References

vavilov

Вавиловский журнал генетики и селекции

Vavilov Journal of Genetics and Breeding

2500-3259

Institute of Cytology and Genetics of Siberian Branch of the RAS

10.18699/VJGB-23-29

vavilov-3734

Research Article

ГЕНЕТИКА ЧЕЛОВЕКА

HUMAN GENETICS

Генетический контроль N-гликозилирования белков плазмы крови человека

Genetic control of N-glycosylation of human blood plasma proteins

https://orcid.org/0000-0003-0279-4900

Шарапов

С. Ж.

Sharapov

S. Zh.

Москва

Moscow

https://orcid.org/0000-0001-8529-4498

Тимощук

А. Н.

Timoshchuk

A. N.

Москва

Moscow

https://orcid.org/0000-0002-7899-1575

Аульченко

Ю. С.

Aulchenko

Y. S.

Москва, Новосибирск

Moscow, Novosibirsk

yurii@bionet.nsc.ru

Институт перспективных исследований проблем искусственного интеллекта и интеллектуальных систем Московского государственного университета им. М.В. ЛомоносоваРоссияMSU Institute for Artificial Intelligence, Lomonosov Moscow State UniversityRussian Federation

Институт перспективных исследований проблем искусственного интеллекта и интеллектуальных систем Московского государственного университета им. М.В. Ломоносова; Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияMSU Institute for Artificial Intelligence, Lomonosov Moscow State University; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian Federation

2023

02062023

273224239

2023

Шарапов С.Ж., Тимощук А.Н., Аульченко Ю.С.

Sharapov S.Z., Timoshchuk A.N., Aulchenko Y.S.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://vavilov.elpub.ru/jour/article/view/3734

Гликозилирование является важной модификацией белков, которая влияет как на их физико-химические свойства, так и на выполняемые ими биологические функции. Масштабные популяционные исследования показали, что уровни различных N-гликанов белков плазмы крови ассоциированы с риском развития ряда мультифакторных заболеваний человека. Найденные ассоциации стали основанием для рассмотрения N-гликанов в качестве потенциального источника биомаркеров и терапевтических мишеней. Биохимические пути N-гликозилирования хорошо изучены, однако понимание механизмов общей и тканеспецифической регуляции этих биохимических реакций in vivo весьма ограниченно. Это затрудняет как интерпретацию наблюдаемых ассоциаций уровней N-гликанов с заболеваниями человека, так и разработку биомаркеров и молекулярных мишеней на их основе. Прогресс в области технологий анализа N-гликозилирования белков позволил к началу 2010-х годов проводить исследования регуляции N-гликозилирования с помощью методов генетического анализа, в том числе полногеномного исследования генетических ассоциаций. Применение этих методов дает возможность находить новые, ранее неизвестные регуляторы N-гликозилирования и расширяет представление о роли N-гликанов в контроле мультифакторных заболеваний и комплексных признаков человека. В данном обзоре мы рассматриваем современное состояние исследований генетического контроля популяционной изменчивости уровней N-гликозилирования белков плазмы крови человека. Описаны современные физико-химические методы измерения N-гликомного профиля, приведены базы данных, содержащие гены, вовлеченные в биосинтез N-гликанов. Систематизированы результаты исследований вклада средовых и генетических факторов в популяционную изменчивость N-гликанов, а также результаты картирования геномных локусов N-гликанов методом полногеномного исследования ассоциаций. Представлены результаты последующих функциональных исследований in vitro и in silico, позволивших предложить новые гены-кандидаты, регулирующие N-гликозилирование белков. В заключение кратко показан текущий прогресс в области гликогеномики человека и описаны возможные пути дальнейших исследований N-гликома.

Glycosylation is an important protein modification, which influences the physical and chemical properties as well as biological function of these proteins. Large-scale population studies have shown that the levels of various plasma protein N-glycans are associated with many multifactorial human diseases. Observed associations between protein glycosylation levels and human diseases have led to the conclusion that N-glycans can be considered a potential source of biomarkers and therapeutic targets. Although biochemical pathways of glycosylation are well studied, the understanding of the mechanisms underlying general and tissue-specific regulation of these biochemical reactions in vivo is limited. This complicates both the interpretation of the observed associations between protein glycosylation levels and human diseases, and the development of glycan-based biomarkers and therapeutics. By the beginning of the 2010s, high-throughput methods of N-glycome profiling had become available, allowing research into the genetic control of N-glycosylation using quantitative genetics methods, including genome-wide association studies (GWAS). Application of these methods has made it possible to find previously unknown regulators of N-glycosylation and expanded the understanding of the role of N-glycans in the control of multifactorial diseases and human complex traits. The present review considers the current knowledge of the genetic control of variability in the levels of N-glycosylation of plasma proteins in human populations. It briefly describes the most popular physical-chemical methods of N-glycome profiling and the databases that contain genes involved in the biosynthesis of N-glycans. It also reviews the results of studies of environmental and genetic factors contributing to the variability of N-glycans as well as the mapping results of the genomic loci of N-glycans by GWAS. The results of functional in vitro and in silico studies are described. The review summarizes the current progress in human glycogenomics and suggests possible directions for further research.

гликомгликаныN-гликозилированиегенетикаПГИА

glycomeglycansN-glycosylationgeneticsGWAS

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