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Terminal 18q deletions are stabilized by neotelomeres

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 a...

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Autores principales: Guilherme, Roberta Santos, Hermetz, Karen E, Varela, Patrícia Teixeira, Perez, Ana Beatriz Alvarez, Meloni, Vera Ayres, Rudd, M Katharine, Kulikowski, Leslie Domenici, Melaragno, Maria Isabel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427916/
https://www.ncbi.nlm.nih.gov/pubmed/25969696
http://dx.doi.org/10.1186/s13039-015-0135-6
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author Guilherme, Roberta Santos
Hermetz, Karen E
Varela, Patrícia Teixeira
Perez, Ana Beatriz Alvarez
Meloni, Vera Ayres
Rudd, M Katharine
Kulikowski, Leslie Domenici
Melaragno, Maria Isabel
author_facet Guilherme, Roberta Santos
Hermetz, Karen E
Varela, Patrícia Teixeira
Perez, Ana Beatriz Alvarez
Meloni, Vera Ayres
Rudd, M Katharine
Kulikowski, Leslie Domenici
Melaragno, Maria Isabel
author_sort Guilherme, Roberta Santos
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13039-015-0135-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-44279162015-05-13 Terminal 18q deletions are stabilized by neotelomeres Guilherme, Roberta Santos Hermetz, Karen E Varela, Patrícia Teixeira Perez, Ana Beatriz Alvarez Meloni, Vera Ayres Rudd, M Katharine Kulikowski, Leslie Domenici Melaragno, Maria Isabel Mol Cytogenet Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13039-015-0135-6) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-13 /pmc/articles/PMC4427916/ /pubmed/25969696 http://dx.doi.org/10.1186/s13039-015-0135-6 Text en © Guilherme et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Guilherme, Roberta Santos
Hermetz, Karen E
Varela, Patrícia Teixeira
Perez, Ana Beatriz Alvarez
Meloni, Vera Ayres
Rudd, M Katharine
Kulikowski, Leslie Domenici
Melaragno, Maria Isabel
Terminal 18q deletions are stabilized by neotelomeres
title Terminal 18q deletions are stabilized by neotelomeres
title_full Terminal 18q deletions are stabilized by neotelomeres
title_fullStr Terminal 18q deletions are stabilized by neotelomeres
title_full_unstemmed Terminal 18q deletions are stabilized by neotelomeres
title_short Terminal 18q deletions are stabilized by neotelomeres
title_sort terminal 18q deletions are stabilized by neotelomeres
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427916/
https://www.ncbi.nlm.nih.gov/pubmed/25969696
http://dx.doi.org/10.1186/s13039-015-0135-6
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