title: Genome-wide copy number variant analysis for congenital ventricular septal defects in Chinese Han population.
abstract: 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 these15 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.
authors.affiliation: Institutes of Biomedical Sciences and Children's Hospital, Fudan University, 131 Dongan Road, Shanghai, 200032, China. ay.fudan@gmail.com.|The State Key Laboratory of Genetic Engineering, Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology, and Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, China. ay.fudan@gmail.com.|Children's Hospital, Fudan University, Shanghai, 201102, China. ay.fudan@gmail.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.affiliation: Jinan Military General Hospital, Jinan, 250022, China. dwy2115@gmail.com.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Duan
authors.affiliation: Children's Hospital, Fudan University, Shanghai, 201102, China. gyhuang@shmu.edu.cn.
authors.forename: Guoying
authors.initials: G
authors.lastname: Huang
authors.affiliation: Capital Institute of Pediatrics, Beijing, 100020, China. cxlwx@sina.com.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chen
authors.affiliation: Capital Institute of Pediatrics, Beijing, 100020, China. 1627433048@qq.com.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biology, Changzhi MedicalCollege, Changzhi, 046000, China. niechenxia2010@163.com.
authors.forename: Chenxia
authors.initials: C
authors.lastname: Nie
authors.affiliation: Children's Hospital, Fudan University, Shanghai, 201102, China. doctorhoujia@hotmail.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Hou
authors.affiliation: Children's Hospital, Fudan University, Shanghai, 201102, China. yhgui@shmu.edu.cn.
authors.forename: Yonghao
authors.initials: Y
authors.lastname: Gui
authors.affiliation: Institutes of Biomedical Sciences and Children's Hospital, Fudan University, 131 Dongan Road, Shanghai, 200032, China. ludwigwu@gmail.com.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wu
authors.affiliation: The State Key Laboratory of Genetic Engineering, Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology, and Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, China. feng.fudan@gmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, 02453, USA. Yiping.Shen@childrens.harvard.edu.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Institutes of Biomedical Sciences and Children's Hospital, Fudan University, 131 Dongan Road, Shanghai, 200032, China. wu_b@fudan.edu.cn.|Children's Hospital, Fudan University, Shanghai, 201102, China. wu_b@fudan.edu.cn.|Department of Laboratory Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, 02453, USA. wu_b@fudan.edu.cn.
authors.forename: Bailin
authors.initials: B
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Obstetrics & Gynecology Hospital, Institute of Reproduction & Development, Fudan University, Shanghai, 200032, China. wanghy@fudan.edu.cn.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D044466:Asian People / Q000235:genetics*; D020029:Base Pairing / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D063990:Gene Ontology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006330:Heart Defects, Congenital / Q000235:genetics*; D006345:Heart Septal Defects, Ventricular / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015398:Signal Transduction / Q000235:genetics