Publications by authors named "Viktor Cerný"

45 Publications

Value of cord blood Treg population properties and function-associated characteristics for predicting allergy development in childhood.

Cent Eur J Immunol 2020 30;45(4):393-402. Epub 2021 Jan 30.

Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.

Allergic diseases represent some of the most common immunological disorders with high clinical and economic impact. Despite intensive research, there are still few universally accepted and reliable biomarkers capable of predicting their development at an early age. There is therefore a pressing need for identification of potential predictive factors and validation of their prognostic value by correlating them with allergy development. Dysbalance of the branches of immune response, most often excessive Th2 polarization, is the principal cause of allergic diseases. Regulatory T cells (Treg) are a crucial population for the timely establishment of physiological immune polarization and induction and maintenance of tolerance against environmental antigens. This makes them a potentially promising candidate for an early marker predicting allergy development. In our study, we analysed samples of cord blood of children of allergic mothers and children of healthy mothers by flow cytometry and retrospectively correlated the data with clinical allergy status of the children at the age of 6 to 10 years. Studied parameters included cord blood Treg population proportions and functional properties - intracellular presence of IL-10 and TGF-b, MFI of FoxP3. We observed higher percentage of Tregs in cord blood of children who did not develop allergy compared with allergic children. Further, we found higher numbers of IL-10+ Tregs in cord blood of healthy children of healthy mothers than in cord blood of children of allergic mothers and decreased TGF-b+ cord blood Tregs in the group of allergic children of allergic mothers compared to all other groups.
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http://dx.doi.org/10.5114/ceji.2020.103413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882409PMC
January 2021

Lower Functional and Proportional Characteristics of Cord Blood Treg of Male Newborns Compared with Female Newborns.

Biomedicines 2021 Feb 9;9(2). Epub 2021 Feb 9.

Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic.

Understanding the early events involved in the induction of immune tolerance to harmless environmental antigens and microbiota compounds could reveal potential targets for allergic disease therapy or prevention. Regulatory T cells (Treg), particularly induced Treg (iTreg), are crucial for the induction and maintenance of tolerance against environmental antigens including allergens. A decrease in the number and/or function of Treg or iTreg could represent an early predictor of allergy development. We analyzed proportional and functional properties of Treg in the cord blood of children of allergic mothers (neonates at high risk of allergy development) and healthy mothers (neonates with relatively low risk of allergy development). We observed a higher number of induced Treg in the cord blood of females compared to males, suggesting an impaired capacity of male immunity to set up tolerance to allergens, which could contribute to the higher incidence of allergy observed in male infants. The decreased proportion of iTreg in cord blood compared with maternal peripheral blood documents the general immaturity of the neonatal immune system. We observed a positive correlation in the demethylation of the Treg-specific demethylated region (TSDR) and the proportion of Treg in cord blood. Our data suggest that immaturity of the neonatal immune system is more severe in males, predisposing them to increased risk of allergy development.
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http://dx.doi.org/10.3390/biomedicines9020170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915235PMC
February 2021

Demographic history and admixture dynamics in African Sahelian populations.

Hum Mol Genet 2020 Oct 26. Epub 2020 Oct 26.

Archaeogenetics Laboratory, Institute of Archaeology of the Czech Academy of Sciences, Prague, Czech Republic.

The Sahel/Savannah belt of Africa is a contact zone between two subsistence systems (nomadic pastoralism and sedentary farming) and of two groups of populations, namely Eurasians penetrating from northern Africa southwards and sub-Saharan Africans migrating northwards. Because pastoralism is characterised by a high degree of mobility, it leaves few significant archaeological traces. Demographic history seen through the lens of population genetic studies complements our historical and archaeological knowledge in this African region. In this review, we highlight recent advances in our understanding of demographic history in the Sahel/Savannah belt as revealed by genetic studies. We show the impact of food-producing subsistence strategies on population structure as well as the somewhat different migration patterns in the western and eastern part of the region. Genomic studies show that the gene pool of various groups of Sahelians consists in a complex mosaic of several ancestries. We also touch upon various signals of genetic adaptations such as lactase persistence, taste sensitivity, and malaria resistance, all of which have different distribution patterns among Sahelian populations. Overall, genetic studies contribute to gain a deeper understanding about the demographic and adaptive history of human populations in this specific African region and beyond.
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http://dx.doi.org/10.1093/hmg/ddaa239DOI Listing
October 2020

Safety of the Geneva Cocktail, a Cytochrome P450 and P-Glycoprotein Phenotyping Cocktail, in Healthy Volunteers from Three Different Geographic Origins.

Drug Saf 2020 11;43(11):1181-1189

Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals and University of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva, Switzerland.

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.
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http://dx.doi.org/10.1007/s40264-020-00983-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575470PMC
November 2020

Sahelian pastoralism from the perspective of variants associated with lactase persistence.

Am J Phys Anthropol 2020 11 19;173(3):423-436. Epub 2020 Aug 19.

Archaeogenetics Laboratory, Institute of Archaeology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic.

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.
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http://dx.doi.org/10.1002/ajpa.24116DOI Listing
November 2020

Subsistence strategy was the main factor driving population differentiation in the bidirectional corridor of the African Sahel.

Am J Phys Anthropol 2020 03 12;171(3):496-508. Epub 2020 Jan 12.

Archaeogenetics Laboratory, Institute of Archaeology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic.

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.
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http://dx.doi.org/10.1002/ajpa.24001DOI Listing
March 2020

Population history and genetic adaptation of the Fulani nomads: inferences from genome-wide data and the lactase persistence trait.

BMC Genomics 2019 Dec 2;20(1):915. Epub 2019 Dec 2.

Human Evolution, Department of Organismal Biology, Evolutionary Biology Centre, Uppsala University, Norbyvägen 18C, SE-752 36, Uppsala, Sweden.

Background: Human population history in the Holocene was profoundly impacted by changes in lifestyle following the invention and adoption of food-production practices. These changes triggered significant increases in population sizes and expansions over large distances. Here we investigate the population history of the Fulani, a pastoral population extending throughout the African Sahel/Savannah belt.

Results: Based on genome-wide analyses we propose that ancestors of the Fulani population experienced admixture between a West African group and a group carrying both European and North African ancestries. This admixture was likely coupled with newly adopted herding practices, as it resulted in signatures of genetic adaptation in contemporary Fulani genomes, including the control element of the LCT gene enabling carriers to digest lactose throughout their lives. The lactase persistence (LP) trait in the Fulani is conferred by the presence of the allele T-13910, which is also present at high frequencies in Europe. We establish that the T-13910 LP allele in Fulani individuals analysed in this study lies on a European haplotype background thus excluding parallel convergent evolution. We furthermore directly link the T-13910 haplotype with the Lactase Persistence phenotype through a Genome Wide Association study (GWAS) and identify another genomic region in the vicinity of the SPRY2 gene associated with glycaemic measurements after lactose intake.

Conclusions: Our findings suggest that Eurasian admixture and the European LP allele was introduced into the Fulani through contact with a North African population/s. We furthermore confirm the link between the lactose digestion phenotype in the Fulani to the MCM6/LCT locus by reporting the first GWAS of the lactase persistence trait. We also explored other signals of recent adaptation in the Fulani and identified additional candidates for selection to adapt to herding life-styles.
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http://dx.doi.org/10.1186/s12864-019-6296-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888939PMC
December 2019

Nomadic pastoralists and sedentary farmers of the Sahel/Savannah Belt of Africa in the light of geometric morphometrics based on facial portraits.

Am J Phys Anthropol 2019 08 29;169(4):632-645. Epub 2019 Apr 29.

Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic.

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.
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http://dx.doi.org/10.1002/ajpa.23845DOI Listing
August 2019

Evidence of Austronesian Genetic Lineages in East Africa and South Arabia: Complex Dispersal from Madagascar and Southeast Asia.

Genome Biol Evol 2019 03;11(3):748-758

Laboratoire Évolution & Diversité Biologique (EDB UMR 5174), Université de Toulouse Midi-Pyrénées, CNRS, IRD, UPS, Toulouse, France.

The Austronesian dispersal across the Indonesian Ocean to Madagascar and the Comoros has been well documented, but in an unexplained anomaly, few to no traces have been found of the Austronesian expansion in East Africa or the Arabian Peninsula. To revisit this peculiarity, we surveyed the Western Indian Ocean rim populations to identify potential Austronesian genetic ancestry. We generated full mitochondrial DNA genomes and genome-wide genotyping data for these individuals and compared them with the Banjar, the Indonesian source population of the westward Austronesian dispersal. We find strong support for Asian genetic contributions to maternal lineages and autosomal variation in modern day Somalia and Yemen. Surprisingly, this input reveals two apparently different geographic origins and timings of admixture for the Austronesian contact; one at a very early phase (likely associated with the early Austronesian dispersals), and a later movement dating to the end of nineteenth century. These Austronesian gene flows come, respectively, from Madagascar and directly from an unidentified location in Island Southeast Asia. This result reveals a far more complex dynamic of Austronesian dispersals through the Western Indian Ocean than has previously been understood and suggests that Austronesian movements within the Indian Ocean may have been part of a lengthy process, probably continuing well into the modern era.
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http://dx.doi.org/10.1093/gbe/evz028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423374PMC
March 2019

Distinct characteristics of Tregs of newborns of healthy and allergic mothers.

PLoS One 2018 26;13(11):e0207998. Epub 2018 Nov 26.

Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Allergic diseases represent a major issue in clinical and experimental immunology due to their high and increasing incidence worldwide. Allergy status of the mother remains the best predictor of an individual's increased risk of allergy development. Dysregulation of the balance between different branches of immune response, chiefly excessive polarization towards Th2, is the underlying cause of allergic diseases. Regulatory T cells (Tregs) play a pivotal role in the timely establishment of physiological immune polarization and are crucial for control of allergy. In our study we used flow cytometry to assess Tregs in cord blood of newborns of healthy (n = 121) and allergic (n = 108) mothers. We observed a higher percentage of Tregs (CD4+CD25+CD127lowFoxP3+) in cord blood of children of allergic mothers. However, the percentage of cells expressing extracellular (PD-1, CTLA-4, GITR) and intracellular (IL-10, TGF-β) markers of function was lower (significantly for PD-1 and IL-10) within Tregs of these children. Furthermore, Helios- induced Tregs in the cord blood of children of allergic mothers were decreased. These results were supported by a decrease in plasma levels of IL-10 and TGF-β in cord blood of newborns of allergic mothers, implying lower tolerogenic capacity on the systemic level. Taken together, these findings reflect deficient function of Tregs in the group with higher risk of allergy development. This may be caused by a lower maturation status of the immune system, specifically Tregs, at birth. Such immaturity may represent an important mechanism involved in the increased risk of allergy in children of allergic mothers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207998PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258229PMC
May 2019

Decreased allergy incidence in children supplemented with E. coli O83:K24:H31 and its possible modes of action.

Eur J Immunol 2018 12 21;48(12):2015-2030. Epub 2018 Oct 21.

Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

The growing knowledge of the key role of microbiota in the maturation of neonatal immune system suggests that manipulation of microbiota could be exploited in hampering allergy development. In this study, Escherichia coli O83:K24:H31 (EcO83) was administered to newborns that were followed prospectively. Several immunological characteristics (cytokines, specific IgE, total T regulatory cells (Treg) and subpopulation of natural Treg (nTreg) and induced Treg (iTreg)) were tested in peripheral blood of 8-year-old children. Incidence of allergic disease was decreased in EcO83 supplemented children and significantly elevated levels of IL-10 and IFN-ɣ were detected in serum of EcO83 supplemented children. Probiotic supplementation did not influence the numbers of the total Treg population but their functional capacity (intracellular expression of IL-10) was significantly increased in children supplemented with EcO83 in comparison to non-supplemented children. Morover, decreased proportion of iTreg was present in peripheral blood of non-supplemented in comparison to EcO83 supplemented children. Finally, stimulation of cord blood cells with EcO83 promoted both gene expression and secretion of IL-10 and IFN-ɣ suggesting that beneficial effect of EcO83 in prevention of allergy development could be mediated by promotion of regulatory responses (by IL-10) and Th1 immune response (by IFN-ɣ).
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http://dx.doi.org/10.1002/eji.201847636DOI Listing
December 2018

Genetic Structure of the Western and Eastern African Sahel/Savannah Belt and the Role of Nomadic Pastoralists as Inferred from the Variation of D-Loop Mitochondrial DNA Sequences.

Hum Biol 2017 10;89(4):281-302

2 Archaeogenetics Laboratory, Institute of Archaeology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic.

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.
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October 2017

The HLA-B landscape of Africa: Signatures of pathogen-driven selection and molecular identification of candidate alleles to malaria protection.

Mol Ecol 2017 Nov 16;26(22):6238-6252. Epub 2017 Oct 16.

Department of Genetics and Evolution - Anthropology Unit, Laboratory of Anthropology, Genetics and Peopling History (AGP), University of Geneva, Geneva, Switzerland.

Human leukocyte antigen (HLA) genes play a key role in the immune response to infectious diseases, some of which are highly prevalent in specific environments, like malaria in sub-Saharan Africa. Former case-control studies showed that one particular HLA-B allele, B*53, was associated with malaria protection in Gambia, but this hypothesis was not tested so far within a population genetics framework. In this study, our objective was to assess whether pathogen-driven selection associated with malaria contributed to shape the HLA-B genetic landscape of Africa. To that aim, we first typed the HLA-A and -B loci in 484 individuals from 11 populations living in different environments across the Sahel, and we analysed these data together with those available for 29 other populations using several approaches including linear modelling on various genetic, geographic and environmental parameters. In addition to relevant signatures of populations' demography and migrations history in the genetic differentiation patterns of both HLA-A and -B loci, we found that the frequencies of three HLA alleles, B*53, B*78 and A*74, were significantly associated with Plasmodium falciparum malaria prevalence, suggesting their increase through pathogen-driven selection in malaria-endemic environments. The two HLA-B alleles were further identified, by high-throughput sequencing, as B*53:01:01 (in putative linkage disequilibrium with one HLA-C allele, C*04:01:01:01) and B*78:01 in all but one individuals tested, making them appropriate candidates to malaria protection. These results highlight the role of environmental factors in the evolution of the HLA polymorphism and open key perspectives for functional studies focusing on HLA peptide-binding properties.
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http://dx.doi.org/10.1111/mec.14366DOI Listing
November 2017

Internal diversification of non-Sub-Saharan haplogroups in Sahelian populations and the spread of pastoralism beyond the Sahara.

Am J Phys Anthropol 2017 10 24;164(2):424-434. Epub 2017 Jul 24.

Archaeogenetics Laboratory, Institute of Archaeology of the Academy of Sciences of the Czech Republic, Czech Republic.

Background: Today, African pastoralists are found mainly in the Sahel/Savannah belt spanning 6,000 km from west to east, flanked by the Sahara to the north and tropical rainforests to the south. The most significant group among them are the Fulani who not only keep cattle breeds of possible West Eurasian ancestry, but form themselves a gene pool containing some paternally and maternally-transmitted West Eurasian haplogroups.

Materials And Methods: We generated complete sequences for 33 mitogenomes belonging to haplogroups H1 and U5 (23 and 10, respectively), and genotyped 16 STRs in 65 Y chromosomes belonging to haplogroup R1b-V88.

Results: We show that age estimates of the maternal lineage H1cb1, occurring almost exclusively in the Fulani, point to the time when the first cattle herders settled the Sahel/Savannah belt. Similar age estimates were obtained for paternal lineage R1b-V88, which occurs today in the Fulani but also in other, mostly pastoral populations. Maternal clade U5b1b1b, reported earlier in the Berbers, shows a shallower age, suggesting another possibly independent input into the Sahelian pastoralist gene pool.

Conclusions: Despite the fact that animal domestication originated in the Near East ∼ 10 ka, and that it was from there that animals such as sheep, goats as well as cattle were introduced into Northeast Africa soon thereafter, contemporary cattle keepers in the Sahel/Savannah belt show uniparental genetic affinities that suggest the possibility of an ancient contact with an additional ancestral population of western Mediterranean ancestry.
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http://dx.doi.org/10.1002/ajpa.23285DOI Listing
October 2017

Different capacity of in vitro generated myeloid dendritic cells of newborns of healthy and allergic mothers to respond to probiotic strain E. coli O83:K24:H31.

Immunol Lett 2017 09 26;189:82-89. Epub 2017 May 26.

Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. Electronic address:

Allergic diseases belong to one of the most common diseases with steadily increasing incidence even among young children. There is an urgent need to identify a prognostic marker pointing to increased risk of allergy development enabling early preventive measures introduction. It has been shown that administration of selected probiotic strains or mixtures could prevent allergy development. In our study, we have tested the capacity of probiotic strain Escherichia coli O83:K24:H31 (E. coli O83) to promote dendritic cell (DC) maturation and polarisation of immune responses. Increased presence of activation marker CD83 was observed on DC stimulated by E. coli O83 and DC of newborns of allergic mothers have significantly more increased cell surface presence of CD83 in comparison to children of healthy mothers. Increased gene expression and secretion of IL-10 was detected in DC stimulated with E. coli O83 being higher in DC of newborns of healthy mothers in comparison to allergic ones. Generally, increased presence of intracellular cytokines (IL-4, IL-13, IFN-gamma, IL-17A, IL-22, IL-10) was detected in CD4+ T cells cocultured with DC of children of allergic mothers in comparison to healthy ones. E. coli O83 primed DC significantly increased IL-10 and IL-17A in CD4 T cells of newborns of healthy mothers in comparison to the levels detected in CD4 T cells cocultured with control non-stimulated DC. We can conclude E. coli O83 induces dendritic cell maturation and IL-10 production in DC. Newborns of allergic mothers have generally increased reactivity of both DC and CD4 T cells which together with decreased capacity of DC of newborns of allergic mothers to produce IL-10 could support inappropriate immune responses development after allergen encounter.
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http://dx.doi.org/10.1016/j.imlet.2017.05.013DOI Listing
September 2017

Alu insertion polymorphisms in the African Sahel and the origin of Fulani pastoralists.

Ann Hum Biol 2017 Sep 31;44(6):537-545. Epub 2017 May 31.

f Department of the Archaeology of Landscape and Archaeobiology, Archaeogenetics Laboratory , Institute of Archaeology of the Academy of Sciences of the Czech Republic , Prague , Czech Republic.

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.
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http://dx.doi.org/10.1080/03014460.2017.1328073DOI Listing
September 2017

Origin and spread of human mitochondrial DNA haplogroup U7.

Sci Rep 2017 04 7;7:46044. Epub 2017 Apr 7.

Evolutionary Biology Group, Estonian Biocentre, Tartu 51010, Estonia.

Human mitochondrial DNA haplogroup U is among the initial maternal founders in Southwest Asia and Europe and one that best indicates matrilineal genetic continuity between late Pleistocene hunter-gatherer groups and present-day populations of Europe. While most haplogroup U subclades are older than 30 thousand years, the comparatively recent coalescence time of the extant variation of haplogroup U7 (~16-19 thousand years ago) suggests that its current distribution is the consequence of more recent dispersal events, despite its wide geographical range across Europe, the Near East and South Asia. Here we report 267 new U7 mitogenomes that - analysed alongside 100 published ones - enable us to discern at least two distinct temporal phases of dispersal, both of which most likely emanated from the Near East. The earlier one began prior to the Holocene (~11.5 thousand years ago) towards South Asia, while the later dispersal took place more recently towards Mediterranean Europe during the Neolithic (~8 thousand years ago). These findings imply that the carriers of haplogroup U7 spread to South Asia and Europe before the suggested Bronze Age expansion of Indo-European languages from the Pontic-Caspian Steppe region.
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http://dx.doi.org/10.1038/srep46044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384202PMC
April 2017

The historical spread of Arabian Pastoralists to the eastern African Sahel evidenced by the lactase persistence -13,915*G allele and mitochondrial DNA.

Am J Hum Biol 2017 May 27;29(3). Epub 2017 Jan 27.

Archaeogenetics Laboratory, Institute of Archaeology of the Academy of Sciences of the Czech Republic, Prague.

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.
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http://dx.doi.org/10.1002/ajhb.22950DOI Listing
May 2017

Comprehensive Analysis of Pan-African Mitochondrial DNA Variation Provides New Insights into Continental Variation and Demography.

J Genet Genomics 2016 Mar 25;43(3):133-43. Epub 2015 Sep 25.

Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Medicina Legal, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia 15782, Spain. Electronic address:

Africa is the cradle of all human beings, and although it has been the focus of a number of genetic studies, there are many questions that remain unresolved. We have performed one of the largest and most comprehensive meta-analyses of mitochondrial DNA (mtDNA) lineages carried out in the African continent to date. We generated high-throughput mtDNA single nucleotide polymorphism (SNP) data (230 SNPs) from 2024 Africans, where more than 500 of them were additionally genotyped for the control region. These data were analyzed together with over 12,700 control region profiles collected from the literature, representing more than 300 population samples from Africa. Insights into the African homeland of humans are discussed. Phylogeographic patterns for the African continent are shown at a high phylogeographic resolution as well as at the population and regional levels. The deepest branch of the mtDNA tree, haplogroup L0, shows the highest sub-haplogroup diversity in Southeast and East Africa, suggesting this region as the homeland for modern humans. Several demographic estimates point to the coast as a facilitator of human migration in Africa, but the data indicate complex patterns, perhaps mirroring the effect of recent continental-scaled demographic events in re-shaping African mtDNA variability.
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http://dx.doi.org/10.1016/j.jgg.2015.09.005DOI Listing
March 2016

The structure-dependent toxicity, pharmacokinetics and anti-tumour activity of HPMA copolymer conjugates in the treatment of solid tumours and leukaemia.

J Control Release 2016 Feb 18;223:1-10. Epub 2015 Dec 18.

Institute of Microbiology, Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic. Electronic address:

Polymer drug carriers that are based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers have been widely used in the development and synthesis of high-molecular-weight (HMW) drug delivery systems for cancer therapy. In this study, we compared linear (Mw ~27kDa, Rh ~4nm) and non-degradable star (Mw ~250kDa, Rh ~13nm) HPMA copolymer conjugates bearing anthracycline antibiotic doxorubicin (DOX) bound via pH-sensitive hydrazone bond. We determined the in vitro and in vivo toxicity of both conjugates and their maximum tolerated dose (MTD). We also compared their anti-tumour activity in mouse B-cell leukaemia (BCL1) and a mouse T-cell lymphoma (EL4) model. We found that MTD was higher for the linear conjugate (85mgDOX/kg) and lower for the star conjugate (22.5mgDOX/kg). An evaluation of the intestinal barrier integrity using FITC-dextran as a gut permeability tracer proved that no pathology was caused by the MTD of either conjugate. However, free DOX showed some damage to the gut barrier. The therapy of BCL1 leukaemia by both of the polymeric conjugates using the MTD or its fraction (i.e., equitoxic dosage) showed better results in the case of the star conjugate. On the other hand, treatment of EL4 lymphoma seemed to be more efficient when the linear conjugate was used. We suppose that the anti-cancer treatment of solid tumours and leukaemias requires different types of drug conjugates. We hypothesise that the most suitable HPMA copolymer-DOX conjugate for the treatment of solid tumours should have an HMW structure with increased Rh that would be stable for three to four days after the conjugate administration and then rapidly disintegrate in the short polymer chains, which are excretable from the body by glomerular filtration. On the other hand, the treatment of leukaemia requires a drug conjugate with a long circulation half-life. This would provide an active drug, whilst slowly degrading to excretable fragments.
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http://dx.doi.org/10.1016/j.jconrel.2015.12.023DOI Listing
February 2016

Comprehensive view of the population history of Arabia as inferred by mtDNA variation.

Am J Phys Anthropol 2016 Apr 22;159(4):607-16. Epub 2015 Dec 22.

Department of Anthropology, University of Florida, Gainesville, FL, 32610-3610.

Objectives: Genetic and archaeological research supports the theory that Arabia was the first region traversed by modern humans as they left Africa and dispersed throughout Eurasia. However, the role of Arabia from the initial migration out of Africa until more recent times is still unclear.

Materials And Methods: We have generated 379 new hypervariable segment 1 (HVS-1) sequences from a range of geographic locations throughout Yemen. We compare these data to published HVS-1 sequences representing Arabia and neighboring regions to build a unique dataset of 186 populations and 14,290 sequences.

Results: We identify 4,563 haplotypes unevenly distributed across Arabia and neighboring regions. Arabia contains higher proportions of shared haplotypes than the regions with which it shares these haplotypes, suggesting high levels of migration through the region. Populations in Arabia show higher levels of population expansion than those in East Africa, but lower levels than the Near East, Middle East or India. Arabian populations also show very high levels of genetic variation that overlaps with variation from most other regions.

Conclusion: We take a population genetics approach to provide a comprehensive view of the relationships of Arabian and neighboring populations. We show that Arabian populations share closest links to the Near East and North Africa, but have a more ancient origin with slower demographic growth and/or lower migration rates. Our conclusions are supported by phylogenetic studies but also suggest that recent migrations have erased signals of earlier events.
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http://dx.doi.org/10.1002/ajpa.22920DOI Listing
April 2016

Variation in NAT2 acetylation phenotypes is associated with differences in food-producing subsistence modes and ecoregions in Africa.

BMC Evol Biol 2015 Dec 1;15:263. Epub 2015 Dec 1.

Department of Genetics and Evolution, Anthropology Unit, Laboratory of Anthropology, Genetics and Peopling History, University of Geneva, 12 Rue Gustave-Revilliod, 1211, Geneva 4, Switzerland.

Background: Dietary changes associated to shifts in subsistence strategies during human evolution may have induced new selective pressures on phenotypes, as currently held for lactase persistence. Similar hypotheses exist for arylamine N-acetyltransferase 2 (NAT2) mediated acetylation capacity, a well-known pharmacogenetic trait with wide inter-individual variation explained by polymorphisms in the NAT2 gene. The environmental causative factor (if any) driving its evolution is as yet unknown, but significant differences in prevalence of acetylation phenotypes are found between hunter-gatherer and food-producing populations, both in sub-Saharan Africa and worldwide, and between agriculturalists and pastoralists in Central Asia. These two subsistence strategies also prevail among sympatric populations of the African Sahel, but knowledge on NAT2 variation among African pastoral nomads was up to now very scarce. Here we addressed the hypothesis of different selective pressures associated to the agriculturalist or pastoralist lifestyles having acted on the evolution of NAT2 by sequencing the gene in 287 individuals from five pastoralist and one agriculturalist Sahelian populations.

Results: We show that the significant NAT2 genetic structure of African populations is mainly due to frequency differences of three major haplotypes, two of which are categorized as decreased function alleles (NAT2*5B and NAT2*6A), particularly common in populations living in arid environments, and one fast allele (NAT2*12A), more frequently detected in populations living in tropical humid environments. This genetic structure does associate more strongly with a classification of populations according to ecoregions than to subsistence strategies, mainly because most Sahelian and East African populations display little to no genetic differentiation between them, although both regions hold nomadic or semi-nomadic pastoralist and sedentary agriculturalist communities. Furthermore, we found significantly higher predicted proportions of slow acetylators in pastoralists than in agriculturalists, but also among food-producing populations living in the Sahelian and dry savanna zones than in those living in humid environments, irrespective of their mode of subsistence.

Conclusion: Our results suggest a possible independent influence of both the dietary habits associated with subsistence modes and the chemical environment associated with climatic zones and biomes on the evolution of NAT2 diversity in sub-Saharan African populations.
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http://dx.doi.org/10.1186/s12862-015-0543-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665893PMC
December 2015

Extensive Admixture and Selective Pressure Across the Sahel Belt.

Genome Biol Evol 2015 Nov 26;7(12):3484-95. Epub 2015 Nov 26.

Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal Faculdade de Medicina da Universidade do Porto, Porto, Portugal

Genome-wide studies of African populations have the potential to reveal powerful insights into the evolution of our species, as these diverse populations have been exposed to intense selective pressures imposed by infectious diseases, diet, and environmental factors. Within Africa, the Sahel Belt extensively overlaps the geographical center of several endemic infections such as malaria, trypanosomiasis, meningitis, and hemorrhagic fevers. We screened 2.5 million single nucleotide polymorphisms in 161 individuals from 13 Sahelian populations, which together with published data cover Western, Central, and Eastern Sahel, and include both nomadic and sedentary groups. We confirmed the role of this Belt as a main corridor for human migrations across the continent. Strong admixture was observed in both Central and Eastern Sahelian populations, with North Africans and Near Eastern/Arabians, respectively, but it was inexistent in Western Sahelian populations. Genome-wide local ancestry inference in admixed Sahelian populations revealed several candidate regions that were significantly enriched for non-autochthonous haplotypes, and many showed to be under positive selection. The DARC gene region in Arabs and Nubians was enriched for African ancestry, whereas the RAB3GAP1/LCT/MCM6 region in Oromo, the TAS2R gene family in Fulani, and the ALMS1/NAT8 in Turkana and Samburu were enriched for non-African ancestry. Signals of positive selection varied in terms of geographic amplitude. Some genomic regions were selected across the Belt, the most striking example being the malaria-related DARC gene. Others were Western-specific (oxytocin, calcium, and heart pathways), Eastern-specific (lipid pathways), or even population-restricted (TAS2R genes in Fulani, which may reflect sexual selection).
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http://dx.doi.org/10.1093/gbe/evv236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700964PMC
November 2015

60,000 years of interactions between Central and Eastern Africa documented by major African mitochondrial haplogroup L2.

Sci Rep 2015 Jul 27;5:12526. Epub 2015 Jul 27.

1] IPATIMUP (Instituto de Patologia e Imunologia Molecular da Universidade do Porto), 4200-465 Porto, Portugal [2] CBMA (Centro de Biologia Molecular e Ambiental), Departamento de Biologia, Universidade do Minho, 4710-057 Braga, Portugal.

Mitochondrial DNA (mtDNA) haplogroup L2 originated in Western Africa but is nowadays spread across the entire continent. L2 movements were previously postulated to be related to the Bantu expansion, but L2 expansions eastwards probably occurred much earlier. By reconstructing the phylogeny of L2 (44 new complete sequences) we provide insights on the complex net of within-African migrations in the last 60 thousand years (ka). Results show that lineages in Southern Africa cluster with Western/Central African lineages at a recent time scale, whereas, eastern lineages seem to be substantially more ancient. Three moments of expansion from a Central African source are associated to L2: (1) one migration at 70-50 ka into Eastern or Southern Africa, (2) postglacial movements (15-10 ka) into Eastern Africa; and (3) the southward Bantu Expansion in the last 5 ka. The complementary population and L0a phylogeography analyses indicate no strong evidence of mtDNA gene flow between eastern and southern populations during the later movement, suggesting low admixture between Eastern African populations and the Bantu migrants. This implies that, at least in the early stages, the Bantu expansion was mainly a demic diffusion with little incorporation of local populations.
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http://dx.doi.org/10.1038/srep12526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515592PMC
July 2015

Genetic stratigraphy of key demographic events in Arabia.

PLoS One 2015 4;10(3):e0118625. Epub 2015 Mar 4.

Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal; Faculdade de Medicina da Universidade do Porto, Porto, Portugal.

At the crossroads between Africa and Eurasia, Arabia is necessarily a melting pot, its peoples enriched by successive gene flow over the generations. Estimating the timing and impact of these multiple migrations are important steps in reconstructing the key demographic events in the human history. However, current methods based on genome-wide information identify admixture events inefficiently, tending to estimate only the more recent ages, as here in the case of admixture events across the Red Sea (~8-37 generations for African input into Arabia, and 30-90 generations for "back-to-Africa" migrations). An mtDNA-based founder analysis, corroborated by detailed analysis of the whole-mtDNA genome, affords an alternative means by which to identify, date and quantify multiple migration events at greater time depths, across the full range of modern human history, albeit for the maternal line of descent only. In Arabia, this approach enables us to infer several major pulses of dispersal between the Near East and Arabia, most likely via the Gulf corridor. Although some relict lineages survive in Arabia from the time of the out-of-Africa dispersal, 60 ka, the major episodes in the peopling of the Peninsula took place from north to south in the Late Glacial and, to a lesser extent, the immediate post-glacial/Neolithic. Exchanges across the Red Sea were mainly due to the Arab slave trade and maritime dominance (from ~2.5 ka to very recent times), but had already begun by the early Holocene, fuelled by the establishment of maritime networks since ~8 ka. The main "back-to-Africa" migrations, again undetected by genome-wide dating analyses, occurred in the Late Glacial period for introductions into eastern Africa, whilst the Neolithic was more significant for migrations towards North Africa.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118625PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349752PMC
December 2015

Lactase persistence variants in Arabia and in the African Arabs.

Hum Biol 2014 ;86(1):7-18

Institute of Archaeology, Academy of Science, Prague, Czech Republic.

Lactase persistence (LP), the state enabling the digestion of milk sugar in adulthood, occurs only in some human populations. The convergent and independent origin of this physiological ability in Europe and Africa is linked with animal domestication that either had started in both places independently or had spread from the Near East by acculturation. However, it has recently been shown that at least in its southern parts, the population of Arabia not only has a different LP-associated mutation profile than the rest of Africa and Europe but also had experienced an independent demographic expansion occurring before the Neolithic around the Pleistocene-Holocene boundary. In Arabia, LP is associated with mutation -13,915*G and not, as in Europe, with -13,910*T or, as in Africa, with -13,907*G and -14,010*C. We show here that, in Arabia, -13,915*G frequency conforms to a partial clinal pattern and that this specific mutation has likely been spread from Arabia to Africa only recently from the sixth century AD onward by nomadic Arabs (Bedouins) looking for new pastures. Arabic populations in Africa that still maintain a nomadic way of life also have more -13,915*G variants and fewer sub-Saharan L-type mitochondrial DNA haplogroups; this observation matches archaeological and historical records suggesting that the migration of Arabic pastoralists was accompanied by gradual sedentarization that allowed for admixture with the local African population.
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http://dx.doi.org/10.3378/027.086.0101DOI Listing
November 2015

The place of Slovakian paternal diversity in the clinal European landscape.

Ann Hum Biol 2015 14;42(6):511-22. Epub 2015 Sep 14.

d Laboratory of Anthropology, Genetics and Peopling History, Department of Genetics and Evolution , University of Geneva , Geneva , Switzerland.

Background: Several demographic events have been postulated to explain the contemporaneous structure of European genetic diversity. First, an initial settlement of the continent by anatomically modern humans; second, the re-settlement of northern latitudes after the Last Glacial Maximum; third, the demic diffusion of Neolithic farmers from the Near East; and, fourth, several historical events such as the Slavic migration.

Aim: The aim of this study was to provide a more integrated picture of male-specific genetic relationships of Slovakia within the broader pan-European genetic landscape.

Subjects And Methods: This study analysed a new Y-chromosome data-set (156 individuals) for both SNP and STR polymorphisms in population samples from five different Slovakian localities.

Results: It was found that the male diversity of Slovakia is embedded in the clinal pattern of the major R1a and R1b clades extending over the continent and a similar pattern of population structure is found with Y-specific SNP or STR variation.

Conclusion: The highly significant correlation between the results based on fast evolving STRs on one hand and slow evolving SNPs on the other hand suggests a recent timeframe for the settlement of the area.
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http://dx.doi.org/10.3109/03014460.2014.974668DOI Listing
August 2016

The genetic impact of the lake chad basin population in North Africa as documented by mitochondrial diversity and internal variation of the L3e5 haplogroup.

Ann Hum Genet 2013 Nov;77(6):513-23

Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic.

The presence of sub-Saharan L-type mtDNA sequences in North Africa has traditionally been explained by the recent slave trade. However, gene flow between sub-Saharan and northern African populations would also have been made possible earlier through the greening of the Sahara resulting from Early Holocene climatic improvement. In this article, we examine human dispersals across the Sahara through the analysis of the sub-Saharan mtDNA haplogroup L3e5, which is not only commonly found in the Lake Chad Basin (∼17%), but which also attains nonnegligible frequencies (∼10%) in some Northwestern African populations. Age estimates point to its origin ∼10 ka, probably directly in the Lake Chad Basin, where the clade occurs across linguistic boundaries. The virtual absence of this specific haplogroup in Daza from Northern Chad and all West African populations suggests that its migration took place elsewhere, perhaps through Northern Niger. Interestingly, independent confirmation of Early Holocene contacts between North Africa and the Lake Chad Basin have been provided by craniofacial data from Central Niger, supporting our suggestion that the Early Holocene offered a suitable climatic window for genetic exchanges between North and sub-Saharan Africa. In view of its younger founder age in North Africa, the discontinuous distribution of L3e5 was probably caused by the Middle Holocene re-expansion of the Sahara desert, disrupting the clade's original continuous spread.
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http://dx.doi.org/10.1111/ahg.12040DOI Listing
November 2013

The first modern human dispersals across Africa.

PLoS One 2013 13;8(11):e80031. Epub 2013 Nov 13.

IPATIMUP (Instituto de Patologia e Imunologia Molecular da Universidade do Porto), Porto, Portugal.

The emergence of more refined chronologies for climate change and archaeology in prehistoric Africa, and for the evolution of human mitochondrial DNA (mtDNA), now make it feasible to test more sophisticated models of early modern human dispersals suggested by mtDNA distributions. Here we have generated 42 novel whole-mtDNA genomes belonging to haplogroup L0, the most divergent clade in the maternal line of descent, and analysed them alongside the growing database of African lineages belonging to L0's sister clade, L1'6. We propose that the last common ancestor of modern human mtDNAs (carried by "mitochondrial Eve") possibly arose in central Africa ~180 ka, at a time of low population size. By ~130 ka two distinct groups of anatomically modern humans co-existed in Africa: broadly, the ancestors of many modern-day Khoe and San populations in the south and a second central/eastern African group that includes the ancestors of most extant worldwide populations. Early modern human dispersals correlate with climate changes, particularly the tropical African "megadroughts" of MIS 5 (marine isotope stage 5, 135-75 ka) which paradoxically may have facilitated expansions in central and eastern Africa, ultimately triggering the dispersal out of Africa of people carrying haplogroup L3 ~60 ka. Two south to east migrations are discernible within haplogroup LO. One, between 120 and 75 ka, represents the first unambiguous long-range modern human dispersal detected by mtDNA and might have allowed the dispersal of several markers of modernity. A second one, within the last 20 ka signalled by L0d, may have been responsible for the spread of southern click-consonant languages to eastern Africa, contrary to the view that these eastern examples constitute relicts of an ancient, much wider distribution.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080031PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827445PMC
July 2014

Multiple and differentiated contributions to the male gene pool of pastoral and farmer populations of the African Sahel.

Am J Phys Anthropol 2013 May 4;151(1):10-21. Epub 2013 Mar 4.

Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic.

The African Sahel is conducive to studies of divergence/admixture genetic events as a result of its population history being so closely related with past climatic changes. Today, it is a place of the co-existence of two differing food-producing subsistence systems, i.e., that of sedentary farmers and nomadic pastoralists, whose populations have likely been formed from several dispersed indigenous hunter-gatherer groups. Using new methodology, we show here that the male gene pool of the extant populations of the African Sahel harbors signatures of multiple and differentiated contributions from different genetic sources. We also show that even if the Fulani pastoralists and their neighboring farmers share high frequencies of four Y chromosome subhaplogroups of E, they have drawn on molecularly differentiated subgroups at different times. These findings, based on combinations of SNP and STR polymorphisms, add to our previous knowledge and highlight the role of differences in the demographic history and displacements of the Sahelian populations as a major factor in the segregation of the Y chromosome lineages in Africa. Interestingly, within the Fulani pastoralist population as a whole, a differentiation of the groups from Niger is characterized by their high presence of R1b-M343 and E1b1b1-M35. Moreover, the R1b-M343 is represented in our dataset exclusively in the Fulani group and our analyses infer a north-to-south African migration route during a recent past.
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http://dx.doi.org/10.1002/ajpa.22236DOI Listing
May 2013