RESUMO
Brazilian quilombos are communities formed by enslaved Africans and their descendants all over the country during slavery and shortly after its abolition. Quilombos harbor a great fraction of the largely unknown genetic diversity of the African diaspora in Brazil. Thus, genetic studies in quilombos have the potential to provide important insights not only into the African roots of the Brazilian population but also into the genetic bases of complex traits and human adaptation to diverse environments. This review summarizes the main results of genetic studies performed on quilombos so far. Here, we analyzed the patterns of African, Amerindian, European, and subcontinental ancestry (within Africa) of quilombos from the five different geographic regions of Brazil. In addition, uniparental markers (from the mtDNA and the Y chromosome) studies are analyzed together to reveal demographic processes and sex-biased admixture that occurred during the formation of these unique populations. Lastly, the prevalence of known malaria-adaptive African mutations and other African-specific variants discovered in quilombos, as well as the genetic bases of health-related traits, are discussed here, together with their implication for the health of populations of African descent.
Assuntos
Aclimatação , População Africana , Nível de Saúde , Humanos , População Africana/genética , Brasil , DNA Mitocondrial , MitocôndriasAssuntos
Anemia Falciforme/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Úlcera da Perna/genética , Proteínas S100/genética , Adulto , Brasil , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Proteínas Filagrinas , Genótipo , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Sequenciamento do Exoma/métodosRESUMO
Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value < 1e-07), representing a 2.369-fold higher risk factor for the disease. Both the AA and AG genotypes were observed more frequently in the age-related macular degeneration group compared to the control group (p = 1.21e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.
Assuntos
Atrofia Geográfica/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Polimorfismo de Nucleotídeo Único , Degeneração Macular Exsudativa/genética , Idoso , Brasil/epidemiologia , Estudos de Casos e Controles , Cromossomos Humanos Par 10/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Atrofia Geográfica/etnologia , Humanos , Masculino , Reação em Cadeia da Polimerase , Degeneração Macular Exsudativa/etnologiaRESUMO
Whole-exome sequencing identified multiple genetic causes in 2 infants with heterogeneous disease. Three gene defects in the first patient explained all symptoms, but manifestations were overlapping (blended phenotype). Two gene defects in the second patient explained nonoverlapping symptoms (composite phenotype). Whole-exome sequencing rapidly and comprehensively resolves heterogeneous genetic disease.
Assuntos
Anormalidades Congênitas/genética , Doenças Genéticas Inatas/diagnóstico , Mutação , Análise de Sequência de DNA/métodos , Amidoidrolases/genética , Hidrolases de Éster Carboxílico/genética , Anormalidades Congênitas/diagnóstico , Exoma/genética , Testes Genéticos/métodos , Genômica , Genótipo , Humanos , Lactente , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos , Testes de Mutagenicidade , Fenótipo , Receptores de Peptídeos/genética , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Introduction: In spite nearly 40% of the variability in blood pressure can be explained by genetic factors, the identification of genes associated to essential high blood pressure is difficult in populations where individuals have different genetic precedents; in these circumstances it is necessary to determinate whether the population is sub-structured because this can bias studies associated with this disease.Objectives: To determine the genetic structure of the population in Bucaramanga from genetic polymorphisms associated with the regulation of blood pressure: 448G>T, 679C>T y 1711C>T from the gene kinase 4 of the dopaminergic receptor linked to the protein G and Glu298Asp, -786T>C and the VNTR of the intron 4 of the gene of endothelial nitric oxide.Methodology: A sample of 552 unrelated individuals was studied through analysis of Restriction fragment length polymorphism. The allelic, haplotypic and genotypic frequencies were calculated, the Hardy-Weinberg equilibrium was determined and a molecular analysis of variance was performed to determine the genetic structure.Results: 38 Haplotypes were identified, with GCCTG4b as the most frequent (21.2%). The most diverse polymorphism was 448G>T with a frequency of 49.9% for heterozygous. The six polymorphisms were found in genetic equilibrium and genetic structure of populations was not evidenced (FST = 0,0038).Conclusion: The population studied does not present a genetic sub-structure and the polymorphisms analyzed were found in genetic equilibrium, this indicates that the population mixes randomly and there are no sub-groups capable of affecting the results of the association studies