Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil
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Published:2022-03-04
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Naslavsky Michel S.ORCID, Scliar Marilia O., Yamamoto Guilherme L., Wang Jaqueline Yu Ting, Zverinova StepankaORCID, Karp Tatiana, Nunes Kelly, Ceroni José Ricardo Magliocco, de Carvalho Diego LimaORCID, da Silva Simões Carlos Eduardo, Bozoklian Daniel, Nonaka Ricardo, dos Santos Brito Silva Nayane, da Silva Souza Andreia, de Souza Andrade HeloísaORCID, Passos Marília Rodrigues Silva, Castro Camila Ferreira Bannwart, Mendes-Junior Celso T.ORCID, Mercuri Rafael L. V., Miller Thiago L. A., Buzzo Jose Leonel, Rego Fernanda O., Araújo Nathalia M., Magalhães Wagner C. S., Mingroni-Netto Regina Célia, Borda Victor, Guio Heinner, Rojas Carlos P., Sanchez Cesar, Caceres OmarORCID, Dean MichaelORCID, Barreto Mauricio L., Lima-Costa Maria Fernanda, Horta Bernardo L.ORCID, Tarazona-Santos Eduardo, Meyer Diogo, Galante Pedro A. F.ORCID, Guryev VictorORCID, Castelli Erick C., Duarte Yeda A. O., Passos-Bueno Maria Rita, Zatz Mayana
Abstract
AbstractAs 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.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences 1) Brazilian Ministry of Health – MoH/Brazil National Programme of Genomic and Precision Health – Genomes Brazil. 2) Rede Mineira de Genomica Populacional e Medicina de Precisão
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference78 articles.
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