Dataset Information

Copy number variation (CNV) identification, interpretation, and database from Brazilian patients.

ABSTRACT: Copy number variations (CNVs) constitute an important class of variation in the human genome and the interpretation of their pathogenicity considering different frequencies across populations is still a challenge for geneticists. Since the CNV databases are predominantly composed of European and non-admixed individuals, and Brazilian genetic constitution is admixed and ethnically diverse, diagnostic screenings on Brazilian variants are greatly difficulted by the lack of populational references. We analyzed a clinical sample of 268 Brazilian individuals, including patients with neurodevelopment disorders and/or congenital malformations. The pathogenicity of CNVs was classified according to their gene content and overlap with known benign and pathogenic variants. A total of 1,504 autosomal CNVs (1,207 gains and 297 losses) were classified as benign (92.9%), likely benign (1.6%), VUS (2.6%), likely pathogenic (0.2%) and pathogenic (2.7%). Some of the CNVs were recurrent and with frequency increased in our sample, when compared to populational open resources of structural variants: 14q32.33, 22q11.22, 1q21.1, and 1p36.32 gains. Thus, these highly recurrent CNVs classified as likely benign or VUS were considered non-pathogenic in our Brazilian sample. This study shows the relevance of introducing CNV data from diverse cohorts to improve on the interpretation of clinical impact of genomic variations.

SUBMITTER: Godoy VCSM

PROVIDER: S-EPMC7783508 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Copy number variation (CNV) identification, interpretation, and database from Brazilian patients.

Godoy Victória Cabral Silveira Monteiro de VCSM Bellucco Fernanda Teixeira FT Colovati Mileny M Oliveira-Junior Hélio Rodrigues de HR Moysés-Oliveira Mariana M Melaragno Maria Isabel MI

Genetics and molecular biology 20201113 4

Copy number variations (CNVs) constitute an important class of variation in the human genome and the interpretation of their pathogenicity considering different frequencies across populations is still a challenge for geneticists. Since the CNV databases are predominantly composed of European and non-admixed individuals, and Brazilian genetic constitution is admixed and ethnically diverse, diagnostic screenings on Brazilian variants are greatly difficulted by the lack of populational references. ...[more]

PMID: 33306777

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Project description:BackgroundArray-based detection of copy number variations (CNVs) is widely used for identifying disease-specific genetic variations. However, the accuracy of CNV detection is not sufficient and results differ depending on the detection programs used and their parameters. In this study, we evaluated five widely used CNV detection programs, Birdsuite (mainly consisting of the Birdseye and Canary modules), Birdseye (part of Birdsuite), PennCNV, CGHseg, and DNAcopy from the viewpoint of performance on the Affymetrix platform using HapMap data and other experimental data. Furthermore, we identified CNVs of 180 healthy Japanese individuals using parameters that showed the best performance in the HapMap data and investigated their characteristics.ResultsThe results indicate that Hidden Markov model-based programs PennCNV and Birdseye (part of Birdsuite), or Birdsuite show better detection performance than other programs when the high reproducibility rates of the same individuals and the low Mendelian inconsistencies are considered. Furthermore, when rates of overlap with other experimental results were taken into account, Birdsuite showed the best performance from the view point of sensitivity but was expected to include many false negatives and some false positives. The results of 180 healthy Japanese demonstrate that the ratio containing repeat sequences, not only segmental repeats but also long interspersed nuclear element (LINE) sequences both in the start and end regions of the CNVs, is higher in CNVs that are commonly detected among multiple individuals than that in randomly selected regions, and the conservation score based on primates is lower in these regions than in randomly selected regions. Similar tendencies were observed in HapMap data and other experimental data.ConclusionsOur results suggest that not only segmental repeats but also interspersed repeats, especially LINE sequences, are deeply involved in CNVs, particularly in common CNV formations.The detected CNVs are stored in the CNV repository database newly constructed by the "Japanese integrated database project" for sharing data among researchers. http://gwas.lifesciencedb.jp/cgi-bin/cnvdb/cnv_top.cgi.

Dataset Information

Copy number variation (CNV) identification, interpretation, and database from Brazilian patients.

Publications

Copy number variation (CNV) identification, interpretation, and database from Brazilian patients.

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