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Background: The Bacillus Calmette-Guérin (BCG), the only vaccine against tuberculosis (TB) currently in use, has shown beneficial effects against unrelated infections and to enhance immune responses to vaccines. However, there is little evidence regarding the influence of BCG vaccination on pertussis. Methods: Here, we studied the ability of BCG to improve the immune responses to diphtheria, tetanus, and acellular (DTaP) or whole-cell pertussis (DTwP) vaccination in a mouse model. We included MTBVAC, an experimental live-attenuated vaccine derived from Mycobacterium tuberculosis, in our studies to explore if it presents similar heterologous immunity as BCG. Furthermore, we explored the potential effect of routine BCG vaccination on pertussis incidence worldwide. Findings: We found that both BCG and MTBVAC when administered before DTaP, triggered Th1 immune responses against diphtheria, tetanus, and pertussis in mice. Immunization with DTaP alone failed to trigger a Th1 response, as measured by the production of IFN-γ. Humoral responses against DTaP antigens were also enhanced by previous immunization with BCG or MTBVAC. Furthermore, exploration of human epidemiological data showed that pertussis incidence was 10-fold lower in countries that use DTaP and BCG compared to countries that use only DTaP. Interpretation: BCG vaccination may have a beneficial impact on the protection against pertussis conferred by DTaP. Further randomized controlled trials are needed to properly define the impact of BCG on pertussis incidence in a controlled setting. This could be a major finding that would support changes in immunization policies.
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Genetic and archaeological data indicate that the initial Paleoindian settlers of South America followed two entry routes separated by the Andes and the Amazon rainforest. The interactions between these paths and their impact on the peopling of South America remain unclear. Analysis of genetic variation in the Peruvian Andes and regions located south of the Amazon River might provide clues on this issue. We analyzed mitochondrial DNA variation at different Andean locations and >360,000 autosomal SNPs from 28 Native American ethnic groups to evaluate different trans-Andean demographic scenarios. Our data reveal that the Peruvian Altiplano was an important enclave for early Paleoindian expansions and point to a genetic continuity in the Andes until recent times, which was only marginally affected by gene flow from the Amazonian lowlands. Genomic variation shows a good fit with the archaeological evidence, indicating that the genetic interactions between the descendants of the settlers that followed the Pacific and Atlantic routes were extremely limited.
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ADN Mitocondrial/genética , Flujo Génico/genética , Genética de Población , Arqueología , Cromosomas Humanos Y/genética , Etnicidad/genética , Variación Genética , Haplotipos , Humanos , Mitocondrias/genética , Polimorfismo de Nucleótido Simple/genética , América del SurRESUMEN
Mennonites are Anabaptist communities that originated in Central Europe about 500 years ago. They initially migrated to different European countries, and in the early 18th century they established their first communities in North America, from where they moved to other American regions. We aimed to analyze an Argentinean Mennonite congregation from a genome-wide perspective by way of investigating >580.000 autosomal SNPs. Several analyses show that Argentinean Mennonites have European ancestry without signatures of admixture with other non-European American populations. Among the worldwide datasets used for population comparison, the CEU, which is the best-subrogated Central European population existing in The 1000 Genome Project, is the dataset showing the closest genome affinity to the Mennonites. When compared to other European population samples, the Mennonites show higher inbreeding coefficient values. Argentinean Mennonites show signatures of genetic continuity with no evidence of admixture with Americans of Native American or sub-Saharan African ancestry. Their genome indicates the existence of an increased endogamy compared to other Europeans most likely mirroring their lifestyle that involve small communities and historical consanguineous marriages.
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Etnicidad/genética , Técnicas de Genotipaje/métodos , Polimorfismo de Nucleótido Simple , Argentina , Consanguinidad , Genética de Población , Genoma Humano , HumanosRESUMEN
BACKGROUND: Unraveling the ancestry of 'Afro-American' communities is hampered by the complex demographic processes that took place during the Transatlantic Slave Trade (TAST) and the (post-)colonization periods. 'Afro-Bolivians' from the subtropical Yungas valleys constitute small and isolated communities that live surrounded by the predominant Native American community of Bolivia. By genotyping >580,000 SNPs in two 'Afro-Bolivians', and comparing these genomic profiles with data compiled from more than 57 African groups and other reference ancestral populations (n = 1,161 in total), we aimed to disentangle the complex admixture processes undergone by 'Afro-Bolivians'. RESULTS: The data indicate that these two genomes constitute a complex mosaic of ancestries that is approximately 80 % of recent African origin; the remaining ~20 % being European and Native American. West-Central Africa contributed most of the African ancestry to 'Afro-Bolivians', and this component is related to populations living along the Atlantic coast (i.e. Senegal, Ghana, Nigeria). Using tract length distribution of genomic segments attributable to distinct ancestries, we could date the time of admixture in about 400 years ago. This time coincides with the maximum importation of slaves to Bolivia to compensate the diminishing indigenous labor force needed for the development of the National Mint of Potosí. CONCLUSIONS: Overall, the data indicate that the genome of 'Afro-Bolivians' was shaped by a complex process of admixture occurring in America among individuals originating in different West-Central African populations; their genomic mosaics received additional contributions of Europeans and local Native Americans (e.g. Aymaras).
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Etnicidad/genética , Genética de Población , Técnicas de Genotipaje , Indio Americano o Nativo de Alaska/genética , Población Negra/genética , Bolivia , Mapeo Cromosómico , Genoma Humano , Genómica , Humanos , Polimorfismo de Nucleótido Simple , Población Blanca/genéticaRESUMEN
Old Order Mennonite communities initially arose in Northern Europe (centered in the Netherlands) and derived from the Anabaptist movement of the 16th century. Mennonites migrated to the New World in the early 18th century, first to North America, and more recently to Mesoamerica and South America. We analyzed Y-chromosome short tandem repeats (STRs) and single nucleotide polymorphisms in males from a community of Mennonites, 'La Nueva Esperanza', which arrived to Argentina in 1985 from colonies in Bolivia and Mexico. Molecular diversity indices coupled with demographic simulations show that Mennonites have a reduced variability when compared with local Argentinean populations and 69 European population samples. Mennonite Y-STR haplotypes were mainly observed in Central Europe. In agreement, multidimensional scaling analyses based on RST genetic distances indicate that Mennonite Y-chromosomes are closely related to Central/Northern Europeans (the Netherlands, Switzerland and Denmark). In addition, statistical inferences made on the most likely geographic origin of Y-chromosome haplotypes point more specifically to the Netherlands as the populations that best represent the majority of the Mennonite Y-chromosomes. Overall, Y-chromosome variation of Mennonites shows the signatures of moderate reduction of variability when compared with source populations, which is in good agreement with their lifestyle in small endogamous demes. These genetic singularities could also help to understand disease conditions that are more prevalent among Mennonites.
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Cromosomas Humanos Y , Genética de Población , Repeticiones de Microsatélite , Américas , Argentina , Bases de Datos Genéticas , Etnicidad/genética , Europa (Continente) , Femenino , Variación Genética , Haplotipos , Migración Humana , Humanos , Masculino , Filogenia , Filogeografía , Grupos Raciales/genéticaRESUMEN
We analyzed the Y chromosome haplotypes (Yfiler) of 978 non-related Chilean males grouped in five sampling regions (Iquique, Santiago de Chile, Concepción, Temuco and Punta Arenas) covering main geo-political regions. Overall, 803 different haplotypes and 688 singletons were observed. Molecular diversity was moderately lower than in other neighboring countries (e.g. Argentina); and AMOVA analysis on Y-STR haplotypes showed that among variation within Chile accounted for only 0.25% of the total variation. Punta Arenas, in the southern cone, showed the lowest haplotype diversity, and discrimination capacity, and also the highest matching probability of the five Chilean samples, probably reflecting its more marked geographic isolation compared to the other regions. Multidimensional scaling (MDS) analysis based on RST genetic distances suggested a close proximity of Chilean Y-chromosome profiles to European ones. Consistently, haplogroups inferred from Y-STR profiles revealed that the Native American component constituted only 8% of all the haplotypes, and this component ranged from 5% in the Centre of the country to 9-10% in the South and 13% in the North, which is in good agreement with the distribution of Native American communities in these regions. AMOVA computed on inferred haplogroups confirmed the very low among variation observed in Chilean populations. The present project provides the first Chilean dataset to the international Y-chromosome STR Haplotype Reference Database (YHRD) and it is also the first reference database for Y-chromosome forensic casework of the country.
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Cromosomas Humanos Y , Repeticiones de Microsatélite , Población Blanca/genética , Chile , Bases de Datos Genéticas , Europa (Continente)/etnología , Genética Forense/métodos , Genética de Población/métodos , Haplotipos , Humanos , Masculino , Grupos Raciales , Población UrbanaRESUMEN
A study of 23 Y-STRs was conducted in 257 individuals living in urban areas from eight Argentinean provinces. The data were meta-analyzed together with 364 profiles obtained from the literature that represent other five provinces. A total of 255 different haplotypes were observed (253 singletons). Genetic structure estimated from analysis of molecular variance (AMOVA) and exploring different grouping scenarios, yielded high within population variance. Not surprisingly, analyses of genetic distances with respect to main ancestral continental populations indicated Argentinean haplotypes to be closely related to European ones. Overall, these results provide a quite complete picture of the patterns of Y chromosome variation in Argentina, notably contributing to increase the previous national database, and consequently allowing a better estimation of parameters of interest in forensic casework and parentage testing.
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Cromosomas Humanos Y , Repeticiones de Microsatélite , Argentina , Genética Forense/métodos , Genética de Población , Haplotipos , Humanos , MasculinoRESUMEN
In 1985, a frozen mummy was found in Cerro Aconcagua (Argentina). Archaeological studies identified the mummy as a seven-year-old Inca sacrifice victim who lived >500 years ago, at the time of the expansion of the Inca Empire towards the southern cone. The sequence of its entire mitogenome was obtained. After querying a large worldwide database of mitogenomes (>28,000) we found that the Inca haplotype belonged to a branch of haplogroup C1b (C1bi) that has not yet been identified in modern Native Americans. The expansion of C1b into the Americas, as estimated using 203 C1b mitogenomes, dates to the initial Paleoindian settlements (~18.3 thousand years ago [kya]); however, its internal variation differs between Mesoamerica and South America. By querying large databases of control region haplotypes (>150,000), we found only a few C1bi members in Peru and Bolivia (e.g. Aymaras), including one haplotype retrieved from ancient DNA of an individual belonging to the Wari Empire (Peruvian Andes). Overall, the results suggest that the profile of the mummy represents a very rare sub-clade that arose 14.3 (5-23.6) kya and could have been more frequent in the past. A Peruvian Inca origin for present-day C1bi haplotypes would satisfy both the genetic and paleo-anthropological findings.
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ADN Mitocondrial/genética , Genoma Mitocondrial/genética , Indígenas Sudamericanos , Momias , Argentina , Niño , ADN Mitocondrial/química , ADN Mitocondrial/clasificación , Haplotipos , Humanos , Filogenia , Religión , Análisis de Secuencia de ADNRESUMEN
During the period of the Transatlantic Slave Trade (TAST) some enslaved Africans were forced to move to Upper Peru (nowadays Bolivia). At first they were sent to Potosí, but later to the tropical Yungas valley where the Spanish colonizers established a so-called "hacienda system" that was based on slave labor, including African-descendants. Due to their isolation, very little attention has been paid so far to 'Afro-Bolivian' communities either within the research field of TAST or in genetic population studies. In this study, a total of 105 individuals from the Yungas were sequenced for their mitochondrial DNA (mtDNA) control region, and mitogenomes were obtained for a selected subset of these samples. We also genotyped 46 Ancestry Informative Markers (AIM) in order to investigate continental ancestry at the autosomal level. In addition, Y-chromosome STR and SNP data for a subset of the same individuals was also available from the literature. The data indicate that the partitioning of mtDNA ancestry in the Yungas differs significantly from that in the rest of the country: 81% Native American, 18% African, and 1% European. Interestingly, the great majority of 'Afro-descendant' mtDNA haplotypes in the Yungas (84%) concentrates in the locality of Tocaña. This high proportion of African ancestry in the Tocaña is also manifested in the Y-chromosome (44%) and in the autosomes (56%). In sharp contrast with previous studies on the TAST, the ancestry of about 1/3 of the 'Afro-Bolivian' mtDNA haplotypes can be traced back to East and South East Africa, which may be at least partially explained by the Arab slave trade connected to the TAST.
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Población Negra/genética , Personas Esclavizadas , Genética de Población , Genómica , Bolivia , Cromosomas Humanos Y , ADN Mitocondrial/genética , Femenino , Variación Genética , Genoma Mitocondrial , Genómica/métodos , Haplotipos , Humanos , Mutación INDEL , Masculino , Anotación de Secuencia Molecular , Filogenia , Filogeografía , Factores SexualesRESUMEN
We have analyzed the specific male genetic component of 226 Bolivians recruited in five different regions ("departments"), La Paz, Cochabamba, Pando, Beni, and Santa Cruz. To evaluate the effect of geography on the distribution of genetic variability, the samples were also grouped into three main eco-geographical regions, namely, Andean, Sub-Andean, and Llanos. All the individuals were genotyped for 17 Y-STR and 32 Y-SNP markers. The average Y-chromosome Native American component in Bolivians is 28%, and it is mainly represented by haplogroup Q1a3a, while the average Y-chromosome European ancestry is 65%, and it is mainly represented by haplogroup R1b1-P25. The data indicate that there exists significant population sub-division in the country in terms of continental ancestry. Thus, the partition of ancestries in Llanos, Sub-Andean, and Andean regions is as follows (respectively): (i) Native American ancestry: 47%, 7%, and 19%, (ii) European ancestry: 46%, 86%, and 75%, and (iii) African ancestry: 7%, 7%, and 6%. The population sub-structure in the country is also well mirrored when inferred from an AMOVA analysis, indicating that among-population variance in the country reaches 9.74-11.15%. This suggests the convenience of using regional datasets for forensic applications in Bolivia, instead of using a global and single country database. By comparing the Y-chromosome patterns with those previously reported on the same individuals on autosomal SNPs and mitochondrial DNA (mtDNA), it becomes clear that Bolivians show a strong gender-bias.
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Cromosomas Humanos Y , Etnicidad/genética , Marcadores Genéticos , Bolivia , Haplotipos , Humanos , Masculino , Repeticiones de Microsatélite , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido SimpleRESUMEN
We have genotyped 46 Ancestry Informative Markers (AIMs) in two of the most populated areas in Bolivia, namely, La Paz (Andean region; n=105), and Chuquisaca (Sub-Andean region; n=73). Using different analytical tools, we inferred admixture proportions of these two American communities by comparing the genetic profiles with those publicly available from the CEPH (Centre d'Etude du Polymorphisme Humain) panel representing three main continental groups (Africa, Europe, and America). By way of simulations, we first evaluated the minimum sample size needed in order to obtain accurate estimates of ancestry proportions. The results indicated that sample sizes above 30 individuals could be large enough to estimate main continental ancestry proportions using the 46 AIMs panel. With the exception of a few individuals, the results also indicated that Bolivians showed a predominantly Native American ancestry with variable levels of European admixture. The proportions of ancestry were statistically different in La Paz and Chuquisaca: the Native American component was 86% and 77% (Mann-Whitney U-test: un-adjusted P-value=2.1×10(-5)), while the European ancestry was 13% and 21% (Mann-Whitney U-test: un-adjusted P-value=3.6×10(-5)), respectively. The African ancestry in Bolivians captured by the AIMs analyzed in the present study was below 2%. The inferred ancestry of Bolivians fits well with previous studies undertaken on haplotype data, indicating a major proportion of Native American lineages. The genetic differences observed in these two groups suggest that forensic genetic analysis should be better performed based on local databases built in the main Bolivian areas.
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Indígenas Sudamericanos/genética , Población Blanca/genética , Población Negra/genética , Bolivia , Simulación por Computador , Dermatoglifia del ADN , Etnicidad/genética , Genética Forense/métodos , Genética Forense/estadística & datos numéricos , Genética de Población , Humanos , Análisis de Componente PrincipalRESUMEN
Only a few genetic studies have been carried out to date in Bolivia. However, some of the most important (pre)historical enclaves of South America were located in these territories. Thus, the (sub)-Andean region of Bolivia was part of the Inca Empire, the largest state in Pre-Columbian America. We have genotyped the first hypervariable region (HVS-I) of 720 samples representing the main regions in Bolivia, and these data have been analyzed in the context of other pan-American samples (>19,000 HVS-I mtDNAs). Entire mtDNA genome sequencing was also undertaken on selected Native American lineages. Additionally, a panel of 46 Ancestry Informative Markers (AIMs) was genotyped in a sub-set of samples. The vast majority of the Bolivian mtDNAs (98.4%) were found to belong to the main Native American haplogroups (A: 14.3%, B: 52.6%, C: 21.9%, D: 9.6%), with little indication of sub-Saharan and/or European lineages; however, marked patterns of haplogroup frequencies between main regions exist (e.g. haplogroup B: Andean [71%], Sub-Andean [61%], Llanos [32%]). Analysis of entire genomes unraveled the phylogenetic characteristics of three Native haplogroups: the pan-American haplogroup B2b (originated â¼21.4 thousand years ago [kya]), A2ah (â¼5.2 kya), and B2o (â¼2.6 kya). The data suggest that B2b could have arisen in North California (an origin even in the north most region of the American continent cannot be disregarded), moved southward following the Pacific coastline and crossed Meso-America. Then, it most likely spread into South America following two routes: the Pacific path towards Peru and Bolivia (arriving here at about â¼15.2 kya), and the Amazonian route of Venezuela and Brazil southwards. In contrast to the mtDNA, Ancestry Informative Markers (AIMs) reveal a higher (although geographically variable) European introgression in Bolivians (25%). Bolivia shows a decreasing autosomal molecular diversity pattern along the longitudinal axis, from the Altiplano to the lowlands. Both autosomes and mtDNA revealed a low impact (1-2%) of a sub-Saharan component in Bolivians.