Functional Annotation of Candidate Disease Genes

Coordinator:    Dr. Andreas Till
Institution: Institut für Klinische Molekularbiologie, Kiel
Susceptibility for chronic inflammatory diseases is influenced by interaction of both environmental factors (nutrition, toxins, stress etc.) and specific genetic variations (mutations). The major aim of the entire research consortium is the identification of genes and their respective variants that contribute to development of these diseases. To comprehensively understand how genetic variants are causatively involved in disease susceptibility, a detailed knowledge about structure and function of these genes is required. The human genome contains more than 25,000 different genes with specific structure and function within the organism. The genomic organization of each gene implies the presence of the following clearly defined regions:
The coding sequence of a gene contains the biochemical information that is translated into a specific amino acid sequence of the respective protein (e.g. representing an enzyme, structural protein, signal molecule etc.). The coding sequence does not represent a linear unit within the DNA but is organized in separate clusters (´exons´) that are combined when the gene expression is activated to give rise to a linear protein sequence. These exons are separated by much larger units (the ´introns´) that do not contain coding sequence but are believed to comprise information for the regulation of the gene. In front of the coding sequence with its exons and interposed introns, a large region is located (the so- called ´promoter´) that is responsible for the regulation of gene expression (i.e. activation / inactivation of the gene and fine-tuning of its expression). The promoter contains a variety of specific sequence motifs that can be bound by regulatory proteins (´transcription factors´). Binding of these proteins to the promoter region results in re-folding of the DNA and altered structural features that ultimately result in differential regulation of the gene activity.
The genetic variations that are linked to susceptibility for disease theoretically can affect each of the region mentioned above and thus can result in altered gene expression (when influencing regulatory regions) but also in modified gene function (when affecting the coding region). Since most human genes have not been characterized so far regarding the details of their genomic organization, regulation and gene function, the main focus of this subproject is to comprehensively dissect these characteristics for the newly identified disease genes.

Additional relevant Internet link:
Leibniz-Institut für Altersforschung - Fritz-Lipmann-Institut
Further Coordinators:
INTRANET (Members login)