SIV prior to the pandemic, and that previous outbreaks may have selected for genetic resistance to immunodeficiency viruses. To test this hypothesis, we examined the genomes of Biaka Western Pygmies, who historically resided in communities within the geograp ...[more]

PMID: 23217182

Similar Datasets

Project description:BackgroundPseudomonas aeruginosa (PA) has a non-clonal, epidemic population with a few widely distributed and frequently encountered sequence types (STs) called 'high-risk clusters'. Clinical P. aeruginosa (clinPA) has been studied in all inhabited continents excepted in Africa, where a very few isolates have been analyzed. Here, we characterized a collection of clinPA isolates from four countries of West and Central Africa.Methodology184 non-redundant isolates of clinPA from hospitals of Senegal, Ivory Coast, Nigeria, and Central African Republic were genotyped by MLST. We assessed their resistance level to antibiotics by agar diffusion and identified the extended-spectrum ?-lactamases (ESBLs) and metallo-?-lactamases (MBLs) by sequencing. The population structure of the species was determined by a nucleotide-based analysis of the entire PA MLST database and further localized on the phylogenetic tree (i) the sequence types (STs) of the present collection, (ii) the STs by continents, (iii) ESBL- and MBL-producing STs from the MLST database.Principal findingsWe found 80 distinct STs, of which 24 had no relationship with any known STs. 'High-risk' international clonal complexes (CC155, CC244, CC235) were frequently found in West and Central Africa. The five VIM-2-producing isolates belonged to CC233 and CC244. GES-1 and GES-9 enzymes were produced by one CC235 and one ST1469 isolate, respectively. We showed the spread of 'high-risk' international clonal complexes, often described as multidrug-resistant on other continents, with a fully susceptible phenotype. The MBL- and ESBL-producing STs were scattered throughout the phylogenetic tree and our data suggest a poor association between a continent and a specific phylogroup.ConclusionsESBL- and MBL-encoding genes are borne by both successful international clonal complexes and distinct local STs in clinPA of West and Central Africa. Furthermore, our data suggest that the spread of a ST could be either due to its antibiotic resistance or to features independent from the resistance to antibiotics.

Project description:BackgroundAfrica contains the most genetically divergent group of continental populations and several studies have reported that African populations show a high degree of population stratification. In this regard, it is important to investigate the potential for population genetic structure or stratification in genetic epidemiology studies involving multiple African populations. The presences of genetic sub-structure, if not properly accounted for, have been reported to lead to spurious association between a putative risk allele and a disease. Within the context of the Africa America Diabetes Mellitus (AADM) Study (a genetic epidemiologic study of type 2 diabetes mellitus in West Africa), we have investigated population structure or stratification in four ethnic groups in two countries (Akan and Gaa-Adangbe from Ghana, Yoruba and Igbo from Nigeria) using data from 372 autosomal microsatellite loci typed in 493 unrelated persons (986 chromosomes).ResultsThere was no significant population genetic structure in the overall sample. The smallest probability is associated with an inferred cluster of 1 and little of the posterior probability is associated with a higher number of inferred clusters. The distribution of members of the sample to inferred clusters is consistent with this finding; roughly the same proportion of individuals from each group is assigned to each cluster with little variation between the ethnic groups. Analysis of molecular variance (AMOVA) showed that the between-population component of genetic variance is less than 0.1% in contrast to 99.91% for the within population component. Pair-wise genetic distances between the four ethnic groups were also very similar. Nonetheless, the small between-population genetic variance was sufficient to distinguish the two Ghanaian groups from the two Nigerian groups.ConclusionThere was little evidence for significant population substructure in the four major West African ethnic groups represented in the AADM study sample. Ethnicity apparently did not introduce differential allele frequencies that may affect analysis and interpretation of linkage and association studies. These findings, although not entirely surprising given the geographical proximity of these groups, provide important insights into the genetic relationships between the ethnic groups studied and confirm previous results that showed close genetic relationship between most studied West African groups.

Project description:BackgroundAdequate antenatal care (ANC) utilization is recognized as one of the important drivers of safe childbirth and positive birth outcomes. The usage of ANC services fluctuates with various personal, socio-economic, and cultural characteristics and in resource-poor settings, adolescent mothers are at a particularly high risk of insufficient ANC utilization.ObjectivesThis paper investigates whether the usage of ANC services and institutional delivery as well as newborn birth weight differ systematically between adolescent and adult mothers in West and Central Africa. Moreover, we explore to what extent differences in birth weight are explained by ANC usage, adolescence, and select socio-economic characteristics of the mother.MethodsWe pooled cross-sectional data from all Demographic and Health Surveys (DHS) and Multi Indicator Cluster Surveys (MICS) conducted in countries in West and Central Africa region between 1986 and 2017 to estimate measures of ANC usage and qualified delivery assistance (along with a combined measure of "adequate maternal healthcare" aggregating these two factors) and newborn birth weight by maternal age group. We estimated various regression models to analyze a) the association between adolescence and adequate prenatal and maternal health care controlling for select socio-economic maternal characteristics as well as the local environment and b) between adolescence, adequate maternal health care, and newborn birth weight outcomes, also controlling for maternal characteristics and the local environment. All regressions were linear probability models for binary outcomes and simple linear models for continuous outcomes.ResultsAdequate maternal health care provision was lowest among adolescent mothers: 23.0% among adolescents vs an average of 29.2% across all other age groups. Moreover, we found maternal education and wealth to be positively and significantly associated with receiving adequate maternal health care. Adolescent mothers had the highest risk of low infantile birth weight with 14.5% (95% confidence interval (CI) = 13.6%-15.5%), which is roughly 1.5-2 times higher than in older mothers. We found that adolescence is still strongly associated with low birth weight even when adequate maternal health care and various socio-economic factors as well as the local environment are controlled for.ConclusionsOur findings suggest that ANC supply in resource-poor settings should be particularly tailored to adolescent mothers' needs and that further research is necessary to explore what individual maternal characteristics beyond socio-economic and physical (eg, BMI) factors drive the prevalence of low birth weight. Moreover, the currently used measures of maternal care quality are heavily dependent on pure quantitative measures (number of ANC visits). New indicators incorporating measures of factual quality and scope ought to be developed and incorporated into large routine household surveys such as DHS and MICS.

Dataset Information

Evidence for selection at HIV host susceptibility genes in a West Central African human population.

Publications

Evidence for selection at HIV host susceptibility genes in a West Central African human population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets