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Detection of mosaicism for segmental and whole chromosome imbalances by targeted sequencing
Author(s) -
Villela Darine,
Barros Juliana Sobral,
da Costa Silvia Souza,
Aguiar Talita F. M.,
Campagnari Francine,
ViannaMorgante Angela M.,
Krepischi Ana C. V.,
Rosenberg Carla
Publication year - 2021
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12402
Subject(s) - copy number variation , biology , genetics , chromosome , microarray , computational biology , comparative genomic hybridization , copy number analysis , whole genome sequencing , genome , gene , gene expression
Mosaic segmental and whole chromosome copy number alterations are postzygotic variations known to be associated with several disorders. We have previously presented an efficient targeted sequencing approach to simultaneously detect point mutations and copy number variations (CNVs). In this study, we evaluated the efficiency of this approach to detect mosaic CNVs, using seven postnatal and 19 tumor samples, previously characterized by chromosomal microarray analyses (CMA). These samples harbored a total of 28 genomic imbalances ranging in size from 0.68 to 171 Mb, and present in 10–80% of the cells. All CNV regions covered by the platform were correctly identified in postnatal samples, and only seven out of 19 CNVs from tumor samples were not identified either because of a lack of target probes in the affected genomic regions or an absence of minimum reads for an alteration call. These results demonstrate that, in a research setting, this is a robust approach for detecting mosaicism in cases of segmental and whole chromosome alterations. Although the current sequencing platform presented a resolution similar to genomic microarrays, it is still necessary to further validate this approach in a clinical setting in order to replace CMA and sequencing analyses by a single test.