Work Package 5 : Genetics
Task 1: Development of a common mutation dataset
We will create a mutation database of exons, 50 bases of the intronic sequence bordering exons (potential splice sites) and 500 bases upstream from the first exon (potential regulatory elements) for the 2 Wolfram genes, 1 Alström gene, 15 Bardet-Biedl Syndrome genes, and genes for other rare disorders including Wolcott-Rallison syndrome and Thiamine Responsive Megaloblastic Anaemia syndrome.
Task 2: Widen availability of genetic testing across the EU.
We will provide access to genetic diagnostic testing through a series of designated specialist centres throughout the EU, including existing centres of expertise. We will use a combination of micro-array and direct sequencing techniques. Centres will be supported to deliver this service.
Task 3: Genotype phenotype correlation.
We will combine clinical and mutation analysis data from the enlarged population of EU patients (100 for each disease). Initially correlations will be sought between specific mutations and the principle features of the syndromes. Investigations will then extend to individuals with incomplete features of the syndromes; we expect to find new cases and novel mutations. The laboratories will offer stage 2 complete gene sequencing for patients from all EU member states; to identify genotype phenotype relations to inform clinical practice and prognosis; and to identify potential targets for other candidate genes.