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Risk genes told about the work of the immune system

13.08.2016

Scientists from the UK have studied how the genes responsible for the risk of contracting a disease work, and have discovered a new mechanism that triggers the processing of energy in our immune cells, activating the fight against infection.

Scientists have identified hundreds of single nucleotide polymorphisms - gene variations that increase or decrease the risk of developing various diseases - from cancer and diabetes to tuberculosis and mental disorders. However, for most of these genes, it is not known how their variants affect the disease. One such gene, C13orf31, is found on chromosome 13. Previously, scientists led by Professor Arthur Kaser of the Cambridge University Department of Medicine showed that a single nucleotide polymorphism in the C13orf31 gene is associated with a risk of contracting the leprosy bacterium and getting chronic inflammatory Crohn's disease and a form of juvenile rheumatoid arthritis.

Now they decided to study the single nucleotide polymorphism of this gene in more depth, for which they used mice in which the equivalent of C13orf31 was changed. It turned out that the gene produces a protein that acts as a key regulator of nuclear metabolic function in a special immune cell, the macrophage. Macrophages engulf foreign organisms, preventing the spread of infection. The protein, which scientists have named FAMIN (Fatty Acid Metabolic Immune Nexus), determines how much energy is released to macrophages.

To edit the genes, the scientists used the CRISPR/Cas9 method, which acts like a biological copy-paste. They edited a single nucleotide in the C13orf31 gene in the mouse genome and showed that even small changes in genetic structures have a big effect: as a result, mice become more susceptible to sepsis. It was found that FAMIN affects the ability of cells to function normally by controlling the ability to kill bacteria and release mediator molecules that trigger an inflammatory response - a key tool in fighting infection and repairing damage to the body.

Thus, by studying the disease risk gene down to the level of a single nucleotide, scientists have discovered a completely new and important mechanism that affects the ability of the immune system to protect the body.

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