Title
Whole-genome sequencing of 1,171 elderly admixed individuals from São Paulo, Brazil
Date Issued
2022
Access level
open access
Resource Type
journal article
Author(s)
Naslavsky M.S.
Scliar M.O.
Yamamoto G.L.
Wang J.Y.T.
Zverinova S.
Karp T.
Nunes K.
Ceroni J.R.M.
de Carvalho D.L.
da Silva Simões C.E.
Bozoklian D.
Nonaka R.
dos Santos Brito Silva N.
da Silva Souza A.
de Souza Andrade H.
Passos M.R.S.
Castro C.F.B.
Mendes-Junior C.T.
Mercuri R.L.V.
Miller T.L.A.
Buzzo J.L.
Rego F.O.
Araújo N.M.
Magalhães W.C.S.
Mingroni-Netto R.C.
Dean M.
Barreto M.L.
Lima-Costa M.F.
Horta B.L.
Meyer D.
Galante P.A.F.
Guryev V.
Castelli E.C.
Duarte Y.A.O.
Passos-Bueno M.R.
Zatz M.
Publisher(s)
Nature Research
Abstract
As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.
Volume
13
Issue
1
Language
English
OCDE Knowledge area
Demografía Geriatría, Gerontología
Scopus EID
2-s2.0-85125792333
PubMed ID
Source
Nature Communications
ISSN of the container
2041-1723
Sponsor(s)
We acknowledge SABE participants for their long-term contribution and Prof. Maria Lúcia Lebrão (in memoriam) for her conceptualization and conduction of SABE. Funding was provided by FAPESP grants and fellowships (CEPID 2013/08028-1, SABE 2014/50649-6, INCT 2014//50931-3, 2013/17084-2, 2017/19223-0, 2012/24731-1, 2018/15579-8, 2015/25020-0, 2020/02413-4) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq INCT 465355/2014-5). S.Z. and V.G. were supported by ALW Open grant ALWOP.662, financed by the Dutch Research Council (NWO). K.N. and D.M. were supported by United States National Institutes of Health—NIH (R01 GM075091). E.T-S group is funded by the Brazilian Ministry of Health—MoH/Brazil National Programme of Genomic and Precision Health—Genomes Brazil and Rede Mineira de Genomica Populacional e Medicina de Precisão (FAPEMIG). We thank the Human Longevity Inc. team that supported and conducted whole-genome sequencing. We acknowledge the staff from HUG-CELL and USP Public Health School. This study makes use of data generated by the Peruvian Genome Diversity Project (OI003-11 and OI-087-13) of the Peruvian National Institute of Health (data provided by C.P.R., C.S., and O.C.).
Sources of information: Directorio de Producción Científica Scopus