...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nucleus >Implications of COMT long-range interactions on the phenotypic variability of 22q11.2 deletion syndrome
【24h】

Implications of COMT long-range interactions on the phenotypic variability of 22q11.2 deletion syndrome

机译：COMT远程相互作用对22q11.2缺失综合征表型变异性的影响

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

22q11.2 deletion syndrome (22q11DS) results from a hemizygous microdeletion on chromosome 22 and is characterized by extensive phenotypic variability. Penetrance of signs, including congenital heart, craniofacial, and neurobe-havioral abnormalities, varies widely and is not well correlated with genotype. The three-dimensionalstructure of the genome may help explain some of this variability. The physical interaction profile of a given gene locus with other genetic elements, such,as enhancers and co-regulated genes, contributes to its regulation. Thus, it is possible that regulatory interactions with elements outside the deletion region are disrupted in the disease state and modulate the resulting spectrum of symptoms. COMT, a gene within the commonly deleted ~3 Mb region has been implicated as a contributor to the neurological features frequently found in 22q11DS patients. We used this locus as bait in a 4C-seq experiment to investigate genome-wide interaction profiles in B lymphocyte and fibroblast cell lines derived from both 22q11DS and unaffected individuals. All normal B lymphocyte lines displayed local, conserved chromatin looping interactions with regions that are lost in atypical and distal deletions, which may mediate similarities between typical, atypical, and distal 22q11 deletion phenotypes. There are also distinct clusterings of cis interactions based on disease state. We identified regions of differential trans interactions present in normal, and lost in deletion-carrying, B lymphocyte cell lines. This data suggests that hemizygous chromosomal deletions such as 22q11DS can have widespread effects on chromatin organization, and may contribute to the inherent phenotypic variability.
机译：22q11.2缺失综合征（22q11DS）是由22号染色体上的半合子微缺失导致的，其特征是广泛的表型变异。先天性心脏，颅面和神经行为异常等体征的渗透率差异很大，并且与基因型没有很好的相关性。基因组的三维结构可能有助于解释这种变异性。给定基因位点与其他遗传元件（例如增强子和共同调控的基因）的物理相互作用谱有助于其调控。因此，有可能在疾病状态下破坏与缺失区域外的元件的调节相互作用，并调节所得的症状谱。 COMT是一种普遍缺失的〜3 Mb区域内的基因，与22q11DS患者经常发现的神经功能有关。我们在4C-seq实验中将此位点用作诱饵，以研究来源于22q11DS和未患病个体的B淋巴细胞和成纤维细胞系中全基因组的相互作用情况。所有正常B淋巴细胞系均显示出与非典型和远端缺失中丢失的区域相关的局部，保守的染色质环相互作用，这可能介导典型，非典型和远端22q11缺失表型之间的相似性。根据疾病状态，顺式相互作用也有不同的聚类。我们确定了正常存在的差异反式相互作用的区域，并在携带缺失的B淋巴细胞细胞系中丢失。该数据表明，诸如22q11DS之类的半合子染色体缺失可对染色质组织产生广泛影响，并可能有助于固有的表型变异性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号