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

• Grant number: 16/09452-0
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2017
• End date: June 30, 2019
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Leslie Domenici Kulikowski
• Grantee: Leslie Domenici Kulikowski
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Chong Ae Kim ; Edmar Zanoteli ; Maria Isabel de Souza Aranha Melaragno

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)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CHEHIMI, SAMAR N.; ZANARDO, EVELIN A.; CERONI, JOSE R. M.; NASCIMENTO, AMOM M.; MADIA, FABRICIA A. R.; DIAS, ALEXANDRE T.; FILHO, GIL M. N.; MONTENEGRO, MARLIA M.; DAMASCENO, JULLIAN; COSTA, THAS V. M. M.; et al. Breakpoint delineation in 5p- patients leads to new insights about microcephaly and the typical high-pitched cry. MOLECULAR GENETICS & GENOMIC MEDICINE, SEP 2019. (16/09452-0)

NOVO-FILHO, GIL M.; CARVALHO, GLEYSON F. S.; NASCIMENTO, AMOM M.; MONTENEGRO, MARILIA M.; DAMASCENO, JULLIAN G.; ZANARDO, EVELIN A.; CHEHIMI, SAMAR N.; OLIVEIRA, YANCA G.; DIAS, ALEXANDRE T.; KIM, CHONG A.; et al. Identifying NAHR mechanism between two distinct Alu elements through breakpoint junction mapping by NGS. META GENE, v. 24, JUN 2020. (16/09452-0)

GASPARINI, YANCA; MONTENEGRO, MARILIA M.; NOVO-FILHO, GIL M.; CERONI, JOSE R. M.; HONJO, RACHEL S.; ZANARDO, EVELIN A.; DIAS, ALEXANDRE T.; NASCIMENTO, AMOM M.; COSTA, THAIS V. M. M.; MADIA, FABRICIA A.; et al. Mosaic Trisomy 12 Associated with Overgrowth Detected in Fibroblast Cell Lines. Cytogenetic and Genome Research, v. 157, n. 3, p. 153-157, 2019. (16/09452-0, 16/19360-5)

NOVO FILHO, G. M.; DIAS, A. T.; NASCIMENTO, A. M.; DAMASCENO, J. G.; ZANARDO, E. A.; CHEHIMI, S. N.; MADIA, F. A. R.; AKL, O. S.; MONTENEGRO, M. M.; OLIVEIRA, Y. G.; et al. Multi-gene panel testing improves diagnosis in Brazilian patients with Early-Onset Epilepsy. European Journal of Human Genetics, v. 27, p. 2-pg., 2019-07-01. (16/09452-0)

CHEHIMI, SAMAR N.; ZANARDO, EVELIN A.; CERONI, JOSE R. M.; NASCIMENTO, AMOM M.; MADIA, FABRICIA A. R.; DIAS, ALEXANDRE T.; FILHO, GIL M. N.; MONTENEGRO, MARLIA M.; DAMASCENO, JULLIAN; COSTA, THAS V. M. M.; et al. Breakpoint delineation in 5p- patients leads to new insights about microcephaly and the typical high-pitched cry. MOLECULAR GENETICS & GENOMIC MEDICINE, v. 8, n. 2, p. 8-pg., 2019-09-30. (16/09452-0)

CHEHIMI, S. N.; ZANARDO, E. A.; MADIA, F. A. R.; DIAS, A. T.; NOVO-FILHO, G. M.; MONTENEGRO, M. M.; NASCIMENTO, A. M.; DAMASCENO, J. G.; OLIVEIRA, Y. G.; VIEIRA, L. L.; et al. Repetitive elements associated with breakpoints of distal 5p deletions suggest mechanisms mediating these rearrangements. European Journal of Human Genetics, v. 27, p. 1-pg., 2019-07-01. (16/09452-0)

CHEHIMI, SAMAR NASSER; ALMEIDA, VANESSA TAVARES; NASCIMENTO, AMOM MENDES; ZANARDO, EVELIN ALINE; DE OLIVEIRA, YANCA GASPARINI; DA SILVA CARVALHO, GLEYSON FRANCISCO; WOLFF, BEATRIZ MARTINS; MONTENEGRO, MARILIA MOREIRA; DE ASSUNCAO, NILSON ANTONIO; KIM, CHONG AE; et al. Novel rearrangements between different chromosomes with direct impact on the diagnosis of 5p-syndrome. Clinics, v. 77, p. 6-pg., 2022-05-28. (16/09452-0, 18/02385-0)