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Quantitative pathway analysis of natural variation in complex disease signaling in C. elegans

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Ancestral genes coding for cancer

Around 60 % of adults die from diseases such as cancer and circulatory system disorders. These diseases have complex disease phenotypes arising from interactions between genetic variants.

Health

Unlike rare monogenic diseases under the control of a single gene, elucidating the mechanisms involved in complex disease pathways is particularly difficult in humans. The next best thing is the use of the nematode worm Caenorhabditis elegans to find the genetic variations responsible for diseases like cancer. C. elegans was used as the animal model in the EU-funded 'Quantitative pathway analysis of natural variation in complex disease signalling in C. elegans' (PANACEA) project. PANACEA developed methods to selectively knock down genes of interest in C. elegans. This helped in the identification of genes and mechanisms involved in cancer pathways. Based on this, mathematical models could identify and predict cancer development in worms. Importantly, scientists were able to compile a list of key cancer regulators that can be used to find human homologues. Homologous genes refer to similar genes passed down through common ancestry. PANACEA used a special database and analysis system to comparatively associate such genetic variations in C. elegans and humans with disease signalling pathways. Through the PANACEA developmental model, new drug targets could be identified that will permit clinicians to tailor therapy to an individual's needs using association studies. Project outcomes have laid the foundation for genetically based cancer screening, therapy and prevention, while considerably improving our understanding of complex genetic diseases.

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