Molecular Genetic Data Research Articles

INNV-10. ULTRA-RAPID INTRAOPERATIVE GLIOMA TUMOR CELL QUANTIFICATION

Abstract The diagnosis and treatment of brain tumors often depends on molecular-genetic data. To date, however, there has been no intraoperative method to rapidly and iteratively utilize tumor-specific genetic alterations to guide brain tumor surgical resections, complicating intraoperative diagnosis and precluding measurement of tumor cell burdens at surgical margins. To address this gap, we developed Ultra-Rapid droplet digital PCR (UR-ddPCR), which can be completed in 15 minutes from tissue to result with an accuracy and sensitivity comparable to standard ddPCR. We demonstrate an UR-ddPCR assay for the IDH1 R132H clonal mutation that is present in many low-grade gliomas. We illustrate the clinical feasibility of UR-ddPCR by performing it intraoperatively for 49 samples from 13 glioma cases, achieving intraoperative quantification in an average of 14 minutes and 54 seconds spanning a wide dynamic range from 0.1% to 94% tumor cell percentages. We further combine UR-ddPCR measurements with UR-stimulated Raman histology intraoperatively to estimate tumor cell densities in addition to tumor cell percentages, across a wide range from < 1 to 1332 cells/mm2. We anticipate that UR-ddPCR, along with future refinements in assay instrumentation, will enable novel point-of-care diagnostics and the development of molecularly-guided brain tumor surgeries that improve clinical outcomes.

Genetic liability estimated from large-scale family data improves genetic prediction, risk score profiling, and gene mapping for major depression

Large biobank samples provide an opportunity to integrate broad phenotyping, familial records, and molecular genetics data to study complex traits and diseases. We introduce Pearson-Aitken Family Genetic Risk Scores (PA-FGRS), a method for estimating disease liability from patterns of diagnoses in extended, age-censored genealogical records. We then apply the method to study a paradigmatic complex disorder, major depressive disorder (MDD), using the iPSYCH2015 case-cohort study of 30,949 MDD cases, 39,655 random population controls, and more than 2 million relatives. We show that combining PA-FGRS liabilities estimated from family records with molecular genotypes of probands improves three lines of inquiry. Incorporating PA-FGRS liabilities improves classification of MDD over and above polygenic scores, identifies robust genetic contributions to clinical heterogeneity in MDD associated with comorbidity, recurrence, and severity and can improve the power of genome-wide association studies. Our method is flexible and easy to use, and our study approaches are generalizable to other datasets and other complex traits and diseases.

New species of the genus Alippistrongylus (Nematoda: Trichostrongylina) parasitic in Delomys dorsalis (Rodentia: Sigmodontinae) in the Atlantic Forest of Rio de Janeiro, Brazil.

We describe a new species of the genus Alippistrongylus (Nematoda: Trichostrongylina) in the small intestine of Delomys dorsalis (Rodentia: Sigmodontinae) found in Itatiaia National Park (Parque Nacional do Itatiaia, PNI), state of Rio de Janeiro, Brazil. The new species can be distinguished between the other two species previously described by the following morphological characteristics: pattern of the rays from the caudal bursa rays in males and the spherical-shaped appendage in the female. Additionally, we provide molecular genetic data from the new species. The discovery of Alippistrongylus itatiaiaensis sp. n. expands our understanding of nematode diversity and underscores the importance of parasite studies in biodiversity conservation. Its occurrence in a preserved area like the PNI emphasises the role of such habitats in maintaining unique ecological interactions.

Genetic Loci Mining and Candidate Gene Analysis for Determining Fatty Acid Composition in Rice

Fatty acid composition and its proportions are critical to the nutritional value and storage quality of rice (Oryza sativa L.) as the third major nutrient component in this staple food. This study involved crossing an indica rice variety, Huazhan (HZ), as the male parent, with a japonica variety, Nekken2, as the female parent, to produce the F1 generation. Subsequently, a population of 120 recombinant inbred lines (RILs) was developed through multiple generations of self-breeding. By utilizing a high-density molecular genetic linkage map and phenotypic data of four fatty acid components, we identified a total of 14 quantitative trait loci (QTLs) related to fatty acid composition across chromosomes 1, 3, 4, 6, 8, and 9. These included two QTLs for C14 content, three for C16:0 content, six for C18:1 content, and three for C18:2 content. Notably, the QTL qCOPT4.2 exhibited a high LOD score of 5.22. Within QTL intervals, genes such as OsACX3 and SLG affecting grain length were identified. The expression of candidate genes within these intervals was assessed and further analyzed by using quantitative real-time PCR. Genes such as LOC_Os01g15000, LOC_Os04g47120, LOC_Os04g49194, LOC_Os06g22080, LOC_Os06g23870, LOC_Os06g24704, LOC_Os06g30780, LOC_Os08g44840, and LOC_Os09g36860 were found to regulate fatty acid synthesis or metabolic pathways, potentially enhancing fatty acid content in rice. These QTLs are indispensable for breeding rice varieties with improved fatty acid profiles, offering new genetic resources for enhancing the nutritional and storage qualities of rice.

Intergroup variability of the khakas based on non-metric cranial traits data

Introduction. The formation of the gene pool of modern Khakas people occurred through the interaction of various groups of ancient inhabitants of the Minusinsk Basin. This article is focused on the inter-group analysis of craniological series representing different Khakassian subethnic groups. Materials and Methods. The cranial series of the Kachins, Koibals, Sagais, and Beltirs was studied using the battery of 36 cranial non-metric characteristics. The obtained data was compared with data on other populations of Southern and Western Siberia: Shors, Tuvans, Telengits, Selkups, Khants, and Mansis. The analysis of the biological diversity of populations was carried out using Smith's mean measure of divergence (MMD) followed by multidimensional scaling and cluster analysis. Results. The Kachins are the most distant from the other Khakas subethnic groups, forming a cluster with the Telengits and Tuvans. The Koibals and Beltirs were positioned quite close to the Shors. The Sagais occupied a separate position in the Khakas cluster, presumably due to a greater proportion of Europoid admixture compared to other Khakas groups. The pooled Khakas sample shares similar cranial non-metric characteristics with Turkic-speaking ethnic groups of Southern Siberia: Shors, Telengits, and Tuvans. Discussion. The nature of phenetic differentiation of the Khakas sub-ethnic groups presumably reveals their complex population history. The position of the Kachins outside the Khakas cluster based on non-metric traits resulted from specificity of their phenofund, which is also supported by molecular genetic data. The similarity in the phenofund of the Khakas groups to those of the Tuvans and Telengits may result from gene flow between Khakas populations and the peoples of Southern Siberia or/and from their common episodes in their ethnogenesis. The similarity between pooled Khakassian sample and the Shors presumably suggests involvement of common genetic components in the gene pools of these peoples, which is consistent with molecular genetic data. Conclusion. The correspondence of the obtained results with genetic data suggests the possibility of using cranial non-metric traits to identify genetic relationships between ancient populations in the absence of direct genetic information.

The Characteristics of Microsatellites and Development of SSR Markers in the Genome of Periplaneta americana

The research was to analyze the number and pattern of microsatellites in Periplaneta americana’s genome, and also developed tetranucleotide SSR markers. We thoroughly scrutinized and dissected the inherent traits that govern the allocation of microsatellite sequences within the profound domain of P. americana’s genome, software MSDBv2 allowed for the utilization of 2.67 Gb. There were precisely 1,498,458 flawless microsatellite sequences, encompassed approximately 1.57%. The cumulative length of microsatellites was 45,076,707 bp, and the abundance of microsatellites was 16889.577 loci/Mb. Out of all the microsatellite repeat variations, the trinucleotide repeats accounted for 44.83% of the total, with a count of 671,830, which were the most abundant type. The tetranucleotide, mononucleotide, pentanucleotide, dinucleotide, and hexanucleotide repeats accounted for 29.01%, 13.62%, 8.37%, 3.70% and 0.47%, respectively. The numbers of different repeat copy categories in each repeat type were also quite different, such as the A in mononucleotide repeat type, the AT in dinucleotides, the AAT in trinucleotides, and AAAT in tetranucleotide were the most of each categories. 143 primers were designed. After undertaking the arduous task of enhancing the initial PCR conditions to perfection, we successfully determined and analyzed a gargantuan number of 38 different polymorphic tetranucleotide microsatellite markers with utmost precision, employed the assistance of two-color fluorescence markers and ingenious genotyping scaned for their comprehensive characterization. The genetic variation in P. americana population involved analyzing the diversity of microsatellite loci, which exhibited varying numbers of alleles per locus ranging from 4 to 21 among the 32 individuals studied. Among them, there were 24 microsatellite loci whose alleles were greater than 10, accounted for 63.16% of the total number of polymorphic microsatellite. The calculated degrees of genetic diversity varied between 0 and 1, the observed heterozygosities was between 0.219 and 1.0, with a mean of 0.6391. The expected heterozygosities was between 0.312 and 0.942, with a mean of 0.7663. The PIC was between 0.296 and 0.923, with a mean of 0.7294, and there were 36 microsatellite loci whose PIC was greater than 0.5, accounted for 94.74%. This study indicated that new development of microsatellite markers for P. americana was feasible. Furthermore, these new development microsatellite markers will provide adequate and reliable molecular genetics data for carrying out the research of molecular ecology and conservation genetics for P. americana.

A high-altitude population of Hyperboreomyzon polaris (Hirudinea: Glossiphoniidae) in Altai Mountains, South Siberia, Russia.

Hyperboreomyzon polaris Bolotov, Eliseeva, Klass & Kondakov, 2022 (Hirudinea: Glossiphoniidae) is an enigmatic freshwater leech that was recently described based on three specimens from two remote regions of the Eurasian Arctic, that is, the Kolguev Island and Putorana Plateau, Russia. Later on, misidentified historical samples of this species were discovered in the Hirudinea collection of Zoological Institute of the Russian Academy of Sciences (St. Petersburg, Russia). These samples were collected by Pavel G. Ignatov, a prominent Russian geographer and traveler, from a remote high-altitude area of the Altai Mountains (South Siberia) in 1901. To collect new samples from this population, we organized a field expedition to the same area (Lake Dzhulukul) in 2023. Molecular genetic data (COI and 18S rRNA) obtained from newly collected specimens revealed that they belong to H. polaris. Hence, this leech could be considered an Arctic-alpine species, the disjunctive range of which covers Arctic areas of Eurasia and Central Asian (South Siberian) mountains. We describe and illustrate living individuals of H. polaris for the first time, update its morphological diagnosis, present a life cycle reconstruction based on the frequency of four size classes in available samples. It is shown that this species prefers small lentic water bodies such as small lakes and lakelets. The crop content of a well-fed specimen from Altai contains DNA of the northern pintail Anas acuta Linnaeus (Aves: Anatidae), indicating that H. polaris feeds on blood of waterfowl. Our results indicate that Hyperboreomyzon may be considered a species adapted to cold high-latitude areas and mountain refugia.

Роль неравновесной динамики численности и генетической структуры популяций в межвидовых взаимодействиях большого (Spermophilus major Pall.) и крапчатого (Spermophilus sulicus Güld.) сусликов в широкой зоне симпатрии

The dynamics of the number and genetic structure of populations is one of the leading factors determining the success of the existence of populations in time and space. Based on observations (changes in numbers) and molecular genetic analysis data (CR and cyt b), the dynamics of the demographic and genetic structure of the populations of russet (Spermophilus major Pall.) and speckled (S. suslicus Güld.) ground squirrels in the sympatry zone were studied. A similar cyclical nature of the temporal dynamics of the genetic structure of populations in both sympatric species is shown.In the russet ground squirrel, a more ecologically plastic species and prone to migratory activity, population genetic processes occur on a large scale.The explosive demographic situation associated with the passage of populations through the “bottleneck” state is one of the factors leading to interspecific hybridization.

MtDNA genetic diversity and phylogeographic insights into giant domestic pigeon (Columba livia domestica) breeds: connections between Central Europe and the Middle East

Humans have selectively bred domestic pigeons (Columba livia domestica) to create breeds with a diversity of shapes, colors and other attributes. Since Darwin, the domestic pigeon has always been a popular model species for scientific research because of its richness of form, colouration and behaviour. It is believed that the world's squab pigeon industry uses breeds and hybrids from the Mediterranean region. An exception is the indigenous giant pigeon breeds of the Carpathian Basin, whose origin is not known. Therefore, our aims were 1) to understand the phylogenetic relationships of giant pigeons, which sheds light on the origin of Hungarian breeds and their relationship to the Mediterranean giant pigeon breed group; 2) to contribute molecular genetic data to the genealogy of 2 Iraqi pigeon breeds close to the pigeon domestication center, including the culturally important Iraqi Red Pigeon, and 3) to compare the genetic diversity of European and Middle Eastern domestic pigeon populations and to draw conclusions on the phylogenetic relationships between pigeon breeds and molecular clues to their different breeding practices of both regions. A 655-bp-long sequence of the cytochrome oxidase 1 (COI) region of the mitochondrial DNA was studied in a total of 276 pigeons (19 breeds). A total of 27 haplotypes were found, of which 22 were unique. The highest genetic diversity was found in the Carpathian Basin, and the lowest in the Iraqi region. STRUCTURE analysis revealed low structurality, K=3 was the most likely. The majority of the samples belong to the most ancient haplotype H_2=219, however the Jacobin pigeon is on a very separate evolutionary branch with a large number of mutations. None of the 19 breeds investigated in this study have been previously studied in phylogenetics, and most of these breeds have potential as squab pigeons, and have good meat forms for utilization, therefore the results of this study may also be of help to the squab pigeon industry.

A genomic framework to assist conservation breeding and translocation success: A case study of a critically endangered turtle

AbstractConservation breeding programs are an effective approach to addressing biodiversity loss. Captive populations are managed to maintain genetic diversity, yet there remains an “implementation gap” in effectively translating molecular genetic data into management. Technological advancements are facilitating rapid generation of genetic data, increasing accessibility for breeding programs. In 2010, Frankham and colleagues proposed a six‐stage process for establishing successful conservation breeding and release programs. Here, we describe the conservation breeding program for the critically endangered Bellinger River turtle (Myuchelys georgesi) and characterize the value of genetic sampling for informing management actions. By generating a chromosome‐level genome and population genetic data, we investigated past and present diversity and assessed relatedness among captive founders. We present a framework modeled on Frankham and colleagues six stages to assist managers in implementing genetic data into actionable conservation strategies. This framework, and worked case study, for managers aims to better guide implementation of genetic approaches into conservation breeding programs.

Diversity assessment of the gene bank collection of the genus <i>Campsis</i> representatives based on the phenotypic and molecular genetic analysis data

Diversity assessment of the gene bank collection of the genus <i>Campsis</i> representatives based on the phenotypic and molecular genetic analysis data

A Novel Molecular-Genetic Approach to the Monitoring of Dynamics of Mitochondrial Function Improvement during Treatment.

Making a correct genetically based diagnosis in patients with diseases associated with mitochondrial dysfunction can be challenging both genetically and clinically, as can further management of such patients on the basis of molecular-genetic data assessing the state of their mitochondria. In this opinion article, we propose a novel approach (which may result in a clinical protocol) to the use of a precise molecular-genetic tool in order to monitor the state of mitochondria (which reflects their function) during treatment of certain conditions, by means of not only signs and symptoms but also the molecular-genetic basis of the current condition. This is an example of application of personalized genomic medicine at the intersection of a person's mitochondrial genome information and clinical care. Advantages of the proposed approach are its relatively low cost (compared to various types of sequencing), an ability to use samples with a low input amount of genetic material, and rapidness. When this approach receives positive outside reviews and gets an approval of experts in the field (in terms of the standards), it may then be picked up by other developers and introduced into clinical practice.

Polygenic risk scores for nicotine use and family history of smoking are associated with smoking behaviour

IntroductionFormal genetics studies show that smoking is influenced by genetic factors; exploring this on the molecular level can offer deeper insight into the etiology of smoking behaviours. MethodsSummary statistics from the latest wave of the GWAS and Sequencing Consortium of Alcohol and Nicotine (GSCAN) were used to calculate polygenic risk scores (PRS) in a sample of ~2200 individuals who smoke/individuals who never smoked. The associations of smoking status with PRS for Smoking Initiation (i.e., Lifetime Smoking; SI-PRS), and Fagerström Test for Nicotine Dependence (FTND) score with PRS for Cigarettes per Day (CpD-PRS) were examined, as were distinct/additive effects of parental smoking on smoking status. ResultsSI-PRS explained 10.56% of variance (Nagelkerke-R2) in smoking status (p=6.45x10−30). In individuals who smoke, CpD-PRS was associated with FTND score (R2=5.03%, p=1.88x10–12). Parental smoking alone explained R2=3.06% (p=2.43×10−12) of smoking status, and 0.96% when added to the most informative SI-PRS model (total R²=11.52%). ConclusionThese results show the potential utility of molecular genetic data for research investigating smoking prevention. The fact that PRS explains more variance than family history highlights progress from formal to molecular genetics; the partial overlap and increased predictive value when using both suggests the importance of combining these approaches.

Заметки о роде Timmia (Bryophyta) в Мурманской области, Россия

During field work in the Murmansk Region, a new species for the North-West of Russia Timmia norvegica was found, and the location of rare species, T. bavarica, has been confirmed since its first discovery in the region almost 90 years ago. Identification of the specimens was confirmed by molecular genetic data — nuclear ribosomal 26S region and trnL-F cpDNA. Four species of the genus Timmia are currently known in the Murmansk Region (T. austriaca, T. bavarica, T. comata, and T. norvegica). Their regional distribution is regarded.

Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype–phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams.

The first Genetic data on <i>Lernaea Cyprinacea</i> Linnaeus, 1758 from the European North of Russia (The Pinega River)

Morphological and molecular genetic data about Lernaea cyprinacea Linnaeus, 1758, collected from pike (Esox lucius Linnaeus, 1758) in the European North of Russia (Pinega river) in 2022, were presented. Molecular genetic studies were carried out based on the analysis of COI mtDNA, 18S rDNA and 28S rDNA gene sequences. A significant genetic distance for the COI gene from individuals of the same species collected in other territories (China, Australia, South Africa, Canada, Austria, Argentina, Pakistan, Iran, India, Japan, Romania, Egypt and Western Siberia) was revealed, which indicates the existence of a cryptic species L. cyprinacea in the European North of Russia. Analysis of 28S rDNA sequences showed the presence of two substitutions fixed in the population, which may indicate a fairly long-standing divergence of sister species. The 18S rDNA gene fragment is less suitable for identifying L. cyprinacea due to low variability compared to the other two gene regions.

Genetic spectrum of sarcoglycanopathies in a cohort of Russian patients

Sarcoglycanopathies encompass four distinct forms of limb-girdle muscular dystrophies (LGMD), denoted as LGMD R3-R6, arising from mutations within the SGCA, SGCB, SGCG, and SGCD genes. The global prevalence of sarcoglycanopathies is low, making it challenging to study these diseases. The principal objective of this study was to explore the spectrum of mutations in a cohort of Russian patients with sarcoglycanopathies and to ascertain the frequency of these conditions in the Russian Federation. We conducted a retrospective analysis of clinical and molecular genetic data from 49 Russian patients with sarcoglycan genes variants. The results indicated that variants in the SGCA gene were found in 71.4% of cases, with SGCB and SGCG genes each exhibiting variants in 12.2 % of patients. SGCD gene variants were detected in 4.1% of cases. Bi-allelic pathogenic and likely pathogenic variants were identified in 46 of the 49 cases of sarcoglycanopathies: LGMD R3 (n = 34), LGMD R4 (n = 4), LGMD R5 (n = 6), and LGMD R6 (n = 2). A total of 31 distinct variants were identified, comprising 25 previously reported and 6 novel variants. Two major variants, c.229C>T and c.271G>A, were detected within the SGCA, constituting 61.4% of all mutant alleles in Russian patients with LGMD R3. Both LGMD R6 cases were caused by the homozygous nonsense variant c.493C>T p.(Arg165Ter) in the SGCD gene. The incidence of sarcoglycanopathies in the Russian Federation was estimated to be at least 1 in 4,115,039, which is lower than the reported incidence in other populations.

Ultra-Rapid Droplet Digital PCR Enables Intraoperative Tumor Quantification.

The diagnosis and treatment of tumors often depends on molecular-genetic data. However, rapid and iterative access to molecular data is not currently feasible during surgery, complicating intraoperative diagnosis and precluding measurement of tumor cell burdens at surgical margins to guide resections. To address this gap, we developed Ultra-Rapid droplet digital PCR (UR-ddPCR), which can be completed in 15 minutes from tissue to result with an accuracy comparable to standard ddPCR. We demonstrate UR-ddPCR assays for the IDH1 R132H and BRAF V600E clonal mutations that are present in many low-grade gliomas and melanomas, respectively. We illustrate the clinical feasibility of UR-ddPCR by performing it intraoperatively for 13 glioma cases. We further combine UR-ddPCR measurements with UR-stimulated Raman histology intraoperatively to estimate tumor cell densities in addition to tumor cell percentages. We anticipate that UR-ddPCR, along with future refinements in assay instrumentation, will enable novel point-of-care diagnostics and the development of molecularly-guided surgeries that improve clinical outcomes.

Outdated latin names of medicinal plants in the monographs of the State Pharmacopoeia of the Russian Federation, XIV edition (review)

Introduction. The State Pharmacopoeia of the Russian Federation, XIV-th edition (SP XIV), includes 107 monographs devoted to medicinal plant materials. The purpose of the study was to identify incorrect Latin names of medicinal plants in the monographs of the XIV edition, study the officially accepted Latin names and taxonomic position of medicinal plants in accordance with the contemporary system of flowering plants, and justify the need to make changes in subsequent editions of the pharmacopoeia.Text. 44 cases of incorrect Latin names were found. This is explained by the fact that when developing new pharmacopoeia monographs, either Latin names historically established in Russian pharmacognosy were used, or names that were legal at the time of the last edition of the Pharmacopoeia. The bulk of nomenclatural changes are associated with the adoption of the new APG system of flowering plants, based on molecular genetic data. The paper contains lists of plants for which the State Pharmacopoeia XIV contains an incorrect name of the genus, species, family or author, indicating the correct name, as well as comments on the rules of modern botanical nomenclature.Conclusion. In connection with the prospects for processing monographs on medicinal plant raw materials for the State Pharmacopoeia XV-th edition, as well as the EAEU Pharmacopoeia, the harmonization of the nomenclature of pharmacopoeial plants with modern international requirements becomes especially relevant.

The Scope of Mendelian Cardiomyopaties Genes

The review is devoted to the analysis of the scope of the genes of Mendelian cardiomyopathies (CM), specifically hypertrophic, dilatational, arrhythmogenic, and restrictive cardiomyopathy. According to Simple ClinVar, pathogenic/probably pathogenic variants of 75 genes lead to the development of one or more types of CM. At the same time, these genes are characterized by their expression in various tissues and organs (not only in the heart and blood vessels, but also in various parts of the brain, gastrointestinal tract, etc.), as well as by their involvement in a variety of metabolic pathways and biological processes. These data are generally consistent with the results of genome-wide association studies (GWAS). Polymorphisms of the CM genes are associated with various types of CM and other cardiovascular diseases, as well as obesity, various diseases of the musculoskeletal and nervous systems, mental, oncological, infectious diseases, and others. In addition to pathological conditions, common variants of the CM genes contributed to the variability of a wide range of quantitative traits, including pathogenetically significant for various multifactorial diseases. The non-randomness of the identified associations of CM genes with a wide range of diseases is evidenced by: comorbidity of CM with GWAS-associated diseases or the involvement of the latter as a symptom, a risk factor for the development of myocardial pathology, a modifier of the clinical presentation; overlapping of the affected organ systems and the spectrum of pathologies associated with common variants (according to GWAS) and to which rare pathogenic variants (according to OMIM) of the CM genes lead; confirmation of the involvement of CM genes in the pathogenesis of pathologies of other organ systems at the molecular level. Thus, the data presented in the review indicate the wide scope of the genes of primary CM, which goes beyond the cardiovascular system. That indicates the relevance of conducting comprehensive studies aimed at determining the cause-and-effect relationships between the CM and pathologies of other organs, including with the involvement of molecular genetic data.