The genetic and evolutionary basis of gene expression variation in East Africans.

Background: Mapping of quantitative trait loci (QTL) associated with molecular phenotypes is a powerful approach for identifying the genes and molecular mechanisms underlying human traits and diseases, though most studies have focused on individuals of European descent. While important progress has been made to study a greater diversity of human populations, many groups remain unstudied, particularly among indigenous populations within Africa. To better understand the genetics of gene regulation in East Africans, we perform expression and splicing QTL mapping in whole blood from a cohort of 162 diverse Africans from Ethiopia and Tanzania.

Impact of natural selection on global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection.

Human genomic diversity has been shaped by both ancient and ongoing challenges from viruses. The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on population health. However, genetic diversity and evolutionary forces impacting host genes related to SARS-CoV-2 infection are not well understood.

Impact of natural selection on global patterns of genetic variation, and association with clinical phenotypes, at genes involved in SARS-CoV-2 infection.

We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection ( , and ). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. At , we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function.

Impact of natural selection on global patterns of genetic variation, and association with clinical phenotypes, at genes involved in SARS-CoV-2 infection.

We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (, , , and ). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. At , we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function.

Correction to: African evolutionary history inferred from whole genome sequence data of 44 indigenous African populations.

Following publication of the original article [1], a typographical error in the formula for calculating d in the "Scans for local adaptation" subsection in the Method section, was identified. The correct formula should be.

African evolutionary history inferred from whole genome sequence data of 44 indigenous African populations.

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.

Genomic evidence for shared common ancestry of East African hunting-gathering populations and insights into local adaptation.

Anatomically modern humans arose in Africa ∼300,000 years ago, but the demographic and adaptive histories of African populations are not well-characterized. Here, we have generated a genome-wide dataset from 840 Africans, residing in western, eastern, southern, and northern Africa, belonging to 50 ethnicities, and speaking languages belonging to four language families. In addition to agriculturalists and pastoralists, our study includes 16 populations that practice, or until recently have practiced, a hunting-gathering (HG) lifestyle.

Antimalarial Activity of Stem Bark Extracts against .

There is an increasing need for innovative drug and prophylaxis discovery against malaria. The aim of the present study was to test antiplasmodial activity of H. (Euphorbiaceae) stem bark extracts from Kenyan folkloric medicine.

Fluorescence In Situ Hybridization (FISH) Assays for Diagnosing Malaria in Endemic Areas.

Malaria is a responsible for approximately 600 thousand deaths worldwide every year. Appropriate and timely treatment of malaria can prevent deaths but is dependent on accurate and rapid diagnosis of the infection. Currently, microscopic examination of the Giemsa stained blood smears is the method of choice for diagnosing malaria.

Directional selection at the pfmdr1, pfcrt, pfubp1, and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with ACT.

Background: The efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria may be threatened by parasites with reduced responsiveness to artemisinins. Among 298 ACT-treated children from Mbita, Kenya, submicroscopic persistence of P. falciparum on day 3 posttreatment was associated with subsequent microscopically detected parasitemia at days 28 or 42.

Limited evidence for adaptive evolution and functional effect of allelic variation at rs702424 in the promoter of the TAS2R16 bitter taste receptor gene in Africa.

Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception.

Genetic origins of lactase persistence and the spread of pastoralism in Africa.

In humans, the ability to digest lactose, the sugar in milk, declines after weaning because of decreasing levels of the enzyme lactase-phlorizin hydrolase, encoded by LCT. However, some individuals maintain high enzyme amounts and are able to digest lactose into adulthood (i.e.

Origin and differential selection of allelic variation at TAS2R16 associated with salicin bitter taste sensitivity in Africa.

Bitter taste perception influences human nutrition and health, and the genetic variation underlying this trait may play a role in disease susceptibility. To better understand the genetic architecture and patterns of phenotypic variability of bitter taste perception, we sequenced a 996 bp region, encompassing the coding exon of TAS2R16, a bitter taste receptor gene, in 595 individuals from 74 African populations and in 94 non-Africans from 11 populations. We also performed genotype-phenotype association analyses of threshold levels of sensitivity to salicin, a bitter anti-inflammatory compound, in 296 individuals from Central and East Africa.

Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence.

Background: Parasite clearance time after artemisinin-based combination therapy (ACT) may be increasing in Asian and African settings. The association between parasite clearance following ACT and transmissibility is currently unknown.

Methods: We determined parasite clearance dynamics by duplex quantitative polymerase chain reaction (qPCR) in samples collected in the first 3 days after treatment of uncomplicated malaria with ACT.

Identifying Darwinian selection acting on different human APOL1 variants among diverse African populations.

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.

Patterns of nucleotide and haplotype diversity at ICAM-1 across global human populations with varying levels of malaria exposure.

Malaria is one of the strongest selective pressures in recent human evolution. African populations have been and continue to be at risk for malarial infections. However, few studies have re-sequenced malaria susceptibility loci across geographically and genetically diverse groups in Africa.

Malaria transmission after artemether-lumefantrine and dihydroartemisinin-piperaquine: a randomized trial.

Background: Artemisinin-based combination therapy (ACT) reduces the potential for malaria transmission, compared with non-ACTs. It is unclear whether this effect differs between ACTs.

Methods: A total of 298 children (age, 6 months to 10 years) with uncomplicated falciparum malaria were randomized to artemether-lumefantrine (AL; n = 153) or dihydroartemisinin-piperaquine (DP; n = 145) in Mbita, a community in western Kenya.

Structural diversity and African origin of the 17q21.31 inversion polymorphism.

The 17q21.31 inversion polymorphism exists either as direct (H1) or inverted (H2) haplotypes with differential predispositions to disease and selection. We investigated its genetic diversity in 2,700 individuals, with an emphasis on African populations.

Changes in genotypes of Plasmodium falciparum human malaria parasite following withdrawal of chloroquine in Tiwi, Kenya.

Chloroquine (CQ) drug was withdrawn in 1998 as a first-line treatment of uncomplicated malaria in Kenya. This was in response to resistance to the drug in Plasmodium falciparum malaria parasite. Investigations were conducted to determine prevalence of CQ resistance genotypes in the parasites in Tiwi, a malaria endemic town in Kenya, before and about a decade after the withdrawal of the drug.

Evolution of functionally diverse alleles associated with PTC bitter taste sensitivity in Africa.

Although human bitter taste perception is hypothesized to be a dietary adaptation, little is known about genetic signatures of selection and patterns of bitter taste perception variability in ethnically diverse populations with different diets, particularly from Africa. To better understand the genetic basis and evolutionary history of bitter taste sensitivity, we sequenced a 2,975 bp region encompassing TAS2R38, a bitter taste receptor gene, in 611 Africans from 57 populations in West Central and East Africa with diverse subsistence patterns, as well as in a comparative sample of 132 non-Africans. We also examined the association between genetic variability at this locus and threshold levels of phenylthiocarbamide (PTC) bitterness in 463 Africans from the above populations to determine how variation influences bitter taste perception.

Haplotype variation and genotype imputation in African populations.

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.

Characterization of genetic variation and natural selection at the arylamine N-acetyltransferase genes in global human populations.

Unlabelled: Functional variability at the arylamine N-acetyltransferase genes is associated with drug response in humans and may have been adaptive in the past owing to selection pressure from diet and exposure to toxins during human evolution.

Aims: We have characterized nucleotide variation at the NAT1 and NAT2 genes, and at the NATP1 pseudogene in global human populations, including many previously under-represented African populations, in order to identify potential functional variants and to understand the role that natural selection has played in shaping variation at these loci in globally diverse populations.

Materials & Methods: We have resequenced approximately 2800 bp for each of the NAT1 and NAT2 gene regions, as well as the pseudogene NATP1, in 197 African and 132 nonAfrican individuals.

Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations.

Malaria has been a very strong selection pressure in recent human evolution, particularly in Africa. Of the one million deaths per year due to malaria, more than 90% are in sub-Saharan Africa, a region with high levels of genetic variation and population substructure. However, there have been few studies of nucleotide variation at genetic loci that are relevant to malaria susceptibility across geographically and genetically diverse ethnic groups in Africa.

Sensitivity of microscopy compared to molecular diagnosis of p. Falciparum: implications on malaria treatment in epidemic areas in kenya.

Detection of Plasmodium species by microscopy has been the gold standard for diagnosis of malaria for more than a century. Despite the fact that there is a significant decline in the number of positive cases reported from microscopy, antimalarial drugs prescriptions are on continuous increase as patients present with symptoms of malaria. This makes it difficult to establish accuracy, sensitivity and specificity of light microscopy in diagnosis of malaria in epidemic areas.