Gene discovery and functional assessment of rare copy-number variants in neurodevelopmental disorders
Gene discovery and functional assessment of rare copy-number variants in neurodevelopmental disorders
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DOI：
10.1093/bfgp/elv018
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发表时间：
2015-09-01
影响因子：
4
通讯作者：
Girirajan, Santhosh
中科院分区：
文献类型：
--
作者：
Iyer, Janani;Girirajan, Santhosh
罕见的拷贝数变异（CNVs）是神经发育障碍的重要原因。人类基因组的序列结构使某些个体倾向于在特定的基因组区域内缺失和重复。虽然对具有不同断点的个体的评估已经确定了某些罕见CNV的致病基因，但推导具有相似断点的罕见CNV的基因-表型相关性一直具有挑战性。我们提出了一个全面的文献综述遗传结构，易于经常性重排，功能评价缺失，重复和候选基因罕见的CNV间隔内使用小鼠，斑马鱼和果蝇模型。很明显，对携带特定CNV的大群体个体进行表型评估和完整的遗传评估以及使用多种动物模型进行功能评估对于了解神经发育障碍的分子遗传基础是必要的。
Rare copy-number variants (CNVs) are a significant cause of neurodevelopmental disorders. The sequence architecture of the human genome predisposes certain individuals to deletions and duplications within specific genomic regions. While assessment of individuals with different breakpoints has identified causal genes for certain rare CNVs, deriving gene-phenotype correlations for rare CNVs with similar breakpoints has been challenging. We present a comprehensive review of the literature related to genetic architecture that is predisposed to recurrent rearrangements, and functional evaluation of deletions, duplications and candidate genes within rare CNV intervals using mouse, zebrafish and fruit fly models. It is clear that phenotypic assessment and complete genetic evaluation of large cohorts of individuals carrying specific CNVs and functional evaluation using multiple animal models are necessary to understand the molecular genetic basis of neurodevelopmental disorders.