1. Genomic Investigation of Balanced Chromosomal Rearrangements in Patients with Abnormal Phenotypes
- Author
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François Artiguenave, Vera Lúcia Gil-da-Silva-Lopes, Andréa Trevas Maciel-Guerra, Isabella Lopes Monlleó, Ilária Cristina Sgardioli, Carlos Eduardo Steiner, Vincent Meyer, Milena Simioni, and Nilma Lúcia Viguetti-Campos
- Subjects
0301 basic medicine ,Genetics ,Breakpoint ,breakpoint cluster region ,Chromosomal translocation ,Karyotype ,Chromosomal rearrangement ,Biology ,Genome ,DNA sequencing ,03 medical and health sciences ,030104 developmental biology ,Original Article ,Gene ,Genetics (clinical) - 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 PCR-Free protocol (Illumina®) 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.
- Published
- 2017