The Sahel/Savannah belt harbors diverse populations with different demographic histories and different subsistence patterns. However, populations from this large African region are notably under-represented in genomic research. To investigate the population structure and adaptation history of populations from the Sahel/Savannah space, we generated dense genome-wide genotype data of 327 individuals-comprising 14 ethnolinguistic groups, including 10 previously unsampled populations. Our results highlight fine-scale population structure and complex patterns of admixture, particularly in Fulani groups and Arabic-speaking populations. Among all studied Sahelian populations, only the Rashaayda Arabic-speaking population from eastern Sudan shows a lack of gene flow from African groups, which is consistent with the short history of this population in the African continent. They are recent migrants from Saudi Arabia with evidence of strong genetic isolation during the last few generations and a strong demographic bottleneck. This population also presents a strong selection signal in a genomic region around the CNR1 gene associated with substance dependence and chronic stress. In Western Sahelian populations, signatures of selection were detected in several other genetic regions, including pathways associated with lactase persistence, immune response, and malaria resistance. Taken together, these findings refine our current knowledge of genetic diversity, population structure, migration, admixture and adaptation of human populations in the Sahel/Savannah belt and contribute to our understanding of human history and health.

• MeSH
• černoši MeSH
• etnicita genetika   MeSH
• haplotypy MeSH
• laktasa genetika   MeSH
• lidé MeSH
• populační genetika * MeSH
• tok genů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION AND OBJECTIVE: Cytochrome P450 enzymes are the major drug-metabolizing enzymes in humans and the importance of drug transport proteins, in particular P-glycoprotein, in the variability of drug response has also been highlighted. Activity of cytochrome P450 enzymes and P-glycoprotein can vary widely between individuals and genotyping and/or phenotyping can help assess their activity. Several phenotyping cocktails have been developed. The Geneva cocktail is composed of a specific probe for six different cytochrome P450 enzymes and one for P-glycoprotein and was used in the context of a research aiming at exploring genotypes and phenotypes in distinct human populations (NCT02789527). The aim of the present study is to solely report the safety results of the Geneva cocktail in the healthy volunteers of these populations.MATERIALS AND METHODS: The Geneva cocktail is composed of caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, midazolam, and fexofenadine. The volunteers fasted and avoided drinking caffeine-containing beverages or food and grapefruit juice overnight before receiving the cocktail orally. They provided blood spots for the probes' concentrations at 2, 3, and 6 h after ingestion and were asked about adverse events. RESULTS: A total of 265 healthy adult volunteers were included from Ethiopia, Oman, and the Czech Republic. The mean plasma concentrations at the 2-h sampling time of each probe drug in the total sample were: 1663 ng/mL for caffeine, 8 ng/mL for bupropion, 789 ng/mL for flurbiprofen, 6 ng/mL for dextromethorphan, 2 ng/mL for midazolam, 35 ng/mL for fexofenadine, and 103 ng/mL for omeprazole. Four adverse events were observed representing an occurrence of 1.5%. All these events were categorized as mild to moderate, non-serious, and resolved spontaneously. A causal link with the cocktail cannot be excluded because of the temporal relationship but is at most evaluated as possible according to the World Health Organization-Uppsala Monitoring Centre causal assessment system. CONCLUSIONS: In this research, healthy volunteers from three different human populations were phenotyped with the Geneva cocktail. Four adverse events were observed, confirming the safety of this cocktail that is given at lower than clinically relevant doses and therefore results in concentrations lower than those reported to cause adverse events.

• MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• genotyp MeSH
• inhibitory cytochromu P450 MeSH
• léčivé přípravky metabolismus   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• P-glykoprotein genetika   metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• substrátová specifita MeSH
• systém (enzymů) cytochromů P-450 genetika   metabolismus   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Etiopie MeSH
• Omán MeSH

• Klíčová slova
• hygienicko-epidemiologická opatření,
• MeSH
• COVID-19 ošetřování   MeSH
• dětské nemocnice MeSH
• koronavirové infekce epidemiologie   prevence a kontrola   MeSH
• krizová intervence MeSH
• pandemie MeSH
• postoj zdravotnického personálu MeSH
• průzkumy a dotazníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Publikační typ
• závěrečné práce

OBJECTIVES: Archeological evidence shows that first nomadic pastoralists came to the African Sahel from northeastern Sahara, where milking is reported by ~7.5 ka. A second wave of pastoralists arrived with the expansion of Arabic tribes in 7th-14th century CE. All Sahelian pastoralists depend on milk production but genetic diversity underlying their lactase persistence (LP) is poorly understood. MATERIALS AND METHODS: We investigated SNP variants associated with LP in 1,241 individuals from 29 mostly pastoralist populations in the Sahel. Then, we analyzed six SNPs in the neighboring fragment (419 kb) in the Fulani and Tuareg with the -13910*T mutation, reconstructed haplotypes, and calculated expansion age and growth rate of this variant. RESULTS: Our results reveal a geographic localization of two different LP variants in the Sahel: -13910*T west of Lake Chad (Fulani and Tuareg pastoralists) and -13915*G east of there (mostly Arabic-speaking pastoralists). We show that -13910*T has a more diversified haplotype background among the Fulani than among the Tuareg and that the age estimate for expansion of this variant among the Fulani (~8.5 ka) corresponds to introduction of cattle to the area. CONCLUSIONS: This is the first study showing that the "Eurasian" LP allele -13910*T is widespread both in northern Europe and in the Sahel; however, it is limited to pastoralists in the Sahel. Since the Fulani haplotype with -13910*T is shared with contemporary Eurasians, its origin could be in a region encompassing the Near East and northeastern Africa in a population ancestral to both Saharan pastoralists and European farmers.

• MeSH
• antropologie fyzická MeSH
• Arabové genetika   statistika a číselné údaje   MeSH
• běloši genetika   statistika a číselné údaje   MeSH
• černoši * genetika   statistika a číselné údaje   MeSH
• dieta MeSH
• etnicita * genetika   statistika a číselné údaje   MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• laktasa genetika   MeSH
• lidé MeSH
• mléko MeSH
• osoby s přechodným pobytem a migranti MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• severní Afrika MeSH

OBJECTIVES: The Sahel belt is occupied by populations who use two types of subsistence strategy, nomadic pastoralism and sedentary farming, and who belong to three linguistic families, Niger-Congo, Nilo-Saharan, and Afro-Asiatic. Little is known, however, about the origins of these two populations and their mutual genetic relationships. MATERIALS AND METHODS: We have built a large dataset of mitochondrial DNA sequences and Y chromosomal STR haplotypes of pastoralists and farmers belonging to all three linguistic phyla in the western, central, and eastern parts of the Sahel. We calculated pairwise genetic, geographic, and linguistic distances between populations and analyzed the effects of geography, language, and subsistence on population genetic structure. RESULTS: We found that subsistence mode significantly contributed to the generally low population structure in the Sahel and that language affiliation plays a more important role for pastoralists than for farmers. We also demonstrated that geographic isolation significantly influenced the population structure of sedentary farmers but not of nomadic pastoralists. Finally, we found haplotypes shared between the Fulani and Arabic-speaking Baggara, supporting the theory of Baggarization, which explains the recent adaptation of Arabic-speaking nomads in the Sahel region through contact with autochthonous sub-Saharan populations. CONCLUSIONS: Based on various genetic and archaeological evidence pertaining to the Sahel, we suggest that the idea of a bidirectional Sahelian corridor is valid, but that pastoralists made a more important contribution to its population structure. It is also possible that agropastoralists diverged into farmers and pastoralists in the early stages of formation of the Sahelian gene pool.

• MeSH
• genetická variace * MeSH
• kulturní evoluce MeSH
• lidé MeSH
• lidský chromozom Y * MeSH
• migrace lidstva MeSH
• mikrosatelitní repetice * MeSH
• mitochondriální DNA analýza   MeSH
• zemědělství klasifikace   MeSH
• životní styl * etnologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• střední Afrika MeSH
• východní Afrika MeSH
• západní Afrika MeSH

OBJECTIVES: The Sahel/Savannah belt is a region where two sympatric human subsistence strategies-nomadic pastoralism and sedentary farming-have been coexisting for millennia. While earlier studies focused on estimating population differentiation and genetic structure of this ecologically remarkable region's inhabitants, less effort has been expended on understanding the morphological variation among local populations. MATERIALS AND METHODS: To fill this gap, we used geometric morphometrics to analyze the facial features of three groups of pastoralists and three groups of sedentary farmers belonging to three language families (Niger-Congo, Nilo-Saharan, and Afro-Asiatic) whose mitochondrial DNA sequences have been published previously. RESULTS: Our results show that pastoralists differ from farmers with several facial features. We also found that individuals who bear maternally inherited haplotypes of Eurasian ancestry do not significantly morphologically differ from individuals whose maternal ancestry is sub-Saharan. CONCLUSIONS: Our study follows up and builds upon population genetic and phylogeographic studies of Eurasian haplogroups in the Fulani pastoralists and sub-Saharan haplogroups in the Arab pastoralists, as well as studies on the spread of lactase persistence mutations and other genetic markers. Our results suggest that recent gene flows across the Sahel/Savannah belt were not strong enough to erase a genetic structure established by Paleolithic foragers and further shaped by the adoption of agropastoral food-producing strategies.

• MeSH
• antropologie fyzická MeSH
• Arabové genetika   statistika a číselné údaje   MeSH
• běloši genetika   statistika a číselné údaje   MeSH
• černoši * genetika   statistika a číselné údaje   MeSH
• dieta statistika a číselné údaje   MeSH
• dospělí MeSH
• haplotypy genetika   MeSH
• lidé MeSH
• mitochondriální DNA genetika   MeSH
• mladý dospělý MeSH
• obličej anatomie a histologie   MeSH
• osoby s přechodným pobytem a migranti statistika a číselné údaje   MeSH
• populační genetika MeSH
• zemědělci statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• severní Afrika MeSH
• subsaharská Afrika MeSH

BACKGROUND: The origin of Western African pastoralism, represented today by the Fulani nomads, has been a highly debated issue for the past decades, and has not yet been conclusively resolved. AIM: This study focused on Alu polymorphisms in sedentary and nomadic populations across the African Sahel to investigate patterns of diversity that can complement the existing results and contribute to resolving issues concerning the origin of West African pastoralism. SUBJECTS AND METHODS: A new dataset of 21 Alu biallelic markers covering a substantial part of the African Sahel has been analysed jointly with several published North African populations. RESULTS: Interestingly, with regard to Alu variation, the relationship of Fulani pastoralists to North Africans is not as evident as was earlier revealed by studies of uniparental loci such as mtDNA and NRY. Alu insertions point rather to an affinity of Fulani pastoralists to Eastern Africans also leading a pastoral lifestyle. CONCLUSIONS: It is suggested that contemporary Fulani pastoralists might be descendants of an ancestral Eastern African population that, while crossing the Sahara in the Holocene, admixed slightly with a population of Eurasian (as evidenced by uniparental polymorphisms) ancestry. It seems that, in the Fulani pastoralists, Alu elements reflect more ancient genetic relationships than do uniparental genetic systems.

• MeSH
• elementy Alu genetika   MeSH
• lidé MeSH
• osoby s přechodným pobytem a migranti * MeSH
• polymorfismus genetický genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• subsaharská Afrika MeSH

OBJECTIVES: Thanks to the ability to digest lactose, Arabian nomads had become less dependent upon their sedentary neighbors and some of these populations spread to Africa. When and by which route they migrated to their current locations have previously been addressed only by historical and archaeological data. METHODS: To address the question of Arab expansion into Africa, we collected samples from several Arabic populations, especially the Baggara in Chad and Sudan. We analyzed mutations associated with lactase persistence and reconstructed the surrounding haplotypes defined by SNP polymorphisms. We also sequenced their mitochondrial DNA to investigate relative proportions of sub-Saharan and Eurasian origins. RESULTS: We estimated the expansion age of the -13,915*G mutation in four different Arabian datasets. The oldest age was identified in Yemen (1,356-1,799 ya) and the youngest in a Sudanese group of Rashaayda Arabs (219-312 ya). We also found a negative correlation between the frequency of the -13,915*G allele and the frequency of sub-Saharan mtDNA haplotypes. CONCLUSIONS: Even if the age of the most recent common ancestor of -13,915*G is ∼4 ka as shown in a previous study, our results suggest that its spread to Africa was more recent, which is consistent with the migrations of Arabic tribes. Because the incidence of sub-Saharan mtDNA haplotypes is negatively correlated with the occurrence of -13,915*G, we suggest that the decrease of its frequency in Africa has been caused by progressive admixture of the Arabian nomads with sub-Saharan populations.

• MeSH
• Arabové genetika   MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus * MeSH
• laktasa genetika   MeSH
• lidé MeSH
• migrace lidstva * MeSH
• mitochondriální DNA genetika   MeSH
• osoby s přechodným pobytem a migranti * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Čad MeSH
• Súdán MeSH

The objective of this study was to provide deeper knowledge of the maternal genetic structure and demographic history of the human populations of the Sahel/Savannah belt, the extensive region lying between the Sahara and tropical rainforests, spanning from the Atlantic Ocean to the Red Sea coast. The study aimed to confirm or disconfirm archaeological and linguistic data indicating that the region's populations underwent diversification as a result of the spread of agropastoral food-producing subsistence lifestyles, over time dividing the region into separate areas of nomadic pastoralism, on the one hand, and sedentary farming, on the other. To perform both descriptive and coalescence analyses from the Sahel/Savannah belt's entire region, including western and eastern rather than just central populations studied previously, we generated a new mitochondrial DNA (mtDNA) data set not only having almost 2,000 samples (875 of which were newly collected) but also encompassing whole mtDNA D-loop segment rather than only the previously studied hypervariable segment 1. While comparing our analyses with previous results from the Lake Chad Basin (central Sahel/Savannah Belt), we found similar intrapopulation diversity measures (i.e., lower values in pastoralists than in farmers). However, the new data set pointed to significant differences in mating strategies between western and eastern pastoralists: our results suggest higher gene flow between the Arabic pastoralists and neighboring farmers in the eastern part than between the Fulani pastoralists and their sedentary neighbors in the western part of the Sahel/Savannah belt. The findings are discussed in light of archaeological and linguistic data, allowing us to postulate that the genetic differentiation of Fulani pastoralists from the common western African agropastoral gene pool occurred at around the same time as the arrival of the Arabic pastoralists to eastern Africa. However, it seems that while the process of divergence of the Fulani pastoralists in the west was accompanied by a loss of Fulani females to other populations, the Arab pastoralists' immigration to the Sahel/Savannah belt conversely resulted in some gain of local females into this Arab population.

• MeSH
• Arabové genetika   MeSH
• archeologie metody   MeSH
• černoši genetika   dějiny   MeSH
• dějiny starověku MeSH
• dějiny středověku MeSH
• emigrace a imigrace MeSH
• genetické struktury MeSH
• jazyk (prostředek komunikace) MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• mitochondriální DNA genetika   MeSH
• osoby s přechodným pobytem a migranti MeSH
• populační genetika MeSH
• tok genů genetika   MeSH
• zemědělství trendy   MeSH
• Check Tag
• dějiny starověku MeSH
• dějiny středověku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• severní Afrika MeSH