Detection of mosaicism for segmental and whole chromosome imbalances by targeted sequencing

Autor(es)

Villela, Darine ^[1] ; de Barros, Juliana Sobral ^[1] ; da Costa, Silvia Souza ^[1] ; Aguiar, Talita F. M. ^[1] ; Campagnari, Francine ^[2] ; Vianna-Morgante, Angela M. ^[1] ; Krepischi, Ana C. V. ^[1] ; Rosenberg, Carla ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Human Genome & Stem Cell Res Ctr, Sao Paulo - Brazil

^[2] Neogen, Indaiatuba - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ANNALS OF HUMAN GENETICS; v. 85, n. 1 AUG 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 16/04785-0 - Estudo de mutações somáticas identificadas em sequenciamento de exoma de hepatoblastoma
• Beneficiário: Talita Ferreira Marques Aguiar
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/17132-0 - Uso de Next Generation Sequencing na avaliação de cariótipos com número variável de cópias do cromossomo X
• Beneficiário: Darine Christina Maia Villela
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado