Breakpoint mapping at nucleotide resolution in X-autosome balanced translocations associated with clinical phenotypes.

Details

Serval ID
serval:BIB_4D586DC5B421
Type
Article: article from journal or magazin.
Collection
Publications
Title
Breakpoint mapping at nucleotide resolution in X-autosome balanced translocations associated with clinical phenotypes.
Journal
European journal of human genetics
Author(s)
Moysés-Oliveira M., Di-Battista A., Zamariolli M., Meloni V.A., Bragagnolo S., Christofolini D.M., Steiner C.E., Kosyakova N., Liehr T., Reymond A., Melaragno M.I.
ISSN
1476-5438 (Electronic)
ISSN-L
1018-4813
Publication state
Published
Issued date
05/2019
Peer-reviewed
Oui
Volume
27
Number
5
Pages
760-771
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Precise breakpoint mapping of balanced chromosomal rearrangements is crucial to identify disease etiology. Ten female patients with X-autosome balanced translocations associated with phenotypic alterations were evaluated, by mapping and sequencing their breakpoints. The rearrangements' impact on the expression of disrupted genes, and inferred mechanisms of formation in each case were assessed. For four patients that presented one of the chromosomal breaks in heterochromatic and highly repetitive segments, we combined cytogenomic methods and short-read sequencing to characterize, at nucleotide resolution, breakpoints that occurred in reference genome gaps. Most of rearrangements were possibly formed by non-homologous end joining and have breakpoints at repeat elements. Seven genes were found to be disrupted in six patients. Six of the affected genes showed altered expression, and the functional impairment of three of them were considered pathogenic. One gene disruption was considered potentially pathogenic, and three had uncertain clinical significance. Four patients presented no gene disruptions, suggesting other pathogenic mechanisms. Four genes were considered potentially affected by position effect and the expression abrogation of one of them was confirmed. This study emphasizes the importance of breakpoint-junction characterization at nucleotide resolution in balanced rearrangements to reveal genetic mechanisms associated with the patients' phenotypes, mechanisms of formation that originated the rearrangements, and genomic nature of disrupted DNA sequences.
Pubmed
Web of science
Create date
25/03/2019 10:04
Last modification date
21/08/2019 6:32
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