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A Swedish study has identified 17 new genes which could be targeted for therapy of psoriasis and eczema, two frequent hereditary skin diseases with no cure.
Pelin Sahlén, senior lecturer in KTH Royal Institute of Technology, says the joint KTH-Karolinska Institutet research team mapped 118 gene targets regarding the skin ailments, psoriasis and atopic dermatitis, using a method that the researcher developed 10 years ago to map the interactions between genetic information in various areas of the body.
The investigation focused on the role played by non-coding genetic variations, in other words, DNA that offers no directions for creating proteins. Approximately 2% of DNA is comprised on protein-coding genes, and the remaining 98 percent is non-coding.
Most of the variants (97%) associated with complex diseases are non-coding, Sahlén says. “It isn’t a straightforward task to determine the gene they govern.”
They seemed in the three-dimensional genome for interactions between gene regulating sequences, called promoters and enhancers, determine which genes are active in a variety of tissues.
These sequences can be seen on a DNA strand either before or after the gene they govern. “They are often far from the genes they regulate,” Sahlén states. “By using the Capture Hi-C (HiCap) method, we can join the distal gene regulating sequences with genes by examining the three-dimensional structure of the skin genome.
“This means that we map the regulatory gene network to find new genes linked to diseases and biological processes.”
Sahlén first released the (HiCap) method in 2015. The method is directed at understanding the contribution of this non-coding genome towards an organism’s well-being, survival and health, she says.
The work was funded by the Swedish Research Council, the Swedish Skin Care foundation and a Type 2 innovation grant from Sanofi Genzyme.
KTH Royal Institute of Technology
Sahlén, P., et al. (2020) Chromatin Interactions in Differentiating Keratinocytes Reveal Novel Atopic Dermatitis and Psoriasis-Associated Genes. Journal of Allergy and Clinical Immunology. doi.org/10.1016/j.jaci.2020.09.035.
