Informatics researchers find computational evidence for genetic disposition to Atopic Dermatitis

Researchers at the Department of Informatics have found computational evidence that people with a certain genetic mutation are predisposed to the skin disorder Atopic Dermatitis. Ribonucleic acids (RNAs) are essential molecules found in all known forms of life and can be classified into two classes protein-coding RNAs and non-coding RNAs. An important type of non-coding RNAs called microRNAs bind to their target protein-coding RNAs to regulate gene expression. The computational analysis found evidence that while the binding of a particular microRNA (miR-519a-3p) to the gene in question (ORAI1) is strong, it is weaker in the mutated version of the gene (when C > T occurs in the 3'UTR), which could explain the susceptibility to develop Atopic Dermatitis in populations with the mutation.

The computational analysis was carried out by Luke Day, Ouala Abdelhadi Ep Souki and Kathleen Steinhofel, from the Algorithms and Bioinformatics group of the Department of Informatics, in collaboration with Andreas Albrecht from Middlesex University. It follows from the hypothesis that in a cell several copies of RNA conformations are present in low free energy states. Mutations can change the conformational landscape and as a result the accessibility of microRNA binding sites which can have an impact on the expression of a gene. Traditionally, computational microRNA target site prediction considers only a single conformation known as the minimum free energy conformation. In this study, the importance of metastable or local minima conformations from the conformational landscape is highlighted. This computational analysis improves on previous lab based findings published by Chang et al., where the frequency of the mutation within ORAI1 is analysed in various populations, along with the susceptibility to Atopic Dermatitis.

For more information about this work, please contact Luke Day or see the following paper:

L. Day, O. Abdelhadi Ep Souki, A.A. Albrecht, K. Steinhofel. Accessibility of microRNA binding sites in meta-stable RNA secondary structures in the presence of SNPs. Bioinformatics, 30(3):343-352, 2014.