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Content archived on 2024-06-10

Integrated analysis of expression and chromosomal organisation of genes localised on human chromosome 1q21: implications for human disease and cancer

Objective



Chromosome 1, which is the largest human chromosome and harbours about 8% of the entire human genomic information, reveals in region lq21 a most remarkable clustering of genes that fulfil important functions in development and differentiation. Among twenty-five individual genes identified and physically mapped so far, fifteen encode structural proteins that are indispensable for terminal differentiation of the human epidermis and ten are genes for S100A small calcium binding proteins involved in signal transduction and cell cycle progression.

Co-localisation of genes coding for calcium binding proteins with genes expressed late during epidermal differentiation is particularly intriguing since calcium levels tightly control the differentiation of epithelial cells and the expression of genes encoding epidermal structural proteins. Moreover, S100 proteins have been found to be differentially regulated in human cancer cells and region lq21 is often rearranged in human tumours. In addition, amplification of region lq21-q22 has recently been identified in human sarcomas.

Since the groups joining for this proposal have previously been engaged in the identification and/or mapping of these important clustered genes, it appears appropriate to concentrate European resources for a combined, multidisciplinary effort aiming at a comprehensive characterisation of all known and novel genes residing in region lq21 and their tissue-, developmental-, and differentiation specific regulation. Likewise, the potential role of these genesin genetic disorders of keratinisation that obliterate the physical and chemical resistance of human epidermis will be analyzed as will be the effects of their disproportionate representation and abnormal regulation in tumorigenesis.

Call for proposal

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Coordinator

Humboldt-Universität zu Berlin
EU contribution
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Address
130,Spandauer Damm
14050 Berlin
Germany

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Total cost
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Participants (8)