Diversity of Late Blight Resistance Genes in the VIR Potato Collection.

Late blight (LB) caused by the oomycete Phytophthora infestans (Mont.) de Bary is the greatest threat to potato production worldwide. Current potato breeding for LB resistance heavily depends on the introduction of new genes for resistance to P. infestans (Rpi genes). Such genes have been discovered in highly diverse wild, primitive, and cultivated species of tuber-bearing potatoes (Solanum L. section Petota Dumort.) and introgressed into the elite potato cultivars by hybridization and transgenic complementation. Unfortunately, even the most resistant potato varieties have been overcome by LB due to the arrival of new pathogen strains and their rapid evolution. Therefore, novel sources for germplasm enhancement comprising the broad-spectrum Rpi genes are in high demand with breeders who aim to provide durable LB resistance. The Genbank of the N.I. Vavilov Institute of Plant Genetic Resources (VIR) in St. Petersburg harbors one of the world's largest collections of potato and potato relatives. In this study, LB resistance was evaluated in a core selection representing 20 species of seven Petota series according to the Hawkes (1990) classification: Bulbocastana (Rydb.) Hawkes, Demissa Buk., Longipedicellata Buk., Maglia Bitt., Pinnatisecta (Rydb.) Hawkes, Tuberosa (Rydb.) Hawkes (wild and cultivated species), and Yungasensa Corr. LB resistance was assessed in 96 accessions representing 18 species in the laboratory test with detached leaves using a highly virulent and aggressive isolate of P. infestans. The Petota species notably differed in their LB resistance: S. bulbocastanum Dun., S. demissum Lindl., S. cardiophyllum Lindl., and S. berthaultii Hawkes stood out at a high frequency of resistant accessions (7-9 points on a 9-point scale). Well-established specific SCAR markers of ten Rpi genes-Rpi-R1, Rpi-R2/Rpi-blb3, Rpi-R3a, Rpi-R3b, Rpi-R8, Rpi-blb1/Rpi-sto1, Rpi-blb2, and Rpi-vnt1-were used to mine 117 accessions representing 20 species from seven Petota series. In particular, our evidence confirmed the diverse Rpi gene location in two American continents. The structural homologs of the Rpi-R2, Rpi-R3a, Rpi-R3b, and Rpi-R8 genes were found in the North American species other than S. demissum, the species that was the original source of these genes for early potato breeding, and in some cases, in the South American Tuberosa species. The Rpi-blb1/Rpi-sto1 orthologs from S. bulbocastanum and S. stoloniferum Schlechtd et Bché were restricted to genome B in the Mesoamerican series Bulbocastana, Pinnatisecta, and Longipedicellata. The structural homologs of the Rpi-vnt1 gene that were initially identified in the South American species S. venturii Hawkes and Hjert. were reported, for the first time, in the North American series of Petota species.

Microwave-Assisted Synthesis of Fluorescent Pyrido[2,3-b]indolizines from Alkylpyridinium Salts and Enaminones.

Pyridinium ylides are well recognized as dipoles for cycloaddition reactions. In its turn, the microwave-assisted interaction of N-(cyanomethyl)-2-alkylpyridinium salts with enaminones unexpectedly proceeds as a domino sequence of cycloisomerization and cyclocondensation reactions, instead of a 1,3-dipolar cycloaddition. The reaction takes place in the presence of sodium acetate as base and employs benign solvents. The optical properties of the resulting pyrido[2,3-b]indolizines were studied, showing green light emission with high fluorescence quantum yields.

Allele rs2010963 C of the VEGFA gene is associated with the decreased risk of primary varicose veins in ethnic Russians.

Objective To study the association of polymorphisms rs699947, rs2010963, rs3025039 in the VEGFA gene region and rs1870377, rs2305949, rs2071559 in the VEGFR2 gene region with the risk of primary varicose veins in ethnic Russians. Methods Genotypes were determined by real-time PCR allelic discrimination. The case group consisted of 448 patients with primary varicose veins and the control group comprised 609 individuals without a history of chronic venous disease. Association was studied by logistic regression analysis. Results Allele rs2010963 C was associated with the decreased risk of varicose veins (additive model of inheritance: odds ratio = 0.73, 95% confidence interval = 0.59-0.91, P = 0.004). Conclusions Our results provide evidence that polymorphism rs2010963 located in the 5' untranslated region of the VEGFA gene can influence genetic susceptibility to primary varicose veins in Russians. Otherwise, it can be in linkage disequilibrium with another functional single nucleotide polymorphism that can alter the level of vascular endothelial growth factor A protein.

Angiopoietin-Like Proteins 4 (ANGPTL4) Gene Polymorphisms and Risk of Brain Arteriovenous Malformation.

BACKGROUND: Brain arteriovenous malformations (BAVMs) are formed by hypertrophied arterial vessels (afferents, feeders), a large number of arteriovenous shunts which become tangled to form a body (nidus) of malformation, which then expands draining proximal veins. The aim of this study was a replication of single nucleotide polymorphism (SNP) rs11672433 association with BAVM development with the subsequent meta-analysis of published data. METHODS: A total of 252 Russian patients with brain BAVMs and 480 control subjects were included in the present study. Genotyping was performed using real-time polymerase chain reaction with competitive hydrolysis probes. RESULTS: In our case-control study, we found no significant association with brain arteriovenous malformation for the SNP rs11672433 of ANGPTL4 gene (odds ratio .82, 95% confidence interval = .57-1.17 P value = .27) as well as in meta-analysis (odds ratio 1.18, 95% confidence interval = .81-1.73, P value = .39). CONCLUSIONS: Our data showed that SNP rs11672433 was not associated with the BAVM Russian population and the following meta-analysis did not detect an association in total. Thus, in spite of the fact that ANGPTL4 (protein) participates in the angiogenesis regulation processes, we consider that SNP rs11672433, a high-frequency locus in the ANGPTL4 gene, does not influence the predisposition to BAVM or its effect is too small to be detected in the present size sample set.

Polymorphisms of GSTM1, GSTT1, GSTP1 genes and chromosomal aberrations in lung cancer patients.

PURPOSE: To study the potential links between genetic polymorphisms in the GSTT1, GSTM1, GSTP1 genes and the frequency of chromosomal aberrations (CAs) in lung cancer patients and healthy residents in Russian Federation. METHODS: 200 cells in well-spread metaphase with 46 chromosomes were examined for 353 newly diagnosed lung cancer patients (males) who received medical treatment in the Kemerovo Regional Oncology Center (Kemerovo, Russian Federation), and 300 healthy males from Kemerovo, Russian Federation. The polymorphisms of the GSTM1 del and GSTT1 del genes were analysed by multiplex PCR. Genotyping of the polymorphic variants in the GSTP1 (A313G, T341C) gene was performed using Real-time PCR with competing TaqMan probes complementary to the polymorphic DNA sites. The data analysis was performed using software STATISTICA 8.0 (StatSoft Inc., USA). RESULTS: We discovered that a GSTM1 del polymorphism increases the frequency of chromosomal damage in smoking patients with lung cancer, a general group of lung cancer patients, donors with non-small cell lung cancer and patients in the latest stages of the malignant process. The synergetic effects of occupational exposure and the malignant process can induce some modifications in the cytogenetic status in lung cancer patients harbouring the GSTM1 del polymorphism. CONCLUSIONS: CAs in peripheral blood lymphocytes can be used as biomarkers of the early biological effects of exposure to genotoxic carcinogens and may predict future cancer incidence in several epidemiologic studies. Genetic changes in genes encoding phase II detoxification enzymes are linked to decreases in the metabolic detoxification of environmentally derived genotoxic carcinogens.

HFE p.C282Y gene variant is associated with varicose veins in Russian population.

Recently, the association of polymorphism rs1800562 (p.C282Y) in the hemochromatosis (HFE) gene with the increased risk of venous ulceration was shown. We hypothesized that HFE gene polymorphism might be involved not only in ulceration process, but also in susceptibility to primary varicose veins. We genotyped HFE p.C282Y (rs1800562) and p.H63D (rs1799945) variants in patients with primary varicose veins (n = 463) and in the control group (n = 754). In our study, p.282Y variant (rs1800562 A allele) was significantly associated with the risk of varicose veins (OR 1.79, 95 % CI = 1.11-2.89, P = 0.02). A borderline significant reverse association of p.63D variant (rs1799945 G allele) with venous leg ulcer development was revealed in Russians (OR 0.25, 95 % CI = 0.06-1.00, P = 0.05), but not in the meta-analysis (P = 0.56). We conclude that the HFE gene polymorphism can affect the risk of developing primary varicose veins.

Association of polymorphisms near the FOXC2 gene with the risk of varicose veins in ethnic Russians.

OBJECTIVE: To investigate the association of polymorphisms located near the FOXC2 gene with the risk of varicose veins in ethnic Russians. METHODS: Allele, genotype, and haplotype frequencies were determined in the sample of 474 patients with primary varicose veins and in the control group of 478 individuals without a history of chronic venous disease. RESULTS: Polymorphisms rs7189489, rs4633732, and rs1035550 showed the association with the increased risk of varicose veins, but none of the observed associations remained significant after correction for multiple testing. Haplotype analysis revealed the association of haplotype rs7189489 C-rs4633732 T-rs34221221 C-rs1035550 C-rs34152738 T-rs12711457 G with the increased risk of varicose veins (OR = 2.67, P = 0.01). CONCLUSIONS: Our results provide evidence that the studied polymorphisms do not play a major role in susceptibility to varicose veins development in the Russian population.

Genome-wide significant association with seven novel multiple sclerosis risk loci.

OBJECTIVE: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. METHODS: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. RESULTS: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10(-8)) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10(-12)), CD28 (rs6435203, p=1.35×10(-9)), LPP (rs4686953, p=3.35×10(-8)), ETS1 (rs3809006, p=7.74×10(-9)), DLEU1 (rs806349, p=8.14×10(-12)), LPIN3 (rs6072343, p=7.16×10(-12)) and IFNGR2 (rs9808753, p=4.40×10(-10)). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. CONCLUSIONS: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases.

Association GSTT1, GSTM1 and GSTP1 (Ile105Val) genetic polymorphisms in mothers with risk of congenital malformations in their children in Western Siberia: a case-control study.

OBJECTIVE: Polymorphisms of glutathione S-transferase (GST) genes in mothers may be involved in teratogenesis in their offspring. This study aims to investigate the association of GST genes (T1, M1 and P1) with the risk of having children with congenital malformations (CMs) in residents of the West Siberian region of Russia. METHOD: We studied 235 women with offspring's with CMs, and 273 women with one or more healthy children. Null genotypes of GSTM1 and GSTT1 were identified through multiplex real-time polymerase chain reaction, and GSTP1 gene (Ile105Val) polymorphism was determined through TaqMan-real-time polymerase chain reaction. RESULTS: The study showed that the maternal genotype GSTT1 «0/0¼ is associated with CMs in the offspring (odd ratio (OR) = 3.63, P = 5.18 × 10(-9) ). A significant association of the maternal genotype GSTT1 «0/0¼ with CMs of the cardiovascular system (OR = 5.03, P = 2.93 × 10(-7) ), urinary system (OR = 4.20, P = 3.51 × 10(-6) ) and central nervous system (OR = 4.40, P = 6.69 × 10(-5) ) was found in the child. No association of maternal GSTM1 (del) and GSTP1 (Ile105Val) genetic polymorphisms with CMs of the child was identified. CONCLUSION: Homozygous deletion of the GSTT1 gene in women of the West Siberian region is a risk factor for birth defects in the child.