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Hum Mutat. 2017 Jul;38(7):751-763. doi: 10.1002/humu.23220. Epub 2017 May 3.

Exomic variants of an elderly cohort of Brazilians in the ABraOM database.

Author information

1
Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
2
Hospital Israelita Albert Einstein, São Paulo, Brazil.
3
Department of Clinical Genetics, Children's Hospital, Medical School, University of São Paulo, São Paulo, Brazil.
4
Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts.
5
Laboratório de Estudos em Antropologia Biológica, Bioarqueologia e Evolução Humana, Instituto de Ciências Humanas e da Informação, Universidade Federal do Rio Grande, Rio Grande, Rio Grande de Sul, Brazil.
6
Radiology Institute, Medical School, University of São Paulo, São Paulo, Brazil.
7
Department of Epidemiology, Public Health School, University of São Paulo, São Paulo, Brazil.
8
School of Nursing, University of São Paulo, São Paulo, Brazil.

Abstract

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.

KEYWORDS:

admixture; aging; pathogenicity interpretation; population genetics; variant database

PMID:
28332257
DOI:
10.1002/humu.23220
[Indexed for MEDLINE]

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