Genomic Investigation of Balanced Chromosomal Rearrangements in Patients with Abnormal Phenotypes

Author(s)

Simioni, Milena ; Artiguenave, Francois ; Meyer, Vincent ; Sgardioli, Ilaria C. ; Viguetti-Campos, Nilma L. ; Monlleo, Isabella Lopes ; Maciel-Guerra, Andrea T. ; Steiner, Carlos E. ; Gil-da-Silva-Lopes, Vera L.

• Document type: Journal article
• Source: MOLECULAR SYNDROMOLOGY; v. 8, n. 4, p. 187-194, 2017.
• Web of Science Citations: 1

Abstract

Balanced chromosomal rearrangements (BCR) are associated with abnormal phenotypes in approximately 6% of balanced translocations and 9.4% of balanced inversions. Abnormal phenotypes can be caused by disruption of genes at the breakpoints, deletions, or positional effects. Conventional cytogenetic techniques have a limited resolution and do not enable a thorough genetic investigation. Molecular techniques applied to BCR carriers can contribute to the characterization of this type of chromosomal rearrangement and to the phenotype-genotype correlation. Fifteen individuals among 35 with abnormal phenotypes and BCR were selected for further investigation by molecular techniques. Chromosomal rearrangements involved 11 reciprocal translocations, 3 inversions, and 1 balanced insertion. Array genomic hybridization (AGH) was performed and genomic imbalances were detected in 20% of the cases, 1 at a rearrangement breakpoint and 2 further breakpoints in other chromosomes. Alterations were further confirmed by FISH and associated with the phenotype of the carriers. In the analyzed cases not showing genomic imbalances by AGH, next-generation sequencing (NGS), using whole genome libraries, prepared following the Illumina TruSeq DNA PCRFree protocol (Illumina((R))) and then sequenced on an Illumina HiSEQ 2000 as 150-bp paired-end reads, was done. The NGS results suggested breakpoints in 7 cases that were similar or near those estimated by karyotyping. The genes overlapping 6 breakpoint regions were analyzed. Follow-up of BCR carriers would improve the knowledge about these chromosomal rearrangements and their consequences. (C) 2017 S. Karger AG, Basel (AU)

• FAPESP's process: 11/23794-7 - Investigative approach in cleft lip and palate and congenital cadiopathy related to 22q11.2 deletion syndrome using open array and aGH techniques
• Grantee: Vera Lúcia Gil da Silva Lopes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/10071-0 - Genomic study of apparently balanced chromosomal rearrangements in individuals with abnormal phenotype
• Grantee: Milena Simioni de Carvalho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral