De novo copy number variants are associated with congenital diaphragmatic hernia.
De novo copy number variants are associated with congenital diaphragmatic hernia.
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DOI：
10.1136/jmedgenet-2012-101135
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发表时间：
2012-10
影响因子：
4
通讯作者：
Chung WK
中科院分区：
文献类型：
--
作者：
Yu L;Wynn J;Ma L;Guha S;Mychaliska GB;Crombleholme TM;Azarow KS;Lim FY;Chung DH;Potoka D;Warner BW;Bucher B;LeDuc CA;Costa K;Stolar C;Aspelund G;Arkovitz MS;Chung WK
先天性腹股沟疝是一种常见的出生缺陷，具有显著的发病率和死亡率。尽管对CDH的病因学仍知之甚少，但来自CDH动物模型和患者的研究表明，遗传因素在CDH的发展中起重要作用。先天性髋脱位有染色体异常的报道。在这项研究中，作者调查的频率染色体异常和拷贝数变异的256个亲子三胞胎的CDH使用临床常规细胞遗传学和微阵列分析。作者还选择了一组CDH相关的训练基因，以优先考虑这些节段性非整倍体中的基因，并确定了可能有助于CDH病因的基因和基因集。作者在该系列的16例患者（6.3%）中鉴定出染色体异常，包括3例非整倍体、2例不平衡易位和11例大小为95 kb至104.6 Mb的新生CNV患者。作者对CNV片段中的基因进行了优先排序，并将KCNA2、LMNA、CACNA1S、MYOG、HLX、LBR、AGT、GATA 4、SOX 7、HYLS 1、FOXC 1、FOXF2、PDGFA、FGF6、COL4A1、COL4A2、HOMER 2、BNC 1、BID和TBX 1确定为可能参与膈肌发育的基因。基因富集分析确定了最相关的基因本体论（GO）类别，如参与组织发育（p=4.4×10−11）或多细胞生物过程调控（p=2.8×10−10）和“受体结合”（p = 8.7×10−14）和“DNA结合转录因子活性”（p= 4.4×10−10）。我们的研究结果支持了染色体异常在CDH中的作用，并提供了一组候选基因，包括FOXC 1，FOXF2，PDGFA，FGF6，COL4A1，COL4A2，SOX 7，BNC 1，BID和TBX 1，用于进一步分析CDH。
Congenital diaphragmatic hernia (CDH) is a common birth defect with significant morbidity and mortality. Although the etiology of CDH remains poorly understood, studies from animal models and patients with CDH suggest that genetic factors play an important role in the development of CDH. Chromosomal anomalies have been reported in CDH. In this study, the authors investigate the frequency of chromosomal anomalies and copy number variants in 256 parent-child trios of CDH using clinical conventional cytogenetic and microarray analysis. The authors also selected a set of CDH related training genes to prioritize the genes in those segmental aneuploidies and identified the genes and gene sets that may contribute to the etiology of CDH. The authors identified chromosomal anomalies in 16 patients (6.3 %) of the series including 3 aneuploidies, 2 unbalanced translocation, and 11 patients with de novo CNVs ranging in size from 95 kb to 104.6 Mb. The authors prioritized the genes in the CNV segments and identified KCNA2, LMNA, CACNA1S, MYOG, HLX, LBR, AGT, GATA4, SOX7, HYLS1, FOXC1, FOXF2, PDGFA, FGF6, COL4A1, COL4A2, HOMER2, BNC1, BID, and TBX1 as genes that may be involved in diaphragm development. Gene enrichment analysis identified the most relevant gene ontology (GO) categories as those involved in tissue development (p=4.4×10−11) or regulation of multicellular organismal processes (p=2.8×10−10) and “receptor binding” (p = 8.7×10−14) and “DNA binding transcription factor activity” (p= 4.4×10−10). Our findings support the role of chromosomal anomalies in CDH and provide a set of candidate genes including FOXC1, FOXF2, PDGFA, FGF6, COL4A1, COL4A2, SOX7,BNC1, BID, and TBX1 for further analysis in CDH.
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DOI：
10.1002/bdra.20613
发表时间：
2010-01-01
影响因子：
--
作者：
Clugston, Robin D.;Zhang, Wei;Greer, John J.
通讯作者：
Greer, John J.
影响因子：
2
作者：
Kantarci, Sibel;Ackerman, Kate G.;Russell, Meaghan K.;Longoni, Mauro;Sougnez, Carrie;Noonan, Kristin M.;Hatchwell, Eli;Zhang, Xiaoyun;Pieretti-Vanmarcke, Rafael;Anyane-Yeboa, Kwame;Dickman, Paul;Wilson, Jay;Donahoe, Patricia K.;Pober, Barbara R.
通讯作者：
Pober, Barbara R.
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG
影响因子：
2
作者：
Kantarci, S;Casavant, D;Pober, BR
通讯作者：
Pober, BR
影响因子：
9.8
作者：
Mefford, Heather C.;Clauin, Severine;Bellanne-Chantelot, Christine
通讯作者：
Bellanne-Chantelot, Christine