Research Institute of Medical Genetics

Tomsk, Russia

Research Institute of Medical Genetics

Tomsk, Russia
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Trifonova E.A.,Research Institute of Medical Genetics | Ganzha O.A.,Siberian State Medical University | Gabidulina T.V.,Siberian State Medical University | Devyatyarova L.L.,Regional Perinatal Center | And 2 more authors.
Akusherstvo i Ginekologiya (Russian Federation) | Year: 2017

Objective. The review highlights the issues associated with a study of the role of genetic components in recurrent miscarriage (RM) susceptibility through generalized quantitative analysis of data. Material and methods. The review includes the results of foreign and Russian meta-analyses published in the past 10 years and found in the Pubmed database on this topic. Results. The data obtained from the meta-analyses of studies of an association of allelic variants of candidate genes with RM were generalized and the functional significance of a number of associated polymorphic markers was characterized. Consideration of the ethnicity of individuals was shown to be important in studying the role of genetic factors in the development of this disease, as well as gene-gene and gene-environmental interactions. Conclusion. Creation of a future database including the results of associative studies with a detailed description of their design (detailed clinical characteristics of the examinees; criteria for group formations; patient ethnicity) will provide statistically significant evidence for the role of genetic components in the structure of RM susceptibility. © 2017, Bionika Media Ltd. All rights reserved.

Smolnikova M.V.,Russian Academy of Sciences | Freidin M.B.,Research Institute of Medical Genetics | Tereshchenko S.Y.,Russian Academy of Sciences
Immunogenetics | Year: 2017

L-ficolin encoded by FCN2 gene is a crucial factor of defence against infection in humans. We studied the prevalence of the two common variants (rs17549193 and rs7851696) in aboriginal and alien populations of the Taymyr-Dolgan-Nenets region of Krasnoyarskiy Kray, East Siberia, Russia (Nenets, Dolgans, Nganasans, Russians). We found a decreased prevalence of the rs17549193*T allele in all aboriginal populations as compared to Russians. Also, its frequency was the lowest in the Nenets among the studied populations, while frequency of the rs7851696*T allele was increased in this population. The results suggest that the Arctic populations of East Siberia are characterised by specificity of genetic make-up responsible for the activity of L-ficolin. Clinical and epidemiological studies are required to discover if these genetic features correlate with the infant infectious morbidity in East Siberian populations. © 2017 Springer-Verlag Berlin Heidelberg

PubMed | Karolinska Institutet, Max Delbrück Center for Molecular Medicine, University of Cologne, University of Quebec at Chicoutimi and 29 more.
Type: | Journal: Nature communications | Year: 2015

Eczema often precedes the development of asthma in a disease course called the atopic march. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

Rowsey R.,Washington State University | Kashevarova A.,Washington State University | Kashevarova A.,Research Institute of Medical Genetics | Murdoch B.,Washington State University | And 5 more authors.
American Journal of Medical Genetics, Part A | Year: 2013

A variety of hypotheses have been proposed to explain the association between trisomy and increasing maternal age in humans, virtually all of which assume that the underlying mechanisms involve meiotic errors. However, recently Hultén and colleagues [Hulten et al., 2010b] proposed a provocative model-the Oocyte Mosaicism Selection Model (OMSM)-that links age-dependent trisomy 21 to pre-meiotic errors in the ovary. Specifically, they propose that nondisjunctional events occur in a proportion of germ cells as they mitotically proliferate, resulting in mosaicism for trisomy 21. Assuming that the presence of an additional chromosome 21 delays meiotic progression, these cells would be ovulated later in reproductive life, resulting in an age-dependent increase in aneuploid eggs. Because this model has important clinical implications, we initiated studies to test it. We first analyzed oocytes from two trisomy 21 fetuses, combining immunostaining with FISH to determine the likelihood of detecting the additional chromosome 21 at different stages of meiosis. The detection of trisomy was enhanced during the earliest stage of prophase (leptotene), before homologs synapsed. Accordingly, in subsequent studies we examined the chromosome content of leptotene oocytes in seven second trimester female fetuses, analyzing three chromosomes commonly associated with human trisomies (i.e., 13, 16, and 21). In contrast to the prediction of the OMSM, we found no evidence of trisomy mosaicism for any chromosome. We conclude that errors in pre-meiotic germ cells are not a major contributor to human aneuploidy and do not provide an explanation for the age-related increase in trisomic conceptions. © 2013 Wiley Periodicals, Inc.

PubMed | The Institute for Obstetrics and Gynecology, Research Institute of Medical Genetics, North East Federal University and Regional Perinatal Center
Type: Journal Article | Journal: Molekuliarnaia biologiia | Year: 2016

Regulatory single nucleotide polymorphisms (rSNPs) are the least-studied group of SNP; however, they play an essential role in the development of human pathology by altering the level of candidate genes expression. In this work, we analyzed 29 rSNPs in 17 new candidate genes associated with preeclampsia (PE) according to the analysis of the transcriptome in placental tissue. Three ethnic groups have been studied (yakut, russian, and buryat). We have detected significant associations of PE with eight rSNPs in six differentially expressed genes, i.e., rs10423795 in the LHB gene; rs3771787 in the HK2 gene; rs72959687 in the INHA gene; rs12678229, rs2227262, and rs3802252 in the NDRG1 gene; rs34845949 in the SASH1 gene; and rs66707428 in the PPP1R12C gene. We used a new approach to detecting genetic markers of multifactorial diseases in the case of PE based on a combination of genomic, transcriptomic, and bioinformatic approaches. This approach proved its efficiency and may be applied to detecting new potential genetic markers in genes involved in disease pathogenesis, which reduces missing heritability in multifactorial diseases.

PubMed | RAS Institute of Cytology and Genetics, Research Institute of Medical Genetics and Novosibirsk State University
Type: | Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases | Year: 2016

Tuberculosis (TB) is a common infectious disease caused by M. tuberculosis. The risk of the disease is dependent on complex interactions between host genetics and environmental factors. Accumulated genomic data, along with novel methodological approaches such as associative networks, facilitate studies into the inherited basis of TB. In the current study, we carried out the reconstruction and analysis of an associative network representing molecular interactions between proteins and genes associated with TB. The network predominantly comprises of well-studied key proteins and genes which are able to govern the immune response against M. tuberculosis. However, this approach also allowed us to reveal 12 proteins encoded by genes, the polymorphisms of which have never been studied in relation to M. tuberculosis infection. These proteins include surface antigens (CD4, CD69, CD79, CD80, MUC16) and other important components of the immune response, inflammation, pathogen recognition, cell migration and activation (HCST, ADA, CP, SPP1, CXCR4, AGER, PACRG). Thus, the associative network approach enables the discovery of new candidate genes for TB susceptibility.

PubMed | Genoanalitika, Research Institute of Medical Genetics, Siberian State Medical University and Research Institute for Complex Issues of Cardiovascular Diseases
Type: Journal Article | Journal: Acta naturae | Year: 2015

Comorbidity or a combination of several diseases in the same individual is a common and widely investigated phenomenon. However, the genetic background for non-random disease combinations is not fully understood. Modern technologies and approaches to genomic data analysis enable the investigation of the genetic profile of patients burdened with several diseases (polypathia, disease conglomerates) and its comparison with the profiles of patients with single diseases. An association study featuring three groups of patients with various combinations of cardiovascular disorders and a control group of relatively healthy individuals was conducted. Patients were selected as follows: presence of only one disease, ischemic heart disease (IHD); a combination of two diseases, IHD and arterial hypertension (AH); and a combination of several diseases, including IHD, AH, type 2 diabetes mellitus (T2DM), and hypercholesterolemia (HC). Genotyping was performed using the My Gene genomic service ( An analysis of 1,400 polymorphic genetic variants and their associations with the studied phenotypes are presented. A total of 14 polymorphic variants were associated with the phenotype IHD only, including those in the APOB, CD226, NKX2-5, TLR2, DPP6, KLRB1, VDR, SCARB1, NEDD4L, and SREBF2 genes, and intragenic variants rs12487066, rs7807268, rs10896449, and rs944289. A total of 13 genetic markers were associated with the IHD and AH phenotype, including variants in the BTNL2, EGFR, CNTNAP2, SCARB1, and HNF1A genes, and intragenic polymorphisms rs801114, rs10499194, rs13207033, rs2398162, rs6501455, and rs1160312. A total of 14 genetic variants were associated with a combination of several diseases of cardiovascular continuum (CVC), including those in the TAS2R38, SEZ6L, APOA2, KLF7, CETP, ITGA4, RAD54B, LDLR, and MTAP genes, along with intragenic variants rs1333048, rs1333049, and rs6501455. One common genetic marker was identified for the IHD only and IHD and AH phenotypes: rs4765623 in the SCARB1 gene; two common genetic markers, rs663048 in SEZ6L and intragenic rs6501455, were identified for the IHD and AH phenotype and a combination of several diseases (syntropy); there were no common genetic markers for the syntropy and IHD only phenotypes. Classificatory analysis of the relationships between the associated genes and metabolic pathways revealed that lipid-metabolizing genes are involved in the development of all three CVC variants, whereas immunity-response genes are specific to the IHD only phenotype. The study demonstrated that comorbidity presents additional challenges in association studies of disease predisposition, since the genetic profile of combined forms of pathology can be markedly different from those for isolated single forms of a disease.

Lopatkina M.E.,Research Institute of Medical Genetics | Kashevarova A.A.,Tomsk State University | Lebedev I.N.,Tomsk State University
Russian Journal of Genetics | Year: 2016

Analysis of the prevalence of copy number variations of the CNTN6 gene, recently selected as a new candidate gene for intellectual disorders, was performed. Real-time PCR did not detect any change in the number of CNTN6 gene copies in a group of 200 patients with impaired intellectual development. However, taking into account our data from the previous aCGH analysis and published data, the overall frequency of microdeletions and microduplications of CNTN6 was estimated as 1: 265 (0.4%). The common phenotypic features of 40 patients with microdeletions and microduplications of CNTN6 appeared to be the autism spectrum disorders, developmental delay, intellectual disability, seizures, cognitive impairment, cardiological defects, and behavioral problems. © 2016, Pleiades Publishing, Inc.

Kashevarova A.A.,Research Institute of Medical Genetics | Lebedev I.N.,Research Institute of Medical Genetics
Russian Journal of Genetics | Year: 2016

The genomic architecture predisposed to the emergence of DNA copy number variation causing a new class of human chromosomal diseases—reciprocal microdeletion and microduplication syndromes— is reviewed in the paper. The molecular mechanisms of such chromosomal abnormalities are described. The problems of the interpretation of their clinical significance and genotype-phenotype correlations are discussed. The classification of phenotypes due to reciprocal chromosomal microdeletions and microduplications is shown. Published by 2015, reciprocal mutations associated with inherited and congenital human pathology and involving 58 chromosomal regions are summarized. © 2016, Pleiades Publishing, Inc.

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