Terminal 18q deletions are stabilized by neotelomeres

Author(s)

Guilherme, Roberta Santos ^[1] ; Hermetz, Karen E. ^[2] ; Varela, Patricia Teixeira ^[3] ; Alvarez Perez, Ana Beatriz ^[1] ; Meloni, Vera Ayres ^[1] ; Rudd, M. Katharine ^[2] ; Kulikowski, Leslie Domenici ^[4] ; Melaragno, Maria Isabel ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Morphol & Genet, BR-04023900 Sao Paulo - Brazil

^[2] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 - USA

^[3] Univ Fed Sao Paulo, Dept Biophys, BR-04023900 Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Dept Pathol, Lab Citogenom, BR-05403000 Sao Paulo - Brazil

• Document type: Journal article
• Source: MOLECULAR CYTOGENETICS; v. 8, MAY 13 2015.
• Web of Science Citations: 4

Abstract

Background: All human chromosomes are capped by tandem repeat (TTAGGG)n sequences that protect them against end-to-end fusion and are essential to chromosomal replication and integrity. Therefore, after a chromosomal breakage, the deleted chromosomes must be stabilized by retaining the telomere or acquiring a new cap, by telomere healing or telomere capture. There are few reports with molecular approaches on the mechanisms involved in stabilization of 18q terminal deletions. Results: In this study we analyzed nine patients with 18q terminal deletion identified by G-banding and genomic array. FISH using PNA probe revealed telomeric signals in all deleted chromosomes tested. We fine-mapped breakpoints with customized arrays and sequenced six terminal deletion junctions. In all six deleted chromosomes sequenced, telomeric sequences were found directly attached to the breakpoints. Little or no microhomology was found at the breakpoints and none of the breaks sequenced were located in low copy repeat (LCR) regions, though repetitive elements were found around the breakpoints in five patients. One patient presented a more complex rearrangement with two deleted segments and an addition of 17 base pairs (bp). Conclusions: We found that all six deleted chromosomes sequenced were probably stabilized by the healing mechanism leading to a neotelomere formation. (AU)

• FAPESP's process: 12/51150-0 - Investigation of the mechanisms involved in the formation and stabilization of ring chromosome, supemumerary markers and terminal deletions
• Grantee: Maria Isabel de Souza Aranha Melaragno
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/15572-7 - Investigation of the mechanisms involved in the formation and stabilization of ring chromosome, supernumerary markers and terminal deletion.
• Grantee: Roberta dos Santos Guilherme
• Support Opportunities: Scholarships in Brazil - Doctorate