Vol 54, No 2 (2018)

Sarcoglycanopathies are a group of autosomal recessive limb-girdle muscular dystrophies (LGMD) caused by mutations in sarcoglycan genes: SGCA (LGMD 2D, MIM 600119), SGCB (LGMD 2E, MIM 604286), SGCG (LGMD 2C, MIM 353700), and SGCD (LGMD 2F, MIM 601287). These genes encode four transmembrane sarcoglycan subunits participating in formation of the large sarcolemmal dystrophin- glycoprotein complex. Clinical symptoms of sarcoglycanopathies resemble the ones in Duchenne/Becker muscular dystrophy and several autosomal recessive LGMD, which causes difficulties in the differential diagnostics between these diseases. This review covers the main aspects of sarcoglycanopathies, such as etiology, spectrum of mutations, clinical features and diagnostics. In addition, we review the fundamental pathogenesis mechanisms leading to sarcoglycanopathies, which can also help to understand the potential options for treatment for patients with muscular dystrophies.

The Drosophila melanogaster Z³³¹⁴ line isolated from a Zvenigorodka (Ukraine) natural population is characterized by the manifestation and emergence of a wide spectrum of molecular aberrations. Among them, two types (the wing venation anomaly and violation of the leg segmentation) were the most represented. It was demonstrated that the frequency of manifestation (penetrance) and the expressiveness of these phenotypic aberrations increase with an increase in the temperature. When the Z³³¹⁴ line is bred in the laboratory, autosomal visible rase (ra: 3–97.3) mutation, which leads to reduction of a part of dorso-central and scutellaria macrochaetae, was detected (isolated and identified). A number of genetic peculiarities that determined the consistency and prospects of the study were found during the mutation process study in the Z³³¹⁴ line. The Z³³¹⁴ line is characterized by a high frequency of the emergence of visible mutations in the X-Z³³¹⁴ chromosome, which persisted for a long time of the breeding under laboratory conditions (from 2003 to 2011). Locus-specific high genetic instability in the singed locus in the X-Z³³¹⁴ chromosome persisted from the moment of emergence of the first mutant alleles in 2006 until the end of the study. The emergence of mutations was observed both during the line breeding “inside” (in the case of brother–sister crossings) and after the crossings of the X-Z³³¹⁴ chromosome carrier males with females of the С(1)DX,ywf/Y laboratory line with linked X chromosomes.

The database of the world gene pool of wheat was scanned by pedigree and the participation of genetic material from T. timopheevii in the creation of 3088 varieties of common wheat was established. The spatial and temporal dynamics of the propagation of these varieties was studied. Using the analysis of pedigrees, a diversity of T. timopheevii donors was studied. The specificity of donors of the genetic material T. timopheevii for the regions of wheat breeding was established. The main source of resistance genes for most varieties is accession D-357-1 from the Georgian variety-population of Zanduri. This significantly reduces the diversity of the genetic material of T. timopheevii used in wheat breeding. In 369 varieties and 184 lines, the genes for resistance to pathogens from T. timopheevii were identified. The genes of T. timopheevii are distributed mainly in winter varieties, as well as spring varieties sown in autumn. The value of donors as sources of T. timopheevii genes is ambiguous, despite the fact that most of them come from the same D-357-1 accession. The Sr36 gene is most commonly found in the United States, Western Europe, and Australia; it was transferred from the Wisconsin-245 line through Arthur or TP-114-1965a. The Pm6 gene is distributed in Western Europe; it was transferred from the pre-breeding line Wisconsin 245/5*Cappelle-Desprez//Hybrid- 46/Cappelle Desprez. The gene Lr18 is more common in the United States; it was transmitted by the Blueboy or Vogel 5 varieties from the Coker-55-9 line. The extremely limited set of genes for resistance to pathogens from T. timopheevii used in commercial varieties and the specificity of their geographical distribution are possibly associated with the uniqueness of the G subgenome and plasmon in this species, its low potential for plasticity, and tolerance to drought. In addition, the imperfection of the methods of pre-breeding and recombination breeding prevents the elimination in translocation of close linkage of target genes with undesirable ones.

The article presents the results of a study of genetic polymorphism for the first time carried out on pomegranate varieties and forms of Azerbaijan origin using molecular markers. In total, 102 PCR fragments were identified, of which 80 were polymorphic. The high level of polymorphism (75.5%) and the rich genetic diversity were identified among the studied pomegranate collection. As a result of data analysis and on the basis of the values of the basic parameters (PIC, EMR, MI, RP, MRP) determining informativeness of markers, all 14 ISSR primers were suitable for genotyping pomegranate accessions. The most effective markers (UBC808, UBC811, UBC834, and UBC840) were identified among the set of primers tested. A dendrogram was constructed on the basis of the data obtained, which made it possible to group genotypes into 16 major clusters. The genetic similarity index ranged from 0.032 to 0.94. The study of the genetic relationship of different pomegranate varieties confirms the effectiveness of the ISSR method, which makes it possible to determine the level of genetic diversity, as well as to establish the relationship among the studied pomegranate accessions.

Cytogenetic analysis of malarial mosquitoes is performed in Kaliningrad and its vicinity. Two species of Anopheles with biotopic specialization are identified: An. messeae and An. maculipennis. А relatively low level of inversion polymorphism at the sex chromosome and the right arm of the third autosome is established for An. messeae. This is quite natural for the northwestern peripheral populations of the species range.

Black garden ant L. niger is known as a dominant species of urban ant fauna in Europe. Successful propagation of L. niger in transformed ecosystems was associated with behavioral traits in many surveys; however, molecular and genetic basis of such adaptation was never studied. In the present study, genomes of populations from the city of Moscow and natural habitats of Moscow oblast are compared. Pooled samples from rural and urban habitats are collected and sequenced with Illumina HiSeq. SNP frequency, Tajima’s D, and fixation index are estimated with PoPoolation and Popoolation2 software. SNP frequencies are significantly different in 64 genes according to Fisher’s exact test. Some of these genes are detected as affected by recent selection. Out of 64 genes, 26 encode retrotransposon proteins. The genes of immune response to viral and fungal infections, fatty acid synthases, and elements of the Hippo/Fat pathway have different SNP frequencies between populations. Certain retrotransposon genes also can be under selection. It is important to note that repressors and mediators of RNA polymerase II are significantly different between urban and rural populations of L. niger. These genes can influence retrotransposon mobility.

The results of screening for BRCA1, BRCA2, ATM, NBN, CHEK2, PALB2, BLM gene mutations in 1000 breast cancer (BC) patients from the Republic of Bashkortostan (RB) are presented. Germline mutations in these genes accounted for 7.5% of breast cancer patients. The wide spectrum of mutations was found in women of Slavic origin, including: c.5266dupC, c.181T>G, and c.4034delA in BRCA1; c.5932G>T in ATM; c.657_661del5 in NBN; c.444+1G>A, c.1100delC, and dele9,10(5kb) in CHEK2; c.509_510delGA and c.172_175delTTGT in PALB2; and c.1642C>T in BLM gene.

The aim of this study was to identify dysregulated pathways for the diagnosis and treatment of dilated cardiomyopathy (DCM) using pathway interaction network analysis. Methods: Transcriptome data of DCM, protein-protein interaction (PPI) data, and pathway data were recruited and preprocessed. Then, the pathway interaction network was constructed based on the gene expression analysis and gene co-expression analysis. Meanwhile, pathway activity analysis was performed, and the pathway with the greatest activity change was defined as the seed pathway. Staring from the seed pathway, the dysregulated pathways that could serve as diagnostic biomarker was extracted from the pathway interaction network using support vector machines. Results: Combining gene expression and co-expression data, we constructed the pathway interaction network, covering 4175 pathway interactions. Via pathway activity analysis, cap-dependent translation initiation with the greatest activity change was defined as the seed pathway. Staring from cap-dependent translation initiation, a total of 21 dysregulated pathways were obtained, which could discriminate DCM samples from controls with the area under the curve value of 0.95. Conclusion: A pathway interaction network was implemented to identify dysrgulated pathways that can best discriminate DCM samples from controls. We identified a total of 21 dysregulated pathways in DCM, which can serve as diagnostic biomarkers for DCM.

Regional association analysis is a new statistical method which simultaneously considers all variants in a selected genome region. This method was created for the analysis of rare genetic variants, whose genotypes are determined by exome or genome sequencing. The gene is usually considered as a region. It was also proposed to use a regional analysis for testing of the association between a complex trait and a set of common variants genotyped by the panels developed for genome-wide association analysis. In this case, overlapping genome regions (sliding windows) are usually considered as a region. Since the size of such regions can be rather large, there is a risk of overestimation (inflation) of the test statistic and an increase in the type I error. In this work, the effect of the size of the region on the type I error was studied for traits with different heritability. The results of simulating experiments demonstrated that the physical size of the region but not the number of genetic variants in it is a limiting factor. The higher the trait heritability, the greater the type I error differs from the declared value. The analysis of a large number of real traits confirmed these conclusions. It is necessary to take into account these results during the interpretation of the results of regional association analysis conducted on large regions using common genetic variants.

The heat stress resistance of Drosophila melanogaster females carrying a hypomorphic mutation of the DILP6 insulin-like protein gene (dilp6⁴¹) under a change in the level of stress-related hormones (juvenile hormone and octopamine) is studied. It is revealed that the dilp6⁴¹ mutation decreases the heat stress resistance of mature D. melanogaster females. An experimental decrease in the level of juvenile hormone is shown to restore the stress resistance of mutant females to the level of stress resistance observed in wild type Canton S females. These data suggest that the effects of the dilp6⁴¹ mutation on the stress resistance of females are mediated by an increased level of juvenile hormone. An experimental increase in the octopamine level that causes an increase in juvenile hormone level supports this hypothesis: the resistance to heat stress decreases in females of both lines and this decrease is more significant in mutant females than in the control line. Thus, it is established for the first time that the effect of the hypomorphic dilp6 gene mutation on the heat stress resistance of D. melanogaster females is mediated by juvenile hormone.