Polymorphism Research Articles

STUDYING THE DIVERSITY OF LENTIL VARIETIES BY ALLELES OF THE EARLY FLOWERING GENE LcELF3 USING MOLECULAR MARKERS

Lentils are one of the most widespread leguminous crops in the world and now Kazakhstan is also experiencing a significant expansion of acreage. Howev-er, late sowing is unacceptable for this crop, since in this case the photoperiod effect and drought lead to loss of crop samples if the flowering period of lentil plants is not optimized. The genes controlling early flowering (EFL3) are associ-ated with the rate of growth and the beginning of flowering and are independent of the length of daylight. In this study, the presence of the early flowering gene LcELF3 was analyzed in 76 collection samples of lentils. As a result of PCR am-plification and sequencing of the LcELF3 gene using the Sanger method, genetic polymorphism was detected and codominant SNP (Single Nucleotide Polymor phism) markers were developed. Further testing of collection samples of lentils by ASQ genotyping allowed us to identify 36 samples with homozygous geno-type aa (late flowering) and 40 samples with homozygous genotype bb (earlier flowering). The use of factor analysis of the productivity elements of lentil sam-ples bearing favorable bb alleles of the early flowering gene LcELF3 made it pos sible to conduct a visual analysis for the studied years. Thus, using the example of lentils, the possibility of sampling samples containing favorable bb alleles of the LcEFL3 gene, controlling early flowering, which are necessary to increase its yield in conditions of prolonged spring and short summer season in the dry steppe zone of Northern Kazakhstan, is shown.

Associations between allelic differences of the fifth group chromosome loci and a complex of agronomically valuable traits in common wheat (Triticum aestivum L.)

Aim. Characterization of recombinant inbred wheat lines by agronomically relevant traits and detection of asso- ciations between their expression level and allelic differences of microsatellite loci of the fifth group chromosomes. Methods. Phenological observations, morphometric indicators, and elements of crop structure. Statistical analysis of the obtained data was carried out in Microsoft Excel. The significance of the difference between samples was assessed by Fisher’s F test. A difference of p < 0.05 was considered statistically significant for all indicators. Results. The poly- morphism of the parental genotypes and the population of 47 recombinant-inbred lines (RILs) F7 from the crossing of the winter wheat varieties Luzanivka odeska and Odeska chervonokolosa over three years (2016–2018) in conditions of the Southern Steppe (Odesa) was evaluated according to eight characteristics: duration of a period prior to heading, plant height, productive tillering, grain number per spike, grain weight per spike, thousand-grain weight, productive tiller number per unit area and grain yield. The comparison of the data of line evaluation by agronomic traits against the data of microsatellite analysis of lines by 14 microsatellite loci of the fifth group chromosomes demonstrated the associations between several loci and grain yield and between two loci and plant height. Conclusions. The changes in grain yield in the most unfavorable year, 2018, were associated with allelic differences of lines at locus Xbarc319- 5A, and in the most favorable year, 2017, – with another locus of chromosome 5A, Xbarc330-5A. In both cases, the lines that had an allele from Odeska chervonokolosa were characterized by a significantly higher level of grain yield compared to the lines that had an allele from the Luzanivka odeska variety. There are at least two QTLs on 5B chromo- some, associated with winter wheat grain yield in favorable growing years. The first of them is located in the region of locus Xbarc88-5B, and the second – in the region of loci Xwmc415-5B, Xgpw3191-5B, and Xcfd7-5B. Based on the alleles of the specified microsatellite loci, which are linked QTLs of grain yield, it is possible to select genotypes at the early stages of selection that will give a higher yield in years with favorable conditions for growing wheat.

Genetic variants of INHA/PstI and VIPR1/HhaI and their relationship with reproductive traits in Ac chicken (Gallus gallus domesticus Brisson)

The Ac chicken (Gallus gallus domesticus Brisson) is commonly raised alongside other domestic chicken breeds in the Mekong Delta region. This study was conducted to analyze the impact of INHA/PstI and VIPR1/HhaI polymorphisms on the reproductive characteristics of this breed. A total of 380 Ac hens from 16-40 weeks of age were used, each placed in a separate cage for data collection . DNA isolation was performed using feather samples, and genotypes were detected by applying the PCR-RFLP technique . Two polymorphisms were identified , namely C829T (INHA /PstI) in exon 1 of the INHA gene an d C429 13T (VIP R1/HhaI) in intron 6 of th e V IPR1 ge ne .At both site s, two po lymo rphism s d id not follow the Hardy -Weinberg e quilibr ium . The IN HA /PstI and VIP R 1/Hh a I po lymo rphism s demo nstrated a statist ically significant association with the tota l number of eggs pro duce d and the la ying r ate (p<0.0 5). S pec ifically , he ns with TT genotype (INHA/PstI ) had the highest egg p rodu ction (7 2.4 eggs /he n/24 laying week s ). In contras t , thos e with t he CC genotype produced approximately 9 fewer eg gs (63.2 eggs /h en ), resu lting in layi ng rates of 4 5.2% and 40 .3%, re specti vel y .Additionally , the INHA/PstI polymorphisms sho wed a notab le and significan t associ at ion with the average age of the first egg (p<0.05). In conclusion , to enhance egg prod uction in Ac ch ickens th roug h selective breeding, it is rec ommended to prioritize the use of birdswith the TT genotype at the INH A/Pst I locu s.

Genotypes and frequencies of the TSLP gene variant rs1837253 in different occupational asthma phenotypes

Introduction. Currently, despite the fact that occupational asthma has long been considered as a separate, independent disease, recent studies pay more and more attention to its heterogeneity. Occupational asthma phenotyping was originally based on the identification of combinations of clinical characteristics of the disease, but now more and more data that allow understanding the cause of clinical differences at the molecular genetic level are emerging. Thus, molecular genotyping opens up new opportunities in the search for a more targeted and personalized approach to the treatment of occupational asthma, as well as in the development of an individual strategy for its prevention. The aim of the study was to determine the genetic risk markers for the development of oc cupational asthma under the influence of sensitizers by assessing the TSLP gene polymor phism rs1837253. Materials and methods. The study was conducted on the basis of the Department of Occupational Diseases and Clinical Pharmacology named after honored scientist of the Russian Federation professor V. V. Kosarev, FSBEI HE Samara State Medical University of the Ministry of Health of the Russian Federation, and the Department of Occupational Pathology, SBHI SR Samara Medical and Sanitary Unit No. 5 of the Kirovsky District. The study involved 170 patients with various phenotypes of occupational bronchial asthma (OBA) and 50 people in the control group: group 1 (42 people) — the phenotype «allergic occupational bronchial asthma», group 2 (36 people) — the phenotype «non-allergic occupational bronchial asthma», group 3 (58 people) — the phenotype «occupational bronchial asthma — occupational chronic obstructive pulmonary disease», group 4 (34 people) — the phenotype «occupational bronchial asthma — metabolic syndrome», group 5 (50 people) — the control group (healthy). As part of the study of genetic predisposition to occupational bronchial asthma,genetic polymorphisms of the rs1837253 TSLP gene were determined. DNA samples were isolated from peripheral venous blood lymphocytes by phenol-chloroform extraction. Genotyping was performed by real-time polymerase chain reaction using primers and probes developed with the PrimerQuest tool (Integrated DNA Technologies, Inc.). Results. Thus, for the first time, genetic risk markers for the development of occupational asthma under the influence of sensitizers have been identified: the TSLP gene polymorphisms rs1837253, which makes it possible to recommend determining these genetic markers during in-depth periodic medical examinations in persons working under exposure to sensitizing and irritating substances in the presence of clinical, functional, and immunological changes. Conclusion. The identified marker profiles of OBA genotypes can optimize the approach to the diagnosis, treatment and prevention of this pathology, as well as expand the range of criteria for predicting the course of the disease. If polymorphisms of the TSLP gene are detected during molecular genetic studies, patients need to be registered with a dispensary and require repeated examinations of the function of external respiration once every 6 months and in-depth periodic medical examinations in a specialized center of occupational pathology with the obligatory participation of a pulmonologist, an allergist-immunologist, an occupational pathologist, as well as conducting extended functional and immunological studies once every 2 years.

A DPD model of soft spheres with waterlike anomalies and poly(a)morphism.

Core-softened approaches have been employed to understand the behavior of a large variety of systems in soft condensed matter, from biological molecules to colloidal crystals, glassy phases, and water-like anomalies. At the same time, dissipative particle dynamics (DPD) is a powerful tool suitable for studying larger length and time scales. In this sense, we propose a simple model of soft molecules that exhibits a wide range of interesting phenomena: polyamorphism, with three amorphous phases, polymorphysm, including a recently found gyroid phase and a cubic diamond structure, reentrant liquid phase, and density, diffusion, and structural water-like anomalies. Each molecule is constituted by two collapsing beads, representing a harder central core and a softer corona. This induces a competition between distinct conformations that leads to their unique behavior. This provides a basis for the development of more accurate water-like DPD models that can then be parameterized for specific systems and even used to model and understand the self-assembly of colloidal crystals.

Genome-Wide Association Study Discovered Favorable Single Nucleotide Poly Morphisms and Candidate Genes Associated with Ramie (Boehmeria Nivea L.) Colloidal Matters

ABSTRACT Ramie (Boehmeria nivea L.) bast fiber is one of the most ancient natural fibers, which is used for textile only after degumming. Hemicellulose, pectin, and hydrotrope are the main colloidal matters in ramie fiber, which are removed when degumming. However, the genetic variation and control loci are poorly understood. Here, we analyzed the genetic variation of the colloidal matters and discovered the favorable single nucleotide poly morphisms (SNP) by genome-wide association study using 319 ramie core germplasms. In total, 21, 5, and 10 SNPs were found to be the significantly key control loci associated with hemicellulose, pectin, and hydrotrope, respectively, which changed the amino acid sequences of the reference genes. Fourteen key genes involved in various sugars biosynthesis and metabolism pathways were identified to regulate the hemicellulose content in ramie. Meanwhile, 7 calcium transporting or binding related genes were identified to involve in the biosynthesis of calcium magnesium pectinate-the main component of pectin. Moreover, 306 genes related to hydrotrope were identified and their function were also discussed. Our study first reveals the genetic variation and candidate genes related to the colloidal matters of ramie bast fiber, and provides tools for marker-assisted selection in improvement of agricultural traits.

Absence of Polymorphisms in Codons 167, 198 and 200 of All Seven β-Tubulin Isotypes of Benzimidazole Susceptible and Resistant Parascaris spp. Specimens from Australia.

Benzimidazoles resistance is widespread in strongyle parasitic nematodes and associated with polym orphisms in the codons 167, 198 and 200 of isotype 1 β-tubulin (tbb-1). In ascarids, benzimidazole (BZ) resistance has rarely been reported and in none of these cases were any of these polymorphisms detected. Here, available genome and transcriptome data from WormBase ParaSite were used to compare the complete β-tubulin reservoirs of Parascaris univalens, Ascaris suum and Ascaris lumbricoides. Adult Parascaris spp. specimens collected in Australia from horses after BZ treatment (susceptible, n = 13) or surviving BZ treatment and collected after ivermectin treatment (resistant, n = 10) were genotyped regarding codons 167, 198 and 200 using Sanger sequencing. Phylogenetic analyses clearly showed that there are no one-to-one ascarid orthologs of strongyle tbb-1 genes. In the reference genomes, as well as phenotypically susceptible and resistant Parascaris spp. from Australia, six out of seven β-tubulin genes showed a BZ-susceptible genotype (F167, E198, F200). The only exception were the testis-specific β-tubulin D genes from all three ascarid species that encode tyrosine at codon 200. This was observed independently of the BZ-susceptibility phenotype of Parascaris spp. These data suggest that different mechanisms lead to BZ resistance in ascarid and strongyle nematodes.

Clinical and genetic factors associated with the risk of recurrent ischemic events in patients with stable stenocardia

The aimof the study was to assess the clinical and genetic factors associated with the risk of recurrent ischemic events in patients with stable stenocardia (SS).Materials and methods.A total of 100 patients with SS were examined and followed-up for 15.3±8.3 months. The patients were divided into subgroups (SG): SG1 (n=51) – persons without events, SG2 (n=49) persons with recurrent ischemic events (hospitalization due to the development of pain syndrome, re-stenting due to stent restenosis, myocardial infarction, cerebral infarction and death from cardiovascular causes), SGB (n=11) – persons with «major» recurrent ischemic events (re-stenting due to stent restenosis, myocardial infarction, cerebral infarction and death from cardiovascular causes) , SGG (n=89) – persons without «major» events. The obtained survey data (general clinical, aggregometry, polymor phism of genes of platelet fibrinogen receptor ITGB3 (T1565C), platelet collagen receptor ITGA2 (C807T), ADP platelet receptor P2RY12, H1/H2 (T744C)) were analyzed using the STATISTICA 10.0 software.Results.In SG2, men predominated (χ2=9.2; p<0.01), past MI was more common (χ2=4.8; p<0.05), more stents were implanted (2.4±1.9 versus 1.7±1.1, p<0.05), TRAP-test values were higher (p<0.05) compared to SG1. In SGB, greater number of stents were implanted (3.1±2.2 versus 1.61±1.57, p<0.05), the carriage of the TC genotype of the ITGB3 gene was more common, (p<0.05), a combination of gene mutations ITGB3 and P2RY12 was more common, (p<0.05) compared to SGG. A logistic regression equation was constructed, including the presence of diabetes mellitus, the number of platelets in the blood test, the ASPI-test values, the carriage of the 1565C allele of the ITGB3 gene, the number of stents implanted, which makes it possible to determine the likelihood of developing «major» recurrent ischemic events with a cut-off threshold LP₀=0.0965, with sensitivity – 81.82 %, specificity – 78.48 %, overall accuracy – 78.89 %.Conclusions.The factors associated with the development of recurrent ischemic events are: male sex, previous MI, a greater number of implanted stents, and high TRAP-test values. The factors associated with the development of recurrent «major» ischemic events are: a greater number of implanted stents, carriage of the TC genotype of the ITGB3 gene, carriage of a combination of mutations of the H1/H2 polymorphic locus of the P2RY12 gene and the T1565C polymorphic locus of the ITGB3 gene, diabetes mellitus, the number of platelets in blood test, ASPI-test values.

Frequency of the rs 14035 polymorphism of RAN gen in recurrent pregnancy loss: A case-control study.

Background Genetic factors could account for recurrent pregnancy loss (RPL). The RAN gene is a member of the "large RAS family" and a small GTPase that is essential for the translocation of Ribonucleic acid (RNA) and proteins through the nuclear pore. Mutation in the RAN constitutive gene could stop DNA synthesis and alter the expression of genes in the uterus, likely playing a role in recurrent miscarriage.Objective The aim was to investigate the frequency of RAN (rs 14035) polymorphism in women with RPL compared with women without abortion history.Materials and Methods In this case-control study, 100 women with at least two consecutive miscarriages before the 20th wk of gestation and having spouses with karyotype and normal sperm parameters as the case group and 100 women with no history of abortion and having at least one successful pregnancy and normal delivery as the control group. The groups were age matched (20-40 yr). The rs 14035 polymorphism of RAN gene was investigated by Polymerase Chain Reaction-Restriction Fragment Length poly morphism technique and the frequency of which was compared between the two groups.ResultsThe frequency of TT, TC, and CC genotypes of RAN gene polymorphism in the case group were 9%, 40%, and 51%, respectively, and in the control group were 11%, 38%, and 51%, respectively. There was no significant difference in the genotypes between two groups (p = 0.882).ConclusionAccording to our results, it seems that RAN polymorphism (rs 14035) is not associated with the risk of RPL in this study population.

Genetic diversity of <i>Lippia rotundifolia</i> Cham. in Minas Gerais, Brazil

Lippia rotundifolia is an aromatic species, endemic from Campos rupestres and isolated by mountains. We aimed with the research to study the genetic variability of cha-de-pedestre ( Lippia rotundifolia Cham.) with natural occurrence in ten places of the State of Minas Gerais, from molecular markers of ISSR type. The places of collection were: Parque Estadual de Serra Nova; Parque Estadual Veredas do Peruacu; Aboboras community; Gigante community; edge of Rio do Peixe; environmental preservation area of Olhos d´agua; private property in Joaquim Felicio; Parque Estadual do Rio Preto; Sao Goncalo do Rio das Pedras and brook of Rio Tigre. After the establishment of the extraction and amplification of DNA fragments with primers ISSR, an array of genetic distance was built. From this matrix, we analyzed the genetic diversity index as the allelic frequency (Na and Ne), Shannos´s index (H´), polymorphism (PLP), heterozygosity (He) and gene flow (Nm). The result showed higher genetic variability within the population (93%). The genetic diversity index was low (He = 0.132; H´= 0.214; Na = 1.111; Ne = 1.183; PLP = 56.67%). In general the species have low genetic diversity. The greatest diversity in populations occurred with an average temperature of 20°C. The Rio Tigre showed higher genetic distance and isolation.

EFFECT OF POLYMORPHISM OF APOE AND SLCO1B1 GENES ON THE COURSE OF MYOCARDIAL INFARCTION ASSOCIATED WITH ACUTE KIDNEY INJURY IN HOSPITAL AND LONG-TERM PERIODS

THE AIM:to assess the effect of APOE and SLCO1B1 gene polymorphism on the course of myocardial infarction (MI) associated with acute kidney injury (AKI) in hospital and long-term periods.PATIENTS AND METHODS:132 patients with МI were examined, which were divided into 2 groups: the first (I) – 68 patients with MI and AKI, the second (II) – 64 people with MI without AKI.RESULTS:In the distribution of genotypes, polymorphism of Leu28Pro of the APOE gene in the studied groups was revealed that LeuPro was more often inherited in patients of group I – 20,6 %, the average value of total cholesterol (TC) – 6,01±0,3 mmol/l, and low density lipoproteins (LDL) – 3,37±0,21 mmol/l, compared with patients of group II, where the LeuPro genotype – 6, 2 %, TC – 5,03±0,3 mmol/l, LDL – 2,38±0,3 mmol/l, p<0,05. A similar situation was typical for the polymor phism Val174Ala SLCO1B1 gene, where ValAla in patients of group I-26,5 %, in II-12,5 %, p<0.05. In heterozygotes I sample TC-5,59±0,3 mmol/l, and LDL – 3,30±0,14 mmol/l, in group II TC – 5,19±0,29 mmol/l, LDL – 2,75±0,23 mmol / l, p<0,05. The clinical picture of the hospital period in patients with MI and AKI, proceeded with the development of a greater number of complications, which reflected in the high mortality in group I – 16,2 %, in group II – 4,7 %, p<0,05. In the posthospital period, against the background of atorvastatin administration in both study groups, there was a positive trend of decrease in TC and LDL, but it was not possible to achieve the targets. Mortality in the long-term period in group I – 15,4 %, in group II-2,0 %, p<0.05.CONCLUSIONS:in patients with MI and AKI on the background of a more severe clinical course of the disease, both in hospital and in the long-term period, rare allelic variants of the genes APOE and SLCO1B1 were more often determined, which negatively affected the lipid profile.

Association Between Two Common Polymorphisms of Vitamin D Binding Protein and the Risk of Coronary Artery Disease: A Case-control Study.

SummaryBackgroundCoronary Artery Disease (CAD) is one of the most widespread non-communicable diseases. Vitamin Dbinding protein (VDBP) and its genetic poly morphisms have been highlighted as the susceptible components for CAD. The aim of the present study was to examine the association of VDBP single nucleotide poly morphisms (SNPs) - rs7041 and rs4588 - with CAD susceptibility among the Iranian population.MethodsA total of 143 men with CAD and 145 healthy age-sex matched controls underwent genotyping for the - rs7041 and rs4588 polymorphisms using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Serum level of 25(OH)D was assayed using microplate colorimetric enzyme immunoassay.ResultsWe found a significant association between GG genotype (rs7041) and CAD (p=0.02, OR=0.537 95% CI =0.306-0.944). Regarding rs4588 polymorphism, a significant difference was observed in which the CA genotype (p=0.00032, OR=2.578, 95% CI=1.579-4.208) and allele A (P=0.028, OR=1.491, 95% CI=1.043-2.132) were significantly higher in CAD patients compared to controls. In spite of lower serum levels of 25(OH)D in CAD patients, we found no significant association between these SNPs and Vitamin D serum concentrations.ConclusionWe concluded that VDBP polymorphisms affect the susceptibility to CAD in Iranian men. Therefore, further studies are required to clarify the association of VDBP phenotypes and its serum levels with CAD.

How a Genetically Stable Extremophile Evolves: Modes of Genome Diversification in the Archaeon Sulfolobus acidocaldarius.

In order to analyze in molecular terms how Sulfolobus genomes diverge, damage-induced mutations and natural polymorphisms (PMs) were identified in laboratory constructs and wild-type isolates, respectively, of Sulfolobus acidocaldarius Among wild-type isolates drawn from one local population, pairwise nucleotide divergence averaged 4 × 10-6, which is about 0.15% of the corresponding divergence reported for Sulfolobus islandicus The most variable features of wild-type S. acidocaldarius genomes were homopolymer (mononucleotide) tracts and longer tandem repeats, consistent with the spontaneous mutations that occur under laboratory conditions. Natural isolates, however, also revealed large insertions/deletions and inversions, which did not occur in any of the laboratory-manipulated strains. Several of the large insertions/deletions could be attributed to the integration or excision of mobile genetic elements (MGEs), and each MGE represented a distinct system of site-specific recombination. The mode of recombination associated with one MGE, a provirus related to Sulfolobus turreted icosahedral virus, was also seen in certain chromosomal inversions. Artificially induced mutations, non-MGE insertions/deletions, and small PMs exhibited different distributions over the genome, suggesting that large-scale patterning of Sulfolobus genomes begins early in the divergence process. Unlike induced mutations, natural base pair substitutions occurred in clusters, and one cluster exhibited properties expected of nonreciprocal recombination (gene conversion) between dispersed imperfect repeats. Taken together, the results identify simple replication errors, slipped-strand events promoted by tandem repeats, homologous recombination, and rearrangements promoted by MGEs as the primary sources of genetic variation for this extremely acidophilic archaeon in its geothermal environment.IMPORTANCE The optimal growth temperatures of hyperthermophilic archaea accelerate DNA decomposition, which is expected to make DNA repair especially important for their genetic stability, yet these archaea lack certain broadly conserved types of DNA repair proteins. In this study, the genome of the extreme thermoacidophile Sulfolobus acidocaldarius was found to be remarkably stable, accumulating few mutations in many (though not all) laboratory manipulations and in natural populations. Furthermore, all the genetic processes that were inferred to diversify these genomes also operate in mesophilic bacteria and eukaryotes. This suggests that a common set of mechanisms produces most of the genetic variation in all microorganisms, despite the fundamental differences in physiology, DNA repair systems, and genome structure represented in the three domains of life.

Mapping genotype-phenotype associations of nsSNPs in coiled-coil oligomerization domains of the human proteome.

We assessed the impact of disease mutations (DMs) versus polymorphisms (PYs) in coiled-coil (CC) domains in UniProt by modeling the structural and functional impact of variants in silico with the CC prediction program Multicoil. The structural impact of variants was evaluated with respect to three main metrics: the oligomerization score-to determine whether the variant is stabilizing or destabilizing-the oligomerization state, and the register-specific score. The functional impact was queried indirectly in several ways. First, we examined marginally stable CCs that were either stabilized or destabilized by the variant. Second, we looked for variants that altered the register of the wild-type CC near wild-type irregularities of likely functional importance, such as skips and stammers. Third, we searched for variants that altered the oligomerization state of the CC. DMs tended to be more destabilizing than PYs; but interestingly, PYs were more frequently associated with predicted changes in the oligomerization state. The functional impact was also queried by testing the association of CC variants with multiple phenotypes, that is, pleiotropy. Mutations in CC regions of proteins cause 155 different phenotypes and are more frequently associated with pleiotropy than proteins in general. Importantly, the CC region itself often encodes the pleiotropy.

Genetic polymorphisms of interleukin-10 and transforming growth factor-β1 and antituberculosis drugs-induced liver injury

Purpose: Drug-induced liver injury is one of the serious adverse reactions resulting in severe morbidity and discontinuation of med ications. Previously, IL-10 gene polymorphism has been reported to be associated with diclofenac-induced hepatitis. In this study, we aimed to investigate the associations between genetic polymorphisms of immune-regulating cytokines (IL-10 and TGF-β1) with antituberculosis drugs (ATD)-induced liver injury. Methods: We enrolled 80 patients with ATD-induced liver injury and 238 ATD-tolerant controls. Two single nucleotide polymor phisms (SNP) of IL-10 (-1082A>G, rs1800896; -819T>C, rs1800871) and one promoter SNP of TGF-β1 gene (-509C>T, rs1800469) were genotyped in both groups. Genotype frequencies of these SNPs were compared between case and control groups. Results: In 2 promoter SNPs of IL-10 gene, there was no significant difference of genotype frequencies between patients with ATD-induced liver injury and controls. In addition, the genotype frequency of TGF-β1 -509C>T SNP in ATD-induced liver injury patients were not different from those of controls. Conclusion: In conclusion, there was no significant association between IL-10 and TGF-β1 gene polymorphisms and ATD-induced liver injury. These findings suggest that IL-10 and TGF-β1 do not play important role in the development of ATD-induced liver injury. (Allergy Asthma Respir Dis 2017:5:41-46)

Association between apolipoprotein B EcoRI polymorphisms and coronary heart disease

The study was carried out to examine the association between apolipoproteinB (ApoB) EcoRI polymorphism (E- vs. E+) (rs1042031) and coronary heart disease (CHD) risk by systematically analyzing multiple independent studies. The Hardy-Weinberg equilibrium (HWE) test was applied to assess genotype frequency distribution in healthy controls. The quality of the studies was assessed using the Newcastle-Ottawa scale (NOS). Power analysis was performed with Power and Precision V4 software. Afixed effect model was used because no deviation from homogeneity was found. Publication bias was quantified and examined with Begg's funnel plot test and Egger's linear regression method. The meta-analysis was performed by Stata12.0 software. Atotal of 21 eligible association studies were merged in this meta-analysis and the pooled sample consisted of 2994 CHD patients and 3258 healthy controls. No significant publication bias and heterogeneity were observed in these studies. The pooled odds ratio (OR) and 95% confidence interval (CI) of E- vs. E+ were 1.18 (1.06-1.32). The pooled OR (95% CI) of E+ E- + E- E- vs. E+ E+ was 1.18 (1.04-1.34). This meta-analysis indicated that ApoB EcoRI confers amoderate risk for CHD and the E- allele at this locus might be asusceptibility allele for the development of CHD.

Phenotype and genotype analysis of in herited dysplasminogenemia caused by plasminogen Ala601Thr mutation

Objective To detectthe phenotype and gene mutations underlying aninherited dysplasminogenemia pedigree and search the virulence gene. Methods The peripheral venous blood samples of the proband and his family members(fourteen subjects of three generations in total)were collected, and their prothrombin time(PT), activated partial thromboplastin time(APTT), thrombin time(TT), fibrinogen(FIB), fibrinogen degradation products(FDP), D-dimmer(D-D)weretested on a STAGO analyzer, the plasminogen activity(PLG: A)and plasminogen antigen(PLG: Ag)were analyzedby thechromogenic substrate assay and rocket immunoelectrophoresis, respectively. All 19 exons, 5' and 3' untranslated regions of PLG were amplified with PCR. Direct DNA sequencing was used to analyze the amplified products, which were confirmed by backward sequencing. Three bioinformatics online softwares(SIFT, PolyPhen-2 and MutationTaster)were used to forecast the possible impact of the mutations on the protein function. At last, the model analysis of mutate site was taken on a Swiss-Pdb Viewer software. Results The PLG: Avalue of the proband and other 6 family members were decreased to the half, while the PLG: Ag was normal. The D-D and FDP value of the proband, his grandma and father were slightly higher. DNA sequencing has revealed that the proband and the other 6 members of this family had the same mutation of g. 38829G>A in exon 15, leading to the missense mutationp.Ala601Thr.The results of bioinformatics softwares showed that the mutation could affect the thePLGfunction. Protein model analysis indicated that the hydrophobic interaction force and hydrogen bond between the amino acids were changed, which might affect the stability of the PLG.In addition, all the members of this family take the heterozygous SNP of g. 2501C>A in the 5'UTR. Conclusions The p. Ala601Thr found in the inherited dysplasminogenemia pedigree in the exon 15 was responsible for the reduced PLG: A of the family, the dysplasminogenemia and this mutation were both reported for the first time in China.(Chin J Lab Med, 2016, 39: 366-371) Key words: Mutation, Missense; Plasminogen; Polymor phism, single nucleotide

Meta-Analysis of Transcriptome Data Related to Hippocampus Biopsies and iPSC-Derived Neuronal Cells from Alzheimer's Disease Patients Reveals an Association with FOXA1 and FOXA2 Gene Regulatory Networks.

Although the incidence of Alzheimer's disease (AD) is continuously increasing in the aging population worldwide, effective therapies are not available. The interplay between causative genetic and environmental factors is partially understood. Meta-analyses have been performed on aspects such as polymorphisms, cytokines, and cognitive training. Here, we propose a meta-analysis approach based on hierarchical clustering analysis of a reliable training set of hippocampus biopsies, which is condensed to a gene expression signature. This gene expression signature was applied to various test sets of brain biopsies and iPSC-derived neuronal cell models to demonstrate its ability to distinguish AD samples from control. Thus, our identified AD-gene signature may form the basis for determination of biomarkers that are urgently needed to overcome current diagnostic shortfalls. Intriguingly, the well-described AD-related genes APP and APOE are not within the signature because their gene expression profiles show a lower correlation to the disease phenotype than genes from the signature. This is in line with the differing characteristics of the disease as early-/late-onset or with/without genetic predisposition. To investigate the gene signature's systemic role(s), signaling pathways, gene ontologies, and transcription factors were analyzed which revealed over-representation of response to stress, regulation of cellular metabolic processes, and reactive oxygen species. Additionally, our results clearly point to an important role of FOXA1 and FOXA2 gene regulatory networks in the etiology of AD. This finding is in corroboration with the recently reported major role of the dopaminergic system in the development of AD and its regulation by FOXA1 and FOXA2.

АSSOCIATION OF VARIOUS GENETIC MARKERS OF CARDIOVASCULAR DISEASES AND SUDDEN CARDIAC DEATH IN MEN

Aim. To search and study the association of some candidate genes polymorphysms of various cardiovascular diseases and sudden cardiac death in men. Material and methods. The sudden cardiac death group (SCD) is collected by the WHO criteria with suddenly died men underwent court-medicine expertise (n=274). Control group was matched by the age and gender from the DNA bank of HAPIEE and MONICA trials. Genotyping of groups was done according to polymorhysms SCN5A, rs187238 gene IL-18, rs1799864 gene CCR2, rs3864180 gene GPC5, rs1799983 gene eNOS, rs2228314 gene SREBF-2, rs1800588 gene HL, rs10757278, rs1333049 with methods of PDRF and realtime PCR. Results. No significant differences found between the SCD group and control group by the prevalence of genotypes SCN5A, rs187238 gene IL-18, rs3864180 gene GPC5, rs1799983 gene eNOS, rs1800588 gene HL. In SCD group the decrease of homozygotes by CC polymorphism rs2228314 found in gene SREBF-2 and the decrease of heterozygotes GC comparing to control group (HR=4,074, 95% CI 1,843-9,002, р=0,0002; HR=0,442, 95% CI 0,302-0,647, р=0,0001, reap.). In SCD group carriers of GG genotype polymorphism rs10757278 and CC poly morphism rs1333049 are significantly more prevalent than in control group (HR=1,814, 95% CI 1,159-2,839, р=0,011; HR=1,744, 95% CI 1,104-2,754, р=0,019, resp.). The part of GA carriers of polymorphism rs1799864 gene CCR2 is more prevalent in SCD group comparing to control (HR=1,558, 95% CI 1,051-2,308, р=0,029). Conclusion. Polymorphisms rs10757278, rs1333049, rs2228314 gene SREBF-2, rs1799864 gene CCR2 are associated with sudden cardiac death in men.

Use of Microsatellite Markers Derived from Genomic and Expressed Sequence Tag (EST) Data to Identify Commercial Watermelon Cultivars

Abstract: This study was carried out to construct a DNA profile database for 102 watermelon cultivars through the comparison of polymorphism level and genetic relatedness using genomic microsatellite (gMS) and expressed sequence tag (EST)-microsatellit e (eMS) markers. Sixteen gMS and 10 eMS primers showed hyper-variability and were able to represent the genetic variation within 102 watermelon cultivars. With gMS markers, an average of 3.63 alleles per marker were detected with a pol ymorphism information content (PIC) value of 0.479, whereas with eMS markers, the average number of alleles per marker was 2.50 and the PIC value was 0.425, indicating that eMS detects a lower polymorphism level compared to gMS. Cluster analysis and Jaccard’sgenetic distance coefficients using the unweighted pair group method with arithmetic average (UPGMA) based on the gMS, eMS, and combined data sets showed that 102 commercial watermelon cultivars could be categorized into 6 to 8 major groups corresponding to phenotypic traits. Moreover, this method was sufficient to identify 78 out of 102 cultivars. Correlation anal ysis with Mantel tests for those clusters using 3 data sets showed high correlation ( r ≥ 0.80). Therefore, the microsatellite markers used in this study may serve as a useful tool for germplasm evaluation, genetic purity assessment, and fingerprinting of waterm elon cultivars.Additional key words: