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Novel genechip technology for simplified detection of molecularly heterogeneous genetic diseases: detection of cystic fibrosis as a model

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ID for cystic fibrosis biomarkers

The study of cystic fibrosis (CF) is important, not only for patients, but for use as a model gene for other inherited diseases. Proteins from the expression of CF genes were analysed and compared with complementary products from non-CF individuals.

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Cystic fibrosis is one of most common, life-shortening, inherited diseases. The CF gene results in the production of a chloride ion channel important in the creation of sweat, digestive juices and mucus. Mutations in this gene can therefore cause a range of problems in all systems involved with these secretions. The original overall objective of the EU-funded CF-CHIP project was to develop a new gene array technology platform. The aim was high-throughput diagnosis of CF and related diseases as well as to use it for a model for other genetic disorders. As part of the research consortium, the University of Lisbon in Portugal selected three cell lines, including nasal epithelial cells. They then analysed gene expression changes which could be linked to the presence of a CF mutation. In order to perform these comparisons, the 40k human micro-array from MWG, a project partner, was used. This comprised of 40,000 genes of the human gene and constituted the perfect tool to identify new target sequences and their functions. Real-time polymerase chain reaction (PCR) analysis of the genes provided further verification of the results together with analyses based on their protein products. As a result, genes were identified that were consistently up- or down-regulated in CF tissues when compared with tissue from non-CF tissues. Further ongoing research based on these results is underway to increase the number of analyses and tissues under study. This may well lead to a more detailed understanding of the CF disease. In particular, the validation of gene expression changes through their protein products could be invaluable in earlier diagnosis and therapy.

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