| title: | Familiar forms of the congenital heart disease in Estonia: identification of the responsible genes and development of molecular diagnostics. |
|---|---|
| reg no: | ETF6573 |
| project type: | Estonian Science Foundation research grant |
| subject: |
3.1. Basic Medicine 3.1. Basic Medicine 3.4. Health Sciences |
| status: | accepted |
| institution: | TU Faculty of Medicine |
| head of project: | Ingrid Kalev |
| duration: | 01.01.2006 - 31.12.2009 |
| description: | Project planned to begin from 01.01.2006 and end to 31.12.2009. Estimated cost is 800 000 EEK. General background: Congenital heart diseases are defined as abnormalities of the heart's structure and function caused by abnormal or disordered heart development before birth. The generation (teke) of disease is caused by different factors, however, in most cases the exact cause of the congenital heart disease is incomprehensible. Important evidence for heredity is the recurrence of the congenital heart defects in the same family (Down and Turner syndromes) and the frequent occurrence of the congenital heart diseases in dysmorphic syndromes. Three different approaches have been used for the identification of the genes of the congenital heart disease: linkage study, microdeletion disorders, and the third is the mapping of balanced translocations. For examine if a candidate gene causes a specific heart defect, have used mainly two different approaches: association study and genetically engineered animal models (knock-outs mice). For the moment few genes are identified for congenital heart disease (~16). In addition to the congenital heart disease complex forms there are inheritant forms, which are able to observed by the pedigree analysis. These defects are caused by the concrete mutation of the firm gene (characterised are ~10 genes), which segregates in the family. Known genes, that influence the origination of the congenital heart disease, have found mainly from the gene families affecting heart morphogenesis: a) genes of transcription factors (TBX5 in Holt-Oram syndrome characterized by heart and limb defects), b) genes of cell’s adhesion molecule (CRELD1 answer for combined atrioventricular septal defect (AVSD) in Ellis-van Creveld syndrome), c) signal transduction bounded genes (PTPN11 mutations causing Noonan syndrome preferentially cause pulmonary stenosis), and cell’s apoptosis bounded genes (JAG1 mutations cause Alagille syndrome). Aims: Afford up-to-date specified molecular diagnostics for familiar congenital heart disease, which allows to correct the theraphy scheme in Estonia. Specific aims and methods: 1) afford for families with monogenic congenital heart disease molecular analysis at the DNA-level for two purpose: a) find out carriers for mutant allele from familiar members by PCR, sequence and resequence methods b) prenatal diagnostics 2) for novel familiar cases the specification of diagnosis by the molecular methods by DGGE method, based on DNA fragments amplification, denaturation and renaturation for segregation homoduplexes from heteroduplexes 3) specification genotype-phenotype correlation for familiar congenital heart disease Afford to give genetic characterizaton to the congenital heart diseases in Estonia for the first time, modernise diagnostics, improve prophylactic (genetic consultation for families with congenital heart disease) and in result it is possible to reduce the frequency of the disease. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Ingrid Kalev | Tartu Ülikool | ||
| 2. | Kai Muru | |||