vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RASvavilov-182Research ArticleСтатьиArticlesОЦЕНКА ПО ТЕХНОЛОГИИ rSNP_Guide SNPs ПРОМОТОРОВ ГЕНОВ АРС И МLH1 ЧЕЛОВЕКА, СВЯЗАННЫХ С РАКОМ ТОЛСТОГО КИШЕЧНИКАrSNP_Guide-BASED EVALUATION OF SNPs IN PROMOTеRS OF THE HUMAN APC AND MLH1 GENES ASSOCIATED WITH COLON CANCERРассказовД. А.RasskazovD. A.pon@bionet.nsc.ruАнтонцеваЕ. В.AntontsevaE. V.pon@bionet.nsc.ruБрызгаловЛ. О.BryzgalovL. O.pon@bionet.nsc.ruМатвееваМ. Ю.MatveevaM. Yu.pon@bionet.nsc.ruКашинаЕ. В.KashinaE. V.pon@bionet.nsc.ruПономаренкоП. М.PonomarenkoP. M.pon@bionet.nsc.ruОрловаГ. В.OrlovaG. V.pon@bionet.nsc.ruПономаренкоМ. П.PonomarenkoM. P.pon@bionet.nsc.ruАфонниковД. А.AfonnikovD. A.pon@bionet.nsc.ruМеркуловаТ. И.MerkulovaT. I.pon@bionet.nsc.ruФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, РоссияРоссияInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaRussian FederationФедеральное государственное бюджетное учреждение науки Институт цитологии и генетики Сибирского отделения Российской академии наук, Новосибирск, Россия Новосибирский национальный исследовательский государственный университет, Новосибирск, РоссияРоссияInstitute of Cytology and Genetics SB RAS, Novosibirsk, Russia Novosibirsk National Research State University, Novosibirsk, RussiaRussian Federation201309012015174/1589598Copyright © Рассказов Д.А., Антонцева Е.В., Брызгалов Л.О., Матвеева М.Ю., Кашина Е.В., Пономаренко П.М., Орлова Г.В., Пономаренко М.П., Афонников Д.А., Меркулова Т.И., 20152015Рассказов Д.А., Антонцева Е.В., Брызгалов Л.О., Матвеева М.Ю., Кашина Е.В., Пономаренко П.М., Орлова Г.В., Пономаренко М.П., Афонников Д.А., Меркулова Т.И.Rasskazov D.A., Antontseva E.V., Bryzgalov L.O., Matveeva M.Y., Kashina E.V., Ponomarenko P.M., Orlova G.V., Ponomarenko M.P., Afonnikov D.A., Merkulova T.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/182

Каждый из 6 регуляторных SNPs (Single nucleotide polymorphisms) генов APC и MLH1 человека (rs75996864, rs76241113, rs78037487, rs80112297, rs80313086 и rs1800734) был оценен по созданной ранее технологии rSNP_Guide на значимость изменения связывания каждого из 40 факторов транскрипции с соответствующими районами ДНК. В результате для каждого SNP все анализируемые белки были ранжированы по убыванию уровня статистической значимости α (t-тест Стьюдента) изменения их сродства к аллельным вариантам указанной ДНК. Установлено, что самыми вероятными проявлениями SNPs rs75996864, rs76241113, rs78037487, rs80112297 и rs80313086 гена APC, а также SNP rs1800734 гена MLH1 человека являются изменения в связывании именно тех транскрипционных факторов (NF-Y, NFkB, c-Myb, RAR, YY-1, Sp-1), для которых ранее было показано участие в развитии рака толстого кишечника. Полученные результаты служат новым основанием для исследований ассоциации SNPs rs75996864, rs76241113, rs78037487, rs80112297, rs80313086 гена APC с раком толстого кишечника общепринятыми медико-генетическими методами.

Six regulatory SNPs (single nucleotide polymorphisms) of two human APC and MLH1 genes (rs75996864, rs76241113, rs78037487, rs80112297, rs80313086 and rs1800734) were evaluated by the previously developed rSNP_Guide method to compute the significance of the changes for binding of the SNP region with 40 transcription factors. For each SNP, all analyzed proteins were ranged according to the significance of the changes for protein binding to the alleles evaluated by Student’s t-test. We found that rs75996864, rs76241113, rs78037487, rs80112297, and rs80313086 of APC, as well as rs1800734 of MLH1 in humans concerned to the greatest extent the binding of transcription factors NF-Y, NFkB, c-Myb, RAR, YY-1, and Sp-1, which are known to be involved in colon cancer development. Our results substantiate investigation of associations of rs75996864, rs76241113, rs78037487, rs80112297, and rs80313086 in the APC gene with colon cancer by using commonly accepted medical and genetic protocols.

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The authors declare that there are no conflicts of interest present.