Data and resources relating to the following areas of research have been generated by the B2B consortia and are available to the scientific community.
Human Genetics Studies
The Congenital Heart Disease GEnetic NEtwork (CHD GENES) Study is a multi-Center, prospective observational genetic study investigating the relationships of genetic factors with phenotypic and clinical outcomes in patients with congenital heart defects. Genotype-phenotype data is distributed through dbGaP.
Congenital Heart Disease Gene Discovery in Mouse Models
A forward genetic screen with mouse ENU mutagenesis is being conducted using fetal ultrasound imaging to recover mouse models with congenital heart defects. Mutations in these mouse lines are identified by whole-exome sequence analysis, and are searchable in the Mouse ENU Mutation Database. The database is also searchable by congenital heart disease diagnosis, as curated using the Mammalian Phenotype Ontology and clinical Fyler disease codes.
Congenital Heart Disease Gene Discovery in Zebrafish
Forward genetics screens of ENU-mutagenized zebrafish identify novel cardiovascular development mutants. MMAPPR allows rapid discovery of mutations in any organism, without requiring parental strain information or a pre-existing snp map, using RNA-seq datasets. Novel transgenics approaches facilitate whole-genome expression profiling in specific cell lineages throughout development. A combination of morpholino injection, mRNA injection, and targeted mutagenesis approaches in zebrafish provides rapid functional testing of candidate cardiovascular development genes.
Epigenomics of Heart Development
Genome-wide approaches to identify chromatin modifications, DNA methylation patterns, transcription factor occupancy and changes in transcriptional regulation during cardiovascular development. Comparisons of these genome-wide events in wildtype and cardiovascular mutants across different organisms (mice, zebrafish, human cell culture) will allow unprecedented analysis of the gene regulatory networks that control congenital heart defects.
Vertebrate Cardiovascular Development Comparative Transcriptomics
Expression profiling of a range of embryonic stages, variety of cardiovascular tissues, and variety of vertebrate species will facilitate an understanding of the evolutionarily significant changes in cardiovascular development and give insights into a wide range of mechanisms underlying human congenital heart defects.