期刊
EUROPEAN JOURNAL OF HUMAN GENETICS
卷 27, 期 5, 页码 760-771出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41431-019-0341-5
关键词
-
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2014/11572-8]
- Swiss National Science Foundation [31003A_160203]
- FAPESP fellowship (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)
- Swiss National Science Foundation (SNF) [31003A_160203] Funding Source: Swiss National Science Foundation (SNF)
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 nonhomologous 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据