Candidate SNP markers of rheumatoid arthritis changing the affinity of TATA-binding protein for the human gene promoters expo disruptive selection of immunoactivative and immunosuppressive genenets that provoke and prevent this disorder, respectively, as if it could be a self-domestication syndrome

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Natalya Klimova¹, Dmitry Oshchepkov², Irina Chadaeva³, Mikhail Ponomarenko⁴, Evgeniya Oshchepkova⁵, academician Vladimir Kozlov^6
1Molecular Genetics Department, Institute of Cytology and Genetics, ICG SB RAS, Novosibirsk, Russia, klimova@bionet.nsc.ru
²Systems Biology Department, Institute of Cytology and Genetics, ICG SB RAS, Novosibirsk, Russia, diman@bionet.nsc.ru
³Systems Biology Department, Institute of Cytology and Genetics, ICG SB RAS, Novosibirsk, Russia, ichadaeva@bionet.nsc.ru
⁴Systems Biology Department, Institute of Cytology and Genetics, ICG SB RAS, Novosibirsk, Russia, pon@bionen.nsc.ru
⁵Systems Biology Department, Institute of Cytology and Genetics, ICG SB RAS, Novosibirsk, Russia, nzhenia@bionet.nsc.ru
⁶Research Institute of Fundamental and Clinical Immunology, RIFCI SB RAS, Novosibirsk, Russia, niiki01@online.nsk.su

Here we conducted a computational genome-wide study of the all known single-nucleotide polymorphism (SNP) of 70 bp proximal promoters of 67 human rheumatoid arthritis (RA)-related genes that displayed disruptive natural selections of immunoactivative or immunosuppressive genes raising or reducing risks of RA, respectively, as if it maybe a domestication syndrome. That is why, we confirmed it in vivo using the genome-wide transcriptome profiling (RNA-seq assay) of the differentially expressed genes (DEGs) within hypothalamus of adult male rats (Rattus norvegicus) of two unique outbred lines bred in aggressiveness and tameness as an animal model of human diseases (statistical significance p_adj < 0.025 at Pearson\’s П‡² criterion with Bonferroni\’s correction).