Mapping of DNA break points and investigation of the mechanisms associated with genomic rearrangements using next generation sequencing.

Abstract

Genomic rearrangements are considered disturbances on DNA structure that cause structural variation associated with a broad range of genetic diseases. Although several factors that mediate genomic rearrangements are now known, there are still many unanswered questions. These rearrangements are due to several known mechanisms, recurrent or not, or also from a single molecular catastrophic event. Each mechanism generates a unique assignment in base pairs next to the breakpoint site. To identify these mechanisms, it is necessary the sequencing of the specific region. The breakpoint analysis of genomic rearrangements can provide important information, leading to a comprehension of the genomic architecture and its role in generating structural abnormalities. These studies are essential for understanding the way which DNA is repaired, which occasion this occurs, what are the consequences to individual health and to elucidate the evolutionary chromosomic differences. In this study, our aim is to sequence the genomic breakpoints in order to identify the mechanisms for formation of the alterations found. We will sequence the breakpoints of samples of 15 patients with clinical phenotype and structural genomic rearrangements by next-generation sequencing (NGS, MiSeq - Illumina). We expect to find genomic elements that allow us to identify the mechanisms for formation in order to better comprehension of the genome repair processes and disease consequences. (AU)