Identifying NAHR mechanism between two distinct Alu elements through breakpoint junction mapping by NGS

Author(s):Show less -

Novo-Filho, Gil M. ^[1] ; Carvalho, Gleyson F. S. ^[1] ; Nascimento, Amom M. ^[1] ; Montenegro, Marilia M. ^[1] ; Damasceno, Jullian G. ^[1] ; Zanardo, Evelin A. ^[1] ; Chehimi, Samar N. ^[1] ; Oliveira, Yanca G. ^[1] ; Dias, Alexandre T. ^[1] ; Kim, Chong A. ^[2] ; Kulikowski, Leslie D. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med FMUSP, Dept Patol, Lab Citogenom, Av Dr Eneas Carvalho Aguiar, 155-2 Andar, Bloco 12, BR-01246100 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Inst Crianca, Unidade Genet, Dept Pediat, Av Dr Eneas Carvalho Aguiar, 647-7 Andar, BR-05403000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: META GENE; v. 24, JUN 2020.
• Web of Science Citations: 0

Abstract

Genomic rearrangements encompass deletions, duplications, inversions, insertions and translocations and may be the cause of several genetic diseases. One of the most frequent mechanisms that generate these rearrangements is the Non-Allelic Homologous Recombination (NAHR). They are caused by a misalignment between regions of high level of similarity, like Low Copy Repeats (LCRs) and Alu sequences. We aimed to sequence the breakpoint of a patient with a single deletion on chromosome 22q13.2 in order to understand the genomic structure of the region involved as well as elucidate the mechanism behind this rearrangement. Investigating breakpoints are of the utmost importance in the understanding the influence of the genomic architecture in clinical assays. We flanked the breakpoint detected by array and then we captured the regions using Illumina Nextera Rapid Capture Custom to sequence with Illumina MiSeq. We found a chimeric read on Chr22:41,026,090, setting a 624,688 bp deletion on Chr22:41,026,112-41,650,780 (hg19). This deletion merges the intronic region of MKL1 and RANGAP1 genes, on two different Alu sequences (AluSx and AluY, respectively). The sequence of the breakpoint reveals that Alu elements are an important characteristic of the human genome on generating rearrangements. (AU)

• FAPESP's process: 16/09452-0 - Mapping of DNA break points and investigation of the mechanisms associated with genomic rearrangements using next generation sequencing.
• Grantee: Leslie Domenici Kulikowski
• Support Opportunities: Regular Research Grants