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1.
Front Immunol ; 15: 1368624, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596677

RESUMO

Introduction: The immune systems of both the mother and the newborn face significant challenges during birth. Proper immune regulation after birth is essential for the survival of neonates. Numerous studies have demonstrated that the neonatal immune system is relatively immature, particularly in its adaptive arm, placing the primary responsibility for immune surveillance on innate immunity. Methods: Given the significant role of neutrophils in protecting the neonate after birth, we conducted a study investigating the properties of neutrophils in newborn cord blood using various methodological approaches. Results: Our findings demonstrate the presence of immature low-density neutrophils in the cord blood, which are likely responsible for the observed elevated expression of genes coding for proteins essential to antimicrobial response, including myeloperoxidase, neutrophils elastase, and defensins. Discussion: We propose that these cells function normally and support the protection of newborns early after birth. Furthermore, our results suggest that the mode of delivery might significantly influence the programming of neutrophil function. The presented findings emphasize the importance of distinct neutrophil subpopulations in neonatal immunity and their potential impact on early postnatal health.


Assuntos
Anti-Infecciosos , Neutrófilos , Recém-Nascido , Humanos , Sangue Fetal , Imunidade Inata , Proteínas/metabolismo , Anti-Infecciosos/metabolismo
3.
Am J Hum Biol ; 36(4): e24008, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37897188

RESUMO

OBJECTIVES: Previous research revealed that in some African populations, food-production strategies are associated with facial shape. Nomadic pastoralists living in the African Sahel/Savannah belt have a different facial morphology than their sedentary neighbors. We investigated whether the lifestyle associated with a subsistence pattern has an impact on sexual dimorphism in the facial structure. METHODS: We employed several methods from geometric morphometrics and demonstrated such effect in four ethnically distinct populations that share the same geographic space. RESULTS: We show that the facial traits which correlate with a subsistence strategy are systematically associated with levels of facial sex-typicality. In particular, we found that faces with more pronounced pastoralist features have on average more masculine facial traits and that this effect is more pronounced in men than in women. CONCLUSIONS: In general, though, the magnitude of overall facial dimorphism does not differ between pastoralists and farmers. Pastoralists (in contrast to farmers) tend to have a more masculine facial morphology but facial differences between the sexes are in both groups the same.


Assuntos
Face , Caracteres Sexuais , Feminino , Humanos , Masculino , População Negra , DNA Mitocondrial , Fenótipo , Face/anatomia & histologia
4.
Genes (Basel) ; 14(3)2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36981029

RESUMO

This review focuses on the Sahel/Savannah belt, a large region of Africa where two alternative subsistence systems (pastoralism and agriculture), nowadays, interact. It is a long-standing question whether the pastoralists became isolated here from other populations after cattle began to spread into Africa (~8 thousand years ago, kya) or, rather, began to merge with other populations, such as agropastoralists, after the domestication of sorghum and pearl millet (~5 kya) and with the subsequent spread of agriculture. If we look at lactase persistence, a trait closely associated with pastoral lifestyle, we see that its variants in current pastoralists distinguish them from their farmer neighbours. Most other (mostly neutral) genetic polymorphisms do not, however, indicate such clear differentiation between these groups; they suggest a common origin and/or an extensive gene flow. Genetic affinity and ecological symbiosis between the two subsistence systems can help us better understand the population history of this African region. In this review, we show that genomic datasets of modern Sahel/Savannah belt populations properly collected in local populations can complement the still insufficient archaeological research of this region, especially when dealing with the prehistory of mobile populations with perishable material culture and therefore precarious archaeological visibility.


Assuntos
Genética Populacional , Polimorfismo Genético , Humanos , Animais , Bovinos , África , Agricultura , Arqueologia
5.
Vaccines (Basel) ; 10(12)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36560450

RESUMO

BACKGROUND: COVID-19 pandemic has led to a loss of human life in millions and devastating socio-economic consequences worldwide. So far, vaccination is the most effective long-term strategy to control and prevent severe COVID-19 disease. The aim of the current study was to evaluate the humoral immune responses raised against the BNT162b2 vaccine in hospital healthcare workers. METHODS: Total number of 173 healthcare workers enrolled in the study. Their blood samples were collected in three different time intervals after the second SARS-CoV-2 vaccination and evaluated by the ELISA method to detect anti-spike protein IgM and IgG antibodies. The baseline characteristics of all participants were collected using questionnaires and were evaluated for finding any significant data. RESULTS: Our results demonstrated that the levels of antibodies were higher in the young group (21-30 years old) and also among male participants. Moreover, the highest levels of antibodies were detected from the group that received the third shot vaccination. CONCLUSIONS: Our results indicate that age, gender and third-dose vaccination can affect the levels of humoral immune responses against the BNT162b2 vaccine in healthcare workers.

6.
Genome Biol Evol ; 14(12)2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-36445690

RESUMO

Variation in genes involved in the absorption, distribution, metabolism, and excretion of drugs (ADME) can influence individual response to a therapeutic treatment. The study of ADME genetic diversity in human populations has led to evolutionary hypotheses of adaptation to distinct chemical environments. Population differentiation in measured drug metabolism phenotypes is, however, scarcely documented, often indirectly estimated via genotype-predicted phenotypes. We administered seven probe compounds devised to target six cytochrome P450 enzymes and the P-glycoprotein (P-gp) activity to assess phenotypic variation in four populations along a latitudinal transect spanning over Africa, the Middle East, and Europe (349 healthy Ethiopian, Omani, Greek, and Czech volunteers). We demonstrate significant population differentiation for all phenotypes except the one measuring CYP2D6 activity. Genome-wide association studies (GWAS) evidenced that the variability of phenotypes measuring CYP2B6, CYP2C9, CYP2C19, and CYP2D6 activity was associated with genetic variants linked to the corresponding encoding genes, and additional genes for the latter three. Instead, GWAS did not indicate any association between genetic diversity and the phenotypes measuring CYP1A2, CYP3A4, and P-gp activity. Genome scans of selection highlighted multiple candidate regions, a few of which included ADME genes, but none overlapped with the GWAS candidates. Our results suggest that different mechanisms have been shaping the evolution of these phenotypes, including phenotypic plasticity, and possibly some form of balancing selection. We discuss how these contrasting results highlight the diverse evolutionary trajectories of ADME genes and proteins, consistent with the wide spectrum of both endogenous and exogenous molecules that are their substrates.


Assuntos
Citocromo P-450 CYP2D6 , Estudo de Associação Genômica Ampla , Humanos , Citocromo P-450 CYP2D6/genética , Xenobióticos , Fenótipo , Genômica
7.
Parasitology ; 149(13): 1720-1728, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36050813

RESUMO

Toxocara canis, a gastrointestinal parasite of canids, is also highly prevalent in many paratenic hosts, such as mice and humans. As with many other helminths, the infection is associated with immunomodulatory effects, which could affect other inflammatory conditions including autoimmune and allergic diseases. Here, we investigated the effect of T. canis infection on the course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Mice infected with 2 doses of 100 T. canis L3 larvae 5 weeks prior to EAE induction (the Tc+EAE group) showed higher EAE clinical scores and greater weight loss compared to the non-infected group with induced EAE (the EAE group). Elevated concentrations of all measured serum cytokines (IL-1α, IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α) were observed in the Tc+EAE group compared to the EAE group. In the CNS, the similar number of regulatory T cells (Tregs; CD4+FoxP3+Helios+) but their decreased proportion from total CD4+ cells was found in the Tc+EAE group compared to the EAE group. This could indicate that the group Tc+EAE harboured significantly more CD4+ T cells of non-Treg phenotype within the affected CNS. Altogether, our results demonstrate that infection of mice with T. canis worsens the course of subsequently induced EAE. Further studies are, therefore, urgently needed to reveal the underlying pathological mechanisms and to investigate possible risks for the human population, in which exposure to T. canis is frequent.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Toxocara canis , Toxocaríase , Humanos , Animais , Camundongos , Encefalomielite Autoimune Experimental/patologia , Camundongos Endogâmicos C57BL , Linfócitos T CD4-Positivos/patologia , Esclerose Múltipla/patologia , Citocinas , Toxocaríase/complicações
8.
Mol Biol Evol ; 39(10)2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36173804

RESUMO

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.


Assuntos
Fluxo Gênico , Genética Populacional , Humanos , População Negra , Etnicidade/genética , Lactase/genética , Haplótipos
9.
Cells ; 11(10)2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35626660

RESUMO

Early postnatal events are important for the development of the neonatal immune system. Harboring the pioneering microorganisms forming the microbiota of the neonatal gastrointestinal tract is important for priming the immune system, as well as inducing appropriate tolerance to the relatively innocuous environmental antigens and compounds of normal healthy microbiota. Early postnatal supplementation of suitable, safe probiotics could accelerate this process. In the current study, the immunomodulatory capacity of the probiotic strain of Escherichia coli O83:K24:H31 (EcO83) was characterized in vitro and in vivo. We compared the capacity of EcO83 with and without hemolytic activity on selected immune characteristics in vitro as determined by flow cytometry and quantitative real-time PCR. Both strains with and without hemolytic activity exerted comparable capacity on the maturation of dendritic cells while preserving the induction of interleukin 10 (Il10) expression in dendritic cells and T cells cocultured with EcO83 primed dendritic cells. Early postnatal supplementation with EcO83 led to massive but transient colonization of the neonatal gastrointestinal tract, as detected by in vivo bioimaging. Early postnatal EcO83 administration promoted gut barrier function by increasing the expression of claudin and occludin and the expression of Il10. Early postnatal EcO83 application promotes maturation of the neonatal immune system and promotes immunoregulatory and gut barrier functions.


Assuntos
Microbiota , Probióticos , Células Dendríticas , Escherichia coli , Humanos , Recém-Nascido , Interleucina-10 , Probióticos/farmacologia
10.
Genes (Basel) ; 13(3)2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35328086

RESUMO

African history has been significantly influenced by the Sahara, which has represented a barrier for migrations of all living beings, including humans. Major exceptions were the gene flow events that took place between North African and sub-Saharan populations during the so-called African Humid Periods, especially in the Early Holocene (11.5 to 5.5 thousand years ago), and more recently in connection with trans-Saharan commercial routes. In this study, we describe mitochondrial DNA (mtDNA) diversity of human populations from both sides of the Sahara Desert, i.e., both from North Africa and the Sahel/Savannah belt. The final dataset of 7213 mtDNA sequences from 134 African populations encompasses 470 newly collected and 6743 previously published samples, which were analyzed using descriptive methods and Bayesian statistics. We completely sequenced 26 mtDNAs from sub-Saharan samples belonging to the Eurasian haplogroup N1. Analyses of these N1 mitogenomes revealed their possible routes to the Sahel, mostly via Bab el-Mandab. Our results indicate that maternal gene flow must have been important in this circum-Saharan space, not only within North Africa and the Sahel/Savannah belt but also between these two regions.


Assuntos
População Negra , DNA Mitocondrial , África do Norte , Teorema de Bayes , DNA Mitocondrial/genética , Fluxo Gênico , Humanos
11.
Am J Biol Anthropol ; 177(3): 540-555, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34846066

RESUMO

OBJECTIVES: Mode of subsistence is an important factor influencing dietary habits and the genetic structure of various populations through differential intensity of gene flow and selection pressures. Previous studies suggest that in Africa Taste 2 Receptor Member 16 (TAS2R16), which encodes the 7-transmembrane receptor protein for bitterness, might also be under positive selection pressure. METHODS: However, since sampling coverage of populations was limited, we created a new TAS2R16 population dataset from across the African Sahel/Savannah belt representing various local populations of differing subsistence modes, linguistic affiliations, and geographic provenience. We sequenced the TAS2R16 exon gene and analyzed 2250 haplotypes among 19 populations. RESULTS: We found no evidence for selection as a driving force of genetic variation at this locus; instead, we discovered a highly significant correlation between TAS2R16 genetic and geographical distances based on provenience of the sampled populations, strongly suggesting that genetic drift most likely prevailed over positive selection at this specific locus. We also found significant correlations with other independent loci, mainly in sedentary farmers. DISCUSSION: Our results do not support the notion that the genetic diversity of TAS2R16 in Sahelian populations was shaped by selective pressures. This could result from several alternative and not mutually exclusive mechanisms, of which the possibility that, due to the pleiotropic nature of TAS2R16, selective pressures on other traits could counterbalance those acting on bitter taste perception, or that the change of diet in the Neolithic generally relaxed selective pressure on this gene.


Assuntos
Papilas Gustativas , Paladar , Humanos , Paladar/genética , África , Estruturas Genéticas , Demografia
12.
Front Immunol ; 13: 1038328, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36703968

RESUMO

Introduction: Probiotic administration seems to be a rational approach to promote maturation of the neonatal immune system. Mutual interaction of the microbiota with the host immune system is critical for the setting of appropriate immune responses including a tolerogenic one and thevmaintenance of homeostasis. On the other hand, our knowledge on the modes of actions of probiotics is still scarce. Methods: In our study, probiotic strain Escherichia coli O83:K24:H31 (EcO83) was administered to neonates of allergic mothers (AMs; neonates with increased risk for allergy development) within 48 h after the delivery, and the impact of this early postnatal supplementation on allergy incidence and selected immune markers has been analyzed 10 years after the primary EcO83 administration. Results: We have observed decreased allergy incidence in 10-year-old children supplemented with EcO83 (13 of 52 children were allergic) in comparison with non-supplemented children of AMs (16 of 42 children were allergic). The early postnatal EcO83 supplementation appeared to limit the allergy in the high-risk group (children of AMs) compared to that in the low-risk group (children of healthy mothers). Dendritic cells (DCs) in the peripheral blood of EcO83-supplemented children do not differ significantly in cell surface presence of CD83. The immunomodulatory capacity of EcO83 on DCs was tested in vitro as well. Both directly isolated myeloid and in vitro monocyte-derived DCs from cord blood increased CD83 expression together with interleukin (IL)-10 secretion after EcO83 stimulation. The effect of early postnatal EcO83 supplementation on the microbiota composition of 10-year-old children was characterized by next-generation sequencing, and we have not observed significant changes in the microbiota composition of EcO83-supplemented and non-supplemented children at the age of 10 years. Conclusions: Early postnatal EcO83 supplementation appears to lower allergy incidence in children of AMs. It seems that the beneficial effect of EcO83 is mediated via modulation of DC functional capacities without impacting the microbiota composition. Larger-scale studies will be necessary to confirm these preliminary findings.


Assuntos
Hipersensibilidade , Microbiota , Probióticos , Feminino , Criança , Recém-Nascido , Humanos , Escherichia coli/fisiologia , Incidência , Hipersensibilidade/epidemiologia , Hipersensibilidade/prevenção & controle , Monócitos , Células Dendríticas
13.
Biomedicines ; 9(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572097

RESUMO

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.

14.
Hum Mol Genet ; 30(R1): R29-R36, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33105478

RESUMO

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 characterized 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 and 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.


Assuntos
População Negra/genética , Genética Populacional/métodos , África Austral/etnologia , Agricultura , DNA Mitocondrial/genética , Pool Gênico , Haplótipos , Migração Humana , Humanos
15.
Drug Saf ; 43(11): 1181-1189, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32851583

RESUMO

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.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Preparações Farmacêuticas/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450/genética , República Tcheca , Combinação de Medicamentos , Etiópia , Feminino , Genótipo , Voluntários Saudáveis , Humanos , Masculino , Omã , Especificidade por Substrato , Adulto Jovem
16.
Am J Phys Anthropol ; 173(3): 423-436, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32812238

RESUMO

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.


Assuntos
População Negra , Etnicidade , Lactase/genética , Polimorfismo de Nucleotídeo Único/genética , África do Norte , Animais , Antropologia Física , Árabes/genética , Árabes/estatística & dados numéricos , População Negra/genética , População Negra/estatística & dados numéricos , Dieta , Etnicidade/genética , Etnicidade/estatística & dados numéricos , Haplótipos , Humanos , Leite , Migrantes , População Branca/genética , População Branca/estatística & dados numéricos
17.
Am J Phys Anthropol ; 171(3): 496-508, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31930493

RESUMO

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.


Assuntos
Cromossomos Humanos Y , DNA Mitocondrial/análise , Variação Genética , Estilo de Vida , Repetições de Microssatélites , África Central , África Oriental , África Ocidental , Agricultura/classificação , Evolução Cultural , Migração Humana , Humanos , Estilo de Vida/etnologia , Masculino
18.
Cent Eur J Immunol ; 45(4): 393-402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33613093

RESUMO

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.

19.
BMC Genomics ; 20(1): 915, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791255

RESUMO

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.


Assuntos
População Negra/genética , Lactase/genética , Europa (Continente) , Evolução Molecular , Fluxo Gênico , Estudo de Associação Genômica Ampla , Humanos , Migrantes
20.
Am J Phys Anthropol ; 169(4): 632-645, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31032542

RESUMO

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.


Assuntos
População Negra , Dieta/estatística & dados numéricos , Face/anatomia & histologia , Fazendeiros/estatística & dados numéricos , Migrantes/estatística & dados numéricos , Adulto , África Subsaariana , África do Norte , Antropologia Física , Árabes/genética , Árabes/estatística & dados numéricos , População Negra/genética , População Negra/estatística & dados numéricos , DNA Mitocondrial/genética , Feminino , Genética Populacional , Haplótipos/genética , Humanos , Masculino , População Branca/genética , População Branca/estatística & dados numéricos , Adulto Jovem
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