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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">vavilov</journal-id><journal-title-group><journal-title xml:lang="ru">Вавиловский журнал генетики и селекции</journal-title><trans-title-group xml:lang="en"><trans-title>Vavilov Journal of Genetics and Breeding</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2500-3259</issn><publisher><publisher-name>Institute of Cytology and Genetics of Siberian Branch of the RAS</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18699/VJ16.197</article-id><article-id custom-type="elpub" pub-id-type="custom">vavilov-853</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>SNP-маркеры в биомедицине</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>SNP markers in biomedicine</subject></subj-group></article-categories><title-group><article-title>Выявление новых регуляторных SNP, ассоциированных с предрасположенностью к развитию колоректального рака</article-title><trans-title-group xml:lang="en"><trans-title>Detection of new regulatory SNPs associated with colorectal cancer predisposition</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Леберфарб</surname><given-names>Е. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Leberfarb</surname><given-names>E. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск, Россия</p></bio><bio xml:lang="en"><p>Novosibirsk, Russia</p></bio><email xlink:type="simple">Leberfarb@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Брызгалов</surname><given-names>Л. О.</given-names></name><name name-style="western" xml:lang="en"><surname>Bryzgalov</surname><given-names>L. O.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск, Россия</p></bio><bio xml:lang="en"><p>Novosibirsk, Russia</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Брусенцов</surname><given-names>И. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Brusentsov</surname><given-names>I. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск, Россия</p></bio><bio xml:lang="en"><p>Novosibirsk, Russia</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Меркулова</surname><given-names>Т. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Merkulova</surname><given-names>T. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск, Россия</p></bio><bio xml:lang="en"><p>Novosibirsk, Russia</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»<country>Россия</country></aff><aff xml:lang="en">Institute of Cytology and Genetics SB RAS<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2016</year></pub-date><pub-date pub-type="epub"><day>02</day><month>02</month><year>2017</year></pub-date><volume>20</volume><issue>6</issue><fpage>797</fpage><lpage>803</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Леберфарб Е.Ю., Брызгалов Л.О., Брусенцов И.И., Меркулова Т.И., 2017</copyright-statement><copyright-year>2017</copyright-year><copyright-holder xml:lang="ru">Леберфарб Е.Ю., Брызгалов Л.О., Брусенцов И.И., Меркулова Т.И.</copyright-holder><copyright-holder xml:lang="en">Leberfarb E.Y., Bryzgalov L.O., Brusentsov I.I., Merkulova T.I.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://vavilov.elpub.ru/jour/article/view/853">https://vavilov.elpub.ru/jour/article/view/853</self-uri><abstract><p>Разработан новый подход к поиску регуляторных SNP (rSNP), основанный на анализе ChIP-seq и RNA-seq данных проекта ENCODE. Подход успешно применен для выявления rSNP, связанных с колоректальным раком. В качестве исходных данных были взяты результаты 15 независимых ChIP-Seq экспериментов, выполненных на клеточной линии колоректального рака HCT-116, что позволило сформировать пул из 7985 SNP, расположенных в регуляторных районах генов. Для дальнейшего отбора регуляторных SNP из этого пула использована выявляемая в экспериментах ChIP-seq аллель-специфичность распределения гистоновых меток и негистоновых белков хроматина в местах локализации гетерозиготных SNP. Это позволило выявить 775 SNP, которые потенциально могут влиять на уровень экспрессии генов в клетках HCT-116. В дальнейшем была проведена оценка асимметричности экспрессии аллелей на основании данных RNA-seq, полученных на той же клеточной линии. В результате была подтверждена функциональность 231 SNP, которые были классифицированы как rSNP. Для отбора из них тех, что могут иметь отношение к развитию колоректального рака, были взяты rSNP, находящиеся в одной группе сцепления (±10 т. п. н.) с SNP, ассоциированными с этим заболеванием, по данным GWAS и ClinVar. Функциональная аннотация генов, содержащих выбранные таким образом SNP, подтвердила полученные ранее данные о роли генов BAIAP2L1 и BUB3 в формировании предрасположенности к раку толстого кишечника. Также были обнаружены новые гены-кандидаты колоректального рака, RRAGD и FZD6, белковые продукты которых являются компонентами RAS/MAРK- и WNT-сигнальных путей, сопряженных с развитием данной патологии. Кроме того, выявлено 14 новых потенциальных генов-кандидатов колоректального рака, перспективных для дальнейшего изучения.</p></abstract><trans-abstract xml:lang="en"><p>A new approach to the search for regulatory SNPs (rSNPs) based on the use of ENCODE project data on ChIP-seq and RNA-seq experiments was developed. The approach was successfully used for the detection of rSNPs associated with colorectal cancer susceptibility. To start out with, we used raw sequence data of 15 independent ChIP-seq experiments run on colorectal cancer cell line HCT-116, which allowed us to generate the initial pool of 7985 SNPs located in regulatory regions. For further selection of functional SNPs, we used the ChIP-seq binding bias analysis and revealed 775 SNPs that are more likely to influence transcription regulation in HCT-116 cells. Then the RNA-seq bias analysis in HCT-116 cells was performed. As a result, we confirmed the functionality of 231 SNPs, which were classified as rSNPs. In order to select rSNPs potentially associated with colorectal cancer we chose those in strong linkage disequilibrium with SNPs asso-ciated with this pathology according to GWAS and ClinVar data. Functional annotation analysis of genes containing the rSNPs selected confirmed the involvement of BAIAP2L1 and BUB3 genes in colorectal cancer predisposition. We also found two genes (RRAGD and FZD6) playing a role in the RAS/MAРK and WNT signaling pathways. Although the involvement of the RAS/MAРK and WNT pathways in colon cancer is a well-known fact, these two genes are still unknown candidates. Moreover, we found 14 new candidate genes with promise for further study of colorectal cancer predisposition.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>регуляторные SNP (rSNP)</kwd><kwd>колоректальный рак</kwd><kwd>полногеномные данные</kwd><kwd>проект ENCODE</kwd></kwd-group><kwd-group xml:lang="en"><kwd>regulatory SNPs (rSNP)</kwd><kwd>colorectal cancer</kwd><kwd>next generation sequencing</kwd><kwd>ENCODE project</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Al-Tassan N., Chmiel N.H., Maynard J., Fleming N., Livingston A.L., Williams G.T., … Cheadle J.P. Inherited variants of MYH associated with somatic G:C→T:A mutations in colorectal tumors. Nat. Genet. 2002;30(2):227-232. http://doi.org/10.1038/ng828.</mixed-citation><mixed-citation xml:lang="en">Al-Tassan N., Chmiel N.H., Maynard J., Fleming N., Livingston A.L., Williams G.T., … Cheadle J.P. 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