BIOLOGICAL SESSION“THE IMPORTANCE OF G. GAMOW'S IDEAS FOR BIOLOGY OF THE 21st CENTURY” AT THE XXI GAMOW INTERNATIONAL ASTRONOMICAL CONFERENCE-SCHOOL IN ODESSA (15-21 AUGUST, 2021)

Третій рік поспіль в межах Гамовської конференції працює Біологічна секція: «Важливість ідей Г.А. Гамова для біології 21-ого століття», організація якої викликана великою повагою до особистості вченого Георгія Антоновича Гамова, наукові інтереси якого об’єднали астрофізику, космологію та молекулярну біологію. Цього року Біологічна секція працювала в режимі on-line 17.08.2021. Роботу секції розпочали з виступу професора Тобіуса Дельбрюка (Institute of Neuroinformatics – ETH and University of Zurich, Zurich, Switzerland), сина видатного фізика, Нобелевського лауреата Макса Дельбрюка (в певний період товариша Г.А. Гамова). Професор Тобіус Дельбрюк назвав свою доповідь – "Out of this world: Recounting Max's Delbruck memories of George Gamow”. Ця доповідь, присвячена феноменальній особистості Г.А. Гамова, придала засіданню біологічної секції емоційну атмосферу наближення до великих ідей, що надали і зараз надають поштовх для розвитку молекулярної біології. Значну зацікавленість учасників секції викликала доповідь Dr. V.N. Korzun (KWS SAAT SE & Co. KGaA (м. Айнбек, Німеччина) «Applications of genetic and genomic research in cereals», що продемонструвала впровадження в селекційний процес сучасних молекулярно-генетичних технологій. З доповіддю «DNA-protein interactions as a tool of synthetic biology», що присвячена високо технологічним розробкам зі створення біосенсорів науково-виробничою фіромою Explogen LLC (EXG) (м. Львів, Україна) виступив к.б.н. Ю. Ребець. Наступна пленарна доповідь «Using the G.A. Gamow’s ideas for molecular genetic diagnostics of infectious and somatic human diseases at the current stage of medical development» була представлена білоруськими вченими, а саме професор С.А. Касцьюк розповіла про молекулярно-генетичні дослідження, що виконуються в Білоруській медичній академії післядипломної освіти. Dr. Yu. Monchak з McGill University (м. Монреаль, Канада) також представив доповідь присвячену впровадженню ДНК-технологій в діагностику патології людини ˗ «Targeted therapy, DNA sequence and the race against neoplasia». Ця доповідь викликала велику зацікавленість учасників біологічної секції. Молоді науковці Іщенко О.О., Жарікова Д.О., Роман І.І., Доля Б., Рошка Н.М., Чубик І.Ю., Попович Ю.А., Топораш М.К., Пидюра М.О. – доктори філософії з біології, кандидати наук, аспіранти, що займаються дослідженнями в галузі молекулярної біології представили дев’ять доповідей, що відбивають результати виконаних досліджень у низці провідних університетів нашої країни, а саме у Львівському національному університеті ім. І. Франка, у Одеському національному університеті імені І.І. Мечникова, у Чернівецькому національному університеті ім. Юрія Федьковича та ДУ «Інституті харчової біотехнології та Геноміки» (м. Київ). Представлені доповіді викликали жвавий інтерес, а формат on-line дозволів об’єднати у роботі секції понад 35 учасників з різних країн ˗ України, Білорусі, Швейцарії, Німеччини, Канади і Казахстану.

Genetics of familial amyotrophic lateral sclerosis

To analyze results of the studies covering modern scientific views on the genetics of familial amyotrophic lateral sclerosis (FALS).We searched for full-text publications containing the key words “amyotrophic lateral sclerosis”, “FALS”, and “genetics” in the literature for the past 10 years in both Russian and English in eLibrary, PubMed, Web of Science, and OMIM databases. In addition, the review includes earlier publications of historical interest.This review summarizes all existing information on four most widespread genes associated with FALS: SOD1, TARDBP, FUS, and C9ORF72. The review also describes the functions of these genes and possible pathogenetic mechanisms of motor neuron death in amyotrophic lateral sclerosis (ALS), such as mitochondrial dysfunction, oxidative stress, glutamate excitotoxicity, damage to axonal transport components, and pathological neurofilament aggregation.As modern methods of molecular genetic diagnostics evolve, our knowledge about multifactorial FALS genetics expands. This information should be taken into consideration in clinical practice of neurologists. Information about the genes associated with ALS and understanding of particular pathogenetic mechanisms of the disease play a key role in the development of effective therapeutic strategies.

Alleles Frequency and Polymorphic Genes Genotypes Associated with Alcoholism in Kazakh Population

Background: There is a category of people with a congenial predisposition to alcohol abuse among the total population. The identification of such persons by molecular genetic diagnostics and the implementation of appropriate preventive measures can significantly reduce the incidence of alcoholism. Objectives: This research aimed to study the genetic foundations of alcohol dependence development in Kazakhs based on the analysis of population frequencies of polymorphic variants of predisposition to alcoholism genes. Materials and Methods: The material for the research was the DNA recovered from the peripheral blood of the recruited control group population, which was represented by 1,800 conditionally healthy individuals of Kazakh nationality. Isolated DNA samples were genotyped by PCR. Conclusions: Kazakhs take an intermediate position between the previously studied European and Asian populations by allele frequencies of nine polymorphic variants of ADH1B (rs2066701, rs1789891), ADH1C (rs1693425, rs698), HTR2C (rs6318), ALDH2 (rs671), CADM2 (rs9841829), KLB (rs11940694), DRD2 (rs1076560) genes. Possible markers of an increased risk of alcoholism development in Kazakhs are G alleles of polymorphic loci rs2066701 of the ADH1B gene and rs671 of the ALDH2 gene, and the protective effect is possible in the presence of A alleles rs2066701 of the ADH1B gene and rs671 of the ALDH2 gene.

Novel gene discovery for hearing loss and other routes to increased diagnostic rates

Despite decades of research, there is much to be learned about the genetic landscape of sensorineural hearing loss. Novel genes for hearing loss remain to be identified while ‘secrets’ of the known genes need to be uncovered. These ‘secrets’ include regulatory mechanisms of gene activity and novel aspects of gene structure. To obtain a more complete picture of the genetics of hearing loss, the available experimental and bioinformatic tools need to be fully exploited. This is also true for data resources such as ENCODE. For the inner ear, however, such data resources and analytical tools need to be developed or extended. Collaborative studies provide opportunities to achieve this and to optimally use those tools and resources that are already available. This will accelerate the discoveries that are necessary for improving molecular genetic diagnostics and genetic counselling and for the development of therapeutic strategies.

Polymorphisms in Genes Involved in Steroidogenesis in the Development of Severe Acne

Background: Acne is a multifactorial disease, in the pathogenesis of which one of the leading factors is the excessive effect of androgens on the hair follicles (HFs) and sebaceous glands (SGs), along with hypersecretion of sebum, pathological follicular hyperkeratosis and an inflammatory response. The search for genotypic markers in patients with varying severity of acne is a difficult task due to the multifactorial pathogenesis and the role of trigger factors in the formation of acne. The aim of this study was to determine SNPs within 3 genes involved in steroidogenesis (MVK, ARPC1B, and CA2) in patients with severe acne. Methods and Results: The study included 70 patients (42 men and 28 women) aged between 15 and 46 years (the median age - 22.1 years). The main group (MG) included 50 patients (29 men and 21 women) with severe acne. The control group (CG) consisted of 20 apparently healthy individuals (13 men and 7 women). Molecular-genetic diagnostics was carried out by the method of high-throughput DNA sequencing (next-generation sequencing). Our study showed that severe acne is associated with 12 polymorphic loci of the MVK gene (4 SNPs in exons and 8 SNPs in introns), 7 SNPs of the ARPC1B gene (2 SNPs in exons and 5 SNPs in introns), and 9 SNPs of the CA2 gene (3 SNPs in exons and 6 SNPs in introns). Conclusion: The revealed features of the SNPs within the MVK, ARPC1B, and CA2 genes in patients with severe acne probably indicate a hereditary determination of steroidogenesis in acne.

Healthcare-associated infections (HAI) in maternity hospitals of Russian Federation (the state of the problem at the beginning of the XXI century)

Over the past decade, the healthcare system of the Russian Federation has undergone progressive changes in the system of maternity care, which relate to the development of infrastructure and the introduction of new organizational models. In particular, a three-level system of providing medical care to mothers and children has been created, including a network of perinatal centers for patients at high perinatal and obstetric risk. Field events of specialists of National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation to the medical organizations of maternity care in various regions of Russia revealed hot spots that require primary attention: acute shortage of staff for the implementation of diagnostic and therapeutic measures at the modern methodological level, as well as for ensuring epidemiological safety in the medical organizations (medical microbiologists (bacteriologists), clinical pharmacologists and epidemiologists); the lack of registration of healthcare-associated infections, which is associated with the prevailing in the country mainly punitive methods of combating hospital infections. In modern conditions of nursing preterm babies, newborns with various severe somatic and surgical pathologies, it is necessary to know the real indicators of morbidity in order to reasonably and promptly carry out therapeutic and preventive measures; the need to organize modern microbiological laboratories in the perinatal centers with the availability of fast methods (proteomic and molecular-genetic) diagnostics, allowing for microbiological monitoring in specialized departments of newborns and promptly respond to the changes in the epidemiological situation in the hospital, to prevent the development of clinically pronounced cases of healthcare-associated infections.

Comprehensive Molecular Genetic Diagnostics of Birt-Hogg-Dube Syndrome in a Russian Patient with Renal Cancer and Lung Cysts: A Case Report

We report a case of Birt-Hogg-Dube syndrome (BHDS), a rare hereditary syndrome, the main visible sign of which is the development of multiple skin fibrofolliculomas. In our case, there was a manifestation of BHDS consisting in the absence of fibrofolliculomas and presence of other characteristic features of this syndrome: lung cysts and renal cancer. The 26-year-old woman was admitted to a clinic for diagnosis and treatment of a neoplasm of the left kidney and had a history of renal cell cancer (RCC) of the right kidney and spontaneous pneumothorax. Multiple tumors of the left kidney and lung cysts were observed upon clinical and laboratory testing. Tumors of the left kidney were resected and diagnosed by a pathologist as chromophobe RCC. Sequencing of <i>FLCN</i> exons 4–14 from blood DNA revealed the heterozygous germline nonsense mutation c.1429C&#x3e;T (p.R477*), confirming the diagnosis of BHDS. Several somatic variants were detected by tumor DNA sequencing using the Comprehensive Cancer Panel and Ion S5 platform. Medical-genetic counseling was conducted, and follow-up management was outlined. To our knowledge, this case report is the first comprehensive clinical and genetic examination of a patient with BHDS in Russia. The p.R477* mutation has been described by other authors in patients with fibrofolliculomas and lung cysts, but not in those with RCC, while RCC was the first manifestation of BHDS in our case. The case report may help geneticists, oncologists, and other specialists to better understand the clinical and genetic heterogeneity of BHDS in various populations.

Molecular genetic diagnostics of Bardet-Biedl syndrome with an MPS-panel

Синдром Барде-Бидля - аутосомно-рецессивное заболевание, характеризующееся ожирением, пигментной дегенерацией сетчатки, полидактилией, задержкой психоречевого развития и структурными повреждениями почек. В работе представлены результаты применения МПС-панели, включающей кодирующие последовательности и прилегающие интронные области 21 гена, ассоциированного с синдромом Барде-Бидля. Впервые была проведена молекулярно-генетическая диагностика в группе из сорока российских пациентов с синдромом Барде-Бидля из неродственных семей. В результате исследования удалось подтвердить диагноз молекулярно-генетическим методом у 40% пациентов (n=16). В генах BBS1, BBS7 и BBS10 встретились повторяющиеся варианты. Частота встречаемости патогенных и вероятно патогенных вариантов в генах BBS1 и BBS10 у российских пациентов соответствует зарубежным данным. Варианты в гене BBS7 встретились у пяти человек, у четырех из них был обнаружен патогенный вариант c.1967_1968delTAinsC, не встречающийся в других популяциях. Результаты, представленные в статье, показывают значительный вклад в заболеваемость синдромом Барде-Бидля в российской популяции патогенных вариантов в гене BBS7. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by obesity, retinitis pigmentosa, polydactyly, development delay, and structural kidney defects. This study shows the results of using an MPS panel that includes coding sequences and intronic areas of 21 genes associated with Bardet-Biedl syndrome. For the first time molecular genetic testing has been provided for the group of 40 Russian patiens with Bardet-Biedl syndrome from unrelated families. As a result of the testing, diagnoses were confirmed for 40% of the patients (n=16). The genes BBS1, BBS7, BBS10 had recurrent variants. The frequency of pathogenic and likely pathogenic variants in the genes BBS1 and BBS10 among Russian patients matches the research data in other countries. Variants in the BBS7 gene were found for five people, four of them had a pathogenic variant c.1967_1968delTAinsC, which is not present among other populations. Results provided in this article show the significant role of pathogenic variants in the BBS7 gene in patients with Bardet-Biedl syndrome in Russian population.

Clinical case of mucopolysaccharidosis type II (Hunter syndrome)

The article presents a rare case of type II mucopolysaccharidosis (MPs) in children. From the age of one and a half, the child was observed by an ENT doctor for 2–3 degree adenoids. At the age of 2, an adenotomy was performed. In the future, a relapse of adenoid hyperplasia. 1 year of age according to the ultrasound revealed hepatosplenomegaly. At the age of three years, type 2 mucopolysaccharidosis was suspected, which was confirmed on the basis of increased levels of heparan sulfate and dermatansulfate in the urine, molecular genetic diagnostics (mutation in exon 3 of IDS Lis135Glu in the hemizygous state. Appointed replacement therapy: Elaprase. Clinical polymorphism, different severity of symptoms combined with rare occurrence cause certain difficulties in early identification of MPs-II. Timely diagnosis is extremely important for referral of such children to specialists of an interdisciplinary center who have experience in specific treatment that is most effective in the early stage of the disease.