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

Author(s)

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]

Affiliation

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

^[2] Neogen, Indaiatuba - Brazil

• Document type: Journal article
• Source: ANNALS OF HUMAN GENETICS; v. 85, n. 1 AUG 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 16/04785-0 - Study of somatic mutations identified in exome sequencing of hepatoblastoma
• Grantee: Talita Ferreira Marques Aguiar
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/17132-0 - Use of Next Generation Sequencing to study karyotypes with different number of X chromosome
• Grantee: Darine Christina Maia Villela
• Support Opportunities: Scholarships in Brazil - Post-Doctoral