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1.
Hum Mutat ; 38(7): 751-763, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28332257

RESUMO

Brazilians are highly admixed with ancestry from Europe, Africa, America, and Asia and yet still underrepresented in genomic databanks. We hereby present a collection of exomic variants from 609 elderly Brazilians in a census-based cohort (SABE609) with comprehensive phenotyping. Variants were deposited in ABraOM (Online Archive of Brazilian Mutations), a Web-based public database. Population representative phenotype and genotype repositories are essential for variant interpretation through allele frequency filtering; since elderly individuals are less likely to harbor pathogenic mutations for early- and adult-onset diseases, such variant databases are of great interest. Among the over 2.3 million variants from the present cohort, 1,282,008 were high-confidence calls. Importantly, 207,621 variants were absent from major public databases. We found 9,791 potential loss-of-function variants with about 300 mutations per individual. Pathogenic variants on clinically relevant genes (ACMG) were observed in 1.15% of the individuals and were correlated with clinical phenotype. We conducted incidence estimation for prevalent recessive disorders based upon heterozygous frequency and concluded that it relies on appropriate pathogenicity assertion. These observations illustrate the relevance of collecting demographic data from diverse, poorly characterized populations. Census-based datasets of aged individuals with comprehensive phenotyping are an invaluable resource toward the improved understanding of variant pathogenicity.


Assuntos
Exoma , Genética Populacional , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Alelos , Brasil , Estudos de Coortes , Biologia Computacional , Bases de Dados Genéticas , Etnicidade , Feminino , Frequência do Gene , Variação Genética , Genótipo , Heterozigoto , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo
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