A New Leu714Arg Variant in the Converter Domain of is Associated with a Severe Form of Familial Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy is the most frequent autosomal dominant disease, yet due to genetic heterogeneity, incomplete penetrance, and phenotype variability, the prognosis of the disease course in pathogenic variant carriers remains an issue. Identifying common patterns among the effects of different genetic variants is important.

Methods: We investigated the cause of familial hypertrophic cardiomyopathy (HCM) in a family with two patients suffering from a particularly severe disease.

Apoptosis Genes as a Key to Identification of Inverse Comorbidity of Huntington's Disease and Cancer.

Cancer and neurodegenerative disorders present overwhelming challenges for healthcare worldwide. Epidemiological studies showed a decrease in cancer rates in patients with neurodegenerative disorders, including the Huntington disease (HD). Apoptosis is one of the most important processes for both cancer and neurodegeneration.

ABCA1 and ABCG1 DNA methylation in epicardial adipose tissue of patients with coronary artery disease.

Background: Recent studies have focused on the potential role of epicardial adipose tissue (EAT) in the development of coronary artery disease (CAD). ABCA1 and ABCG1 transporters regulate cell cholesterol content and reverse cholesterol transport. We aimed to determine whether DNA methylation and mRNA levels of the ABCA1 and ABCG1 genes in EAT and subcutaneous adipose tissue (SAT) were associated with CAD.

Genome-wide sequence analyses of ethnic populations across Russia.

The Russian Federation is the largest and one of the most ethnically diverse countries in the world, however no centralized reference database of genetic variation exists to date. Such data are crucial for medical genetics and essential for studying population history. The Genome Russia Project aims at filling this gap by performing whole genome sequencing and analysis of peoples of the Russian Federation.

Between Lake Baikal and the Baltic Sea: genomic history of the gateway to Europe.

Background: The history of human populations occupying the plains and mountain ridges separating Europe from Asia has been eventful, as these natural obstacles were crossed westward by multiple waves of Turkic and Uralic-speaking migrants as well as eastward by Europeans. Unfortunately, the material records of history of this region are not dense enough to reconstruct details of population history. These considerations stimulate growing interest to obtain a genetic picture of the demographic history of migrations and admixture in Northern Eurasia.

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases.

Genomic structural variations for cardiovascular and metabolic comorbidity.

The objective of this study was to identify genes targeted by both copy number and copy-neutral changes in the right coronary arteries in the area of advanced atherosclerotic plaques and intact internal mammary arteries derived from the same individuals with comorbid coronary artery disease and metabolic syndrome. The artery samples from 10 patients were screened for genomic imbalances using array comparative genomic hybridization. Ninety high-confidence, identical copy number variations (CNVs) were detected.

Meta-analysis identifies seven susceptibility loci involved in the atopic march.

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.

A comparison of genome-wide DNA methylation patterns between different vascular tissues from patients with coronary heart disease.

Epigenetic mechanisms of gene regulation in context of cardiovascular diseases are of considerable interest. So far, our current knowledge of the DNA methylation profiles for atherosclerosis affected and healthy human vascular tissues is still limited. Using the Illumina Infinium Human Methylation27 BeadChip, we performed a genome-wide analysis of DNA methylation in right coronary artery in the area of advanced atherosclerotic plaques, atherosclerotic-resistant internal mammary arteries, and great saphenous veins obtained from same patients with coronary heart disease.

Mutations in genes underlying atypical familial mycobacteriosis are not found in tuberculosis patients from Siberian populations.

Objectives: Atypical familial mycobacteriosis (AFM, OMIM #209950) is caused by mutations in genes regulating IL12/IFNG pathway. Some of the mutations exhibit incomplete penetrance, and they have been proposed to be involved in the common (polygenic) predisposition to tuberculosis (TB). We set out to test this hypothesis in two populations from Siberian region of Russia with high prevalence of TB.

Opisthorchis felineus liver fluke invasion is an environmental factor modifying genetic risk of atopic bronchial asthma.

According to epidemiological observations, Opisthorchis felineus liver fluke invasion is negatively associated with the development and severity of allergic diseases in endemic regions of Russia. We hypothesized that the invasion is an important factor in gene-environmental interactions (GEI) underlying allergy. To prove this, we tested 10 single nucleotide polymorphisms of immune response modifying genes in 428 individuals stratified by atopic bronchial asthma presence and O.

Insights into pathophysiology of dystropy through the analysis of gene networks: an example of bronchial asthma and tuberculosis.

Co-existence of bronchial asthma (BA) and tuberculosis (TB) is extremely uncommon (dystropic). We assume that this is caused by the interplay between genes involved into specific pathophysiological pathways that arrest simultaneous manifestation of BA and TB. Identification of common and specific genes may be important to determine the molecular genetic mechanisms leading to rare co-occurrence of these diseases and may contribute to the identification of susceptibility genes for each of these dystropic diseases.

Association of SNPs of CD40 gene with multiple sclerosis in Russians.

Multiple sclerosis (MS) is a serious, incurable neurological disease. In 2009, the ANZgene studies detected the suggestive association of located upstream of CD40 gene in chromosome 20q13 (p = 1.3×10(-7)).

Genetic variability of 15 autosomal STR loci in Russian populations.

Allele frequencies for 15 STRs (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, Penta D, Penta E, THO1, TPOX, and vWA) in the PowerPlex 16 System (Promega Corporation) were assessed in 386 individuals from five Russian urban populations. No significant between-population differences in frequencies and molecular variance of 15 microsatellites were revealed. For all 15 loci, the combined matching probability is 3.

Leprosy and the adaptation of human toll-like receptor 1.

Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.

Syntropy, genetic testing and personalized medicine.

The concept of syntropic diseases was proposed at the beginning of the last century to emphasize the phenomenon of nonrandom co-occurrence of human disorders. Common genes underlying specific syntropic diseases were called syntropic genes. The application of this concept to contemporary genomic studies will facilitate the understanding of the molecular basis of complex diseases, provide future direction for discovering new targets for therapy and prognosis, and may even lead to the reassessment of disease classification for the practice of more precise personalized medicine.

An epidemiologic-based survey of public attitudes towards predictive genetic testing in Russia.

Many new genetic tests for common multifactorial disorders are becoming available to individuals, including direct-to-consumer genotyping services. Typically, studies of public attitudes reveal a high level of interest for individual genotyping. In a Russian urban population, 85% of 2000 respondents answered positively to a question about their own willingness to undergo predictive genetic testing for preventable health conditions.

Short oligonucleotide tandem ligation assay for genotyping of single-nucleotide polymorphisms in Y chromosome.

We propose a novel universal methodology, Short Oligonucleotide Tandem Ligation Assay (SOTLA), for SNP genotyping. SOTLA is based on using a tandem of short oligonucleotide (TSO) probes consisting of three fragments: the core oligonucleotide and two flanking oligomers, one of which is immobilized onto a solid support and another one contains the biotin label. TSO is self-associated on a complementary DNA template, forms the complex containing two nicks, which are efficiently ligated with DNA ligase giving biotinylated oligonucleotide covalently bound to polymer beads.

Chromosome 12q24.3 controls sensitization to cat allergen in patients with asthma from Siberia, Russia.

In Russian population of Siberia asthma is usually concomitant with high sensitization to indoor allergens (cat, dog and house dust mites), overproduction of total immunoglobulin E (IgE) and airway hyperreactivity. Definition of genes that predispose to development of various sub-components of the asthma phenotype is important for understanding of etiology of this disease. To map genes predisposing to asthma, we tested 21 microsatellite markers from candidate chromosomal regions in 136 Russian nuclear families with asthma from Siberia.

Public interest and expectations concerning commercial genotyping and genetic risk assessment.

In contrast to the modest progress made in the interpretation and clinical application of genomic data, genotyping technologies have experienced great progress. Genotyping costs are progressively decreasing making individual genotyping more commonly available. Financial availability of individual genome analysis and the strong desire of many people to know about their individual genomic characteristics, promotes the marketing of genetic tests of variable predictive value directly to the public.

Searching for the origin of Gagauzes: inferences from Y-chromosome analysis.

The Gagauzes are a small Turkish-speaking ethnic group living mostly in southern Moldova and northeastern Bulgaria. The origin of the Gagauzes is obscure. They may be descendants of the Turkic nomadic tribes from the Eurasian steppes, as suggested by the "Steppe" hypothesis, or have a complex Anatolian-steppe origin, as postulated by the "Seljuk" or "Anatolian" hypothesis.

Association of polymorphisms in the human IL4 and IL5 genes with atopic bronchial asthma and severity of the disease.

Two polymorphisms in the IL4 (G/C 3'-UTR) and IL5 (C-703T) genes were studied in a sample of families whose probands had atopic bronchial asthma (BA) (66 families, n = 183) and in a group of non-cognate individuals with the severe form of the disease (n = 34). The samples were collected from the Russian population in the city of Tomsk (Russia). Using the transmission/disequilibrium test (TDT), a significant association of allele C-703 IL5 with BA was established (TDT = 4.

Global pharmacogenetics: genetic substructure of Eurasian populations and its effect on variants of drug-metabolizing enzymes.

Aims: To study the frequency distribution of cytochrome P450 (CYP) functional genetic variants in five Eurasian populations from the territory of Siberia in Russia.

Materials & Methods: Unrelated healthy Tuvinians, Buryats, Altaians, Yakuts and Russians (n = 87-88) were genotyped for CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP3A5*3 and CYP3A5*6. Standard pairwise genetic distances, locus-specific and global Fst statistics were calculated.

Disuniting uniformity: a pied cladistic canvas of mtDNA haplogroup H in Eurasia.

It has been often stated that the overall pattern of human maternal lineages in Europe is largely uniform. Yet this uniformity may also result from an insufficient depth and width of the phylogenetic analysis, in particular of the predominant western Eurasian haplogroup (Hg) H that comprises nearly a half of the European mitochondrial DNA (mtDNA) pool. Making use of the coding sequence information from 267 mtDNA Hg H sequences, we have analyzed 830 mtDNA genomes, from 11 European, Near and Middle Eastern, Central Asian, and Altaian populations.