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Vol 54(2020) N 5 p. 730-738; DOI 10.1134/S0026893320040160 Full Text

A.S. Ustiugova1*, M.A. Afanasyeva1

Noncoding Polymorphism rs6832151 Is an Attractive Candidate for Genome Editing Aimed at Finding New Molecular Mechanisms of Autoimmune Diseases

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia

*ustugovaalina@yandex.ru
Received - 2020-03-02; Revised - 2020-03-18; Accepted - 2020-03-18

Currently only a small fraction of the proteins encoded in the human genome serve as pharmaceutical targets. Genome-wide association studies are a powerful tool to uncover new genetic loci responsible for predisposition to complex diseases, such as autoimmune disorders. However, further work is still required to identify causative single-nucleotide polymorphisms (SNPs) which directly mediate the disease risk at these loci, and to determine their target genes. These genes can be located millions base pairs away from the regulatory SNPs. Here, by using bioinformatic tools and databases, we identified five intergenic autoimmunity-associated polymorphisms with high probability of being causative, for which the target genes are still unknown. We tested their ability to influence gene expression using luciferase reporter system. The polymorphism rs6832151 affected the reporter expression in the CEM human T-cell line upon the highest enhancer activity. Target genes of this SNP could be further identified by introducing point mutations to the genome and comparison of transcriptomes of the derivative cell sublines carrying alternative alleles of rs6832151.

SNP, post-GWAS, enhancer, autoimmune diseases, luciferase reporter assay



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