Laboratory of Genetic Epidemiology

115478, г. Москва, ул. Москворечье, д.1
Телефоны: +7 (499) 326-60-90; +7 (499) 612-98-90.

Genogeography and epidemiology of hereditary disorders in the Russian populations: the study of mechanisms of hereditary diseases distribution in different populations and ethnic groups.

Since the foundation, the Laboratory has been focusing on the genogeography and epidemiology of hereditary diseases and conditionally neutral DNA markers, as well as identification of leading factors of population dynamics and genetic structure in formation of the genetic load and the range of monogenic hereditary diseases in Russian populations. The project is carried out on the basis of the material obtained during field studies in a number of regions of the Russian Federation and the neighboring countries. The aim of these studies is to investigate the genetic diversity and describe "genetic portraits" of indigenous peoples of Russia through various genetic systems: genes of hereditary diseases, DNA polymorphisms, methods of population statistics. The study allows to understand the geographical variability of hereditary diseases, to identify the areas of their accumulation, and to identify diseases peculiar to certain ethnic groups. The hereditary load of autosomal dominant, autosomal recessive and X-linked recessive diseases in 13 regions of Russia has been determined. The differentiation between populations with various hierarchical levels has been found based on the hereditary load and the range of hereditary diseases, as well as main population genetic parameters. The range of common and rare hereditary disorders for all the surveyed regions of the European part of Russia has been described. Allele and locus heterogeneity of populations and ethnic groups of the Russian Federation for many hereditary diseases is identified. These studies also create a scientific basis for regional registers of hereditary disorders helping to optimize population-based primary medical genetics healthcare by focusing on regional peculiarities of hereditary abnormalities.

Genetic epidemiological studies are also conducted for individual groups of hereditary diseases, taking into account the target system: epidemiology of hereditary ophthalmopathology, hereditary osteochondrodysplasias, hereditary genodermatoses, and hereditary diseases of the nervous system in various regions of the Russian Federation.

Studies of hereditary ophthalmopathology.

Since 2007, the Laboratory has been actively studying the clinical, molecular, and genetic characteristics of the hereditary eye pathology. Molecular genetic diagnosis of individual forms of hereditary ophthalmopathology using NGS methods is carried out. In-house protocols of clinical, molecular, and genetic diagnosis of eye pathology are developed. On the basis of the results obtained, methodical technologies for individual regions of the Russian Federation are being developed to prevent the development of hereditary ophthalmopathology and to provide early adequate treatment. The following patent was obtained: "Method of differential and confirming molecular-genetic diagnosis of congenital aniridia and WAGR syndrome" (registration number RU 2641254, date: August 18, 2017). Three PhD theses were defended under the scope of the project.

The study of hereditary genodermatoses.

The main differential diagnostic criteria for clinical, laboratory and molecular diagnostics of various types of congenital isolated total hypotrichosis widespread among some ethnic groups in the Volga-Ural region have been developed. The LIPH gene was mapped and a causative mutation was identified. Ongoing research in this field demonstrated a new mutation in the receptor gene P2PY5 and subsequently in the KRT25 gene in patients with a hypotrichosis-like phenotype. Clinical and genetic aspects are studied in patients with moniletrix and mutations in the hHb6 gene as well as with ichthyosis vulgaris and mutations in the FLG gene. Three PhD theses are defended under the scope of the project.

The study of hereditary forms of hearing loss.

Since 2000, the laboratory has developed the basic differential diagnostic criteria for clinical genetic diagnosis of various forms of hereditary hearing loss, both isolated and syndromic. A considerable amount of material has been collected from patients with deafness from various ethnic groups. At the moment, the laboratory performs DNA diagnostics in patients with isolated non-syndromic hearing loss using NGS methods. Five PhD theses are defended under the scope of the project.

Molecular genetics of cystic fibrosis in Russia.

Since 1989, the Laboratory has been actively conducting DNA diagnostics (including prenatal diagnosis) for families with a history cystic fibrosis. Laboratory staff along with the Department of cystic fibrosis is constantly participating in international symposia on cystic fibrosis as well as in the Best Practice and Quality Management control on cystic fibrosis molecular diagnosis organized by the Cystic Fibrosis European Network according to the standards of management of patients with cystic fibrosis. Research staff of the Laboratory includes a member of the European Cystic Fibrosis Society, a member of the Steering Committee of three groups of European experts for neonatal screening of cystic fibrosis and for the European registry of patients with cystic fibrosis. Five PhD theses are defended under the scope of the project.

Complex disorders and the study of polymorphisms of genes encoding enzymes of biotransformation of xenobiotic compounds in Russian populations.

From the very first days of the laboratory's foundation, the researchers have been actively studying the genetics of complex (or multifactorial) diseases: diabetes mellitus, uterine myoma, psoriasis, bronchial asthma, etc. More than 10 PhD theses are defended as part of the project. Together with the Department of cystic fibrosis, the influence of the first phase biotransformation genes of xenobiotics on the course of cystic fibrosis and the response to antibiotic therapy for cystic fibrosis are studied.

Analysis of gene mutations in frequent hereditary diseases in different ethnic groups of Russia.

The range of frequent mutations in some of the most common autosomal recessive diseases in Russia or in certain ethnic groups (Maris, Chuvashs, Udmurts, Bashkirs, Tatars, Karachays, Nogays, Cherkess, Abazins, Ossetians, Russians) is analyzed. The following diseases are analyzed: A) Frequency analysis of 13 common mutations in the CFTR gene; B) Analysis of the frequency of mutations C282Y and H63D in the HFE gene associated with hemochromatosis; C) Analysis of the frequency of exon 4 deletion in the LIPH gene; D) Analysis of the frequency of the 35delG mutation in the GJB2 gene.

The Laboratory of Genetic Epidemiology cooperates closely with the medical and genetic counseling units of the Russian Federation (Rostov and Kirov Regions, Chuvashia, Mari El, Udmurtia, Tatarstan, Karachay-Cherkess Republic, North Ossetia Alania) and Russian research institutes. The laboratory conducted joint scientific research with colleagues from the Czech Republic and the United States.

The staff of the Laboratory of Genetic Epidemiology constantly takes an active part in the Russian and international conferences, provides lectures on contemporary problems of medical and molecular genetics, reviews publications in leading scientific journals, joins the editorial committees of journals, and are the scientific supervisors of PhD students themes carried out on the basis of the laboratory.

Based on the materials of the research of the Laboratory, 70 PhD theses are defended, of which 52 are candidate, and 18 are doctoral.

По материалам исследований лаборатории защищено 58 кандидатских диссертаций, и 20 – докторских. За 2022-2024 гг. защищена 1 докторская диссертация: «Наследственные заболевания глаз: эпидемиология, генетическая гетерогенность, клинический полиморфизм», Кадышев В.В. на соискание доктора медицинских наук по специальностям 1.5.7. – Генетика, 3.1.5. – Офтальмология,) и 2 кандидатские «Эпидемиологические и клинико-генетические характеристики спинальной мышечной атрофии 5q и первичных иммунодефицитных состояний в России по данным пилотного проекта неонатального скрининга», Ефимова И.Ю. и «Клинико-функциональная характеристика различных форм врожденной аниридии», Суханова Н.В.

Doctorate theses

1. Revazov A.A. Dynamics of parameters of genetic structure and genetic load in modern human populations. Moscow, 1985.
2. Golubtsov V.I. Influence of factors of population dynamics on the load of hereditary diseases of the population of the Krasnodar Krai. Kiev, 1991.
3. Turaeva Sh.M. The genogeography of hereditary diseases in the Turkmen SSR and the development of regional principles of medical genetic counseling. Moscow, 1992.
4. Petrin A.N. Hereditary diseases in populations with different genetic structure. Moscow, 1992.
5. Panteleyeva O.A. Clinical and genetic analysis of refractive errors and associated syndromes. Moscow, 1997.
6. Nurbaev S.D. Methodology for assessing the reliability of mathematical models in population genetic studies. Moscow, 1998.
7. Balanovskaya E.V. New technologies for studying the spatial structure of the gene pool. Moscow, 1998.
8. Rudenskaya G.E. Hereditary diseases of the nervous system in the Russian and Middle Asian populations: clinical genetic and epidemiological study. Moscow, 1998.
9. Khlebnikova O.V. Hereditary pathology of the organ of vision in populations with different genetic structure. Moscow, 1998.
10. Dadali E.L. Hereditary neuromuscular diseases: diagnosis and medical genetic counseling. Moscow,1999.
11. El’chinova G.I. Experience in the application of methods of population-genetic analysis in the study of populations of Russia with a different genetic and demographic structure. Moscow, 2001.
12. Zinchenko R.A. Epidemiology of hereditary diseases in Russian populations. Moscow, 2001.
13. Polyakov A.V. The strategy of identification of genetic loci in heterogeneous Mendelian hereditary diseases. Moscow, 2002.
14. Berezina G.M. Genetic and demographic processes in rural populations of Kazakhstan and their genetic differentiation by mitochondrial DNA. Moscow, 2005.
15. Amelina S.S. Epidemiology of monogenic hereditary pathology and congenital malformations in the population of the Rostov region. Moscow, 2006.
16. Kirillov A.G. Hereditary diseases in the Chuvash Republic. Moscow, 2008.
17. Petrova N.V. Molecular genetic and genotype–genotype features of cystic fibrosis in Russian populations. Moscow, 2009.
18. Batozhargalova B.C. Clinical, epidemiological, genetic and ethnic features of asthma in adolescents Transbaikalia. Moscow, 2015.

PhD theses

1. Altshuler B.A. Genetic studies of peptic ulcer. Moscow, 1978.
2. Tarlycheva L.V. Studying the factors of marital assortativeness in the North of the Non-Chernozemic zone of the RSFSR. Moscow, 1980.
3. Luchkina E.M. Genetic analysis of the structure of the relationships between the indices of blood pressure, cholesterol levels and the sugar curve. Moscow, 1980.
4. Solovyova N.P. Phenotypic and genetic variability of small hemoglobin fractions. Moscow, 1981
5. Pobedimskaya T.D. Factors of population dynamics and the spread of hereditary diseases of the nervous system in Tajikistan. Moscow, 1981.
6. Petrin A.N. Genetic analysis of fluorescent Q-polymorphism of chromosomes in the Turkmen population (frequencies and segregation of Q-variants of chromosomes). Москва,1983.
7. Turaeva Sh.M. Ways of spreading hereditary diseases in Turkmenistan (population and clinical genealogy analysis). Москва,1983.
8. Zakharova G.Yu. Clinical and genealogical studies of peripheral vitreochorioretinal dystrophies. Moscow, 1983.
9. Tsudik A.Z. Genetic analysis of liver cirrhosis. Moscow, 1983.
10. Keremi N.B. Genetics of diabetes mellitus taking into account the age of onset. Moscow, 1983.
11. Yakimova M.A. The role of genetic factors in the development of bronchial asthma. Moscow, 1984.
12. Korchagin N.V. A formalized description of the types of inheritance of traits using the values of penetration of gene allelotypes. Moscow, 1985.
13. Budagova K.A. The genetic load of hereditary pathology in populations with positive marital assortativeness. Moscow, 1986.
14. Bolshakova L.P. Studying the phenomena of reproductive compensation of heritability of fertility in human populations. Moscow, 1986.
15. Lemza S.V. Genetic-demographic structure and the relationship of genetic polymorphism with the variability of quantitative traits in the population of the Northern Khanks. Moscow, 1986.
16. Korolova A.G. Efficiency of complex segregation analysis depending on the informativeness of family data. Moscow, 1987.
17. Khisamova M.V. A comparative study of the burden of hereditary pathology of the urban and surrounding rural population. Moscow, 1988.
18. Paradeeva G.M. Factors of the subdivision of Russian populations of the Non-Black Earth Region. Moscow, 1987.
19. Hajiyev B.O. Biochemical polymorphism of serum cholinesterase in Azerbaijan.Moscow, 1989.
20. El’chinova G.I. Reconstruction of the population structure from non-genetic parameters. Moscow, 1989.
21. Svyatova G.S. Genetic and demographic characteristics of a large cosmopolitan city. Moscow, 1989.
22. Kurbanova M.H. The role of genetic factors in the development of uterine myomas. Moscow, 1989.
23. Izhevsky P.V. Genetic-epidemiological analysis of peptic ulcer. Moscow, 1989.
24. Kadoshnikova M.Yu. Comparative analysis of the burden of hereditary pathology of the Adygeans and Russian populations of the Adyghe Autonomous Region of the Krasnodar Krai.Moscow, 1990.
25. Galkina V.A. Distribution of hereditary diseases among the population of the Krasnodar Krai and medical genetic counseling. Moscow, 1991.
26. Mamedova R.A. The influence of genetic drift on the territorial distribution of genetic load as well as the spectrum of hereditary diseases in populations of the Kirov region. Moscow, 1993.
27. Kolesnikova TN Molecular genetic heterogeneity of beta-thalassemia in some regions of Central Asia. Moscow, 1993.
28. Semina E.V. Comparative analysis of DNA polymorphism, revealed by hypervariable DNA probe of M13 phage in human populations. Moscow, 1993.
29. Petrova N.V. Determination of the relative frequencies of some mutations of the CFTR gene and analysis of haplotypes of the linked DNA loci in populations of Russia. Moscow, 1996.
30. Kirillov A.G. Autosomal recessive osteopetrosis in Chuvashia. Moscow, 2005.
31. Kriventsova N.V. Population and genetic characteristics of the population of the region with a high level of immigration. Moscow, 2006.
32. Osipova E.V. Medical and population genetic study of the population of the Republic of Udmurtia. Moscow, 2006.
33. Shokarev R.A. Prevalence and genetic heterogeneity of hereditary hearing loss in the Rostov region. Moscow, 2006.
34. Zinchenko S.P. Genetic-epidemiological study of hereditary deafness in the Republic of Chuvashia. Moscow, 2007.
35. Abrukova A.V. Epidemiological and clinical genetic study of hereditary hypotrichosis in the Republic of Chuvashia. Moscow, 2007.
36. Timkovskaya E.E. Analysis of a number of genes as possible gene-modifiers of the clinical picture of cystic fibrosis in patients from Russia. Moscow, 2007.
37. Mukhay M.B. Clinical and genetic features of hereditary ophthalmopathology with optimization of medical and genetic care for the population of the Tver region. Moscow, 2008.
38. Balinova N.V. Anthropogenetic aspects of the formation of the structure of populations in Kalmykia. Moscow, 2008.
39. Grinberg Ya.I. Complex medical and population genetic study of the population of the Republic of Bashkortostan. Moscow, 2009
40. Beklemishcheva N.A. Principles of creating an information retrieval diagnostic system for hereditary diseases of the organ of vision. Moscow, 2009
41. Marakhonov A.V. Study of the structure and function of antisense transcripts of human AFAP1, ASCL1, MAP3K13 genes. Moscow, 2011.
42. Nefedova E.D. Alopecia areata: clinical and genetic predictors of severe forms of disease. Moscow, 2011.
43. Osetrova A.A. Genetic and epidemiological study of hereditary deafness in the Kirov region. Moscow, 2011.
44. Kusova Z.A. The effectiveness of the program of mass screening of newborns for cystic fibrosis. Moscow, 2011.
45. Kadyshev V.V. Epidemiology and clinical genetic features isolated hereditary ophthalmopathology Kirov region. Moscow, 2011.
46. Kireeva O.L. Clinical and genetic features of the spread of ophthalmopathology in the Rostov region. Moscow, 2012.
47. Vekshina A.B. Development and software implementation of the adaptive model of the genogeographic forecast based on the methods of optimal estimation and design of the experiment. Moscow, 2012.
48. Shurygina M.F. Clinical and molecular genetic aspects of the diagnosis of Stargardt disease in the Russian Federation. Moscow, 2013.
49. Akhmedova P.G. Epidemiology of hereditary neuromuscular diseases in the Republic of Dagestan. Development of the basics of neuroregistry. Moscow, 2015.
50. Amelina M.A. Epidemiology and phenotypic and genetic characteristics of phenylketonuria in the Rostov Region. Moscow, 2016.
51. Gundorova P. Molecular genetic features of hyperphenylalaninemia in the Karachay-Cherkess Republic. Moscow, 2017.
52. Valkov R.A. Genetic epidemiology of hereditary skeletal diseases in the Rostov region. Moscow, 2017.

Monographs

1. Medical genetic description of the population of Adygea. Ed. E.K. Ginter. Maykop, 1997. 226 p.
2. Mordovtsev V.N., Keshilyova Z.B., Sergeev A.S. Genetics in Dermatology: A Brief Guide to the Faculties of Postgraduate Advanced Physicians. - Almaty: "Medicine of the Baspasy", 2001. 84 p.
3. Mordovtsev V.N., Alieva P.M., Sergeev A.S. Skin diseases with hereditary predisposition. Makhachkala, 2002. 260 p.
4. Hereditary diseases in human populations. Ed. E.K. Ginter. M .: Medicine, 2002. 303 p.
5. Genetic structure and hereditary diseases of the Chuvash population. Collective monograph edited by Ginter E.K., Zinchenko R.A. Cheboksary: the publishing house "Pegasus", 2006. 232 p.
6. Tarskaya L.A., Gogolev A.I., El’chinova G.I., Egorova A.G., Limborskaya S.A. Ethnic genomics of the Yakuts (Sakha people). Genetic features and population history. Moscow: Nauka, 2009. 271 p.
7. Clinical and genetic aspects of congenital and hereditary pathology in the population of the Rostov region. Collective monograph edited by Zinchenko R.A., Savisko A.A., Amelina S.S. Rostov-on-Don: Publishing House RosGMU, 2010. 522 p.
8. E. K. Ginter, R. A. Zinchenko. Epidemiology of hereditary diseases in European Sector of Russia in “Genomics And Health In The Developing World’” Editor by Dhavendra Kumar. Oxford University Press. New York, USA. 2012. P. 1281-1314.
9. Petrova N.V., Ginter E.K. Chapter 2. Molecular-genetic aspects of cystic fibrosis. In the book: Cystic fibrosis. Ed. Kapranova N.I., Kashirskaya N.Yu. Moscow: Publishing House Medpraktika-M, 2014. 672 p.

Selected articles in scientific journals

1. Kazantseva L., Goltsov A., Zinchenko R., Grigorenko A.P., Abrukova A.V., Y.K. Moliaka, Kirillov A.G., Guo Z., Lyle S., Ginter E.K., Rogaev E.I.. Human Hair Growth Deficiency Is Linked to a Genetic Defect in the Phospholipase Gene LIPH. Science. 2006. Nov.110. 314(5801):982–985.
2. Shmarina G., Pukhalsky A., Petrova N., Zakharova E., Avakian L., Kapranov N., AlioshkinV. TNF gene polymorphism in cystic fibrosis patients: contribution to the disease progression. Journal of Translational Medicine. 2013. 11:19-26.
3. Meshcheryakova T.I., Zinchenko R.A., Vasilyeva T.A., Marakhonov A.Y., Zhylina S.S., Petrova N.Y., Kozhanova T.V., Belenikin M.S., Petrin A.N., Mutovin G.R.. A clinical and molecular analysis of branchio-oculo-facial syndrome patients in Russia revealed new mutations in TFAP2A. Annals of Human Genetics. 2015. Jan 15. doi: 10.1111/ahg.12098.
4. Zernov N.V., Skoblov M.Y., Marakhonov A.V., Shimomura Y., Vasilyeva T.A., Konovalov F.A., Abrukova A.V., Zinchenko R.A. A novel type of autosomal recessive hypotrichosis with woolly hair is caused by а homozygous mutation in KRT25. J Invest Dermatol. 2016 Feb 20. doi: 10.1016/j.jid.2016.01.037.
5. Petrova N.V., Kashirskaya N.Yu., Vasilieva T.A.,Timkovskaya E.E., Voronkova A.Yu., Shabalova L.A., Kondrateva E.I., Sherman V.D., Kapranov N.I., Zinchenko R.A.,Ginter E.K., Makaov A.Kh-M., Kerem B. High proportion of W1282X mutation in CF patients from Karachai-Cherkessia // J of Cystic Fibrosis. 2016 Mar 3. doi: 10.1016/j.jcf.2016.02.003.
6. Kashirskaya N.Y., Kapranov N.I., Sander-Struckmeier S., Kovalev V. Safety and efficacy of Creon® Micro in children with exocrine pancreatic insufficiency due to cystic fibrosis // J of Cystic Fibrosis. 2015. Mar. 14.. doi: 10.1016/j.jcf.2014.07.006.
7. Andreeva T.V., Tyazhelova T.V., Rykalina V.N., Gusev F.E. , Goltsov A.Yu., Zolotareva O.I., Aliseichik M.P., Borodina Т.A., Grigorenko A.P., Reshetov D.A., Ginter E.K., Amelina S.S., Zinchenko R.A. and Rogaev E.I. Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies. Scientific Reports.2016. May 24. doi: 10.1038/srep26440.
8. Barben J, Castellani C, Dankert-Roelse J, Gartner S, Kashirskaya N, Linnane B, Mayell S, Munck A, Sands D, Sommerburg O, Pybus S, Winters V, Southern KW. The expansion and performance of national newborn screening programmes for cystic fibrosis in Europe // J of Cystic Fibrosis. 2017 Mar;16(2):207-213. doi: 10.1016/j.jcf.2016.12.012
9. Voskresenskaya A, Pozdeyeva N, Vasilyeva T, Batkov Y, Shipunov A, Gagloev B, Zinchenko R. Clinical and morphological manifestations of aniridia-associated keratopathy on anterior segment optical coherence tomography and in vivo confocal microscopy. The Ocular Surface. 2017 Jul 8. doi: 10.1016/j.jtos.2017.07.001.
10. Vasilyeva T.A., Voskresenskaya A.A., Käsmann-Kellner B., Khlebnikova O.V., Pozdeyeva N.A., Bayazutdinova G.M., Kutsev S.I., Ginter E.K., Semina E.V., Marakhonov A.V., Zinchenko R.A. Molecular Analysis of Patients with Aniridia in Russian Federation Broadens the Spectrum of PAX6 Mutations. Clinical Genetics. 2017. Aug 2. doi:10.1111/cge.13019.
11. Marakhonov A.V., Konovalov F.A., Makaov A.Kh., Vasilyeva T.A., Kadyshev V.V., Galkina V.A., Dadali E.L., Kutsev S.I., Zinchenko R.A. Primary microcephaly case from the Karachay-Cherkess Republic poses an additional support for microcephaly and Seckel syndrome spectrum disorders. BMC Medical Genomics. 2018. doi:10.1186/s12920-018-0326-1