Candidate SNP markers of atherosclerosis reliably altering the affinity of TATA-binding protein for human gene promoters point to stabilizing natural selection as sum of neutral drift spuring atherogenesis and directional natural selection preventing it

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Dmitry Rasskazov¹, Irina Chadaeva², Mikhail Ponomarenko³, Ekaterina Sharypova⁴, Irina Drachkova⁵, Maria Nazarenko^6
1Systems Biology Department, Institute of Cytology and Genetics (ICG SB RAS), Novosibirsk, Russia, rassk@bionen.nsc.ru
²Systems Biology Department, Institute of Cytology and Genetics (ICG SB RAS), Novosibirsk, Russia, ichadaeva@bionet.nsc.ru
³Systems Biology Department, Institute of Cytology and Genetics (ICG SB RAS), Novosibirsk, Russia, pon@bionen.nsc.ru
⁴Molecular Genetics Department, Institute of Cytology and Genetics (ICG SB RAS), Novosibirsk, Russia, sharypova@bionet.nsc.ru
⁵Molecular Genetics Department, Institute of Cytology and Genetics (ICG SB RAS), Novosibirsk, Russia, drachkova@bionet.nsc.ru
⁶Population Genetics Laboratory, Institute of Medical Genetics (IMG TNRMC RAS), Tomsk, Russia, maria.nazarenko@medgenetics.ru

In this work we carried out a computer-based whole-genome search for all variants of single-nucleotide polymorphism (SNP) within 70 bp regions upstream the all experimentally proven transcription start sites of the human genes associated with atherogenesis according to the current release #151 of the dbSNP database and GRCh38/hg38 assembly of the human reference genome, both of which are publicly available due to the UCSC Genome Browser. In the end, we first found atherosclerosis-related candidate SNP markers signoficantly changing the affinity of TATA-binding protein for promoters of these human gene, frequencies of which differes from the commonly accepted genome-wide norm as if they were under pressure of stabilizing natural selection, which summing up neutral drift accelerating atherogenesis and directional natural selection slowing it down