4.6 Article

A Novel Non-Allelic Homologous Recombination Event in a Parent with an 11;22 Reciprocal Translocation Leading to 22q11.2 Deletion Syndrome

期刊

GENES
卷 13, 期 9, 页码 -

出版社

MDPI
DOI: 10.3390/genes13091668

关键词

22q11; 2 Deletion Syndrome; microdeletion; optical mapping; recombination; structural variation

资金

  1. NIH [GM125757, P01 HD070454]
  2. Charles E.H. Upham chair in Pediatrics

向作者/读者索取更多资源

The most common microdeletion in humans occurs at the 22q11.2 region, which is rich in low copy repeats (LCR22s). The complex structure of this region has been difficult to characterize. Optical mapping has been used to study the structure and variations of LCR22s. This study identified all structures involving a rearranged chromosome 22 that contribute to the 22q11.2 deletion.
The most prevalent microdeletion in the human population occurs at 22q11.2, a region rich in chromosome-specific low copy repeats (LCR22s). The structure of this region has eluded characterization due to a combination of size, regional complexity, and haplotype diversity. To further complicate matters, it is not well represented in the human reference genome. Most individuals with 22q11.2 deletion syndrome (22q11.2DS) carry a de novo, hemizygous deletion approximately 3 Mbp in size occurring by non-allelic homologous recombination (NAHR) mediated by the LCR22s. The ability to fully delineate an individual's 22q11.2 regional structure will likely be important for studies designed to assess an unaffected individual's risk for generating rearrangements in germ cells, potentially leading to offspring with 22q11.2DS. Towards understanding these risk factors, optical mapping has been previously employed to successfully elucidate the structure and variation of LCR22s across 30 families affected by 22q11.2DS. The father in one of these families carries a t(11;22)(q23;q11) translocation. Surprisingly, it was determined that he is the parent-of-deletion-origin. NAHR, which occurred between his der(22) and intact chromosome 22, led to a 22q11.2 deletion in his affected child. The unaffected sibling of the proband with 22q11.2DS inherited the father's normal chromosome 22, which did not aberrantly recombine. This unexpected observation definitively shows that haplotypes that engage in NAHR can also be inherited intact. This study is the first to identify all structures involving a rearranged chromosome 22 that also participates in NAHR leading to a 22q11.2 deletion.

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。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据