Head of Laboratory Edward V Generozov
Senior staff scientist Tatyana V Pogoda
Senior staff scientist Elena B Khomyakova
Scientific associate Natalya B Zaharjevskaya
Scientific associate Vladimir A Naumov
Postgraduate student Nikolay A Kulemin
Laboratory assistant Elizaveta A Babikova
Topics of scientific interest and lines of research
Laboratory of Human Molecular Genetics was founded in 2004, and is a part of the Department of Molecular Biology and Genetics.
Achievements of contemporary molecular biology indicate that genetically determined events play a significant role in the development of many widespread diseases that are not traditionally considered as genetic ones. Single point mutations in the nucleotide sequence of a DNA molecule or single nucleotide polymorphisms (SNPs) can act as such factors. A certain combination of genetically determined changes specifies the level of risk for disease development. The information on these combinations, obtained through genetic analysis, will be able to predict the susceptibility of an individual to future diseases.
In addition to hereditary factors, among which are the above mentioned genetic polymorphisms, genetic defects and breakages at the somatic level are another cause for the development of many diseases, especially cancer. A spectrum of somatic mutations is a mandatory attribute of malignant enoplasms. Aberrant DNA hypermethylation, which is observed in tumor tissue, is also related to these changes.
The main lines of research currently going on in the laboratory are performed using the model of colorectal cancer, one of the most significant cancers. Colorectal cancer is among the leading causes of cancer-related deaths. The laboratory is striving to identify which of inherited, somatic, and epigenetic markers of colorectal cancer are most informative. In the framework of this project, our research encompasses, on the one hand, an investigation aimed at identifying the combination of genetic markers of individual susceptibility to the disease, and, on the other hand, an analysis of specific profiles of genetic and epigenetic (namely DNA methylation) changes in tumor tissue to select those that are most informative and, hence, can be used to design diagnostic tests.
So far, we accomplished the work on the analysis of the colorectal cancer methylome, through the high-density DNA microarray technique to measure the density of methylation. We currently carry out the work on the development of a non-invasive genetic test for colorectal cancer. Another research line related to colorectal cancer is an analysis of microscopic subcellular components such as microvesicles or exosomes, which are secreted by normal, viable cells of body’s different tissues. It has been shown that the quantitative and qualitative composition of microvesicles sufficiently changes in the course of oncological diseases. Microvesicles are suggested to play a role in the inter-cellular communication. The presence of microRNA in microvesicles suggests that these subcellular components may be implicated in the regulation of gene expression. The possibility that tumor specific microvesicles can be isolated from peripheral blood allows consider them as a promising marker for early diagnostics of the disease.
In addition to the work relating to cancer, the laboratory has other lines of research. Among them is an analysis of possible molecular mechanisms of realization of genetic markers of age-related macular dystrophy. This work is nearing completion. Age-related retinal dystrophy is one of causes of vision loss among the elderly. Recent international research led to the identification of several candidate genes that may be responsible for the increased risk of this disease. A current study is aimed at identifying molecular mechanisms for the pathogenic effect of mutations in the complement factor H (CFH) gene.
The laboratory is also involved in investigating pro-tumor and anti-tumor effects of different types of ionizing radiation among the population of ЗАТО and workers of atomic enterprises.
A set of equipment for the comprehensive genetic analysis is available:
- Low temperature and domestic refrigerators
- Desktop centrifuge with cooling and without
- Boxes for setting the amplification reactions
- Thermocycler DNA ENGINE TETRADTM (MJ Research)
- MALDI ToF mass spectrometer MICROFLEX (Bruker Daltoniks)
- Sequencer ABI Prism-3730 Genetic Analyzer (Applied Biosystems, USA; Hita-chi, Japan)
- Ion Personal Genome Machine® (PGM™) System (Applied Biosystems, USA)
- SOLiD 4 (Applied Biosystems, USA)
- GS FLX+ Sequensing System (Roche)
- TECAN Freedom Evo Workstation (Illumina, USA)
- iScan (Illumina, USA)
- Electrophoretic Equipment
- London School of Hygiene & Tropical Medicine, London, UK
- University of Lethbridge, Lethbridge, Canada
- Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia
- State Scientific Center of Coloproctology, Moscow, Russia
- Moscow State University, Moscow, Russia
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
- I.M. Sechenov First Moscow State Medical University, Moscow, Russia
- Institute of Internal Medicine, Siberian Branch of the Russian Academy of Medical Science, Novosibirsk, Russia
- Institute of Cytology and Genetics, Novosibirsk, Russia.
Research & Development “Development of high-throughput method for genetic polymorphisms analysis for fundamental studies of socially significant diseases in humans” (2009-2011) in the frames of Federal Target Program "Research and Scientific-Pedagogical Personnel of Innovative Russia in 2009-2013.
Research & Development “Characterization of pharmacogenomic markers, causing individual, genetically determined sensitivity/resistance to the drugs used in the treatment of cancer” 2012. funded by the Ministry of Health Care and Social Development of Russian Federation
- Genome-scale analysis of DNA methylation in colorectal cancer using Infinium HumanMethylation450 BeadChips. Naumov VA, Generozov EV, Zaharjevskaya NB, Matushkina DS, Larin AK, Chernyshov SV, Alekseev MV, Shelygin YA, Govorun VM. Epigenetics. 2013 Jul 17;8(9)
- Contemporary pharmacogenetic approaches to the treatment of age-related macular degeneration. Budzinskaia MV, Pogoda TV, Generozov EV, Chikun EA, Gurova IV, Shchegoleva IV, Sizova MV.Vestn Oftalmol. 2013 Sep-Oct;129(5):128-35
- Association of FGFR3 and MDM2 gene nucleotide polymorphisms with bone tumors. Naumov VA, Generozov EV, Solovyov YN, Aliev MD, Kushlinsky NE. Bull Exp Biol Med. 2012 Oct;153(6):869-73. English, Russian.
- Coronary heart disease diagnostics by artificial neural networks including genetic polymorphisms and clinical parameters. O.Y. Atkov, Svetlana G. Gorokhova, Alexandr G. Sboev, Eduard V. Generozov, Svetlana Y. Moroshkina, Elena V. Muraseyeva, Nadezhda N. Cherniy. Journal of Cardiology. 2012 59, 190-194.
- Hypermethylation of the CDH1, SEPT9, HLTF and ALX4 genes and their diagnostic significance in colorectal cancer. Kostin PA, Zakharzhevskaia NB, Generozov EV, Govorun VM, Chernyshov SV, Shchelygin IuA.Vopr Onkol. 2010;56(2):162-8.
Links to online resources
Database for medically significant polymorphisms of the human genome (project supported by grants RFBR N 05-07-90121 and 08-07-0037)
The goal of the project is identification of human genome polymorphisms (single nucleotide polymorphism (SNP)), associated with altered predisposition to different multifactorial diseases using reference data from public databases. The constructed database includes gene polymorphisms, associated with altered predisposition to coronary artery, cancer, pulmonary, neurodegenerative and other multifactorial diseases. This is combined database which contains as factual data (precise genome position, reference DNA/RNA sequences, allele frequency data, odd ratios) as well as descriptive data (publication references and full-text publications). The opportunity of the comparative analysis of new experimental data with previously collected factual and the bibliographic information is realized by using of hyperlinks. In addition to experimental data a theoretical information block of a database which includes new genes and medically relevant SNPs has been added. Constructed database may be useful tool for appropriated experimental design in human molecular genetic studies, for development of new diagnostic genetic tests; and also it can be considered as a reference informational source for specialists working in the field of medical genetics.