Database
Collaboratively charting the gene-to-phenotype network of human congenital heart defects
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* Corresponding author: Yves Moreau Yves.Moreau@esat.kuleuven.be
- † Equal contributors
1 Bioinformatics Group, Department of Electrical Engineering, ESAT-SCD, Katholieke Universiteit Leuven, Kasteelpark Arenberg 10, B-3001 Leuven, Belgium
2 Université de Toulouse, UPS, Laboratoire de Microbiologie et Génétique Moléculaires, 118 route de Narbonne, F-31000 Toulouse, France
3 Centre National de la Recherche Scientifique, LMGM, 118 route de Narbonne, F-31000 Toulouse, France
4 Center for Human Genetics, University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium
5 Laboratory of Molecular Signalling and Laboratory of Developmental Genetics and Imprinting, Babraham Research Campus, Cambridge CB22 3AT, UK
6 Department of Molecular and Developmental Genetics, VIB, Herestraat 49, box 602, B-3000 Leuven, Belgium
7 Department of Pediatric Cardiology, University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium
Genome Medicine 2010, 2:16 doi:10.1186/gm137
Published: 1 March 2010Additional files
Additional file 1:
A figure of nonsense mutations encoded in the CHDWiki for the proteins NKX2-5 and TBX5. Displayed here are mutations in NKX2-5 and TBX5 present in CHDWiki. Missense mutations (asterisks) are significantly enriched in functional domains (P-values: NKX2-5, 1 × 10-3; TBX5, 0.05; across all nonsydromic genes, 1 × 10-4). This finding is independent of the ascertainment bias associated with preferential classification of mutations affecting protein domains as pathogenic: missense mutations identified through linkage analysis in multiple individuals similarly affect preferentially protein domains (P-values: NKX2-5, 0.02; TBX5, 0.05; all nonsyndromic genes combined, 0.03). This graphical representation moreover enables straightforward genotype-phenotype correlations: missense mutations causing atrial septal defects are preferentially affecting the homeobox domain (P-value: 1 × 10-4).
Format: TIFF Size: 79KB Download file
Additional file 2:
A figure showing a network with genes sharing syndromic cardiac phenotypes when mutated. Network with genes (nodes) sharing syndromic cardiac phenotypes when mutated (edges). As members of the RAS-MAP kinase pathway (PTPN11, SOS1, BRAF, KRAS, MAP2K1, MAP2K2, SHOC2 and NF1) clearly form a phenotypic cluster, they seem to be involved in the same developmental cardiac cell lineages.
Format: TIFF Size: 118KB Download file