Journal article
Congenital diaphragmatic hernia interval on chromosome 8p23.1 characterized by genetics and protein interaction networks
Massachusetts General Hospital1
Kaiser Permanente2
Mitsubishi Chemical Holdings Corporation3
Mercy Children's Hospital4
Universitätsklinikum Essen5
The Children's Hospital of Philadelphia6
Massachusetts General Hospital/Harvard Medical School7
Department of Systems Biology, Technical University of Denmark8
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark9
University of Mississippi10
King Edward Memorial Hospital11
University of Utah12
University Hospital Leuven13
Mackay Memorial Hospital Taiwan14
Lübeck University of Applied Sciences15
...and 5 moreChromosome 8p23.1 is a common hotspot associated with major congenital malformations, including congenital diaphragmatic hernia (CDH) and cardiac defects. We present findings from high‐resolution arrays in patients who carry a loss (n = 18) or a gain (n = 1) of sub‐band 8p23.1. We confirm a region involved in both diaphragmatic and heart malformations.
Results from a novel CNVConnect algorithm, prioritizing protein–protein interactions between products of genes in the 8p23.1 hotspot and products of previously known CDH causing genes, implicated GATA4, NEIL2, and SOX7 in diaphragmatic defects. Sequence analysis of these genes in 226 chromosomally normal CDH patients, as well as in a small number of deletion 8p23.1 patients, showed rare unreported variants in the coding region; these may be contributing to the diaphragmatic phenotype.
We also demonstrated that two of these three genes were expressed in the E11.5–12.5 primordial mouse diaphragm, the developmental stage at which CDH is thought to occur. This combination of bioinformatics and expression studies can be applied to other chromosomal hotspots, as well as private microdeletions or microduplications, to identify causative genes and their interaction networks. © 2012 Wiley Periodicals, Inc.
Language: | English |
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Publisher: | Wiley Subscription Services, Inc., A Wiley Company |
Year: | 2012 |
Pages: | 3148-3158 |
ISSN: | 10403787 , 15524825 and 15524833 |
Types: | Journal article |
DOI: | 10.1002/ajmg.a.35665 |
Animals CNVConnect Chromosome Deletion Chromosomes, Human, Pair 8 DNA DNA Glycosylases DNA copy number variants DNA-(Apurinic or Apyrimidinic Site) Lyase Female GATA4 GATA4 Transcription Factor GATA4 protein, human Heart Defects, Congenital Hernia, Diaphragmatic Hernias, Diaphragmatic, Congenital Humans Karyotyping Mice Mice, Inbred C57BL NEIL2 NEIL2 protein, human Phenotype Pregnancy Protein Interaction Maps SOX7 SOX7 protein, human SOXF Transcription Factors congenital diaphragmatic hernia congenital heart defect deletion 8p23 1 duplication 8p23 1