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The Brazilian Rare Genomes Project: Validation of Whole Genome Sequencing for Rare Diseases Diagnosis

Authors :
Antonio Victor Campos Coelho
Bruna Mascaro-Cordeiro
Danielle Ribeiro Lucon
Maria Soares Nóbrega
Rodrigo de Souza Reis
Rodrigo Bertollo de Alexandre
Livia Maria Silva Moura
Gustavo Santos de Oliveira
Rafael Lucas Muniz Guedes
Marcel Pinheiro Caraciolo
Nuria Bengala Zurro
Murilo Castro Cervato
João Bosco Oliveira
Source :
Frontiers in Molecular Biosciences, Vol 9 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Rare diseases affect up to 13.2 million individuals in Brazil. The Brazilian Rare Genomes Project is envisioned to further the implementation of genomic medicine into the Brazilian public healthcare system. Here we report the validation results of a whole genome sequencing (WGS) procedure for implementation in clinical laboratories. In addition, we report data quality for the first 1,200 real-world patients sequenced. We sequenced a well-characterized group of 76 samples, including seven gold standard genomes, using a PCR-free WGS protocol on Illumina Novaseq 6,000 equipment. We compared the observed variant calls with their expected calls, observing good concordance for single nucleotide variants (SNVs; mean F-measure = 99.82%) and indels (mean F-measure = 99.57%). Copy number variants and structural variants events detection performances were as expected (F-measures 96.6% and 90.3%, respectively). Our WGS protocol presented excellent intra-assay reproducibility (coefficients of variation ranging between 0.03% and 0.20%) and inter-assay reproducibility (coefficients of variation ranging between 0.02% and 0.09%). Limitations of the WGS protocol include the inability to confidently detect variants such as uniparental disomy, balanced translocations, repeat expansion variants, and low-level mosaicism. In summary, the observed performance of the WGS protocol was in accordance with that seen in the best centers worldwide. The Rare Genomes Project is an important initiative to bring pivotal improvements to the quality of life of the affected individuals.

Details

Language :
English
ISSN :
2296889X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
Frontiers in Molecular Biosciences
Publication Type :
Academic Journal
Accession number :
edsdoj.5119c6c2b3948508f5dfa34f830ae7b
Document Type :
article
Full Text :
https://doi.org/10.3389/fmolb.2022.821582