Asunto(s)

Hemofilia B/genética , Mutación , Adolescente , Adulto , Brasil , Niño , Preescolar , Factor IX/química , Factor IX/genética , Factor IX/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Moleculares , Conformación Proteica , Adulto Joven

Asunto(s)

Pollos/genética , ADN Mitocondrial/genética , Haplotipos , Animales , Brasil

Asunto(s)

Factor VIII/genética , Hemofilia A/genética , MicroARNs/metabolismo , Regiones no Traducidas 3' , Alelos , Sitios de Unión , Brasil , Factor VIII/antagonistas & inhibidores , Factor VIII/metabolismo , Frecuencia de los Genes , Mutación de Línea Germinal , Hemofilia A/patología , Humanos , Masculino , MicroARNs/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Índice de Severidad de la Enfermedad

RESUMEN

N-acetyltransferase 2 (NAT2) is responsible for metabolizing xenobiotics; NAT2 polymorphisms lead to three phenotypes: rapid, intermediate and slow acetylators. We aimed to investigate NAT2 diversity in Native Americans. NAT2 exon 2 was sequenced for 286 individuals from 21 populations (Native American and American Mestizos). Excluding the basal/rapid haplotype NAT2*4, the most frequent haplotypes are NAT2*5B (35.95%) in hunter-gatherers and NAT2*7B (20.61%) and NAT2*5B (19.08%) in agriculturalists that were related to the slow phenotype. A new haplotype was identified in two Amerindians. Data from the ~44 kb region surrounding NAT2 in 819 individuals from Africa, East-Asia, Europe and America were used in additional analyses. No significant differences in the acetylator NAT2 haplotype and phenotype distributions were found between Native American populations practicing farming and/or herding and those practicing hunting and gathering, probably because of the absence or weakness of selection pressures and presence of demographic and random processes preventing detection of any selection signal.

Asunto(s)

Indio Americano o Nativo de Alaska/genética , Arilamina N-Acetiltransferasa/genética , Evolución Molecular , Variación Genética , Acetilación , Agricultura , Américas , Animales , Arilamina N-Acetiltransferasa/metabolismo , Dieta/etnología , Conducta Alimentaria/etnología , Frecuencia de los Genes , Haplotipos , Humanos , Cinética , Fenotipo , Conducta Predatoria , Xenobióticos/metabolismo

Asunto(s)

Estudio de Asociación del Genoma Completo/métodos , Haplotipos/genética , Repeticiones de Minisatélite/genética , Polimorfismo de Nucleótido Simple , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Humanos

RESUMEN

The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Evidence for association with tuberculosis (TB) is more consistent for class II than for class I HLA genes. TB is important among indigenous peoples in South America, not only because of its historical role in regional depopulation, but also because it is still widespread. The aim of this study was to evaluate the association of HLA class II alleles, haplotypes and genotypes and tuberculin skin test response (TST) in 76 individuals of the Aché population. Poisson Regression was employed to assess risk genotypes. DRB1*04, DQA1*03 and DQB1*03:02 were associated with TST response in this population.

Asunto(s)

Alelos , Antígeno HLA-DR4/genética , Haplotipos , Indígenas Sudamericanos , Tuberculosis/genética , Brasil , Femenino , Cadenas alfa de HLA-DQ/genética , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Humanos , Masculino , Prueba de Tuberculina

RESUMEN

SETTING: Cytokines play an important role in anti-tuberculosis immune response, combined with antigen-presenting cells and lymphocytes. Immune response gene polymorphisms have been reported to be associated with tuberculosis (TB) susceptibility in some but not all studies. OBJECTIVE: To evaluate the association of immune response genes with susceptibility to tuberculin skin test (TST) reactivity and/or TB. DESIGN: Fourteen single nucleotide polymorphisms were genotyped in 96 individuals of the Aché, a native Paraguayan population, by allelic discrimination using real-time polymerase chain reaction. Univariate and multivariate Poisson regression were employed to assess risk genotypes. RESULTS: A higher prevalence of purified protein derivative reactivity was associated with the TNF-α CCA/TCG haplotype (PR 1.298, 95%CI 1.059-1.589) and with the IL-10 AT/CC diplotype (PR 1.181, 95% CI 1.024-1.362), and the presence of the IL-8 rs4073 T allele was associated with protection against TB (PR 0.482, 95%CI 0.273-0.851). CONCLUSIONS: These results suggest that polymorphisms in genes associated with immune response are involved in TST reactivity and susceptibility to TB in the Aché population.

Asunto(s)

Interleucina-10/genética , Interleucina-8/genética , Tuberculosis/epidemiología , Factor de Necrosis Tumoral alfa/genética , Adulto , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Indígenas Sudamericanos/genética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Paraguay , Distribución de Poisson , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Regresión , Prueba de Tuberculina , Tuberculosis/genética , Tuberculosis/inmunología , Adulto Joven

RESUMEN

Native American populations generally have a higher prevalence of infectious diseases than non-Native populations and this fact can induce different pressures in their immune system. We investigated the patterns of population differentiation (FST ) of 32 polymorphisms related to adaptive immune response in four Native American populations (Aché, Guarani-Kaiowá, Guarani-Ñandeva and Kaingang), and the results were compared with the three major world population data [Yoruba of Ibadan, Nigeria (YRI), Utah residents with northern and Western Europe ancestry (CEU) and Han Chinese of Beijing, China (CHB)] available in the HapMap database. The Aché clearly differentiated from the other Amerindians, but when all Native Americans were compared with the samples of other ethnic groups the lowest difference (0.08) was found with CHB (Asians), the second lowest (0.15) with YRI (Africans) and the most marked with CEU (European-derived). The considerable intra and interethnic differences found can be explained both in terms of diverse evolutionary distances and more recent environmental pathogen exposures; and they should be appropriately considered prior to any specific public health action.

Asunto(s)

Citocinas/genética , Inmunidad Innata , Indígenas Sudamericanos , Polimorfismo de Nucleótido Simple , Dinámica Poblacional , Pueblo Asiatico , Evolución Biológica , Población Negra , Brasil/etnología , Citocinas/inmunología , Bases de Datos Genéticas , Proyecto Mapa de Haplotipos , Humanos , Antígenos de Histocompatibilidad Menor , Proteínas Nucleares/genética , Proteínas Nucleares/inmunología , Filogeografía , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 22/inmunología , Receptores de Calcitriol/genética , Receptores de Calcitriol/inmunología , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/inmunología , Población Blanca

RESUMEN

A total of 76 unrelated male patients with mild (n = 55) or moderate (n = 21) haemophilia A living in the southern Brazilian state of Rio Grande do Sul were studied by direct sequencing of all F8 26 exons, the 5' UTR and 3' UTR, intron-exon junctions and the promoter region. When no mutation was found, a multiplex ligation-dependent probe amplification analysis was performed. We identified the disease-causing mutations in 69 patients, who showed 33 different mutations: 27 missense, one small deletion, two small duplications and three splice site mutations. Seven missense and two splice site mutations were not previously reported in HAMSTeRS and were not identified in any current literature search. Nine recurrent mutations were found, one of them never described before (p.Tyr1786Phe). Haplotype analysis indicated that this mutation had originated in the Brazilian population as a single event in a common ancestor. The possible influence of these mutations in the determination of the disease was carefully considered, including bioinformatic tools. These data add to the general knowledge of the disease and can also be useful for HA diagnosis and detection of carriers in the southern Brazilian population.

Asunto(s)

Factor VIII/genética , Hemofilia A/genética , Hemofilia A/patología , Mutación , Regiones no Traducidas 3' , Regiones no Traducidas 5' , Adolescente , Adulto , Anciano , Brasil , Niño , Preescolar , Exones , Genotipo , Haplotipos , Hemofilia A/tratamiento farmacológico , Humanos , Lactante , Intrones , Masculino , Persona de Mediana Edad , Patología Molecular , Fenotipo , Adulto Joven

Asunto(s)

Factor VIII/antagonistas & inhibidores , Hemofilia A/genética , Sistema Inmunológico/metabolismo , Polimorfismo Genético , Alelos , Brasil , Antígeno CTLA-4/genética , Antígenos HLA-G/genética , Hemofilia A/inmunología , Humanos , Interleucina-10/genética , Interleucina-4/genética , Oportunidad Relativa , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Receptores de Interleucina-4/genética , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/genética

RESUMEN

Habitat fragmentation may disrupt original patterns of gene flow and lead to drift-induced differentiation among local population units. Top predators such as the jaguar may be particularly susceptible to this effect, given their low population densities, leading to small effective sizes in local fragments. On the other hand, the jaguar's high dispersal capabilities and relatively long generation time might counteract this process, slowing the effect of drift on local populations over the time frame of decades or centuries. In this study, we have addressed this issue by investigating the genetic structure of jaguars in a recently fragmented Atlantic Forest region, aiming to test whether loss of diversity and differentiation among local populations are detectable, and whether they can be attributed to the recent effect of drift. We used 13 microsatellite loci to characterize the genetic diversity present in four remnant populations, and observed marked differentiation among them, with evidence of recent allelic loss in local areas. Although some migrant and admixed individuals were identified, our results indicate that recent large-scale habitat removal and fragmentation among these areas has been sufficiently strong to promote differentiation induced by drift and loss of alleles at each site. Low estimated effective sizes supported the inference that genetic drift could have caused this effect within a short time frame. These results indicate that jaguars' ability to effectively disperse across the human-dominated landscapes that separate the fragments is currently very limited, and that each fragment contains a small, isolated population that is already suffering from the effects of genetic drift.

Asunto(s)

Ecosistema , Estructuras Genéticas , Genética de Población , Panthera/genética , Árboles/genética , Animales , Brasil , Flujo Genético , Variación Genética , Humanos , Repeticiones de Microsatélite , Familia de Multigenes

RESUMEN

After a brief introduction about present approaches in evolutionary thinking and systems biology, I present a review about the most recent research of our group, with special reference to the genomics of Amerindians. This information was integrated with the present knowledge and concepts in this area. Human microevolutionary approaches are faced with special challenges, and proper interpretation demands the consideration of our unique specificity: culture.

Asunto(s)

Evolución Biológica , Indígenas Norteamericanos/genética , Emigración e Inmigración , Genómica , Humanos

Asunto(s)

Perros/anatomía & histología , Perros/genética , Cabeza/anatomía & histología , Proteínas Nucleares/genética , Alelos , Animales , ADN/química , ADN/genética , Reacción en Cadena de la Polimerasa/veterinaria , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple

RESUMEN

A total of 107 unrelated severe haemophilia A patients living in the southern Brazilian state of Rio Grande do Sul were studied in relation to the prevalence of inversions present in introns 22 and 1 and a subsample of them (95) tested for the presence of Factor VIII inhibitors. These data were then incorporated with those from 15 other countries and 3871 patients. The frequencies of these two inversions show a remarkable homogeneity in series collected in different continents, from people with diverse ethnic extraction. The prevalence of inhibitors among patients with inversion 22, on the other hand, varies widely (5-51%; seven countries, 1482 patients), the value observed by us being the highest. The importance of obtaining data from patients throughout the world to clarify the aetiology of this important complicating factor in the therapeutics of the disease is emphasized.

Asunto(s)

Inversión Cromosómica , Factor VIII/inmunología , Hemofilia A/genética , Isoanticuerpos/sangre , Adolescente , Adulto , Niño , Hemofilia A/inmunología , Humanos , Intrones/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Factores de Riesgo , Adulto Joven

RESUMEN

Blood samples collected in four Amerindian French Guiana populations (Palikur, Emerillon, Wayampi and Kali'na) in the early 1980s were screened for selected mtDNA and Y-chromosome length polymorphisms, and sequenced for the mtDNA hypervariable segment I (HVS-I). In addition, two other Amerindian populations (Apalaí and Matsiguenga) were examined for the same markers to establish the genetic relationships in the area. Strong dissimilarities were observed in the distribution of the founding Amerindian haplogroups, and significant p-values were obtained from F(ST) genetic distances. Interpopulation similarities occurred mainly due to geography. The Palikur did not show obvious genetic similarity to the Matsiguenga, who speak the same language and live in a region from where they could have migrated to French Guiana. The African-origin admixture observed in the Kali'na probably derives from historical contacts they had with the Bushinengue (Noir Marron), a group of escaped slaves who now lead independent lives in a nearby region. This analysis has identified significant clues about the Amerindian peopling of the North-East Amazonian region.

Asunto(s)

Cromosomas Humanos Y , ADN Mitocondrial/genética , Genética de Población , Indígenas Sudamericanos/genética , Polimorfismo Genético , Secuencia de Bases , Emigración e Inmigración , Guyana Francesa , Marcadores Genéticos , Geografía , Haplotipos , Humanos , Indígenas Sudamericanos/clasificación , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Secuencia de ADN

RESUMEN

The frequencies of the deltaF508 deletion, the most common cystic fibrosis mutation in Europeans and European-derived populations, and the XV2C and KM19 restriction fragment length polymorphisms that are tightly linked to the CFTR locus vary among populations. To determine the distribution of these extragenic markers and of the deltaF508 mutation, we analyzed 326 chromosomes of individuals from two South American Indian populations, the Guarani and the Kaingang. The allele and haplotype frequencies differed greatly between the two populations as well as among Amerindians and normal European Brazilians and European Brazilian cystic fibrosis patients. The absence of the deltaF508 mutation and the B haplotype are in agreement with the hypothesis that the deltaF508 mutation occurred after the divergence of these two populations. This finding is useful for populations containing a large Amerindian component and helps us to understand the origins of the deltaF508 deletion, the most common cystic fibrosis mutation in Europeans and European-derived populations, as well as the different incidences of cystic fibrosis in continental groups.

Asunto(s)

Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/genética , Frecuencia de los Genes , Genética de Población/métodos , Haplotipos/genética , Indígenas Sudamericanos/genética , Mutación , Brasil , Humanos , Polimorfismo de Longitud del Fragmento de Restricción

RESUMEN

A total of 1558 base pairs in the 16p13.3 region were investigated in 98 individuals of Mongolian, Northern Arctic and Amerindian affiliation, and the results compared with those obtained in a previous worldwide study of the same genomic region. Fifty-five polymorphic sites could be classified into thirty-five haplotypes from the total data. A median joining network based on the haplotypes revealed two distinct clusters: one with low diversity, with haplotypes found in all five geographic-ethnic categories; while the other, with the most divergent haplotypes, was composed mainly of Africans and a few Amerindians. Almost all neutrality parameters yielded significantly negative values. Demographic simulations with the exclusively Amerindian dataset rejected all scenarios, including a bottleneck beginning more than 12,000 years ago. The demographic scenarios tested considering population growth were similar among the Amerindian and worldwide or Eurasian data sets. The results suggest that Amerindians are a representative sample of Eurasian populations, preserving the signal of demographic growth from the out of Africa exodus and, together with data from uniparental markers, support a scenario of a bottleneck of moderate intensity during the peopling of the New World.

Asunto(s)

Indio Americano o Nativo de Alaska/genética , Cromosomas Humanos Par 16/genética , Variación Genética , Pueblo Asiatico/genética , Emigración e Inmigración , Etnicidad/genética , Haplotipos , Humanos

RESUMEN

The geographical distribution, ecological characteristics, flowering and fruiting times, and pollinating agents of Passiflora alata are considered and related to molecular genetic data gathered simultaneously. The first report on this species in Rio Grande do Sul was made in 1934, only in cultivated gardens. Approximately 20 years later, however, the species was already classified as efferata (wild) in Porto Alegre's suburbs. The data presented here, together with the DNA investigations, indicate that P. alata is actively colonizing previously unoccupied areas of this region.

Asunto(s)

Ecosistema , Evolución Molecular , Passiflora/fisiología , Adaptación Fisiológica , Brasil , Humanos , Passiflora/genética , Passiflora/crecimiento & desarrollo , Dinámica Poblacional , Estaciones del Año

RESUMEN

The geographical distribution, ecological characteristics, flowering and fruiting times, and pollinating agents of Passiflora alata are considered and related to molecular genetic data gathered simultaneously. The first report on this species in Rio Grande do Sul was made in 1934, only in cultivated gardens. Approximately 20 years later, however, the species was already classified as efferata (wild) in Porto Alegre's suburbs. The data presented here, together with the DNA investigations, indicate that P. alata is actively colonizing previously unoccupied areas of this region.

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A distribuição geográfica, as características ecológicas, as épocas de florescimento e frutificação, e os agentes polinizadores de Passiflora alata são considerados e relacionados a estudos genético-moleculares desenvolvidos simultaneamente. O primeiro registro da espécie no Rio Grande do Sul foi feito em 1934, apenas em área cultivada. Cerca de 20 anos depois, no entanto, a espécie já era classificada como efferata (selvagem) nos subúrbios de Porto Alegre. Os dados aqui apresentados, junto com as investigações de DNA, indicam que P. alata está colonizando ativamente áreas previamente não ocupadas desta região.

Asunto(s)

Humanos , Ecosistema , Evolución Molecular , Passiflora/fisiología , Adaptación Fisiológica , Brasil , Dinámica Poblacional , Passiflora/genética , Passiflora/crecimiento & desarrollo , Estaciones del Año

RESUMEN

A sample of 103 randomly chosen healthy individuals from Alegrete, RS, Brazil, was tested for the CCR5delta32 allele, which is known to influence susceptibility to HIV-1 infection. The CCR5delta32 allele was identified by PCR amplification using specific primers flanking the region of deletion, followed by electrophoresis on a 3 percent agarose gel. The data obtained were compared to those reported for other populations and interpreted in terms of Brazilian history. The individuals studied came from a highly admixed population. Most of them were identified as white (N = 59), while blacks and browns (mulattoes) were N = 13 and N = 31, respectively. The observed frequencies, considering the white, black and brown samples (6.8, 3.8, and 6.4 percent, respectively), suggest an important European parental contribution, even in populations identified as black and brown. However, in Brazil as a whole, this allele shows gradients indicating a relatively good correlation with the classification based on skin color and other physical traits, used here to define major Brazilian population groups.

Asunto(s)

Humanos , Alelos , Frecuencia de los Genes/genética , /genética , Población Negra/genética , Brasil/etnología , Electroforesis en Gel de Agar , Población Blanca/genética , Genotipo , Genética de Población/métodos , Indígenas Sudamericanos/genética , Reacción en Cadena de la Polimerasa