Genetic control of N-glycosylation of human blood plasma proteins
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 dise...
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| Format: | Article |
| Language: | English |
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2023-06-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/3734 |
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| author | S. Zh. Sharapov A. N. Timoshchuk Y. S. Aulchenko |
| author_facet | S. Zh. Sharapov A. N. Timoshchuk Y. S. Aulchenko |
| author_sort | S. Zh. Sharapov |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7b3f93874eca4dee81c2af49a109d421 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2023-06-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-7b3f93874eca4dee81c2af49a109d4212025-02-01T09:58:12ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592023-06-0127322423910.18699/VJGB-23-291348Genetic control of N-glycosylation of human blood plasma proteinsS. Zh. Sharapov0A. N. Timoshchuk1Y. S. Aulchenko2MSU Institute for Artificial Intelligence, Lomonosov Moscow State UniversityMSU Institute for Artificial Intelligence, Lomonosov Moscow State UniversityMSU Institute for Artificial Intelligence, Lomonosov Moscow State University; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesGlycosylation 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.https://vavilov.elpub.ru/jour/article/view/3734glycomeglycansn-glycosylationgeneticsgwas |
| spellingShingle | S. Zh. Sharapov A. N. Timoshchuk Y. S. Aulchenko Genetic control of N-glycosylation of human blood plasma proteins Вавиловский журнал генетики и селекции glycome glycans n-glycosylation genetics gwas |
| title | Genetic control of N-glycosylation of human blood plasma proteins |
| title_full | Genetic control of N-glycosylation of human blood plasma proteins |
| title_fullStr | Genetic control of N-glycosylation of human blood plasma proteins |
| title_full_unstemmed | Genetic control of N-glycosylation of human blood plasma proteins |
| title_short | Genetic control of N-glycosylation of human blood plasma proteins |
| title_sort | genetic control of n glycosylation of human blood plasma proteins |
| topic | glycome glycans n-glycosylation genetics gwas |
| url | https://vavilov.elpub.ru/jour/article/view/3734 |
| work_keys_str_mv | AT szhsharapov geneticcontrolofnglycosylationofhumanbloodplasmaproteins AT antimoshchuk geneticcontrolofnglycosylationofhumanbloodplasmaproteins AT ysaulchenko geneticcontrolofnglycosylationofhumanbloodplasmaproteins |