Genome-wide copy number variant analysis for congenital ventricular septal defects in Chinese Han population

被引:20
作者
An, Yu [1 ,2 ,3 ,4 ,6 ]
Duan, Wenyuan [5 ]
Huang, Guoying [6 ]
Chen, Xiaoli [7 ]
Li, Li [7 ]
Nie, Chenxia [8 ]
Hou, Jia [6 ]
Gui, Yonghao [6 ]
Wu, Yiming [1 ,2 ]
Zhang, Feng [3 ,4 ]
Shen, Yiping [9 ]
Wu, Bailin [1 ,2 ,6 ,9 ]
Wang, Hongyan [10 ]
机构
[1] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China
[2] Fudan Univ, Childrens Hosp, Shanghai 200032, Peoples R China
[3] Fudan Univ, State Key Lab Genet Engn, Minist Educ MOE, Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China
[4] Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, Shanghai 200433, Peoples R China
[5] Jinan Mil Gen Hosp, Jinan 250022, Peoples R China
[6] Fudan Univ, Childrens Hosp, Shanghai 201102, Peoples R China
[7] Capital Inst Pediat, Beijing 100020, Peoples R China
[8] Changzhi MedicalColl, Dept Biol, Changzhi 046000, Peoples R China
[9] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Lab Med, Boston, MA 02453 USA
[10] Fudan Univ, Inst Reprod & Dev, Sch Life Sci, Obstet & Gynecol Hosp, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
Ventricular septal defect; aCGH; Congenital heart defect; Copy number variants; HEART-DEFECTS; ARRAY-CGH; GENE; CHILDREN; DATABASE; ABNORMALITIES; CANDIDATE; LOCI; LBX1;
D O I
10.1186/s12920-015-0163-4
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Ventricular septal defects (VSDs) constitute the most prevalent congenital heart disease (CHD), occurs either in isolation (isolated VSD) or in combination with other cardiac defects (complex VSD). Copy number variation (CNV) has been highlighted as a possible contributing factor to the etiology of many congenital diseases. However, little is known concerning the involvement of CNVs in either isolated or complex VSDs. Methods: We analyzed 154 unrelated Chinese individuals with VSD by chromosomal microarray analysis. The subjects were recruited from four hospitals across China. Each case underwent clinical assessment to define the type of VSD, either isolated or complex VSD. CNVs detected were categorized into syndrom related CNVs, recurrent CNVs and rare CNVs. Genes encompassed by the CNVs were analyzed using enrichment and pathway analysis. Results: Among 154 probands, we identified 29 rare CNVs in 26 VSD patients (16.9 %, 26/154) and 8 syndrome-related CNVs in 8 VSD patients (5.2 %, 8/154). 12 of the detected 29 rare CNVs (41.3 %) were recurrently reported in DECIPHER or ISCA database as associated with either VSD or general heart disease. Fifteen genes (5 %, 15/285) within CNVs were associated with a broad spectrum of complicated CHD. Among these 15 genes, 7 genes were in "abnormal interventricular septum morphology" derived from the MGI (mouse genome informatics) database, and nine genes were associated with cardiovascular system development (GO:0072538). We also found that these VSD-related candidate genes are enriched in chromatin binding and transcription regulation, which are the biological processes underlying heart development. Conclusions: Our study demonstrates the potential clinical diagnostic utility of genomic imbalance profiling in VSD patients. Additionally, gene enrichment and pathway analysis helped us to implicate VSD related candidate genes.
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页数:10
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