Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia

Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the lack of accessibility to these tests, patients can receive an incomplete diagnosis. In these cases, genetic studies reinforce the clinical diagnosis. The present study characterized the molecular genetic basis of 11 HA, three HB, and five VWD patients by sequencing the F8, F9, or the VWF gene. Twelve variations were found in HA patients, four in HB patients, and 19 in WVD patients. From these variations a total of 25 novel variations were found. Disease-causing variations were used as positive controls for validation of the high-resolution melting (HRM) variant-scanning technique. This approach is a low-cost genetic diagnostic method proposed to be incorporated in developing countries. For the data analysis, we developed an accessible open-source code in Python that improves HRM data analysis with better sensitivity of 95% and without bias when using different HRM equipment and software. Analysis of amplicons with a length greater than 300 bp can be performed by implementing an analysis by denaturation domains.

Estimation of Genetic Diversity among Canola Accessions using Simple Sequence Repeat Markers

Genetic studies through molecular markers proved important to find out the genetic diversity of canola. In this study, 50 lines of canola were used to find the polymorphism using 15 SSR primers and investigated the genetic diversity, PIC values, frequency-based genetic distance, and allelic frequencies. Mean gene diversity, frequency-based genetic distance, and PIC values were 0.8777, 0.233 and 0.8666, respectively for the canola lines. A good range of genetic diversity was found among studied canola lines with value 85.91% polymorphism. Maximum and minimum genetic distances among 50 lines were 1 and 0.26, respectively. Accessions ACC-26068, ACC-24241, ACC-24244, ACC-24233, ACC-24423 and ACC-24224 have maximum genetic distance. Accessions ACC-24879 and ACC-24169 had minimum genetic distance i.e., 0.26. Dendrogram based on genetic distances showed four main clusters that were further dividing into several sub-clusters. The primers utilized in the present study, were valuable to identify different accessions of canola to find the variability present. This variability will be helpful to initiate the breeding program with their molecular genetic basis.

Role of DYSF Genetic Variant in Limb Girdle Muscular Dystrophy: A Case Report

Introduction: Muscular dystrophy is a hereditary degenerative muscle disease which progressively reduces the strength of the muscles that control movement. In this study, we tried to investigate genetic variants in muscular dystrophy using sequencing of whole exons. Case Presentation: A family with two affected patients with muscular dystrophy was referred for genetic counseling followed by exome sequencing testing on the proband. After filling out informed consent, blood samples were obtained from each available family member. Candidate genetic variant was confirmed using Sanger sequencing. Conclusions: Exome data analysis revealed a variant of c.2864 + 1G > A in the proband, which altered the exon-intron 26 splice site within the DYSF gene. Genetic changes in this gene are known to be associated with muscular disorders, such as limb-girdle muscular dystrophy and other dysferlinopathies. Assessment of this genetic variant in the patient's sister also showed homozygous variant. Since the patient's sister was married to her cousin, the same variant was tested in her husband, which was normal homozygous. NGS-based techniques, including whole-exome sequencing, can identify the molecular genetic basis of the disease in families with limb-girdle muscular dystrophy. The results can be helpful in identifying potential carriers in the family and in prenatal diagnosis to the families involved.

Clinical and genetic parallels of the classification and diagnosis of Ehlers-Danlos syndrome

Статья посвящена обсуждению подходов к классификации и обзору доступных литературных данных о клинической вариабельности и молекулярно-генетических основах патогенеза редкого наследственного заболевания - синдрома Элерса-Данло. Представленный обзор расширит представление о патогенезе и позволит оптимизировать диагностику данного синдрома, определить тактику лечения и медико-генетического консультирования отягощенных семей как клиническим генетикам, специалистам в области изучения орфанных заболеваний, так и врачам терапевтам, специалистам семейной медицины и общей врачебной практики. The article is devoted to the discussion of approaches to the classification and review of the available literature data on clinical variability and the molecular genetic basis of the pathogenesis of a rare hereditary disease - Ehlers-Danlos syndrome. The presented review will expand the understanding of the pathogenesis and allow to optimize the diagnosis of this syndrome, to determine the tactics of treatment and medical and genetic counseling of burdened families, both to clinical geneticists, specialists in the study of orphan diseases, and to general practitioners, specialists in family medicine and general medical practice.

REGENERATIVE REHABILITATION OF SKELETAL MUSCLES DAMAGES

The article is devoted to the analysis of the current state of regenerative and rehabilitative treatments of skeletal muscles, the possibilities of restoring the functioning of tissue lost due to aging, injuries or diseases. The study of the molecular genetic basis of mechanotransduction and mechanotherapy will allow the identification of genes and molecules, the expression levels of which can serve as biomarkers of the effectiveness of regenerative-rehabilitation measures. These mechanisms are potential therapeutic targets for stimulating of regeneration of skeletal muscles. The focus of the article is on the choice of an individual approach, both when conducting basic scientific research and developing rehabilitation programs. All this will significantly improve patient outcomes.

Regenerative Rehabilitation for Bone Tissue Damage

The article is devoted to the analysis of the current state of regenerative and rehabilitative treatments in orthopedics, the possibilities of restoring of bone lost due to injuries or diseases. An overview of the main methods and approaches to enable effective regenerative and rehabilitation measures is given. The study of the molecular genetic basis of mechanotransduction and mechanotherapy will allow the identification of genes and molecules, the expression levels of which can serve as biomarkers of the effectiveness of regenerative-rehabilitation measures. These mechanisms are potential therapeutic targets for stimulating of regeneration of bones. A special section is devoted to the study of the characteristics of cellular technologies in the treatment of injuries and diseases of these tissues. The focus of the article is on the choice of an individual approach, both when conducting basic scientific research and developing rehabilitation programs. All this will significantly improve patient outcomes.

Polymorphism of ACE, AGT, AGTR1 genes as genetic predictors of hypertension

The genetic architecture of blood pressure (BP) includes more than 30 genes, the polymorphic variants of which cause phenotypic heterogeneity of BP. Given that a human genetic information is largely stable from birth, it can act as an early predictor of hypertension (HTN). Identification of polymorphic variants of genes associated with a high HTN risk may be one of the promising areas of early diagnosis and prevention of this disease. In addition, the availability of this data will make it possible to clarify the prognosis of patients already with HTN, as well as to personalize the treatment approach. The review analyzes the papers devoted to the molecular genetic basis of hypertension and identifies the possible role of gene polymorphism of the renin-angiotensin-aldosterone system in hypertension development. A large number of studies have revealed an association between HTN and polymorphic variants of the ACE, AGT, AGTR1 genes. In addition, polymorphism of these genes is involved in the development of atherosclerosis and related diseases, kidney and central nervous system disorders, and justifies the effectiveness of angiotensin-converting enzyme inhibitors in the treatment of HTN.