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Sample records for harbors genetic polymorphisms

  1. Genetic polymorphism in bladder cancer.

    PubMed

    Wu, Xifeng; Lin, Xin; Dinney, Colin P; Gu, Jian; Grossman, H Barton

    2007-01-01

    Individual variation in the genetic constitution of humans may affect the host responses to constant assaults from exogenous and endogenous carcinogens, which will eventually impact cancer risk, disease prognosis and clinical outcome. Bladder cancer is one of the most common cancers in the world. In this review, the published research articles studying the association between genetic polymorphisms and bladder cancer risk and disease progression are summarized. Genetic polymorphisms are categorized based on their primary cellular functions: genes in carcinogen metabolism, DNA repair, cell cycle control, inflammation, apoptosis, methylation, genes functioning as G proteins, and cell adhesion molecules. Furthermore, we discuss a number of limitations of current genetic susceptibility research and suggest future directions in molecular epidemiology study. This review presents an overview of current molecular epidemiology of bladder cancer and provides a useful resource for understanding the pathogenesis of bladder cancer. PMID:17127293

  2. Cytogenetic biomarkers and genetic polymorphisms.

    PubMed

    Norppa, Hannu

    2004-04-01

    Cytogenetic biomarkers have long been applied in surveillance of human genotoxic exposure and early effects of genotoxic carcinogens. Due to their wide use, it has been possible to evaluate, in international collaborative studies, if a high level of these biomarkers in peripheral lymphocytes is predictive of cancer risk. Thus far, such an association has been observed for chromosomal aberrations (CAs), but not for sister chromatid exchanges (SCEs) or micronuclei (MN). The cancer risk predictivity of CAs was not dependent on the time between CA analysis and cancer detection and did not appear to be explained by tobacco smoking or occupational exposure to carcinogens but was seen in unexposed non-smokers as well. This suggests a role for individual susceptibility factors. Genetic polymorphisms of various xenobiotic-metabolising enzymes, influencing the metabolic activation and detoxification of carcinogens, have been associated with cancer risk, and some of them also appear to affect cytogenetic biomarkers. The lack of glutathione S-transferase M1 (GSTM1 null genotype) is associated with increased sensitivity to genotoxicity of tobacco smoke, and GSTM1 null smokers also show an increased frequency of CAs and SCEs. N-Acetyltransferase (NAT2) slow acetylation genotype and glutathione S-transferase T1 (GSTT1) null genotype seem to elevate the baseline level of CAs and SCEs and CAs, respectively--possibly because of reduced capacity to detoxify some wide-spread or endogenous genotoxins. For some chemicals, in vitro cytogenetic studies with lymphocyte donors representing different genotypes have been able to predict a differential in vivo response. For instance, in vitro SCE induction by styrene and by epoxide metabolites of 1,3-butadiene is modified by GSTM1 and GSTT1 genotypes--which also influence the excretion of specific mercapturic acids in humans exposed to butadiene and styrene. Polymorphisms of DNA repair and folate metabolism are expected to be of special importance in modulating genotoxic effects. Some evidence exists for the effects of X-ray cross complementation group 1 (XRCC1) codon 280 and (in smokers) Xeroderma pigmentosum group D (XPD) codon 23 polymorphisms on baseline CAs, for XRCC1 codon 399 polymorphism on SCEs in smokers, and for methylene tetrahydrofolate reductase (MTHFR) codon 677 and methionine synthase reductase (MTRR) polymorphisms on spontaneous MN. PMID:15093278

  3. Genetics Home Reference: Catecholaminergic polymorphic ventricular tachycardia

    MedlinePLUS

    ... Where can I find information about diagnosis or management of catecholaminergic polymorphic ventricular tachycardia? These resources address the diagnosis or management of catecholaminergic polymorphic ventricular tachycardia and may include ...

  4. Turner syndrome and genetic polymorphism: a systematic review

    PubMed Central

    de Marqui, Alessandra Bernadete Trovó

    2015-01-01

    Objective: To present the main results of the literature on genetic polymorphisms in Turner syndrome and their association with the clinical signs and the etiology of this chromosomal disorder. Data sources: The review was conducted in the PubMed database without any time limit, using the terms Turner syndrome and genetic polymorphism. A total of 116 articles were found, and based on the established inclusion and exclusion criteria 17 were selected for the review. Data synthesis: The polymorphisms investigated in patients with Turner syndrome were associated with growth deficit, causing short stature, low bone mineral density, autoimmunity and cardiac abnormalities, which are frequently found in patients with Turner syndrome. The role of single nucleotide polymorphisms in the etiology of Turner syndrome, i.e., in chromosomal nondisjunction, was also confirmed. Conclusions: Genetic polymorphisms appear to be associated with Turner syndrome. However, in view of the small number of published studies and their contradictory findings, further studies in different populations are needed in order to clarify the role of genetic variants in the clinical signs and etiology of the Turner syndrome. PMID:25765448

  5. Genetics of Color Polymorphism in the Pea Aphid, Acyrthosiphon pisum

    PubMed Central

    Caillaud, Marina C.; Losey, John E.

    2010-01-01

    The genetic basis of color polymorphism is explored in the pea aphid, Acyrthosiphon pisum (Harris) (Homoptera: Sternorrhyncha), in which two color morphs have been described (pink or green). Laboratory crosses and a Mendelian genetic analysis reveal that color polymorphism in pea aphids is determined by a single biallelic locus, which we name colorama, with alleles P and p, pink being dominant to green. The putative genotypes are Pp or PP for pink morphs, and pp for green morphs. This locus is shown to be autosomal. Last, there was no evidence of influence of the direction of the cross on color inheritance, thus showing that cytoplasmic effects and/or maternally-inherited symbionts play no role in the inheritance of color polymorphism in pea aphids. The existence of a simple genetic determinism for color polymorphism in a system in which genetic investigation is possible may facilitate investigations on the physiological and molecular mechanisms of genetically-based color morph variation, and the establishment of a link between this locus and fitness in a range of ecological conditions. PMID:20673119

  6. The genetic polymorphism of drug transporters: functional analysis approaches.

    PubMed

    Ishikawa, Toshihisa; Tsuji, Akira; Inui, Kenichi; Sai, Yoshimichi; Anzai, Naohiko; Wada, Morimasa; Endou, Hitoshi; Sumino, Yasuhiro

    2004-01-01

    Evidence is accumulating to strongly suggest that drug transporters are one of the determining factors governing the pharmacokinetic profile of drugs. To date, a variety of drug transporters have been cloned and classified as solute carriers and ATP-binding cassette transporters. Such drug transporters are expressed in various tissues such as the intestine, brain, liver, and kidney, and play critical roles in the absorption, distribution and excretion of drugs. However, at the present time, information is limited regarding the genetic polymorphism of drug transporters and its impact on their function. In this context, we have undertaken the functional analyses of the polymorphisms identified in drug transporter genes. This article aims to provide an overview on the functional aspects of the non-synonymous polymorphisms of drug transporters and to present standard methods for the evaluation of the effect of polymorphisms on their function. PMID:14683421

  7. Genetic polymorphisms in Pakistani women with polycystic ovary syndrome.

    PubMed

    Liaqat, Irfana; Jahan, Nusrat; Krikun, Graciela; Taylor, Hugh S

    2015-03-01

    Polycystic ovary syndrome (PCOS) is the major cause of anovulatory infertility. Although the genetic basis of PCOS is not well understood, it is a common metabolic and endocrine disorder. This study investigates the possible genomic variants associated with PCOS in Pakistani women from the Punjab region. DNA samples from 96 patients with genetically unrelated PCOS and 96 controls were analyzed by direct sequencing to determine the polymorphisms of different loci on follicle-stimulating hormone receptor (fshr), follicle-stimulating hormone ? (fshr?), luteinizing hormone chorionic gonadotropin (lhcgr), luteinizing hormone ? (lh?), estrogen receptor ? (esr1), and estrogen receptor ? (esr2) genes. Significant associations were observed within the genotype frequencies, allele frequencies, and multi-single-nucleotide polymorphism (SNP) haplotype analysis of most polymorphisms studied. This study identified new SNPs at positions 605+52 Del/T in lhcgr genes occurring in this particular subpopulation. The strong r (2) value suggests that polymorphisms in the fshr and esr1 genes were in linkage disequilibrium. Our study provides evidence of statistically significant associations between susceptibility to PCOS in Pakistani women and the gene polymorphisms mentioned earlier. This suggests that the susceptible loci for PCOS lie within or very close to the chromosomal regions spanning these genes. PMID:25100445

  8. Characteristics of myotonic dystrophy in Istria: molecular genetic approach. Part II: Analysis of genetic polymorphisms.

    PubMed

    Medica, I; Logar, N; Peterlin, B

    2000-12-01

    One of the world highest prevalence estimates of myotonic dystrophy (DM) has been reported in the Croatian region Istria. To analyse the population genetic characteristics of DM locus in Istria, two intragenic and three extragenic polymorphic markers were tested. The Southern blot technique was used for D19S63 locus analysis, whereas PCR analysis was performed for CKMM, Alu polymorphism, DMPK (G/T) intron 9/HinfI polymorphism, and D19S207 genetic markers. The compound haplotypes segregating with DM were established. A complete association between the DM mutation and D19S63, D19S207, intron 9/HinfI polymorphism and Alu polymorphism markers were found. In all DM chromosomes: D19S63 and Alu markers had the allele 1 in common; D19S207 had the allele 3 in common, DMPK (G/T) intron 9/HinfI marker had the allele 2 in common. The analysis of CKMM polymorphism revealed genotype heterogeneity; in DM chromosomes either allele 2 or allele 4 were found. The haplotype analysis in the population of Croatian Istria supports the linkage disequilibrium between the DM mutation and Alu polymorphism, intron 9/HinfI polymorphism, D19S63 and D19S207 markers as reported worldwide. The results of the haplotype analysis suggest a common origin of the mutation in Istrian population. PMID:11216395

  9. Role of genetic polymorphisms in hepatitis C virus chronic infection

    PubMed Central

    Coppola, Nicola; Pisaturo, Mariantonietta; Sagnelli, Caterina; Onorato, Lorenzo; Sagnelli, Evangelista

    2015-01-01

    AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC). METHODS: We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article. RESULTS: Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation. CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies. PMID:26380828

  10. Population Genetics of Polymorphism and Divergence

    PubMed Central

    Sawyer, S. A.; Hartl, D. L.

    1992-01-01

    Frequencies of mutant sites are modeled as a Poisson random field in two species that share a sufficiently recent common ancestor. The selective effect of the new alleles can be favorable, neutral, or detrimental. The model is applied to the sample configurations of nucleotides in the alcohol dehydrogenase gene (Adh) in Drosophila simulans and Drosophila yakuba. Assuming a synonymous mutation rate of 1.5 X 10(-8) per site per year and 10 generations per year, we obtain estimates for the effective population size (N(e) = 6.5 X 10(6)), the species divergence time (t(div) = 3.74 million years), and an average selection coefficient (? = 1.53 X 10(-6) per generation for advantageous or mildly detrimental replacements), although it is conceivable that only two of the amino acid replacements were selected and the rest neutral. The analysis, which includes a sampling theory for the independent infinite sites model with selection, also suggests the estimate that the number of amino acids in the enzyme that are susceptible to favorable mutation is in the range 2-23 at any one time. The approach provides a theoretical basis for the use of a 2 X 2 contingency table to compare fixed differences and polymorphic sites with silent sites and amino acid replacements. PMID:1459433

  11. Associations of genetic polymorphisms of SAA1 with cerebral infarction

    PubMed Central

    2013-01-01

    Background Serum amyloid A protein (SAA) is both an inflammatory factor and an apolipoprotein. However, the relation between genetic polymorphisms of SAA and cerebral infarction (CI) remains unclear. Methods and results The previously reported 4 Single Nucleotide Polymorphisms (rs12218, rs4638289, rs7131332, and rs11603089) of SAA1 gene were genotyped by TaqMan method in a case–control study including 287 cerebral infarction patients and 376 control subjects. We found rs12218 CC genotype and rs7131332 AA genotype were more frequent among CI patients than among controls (9.76% versus 3.19%, P?=?0.001; 32.75% versus 24.20%; p?=?0.017; respectively). After adjustment of confounding factors such as sex, age, smoking, drinking, hypertension, diabetes, and lipids profile, the difference remained significant in rs12218 (P?Genetic polymorphism of SAA1 may be a genetic maker of cerebral infarction in Chinese. PMID:23987125

  12. High volume molecular genetic identification of single nucleotide polymorphisms using Genetic Bit Analysis Application to human genetic diagnosis

    SciTech Connect

    Boyce-Jacino, M.T.; Reynolds, J.; Nikiforov, T.

    1994-09-01

    The most common type of genetic disease-associated mutation is the single nucleotide polymorphism (SNP). Because most genetic diseases can be caused by multiple SNPs in the same gene, effective routine diagnosis of complex genetic diseases is dependent on a simple and reliable method of interrogating SNP sites. Molecular Tool`s solid phase assay capable of direct genotyping (single base sequencing) of SNP sites, Genetic Bit Analysis (GBA), involves hybridization-capture of a single-stranded PCR product to a sequence-specific, microtiter plate-bound oligonucleotide primer. The captured PCR product then acts as template for single-base extension of the capture primer across the polymorphic site, enabling direct determination of the base composition of the polymorphism through a simple colormetric assay. Genotyping in a high volume, semi-automated, processing system with a current capacity of 100 SNP interrogations per technician per day enables the screening of candidate mutations rapidly and cost-effectively, critically important to comprehensive genetic diagnosis. Using this gel-free technology, we have developed prototype diagnostic tests for CFTR and ApoE polymorphisms which enable direct sequencing of the polymorphic base at each site of interest. Routine clinical diagnosis of genetically complex diseases such as cystic fibrosis is dependent on this combination of robust biochemistry and simple format. Additionally, the ability to transfer the format and biochemistry to any disease gene of interest enables the broad application of this technology to clinical diagnostics, especially for genetically complex diseases.

  13. Interethnic genetic differentiation: GM polymorphism in eastern Senegal.

    PubMed Central

    Blanc, M; Sanchez-Mazas, A; Van Blyenburgh, N H; Sevin, A; Pison, G; Langaney, A

    1990-01-01

    Analysis of GM polymorphism has been performed on 1,806 individuals representing three sympatric ethnic groups--Bedik, Fulani, and Mandenkalu--of eastern Senegal. Haplotype frequencies estimated by maximum likelihood have been used to compute common genetic pools between the three samples and a number of other sub-Saharan African populations. Despite extreme linguistic and sociocultural differentiations and very high levels of endogamy, especially in the Bedik and Niokholo Mandenkalu, the three populations share about 90%-95% of their haplotype frequencies in a system which commonly provides strong genetic differentiations. This supports the view that, despite its importance at a large continental scale level, as it is discussed for a set of populations from many regions of sub-Saharan Africa, sociocultural differentiation usually has little effect on local genetic diversity. PMID:2105642

  14. Potential for Incorporation of Genetic Polymorphism Data in Human Health Risk Assessment

    EPA Science Inventory

    This overview summarizes several EPA assessment publications evaluating the potential impact of genetic polymorphisms in ten metabolizing enzymes on the variability in enzyme function across ethnically diverse populations.

  15. From twins to genetic polymorphisms: behavioral genetic research in Poland.

    PubMed

    Oniszczenko, W?odzimierz; Dragan, Wojciech ?ukasz

    2014-10-01

    Behavioral genetic research has been conducted at the University of Warsaw for the past 20 years. The work done at the University focuses primarily on the origins of individual differences in temperament and other personality traits. In particular, research is directed toward the traits postulated in the Regulative Theory of Temperament. We also focused on the heritability of socio-political attitudes, risk factors for human health, and post-traumatic stress disorder. The majority of the research that has been carried out is grounded in twin and family studies, although recent work based on molecular techniques has also been developed. This article reviews the most important directions and findings of behavioral genetics research at the University of Warsaw. PMID:25091033

  16. Genetic maps of polymorphic DNA loci on rat chromosome 1

    SciTech Connect

    Ding, Yan-Ping; Remmers, E.F.; Longman, R.E.

    1996-09-01

    Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome 1 were constructed by genotyping F2 progeny of F344/N x LEW/N, BN/SsN x LEW/N, and DA/Bkl x F344/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers were associated with genes. Six markers for five genes, {gamma}-aminobutyric acid receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}1 (Adrb1), carcinoembryonic antigen gene family member 1 (Cgm1), and lipogenic protein S14 (Lpgp), and 20 anonymous loci were not previously reported. Thirteen gene loci (Myl2, Aldoa, Tnt, Igf2, Prkcg, Cgm4, Calm3, Cgm3, Psbp1, Sa, Hbb, Ins1, and Tcp1) were previously mapped. Comparative mapping analysis indicated that the large portion of rat chromosome 1 is homologous to mouse chromosome 7, although the homologous to mouse chromosome 7, although the homologs of two rat genes are located on mouse chromosomes 17 and 19. Homologs of the rat chromosome 1 genes that we mapped are located on human chromosomes 6, 10, 11, 12, 15, 16, and 19. 38 refs., 1 fig., 3 tabs.

  17. Genetic Polymorphisms Related to Testosterone Metabolism in Intellectually Gifted Boys

    PubMed Central

    Celec, Peter; Tretinárová, Denisa; Minárik, Gabriel; Ficek, Andrej; Szemes, Tomáš; Lakatošová, Silvia; Schmidtová, Eva; Tur?a, Ján; Kádaši, ?udevít; Ostatníková, Daniela

    2013-01-01

    Prepubertal testosterone levels are lower in intellectually gifted boys. The aim of this pilot study was to analyze potential genetic factors related to testosterone metabolism in control and gifted boys. Intellectually gifted (IQ>130; n?=?95) and control (n?=?67) boys were genotyped. Polymorphisms of interests were chosen in genes including androgen and estrogen receptors, 5-alpha reductase, aromatase and sex hormone binding globulin. Significant differences between control and gifted boys in genotype distributions were found for ESR2 (rs928554) and SHBG (rs1799941). A significantly lower number of CAG repeats in the AR gene were found in gifted boys. Our results support the role of genetic factors related to testosterone metabolism in intellectual giftedness. Increased androgen signaling might explain previous results of lower testosterone levels in intellectually gifted boys and add to the understanding of variability in cognitive abilities. PMID:23382957

  18. The role of genetic polymorphisms in environmental health.

    PubMed Central

    Kelada, Samir N; Eaton, David L; Wang, Sophia S; Rothman, Nathaniel R; Khoury, Muin J

    2003-01-01

    Interest is increasing in the role of variations in the human genome (polymorphisms) in modifying the effect of exposures to environmental health hazards (often referred to as gene-environment interaction), which render some individuals or groups in the population more or less likely to develop disease after exposure. This review is intended for an audience of environmental health practitioners and students and is designed to raise awareness about this rapidly growing field of research by presenting established and novel examples of gene-environment interaction that illustrate the major theme of effect modification. Current data gaps are identified and discussed to illustrate limitations of past research and the need for the application of more robust methods in future research projects. Two primary benefits of incorporating genetics into the existing environmental health research framework are illustrated: a) the ability to detect different levels of risk within the population, and b) greater understanding of etiologic mechanisms. Both offer opportunities for developing new methods of disease prevention. Finally, we describe a basic framework for researchers interested in pursuing health effects research that incorporates genetic polymorphisms. PMID:12826477

  19. Genetic Polymorphism and Expression of CXCR4 in Breast Cancer

    PubMed Central

    Okuyama Kishima, Marina; Brajão de Oliveira, Karen; Ariza, Carolina Batista; de Oliveira, Carlos Eduardo Coral; Losi Guembarovski, Roberta; Banin Hirata, Bruna Karina; de Almeida, Felipe Campos; Vitiello, Glauco Akelinghton Freire; Trugilo, Kleber Paiva; Guembarovski, Alda Fiorina Maria Losi; Jorge Sobrinho, Walter; Campos, Clodoaldo Zago; Watanabe, Maria Angelica Ehara

    2015-01-01

    CXCR4 genetic polymorphisms, as well as their expression level, have been associated with cancer development and prognosis. The present study aimed to investigate the influence of CXCR4 rs2228014 polymorphism on its mRNA and protein expression in breast cancer samples. It was observed that patients presented higher CXCR4 mRNA relative expression (5.7-fold) than normal mammary gland, but this expression was not correlated with patients clinicopathological features (nuclear grade, nodal status, ER status, PR status, p53 staining, Ki67 index, and HER-2 status). Moreover, CXCR4 mRNA relative expression also did not differ regarding the presence or absence of T allele (p = 0.301). In the immunohistochemical assay, no difference was observed for CXCR4 cytoplasmic protein staining in relation to different genotypes (p = 0.757); however, high cytoplasmic CXCR4 staining was verified in invasive breast carcinoma (p < 0.01). All in all, the results from present study indicated that rs2228014 genetic variant does not alter CXCR4 mRNA or protein expression. However, this receptor was more expressed in tumor compared to normal tissue, in both RNA and protein levels, suggesting its promising applicability in the general context of mammary carcinogenesis. PMID:26576337

  20. Genetic polymorphisms of matrix metalloproteinase 3 in primary sclerosing cholangitis

    PubMed Central

    Juran, Brian D.; Atkinson, Elizabeth J.; Schlicht, Erik M.; Larson, Joseph J.; Ellinghaus, David; Franke, Andre; Lazaridis, Konstantinos N.

    2011-01-01

    Background The damaging cholestasis inherent to primary sclerosing cholangitis (PSC) results from bile duct stricturing because of progressive fibrosis. The matrix metalloproteinase 3 (MMP3) degrades a wide range of matrix components and is expressed by activated liver stellate cells, and so is a candidate for involvement with the fibrotic processes underlying PSC. Moreover, the MMP3 gene harbours polymorphisms associated with variation in its activity directly impacting clinical phenotypes. Aims We aimed to examine the influence of MMP3 polymorphisms on PSC risk and progression. Methods Nine single nucleotide polymorphisms (SNPs) tagging the common genetic variation of MMP3 were genotyped in 266 PSC patients and 407 controls. SNPs and inferred haplotypes were assessed for PSC association by logistic regression and score tests. The effect of SNPs on survival to liver transplant or death was analysed using Cox regression, and Kaplan–Meier curves were constructed. Results No association of PSC with individual SNPs or haplotypes of MMP3 was detected. However, progression to death or liver transplant was significantly associated with homozygosity for minor alleles of rs522616, rs650108 and rs683878, particularly among PSC patients with concurrent ulcerative colitis (UC) (strongest in redundant SNPs rs650108/rs683878, hazard ratio = 3.23, 95% confidence interval 1.45–7.25, P = 0.004). Conclusions Genetic variation in MMP3 influences PSC progression, possibly in the context of coexisting UC. While the functional variants and specific mechanisms remain unknown, this finding implicates the turnover of the extracellular matrix as an important and variable component of PSC pathogenesis. Efforts to understand this process could form the basis for developing effective treatments, which are currently lacking for PSC. PMID:21134112

  1. Harbor porpoise Phocoena phocoena strandings on the Dutch coast: No genetic structure, but evidence of inbreeding

    NASA Astrophysics Data System (ADS)

    van der Plas-Duivesteijn, Suzanne J.; Smit, Femmie J. L.; van Alphen, Jacques J. M.; Kraaijeveld, Ken

    2015-03-01

    Conservation management in the North Sea is often motivated by the population size of marine mammals, like harbor porpoises Phocoena phocoena. In the Dutch part of the North Sea, sighting and stranding data are used to estimate population sizes, but these data give little insight into genetic structuring of the population. In this study we investigated genetic structure among animals stranded at different locations and times of year. We also tested whether there is a link between stranding and necropsy data, and genetic diversity. We made use of both mitochondrial (mtDNA) and microsatellite DNA analysis of samples from dead stranded porpoises along the Dutch coast during 2007. mtDNA analysis showed 6 variable positions in the control region, defining 3 different haplotypes. mtDNA haplotypes were not randomly distributed along the Dutch coastline. However, microsatellite analysis showed that these mtDNA haplotypes did not represent separate groups on a nuclear level. Furthermore, microsatellite analysis revealed no genotypic differences between seasons, locations or genders. The results of this study indicate that the Dutch population is panmictic. In contrast, heterozygosity levels were low, indicating some level of inbreeding in this population. However, this was not corroborated by other indices of inbreeding. This research provided insight into genetic structuring of stranded porpoises in 2007, but data from multiple years should be included to be able to help estimate population sizes.

  2. Single nucleotide polymorphism markers for genetic mapping in Drosophila melanogaster

    SciTech Connect

    Hoskins, Roger A.; Phan, Alexander C.; Naeemuddin, Mohammed; Mapa, Felipa A.; Ruddy, David A.; Ryan, Jessica J.; Young, Lynn M.; Wells, Trent; Kopczynski, Casey; Ellis, Michael C.

    2001-04-16

    For nearly a century, genetic analysis in Drosophila melanogaster has been a powerful tool for analyzing gene function, yet Drosophila lacks the molecular genetic mapping tools that have recently revolutionized human, mouse and plant genetics. Here, we describe the systematic characterization of a dense set of molecular markers in Drosophila using an STS-based physical map of the genome. We identify 474 biallelic markers in standard laboratory strains of Drosophila that the genome. The majority of these markers are single nucleotide polymorphisms (SNPs) and sequences for these variants are provided in an accessible format. The average density of the new markers is 1 marker per 225 kb on the autosomes and 1 marker per 1 Mb on the X chromosome. We include in this survey a set of P-element strains that provide additional utility for high-resolution mapping. We demonstrate one application of the new markers in a simple set of crosses to map a mutation in the hedgehog gene to an interval of <1 Mb. This new map resource significantly increases the efficiency and resolution of recombination mapping and will be of immediate value to the Drosophila research community.

  3. Candida milleri species reveals intraspecific genetic and metabolic polymorphisms.

    PubMed

    Vigentini, Ileana; Antoniani, Davide; Roscini, Luca; Comasio, Andrea; Galafassi, Silvia; Picozzi, Claudia; Corte, Laura; Compagno, Concetta; Dal Bello, Fabio; Cardinali, Gianluigi; Foschino, Roberto

    2014-09-01

    Candida milleri, together with Candida humilis, is the most representative yeast species found in type I sourdough ecosystems. In this work, comparison of the ITS region and the D1/D2 domain of 26S rDNA gene partial sequences, karyotyping, mtDNA-RFLP analysis, Intron Splice Site dispersion (ISS-PCR) and (GTG)5 microsatellite analyses, assimilation test of different carbohydrates, and metabolome assessment by FT-IR analysis, were investigated in seventeen strains isolated from four different companies as well as in type strains CBS6897(T) and CBS5658(T). Most isolates were ascribed to C. milleri, even if a strong relatedness was confirmed with C. humilis as well, particularly for three strains. Genetic characterization showed a high degree of intraspecific polymorphism since 12 different genotypes were discriminated. The number of chromosomes varied from 9 to 13 and their size ranged from less than 0.3 to over 2 Mbp. Phenotypic traits let to recognize 9 different profiles of carbon sources assimilation. FT-IR spectra from yeast cells cultivated in different media and collected at different growth phases revealed a diversity of behaviour among strains in accordance with the results of PCR-based fingerprinting. A clear evidence of the polymorphic status of C. milleri species is provided thus representing an important feature for the development of technological applications in bakery industries. PMID:24929720

  4. Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression.

    PubMed

    Zhang, Zhang; Zhang, Yan; Shi, Minglei; Ye, Bingyu; Shen, Wenlong; Li, Ping; Xing, Lingyue; Zhang, Xiaopeng; Hou, Lihua; Xu, Junjie; Zhao, Zhihu; Chen, Wei

    2015-01-01

    Anthrax toxin causes anthrax pathogenesis and expression levels of ANTXR2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. Previous studies found that ANTXR2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eQTLs (expression quantitative trait loci) have been identified. By using 3C (chromatin conformation capture), CRISPR-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing cis-regulatory elements of ANTXR2 were localized. Two SNPs (single nucleotide polymorphism) at the conserved CREB-binding motif, rs13140055 and rs80314910 in the promoter region of the gene, modulating ANTXR2 promoter activity were identified. Combining these two regulatory SNPs with a previously reported SNP, rs12647691, for the first time, a statistically significant correlation between human genetic variations and anthrax toxin sensitivity was observed. These findings further our understanding of human variability in ANTXR2 expression and anthrax toxin susceptibility. PMID:26703731

  5. Associations between heat shock protein 70 genetic polymorphisms and calving traits in crossbred Brahman cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stressors such as heat, cold, toxins, and oxygen deprivation are known to induce heat shock proteins. Genetic polymorphisms associated with heat shock protein genes have been associated with decreased male and female fertility. Our objectives were to 1) confirm single nucleotide polymorphisms (SNP) ...

  6. Population Genetics of Speciation in Nonmodel Organisms: I. Ancestral Polymorphism in Mangroves

    E-print Network

    Yang, Ziheng

    Population Genetics of Speciation in Nonmodel Organisms: I. Ancestral Polymorphism in Mangroves sequences of ;60 genes from 4 species of Sonneratia, a common genus of mangroves on the Indo-Pacific coasts

  7. KCNJ11: Genetic Polymorphisms and Risk of Diabetes Mellitus

    PubMed Central

    Haghvirdizadeh, Polin; Mohamed, Zahurin; Abdullah, Nor Azizan; Haghvirdizadeh, Pantea; Haerian, Monir Sadat; Haerian, Batoul Sadat

    2015-01-01

    Diabetes mellitus (DM) is a major worldwide health problem and its prevalence has been rapidly increasing in the last century. It is caused by defects in insulin secretion or insulin action or both, leading to hyperglycemia. Of the various types of DM, type 2 occurs most frequently. Multiple genes and their interactions are involved in the insulin secretion pathway. Insulin secretion is mediated through the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. This channel is a heteromeric protein, composed of four inward-rectifier potassium ion channel (Kir6.2) tetramers, which form the pore of the KATP channel, as well as sulfonylurea receptor 1 subunits surrounding the pore. Kir6.2 is encoded by the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene, a member of the potassium channel genes. Numerous studies have reported the involvement of single nucleotide polymorphisms of the KCNJ11 gene and their interactions in the susceptibility to DM. This review discusses the current evidence for the contribution of common KCNJ11 genetic variants to the development of DM. Future studies should concentrate on understanding the exact role played by these risk variants in the development of DM. PMID:26448950

  8. The Role of Genetic Polymorphisms in Antioxidant Enzymes and Potential Antioxidant Therapies in Neonatal Lung Disease

    PubMed Central

    Poggi, Chiara

    2014-01-01

    Abstract Significance: Oxidative stress is involved in the development of newborn lung diseases, such as bronchopulmonary dysplasia and persistent pulmonary hypertension of the newborn. The activity of antioxidant enzymes (AOEs), which is impaired as a result of prematurity and oxidative injury, may be further affected by specific genetic polymorphisms or an unfavorable combination of more of them. Recent Advances: Genetic polymorphisms of superoxide dismutase and catalase were recently demonstrated to be protective or risk factors for the main complications of prematurity. A lot of research focused on the potential of different antioxidant strategies in the prevention and treatment of lung diseases of the newborn, providing promising results in experimental models. Critical Issues: The effect of different genetic polymorphisms on protein synthesis and activity has been poorly detailed in the newborn, hindering to derive conclusive results from the observed associations with adverse outcomes. Therapeutic strategies that aimed at enhancing the activity of AOEs were poorly studied in clinical settings and partially failed to produce clinical benefits. Future Directions: The clarification of the effects of genetic polymorphisms on the proteomics of the newborn is mandatory, as well as the assessment of a larger number of polymorphisms with a possible correlation with adverse outcome. Moreover, antioxidant treatments should be carefully translated to clinical settings, after further details on optimal doses, administration techniques, and adverse effects are provided. Finally, the study of genetic polymorphisms could help select a specific high-risk population, who may particularly benefit from targeted antioxidant strategies. Antioxid. Redox Signal. 21, 1863–1880. PMID:24382101

  9. Influence of Multiple Genetic Polymorphisms on Genitourinary Morbidity After Carbon Ion Radiotherapy for Prostate Cancer

    SciTech Connect

    Suga, Tomo; Iwakawa, Mayumi; Tsuji, Hiroshi; Ishikawa, Hitoshi; Oda, Eisei; Noda, Shuhei; Otsuka, Yoshimi; Ishikawa, Atsuko; Ishikawa, Ken-Ichi; Shimazaki, Jun; Mizoe, Jun-Etsu; Tsujii, Hirohiko; Imai, Takashi

    2008-11-01

    Purpose: To investigate the genetic risk of late urinary morbidity after carbon ion radiotherapy in prostate cancer patients. Methods and Materials: A total of 197 prostate cancer patients who had undergone carbon ion radiotherapy were evaluated for urinary morbidity. The distribution of patients with dysuria was as follows: Grade 0, 165; Grade 1, 28; and Grade 2, 4 patients. The patients were divided (2:1) consecutively into the training and test sets and then categorized into control (Grade 0) and case (Grade 1 or greater) groups. First, 450 single nucleotide polymorphisms (SNPs) in 118 candidate genes were genotyped in the training set. The associations between the SNP genotypes and urinary morbidity were assessed using Fisher's exact test. Then, various combinations of the markers were tested for their ability to maximize the area under the receiver operating characteristics (AUC-ROC) curve analysis results. Finally, the test set was validated for the selected markers. Results: When the SNP markers in the SART1, ID3, EPDR1, PAH, and XRCC6 genes in the training set were subjected to AUC-ROC curve analysis, the AUC-ROC curve reached a maximum of 0.86. The AUC-ROC curve of these markers in the test set was 0.77. The SNPs in these five genes were defined as 'risk genotypes.' Approximately 90% of patients in the case group (Grade 1 or greater) had three or more risk genotypes. Conclusions: Our results have shown that patients with late urinary morbidity after carbon ion radiotherapy can be stratified according to the total number of risk genotypes they harbor.

  10. Global Mercury Partnership ECOGENETICS OF MERCURY: FROM GENETIC POLYMORPHISMS AND EPIGENETICS

    E-print Network

    Global Mercury Partnership ECOGENETICS OF MERCURY: FROM GENETIC POLYMORPHISMS AND EPIGENETICS to document genetic and epigenetic factors that may indeed influence the toxicokinetics or toxicodynamics, rodents) are showing Hg exposures to be related to epigenetic marks such as DNA methylation. Such findings

  11. A Web-Based Genetic Polymorphism Learning Approach for High School Students and Science Teachers

    ERIC Educational Resources Information Center

    Amenkhienan, Ehichoya; Smith, Edward J.

    2006-01-01

    Variation and polymorphism are concepts that are central to genetics and genomics, primary biological disciplines in which high school students and undergraduates require a solid foundation. From 1998 through 2002, a web-based genetics education program was developed for high school teachers and students. The program included an exercise on using…

  12. Chromosome 12q harbors multiple genetic loci related to asthma and asthma-related phenotypes.

    PubMed

    Raby, Benjamin A; Silverman, Edwin K; Lazarus, Ross; Lange, Christoph; Kwiatkowski, David J; Weiss, Scott T

    2003-08-15

    Chromosome 12q13-24 is among the regions most frequently identified in genome-wide surveys for asthma susceptibility loci, with reports of two distinct clusters of positive linkage signals: one near the interferon gamma locus, the other near the nitric oxide synthase 1 locus. These results suggest that 12q harbors several asthma susceptibility loci. We evaluated this possibility in a subset of families ascertained through the Childhood Asthma Management Program (CAMP) Genetics Ancillary Study. Fifty-five nuclear families with at least two asthmatic siblings (212 individuals) were genotyped using 32 microsatellite markers. Non-parametric linkage analysis was performed for the asthma phenotype (qualitative). Multipoint variance component-based linkage analysis was performed for five quantitative asthma-related traits: (i) percent predicted forced expiratory volume in one second (FEV(1)); (ii) dose of methacholine resulting in 20% fall in FEV(1) from baseline (PC(20)); (iii) post-bronchodilator percent change in FEV(1) (BDPR); (iv) serum eosinophil levels (EOS); and (v) total serum IgE levels (IgE). Three separate and distinct loci demonstrated evidence suggestive of linkage: asthma at 68 cM (exact P-value=0.05), airways responsiveness (PC(20)) at 147 cM (P=0.01), and indices of pulmonary function (FEV1, BDPR) at 134 cM (P=0.05 and P<0.01, respectively). No linkage was observed for the atopy-related phenotypes. We provide further evidence supporting the presence of an asthma susceptibility locus at the proximal end of chromosome 12q, as well as new evidence for additional loci more distally that account for unique features of the asthma phenotype. Fine mapping efforts for these loci are warranted. PMID:12913068

  13. eNOS Genetic Polymorphisms and Cancer Risk

    PubMed Central

    Gao, Xueren; Wang, Jie; Wang, Wenjun; Wang, Mingxi; Zhang, Jianqiong

    2015-01-01

    Abstract The association between endothelial nitric oxide synthase (eNOS) polymorphisms (intron 4a/b, -786T>C and 894G>T) and cancer risk remains elusive. In addition, no studies focused on their associations with the risk of breast cancer in Chinese Han population. Thus, a meta-analysis was conducted to determine the relationship between eNOS polymorphisms and cancer risk, and then a case–control study in Chinese Han population was performed to assess their associations with breast cancer susceptibility. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The pooled analysis indicated that eNOS intron 4a/b and -786T>C polymorphisms were significantly associated with an increased risk of overall cancer. In subgroup analyses based on cancer type, the significant association was found between eNOS intron 4a/b polymorphism and prostate cancer risk, eNOS -786T>C polymorphism and risk of prostate, bladder and breast cancers, and eNOS 894G>T polymorphism and breast cancer risk. In subgroup analyses based on ethnicity, eNOS intron 4a/b and -786T>C polymorphisms were associated with an increased risk of cancer in Caucasians. In consistent with our meta-analysis results, a case–control study in Chinese Han population showed significant associations of eNOS -786T>C and 894G>T polymorphisms with the increased risk of breast cancer. In addition, stratified analyses based on pathological type showed that eNOS 894G>T polymorphism was only associated with the risk of infiltrative ductal carcinoma. Stratified analyses by tumor stage showed that eNOS -786T>C polymorphism was only associated with the risk of tumor stage III and IV. In conclusion, our meta-analysis and case–control study suggest that eNOS -786T>C and 894G>T polymorphisms are associated with the increased risk of breast cancer. PMID:26131841

  14. Polymorphs

    E-print Network

    Prankerd, Richard

    2006-10-26

    the higher melting point and the higher heat capacity (at fixed T), they are enantiotropically related ? The Cp value is more difficult to measure From Lohani and Grant, Thermodynamics of polymorphs, in Hilfiker, Polymorphism, Wiley-VCH (2005) Ch. 2 9 17....vcp.monash.edu.au Polymorphism Richard J. Prankerd, PhD Department of Pharmaceutics Faculty of Pharmacy Monash University Melbourne AUSTRALIA www.vcp.monash.edu.au Solid State Stability 2 Seminar overview ? Literature ? Definition ? Thermodynamics ? Importance in pharmaceuticals...

  15. MTHFR genetic polymorphism increases the risk of preterm delivery

    PubMed Central

    Nan, Yanrong; Li, Hongmei

    2015-01-01

    Aims: This study aimed to investigate the association between the methylene tetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and premature delivery susceptibility. Methods: With matched age and gender, 108 premature delivery pregnant women as cases and 108 healthy pregnant women as controls were recruited in this case-control study. The cases and controls had same gestational weeks. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was adopted to analyze C677T and A1298C polymorphisms of the participants. Linkage disequilibrium (LD) and haplotype analysis were conducted by Haploview software. The differences for frequencies of gene type, allele and haplotypes in cases and controls were tested by chi-square test. The relevant risk of premature delivery was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: TT gene type frequency of C677T polymorphsim was higher in cases than the controls (P=0.004, OR=3.077, 95% CI=1.469-6.447), so was allele T (P=0.002, OR=1.853, 95% CI=1.265-2.716). Whereas, CC gene type of A1298C polymorphism had a lower distribution in cases than the controls (P=0.008, OR=0.095, 95% CI=0.012-0.775), so was allele C (P=0.047, OR=0.610, 95% CI=0.384-0.970). Haplotype analysis and linkage disequilibrium test conducted on the alleles of two polymorphisms in MTHFR gene, we discovered that haplotype T-A had a higher distribution in cases, which indicated that susceptible haplotype T-A was the candidate factor for premature delivery. Conclusions: Gene type TT of MTHFR C677T polymorphism might make premature delivery risk rise while gene type CC of A1298C polymorphism might have protective influence on premature delivery. PMID:26261642

  16. A Simplified Technique for Evaluating Human "CCR5" Genetic Polymorphism

    ERIC Educational Resources Information Center

    Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda

    2013-01-01

    To involve students in thinking about the problem of AIDS (which is important in the view of nondecreasing infection rates), we established a practical lab using a simplified adaptation of Thomas's (2004) method to determine the polymorphism of HIV co-receptor CCR5 from students' own epithelial cells. CCR5 is a receptor involved in…

  17. GENETIC MAPPING PORCINE EST SEQUENCES USING LENGTH POLYMORPHISMS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The current priority of the MARC swine genome group is to identify and map SNPs (single nucleotide polymorphisms) associated with EST sequences to develop the comparative map and provide a large number of validated SNP markers for the porcine genome. Our approach is based on sequencing amplicons fr...

  18. Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival

    PubMed Central

    Kong, Jinyu; Xu, Fangxiu; Qu, Jinli; Wang, Yu; Gao, Ming; Yu, Herbert; Qian, Biyun

    2015-01-01

    Studies have suggested that vitamin D may have protective effects against cancer development or tumor progression. To search for additional evidence, we investigated the role of genetic polymorphisms involved in the vitamin D pathway in non-small cell lung cancer (NSCLC). We evaluated common genetic polymorphisms associated with the vitamin D pathway in relation to NSCLC in a case-control study of 603 newly diagnosed NSCLC patients and 661 matched healthy controls. Seven single nucleotide polymorphisms (SNPs) were genotyped, the expression of CYP27B1 and CYP24A1 were measured in 153 tumor samples and their associations with genotypes and patient survival were also analyzed. In the case-control comparison, we found SNP rs3782130 (CYP27B1), rs7041 (GC), rs6068816 and rs4809957 (CYP24A1) associated with NSCLC risk. The risk of NSCLC was increased with the number of risk alleles. CYP27B1 and CYP24A1 expression were significantly different between tumor and normal tissues in NSCLC. High CYP27B1 expression was associated with better overall survival, and the expression was different by the rs3782130 genotype. The study suggests that some genetic polymorphisms involved in the vitamin D pathway may associate with NSCLC risk, and one of the polymorphisms (rs3782130) may affect gene expression and patient survival. PMID:25544771

  19. Stability of underdominant genetic polymorphisms in population networks.

    PubMed

    Láruson, Áki J; Reed, Floyd A

    2016-02-01

    Heterozygote disadvantage is potentially a potent driver of population genetic divergence. Also referred to as underdominance, this phenomena describes a situation where a genetic heterozygote has a lower overall fitness than either homozygote. Attention so far has mostly been given to underdominance within a single population and the maintenance of genetic differences between two populations exchanging migrants. Here we explore the dynamics of an underdominant system in a network of multiple discrete, yet interconnected, populations. Stability of genetic differences in response to increases in migration in various topological networks is assessed. The network topology can have a dominant and occasionally non-intuitive influence on the genetic stability of the system. PMID:26656110

  20. Genetic Association Between Angiotensinogen Polymorphisms and Lung Cancer Risk

    PubMed Central

    Wang, Hong; Zhang, Kun; Qin, Haifeng; Yang, Lin; Zhang, Liyu; Cao, Yanyan

    2015-01-01

    Abstract Earlier published studies investigating the association between polymorphisms in the angiotensinogen gene and lung cancer risk showed no consistent results. In this study, we have summarized all currently available data to examine the correlation by meta-analysis. Case–control studies addressing the association being examined were identified through Embase, the Cochrane Library, ISI Web of Science (Web of Knowledge), Google Scholar, PubMed, and CNKI databases. Risk of lung cancer (odds ratio [OR] and 95% confidence interval [CI]) was estimated with the fixed or the random effects model assuming homozygous, allele, heterozygous, dominant, and recessive models for all angiotensinogen polymorphisms. We identified a total of 10 articles in this meta-analysis, including 7 for Leu84Phe, 4 for Ile143Val, and 3 for Leu53Leu. In the meta-analysis of Leu84Phe polymorphism, the homozygous model provided an OR of 1.44 (Phe/Phe vs Ile/Ile: OR?=?1.44, 95% CI?=?1.04–1.99, P values for heterogeneity test (Q-test) [PHet]?=?0.382). The significantly increased risk was similarly indicated in the recessive model (Phe/Phe vs Phe/Ile?+?Ile/Ile: OR?=?1.41, 95% CI?=?1.02–1.95, PHet?=?0.381). We also observed a positive association in the Caucasian subgroup. The heterozygous model and the dominant model tested for the Ile143Val polymorphism showed a marginally increased risk (Ile/Val vs Ile/Ile: OR?=?1.16, 95% CI?=?1.00–1.36, PHet?=?0.323; Val/Val?+?Ile/Val vs Ile/Ile: OR?=?1.15, 95% CI?=?0.99–1.34, PHet?=?0.253). These data suggest that Leu84Phe and Ile143Val polymorphisms in the angiotensinogen gene may be useful biomarkers for lung cancer in some specific populations. PMID:26376373

  1. Genetic mapping of the human tryptophan hydroxylase gene on chromosome 11, using an intronic conformational polymorphism

    SciTech Connect

    Nielsen, D.A.; Goldman, D. ); Dean, M. )

    1992-12-01

    The identification of polymorphic alleles at loci coding for functional genes is crucial for genetic association and linkage studies. Since the tryptophan hydroxylase (TPH) gene codes for the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin, it would be advantageous to identify a polymorphism in this gene. By examining introns of the human TPH gene by PCR amplification and analysis by the single-strand conformation polymorphism (SSCP) technique, an SSCP was revealed with two alleles that occur with frequencies of .40 and .60 in unrelated Caucasians. DNAs from 24 informative CEPH families were typed for the TPH intron polymorphism and analyzed with respect to 10 linked markers on chromosome 11, between p13 and p15, with the result that TPH was placed between D11S151 and D11S134. This region contains loci for several important genes, including those for Beckwith-Wiedemann syndrome and tyrosine hydroxylase. 37 refs., 2 figs., 1 tab.

  2. Genetic diversity and relationship of chicory (Cichorium intybus L.) using sequence-related amplified polymorphism markers.

    PubMed

    Liang, X Y; Zhang, X Q; Bai, S Q; Huang, L K; Luo, X M; Ji, Y; Jiang, L F

    2014-01-01

    Chicory is a crop with economically important roles and is cultivated worldwide. The genetic diversity and relationship of 80 accessions of chicories and endives were evaluated by sequence-related amplified polymorphism (SRAP) markers to provide a theoretical basis for future breeding programs in China. The polymorphic rate was 96.83%, and the average polymorphic information content was 0.323, suggesting the rich genetic diversity of chicory. The genetic diversity degree of chicory was higher (GS = 0.677) than that of endive (GS = 0.701). The accessions with the highest genetic diversity (effective number of alleles, NE = 1.609; Nei's genetic diversity, H = 0.372; Shannon information index, I = 0.556) were from Italy. The richest genetic diversity was revealed in a chicory line (NE = 1.478, H = 0.289, I = 0.443) among the 3 types (line, wild, and cultivar). The chicory genetic structure of 8 geographical groups showed that the genetic differentiation coefficient (GST) was 14.20% and the number of immigrants per generation (Nm) was 3.020. A GST of 6.80% and an Nm of 6.853 were obtained from different types. This observation suggests that these chicory lines, especially those from the Mediterranean region, have potential for providing rich genetic resources for further breeding programs, that the chicory genetic structure among different countries obviously differs with a certain amount of gene flow, and that SRAP markers could be applied to analyze genetic relationships and classifications of Cichorium intybus and C. endivia. PMID:25299087

  3. Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus.

    PubMed

    Zhao, Jian; Wu, Hui; Langefeld, Carl D; Kaufman, Kenneth M; Kelly, Jennifer A; Bae, Sang-Cheol; Alarcón, Graciela S; Anaya, Juan-Manuel; Criswell, Lindsey A; Freedman, Barry I; Kamen, Diane L; Gilkeson, Gary S; Jacob, Chaim O; James, Judith A; Merrill, Joan T; Gaffney, Patrick M; Sivils, Kathy Moser; Niewold, Timothy B; Petri, Michelle A; Song, Seung Taek; Jeong, Hye-Jin; Ramsey-Goldman, Rosalind; Reveille, John D; Scofield, R Hal; Stevens, Anne M; Boackle, Susan A; Vilá, Luis M; Chang, Deh-Ming; Song, Yeong Wook; Vyse, Timothy J; Harley, John B; Brown, Elizabeth E; Edberg, Jeffrey C; Kimberly, Robert P; Hahn, Bevra H; Grossman, Jennifer M; Tsao, Betty P; La Cava, Antonio

    2015-12-01

    Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE. PMID:26385092

  4. Correlation between survivin genetic polymorphisms and lung cancer susceptibility

    PubMed Central

    Guo, Guifang; Zhang, Qiang; Yu, Zhengang; Li, Junjuan; Ding, Zhaolei; Li, Juan; Tan, Wei

    2015-01-01

    Aims: The purpose of the study was to analyze the relationship of survivin polymorphisms including -31G/C, -625G/C, 9194A/G and 9809T/C with the susceptibility to lung cancer. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the polymorphisms of -31G/C, -625G/C, 9194A/G and 9809T/C in 104 patients with lung cancer and 104 healthy controls. Then, linkage disequilibrium and haplotypes were analyzed by HaploView software. The differences of genotype, allele and haplotype frequencies in case and control group were assessed via chi-square test. Odds ratio (OR) with 95% CI were used to evaluate the correlation of survivin polymorphisms with lung cancer. Results: Genotype distribution of each polymorphism site in control group was in agreement with Hardy-Weinberg equilibrium (HWE) (P>0.05). The frequency of -31G/C CC genotype and C allele in case group were much higher than that of controls, respectively (CC: 33.6% vs. 22.1%; C: 57.2% vs. 46.6%) and CC genotype as well as C allele were appeared to be risk factors for lung cancer. Meanwhile, 9194A/G GG genotype could increase the risk for lung cancer (OR=2.86, 95% CI=1.14-7.20). The risk of G allele carriers for lung caner was higher than that of A allele (OR=1.63, 95% CI=1.08-2.47). The haplotypes analysis indicated that CGGC and GCAT were associated with the susceptibility to lung cancer (OR=2.79, 95% CI=1.58-4.92; OR=2.36, 95% CI=1.29-4.30). Conclusions: Survivin -31G/C and 9194A/G polymorphisms were associated with the risk of lung cancer. The CGGC and GCAT haplotypes carriers were more likely to develop lung cancer. PMID:26261647

  5. The application and performance of single nucleotide polymorphism markers for population genetic analyses of Lepidoptera

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single nucleotide polymorphisms (SNPs) are nucleotide substitution mutations that tend to be at high densities within eukaryotic genomes. The development of assays that detect allelic variation at SNP loci is attractive for genome mapping, population genetics, and phylogeographic applications. A p...

  6. RNA replication kinetics, genetic polymorphism and selection in the case of the hepatitis C virus

    E-print Network

    RNA replication kinetics, genetic polymorphism and selection in the case of the hepatitis C virus theoretical quasispecies model that the replication dynamics of hepatitis C virus and a related model et al. 1998), the hepatitis C virus (HCV) has been the most thoroughly screened human virus

  7. Genetic Diversity of Eurycoma longifolia Inferred from Single Nucleotide Polymorphisms1[w

    E-print Network

    Sinskey, Anthony J.

    Genetic Diversity of Eurycoma longifolia Inferred from Single Nucleotide Polymorphisms1[w] Asiah, Anthony J. Sinskey, ChoKyun Rha*, and David E. Housman Malaysia-MIT Biotechnology Partnership Programme (A.E.H.), Department of Biology (P.A.L., A.J.S.), and Biomaterials Science and Engineering Laboratory (C

  8. Color Polymorphism and Genetic Structure in the Sea Star Pisaster ochraceus

    E-print Network

    Grosberg, Rick

    Color Polymorphism and Genetic Structure in the Sea Star Pisaster ochraceus C. D. G. HARLEY,1 of Zoology, Seattle, Washington 98105 Abstract. The sea star Pisaster ochraceus is one of the more striking, 1974; Tarjuelo et al., 2004). The sea star Pisaster ochraceus (Brandt, 1835) is a sig- nificant

  9. Genetic polymorphism of LDLR (rs688) is associated with primary intracerebral hemorrhage.

    PubMed

    Lee, Jiann-Der; Hsiao, Kuang-Ming; Lee, Tsong-Hai; Kuo, Ya-Wen; Huang, Yen-Chu; Hsu, Huan-Lin; Lin, Ya-Hui; Wu, Chih-Ying; Huang, Ying-Chih; Lee, Meng; Yang, Hsin-Ta; Hsu, Chia-Yu; Pan, Yi-Ting

    2014-02-01

    Intracranial hemorrhage is the third most common cause of cerebrovascular disease. Some polymorphisms that affect clotting factors increase the risk of thrombosis. However, few reports have analyzed the effect of polymorphisms on the hemostatic state in bleeding disorders. The low-density lipoprotein receptor (LDLR) has been shown to contribute to factor VIII (FVIII) homeostasis, which represents a link between LDLR and hemostasis. FVIII plays a pivotal role in the coagulation cascade. Patients with high levels of FVIII are at an increased risk of arterial and venous thrombosis. On the other hand, patients with insufficient FVIII tend to bleed excessively, such as in hemophilia A. In a previous study, analysis of the genetic LDLR variant rs688 provided evidence suggesting that genetic polymorphisms of rs688 are associated with thrombotic cardiovascular diseases. The current study aimed to investigate the potential role of rs688 in primary intracerebral hemorrhage (PICH). This genetic association study was conducted within an isolated Taiwanese population (447 PICH patients and 430 controls). Genotypes C/C and C/T were used as the reference genotypes, and the genotype T/T was found to be associated with a 73% decreased risk of PICH. The preliminary evidence suggests that genetic polymorphisms of LDLR are associated with PICH. PMID:24295502

  10. [Genetic polymorphisms: implications in the pathogenesis of medullary thyroid carcinoma].

    PubMed

    Rocha, Andreia Possatti da; Magalhães, Patrícia K Ribeiro; Maia, Ana Luiza; Maciel, Lea Maria Zanini

    2007-07-01

    Medullary thyroid carcinoma (MTC) is a rare malignant neoplasia, which may occur on sporadic form or on a hereditary basis. Germ line mutations in the RET proto-oncogene is responsible for hereditary MTC. However, most MTC occur in individuals without family history where the pathogenesis is still unclear. Single nucleotide polymorphisms (SNPs) of the RET gene have been described in the general population as well as in patients with MTC. Even though these allelic variants do not seem to confer any transforming activity to the tyrosine kinase domain of the RET protein, cumulative studies suggest that they could modify disease susceptibility and clinical phenotype in patients with sporadic or hereditary MTC. Polymorphisms located in exons 11 (G691S), 13 (L769L), 14 (S836S), and 15 (S904S) seem to be over-represented in sporadic MTC patients from American and European countries. Here, we discuss the results obtained in different studies as well as describe the frequency of RET polymorphisms in Brazilian patients with sporadic MTC. PMID:17891235

  11. Development and characterization of highly polymorphic long TC repeat microsatellite markers for genetic analysis of peanut

    PubMed Central

    2012-01-01

    Background Peanut (Arachis hypogaea L.) is a crop of economic and social importance, mainly in tropical areas, and developing countries. Its molecular breeding has been hindered by a shortage of polymorphic genetic markers due to a very narrow genetic base. Microsatellites (SSRs) are markers of choice in peanut because they are co-dominant, highly transferrable between species and easily applicable in the allotetraploid genome. In spite of substantial effort over the last few years by a number of research groups, the number of SSRs that are polymorphic for A. hypogaea is still limiting for routine application, creating the demand for the discovery of more markers polymorphic within cultivated germplasm. Findings A plasmid genomic library enriched for TC/AG repeats was constructed and 1401 clones sequenced. From the sequences obtained 146 primer pairs flanking mostly TC microsatellites were developed. The average number of repeat motifs amplified was 23. These 146 markers were characterized on 22 genotypes of cultivated peanut. In total 78 of the markers were polymorphic within cultivated germplasm. Most of those 78 markers were highly informative with an average of 5.4 alleles per locus being amplified. Average gene diversity index (GD) was 0.6, and 66 markers showed a GD of more than 0.5. Genetic relationship analysis was performed and corroborated the current taxonomical classification of A. hypogaea subspecies and varieties. Conclusions The microsatellite markers described here are a useful resource for genetics and genomics in Arachis. In particular, the 66 markers that are highly polymorphic in cultivated peanut are a significant step towards routine genetic mapping and marker-assisted selection for the crop. PMID:22305491

  12. Footprints of ancient-balanced polymorphisms in genetic variation data from closely related species

    PubMed Central

    Gao, Ziyue; Przeworski, Molly; Sella, Guy

    2015-01-01

    When long-lasting, balancing selection can lead to “trans-species” polymorphisms that are shared by two or more species identical by descent. In such cases, the gene genealogy at the selected site clusters by allele instead of by species, and nearby neutral sites also have unusual genealogies because of linkage. While this scenario is expected to leave discernible footprints in genetic variation data, the specific patterns remain poorly characterized. Motivated by recent findings in primates, we focus on the case of a biallelic polymorphism under ancient balancing selection and derive approximations for summaries of the polymorphism data from two species. Specifically, we characterize the length of the segment that carries most of the footprints, the expected number of shared neutral single nucleotide polymorphisms (SNPs), and the patterns of allelic associations among them. We confirm the accuracy of our approximations by coalescent simulations. We further show that for humans and chimpanzees—more generally, for pairs of species with low genetic diversity levels—these patterns are highly unlikely to be generated by neutral recurrent mutations. We discuss the implications for the design and interpretation of genome scans for ancient balanced polymorphisms in primates and other taxa. PMID:25403856

  13. Footprints of ancient-balanced polymorphisms in genetic variation data from closely related species.

    PubMed

    Gao, Ziyue; Przeworski, Molly; Sella, Guy

    2015-02-01

    When long-lasting, balancing selection can lead to "trans-species" polymorphisms that are shared by two or more species identical by descent. In such cases, the gene genealogy at the selected site clusters by allele instead of by species, and nearby neutral sites also have unusual genealogies because of linkage. While this scenario is expected to leave discernible footprints in genetic variation data, the specific patterns remain poorly characterized. Motivated by recent findings in primates, we focus on the case of a biallelic polymorphism under ancient balancing selection and derive approximations for summaries of the polymorphism data from two species. Specifically, we characterize the length of the segment that carries most of the footprints, the expected number of shared neutral single nucleotide polymorphisms (SNPs), and the patterns of allelic associations among them. We confirm the accuracy of our approximations by coalescent simulations. We further show that for humans and chimpanzees-more generally, for pairs of species with low genetic diversity levels-these patterns are highly unlikely to be generated by neutral recurrent mutations. We discuss the implications for the design and interpretation of genome scans for ancient balanced polymorphisms in primates and other taxa. PMID:25403856

  14. Effect of CYP1A1 and GSTM1 genetic polymorphisms on bone tumor susceptibility.

    PubMed

    Li, L; Li, J G; Liu, C Y; Ding, Y J

    2015-01-01

    Tumor gene polymorphisms are often associated with individual susceptibility to genetic diseases. Cytochrome P4501A1 (CYP1A1) and glutathione S-transferase mu 1 (GSTM1) gene polymorphisms are closely related to the susceptibility of the body to chemical carcinogens in the environment. Therefore, we explored the relationship between CYP1A1 and GSTM1 gene polymorphisms and susceptibility to bone tumors. Multiplex-polymerase chain reaction (PCR), allelic-specific PCR, and PCR-restriction fragment length polymorphism techniques were used to analyze CYP1A1 and GSTM1 gene polymorphisms in 52 bone tumor patients and 100 healthy subjects. The allelic variation frequency of the CYP1A1 gene at exon 7 (Ile 462 Val) in bone tumor patients was 0.462, which was significantly higher than that in the normal controls (0.223). The frequency of the absence of the GSTM1 homozygous genotype in the patients (0.65) was also markedly higher than that in the control group (0.41). Subjects with CYP1A1 Val/Val homozygous mutations and absence of the GSTM1 homozygous genotype were at markedly increased risk of developing bone tumors [ORs 4.15 (95%CI: 1.268-13.30) and 2.35 (95%CI: 1.15-4.85), respectively]. The OR for the combined effect of the CYP1A1 and GSTM1 gene polymorphisms was 8.55 (95%CI: 1.75-41.50). CYP1A1 and GSTM1 polymorphisms are genetic risk factors in patients with bone tumors, and the allelic variation of these genes increases the risk of bone tumor occurrence. PMID:26681006

  15. Association between interleukin-22 genetic polymorphisms and bladder cancer risk

    PubMed Central

    Zhao, Tao; Wu, XiaoHou; Liu, JiaJi

    2015-01-01

    OBJECTIVE: The cytokine interleukin-22 (IL-22), which is produced by T cells and natural killer cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in bladder cancer has not been investigated. MATERIALS AND METHODS: A prospective hospital-based case-control study comprising 210 patients with pathologically proven bladder cancer and 210 age- and gender-matched healthy controls was conducted. The genotypes of 3 common polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) of the IL-22 gene were determined with fluorogenic 5' exonuclease assays. RESULTS: Patients with bladder cancer had a significantly higher frequency of the IL-22 -429 TT genotype [odds ratio (OR)=2.04, 95% confidence interval (CI)=1.19, 3.49; p=0.009] and -429 T allele (OR=1.42, 95% CI=1.08, 1.87; p=0.01) than the healthy controls. These findings were still significant after a Bonferroni correction. When stratifying according to the stage of bladder cancer, we found that patients with superficial bladder cancer had a significantly lower frequency of the IL-22 -429 TT genotype (OR=0.48, 95% CI=0.23, 0.98; p=0.04). When stratifying according to the grade and histological type of bladder cancer, we found no statistical association. The IL-22 +1046 T/A and IL-22 +1995 A/C gene polymorphisms were not associated with the risk of bladder cancer. CONCLUSION: To the authors' knowledge, this is the first report documenting that the IL-22 -429 C/T gene polymorphism is associated with bladder cancer risk. Additional studies are required to confirm this finding. PMID:26598081

  16. USF-1 genetic polymorphisms confer a high risk of nonalcoholic fatty liver disease in Chinese population

    PubMed Central

    Wang, Ying; Wang, Bai-Fang; Tong, Jing; Chang, Bing; Wang, Bing-Yuan

    2015-01-01

    Genetic polymorphisms in upstream transcription factor 1 (USF1) were investigated for their links to increased risk of nonalcoholic fatty liver disease (NAFLD) in Chinese population. Between January 2013 and April 2014, 174 patients with NAFLD in the First Affiliated Hospital of China Medical University were selected for this study. A group of 100 healthy subjects were identified as the control group. The MALDI-TOF-MS, a mass spectrometry based technique, was used to detect USF-1 genetic polymorphisms using PCR amplified DNA products. Furthermore, Automatic Chemistry Analyzer (ACA) was used to determine the clinical indicators. Genotypes, allele frequencies and clinical indicators were measured to assess NAFLD risk in relation to the SNPs. USF-1 rs6427573 genetic polymorphisms were associated with an increased risk of NAFLD (AA vs. GG: OR = 3.16, 95% CI = 1.56-6.43, P = 0.001; GA + AA vs. GG: OR = 1.87, 95% CI = 1.13-3.09, P = 0.015; GG + AA vs. AA: OR = 2.96, 95% CI = 1.49-5.88, P = 0.001; G vs. A: OR = 2.10, 95% CI = 1.43-3.09, P < 0.001). Similarly, rs2516839 polymorphisms also conferred a risk for NAFLD (AA vs. GG: OR = 2.49, 95% CI = 1.43-4.34, P = 0.001; GA + AA vs. GG: OR = 1.69, 95% CI = 1.02-2.78, P = 0.041). On the other hand, rs3737787 and rs2774279 showed no statistical significances in the NAFLD group and control group (P > 0.05). Two USF-1 genetic polymorphisms, rs6427573 and rs2516839, may present an increased risk of NAFLD. PMID:25932200

  17. Genetic association of apolipoprotein E polymorphisms with inflammatory bowel disease

    PubMed Central

    Al-Meghaiseeb, Ebtissam Saleh; Al-Otaibi, Mulfi Mubarak; Al-Robayan, Abdulrahman; Al-Amro, Reem; Al-Malki, Ahmd Saad; Arfin, Misbahul; Al-Asmari, Abdulrahman K

    2015-01-01

    AIM: To study the association of apolipoprotein E (APOE) polymorphisms with the susceptibility of inflammatory bowel disease (IBD) in Saudi patients. METHODS: APOE genotyping was performed to evaluate the allele and genotype frequencies in 378 Saudi subjects including IBD patients with ulcerative colitis (n = 84) or Crohn’s disease (n = 94) and matched controls (n = 200) using polymerase chain reaction and reverse-hybridization techniques. RESULTS: The frequencies of the APOE ?2 allele and ?2/?3 and ?2/?4 genotypes were significantly higher in IBD patients than in controls (P < 0.05), suggesting that the ?2 allele and its heterozygous genotypes may increase the susceptibility to IBD. On the contrary, the frequencies of the ?3 allele and ?3/?3 genotype were lower in IBD patients as compared to controls, suggesting a protective effect of APOE ?3 for IBD. The prevalence of the ?4 allele was also higher in the patient group compared to controls, suggesting that the ?4 allele may also increase the risk of IBD. Our results also indicated that the APOE ?4 allele was associated with an early age of IBD onset. No effect of gender or type of IBD (familial or sporadic) on the frequency distribution of APOE alleles and genotypes was noticed in this study. CONCLUSION: APOE polymorphism is associated with risk of developing IBD and early age of onset in Saudi patients, though further studies with a large-size population are warranted. PMID:25624723

  18. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

    PubMed Central

    Sterpone, Silvia; Cozzi, Renata

    2010-01-01

    It is well known that ionizing radiation (IR) can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs) of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER). In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer. PMID:20798883

  19. Genetic predisposition to essential hypertension in children: analysis of 17 single nucleotide polymorphisms.

    PubMed

    Goncharov, S V; Gurianova, V L; Stroy, D O; Drevytska, T I; Kaplinskii, S P; Nastenko, E A; Litvinenko, M; Terletskiy, R V; Khaitovych, M V; Moibenko, O O; Dosenko, V E

    2013-01-01

    Study of 17 single nucleotide polymorphisms has been performed to determine the factors of genetic predisposition to essential hypertension. Polymerase chain reaction (PCR) with subsequent analysis of restriction fragment length, allele specific PCR or real-time PCR was used for genotyping of 17 single nucleotide polymorphisms in 14 genes in 145 children with essential hypertension and 144 healthy persons with following complex multivariate statistical analysis. Two single nucleotide polymorphisms--MMP9 (C(-1562) --> T) and NOS3 (Glu298 --> Asp)--rs3918242 and rs1799983--were shown to represent the main independent effects with the highest predictive potential (77.1% as indicated by binary logistic regression and 74.6% testing accuracy shown by Multifactorial Dimensionality Reduction). MMP9 (C(-1562 --> T) and NOS3 (Glu298 --> Asp) potentially may be used to create predictive algorithm for determination of predisposition to arterial hypertension in children. PMID:24605586

  20. Genetic Polymorphism in Extracellular Regulators of Wnt Signaling Pathway

    PubMed Central

    Sharma, Ashish Ranjan; Seo, Eun-Min; Nam, Ju-Suk

    2015-01-01

    The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively. PMID:25945348

  1. Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population.

    PubMed

    Yan, Xiaojuan; Yang, Feng; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Ma, Kezhong; Li, Yi; Zhu, Jun; Ding, Jianqiang

    2015-01-01

    BACKGROUND VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1-1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. MATERIAL AND METHODS A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1-1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. RESULTS Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1-1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1-1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05). CONCLUSIONS VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose. PMID:26583785

  2. Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population

    PubMed Central

    Yan, Xiaojuan; Yang, Feng; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Ma, Kezhong; Li, Yi; Zhu, Jun; Ding, Jianqiang

    2015-01-01

    Background VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1–1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. Material/Methods A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1–1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. Results Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1–1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1–1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05). Conclusions VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose. PMID:26583785

  3. Genetic polymorphisms associated with breast cancer in malaysian cohort.

    PubMed

    Chahil, Jagdish Kaur; Munretnam, Khamsigan; Samsudin, Nurulhafizah; Lye, Say Hean; Hashim, Nikman Adli Nor; Ramzi, Nurul Hanis; Velapasamy, Sharmila; Wee, Ler Lian; Alex, Livy

    2015-04-01

    Genome-wide association studies have discovered multiple single nucleotide polymorphisms (SNPs) associated with the risk of common diseases. The objective of this study was to demonstrate the replication of previously published SNPs that showed statistical significance for breast cancer in the Malaysian population. In this case-control study, 80 subjects for each group were recruited from various hospitals in Malaysia. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. A total of three SNPs were found to be associated with increased risk of breast cancer while six SNPs showed protective effect. All nine were statistically significant SNPs (p ? 0.01), five SNPs from previous studies were successfully replicated in our study. Significant modifiable (diet) and non-modifiable (family history of breast cancer in first degree relative) risk factors were also observed. We identified nine SNPs from this study to be either conferring susceptibility or protection to breast cancer which may serve as potential markers in risk prediction. PMID:25883419

  4. The Roles of Genetic Polymorphisms and Human Immunodeficiency Virus Infection in Lipid Metabolism

    PubMed Central

    de Almeida, Elaine Regina Delicato; Reiche, Edna Maria Vissoci; Flauzino, Tamires; Watanabe, Maria Angelica Ehara

    2013-01-01

    Dyslipidemia has been frequently observed among individuals infected with human immunodeficiency virus type 1 (HIV-1), and factors related to HIV-1, the host, and antiretroviral therapy (ART) are involved in this phenomenon. This study reviews the roles of genetic polymorphisms, HIV-1 infection, and highly active antiretroviral therapy (HAART) in lipid metabolism. Lipid abnormalities can vary according to the HAART regimen, such as those with protease inhibitors (PIs). However, genetic factors may also be involved in dyslipidemia because not all patients receiving the same HAART regimen and with comparable demographic, virological, and immunological characteristics develop variations in the lipid profile. Polymorphisms in a large number of genes are involved in the synthesis of structural proteins, and enzymes related to lipid metabolism account for variations in the lipid profile of each individual. As some genetic polymorphisms may cause dyslipidemia, these allele variants should be investigated in HIV-1-infected patients to identify individuals with an increased risk of developing dyslipidemia during treatment with HAART, particularly during therapy with PIs. This knowledge may guide individualized treatment decisions and lead to the development of new therapeutic targets for the treatment of dyslipidemia in these patients. PMID:24319689

  5. Lack of genetic polymorphism among peregrine falcons Falco peregrinus of Fiji

    USGS Publications Warehouse

    Talbot, Sandra; Palmer, A.G.; Sage, G.K.; Sonsthagen, Sarah A.; Swem, T.; Brimm, D.J.

    2014-01-01

    We compared levels of genetic diversity and isolation among peregrine falcons Falco peregrinus from two South Pacific island complexes (Fiji and Vanuatu: F. p. nesiotes), relative to other island and mainland populations. Fragment data from 12 microsatellite loci and sequence information from the control region of the mitochondrial DNA indicated levels of genetic variation in the South Pacific populations were lower than other island and mainland populations. Indeed, diversity varied from extremely low (Vanuatu) to completely absent (Fiji). We find little support for a hypothesis that populations on Fiji or Vanuatu were colonized via Australia. The complete lack of polymorphism in peregrine falcons of Fiji is remarkable, and to our knowledge has not been observed in a natural avian population. This lack of polymorphism, and the inability to test for decrease in polymorphism using museum samples, precludes testing whether the lack of genetic diversity in the population on Fiji is due to a recent bottleneck, or sustained isolation over evolutionary time. Increased fertility in eggs of Fiji peregrines upon outbreeding with males from other areas is consistent with inbreeding depression within a population typified by heterozygote deficiency.

  6. Lack of genetic polymorphism among peregrine falcons Falco peregrinus of Fiji

    USGS Publications Warehouse

    Talbot, S.L.; Palmer, A.G.; Sage, G.K.; Sonsthagen, S.A.; Swem, T.; Brimm, D.J.; White, C.M.

    2011-01-01

    We compared levels of genetic diversity and isolation among peregrine falcons Falco peregrinus from two South Pacific island complexes (Fiji and Vanuatu: F. p. nesiotes), relative to other island and mainland populations. Fragment data from 12 microsatellite loci and sequence information from the control region of the mitochondrial DNA indicated levels of genetic variation in the South Pacific populations were lower than other island and mainland populations. Indeed, diversity varied from extremely low (Vanuatu) to completely absent (Fiji). We find little support for a hypothesis that populations on Fiji or Vanuatu were colonized via Australia. The complete lack of polymorphism in peregrine falcons of Fiji is remarkable, and to our knowledge has not been observed in a natural avian population. This lack of polymorphism, and the inability to test for decrease in polymorphism using museum samples, precludes testing whether the lack of genetic diversity in the population on Fiji is due to a recent bottleneck, or sustained isolation over evolutionary time. Increased fertility in eggs of Fiji peregrines upon outbreeding with males from other areas is consistent with inbreeding depression within a population typified by heterozygote deficiency. ?? 2011 The Authors.

  7. Relationship between genetic polymorphism of cytochrome P450IIE1 and fatty liver

    PubMed Central

    Piao, Yun-Feng; Li, Jing-Tao; Shi, Yang

    2003-01-01

    AIM: To study the correlation between genetic polymorphism of cytochrome P450IIE1 (CYPIIE1) and fatty liver. METHODS: Peripheral blood mononuclear cells were collected in 56 patients with fatty liver, 26 patients without fatty liver and 20 normal controls. Then PCR-RFLP was used to analyze genetic polymorphism of CYPIIE1 in monocytes on the region of Pst I and Rsa I. RESULTS: The frequency of homozygotic C1 gene in patients with alcoholic fatty liver (28.6%), obese fatty liver (38.5%), or diabetic fatty liver (33.3%) was significantly lower than that of the corresponding patients without fatty liver (100%, 100% and 80% respectively), while the frequency of C2 genes, including C1/C2 and C2/C2, was significantly higher (71.4%/0%, 61.5%/0%, and 66.7%/20%) (P < 0.01). The frequency distribution of the above genes of non-fatty liver patients (100%/0, 100%/0, and 80%/20%) was not significantly different from that of the normal controls (85%/15%) (P > 0.05). CONCLUSION: The genetic polymorphism of CYPIIE1 on the position of Pst I and Rsa I is related to the susceptibility of fatty liver. Besides, C2 gene may play a key role in the pathogenesis of fatty liver. PMID:14606109

  8. Interleukin-18 genetic polymorphisms contribute differentially to the susceptibility to Crohn’s disease

    PubMed Central

    Gao, Su-Jun; Zhang, Li; Lu, Wei; Wang, Lu; Chen, Lei; Zhu, Zhen; Zhu, Hai-Hang

    2015-01-01

    AIM: To investigate the correlation between interleukin-18 (IL-18) gene polymorphisms and the risk of developing Crohn’s disease (CD). METHODS: The PubMed, CISCOM, CINAHL, Web of Science, EBSCO, Cochrane Library, MEDLINE, EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1st, 2013. Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis. A meta-analysis was conducted using a random-effects model with STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated. RESULTS: Seven case-control studies, with a total of 1930 CD cases and 1930 healthy subjects, met our inclusion criteria. The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238 G>C polymorphisms may correlate with an increased risk of CD under five genetic models (all P < 0.05). Furthermore, we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models (C allele vs A allele: OR = 2.03, 95%CI: 1.20-3.43, P = 0.008; CC vs AA+AC: OR = 2.39, 95%CI: 1.2-4.43, P = 0.006; CC vs AC: OR = 2.31, 95%CI: 1.22-4.38, P = 0.010). However, such associations were not found for the IL-18 rs917997 C>T, codon 35 A>C and rs1946519 G>T polymorphisms (all P > 0.05). A subgroup analysis was conducted to investigate the effect of ethnicity on an individual’s susceptibility to CD. Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans (all P < 0.05), but not among Caucasians (all P > 0.05). CONCLUSION: This meta-analysis indicated that the IL-18 rs1946518 A>C, rs187238 G>C and rs360718 A>C polymorphisms may contribute to susceptibility to CD, especially among Asians and Africans. These polymorphisms are known to reduce IL-18 mRNA and protein levels. PMID:26229413

  9. Genetic Analysis of 430 Chinese Cynodon dactylon Accessions Using Sequence-Related Amplified Polymorphism Markers

    PubMed Central

    Huang, Chunqiong; Liu, Guodao; Bai, Changjun; Wang, Wenqiang

    2014-01-01

    Although Cynodon dactylon (C. dactylon) is widely distributed in China, information on its genetic diversity within the germplasm pool is limited. The objective of this study was to reveal the genetic variation and relationships of 430 C. dactylon accessions collected from 22 Chinese provinces using sequence-related amplified polymorphism (SRAP) markers. Fifteen primer pairs were used to amplify specific C. dactylon genomic sequences. A total of 481 SRAP fragments were generated, with fragment sizes ranging from 260–1800 base pairs (bp). Genetic similarity coefficients (GSC) among the 430 accessions averaged 0.72 and ranged from 0.53–0.96. Cluster analysis conducted by two methods, namely the unweighted pair-group method with arithmetic averages (UPGMA) and principle coordinate analysis (PCoA), separated the accessions into eight distinct groups. Our findings verify that Chinese C. dactylon germplasms have rich genetic diversity, which is an excellent basis for C. dactylon breeding for new cultivars. PMID:25338051

  10. Polymorphic simple sequence repeat regions in chloroplast genomes: applications to the population genetics of pines.

    PubMed Central

    Powell, W; Morgante, M; McDevitt, R; Vendramin, G G; Rafalski, J A

    1995-01-01

    Simple sequence repeats (SSRs), consisting of tandemly repeated multiple copies of mono-, di-, tri-, or tetranucleotide motifs, are ubiquitous in eukaryotic genomes and are frequently used as genetic markers, taking advantage of their length polymorphism. We have examined the polymorphism of such sequences in the chloroplast genomes of plants, by using a PCR-based assay. GenBank searches identified the presence of several (dA)n.(dT)n mononucleotide stretches in chloroplast genomes. A chloroplast (cp) SSR was identified in three pine species (Pinus contorta, Pinus sylvestris, and Pinus thunbergii) 312 bp upstream of the psbA gene. DNA amplification of this repeated region from 11 pine species identified nine length variants. The polymorphic amplified fragments were isolated and the DNA sequence was determined, confirming that the length polymorphism was caused by variation in the length of the repeated region. In the pines, the chloroplast genome is transmitted through pollen and this PCR assay may be used to monitor gene flow in this genus. Analysis of 305 individuals from seven populations of Pinus leucodermis Ant. revealed the presence of four variants with intrapopulational diversities ranging from 0.000 to 0.629 and an average of 0.320. Restriction fragment length polymorphism analysis of cpDNA on the same populations previously failed to detect any variation. Population subdivision based on cpSSR was higher (Gst = 0.22, where Gst is coefficient of gene differentiation) than that revealed in a previous isozyme study (Gst = 0.05). We anticipate that SSR loci within the chloroplast genome should provide a highly informative assay for the analysis of the genetic structure of plant populations. Images Fig. 2 PMID:7644491

  11. COMT val158met and 5-HTTLPR genetic polymorphisms moderate executive control in cannabis users.

    PubMed

    Verdejo-García, Antonio; Fagundo, Ana Beatriz; Cuenca, Aida; Rodriguez, Joan; Cuyás, Elisabet; Langohr, Klaus; de Sola Llopis, Susana; Civit, Ester; Farré, Magí; Peña-Casanova, Jordi; de la Torre, Rafael

    2013-07-01

    The adverse effects of cannabis use on executive functions are still controversial, fostering the need for novel biomarkers able to unveil individual differences in the cognitive impact of cannabis consumption. Two common genetic polymorphisms have been linked to the neuroadaptive impact of ?9-tetrahydrocannabinol (THC) exposure and to executive functions in animals: the catechol-O-methyltransferase (COMT) gene val158met polymorphism and the SLC6A4 gene 5-HTTLPR polymorphism. We aimed to test if these polymorphisms moderate the harmful effects of cannabis use on executive function in young cannabis users. We recruited 144 participants: 86 cannabis users and 58 non-drug user controls. Both groups were genotyped and matched for genetic makeup, sex, age, education, and IQ. We used a computerized neuropsychological battery to assess different aspects of executive functions: sustained attention (CANTAB Rapid Visual Information Processing Test, RVIP), working memory (N-back), monitoring/shifting (CANTAB ID/ED set shifting), planning (CANTAB Stockings of Cambridge, SOC), and decision-making (Iowa Gambling Task, IGT). We used general linear model-based analyses to test performance differences between cannabis users and controls as a function of genotypes. We found that: (i) daily cannabis use is not associated with executive function deficits; and (ii) COMT val158met and 5-HTTLPR polymorphisms moderate the link between cannabis use and executive performance. Cannabis users carrying the COMT val/val genotype exhibited lower accuracy of sustained attention, associated with a more strict response bias, than val/val non-users. Cannabis users carrying the COMT val allele also committed more monitoring/shifting errors than cannabis users carrying the met/met genotype. Finally, cannabis users carrying the 5-HTTLPR s/s genotype had worse IGT performance than s/s non-users. COMT and SLC6A4 genes moderate the impact of cannabis use on executive functions. PMID:23449176

  12. Relationship between CYP17A1 Genetic Polymorphism and Essential Hypertension in a Chinese Population

    PubMed Central

    Dai, Chuan-Fang; Xie, Xiang; Ma, Yi-Tong; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Liu, Fen; Chen, Bang-Dang; Gai, Min-Tao

    2015-01-01

    The relationship between CYP17A1 genetic polymorphisms and essential hypertension (EH) remains unclear. The aim of this study was to investigate the association of CYP17A1 genetic polymorphisms with EH in Han and Uighur populations in China. A Han population including 558 people (270 EH patients and 288 controls) and a Uighur population including 473 people (181 EH patients and 292 controls) were selected. Five single-nucleotide polymorphisms (SNPs) (rs4919686, rs1004467, rs4919687, rs10786712, and rs2486758) were genotyped using real-time PCR (TaqMan). In the Uighur population, for the total and the men, rs4919686, rs4919687 and rs10786712 were found to be associated with EH (rs4919686: P?0.02, rs4919687: P?0.002, rs10786712: P?0.004, respectively). The difference remained statistically significant after the multivariate adjustment (all P<0.05). The overall distributions of the haplotypes established by SNP1-SNP3, SNP1-SNP4, SNP1-SNP3-SNP5 and SNP1-SNP4-SNP5 were significantly different between the EH patients and the control subjects (for the total: P=0.013, P=0.008, P=0.032, P=0.010, for men: P<0.001, P=0.001, P=0.010, P=0.00). In the Han population, for men, rs2486758 was found to be associated with EH in a recessive model (P=0.007); the significant difference was not retained after the adjustment for the covariates (date not shown). The A allele of rs4919686 could be a susceptible genetic marker, and the T allele of rs10786712 could be a protective genetic marker of EH. The AC genotype of rs4919686, the AG genotype of rs4919687 and the TT genotype of rs10786712 could be protective genetic markers of EH. PMID:26618050

  13. Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

    PubMed Central

    Skjelbred, Camilla F; Sæbø, Mona; Hjartåker, Anette; Grotmol, Tom; Hansteen, Inger-Lise; Tveit, Kjell M; Hoff, Geir; Kure, Elin H

    2007-01-01

    Background The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population. Methods We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls) to test the association between dietary factors (meat versus fruit, berries and vegetables) genetic polymorphisms in biotransformation genes (GSTM1, GSTT1, GSTP1 Ile105Val, EPHX1 Tyr113His and EPHX1 His139Arg), and risk of colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression. Results A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2nd quartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele) of the EPHX1 codon 113 polymorphism. An association was also observed for the EPHX1 codon 113 polymorphism in the low-risk adenomas, although not as obvious. Conclusion Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma. PMID:18093316

  14. Genetic Analysis of Diversity within a Chinese Local Sugarcane Germplasm Based on Start Codon Targeted Polymorphism

    PubMed Central

    Que, Youxiong; Pan, Yongbao; Lu, Yunhai; Yang, Cui; Yang, Yuting; Huang, Ning; Xu, Liping

    2014-01-01

    In-depth information on sugarcane germplasm is the basis for its conservation and utilization. Data on sugarcane molecular markers are limited for the Chinese sugarcane germplasm collections. In the present study, 20 start codon targeted (SCoT) marker primers were designed to assess the genetic diversity among 107 sugarcane accessions within a local sugarcane germplasm collection. These primers amplified 176 DNA fragments, of which 163 were polymorphic (92.85%). Polymorphic information content (PIC) values ranged from 0.783 to 0.907 with a mean of 0.861. Unweighted pair group method of arithmetic averages (UPGMA) cluster analysis of the SCoT marker data divided the 107 sugarcane accessions into six clusters at 0.674 genetic similarity coefficient level. Relatively abundant genetic diversity was observed among ROC22, ROC16, and ROC10, which occupied about 80% of the total sugarcane acreage in China, indicating their potential breeding value on Mainland China. Principal component analysis (PCA) partitioned the 107 sugarcane accessions into two major groups, the Domestic Group and the Foreign Introduction Group. Each group was further divided based on institutions, where the sugarcane accessions were originally developed. The knowledge of genetic diversity among the local sugarcane germplasm provided foundation data for managing sugarcane germplasm, including construction of a core collection and regional variety distribution and subrogation. PMID:24779012

  15. Random Amplified Polymorphic Markers as Indicator for Genetic Conservation Program in Iranian Pheasant (Phasianus colchicus)

    PubMed Central

    Elyasi Zarringhabaie, Ghorban; Javanmard, Arash; Pirahary, Ommolbanin

    2012-01-01

    The objective of present study was identification of genetic similarity between wild Iran and captive Azerbaijan Pheasant using PCR-RAPD markers. For this purpose, in overall, 28 birds were taken for DNA extraction and subsequently 15 arbitrary primers were applied for PCR-RAPD technique. After electrophoresis, five primers exhibited sufficient variability which yielded overall 65 distinct bands, 59 polymorphic bands, for detalis, range of number of bands per primer was 10 to 14, and produced size varied between 200 to 1500?bp. Highest and lowest polymorphic primers were OPC5, OPC16 (100%) and OPC15 (81%), respectively. Result of genetic variation between two groups was accounted as nonsignificant (8.12%) of the overall variation. According to our expectation the wild Iranian birds showed higher genetic diversity value than the Azerbaijan captive birds. As general conclusion, two pheasant populations have almost same genetic origin and probably are subpopulations of one population. The data reported herein could open the opportunity to search for suitable conservation strategy to improve richness of Iran biodiversity and present study here was the first report that might have significant impact on the breeding and conservation program of Iranian pheasant gene pool. Analyses using more regions, more birds, and more DNA markers will be useful to confirm or to reject these findings. PMID:23002388

  16. Genetic Diversity Analysis of Hypsizygus marmoreus with Target Region Amplification Polymorphism

    PubMed Central

    Qiu, Chengshu; Yan, Wenjuan; Deng, Wangqiu; Song, Bin; Li, Taihui

    2014-01-01

    Hypsizygus marmoreus is an industrialized edible mushroom. In the present paper, the genetic diversity among 20 strains collected from different places of China was evaluated by target region amplification polymorphism (TRAP) analysis; the common fragment of TRAPs was sequenced and analyzed. Six fixed primers were designed based on the analysis of H. marmoreus sequences from GenBank database. The genomic DNA extracted from H. marmoreus was amplified with 28 TRAP primer combinations, which generated 287 bands. The average of amplified bands per primer was 10.27 (mean polymorphism is 69.73%). The polymorphism information content (PIC) value for TRAPs ranged from 0.32 to 0.50 (mean PIC value per TRAP primer combination is 0.48), which indicated a medium level of polymorphism among the strains. A total of 36 sequences were obtained from TRAP amplification. Half of these sequences could encode the known or unknown proteins. According to the phylogenetic analysis based on TRAP result, the 20 strains of H. marmoreus were classified into two main groups. PMID:25013861

  17. Genetic polymorphism of APOB is associated with diabetes mellitus in sickle cell disease

    PubMed Central

    Zhang, Xu; Zhang, Wei; Saraf, Santosh L.; Nouraie, Mehdi; Han, Jin; Gowhari, Michel; Hassan, Johara; Miasnikova, Galina; Sergueeva, Adelina; Nekhai, Sergei; Kittles, Rick; Machado, Roberto F.; Garcia, Joe G N; Gladwin, Mark T.; Steinberg, Martin H.; Sebastiani, Paola; McClain, Donald A.; Gordeuk, Victor R.

    2015-01-01

    Environmental variations have strong influences in the etiology of type 2 diabetes mellitus. In this study, we investigated the genetic basis of diabetes in patients with sickle cell disease (SCD), a Mendelian disorder accompanied by distinct physiological conditions of hypoxia and hyperactive erythropoiesis. Compared to the general African-American population, the prevalence of diabetes as assessed in two SCD cohorts of 856 adults was low, but it markedly increased with older age and overweight. Meta-analyses of over 5 million single nucleotide polymorphisms (SNPs) in the two SCD cohorts identified a SNP, rs59014890, the C allele of which associated with diabetes risk at P= 3.2×10-8 and, surprisingly, associated with decreased APOB expression in peripheral blood mononuclear cells (PBMCs). The risk allele of the APOB polymorphism was associated with overweight in 181 SCD adolescents, with diabetes risk in 592 overweight, non-SCD African Americans ?45 years of age, and with elevated plasma lipid concentrations in general populations. In addition, lower expression level of APOB in PBMCs was associated with higher values for percent hemoglobin A1C and serum total cholesterol and triglyceride concentrations in patients with Chuvash polycythemia, a congenital disease with elevated hypoxic responses and increased erythropoiesis at normoxia. Our study reveals a novel, environment-specific genetic polymorphism that may affect key metabolic pathways contributing to diabetes in SCD. PMID:26025476

  18. Genetic polymorphism of APOB is associated with diabetes mellitus in sickle cell disease.

    PubMed

    Zhang, Xu; Zhang, Wei; Saraf, Santosh L; Nouraie, Mehdi; Han, Jin; Gowhari, Michel; Hassan, Johara; Miasnikova, Galina; Sergueeva, Adelina; Nekhai, Sergei; Kittles, Rick; Machado, Roberto F; Garcia, Joe G N; Gladwin, Mark T; Steinberg, Martin H; Sebastiani, Paola; McClain, Donald A; Gordeuk, Victor R

    2015-08-01

    Environmental variations have strong influences in the etiology of type 2 diabetes mellitus. In this study, we investigated the genetic basis of diabetes in patients with sickle cell disease (SCD), a Mendelian disorder accompanied by distinct physiological conditions of hypoxia and hyperactive erythropoiesis. Compared to the general African American population, the prevalence of diabetes as assessed in two SCD cohorts of 856 adults was low, but it markedly increased with older age and overweight. Meta-analyses of over 5 million single-nucleotide polymorphisms (SNPs) in the two SCD cohorts identified a SNP, rs59014890, the C allele of which associated with diabetes risk at P = 3.2 × 10(-8) and, surprisingly, associated with decreased APOB expression in peripheral blood mononuclear cells (PBMCs). The risk allele of the APOB polymorphism was associated with overweight in 181 SCD adolescents, with diabetes risk in 592 overweight, non-SCD African Americans ? 45 years of age, and with elevated plasma lipid concentrations in general populations. In addition, lower expression level of APOB in PBMCs was associated with higher values for percent hemoglobin A1C and serum total cholesterol and triglyceride concentrations in patients with Chuvash polycythemia, a congenital disease with elevated hypoxic responses and increased erythropoiesis at normoxia. Our study reveals a novel, environment-specific genetic polymorphism that may affect key metabolic pathways contributing to diabetes in SCD. PMID:26025476

  19. Color polymorphism and genetic structure in the sea star Pisaster ochraceus.

    PubMed

    Harley, C D G; Pankey, M S; Wares, J P; Grosberg, R K; Wonham, M J

    2006-12-01

    The sea star Pisaster ochraceus is one of the more striking species on the rocky shores of the Northeast Pacific, in part due to the dramatic color polymorphism of the adults. Along the open Pacific coast, Pisaster populations are 6%-28% orange, with a small percentage of brilliant purple stars and a large percentage of reddish-brown to dull purple ones. However, populations in the San Juan Island Archipelago (Washington, USA) and the southern Strait of Georgia (British Columbia, Canada) are almost entirely brilliant purple. The factors that maintain the color polymorphism, and those that contribute to among-site variation in color frequencies, remain unknown. We examined the relationships between color frequencies and several ecological and morphological variables, and conducted a large-scale phylogeographic survey of Pisaster populations. We found very low population genetic structure, suggesting that gene flow is high and geographic variation in color frequencies is not a vestige of Pleistocene glacial refugia. Color frequencies are also unrelated to adult size and to the frequency of injury within a population. However, there are suggestive relationships between color frequency and diet, and with areas of potentially low salinity. We propose that, although the color polymorphism may have an underlying genetic component, the regional-scale variation in color frequency is ecologically controlled. PMID:17179384

  20. The Application and Performance of Single Nucleotide Polymorphism Markers for Population Genetic Analyses of Lepidoptera

    PubMed Central

    Coates, Brad Steven; Bayles, Darrell O.; Wanner, Kevin W.; Robertson, Hugh M.; Hellmich, Richard L.; Sappington, Thomas W.

    2011-01-01

    Microsatellite markers are difficult to apply within lepidopteran studies due to the lack of locus-specific PCR amplification and the high proportion of “null” alleles, such that erroneous estimations of population genetic parameters often result. Herein single nucleotide polymorphism (SNP) markers are developed from Ostrinia nubilalis (Lepidoptera: Crambidae) using next generation expressed sequence tag (EST) data. A total of 2742 SNPs were predicted within a reference assembly of 7414 EST contigs, and a subset of 763 were incorporated into 24 multiplex PCR reactions. To validate this pipeline, 5 European and North American sample sites were genotyped at 178 SNP loci, which indicated 84 (47.2%) were in Hardy–Weinberg equilibrium. Locus-by-locus FST, analysis of molecular variance, and STRUCTURE analyses indicate significant genetic differentiation may exist between European and North American O. nubilalis. The observed genetic diversity was significantly lower among European sites, which may result from genetic drift, natural selection, a genetic bottleneck, or ascertainment bias due to North American origin of EST sequence data. SNPs are an abundant source of mutation data for molecular genetic marker development in non-model species, with shared ancestral SNPs showing application within closely related species. These markers offer advantages over microsatellite markers for genetic and genomic analyses of Lepidoptera, but the source of mutation data may affect the estimation of population parameters and likely need to be considered in the interpretation of empirical data. PMID:22303334

  1. A worldwide population study of the Ag-system haplotypes, a genetic polymorphism of human low-density lipoprotein.

    PubMed Central

    Breguet, G; Bütler, R; Bütler-Brunner, E; Sanchez-Mazas, A

    1990-01-01

    The aim of this investigation is to examine the distribution of the Ag immunological polymorphism in human populations on a worldwide scale and to look for possible explanations of this distribution in the field of modern human peopling history and Ag-system evolution. Extensive Ag-antigene typings were carried out on 13 human population samples, including sub-Saharan African, European, west and east Asiatic, Melanesian, Australian aborigine, and Amerindian groups. Complete Ag-haplotype frequencies were estimated by maximum-likelihood-score procedures, and the data were analyzed by genetic distance computations and principal coordinate projections. With the exception of the Amerindian sample, the Ag polymorphism is shown to be highly polymorphic in all the populations tested. Their genetic relationships appear to be closely correlated to their geographical distribution. This suggests that the Ag system has evolved as a neutral or nearly neutral polymorphism and that it is highly informative for modern human peopling history studies. From the worldwide Ag haplotypic distributions, a model for the Ag molecular structure is derived. According to this model and to the most recent results obtained from molecular data, the establishment of the Ag polymorphism could be explained by several mutations and recombination events between the haplotypes most frequently found in human populations today. As a conclusion, genetic and paleontological data suggest that the genetic structure of caucasoid populations (located from North Africa to India) may be the least differentiated from an ancestral genetic stock. Worldwide genetic differentiations are properly explained as the results of westward and eastward human migrations from a Near East-centered but undefined geographical area where modern humans may have originated. The importance of Ag polymorphism analyses for the reconstruction of human settlement history and origins is discussed in the light of the main conclusions of the most recent genetic polymorphism studies. PMID:1689953

  2. Comparison of Randomly Amplified Polymorphic DNA with Amplified Fragment Length Polymorphism To Assess Genetic Diversity and Genetic Relatedness within Genospecies III of Pseudomonas syringae

    PubMed Central

    Clerc, Agathe; Manceau, Charles; Nesme, Xavier

    1998-01-01

    Recently, DNA pairing analyses showed that Pseudomonas syringae pv. tomato and related pathovars, including P. syringae pv. maculicola, form a genomic species (Pseudomonas tomato) (L. Gardan, H. L. Shafik, and P. A. D. Grimont, p. 445–448, in K. Rudolph, T. J. Burr, J. W. Mansfield, D. Stead, A. Vivian, and J. von Kietzell, ed., Pseudomonas syringae Pathovars and Related Pathogens, 1997). The genetic diversity of 23 strains belonging to this genomic species and 4 outgroup strains was analyzed with randomly amplified polymorphic DNA (RAPD) and amplified fragment length polymorphic (AFLP) techniques. Simple boiling of P. syringae cells was suitable for subsequent DNA amplification to obtain reliable patterns in RAPD and AFLP analyses. In general, the grouping of P. syringae strains by both analysis techniques corresponded well with the classification obtained from an RFLP analysis of ribosomal DNA operons, DNA pairing studies, and an analysis of pathogenicity data. However, two strains of P. syringae pv. maculicola produced distinct DNA patterns compared to the DNA patterns of other P. syringae pv. maculicola strains; these patterns led us to assume that horizontal transfer of DNA could occur between bacterial populations. Both techniques used in this study have high discriminating power because strains of P. syringae pv. tomato and P. syringae pv. maculicola which were indistinguishable by other techniques, including pathogenicity tests on tomato, were separated into two groups by both RAPD and AFLP analyses. In addition, data analysis showed that the AFLP method was more efficient for assessing intrapathovar diversity than RAPD analysis and allowed clear delineation between intraspecific and interspecific genetic distances, suggesting that it could be an alternative to DNA pairing studies. However, it was not possible to distinguish the two races of P. syringae pv. tomato on the basis of an analysis of the data provided by either the AFLP or RAPD technique. PMID:16349533

  3. Adaptation to abiotic stress in the oyster Crassostrea angulata relays on genetic polymorphisms.

    PubMed

    Cross, Ismael; Merlo, Manuel A; Rodríguez, María E; Portela-Bens, Silvia; Rebordinos, Laureana

    2014-12-01

    Here we describe the whole genome re-sequencing of the Portuguese oyster Crassostrea angulata, an edible cupped oyster of major commercial importance with an important role as biosensor of coastal water pollution. We sequenced the genome of the C. angulata to 29.3-fold coverage using ABI SOLID system. Comparisons of the sequences with the reference assembly of the Pacific oyster (Crassostrea gigas), yielded 129 million SNPs, 151,620 from which were located in 20,908 genes from the C. gigas database. The analysis of Gene Ontology (GO) terms associated with gene regions containing SNPs, revealed that significant GO terms showing differences between the two oyster species, were related to activities of response to stress caused both by drying and by metal contamination. In the Biological Process domain, the GO terms ion transport, phosphorylation and proteolysis processes, among others, showed many polymorphic genes in C. angulata. These processes are related to combating genotoxic and hypo-osmotic stress in the oyster. It is noteworthy that more than 200 polymorphic genes were associated with DNA repair processes. These results reveal that most of the gene polymorphisms observed in C. angulata are associated with processes related to genome adaptation to abiotic stress in estuarine regions and support that genetic polymorphisms may be the base to the observed ability of C. angulata to retain the phenomenally high concentrations of toxic heavy metals. Our results also provide the framework for future investigations to establish the molecular basis of phenotypic variation of adaptive traits and should contribute to the management of the species' genetic resources. PMID:25462456

  4. Genetic polymorphisms of serum amyloid A1 and coronary artery disease risk.

    PubMed

    Xie, X; Ma, Y-T; Yang, Y-N; Li, X-M; Zheng, Y-Y; Liu, F; Ma, X; Fu, Z-Y; Yu, Z-X; Chen, Y; Chen, B-D; Huang, Y

    2015-03-01

    Serum amyloid A (SAA) protein is not only an inflammatory factor but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein cholesterol (HDL-C). However, the relationship between genetic polymorphisms of SAA and coronary artery disease (CAD) remains unclear. A total of four single nucleotide polymorphisms (rs12218, rs4638289, rs7131332, and rs11603089) of the SAA gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in two independent case-control studies, one of the Han population (1416 CAD patients and 1373 control subjects) and the other of the Uygur population (588 CAD patients and 529 control subjects). We found that the rs12218 CC genotype was more frequent among the CAD patients than among the controls in both the Han (8.3% vs. 4.8%, P?Genetic polymorphisms in SAA1 are associated with CAD in the Han and Uygur populations in western China. PMID:25656165

  5. Genetic Association Between CDKN1B rs2066827 Polymorphism and Susceptibility to Cancer

    PubMed Central

    Lu, Yongchao; Gao, Kejian; Zhang, Miao; Zhou, Aiyan; Zhou, Xiaoming; Guan, Zhongan; Shi, Xuewen; Ge, Shujian

    2015-01-01

    Abstract Much attention has been directed to the association between cancer risk and rs2066827 polymorphism of the CDKN1B gene. However, the results are indefinitive and inconclusive. This study was devised to evaluate the hypothesis that rs2066827 polymorphism is associated with the risk of cancer. Computer-based databases (EMBASE, PubMed, and CNKI) were used to seek all case–control studies evaluating rs2066827 polymorphism and susceptibility to cancer. The genetic risk was assessed by calculating pooled odds ratio (OR) with its corresponding 95% confidence interval (CI). Fixed-effects pooled ORs were calculated by the Mantel–Haenszel method (Ph?>?0.05), and random-effects pooled ORs were estimated by the DerSimonian–Laird method (Ph?polymorphism and cancer risk were available for 9038 cancer cases and 11,596 controls participating in 17 studies. Carriage of a TG genotype was associated with a minor but significant decrease in the risk of cancer (pooled OR 0.92, 95% CI: 0.86–0.99; model, TG vs. TT). We observed a moderately decreased risk of ovarian cancer based on 1829 cases and 2868 controls (pooled OR 0.85, 95% CI: 0.74–0.97; model, TG vs. TT). A slightly deceased risk of cancer was also indicated in Caucasians consisting of 6707 cases and 8279 controls (pooled OR 0.91, 95% CI: 0.85–0.98; model, TG vs. TT). These data suggest that carriage of a TG genotype at rs2066827 polymorphism may be associated with decreased susceptibility to cancer, ovarian cancer in particular. PMID:26579796

  6. Genetic Polymorphisms in Non-alcoholic Fatty Liver Disease in Obese Egyptian Children

    PubMed Central

    El-Koofy, Nehal M.; El-Karaksy, Hanaa M.; Mandour, Iman M.; Anwar, Ghada M.; El-Raziky, Mona S.; El-Hennawy, Ahmad M.

    2011-01-01

    Background/Aim: Polymorphisms in the promoter of microsomal triglyceride transfer protein (MTP) lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis (NASH). The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children. Patients and Methods: A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Children's Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism for the –493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD). Results: Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype (P = 0.002, CI: 2.9–392) compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype. Conclusion: Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype. PMID:21727734

  7. Amplified fragment length polymorphism (AFLP) analysis of genetic variation in Moringa oleifera Lam

    PubMed

    Muluvi; Sprent; Soranzo; Provan; Odee; Folkard; McNicol; Powell

    1999-03-01

    Moringa oleifera is an important multipurpose tree introduced to Africa from India at the turn of this century. Despite limited knowledge of the levels of genetic diversity and relatedness of introduced populations, their utilization as a source of seed for planting is widespread. In order to facilitate reasoned scientific decisions on its management and conservation and prepare for a selective breeding programme, genetic analysis of seven populations was performed using amplified fragment length polymorphism (AFLP) markers. The four pairs of AFLP primers (PstI/MseI) generated a total of 236 amplification products of which 157 (66.5%) were polymorphic between or within populations. Analysis of molecular variance (AMOVA) revealed significant differences between regions and populations, even though outcrossing perennial plants are expected to maintain most variation within populations. A phenetic tree illustrating relationships between populations suggested at least two sources of germplasm introductions of Kenya. The high levels of population differentiation detected suggest that provenance source is an important factor in the conservation and exploitation of M. oleifera genetic resources. PMID:10199008

  8. Closure of a genetic linkage map of human chromosome 7q with centromere and telomere polymorphisms

    SciTech Connect

    Helms, C.; Mishra, S.K.; Burgess, A.K.; Ramachandra, S.; Tierney, C.; Dorsey, D.; Donis-Keller, H. ); Riethman, H. )

    1992-12-01

    The authors have constructed a 2.4-cM resolution genetic linkage map for chromosome 7q that is bounded by centromere and telomere polymorphisms and contains 66 loci (88 polymorphic systems), 38 of which are uniquely placed with odds for order of at least 1000:1. Ten genes are included in the map and 11 markers have heterozygosities of at least 70%. This map is the first to incorporate several highly informative markers derived from a telomere YAC clone HTY146 (locus D7S427), including HTY146c3 (HET 92%). The telomere locus markers span at least 200 kb of the 7q terminus and no crossovers within the physical confines of the locus were observed in approximately 240 jointly informative meioses. The sex-equal map length is 158 cM and the largest genetic interval between uniquely localized markers in this map is 11 cM. The female and male map lengths are 181 and 133 cM, respectively. The map is based on the CEPH reference pedigrees and includes over 4000 new genotypes, the previously reported data plus 29 allele systems from the published CEPH version 5 database, and was constructed using the program package CRI-MAP. This genetic linkage map can be considered a baseline map for 7q, and will be useful for defining the extent of chromosome deletions previously reported for breast and prostate cancers, for developing additional genetic maps such as index marker and 1-cM maps, and ultimately for developing a fully integrated genetic and physical map for this chromosome. 63 refs., 4 figs., 1 tab.

  9. Development of polymorphic microsatellite loci for conservation genetic studies of the coral reef fish Centropyge bicolor.

    PubMed

    Herrera, M; Saenz-Agudelo, P; Nanninga, G B; Berumen, M L

    2015-09-01

    A total of 23 novel polymorphic microsatellite marker loci were developed for the angelfish Centropyge bicolor through 454 sequencing, and further tested on two spatially separated populations (90 individuals each) from Kimbe Bay in Papua New Guinea. The mean ± s.e. number of alleles per locus was 14·65 ± 1·05, and mean ± s.e. observed (HO ) and expected (HE ) heterozygosity frequencies were 0·676 ± 0·021 and 0·749 ± 0·018, respectively. The markers reported here constitute the first specific set for this genus and will be useful for future conservation genetic studies in the Indo-Pacific region. PMID:26272332

  10. Genetic polymorphism of cytochrome P450s in beagles: possible influence of CYP1A2 deficiency on toxicological evaluations.

    PubMed

    Kamimura, H

    2006-11-01

    A number of human cytochrome P450 (CYP) isozymes have been shown to be genetically polymorphic, and extensive pharmaceutical studies have been conducted to characterize the clinical relevance of the polymorphism. Although the beagle is extensively used in the safety assessment studies of new drug candidates and agricultural chemicals, only a limited number of studies have been reported on the significance of the CYP isozyme polymorphism in dogs. Recently, a single nucleotide polymorphism that results in a deficiency of canine CYP1A2 was discovered. This deficiency was shown to significantly alter the pharmacokinetic behavior of two drugs, and can be associated with a large inter-individual difference in the kinetic behavior of a third. In this article, the five genetically polymorphic canine CYP isozymes that have been reported so far are reviewed, and the altered pharmacokinetics of the drugs concerned are described. Although little information on toxicological relevance has been reported, it is possible that the modified pharmacokinetics may also cause altered toxic responses as well. This phenomenon may occur only with the types of chemicals that are eliminated mainly through polymorphic-enzyme mediated metabolism. However, it is recommended that genetically pure beagles are used for the toxicity studies and safety assessment of new chemical entities in order to reduce the potential inter-individual differences. PMID:16639591

  11. Single nucleotide polymorphisms for assessing genetic diversity in castor bean (Ricinus communis)

    PubMed Central

    2010-01-01

    Background Castor bean (Ricinus communis) is an agricultural crop and garden ornamental that is widely cultivated and has been introduced worldwide. Understanding population structure and the distribution of castor bean cultivars has been challenging because of limited genetic variability. We analyzed the population genetics of R. communis in a worldwide collection of plants from germplasm and from naturalized populations in Florida, U.S. To assess genetic diversity we conducted survey sequencing of the genomes of seven diverse cultivars and compared the data to a reference genome assembly of a widespread cultivar (Hale). We determined the population genetic structure of 676 samples using single nucleotide polymorphisms (SNPs) at 48 loci. Results Bayesian clustering indicated five main groups worldwide and a repeated pattern of mixed genotypes in most countries. High levels of population differentiation occurred between most populations but this structure was not geographically based. Most molecular variance occurred within populations (74%) followed by 22% among populations, and 4% among continents. Samples from naturalized populations in Florida indicated significant population structuring consistent with local demes. There was significant population differentiation for 56 of 78 comparisons in Florida (pairwise population ?PT values, p < 0.01). Conclusion Low levels of genetic diversity and mixing of genotypes have led to minimal geographic structuring of castor bean populations worldwide. Relatively few lineages occur and these are widely distributed. Our approach of determining population genetic structure using SNPs from genome-wide comparisons constitutes a framework for high-throughput analyses of genetic diversity in plants, particularly in species with limited genetic diversity. PMID:20082707

  12. Genetic polymorphisms in ?-defensin II gene in Amazon sheep from Brazil.

    PubMed

    Souza, B B; Barbosa, E M; Azevedo, J S N; Campelo, J E G; Rodrigues, L F S; Pinheiro, L M L; Silva, S C B; Schierholt, A S; Souza, P H; Gonçalves, E C; Silva Filho, E

    2015-01-01

    The northern region of Brazil produces a large number of sheep, with Pará being the largest sheep breeding state in the region. In the Amazon region, livestock production is a challenge due to the high diversity of pathogens affecting humans and animals. Defensins are antimicrobial peptides acting as a first barrier against micro-organisms and present high variation in different organisms. The objective of this study was to detect polymorphisms in exon II in ?-defensin II in Amazon sheep. The gene was amplified by PCR from DNA extracted from 47 sheep blood samples from the Santa Inês breed. Products were sequenced, aligned and analyzed. Three single nucleotide polymorphism (SNP) positions were observed with transition substitutions (A?G) at positions 1643, 1659, and 1750. The 1643 and 1750 SNPs showed a low variability and significant deviations from Hardy-Weinberg equilibrium (HWE) (P < 0.05) meanwhile the SNP 1659 showed moderate absence of genetic variability and deviation from HWE (P > 0.05). Polymorphisms at 1643 and 1659 were predicted to modify amino acids in the peptide chain (isoleucine to valine and arginine to lysine, respectively) with no effects on protein function. Results from this study suggest that SNPs are important markers for ?-defensin II efficiency studies on the immune system of sheep in the Brazilian Amazon. PMID:26505431

  13. Genetic Effects of Polymorphisms in Myogenic Regulatory Factors on Chicken Muscle Fiber Traits

    PubMed Central

    Yang, Zhi-Qin; Qing, Ying; Zhu, Qing; Zhao, Xiao-Ling; Wang, Yan; Li, Di-Yan; Liu, Yi-Ping; Yin, Hua-Dong

    2015-01-01

    The myogenic regulatory factors is a family of transcription factors that play a key role in the development of skeletal muscle fibers, which are the main factors to affect the meat taste and texture. In the present study, we performed candidate gene analysis to identify single-nucleotide polymorphisms in the MyoD, Myf5, MyoG, and Mrf4 genes using polymerase chain reaction-single strand conformation polymorphism in 360 Erlang Mountain Chickens from three different housing systems (cage, pen, and free-range). The general linear model procedure was used to estimate the statistical significance of association between combined genotypes and muscle fiber traits of chickens. Two polymorphisms (g.39928301T>G and g.11579368C>T) were detected in the Mrf4 and MyoD gene, respectively. The diameters of thigh and pectoralis muscle fibers were higher in birds with the combined genotypes of GG-TT and TT-CT (p<0.05). Moreover, the interaction between housing system and combined genotypes has no significant effect on the traits of muscle fiber (p>0.05). Our findings suggest that the combined genotypes of TT-CT and GG-TT might be advantageous for muscle fiber traits, and could be the potential genetic markers for breeding program in Erlang Mountain Chickens. PMID:25925055

  14. Gene-Based Single Nucleotide Polymorphism Markers for Genetic and Association Mapping in Common Bean

    PubMed Central

    2012-01-01

    Background In common bean, expressed sequence tags (ESTs) are an underestimated source of gene-based markers such as insertion-deletions (Indels) or single-nucleotide polymorphisms (SNPs). However, due to the nature of these conserved sequences, detection of markers is difficult and portrays low levels of polymorphism. Therefore, development of intron-spanning EST-SNP markers can be a valuable resource for genetic experiments such as genetic mapping and association studies. Results In this study, a total of 313 new gene-based markers were developed at target genes. Intronic variation was deeply explored in order to capture more polymorphism. Introns were putatively identified after comparing the common bean ESTs with the soybean genome, and the primers were designed over intron-flanking regions. The intronic regions were evaluated for parental polymorphisms using the single strand conformational polymorphism (SSCP) technique and Sequenom MassARRAY system. A total of 53 new marker loci were placed on an integrated molecular map in the DOR364?×?G19833 recombinant inbred line (RIL) population. The new linkage map was used to build a consensus map, merging the linkage maps of the BAT93?×?JALO EEP558 and DOR364?×?BAT477 populations. A total of 1,060 markers were mapped, with a total map length of 2,041?cM across 11 linkage groups. As a second application of the generated resource, a diversity panel with 93 genotypes was evaluated with 173 SNP markers using the MassARRAY-platform and KASPar technology. These results were coupled with previous SSR evaluations and drought tolerance assays carried out on the same individuals. This agglomerative dataset was examined, in order to discover marker-trait associations, using general linear model (GLM) and mixed linear model (MLM). Some significant associations with yield components were identified, and were consistent with previous findings. Conclusions In short, this study illustrates the power of intron-based markers for linkage and association mapping in common bean. The utility of these markers is discussed in relation with the usefulness of microsatellites, the molecular markers by excellence in this crop. PMID:22734675

  15. Mapping quantitative trait loci for milk production and genetic polymorphisms of milk proteins in dairy sheep

    PubMed Central

    2005-01-01

    In this paper, we present recent advances in the molecular dissection of complex traits in dairy sheep and discuss their possible impact on breeding schemes. In the first step, we review the literature data on genetic polymorphisms and the effects of sheep ?s1-casein and ?-lactoglobulin loci. It is concluded that the results are rather inconsistent and cannot be used in dairy sheep selection. In a second step, we describe the strategy implemented in France, Italy and Spain taking advantage of the genetic maps for QTL detection. These studies were part of a European project, called "genesheepsafety", which investigated both milk production and functional traits. Preliminary QTL results are presented for production traits. PMID:15601591

  16. [Genetic Polymorphism of Durum Wheat (Triticum durum Desf.) Accessions of Azerbaijan].

    PubMed

    Hajiyev, E S; Akparov, Z I; Aliyev, R T; Seidova, S V; Izzatullayeva, V I; Babayeva, S M; Abbasov, M A

    2015-09-01

    The genetic diversity of 110 durum wheat genotypes of Azerbaijan was evaluated by ISSR markers. A total of 107 fragments were determined, ranging from 9 to 18 per locus. ISSR primers have revealed a high level of polymorphism (average 82%) among different durum wheat varieties and botanical varieties. The ISSR markers used in the study were quite informative and made it possible to distinguish all durum wheat accessions from each other. Cluster analysis based on ISSR data classified the accessions into 11 major groups. No linkage was observed between the collection site and genetic structure of the samples. On the other hand, a few accessions were detected as unique genotypes and tended to form separate clusters. The estimated gene diversity value was high, both within the whole collection and within the different groups of botanical varieties. PMID:26606797

  17. Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson’s disease susceptibility in Chinese Han population

    PubMed Central

    Dai, Yi; Wu, Yuquan; Li, Yansheng

    2015-01-01

    Objective: The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson’s disease (PD) susceptibility in Chinese Han population. Methods: The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using ?2 test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. Results: On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). Conclusions: COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association. PMID:26722563

  18. Genetic polymorphisms of pharmacogenomic VIP variants in the lhoba population of southwest China

    PubMed Central

    He, Yongjun; Yang, Hua; Geng, Tingting; Feng, Tian; Yuan, Dongya; Kang, Longli; Luo, Manling; Jin, Tianbo

    2015-01-01

    Background: It is well-established that differences among ethnic groups in drug responses are primarily due to the genetic diversity of pharmacogenes. A number of genes or variants that play a crucial role in drug responses have been designated Very Important Pharmacogenes (VIP) by the PharmGKB database. Clarifying the polymorphic distribution of VIPs in different ethnic groups will aid in personalized medicine for specific populations. Methods: We sequenced 85 VIP variants in the Lhoba population based on the PharmGKB database. The polymorphic distribution of the 85 VIP variants in 100 Lhoba subjects was determined and compared with that of 11 major HapMap populations, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI. We used ?2 tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations. Results: Based on comparisons of selected available loci, we found that 23, 28, 16, 10, 20, 16, 24, 19, 22, 21 and 36 of the selected VIP variant genotype frequencies in the Lhoba population differed from those of the ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI populations, respectively. In addition, Pairwise FST values and clustering analyses also showed the VIP variants in Lhoba exhibited a close genetic affinity with CHD, CHB and JPT populations. Conclusion: Our results complement pharmacogenomic data on the Lhoba ethnic group and may be helpful in the diagnosis of certain diseases in minorities. PMID:26722533

  19. Genetic polymorphisms of metabolic enzymes and the pharmacokinetics of indapamide in Taiwanese subjects.

    PubMed

    Wang, Teng-Hsu; Hsiong, Cheng-Huei; Ho, Hsin-Tien; Shih, Tung-Yuan; Yen, San-Jan; Wang, Hui-Hung; Wu, Jer-Yuarn; Kuo, Benjamin Pei-Chung; Chen, Yuan-Tsong; Ho, Shung-Tai; Hu, Oliver Yoa-Pu

    2014-03-01

    To understand the genetic makeup and impact on pharmacokinetics (PK) in the Taiwanese population, we analyzed the pharmacogenetic (PG) profile and demonstrated its effects on enzyme metabolism using indapamide as an example. A multiplex mass spectrometry method was used to examine the single nucleotide polymorphism (SNP) profile of eight major phases I and II metabolic enzymes in 1,038 Taiwanese subjects. A PG/PK study was conducted in 24 healthy subjects to investigate the possible effects of 28 SNPs on drug biotransformation. Among the genetic profile analyzed, eight SNPs from CYP2A6, CYP2C19, CYP2D6, CYP2E1, CYP3A5, and UGT2B7 showed higher variant frequencies than those previously reported in Caucasians or Africans. For instance, we observed 14.7% frequency of the SNP rs5031016 (I471T) from CYP2A6 in Taiwanese, whereas 0% variation was reported in Caucasians and Africans. The PG/PK study of indapamide demonstrated that the polymorphic SNPs CYP2C9 rs4918758 and CYP2C19 rs4244285 appeared to confer lowered enzyme activity, as indicated by increased C max (25%???64%), increased area under the plasma level-time curves (30~76%), increased area under the time infinity (43%???80%), and lower apparent clearance values than PK for wild-type indapamide. Our results reinforce the biochemical support of CYP2C19 in indapamide metabolism and identify a possible new participating enzyme CYP2C9. The PG/PK approach contributed toward understanding the genetic makeup of different ethnic groups and associations of enzymes in drug metabolism. It could be used to identify two genetic markers that enable to differentiate subjects with varied PK outcomes of indapamide. PMID:24357089

  20. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

    PubMed Central

    Hsu, Ling-I; Wu, Meei-Maan; Wang, Yuan-Hung; Lee, Cheng-Yeh; Yang, Tse-Yen; Hsiao, Bo-Yu; Chen, Chien-Jen

    2015-01-01

    Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated. PMID:26295053

  1. Genetic Polymorphism G894T and the Prognosis of Heart Failure Outpatients

    PubMed Central

    Tardin, Oziel Marcio Araujo; Pereira, Sabrina Bernardez; Velloso, Monica Wanderley Monçores; Balieiro, Henrique Miller; Costa, Bruno; Alves, Thiago Oliveira e; Giro, Camila; Pessoa, Leandro Pontes; Ribeiro, Georgina Severo; Mesquita, Evandro Tinoco

    2013-01-01

    Background Previous studies have analyzed the role of the genetic polymorphism of endothelial nitric oxide synthase on heart failure prognosis. However, there are no studies relating the G894T and heart failure in Brazil. Objective To evaluate the association between G894T GP and the prognosis of a sample of Brazilian outpatients with heart failure. Methods Cohort study included 145 patients with systolic heart failure, followed for up to 40 months (mean = 22), at two university hospitals, in the State of Rio de Janeiro. We evaluated the relationship between G894T and the following outcomes: reverse remodeling, improvement in functional class (NYHA), and mortality and hospitalization rates. The diameters of the left atrium and ventricle, as well as the ejection fraction of the left ventricle, were evaluated at baseline and at 6 months to assess reverse remodeling. The improvement in functional class was evaluated after 6 months, and mortality rate and hospitalization were evaluated during follow-up. Race was self-declared. G894T polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Results The genotypic frequencies were GG (40%), GT (48.3%) and TT (11.7%). The allele frequency was guanine (64.1%) and thiamine (35.8%). There were no differences between the genotype or allelic frequencies according to self declared race, either as baseline characteristics. There was no relationship between genotype or allele frequency and the outcome measures. Conclusion No association was observed between the G894T polymorphism (Glu298Asp) and prognosis in this sample of Brazilian outpatients with systolic heart failure. PMID:23949326

  2. A genetic polymorphism in RBP4 is associated with coronary artery disease.

    PubMed

    Wan, Ke; Zhao, Jianxun; Deng, Ying; Chen, Xi; Zhang, Qing; Zeng, Zhi; Zhang, Li; Chen, Yucheng

    2014-01-01

    Insulin resistance and obesity is influenced by the retinol binding protein 4 (RBP4) adipokine. This study aims to determine if genetic polymorphisms in RBP4 are associated with the risk of coronary artery disease (CAD) in Chinese patients. RBP4 polymorphisms were analyzed by high resolution melting (HRM) analysis in a case-control study of 392 unrelated CAD patients and 368 controls from China. The Gensini score was used to determine the severity of CAD. The genotypic and allelic frequencies of RBP4 single-nucleotide polymorphisms were evaluated for associations with CAD and severity of disease. The A allele frequency was significantly higher in CAD case groups compared to control groups (16.7% vs. 8.8%) at the RBP4 rs7094671 locus. Compared to the G allele, this allele was associated with a higher risk of CAD (OR = 2.07 (1.50-2.84)). Polymorphisms at rs7094671 were found to associate with CAD using either a dominant or recessive model (OR, 95% CI: 1.97, 1.38-2.81; 3.81, 1.53-9.51, respectively). Adjusting for sex, history of smoking, serum TC, TG, LDL-c, and HDL-c, the risk of CAD for carriers remained signi?cantly higher in both dominant and recessive models (OR, 95% CI: 1.68, 1.12-2.51; 2.74, 1.00-7.52, respectively). However, this SNP was not significantly associated with severity of CAD using angiographic scores in multivariable linear regression models (p = 0.373). The RBP4 rs7094671 SNP is associated with CAD; however, our results do not indicate that this locus is associated with clinical severity of CAD or the extent of coronary lesions. PMID:25479076

  3. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan.

    PubMed

    Hsu, Ling-I; Wu, Meei-Maan; Wang, Yuan-Hung; Lee, Cheng-Yeh; Yang, Tse-Yen; Hsiao, Bo-Yu; Chen, Chien-Jen

    2015-01-01

    Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01-8.83; OR = 2.04, 95% CI = 0.99-4.27; OR = 1.74, 95% CI = 1.00-3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated. PMID:26295053

  4. Investigating the genetic basis of altruism: the role of the COMT Val158Met polymorphism

    PubMed Central

    Frenzel, Clemens; Walter, Nora T.; Markett, Sebastian; Montag, Christian

    2011-01-01

    Findings from twin studies yield heritability estimates of 0.50 for prosocial behaviours like empathy, cooperativeness and altruism. First molecular genetic studies underline the influence of polymorphisms located on genes coding for the receptors of the neuropeptides, oxytocin and vasopressin. However, the proportion of variance explained by these gene loci is rather low indicating that additional genetic variants must be involved. Pharmacological studies show that the dopaminergic system interacts with oxytocin and vasopressin. The present experimental study tests a dopaminergic candidate polymorphism for altruistic behaviour, the functional COMT Val158Met SNP. N?=?101 healthy Caucasian subjects participated in the study. Altruism was assessed by the amount of money donated to a poor child in a developing country, after having earned money by participating in two straining computer experiments. Construct validity of the experimental data was given: the highest correlation between the amount of donations and personality was observed for cooperativeness (r?=?0.32, P???0.001). Carriers of at least one Val allele donated about twice as much money as compared with those participants without a Val allele (P?=?0.01). Cooperativeness and the Val allele of COMT additively explained 14.6% of the variance in donation behaviour. Results indicate that the Val allele representing strong catabolism of dopamine is related to altruism. PMID:21030481

  5. Genetic and Molecular Basis of QTL of Diabetes in Mouse: Genes and Polymorphisms

    PubMed Central

    Gao, Peng; Jiao, Yan; Xiong, Qing; Wang, Cong-Yi; Gerling, Ivan; Gu, Weikuan

    2008-01-01

    A systematic study has been conducted of all available reports in PubMed and OMIM (Online Mendelian Inheritance in Man) to examine the genetic and molecular basis of quantitative genetic loci (QTL) of diabetes with the main focus on genes and polymorphisms. The major question is, What can the QTL tell us? Specifically, we want to know whether those genome regions differ from other regions in terms of genes relevant to diabetes. Which genes are within those QTL regions, and, among them, which genes have already been linked to diabetes? whether more polymorphisms have been associated with diabetes in the QTL regions than in the non-QTL regions. Our search revealed a total of 9038 genes from 26 type 1 diabetes QTL, which cover 667,096,006 bp of the mouse genomic sequence. On one hand, a large number of candidate genes are in each of these QTL; on the other hand, we found that some obvious candidate genes of QTL have not yet been investigated. Thus, the comprehensive search of candidate genes for known QTL may provide unexpected benefit for identifying QTL genes for diabetes. PMID:19471607

  6. Genetic polymorphism of six DNA loci in six population groups of India.

    PubMed

    Ahmad, Shazia; Seshadri, M

    2007-08-01

    The genetic profile based on autosomal markers, four microsatellite DNA markers (D8S315, FES, D8S592, and D2S1328) and two minisatellite DNA markers (TPMT and PDGFA), were analyzed in six endogamous populations to examine the effect of geographic and linguistic affiliation on the genetic affinities among the groups. The six populations are from three different states of India and are linguistically different. Marathas from western India speak Marathi, an Indo-European language. Arayas, Muslims, Ezhavas, and Nairs from Kerala state of South India speak Malayalam, and Iyers from Tamil Nadu state speak Tamil. Genomic DNA was extracted from peripheral blood samples of random, normal, healthy individuals. Locus-specific PCR amplification was carried out, followed by electrophoresis of the amplicons and genotyping. All the loci were highly polymorphic and followed Hardy-Weinberg equilibrium, except for loci D8S315 and PDGFA in Iyers and Marathas, respectively. All six loci had high heterozygosity (average heterozygosity ranged from 0.73 to 0.76) and high polymorphism information content (0.57-0.90). The extent of gene differentiation among the six populations (G(ST) = 0.030) was greater than that for four Kerala populations (G(ST) = 0.011), suggesting proximity between the four Kerala populations. This result conforms with the cultural and linguistic background of the populations. The extent of diversity found among the populations probably resulted from the strict endogamous practices that they follow. PMID:18075006

  7. Fatal Methadone Toxicity: Potential Role of CYP3A4 Genetic Polymorphism

    PubMed Central

    Richards-Waugh, Lauren L.; Primerano, Donald A.; Dementieva, Yulia; Kraner, James C.; Rankin, Gary O.

    2014-01-01

    Methadone is difficult to administer as a therapeutic agent because of a wide range of interindividual pharmacokinetics, likely due to genetic variability of the CYP450 enzymes responsible for metabolism to its principal metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). CYP3A4 is one of the primary CYP450 isoforms responsible for the metabolism of methadone to EDDP in humans. The purpose of this study was to evaluate the role of CYP3A4 genetic polymorphisms in accidental methadone fatalities. A study cohort consisting of 136 methadone-only and 92 combined methadone/benzodiazepine fatalities was selected from cases investigated at the West Virginia and Kentucky Offices of the Chief Medical Examiner. Seven single nucleotide polymorphisms (SNPs) were genotyped within the CYP3A4 gene. Observed allelic and genotypic frequencies were compared with expected frequencies obtained from The National Center for Biotechnology Information dbSNP database. SNPs rs2242480 and rs2740574 demonstrated an apparent enrichment within the methadone-only overdose fatalities compared with the control group and the general population. This enrichment was not apparent in the methadone/benzodiazepine cases for these two SNPs. Our findings indicate that there may be two or more SNPs on the CYP3A4 gene that cause or contribute to the methadone poor metabolizer phenotype. PMID:25217544

  8. Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism

    PubMed Central

    Krueger, Sharon K.; Williams, David E.

    2005-01-01

    Flavin-containing monooxygenase (FMO) oxygenates drugs and xenobiotics containing a “soft-nucleophile”, usually nitrogen or sulfur. FMO, like cytochrome P450 (CYP), is a monooxygenase, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. FMO and CYP also exhibit similar tissue and cellular location, molecular weight, substrate specificity, and exist as multiple enzymes under developmental control. The human FMO functional gene family is much smaller (5 families each with a single member) than CYP. FMO does not require a reductase to transfer electrons from NADPH and the catalytic cycle of the 2 monooxygenases is strikingly different. Another distinction is the lack of induction of FMOs by xenobiotics. In general, CYP is the major contributor to oxidative xenobiotic metabolism. However, FMO activity may be of significance in a number of cases and should not be overlooked. FMO and CYP have overlapping substrate specificities, but often yield distinct metabolites with potentially significant toxicological/pharmacological consequences. The physiological function(s) of FMO are poorly understood. Three of the 5 expressed human FMO genes, FMO1, FMO2 and FMO3, exhibit genetic polymorphisms. The most studied of these is FMO3 (adult human liver) in which mutant alleles contribute to the disease known as trimethylaminuria. The consequences of these FMO genetic polymorphisms in drug metabolism and human health are areas of research requiring further exploration. PMID:15922018

  9. Characterization of polymorphic microsatellite markers and genetic diversity in wild bronze featherback, Notopterus notopterus (Pallas, 1769).

    PubMed

    Gupta, Arti; Lal, Kuldeep K; Punia, Peyush; Singh, Rajeev K; Mohindra, Vindhya; Sah, Rama S; Kumar, Rajesh; Luhariya, Rupesh K; Dwivedi, Arvind K; Masih, Prachi; Mishra, R M; Jena, J K

    2013-12-01

    Six polymorphic microsatellite DNA loci were identified in the primitive fish, bronze featherback, Notopterus notopterus for the first time and demonstrated significant population genetic structure. Out of the six primers, one primer (NN90) was specific to N. notopterus (microsatellite sequence within the RAG1 gene) and five primers were product of successful cross-species amplification. Sixty-four primers available from 3 fish species of order Osteoglossiformes and families Notopteridae and Osteoglossidae were tested to amplify homologous microsatellite loci in N. notopterus. Fifteen primer pairs exhibited successful cross-priming PCR product. However, polymorphism was detected only at five loci. To assess the significance of these six loci (including NN90) in population genetic study, 215 samples of N. notopterus from five rivers, viz Satluj, Gomti, Yamuna, Brahmaputra and Mahanadi were analyzed. The five sample sets displayed different diversity levels and observed heterozygosity ranged from 0.6036 to 0.7373. Significant genotype heterogeneity (P < 0.0001) and high FST (0.2205) over all loci indicated that the samples are not drawn from the same genepool. The identified microsatellite loci are promising for use in fine-scale population structure analysis of N. notopterus. PMID:24072656

  10. Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer

    PubMed Central

    Thomas, F; Motsinger-Reif, A A; Hoskins, J M; Dvorak, A; Roy, S; Alyasiri, A; Myerson, R J; Fleshman, J W; Tan, B R; McLeod, H L

    2011-01-01

    Background: There is a large degree of variation in tumour response and host toxicities associated with neoadjuvant chemoradiation for rectal cancer patients. We performed a complimentary pharmacogenetic study to investigate germline polymorphisms of genes involved in 5-fluorouracil (5-FU) and irinotecan pathways and their potential association with clinical outcomes and toxicities from neoadjuvant chemoradiation in patients with rectal cancer treated in a prospective genotype-directed study. Methods: The germline DNA of 131 patients was genotyped for 10 variants in TYMS, MTHFR, DPYD, UGT1A1, ABCC1 and SLCO1B1 genes. Ninety-six patients were treated with 5-FU/radiotherapy (RT) and 35 received 5-FU/RT/irinotecan. Relationships between genetic variants and adverse events, tumour response, overall and disease-free survivals were assessed. Results: MTHFR 1298A>C and MTHFR diplotypes (for 677C>T and 1298A>C) were associated with chemoradiation-related toxicity when 5-FU was used alone. MTHFR haplotypes (677C–1298C) and diplotypes (CA–TA and TA–TA) showed, respectively, a protective and a negative effect on the incidence of severe diarrhoea or mucositis. No association was observed between genetic markers and drug response. Conclusion: MTHFR polymorphisms can potentially predict toxicity in patients treated with 5-FU as a single chemotherapeutic drug. PMID:22045187

  11. Neanderthal and Denisova genetic affinities with contemporary humans: introgression versus common ancestral polymorphisms.

    PubMed

    Lowery, Robert K; Uribe, Gabriel; Jimenez, Eric B; Weiss, Mark A; Herrera, Kristian J; Regueiro, Maria; Herrera, Rene J

    2013-11-01

    Analyses of the genetic relationships among modern humans, Neanderthals and Denisovans have suggested that 1-4% of the non-Sub-Saharan African gene pool may be Neanderthal derived, while 6-8% of the Melanesian gene pool may be the product of admixture between the Denisovans and the direct ancestors of Melanesians. In the present study, we analyzed single nucleotide polymorphism (SNP) diversity among a worldwide collection of contemporary human populations with respect to the genetic constitution of these two archaic hominins and Pan troglodytes (chimpanzee). We partitioned SNPs into subsets, including those that are derived in both archaic lineages, those that are ancestral in both archaic lineages and those that are only derived in one archaic lineage. By doing this, we have conducted separate examinations of subsets of mutations with higher probabilities of divergent phylogenetic origins. While previous investigations have excluded SNPs from common ancestors in principal component analyses, we included common ancestral SNPs in our analyses to visualize the relative placement of the Neanderthal and Denisova among human populations. To assess the genetic similarities among the various hominin lineages, we performed genetic structure analyses to provide a comparison of genetic patterns found within contemporary human genomes that may have archaic or common ancestral roots. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Our results suggest that Neanderthal genetic associations with contemporary non-Sub-Saharan African populations, as well as the genetic affinities observed between Denisovans and Melanesians most likely result from the retention of ancient mutations in these populations. PMID:23872234

  12. Characterization of genetic diversity in chickpea using SSR markers, Start Codon Targeted Polymorphism (SCoT) and Conserved DNA-Derived Polymorphism (CDDP).

    PubMed

    Hajibarat, Zahra; Saidi, Abbas; Hajibarat, Zohreh; Talebi, Reza

    2015-07-01

    To evaluate the genetic diversity among 48 genotypes of chickpea comprising cultivars, landraces and internationally developed improved lines genetic distances were evaluated using three different molecular marker techniques: Simple Sequence Repeat (SSR); Start Codon Targeted (SCoT) and Conserved DNA-derived Polymorphism (CDDP). Average polymorphism information content (PIC) for SSR, SCoT and CDDP markers was 0.47, 0.45 and 0.45, respectively, and this revealed that three different marker types were equal for the assessment of diversity amongst genotypes. Cluster analysis for SSR and SCoT divided the genotypes in to three distinct clusters and using CDDP markers data, genotypes grouped in to five clusters. There were positive significant correlation (r?=?0.43, P?polymorphism for varieties were higher than that of genotypes, and CDDP had superiority over SCoT and SSR markers. These results suggest that efficiency of SSR, SCOT and CDDP markers was relatively the same in fingerprinting of chickpea genotypes. To our knowledge, this is the first detailed report of using targeted DNA region molecular marker (CDDP) for genetic diversity analysis in chickpea in comparison with SCoT and SSR markers. Overall, our results are able to prove the suitability of SCoT and CDDP markers for genetic diversity analysis in chickpea for their high rates of polymorphism and their potential for genome diversity and germplasm conservation. PMID:26261401

  13. Genetic Contributions to Age-Related Decline in Executive Function: A 10-Year Longitudinal Study of COMT and BDNF Polymorphisms

    PubMed Central

    Erickson, Kirk I.; Kim, Jennifer S.; Suever, Barbara L.; Voss, Michelle W.; Francis, B. Magnus; Kramer, Arthur F.

    2008-01-01

    Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age. PMID:18958211

  14. Genetic map of randomly amplified DNA polymorphisms closely linked to the mating type locus of tetrahymenta thermophila

    SciTech Connect

    Lynch, T.J.; Brickner, J.; Orias, E.; Nakano, K.J.

    1995-12-01

    We have used the PCR-based randomly amplified polymorphic DNA (RAPD) method to efficiently identify and map DNA polymorphisms in the ciliated protozoan Tetrahymena thermophila. The polymorphisms segregate as Mendelian genetic markers. A targeted screen, using DNA from pooled meiotic segregants, yielded the polymorphisms most closely linked to the mat locus. A total of 10 polymorphisms linked to the mat-Pmr segment of the left arm of micronuclear chromosome 2 have been identified. This constitutes the largest linkage group described in T. thermophila. We also provide here the first crude estimate of the frequency of meiotic recombination in the mat region, 20 kb/cM. This frequency is much higher than that observed in most other eukaryotes. Special features of Tetrahymena genetics enhanced the power of the RAPD method: the ability to obtain in a single step meiotic segregants that are whole-genome homozygotes and the availability of nullisomic strains permitting quick deletion mapping of polymorphisms to micronuclear chromosomes or chromosomes segments. The RAPD method appears to provide a practical and relatively inexpensive approach to the construction of a high-resolution map of the Tetrahymena genome. 39 refs., 5 figs., 4 tabs.

  15. Association between Genetic Polymorphisms in DEFB1 and Susceptibility to Digestive Diseases

    PubMed Central

    Huang, Yin-Peng; Wang, Tian-Yi; Wang, Wei; Sun, Hong-Zhi

    2015-01-01

    Background Aberrant expression of defensins is implicated in the pathogenesis of digestive diseases. However, the contribution of specific defensins and the influence of their genetic polymorphisms on the progression of digestive diseases remain controversial. In the present meta-analysis, we investigated the association between DEFB1 SNPs and the susceptibility to digestive diseases. Material/Methods Case-control studies that reported the correlation between DEFB1 SNPs and the susceptibility to digestive diseases were identified through electronic databases searches, and high-quality studies that satisfied our inclusion criteria were selected for this meta-analysis. Statistical analyses were performed utilizing STATA software version 12.0. Results The present meta-analysis revealed that patients with digestive diseases exhibited higher frequencies of the DEFB1 genetic variants rs11362G>A, rs1800972C>G, and rs1799946G>A compared to healthy controls under the allele model. Subgroup analysis based on country showed that the rs1800972C>G variant under allele model and rs1799946G>A are associated with the susceptibility to digestive diseases in Hungarian and Italian populations, respectively. Subgroup analysis based on disease type showed that: (1) rs11362G>A variant was strongly associated with severe acute pancreatitis (SAP) and chronic gastritis, (2) frequency of rs1800972C>G variant was higher in SAP subgroup, and (3) frequency of rs1799946G>A variant was positively associated with the susceptibility to Crohn’s disease (CD) under the allele model and with SAP. Conclusions Our meta-analysis provides evidence that DEFB1 genetic polymorphisms rs11362G>A, rs1800972C>G and rs1799946G>A are important contributing factors to the development of digestive diseases. PMID:26232989

  16. Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility

    PubMed Central

    Kumar, Pradeep; Yadav, Upendra; Rai, Vandana

    2015-01-01

    There are several evidences supporting the role of 5–10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in breast cancer (BC). Case control association studies on breast cancer have been repeatedly performed over the last two decades, but results are inconsistent. We performed a meta-analysis to confirm the association between MTHFR C677T polymorphism and BC risk. The articles were retrieved by searching the PubMed, Google Scholar, and Springer Link databases. Crude odds ratios (OR) with 95% confidence intervals (CIs) was used to assess the strength of association between C677T polymorphism and BC. Publication bias was assessed by Egger's and Begg-Mazumdar tests. Meta-analysis was performed with Open Meta Analyst. Total 75 studies with 31,315 cases and 35, 608 controls were found suitable for the inclusion in the present meta-analysis. The results of meta-analysis suggested that there were moderate significant association between C677T polymorphism and BC risk using overall comparisons in five genetic models (T vs. C: OR = 1.08, 95% CI = 1.03–1.13, p = < 0.001; TT + CT vs. CC: OR = 1.06, 95% CI = 1.02–1.09, p = < 0.001; TT vs. CC: OR = 1.17, 95% CI = 1.06–1.28, p = 0.001; CT vs. CC OR = 1.05, 95% CI = 1.01–1.08, p = 0.005; TT vs. CT + CC: OR = 1.12, 95% CI = 1.03–1.22, p = 0.005). In conclusion, results of present meta-analysis showed modest association between MTHFR C677T polymorphism with breast cancer in total studies. However, sub-group analysis results based on ethnicity showed strong significant association between TT genotype and breast cancer (TT vs. CC; OR°=°1.26; 95% CI: 1.06–1.51; p = 0.009) in Asian population but in Caucasian population such association was not observed (TT vs. CC; OR°=°1.08; 95% CI: 0.99–1.14; p = 0.05). PMID:26629412

  17. Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility.

    PubMed

    Kumar, Pradeep; Yadav, Upendra; Rai, Vandana

    2015-12-01

    There are several evidences supporting the role of 5-10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in breast cancer (BC). Case control association studies on breast cancer have been repeatedly performed over the last two decades, but results are inconsistent. We performed a meta-analysis to confirm the association between MTHFR C677T polymorphism and BC risk. The articles were retrieved by searching the PubMed, Google Scholar, and Springer Link databases. Crude odds ratios (OR) with 95% confidence intervals (CIs) was used to assess the strength of association between C677T polymorphism and BC. Publication bias was assessed by Egger's and Begg-Mazumdar tests. Meta-analysis was performed with Open Meta Analyst. Total 75 studies with 31,315 cases and 35, 608 controls were found suitable for the inclusion in the present meta-analysis. The results of meta-analysis suggested that there were moderate significant association between C677T polymorphism and BC risk using overall comparisons in five genetic models (T vs. C: OR = 1.08, 95% CI = 1.03-1.13, p = < 0.001; TT + CT vs. CC: OR = 1.06, 95% CI = 1.02-1.09, p = < 0.001; TT vs. CC: OR = 1.17, 95% CI = 1.06-1.28, p = 0.001; CT vs. CC OR = 1.05, 95% CI = 1.01-1.08, p = 0.005; TT vs. CT + CC: OR = 1.12, 95% CI = 1.03-1.22, p = 0.005). In conclusion, results of present meta-analysis showed modest association between MTHFR C677T polymorphism with breast cancer in total studies. However, sub-group analysis results based on ethnicity showed strong significant association between TT genotype and breast cancer (TT vs. CC; OR°=°1.26; 95% CI: 1.06-1.51; p = 0.009) in Asian population but in Caucasian population such association was not observed (TT vs. CC; OR°=°1.08; 95% CI: 0.99-1.14; p = 0.05). PMID:26629412

  18. Detection of genomic variations and DNA polymorphisms and impact on analysis of meiotic recombination and genetic mapping.

    PubMed

    Qi, Ji; Chen, Yamao; Copenhaver, Gregory P; Ma, Hong

    2014-07-01

    DNA polymorphisms are important markers in genetic analyses and are increasingly detected by using genome resequencing. However, the presence of repetitive sequences and structural variants can lead to false positives in the identification of polymorphic alleles. Here, we describe an analysis strategy that minimizes false positives in allelic detection and present analyses of recently published resequencing data from Arabidopsis meiotic products and individual humans. Our analysis enables the accurate detection of sequencing errors, small insertions and deletions (indels), and structural variants, including large reciprocal indels and copy number variants, from comparisons between the resequenced and reference genomes. We offer an alternative interpretation of the sequencing data of meiotic products, including the number and type of recombination events, to illustrate the potential for mistakes in single-nucleotide polymorphism calling. Using these examples, we propose that the detection of DNA polymorphisms using resequencing data needs to account for nonallelic homologous sequences. PMID:24958856

  19. Analysis of multiple genetic polymorphisms in aggressive- and slow-growing abdominal aortic aneurysms

    PubMed Central

    Duellman, Tyler; Warren, Christopher L.; Matsumura, Jon; Yang, Jay

    2014-01-01

    Introduction The natural history of abdominal aortic aneurysm (AAA) suggests that some remain slow in growth rate while many develop a more accelerated growth rate reaching a threshold for intervention. We hypothesized that different mechanisms are responsible for AAA that remain slow-growth and never become actionable versus the aggressive-AAA that require intervention may be reflected by distinct associations with genetic polymorphisms. Methods 168 control and 141 AAA subjects all with ultrasound or CT imaging studies covering about 5 years were identified and the AAA growth rate determined from the serial imaging data. Genetic polymorphisms all previously reported as showing significant correlation with AAA: angiotensin 1 receptor (AT1R) (rs5186), interleukin-10 (IL-10) (rs1800896), methyl-tetrahydrofolate reductase (MTHFR) (rs1801133), low density lipoprotein receptor-related protein 1 (LRP1) (rs1466535), angiotensin converting enzyme (ACE) (rs1799752) and several MMP9 SNPs with functional effects on the expression or function were determined by analysis of the genomic DNA. Results AAA subjects were classified as slow-growth rate- (<3.25 mm /yr; n=81) vs. aggressive-AAA (growth rate >3.25 mm /yr, those presenting with a rupture, or those with maximal aortic diameter >5.5 cm (male) or >5.0 cm (female); n=60) and discriminating confounds between the groups identified by logistic regression. Analyses identified MMP9 p-2502 SNP (P=0.029, OR=0.54 (0.31-0.94)) as a significant confound discriminating between control- vs. slow-growth AAA, MMP-9 D165N (P=0.035) and LRP1 (P=0.034) between control vs. aggressive-AAA, and MTHFR (P=0.048, OR=2.99 (1.01-8.86)), MMP9 p-2502 (P=0.037, OR=2.19 (1.05-4.58), and LRP1 (P=0.046, OR= 4.96 (1.03-23.9)) as the statistically significant confounds distinguishing slow- vs. aggressive-AAA. Conclusion Logistic regression identified different genetic confounds for the slow-growth rate-and aggressive-AAA indicating a potential for different genetic influences on AAA of distinct aggressiveness. Future logistic regression studies investigating for potential genetic or clinical confounds for this disease should take into account the growth rate and size of AAA to better identify confounds likely to be associated with aggressive AAA likely to require intervention. PMID:24801553

  20. Assessing genetic polymorphisms using DNA extracted from cells present in saliva samples

    PubMed Central

    2011-01-01

    Background Technical advances following the Human Genome Project revealed that high-quality and -quantity DNA may be obtained from whole saliva samples. However, usability of previously collected samples and the effects of environmental conditions on the samples during collection have not been assessed in detail. In five studies we document the effects of sample volume, handling and storage conditions, type of collection device, and oral sampling location, on quantity, quality, and genetic assessment of DNA extracted from cells present in saliva. Methods Saliva samples were collected from ten adults in each study. Saliva volumes from .10-1.0 ml, different saliva collection devices, sampling locations in the mouth, room temperature storage, and multiple freeze-thaw cycles were tested. One representative single nucleotide polymorphism (SNP) in the catechol-0-methyltransferase gene (COMT rs4680) and one representative variable number of tandem repeats (VNTR) in the serotonin transporter gene (5-HTTLPR: serotonin transporter linked polymorphic region) were selected for genetic analyses. Results The smallest tested whole saliva volume of .10 ml yielded, on average, 1.43 ± .77 ?g DNA and gave accurate genotype calls in both genetic analyses. The usage of collection devices reduced the amount of DNA extracted from the saliva filtrates compared to the whole saliva sample, as 54-92% of the DNA was retained on the device. An "adhered cell" extraction enabled recovery of this DNA and provided good quality and quantity DNA. The DNA from both the saliva filtrates and the adhered cell recovery provided accurate genotype calls. The effects of storage at room temperature (up to 5 days), repeated freeze-thaw cycles (up to 6 cycles), and oral sampling location on DNA extraction and on genetic analysis from saliva were negligible. Conclusions Whole saliva samples with volumes of at least .10 ml were sufficient to extract good quality and quantity DNA. Using 10 ng of DNA per genotyping reaction, the obtained samples can be used for more than one hundred candidate gene assays. When saliva is collected with an absorbent device, most of the nucleic acid content remains in the device, therefore it is advisable to collect the device separately for later genetic analyses. PMID:22182470

  1. A preliminary report on the genetic variation in pointed gourd (Trichosanthes dioica Roxb.) as assessed by random amplified polymorphic DNA.

    PubMed

    Adhikari, S; Biswas, A; Bandyopadhyay, T K; Ghosh, P D

    2014-06-01

    Pointed gourd (Trichosanthes dioica Roxb.) is an economically important cucurbit and is extensively propagated through vegetative means, viz vine and root cuttings. As the accessions are poorly characterized it is important at the beginning of a breeding programme to discriminate among available genotypes to establish the level of genetic diversity. The genetic diversity of 10 pointed gourd races, referred to as accessions was evaluated. DNA profiling was generated using 10 sequence independent RAPD markers. A total of 58 scorable loci were observed out of which 18 (31.03%) loci were considered polymorphic. Genetic diversity parameters [average and effective number of alleles, Shannon's index, percent polymorphism, Nei's gene diversity, polymorphic information content (PIC)] for RAPD along with UPGMA clustering based on Jaccard's coefficient were estimated. The UPGMA dendogram constructed based on RAPD analysis in 10 pointed gourd accessions were found to be grouped in a single cluster and may represent members of one heterotic group. RAPD analysis showed promise as an effective tool in estimating genetic polymorphism in different accessions of pointed gourd. PMID:24873909

  2. Selection of single nucleotide polymorphisms and genotype quality for genomic prediction of genetic merit in dairy cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A process to prepare high-density genotypic data for use in genomic prediction of genetic merit was developed. Marker genotypes from over 51,000 single nucleotide polymorphisms (SNP) were generated for 3,139 Holstein bulls on the Illumina Bovine SNP50™ chip. The SNP were categorized by minor allele ...

  3. ASSOCIATIONS OF THE PORCINE IMMUNE RESPONSE AND GENETIC POLYMORPHISMS WITH THE SHEDDING OF SALMONELLA ENTERICA SEROVAR TYPHIMURIUM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major focus of our collaborative research is to investigate the porcine response to infection with Salmonella to 1) identify porcine genes differentially regulated during infection and 2) identify and associate genetic polymorphisms within these genes with infection status across swine populations...

  4. Additive genetic risk from five serotonin system polymorphisms interacts with interpersonal stress to predict depression.

    PubMed

    Vrshek-Schallhorn, Suzanne; Stroud, Catherine B; Mineka, Susan; Zinbarg, Richard E; Adam, Emma K; Redei, Eva E; Hammen, Constance; Craske, Michelle G

    2015-11-01

    Behavioral genetic research supports polygenic models of depression in which many genetic variations each contribute a small amount of risk, and prevailing diathesis-stress models suggest gene-environment interactions (G×E). Multilocus profile scores of additive risk offer an approach that is consistent with polygenic models of depression risk. In a first demonstration of this approach in a G×E predicting depression, we created an additive multilocus profile score from 5 serotonin system polymorphisms (1 each in the genes HTR1A, HTR2A, HTR2C, and 2 in TPH2). Analyses focused on 2 forms of interpersonal stress as environmental risk factors. Using 5 years of longitudinal diagnostic and life stress interviews from 387 emerging young adults in the Youth Emotion Project, survival analyses show that this multilocus profile score interacts with major interpersonal stressful life events to predict major depressive episode onsets (hazard ratio [HR] = 1.815, p = .007). Simultaneously, there was a significant protective effect of the profile score without a recent event (HR = 0.83, p = .030). The G×E effect with interpersonal chronic stress was not significant (HR = 1.15, p = .165). Finally, effect sizes for genetic factors examined ignoring stress suggested such an approach could lead to overlooking or misinterpreting genetic effects. Both the G×E effect and the protective simple main effect were replicated in a sample of early adolescent girls (N = 105). We discuss potential benefits of the multilocus genetic profile score approach and caveats for future research. (PsycINFO Database Record PMID:26595467

  5. Evolution of a genetic polymorphism with climate change in a Mediterranean landscape.

    PubMed

    Thompson, John; Charpentier, Anne; Bouguet, Guillaume; Charmasson, Faustine; Roset, Stephanie; Buatois, Bruno; Vernet, Philippe; Gouyon, Pierre-Henri

    2013-02-19

    Many species show changes in distribution and phenotypic trait variation in response to climatic warming. Evidence of genetically based trait responses to climate change is, however, less common. Here, we detected evolutionary variation in the landscape-scale distribution of a genetically based chemical polymorphism in Mediterranean wild thyme (Thymus vulgaris) in association with modified extreme winter freezing events. By comparing current data on morph distribution with that observed in the early 1970s, we detected a significant increase in the proportion of morphs that are sensitive to winter freezing. This increase in frequency was observed in 17 of the 24 populations in which, since the 1970s, annual extreme winter freezing temperatures have risen above the thresholds that cause mortality of freezing-sensitive morphs. Our results provide an original example of rapid ongoing evolutionary change associated with relaxed selection (less extreme freezing events) on a local landscape scale. In species whose distribution and genetic variability are shaped by strong selection gradients, there may be little time lag associated with their ecological and evolutionary response to long-term environmental change. PMID:23382198

  6. Genetic polymorphisms in ethanol metabolism: issues and goals for physiologically based pharmacokinetic modeling.

    PubMed

    Pastino, G M; Flynn, E J; Sultatos, L G

    2000-02-01

    Chronic exposure to excessive ethanol consumption has adverse effects on virtually all organs and tissues in the body, including but not limited to the liver, pancreas, reproductive organs, central nervous system, and the fetus. Exposure to ethanol can also enhance the toxicity of other chemicals. Not all persons exposed to the same amount of ethanol experience the same degree of adverse effects. For example, only 12% to 13% of alcohol abusers develop cirrhosis. Possible factors which may alter susceptibility include age, sex, nutritional status, health status (i.e., smokers) and race. Some of these factors affect susceptibility because they alter ethanol metabolism, which occurs primarily in the liver by alcohol dehydrogenase (ADH). Genetic polymorphisms for ADH partially account for the observed differences in ethanol elimination rates among various populations but the relative contribution to susceptibility is not completely understood. Incorporation of the kinetic parameters associated with ADH polymorphisms into a physiologically based pharmacokinetic (PBPK) model for ethanol will aid in assessing the relative contribution to susceptibility. The specific information required to develop this model includes Km and Kcat values for each ADH isoform and the amount of each isoform present in the liver. Blood ethanol concentrations (BEC) from various populations with known ADH phenotypes are also necessary to validate the model. The impact of inclusion of these data on PBPK model predictions was examined using available information from adult white and African American males. PMID:10711397

  7. Single-strand conformation polymorphism (SSCP) for the analysis of genetic variation.

    PubMed

    Gasser, Robin B; Hu, Min; Chilton, Neil B; Campbell, Bronwyn E; Jex, Aaron J; Otranto, Domenico; Cafarchia, Claudia; Beveridge, Ian; Zhu, Xingquan

    2006-01-01

    The accurate analysis of genetic variation has major implications in many areas of biomedical research, including the identification of infectious agents (such as parasites), the diagnosis of infections, and the detection of unknown or known disease-causing mutations. Mutation scanning methods, including PCR-coupled single-strand conformation polymorphism (SSCP), have significant advantages over many other nucleic acid techniques for the accurate analysis of allelic and mutational sequence variation. The present protocol describes the SSCP method of analysis, including all steps from the small-scale isolation of genomic DNA and PCR amplification of target sequences, through to the gel-based separation of amplicons and scanning for mutations by SSCP (either by the analysis of radiolabeled amplicons in mutation detection enhancement (MDE) gels or by non-isotopic SSCP using precast GMA gels). The subsequent sequence analysis of polymorphic bands isolated from gels is also detailed. The SSCP protocol can readily detect point mutations for amplicon sizes of up to 450-500 bp, and usually takes 1-2 days to carry out. This user-friendly, low-cost, potentially high-throughput platform has demonstrated the utility to study a wide range of pathogens and diseases, and has the potential to be applied to any gene of any organism. PMID:17406575

  8. Fas promoter polymorphisms: genetic predisposition to sarcoidosis in African-Americans

    PubMed Central

    Wasfi, Y. S.; Silveira, L. J.; Jonth, A.; Hokanson, J. E.; Fingerlin, T.; Sato, H.; Parsons, C. E.; Lympany, P.; Welsh, K.; du Bois, R. M.; Newman, L. S.; Maier, L. A.

    2011-01-01

    Apoptosis may perpetuate some forms of inflammation. Of the apoptotic pathway proteins, Fas is particularly overexpressed in sarcoidosis. We hypothesized that Fas promoter single nucleotide polymorphisms (SNPs) contribute to the development and severity of sarcoidosis. Associations of known Fas promoter SNPs (?670, ?690 and ?1377) and deduced haplotypes with sarcoidosis and sarcoidosis severity were evaluated using matched case–control (n = 656 pairs) and case–comparison (n = 656) studies, respectively, using conditional logistic regression. Hardy–Weinberg equilibrium was confirmed for all three polymorphisms in African-Americans (AA), and for the ?670 and ?1377 in whites. Genotype and allele frequencies were significantly different between whites and AA. Race-stratified analysis revealed that a common haplotype, ?1377G/?690T/?670G, was associated with sarcoidosis [odds ratio (OR) = 1.78, P = 0.05] only in AA. The haplotype ?1377G/?690C/?670A was negatively associated with sarcoidosis (OR = 0.39, P = 0.03) only in AA. In conclusion, the consistency of these findings suggests that Fas promoter genetic variants may be related to sarcoidosis disease risk in AA. PMID:18588573

  9. A genetic variation map for chicken with 2.8 million single nucleotide polymorphisms

    SciTech Connect

    Wong, G K; Hillier, L; Brandstrom, M; Croojmans, R; Ovcharenko, I; Gordon, L; Stubbs, L; Lucas, S; Glavina, T; Kaiser, P; Gunnarsson, U; Webber, C; Overton, I

    2005-02-20

    We describe a genetic variation map for the chicken genome containing 2.8 million single nucleotide polymorphisms (SNPs), based on a comparison of the sequences of 3 domestic chickens (broiler, layer, Silkie) to their wild ancestor Red Jungle Fowl (RJF). Subsequent experiments indicate that at least 90% are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about 5 SNP/kb for almost every possible comparison between RJF and domestic lines, between two different domestic lines, and within domestic lines--contrary to the idea that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated prior to domestication, and there is little to no evidence of selective sweeps for adaptive alleles on length scales of greater than 100 kb.

  10. Ancient Genetic Signatures of Orang Asli Revealed by Killer Immunoglobulin-Like Receptor Gene Polymorphisms

    PubMed Central

    NurWaliyuddin, Hanis Z. A.; Norazmi, Mohd N.; Edinur, Hisham A.; Chambers, Geoffrey K.; Panneerchelvam, Sundararajulu; Zafarina, Zainuddin

    2015-01-01

    The aboriginal populations of Peninsular Malaysia, also known as Orang Asli (OA), comprise three major groups; Semang, Senoi and Proto-Malays. Here, we analyzed for the first time KIR gene polymorphisms for 167 OA individuals, including those from four smallest OA subgroups (Che Wong, Orang Kanaq, Lanoh and Kensiu) using polymerase chain reaction-sequence specific primer (PCR-SSP) analyses. The observed distribution of KIR profiles of OA is heterogenous; Haplotype B is the most frequent in the Semang subgroups (especially Batek) while Haplotype A is the most common type in the Senoi. The Semang subgroups were clustered together with the Africans, Indians, Papuans and Australian Aborigines in a principal component analysis (PCA) plot and shared many common genotypes (AB6, BB71, BB73 and BB159) observed in these other populations. Given that these populations also display high frequencies of Haplotype B, it is interesting to speculate that Haplotype B may be generally more frequent in ancient populations. In contrast, the two Senoi subgroups, Che Wong and Semai are displaced toward Southeast Asian and African populations in the PCA scatter plot, respectively. Orang Kanaq, the smallest and the most endangered of all OA subgroups, has lost some degree of genetic variation, as shown by their relatively high frequency of the AB2 genotype (0.73) and a total absence of KIR2DL2 and KIR2DS2 genes. Orang Kanaq tradition that strictly prohibits intermarriage with outsiders seems to have posed a serious threat to their survival. This present survey is a demonstration of the value of KIR polymorphisms in elucidating genetic relationships among human populations. PMID:26565719

  11. Association of genetic polymorphisms in the telomerase reverse transcriptase gene with prostate cancer aggressiveness.

    PubMed

    Wu, Dapeng; Yu, Hongjie; Sun, Jielin; Qi, Jun; Liu, Qiang; Li, Ruipeng; Zheng, Siqun Lily; Xu, Jianfeng; Kang, Jian

    2015-07-01

    Telomerase reverse transcriptase (TERT), encoded by the TERT gene, is an essential component of telomerase, essential for the maintenance of telomere DNA length, chromosomal stability and cellular immortality. The aim of the present study was to evaluate the association between common genetic variations across the TERT gene region and prostate cancer (PCa) aggressiveness in a Chinese population. A total of 12 TERT tagging single-nucleotide polymorphisms (SNPs) were genotyped on the Sequenom Mass-ARRAY iPLEX® platform in a case-case study with 1,210 Chinese patients with PCa. Unconditional logistic regression was used to investigate the association of genotypes with PCa aggressiveness, Gleason grade and risk of developing early-onset PCa. It was observed that the C allele of the TERT intron 2 SNP (rs2736100) was significantly associated with reduced risk of PCa aggressiveness [odds ratio (OR)=0.81; 95% confidence interval (CI): 0.66-0.99; P=0.037]. This allele was also significantly correlated with a reduced risk of developing a tumor with a high Gleason score (>7; OR=0.83; 95% CI: 0.70-0.99; P=0.039). The T allele of the intron 4 SNP (rs10069690) was found to be significantly associated with a decreased risk for an aggressive form of PCa (OR=0.76; 95% CI: 0.59-0.97; P=0.030). In addition, the A allele of rs10078761 located at the 3' end of the TERT gene exhibited a statistically significant association with the reduced risk of developing a higher grade disease (OR=0.48; 95% CI: 0.28-0.81; P=0.006). However, no association between TERT polymorphisms and age at diagnosis was observed in the present study. The present findings demonstrated for the first time, to the best of our knowledge, that genetic variations across the TERT gene are associated with PCa aggressiveness in a Chinese Han population. PMID:25738283

  12. The DRD2 C957T polymorphism and the attentional blink--a genetic association study.

    PubMed

    Felten, Andrea; Montag, Christian; Kranczioch, Cornelia; Markett, Sebastian; Walter, Nora T; Reuter, Martin

    2013-08-01

    The attentional blink phenomenon (AB) describes a transient deficit in temporally selective visual attention regarding the processing of the second of two target stimuli in a rapid serial visual presentation (RSVP) task. The AB is a very prominent paradigm in the Cognitive Neurosciences that has been extensively studied by diverse psychophysiological techniques such as EEG or fMRI. Association studies from molecular genetics are scarce although the high heritability of higher cognitive functioning is proven. Only one seminal study reported an association between AB magnitude and the dopamine receptor D2 (DRD2) C957T polymorphism (Colzato et al., 2011). This functional polymorphism influences striatal D2 receptor binding affinity and thereby the efficacy of dopaminergic neurotransmission which is important for working memory and attentional processes. Colzato et al. (2011) reported that DRD2 C957T T/T-carriers exhibit a significant smaller AB than C-allele carriers. In the present study this influence of the DRD2 SNP on the AB could not be replicated in N=211 healthy participants. However, a significantly larger lag 1 sparing was observed for homozygous T/T-carriers. Moreover, carriers of at least one T-allele showed a significantly poorer performance in the identification of T1. In general, these results support the notion of a role of the dopaminergic system on the AB. However, as our results do not parallel previous findings the exact nature of this influence and its dependence on task parameters will have to be examined in further genetic association studies. PMID:23084608

  13. Harboring chaos

    E-print Network

    Anderson, Jeffrey A. (Jeffrey Arthur)

    2007-01-01

    Hurricane shelters have become the unknown point of last resort for many coastal communities. Harboring displaced populations during a hurricane and it's chaotic aftermath are no longer seen as a need in a coastal communities ...

  14. Effective utilization of genetic information for athletes and coaches: focus on ACTN3 R577X polymorphism

    PubMed Central

    Kikuchi, Naoki; Nakazato, Koichi

    2015-01-01

    Training variants (type, intensity, and duration of exercise) can be selected according to individual aims and fitness assessment. Recently, various methods of resistance and endurance training have been used for muscle hypertrophy and VO2max improvement. Although several genetic variants are associated with elite athletic performance and muscle phenotypes, genetic background has not been used as variant for physical training. ACTN3 R577X is a well-studied genetic polymorphism. It is the only genotype associated with elite athletic performance in multiple cohorts. This association is strongly supported by mechanistic data from an Actn3-knockout mouse model. In this review, possible guidelines are discussed for effective utilization of ACTN3 R577X polymorphism for physical training. PMID:26526670

  15. Effective utilization of genetic information for athletes and coaches: focus on ACTN3 R577X polymorphism.

    PubMed

    Kikuchi, Naoki; Nakazato, Koichi

    2015-09-01

    Training variants (type, intensity, and duration of exercise) can be selected according to individual aims and fitness assessment. Recently, various methods of resistance and endurance training have been used for muscle hypertrophy and VO2max improvement. Although several genetic variants are associated with elite athletic performance and muscle phenotypes, genetic background has not been used as variant for physical training. ACTN3 R577X is a well-studied genetic polymorphism. It is the only genotype associated with elite athletic performance in multiple cohorts. This association is strongly supported by mechanistic data from an Actn3-knockout mouse model. In this review, possible guidelines are discussed for effective utilization of ACTN3 R577X polymorphism for physical training. PMID:26526670

  16. Identifying Litchi (Litchi chinensis Sonn.) Cultivars and Their Genetic Relationships Using Single Nucleotide Polymorphism (SNP) Markers

    PubMed Central

    Liu, Wei; Xiao, Zhidan; Bao, Xiuli; Yang, Xiaoyan; Fang, Jing; Xiang, Xu

    2015-01-01

    Litchi is an important fruit tree in tropical and subtropical areas of the world. However, there is widespread confusion regarding litchi cultivar nomenclature and detailed information of genetic relationships among litchi germplasm is unclear. In the present study, the potential of single nucleotide polymorphism (SNP) for the identification of 96 representative litchi accessions and their genetic relationships in China was evaluated using 155 SNPs that were evenly spaced across litchi genome. Ninety SNPs with minor allele frequencies above 0.05 and a good genotyping success rate were used for further analysis. A relatively high level of genetic variation was observed among litchi accessions, as quantified by the expected heterozygosity (He = 0.305). The SNP based multilocus matching identified two synonymous groups, ‘Heiye’ and ‘Wuye’, and ‘Chengtuo’ and ‘Baitangli 1’. A subset of 14 SNPs was sufficient to distinguish all the non-redundant litchi genotypes, and these SNPs were proven to be highly stable by repeated analyses of a selected group of cultivars. Unweighted pair-group method of arithmetic averages (UPGMA) cluster analysis divided the litchi accessions analyzed into four main groups, which corresponded to the traits of extremely early-maturing, early-maturing, middle-maturing, and late-maturing, indicating that the fruit maturation period should be considered as the primary criterion for litchi taxonomy. Two subpopulations were detected among litchi accessions by STRUCTURE analysis, and accessions with extremely early- and late-maturing traits showed membership coefficients above 0.99 for Cluster 1 and Cluster 2, respectively. Accessions with early- and middle-maturing traits were identified as admixture forms with varying levels of membership shared between the two clusters, indicating their hybrid origin during litchi domestication. The results of this study will benefit litchi germplasm conservation programs and facilitate maximum genetic gains in litchi breeding programs. PMID:26261993

  17. Muju Virus, Harbored by Myodes regulus in Korea, Might Represent a Genetic Variant of Puumala Virus, the Prototype Arvicolid Rodent-Borne Hantavirus

    PubMed Central

    Lee, Jin Goo; Gu, Se Hun; Baek, Luck Ju; Shin, Ok Sarah; Park, Kwang Sook; Kim, Heung-Chul; Klein, Terry A.; Yanagihara, Richard; Song, Jin-Won

    2014-01-01

    The genome of Muju virus (MUJV), identified originally in the royal vole (Myodes regulus) in Korea, was fully sequenced to ascertain its genetic and phylogenetic relationship with Puumala virus (PUUV), harbored by the bank vole (My. glareolus), and a PUUV-like virus, named Hokkaido virus (HOKV), in the grey red-backed vole (My. rufocanus) in Japan. Whole genome sequence analysis of the 6544-nucleotide large (L), 3652-nucleotide medium (M) and 1831-nucleotide small (S) segments of MUJV, as well as the amino acid sequences of their gene products, indicated that MUJV strains from different capture sites might represent genetic variants of PUUV, the prototype arvicolid rodent-borne hantavirus in Europe. Distinct geographic-specific clustering of MUJV was found in different provinces in Korea, and phylogenetic analyses revealed that MUJV and HOKV share a common ancestry with PUUV. A better understanding of the taxonomic classification and pathogenic potential of MUJV must await its isolation in cell culture. PMID:24736214

  18. Genetic Polymorphisms Analysis of Pharmacogenomic VIP Variants in Miao Ethnic Group of Southwest China.

    PubMed

    Jin, Tianbo; Aikemu, Ainiwaer; Zhang, Mingxi; Geng, Tingting; Feng, Tian; Kang, Longli; Luo, Man Lin

    2015-01-01

    BACKGROUND Genetic polymorphisms have a potential clinical role in determining both inter-individual and inter-ethnic differences in drug efficacy, but we have not found any pharmacogenomics information regarding minorities, such as the Miao ethnic group. Our study aimed to screen numbers of the Miao ethnic group for genotype frequencies of VIP variants and to determine differences between the Miao and other human populations worldwide. MATERIAL AND METHODS In this study, we genotyped 66 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 98 unrelated, healthy Miao individuals from the Guizhou province and compared our data with 12 other populations, including 11 populations from the HapMap data set and Xi'an Han Chinese. RESULTS Using the ?2 test, we found that the allele frequencies of the VDR rs1544410 and VKORC1 (rs9934438) variants in the Miao population are quite different from that in other ethnic groups. Furthermore, we found that genotype frequencies of rs1801133 (MTHFR) in the 13 selected populations are significantly different. Population structure and F-statistics (Fst) analysis show that the genetic background of the Miao is relatively close to that of Chinese in metropolitan Denver, CO, USA (CHD). CONCLUSIONS Our results help complete the information provided by the pharmacogenomics database of the Miao ethnic group and provide a theoretical basis for safer drug administration, which may be useful for diagnosing and treating diseases in this population. PMID:26632549

  19. Ecogenetics of mercury: from genetic polymorphisms and epigenetics to risk assessment and decision-making.

    PubMed

    Basu, Niladri; Goodrich, Jaclyn M; Head, Jessica

    2014-06-01

    The risk assessment of mercury (Hg), in both humans and wildlife, is made challenging by great variability in exposure and health effects. Although disease risk arises following complex interactions between genetic ("nature") and environmental ("nurture") factors, most Hg studies thus far have focused solely on environmental factors. In recent years, ecogenetic-based studies have emerged and have started to document genetic and epigenetic factors that may indeed influence the toxicokinetics or toxicodynamics of Hg. The present study reviews these studies and discusses their utility in terms of Hg risk assessment, management, and policy and offers perspectives on fruitful areas for future research. In brief, epidemiological studies on populations exposed to inorganic Hg (e.g., dentists and miners) or methylmercury (e.g., fish consumers) are showing that polymorphisms in a number of environmentally responsive genes can explain variations in Hg biomarker values and health outcomes. Studies on mammals (wildlife, humans, rodents) are showing Hg exposures to be related to epigenetic marks such as DNA methylation. Such findings are beginning to increase understanding of the mechanisms of action of Hg, and in doing so they may help identify candidate biomarkers and pinpoint susceptible groups or life stages. Furthermore, they may help refine uncertainty factors and thus lead to more accurate risk assessments and improved decision-making. PMID:24038486

  20. Genetic Polymorphisms Analysis of Pharmacogenomic VIP Variants in Miao Ethnic Group of Southwest China

    PubMed Central

    Jin, Tianbo; Aikemu, Ainiwaer; Zhang, Mingxia; Geng, Tingting; Feng, Tian; Kang, Longli; Luo, Manlin

    2015-01-01

    Background Genetic polymorphisms have a potential clinical role in determining both inter-individual and inter-ethnic differences in drug efficacy, but we have not found any pharmacogenomics information regarding minorities, such as the Miao ethnic group. Our study aimed to screen numbers of the Miao ethnic group for genotype frequencies of VIP variants and to determine differences between the Miao and other human populations worldwide. Material/Methods In this study, we genotyped 66 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 98 unrelated, healthy Miao individuals from the Guizhou province and compared our data with 12 other populations, including 11 populations from the HapMap data set and Xi’an Han Chinese. Results Using the ?2 test, we found that the allele frequencies of the VDR rs1544410 and VKORC1 (rs9934438) variants in the Miao population are quite different from that in other ethnic groups. Furthermore, we found that genotype frequencies of rs1801133 (MTHFR) in the 13 selected populations are significantly different. Population structure and F-statistics (Fst) analysis show that the genetic background of the Miao is relatively close to that of Chinese in metropolitan Denver, CO, USA (CHD). Conclusions Our results help complete the information provided by the pharmacogenomics database of the Miao ethnic group and provide a theoretical basis for safer drug administration, which may be useful for diagnosing and treating diseases in this population. PMID:26632549

  1. Impact of the BDNF Val66Met Polymorphism on Cognition: Implications for Behavioral Genetics

    PubMed Central

    Dincheva, Iva; Glatt, Charles E.; Lee, Francis S.

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor family and is implicated as a modulator of neuronal survival and differentiation, synaptic plasticity, and higher order cognitive functions such as learning and memory. A common single-nucleotide polymorphism (SNP) has been identified in the human BDNF gene (BDNF Val66Met) that leads to decreased BDNF secretion and impairments in specific forms of learning in humans. To better understand the impact of this SNP on biological function, the authors generated a mouse model containing the BDNF Met allele, which they found to replicate the key phenotypes observed in humans and provided further insight into the functional impact of this SNP in vivo. They used a “bottom-up” approach to study the BDNF SNP, which provided external validation in biologically less complex, genetically uniform systems, which minimized the variability inherent in human studies. In this review, the authors discuss the impact of the BDNF SNP on learning and memory while providing arguments for the relevance of a vertically integrated approach to studying human genetic variants. PMID:22367929

  2. Lack of genetic association of cholesteryl ester transfer protein polymorphisms with late onset Alzheimers disease.

    PubMed

    Zhu, Haiyan; Gopalraj, Rangaraj K; Kelly, Jeremiah F; Bennett, David A; Estus, Steven

    Dysregulation of cholesterol homeostasis may be associated with the pathogenesis of coronary artery disease (CAD) and Alzheimers disease (AD). Recently, several single nucleotide polymorphisms (SNPs) in cholesteryl ester transfer protein (CETP) were associated with altered plasma CETP concentrations, cholesterol concentrations and CAD. Hence, these CETP SNPs represent excellent candidates for evaluating association with AD. To date, one study has evaluated the association between a single CETP SNP and AD. In this study, we examined three CETP SNPs to evaluate the genetic association of CETP with late onset AD on two study cohorts: the Religious Orders Study (ROS) series, including 85 AD and 70 non-AD individuals, and the University of Kentucky (UKY) series, including 78 AD and 84 non-AD individuals. Significant association between CETP genotypes or haplotypes and late onset AD was not detected in these two study cohorts. Moreover, the CETP genotypes and haplotypes were not significantly associated with AD when the populations were stratified for the presence or absence of apolipoprotein E4 (apoE4). In summary, CETP genetic variants were not associated with AD in two series. PMID:15882786

  3. The genetic polymorphisms and colonization process of olive fly populations in Turkey.

    PubMed

    Dogaç, Ersin; Kandemir, ?rfan; Taskin, Vatan

    2013-01-01

    The olive fruit fly, Bactrocera oleae, is the most important pest of olives in olive growing regions worldwide, especially in the Mediterranean basin and North America. Despite the economic importance of the olive fly, the colonization route of this species is unclear. We used nuclear microsatellite markers and mitochondrial DNA to provide information about the population structure and invasion route of olive fly populations in Turkey, as representative of the Eastern Mediterranean region. Adult fly samples were collected from 38 sublocations covering all olive growing regions in Turkey. The simple sequence variability data revealed a significant genetic variability in olive fly populations and a certain degree of differentiation between Mediterranean and Aegean populations. Mediterranean populations harbor higher levels of microsatellite variation than Aegean populations, which points to the eastern part of the Mediterranean as the putative source of invasion. mtDNA results suggest olive flies from the western part of Turkey are closely related to Italo-Aegean flies of the Mediterranean basin and the olive fly populations have invaded the northern part of the Mediterranean basin through western Turkey. In addition, finding specific American haplotypes in high frequencies might indicate that Turkey is the possible source of American olive fly populations. In order to more precisely characterize the population structure and invasion routes of this organism, more DNA-based sequence analysis should be carried out worldwide. PMID:23457499

  4. Regional Brain Shrinkage over Two Years: Individual Differences and Effects of Pro-Inflammatory Genetic Polymorphisms

    PubMed Central

    Persson, N.; Ghisletta, P.; Dahle, C.L.; Bender, A.R.; Yang, Y.; Yuan, P.; Daugherty, A.M.; Raz, N.

    2014-01-01

    We examined regional changes in brain volume in healthy adults (N = 167, age 19-79 years at baseline; N = 90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (HC), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the HC, CbH, In, OF, and the PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants mediated shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1? (IL-1?C-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFRC677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ?4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan. PMID:25264227

  5. Genetic association analysis between polymorphisms of HAIRY-AND-ENHANCER-OF SPLIT-7 and congenital scoliosis

    PubMed Central

    Gu, Zuchao; Qiu, Guixing; Zhang, Yu

    2015-01-01

    Objective: We explored the association between genetic polymorphisms of HAIRY-AND-ENHANCER-OF-SPLIT-7 (HES7) and congenital scoliosis (CS) in 246 cases of congenital scoliosis and non-congenital controls, in which the age and sex were fully matched. All participants were Chinese Han population. Methods: The genome DNA was extracted from peripheral blood sample. Two SNPs were defined for HES7 using NCBI database. The genotypes of two SNPs were determined by SNP stream UHT Genotyping System. Results: Polymorphisms were found in both SNPs and in accordance with Hardy-Weinberg equilibrium. For SNP rs3027279, the difference of two alleles (C and A) frequencies between CS and control groups Was statistically significant. Analysis also showed the difference of two genotypes (C/C and C/A) frequencies between two groups was significant (?2=5.857, P<0.05). For SNP rs1442849, both difference of two alleles (A and G) frequencies and difference of three genotypes (G/G, G/A and AA) frequencies between two groups were shown statistically significant. Conclusions: The unconditional Logistic regression analysis showed A/A genotype of SNP rsl442849 may be a protective factor (P=0.018<0.05, OR-0.35, 95% CI=0.17-0.74) for the onset of CS, while C/A genotype of SNP rs3027279 increased the onset risk (P=0.015<0.05, OR=1.93, 95% CI=1.13-3.30) of CS. Linkage disequilibrium analysis demonstrated the existence of linkage disequilibrium between the two SNPs.

  6. Impact of Intercellular Adhesion Molecule-1 Genetic Polymorphisms on Coronary Artery Disease Susceptibility in Taiwanese Subjects.

    PubMed

    Chou, Chi-Hung; Ueng, Kwo-Chang; Liu, Yu-Fan; Wu, Chih-Hsien; Yang, Shun-Fa; Wang, Po-Hui

    2015-01-01

    The principal pathogenesis of coronary artery disease (CAD) is coronary artery atherosclerosis, a chronic inflammatory disease of the vessel walls of the coronary artery. Intercellular adhesion molecule-1 (ICAM-1) displays an important role in the development of the inflammation reaction and atherosclerosis. Few studies report the association of ICAM-1 genetic polymorphisms with CAD in Taiwanese subjects. Therefore, we conducted a study to associate the single nucleotide polymorphisms (SNPs) of ICAM-1, rs5491, rs5498, rs281432 and rs3093030 with CAD. Five hundred and twenty-five male and female subjects, who received elective coronary angiography in Taiwan Chung Shan Medical University Hospital, were recruited to determine four ICAM-1 SNPs by real time-polymerase chain reaction and genotyping. The relationships among ICAM-1 SNPs, haplotypes, demographic and characteristics and CAD were analyzed. This study showed that rs281432 (C8823G) was the only ICAM-1 SNP which affect the development of CAD. Multivariate analysis revealed that ICAM-1 SNP rs281432 CC/CG [p=0.016; odds ratio (OR): 2.56, 95% confidence interval (CI): 1.19-5.56], male gender (p=0.018; OR: 1.66, 95% CI: 1.09-2.51), aspirin use in the past 7 days (p=0.001; OR: 2.05, 95% CI: 1.33-3.14), hypertension (p<0.001; OR: 2.15, 95% CI: 1.42-3.25), serum cardiac troponin I elevation (p<0.001; OR: 2.14, 95% CI: 1.47-3.24) and severe angina in recent 24 hours (p=0.001; OR: 1.97, 95% CI: 1.31- 2.95) increase the risk of CAD. In conclusion, ICAM-1 SNP rs281432 is an independent factor to predict the development of CAD. ICAM-1 SNP rs281432 homozygotic mutant GG can reduce the susceptibility to the CAD in Taiwanese subjects. PMID:26078712

  7. Plasmodium falciparum and Plasmodium vivax specific lactate dehydrogenase: genetic polymorphism study from Indian isolates.

    PubMed

    Keluskar, Priyadarshan; Singh, Vineeta; Gupta, Purva; Ingle, Sanjay

    2014-08-01

    Control and eradication of malaria is hindered by the acquisition of drug resistance by Plasmodium species. This has necessitated a persistent search for novel drugs and more efficient targets. Plasmodium species specific lactate dehydrogenase is one of the potential therapeutic and diagnostic targets, because of its indispensable role in endoerythrocytic stage of the parasite. A target molecule that is highly conserved in the parasite population can be more effectively used in diagnostics and therapeutics, hence, in the present study polymorphism in PfLDH (Plasmodiumfalciparum specific LDH) and PvLDH (Plasmodiumvivax specific LDH) genes was analyzed using PCR-single strand confirmation polymorphism (PCR-SSCP) and sequencing. Forty-six P. falciparum and thirty-five P. vivax samples were screened from different states of India. Our findings have revealed presence of a single PfLDH genotype and six PvLDH genotypes among the studied samples. Interestingly, along with synonymous substitutions, nonsynonymous substitutions were reported to be present for the first time in the PvLDH genotypes. Further, through amino acid sequence alignment and homology modeling studies we observed that the catalytic residues were conserved in all PvLDH genotypes and the nonsynonymous substitutions have not altered the enzyme structure significantly. Evolutionary genetics studies have confirmed that PfLDH and PvLDH loci are under strong purifying selection. Phylogenetic analysis of the pLDH gene sequences revealed that P. falciparum compared to P. vivax, has recent origin. The study therefore supports PfLDH and PvLDH as suitable therapeutic and diagnostic targets as well as phylogenetic markers to understand the genealogy of malaria species. PMID:24953504

  8. Prediction Formulas for Individual Opioid Analgesic Requirements Based on Genetic Polymorphism Analyses

    PubMed Central

    Yoshida, Kaori; Nishizawa, Daisuke; Ichinomiya, Takashi; Ichinohe, Tatsuya; Hayashida, Masakazu; Fukuda, Ken-ichi; Ikeda, Kazutaka

    2015-01-01

    Background The analgesic efficacy of opioids is well known to vary widely among individuals, and various factors related to individual differences in opioid sensitivity have been identified. However, a prediction model to calculate appropriate opioid analgesic requirements has not yet been established. The present study sought to construct prediction formulas for individual opioid analgesic requirements based on genetic polymorphisms and clinical data from patients who underwent cosmetic orthognathic surgery and validate the utility of the prediction formulas in patients who underwent major open abdominal surgery. Methods To construct the prediction formulas, we performed multiple linear regression analyses using data from subjects who underwent cosmetic orthognathic surgery. The dependent variable was 24-h postoperative or perioperative fentanyl use, and the independent variables were age, gender, height, weight, pain perception latencies (PPL), and genotype data of five single-nucleotide polymorphisms (SNPs). To examine the utility of the prediction formulas, we performed simple linear regression analyses using subjects who underwent major open abdominal surgery. Actual 24-h postoperative or perioperative analgesic use and the predicted values that were calculated using the multiple regression equations were incorporated as dependent and independent variables, respectively. Results Multiple linear regression analyses showed that the four SNPs, PPL, and weight were retained as independent predictors of 24-h postoperative fentanyl use (R2 = 0.145, P = 5.66 × 10-10) and the two SNPs and weight were retained as independent predictors of perioperative fentanyl use (R2 = 0.185, P = 1.99 × 10-15). Simple linear regression analyses showed that the predicted values were retained as an independent predictor of actual 24-h postoperative analgesic use (R2 = 0.033, P = 0.030) and perioperative analgesic use (R2 = 0.100, P = 1.09 × 10-4), respectively. Conclusions We constructed prediction formulas, and the possible utility of these prediction formulas was found in another type of surgery. PMID:25615449

  9. Genetic Polymorphisms in Inflammasome-Dependent Innate Immunity among Pediatric Patients with Severe Renal Parenchymal Infections

    PubMed Central

    Cheng, Chi-Hui; Lee, Yun-Shien; Chang, Chee-Jen; Lin, Jui-Che; Lin, Tzou-Yien

    2015-01-01

    Background Inflammasome innate immune response activation has been demonstrated in various inflammatory diseases and microbial infections. However, to our knowledge, no study has examined the inflammasome-dependent pathways in patients with urinary tract infection. Defective or variant genes associated with innate immunity are believed to alter the host’s susceptibility to microbial infection. This study investigated genetic polymorphisms in genes encoding inflammasomes and the subsequent released cytokines in pediatric patients with severe renal parenchymal infections. Methodology This study included patients diagnosed with acute pyelonephritis (APN) and acute lobar nephronia (ALN) who had no underlying disease or structural anomalies other than vesicoureteral reflux (VUR). Single nucleotide polymorphism (SNP) genotyping was performed in the genes associated with inflammasome formation and activation (NLRP3, CARD8) and subsequent IL–1? cytokine generation (IL–1?). Principal Findings A total of 40 SNPs were selected for initial genotyping. Analysis of samples from 48 patients each and 96 controls revealed that only nine SNPs (five SNPs in NLRP3; three SNPs in CARD8; one SNP in IL–1?) had heterozygosity rates >0.01. Hardy–Weinberg equilibrium was satisfied for the observed genotype frequencies of these SNPs. Analysis excluding patients with VUR, a well-known risk factor for severe UTIs, revealed a lower frequency of the CC genotype in NLRP3 (rs4612666) in patients with APN and ALN than in controls. Correction for multiple-SNP testing showed that the non-VUR subgroup of the APN+ALN combined patient groups remained significantly different from the control group (P < 0.0055). Conclusions This study is the first to suggest that the inflammasome-dependent innate immunity pathway is associated with the pathogenesis of pediatric severe renal parenchymal infections. Further investigation is warranted to clarify its pathogenic mechanism. PMID:26444566

  10. Start codon targeted (SCoT) polymorphism reveals genetic diversity in wild and domesticated populations of ramie (Boehmeria nivea L. Gaudich.), a premium textile fiber producing species.

    PubMed

    Satya, Pratik; Karan, Maya; Jana, Sourav; Mitra, Sabyasachi; Sharma, Amit; Karmakar, P G; Ray, D P

    2015-02-01

    Twenty-four start codon targeted (SCoT) markers were used to assess genetic diversity and population structure of indigenous, introduced and domesticated ramie (Boehmeria nivea L. Gaudich.). A total of 155 genotypes from five populations were investigated for SCoT polymorphism, which produced 136 amplicons with 87.5% polymorphism. Polymorphism information content and resolving power of the SCoT markers were 0.69 and 3.22, respectively. The Indian ramie populations exhibited high SCoT polymorphism (> 50%), high genetic differentiation (GST = 0.27) and moderate gene flow (Nm = 1.34). Analysis of molecular variance identified significant differences for genetic polymorphism among the populations explaining 13.1% of the total variation. The domesticated population exhibited higher genetic polymorphism and heterozygosity compared to natural populations. Cluster analysis supported population genetic analysis and suggested close association between introduced and domesticated genotypes. The present study shows effectiveness of employing SCoT markers in a cross pollinated heterozygous species like Boehmeria, and would be useful for further studies in population genetics, conservation genetics and cultivar improvement. PMID:25750860

  11. Start codon targeted (SCoT) polymorphism reveals genetic diversity in wild and domesticated populations of ramie (Boehmeria nivea L. Gaudich.), a premium textile fiber producing species

    PubMed Central

    Satya, Pratik; Karan, Maya; Jana, Sourav; Mitra, Sabyasachi; Sharma, Amit; Karmakar, P.G.; Ray, D.P.

    2015-01-01

    Twenty-four start codon targeted (SCoT) markers were used to assess genetic diversity and population structure of indigenous, introduced and domesticated ramie (Boehmeria nivea L. Gaudich.). A total of 155 genotypes from five populations were investigated for SCoT polymorphism, which produced 136 amplicons with 87.5% polymorphism. Polymorphism information content and resolving power of the SCoT markers were 0.69 and 3.22, respectively. The Indian ramie populations exhibited high SCoT polymorphism (> 50%), high genetic differentiation (GST = 0.27) and moderate gene flow (Nm = 1.34). Analysis of molecular variance identified significant differences for genetic polymorphism among the populations explaining 13.1% of the total variation. The domesticated population exhibited higher genetic polymorphism and heterozygosity compared to natural populations. Cluster analysis supported population genetic analysis and suggested close association between introduced and domesticated genotypes. The present study shows effectiveness of employing SCoT markers in a cross pollinated heterozygous species like Boehmeria, and would be useful for further studies in population genetics, conservation genetics and cultivar improvement. PMID:25750860

  12. Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle, Fujian Province

    PubMed Central

    Cai, Lin; Yu, Shun-Zhang; Zhang, Zuo-Feng

    2001-01-01

    AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristcs, diet intake, and alcohol and tobacco consumption of indivduals in our study were completed by a standardized questionnaire. PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 indivduals in gastric cancer group (6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significan difference between the two groups (two-tailed Fisher’s exact test, P = 0.066). Indivduals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR = 1.50) and C2/C2 (OR = 7.34) than indivduals in control group (?² = 4.597, for trend P = 0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among indivduals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that indivduals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effct in the development of gastric cancer in Changle county, Fujian Province. PMID:11854903

  13. Relationship of Genetic Polymorphisms of the Chemokine, CCL5, and Its Receptor, CCR5, with Coronary Artery Disease in Taiwan

    PubMed Central

    Ting, Ke-Hsin; Ueng, Kwo-Chang; Chiang, Whei-Ling; Chou, Ying-Erh; Yang, Shun-Fa; Wang, Po-Hui

    2015-01-01

    The chemokine receptor CCR5 polymorphism, which confers resistance to HIV infection, has been associated with reduced risk of cardiovascular disease. However, the association of the chemokine, CCL5, and its receptor, CCR5, polymorphism and coronary artery disease (CAD) in the Taiwanese has not been studied. In this study, 483 subjects who received elective coronary angiography were recruited from Chung Shan Medical University Hospital. CCL5-403 and CCR5-59029 were determined by polymerase chain reaction-restriction fragment length polymorphism. We found that CCL5-403 with TT genotype frequencies was significantly associated with the risk of CAD group (odds ratio = 3.063 and p = 0.012). Moreover, the frequencies of CCR5-59029 with GG or GA genotype were higher than AA genotype in acute coronary syndrome individuals (odds ratio = 1.853, CI = 1.176–2.921, p = 0.008). In conclusion, we found that CCL5-403 polymorphism may increase genetic susceptibility of CAD. CCL5-403 or CCR5-59029 single nucleotide polymorphism may include genotype score and it may predict cardiovascular event. PMID:26688689

  14. Relationship of Genetic Polymorphisms of the Chemokine, CCL5, and Its Receptor, CCR5, with Coronary Artery Disease in Taiwan.

    PubMed

    Ting, Ke-Hsin; Ueng, Kwo-Chang; Chiang, Whei-Ling; Chou, Ying-Erh; Yang, Shun-Fa; Wang, Po-Hui

    2015-01-01

    The chemokine receptor CCR5 polymorphism, which confers resistance to HIV infection, has been associated with reduced risk of cardiovascular disease. However, the association of the chemokine, CCL5, and its receptor, CCR5, polymorphism and coronary artery disease (CAD) in the Taiwanese has not been studied. In this study, 483 subjects who received elective coronary angiography were recruited from Chung Shan Medical University Hospital. CCL5-403 and CCR5-59029 were determined by polymerase chain reaction-restriction fragment length polymorphism. We found that CCL5-403 with TT genotype frequencies was significantly associated with the risk of CAD group (odds ratio = 3.063 and p = 0.012). Moreover, the frequencies of CCR5-59029 with GG or GA genotype were higher than AA genotype in acute coronary syndrome individuals (odds ratio = 1.853, CI = 1.176-2.921, p = 0.008). In conclusion, we found that CCL5-403 polymorphism may increase genetic susceptibility of CAD. CCL5-403 or CCR5-59029 single nucleotide polymorphism may include genotype score and it may predict cardiovascular event. PMID:26688689

  15. SOCS3 Genetic Polymorphism Is Associated With Clinical Features and Prognosis of Hepatocellular Carcinoma Patients Receiving Hepatectomy

    PubMed Central

    Jiang, Bei-ge; Yang, Yuan; Liu, Hui; Gu, Fang-ming; Yang, Yun; Zhao, Lin-Hao; Yuan, Sheng-xian; Wang, Ruo-yu; Zhang, Jin; Zhou, Wei-ping

    2015-01-01

    Abstract Previous studies showed that suppressor of cytokine signaling 3 (SOCS3) protein is associated with incidence and progression of hepatocellular carcinoma (HCC); however, the association between the genetic polymorphism of SOCS3 gene and HCC remains unknown. A total of 254 HCC patients and 354 healthy controls were enrolled. All HCC patients underwent partial hepatectomy as initial treatment and were followed. Three SOCS3 gene polymorphisms, namely, rs4969170 A>G, rs8064821 C>T, and rs12953258 C>A were determined. Our data show that the rs4969170 A>G polymorphism dramatically affects the susceptibility to HCC in our cohorts. Logistic regression analyses revealed that the rs4969170 GG is a risk factor for HCC after the adjustment with confounding factors. The rs4969170A>G polymorphism is also associated with the clinical features of HCC patients and predicts the postoperative relapse-free survival and overall survival. The rs4969170GG genotype carrier had a worse prognosis than the rs4969170AG and rs4969170AA carrier. Our findings suggest that the rs4969170A>G polymorphism of SOCS3 gene may be used as a prognostic predictor for HCC patients who underwent surgical treatment. PMID:26447993

  16. Genetic Polymorphisms of Interleukin-1 Alpha and the Vitamin D Receptor in Mexican Mestizo Patients with Intervertebral Disc Degeneration

    PubMed Central

    Cervin Serrano, Salvador; González Villareal, Dalia; Aguilar-Medina, Maribel; Romero-Navarro, Jose Guillermo; Romero Quintana, Jose Geovanni; Arámbula Meraz, Eliakym; Osuna Ramírez, Ignacio; Picos-Cárdenas, Veronica; Granados, Julio; Estrada-García, Iris; Sánchez-Schmitz, Guzman; Ramos-Payán, Rosalío

    2014-01-01

    Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population. PMID:25506053

  17. Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity.

    PubMed

    Gialeraki, Argyri; Markatos, Christos; Grouzi, Elisabeth; Merkouri, Efrosyni; Travlou, Anthi; Politou, Marianna

    2010-04-01

    Acenocoumarol is mainly catabolized by CYP2C9 isoform of cytochrome P450 (CYP) liver complex and exerts its anticoagulant effect through the inhibition of Vitamin K Epoxide Reductase (VKOR). The most important genetic polymorphisms which lead to an impaired enzymatic activity and therefore predispose to acenocoumarol sensitivity, are considered to be CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A, respectively. In this study we compared the results of the PGXThrombo StripAssay kit (ViennaLab Diagnostics,Vienna, Austria) with direct DNA sequencing and in house Restriction Fragment Length Polymorphisms (RFLP) for the detection of the aforementioned Single Nucleotide Polymorphisms (SNPs). The reverse hybridization StripAssay was found to be equally effective with RFLP and direct DNA sequencing for the detection of CYP2C9*2 and CYP2C9*3 polymorphisms, respectively. The comparison of the RFLP reference method with the reverse hybridization StripAssay for the detection of VKORC1-1639 G>A polymorphism showed that the reverse hybridization StripAsssay might misclassify some A/A homozygotes as heterozygotes. Optimization of the hybridization procedures may eliminate the extra low signal band observed in some samples at the reverse hybridization StripAssay and improve its diagnostic value. PMID:19562511

  18. Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders?

    PubMed Central

    Bennabi, Meriem; Delorme, Richard; Oliveira, José; Fortier, Catherine; Lajnef, Mohamed; Boukouaci, Wahid; Feugeas, Jean-Paul; Marzais, François; Gaman, Alexandru; Charron, Dominique; Ghaleh, Bijan; Krishnamoorthy, Rajagopal; Leboyer, Marion; Tamouza, Ryad

    2015-01-01

    Introduction In autism spectrum disorders (ASD), complex gene-environment interactions contribute to disease onset and progress. Given that gastro-intestinal dysfunctions are common in ASD, we postulated involvement of microbial dysbiosis in ASD and investigated, under a case-control design, the influence of DNA polymorphisms in the CLEC7A gene that encodes a pivotal fungal sensor, Dectin-1. Material and methods DNAs from 478 ASD patients and 351 healthy controls (HC) were analyzed for the CLEC7A rs16910631G/A and rs2078178 A/G single nucleotide polymorphisms (SNPs). Differences in the distribution of allele, genotype and haplotype by Chi-square testing and nonparametric analysis by Kruskal-Wallis/Mann–Whitney tests, where appropriate, were performed. The free statistical package R.2.13 software was used for the statistical analysis. Results We found that the CLEC7A rs2078178 G allele and GG genotype were more prevalent in HC as compared to ASD but failed to reach statistical significance for the latter (pc = 0.01, 0.06 respectively). However, after phenotype-based stratification, the CLEC7A rs2078178 G allele and GG genotype were found to be significantly more frequent in the Asperger group as compared to other ASD subsets (pc = 0.02, 0.01), a finding reinforced by haplotype analysis (rs2078178/rs16910631 G-G/G-G) (pc = 0.002). Further, intellectual quotient (IQ)-based stratification of ASD patients revealed that IQ values increase linearly along the CLEC7A rs2078178 AA, AG and GG genotypes (p = 0.05) and in a recessive manner (GG vs. AA+AG p = 0.02), further confirmed by haplotype distribution (CLEC7A rs2078178-16910631; A-G/A-G, A-G/G-G and G-G/G-G, p = 0.02, G-G/G-G vs. others, p = 0.01). Conclusion Our data suggest that the genetic diversity of CLEC7A gene influences the ASD phenotype by behaving as a disease specifier and imply that the genetic control of innate immune response could determine the ASD phenotype. PMID:26352598

  19. Relationships between genetic polymorphisms of E670G in PCSK9 gene and coronary artery disease: a meta-analysis

    PubMed Central

    Adi, Dilare; Xie, Xiang; Liu, Fen; Ma, Yi-Tong; Abudoukelimu, Mayila; Wu, Yun; An, Yong; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Wang, Yong-Tao; Chen, Bang-Dang

    2015-01-01

    Objective: Proprotein convertase subtilisin-like kexin type 9 (PCSK9) gene E670G Polymorphism has been reported to be associated with coronary artery disease (CAD) and risk factors. However, the results remain controversial. We sought to perform a meta-analysis to investigate the relationships between genetic polymorphisms of E670G in PCSK9 gene and the risk of CAD. Methods: Literature searches were performed to identify all published relevant case-control studies without any language restrictions. Meta-analysis was conducted using the Review Manager software (version 5.2). Heterogeneity was investigated and measured using Cochran’s Q-statistic and the inconsistency index (I2) test; Crude odds ratios (OR) with their corresponding 95% confidence interval (CI) were calculated. Results: A total of 5 case-control studies among 871 patients with CAD and 1144 control subjects were included in the meta-analysis. we found a correlation between PCSK9 genetic polymorphisms and increased risk for CAD under all of the genetic model (allele model: OR: 1.56, 95% CI: 1.21-2.01, P < 0.001; dominant model: OR: 1.46, 95% CI: 1.14-1.88, P = 0.003; recessive model: OR: 3.46, 95% CI: 1.19-10.10, P = 0.02; homozygous model: OR: 3.89, 95% CI: 1.35-11.20, P = 0.01; Heterozygous model: OR: 1.43, 95% CI: 1.08-1.92, P = 0.01; respectively). Conclusion: The results of the meta-analysis indicated that genetic polymorphism of E670G in PCSK9 gene might be involved in pathogenesis of CAD; the 670G carriers may be closely related to the risk of CAD. PMID:26550250

  20. Genetic Analysis Workshop 14: microsatellite and single-nucleotide polymorphism marker loci for genome-wide scans

    E-print Network

    2005-12-30

    Allen, Christopher I. Amos, Allison Ashley-Koch, Melissa Austin, Larry Atwood, Michael Badzioch, Agnes Baffoe-Bonnie, M. Michael Barmada, Terri Beaty, Lars Beckmann, Laura Bierut, Timothy Bishop, Michael Boehnke, Stefan Bohringer, George Bonney... AcceIntroduction Genetic Analysis Workshop 14: microsatellite and single-nucleotide polymorphism marker loci for genome-wide scans Joan E Bailey-Wilson*1, Laura Almasy2, Mariza de Andrade3, Julia Bailey4, Heike Bickeböller5, Heather J Cordell6, E...

  1. Genetic diversity and phylogenetic relationship among Tunisian cactus species (Opuntia) as revealed by random amplified microsatellite polymorphism markers.

    PubMed

    Bendhifi Zarroug, M; Baraket, G; Zourgui, L; Souid, S; Salhi Hannachi, A

    2015-01-01

    Opuntia ficus indica is one of the most economically important species in the Cactaceae family. Increased interest in this crop stems from its potential contribution to agricultural diversification, application in the exploitation of marginal lands, and utility as additional income sources for farmers. In Tunisia, O. ficus indica has been affected by drastic genetic erosion resulting from biotic and abiotic stresses. Thus, it is imperative to identify and preserve this germplasm. In this study, we focused on the use of random amplified microsatellite polymorphisms to assess genetic diversity among 25 representatives of Tunisian Opuntia species maintained in the collection of the National Institute of Agronomic Research of Tunisia. Seventy-two DNA markers were screened to discriminate accessions using 16 successful primer combinations. The high percentage of polymorphic band (100%), the resolving power value (5.68), the polymorphic information content (0.94), and the marker index (7.2) demonstrated the efficiency of the primers tested. Therefore, appropriate cluster analysis used in this study illustrated a divergence among the cultivars studied and exhibited continuous variation that occurred independently of geographic origin. O. ficus indica accessions did not cluster separately from the other cactus pear species, indicating that their current taxonomical classifications are not well aligned with their genetic variability or locality of origin. PMID:25730081

  2. [Pearl Harbor.

    ERIC Educational Resources Information Center

    Johnson, Jennifer, Ed.

    1992-01-01

    This issue of "Loblolly Magazine" was written in observance of the 50th anniversary of the U.S. entrance into World War II. The publication features interviews conducted by East Texas high school students with Clarence Otterman, one of the few survivors of the crew of the USS Arizona, which was bombed during the attack on Pearl Harbor, and with a…

  3. Genetic differentiation of Octopus minor (Mollusca, Cephalopoda) off the northern coast of China as revealed by amplified fragment length polymorphisms.

    PubMed

    Yang, J M; Sun, G H; Zheng, X D; Ren, L H; Wang, W J; Li, G R; Sun, B C

    2015-01-01

    Octopus minor (Sasaki, 1920) is an economically impor-tant cephalopod that is found in the northern coastal waters of China. In this study, we investigated genetic differentiation in fishery populations using amplified fragment length polymorphisms (AFLPs). A total of 150 individuals were collected from five locations: Dalian (DL), Yan-tai (YT), Qingdao (QD), Lianyungang (LY), and Zhoushan (ZS), and 243 reproducible bands were amplified using five AFLP primer com-binations. The percentage of polymorphic bands ranged from 53.33 to 76.08%. Nei's genetic identity ranged from 0.9139 to 0.9713, and the genetic distance ranged from 0.0291 to 0.0900. A phylogenetic tree was constructed using the unweighted pair group method with arithmetic mean, based on the genetic distance. The DL and YT populations origi-nated from one clade, while the QD, LY, and ZS populations originated from another. The results indicate that the O. minor stock consisted of two genetic populations with an overall significantly analogous FST value (0.1088, P < 0.05). Most of the variance was within populations. These findings will be important for more sustainable octopus fisheries, so that this marine resource can be conserved for its long-term utilization. PMID:26634529

  4. Associations between Salivary Testosterone Levels, Androgen-Related Genetic Polymorphisms, and Self-Estimated Ejaculation Latency Time

    PubMed Central

    Jern, Patrick; Westberg, Lars; Ankarberg-Lindgren, Carina; Johansson, Ada; Gunst, Annika; Sandnabba, N Kenneth; Santtila, Pekka

    2014-01-01

    Introduction Recently, testosterone (T) has been shown to be associated with premature ejaculation (PE) symptoms in the literature. Furthermore, studies suggest that the etiology of PE is partly under genetic control. Aim The aim of this study was to reassess findings suggesting an association between testosterone (T) and a key symptom of PE, ejaculation latency time (ELT), as well as exploratively investigating associations between six androgen-related genetic polymorphisms and ELT. Materials and Methods Statistical analyses were performed on a population-based sample of 1,429 Finnish men aged 18–45 years (M = 26.9, SD = 4.7). Genotype information was available for 1,345–1,429 of these (depending on the polymorphism), and salivary T samples were available from 384 men. Two androgen receptor gene-linked, two 5-alpha-reductase type 2-gene-linked, and two sex hormone-binding globuline gene-linked polymorphisms were genotyped. Main Outcome Measures Ejaculatory function was assessed using self-reported ELT. Results We found no association between salivary T levels and ELT. We found a nominally significant association between a 5-alpha-reductase type 2-gene-linked polymorphism (rs2208532) and ELT, but this association did not remain significant after correction for multiple testing. One single nucleotide polymorphism in the sex hormone-binding globulin gene (rs1799941) moderated (significantly after correction for multiple testing) the association between salivary T and ELT, so that A:A genotype carriers had significantly lower salivary T levels as a function of increasing ELT compared with other genotype groups. Conclusions We were unable to find support for the hypothesis suggesting an association between T levels and ELT, possibly because of the low number of phenotypically extreme cases (the sample used in the present study was population based). Our results concerning genetic associations should be interpreted with caution until replication studies have been conducted. Jern P, Westberg L, Ankarberg-Lindgren C, Johansson A, Gunst A, Sandnabba NK, and Santtila P. Associations between salivary testosterone levels, androgen-related genetic polymorphisms, and self-estimated ejaculation latency time. Sex Med 2014;2:107–114. PMID:25356307

  5. [Study on mitochondrial DNA genetic polymorphism of some yak breeds in China].

    PubMed

    Lai, Song-Jia; Wang, Ling; Liu, Yi-Ping; Li, Xue-Wei

    2005-05-01

    This study determined yak's complete sequence of mitochondrial DNA control region (D-loop) of 35 individuals in 5 yak breeds at the first time. The result showed that the length of D-loop in yak was 891 -895 bp. Content of nucleotide T, C, A, G were 28.5%, 25.3%, 32.5% and 13.7% respectively. There were 55 polymorphic sites (6.16% in total analyzed sites). The transition,transversion and insertion/deletion were found in this region.24 haplotypes was defined in this study, in which haplotype H4 and H6 were major haplotypes of Chinese yak. The distribution of all the haplotypes among the breeds was disequilibrium. The average diversity of haplotypes were 0.9697 +/-0.0180, indicating the abundance of haplotypes of yak's D-loop. The average nucleotide difference and the nucleotide diversity in Chinese yak breeds were 10.936% and 1.231% respectively. Nucleotide divergence and Kimura 2-parameter distance between yak breeds were 0.760% -2.155%, and 0.000-0.029 respectively. The results indicated that the genetic diversity of Chinese yak was very abundant. Analysis of molecular variance and network construction results indicated that there was significant divergence among Chinese yak breeds. The network construction indicated that Chinese yak had been divided into 2 types and had probably 2 maternal origins or 2 domesticated places. PMID:16018255

  6. Genetic influences on insight problem solving: the role of catechol-O-methyltransferase (COMT) gene polymorphisms

    PubMed Central

    Jiang, Weili; Shang, Siyuan; Su, Yanjie

    2015-01-01

    People may experience an “aha” moment, when suddenly realizing a solution of a puzzling problem. This experience is called insight problem solving. Several findings suggest that catecholamine-related genes may contribute to insight problem solving, among which the catechol-O-methyltransferase (COMT) gene is the most promising candidate. The current study examined 753 healthy individuals to determine the associations between 7 candidate single nucleotide polymorphisms on the COMT gene and insight problem-solving performance, while considering gender differences. The results showed that individuals carrying A allele of rs4680 or T allele of rs4633 scored significantly higher on insight problem-solving tasks, and the COMT gene rs5993883 combined with gender interacted with correct solutions of insight problems, specifically showing that this gene only influenced insight problem-solving performance in males. This study presents the first investigation of the genetic impact on insight problem solving and provides evidence that highlights the role that the COMT gene plays in insight problem solving. PMID:26528222

  7. Autoimmune Hepatitis in Brazilian Children: IgE and Genetic Polymorphisms in Associated Genes

    PubMed Central

    de Oliveira, Léa Campos; Goldberg, Anna Carla; Marin, Maria Lucia Carnevale; Schneidwind, Karina Rosa; Frade, Amanda Farage; Kalil, Jorge; Miura, Irene Kasue; Pugliese, Renata Pereira Sustovich; Danesi, Vera Lucia Baggio; Porta, Gilda

    2015-01-01

    Pediatric autoimmune hepatitis (AIH) patients present hypergammaglobulinemia, periportal CD8+ cytotoxic T cell infiltration, and cirrhosis. Autoantibody profile defines AIH types 1 and 2 in addition to strong association with HLA-DRB1. We previously detected increased IgE serum levels and sought to compare clinical and histological features according to IgE levels in AIH (n = 74, ages 1–14 years) patients. Additionally, we typed 117 patients and 227 controls for functional polymorphisms of IL4, IL13, IL5, and IL4RA genes involved in IgE switching and eosinophil maturation that might contribute to overall genetic susceptibility to AIH. Serum IgE levels were high in 55% of AIH-1, but only in 12% of AIH-2 (P = 0.003) patients. Liver IgE was present in 91.3% of AIH-1 patients. The A alleles at both IL13 rs20541 and IL4RA rs1805011 were associated with AIH-1 (P = 0.024, OR = 1.55 and P < 0.0001, OR = 2.15, resp.). Furthermore, individuals presenting homozygosis for the A allele at IL4RA rs1805011 and HLA-DRB1?03 and/or ?13 allele had sixfold greater risk to develop the disease (OR = 14.00, P < 0.001). The novel association suggests an additional role for IgE-linked immune response genes in the pathogenesis of AIH. PMID:26693492

  8. Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms.

    PubMed

    Figueroa, Jonine D; Koutros, Stella; Colt, Joanne S; Kogevinas, Manolis; Garcia-Closas, Montserrat; Real, Francisco X; Friesen, Melissa C; Baris, Dalsu; Stewart, Patricia; Schwenn, Molly; Johnson, Alison; Karagas, Margaret R; Armenti, Karla R; Moore, Lee E; Schned, Alan; Lenz, Petra; Prokunina-Olsson, Ludmila; Banday, A Rouf; Paquin, Ashley; Ylaya, Kris; Chung, Joon-Yong; Hewitt, Stephen M; Nickerson, Michael L; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Malats, Núria; Fraumeni, Joseph F; Chanock, Stephen J; Chatterjee, Nilanjan; Rothman, Nathaniel; Silverman, Debra T

    2015-11-01

    Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (P interaction ? .001), rs11892031 (UGT1A, P interaction = .01), and rs798766 (TMEM129-TACC3-FGFR3, P interaction = .03). There was limited evidence for multiplicative interactions. When we examined detailed data on a prevalent occupational exposure associated with increased bladder cancer risk, straight metalworking fluids, we also observed statistically significant additive interaction for rs798766 (TMEM129-TACC3-FGFR3, P interaction = .02), with the interaction more apparent in patients with tumors positive for FGFR3 expression. All statistical tests were two-sided. The interaction we observed for rs798766 (TMEM129-TACC3-FGFR3) with specific exposure to straight metalworking fluids illustrates the value of integrating germline genetic variation, environmental exposures, and tumor marker data to provide insight into the mechanisms of bladder carcinogenesis. PMID:26374428

  9. The genetic architecture of 3'untranslated region of the MICA gene: polymorphisms and haplotypes.

    PubMed

    Luo, Jia; Tian, Wei; Liu, Xue Xiang; Yu, JunLong; Li, LiXin; Pan, FengHua

    2013-10-01

    In this study, the 3'untranslated region (3'UTR) of MHC class I chain-related gene A (MICA) were investigated in 104 healthy, unrelated Han individuals recruited from northern China, using PCR-sequencing method. Nine polymorphic sites were detected, which were in very strong linkage disequilibrium with each other .Seven different MICA 3'UTR alleles were identified, among which UTR1 predominated (0.6971),followed by UTR2 (0.2356). Twenty-one extended haplotypes incorporating the 3'UTR and MICA exons 2-5 were observed in this population. Phylogenetic analysis revealed the existence of two MICA lineages, each with multiple subsets. The 2 lineages were primarily linked to UTR1 and UTR2 in the 3'UTR, respectively. Ewens-Watterson homozygosity statistics at MICA coding and 3'UTR regions were consistent with neutral expectations. Our data provided for the first time the data of genetic variation in the 3'UTR of MICA gene in human populations. The findings are valuable for future studies of the mechanisms underlying MICA post-transcriptional regulation, and will inform studies of evolution of the MHC gene complex. PMID:23806266

  10. Genetic polymorphisms in very important pharmacogenomic (VIP) variants in the Tibetan population.

    PubMed

    Jin, T B; Xun, X J; Shi, X G; Yuan, D Y; Feng, T; Geng, T T; Kang, L L

    2015-01-01

    Genetic polymorphisms of very important pharmacogenomic (VIP) variants are important for personalized medicine. However, these have not been extensively studied in the Tibetan population. In this study, 82 VIP variants were detected in the Tibetan and Han (HAN) populations from northwestern China. Subsequently, we compared the differences between the Tibetan population and ten populations, including the HAN, Japanese in Tokyo (JPT), Mexican ancestry in Los Angeles (MEX), Toscans in Italy (TSI), African ancestry in Southwest USA (ASW), Luhya in California Webuye, Kenya (LWK), Gujarati Indians in Houston, Texas (GIH), Maasai in Kinyawa, Kenya (MKK), Yoruba in Ibadan, Nigeria (YRI), and Utah residents with Northern and Western European ancestry from the CEPH collection (CEU). Using the ?(2) test, we identified differences in the frequency distribution of 4, 4, 7, 10, 11, 11, 13, 15, 19, and 20 loci in the Tibetan population, compared to the HAN, JPT, MEX, TSI, ASW, LWK, GIH, MKK, YRI, and CEU populations, respectively [P < 0.05/(82*10)]. rs2115819, rs9934438, and rs689466, located in the ALOX5 (arachidonate 5-lipoxygenase), VKORC1 (vitamin K epoxide reductase complex, subunit 1) and PTGS2 (prostaglandin-endoperoxide synthase 2) genes, respectively, in the Tibetan population were different from those in most of the populations. Our results complement the information provided by the database of pharmacogenomics on Tibetan people, and provide an avenue for personalized treatment in the Tibetan population. PMID:26505400

  11. Cyclic AMP-Responsive Element Modulator ? Polymorphisms Are Potential Genetic Risks for Systemic Lupus Erythematosus

    PubMed Central

    Guo, Qian; Chen, Xuyong; Du, Yan; Guo, Jianping; Su, Yin

    2015-01-01

    To investigate whether the cyclic AMP-responsive element modulator ? (CREM?) polymorphisms are novel susceptibility factors for systemic lupus erythematosus (SLE), four tag SNPs, rs1057108, rs2295415, rs11592925, and rs1148247, were genotyped in 889 SLE cases and 825 healthy controls. Association analyses were performed on whole dataset or clinical/serologic subsets. Association statistics were calculated by age and sex adjusted logistic regression. The G allele frequencies of rs2295415 and rs1057108 were increased in SLE patients, compared with healthy controls (rs2295415: 21.2% versus 17.8%, OR 1.244, P = 0.019; rs1057108: 30.8% versus 27.7%, OR 1.165, P = 0.049). The haplotype constituted by the two risk alleles “G-G” from rs1057108 and rs2295415 displayed strong association with SLE susceptibility (OR 1.454, P = 0.00056). Following stratification by clinical/serologic features, a suggestive association was observed between rs2295415 and anti-Sm antibodies-positive SLE (OR 1.382, P = 0.044). Interestingly, a potential protective effect of rs2295415 was observed for SLE patients with renal disorder (OR 0.745, P = 0.032). Our data provide first evidence that CREM? SNPs rs2295415 and rs1057108 maybe novel genetic susceptibility factors for SLE. SNP rs2295415 appears to confer higher risk to develop anti-Sm antibodies-positive SLE and may play a protective role against lupus nephritis. PMID:26601115

  12. Genetic polymorphisms in methyl-group metabolism and epigenetics: Lessons from humans and mouse models

    PubMed Central

    Zeisel, Steven H.

    2008-01-01

    Choline is an essential nutrient that is critical during fetal brain development. Choline deficiency, through disturbing methyl metabolism, may alter DNA methylation and thereby influence neural precursor cell proliferation and apoptosis. This results in long term alterations in brain structure and function, specifically memory function. A recommended dietary intake for choline in humans was set in 1998, and a portion of the choline requirement can be met via endogenous de novo synthesis of phosphatidylcholine catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT) in the liver. Though many foods contain choline, many humans do not get enough in their diets. When deprived of dietary choline, most adult men and postmenopausal women developed signs of organ dysfunction (fatty liver, liver or muscle cell damage). However, only a portion of premenopausal women developed such problems. The difference in requirement occurs because estrogen induces expression of the PEMT gene and allows premenopausal women to make more of their needed choline endogenously. In addition, there is significant variation in the dietary requirement for choline that can be explained by common genetic variants (single nucleotide polymorphisms; SNPs) in genes of choline and folate metabolism. Some of these increase the risk of choline deficiency many fold. These variations in choline requirement could have important implications for brain development. PMID:18789905

  13. Genetic Polymorphism, Telomere Biology and Non-Small Lung Cancer Risk.

    PubMed

    Wei, Rongrong; DeVilbiss, Frank T; Liu, Wanqing

    2015-10-20

    Recent genome-wide association studies (GWAS) have identified a number of chromosomal regions associated with the risk of lung cancer. Of these regions, single-nucleotide polymorphisms (SNPs), especially rs2736100 located in the telomerase reverse transcriptase (TERT) gene show unique and significant association with non-small cell lung cancer (NSCLC) in a few subpopulations including women, nonsmokers, East Asians and those with adenocarcinoma. Recent studies have also linked rs2736100 with a longer telomere length and lung cancer risk. In this review, we seek to summarize the relationship between these factors and to further link the underlying telomere biology to lung cancer etiology. We conclude that genetic alleles combined with environmental (e.g., less-smoking) and physiological factors (gender and age) that confer longer telomere length are strong risk factors for NSCLC. This linkage may be particularly relevant in lung adenocarcinoma driven by epidermal growth factor receptor (EGFR) mutations, as these mutations have also been strongly linked to female gender, less-smoking history, adenocarcinoma histology and East Asian ethnicity. By establishing this connection, a strong argument is made for further investigating of the involvement of these entities during the tumorigenesis of NSCLC. PMID:26554909

  14. Glutathione S-Transferase Gene Polymorphisms: Modulator of Genetic Damage in Gasoline Pump Workers.

    PubMed

    Priya, Kanu; Yadav, Anita; Kumar, Neeraj; Gulati, Sachin; Aggarwal, Neeraj; Gupta, Ranjan

    2015-11-01

    This study investigated genetic damage in gasoline pump workers using the cytokinesis blocked micronucleus (CBMN) assay. Blood and urine samples were collected from 50 gasoline pump workers and 50 control participants matched with respect to age and other confounding factors except for exposure to benzene through gasoline vapors. To determine the benzene exposure, phenol was analyzed in urinary samples of exposed and control participants. Urinary mean phenol level was found to be significantly high (P < 0.05) in exposed workers. The CBMN frequency was found to be significantly higher in gasoline pump workers (6.70 ± 1.78) when compared to control individuals (2.20 ± 0.63; P < 0.05). We also investigated influence of polymorphisms of GSTM1, GSTT1, and GSTP1 genes on CBMN frequency. The individuals having GSTM1 and GSTT1 null genotypes had significantly higher frequency of CBMN (P < 0.05). Our study indicates that chronic and long-term exposure of gasoline vapors can increase genotoxic risk in gasoline pump workers. PMID:26467191

  15. The Association between PTPN22 Genetic Polymorphism and Juvenile Idiopathic Arthritis (JIA) Susceptibility: An Updated Meta-Analysis

    PubMed Central

    DI, Yazhen; ZHONG, Shilling; WU, Ling; LI, Yunyan; SUN, Nan

    2015-01-01

    Background: Limited studies have focused on the association between the protein tyrosine phosphates non-receptor type 22 (PTPN22) genetic polymorphisms and Juvenile idiopathic arthritis (JIA) susceptibility in different populations, but the results were inconclusive. Therefore, this meta-analysis of PTPN22 polymorphism (1858 C>T) was performed to get a precise systematic estimation. The “rs” number of the PTPN22 polymorphism (1858 C>T) is 4. Methods: A systematic literature search strategy was carried out using English databases (PubMed, Embase.) for the eligible studies. We ultimately identified 11 records from 10 articles involving the relationship between PTPN22 genetic polymorphisms and JIA risk from PubMed and Embase databases. Overall, 4552 cases and 10161 controls were investigated in this study to evaluate the association between PTPN22 (C allele vs. T allele) genotype and JIA susceptibility. Results: Analysis using random effects model showed an increased risk of JIA with T allele of rs2476601 vs. A allele (P<0.001). Subgroup analysis suggested that the PTPN22 polymorphism (1858C>T) was significantly associated with JIA risk in America population (OR=1.52, 95% CI:1.30–1.78). Additionally, the subgroup analysis also showed that the associations were still significant in case number more than 500 (OR=1.38, 95% CI: 1.04–1.83), while in the case number less than 500 was OR=1.55, 95% CI: 1.39–1.72. Conclusions: SNPs of PTPN22 (1858C>T) showed an increased risk of developing JIA. PMID:26587490

  16. Effect of combined genetic polymorphisms on lung cancer risk in northern Thai women.

    PubMed

    Klinchid, Jaewwaew; Chewaskulyoung, Busyamas; Saeteng, Somchareon; Lertprasertsuke, Nirush; Kasinrerk, Watchara; Cressey, Ratchada

    2009-12-01

    Lung cancer is a major cause of cancer-related death in developed countries, and its incidence in developing countries is increasing. In Thailand, cancer incidences differ greatly from region to region, and lung cancer is the most common cancer in the northern Thai population. The polymorphic frequency of 10 genetic susceptibility genes and their association with lung cancer were examined in a northern Thai population: CYP1A1 (MspI), CYP1A1 (Ile462Val), CYP2E1 (PstI), CYP2E1 (DraI), GSTM1, GSTT1, MPO (AciI), OGG1 (Ser326Cys), TP53 (Arg72Pro), and MMP1(AluI). The 173 subjects were 91 lung cancer patients and 82 healthy volunteers. Although no significant association between any single genetic variant and lung cancer risk was observed, when genetic variants were analyzed in combination, a significant effect on lung cancer risk was found for the variant allele in a combination of five genes involved in oxidative stress and inflammatory response: GSTM1 (null), MPO (-463A), OGG1 (326Cys), TP53 (72Pro) (alias p53), MMP1 (2G). With a reference group of individuals carrying at least two wild-type genotypes of these five genes, it was found that an individual carrying three or more variant genotypes is at significantly higher risk of developing lung cancer with the increasing of odds ratios (OR) in concurrence with the number of variant genes. The OR was 2.41 (95% CI = 0.76-7.64), 3.90 (95% CI = 1.23-12.34), and 5.20 (95% CI = 1.31-20.54) for individuals carrying three, four, and five variants, respectively. After stratifying by sex, the OR was higher for women: OR 4.05 (95% CI = 0.44-36.94), 9.00 (95% CI = 0.95-84.89) and 18.00 (95% CI = 1.49-216.62) for three, four, and five variant genotypes, respectively. This augmented effect on lung cancer risk of variant genes involved in oxidative stress and inflammatory response in women with a low prevalence of smoking indicates their modifying effect on other risk factors, such as environmental cigarette smoke, air pollution, radon radiation, or infection of the airway. Confirmation would require further investigations with larger sample sizes. PMID:19963114

  17. Genetic variation and genetic structure of the endangered species Sinowilsonia henryi Hemsi. (Hamamelidaceae) revealed by amplified fragment length polymorphism (AFLP) markers.

    PubMed

    Zhang, H; Ji, W L; Li, M; Zhou, L Y

    2015-01-01

    Comprehensive research of genetic variation is crucial in designing conservation strategies for endangered and threatened species. Sinowilsonia henryi Hemsi. is a tertiary relic with a limited geographical distribution in the central and western areas of China. It is endangered because of climate change and habitat fragmentation over the last thousands of years. In this study, amplified fragment length polymorphism markers were utilized to estimate genetic diversity and genetic structure in and among S. henryi. In this study, Nei's genetic diversity and Shannon's information index were found to be 0.192 and 0.325 respectively, indicating a moderate-to-high genetic diversity in species. According to analysis of molecular variation results, 32% of the genetic variation was shown to be partitioned among populations, demonstrating a relatively high genetic divergence; this was supported by principal coordinate analysis and unweighted pair-group method with arithmetic average analysis. Moreover, the Mantel test showed that there was no significant correlation between genetic and geographical distances. The above results can be explained by the effects of habitat fragmentation?history traits, and gene drift. Based on the results, several implications were indicated and suggestions proposed for preservation strategies for this species. PMID:26505383

  18. Impact of ESR1 Gene Polymorphisms on Migraine Susceptibility

    PubMed Central

    Li, Li; Liu, Ruozhuo; Dong, Zhao; Wang, Xiaolin; Yu, Shengyuan

    2015-01-01

    Abstract An increasing number of studies have explored genetic associations between the functionally important polymorphisms in estrogen receptor 1 (ESR1) gene and migraine susceptibility. The previously reported associations have nevertheless been inconsistent. The present work incorporating the published data derived from 8 publications was performed to assess the impact of these polymorphisms on incident migraine. Strength of the genetic risk was estimated by means of an odds ratio along with the 95% confidence interval (OR and 95% CI). From the results, we found individuals who harbored the 325-GG genotype, compared with those harboring the CC genotype or CG and CC combined genotypes, had almost 50% greater risk of migraine. The same genetic models showed notable associations in subgroups of Caucasians and migraine with aura (MA). For 594G>A, a moderately increased risk of migraine was seen under AG versus GG. The AA?+?AG versus GG model, however, showed a borderline association with migraine. Subgroup analyses according to ethnicity and subtype of migraine provided statistical evidence of significantly increased risk of migraine in Caucasians and of a marginal association with MA, respectively. Both 325C>G and 594G>A polymorphisms showed no major effects either in males or in females. Based on the statistical data, we conclude some of the ESR1 gene polymorphisms may have major contributions to the pathogenesis of migraine in Caucasian populations. PMID:26334887

  19. Genetic Diversity and Relatedness of Sweet Cherry (Prunus Avium L.) Cultivars Based on Single Nucleotide Polymorphic Markers

    PubMed Central

    Fernandez i Marti, Angel; Athanson, Blessing; Koepke, Tyson; Font i Forcada, Carolina; Dhingra, Amit; Oraguzie, Nnadozie

    2012-01-01

    Most previous studies on genetic fingerprinting and cultivar relatedness in sweet cherry were based on isoenzyme, RAPD, and simple sequence repeat (SSR) markers. This study was carried out to assess the utility of single nucleotide polymorphism (SNP) markers generated from 3? untranslated regions (UTR) for genetic fingerprinting in sweet cherry. A total of 114 sweet cherry germplasm representing advanced selections, commercial cultivars, and old cultivars imported from different parts of the world were screened with seven SSR markers developed from other Prunus species and with 40 SNPs obtained from 3? UTR sequences of Rainier and Bing sweet cherry cultivars. Both types of marker study had 99 accessions in common. The SSR data was used to validate the SNP results. Results showed that the average number of alleles per locus, mean observed heterozygosity, expected heterozygosity, and polymorphic information content values were higher in SSRs than in SNPs although both set of markers were similar in their grouping of the sweet cherry accessions as shown in the dendrogram. SNPs were able to distinguish sport mutants from their wild type germplasm. For example, “Stella” was separated from “Compact Stella.” This demonstrates the greater power of SNPs for discriminating mutants from their original parents than SSRs. In addition, SNP markers confirmed parentage and also determined relationships of the accessions in a manner consistent with their pedigree relationships. We would recommend the use of 3? UTR SNPs for genetic fingerprinting, parentage verification, gene mapping, and study of genetic diversity in sweet cherry. PMID:22737155

  20. The effect of genetic polymorphisms of TLR2 and TLR4 in Turkish patients with coronary artery disease.

    PubMed

    Guven, Mehmet; Ismailoglu, Ziya; Batar, Bahadir; Unal, Selin; Onaran, Ilhan; Karadag, Bilgehan; Ongen, Zeki

    2015-03-01

    Coronary artery disease (CAD), being a multifactorial disease process, has been suggested to be associated by the interaction of both environmental and genetic risk factors. Toll-like receptors (TLRs) are related to the receptors of the innate immune system which serves as the recognition of the conserved pathogen motifs and the activation of the signals that stimulate inflammatory genes. In this study, we investigated the relationship between the polymorphisms in the TLR2-Arg753Gly, TLR4-Asp299Gly and Thr399Ile gene and CAD. The study population consisted of 300 patients (149 men, 151 women) with angiographically documented CAD. The polymorphisms were genotyped by real time PCR. No association between TLR2-Arg677Trp or TLR4-Asp299Gly and -Thr399Ile gene polymorphisms and the presence or the severity of CAD was observed. On the other hand, the TLR2-Arg753Arg genotype seemed to have a protective effect against development of CAD (OR=0.17; 95% CI=0.04-0.83). Our findings suggest that TLR2-Arg753Gly polymorphism is associated with CAD susceptibility in Turkish patients. PMID:25542811

  1. Genetic distribution and association analysis of DRD2 gene polymorphisms with major depressive disorder in the Chinese Han population

    PubMed Central

    He, Mei; Yan, Hong; Duan, Zhao-Xia; Qu, Wei; Gong, Hai-Yan; Fan, Zheng-Li; Kang, Jian-Yi; Li, Bing-Cang; Wang, Jian-Min

    2013-01-01

    Dopamine D2 receptor is involved in reward-mediating mesocorticolimbic pathways. It plays an important role in major depressive disorder (MDD). Three gene polymorphisms Taq1A, C957T and -141C ins/del, were identified in the DRD2 gene among the Western population. These variants in the DRD2 gene might be associated with the susceptibility of MDD patients through affecting the bioeffects of endogenous dopamine neurotransmission. However, little is known about their occurrence in Chinese population and their association with the susceptibility of patients with major depressive disorder. In this study, a total of 338 unrelated adult Chinese Han population, including 224 healthy volunteers and 114 patients with major depressive disorder, were recruited. DRD2 polymorphisms (Taq1A and -141C ins/del) were detected using restriction fragment length polymorphism (RFLP) analysis and the C957T were detected by sequencing directly. As a result, three polymorphisms were identified in Chinese Han population and all were common SNP. However, we could detect no evidence of genetic association between 3 markers in DRD2 and major depressive disorder in the Chinese Han population. To conclude, this result suggests that Taq1A, C957T and -141C ins/del of DRD2 gene may not be associated with major depressive disorder, also may be the sample sizes too small to allow a meaningful test. PMID:23696934

  2. Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population

    PubMed Central

    2010-01-01

    Background The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored. Methods In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP. Results We found an increased NPC risk associated with the MDM2 GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58). Conclusion The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing NPC. PMID:20398418

  3. Association of VEGF Genetic Polymorphisms with Recurrent Spontaneous Abortion Risk: A Systematic Review and Meta-Analysis

    PubMed Central

    Xu, Xinghua; Du, Chigang; Li, Huihui; Du, Jing; Yan, Xue; Peng, Lina; Li, Guangyao; Chen, Zi-Jiang

    2015-01-01

    Background Studies of the associations between the genetic polymorphisms of the vascular endothelial growth factor (VEGF) gene and recurrent spontaneous abortion (RSA) have revealed conflicting results. The present meta-analysis was performed to provide a more precise estimation of these relationships and to explore potential sources of heterogeneity that may have influenced the reported disparities. Methods An extensive literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library through June 6, 2014. Crude odds ratio (OR) with 95% confidence intervals were calculated. Results 10 case-control studies including 1,832 RSA patients and 2,271 healthy controls were identified. Meta-analysis indicated that rs1570360, rs3025039, rs2010963, and rs3025020 polymorphisms in the VEGF gene correlated with elevated RSA risk. The rs1570360 variant was statistically significantly relevant to RSA risk among non-Asian populations. Interestingly, the rs3025039 variant was statistically significantly relevant to RSA risk among Asian populations. Conclusions The current meta-analysis indicates that rs1570360, rs3025039, rs2010963, and rs3025020 polymorphisms increase RSA susceptibility. Moreover, rs1570360 and rs3025039 polymorphisms may play various roles in RSA susceptibility in various geographic groups. PMID:25894555

  4. Identification of Pyrus single nucleotide polymorphisms (SNPs) and evaluation for genetic mapping in European pear and interspecific Pyrus hybrids.

    PubMed

    Montanari, Sara; Saeed, Munazza; Knäbel, Mareike; Kim, YoonKyeong; Troggio, Michela; Malnoy, Mickael; Velasco, Riccardo; Fontana, Paolo; Won, KyungHo; Durel, Charles-Eric; Perchepied, Laure; Schaffer, Robert; Wiedow, Claudia; Bus, Vincent; Brewer, Lester; Gardiner, Susan E; Crowhurst, Ross N; Chagné, David

    2013-01-01

    We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear ('Old Home'×'Louise Bon Jersey') and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality. PMID:24155917

  5. Identification of Pyrus Single Nucleotide Polymorphisms (SNPs) and Evaluation for Genetic Mapping in European Pear and Interspecific Pyrus Hybrids

    PubMed Central

    Troggio, Michela; Malnoy, Mickael; Velasco, Riccardo; Fontana, Paolo; Won, KyungHo; Durel, Charles-Eric; Perchepied, Laure; Schaffer, Robert; Wiedow, Claudia; Bus, Vincent; Brewer, Lester; Gardiner, Susan E.; Crowhurst, Ross N.; Chagné, David

    2013-01-01

    We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear (‘Old Home’בLouise Bon Jersey’) and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality. PMID:24155917

  6. Genetic polymorphisms and haplotypes of TRAIL gene correlate with NSCLC susceptibility in a group of Chinese patients

    PubMed Central

    Luo, Jun; Xiong, Jinmeng; Wu, Jianghua; Ye, Xujun

    2015-01-01

    The association between genetic polymorphisms and haplotypes of TNF-related apoptosis-inducing ligand (TRAIL) and the NSCLC development was investigated in 592 Chinese patients and the prevalence of G1525A, G1588A, and C1595T gene polymorphisms compared between the NSCLC patients and control group in this study. It was found that the frequencies of variant allele A and genotype GA+AA of G1525A were significantly lower and those of variant alleles A and T of G1588A and C1595T significantly higher in the NSCLC patients compared with those in control. The frequencies of variant allele T and genotype CT+TT of C1595T were significantly higher in stage III and IV than in stage I and II of the patients. Moreover, the frequencies of variant allele A and genotype GA+AA of G1525A were significantly higher in stage III and IV than in stage I and II of the patients. In addition, TRAIL gene variants G1525A/G1588A/C1595T were found to be in complete linkage disequilibrium in all patients. Compared with the healthy people, the frequency of AAT haplotype was significantly lower whereas that of GAT haplotype significantly higher in NSCLC patients. The results indicated that the genetic polymorphisms and haplotypes of TRAIL gene correlated significantly with the NSCLC susceptibility in the group of Chinese patients.

  7. Genetic Dissection of New Genotypes of Drumstick Tree (Moringa oleifera Lam.) Using Random Amplified Polymorphic DNA Marker

    PubMed Central

    Rufai, Shamsuddeen; Hanafi, M. M.; Rafii, M. Y.; Ahmad, S.; Arolu, I. W.; Ferdous, Jannatul

    2013-01-01

    The knowledge of genetic diversity of tree crop is very important for breeding and improvement program for the purpose of improving the yield and quality of its produce. Genetic diversity study and analysis of genetic relationship among 20 Moringa oleifera were carried out with the aid of twelve primers from, random amplified polymorphic DNA marker. The seeds of twenty M. oleifera genotypes from various origins were collected and germinated and raised in nursery before transplanting to the field at University Agricultural Park (TPU). Genetic diversity parameter, such as Shannon's information index and expected heterozygosity, revealed the presence of high genetic divergence with value of 1.80 and 0.13 for Malaysian population and 0.30 and 0.19 for the international population, respectively. Mean of Nei's gene diversity index for the two populations was estimated to be 0.20. In addition, a dendrogram constructed, using UPGMA cluster analysis based on Nei's genetic distance, grouped the twenty M. oleifera into five distinct clusters. The study revealed a great extent of variation which is essential for successful breeding and improvement program. From this study, M. oleifera genotypes of wide genetic origin, such as T-01, T-06, M-01, and M-02, are recommended to be used as parent in future breeding program. PMID:23862149

  8. Genetic polymorphisms as determinants for disease preventive effects of vitamin E

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polymorphisms in genes involved in vitamin E uptake, distribution, metabolism and molecular action may be important determinants for the protective effects of vitamin E supplementation. The haptoglobin 2-2 polymorphism is associated with increased production of oxygen free radicals and the consequen...

  9. Morph-specific genetic and environmental variation in innate and acquired immune response in a color polymorphic raptor.

    PubMed

    Gangoso, Laura; Roulin, Alexandre; Ducrest, Anne-Lyse; Grande, Juan Manuel; Figuerola, Jordi

    2015-08-01

    Genetic color polymorphism is widespread in nature. There is an increasing interest in understanding the adaptive value of heritable color variation and trade-off resolution by differently colored individuals. Melanin-based pigmentation is often associated with variation in many different life history traits. These associations have recently been suggested to be the outcome of pleiotropic effects of the melanocortin system. Although pharmacological research supports that MC1R, a gene with a major role in vertebrate pigmentation, has important immunomodulatory effects, evidence regarding pleiotropy at MC1R in natural populations is still under debate. We experimentally assessed whether MC1R-based pigmentation covaries with both inflammatory and humoral immune responses in the color polymorphic Eleonora's falcon. By means of a cross-fostering experiment, we disentangled potential genetic effects from environmental effects on the covariation between coloration and immunity. Variation in both immune responses was primarily due to genetic factors via the nestlings' MC1R-related color genotype/phenotype, although environmental effects via the color morph of the foster father also had an influence. Overall, dark nestlings had lower immune responses than pale ones. The effect of the color morph of the foster father was also high, but in the opposite direction, and nestlings raised by dark eumelanic foster fathers had higher immune responses than those raised by pale foster fathers. Although we cannot completely discard alternative explanations, our results suggest that MC1R might influence immunity in this species. Morph-specific variation in immunity as well as pathogen pressure may therefore contribute to the long-term maintenance of genetic color polymorphism in natural populations. PMID:25834999

  10. GENETIC DIVERSITY AND STRUCTURE OF AN ESTUARINE FISH (FUNDULUS HETEROCLITUS) INDIGENOUS TO A HIGHLY CONTAMINATED URBAN HARBOR

    EPA Science Inventory

    Intense directional selection on isolated populations can result in loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that toxic pollutants, specifically, polychlor...

  11. GENETIC DIVERSITY AND STRUCTURE OF AN ESTUARINE FISH (FUNDULUS HETEROCLITIS) INDIGENOUS TO SITES ASSOCIATED WITH A HIGHLY CONTAMINATED URBAN HARBOR

    EPA Science Inventory

    Intense directional selection on isolated populations can result in loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that toxic pollutants, specifically, polychlor...

  12. Development of an Ultra-Dense Genetic Map of the Sunflower Genome Based on Single-Feature Polymorphisms

    PubMed Central

    Bowers, John E.; Nambeesan, Savithri; Corbi, Jonathan; Barker, Michael S.; Rieseberg, Loren H.; Knapp, Steven J.; Burke, John M.

    2012-01-01

    The development of ultra-dense genetic maps has the potential to facilitate detailed comparative genomic analyses and whole genome sequence assemblies. Here we describe the use of a custom Affymetrix GeneChip containing nearly 2.4 million features (25 bp sequences) targeting 86,023 unigenes from sunflower (Helianthus annuus L.) and related species to test for single-feature polymorphisms (SFPs) in a recombinant inbred line (RIL) mapping population derived from a cross between confectionery and oilseed sunflower lines (RHA280×RHA801). We then employed an existing genetic map derived from this same population to rigorously filter out low quality data and place 67,486 features corresponding to 22,481 unigenes on the sunflower genetic map. The resulting map contains a substantial fraction of all sunflower genes and will thus facilitate a number of downstream applications, including genome assembly and the identification of candidate genes underlying QTL or traits of interest. PMID:23284684

  13. A primary genetic linkage map of 14 polymorphic loci for the short arm of human chromosome 8

    SciTech Connect

    Emi, Mitsuru; Fujiwara, Yoshiyuki; Nakamura, Yusuke )

    1993-03-01

    A genetic linkage map of markers for the short arm of human chromosome 8 has been constructed with 14 polymorphic DNA markers on the basis of genotypes obtained in 40 CEPH reference families. This unbroken map spans 45 cM in males and 79 cM in females. The 14 markers include three genes, MSR, LPL, and NEFL, and one anonymous DNA segment that were previously assigned to chromosome 8. The other 10 marker had been isolated from a chromosome 8-specific cosmid library and physically localized to chromosomal bands by fluorescence in situ hybridization. The order of loci determined by genetic linkage was consistent with their physical locations. This map will facilitate efficient linkage studies of human genetic diseases that may be segregating on chromosome 8p and will provide anchor points for development of high-resolution maps for this chromosomal region. 21 refs., 2 figs., 3 tabs.

  14. Genetic Polymorphisms in Monoamine Systems and Outcome of Cognitive Behavior Therapy for Social Anxiety Disorder

    PubMed Central

    Andersson, Evelyn; Rück, Christian; Lavebratt, Catharina; Hedman, Erik; Schalling, Martin; Lindefors, Nils; Eriksson, Elias; Carlbring, Per; Andersson, Gerhard; Furmark, Tomas

    2013-01-01

    Objective The role of genetics for predicting the response to cognitive behavior therapy (CBT) for social anxiety disorder (SAD) has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR), the catechol-o-methyltransferase (COMT) val158met, and the tryptophan hydroxylase-2 (TPH2) G-703Tpolymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients. Method Participants were recruited from two separate randomized controlled CBT trials (trial 1: n?=?112, trial 2: n?=?202). Genotyping were performed on DNA extracted from blood or saliva samples. Effects were analyzed at follow-up (6 or 12 months after treatment) for both groups and for each group separately at post-treatment. The main outcome measure was the Liebowitz Social Anxiety Scale Self-Report. Results At long-term follow-up, there was no effect of any genotype, or gene × gene interactions, on treatment response. In the subsamples, there was time by genotype interaction effects indicating an influence of the TPH2 G-703T-polymorphism on CBT short-term response, however the direction of the effect was not consistent across trials. Conclusions None of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD. Trial Registration ClinicalTrials.gov (ID-NCT0056496) PMID:24260145

  15. Genetic polymorphism directs IL-6 expression in fibroblasts but not selected other cell types.

    PubMed

    Noss, Erika H; Nguyen, Hung N; Chang, Sook Kyung; Watts, Gerald F M; Brenner, Michael B

    2015-12-01

    Interleukin (IL)-6 blockade is an effective treatment for rheumatoid arthritis (RA), and synovial fibroblasts are a major IL-6 producer in the inflamed joint. We found that human RA and osteoarthritis (OA) synovial fibroblasts derived from independent donors reproducibly segregated into low, medium, and high IL-6 producers, independent of stimulus, cell passage, or disease state. IL-6 expression pattern correlated strongly with total mRNA expression, not mRNA stability, suggesting transcriptional rather than posttranscriptional regulation. High-fibroblast IL-6 expression was significantly associated with the IL-6 proximal promoter single nucleotide polymorphism (SNP) rs1800795 minor allele (CC) genotype. In contrast, no association between this SNP and IL-6 production was detected in CD14(+) monocytes, another major producer of synovial IL-6. Luciferase expression assays confirmed that this SNP was associated with differential IL-6 expression in fibroblasts. To date, several association studies examining rs1800795 allele frequency and disease risk have reported seemingly conflicting results ranging from no association to association with either the major or minor allele across a spectrum of conditions, including cancer and autoimmune, cardiovascular, infectious, and metabolic diseases. This study points to a prominent contribution from promoter genetic variation in fibroblast IL-6 regulation, but not in other IL-6-producing cell types. We propose that some of the heterogeneity in these clinical studies likely reflects the cellular source of IL-6 in specific diseases, much of which may be produced by nonhematopoietic cells. These results highlight that functional analysis of disease-associated SNPs on gene expression and pathologic processes must consider variation in diverse cell types. PMID:26578807

  16. GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh

    PubMed Central

    Rodrigues, Ema G.; Kile, Molly; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Hsueh, Yumei; Christiani, David C.

    2012-01-01

    We determined whether single nucleotide polymorphisms (SNPs) in the glutathione S-transferase omega (GSTO) and arsenic(III)methyltransferase (AS3MT) genes were associated with concentrations of urinary arsenic metabolites among 900 individualswithout skin lesions in Bangladesh. Four SNPs were assessed in these genes. A pathway analysis evaluated the association between urinary arsenic metabolites and SNPs. GSTO1 rs4925 homozygous wild type was significantly associated with higher monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) urinary concentrations, whereas wild type AS3MT rs11191439 had significantly lower levels of AsIII and MMA. Genetic polymorphisms GSTO and As3MT modify arsenic metabolism as evidenced by altered urinary arsenic excretion. PMID:22339537

  17. Genetic polymorphisms of inflammatory response gene TNF-? and its influence on sporadic pancreatic neuroendocrine tumors predisposition risk.

    PubMed

    Karakaxas, Dimitrios; Gazouli, Maria; Coker, Ahmet; Agalianos, Christos; Papanikolaou, Ioannis S; Patapis, Pavlos; Liakakos, Theodoros; Dervenis, Christos

    2014-10-01

    The diagnosed incidence of pancreatic neuroendocrine tumors (pNETs) is increasing; however, their etiology remains poorly understood. PNETs are a rare, heterogeneous group of tumors arising from the endocrine cells of the pancreas, and genetic risk factors for sporadic pNETs are inadequately understood. It is known that pNETs secrete biogenic amines, hormones and growth factors, tumor necrosis factor-a (TNF-?) being one of them. Furthermore, cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. The aim of our study was to analyze TNF-? promoter gene polymorphisms as risk factors for pNETs using germline DNA collected in a population-based case-control study of pancreatic cancer [42 pNET cases, 78 pancreatic ductal adenocarcinoma (PDAC) cases, 17 intraductal papillary mucinous neoplasm (IPMN) and 98 healthy controls] conducted in the Athens, Greece and Izmir, Turkey areas. For subsequent analysis, we excluded cases and controls with known genetic syndromes. The CC genotype at the -1031 position was more frequent in pNET and IPMN patients (p=0.0002 and p=0.009, respectively), suggesting its possible role in pNET development. Furthermore, the AA genotype at the -308 position was overrepresented in IPMN cases (p=0.03), and AA genotype at the -238 position was more frequent in PDAC cases (p=0.03) compared to healthy individuals. With regard to tumor characteristics, no statistically significant association was detected. Our findings suggest the putative role of TNF-? -1031 polymorphism in the development of pNET and IPMN, whereas the -308 polymorphism seems to be overrepresented among IPMN cases and -238 polymorphism among PDAC cases. PMID:25213764

  18. Association of TCF7L2 Genetic Polymorphisms with Type 2 Diabetes Mellitus in the Uygur Population of China

    PubMed Central

    Yao, Hua; Wang, Zhiqiang; Wang, Tingting; Ma, Yan; Su, Yinxia; Ma, Qi; Wang, Li; Zhu, Jun

    2015-01-01

    Background: Genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene have been reported to be strongly associated with type 2 diabetes mellitus (T2DM) in Icelandic, Danish and American populations and further replicated in other European populations, African Americans, Mexican Americans, and Asian populations. The aim of the present study was to investigate the association of TCF7L2 gene polymorphisms with T2DM in a Uygur population of China. Methods: 877 T2DM patients and 871 controls were selected for the present study. Two single nucleotide polymorphisms (SNPs) (rs12255372 and rs7901695) were genotyped by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The associations of SNPs and haplotypes with T2DM and linkage disequilibrium (LD) structure of the TCF7L2 gene were analyzed. Results: For total participants and male, the distribution of rs12255372 alleles and the dominant model (Guanine Guanine (GG) genotype vs. Guanine Thymine (GT) genotype + Thymine Thymine (TT) genotype) showed significant difference between T2DM and control subjects (for allele: p = 0.013 and p = 0.002, respectively; for dominant model: p = 0.028 and p = 0.008, respectively). The distribution of rs7901695 alleles and the dominant model (TT genotype vs. Thymine Cytosine (TC) genotype + Cytosine Cytosine (CC) genotype) for total participants and male showed significant difference between T2DM and control subjects (for allele: both p = 0.001; for dominant model: p = 0.006 and p = 0.008, respectively). Conclusions: Our data suggested that the genetic polymorphisms of the TCF7L2 gene were associated with T2DM in the Uygur population of China. PMID:26393635

  19. p53 Codon 72 Genetic Polymorphism in Asthmatic Children: Evidence of Interaction With Acid Phosphatase Locus 1

    PubMed Central

    Verrotti, Alberto; Giannini, Cosimo; Verini, Marcello; Chiarelli, Francesco; Neri, Anna; Magrini, Andrea

    2014-01-01

    Several lines of evidence are implicating an increased persistence of apoptotic cells in patients with asthma. This is largely due to a combination of inhibition, or defects in the apoptotic process and/or impaired apoptotic cell removal mechanisms. Among apoptosis-inducing genes, an important role is played by p53. In the present study, we have investigated the possible relationship between p53 codon 72 polymorphism and asthma and the interaction with ACP1, a genetic polymorphism involved in the susceptibility to allergic asthma. We studied 125 asthmatic children and 123 healthy subjects from the Caucasian population of Central Italy. p53 codon 72 and ACP1 polymorphisms were evaluated using a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method. There is a statistically significant association between p53 codon 72 polymorphism and allergic asthma: Arg/Arg genotype is more represented in asthmatic patients than in controls (P=0.018). This association, however, is present in subjects with low ACP1 activity A/A and A/B only (P=0.023). The proportion of children with A/A and A/B genotype carrying Arg/Arg genotype is significantly high in asthmatic children than in controls (OR=1.941; 95% C.I. 1.042-3.628). Our finding could have important clinical implications since the subjects with A/A and A/B genotypes of ACP1 carrying Arg/Arg genotype are more susceptible to allergic asthma than Pro/Pro genotype. PMID:24843801

  20. Effect of genetic polymorphisms in CA6 gene on the expression and catalytic activity of human salivary carbonic anhydrase VI.

    PubMed

    Aidar, M; Marques, Rocha; Valjakka, J; Mononen, N; Lehtimäki, T; Parkkila, S; de Souza, A P; Line, S R Peres

    2013-01-01

    Carbonic anhydrase isoenzyme VI (CA VI) plays an important role in the homeostasis of oral tissues participating in the processes of taste, protection of dental tissues against the loss of minerals, caries, and possibly in the formation of dental calculus in periodontal disease. This study aimed to verify the correlation between changes in the expression and activity of human salivary carbonic anhydrase VI and genetic polymorphisms in its gene (CA6). The study population consisted of 182 healthy volunteers (female and male, aged 18-22). Samples of total saliva were assayed for CA VI concentrations using a specific time-resolved immunofluorometric assay. CA VI catalytic activity was detected by a modified protocol of Kotwica et al. [J Physiol Pharmacol 2006;57(suppl 8):107-123], adapted to CA VI in saliva. Samples of genomic DNA were genotyped for polymorphisms rs2274327 (C/T), rs2274328 (A/C) and rs2274333 (A/G) by TaqMan® SNP Genotyping Assays. The concentration and catalytic activity of the salivary CA VI obtained for the different genotypes were analyzed using the Kruskal-Wallis nonparametric test and the Dunn test. The results showed that individuals with TT genotype (rs2274327) had significantly lower CA VI concentrations than the individuals with genotypes CT or CC (p < 0.05). There was also an association between polymorphism rs2274333 and salivary CA VI concentrations. There were no associations between the three polymorphisms analyzed and variations in CA VI activity. Our results suggest that polymorphisms in the CA6 gene are associated with the concentrations of secreted CA VI. PMID:23652931

  1. Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population

    PubMed Central

    Ban, Yoshiyuki; Taniyama, Matsuo; Yanagawa, Tatsuo; Yamada, Satoru; Maruyama, Taro; Kasuga, Akira; Ban, Yoshio

    2001-01-01

    Background Vitamin D has been shown to exert manifold immunomodulatory effects. Type 1 diabetes mellitus (T1DM) is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse. We studied the association between T1DM and the initiation codon polymorphism in exon 2 of the vitamin D receptor gene in a Japanese population. We also investigated associations between the vitamin D receptor polymorphism and GAD65-antibody (Ab) positivity. We carried out polymerase chain reaction-restriction fragment length polymorphism analysis in 110 Japanese T1DM patients and 250 control subjects. GAD65 antibodies were assessed in 78 patients with T1DM. Results We found a significantly higher prevalence of the F allele / the FF genotype in the patients compared to the controls (P = 0.0069 and P = 0.014, respectively). Genotype and allele frequencies differed significantly between GAD65-Ab-positive patients and controls (P = 0.017 and P = 0.012, respectively), but neither between GAD65-Ab-negative patients and controls (P = 0.68 and P = 0.66, respectively) nor between GAD65-Ab-positive and -negative patients (P = 0.19 and P = 0.16, respectively). Conclusions Our findings suggest that the vitamin D receptor initiation codon polymorphism influences genetic susceptibility to T1DM among the Japanese. This polymorphism is also associated with GAD65-Ab-positive T1DM, although the absence of a significant difference between GAD65-Ab-negative patients and controls might be simply due to the small sample size of patients tested for GAD65 antibodies. PMID:11445000

  2. Genetic polymorphism of estrogen receptor alpha gene in Egyptian women with type II diabetes mellitus

    PubMed Central

    Motawi, Tarek M.K.; El-Rehany, Mahmoud A.; Rizk, Sherine M.; Ramzy, Maggie M.; el-Roby, Doaa M.

    2015-01-01

    Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha gene including the XbaI and PvuII restriction enzyme polymorphisms. The aim of this study was to determine if ESR? gene polymorphisms are associated with type 2 diabetes mellitus and correlated with lipid profile. Ninety diabetic Egyptian patients were compared with forty healthy controls. ESR? genotyping of PvuII and XbaI was performed using restriction fragment length polymorphism analysis. Our study showed that there is more significant difference in the frequency of C and G polymorphic allele between patients and control groups in PvuII and XbaI respectively. Also carriers of minor C and G alleles of PvuII and XbaI gene polymorphisms were associated with increased fasting blood glucose and disturbance in lipid profile as there is an increase in total cholesterol, triglycerides and Low density lipoprotein. So findings of present study suggest the possibility that PvuII and XbaI polymorphisms in ER? are related to T2DM and with increased serum lipids among Egyptian population. PMID:26401488

  3. Genetic polymorphism of estrogen receptor alpha gene in Egyptian women with type II diabetes mellitus.

    PubMed

    Motawi, Tarek M K; El-Rehany, Mahmoud A; Rizk, Sherine M; Ramzy, Maggie M; El-Roby, Doaa M

    2015-12-01

    Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha gene including the XbaI and PvuII restriction enzyme polymorphisms. The aim of this study was to determine if ESR? gene polymorphisms are associated with type 2 diabetes mellitus and correlated with lipid profile. Ninety diabetic Egyptian patients were compared with forty healthy controls. ESR? genotyping of PvuII and XbaI was performed using restriction fragment length polymorphism analysis. Our study showed that there is more significant difference in the frequency of C and G polymorphic allele between patients and control groups in PvuII and XbaI respectively. Also carriers of minor C and G alleles of PvuII and XbaI gene polymorphisms were associated with increased fasting blood glucose and disturbance in lipid profile as there is an increase in total cholesterol, triglycerides and Low density lipoprotein. So findings of present study suggest the possibility that PvuII and XbaI polymorphisms in ER? are related to T2DM and with increased serum lipids among Egyptian population. PMID:26401488

  4. Genetic Diversity among Rhizobium leguminosarum bv. Trifolii Strains Revealed by Allozyme and Restriction Fragment Length Polymorphism Analyses

    PubMed Central

    Demezas, David H.; Reardon, Terry B.; Watson, John M.; Gibson, Alan H.

    1991-01-01

    Allozyme electrophoresis and restriction fragment length polymorphism (RFLP) analyses were used to examine the genetic diversity of a collection of 18 Rhizobium leguminosarum bv. trifolii, 1 R. leguminosarum bv. viciae, and 2 R. meliloti strains. Allozyme analysis at 28 loci revealed 16 electrophoretic types. The mean genetic distance between electrophoretic types of R. leguminosarum and R. meliloti was 0.83. Within R. leguminosarum, the single strain of bv. viciae differed at an average of 0.65 from strains of bv. trifolii, while electrophoretic types of bv. trifolii differed at a range of 0.23 to 0.62. Analysis of RFLPs around two chromosomal DNA probes also delineated 16 unique RFLP patterns and yielded genetic diversity similar to that revealed by the allozyme data. Analysis of RFLPs around three Sym (symbiotic) plasmid-derived probes demonstrated that the Sym plasmids reflect genetic divergence similar to that of their bacterial hosts. The large genetic distances between many strains precluded reliable estimates of their genetic relationships. PMID:16348600

  5. First Insights into the Genetic Diversity of the Pinewood Nematode in Its Native Area Using New Polymorphic Microsatellite Loci

    PubMed Central

    Mallez, Sophie; Castagnone, Chantal; Espada, Margarida; Vieira, Paulo; Eisenback, Jonathan D.; Mota, Manuel; Guillemaud, Thomas; Castagnone-Sereno, Philippe

    2013-01-01

    The pinewood nematode, Bursaphelenchus xylophilus, native to North America, is the causative agent of pine wilt disease and among the most important invasive forest pests in the East-Asian countries, such as Japan and China. Since 1999, it has been found in Europe in the Iberian Peninsula, where it also causes significant damage. In a previous study, 94 pairs of microsatellite primers have been identified in silico in the pinewood nematode genome. In the present study, specific PCR amplifications and polymorphism tests to validate these loci were performed and 17 microsatellite loci that were suitable for routine analysis of B. xylophilus genetic diversity were selected. The polymorphism of these markers was evaluated on nematodes from four field origins and one laboratory collection strain, all originate from the native area. The number of alleles and the expected heterozygosity varied between 2 and 11 and between 0.039 and 0.777, respectively. First insights into the population genetic structure of B. xylophilus were obtained using clustering and multivariate methods on the genotypes obtained from the field samples. The results showed that the pinewood nematode genetic diversity is spatially structured at the scale of the pine tree and probably at larger scales. The role of dispersal by the insect vector versus human activities in shaping this structure is discussed. PMID:23554990

  6. HLA-DR polymorphism in a Senegalese Mandenka population: DNA oligotyping and population genetics of DRB1 specificities.

    PubMed Central

    Tiercy, J M; Sanchez-Mazas, A; Excoffier, L; Shi-Isaac, X; Jeannet, M; Mach, B; Langaney, A

    1992-01-01

    HLA class II loci are useful markers in human population genetics, because they are extremely variable and because new molecular techniques allow large-scale analysis of DNA allele frequencies. Direct DNA typing by hybridization with sequence-specific oligonucleotide probes (HLA oligotyping) after enzymatic in vitro PCR amplification detects HLA allelic polymorphisms for all class II loci. A detailed HLA-DR oligotyping analysis of 191 individuals from a geographically, culturally, and genetically well-defined western African population, the Mandenkalu, reveals a high degree of polymorphism, with at least 24 alleles and a heterozygosity level of .884 for the DRB1 locus. The allele DRB1*1304, defined by DNA sequencing of the DRB1 first-domain exon, is the most frequent allele (27.1%). It accounts for an unusually high DR13 frequency, which is nevertheless within the neutral frequency range. The next most frequent specificities are DR11, DR3, and DR8. Among DRB3-encoded alleles, DR52b (DRB3*02) represents as much as 80.7% of all DR52 haplotypes. A survey of HLA-DR specificities in populations from different continents shows a significant positive correlation between genetic and geographic differentiation patterns. A homozygosity test for selective neutrality of DR specificities is not significant for the Mandenka population but is rejected for 20 of 24 populations. Observed high heterozygosity levels in tested populations are compatible with an overdominant model with a small selective advantage for heterozygotes. PMID:1496990

  7. Genetic polymorphism and molecular epidemiology of Leishmania (Viannia) braziliensis from different hosts and geographic areas in Brazil.

    PubMed

    Cupolillo, Elisa; Brahim, Lúcia Regina; Toaldo, Cristiane B; de Oliveira-Neto, Manoel Paes; de Brito, Maria Edileuza Felinto; Falqueto, Aloisio; de Farias Naiff, Maricleide; Grimaldi, Gabriel

    2003-07-01

    Numerical zymotaxonomy and variability of the internal transcribed spacers (ITS) between the small and large subunits of the rRNA genes were used to examine strain variation and relationships in natural populations of Leishmania (Viannia) braziliensis. A total of 101 strains from distinct hosts and Brazilian geographic regions were assigned to 15 zymodemes clustered in two major genetic groups. The great number of isolates (48.5%) placed in zymodeme IOC/Z-27 were collected on the Atlantic coast. The high molecular diversity found in populations in the Amazon Basin was related to the great number of sandfly vector(s) in that region. The results of the restriction fragment length polymorphism analysis of the ITS depicted considerable intraspecific variation. Genotypic groups A, B, and C contained 39, 40, and 22 isolates, which were divided into 16, 10, and 15 genotypes, respectively. The genetic polymorphism observed demonstrates the degree of diversity of L. (V.) braziliensis strains from different regions where they are endemic. The results reinforce the clonal theory for Leishmania parasites showing the genetic diversity of this pathogen and an association of L. (V.) braziliensis genotypes with specific transmission cycles, probably reflecting an adaptation of different clones to the vector species involved. PMID:12843052

  8. First insights into the genetic diversity of the pinewood nematode in its native area using new polymorphic microsatellite loci.

    PubMed

    Mallez, Sophie; Castagnone, Chantal; Espada, Margarida; Vieira, Paulo; Eisenback, Jonathan D; Mota, Manuel; Guillemaud, Thomas; Castagnone-Sereno, Philippe

    2013-01-01

    The pinewood nematode, Bursaphelenchus xylophilus, native to North America, is the causative agent of pine wilt disease and among the most important invasive forest pests in the East-Asian countries, such as Japan and China. Since 1999, it has been found in Europe in the Iberian Peninsula, where it also causes significant damage. In a previous study, 94 pairs of microsatellite primers have been identified in silico in the pinewood nematode genome. In the present study, specific PCR amplifications and polymorphism tests to validate these loci were performed and 17 microsatellite loci that were suitable for routine analysis of B. xylophilus genetic diversity were selected. The polymorphism of these markers was evaluated on nematodes from four field origins and one laboratory collection strain, all originate from the native area. The number of alleles and the expected heterozygosity varied between 2 and 11 and between 0.039 and 0.777, respectively. First insights into the population genetic structure of B. xylophilus were obtained using clustering and multivariate methods on the genotypes obtained from the field samples. The results showed that the pinewood nematode genetic diversity is spatially structured at the scale of the pine tree and probably at larger scales. The role of dispersal by the insect vector versus human activities in shaping this structure is discussed. PMID:23554990

  9. Protein polymorphisms in natural populations The rise of biochemical genetics (1950-60s).

    E-print Network

    Etges, William J.

    Strong Inference 1. Lead to functional studies of enzyme adaptations, eg. LDH:412-417. "Only one of the 43 polymorphisms results in an amino acid change, the one all natural populations. The implication is that most amino acid changes

  10. Investigation of genetic polymorphisms and smoking in a bladder cancer casecontrol study in Argentina

    E-print Network

    California at Berkeley, University of

    associated with GSTM1 and GSTT1 null genotypes were found in smokers. Having both null polymorphisms cancer. q 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Tobacco; MTHFR; GSTM1; GSTT1; NQO1

  11. Genetic diversity of Brucella abortus isolates as determined by amplified fragment length polymorphism (AFLP) analysis 

    E-print Network

    Bliss, Katherine Ann

    2013-02-22

    Although Brucella abortus, the causative agent of brucellosis, is mainly under control in the United States, outbreaks do occur, particularly in wild animal herds. This study coupled amplified fragment length polymorphism (AFLP) analysis...

  12. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients.

    PubMed

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

    2014-06-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients. PMID:25071398

  13. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients

    PubMed Central

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

    2014-01-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45–4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients. PMID:25071398

  14. Genetic Diversity of Thottapalayam Virus, a Hantavirus Harbored by the Asian House Shrew (Suncus murinus) in Nepal

    PubMed Central

    Kang, Hae Ji; Kosoy, Michael Y.; Shrestha, Sanjaya K.; Shrestha, Mrigendra P.; Pavlin, Julie A.; Gibbons, Robert V.; Yanagihara, Richard

    2011-01-01

    Despite the recent discovery of genetically divergent hantaviruses in shrews of multiple species in widely separated geographic regions, data are unavailable about the genetic diversity and phylogeography of Thottapalayam virus (TPMV), a hantavirus originally isolated from an Asian house shrew (Suncus murinus) captured in southern India more than four decades ago. To bridge this knowledge gap, the S, M, and L segments of hantavirus RNA were amplified by reverse transcription polymerase chain reaction from archival lung tissues of Asian house shrews captured in Nepal from January to September 1996. Pair-wise alignment and comparison revealed approximately 80% nucleotide and > 94% amino acid sequence similarity to prototype TPMV. Phylogenetic analyses, generated by maximum likelihood and Bayesian methods, showed geographic-specific clustering of TPMV, similar to that observed for rodent- and soricid-borne hantaviruses. These findings confirm that the Asian house shrew is the natural reservoir of TPMV and suggest a long-standing virus–host relationship. PMID:21896819

  15. Genetic polymorphisms and phenotypic analysis of drug-metabolizing enzyme CYP2C19 in a Li Chinese population

    PubMed Central

    Ding, Yipeng; Xu, Dongchuan; Zhang, Xiyang; Yang, Hua; Geng, Tingting; He, Ping; Yao, Jinjian; Yi, Shengyang; Xu, Heping; Wu, Duoyi; Wang, Xiang; Jin, Tianbo

    2015-01-01

    CYP2C19 is a highly polymorphic gene and CYP2C19 enzyme results in broad inter-individual variability in response to certain clinical drugs, while little is known about the genetic variation of CYP2C19 in Li Chinese population. The aim of this study was to identify different CYP2C19 mutant alleles and determine their frequencies, along with genotype frequencies, in the Li Chinese population. We used DNA sequencing to investigate promoter, exons, introns, and 3’UTR of the CYP2C19 gene in 100 unrelated healthy Li individuals from Hainan Province, China. We also used SIFT and PolyPhen-2 to predict the protein function of the non-synonymous mutation in CYP2C19 coding regions. We identified 22 different CYP2C19 polymorphisms in the Li Chinese population, including three novel variants (-254A > G, 17807T > C and 58025C > T). The allele frequencies of CYP2C19*1A, *1B, *2A and *3A were 50%, 24%, 24.5%, and 1.5%, respectively. The most common genotype combinations were *1A/*1B (48%) and *1A/*2A (49%). Additionally, the mutation Ala161Pro was predicted to be intolerant and possibly damaging by SIFT and PolyPhen-2, respectively. Our results shed new light on CYP2C19 polymorphisms in Li individuals, which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group. PMID:26722519

  16. [Molecular-genetic polymorphism of wheat cell lines resistant to metabolites of G. graminis var. tritici and osmotic stress].

    PubMed

    Bavol, A V; Zinchenko, M O; Dubrovna, O V

    2014-01-01

    It was analyzed polymorphism of DNA loci, flanked by inverted repeats of LTR retrotransposon Cassandra, in cell lines of bread wheat, resistant to the metabolites of ophiobolus root rot (G. graminis var. tritici), under osmotic stress and induced from them plant-regenerants. The differences in the polynucleotide sequences of DNA at the direct and step cell selection it was identified. Assessment of the level of genetic divergence showed that calluses obtained at the direct selection and calluses in the later stages of step selection were the most genetically distant from the original forms (D(NL) = 0.4855), this means that at the sublethal doses of selective factors occur the most significant changes at the genome of the investigated objects. In contrast to the original form at the spectra of products DNA amplification of calluses and regenerated plants showed the emergence of bands approximately 638 bp length, which may indicate the activation of retrotransposon Cassandra. PMID:24791474

  17. Population genetic analysis of insertion-deletion polymorphisms in a Brazilian population using the Investigator DIPplex kit.

    PubMed

    Ferreira Palha, Teresinha de Jesus Brabo; Ribeiro Rodrigues, Elzemar Martins; Cavalcante, Giovanna Chaves; Marrero, Andrea; de Souza, Ilíada Rainha; Seki Uehara, Clineu Julien; Silveira da Motta, Carlos Henrique Ares; Koshikene, Daniela; da Silva, Dayse Aparecida; de Carvalho, Elizeu Fagundes; Chemale, Gustavo; Freitas, Jorge M; Alexandre, Lídia; Paranaiba, Renato T F; Soler, Mirella Perruccio; Santos, Sidney

    2015-11-01

    The aim of this study was to estimate the diversity of 30 insertion/deletion (INDEL) markers (Investigator(®) DIPplex kit) in a sample of 519 individuals from six Brazilian states and to evaluate their applicability in forensic genetics. All INDEL markers were found to be highly polymorphic in the Brazilian population and were in Hardy-Weinberg equilibrium. To determine their forensic suitability in the Brazilian population, the markers were evaluated for discrimination power, match probability and exclusion power. The combined discrimination power (CDP), combined match power (CMP) and combined power of exclusion (CPE) were higher than 0.999999, 3.4×10(-13) and 0.9973, respectively. Further comparison of 29 worldwide populations revealed significant genetic differences between continental populations and a closer relationship between the Brazilian and European populations. PMID:26036184

  18. Description of the data from the Collaborative Study on the Genetics of Alcoholism (COGA) and single-nucleotide polymorphism genotyping for Genetic Analysis Workshop 14

    PubMed Central

    Edenberg, Howard J; Bierut, Laura J; Boyce, Paul; Cao, Manqiu; Cawley, Simon; Chiles, Richard; Doheny, Kimberly F; Hansen, Mark; Hinrichs, Tony; Jones, Kevin; Kelleher, Mark; Kennedy, Giulia C; Liu, Guoying; Marcus, Gregory; McBride, Celeste; Murray, Sarah Shaw; Oliphant, Arnold; Pettengill, James; Porjesz, Bernice; Pugh, Elizabeth W; Rice, John P; Rubano, Todd; Shannon, Stu; Steeke, Rhoberta; Tischfield, Jay A; Tsai, Ya Yu; Zhang, Chun; Begleiter, Henri

    2005-01-01

    The data provided to the Genetic Analysis Workshop 14 (GAW 14) was the result of a collaboration among several different groups, catalyzed by Elizabeth Pugh from The Center for Inherited Disease Research (CIDR) and the organizers of GAW 14, Jean MacCluer and Laura Almasy. The DNA, phenotypic characterization, and microsatellite genomic survey were provided by the Collaborative Study on the Genetics of Alcoholism (COGA), a nine-site national collaboration funded by the National Institute of Alcohol and Alcoholism (NIAAA) and the National Institute of Drug Abuse (NIDA) with the overarching goal of identifying and characterizing genes that affect the susceptibility to develop alcohol dependence and related phenotypes. CIDR, Affymetrix, and Illumina provided single-nucleotide polymorphism genotyping of a large subset of the COGA subjects. This article briefly describes the dataset that was provided. PMID:16451628

  19. French invasive Asian tiger mosquito populations harbor reduced bacterial microbiota and genetic diversity compared to Vietnamese autochthonous relatives

    PubMed Central

    Minard, G.; Tran, F. H.; Van, Van Tran; Goubert, C.; Bellet, C.; Lambert, G.; Kim, Khanh Ly Huynh; Thuy, Trang Huynh Thi; Mavingui, P.; Valiente Moro, C.

    2015-01-01

    The Asian tiger mosquito Aedes albopictus is one of the most significant pathogen vectors of the twenty-first century. Originating from Asia, it has invaded a wide range of eco-climatic regions worldwide. The insect-associated microbiota is now recognized to play a significant role in host biology. While genetic diversity bottlenecks are known to result from biological invasions, the resulting shifts in host-associated microbiota diversity has not been thoroughly investigated. To address this subject, we compared four autochthonous Ae. albopictus populations in Vietnam, the native area of Ae. albopictus, and three populations recently introduced to Metropolitan France, with the aim of documenting whether these populations display differences in host genotype and bacterial microbiota. Population-level genetic diversity (microsatellite markers and COI haplotype) and bacterial diversity (16S rDNA metabarcoding) were compared between field-caught mosquitoes. Bacterial microbiota from the whole insect bodies were largely dominated by Wolbachia pipientis. Targeted analysis of the gut microbiota revealed a greater bacterial diversity in which a fraction was common between French and Vietnamese populations. The genus Dysgonomonas was the most prevalent and abundant across all studied populations. Overall genetic diversities of both hosts and bacterial microbiota were significantly reduced in recently established populations of France compared to the autochthonous populations of Vietnam. These results open up many important avenues of investigation in order to link the process of geographical invasion to shifts in commensal and symbiotic microbiome communities, as such shifts may have dramatic impacts on the biology and/or vector competence of invading hematophagous insects. PMID:26441903

  20. Genetic variation in agronomically important species of Stylosanthes determined using random amplified polymorphic DNA markers.

    PubMed

    Kazan, K; Manners, J M; Cameron, D F

    1993-02-01

    Random amplified polymorphic DNA (RAPD) markers were generated from 20 cultivars and accessions representing four agronomically important species of Stylosanthes, S. scabra, S. hamata, S. guianensis, and S. humilis. Approximately 200 fragments generated by 22 primers of arbitrary sequence were used to assess the level of DNA variation. Relatively low levels of polymorphism (0-16% of total bands in pairwise comparisons) were found within each species, while polymorphisms between the species were much higher (up to 46%). Very few polymorphisms (0-2%) were detected between the individuals of the same cultivar or accession. A phenogram of relationships among the species was constructed based on band sharing. Four main clusters corresponding to each species were readily distinguished on this phenogram. The allotetraploid species S. hamata and its putative diploid progenitor, S. humilis, were more similar to each other than to S. scabra and S. guianensis. No variation in RAPD markers was found between the two commercial S. hamata cvs 'Verano' and 'Amiga'. Cultivar 'Oxley' in S. guianensis was considerably different from the other cultivars and accessions of this species. The phylogenetic distinctions obtained with RAPDs were in agreement with other studies from morphology, cytology, and enzyme electrophoresis. The low level of polymorphisms observed within each species suggested that interspecific crosses may be a better vehicle for the construction of RAPD linkage maps in Stylosanthes. PMID:24196064

  1. Genetic polymorphisms of PCSK2 are associated with glucose homeostasis and progression to type 2 diabetes in a Chinese population

    PubMed Central

    Chang, Tien-Jyun; Chiu, Yen-Feng; Sheu, Wayne H-H.; Shih, Kuang-Chung; Hwu, Chii-Min; Quertermous, Thomas; Jou, Yuh-Shan; Kuo, Shan-Shan; Chang, Yi-Cheng; Chuang, Lee-Ming

    2015-01-01

    Proprotein convertase subtilisin/kexin type 2 (PCSK2) is a prohormone processing enzyme involved in insulin and glucagon biosynthesis. We previously found the genetic polymorphism of PCSK2 on chromosome 20 was responsible for the linkage peak of several glucose homeostasis parameters. The aim of this study is to investigate the association between genetic variants of PCSK2 and glucose homeostasis parameters and incident diabetes. Total 1142 Chinese participants were recruited from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study, and 759 participants were followed up for 5 years. Ten SNPs of the PCSK2 gene were genotyped. Variants of rs6044695 and rs2284912 were associated with fasting plasma glucose, and variants of rs2269023 were associated with fasting plasma glucose and 1-hour plasma glucose during OGTT. Haplotypes of rs4814605/rs1078199 were associated with fasting plasma insulin levels and HOMA-IR. Haplotypes of rs890609/rs2269023 were also associated with fasting plasma glucose, fasting insulin and HOMA-IR. In the longitudinal study, we found individuals carrying TA/AA genotypes of rs6044695 or TC/CC genotypes of rs2284912 had lower incidence of diabetes during the 5-year follow-up. Our results indicated that PCSK2 gene polymorphisms are associated with pleiotropic effects on various traits of glucose homeostasis and incident diabetes. PMID:26607656

  2. BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related SCT.

    PubMed

    Piras, I S; Angius, A; Andreani, M; Testi, M; Lucarelli, G; Floris, M; Marktel, S; Ciceri, F; La Nasa, G; Nasa, G La; Fleischhauer, K; Roncarolo, M G; Bulfone, A; Gregori, S; Bacchetta, R

    2014-11-01

    The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied whole-genome analysis to investigate genetic variants-other than HLA class I and II-associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 ?-Thalassemic patients. We identified two single-nucleotide polymorphisms (SNPs) in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong linkage disequilibrium between each other (R(2)=0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P<0.00001 for BAT2 SNP rs11538264, and P<0.0001 for BAT3 SNP rs10484558), whereas the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs 2.6%, nominal P=1.15 × 10(-8); and adjusted P=0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent a novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT. PMID:25111513

  3. BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related stem cell transplantation

    PubMed Central

    Piras, Ignazio Stefano; Angius, Andrea; Andreani, Marco; Testi, Manuela; Lucarelli, Guido; Floris, Matteo; Marktel, Sarah; Ciceri, Fabio; La Nasa, Giorgio; Fleischhauer, Katharina; Roncarolo, Maria Grazia; Bulfone, Alessandro

    2014-01-01

    The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We applied a whole genome analysis to investigate genetic variants - other than HLA class I and II - associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 ?-Thalassemic patients. We identified two single nucleotide polymorphisms in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong Linkage Disequilibrium between each other (R2=0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P < 0.00001 for BAT2 SNP rs11538264, and P < 0.0001 for BAT3 SNP rs10484558). Whereas, the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs. 2.6%, nominal P = 1.15×10?8; and adjusted P = 0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT. PMID:25111513

  4. Genetic analysis of ABCG2 and SLC2A9 gene polymorphisms in gouty arthritis in a Korean population

    PubMed Central

    Kim, Yun Sung; Kim, Yunsuek; Park, Geon; Kim, Seong-Kyu; Choe, Jung-Yoon; Park, Byung Lae; Kim, Hyun Sook

    2015-01-01

    Background/Aims: Gout is a common inf lammatory arthritis triggered by the crystallization of uric acid in the joints. Serum uric acid levels are highly heritable, suggesting a strong genetic component. Independent studies to confirm the genetic associations with gout in various ethnic populations are warranted. We investigated the association of polymorphisms in the ABCG2 and SLC2A9 genes with gout in Korean patients and healthy individuals. Methods: We consecutively enrolled 109 patients with gout and 102 healthy controls. The diagnosis of gout was based on the preliminary criteria of the America College of Rheumatology. Genomic DNA was extracted from whole blood samples. We identified single nucleotide polymorphism (SNP) changes in the ABCG2 and SLC2A9 genes using a direct sequencing technique. rs2231142 in ABCG2 and rs6449213 and rs16890979 in SLC2A9 and nearby regions were amplified by polymerase chain reaction. Results: Patients with gout had significantly higher A/A genotype (29.3% vs. 4.9%, respectively) and A allele (52.8% vs. 26.5%, respectively) frequencies of rs2231142 in ABCG2 than did controls (?2 = 29.42, p < 0.001; odds ratio, 3.32; 95% confidence interval, 2.11 to 5.20). We found novel polymorphisms (c.881A>G and c.1002+78G>A) in the SLC2A9 gene. The univariate logistic regression analysis revealed that the c.881A>G and c.1002+78G>A SNPs were significantly higher in patients than in controls. Conclusions: We demonstrated a significant association between rs2231142 in the ABCG2 gene and gout and identified novel SNPs, c.881A>G and c.1002+78G>A, in the SLC2A9 gene that may be associated with gout in a Korean population. PMID:26552468

  5. A regimen combining the Wee1 inhibitor AZD1775 with HDAC inhibitors targets human acute myeloid leukemia cells harboring various genetic mutations

    PubMed Central

    Zhou, Liang; Zhang, Yu; Chen, Shuang; Kmieciak, Maciej; Leng, Yun; Lin, Hui; Rizzo, Kathryn A.; Dumur, Catherine I.; Ferreira-Gonzalez, Andrea; Dai, Yun; Grant, Steven

    2015-01-01

    AZD1775 targets the cell cycle checkpoint kinase Wee1 and potentiates genotoxic agent cytotoxicity through p53-dependent or -independent mechanisms. Here, we report that AZD1775 interacted synergistically with histone deacetylase inhibitors (HDACIs e.g., Vorinostat), which interrupt the DNA damage response (DDR), to kill p53-wild type or -deficient as well as FLT3-ITD leukemia cells in association with pronounced Wee1 inhibition and diminished cdc2/Cdk1 Y15 phosphorylation. Similarly, Wee1 shRNA knock-down significantly sensitized cells to HDACIs. While AZD1775 induced Chk1 activation, reflected by markedly increased Chk1 S296/S317/S345 phosphorylation leading to inhibitory T14 phosphorylation of cdc2/Cdk1, these compensatory responses were sharply abrogated by HDACIs. This was accompanied by premature mitotic entry, multiple mitotic abnormalities, and accumulation of early S-phase cells displaying increased newly replicated DNA, culminating in robust DNA damage and apoptosis. The regimen was active against patient-derived AML cells harboring either wild type or mutant p53, and various NGS-defined mutations. Primitive CD34+/CD123+/CD38? populations enriched for leukemia-initiating progenitors, but not normal CD34+ hematopoietic cells, were highly susceptible to this regimen. Finally, combining AZD1775 with Vorinostat in AML murine xenografts significantly reduced tumor burden and prolonged animal survival. A strategy combining Wee1 with HDACI inhibition warrants further investigation in AML with poor prognostic genetic aberrations. PMID:25283841

  6. A regimen combining the Wee1 inhibitor AZD1775 with HDAC inhibitors targets human acute myeloid leukemia cells harboring various genetic mutations.

    PubMed

    Zhou, L; Zhang, Y; Chen, S; Kmieciak, M; Leng, Y; Lin, H; Rizzo, K A; Dumur, C I; Ferreira-Gonzalez, A; Dai, Y; Grant, S

    2015-04-01

    AZD1775 targets the cell cycle checkpoint kinase Wee1 and potentiates genotoxic agent cytotoxicity through p53-dependent or -independent mechanisms. Here, we report that AZD1775 interacted synergistically with histone deacetylase inhibitors (HDACIs, for example, Vorinostat), which interrupt the DNA damage response, to kill p53-wild type (wt) or -deficient as well as FLT3-ITD leukemia cells in association with pronounced Wee1 inhibition and diminished cdc2/Cdk1 Y15 phosphorylation. Similarly, Wee1 shRNA knockdown significantly sensitized cells to HDACIs. Although AZD1775 induced Chk1 activation, reflected by markedly increased Chk1 S296/S317/S345 phosphorylation leading to inhibitory T14 phosphorylation of cdc2/Cdk1, these compensatory responses were sharply abrogated by HDACIs. This was accompanied by premature mitotic entry, multiple mitotic abnormalities and accumulation of early S-phase cells displaying increased newly replicated DNA, culminating in robust DNA damage and apoptosis. The regimen was active against patient-derived acute myelogenous leukemia (AML) cells harboring either wt or mutant p53 and various next-generation sequencing-defined mutations. Primitive CD34(+)/CD123(+)/CD38(-) populations enriched for leukemia-initiating progenitors, but not normal CD34(+) hematopoietic cells, were highly susceptible to this regimen. Finally, combining AZD1775 with Vorinostat in AML murine xenografts significantly reduced tumor burden and prolonged animal survival. A strategy combining Wee1 with HDACI inhibition warrants further investigation in AML with poor prognostic genetic aberrations. PMID:25283841

  7. Genetic polymorphism in three glutathione s-transferase genes and breast cancer risk

    SciTech Connect

    Woldegiorgis, S.; Ahmed, R.C.; Zhen, Y.; Erdmann, C.A.; Russell, M.L.; Goth-Goldstein, R.

    2002-04-01

    The role of the glutathione S-transferase (GST) enzyme family is to detoxify environmental toxins and carcinogens and to protect organisms from their adverse effects, including cancer. The genes GSTM1, GSTP1, and GSTT1 code for three GSTs involved in the detoxification of carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and benzene. In humans, GSTM1 is deleted in about 50% of the population, GSTT1 is absent in about 20%, whereas the GSTP1 gene has a single base polymorphism resulting in an enzyme with reduced activity. Epidemiological studies indicate that GST polymorphisms increase the level of carcinogen-induced DNA damage and several studies have found a correlation of polymorphisms in one of the GST genes and an increased risk for certain cancers. We examined the role of polymorphisms in genes coding for these three GST enzymes in breast cancer. A breast tissue collection consisting of specimens of breast cancer patients and non-cancer controls was analyzed by polymerase chain reaction (PCR) for the presence or absence of the GSTM1 and GSTT1 genes and for GSTP1 single base polymorphism by PCR/RFLP. We found that GSTM1 and GSTT1 deletions occurred more frequently in cases than in controls, and GSTP1 polymorphism was more frequent in controls. The effective detoxifier (putative low-risk) genotype (defined as presence of both GSTM1 and GSTT1 genes and GSTP1 wild type) was less frequent in cases than controls (16% vs. 23%, respectively). The poor detoxifier (putative high-risk) genotype was more frequent in cases than controls. However, the sample size of this study was too small to provide conclusive results.

  8. Genetic polymorphisms and activity of PON1 in a Mexican population

    SciTech Connect

    Rojas-Garcia, A.E.; Solis-Heredia, M.J.; Pina-Guzman, B.; Vega, L.; Lopez-Carrillo, L.; Quintanilla-Vega, B. . E-mail: mquintan@cinvestav.mx

    2005-06-15

    Human paraoxonase (PON1) plays a role in detoxification of organophosphorus (OP) compounds by hydrolyzing the bioactive oxons, and in reducing oxidative low-density lipoproteins, which may protect against atherosclerosis. Some PON1 polymorphisms have been found to be responsible for variations in catalytic activity and expression and have been associated with susceptibility to OP poisoning and vascular diseases. Both situations are of public health relevance in Mexico. Therefore, the aim of this study was to evaluate PON1 phenotype and the frequencies of polymorphisms PON1 -162, -108, 55, and 192 in a Mexican population. The studied population consisted of unrelated individuals (n = 214) of either gender, 18-52 years old. Serum PON1 activity was assayed using phenylacetate and paraoxon as substrates. PON1 variants, -162, 55, and 192, were determined by real-time PCR using the TaqMan System, and PON1 -108 genotype by PCR-RFLP. We found a wide interindividual variability of PON1 activity with a unimodal distribution; the range of enzymatic activity toward phenylacetate was 84.72 to 422.0 U/mL, and 88.37 to 1645.6 U/L toward paraoxon. All four PON1 polymorphisms showed strong linkage disequilibrium (D% >90). PON1 polymorphisms -108, 55, and 192 were independently associated with arylesterase activity; whereas the activity toward paraoxon was related only with PON1 192 polymorphism, suggesting that this polymorphism is determinant to infer PON1 activity. A better understanding of the phenotype and genotypes of PON1 in Mexican populations will facilitate further epidemiological studies involving PON1 variability in OP poisoning and in the development of atherosclerosis.

  9. Genetic and phenotypic variation among four Nguni sheep breeds using random amplified polymorphic DNA (RAPD) and morphological features.

    PubMed

    Gwala, Phiwamandla Emanuel; Kunene, Nokuthula Winfred; Bezuidenhout, Cornelius Carlos; Mavule, Bafowethu Sibanda

    2015-10-01

    This study was conducted to investigate phenotypic and genetic differentiation among the four Nguni sheep breeds. Sheep with two permanent incisors and above were sampled from areas, namely KwaZulu-Natal (Zulu sheep), Limpopo (Pedi sheep), Mozambique (Landim sheep) and Swaziland (Swazi sheep). The Dorper was used as an out-group. Eight morphometric variables were measured from each animal, and blood samples were collected (n?=?50 per population) for genetic characterization. The mean body weights for sheep were 30.41?±?0.41, 35.34?±?0.43, 35.23?±?0.43, 37.63?±?0.42 and 52.84?±?0.30 for Swazi, Zulu, Landim, Pedi and Dorper, respectively. Morphometric cluster analysis showed the Landim, Swazi and Zulu breeds in one cluster. The Pedi sheep were closer to the Dorper than to the other Nguni sheep. Random amplified polymorphic DNA (RAPD) technique was used to assess genetic variation. Eight primers were selected for analysis based on band pattern quality, reproducibility and the presence of distinctive bands. The Swazi sheep formed a cluster with Zulu sheep, and the Pedi formed a cluster with the Dorper. These results confirm indications by other researchers that Pedi sheep are genetically distant from Zulu and Swazi sheep breeds. This could indicate the possibility of cross breeding Zulu and Swazi sheep as a possible conservation strategy to control inbreeding. The mtDNA should be analyzed to trace the relationships between Pedi and the three Nguni sheep breeds through maternal lines. PMID:26178370

  10. Genetic differentiation among 6 populations of red deer (Cervus elaphus L.) in Poland based on microsatellite DNA polymorphism.

    PubMed

    Radko, Anna; Zalewski, D; Rubi?, Dominika; Szumiec, Agnieszka

    2014-12-01

    Recently, there has been considerable interest in genetic differentiation in the Cervidae family. A common tool used to determine genetic variation in different species, breeds and populations is DNA analysis, which allows for direct determination of the differences and changes within a group of animals. Because the analysis of microsatellite polymorphism in different Cervidae populations revealed considerable genetic variability in individual populations, it was important to test a set of markers in animals from these populations.The study was performed with muscle tissue and blood samples collected from a total of 793 red deer. Six groups (subpopulations) of red deer were defined according to region: Masurian (330 animals), Bieszczady (194 animals), Ma?opolska (80 animals), Sudety (76 animals), Lower Silesian (62 animals) and Lubusz (51 animals). The analysis involved 12 STR markers (BM1818, OarAE129, OarFCB5, OarFCB304, RM188, RT 1, RT 13, T26, T156, T193, T501, TGLA53), for which conditions for simultaneous amplification were established.Based on this study, it is concluded that the chosen set of 12 microsatellite markers could be used to evaluate the genetic structure and to monitor changes in Poland's red deer population. PMID:25475981

  11. Adaptive Color Polymorphism and Unusually High Local Genetic Diversity in the Side-Blotched Lizard, Uta stansburiana

    PubMed Central

    Micheletti, Steven; Parra, Eliseo; Routman, Eric J.

    2012-01-01

    Recently, studies of adaptive color variation have become popular as models for examining the genetics of natural selection. We examined color pattern polymorphism and genetic variation in a population of side-blotched lizards (Uta stansburiana) that is found in habitats with both dark (lava) and light colored (granite) substrates. We conducted a limited experiment for adult phenotypic plasticity in laboratory conditions. We recorded both substrate and lizard color patterns in the field to determine whether lizards tended to match their substrate. Finally we examined genetic variation in a gene (melanocortin 1 receptor) that has been shown to affect lizard color in other species and in a presumably neutral gene (mitochondrial cytochrome b). Populations were sampled in the immediate area of the lava flows as well as from a more distant site to examine the role of population structure. Our captive Uta did not change color to match their background. We show that side-blotched lizards tend to match the substrate on which it was caught in the field and that variation in the melanocortin 1 receptor gene does not correlate well with color pattern in this population. Perhaps the most remarkable result is that this population of side-blotched lizards shows extremely high levels of variation at both genetic markers, in the sense of allele numbers, with relatively low levels of between-allele sequence variation. Genetic variation across this small region was as great or greater than that seen in samples of pelagic fish species collected worldwide. Statistical analysis of genetic variation suggests rapid population expansion may be responsible for the high levels of variation. PMID:23133520

  12. Population genetic structure of clinical and environmental isolates of Blastomyces dermatitidis, Based on 27 Polymorphic Microsatellite Markers

    USGS Publications Warehouse

    Meece, J.K.; Anderson, J.L.; Fisher, M.C.; Henk, D.A.; Sloss, Brian L.; Reed, K.D.

    2011-01-01

    Blastomyces dermatitidis, a thermally dimorphic fungus, is the etiologic agent of North American blastomycosis. Clinical presentation is varied, ranging from silent infections to fulminant respiratory disease and dissemination to skin and other sites. Exploration of the population genetic structure of B. dermatitidis would improve our knowledge regarding variation in virulence phenotypes, geographic distribution, and difference in host specificity. The objective of this study was to develop and test a panel of microsatellite markers to delineate the population genetic structure within a group of clinical and environmental isolates of B. dermatitidis. We developed 27 microsatellite markers and genotyped B. dermatitidis isolates from various hosts and environmental sources (n = 112). Assembly of a neighbor-joining tree of allele-sharing distance revealed two genetically distinct groups, separated by a deep node. Bayesian admixture analysis showed that two populations were statistically supported. Principal coordinate analysis also reinforced support for two genetic groups, with the primary axis explaining 61.41% of the genetic variability. Group 1 isolates average 1.8 alleles/locus, whereas group 2 isolates are highly polymorphic, averaging 8.2 alleles/locus. In this data set, alleles at three loci are unshared between the two groups and appear diagnostic. The mating type of individual isolates was determined by PCR. Both mating type-specific genes, the HMG and ??-box domains, were represented in each of the genetic groups, with slightly more isolates having the HMG allele. One interpretation of this study is that the species currently designated B. dermatitidis includes a cryptic subspecies or perhaps a separate species. ?? 2011, American Society for Microbiology.

  13. Genetic Association Between NFKBIA -881A>G Polymorphism and Cancer Susceptibility

    PubMed Central

    Geng, Peiliang; Ou, Juanjuan; Li, Jianjun; Liao, Yunmei; Wang, Ning; Sa, Rina; Xiang, Lisha; Liang, Houjie

    2015-01-01

    Abstract Several epidemiological studies have focused on the role of nuclear factor-kappa-B inhibitor-alpha (NFKBIA) -881 A>G polymorphism in cancer susceptibility. However, the published data have led to contentious results. This study was designed to examine the association between -881 A>G polymorphism and cancer risk. Comprehensive search of PubMed, Web of science and Embase, identified a total of 5 case-control studies. To assess the association, comparison among all subjects plus subgroup analysis by ethnicity was performed and odds ratio (OR) along with 95% confidence interval (CI) was calculated with the fixed-effect model or the random-effects model dependent on the heterogeneity. The pooling data consisting of 1965 cancer cases and 2717 cancer-free controls demonstrated no significant association with overall cancer risk. However, the subgroup of Asian populations showed statistical evidence for an increase in risk of cancer (GG vs. AA, OR, 2.14; 95% CI, 1.03–4.46; GG?+?GA vs. AA, OR, 1.22; 95% CI, 1.01–1.47; GG vs. GA?+?AA, OR, 2.09; 95% CI, 1.01–4.34). This investigation on the association of -881 A>G polymorphism and cancer susceptibility reveals that -881 A>G polymorphism may act as a candidate for cancer development in Asian populations. PMID:26252270

  14. Verification of genetic identity of introduced cacao germplasm in Ghana using single nucleotide polymorphism (SNP) markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accurate identification of individual genotypes is important for cacao (Theobroma cacao L.) breeding, germplasm conservation and seed propagation. The development of single nucleotide polymorphism (SNP) markers in cacao offers an effective way to use a high-throughput genotyping system for cacao gen...

  15. HLA-DR polymorphism in a senegalese mandenka population: DNA oligotyping and population genetics of DRB1 specificities

    SciTech Connect

    Tiercy, J.M.; Shi-Isaac, X.; Jeannet, M.; Sanchez-Mazas, A.; Langaney, A.; Mach, B.; Excoffier, L.

    1992-09-01

    HLA class II loci are useful markers in human population genetics, because they are extremely variable and because new molecular techniques allow large-scale analysis of DNA allele frequencies. Direct DNA typing by hybridization with sequence-specific oligonucleotide probes (HLA oligotyping) after enzymatic in vitro PCR amplification detects HLA allelic polymorphisms for all class II loci. A detailed HLA-DR oligotyping analysis of 191 individuals from a geographically, culturally, and genetically well-defined western African population, the Mandenkalu, reveals a high degree of polymorphism, with at least 24 alleles and a heterozygosity level of .884 for the DRB1 locus. The allele DRB1[sup *]1304, defined by DNA sequencing of the DRB1 first-domain exon, is the most frequent allele (27.1%). It accounts for an unusually high DR13 frequency, which is nevertheless within the neutral frequency range. The next most frequency specificities are DR11, DR3, and DR8. Among DRB3-encoded alleles, DR52B (DRB3[sup *]02) represents as much as 80.7% of all DR52 halotypes. A survey of HLA-DR specificities in populations from different continents shows a significant positive correlation between genetic and geographic differentiation patterns. A homozygosity test for selective neutrality of DR specificities is not significant for the mandenka population but is rejected for 20 of 24 populations. Observed high heterozygosity levels in tested populations are compatible with an overdominant model with a small selective advantage for heterozygotes. 91 refs., 5 figs., 5 tabs.

  16. Predisposition to Childhood Otitis Media and Genetic Polymorphisms within the Toll-Like Receptor 4 (TLR4) Locus

    PubMed Central

    Kentala, Erna; Hammarén-Malmi, Sari; Bhutta, Mahmood F.; MacArthur, Carol J.; Wilmot, Beth; Casselbrant, Margaretha; Conley, Yvette P.; Weeks, Daniel E.; Mandel, Ellen M.; Vaarala, Outi; Kallio, Anna; Melin, Merit; Nieminen, Janne K.; Leinonen, Eira; Kere, Juha; Mattila, Petri S.

    2015-01-01

    Background Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts. Methods We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls. Results In the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P = .003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P = .002) and rs1329057 (OR 1.29, P = .003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNF? secretion in myeloid dendritic cells. Conclusions The TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM. PMID:26177520

  17. The frequency of CYP2C19 genetic polymorphisms in Russian patients with peptic ulcers treated with proton pump inhibitors

    PubMed Central

    Sychev, DA; Denisenko, NP; Sizova, ZM; Grachev, AV; Velikolug, KA

    2015-01-01

    Introduction Proton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcers, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19). CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultra-rapid metabolism of proton pump inhibitors. Genetic polymorphisms of CYP2C19 could be of clinical concern in the treatment of peptic ulcers with proton pump inhibitors. Aim To investigate the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers. Methods We retrospectively reviewed the cases of 971 patients of Caucasian origin with Russian nationality from Moscow region with endoscopically and histologically proven ulcers, 428 males (44%) and 543 females (56%). The mean age was 44.6±11.9 years (range: 15–88 years). DNA was extracted from ethylenediaminetetraacetic acid whole blood samples (10 mL). The polymorphisms CYP2C19 681G.A (CYP2C19*2, rs4244285), CYP2C19 636 G.A (CYP2C19*3, rs4986893) and CYP2C19 -806 C.T (CYP2C19*17, rs12248560) were evaluated using real-time polymerase chain reaction. Results Regarding CYP2C19 genotype, 317 patients (32.65%) out of 971 were CYP2C19*1/*1 carriers classified as extensive metabolizers. Three hundred and eighty-six (39.75%) with CYP2C19*1/*17 or CYP2C19*17/*17 genotype were ultra-rapid metabolizers. Two hundred and fifty-one people (25.85%) were intermediate metabolizers with CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*1/*3, CYP2C19*3/*17 genotypes. Seventeen patients (1.75%) with CYP2C19*2/*2, CYP2C19*3/*3, CYP2C19*2/*3 genotypes were poor metabolizers. The allele frequencies were the following: CYP2C19*2 – 0.140, CYP2C19*3 – 0.006, CYP2C19*17 – 0.274. Conclusion There is a high frequency of CYP2C19 genotypes associated with modified response to proton pump inhibitors in Russian patients with peptic ulcers. Genotyping for CYP2C19 polymorphisms is suggested to be a useful tool for personalized dosing of proton pump inhibitors. PMID:26109874

  18. Cyclooxygenase 2 genetic polymorphism may increase the risk of developing leukoaraiosis in Chinese.

    PubMed

    Shan, Xiao-yun; Chen, Guo-zhong; Cheng, Gan-ping; Tao, Hong-miao

    2013-10-01

    Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins, which are important mediators of inflammation. To clarify the role of inflammation in the pathogenesis of cerebral small vessel disease (SVD), we investigate the possible modulating effect of the functional COX-2 polymorphisms -1195G > A (rs689466) and -765G > C (rs20417) on the risk for development of cerebral SVD in a Chinese population. Genomic DNA of 116 patients with lacunar infarction (LI), 334 patients with leukoaraiosis (LA) and 450 control subjects was genotyped for the COX-2 -1195G > A and -765G > C polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. Distribution of genotypes and haplotypes in patients and controls were compared. The genotype distribution of the -765G > C polymorphism was not different between the patients with LI or LA and the control group. The 1195A allele carriers was identified independently to be related with LA (adjusted OR = 1.41, 95 % confidence interval (CI) = 1.09-2.10, P = 0.03) but not associated with LI. The linkage disequilibrium analysis showed that -1195G > A and -765G > C SNPs are moderate linkage disequilibrium in this study population (D' = 0.70, r(2) = 0.16). Compared with G-1195-G-765 haplotype, the haplotype of A-1195-G-765 showed significantly increased the risk of LA (OR = 1.24, 95 % CI = 1.10-1.55, P = 0.04) but not LI. In conclusion, we found that -1195G > A polymorphism and A-1195-G-765 haplotype of COX-2 were associated with susceptibility to LA in a Chinese population. PMID:23852948

  19. Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations.

    PubMed

    Will, Britta; Zhou, Li; Vogler, Thomas O; Ben-Neriah, Susanna; Schinke, Carolina; Tamari, Roni; Yu, Yiting; Bhagat, Tushar D; Bhattacharyya, Sanchari; Barreyro, Laura; Heuck, Christoph; Mo, Yonkai; Parekh, Samir; McMahon, Christine; Pellagatti, Andrea; Boultwood, Jacqueline; Montagna, Cristina; Silverman, Lewis; Maciejewski, Jaroslaw; Greally, John M; Ye, B Hilda; List, Alan F; Steidl, Christian; Steidl, Ulrich; Verma, Amit

    2012-09-01

    Even though hematopoietic stem cell (HSC) dysfunction is presumed in myelodysplastic syndrome (MDS), the exact nature of quantitative and qualitative alterations is unknown. We conducted a study of phenotypic and molecular alterations in highly fractionated stem and progenitor populations in a variety of MDS subtypes. We observed an expansion of the phenotypically primitive long-term HSCs (lineage(-)/CD34(+)/CD38(-)/CD90(+)) in MDS, which was most pronounced in higher-risk cases. These MDS HSCs demonstrated dysplastic clonogenic activity. Examination of progenitors revealed that lower-risk MDS is characterized by expansion of phenotypic common myeloid progenitors, whereas higher-risk cases revealed expansion of granulocyte-monocyte progenitors. Genome-wide analysis of sorted MDS HSCs revealed widespread methylomic and transcriptomic alterations. STAT3 was an aberrantly hypomethylated and overexpressed target that was validated in an independent cohort and found to be functionally relevant in MDS HSCs. FISH analysis demonstrated that a very high percentage of MDS HSC (92% ± 4%) carry cytogenetic abnormalities. Longitudinal analysis in a patient treated with 5-azacytidine revealed that karyotypically abnormal HSCs persist even during complete morphologic remission and that expansion of clonotypic HSCs precedes clinical relapse. This study demonstrates that stem and progenitor cells in MDS are characterized by stage-specific expansions and contain epigenetic and genetic alterations. PMID:22753872

  20. Genetic diversity analysis among male and female Jojoba genotypes employing gene targeted molecular markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) markers

    PubMed Central

    Heikrujam, Monika; Kumar, Jatin; Agrawal, Veena

    2015-01-01

    To detect genetic variations among different Simmondsia chinensis genotypes, two gene targeted markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) were employed in terms of their informativeness and efficiency in analyzing genetic relationships among different genotypes. A total of 15 SCoT and 17 CBDP primers detected genetic polymorphism among 39 Jojoba genotypes (22 females and 17 males). Comparatively, CBDP markers proved to be more effective than SCoT markers in terms of percentage polymorphism as the former detecting an average of 53.4% and the latter as 49.4%. The Polymorphic information content (PIC) value and marker index (MI) of CBPD were 0.43 and 1.10, respectively which were higher than those of SCoT where the respective values of PIC and MI were 0.38 and 1.09. While comparing male and female genotype populations, the former showed higher variation in respect of polymorphic percentage and PIC, MI and Rp values over female populations. Nei's diversity (h) and Shannon index (I) were calculated for each genotype and found that the genotype “MS F” (in both markers) was highly diverse and genotypes “Q104 F” (SCoT) and “82–18 F” (CBDP) were least diverse among the female genotype populations. Among male genotypes, “32 M” (CBDP) and “MS M” (SCoT) revealed highest h and I values while “58-5 M” (both markers) was the least diverse. Jaccard's similarity co-efficient of SCoT markers ranged from 0.733 to 0.922 in female genotypes and 0.941 to 0.746 in male genotype population. Likewise, CBDP data analysis also revealed similarity ranging from 0.751 to 0.958 within female genotypes and 0.754 to 0.976 within male genotype populations thereby, indicating genetically diverse Jojoba population. Employing the NTSYS (Numerical taxonomy and multivariate analysis system) Version 2.1 software, both the markers generated dendrograms which revealed that all the Jojoba genotypes were clustered into two major groups, one group consisting of all female genotypes and another group comprising of all male genotypes. During the present investigation, CBDP markers proved more informative in studying genetic diversity among Jojoba. Such genetically diverse genotypes would thus be of great significance for breeding, management and conservation of elite (high yielding) Jojoba germplasm. PMID:26110116

  1. Am. J. Hum. Genet. 74:11021110, 2004 The T Allele of a Single-Nucleotide Polymorphism 13.9 kb Upstream

    E-print Network

    Weale, Michael E.

    Ayele Tarekegn,1 Dallas M. Swallow,2 Neil Bradman,1 and Mark G. Thomas1 1 The Centre for Genetic adults cannot digest lactose effectively (reviewed in Swallow and Hollox 2000). However, in humans Mendelian polymorphic trait (Sahi 1974; Swallow and Harvey 1993). Received December 2, 2003; accepted

  2. Cacao single-nucleotide polymorphism (SNP) markers: A discovery strategy to identify SNPs for genotyping, genetic mapping and genome wide association studies (GWAS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single-nucleotide polymorphisms (SNPs) are the most common genetic markers in Theobroma cacao, occurring approximately once in every 200 nucleotides. SNPs, like microsatellites, are co-dominant and PCR-based, but they have several advantages over microsatellites. They are unambiguous, so that a SN...

  3. Role of 5-HTTLPR Polymorphism in the Development of the Inward/Outward Personality Organization: A Genetic Association Study

    PubMed Central

    Nardi, Bernardo; Marini, Alessandra; Turchi, Chiara; Arimatea, Emidio; Tagliabracci, Adriano; Bellantuono, Cesario

    2013-01-01

    Reciprocity with primary caregivers affects subjects' adaptive abilities toward the construction of the most useful personal meaning organization (PMO) with respect to their developmental environment. Within cognitive theory the post-rationalist approach has outlined two basic categories of identity construction and of regulation of cognitive and emotional processes: the Outward and the Inward PMO. The presence of different, consistent clinical patterns in Inward and Outward subjects is paralleled by differences in cerebral activation during emotional tasks on fMRI and by different expression of some polymorphisms in serotonin pathways. Since several lines of evidence support a role for the 5-HTTLPR polymorphism in mediating individual susceptibility to environmental emotional stimuli, this study was conducted to investigate its influence in the development of the Inward/Outward PMO. PMO was assessed and the 5-HTTLPR polymorphism investigated in 124 healthy subjects who were subdivided into an Inward (n?=?52) and an Outward (n?=?72) group. Case-control comparisons of short allele (S) frequencies showed significant differences between Inwards and Outwards (p?=?0.036, ?2 test; p?=?0.026, exact test). Genotype frequencies were not significantly different although values slightly exceeded p?0.05 (p?=?0.056, ?2 test; p?=?0.059, exact test). Analysis of the 5-HTTLPR genotypes according to the recessive inheritance model showed that the S/S genotype increased the likelihood of developing an Outward PMO (p?=?0.0178, ?2 test; p?=?0.0143, exact test; OR?=?3.43, CI (95%)?=?1.188–9.925). A logistic regression analysis confirmed the association between short allele and S/S genotypes with the Outward PMO also when gender and age were considered. However none of the differences remained significant after correction for multiple testing, even though using the recessive model they approach significance. Overall our data seem to suggest a putative genetic basis for interindividual differences in PMO development. PMID:24358153

  4. Association between ErbB3 genetic polymorphisms and coronary artery disease in the Han and Uyghur populations of China

    PubMed Central

    Maitusong, Buamina; Xie, Xiang; Ma, Yi-Tong; Fu, Zhen-Yan; Yang, Yi-Ning; Li, Xiao-Mei; Liu, Fen; Chen, Bang-Dang; Gai, Min-Tao

    2015-01-01

    Background: ErbB3 is a member of the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinases. Recent research has shown that amplification of this gene is related to prostate, bladder and breast cancers, as well as low-density lipoprotein cholesterol (LDL-C) metabolism. LDL-C plays a considerable role in the development of cardiovascular disease. Thus, the present study assessed the association between human ErbB3 gene polymorphisms and coronary artery disease (CAD) in Han and Uygur populationsin China. Methods: We performed two independent case-control studies with a Han population (339 CAD patients and 395 control subjects) and a Uygur population (306 CAD patients and 325 control subjects). All of the CAD patients and controls were genotyped for the same three single nucleotide polymorphisms (rs877636, rs705708, and rs10783779) in the ErbB3 gene by real-time PCR. Results: In the Han population, rs877636 polymorphisms were associated with CAD on the basis of the genotypes, dominant model, additive model, and allele frequency (for genotypes: P = 0.008; for dominant model: P = 0.003; for additive model: P = 0.004; for allele: P = 0.008), and these significant difference was retained (all P < 0.05) after adjusting for the major confounding factors. Conclusion: The CT genotype and C allele of rs877636 in the ErbB3 gene could be a genetic marker of CAD risk for the Han population in China. PMID:26629179

  5. Genetic association of Toll-like-receptor 4 and tumor necrosis factor-alpha polymorphisms with Plasmodium falciparum blood infection levels.

    PubMed

    Basu, Madhumita; Maji, Ardhendu Kumar; Chakraborty, Arindom; Banerjee, Rahul; Mullick, Shrabanee; Saha, Pabitra; Das, Sonali; Kanjilal, Sumana Datta; Sengupta, Sanghamitra

    2010-07-01

    Dysregulated innate immune responses due to inappropriate signaling by Toll-like receptors (TLRs) and aberrant production of pro-inflammatory cytokines are implicated in the immunopathology and disease outcome in Plasmodium falciparum malaria. This study investigates the relationship between polymorphic variability of candidate genes including TLR-2, -4, -9, tumor necrosis factor-alpha and lymphotoxin-alpha and blood infection level in Indian mild malaria patients. Genotyping was carried out by PCR-RFLP and sequencing. Association of parasite load with genotypes was examined using model based and model free approaches. Allele and haplotype based risk assessment for disease severity was performed by stratifying the patients into high and low parasitemic groups on the basis of a threshold value derived by employing a two-component mixture model and expectation-maximization algorithm. The mean parasitemia was significantly increased for variant homozygous genotype (C/C) at TNF-alpha promoter -1031 and major homozygous genotypes encoding Asp/Asp and Thr/Thr at codons 299 and 399, respectively, on TLR4 polypeptide. Individuals harboring combined genotype C/C-Asp/Asp-Thr/Thr on TNF-alpha and TLR4 presented the highest parasite load. The frequencies of variant allele C in TNF-1031 (OR=1.91 with 95% CI=1.24-2.94) and TNF-alpha promoter haplotypes C-C-G-G (OR=1.99 with 95% CI=1.21-3.27) and C-C-G-A (OR=2.96 with 95% CI=1.19-7.37) pertaining to loci TNF-1031/-857/-308/-238 were significantly elevated in the high parasitemic group. On the contrary, the frequencies of variant allele encoding Ile at 399 (OR=0.55 with 95% CI=0.32-0.94) and haplotype corresponding to Gly-Ile (299-399) (OR=0.51 with 95% CI=0.28-0.9) in TLR4 were higher in low parasitemic group. In silico analysis indicate differential binding of transcription factors to TNF-alpha promoter haplotypes and alteration in the surface charge distribution of the TLR4 variant proteins. Our results support a genetic role of TLR4 and TNF-alpha in controlling the blood infection level in mild malaria. PMID:20307689

  6. Comparative population genetics of the panicoid grasses: sequence polymorphism, linkage disequilibrium and selection in a diverse sample of sorghum bicolor.

    PubMed Central

    Hamblin, Martha T; Mitchell, Sharon E; White, Gemma M; Gallego, Javier; Kukatla, Rakesh; Wing, Rod A; Paterson, Andrew H; Kresovich, Stephen

    2004-01-01

    Levels of genetic variation and linkage disequilibrium (LD) are critical factors in association mapping methods as well as in identification of loci that have been targets of selection. Maize, an outcrosser, has a high level of sequence variation and a limited extent of LD. Sorghum, a closely related but largely self-pollinating panicoid grass, is expected to have higher levels of LD. As a first step in estimation of population genetic parameters in sorghum, we surveyed 27 diverse S. bicolor accessions for sequence variation at a total of 29,186 bp in 95 short regions derived from genetically mapped RFLPs located throughout the genome. Consistent with its higher level of inbreeding, the extent of LD is at least severalfold greater in sorghum than in maize. Total sequence variation in sorghum is about fourfold lower than that in maize, while synonymous variation is fivefold lower, suggesting a smaller effective population size in sorghum. Because we surveyed a species-wide sample, the mating system, which primarily affects population-level diversity, may not be primarily responsible for this difference. Comparisons of polymorphism and divergence suggest that both directional and diversifying selection have played important roles in shaping variation in the sorghum genome. PMID:15166170

  7. Genetic associations of FCRL3 polymorphisms with the susceptibility of Graves ophthalmopathy in a Chinese population

    PubMed Central

    Wu, Shanshan; Cai, Ting; Chen, Feng; He, Xuefei; Cui, Zhihua

    2015-01-01

    Background: Graves ophthalmopathy (GO) is a form of autoimmune thyroid disease commonly found in approximately 25-50% patients with Graves’ disease. Both the thyroid-specific genes and immune-modulating genes are involved in susceptibility to GO. However, even though FCRL3 polymorphisms were also autoimmune-associated genes, no study has been performed regarding the association of FCRL3 with GO. Therefore, the objective of the current study was to conduct a basic case-control study in a Chinese population. Methods and materials: Seven SNPs were selected in this case-control study and 577 GD patients and 608 controls were recruited. Odds ratio and 95% confidence interval were used to assess the association between susceptibility of GO and FCRL3 polymorphisms with Stata software (Version 11.0, Stata Corp LP, USA). Results: The case-control analysis showed that three polymorphisms, FCRL3_3C, FCRL3_5C, FCRL3_6A, were significantly associated with raised risk of GO in a Chinese Han population in the allelic model [OR = 1.28, 95% CI: 1.09-1.51, P = 0.003; OR = 1.26, 95% CI: 1.07-1.48, P = 0.005; OR = 1.25, 95% CI: 1.06-1.47, P = 0.007]. Conclusions: This case-control analysis confirmed that the FCRL3_3, FCRL3_5 and FCRL3_6 polymorphisms were associated with significantly increased risk of GO in a Chinese population.

  8. Functional genetic polymorphisms and female reproductive disorders: Part I: polycystic ovary syndrome and ovarian response

    PubMed Central

    Simoni, M.; Tempfer, C.B.; Destenaves, B.; Fauser, B.C.J.M.

    2008-01-01

    BACKGROUND The identification of polymorphisms associated with a disease can help to elucidate its pathogenesis, and this knowledge can be used to improve prognosis for women with a particular disorder, such as polycystic ovary syndrome (PCOS). Since an altered response to ovarian stimulation is also a characteristic of the disease, further knowledge about its aetiology could help in defining the parameters that determine the response of an individual to ovarian stimulation. METHODS PubMed and EMBASE databases were systematically searched for gene association studies published until the end of August 2007, using search criteria relevant to PCOS and ovarian response to stimulation. Data from additional papers identified through hand searches were also included; 139 publications were reviewed. RESULTS Several genes involved in ovarian function and metabolism are associated with increased susceptibility to PCOS, but none is strong enough to correlate alone with susceptibility to the disease, or response to therapy. A single-nucleotide polymorphism in exon 10 of the FSH receptor (FSHR) gene, FSHR p.N680S, was consistently identified as having a significant association with ovarian response to FSH. CONCLUSIONS No consistent association between gene polymorphism and PCOS could be identified. The FSHR gene may play a significant role in the success of ovarian stimulation, and can be used as a marker to predict differences in FSHR function and ovarian response to FSH. Genotyping the FSHR p.N680S polymorphism may provide a means of identifying a population of poor responders before in vitro fertilization procedures are initiated. PMID:18603647

  9. Genetic polymorphisms in estrogen-related genes and the risk of breast cancer among Han Chinese women.

    PubMed

    Sun, Min-Ying; Du, Hong-Yan; Zhu, An-Na; Liang, Hui-Ying; de Garibay, Gorka Ruiz; Li, Fen-Xia; Li, Ming; Yang, Xue-Xi

    2015-01-01

    Exposure to high levels of estrogen is considered an important risk factor for susceptibility to breast cancer. Common polymorphisms in genes that affect estrogen levels may be associated with breast cancer risk, but no comprehensive study has been performed among Han Chinese women. In the present study, 32 single-nucleotide polymorphisms (SNPs) in estrogen-related genes were genotyped using the MassARRAY IPLEX platform in 1076 Han Chinese women. Genotypic and allelic frequencies were compared between case and control groups. Unconditional logistic regression was used to assess the effects of SNPs on breast cancer risk. Associations were also evaluated for breast cancer subtypes stratified by estrogen receptor (ER) and progesterone receptor (PR) status. Case-control analysis showed a significant relation between heterozygous genotypes of rs700519 and rs2069522 and breast cancer risk (OR = 0.723, 95% CI = 0.541-0.965, p = 0.028 and OR = 1.500, 95% CI = 1.078-2.087, p = 0.016, respectively). Subgroup comparisons revealed that rs2446405 and rs17268974 were related to ER status, and rs130021 was associated with PR status. Our findings suggest that rs700519 and rs2069522 are associated with susceptibility to breast cancer among the Han Chinese population and have a cumulative effect with three other identified SNPs. Further genetic and functional studies are needed to identify additional SNPs, and to elucidate the underlying molecular mechanisms. PMID:25689428

  10. Genetic Polymorphisms in Plasmodium vivax Dihydrofolate Reductase and Dihydropteroate Synthase in Isolates from the Philippines, Bangladesh, and Nepal

    PubMed Central

    Thongdee, Pimwan; Kuesap, Jiraporn; Rungsihirunrat, Kanchana; Dumre, Shyam Prakash; Espino, Effie; Noedl, Harald; Na-Bangchang, Kesara

    2015-01-01

    Genetic polymorphisms of pvdhfr and pvdhps genes of Plasmodium vivax were investigated in 83 blood samples collected from patients in the Philippines, Bangladesh, and Nepal. The SNP-haplotypes of the pvdhfr gene at the amino acid positions 13, 33, 57, 58, 61, 117, and 173, and that of the pvdhps gene at the positions 383 and 553 were analyzed by nested PCR-RFLP. Results suggest diverse polymorphic patterns of pvdhfr alone as well as the combination patterns with pvdhps mutant alleles in P. vivax isolates collected from the 3 endemic countries in Asia. All samples carried mutant combination alleles of pvdhfr and pvdhps. The most prevalent combination alleles found in samples from the Philippines and Bangladesh were triple mutant pvdhfr combined with single mutant pvdhps allele and triple mutant pvdhfr combined with double wild-type pvdhps alleles, respectively. Those collected from Nepal were quadruple mutant pvdhfr combined with double wild-type pvdhps alleles. New alternative antifolate drugs which are effective against sulfadoxine-pyrimethamine (SP)-resistant P. vivax are required. PMID:25925184

  11. Genetic Polymorphisms in Plasmodium vivax Dihydrofolate Reductase and Dihydropteroate Synthase in Isolates from the Philippines, Bangladesh, and Nepal.

    PubMed

    Thongdee, Pimwan; Kuesap, Jiraporn; Rungsihirunrat, Kanchana; Dumre, Shyam Prakash; Espino, Effie; Noedl, Harald; Na-Bangchang, Kesara

    2015-04-01

    Genetic polymorphisms of pvdhfr and pvdhps genes of Plasmodium vivax were investigated in 83 blood samples collected from patients in the Philippines, Bangladesh, and Nepal. The SNP-haplotypes of the pvdhfr gene at the amino acid positions 13, 33, 57, 58, 61, 117, and 173, and that of the pvdhps gene at the positions 383 and 553 were analyzed by nested PCR-RFLP. Results suggest diverse polymorphic patterns of pvdhfr alone as well as the combination patterns with pvdhps mutant alleles in P. vivax isolates collected from the 3 endemic countries in Asia. All samples carried mutant combination alleles of pvdhfr and pvdhps. The most prevalent combination alleles found in samples from the Philippines and Bangladesh were triple mutant pvdhfr combined with single mutant pvdhps allele and triple mutant pvdhfr combined with double wild-type pvdhps alleles, respectively. Those collected from Nepal were quadruple mutant pvdhfr combined with double wild-type pvdhps alleles. New alternative antifolate drugs which are effective against sulfadoxine-pyrimethamine (SP)-resistant P. vivax are required. PMID:25925184

  12. Genetic polymorphisms of Trim5a are associated with disease progression in acutely and chronically HIV-infected patients

    PubMed Central

    Sun, Xin; Li, Wei; Liu, Wenzhen; Wang, Rui; Li, Qunhui; Wu, Hao

    2015-01-01

    Background: The tripartite interaction motif 5a (Trim5a) plays critical roles in restricting various kinds of retroviruses in different species. It has been shown that Trim5a could inhibit HIV-1 inhibition in vitro. Methods: In this study, 16 SNPs of Trim5a gene were screened in 236 acutely HIV-infected patients (169 common type (CT) patients and 67 patients with rapid disease progression). In addition, they were screened in 162 chronically HIV-infected patients (147 common type patients and 15 long-term non-progressors (LTNP)). The potential effects of polymorphisms at Trim5a genes on HIV-infection disease progression were analyzed. Results: Among all tested SNP sites, 3 SNPs (rs3824949, rs2291841 and rs11038628) were identified to be associated with rapid disease progression in acutely HIV-infected patients. Carriage of rs3824949 allele G, rs2291841 allele C or rs11038628 allele T associated with rapid disease progression. In chronically HIV-infected patients, Patients carrying rs3802981 allele C or rs3802980 allele A had increased opportunity to be LTNP. We also found that greater age was associated with disease deterioration. Conclusions: Different genetic polymorphisms of Trim5a may have an impact on the clinical course of both acute and chronic stages of HIV-infection. PMID:26629134

  13. Genetic association of single nucleotide polymorphisms in dystrobrevin binding protein 1 gene with schizophrenia in a Malaysian population.

    PubMed

    Tan, Grace Kang Ning; Tee, Shiau Foon; Tang, Pek Yee

    2015-05-01

    Dystrobrevin binding protein 1 (DTNBP1) gene is pivotal in regulating the glutamatergic system. Genetic variants of the DTNBP1 affect cognition and thus may be particularly relevant to schizophrenia. We therefore evaluated the association of six single nucleotide polymorphisms (SNPs) with schizophrenia in a Malaysian population (171 cases; 171 controls). Associations between these six SNPs and schizophrenia were tested in two stages. Association signals with p < 0.05 and minor allele frequency > 0.05 in stage 1 were followed by genotyping the SNPs in a replication phase (stage 2). Genotyping was performed with sequenced specific primer (PCR-SSP) and restriction fragment length polymorphism (PCR-RFLP). In our sample, we found significant associations between rs2619522 (allele p = 0.002, OR = 1.902, 95%CI = 1.266 - 2.859; genotype p = 0.002) and rs2619528 (allele p = 0.008, OR = 1.606, 95%CI = 1.130 - 2.281; genotype p = 6.18 × 10(-5)) and schizophrenia. Given that these two SNPs may be associated with the pathophysiology of schizophrenia, further studies on the other DTNBP1 variants are warranted. PMID:26273215

  14. Genetic Association Between CD143 rs4340 Polymorphism and Pneumonia risk: A Meta Analysis.

    PubMed

    Wang, Hong; Zhang, Kun; Qin, Haifeng; Yang, Lin; Zhang, Liyu; Cao, Yanyan

    2015-07-01

    rs4340 polymorphism at intron 16 of the angiotensin-converting enzyme (CD143) gene was reported to repress cough reflex by reducing bradykinin and substance P levels, thus increasing the likelihood to develop pneumonia. There have been different reports regarding the correlation of CD143 rs4340 genotypes with pneumonia risk, which prompted us to perform a meta-analysis to determine the elusive association.We combined multiple keywords to identify the studies addressing the association between CD143 rs4340 genotypes and pneumonia risk covered in the EMBASE, Google Scholar, PubMed, and CNKI databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the risk of pneumonia. The fixed-effects model (FEM) was used.A total of 10 studies were analyzed in this quantitative analysis. We found a strong association between rs4340 single nucleotide polymorphism (SNP) and pneumonia risk using the recessive model (FEM: OR 1.33, 95% CI 1.13-1.57). A significantly increased risk was also indicated under the recessive model in Asian populations (FEM: OR 1.57, 95% CI 1.19-2.07), community-acquired pneumonia (CAP) (FEM: OR 1.31, 95% CI 1.08-1.60), and nosocomial pneumonia (NP) (FEM: OR 1.52, 95% CI 1.06-2.19).Our meta-analysis demonstrates that CD143 rs4340 polymorphism may represent a risk factor for pneumonia. PMID:26222869

  15. Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3

    SciTech Connect

    Michelini, S.; Urbanek, M.; Goldman, D.

    1995-06-19

    Centrally administered oxytocin has been reported to facilitate affiliative and social behaviors, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3{prime} untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. 53 refs., 2 figs., 1 tab.

  16. A Genetic Polymorphism of the Endogenous Opioid Dynorphin Modulates Monetary Reward Anticipation in the Corticostriatal Loop

    PubMed Central

    Votinov, Mikhail; Pripfl, Juergen; Windischberger, Christian; Kalcher, Klaudius; Zimprich, Alexander; Zimprich, Fritz; Moser, Ewald

    2014-01-01

    The dynorphin/?-opioid receptor (KOP-R) system has been shown to play a role in different types of behavior regulation, including reward-related behavior and drug craving. It has been shown that alleles with 3 or 4 repeats (HH genotype) of the variable nucleotide tandem repeat (68-bp VNTR) functional polymorphism of the prodynorphin (PDYN) gene are associated with higher levels of dynorphin peptides than alleles with 1 or 2 repeats (LL genotype). We used fMRI on N?=?71 prescreened healthy participants to investigate the effect of this polymorphism on cerebral activation in the limbic-corticostriatal loop during reward anticipation. Individuals with the HH genotype showed higher activation than those with the LL genotype in the medial orbitofrontal cortex (mOFC) when anticipating a possible monetary reward. In addition, the HH genotype showed stronger functional coupling (as assessed by effective connectivity analyses) of mOFC with VMPFC, subgenual anterior cingulate cortex, and ventral striatum during reward anticipation. This hints at a larger sensitivity for upcoming rewards in individuals with the HH genotype, resulting in a higher motivation to attain these rewards. These findings provide first evidence in humans that the PDYN polymorphism modulates neural processes associated with the anticipation of rewards, which ultimately may help to explain differences between genotypes with respect to addiction and drug abuse. PMID:24587148

  17. Genetic polymorphisms of blood and milk and reproduction in Holstein cattle.

    PubMed

    Hargrove, G L; Kiddy, C A; Young, C W; Hunter, A G; Trimberger, G W; Mather, R E

    1980-07-01

    Associations of blood and milk protein polymorphisms with reproductive performance were examined in more than 32,000 services in 15,000 service periods of 6,000 cows and 700 service sires in Holsteins. Seven blood groups, one serum protein, and four milk proteins were analyzed for relation to reproductive traits including conception rate and days open. Associations between polymorphic systems and reproductive traits in 15 of 112 analyses were significant. The S blood system appeared most influential, having statistical significance in five of ten traits. These were conception rates in all services for female phenotypes, male phenotypes, and male by female phenotypes combined, conception rate in first services for female phenotypes, and probability of conception for female phenotypes. The FV system influenced conception rates in all services and in first services for male by female phenotypes combined. Four of the polymorphic systems had no effect on any of the reproductive traits. Maternal-fetal incompatibility was not evident from comparing parental combinations of aborted fetuses and normal calves. Conception rates declined with age of cow. For animals that ultimately conceived, conception rates did not decline consistently from first to later services within a service period. PMID:7419774

  18. Genetic Association Between CD143 rs4340 Polymorphism and Pneumonia risk

    PubMed Central

    Wang, Hong; Zhang, Kun; Qin, Haifeng; Yang, Lin; Zhang, Liyu; Cao, Yanyan

    2015-01-01

    Abstract rs4340 polymorphism at intron 16 of the angiotensin-converting enzyme (CD143) gene was reported to repress cough reflex by reducing bradykinin and substance P levels, thus increasing the likelihood to develop pneumonia. There have been different reports regarding the correlation of CD143 rs4340 genotypes with pneumonia risk, which prompted us to perform a meta-analysis to determine the elusive association. We combined multiple keywords to identify the studies addressing the association between CD143 rs4340 genotypes and pneumonia risk covered in the EMBASE, Google Scholar, PubMed, and CNKI databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the risk of pneumonia. The fixed-effects model (FEM) was used. A total of 10 studies were analyzed in this quantitative analysis. We found a strong association between rs4340 single nucleotide polymorphism (SNP) and pneumonia risk using the recessive model (FEM: OR 1.33, 95% CI 1.13–1.57). A significantly increased risk was also indicated under the recessive model in Asian populations (FEM: OR 1.57, 95% CI 1.19–2.07), community-acquired pneumonia (CAP) (FEM: OR 1.31, 95% CI 1.08–1.60), and nosocomial pneumonia (NP) (FEM: OR 1.52, 95% CI 1.06–2.19). Our meta-analysis demonstrates that CD143 rs4340 polymorphism may represent a risk factor for pneumonia. PMID:26222869

  19. Population variation in total genetic risk of Hirschsprung disease from common RET, SEMA3 and NRG1 susceptibility polymorphisms.

    PubMed

    Kapoor, Ashish; Jiang, Qian; Chatterjee, Sumantra; Chakraborty, Prakash; Sosa, Maria X; Berrios, Courtney; Chakravarti, Aravinda

    2015-05-15

    The risk of Hirschsprung disease (HSCR) is ?15/100 000 live births per newborn but has been reported to show significant inter-individual variation from the effects of seven common susceptibility alleles at the RET, SEMA3 and NRG1 loci. We show, by analyses of these variants in 997 samples from 376 HSCR families of European ancestry, that significant genetic risk can only be detected at RET (rs2435357 and rs2506030) and at SEMA3 (rs11766001), but not at NRG1. RET rs2435357 also showed significant frequency differences by gender, segment length of aganglionosis and familiality. Further, in combination, disease risk varied >30-fold between individuals with none and up to 6 susceptibility alleles. Thus, these polymorphisms can be used to stratify the newborn population into distinct phenotypic classes with defined risks to understand HSCR etiology. PMID:25666438

  20. Polymorphic populations of Dactylorhiza incarnata s.l. (Orchidaceae) on the Baltic island of Gotland: morphology, habitat preference and genetic differentiation

    PubMed Central

    Hedrén, Mikael; Nordström, Sofie

    2009-01-01

    Background and Aims Organisms may be polymorphic within natural populations, but often the significance and genetic background to such polymorphism is not known. To understand the colour polymorphism expressed in the diploid marsh-orchids Dactylorhiza incarnata, morphological, habitat and genetic differentiation was studied in mixed populations on the island of Gotland, supplemented with genetic marker data from adjacent areas. Methods A total of 398 accessions was investigated for plastid haplotype and three nuclear microsatellites. Morphometric data and vegetation data were obtained from a subset of 104 plants. Key Results No clear pattern of habitat differentiation was found among the colour morphs. Within sites, the yellow-flowered morph (ochroleuca) was slightly larger than the others in some flower characters, whereas the purple-flowered morph with spotted leaves (cruenta) was on average smaller. However, populations of the same colour morph differed considerably between sites, and there was also considerable overlap between morphs. Morphs were often genetically differentiated but imperfectly separated within sites. Most populations were characterized by significant levels of inbreeding. The ochroleuca morph constitutes a coherent, highly homozygous sublineage, although introgression from purple-flowered morphs occurs at some sites. The cruenta morph was genetically variable, although Gotland populations formed a coherent group. Purple-flowered plants with unspotted leaves (incarnata in the strict sense) were even more variable and spanned the entire genetic diversity seen in the other morphs. Conclusions Colour polymorphism in D. incarnata is maintained by inbreeding, but possibly also by other ecological factors. The yellow-flowered morph may best be recognized as a variety of D. incarnata, var. ochroleuca, and the lack of anthocyanins is probably due to a particular recessive allele in homozygous form. Presence of spotted leaves is an uncertain taxonomic character, and genetic differentiation within D. incarnata would be better described by other morphological characters such as leaf shape and stature and size and shape of lip and spur. PMID:19458026

  1. The case-only independence assumption: associations between genetic polymorphisms and smoking among controls in two population-based studies

    PubMed Central

    Hodgson, M Elizabeth; Olshan, Andrew F; North, Kari E; Poole, Charles L; Zeng, Donglin; Tse, Chiu-Kit; Keku, Tope O; Galanko, Joseph; Sandler, Robert; Millikan, Robert C

    2012-01-01

    The independence assumption for a case-only analysis of statistical interaction, i. e. that genetic (G) and environmental exposures (E) are not associated in the source population, is often checked in surrogate populations. Few studies have examined G-E association in empirical data, particularly in controls from population-based studies, the type of controls expected to provide the most valid surrogate estimates of G-E association. We used controls from two population-based case-control studies to evaluate G-E independence for 43 selected genetic polymorphisms and smoking behavior. The odds ratio (ORz) was used to estimate G-E association and, therefore, the magnitude of bias introduced into the case-only odds ratio (COR). Odds ratios of moderate magnitude [mmORz], defined as ORz?0.7 or ORz?1.4, were found at least one of the six smoking measures (ever, former, current, cig/day, years smoked, pack-years) for 45% and 59% of the SNPs examined in the control groups of two independently conducted North Carolina studies, respectively. Consequently, case-only estimates of G-E interaction in the context of a multiplicative benchmark would be biased for these SNPs and smoking measures. MmORzs were found more often for smoking amount than smoking status. We recommend that a stand-alone case-only study should only be conducted when G-E independence can be verified for each polymorphism and exposure metric with population-specific data. Our results suggest that ORz is specific to each underlying population rather than an estimate of a ‘universal’ ORz for that SNP and smoking measure. Further, misspecification of smoking is likely to introduce bias into the COR. PMID:23205185

  2. Genetic association of BACE1 gene polymorphism C786G with late-onset Alzheimer's disease in Chinese.

    PubMed

    Kan, Rui; Wang, Binbin; Zhang, Chuanfang; Jin, Feng; Yang, Ze; Ji, Shun; Lu, Zeping; Zheng, Chenguang; Wang, Li

    2005-01-01

    Beta-amyloid (Abeta) peptides are derived from the endoproteolytic processing of amyloid precursor protein (APP) and play a key role in the pathogenesis of Alzheimer's disease (AD). Beta-site APP-cleaving enzyme 1 ([BACE1] also known as beta-secretase) is responsible for cleaving APP to generate neurotoxic Abeta peptides in patients with AD. The BACE1 gene is located on chromosome 11q23.3, near the recently identified region with increased lod scores for AD. The biological functional and genetic association studies indicated that the BACE1 gene might be a genetic risk factor for late-onset Alzheimer's disease (LOAD). To investigate an association between the BACE1 C786G polymorphism and sporadic LOAD in Chinese, we examined 105 LOAD patients and 130 healthy controls. Our results showed higher frequency of the 786G-allele in LOAD patients (38.6%) than that in controls (28.5%), and a statistical significance was observed for an association of the G-allele with LOAD (odds ratio [OR] = 1.58, 95% confidence interval [CI] 1.07-2.23, p = 0.02). We also found a synergetic interaction between the G-allele and apolipoprotein E allele 4 (APOE e4) status on the risk of LOAD (OR = 1.91, 95% CI 1.23-2.95, p = 0.003). These results suggest that BACE1 gene polymorphism C786G might act as an APOE epsilon4 allele-dependent risk factor for developing LOAD in Chinese. PMID:15784960

  3. Genetic variability and chromosome-length polymorphisms of the witches' broom pathogen Crinipellis perniciosa from

    E-print Network

    Griffith, Gareth

    variability Microsatellite primers Pulsed-field gel electrophoresis Theobroma cacao a b s t r a c of unrelated plant families. In this study, genetic variability is shown for 27 C (Cacao), 4 S (Solanum), and 7 America. The objective was to investigate the genetic variability of the pathogen in the cacao

  4. Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism.

    PubMed

    Oldridge, Derek A; Wood, Andrew C; Weichert-Leahey, Nina; Crimmins, Ian; Sussman, Robyn; Winter, Cynthia; McDaniel, Lee D; Diamond, Maura; Hart, Lori S; Zhu, Shizhen; Durbin, Adam D; Abraham, Brian J; Anders, Lars; Tian, Lifeng; Zhang, Shile; Wei, Jun S; Khan, Javed; Bramlett, Kelli; Rahman, Nazneen; Capasso, Mario; Iolascon, Achille; Gerhard, Daniela S; Guidry Auvil, Jaime M; Young, Richard A; Hakonarson, Hakon; Diskin, Sharon J; Look, A Thomas; Maris, John M

    2015-12-17

    Neuroblastoma is a paediatric malignancy that typically arises in early childhood, and is derived from the developing sympathetic nervous system. Clinical phenotypes range from localized tumours with excellent outcomes to widely metastatic disease in which long-term survival is approximately 40% despite intensive therapy. A previous genome-wide association study identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility and oncogenic addiction to LMO1 in the tumour cells. Here we investigate the causal DNA variant at this locus and the mechanism by which it leads to neuroblastoma tumorigenesis. We first imputed all possible genotypes across the LMO1 locus and then mapped highly associated single nucleotide polymorphism (SNPs) to areas of chromatin accessibility, evolutionary conservation and transcription factor binding sites. We show that SNP rs2168101 G>T is the most highly associated variant (combined P?=?7.47?×?10(-29), odds ratio 0.65, 95% confidence interval 0.60-0.70), and resides in a super-enhancer defined by extensive acetylation of histone H3 lysine 27 within the first intron of LMO1. The ancestral G allele that is associated with tumour formation resides in a conserved GATA transcription factor binding motif. We show that the newly evolved protective TATA allele is associated with decreased total LMO1 expression (P?=?0.028) in neuroblastoma primary tumours, and ablates GATA3 binding (P?polymorphism within a super-enhancer element in the first intron of LMO1 influences neuroblastoma susceptibility through differential GATA transcription factor binding and direct modulation of LMO1 expression in cis, and this leads to an oncogenic dependency in tumour cells. PMID:26560027

  5. Genetic Polymorphisms of CYP2C8 in the Czech Republic

    PubMed Central

    Buzkova, Helena; Matouskova, Olga; Perlik, Frantisek

    2012-01-01

    Aim: CYP2C8 represents 7% of the hepatic cytochrome system and metabolizes around 5% of drugs in phase I processes. It also plays a significant role in metabolism of endogenous compounds. More than 20 single-nucleotide polymorphisms (SNPs) have been noted, mainly in exons 3, 5, and 8. The most studied SNPs may lead to decreased enzyme activity and may have impact on drug metabolism. Variant alleles are called CYP2C8*2 (I269F), CYP2C8*3 (R139K, K399R), and CYP2C8*4(I264M). Our aim was to investigate the frequency of major functional SNPs among the Czech population. Material and methods: DNA was isolated from whole blood of 161 healthy, young, and unrelated subjects (94 men and 67 women, aged from 23 to 28 years). The genotypes of polymorphic positions CYP2C8*2, CYP2C8*3 (G416A, A1196G), and CYP2C8*4 were determined by polymerase chain reaction–restriction fragment length polymorphism. Results and conclusion: Observed allele frequencies were 10.9%, 5.9%, and 0.3% for the alleles CYP2C8*3, CYP2C8*4, and CYP2C8*2, respectively. Both CYP2C8*3 (G416A, A1196G) alleles have been found in complete linkage disequilibrium. The allele distribution complies well with Hardy–Weinberg equilibrium. Allele frequencies of functionally important CYP2C8 variants in the Czech population are similar to that of other Caucasian populations. PMID:22313047

  6. Genetic association between CALHM1, 2, and 3 polymorphisms and Alzheimer's disease in a Japanese population.

    PubMed

    Shibata, Nobuto; Kuerban, Bolati; Komatsu, Miwa; Ohnuma, Tohru; Baba, Hajime; Arai, Heii

    2010-01-01

    A recent paper reported that a variant (rs2986017) of the calcium homeostasis modulator 1 (CALHM1) gene affects risk for late-onset Alzheimer's disease (AD). This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the CALHM1 gene are associated with AD. SNPs in the genes of two other CALHM subtypes, CALHM2 and CALHM3, were also studied. Our study failed to detect any association between the SNPs of the three genes and AD. Although rs729211 showed marginal association in the APOE4 negative group, the linkage disequilibrium analysis results suggest this to be a false positive. PMID:20164573

  7. A deletion polymorphism in the human COL1A2 gene. Genetic evidence for a non-African population whose descendants spread to all continents

    E-print Network

    Mitchell, R. J.; Howlett, S.; White, N. G.; Federle, L.; Papiha, S. S.; Briceno, I.; Comb, J. MC; Schanfield, M. S.; Tyler-Smith, C.; Osipova, Ludmila P.; Livshits, Gregory; Crawford, Michael H.

    1999-12-01

    - ment as closely as possible those scored for COL1A2 . The distribution of a newly reported single nucleotide polymorphism further supports the obser- vations for COL1A2 and GM*A,X G (Pompei et al. 1998). The nucleotide 107 point mutation, ? - > T... Polymorphism in the Human C0L1A2 Gene: Genetic Evidence of a Non- African Population Whose Descendants Spread to All Continents R.J. MITCHELL,1 S.HOWLETT,1 N.G. WHITE,1 L. FEDERLE,1 S.S. PAPIHA,2 I. BRICENO,2 J. MC COMB,3 M.S. SCHANFIELD,4 C.TYLER-SMITH,5 L...

  8. AFLP Polymorphisms Allow High Resolution Genetic Analysis of American Tegumentary Leishmaniasis Agents Circulating in Panama and Other Members of the Leishmania Genus

    PubMed Central

    Restrepo, Carlos M.; De La Guardia, Carolina; Sousa, Octavio E.; Calzada, José E.; Fernández, Patricia L.; Lleonart, Ricardo

    2013-01-01

    American Tegumentary Leishmaniasis is caused by parasites of the genus Leishmania, and causes significant health problems throughout the Americas. In Panama, Leishmania parasites are endemic, causing thousands of new cases every year, mostly of the cutaneous form. In the last years, the burden of the disease has increased, coincident with increasing disturbances in its natural sylvatic environments. The study of genetic variation in parasites is important for a better understanding of the biology, population genetics, and ultimately the evolution and epidemiology of these organisms. Very few attempts have been made to characterize genetic polymorphisms of parasites isolated from Panamanian patients of cutaneous leishmaniasis. Here we present data on the genetic variability of local isolates of Leishmania, as well as specimens from several other species, by means of Amplified Fragment Length Polymorphisms (AFLP), a technique seldom used to study genetic makeup of parasites. We demonstrate that this technique allows detection of very high levels of genetic variability in local isolates of Leishmania panamensis in a highly reproducible manner. The analysis of AFLP fingerprints generated by unique selective primer combinations in L. panamensis suggests a predominant clonal mode of reproduction. Using fluorescently labeled primers, many taxon-specific fragments were identified which may show potential as species diagnostic fragments. The AFLP permitted a high resolution genetic analysis of the Leishmania genus, clearly separating certain groups among L. panamensis specimens and highly related species such as L. panamensis and L. guyanensis. The phylogenetic networks reconstructed from our AFLP data are congruent with established taxonomy for the genus Leishmania, even when using single selective primer combinations. Results of this study demonstrate that AFLP polymorphisms can be informative for genetic characterization in Leishmania parasites, at both intra and inter-specific levels. PMID:24039881

  9. Single Nucleotide Polymorphism Array Analysis of Bone Marrow Failure Patients Reveals Characteristic Patterns of Genetic Changes

    PubMed Central

    Babushok, Daria V.; Xie, Hongbo M.; Roth, Jacquelyn J.; Perdigones, Nieves; Olson, Timothy S.; Cockroft, Joshua D.; Gai, Xiaowu; Perin, Juan C.; Li, Yimei; Paessler, Michele E.; Hakonarson, Hakon; Podsakoff, Gregory M.; Mason, Philip J.; Biegel, Jaclyn A.; Bessler, Monica

    2013-01-01

    Summary The bone marrow failure syndromes (BMFS) are a heterogeneous group of rare blood disorders characterized by inadequate haematopoiesis, clonal evolution, and increased risk of leukaemia. Single nucleotide polymorphism arrays (SNP-A) have been proposed as a tool for surveillance of clonal evolution in BMFS. To better understand the natural history of BMFS and to assess the clinical utility of SNP-A in these disorders, we analysed 124 SNP-A from a comprehensively characterized cohort of 91 patients at our BMFS centre. SNP-A were correlated with medical histories, haematopathology, cytogenetic and molecular data. To assess clonal evolution, longitudinal analysis of SNP-A was performed in 25 patients. We found that acquired copy number-neutral loss of heterozygosity (CN-LOH) was significantly more frequent in acquired aplastic anaemia (aAA) than in other BMFS (odds ratio 12.2, p<0.01). Homozygosity by descent was most common in congenital BMFS, frequently unmasking autosomal recessive mutations. Copy number variants (CNVs) were frequently polymorphic, and we identified CNVs enriched in neutropenia and aAA. Our results suggest that acquired CN-LOH is a general phenomenon in aAA that is probably mechanistically and prognostically distinct from typical CN-LOH of myeloid malignancies. Our analysis of clinical utility of SNP-A shows the highest yield of detecting new clonal haematopoiesis at diagnosis and at relapse. PMID:24116929

  10. Superoxide Dismutase 2 Polymorphisms and Osteoporosis in Asian Indians: A Genetic Association Analysis.

    PubMed

    Botre, Chaitali; Shahu, Arjun; Adkar, Neeraj; Shouche, Yogesh; Ghaskadbi, Saroj; Ashma, Richa

    2015-12-01

    Oxidative stress plays an important role in the development of osteoporosis. The present cross-sectional study focuses on mapping single nucleotide polymorphisms (SNPs) in the mitochondrial manganese superoxide dismutase (SOD2) gene in Asian Indians. The bone mineral density (BMD) of study subjects was assessed by dual x-ray absorptiometry. Individuals were classified as normal (n = 82) or osteoporotic (n = 98). Biochemical parameters such as vitamin D, total oxidant status (TOS) and SOD2 enzyme activity were estimated from plasma samples. Semi-quantitative PCR was carried out using GAPDH as an endogenous control. Genomic DNA was isolated from whole blood and SNPs were evaluated by PCR sequencing. Thirteen SNPs are reported in the examined region of the SOD2 gene, out of which in our samples SNPs rs5746094 and rs4880 were found to be polymorphic. Allele G of rs5746094 (intronic) and allele C of rs4880 (exonic) are significantly higher in the osteoporotic individuals. Presence of allele C of rs4880 and increased level of TOS among osteoporotic individuals were found to be associated with disease risk. PMID:26336112

  11. Analysis of the genetic effects of CAPN1 gene polymorphisms on chicken meat tenderness.

    PubMed

    Shu, J T; Zhang, M; Shan, Y J; Xu, W J; Chen, K W; Li, H F

    2015-01-01

    The micromolar calcium-activated neutral protease gene (CAPN1) is a physiological candidate gene for meat tenderness. Four previously identified single nucleotide polymorphism (SNP) markers located within the CAPN1 gene were evaluated for their associations with variation in the meat tenderness of a Chinese indigenous chicken breed, a higher meat quality breed (i.e., Qingyuan partridge chicken), and the commercial Recessive White chicken breed. Warner-Bratzler shear force measurements were used to determine tenderness phenotypes for all animals; intramuscular fat (IMF) content and rate of water loss in the breast muscles were also measured. Genotyping was performed by the polymerase chain reaction-ligase detection reaction method. Polymorphisms were identified for all markers, except CAPN1 2546. The frequency of allele T was zero, and allele C was fixed for CAPN1 2546 in the studied populations. The SNP CAPN1 3535 in the CAPN1 gene was significantly associated with tenderness and other meat quality traits, where animals inheriting the AA genotype had smaller shear force values, lower water loss rates, and higher IMF contents. Moreover, H1 (AAA) was the most advantageous haplotype for meat tenderness. The results of this study confirm some previously documented associations. Furthermore, novel associations have been identified that, following validation in other populations, could be incorporated into breeding programs to improve meat quality. PMID:25730078

  12. Genetic polymorphisms of CYP1A1 and risk of leukemia: a meta-analysis

    PubMed Central

    Lu, Jun; Zhao, Qian; Zhai, Ya-Jing; He, Hai-Rong; Yang, Li-Hong; Gao, Fan; Zhou, Rong-Sheng; Zheng, Jie; Ma, Xian-Cang

    2015-01-01

    The associations between CYP1A1 polymorphisms and risk of leukemia have been studied extensively, but the results have been inconsistent. Therefore, in this study, we performed a meta-analysis to clarify associations of three CYP1A1 polymorphisms (T3801C, A2455G, and C4887A) with the risks of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Medline, EMBASE, and China National Knowledge Infrastructure databases were searched to collect relevant studies published up to April 20, 2015. The extracted data were analyzed statistically, and pooled odds ratios with 95% confidence intervals were calculated to quantify the associations. Overall, 26 publications were included. Finally, T3801C was associated with an increased risk of AML in Asians under the dominant model. For A2455G, the risk of ALL was increased among Caucasians in the recessive model and the allele-contrast model; A2455G was also associated with an increased risk of CML among Caucasians under the recessive model, dominant model, and allele-contrast model. For C4887A, few of the included studies produced data. In conclusion, the results suggest that Asians carrying the T3801C C allele might have an increased risk of AML and that Caucasians with the A2455G GG genotype might have an increased risk of ALL. Further investigations are needed to confirm these associations. PMID:26491362

  13. Genetic relationships and evolution in Cucurbita pepo (pumpkin, squash, gourd) as revealed by simple sequence repeat polymorphisms.

    PubMed

    Gong, Li; Paris, Harry S; Nee, Michael H; Stift, Gertraud; Pachner, Martin; Vollmann, Johann; Lelley, Tamas

    2012-03-01

    Genetic relationships among 104 accessions of Cucurbita pepo were assessed from polymorphisms in 134 SSR (microsatellite) and four SCAR loci, yielding a total of 418 alleles, distributed among all 20 linkage groups. Genetic distance values were calculated, a dendrogram constructed, and principal coordinate analyses conducted. The results showed 100 of the accessions as distributed among three clusters representing each of the recognized subspecies, pepo, texana, and fraterna. The remaining four accessions, all having very small, round, striped fruits, assumed central positions between the two cultivated subspecies, pepo and texana, suggesting that they are relicts of undescribed wild ancestors of the two domesticated subspecies. In both, subsp. texana and subsp. pepo, accessions belonging to the same cultivar-group (fruit shape) associated with one another. Within subsp. pepo, accessions grown for their seeds or that are generalists, used for both seed and fruit consumption, assumed central positions. Specialized accessions, grown exclusively for consumption of their young fruits, or their mature fruit flesh, or seed oil extraction, tended to assume outlying positions, and the different specializations radiated outward from the center in different directions. Accessions of the longest-fruited cultivar-group, Cocozelle, radiated bidirectionally, indicating independent selection events for long fruits in subsp. pepo probably driven by a common desire to consume the young fruits. Among the accessions tested, there was no evidence for crossing between subspecies after domestication. PMID:22101929

  14. Investigation of genetic divergence and polymorphism of nuclear DNA in species and populations of domestic and wild sheep

    SciTech Connect

    Mel`nikova, M.N.; Grechko, V.V.; Mednikov, B.M.

    1995-08-01

    Genetic divergence in repetitive sequences of nuclear DNA of wild and domestic sheep was studied by general restriction endonuclease mapping (i.e., the taxonoprint method). The PCR RAPD method with one and two arbitrary primers was also used to analyze the nuclear DNA polymorphism in some other regions. The taxonoprint method, performed using six endonucleases, showed specificity and virtually complete similarity in the patterns of repetitive DNA sequences of two wild forms, argali and moufflon, and five domestic sheep breeds. Central Asian breeds, Kazakh fine-fleeced, karakuk, ghissar, and eadeelbay, and an English breed, Lincoln, were examined. The results confirm the opinion that wild and domestic sheep may be considered one polytypic species. The PCR-RAPD method, both with one and two arbitrary primers, revealed a closer similarity of all the sheep breeds examined when aragali, rather than with moufflon, was used. These results indicate that the domestication area of sheep was much more broader than was earlier presumed. Otherwise, hybridizations of domestic and wild forms could occasionally occur in the area of their coexistence. The amplification patterns of PCR-RAPD products are the most promising population genetic markers. 27 refs., 4 figs., 7 tabs.

  15. Genetic Polymorphism of Human Y Chromosome and Risk Factors for Cardiovascular Diseases: A Study in WOBASZ Cohort

    PubMed Central

    Kostrzewa, Gra?yna; Broda, Gra?yna; Konarzewska, Magdalena; Krajewki, Pawe?; P?oski, Rafa?

    2013-01-01

    Genetic variants of Y chromosome predispose to hypertension in rodents, whereas in humans the evidence is conflicting. Our purpose was to study the distribution of a panel of Y chromosome markers in a cohort from a cross-sectional population-based study on the prevalence of cardiovascular risk factors in Poland (WOBASZ study). The HindIII, YAP Y chromosome variants, previously shown to influence blood pressure, lipid traits or height, as well as SNPs defining main Y chromosome haplogroups, were typed in 3026, 2783 and 2652 samples, respectively. In addition, 4 subgroups (N?100 each) representing extremes of LDL concentration or blood pressure (BP) were typed for a panel of 17 STRs. The HindIII and YAP polymorphism were not associated with any of the studied traits. Analysis of the haplogroup distribution showed an association between higher HDL level and hg I-M170 (P?=?0.02), higher LDL level and hg F*(xI-M170, J2-M172, K-M9) (P?=?0.03) and lower BMI and hg N3-Tat (P?=?0.04). Analysis of STRs did not show statistically significant differences. Since all these associations lost statistical significance after Bonferroni correction, we conclude that a major role of Y chromosome genetic variation (defined by HindIII, YAP or main Y chromosome haplogroups) in determining cardiovascular risk in Poles is unlikely. PMID:23935855

  16. Genetic polymorphism of human Y chromosome and risk factors for cardiovascular diseases: a study in WOBASZ cohort.

    PubMed

    Kostrzewa, Gra?yna; Broda, Gra?yna; Konarzewska, Magdalena; Krajewki, Pawe?; P?oski, Rafa?

    2013-01-01

    Genetic variants of Y chromosome predispose to hypertension in rodents, whereas in humans the evidence is conflicting. Our purpose was to study the distribution of a panel of Y chromosome markers in a cohort from a cross-sectional population-based study on the prevalence of cardiovascular risk factors in Poland (WOBASZ study). The HindIII, YAP Y chromosome variants, previously shown to influence blood pressure, lipid traits or height, as well as SNPs defining main Y chromosome haplogroups, were typed in 3026, 2783 and 2652 samples, respectively. In addition, 4 subgroups (N~100 each) representing extremes of LDL concentration or blood pressure (BP) were typed for a panel of 17 STRs. The HindIII and YAP polymorphism were not associated with any of the studied traits. Analysis of the haplogroup distribution showed an association between higher HDL level and hg I-M170 (P = 0.02), higher LDL level and hg F*(xI-M170, J2-M172, K-M9) (P = 0.03) and lower BMI and hg N3-Tat (P = 0.04). Analysis of STRs did not show statistically significant differences. Since all these associations lost statistical significance after Bonferroni correction, we conclude that a major role of Y chromosome genetic variation (defined by HindIII, YAP or main Y chromosome haplogroups) in determining cardiovascular risk in Poles is unlikely. PMID:23935855

  17. Genetic polymorphism in domain I of the apical membrane antigen-1 among Plasmodium knowlesi clinical isolates from Peninsular Malaysia.

    PubMed

    Fong, Mun Yik; Wong, Shen Siang; Silva, Jeremy Ryan De; Lau, Yee Ling

    2015-12-01

    The simian malaria parasite Plasmodium knowlesi is now recognized as a species that can cause human malaria. The first report of large scale human knowlesi malaria was in 2004 in Malaysia Borneo. Since then, hundreds of human knowlesi malaria cases have been reported in Southeast Asia. The present study investigates the genetic polymorphism of P. knowlesi DI domain of the apical membrane antigen-1 (AMA-1), a protein considered as a promising vaccine candidate for malaria. The DI domain of AMA-1 gene of P. knowlesi clinical isolates from Peninsular Malaysia was amplified by PCR, cloned into Escherichia coli, then sequenced and analysed. Ninety-seven DI domain sequences were obtained. Comparison at the nucleotide level against P. knowlesi strain H as reference sequence showed 21 synonymous and 25 nonsynonymous mutations. Nonetheless, nucleotide sequence analysis revealed low genetic diversity of the DI domain, and it was under purifying (negative) selection. At the amino acid level, 26 different haplotypes were identified and 2 were predominant haplotypes (H1, H2) with high frequencies. Phylogenetic analysis revealed that the 26 haplotypes could be clustered into 2 distinct groups (I and II). Members of the groups were basically derived from haplotypes H1 and H2, respectively. PMID:26384455

  18. Association of Genetic Polymorphisms on Vascular Endothelial Growth Factor and its Receptor Genes with Susceptibility to Coronary Heart Disease.

    PubMed

    Li, Lei; Pan, Yongquan; Dai, Li; Liu, Bing; Zhang, Dongming

    2016-01-01

    BACKGROUND Coronary heart disease (CHD) is a cardiovascular disease characterized by high morbidity and mortality. Vascular endothelial growth factor (VEGF) and its receptor, named kinase insert domain-containing receptor (KDR, or VEGFR2), which are involved with angiogenesis and vascular repair, could partly contribute to the development of CHD. The aim of this study, therefore, was to investigate the potential correlations between genetic polymorphisms on VEGF and KDR and susceptibility to CHD, and the integrative role of SNPs combined on susceptibility to CHD were also studied. MATERIAL AND METHODS Venous blood samples gathered from 533 DCM patients and 533 healthy controls were used to genotype tag-SNPs of VEGF (rs699947, rs2010963, and rs3025010) and KDR (rs2071559, rs2305948, and rs1870377) by polymerase chain reaction (PCR) and SNaPshot assay. Investigations of potential haplotypes were conducted on the basis of SHEsis software. The odds ratio (ORs) and relevant 95% confidence intervals (95% CI) were used to estimate associations of SNPs/haplotypes with risk of CHD. Multivariate logistic regression was also performed, taking certain clinical characteristics (e.g., BMI, smoking, alcohol consumption, diabetes, and hypertension) into consideration. All statistical analyses were done with STATA Version 12.0 software. RESULTS Our results suggest that rs699947 (T>C) on KDR are associated with susceptibility to CHD under the dominant model before (OR=1.35, 95% CI: 1.05-1.73, P=0.019) and after (OR=1.33, 95% CI: 1.01-1.76, P=0.044), allowing for clinical characteristics (e.g., BMI, smoking, alcohol consumption, diabetes, and hypertension). rs2305948 (G>A) and rs1870377 (A>T) on VEGF were also found to be associated with risk of CHD under the recessive model after adjustment with multivariate regression analyses (OR=1.21, 95% CI: 1.02-1.43, P=0.029; OR=2.54, 95% CI: 1.13-5.75, P=0.025); OR=2.83, 95% CI: 1.47-5.46, P=0.002, respectively). Additionally, haplotype analyses revealed that integration of 5 SNPs would either raise (e.g. C-C-T-G-T and T-G-T-G-T) or reduce (e.g. C-C-C-G-T, T-C-T-G-A, T-C-T-G-T, and T-G-T-G-A) risk of CHD. CONCLUSIONS Genetic polymorphisms on VEGF (rs699947) and KDR (rs2305948and rs1870377), as well as relevant haplotypes, may serve as genetic markers that might be useful in future investigations on the pathogenesis of CHD. PMID:26726843

  19. CHARLOTTE HARBOR IR, 2002

    EPA Science Inventory

    The 2002 Charlotte Harbor Implementation Review (IR) summarizes the progress and challenges ahead for the Charlotte Harbor National Estuary Program (CHNEP). The implementation review report requires seven components: Status of CCMP implementation (programmatic progress); Environm...

  20. Paraoxonase-1 genetic polymorphisms and susceptibility to DNA damage in workers occupationally exposed to organophosphate pesticides

    SciTech Connect

    Singh, Satyender; Kumar, Vivek; Thakur, Sachin; Banerjee, Basu Dev; Rautela, Rajender Singh; Grover, Shyam Sunder; Rawat, Devendra Singh; Pasha, Syed Tazeen; Jain, Sudhir Kumar; Ichhpujani, Rattan Lal; Rai, Arvind

    2011-04-15

    Human paraoxonase 1 (PON1) is a lipoprotein-associated enzyme involved in the detoxification of organophosphate pesticides (OPs) by hydrolyzing the bioactive oxons. Polymorphisms of the PON1 gene are responsible for variation in the expression and catalytic activity of PON1 enzyme. In the present study, we have determined (a) the prevalence of two common PON1 polymorphisms, (b) the activity of PON1 and acetylcholinesterase enzymes, and (c) the influence of PON1 genotypes and phenotypes variation on DNA damage in workers exposed to OPs. We examined 230 subjects including 115 workers exposed to OPs and an equal number of normal healthy controls. The results revealed that PON1 activity toward paraoxon (179.19 {+-} 39.36 vs. 241.52 {+-} 42.32 nmol/min/ml in controls) and phenylacetate (112.74 {+-} 17.37 vs. 134.28 {+-} 25.49 {mu}mol/min/ml in controls) was significantly lower in workers than in control subjects (p < 0.001). No significant difference was observed in the distribution of genotypes and allelic frequencies of PON1{sub 192}QR (Gln/Arg) and PON1{sub 55}LM (Leu/Met) in workers and control subjects (p > 0.05). The PON1 activity toward paraoxonase was found to be significantly higher in the R/R (Arg/Arg) genotypes than Q/R (Gln/Arg) and lowest in Q/Q (Gln/Gln) genotypes in both workers and control subjects (p < 0.001). For PON1{sub 55}LM (Leu/Met), PON1 activity toward paraoxonase was observed to be higher in individuals with L/L (Leu/Leu) genotypes and lowest in individuals with M/M (Met/Met) genotypes in both groups (p < 0.001). No influence of PON1 genotypes and phenotypes was seen on the activity of acetylcholinesterase and arylesterase. The DNA damage was observed to be significantly higher in workers than in control subjects (p < 0.05). Further, the individuals who showed least paraoxonase activity i.e., those with (Q/Q [Gln/Gln] and M/M [Met/Met]) genotypes showed significantly higher DNA damage compared to other isoforms in workers exposed to OPs (p < 0.05). The results indicate that the individuals with PON1 Q/Q and M/M genotypes are more susceptible toward genotoxicity. In conclusion, the study suggests wide variation in enzyme activities and DNA damage due to polymorphisms in PON1 gene, which might have an important role in the identification of individual risk factors in workers occupationally exposed to OPs.

  1. Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam

    SciTech Connect

    Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Tu Binh Minh; Pham Thi Kim Trang; Pham Hung Viet; Tanabe, Shinsuke

    2010-02-01

    To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for GST omega1 (GSTO1) Ala140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST omega2 (GSTO2) Asn142Asp, GST pi1 (GSTP1) Ile105Val, GST mu1 (GSTM1) wild/null, and GST theta1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu155del hetero type showed higher urinary concentration of As{sup V} than the wild homo type. Higher percentage of DMA{sup V} in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As{sup V} to As{sup III}. Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+ 3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of GST superfamily with arsenic metabolism in a Vietnamese population.

  2. Genetic Polymorphisms of Functional Candidate Genes and Recurrent Acute Otitis Media With or Without Tympanic Membrane Perforation

    PubMed Central

    Esposito, Susanna; Marchisio, Paola; Orenti, Annalisa; Spena, Silvia; Bianchini, Sonia; Nazzari, Erica; Rosazza, Chiara; Zampiero, Alberto; Biganzoli, Elia; Principi, Nicola

    2015-01-01

    Abstract Evaluation of the genetic contribution to the development of recurrent acute otitis media (rAOM) remains challenging. This study aimed to evaluate the potential association between single nucleotide polymorphisms (SNPs) in selected genes and rAOM and to analyze whether genetic variations might predispose to the development of complicated recurrent cases, such as those with tympanic membrane perforation (TMP). A total of 33 candidate genes and 47 SNPs were genotyped in 200 children with rAOM (116 with a history of TMP) and in 200 healthy controls. INF? rs 12369470CT was significantly less common in the children with rAOM than in healthy controls (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.25–1, P?=?0.04). Although not significant, interleukin (IL)-1? rs 1143627G and toll-like receptor (TLR)-4 rs2737191AG were less frequently detected in the children with rAOM than in controls. The opposite was true for IL-8 rs2227306CT, which was found more frequently in the children with rAOM than in healthy controls. The IL-10 rs1800896TC SNP and the IL-1? rs6746923A and AG SNPs were significantly more and less common, respectively, among children without a history of TMP than among those who suffered from this complication (OR 2.17, 95% CI 1.09–4.41, P?=?0.02, and OR 0.42, 95% CI 0.21–0.84, P?=?0.01). This study is the first report suggesting an association between variants in genes encoding for factors of innate or adaptive immunity and the occurrence of rAOM with or without TMP, which confirms the role of genetics in conditioning susceptibility to AOM. PMID:26496338

  3. PERMANENT GENETIC RESOURCES: Twelve polymorphic microsatellite markers for the bonefish, Albula vulpes and two congeners.

    PubMed

    Seyoum, Seifu; Wallace, Elizabeth M; Tringali, Michael D

    2008-03-01

    Twelve polymorphic microsatellite loci were isolated for the bonefish, Albula vulpes using a polymerase chain reaction-based procedure. The number of alleles ranged from two to 23 (mean = 8.8) in 37 specimens from south Florida. Observed and expected heterozygosities ranged from 0.07 to 0.77 (mean = 0.42) and from 0.07 to 0.84 (mean = 0.48), respectively. There were no significant departures from Hardy-Weinberg equilibrium and no evidence of genotypic disequilibrium between any pair of loci. In a cross-amplification test, all markers yielded appropriately sized alleles for specimens of the provisional Albula sp. B and 11 of the 12 loci amplified for those of Albula glossodonta. PMID:21585790

  4. Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: A Nested Case-Control Study

    PubMed Central

    Koenig, Karen L.; Axelsson, Tomas; Liu, Mengling; Afanasyeva, Yelena; Andersson, Anne; Arslan, Alan A.; Chen, Yu; Hallmans, Göran; Lenner, Per; Kirchhoff, Tomas; Lundin, Eva; Shore, Roy E.; Sund, Malin; Zeleniuch-Jacquotte, Anne

    2015-01-01

    Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH)D concentration in GWAS were also associated with plasma 25(OH)D in our study (p-trend <0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH)D with breast cancer risk, do not support an association between vitamin D and breast cancer risk. PMID:26488576

  5. Joint Effect of Urinary Total Arsenic Level and VEGF-A Genetic Polymorphisms on the Recurrence of Renal Cell Carcinoma

    PubMed Central

    Yang, Shu-Mei; Huang, Chao-Yuan; Shiue, Horng-Sheng; Huang, Shu-Pin; Pu, Yeong-Shiau; Chen, Wei-Jen; Lin, Ying-Chin; Hsueh, Yu-Mei

    2015-01-01

    The results of our previous study suggested that high urinary total arsenic levels were associated with an increased risk of renal cell carcinoma (RCC). Germline genetic polymorphisms might also affect cancer risk and clinical outcomes. Vascular endothelial growth factor (VEGF) plays an important role in vasculogenesis and angiogenesis, but the combined effect of these factors on RCC remains unclear. In this study, we explored the association between the VEGF-A -2578C>A, -1498T>C, -1154G>A, -634G>C, and +936C>T gene polymorphisms and RCC. We also evaluated the combined effects of the VEGF-A haplotypes and urinary total arsenic levels on the prognosis of RCC. This case-control study was conducted with 191 RCC patients who were diagnosed with renal tumors on the basis of image-guided biopsy or surgical resections. An additional 376 age- and gender-matched controls were recruited. Concentrations of urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotyping was investigated using fluorescent-based TaqMan allelic discrimination. We observed no significant associations between VEGF-A haplotypes and RCC risk. However, the VEGF-A ACGG haplotype from VEGF-A -2578, -1498, -1154, and -634 was significantly associated with an increased recurrence of RCC (OR = 3.34, 95% CI = 1.03–10.91). Urinary total arsenic level was significantly associated with the risk of RCC in a dose-response manner, but it was not related to the recurrence of RCC. The combination of high urinary total arsenic level and VEGF-A risk haplotypes affected the OR of RCC recurrence in a dose-response manner. This is the first study to show that joint effect of high urinary total arsenic and VEGF-A risk haplotypes may influence the risk of RCC recurrence in humans who live in an area without obvious arsenic exposure. PMID:26701102

  6. Association between Genetic Polymorphism in the Swine Leukocyte Antigen-DRA Gene and Piglet Diarrhea in Three Chinese Pig Breeds

    PubMed Central

    Yang, Q. L.; Zhao, S. G.; Wang, D. W.; Feng, Y.; Jiang, T. T.; Huang, X. Y.; Gun, S. B.

    2014-01-01

    The swine leukocyte antigen (SLA)-DRA locus is noteworthy among other SLA class II loci for its limited variation and has not been investigated in depth. This study was investigated to detect polymorphisms of four exons of SLA-DRA gene and its association with piglet diarrhea in Landrace, Large White and Duroc pigs. No polymorphisms were detected in exon 3, while 2 SNPs (c.178G>A and c.211T>C), 2 SNPs (c.3093A>C and c.3104C>T) and 5 SNPs (c.4167A>G, c.4184A>G, c.4194A>G, c.4246A>G and c.4293G>A) were detected in exon 1, exon 2 and exon 4 respectively, and 1 SNP (c.4081T>C) in intron 3. Statistical results showed that genotype had significant effect on piglet diarrhea, individuals with genotype BC had a higher diarrhea score when compared with the genotypes AA, AB, AC and CC. Futhermore, genotype AC had a higher diarrhea score than the genotype CC in exon 1 (p<0.05); diarrhea scores of genotype AA and BB were higher than those of genotypes AC and CC in exon 2 (p<0.05); individuals with genotype AA had a higher diarrhea score than individuals with genotype AB and BB in exon 4 (p<0.05). Fourteen common haplotypes were founded by haplotype constructing of all SNPs in the three exons, its association with piglet diarrhea appeared that Hap2, 5, 8, 10, and 14 may be the susceptible haplotypes and Hap9 may be the resistant haplotype to piglet diarrhea. The genetic variations identified of the SLA-DRA gene may potentially be functional mutations related to piglet diarrhea. PMID:25178364

  7. Genetic Polymorphisms Associated with Hearing Threshold Shift in Subjects during First Encounter with Occupational Impulse Noise

    PubMed Central

    Grondin, Yohann; Bortoni, Magda E.; Sepulveda, Rosalinda; Ghelfi, Elisa; Bartos, Adam; Cotanche, Douglas; Clifford, Royce E.; Rogers, Rick A.

    2015-01-01

    Noise-induced hearing loss (NIHL) is the most significant occupational health issue worldwide. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with hearing threshold shift in young males undergoing their first encounter with occupational impulse noise. We report a significant association of SNP rs7598759 (p < 5 x 10-7; p = 0.01 after permutation and correction; Odds Ratio = 12.75) in the gene coding for nucleolin, a multifunctional phosphoprotein involved in the control of senescence and protection against apoptosis. Interestingly, nucleolin has been shown to mediate the anti-apoptotic effect of HSP70, a protein found to prevent ototoxicity and whose polymorphisms have been associated with susceptibility to NIHL. Increase in nucleolin expression has also been associated with the prevention of apoptosis in cells undergoing oxidative stress, a well-known metabolic sequela of noise exposure. To assess the potential role of nucleolin in hearing loss, we tested down-regulation of nucleolin in cochlear sensory cells HEI-OC1 under oxidative stress conditions and report increased sensitivity to cisplatin, a chemotherapeutic drug with ototoxic side effects. Additional SNPs were found with suggestive association (p < 5 x 10-4), of which 7 SNPs were located in genes previously reported to be related to NIHL and 43 of them were observed in 36 other genes previously not reported to be associated with NIHL. Taken together, our GWAS data and in vitro studies reported herein suggest that nucleolin is a potential candidate associated with NIHL in this population. PMID:26121033

  8. Genetic polymorphisms of DAT1 and COMT differentially associate with actigraphy-derived sleep-wake cycles in young adults.

    PubMed

    Valomon, Amandine; Holst, Sebastian C; Bachmann, Valérie; Viola, Antoine U; Schmidt, Christina; Zürcher, Jurian; Berger, Wolfgang; Cajochen, Christian; Landolt, Hans-Peter

    2014-06-01

    Accumulating evidence suggests that dopamine plays a key role in sleep-wake regulation. Cerebral dopamine levels are regulated primarily by the dopamine transporter (DAT) in the striatum and by catechol-O-methyl-transferase (COMT) in the prefrontal cortex. We hypothesized that the variable-number-tandem-repeat (VNTR) polymorphism in the 3'-untranslated region of the gene encoding DAT (DAT1, SLC6A3; rs28363170) and the Val158Met polymorphism of COMT (rs4680) differently affect actigraphy-derived rest-activity cycles and sleep estimates in healthy adults (65 men; 45 women; age range: 19-35 years). Daytime sleepiness, continuous rest-actigraphy and sleep diary data during roughly 4-weeks were analyzed. Nine-repeat (9R) allele carriers of DAT1 (n?=?48) more often reported elevated sleepiness (Epworth sleepiness score ?10) than 10-repeat (10R) allele homozygotes (n?=?62, p?genetically-determined differences in cerebral dopaminergic neurotransmission with daytime sleepiness and individual rest-activity profiles, as well as other sleep-associated health characteristics such as the regulation of BMI. The differential associations of DAT1 and COMT polymorphisms may reflect the distinct local expression of the encoded proteins in the brain. PMID:24625311

  9. Genetic Association Study of TNFAIP3, IFIH1, IRF5 Polymorphisms with Polymyositis/Dermatomyositis in Chinese Han Population

    PubMed Central

    Li, Yuan; Li, Ping; Sun, Fei; Zheng, Wenjie; Wu, Qingjun; Wu, Chanyuan; Deng, Chuiwen; Zhang, Fengchun; Li, Yongzhe

    2014-01-01

    Background Single-nucleotide polymorphisms (SNPs) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and idiopathic inflammatory myopathies (IIMs) were not reported. This study aimed to investigate whether TNFAIP3, IFIH1, and IRF5 gene polymorphisms confer susceptibility for the IIMs in Chinese Han population. Methods A large case–control study of Chinese subjects with polymyositis (PM) (n?=?298) and dermatomyositis (DM) (n?=?530) was accomplished. 968 healthy and ethnically matched controls were available for comparison. Six SNPs in the TNFAIP3 region (rs2230926 and rs5029939), the IFIH1 gene (rs1990760 and rs3747517) and the IRF5 region (rs4728142 and rs729302) were assessed and genotyped using the Sequenom MassArray iPLEX platform. Results Our study indicated a strong allele association was observed in PM/DM and PM patients for rs2230926 (OR: 1.61, 95%CI: 1.20–2.16, Pc?=?7.5×10?3; OR: 1.88, 95%CI: 1.30–2.74, Pc?=?4.0×10?3, respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21–2.21, Pc?=?6.0×10?3; OR: 1.88, 95%CI: 1.28–2.76, Pc?=?5.5×10?3,respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (Pc?=?0.04 and Pc?=?0.016; Pc?=?0.02 and Pc?=?0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (Pc?=?0.026 and Pc?=?0.048, respectively). Further analysis with three logistic regression genetic models revealed statistically significant difference in the genotypic distribution in the PM/DM, PM or DM patients when the additive and dominant models were used. Conclusions This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population. PMID:25337792

  10. Abstract Amplified fragment length polymorphisms (AFLPs) were used to evaluate genetic relationships

    E-print Network

    Gepts, Paul

    relationships within cowpea [Vigna unguiculata (L.) Walp.] and to assess the organization of its genetic cowpea (ssp. ungui- culata var. unguiculata), 52 wild and weedy annuals (ssp. unguiculata var. spontanea on their geographical origin (western, eastern and southern Africa). Wild annual cowpea (var. spontanea) (HT=0

  11. Detection of Genetic Variation in Wild Populations of Three Allium Species Using Amplified Fragment Length Polymorphisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three wild onion species native to the intermountain west in the United States - Allium acuminatum, A. brandegei, and A. passeyi - show horticultural potential, but little is known about patterns of genetic diversity among localized populations and geographical regions. We examined amplified fragme...

  12. Genetic variability of the stable fly assessed on a global scale using amplified fragment length polymorphism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The stable fly, Stomoxys calcitrans (L) (Diptera: Muscidae), is a blood-feeding, economically important pest of animals and humans worldwide. Improved management strategies are essential and their development would benefit from studies on genetic diversity of stable flies. Such research, especially ...

  13. Target Region Amplification Polymorphism (TRAP) as a Tool for Detecting Genetic Variation in the Genus Pelargonium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pelargonium is one of the priority genera collected by the Ornamental Plant Germplasm Center (OPGC). In order to protect future breeders from a loss of genetic diversity, OPGC collects heirloom cultivars, breeding lines and wild species. The current Pelargonium collection at OPGC consists primaril...

  14. Genetic Polymorphisms in Organic Cation Transporter 1 (OCT1) in Chinese and Japanese Populations Exhibit Altered

    E-print Network

    Sali, Andrej

    .Sa., K.M.G.) and Neurology (J.S.), University of California, San Francisco, California; Diabetes Center- betic drug metformin. Genetic variants in OCT1 have been identified largely in European populations. Metformin is in- creasingly being used in Asian populations where the incidence of type 2 diabetes (T2D

  15. Effect of polymorphisms in the leptin, leptin receptor and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) genes and genetic polymorphism of milk proteins on bovine milk composition.

    PubMed

    Glantz, Maria; Lindmark Månsson, Helena; Stålhammar, Hans; Paulsson, Marie

    2012-02-01

    The relations between cow genetics and milk composition have gained a lot of attention during the past years, however, generally only a few compositional traits have been examined. The aim of this study was to determine if polymorphisms in the leptin (LEP), leptin receptor (LEPR) and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) genes as well as genetic polymorphism of ?-casein (?-CN), ?-CN and ?-lactoglobulin (?-LG) impact several bovine milk composition traits. Individual milk samples from the Swedish Red and Swedish Holstein breeds were analyzed for components in the protein, lipid, carbohydrate and mineral profiles. Cow alleles were determined on the following SNP: A1457G, A252T, A59V and C963T on the LEP gene, T945M on the LEPR gene and Nt984+8(A-G) on the DGAT1 gene. Additionally, genetic variants of ?-CN, ?-CN and ?-LG were determined. For both the breeds, the same tendency of minor allele frequency was found for all SNPs and protein genes, except on LEPA1457G and LEPC963T. This study indicated significant (P<0·05) associations between the studied SNPs and several compositional parameters. Protein content was influenced by LEPA1457G (G>A) and LEPC963T (T>C), whereas total Ca, ionic Ca concentration and milk pH were affected by LEPA1457G, LEPA59V, LEPC963T and LEPRT945M. However, yields of milk, protein, CN, lactose, total Ca and P were mainly affected by ?-CN (A2>A1) and ?-CN (A>B>E). ?-LG was mainly associated with whey protein yield and ionic Ca concentration (A>B). Thus, this study shows possibilities of using these polymorphisms as markers within genetic selection programs to improve and adjust several compositional parameters. PMID:22127264

  16. Untangling the evolutionary history of a highly polymorphic species: introgressive hybridization and high genetic structure in the desert cichlid fish Herichtys minckleyi.

    PubMed

    Magalhaes, Isabel S; Ornelas-Garc?a, Claudia Patricia; Leal-Cardin, Mariana; Ramírez, Tania; Barluenga, Marta

    2015-09-01

    Understanding the origin of biodiversity requires knowledge on the evolutionary processes that drive divergence and speciation, as well as on the processes constraining it. Intraspecific polymorphisms can provide insight into the mechanisms that generate and maintain phenotypic, behavioural and life history diversification, and can help us understand not only the processes that lead to speciation but also the processes that prevent local fixation of morphs. The 'desert cichlid' Herichtys minckleyi is a highly polymorphic species endemic to a biodiversity hotspot in northern Mexico, the Cuatro Ciénegas valley. This species is polymorphic in body shape and trophic apparatus, and eco-morphotypes coexist in small spring-fed lagoons across the valley. We investigated the genetic structure of these polymorphisms and their phylogeographic history by analysing the entire control region of the mitochondrial DNA and 10 nuclear microsatellite markers in several populations from different sites and morphs. We found two very divergent mitochondrial lineages that most likely predate the closing of the valley and are not associated with morphotypes or sites. One of these lineages is also found in the sister species Herichthys cyanoguttatus. Data from neutral microsatellite markers suggest that most lagoons or drainages constitute their own genetic cluster with sympatric eco-morphotypes forming panmictic populations. Alternative mechanisms such as phenotypic plasticity and a few loci controlled traits provide possible explanations for the sympatric coexistence of discrete nonoverlapping eco-morphotypes with apparent lack of barriers to gene flow within multiple lagoons and drainages. PMID:26175313

  17. Genetic Polymorphisms of Glutathione-Related Enzymes (GSTM1, GSTT1, and GSTP1) and Schizophrenia Risk: A Meta-Analysis

    PubMed Central

    Kim, Su Kang; Kang, Sang Wook; Chung, Joo-Ho; Park, Hae Jeong; Cho, Kyu Bong; Park, Min-Su

    2015-01-01

    The association between polymorphisms of glutathione-related enzyme (GST) genes and the risk of schizophrenia has been investigated in many published studies. However, their results were inconclusive. Therefore, we performed a meta-analysis to explore the association between the GSTM1, GSTT1, and GSTP1 polymorphisms and the risk of schizophrenia. Twelve case-control studies were included in this meta-analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Our meta-analysis results revealed that GSTM1, GSTT1, and GSTP1 polymorphisms were not related to risk of schizophrenia (p > 0.05 in each model). Further analyses based on ethnicity, GSTM polymorphism showed weak association with schizophrenia in East Asian population (OR = 1.314, 95% CI = 1.025–1.684, p = 0.031). In conclusion, our meta-analysis indicated the GSTM1 polymorphism may be the only genetic risk factor for schizophrenia in East Asian population. However, more meta-analysis with a larger sample size were needed to provide more precise evidence. PMID:26295386

  18. Genetic Polymorphisms of Glutathione-Related Enzymes (GSTM1, GSTT1, and GSTP1) and Schizophrenia Risk: A Meta-Analysis.

    PubMed

    Kim, Su Kang; Kang, Sang Wook; Chung, Joo-Ho; Park, Hae Jeong; Cho, Kyu Bong; Park, Min-Su

    2015-01-01

    The association between polymorphisms of glutathione-related enzyme (GST) genes and the risk of schizophrenia has been investigated in many published studies. However, their results were inconclusive. Therefore, we performed a meta-analysis to explore the association between the GSTM1, GSTT1, and GSTP1 polymorphisms and the risk of schizophrenia. Twelve case-control studies were included in this meta-analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Our meta-analysis results revealed that GSTM1, GSTT1, and GSTP1 polymorphisms were not related to risk of schizophrenia (p > 0.05 in each model). Further analyses based on ethnicity, GSTM polymorphism showed weak association with schizophrenia in East Asian population (OR = 1.314, 95% CI = 1.025-1.684, p = 0.031). In conclusion, our meta-analysis indicated the GSTM1 polymorphism may be the only genetic risk factor for schizophrenia in East Asian population. However, more meta-analysis with a larger sample size were needed to provide more precise evidence. PMID:26295386

  19. Characterization of drug resistance associated genetic polymorphisms among Plasmodium falciparum field isolates in Ujjain, Madhya Pradesh, India

    PubMed Central

    2014-01-01

    Background Since 2011, artesunate?+?sulphadoxine-pyrimethamine (ASP), instead of chloroquine, has been recommended for treatment of uncomplicated malaria in India. In Ujjain, central India, with an annual parasite index <0.1, the prevalence of drug-resistant Plasmodium falciparum is unknown. In other parts of India chloroquine and sulphadoxine-pyrimethamine-resistant P. falciparum is prevalent. The aim of this study was to determine the prevalence of anti-malarial drug resistance-associated genetic polymorphisms in P. falciparum collected in Ujjain in 2009 and 2010, prior to the introduction of ASP. Methods Blood samples from 87 patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons Pfcrt 72–76, pfmdr1 1034–1246, pfdhfr 16–185, pfdhps 436–632 and pfnhe1 ms4760 haplotypes were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism, and pfmdr1 gene copy number by real-time PCR. Results Sulphadoxine-pyrimethamine resistance-associated pfdhfr 108 N and 59R alleles were found in 75/78 (96%) and 70/78 (90%) samples, respectively, and pfdhps 437G was found in 7/77 (9%) samples. Double mutant pfdhfr 59R?+?108 N were found in 62/76 (82%) samples. Triple mutant pfdhfr 59R?+?108 N and pfdhps 437G were found in 6/76 (8%) samples. Chloroquine-resistance-associated pfcrt 76 T was found in 82/87 (94%). The pfcrt 72–76 haplotypes found were: 80/84 (95%) SVMNT, 3/84 (4%) CVMNK and 1/84 (1%) CVMNT. Pfmdr1 N86 and 86Y were identified in 70/83 (84%) and 13/83 (16%) samples, respectively. Pfmdr1 S1034?+?N1042?+?D1246 were identified together in 70/72 (97%) of successfully sequenced samples. One pfmdr1 gene copy was found in 74/75 (99%) successfully amplified samples. Conclusion This is the first characterization of key anti-malarial drug resistance-associated genetic markers among P. falciparum collected in Ujjain, Madhya Pradesh, India. The results indicate that the efficacy of standard dose chloroquine at the time of the study was likely to be poor, whereas ASP was likely to be efficacious, supporting the changed drug treatment policy. However, P. falciparum with reduced susceptibility to sulphadoxine-pyrimethamine is highly prevalent, highlighting the need for continuous surveillance of ASP efficacy in the study area. PMID:24885535

  20. Dose-dependent influence of genetic polymorphisms on DNA damage induced by styrene oxide, ethylene oxide and gamma-radiation.

    PubMed

    Godderis, Lode; Aka, Peter; Mateuca, Raluca; Kirsch-Volders, Micheline; Lison, Dominique; Veulemans, Hendrik

    2006-02-15

    Styrene oxide (SO), ethylene oxide (EO) and gamma-radiation (G) are agents with a well-described metabolism and genotoxicity. EPHX1 and GSTs play an important role in the detoxification of electrophiles and oxidative stress. Enzymes involved in base excision repair (hOGG1, XRCC1), in rejoining single strand breaks (XRCC1) and in repair of cross-links and chromosomal double strand breaks (XRCC3) might have an impact on genotoxicity as well. In this study we assessed the dose-dependent effect of genetic polymorphisms in biotransforming (EPHX (Tyr113/His113 and His139/Arg139), GSTP1 (Ile105/Val105), GSTM1 and GSTT1) and DNA repair enzymes (hOGG1 (Ser326/Cys326), XRCC1 (Arg194/Trp194, Arg280/His280, Arg399/Gln399), XRCC3 (Thr241/Met241)) on the induced genotoxicity. Peripheral blood mononuclear cells from 20 individuals were exposed to 3 doses per agent (+control). Genotoxicity was evaluated by measuring comet tail length (TL) and micronucleus frequencies in binucleated cells (MNCB). Dose-dependent DNA damage was found for all agents and end-points, with the exception of MNCB induced by EO. Repeated measure ANOVA revealed a significant contribution of hOGG1 and XRCC3 genotypes to the inter-individual variability of TL and MNCB in cells exposed to EO and G. Homozygous hOGG1326 wild cells showed significantly lower EO-induced TL than the heterozygous cells. Significantly higher TL and MNCB were found in EO-exposed cells carrying the XRCC3(241)Met variant and the influence on TL was more pronounced at higher dose. In G-irradiated cells, TL was significantly higher in the hOGG1326 homozygous wild types compared with mutated genotypes. The influence of hOGG1326 on TL was borderline dose-dependent. We conclude that the influence of genetic polymorphisms of enzymes involved in DNA repair on induced genotoxicity depends on exposure dose. PMID:16386346

  1. Novel polymorphisms within the Dlk1-Dio3 imprinted locus in rat: a putative genetic basis for strain-specific allelic gene expression

    PubMed Central

    Sittig, Laura J.; Redei, Eva E.

    2012-01-01

    The imprinted iodothyronine deiodinase-III (Dio3) thyroid hormone metabolizing gene exhibits paternal expression in most fetal tissues, yet exhibits aberrant, maternal expression in the hippocampus in F1 offspring of Sprague Dawley (SD) × Brown Norway (BN) rats. The maternal hippocampal expression is associated with lower Dio3 mRNA levels specifically in the hippocampus. Here, we tested the hypothesis that genetic polymorphisms between the SD and BN parent strains cause this aberrant allelic Dio3 expression and contribute to behavioral sequelae of higher thyroid hormone levels locally in the hippocampus, including anxiety-related behavior. We mapped and sequenced the Dio3 gene and several previously unmapped regions in the Dlk1-Dio3 locus that could regulate imprinting of the Dio3 gene. In the Dio3 promoter we identified four novel polymorphisms between the BN and SD strains. Next we took advantage of the fact that the Long Evans (LE) strain exhibits identical polymorphisms as the SD strain in the region 5' and including the Dio3 gene. By reciprocally crossing LE and BN strains we tested the relationship among Dio3 promoter region polymorphisms and Dio3 mRNA expression in the hippocampus. Aberrant strain-specific hippocampal Dio3 allelic expression replicated in the LE-BN reciprocal crosses, suggesting that hippocampal-specific imprinting of the Dio3 gene is not the result of a unique genetic or epigenetic characteristic of the SD rat strain, or a unique epistatic interaction between SD and BN. To our knowledge no other studies have reported a genetic × epigenetic interaction of genetic origin in the brain. PMID:23248649

  2. MODIFICATION OF NEUROBEHAVIORAL EFFCTS OF MERCURY BY A GENETIC POLYMORPHISM OF COPROPORPHYRINOGEN OXIDASE IN CHILDREN

    PubMed Central

    Woods, James S.; Heyer, Nicholas J.; Echeverria, Diana; Russo, Joan E.; Martin, Michael D.; Bernardo, Mario F.; Luis, Henrique S.; Vaz, Lurdes; Farin, Federico M.

    2012-01-01

    Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that CPOX4, a genetic variant of the heme pathway enzyme coproporphyrinogen oxidase (CPOX) that affects susceptibility to mercury toxicity in adults, also modifies the neurotoxic effects of Hg in children. Five hundred seven children, 8–12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings in children. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary mercury levels. Following the completion of the clinical trial, genotyping assays for CPOX4 allelic status were performed on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between CPOX4 status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant CPOX4-Hg interactions or independent main effects for Hg or CPOX4 were observed. In contrast, among boys, numerous significant interaction effects between CPOX4 and Hg were observed spanning all 5 domains of neurobehavioral performance. All underlying dose-response associations between Hg exposure and test performance were restricted to boys with the CPOX4 variant, and all of these associations were in the expected direction where increased exposure to Hg decreased performance. These findings are the first to demonstrate genetic susceptibility to the adverse neurobehavioral effects of Hg exposure in children. The paucity of responses among same-age girls with comparable Hg exposure provides evidence of sexual dimorphism in genetic susceptibility to the adverse neurobehavioral effects of Hg in children and adolescents. PMID:22765978

  3. Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer

    PubMed Central

    Garcia-Closas, Montserrat; Rothman, Nathaniel; Figueroa, Jonine D.; Prokunina-Olsson, Ludmila; Han, Summer S.; Baris, Dalsu; Jacobs, Eric J; Malats, Nuria; De Vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P; Sharma, Sapna; Fu, Yi-Ping; Kogevinas, Manolis; Wang, Zhaoming; Tang, Wei; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R; Schned, Alan; Andriole, Gerald; Grubb, Robert; Black, Amanda; Gapstur, Susan M; Thun, Michael; Diver, W Ryan; Weinstein, Stephanie J; Virtamo, Jarmo; Hunter, David J; Caporaso, Neil; Landi, Maria Teresa; Hutchinson, Amy; Burdett, Laurie; Jacobs, Kevin B; Yeager, Meredith; Fraumeni, Joseph F; Chanock, Stephen J; Silverman, Debra T; Chatterjee, Nilanjan

    2013-01-01

    Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to evaluate the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually and combined as a polygenic risk score (PRS). Thirty-year absolute risks and risk differences by levels of the PRS were estimated for US-males aged 50-years. Six out of 12 variants showed significant additive gene-environment interactions, most notably NAT2 (P=7×10-4) and UGT1A6 (P=8×10-4). The 30-year absolute risk of bladder cancer in US males was 6.2% for all current smokers. This risk ranged from 2.9% for current smokers in the lowest quartile of the PRS to 9.9% for current smokers in the upper quartile. Risk difference estimates indicated that 8,200 cases would be prevented if elimination of smoking occurred in 100,000 men in the upper PRS quartile, compared to 2,000 cases prevented by a similar effort in the lowest PRS quartile (P-additive =1×10-4). The impact of eliminating smoking the on number of bladder cancer cases prevented is larger for individuals at higher than lower genetic risk. Our findings could have implications for targeted prevention strategies. However, other smoking-related diseases, as well as practical and ethical considerations, need to be considered before any recommendations could be made. PMID:23536561

  4. Genetic caste polymorphism and the evolution of polyandry in Atta leaf-cutting ants

    NASA Astrophysics Data System (ADS)

    Evison, Sophie Elizabeth Frances; Hughes, William O. H.

    2011-08-01

    Multiple mating by females with different males (polyandry) is difficult to explain in many taxa because it carries significant costs to females, yet benefits are often hard to identify. Polyandry is a derived trait in social insects, the evolutionary origins of which remain unclear. One of several leading hypotheses for its evolution is that it improves division of labour by increasing intra-colonial genetic diversity. Division of labour is a key player in the ecological success of social insects, and in many successful species of ants is based on morphologically distinct castes of workers, each with their own task specialisations. Atta leaf-cutting ants exhibit one of the most extreme and complicated forms of morphologically specialised worker castes and have been reported to be polyandrous but with relatively low mating frequencies (~2.5 on average). Here, we show for the first time that there is a significant genetic influence on worker size in Atta colombica leaf-cutting ants. We also provide the first estimate of the mating frequency of Atta cephalotes (four matings) and, by analysing much higher within-colony sample sizes, find that Atta are more polyandrous than previously thought (approximately six to seven matings). The results show that high polyandry and a genetic influence on worker caste are present in both genera of leaf-cutting ants and add weight to the hypothesis that division of labour is a potential driver of the evolution of polyandry in this clade of ants.

  5. Genetic polymorphism study at 15 autosomal locus in central Indian population.

    PubMed

    Shrivastava, Pankaj; Jain, Toshi; Trivedi, Veena Ben

    2015-01-01

    The analysis of 15 autosomal STR locus (TH01, D3S1358, vWA, D21S11, TPOX, D7S820, D19S433, D5S818, D2S1338, D16S539, CSF1PO, D13S317, FGA, D18S51, D8S1179) was done in 582 healthy unrelated individuals (Male-366, Female-216) originating from the various geographical regions of Madhya Pradesh, India. All locus fall under Hardy-Weinberg equilibrium except TPOX. These STR loci were highly informative and discriminating with combined power of discrimination (CPD) >0.99999. Locus wise allele frequencies of the studied population were compared with the other published populations. Also the Clustering pattern and genetic distance of studied populations is compared and presented with various populations. The studied population showed the genetic proximity with geographically close populations of India and significant genetic variation with distant populations which is also evident by clustering pattern of the NJ tree and the PCA plot. PMID:26543701

  6. Genetic Identification of the Main Opportunistic Mucorales by PCR-Restriction Fragment Length Polymorphism

    PubMed Central

    Machouart, M.; Larché, J.; Burton, K.; Collomb, J.; Maurer, P.; Cintrat, A.; Biava, M. F.; Greciano, S.; Kuijpers, A. F. A.; Contet-Audonneau, N.; de Hoog, G. S.; Gérard, A.; Fortier, B.

    2006-01-01

    Mucormycosis is a rare and opportunistic infection caused by fungi belonging to the order Mucorales. Recent reports have demonstrated an increasing incidence of mucormycosis, which is frequently lethal, especially in patients suffering from severe underlying conditions such as immunodeficiency. In addition, even though conventional mycology and histopathology assays allow for the identification of Mucorales, they often fail in offering a species-specific diagnosis. Due to the lack of other laboratory tests, a precise identification of these molds is thus notoriously difficult. In this study we aimed to develop a molecular biology tool to identify the main Mucorales involved in human pathology. A PCR strategy selectively amplifies genomic DNA from molds belonging to the genera Absidia, Mucor, Rhizopus, and Rhizomucor, excluding human DNA and DNA from other filamentous fungi and yeasts. A subsequent digestion step identified the Mucorales at genus and species level. This technique was validated using both fungal cultures and retrospective analyses of clinical samples. By enabling a rapid and precise identification of Mucorales strains in infected patients, this PCR-restriction fragment length polymorphism-based method should help clinicians to decide on the appropriate treatment, consequently decreasing the mortality of mucormycosis. PMID:16517858

  7. DNA damage repair and genetic polymorphisms: Assessment of individual sensitivity and repair capacity

    SciTech Connect

    Cornetta, Tommaso; Festa, Fabiola; Testa, Antonella; Cozzi, Renata Prof. . E-mail: cozzi@uniroma3.it

    2006-10-01

    Purpose: To study the repair capacity after X-ray irradiation in human peripheral blood cells of healthy subjects, in relation to their genotypes. Methods and Materials: The peripheral blood of 50 healthy subjects was irradiated in vitro with 2 Gy of X rays and the induced DNA damage was measured by Comet assay immediately after irradiation. DNA repair was detected by analyzing the cells at defined time intervals after the exposure. Furthermore, all subjects were genotyped for XRCC1, OGG1, and XPC genes. Results: After X-ray irradiation, persons bearing XRCC1 homozygous variant (codon 399) genotype exhibited significantly lower Tail DNA values than those bearing wild-type and heterozygous genotypes. These results are also confirmed at 30 and 60 min after irradiation. Furthermore, XPC heterozygous subjects (variant codon 939) showed lower residual DNA damage 60 min after irradiation compared with wild-type and homozygous genotypes. Conclusion: The results of the present study show that polymorphisms in DNA repair genes could influence individual DNA repair capacity.

  8. Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits

    PubMed Central

    Jagirdar, Kasturee; Smit, Darren J.; Ainger, Stephen A.; Lee, Katie J.; Brown, Darren L.; Chapman, Brett; Zhao, Zhen Zhen; Montgomery, Grant W.; Martin, Nicholas G.; Stow, Jennifer L.; Duffy, David L.; Sturm, Richard A.

    2014-01-01

    Summary We have compared the melanogenic activities of cultured melanocytes carrying two common TYR alleles as homozygous 192S-402R wildtype, heterozygous and homozygous variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wildtype strains on average had higher levels of TYR protein and enzyme activity than other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR protein, displayed altered trafficking and glycosylation, with reduced DOPAoxidase. However, near wildtype TYR activity levels could be recovered at lower growth temperature. In a sample population from Southeast Queensland these two polymorphisms were present on four TYR haplotypes, designated as WT 192S-402R, 192Y-402R, 192S-402Q with a double variant 192Y-402Q of low frequency at 1.9%. Based on cell culture findings and haplotype associations, we have used an additive model to assess the penetrance of the ten possible TYR genotypes derived from the combination of these haplotypes. PMID:24739399

  9. Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits.

    PubMed

    Jagirdar, Kasturee; Smit, Darren J; Ainger, Stephen A; Lee, Katie J; Brown, Darren L; Chapman, Brett; Zhen Zhao, Zhen; Montgomery, Grant W; Martin, Nicholas G; Stow, Jennifer L; Duffy, David L; Sturm, Richard A

    2014-07-01

    We have compared the melanogenic activities of cultured melanocytes carrying two common TYR alleles as homozygous 192S-402R wild-type, heterozygous and homozygous variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wild-type strains on average had higher levels of TYR protein and enzyme activity than other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR protein, displayed altered trafficking and glycosylation, with reduced DOPAoxidase. However, near wild-type TYR activity levels could be recovered at lower growth temperature. In a sample population from Southeast Queensland, these two polymorphisms were present on four TYR haplotypes, designated as WT 192S-402R, 192Y-402R and 192S-402Q with a double-variant 192Y-402Q of low frequency at 1.9%. Based on cell culture findings and haplotype associations, we have used an additive model to assess the penetrance of the ten possible TYR genotypes derived from the combination of these haplotypes. PMID:24739399

  10. A meta-analysis of glutathione S-transferase M1 and T1 genetic polymorphism in relation to susceptibility to nasopharyngeal carcinoma

    PubMed Central

    Liu, Rong-Rong; Chen, Ji-Chuan; Li, Ming-Dong; Li, Te; Tan, Yun; Zhang, Min

    2015-01-01

    Objective: To investigate the relationship between glutathione S-transferase M1 (GSTM1), and T1 (GSTT1) genetic polymorphism and susceptibility to nasopharyngeal carcinoma (NPC) using meta-analysis method. Methods: Data of published case-control studies on the relationship between GSTT1, GSTM1 genetic polymorphism and susceptibility to NPC were collected from EMBASE, PubMed, Web of Science, China Academic Journals Full-text Database, Chinese Biomedical Literature Database, and Wanfang Database. Meta-analysis was conducted using Revman 5.2 software. Results: Nine studies were included for meta-analysis with a total of 1295 cases of NPC patients and 1967 control individuals. Meta-analysis showed that the risk of NPC was significantly higher in population with GSTM1 gene deletion (OR=1.43, 95% CI: 1.42-1.65; P<0.001). Similarly, the risk of NPC was significantly higher in Chinese population with GSTM1 gene deletion (OR=1.38, 95% CI: 1.18-1.62; P<0.001). We did not find association between GSTT1 gene deletion and NPC risk not only in total population (OR=1.32, 95% CI: 0.92-1.87; P=0.12), but in Chinese population (OR=1.41, 95% CI: 0.97-2.04; P=0.07). Conclusion: GSTM1 genetic polymorphism, but GSTT1, is associated with susceptibility to NPC. PMID:26379853

  11. Genetic polymorphisms of CYP2C19 and IL1B have no influence on esomeprazole treatment for mild erosive esophagitis.

    PubMed

    Hsu, Wen-Hung; Kuo, Fu-Chen; Hu, Huang-Ming; Hsu, Ping-I; Wu, Deng-Chyang; Kuo, Chao-Hung

    2015-05-01

    Interleukin (IL)-1? is a potent inhibitor of gastric acid secretion and its genetic polymorphism is linked to the severity of reflux esophagitis. Proton-pump inhibitor (PPI) metabolized by P450 2C19 (CYP2C19) is the chief medication in reflux esophagitis treatment. The CYP2C19 genotype may influence the therapeutic effect of PPI for reflux esophagitis. From November 2009 to June 2012, 184 patients were enrolled in this study with endoscopy examination, 8 weeks of esomeprazole treatment, and 20 weeks of follow-up with questionnaire. These patients also received endoscopy examination after 20 weeks. Blood was collected for genetic polymorphism analysis with polymerase chain reaction. After 8 weeks of treatment with esomeprazole, all of these 184 patients had achieved complete symptom relief. However, in the following 12 weeks, 58.70% (108/184) complained of symptom relapse, 45.65% (84/184) patients had persistent esophageal erosion verified by endoscopy, and in total, 76.09% (140/184) patients had treatment failure at the end of 20 weeks. There were no influences between the genetic polymorphisms of CYP2C19 and IL1B to treatment failure (p = 0.896). Therefore, prolonging PPI treatment and further lifestyle modification might be warranted for symptomatic mild esophagitis. There were no relationships between IL-1? and CYP2C19 in the treatment effect in mild reflux esophagitis. PMID:25910560

  12. Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response

    PubMed Central

    Naga, Mazen; Amin, Mona; Algendy, Dina; Elbadry, Ahmed; Fawzi, May; Foda, Ayman; Esmat, Serag; Sabry, Dina; Rashed, Laila; Gabal, Samia; Kamal, Manal

    2015-01-01

    AIM: To correlate a genetic polymorphism of the low-density lipoprotein (LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus (HCV) patients. METHODS: Our study included 657 HCV-infected patients with genotype 4 who received interferon-based combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index (BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction (PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor (LDLR) genotype study of LDLR exon8c.1171G>A and exon10c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases. RESULTS: There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8c.1171G>A genotype between cases (AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls (AA: 3.8%, GA: 53.1% and GG: 43.1%) (P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders (AA: 3.6%, GA: 15.2%, GG: 81.2%) and non-responders (AA: 52.2%, GA: 30.6%, GG: 17.2%) (P < 0.001). The G allele of LDL receptor exon8c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders (P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for non-response. There was a significant association between LDL receptors exon8 c.1171G>A and HAI (P < 0.011). There was a significant association between LDL receptors exon8c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype (28.7 ± 4.7 kg/m2) followed by the GA genotype (28.1 ± 4.8 kg/m2). The lowest BMI was the GG genotype (26.6 ± 4.3 kg/m2) (P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis (P < 0.001). CONCLUSION: LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptians infected with chronic HCV. PMID:26494968

  13. Genetic polymorphisms in AS3MT and arsenic metabolism in residents of the Red River Delta, Vietnam

    SciTech Connect

    Agusa, Tetsuro; Iwata, Hisato Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Minh, Tu Binh; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke

    2009-04-15

    To elucidate the role of genetic factors in arsenic (As) metabolism, we studied associations of single nucleotide polymorphisms (SNPs) in As (+ 3 oxidation state) methyltransferase (AS3MT) with the As concentrations in hair and urine, and urinary As profile in residents in the Red River Delta, Vietnam. Concentrations of total As in groundwater were 0.7-502 {mu}g/l. Total As levels in groundwater drastically decreased by using sand filter, indicating that the filter could be effective to remove As from raw groundwater. Concentrations of inorganic As (IAs) in urine and total As in hair of males were higher than those of females. A significant positive correlation between monomethylarsonic acid (MMA)/IAs and age in females indicates that older females have higher methylation capacity from IAs to MMA. Body mass index negatively correlated with urinary As concentrations in males. Homozygote for SNPs 4602AA, 35991GG, and 37853GG, which showed strong linkage disequilibrium (LD), had higher percentage (%) of dimethylarsinic acid (DMA) in urine. SNPs 4740 and 12590 had strong LD and associated with urinary %DMA. Although SNPs 6144, 12390, 14215, and 35587 comprised LD cluster, homozygotes in SNPs 12390GG and 35587CC had lower DMA/MMA in urine, suggesting low methylation capacity from MMA to DMA in homo types for these SNPs. SNPs 5913 and 8973 correlated with %MMA and %DMA, respectively. Heterozygote for SNP 14458TC had higher MMA/IAs in urine than TT homozygote, indicating that the heterozygote may have stronger methylation ability of IAs. To our knowledge, this is the first study on the association of genetic factors with As metabolism in Vietnamese.

  14. Genetic Profiling by Single-Nucleotide Polymorphism-Based Array Analysis Defines Three Distinct Subtypes of Orbital Meningioma

    PubMed Central

    Ho, Cheng-Ying; Mosier, Stacy; Safneck, Janice; Salomao, Diva R.; Miller, Neil R.; Eberhart, Charles G.; Gocke, Christopher D.; Batista, Denise A. S.; Rodriguez, Fausto J.

    2015-01-01

    Orbital meningiomas can be classified as primary optic nerve sheath (ON) meningiomas, primary intraorbital ectopic (Ob) meningiomas and spheno-orbital (Sph-Ob) meningiomas based on anatomic site. Single-nucleotide polymorphism (SNP)-based array analysis with the Illumina 300K platform was performed on formalin-fixed, paraffin-embedded tissue from 19 orbital meningiomas (5 ON, 4 Ob and 10 Sph-Ob meningiomas). Tumors were World Health Organization (WHO) grade I except for two grade II meningiomas, and one was NF2-associated. We found genomic alterations in 68% (13 of 19) of orbital meningiomas. Sph-Ob tumors frequently exhibited monosomy 22/22q loss (70%; 7/10) and deletion of chromosome 1p, 6q and 19p (50% each; 5/10). Among genetic alterations, loss of chromosome 1p and 6q were more frequent in clinically progressive tumors. Chromosome 22q loss also was detected in the majority of Ob meningiomas (75%; 3/4) but was infrequent in ON meningiomas (20%; 1/5). In general, Ob tumors had fewer chromosome alterations than Sph-Ob and ON tumors. Unlike Sph-Ob meningiomas, most of the Ob and ON meningiomas did not progress even after incomplete excision, although follow-up was limited in some cases. Our study suggests that ON, Ob and Sph-Ob meningiomas are three molecularly distinct entities. Our results also suggest that molecular subclassification may have prognostic implications. PMID:24773246

  15. The role of CYP2C9 genetic polymorphisms in the oxidative metabolism of diclofenac in vitro.

    PubMed

    Xia, Meng-Ming; Wang, Li; PAan, Pei-Pei; Wang, Hai-Yun; Chen, Meng-Chun; Chen, Yi; Dai, Da-Peng; Cai, Jian-Ping; Hu, Guo-Xin

    2014-12-01

    CYP2C9 is one of four known members of the human cytochrome P450 CYP2C superfamily, with at least 57 CYP2C9 alleles being previously identified. Genetic polymorphisms of CYP2C9 significantly influence the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure. The purpose of the present study was to clarify the role of 36 CYP2C9 alleles, 21 novel alleles (*36-*56) found in the Chinese population, in the oxidative metabolism of diclofenac in vitro. Insect microsomes expressing the 36 human CYP2C9 alleles were incubated with 2-100 ?M diclofenac for 30 min at 37 degrees C and terminated by the addition of 30 ?L 0.1 M HCl. Diclofenac and 4'-hydroxyl (OH)-diclofenac, the major diclofenac metabolite, were analyzed by high-performance liquid chromatography (HPLC). Compared with wild-type CYP2C9*1, most variants showed significantly altered values in V(max), K(m) and intrinsic clearance (V(max)/K(m)). Only one variant exhibited markedly increased intrinsic clearance value, whereas 31 variants exhibited significantly decreased values. Thus, this study demonstrated that more attention should be given to subjects carrying these CYP2C9 alleles when administering diclofena. PMID:25951663

  16. Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis

    PubMed Central

    Mabrouk, Mai S.; Eldeib, Ayman M.

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease which has a significant socio-economic impact. The aim of the current study was to investigate eight candidate RA susceptibility loci to identify the associated variants in Egyptian population. Eight single nucleotide polymorphisms (SNPs) (MTHFR—C677T and A1298C, TGF?1 T869C, TNFB A252G, and VDR—ApaI, BsmI, FokI, and TaqI) were tested by genotyping patients with RA (n = 105) and unrelated controls (n = 80). Associations were tested using multiplicative, dominant, recessive, and co-dominant models. Also, the linkage disequilibrium (LD) between the VDR SNPs was measured to detect any indirect association. By comparing RA patients with controls (TNFB, BsmI, and TaqI), SNPs were associated with RA using all models. MTHFR C677T was associated with RA using all models except the recessive model. TGF?1 and MTHFR A1298C were associated with RA using the dominant and the co-dominant models. The recessive model represented the association for ApaI variant. There were no significant differences for FokI and the presence of RA disease by the used models examination. For LD results, There was a high D? value between BsmI and FokI (D? = 0.91), but the r2 value between them was poor. All the studied SNPs may contribute to the susceptibility of RA disease in Egyptian population except for FokI SNP. PMID:26147289

  17. Genetic Association of Objective Sleep Phenotypes with a Functional Polymorphism in the Neuropeptide S Receptor Gene

    PubMed Central

    Spada, Janek; Sander, Christian; Burkhardt, Ralph; Häntzsch, Madlen; Mergl, Roland; Scholz, Markus; Hegerl, Ulrich; Hensch, Tilman

    2014-01-01

    Background The neuropeptide S receptor (NPSR1) and its ligand neuropeptide S (NPS) have received increased attention in the last few years, as both establish a previously unknown system of neuromodulation. Animal research studies have suggested that NPS may be involved in arousal/wakefulness and may also have a crucial role in sleep regulation. The single nucleotide polymorphism (SNP) rs324981 in NPSR1 has begun to shed light on a function of the NPS-system in human sleep regulation. Due to an amino acid exchange, the T-allele leads to an increased sensitivity of the NPSR1. In the only genome-wide association study to date on circadian sleep parameters in humans, an association was found between rs324981 and regular bedtime. However, the sleep parameters in this study were only measured by self-rating. Therefore, our study aimed to replicate these findings using an objective measure of sleep. Methods The study included n?=?393 white subjects (62–79 years) who participated in an actigraphic assessment for determining sleep duration, rest duration, sleep onset, rest onset and sleep onset latency. Genotyping of the SNP rs324981 was performed using the TaqMan OpenArray System. Results The genotype at rs324981 was not significantly associated with rest onset (bedtime) or sleep onset (p?=?.146 and p?=?.199, respectively). However, the SNP showed a significant effect on sleep- and rest duration (p?=?.007 and p?=?.003, respectively). Subjects that were homozygous for the minor T-allele had a significantly decreased sleep- and rest duration compared to A-allele carriers. Conclusion The results of this study indicate that the sleep pattern in humans is influenced by the NPS-system. However, the previously reported association between bedtime and rs324981 could not be confirmed. The current finding of decreased sleep duration in T/T allele carriers is in accordance with studies in rodents reporting similar results after NPS application. PMID:24896296

  18. Genetic associations of CLU rs9331888 polymorphism with Alzheimer's disease: A meta-analysis.

    PubMed

    Shuai, Ping; Liu, Yuping; Lu, Wenxue; Liu, Qiaolan; Li, Tinxin; Gong, Bo

    2015-03-30

    Recent studies showed the Clusterin gene (CLU) is associated with Alzheimer's disease (AD). However, studies investigating the association of CLU single-nucleotide polymorphism (SNP) rs9331888 with AD are controversial. We then performed a meta-analysis to assess the association between CLU SNP rs9331888 and AD. Computerized bibliographic searches of PUBMED and AlzGene database were conducted for the period up to July, 2014. The strength of the association between SNP rs9331888 and AD was estimated by odds ratios (ORs) and OR 95% confidence intervals (CIs). A total of 11 studies composed of 8766 AD cases and 11,366 controls were included in this study. Significant association of SNP rs9331888 with AD was found in Caucasian population among allelic model (C vs. G: OR=1.12, 95%CI=1.06-1.17, P<0.001), additive model (CC vs. GG: OR=1.25, 95%CI=1.12-1.40, P<0.001), recessive model (CC vs. CG+GG: OR=1.20, 95%CI=1.07-1.34, P=0.001), and dominant model (CC+CG vs. GG: OR=1.13, 95%CI=1.06-1.21, P<0.001). No significant association among these models was found in Asian and overall populations. Sensitivity analysis found that one study caused the distinct heterogeneity in Asian subgroup. Our analysis demonstrated that CLU SNP rs9331888 might be associated with an increased AD risk in Caucasian population, but not in Asian population. PMID:25703218

  19. The development of 10 novel polymorphic microsatellite markers through next generation sequencing and a preliminary population genetic analysis for the endangered Glenelg spiny crayfish, Euastacus bispinosus.

    PubMed

    Miller, Adam D; Van Rooyen, Anthony; Sweeney, Oisín F; Whiterod, Nick S; Weeks, Andrew R

    2013-07-01

    The Glenelg spiny crayfish, Euastacus bispinosus, is an iconic freshwater invertebrate of south eastern Australia and listed as 'endangered' under the Environment Protection and Biodiversity Conservation Act 1999, and 'vulnerable' under the International Union for Conservation of Nature's Red List. The species has suffered major population declines as a result of over-fishing, low environmental flows, the introduction of invasive fish species and habitat degradation. In order to develop an effective conservation strategy, patterns of gene flow, genetic structure and genetic diversity across the species distribution need to be clearly understood. In this study we develop a suite of polymorphic microsatellite markers by next generation sequencing. A total of 15 polymorphic loci were identified and 10 characterized using 22 individuals from the lower Glenelg River. We observed low to moderate genetic variation across most loci (mean number of alleles per locus = 2.80; mean expected heterozygosity = 0.36) with no evidence of individual loci deviating significantly from Hardy-Weinberg equilibrium. Marker independence was confirmed with tests for linkage disequilibrium, and analyses indicated no evidence of null alleles across loci. Individuals from two additional sites (Crawford River, Victoria; Ewens Ponds Conservation Park, South Australia) were genotyped at all 10 loci and a preliminary investigation of genetic diversity and population structure was undertaken. Analyses indicate high levels of genetic differentiation among sample locations (F ST = 0.49), while the Ewens Ponds population is genetically homogeneous, indicating a likely small founder group and ongoing inbreeding. Management actions will be needed to restore genetic diversity in this and possibly other at risk populations. These markers will provide a valuable resource for future population genetic assessments so that an effective framework can be developed for implementing conservation strategies for E. bispinosus. PMID:23644985

  20. Genetic polymorphisms of ADH1B, ADH1C and ALDH2 in Turkish alcoholics: lack of association with alcoholism and alcoholic cirrhosis

    PubMed Central

    Vatansever, Sezgin; Tekin, Fatih; Salman, Esin; Altintoprak, Ender; Coskunol, Hakan; Akarca, Ulus Salih

    2015-01-01

    No data exists regarding the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) gene polymorphisms in Turkish alcoholic cirrhotics. We studied the polymorphisms of ADH1B, ADH1C and ALDH2 genes in alcoholic cirrhotics and compared the results with non-cirrhotic alcoholics and healthy volunteers. Overall, 237 subjects were included for the study: 156 alcoholic patients (78 cirrhotics, 78 non-cirrhotic alcoholics) and 81 healthy volunteers. Three different single-nucleotide-polymorphism genotyping methods were used. ADH1C genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism method. The identified ADH1C genotypes were named according to the presence or absence of the enzyme restriction sites. ADH1B (Arg47Hys) genotyping was performed using the allele specific primer extension method, and ALDH2 (Glu487Lys) genotyping was performed by a multiplex polymerase chain reaction using two allele-specific primer pairs. For ADH1B, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 97.4%, 94.9% and 99.4%, respectively. For ADH1C, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 47%, 36.3% and 45%, respectively. There was no statistical difference between the groups for ADH1B and ADH1C (p>0.05). All alcoholic and non-alcoholic subjects (100%) had the allele *1 for ALDH2. The obtained results for ADH1B, ADH1C, and ALDH gene polymorphisms in the present study are similar to the results of Caucasian studies. ADH1B and ADH1C genetic variations are not related to the development of alcoholism or susceptibility to alcoholic cirrhosis. ALDH2 gene has no genetic variation in the Turkish population. PMID:26042511

  1. Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria

    PubMed Central

    Diallo, Karidia; Zheng, Du-Ping; Rottinghaus, Erin K.; Bassey, Orji; Yang, Chunfu

    2015-01-01

    Studying the genetic diversity and natural polymorphisms of HIV-1 would benefit our understanding of HIV drug resistance (HIVDR) development and predict treatment outcomes. In this study, we have characterized the HIV-1 genetic diversity and natural polymorphisms at the 5? region of the pol gene encompassing the protease (PR) and reverse transcriptase (RT) from 271 plasma specimens collected in 2008 from HIV-1-infected patients who were eligible for initiating antiretroviral therapy in Abuja (Nigeria). The analysis indicated that the predominant subtype was subtype G (31.0%), followed by CRF02-AG (19.2 %), CRF43-02G (18.5%), and A/CRF36-cpx (11.4%); the remaining (19.9%) were other subtypes and circulating (CRF) and unique (URF) recombinant forms. Recombinant viruses (68.6%) were the major viral strains in the region. Eighty-four subtype G sequences were further mainly classified into two major and two minor clusters; sequences in the two major clusters were closely related to the HIV-1 strains in two of the three major subtype G clusters detected worldwide. Those in the two minor clusters appear to be new subtype G strains circulating only in Abuja. The pretreatment DR prevalence was < 3%; however, numerous natural polymorphisms were present. Eleven polymorphic mutations (G16E, K20I, L23P, E35D, M36I, N37D/S/T, R57K, L63P, and V82I) were detected in the PR that were subtype or CRF specific while only three mutations (D123N, I135T, and I135V) were identified in the RT. Overall, this study indicates an evolving HIV-1 epidemic in Abuja with recombinant viruses becoming the dominant strains and the emergence of new subtype G strains; pretreatment HIVDR was low and the occurrence of natural polymorphism in the PR region was subtype or CRF dependent. PMID:25582324

  2. Relationship between Arginase 1 and Arginase 2 levels and genetic polymorphisms with erectile dysfunction.

    PubMed

    Lacchini, Riccardo; Muniz, Jaqueline J; Nobre, Yuri T D A; Cologna, Adauto J; Martins, Antonio C P; Tanus-Santos, Jose E

    2015-12-01

    Arginase 1 and Arginase 2 are homologous enzymes that convert l-Arginine to Urea and l-ornithine and compete with nitric oxide synthases for l-Arginine. Increased Arginase 1 and 2 activity may reduce nitric oxide production by the endothelium in disease states, including erectile dysfunction (ED). Here we aimed at assessing whether Arginase 1 and 2 plasma levels, plasma arginase activity, or genetic factors are associated with ED risk and severity. Blood samples were collected from healthy controls (n = 106) and from patients with ED (n = 110) after completion of the IIEF questionnaire (international index of erectile function). Plasma Arginase 1 and 2 concentrations were assessed by ELISA, while plasma arginase activity was measured by spectrophotometry. Genotypes of ARG1 (rs2781659, rs2781667, rs2246012 and rs17599586) and ARG2 (rs3742879 and rs10483801) were determined by Taqman genotyping assays by real-time polymerase chain reaction. Increased Arginase 2 concentrations were found in clinical ED and are associated with increased risk for ED. ARG1 rs2781659 AA and rs2781667 TT genotypes are associated with lower IIEF scores (higher severity) only in clinical ED. Similarly, the ARG1 GTCC haplotype is associated with higher IIEF scores in clinical ED. This study shows that plasma Arginase 2 concentrations may serve as risk factor for ED. Besides, Arginase 1 genetic variations affect ED severity. PMID:26537638

  3. Genetic polymorphisms, their allele combinations and IFN-? treatment response in Irish multiple sclerosis patients

    PubMed Central

    O’Doherty, Catherine; Favorov, Alexander; Heggarty, Shirley; Graham, Colin; Favorova, Olga; Ochs, Michael; Hawkins, Stanley; Hutchinson, Michael; O’Rourke, Killian; Vandenbroeck, Koen

    2009-01-01

    Introduction IFN-? is widely used as first-line immunomodulatory treatment for multiple sclerosis. Response to treatment is variable (30–50% of patients are nonresponders) and requires a long treatment duration for accurate assessment to be possible. Information about genetic variations that predict responsiveness would allow appropriate treatment selection early after diagnosis, improve patient care, with time saving consequences and more efficient use of resources. Materials & methods We analyzed 61 SNPs in 34 candidate genes as possible determinants of IFN-? response in Irish multiple sclerosis patients. Particular emphasis was placed on the exploration of combinations of allelic variants associated with response to therapy by means of a Markov chain Monte Carlo-based approach (APSampler). Results The most significant allelic combinations, which differed in frequency between responders and nonresponders, included JAK2–IL10RB–GBP1–PIAS1 (permutation p-value was pperm = 0.0008), followed by JAK2–IL10–CASP3 (pperm = 0.001). Discussion The genetic mechanism of response to IFN-? is complex and as yet poorly understood. Data mining algorithms may help in uncovering hidden allele combinations involved in drug response versus nonresponse. PMID:19604093

  4. Genetic polymorphism, molecular characterization and relatedness of Macrobrachium species (Palaemonidae) based on RAPD-PCR.

    PubMed

    Guerra, A L; Lima, A V B; Taddei, F G; Castiglioni, L

    2010-01-01

    The prawn genus Macrobrachium belongs to the family Palaemonidae. Its species are widely distributed in lakes, reservoirs, floodplains, and rivers in tropical and subtropical regions of South America. Globally, the genus Macrobrachium includes nearly 210 known species, many of which have economic and ecological importance. We analyzed three species of this genus (M. jelskii, M. amazonicum and M. brasiliense) using RAPD-PCR to assess their genetic variability, genetic structure and the phylogenetic relationship between them and to look for molecular markers that enable separation of M. jelskii and M. amazonicum, which are closely related syntopic species. Ten different random decamer primers were used for DNA amplification, yielding 182 fragments. Three of these fragments were monomorphic and exclusive to M. amazonicum or M. jelskii and can be used as specific molecular markers to identify and separate these two species. Similarity indices and a phylogenetic tree showed that M. amazonicum and M. jelskii are closest to each other, while M. brasiliense was the most differentiated species among them; this may be attributed to the different habitat conditions to which these species have been submitted. This information will be useful for further studies on these important crustacean species. PMID:21128212

  5. Rifampicin-resistance, rpoB polymorphism and RNA polymerase genetic engineering.

    PubMed

    Alifano, Pietro; Palumbo, Carla; Pasanisi, Daniela; Talà, Adelfia

    2015-05-20

    Following its introduction in 1967, rifampicin has become a mainstay of therapy in the treatment of tuberculosis, leprosy and many other widespread diseases. Its potent antibacterial activity is due to specific inhibition of bacterial RNA polymerase. However, resistance to rifampicin was reported shortly after its introduction in the medical practice. Studies in the model organism Escherichia coli helped to define the molecular mechanism of rifampicin-resistance demonstrating that resistance is mostly due to chromosomal mutations in rpoB gene encoding the RNA polymerase ? chain. These studies also revealed the amazing potential of the molecular genetics to elucidate the structure-function relationships in bacterial RNA polymerase. The scope of this paper is to illustrate how rifampicin-resistance has been recently exploited to better understand the regulatory mechanisms that control bacterial cell physiology and virulence, and how this information has been used to maneuver, on a global scale, gene expression in bacteria of industrial interest. In particular, we reviewed recent literature regarding: (i) the effects of rpoB mutations conferring rifampicin-resistance on transcription dynamics, bacterial fitness, physiology, metabolism and virulence; (ii) the occurrence in nature of "mutant-type" or duplicated rifampicin-resistant RNA polymerases; and (iii) the RNA polymerase genetic engineering method for strain improvement and drug discovery. PMID:25481100

  6. New RB1 oncogenic mutations and intronic polymorphisms in Serbian retinoblastoma patients: genetic counseling implications.

    PubMed

    Kontic, Milica; Palacios, Iciar; Gámez, Angelo; Camino, Isabel; Latkovic, Zoran; Rasic, Dejan; Krstic, Vera; Bunjevacki, Vera; Alonso, Javier; Pestaña, Angel

    2006-01-01

    The purpose of this work was to identify germ line RB1 mutations in 16 Serbian retinoblastoma patients for genetic counselling. Mutation analysis was carried out by PCR directed sequencing of the 27 exons. Loss of heterozygosity for two RB1 intragenic markers was also analyzed in 14 tumour samples. Five new RB1 oncogenic mutations (g.2078 del C, g.77047_48 del GC, g.78117_8 del TT, g.160797 del T, and g.64439+2 T>C) and two recurrences (R445X and Q383X) have been found in this study. In addition, four intronic variants were observed germ line in some unilateral patients. Two of these variants (g.44668-15T/G, and g.166204-8T/A) are discussed as potential oncogenic mutation candidates. The results show the relevance of studies aimed to investigate the role of intronic variants in exon splicing regulation. Such studies will help to disclose hidden retinoblastoma susceptibilities, important for accurate genetic counselling. PMID:16972022

  7. A pilot study to determine genetic polymorphism in Mycobacterium tuberculosis isolates in Central India.

    PubMed

    Desikan, P; Chauhan, D S; Sharma, P; Panwalkar, N; Gautam, S; Katoch, V M

    2012-01-01

    This study was carried out to identify predominant spoligotypes responsible for transmission and prevalence of tuberculosis in central India since there is no data available about the genetic biodiversity of Mycobacterium tuberculosis isolates from patients with tuberculosis in this region. 35 strains of Mycobacterium tuberculosis were subjected to spoligotyping according to the standard protocol. A total of 25 strains out of the 35 (71.42%) could be grouped in to 6 clusters. The largest cluster comprised 8 isolates. Unique (Non-clustered) spoligotypes were seen in 10 isolates, Nine strains did not match the data base (Spol DB-4 data base). The results indicate that there may be a number of orphan strains unique to this geographical area. Further studies on a larger sample size derived from this area would help us delineate the epidemiology of Mycobacterium tuberculosis infection in this area. PMID:23183476

  8. Intraisolate Mitochondrial Genetic Polymorphism and Gene Variants Coexpression in Arbuscular Mycorrhizal Fungi

    PubMed Central

    Beaudet, Denis; de la Providencia, Ivan Enrique; Labridy, Manuel; Roy-Bolduc, Alice; Daubois, Laurence; Hijri, Mohamed

    2015-01-01

    Arbuscular mycorrhizal fungi (AMF) are multinucleated and coenocytic organisms, in which the extent of the intraisolate nuclear genetic variation has been a source of debate. Conversely, their mitochondrial genomes (mtDNAs) have appeared to be homogeneous within isolates in all next generation sequencing (NGS)-based studies. Although several lines of evidence have challenged mtDNA homogeneity in AMF, extensive survey to investigate intraisolate allelic diversity has not previously been undertaken. In this study, we used a conventional polymerase chain reaction -based approach on selected mitochondrial regions with a high-fidelity DNA polymerase, followed by cloning and Sanger sequencing. Two isolates of Rhizophagus irregularis were used, one cultivated in vitro for several generations (DAOM-197198) and the other recently isolated from the field (DAOM-242422). At different loci in both isolates, we found intraisolate allelic variation within the mtDNA and in a single copy nuclear marker, which highlighted the presence of several nonsynonymous mutations in protein coding genes. We confirmed that some of this variation persisted in the transcriptome, giving rise to at least four distinct nad4 transcripts in DAOM-197198. We also detected the presence of numerous mitochondrial DNA copies within nuclear genomes (numts), providing insights to understand this important evolutionary process in AMF. Our study reveals that genetic variation in Glomeromycota is higher than what had been previously assumed and also suggests that it could have been grossly underestimated in most NGS-based AMF studies, both in mitochondrial and nuclear genomes, due to the presence of low-level mutations. PMID:25527836

  9. Development of a multiplex PCR assay for fine-scale population genetic analysis of the Komodo monitor Varanus komodoensis based on 18 polymorphic microsatellite loci.

    PubMed

    Ciofi, Claudio; Tzika, Athanasia C; Natali, Chiara; Watts, Phillip C; Sulandari, Sri; Zein, Moch S A; Milinkovitch, Michel C

    2011-05-01

    Multiplex PCR assays for the coamplification of microsatellite loci allow rapid and cost-effective genetic analyses and the production of efficient screening protocols for international breeding programs. We constructed a partial genomic library enriched for di-nucleotide repeats and characterized 14 new microsatellite loci for the Komodo monitor (or Komodo dragon, Varanus komodoensis). Using these novel microsatellites and four previously described loci, we developed multiplex PCR assays that may be loaded on a genetic analyser in three separate panels. We tested the novel set of microsatellites for polymorphism using 69 individuals from three island populations and evaluated the resolving power of the entire panel of 18 loci by conducting (i) a preliminary assignment test to determine population(s) of origin and (ii) a parentage analysis for 43 captive Komodo monitors. This panel of polymorphic loci proved useful for both purposes and thus can be exploited for fine-scale population genetic analyses and as part of international captive breeding programs directed at maintaining genetically viable ex situ populations and reintroductions. PMID:21481213

  10. Analysis of genetic variability in endemic medicinal plants of genus Chlorophytum from the Indian subcontinent using amplified fragment length polymorphism marker.

    PubMed

    Patil, Swapnil Mahadeo; Chandanshive, Vishal Vinayak; Tamboli, Asif Shabodin; Adsul, Avinash Asraji; Yadav, Shrirang Ramchandra; Govindwar, Sanjay Prabhu

    2015-12-01

    The genus Chlorophytum consists of medicinally important species like Chlorophytum borivilianum, C. tuberosum and C. attenuatum. Uncontrolled harvest of this plant from wild habitat due to its high commercial value made the species of this genus be listed in the Red Data Book of Indian plants as an endangered species. In India, approximately nineteen species of Chlorophytum are found; out of these, only C. borivilianum is cultivated commercially. The objective of this study was to measure genetic diversity, population structure and phylogenetic relationship among the species using Amplified Fragment Length Polymorphisms (AFLP). Fifteen pairs of primer (out of 64 primer pairs screened) were used to analyse the genetic diversity in eighteen species of genus Chlorophytum. Cluster analysis, estimation of the gene flow among the species and of the phylogeographic distribution of this genus were carried out using an AFLP data matrix. A high level of genetic diversity was observed on the basis of the percentage of polymorphic bands (99.91%), Shannon's information index (0.3592) and Nei's gene diversity (0.2085) at species level. Cluster analysis of UPGMA dendrogram, principal component analysis and Bayesian method analysis resolved these species in three different clusters, which was supported by morphological information. The Mantel test (r=0.4432) revealed a significant positive correlation between genetic and geographic distances. The collected data have an important implication in the identification, authentication, and conservation of the species of the genus Chlorophytum. PMID:26573876

  11. Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals.

    PubMed

    Boraxbekk, C J; Ames, David; Kochan, Nicole A; Lee, Teresa; Thalamuthu, Anbupalam; Wen, Wei; Armstrong, Nicola J; Kwok, John B J; Schofield, Peter R; Reppermund, Simone; Wright, Margaret J; Trollor, Julian N; Brodaty, Henry; Sachdev, Perminder; Mather, Karen A

    2015-11-01

    The variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure. However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145 and rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65-90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippocampal volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing occasions). Overall we did not find support for an association of KIBRA either alone or in combination with CLSTN2 with memory performance or hippocampal volume, nor did variation in these genes influence longitudinal memory decline or hippocampal atrophy in two cohorts of older adults. PMID:26415670

  12. Genetic polymorphisms in Japanese fragrant landraces and novel fragrant allele domesticated in northern Japan.

    PubMed

    Ootsuka, Kenta; Takahashi, Ikuya; Tanaka, Katsunori; Itani, Tomio; Tabuchi, Hiroaki; Yoshihashi, Tadashi; Tonouchi, Akio; Ishikawa, Ryuji

    2014-06-01

    Rice fragrance is an important characteristic for Southeast Asian consumers, and fragrant landraces from Japan were first recorded in the 17th century. Principal component analysis clearly showed that Japanese fragrant landraces were genetically different from non-Japanese fragrant landraces. Japanese fragrant landraces were composed of six clades, none of which carried the most common fragrance mutation, an 8-bp deletion in exon 7 of Badh2. Fragrant landraces comprised two major groups carrying different Badh2 mutations. One group carried a known SNP at exon13 and the other a SNP at the exon1-intron1 junction as splicing donor site. The latter was considered to be a potential splicing mutant group as a novel allele at Badh2. Heterozygosity (He) scores in the two fragrant groups were not significantly different from non-fragrant landraces and modern cultivars. However, lower He scores were found around the Badh2 locus in the two groups. The potential splicing mutant group showed a more extended haplotype than the E13 SNP group. A likely causal factor responsible for loss of function is a novel splicing mutation allele that may have been generated quite recently. The fragrance allele has dispersed as a result of out-crossing under local environmental conditions. PMID:24987297

  13. Characterization of Capsicum annuum Genetic Diversity and Population Structure Based on Parallel Polymorphism Discovery with a 30K Unigene Pepper GeneChip

    PubMed Central

    Hill, Theresa A.; Ashrafi, Hamid; Reyes-Chin-Wo, Sebastian; Yao, JiQiang; Stoffel, Kevin; Truco, Maria-Jose; Kozik, Alexander; Michelmore, Richard W.; Van Deynze, Allen

    2013-01-01

    The widely cultivated pepper, Capsicum spp., important as a vegetable and spice crop world-wide, is one of the most diverse crops. To enhance breeding programs, a detailed characterization of Capsicum diversity including morphological, geographical and molecular data is required. Currently, molecular data characterizing Capsicum genetic diversity is limited. The development and application of high-throughput genome-wide markers in Capsicum will facilitate more detailed molecular characterization of germplasm collections, genetic relationships, and the generation of ultra-high density maps. We have developed the Pepper GeneChip® array from Affymetrix for polymorphism detection and expression analysis in Capsicum. Probes on the array were designed from 30,815 unigenes assembled from expressed sequence tags (ESTs). Our array design provides a maximum redundancy of 13 probes per base pair position allowing integration of multiple hybridization values per position to detect single position polymorphism (SPP). Hybridization of genomic DNA from 40 diverse C. annuum lines, used in breeding and research programs, and a representative from three additional cultivated species (C. frutescens, C. chinense and C. pubescens) detected 33,401 SPP markers within 13,323 unigenes. Among the C. annuum lines, 6,426 SPPs covering 3,818 unigenes were identified. An estimated three-fold reduction in diversity was detected in non-pungent compared with pungent lines, however, we were able to detect 251 highly informative markers across these C. annuum lines. In addition, an 8.7 cM region without polymorphism was detected around Pun1 in non-pungent C. annuum. An analysis of genetic relatedness and diversity using the software Structure revealed clustering of the germplasm which was confirmed with statistical support by principle components analysis (PCA) and phylogenetic analysis. This research demonstrates the effectiveness of parallel high-throughput discovery and application of genome-wide transcript-based markers to assess genetic and genomic features among Capsicum annuum. PMID:23409153

  14. SNP genetic polymorphisms of MDR-1, CYP1A2 and CYPB11 genes in four canine breeds upon toxicological evaluation.

    PubMed

    Gagliardi, Rosa; Llambí, Silvia; Arruga, M Victoria

    2015-09-01

    The fields of pharmacogenetics and pharmacogenomics have become increasingly promising regarding the clinical application of genetic data to aid in prevention of adverse reactions. Specific screening tests can predict which animals express modified proteins or genetic sequences responsible for adverse effects associated with a drug. Among the genetic variations that have been investigated in dogs, the multidrug resistance gene (MDR) is the best studied. However, other genes such as CYP1A2 and CYP2B11 control the protein syntheses involved in the metabolism of many drugs. In the present study, the MDR-1, CYP1A2 and CYP2B11 genes were examined to identify SNP polymorphisms associated with these genes in the following four canine breeds: Uruguayan Cimarron, Border Collie, Labrador Retriever and German Shepherd. The results revealed that several SNPs of the CYP1A2 and CYP2B11 genes are potential targets for drug sensitivity investigations. PMID:25797294

  15. SNP genetic polymorphisms of MDR-1, CYP1A2 and CYPB11 genes in four canine breeds upon toxicological evaluation

    PubMed Central

    Gagliardi, Rosa; Llambí, Silvia

    2015-01-01

    The fields of pharmacogenetics and pharmacogenomics have become increasingly promising regarding the clinical application of genetic data to aid in prevention of adverse reactions. Specific screening tests can predict which animals express modified proteins or genetic sequences responsible for adverse effects associated with a drug. Among the genetic variations that have been investigated in dogs, the multidrug resistance gene (MDR) is the best studied. However, other genes such as CYP1A2 and CYP2B11 control the protein syntheses involved in the metabolism of many drugs. In the present study, the MDR-1, CYP1A2 and CYP2B11 genes were examined to identify SNP polymorphisms associated with these genes in the following four canine breeds: Uruguayan Cimarron, Border Collie, Labrador Retriever and German Shepherd. The results revealed that several SNPs of the CYP1A2 and CYP2B11 genes are potential targets for drug sensitivity investigations. PMID:25797294

  16. Risk of carotid atherosclerosis associated with genetic polymorphisms of apolipoprotein E and inflammatory genes among arsenic exposed residents in Taiwan

    SciTech Connect

    Hsieh, Y.-C.; Hsieh, F.-I; Lien, L.-M.; Chou, Y.-L.; Chiou, H.-Y. Chen, C.-J.

    2008-02-15

    Arsenic had been reported to be associated with carotid atherosclerosis. However, there were few studies to evaluate the association between the susceptible gene of lipid metabolism and inflammation and carotid atherosclerosis among arsenic exposure residents. The aim of the study was to investigate the associations between the genetic polymorphisms of APOE and MCP-1 and the risk of carotid atherosclerosis among residents of Lanyang Basin in Taiwan which was a newly confirmed arsenic-endemic area. In total, 479 residents who had been genotyped of these two genes and examined the severity of carotid atherosclerosis were included in this study. The study subjects with carotid intima media thickness (IMT) {>=} 1.0 mm or with the observable plaque in the extracranial carotid artery were diagnosed as carotid atherosclerosis. A significantly age- and gender-adjusted odds ratio of 2.0 for the development of carotid atherosclerosis was observed in study subjects with {epsilon}4 allele of APOE than those without {epsilon}4 allele. Compared with study subjects who carried wild genotypes of APOE and MCP-1, those with both risk genotypes of APOE and MCP-1 had 2.5-fold risk of carotid atherosclerosis after adjustment for age and gender, revealing a significant dose-response relationship between number of risk genotypes of these genes and risk of carotid atherosclerosis. Additionally, study subjects with two risk genotypes of APOE and MCP-1 and either had ingested well water contained arsenic level > 10 {mu}g/L or had arsenic exposure > 0.22 mg/L-year would have strikingly highest risk of 10.3-fold and 15.7-fold, respectively, for the development carotid atherosclerosis, showing significant joint effect of arsenic exposure and risk genotypes of APOE and MCP-1.

  17. Genetic polymorphisms regulating dopamine signaling in the frontal cortex interact to affect target detection under high working memory load

    PubMed Central

    Smith, Christopher T.; Swift-Scanlan, Theresa; Boettiger, Charlotte A.

    2013-01-01

    Frontal-dependent task performance is typically modulated by dopamine (DA) according to an inverted-U pattern, whereby intermediate levels of DA signaling optimizes performance. Numerous studies implicate trait differences in DA signaling based on differences in the catechol-O-methyltransferase (COMT) gene in executive function task performance. However, little work has investigated genetic variations in DA signaling downstream from COMT. One candidate is the dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), which mediates signaling through the DA D1-type receptor, the dominant DA receptor in the frontal cortex. Using an n-back task, we used signal detection theory to measure performance in a healthy adult population (n=97) genotyped for single nucleotide polymorphisms in the COMT (rs4680) and DARPP-32 (rs907094) genes. Correct target detection (hits), and false alarms were used to calculate d' measures for each working memory load (0-, 2-, and 3-back). At the highest load (3-back) only, we observed a significant COMT×DARPP-32 interaction, such that the DARPP-32 T/T genotype enhanced target detection in COMTValVal individuals, but impaired target detection in COMTMet carriers. These findings suggest that enhanced dopaminergic signaling via the DARPP-32 T allele aids target detection in individuals with presumed low frontal DA (COMTValVal) but impairs target detection in those with putatively higher frontal DA levels (COMTMet carriers). Moreover, these data support an inverted-U model with intermediate levels of DA signaling optimizing performance on tasks requiring maintenance of mental representations in working memory. PMID:24144248

  18. Breast Cancer Risk Reduction and Membrane-Bound Catechol O-Methyltransferase Genetic Polymorphisms

    PubMed Central

    Ji, Yuan; Olson, Janet; Zhang, Jianping; Hildebrandt, Michelle; Wang, Liewei; Ingle, James; Fredericksen, Zachary; Sellers, Thomas; Miller, William R.; Dixon, J. Michael; Brauch, Hiltrud; Eichelbaum, Michel; Justenhoven, Christina; Hamann, Ute; Ko, Yon; Brüning, Thomas; Chang-Claude, Jenny; Wang-Gohrke, Shan; Schaid, Daniel; Weinshilboum, Richard

    2008-01-01

    Catechol O-methyltransferase (COMT)-catalyzed methylation of catecholestrogens has been proposed to play a protective role in estrogen-induced genotoxic carcinogenesis. We have taken a comprehensive approach to test the hypothesis that genetic variation in COMT might influence breast cancer risk. Fifteen COMT SNPs selected on the basis of in-depth resequencing of the COMT gene were genotyped in 1482 DNA samples from a Mayo Clinic breast cancer case-control study. Two common SNPs in the distal promoter for membrane-bound (MB) COMT, rs2020917 and rs737865, were associated with breast cancer risk reduction in premenopausal women in the Mayo Clinic study, with allele-specific odds ratios of 0.70 (95% CI = 0.52–0.95) and 0.68 (95% CI = 0.51–0.92), respectively. These two SNPs were then subjected to functional genomic analysis and were genotyped in an additional 3683 DNA samples from two independent case-control studies (GENICA and GESBC). Functional genomic experiments showed that these SNPs could up-regulate transcription and that they altered DNA-protein binding patterns. Furthermore, substrate kinetic and exon array analyses suggested a role for MB-COMT in catecholestrogen inactivation. The GENICA results were similar to the Mayo case-control observations, with ORs of 0.85 (95% CI = 0.72–1.00) and 0.85 (95% CI = 0.72–1.01) for the two SNPs. No significant effect was observed in the GESBC study. These studies demonstrated that two SNPs in the COMT distal promoter were associated with breast cancer risk reduction in 2 of 3 case-control studies, compatible with the results of functional genomic experiments, suggesting a role for MB-COMT in breast cancer risk. PMID:18632656

  19. Variation in milk protein concentrations associated with genetic polymorphism and environmental factors.

    PubMed

    NG-Kwai-Hang, K F; Hayes, J F; Moxley, J E; Monardes, H G

    1987-03-01

    Concentrations of alpha s-casein, beta-casein, kappa-casein, beta-lactoglobulin, alpha-lactalbumin, serum albumin, and immunoglobulin in milk from 1888 Holstein cows were determined monthly over the lactation period. Cows were phenotyped for genetic variants of alpha s1-casein, beta-casein, kappa-casein, and beta-lactoglobulin. Least squares analyses showed variations in individual proteins due to parity number, month of test, stage of lactation, somatic cell count, fat content, milk yield, and phenotypes of cows for milk proteins. beta-Casein declined and serum proteins increased with advancing age of cows. Concentration of individual proteins decreased during the first 2 to 3 mo in lactation and then increased as lactation progressed. alpha s1-Casein variants significantly affected concentrations of alpha s-casein (BC greater than BB greater than AB) and beta-lactoglobulin (AB greater than BB greater than BC). Variant B for beta-casein is associated with lower alpha s-casein, beta-lactoglobulin, immunoglobulins, and higher beta-casein and alpha-lactalbumin concentrations than variant A1, A2, or A3. Milk from BB kappa-casein, and BB beta-lactoglobulin cows contained more alpha s-casein, kappa-casein, and less beta-lactoglobulin than milk from AA cows for the two proteins. Concentrations of all proteins were negatively correlated with milk production. Increased somatic cell counts were associated with lower beta-casein and higher concentrations of other proteins. Fat content of milk was positively correlated with the three casein fractions and beta-lactoglobulin. PMID:3584600

  20. Genetic analysis of litchi (Litchi chinensis Sonn.) in southern China by improved random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR).

    PubMed

    Long, Yan; Cheng, Jingliang; Mei, Zhiqiang; Zhao, Ling; Wei, Chunli; Fu, Shelly; Khan, Md Asaduzzaman; Fu, Junjiang

    2015-01-01

    Litchi (Litchi chinensis Sonn., L. chinensis), a type of tree growing in most areas of southern China, produces an edible fruit that is also a source of traditional medicine. Genetic identification of litchi species or cultivars using molecular markers is very important. In this study, a total of six litchi samples from Fujian, Hainan, Guangdong, Guangxi and Sichuan province, as well as one wild Dimocarpus confinis (D. confinis) sample from Guangxi province were collected for genetic analysis. The cluster dendrograms were constructed for genetic analysis on the basis of DNA amplification results by RAPD and ISSR. The improved RAPD amplified DNA with consistent and clear banding patterns. A total of 176 bands were found, indicating a 72.7 % polymorphism in L. chinensis DNA samples. Significant genetic distances were found among the different species or cultivars, with an index of similarity coefficient ranging from 0.59 to 0.87. Similar to RAPD results, ISSR analysis of the L. chinensis DNA samples showed a range of 0.70-0.93 similarity coefficients. The genetic distance between Hainan sample and Sichuan samples was the farthest, which is consistent with their geographic distance. Furthermore, the index of similarity coefficient between D. confinis and L. chinensis was 0.35-0.41 by RAPD and 0.38-0.48 by ISSR, indicating that these two species have significant genetic difference. This study reveals the high level of genetic differences between different litchi species or cultivars, and confirms the significance of the improved RAPD method in genetic characterization of organisms. Taken together, the improved RAPD combined with ISSR analysis can be used frequently for the genetic diversity, germplasm resources preservation, molecular-assisted breeding, and genetic characterization of various organisms. PMID:25249227

  1. Personality in Relation to Genetic Liability for Schizophrenia and Bipolar Disorder: Differential Associations with the COMT Val108/158Met Polymorphism

    PubMed Central

    Silberschmidt, Amy L.; Sponheim, Scott R.

    2009-01-01

    Schizophrenia and bipolar disorder may share aspects of genetic etiology. Evidence supports the Val108/158Met polymorphism of the Catechol-o-Methyltransferase (COMT) gene as potentially contributing to the etiology of both disorders. To determine whether the COMT gene is associated with personality traits related to genetic risk for either schizophrenia or bipolar disorder, we examined dimensions of personality psychopathology in biological relatives of individuals with the disorders. Specifically, we contrasted personality characteristics of first-degree relatives of people with schizophrenia, first-degree relatives of people with bipolar-I disorder, and nonpsychiatric control participants using scores from the Dimensional Assessment of Personality Pathology – Brief Questionnaire (DAPP-BQ). We also characterized the COMT Val108/158Met polymorphism of subjects. Compared to controls, relatives of schizophrenia patients scored lower on stimulus seeking and higher on restrictive expression and social avoidance. Compared to relatives of bipolar patients, relatives of schizophrenia patients had lower scores on narcissism, rejectionality (i.e., rejection of ideas of others), stimulus seeking, passive-aggressive oppositionality, and self-harm. The subset of relatives of schizophrenia patients who were COMT val homozygotes exhibited lower scores on narcissism, rejectionality, and stimulus seeking than met homozygote relatives of schizophrenia patients and control participants. Although relatives of bipolar patients showed scale elevations consistent with emotional dysregulation, the scores failed to be associated with the Val108/158Met polymorphism. Abnormally low narcissism and rejectionality in val homozygote relatives of schizophrenia patients suggests that the val allele of the COMT polymorphism may be associated with an underdeveloped self-concept phenomenologically similar to made volition and passivity experiences comprising first-rank symptoms of schizophrenia. PMID:18201871

  2. Effects of genetic polymorphisms of metabolic enzymes on cytokinesis-block micronucleus in peripheral blood lymphocyte among coke-oven workers

    SciTech Connect

    Shuguang Leng; Yufei Dai; Yong Niu; Zufei Pan; Xiaohua Li; Juan Cheng; Fengsheng He; Yuxin Zheng

    2004-10-15

    Exploring the associations between genetic polymorphisms of metabolic enzymes and susceptibility to polycyclic aromatic hydrocarbon (PAH)-induced chromosomal damage is of great significance for understanding PAH carcinogenesis. Cytochrome P450, glutathione S-transferase, microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, and N-acetyltransferase are PAH-metabolizing enzymes. In this study, we genotyped for the polymorphisms of these genes and assessed their effects on cytokinesis-block micronucleus (CBMN) frequencies in peripheral blood lymphocytes among 141 coke-oven workers and 66 non-coke-oven worker controls. The geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the controls were 12.0 and 0.7 {mu}mol/mol creatinine, respectively. The CBMN frequency (number of micronuclei per 1,000 binucleated lymphocytes) was significantly higher in coke-oven workers (9.5 {+-} 6.6) than in the controls. Among the coke-oven workers, age was positively associated with CBMN frequency; the mEH His{sup 113} variant genotype exhibited significantly lower CBMN frequency than did the Tyr{sup 113}/Tyr{sup 113} genotype; the low mEH activity phenotype exhibited a lower CBMN frequency than did the high mEH activity phenotype; the GSTP1 Val{sup 105}/Val{sup 105} genotype exhibited a higher CBMN frequency than did the GSTP1 Ile{sup 105}/Ile{sup 105} or Ile{sup 105}/Val{sup 105} genotypes; the joint effect of high mEH activity phenotype and GSTM1 null genotype on CBMN frequencies was also found. Gene-environment interactions between occupational PAH exposure and polymorphisms of mEH and/or GSTM1 were also evident. These results indicate that the mEH, GSTP1, and GSTM1 polymorphisms may play a role in sensitivity or genetic susceptibility to the genotoxic effects of PAH exposure in the coke-oven workers.

  3. The influence of genetic polymorphisms in XRCC3 and ADH5 genes on the frequency of genotoxicity biomarkers in workers exposed to formaldehyde.

    PubMed

    Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, Manuel C; Brito, Miguel

    2013-04-01

    The International Agency for Research on Cancer classified formaldehyde as carcinogenic to humans because there is "sufficient epidemiological evidence that it causes nasopharyngeal cancer in humans". Genes involved in DNA repair and maintenance of genome integrity are critically involved in protecting against mutations that lead to cancer and/or inherited genetic disease. Association studies have recently provided evidence for a link between DNA repair polymorphisms and micronucleus (MN) induction. We used the cytokinesis-block micronucleus (CBMN assay) in peripheral lymphocytes and MN test in buccal cells to investigate the effects of XRCC3 Thr241Met, ADH5 Val309Ile, and Asp353Glu polymorphisms on the frequency of genotoxicity biomarkers in individuals occupationally exposed to formaldehyde (n = 54) and unexposed workers (n = 82). XRCC3 participates in DNA double-strand break/recombination repair, while ADH5 is an important component of cellular metabolism for the elimination of formaldehyde. Exposed workers had significantly higher frequencies (P < 0.01) than controls for all genotoxicity biomarkers evaluated in this study. Moreover, there were significant associations between XRCC3 genotypes and nuclear buds, namely XRCC3 Met/Met (OR = 3.975, CI 1.053-14.998, P = 0.042) and XRCC3 Thr/Met (OR = 5.632, CI 1.673-18.961, P = 0.005) in comparison with XRCC3 Thr/Thr. ADH5 polymorphisms did not show significant effects. This study highlights the importance of integrating genotoxicity biomarkers and genetic polymorphisms in human biomonitoring studies. PMID:23355119

  4. Genetic association of IFN-? +874T/A polymorphism in Mexican patients with drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

    PubMed

    Charli-Joseph, Yann; Lima, Guadalupe; Ramos-Bello, Dolores; Aguilar, Diana; Orozco-Topete, Rocío; Llorente, Luis

    2013-05-01

    Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, but potentially life-threatening diseases, characterized by widespread epidermal necrosis and are predominantly drug induced. There is a paucity of data regarding the role of cytokine and cytokine receptors polymorphisms in the pathoimmunology of SJS/TEN. The aim of this study was to investigate the role of TNF-?-308, IFN-? +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg gene polymorphisms in SJS/TEN in Mexican Mestizo patients. Twenty-nine unrelated SJS/TEN patients and 128 unrelated healthy individuals were studied. Genomic extraction was carried out from complete blood samples using the salting out method. The PCR-RFLP method was used to amplify the following polymorphisms: TNF-?-308, IFN-? +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg. TNF-?-308, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg polymorphisms were not associated with the genetic susceptibility to SJS/TEN. The distribution of TT, TA, AA genotypes of IFN-? +874 was significantly different in SJS/TEN patients compared with controls (pC = 0.012). TA and AA genotypes were grouped to highlight the differences between patients and controls given by the absence of the AA genotype in the group of patients (pC = 0.03, OR = 3.61 95 % CI 1.20-11.6). This preliminary study suggests that IFN-? +874 T/A polymorphism is associated with SJS/TEN. PMID:23224615

  5. A new high-throughput AFLP approach for identification of new genetic polymorphism in the genome of the clonal microorganism Mycobacterium tuberculosis.

    PubMed

    van den Braak, Nicole; Simons, Guus; Gorkink, Roy; Reijans, Martin; Eadie, Kimberly; Kremers, Kristin; van Soolingen, Dick; Savelkoul, Paul; Verbrugh, Henri; van Belkum, Alex

    2004-01-01

    We have here applied high-throughput amplified fragment length polymorphism (htAFLP) analysis to strains belonging to the five classical species of the Mycobacterium tuberculosis complex. Using 20 strains, three enzyme combinations and eight selective amplification primer pairs, 24 AFLP reactions were performed per strain. Overall, this resulted in 480 DNA fingerprints and more than 1200 htAFLP-amplified PCR fragments were visualised per strain. The cumulative dendrogram correctly clustered strains from the various species, albeit within a distance of 6.5% for most of them. The single isolate of Mycobacterium canettii presented separately at 19% distance. All over, 169 fragments (14%) appeared to be polymorphic. Sixty-eight were specific for M. canetti and forty-five for Mycobacterium bovis. For the 10 different M. tuberculosis strains included in the present analysis, 56 polymorphic markers were identified. Upon sequencing 20 of these marker regions and comparisons with the H37Rv genome sequence, 25% appeared to share homology to members of the antigenically variable PE/PPE surface protein encoding gene family confirming previous findings on the genetic heterogeneity within these genes. In addition, homologues for phage genes and insertion element-encoded genes were detected. Forty-five percent of the sequences derived from ORFs with a currently unknown function, which was corroborated by genome sequence comparison for the clinical M. tuberculosis CD 1551 isolate. Sequence variation in M. tuberculosis was assessed in more detail for a subset of these loci by newly designed PCR restriction fragment length polymorphism (RFLP) tests and direct sequencing. Fourteen novel PCR RFLP tests were developed and twelve novel single nucleotide polymorphisms (SNPs) were identified, all suited for epidemiological analysis of M. tuberculosis. The tests allowed for identification of the major Mycobacterium species and M. tuberculosis variants and clones. PMID:14706750

  6. Polymorphisms in migraine-associated gene, atp1a2, and ischemic stroke risk in a biracial population: the genetics of early onset stroke study.

    PubMed

    Harriott, Andrea M; Dueker, Nicole; Cheng, Yu-Ching; Ryan, Kathleen A; O'Connell, Jeffrey R; Stine, O Colin; McArdle, Patrick F; Wozniak, Marcella A; Stern, Barney J; Mitchell, Braxton D; Kittner, Steven J; Cole, John W

    2013-12-01

    In a recent meta-analysis migraine was associated with a two-fold increase in stroke risk. While the mechanism driving this association is unknown, one intriguing hypothesis is that migraineurs are genetically predisposed to developing ischemic stroke. Mutations in the ATP1A2 gene are implicated in familial hemiplegic migraine type II and increase the severity of ischemic brain injury in animal models. To further explore these observations, we assessed the association between ATP1A2 polymorphisms, migraine, and the risk of ischemic stroke in participants of the Genetics of Early-Onset Stroke Study, a population-based case-control study of ischemic stroke among men and women aged 15-49. Using responses to a headache symptoms questionnaire, subjects were classified as having no migraine, or migraine with or without visual aura. Evaluating a total of 134 ATP1A2 polymorphisms genotyped using a combination of Illumina platforms (Cardiovascular Gene-centric 50 K SNP Array and HumanOmni1-Quad_v1-0_B Bead Chip), only one polymorphism (rs2070704) demonstrated a nominally significant association with stroke in an age-, gender-, ethnicity-adjusted model (OR?=?0.83, 95% CI?=?0.71-0.98, p?=?0.025) and in a vascular risk factor model adjusting for age, gender, ethnicity, hypertension, diabetes, smoking, and myocardial infarction (OR?=?0.74, 95% CI?=?0.63-0.89, p?=?0.001). Ethnicity-stratified analyses demonstrated a significant association for rs2070704 among African-Americans (OR?=?0.68, 95% CI?=?0.53-0.90, p?=?0.005) but not Caucasians (OR?=?0.82, 95% CI?=?0.64-1.04, p?=?0.107). These associations were unchanged when migraine subtypes were included as co-variates. We did not observe an association between ATP1A2 polymorphisms and migraine. While our results do not demonstrate a strong relationship between ATP1A2 polymorphisms and migraine associated stroke risk, the results are hypothesis generating and indicate that an association between ATP1A2 polymorphisms and stroke risk may exist. Additional studies are required. PMID:23459313

  7. Novel Polymorphic Microsatellite Loci for the Korean Black Scraper (Thamnaconus modestus), and Their Application to the Genetic Characterization of Wild and Farmed Populations

    PubMed Central

    An, Hye Suck; Kim, Eun Mi; Lee, Jang Wook; Dong, Chun Mae; Lee, Bai Ik; Kim, Yi Cheong

    2011-01-01

    In this study, we developed 20 polymorphic microsatellite markers for the Korean black scraper, Thamnaconus modestus (Günther, 1877), Monacanthidae, and used them to compare allelic variation between wild and hatchery populations in Korea. All loci were readily amplified and demonstrated allelic variability, with the number of alleles ranging from 5–35 in the wild population and 5–22 in the farmed population. The average observed and expected heterozygosities were estimated, respectively, as 0.74 and 0.80 in the hatchery samples and 0.78 and 0.81 in the wild ones. These results indicate lower genetic variability in the hatchery population than in the wild population and minor, but significant, genetic differentiation between the two populations (FST = 0.005, P < 0.01). Additionally, cross-amplification was tested in another monacanthid species, Stephanolepis cirrhifer; many loci were found that yielded useful information. The high degree of polymorphism exhibited by the 20 microsatellites will be useful in future aquaculture and population genetic studies for developing conservation and management plans. PMID:21747727

  8. Human heredity and politics: A comparative institutional study of the Eugenics Record Office at Cold Spring Harbor (United States), the Kaiser Wilhelm Institute for Anthropology, Human Heredity, and Eugenics (Germany), and the Maxim Gorky Medical Genetics Institute (USSR).

    PubMed

    Adams, Mark B; Allen, Garland E; Weiss, Sheila Faith

    2005-01-01

    Despite the fact that much has been written in recent years about the science of heredity under the Third Reich, there is as yet no satisfying analysis of two central questions: What, if anything, was peculiarly "Nazi" about human genetics under National Socialism? How, under whatever set of causes, did at least some of Germany's most well-known and leading biomedical practioners become engaged in entgrenzte Wissenschaft (science without moral boundaries)? This paper attempts to provide some answers to these two questions comparing three institutes that studied eugenics and human heredity in the 1920s and 1930s: the Eugenics Record Office at Cold Spring Harbor, New York, directed by Charles B. Davenport; the Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics, in Berlin, directed by Eugen Fischer; and the Maxim Gorky Medical Genetics Institute in Moscow, directed by Solomon G. Levit. The institutes are compared on the basis of the kind and quality of their research in eugenics and medical genetics, organizational structure, leadership, patronage (private or state), and the economic-social-political context in which they functioned. PMID:20503765

  9. PERMANENT GENETIC RESOURCES: Isolation of 60 polymorphic microsatellite loci in EST libraries of four sibling species of the phytopathogenic fungal complex Microbotryum.

    PubMed

    Giraud, T; Yockteng, R; Marthey, S; Chiapello, H; Jonot, O; Lopez-Villavicencio, M; DE Vienne, D M; Hood, M E; Refregier, G; Gendrault-Jacquemard, A; Wincker, P; Dossat, C

    2008-03-01

    We report the development of 60 microsatellite markers on four species of the fungal complex Microbotryum, causing anther smut of the Caryophyllaceae. Microsatellites were found in four expressed sequence tag (EST) libraries, built from isolates of M. lychnis-dioicae, M. violaceum sensus stricto, M. lagerheimii and M. dianthorum, collected, respectively, from the plants Silene latifolia, S. nutans, S. vulgaris and Dianthus carthusianorum. Intrapopulation polymorphism was investigated using 24 isolates, and cross-amplification was explored using 23 isolates belonging to at least 10 different Microbotryum species. This study provides numerous microsatellite markers for population genetics and mapping studies. PMID:21585800

  10. Association of genetic polymorphisms on BTNL2 with susceptibility to and prognosis of dilated cardiomyopathy in a Chinese population

    PubMed Central

    Cheng, Liang; Zhao, Rong; Jin, ZhenXiao; Ren, Kai; Deng, Chao; Yu, Shiqiang

    2015-01-01

    Background: Dilated cardiomyopathy (DCM) is one type of primary myocardial disease, partly caused by immunity dysfunctions. BTNL2 (butyrophilin-like 2) has already been confirmed to be involved in the etiology of autoimmune disorders and GWAS (genome wide association study) has also identified mutants of a SNP (single nucleotide polymorphism) near BTNL2 could modulate risk of coronary heart disease (also cardiomyopathy). The current study, therefore, was aimed to investigate whether polymorphisms within or around BTNL2 would be correlated with susceptibility to and prognosis of DCM. Material and methods: Peripheral blood samples were gathered from 82 DCM patients and 75 healthy controls. Nine tag-SNPs within or near BTNL2 were obtained from HapMap Database and previously published studies. Eligible haplotypes were gained on the basis of SHesis software. Genotyping of SNPs was implemented with aid of Sequenom MassArray iPLEX platform and subsequently analyzed via MALDI-TOF mass spectrometry. The odd ratios and their 95% confidence interval (95% CI) were utilized to evaluate the correlations between SNPs/haplotypes and DCM risks. Finally, Cox proportional hazard models and Kaplan-Meier curves were performed to assess association of SNPs/haplotypes with prognosis of DCM patients. The statistical analyses were conducted with SPSS 19.0 software. Results: Under the allelic model, rs3763313 (A > C), rs9268494 (C > A), rs9268492 (C > G) and rs9268402 (A > G) were remarkably associated with susceptibility to grade IV of DCM classified by NYHA (New York heart association) (OR = 0.43, 95% CI: 0.22-0.84; P = 0.018; OR = 0.49, 95% CI: 0.27-0.91; P = 0.024; OR = 0.50, 95% CI: 0.27-0.94; P = 0.035; OR = 0.53, 95% CI: 0.28-0.97; P = 0.048). Haplotype C-C-A-T (rs9268492, rs9268494, rs3763313 and rs3763317 synthesized) was also regarded as a protective factor for DCM patients compared with carriers of other haplotypes (OR = 0.50, 95% CI: 0.26-0.97, P = 0.038). Moreover, the univariate survival analysis and multivariate Cox regression analysis both indicated noticeable correlations between rs9268402 and haplotype C-C-A-T and prognosis of DCM patients (NYHA IV), respectively (Long-Rank P = 0.029, HR: 0.241, 95% CI: 0.089-0.650, P = 0.005; Long-Rank P = 0.036; HR = 0.126, 95% CI: 0.035-0.457, P = 0.002). Nonetheless, rs3763313 was found only associated with prognosis of DCM patients (NYHA IV) expressed in the Kaplan-Meier curve (P = 0.009). Conclusion: The genetic mutations within or around BTNL2 (rs3763313, rs9268494, rs9268492 and rs9268402) could alter susceptibility to grade IV of DCM in a Chinese population, and the 2 SNPs (rs3763313 and rs9268402) therein added with haplotype C-C-A-T might separately predict the prognosis of DCM patients. However, additional studies regarding diverse ethnicities need to be furthered to validate our results. PMID:26617759

  11. ESTIMATING GENETIC RELATIONSHIPS AMONG HISTORICAL SOURCES OF ALFALFA GERMPLASM AND SELECTED CULTIVARS WITH SEQUENCE RELATED AMPLIFIED POLYMORPHISMS (SRAP)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fifteen alfalfa populations, consisting of six public cultivars and nine historically recognized sources of alfalfa germplasm in North American cultivars were examined using sequence related amplified polymorphisms (SRAPs). Three bulk DNA samples from each population were evaluated with fourteen dif...

  12. Genetic mapping of the beta 1 GABA receptor gene to human chromosome 4, using a tetranucleotide repeat polymorphism.

    PubMed Central

    Dean, M; Lucas-Derse, S; Bolos, A; O'Brien, S J; Kirkness, E F; Fraser, C M; Goldman, D

    1991-01-01

    As more coding loci for functional human genes are described, there is a growing need to identify DNA polymorphisms in specific genes. By examining DNA sequences within the introns of the beta 1 subunit of the gamma-aminobutyric acid receptor gene, GABARB1, we found a tetranucleotide repeat sequence (GATA). Amplification of this region by using PCR revealed seven alleles and a high degree of polymorphism (PIC = .75) in human populations. DNAs from the CEPH families were typed for the GABARB1 intron polymorphism and were analyzed with respect to 20 linked markers on chromosome 4. The results permit placement of GABARB1 on the linkage map of chromosome 4, between D4S104 and ALB. These results affirm that sequence analysis of noncoding segments included within or adjacent to functional genes has value as a strategy to detect highly informative polymorphisms. Images Figure 2 PMID:1652891

  13. Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

    PubMed Central

    Ozbek, Emin; Otunctemur, Alper; Simsek, Abdulmuttalip; Polat, Emre Can; Ozcan, Levent; Köse, Osman; Cekmen, Mustafa

    2014-01-01

    OBJECTIVES: Serotonin plays a central role in ejaculation and selective serotonin reuptake inhibitors have been successfully used to treat premature ejaculation. Here, we evaluated the relationship between a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response of patients with premature ejaculation to SSRI medication. METHODS: Sixty-nine premature ejaculation patients were treated with 20 mg/d paroxetine for three months. The Intravaginal Ejaculatory Latency Time and International Index of Erectile Function scores were compared with baseline values. The patients were scored as having responded to therapy when a 2-fold or greater increase was observed in Intravaginal Ejaculatory Latency Time compared with baseline values after three months. Three genotypes of 5-HTTLPR were studied: LL, LS and SS. The appropriateness of the allele frequencies in 5-HTTLPR were analyzed according to Hardy-Weinberg equilibrium using the ?2-test. RESULTS: The short (S) allele of 5-HTTLPR was significantly more frequent in responders than in nonresponders (p<0.05). Out of the 69 total PE patients, 41 patients (59%) responded to therapy. There was no significant difference in the International Index of Erectile Function score at the end of therapy between the responder and nonresponder groups. The frequencies of the L allele and S allele were 20% and 39%, respectively, in the responder group (p<0.05). CONCLUSION: We conclude that premature ejaculation patients with the SS genotype respond well to selective serotonin reuptake inhibitor therapy. Further studies with large patient groups are necessary to confirm this conclusion. PMID:25518026

  14. Neuropsychiatric Genetics of Happiness, Friendships, and Politics: Hypothesizing Homophily (“Birds of a Feather Flock Together”) as a Function of Reward Gene Polymorphisms

    PubMed Central

    Blum, Kenneth; Oscar-Berman, Marlene; Bowirrat, Abdalla; Giordano, John; Madigan, Margaret; Braverman, Eric R.; Barh, Debmayla; Hauser, Mary; Borsten, Joan; Simpatico, Thomas

    2013-01-01

    Mindful of the new evolutionary ideas related to an emerging scientific focus known as omics, we propose that spiritual, social, and political behaviors may be tied in part to inheritable reward gene polymorphisms, as has been demonstrated for the addictions. If so, analyses of gene polymorphisms may assist in predicting liberalism or conservatism in partisan attachments. For example, both drinking (alcohol) and obesity seem to cluster in large social networks and are influenced by friends having the same genotype, in particular the DRD2 A1 allele. Likewise, voting, voting turnout and attachment to a particular political ideology is differentially related to various reward genes (e.g., 5HTT, MOA, DRD2, and DRD4), possibly predicting liberalism or conservatism. Moreover, voters’ genetic information may predict presidential outcomes more than the actual issues at hand or the presidential candidates themselves. Thus, political discussions on TV, radio, or other media may be morphed by one’s reward gene polymorphisms and as such, may explain the prevalence of generations of die-hard republicans and equally entrenched democratic legacies. Indeed, even in politics, birds of a feather (homophily) flock together. We caution that our proposal should be viewed mindfully awaiting additional research before definitive statements or conclusions can be derived from the studies to date, and we encourage large scale studies to confirm these earlier reports. PMID:23336089

  15. Genetic Polymorphisms of Multidrug Resistance Gene-1 (MDR1/ABCB1) and Glutathione S-Transferase Gene and the Risk of Inflammatory Bowel Disease among Moroccan Patients

    PubMed Central

    Senhaji, Nezha; Kassogue, Yaya; Fahimi, Mina; Serbati, Nadia; Badre, Wafaa; Nadifi, Sellama

    2015-01-01

    Inflammatory bowel diseases (IBD) are multifactorial disorders resulting from environmental and genetic factors. Polymorphisms in MDR1 and GSTs genes might explain individual differences in susceptibility to IBD. We carried out a case-control study to examine the association of MDR1 (C1236T and C3435T), GSTT1, and GSTM1 polymorphisms with the risk of IBD. Subjects were genotyped using PCR-RFLP for MDR1 gene and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was performed to test the association of variant allele carriage with IBD risk. We report that GSTT1 null genotype is significantly associated with the risk of CD (OR: 2.5, CI: 1.2–5, P = 0.013) and UC (OR: 3.5, CI: 1.5–8.5, P = 0.004) and can influence Crohn's disease behavior. The interaction between GSTT1 and GSTM1 genes showed that the combined null genotypes were associated with the risk of UC (OR: 3.1, CI: 1.1–9, P = 0.049). Furthermore, when compared to combined 1236CC/CT genotypes, the 1236TT genotype of MDR1 gene was associated with the risk of UC (OR: 3.7, CI: 1.3–10.7, P = 0.03). Meta-analysis demonstrated significantly higher frequencies of 3435T carriage in IBD patients. Our results show that GSTT1 null and MDR1 polymorphisms could play a role in susceptibility to IBD. PMID:26604430

  16. Neuropsychiatric Genetics of Happiness, Friendships, and Politics: Hypothesizing Homophily ("Birds of a Feather Flock Together") as a Function of Reward Gene Polymorphisms.

    PubMed

    Blum, Kenneth; Oscar-Berman, Marlene; Bowirrat, Abdalla; Giordano, John; Madigan, Margaret; Braverman, Eric R; Barh, Debmayla; Hauser, Mary; Borsten, Joan; Simpatico, Thomas

    2012-04-13

    Mindful of the new evolutionary ideas related to an emerging scientific focus known as omics, we propose that spiritual, social, and political behaviors may be tied in part to inheritable reward gene polymorphisms, as has been demonstrated for the addictions. If so, analyses of gene polymorphisms may assist in predicting liberalism or conservatism in partisan attachments. For example, both drinking (alcohol) and obesity seem to cluster in large social networks and are influenced by friends having the same genotype, in particular the DRD2 A1 allele. Likewise, voting, voting turnout and attachment to a particular political ideology is differentially related to various reward genes (e.g., 5HTT, MOA, DRD2, and DRD4), possibly predicting liberalism or conservatism. Moreover, voters' genetic information may predict presidential outcomes more than the actual issues at hand or the presidential candidates themselves. Thus, political discussions on TV, radio, or other media may be morphed by one's reward gene polymorphisms and as such, may explain the prevalence of generations of die-hard republicans and equally entrenched democratic legacies. Indeed, even in politics, birds of a feather (homophily) flock together. We caution that our proposal should be viewed mindfully awaiting additional research before definitive statements or conclusions can be derived from the studies to date, and we encourage large scale studies to confirm these earlier reports. PMID:23336089

  17. RAD51 G135C genetic polymorphism and their potential role in gastric cancer induced by Helicobacter pylori infection in Bhutan.

    PubMed

    Trang, T T H; Nagashima, H; Uchida, T; Mahachai, V; Vilaichone, R-K; Tshering, L; Binh, T T; Yamaoka, Y

    2016-01-01

    In order to evaluate the role of the RAD51 G135C genetic polymorphism on the risk of gastric cancer induced by Helicobacter pylori infection, we determined allele frequency and genotype distribution of this polymorphism in Bhutan - a population documented with high prevalence of gastric cancer and extremely high prevalence of H. pylori infection. The status of RAD51 G135C was examined by restriction fragment length polymorphism analysis of PCR amplified fragments and sequencing. Histological scores were evaluated according to the updated Sydney system. G135C carriers showed significantly higher scores for intestinal metaplasia in the antrum than G135G carriers [mean (median) 0·33 (0) vs. 0·08 (0), P = 0·008]. Higher scores for intestinal metaplasia of G135C carriers compared to those of G135G carriers were also observed in H. pylori-positive patients [0·3 (0) vs. 0·1 (0), P = 0·002] and H. pylori-positive patients with gastritis [0·4 (0) vs. 0·1 (0), P = 0·002] but were not found in H. pylori-negative patients. Our findings revealed that a combination of H. pylori infection and RAD51 G135C genotype of the host showed an increasing score for intestinal metaplasia. Therefore, RAD51 G135C might be the important predictor for gastric cancer of H. pylori-infected patients. PMID:26119522

  18. Association Analysis between g.18873C>T and g.27522G>A Genetic Polymorphisms of OPG and Bone Mineral Density in Chinese Postmenopausal Women

    PubMed Central

    Wang, Fei; Cao, Yi; Li, Fang; Shan, Jianlin; Wen, Tianlin

    2014-01-01

    Several studies report that the OPG is an important candidate gene in the pathogenesis of osteoporosis. This study aimed to detect the potential association of OPG gene polymorphisms with osteoporosis in postmenopausal women. We recruited 928 subjects containing 463 with primary postmenopausal osteoporosis and 465 healthy volunteers as controls. The BMD of neck hip, lumbar spine (L2–4), and total hip were assessed by dual-energy X-ray absorptiometry (DEXA). Through the created restriction site-polymerase chain reaction (CRS-PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and DNA sequencing methods, the g.18873C>T and g.27522G>A have been investigated. As for g.18873C>T, our data indicated that subjects with CC genotype have significantly higher BMD value than those of CT and TT genotypes (all P values A, the BMD values of subjects with GG genotype were significantly higher than those of GA and AA genotypes (all P values T and g.27522G>A genetic polymorphisms are associated with the decreased risk for osteoporosis in Chinese postmenopausal women. PMID:25580430

  19. Associations between the Genetic Polymorphisms of Osteopontin Promoter and Susceptibility to Cancer in Chinese Population: A Meta-Analysis

    PubMed Central

    Zhang, Jixiang; Wang, Jun; Li, Kui; Dong, Weiguo

    2015-01-01

    Background and Aim Several studies have been conducted to examine the associations between osteopontin (OPN) promoter gene SPP1 polymorphisms with human cancers in Chinese population, but the results remain inconsistent. The aim of this meta-analysis is to clarify the associations between SPP1 polymorphisms and cancer susceptibility. Methods All eligible case-control studies published up to March 2015 were identified by searching PubMed, Web of Science, Embase, and Cochrane Library without language restrictions. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using fixed- or random-effect model. Results A total of 11 case-control studies were included; of those, there were eleven studies (3130 cases and 3828 controls) for -443T>C polymorphism, ten studies (3019 cases and 3615 controls) for -156G>GG polymorphism, eight studies (2258 cases and 2846 controls) for -66T>G polymorphism. Overall, no evidence indicated that the -443 T>C polymorphism was associated with cancer risk (OR = 0.93, 95%CI 0.62–1.38 for dominant model, OR = 1.06, 95%CI 0.73–1.55 for recessive model, OR = 0.88, 95%CI 0.62–1.26 for CT vs TT model, OR = 1.03, 95%CI 0.61–1.73 for CC vs TT model). While, a significantly increase risk was found for -156 G>GG polymorphism (OR = 1.22, 95%CI 1.10–1.35 for dominant model, OR = 1.25, 95%CI 1.10–1.41 for recessive model, OR = 1.18, 95%CI 1.06–1.32 for GGG vs GG model, OR = 1.35, 95%CI 1.09–1.68 for GGGG vs GG model). For -66T>G polymorphism, we found a decrease risk of cancer (OR = 0.84, 95% CI 0.71–0.98 for dominant model), but this result changed (OR = 0.93, 95% CI 0.77–1.12 for dominant model) when we excluded a study. Conclusion This meta-analysis suggests that in Chinese population the -156G>GG polymorphism of SPP1 might be a risk factor for human cancers, while -443T>C mutation is not associated with cancer risk. For -66T>G polymorphism, it may be a protective factor for human cancers. PMID:26267616

  20. Genetic Modulation of Training and Transfer in Older Adults: BDNF Val66Met Polymorphism is Associated with Wider Useful Field of View

    PubMed Central

    Colzato, Lorenza S.; van Muijden, Jesse; Band, Guido P. H.; Hommel, Bernhard

    2011-01-01

    Western society has an increasing proportion of older adults. Increasing age is associated with a general decrease in the control over task-relevant mental processes. In the present study we investigated the possibility that successful transfer of game-based cognitive improvements to untrained tasks in elderly people is modulated by preexisting neuro-developmental factors as genetic variability related to levels of the brain-derived neurotrophic factor (BDNF), an important neuromodulator underlying cognitive processes. We trained participants, genotyped for the BDNF Val66Met polymorphism, on cognitive tasks developed to improve dynamic attention. Pre-training (baseline) and post-training measures of attentional processes (divided and selective attention) were acquired by means of the useful field of view task. As expected, Val/Val homozygous individuals showed larger beneficial transfer effects than Met/-carriers. Our findings support the idea that genetic predisposition modulates transfer effects. PMID:21909331

  1. Toward autonomous harbor surveillance

    E-print Network

    Johannsson, Hordur

    2010-01-01

    In this thesis we address the problem of drift-free navigation for underwater vehicles performing harbor surveillance and ship hull inspection. Maintaining accurate localization for the duration of a mission is important ...

  2. Genomic single-nucleotide polymorphisms confirm that Gunnison and Greater sage-grouse are genetically well differentiated and that the Bi-State population is distinct

    USGS Publications Warehouse

    Oyler-McCance, Sara J.; Cornman, Robert S.; Jones, Kenneth L.; Fike, Jennifer

    2015-01-01

    Sage-grouse are iconic, declining inhabitants of sagebrush habitats in western North America, and their management depends on an understanding of genetic variation across the landscape. Two distinct species of sage-grouse have been recognized, Greater (Centrocercus urophasianus) and Gunnison sage-grouse (C. minimus), based on morphology, behavior, and variation at neutral genetic markers. A parapatric group of Greater Sage-Grouse along the border of California and Nevada ("Bi-State") is also genetically distinct at the same neutral genetic markers, yet not different in behavior or morphology. Because delineating taxonomic boundaries and defining conservation units is often difficult in recently diverged taxa and can be further complicated by highly skewed mating systems, we took advantage of new genomic methods that improve our ability to characterize genetic variation at a much finer resolution. We identified thousands of single-nucleotide polymorphisms (SNPs) among Gunnison, Greater, and Bi-State sage-grouse and used them to comprehensively examine levels of genetic diversity and differentiation among these groups. The pairwise multilocus fixation index (FST) was high (0.49) between Gunnison and Greater sage-grouse, and both principal coordinates analysis and model-based clustering grouped samples unequivocally by species. Standing genetic variation was lower within the Gunnison Sage-Grouse. The Bi-State population was also significantly differentiated from Greater Sage-Grouse, albeit more weakly (FST = 0.09), and genetic clustering results were consistent with reduced gene flow with Greater Sage-Grouse. No comparable genetic divisions were found within the Greater Sage-Grouse sample, which spanned the southern half of the range. Thus, we provide much stronger genetic evidence supporting the recognition of Gunnison Sage-Grouse as a distinct species with low genetic diversity. Further, our work confirms that the Bi-State population is differentiated from other Greater Sage-Grouse. The level of differentiation is much less than the divergence between Greater and Gunnison sage-grouse, supporting the idea that the Bi-State represents a unique population within the Greater Sage-Grouse. New genomic methods like the restriction-site-associated DNA (RAD-tag) method used here illustrate how increasing the number of markers and coverage of the genome can better characterize patterns of genetic variation, particularly among recently diverged taxa, providing vital information for conservation and management.

  3. Association of genetic polymorphisms in GADD45A, MDM2, and p14{sup ARF} with the risk of chronic benzene poisoning in a Chinese occupational population

    SciTech Connect

    Sun Pin; Zhang Zhongbin; Wan Junxiang; Zhao Naiqing; Jin Xipeng; Xia Zhaolin

    2009-10-01

    Benzene reactive metabolites can lead to DNA damage and trigger the p53-dependent defense responses to maintain genomic stability. We hypothesized that the p53-dependent genes may play a role in the development of chronic benzene poisoning (CBP). In a case-control study of 303 patients with benzene poisoning and 295 workers occupationally exposed to benzene in south China, we investigated associations between the risk of CBP and polymorphisms in three p53-dependent genes. Potential interactions of these polymorphisms with lifestyle factors were also explored. We found p14{sup ARF} rs3731245 polymorphism was associated with risk of CBP (P = 0.014). Compared with those carrying the GG genotype, individuals carrying p14{sup ARF} rs3731245 GA+AA genotypes had a reduced risk of CBP ([adjusted odds ratio (OR{sub adj}) = 0.57, 95%CI = 0.36-0.89]. Further analysis showed p14{sup ARF} TGA/TAG diplotype was associated with an increased risk of CBP (P = 0.0006), whereas p14{sup ARF} TGG/TAA diplotype was associated with a decreased risk of CBP (P = 0.0000001). In addition, we found individuals carrying both MDM2 Del1518 WW genotype and p14{sup ARF} rs3731245 GA+AA genotypes had a lower risk of CBP (OR{sub adj} = 0.25; 95%CI = 0.10-0.62; P = 0.003). Although these results require confirmation and extension, our findings suggest that genetic polymorphisms in p14{sup ARF} may have an impact on the risk of CBP in the study population.

  4. Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study

    PubMed Central

    2012-01-01

    Background Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD), which constitutes a serious public health problem. Objective To investigate whether single nucleotide polymorphisms (SNPs) located in genes related to immune and inflammatory processes, could be associated with ESRD development. Design and methods A retrospective case-control study was carried out on 276 patients with ESRD and 288 control subjects. Forty-eight SNPs were genotyped via SNPlex platform. Logistic regression was used to assess the relationship between each sigle polymorphism and the development of ESRD. Results Four polymorphisms showed association with ESRD: rs1801275 in the interleukin 4 receptor (IL4R) gene (OR: 0.66 (95%CI?=?0.46-0.95); p?=?0.025; overdominant model), rs4586 in chemokine (C-C motif) ligand 2 (CCL2) gene (OR: 0.70 (95%CI?=?0.54-0.90); p?=?0.005; additive model), rs301640 located in an intergenic binding site for signal transducer and activator of transcription 4 (STAT4) (OR: 1.82 (95%CI?=?1.17-2.83); p?=?0.006; additive model) and rs7830 in the nitric oxide synthase 3 (NOS3) gene (OR: 1.31 (95%CI?=?1.01-1.71); p?=?0.043; additive model). After adjusting for multiple testing, results lost significance. Conclusion Our preliminary data suggest that four genetic polymorphisms located in genes related to inflammation and immune processes could help to predict the risk of developing ESRD. PMID:22817530

  5. Association of the CYP4F2 rs2108622 genetic polymorphism with hypertension: a meta-analysis.

    PubMed

    Luo, X-H; Li, G-R; Li, H-Y

    2015-01-01

    Previous case-control studies on the relationship between the CYP4F2 gene rs2108622 polymorphism and hypertension have produced contrasting results. In this study, we aimed to further evaluate the relationship between the CYP4F2 gene rs2108622 polymorphism and hypertension. We selected four case-control studies related to the CYP4F2 gene rs2108622 polymorphism and hypertension by searching PubMed, EMBase, the Chinese Biomedical Literature Database, and the Wanfang database. We utilized the Cochran Q-test and the I2 index to measure the heterogeneity across studies. To merge the odds ratio (OR) and the 95% confidence interval (95%CI), we utilized the fixed and random-effect models during the analyses. The present study included 1878 patients with hypertension and 1512 healthy control subjects. By meta-analysis, we did not find any association of the CYP4F2 gene rs2108622 polymorphism with hypertension in either genotype or allele distribution [AA+AG vs GG: OR = 1.18, 95%CI (0.91-1.54), P = 0.21; GG+AG vs AA: OR = 0.91, 95%CI (0.80-1.05), P = 0.20; A allele vs G allele: OR = 1.04, 95%CI (0.93-1.16), P = 0.53]. We concluded that the CYP4F2 gene rs2108622 polymorphism was not associated with hypertension. PMID:26634476

  6. Association between serotonin-related genetic polymorphisms and CCK-4-induced panic attacks with or without 5-hydroxytryptophan pretreatment in healthy volunteers.

    PubMed

    Maron, Eduard; Tasa, Gunnar; Tõru, Innar; Lang, Aavo; Vasar, Veiko; Shlik, Jakov

    2004-07-01

    Genetic regulation of the function of serotonin (5-HT) may be important for the neurobiology of panic disorder. In order to evaluate the influence of 5-HT-related gene variants on the vulnerability to panic attacks, we genotyped 32 healthy volunteers who participated in the study of the effect of 5-hydroxytryptophan on panic attacks induced with cholecystokinin tetrapeptide (CCK-4). The polymorphisms of interest included those of 5-HT transporter (5-HTTLPR) and monoamine oxidase A (MAO-A promoter region) genes. The results showed significant associations between certain genotypes and panic rate in females but not in male volunteers. Specifically, there was a significantly lower rate of CCK-4-induced panic attacks in female subjects who had MAO-A longer alleles or 5-HTTLPR short allele gene variants. These data suggest that functional genetic polymorphisms of the 5-HT system may influence the vulnerability to panic attacks and add to the growing evidence of inhibitory function of 5-HT in the neuronal circuitry of panic. PMID:15346539

  7. Homoduplex and Heteroduplex Polymorphisms of the Amplified Ribosomal 16S-23S Internal Transcribed Spacers Describe Genetic Relationships in the “Bacillus cereus Group”

    PubMed Central

    Daffonchio, Daniele; Cherif, Ameur; Borin, Sara

    2000-01-01

    Bacillus anthracis, Bacillus cereus, Bacillus mycoides, Bacillus pseudomycoides, Bacillus thuringiensis, and Bacillus weihenstephanensis are closely related in phenotype and genotype, and their genetic relationship is still open to debate. The present work uses amplified 16S-23S internal transcribed spacers (ITS) to discriminate between the strains and species and to describe the genetic relationships within the “B. cereus group,” advantage being taken of homoduplex-heteroduplex polymorphisms (HHP) resolved by polyacrylamide gel electrophoresis and silver staining. One hundred forty-one strains belonging to the six species were investigated, and 73 ITS-HHP pattern types were distinguished by MDE, a polyacrylamide matrix specifically designed to resolve heteroduplex and single-strand conformation polymorphisms. The discriminating bands were confirmed as ITS by Southern hybridization, and the homoduplex or heteroduplex nature was identified by single-stranded DNA mung bean nuclease digestion. Several of the ITS-HHP types corresponded to specific phenotypes such as B. anthracis or serotypes of B. thuringiensis. Unweighted pair group method arithmetic average cluster analysis revealed two main groups. One included B. mycoides, B. weihenstephanensis, and B. pseudomycoides. The second included B. cereus and B. thuringiensis, B. anthracis appeared as a lineage of B. cereus. PMID:11097928

  8. Difference in cultivation characteristics and genetic polymorphism between Chinese and Japanese strains of Wolfiporia cocos Ryvarden et Gilbertson (Poria cocos Wolf).

    PubMed

    Kobira, Sayuri; Atsumi, Toshiyuki; Kakiuchi, Nobuko; Mikage, Masayuki

    2012-07-01

    Poria, a dried sclerotium of Wolfiporia cocos Ryvarden et Gilbertson (Polyporaceae) has been used as a crude drug in both Chinese and Japanese (Kampo) traditional medicines. Recently, cultivated products of Chinese Poria strains have accounted for most of the market, while the cultivation of Japanese Poria strains has not been successful. Aiming to determine the relationship between the differences in cultivation characteristics and genetic polymorphism, we conducted a field cultivation experiment, a rot test, and rapid amplification of polymorphic DNA (RAPD) analysis of Poria strains collected from China and Japan: 3 Chinese and 7 Japanese strains. In field cultivation, although there was no marked inferiority of Japanese strains to Chinese ones in either mycelium propagation or the rate of sclerotium formation, Chinese strains formed whiter sclerotia with a mean size more than twice that of Japanese ones. Representatives of Chinese and Japanese strains, Yunnan and Kaimondake, respectively, were tested for wood-rotting ability. More wood was utilized and the wood color was darker in trials of the Yunnan strain. Amplifications of total DNA of these 10 fungal strains with 2 primers, PC-6 and PC-11, in RAPD analysis showed a difference in the amplicon profile between Japanese and Chinese strains, suggesting differences in their genetic background. PMID:22127530

  9. Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease

    PubMed Central

    Urabe, Shigetoshi; Isomoto, Hajime; Ishida, Tetsuya; Maeda, Kazumi; Inamine, Tatsuo; Kondo, Shinji; Higuchi, Norihide; Sato, Kayoko; Uehara, Ryohei; Yajima, Hiroyuki; Machida, Haruhisa; Chen, Chun Chuan; Fukuda, Yasuhiro; Takeshima, Fuminao; Nakao, Kazuhiko; Tsukamoto, Kazuhiro

    2015-01-01

    Background. We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohn's disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in candidate genes in the interleukin- (IL-) 17 signaling pathway with response to IFX after 1 year of treatment. Methods. A total of 103 patients were divided into two groups, responders and nonresponders. Twenty-eight tag SNPs in 5 genes were genotyped. The frequencies of alleles and genotypes of each SNP were compared between responders and nonresponders in three different inheritance models. A genetic test was performed using a combination of the associated SNPs as biomarkers. Results. Multivariate logistic regression analysis indicated that the four variable factors, concomitant use of immunomodulators, penetrating disease, a G/G genotype of rs766748 in IL-17F, and a C/C or C/A genotype of rs1883136 in TRAF3IP2, independently contributed to response to IFX after 1 year of treatment. Genetic test using the polymorphisms of these genes perfectly predicted the responder and nonresponder CD patients with both concomitant use of immunomodulators and penetrating disease. Conclusion. IL17F and TRAF3IP2 are one of IFX-related genes, useful as biomarkers of IFX response, and may be target molecules for new therapeutic drugs. PMID:26558270

  10. Genetic Polymorphisms in Endothelin-1 as Predictors for Long-Term Survival and the Cardiac Index in Patients Undergoing On-Pump Cardiac Surgery

    PubMed Central

    Popov, Aron Frederik; Milenovic, Sinisa; Bireta, Christian; Weymann, Alexander; Schotola, Hanna; Wiese, Christoph H.; Beissbarth, Tim; Tzvetkov, Mladen; Hinz, José

    2015-01-01

    Genetic variants within the endothelin-1 gene (EDN1) have been associated with several cardiovascular diseases and may act as genetic prognostic markers. Here, we explored the overall relevance of EDN1 polymorphisms for long-term survival in patients undergoing on-pump cardiac surgery. A prospectively collected cohort of 455 Caucasian patients who underwent cardiac surgery with cardiopulmonary bypass was followed up for 5 years. The obtained genotypes and inferred haplotypes were analyzed for their associations with the five-year mortality rate (primary endpoint). The EDN1 T-1370G and K198N genotype distributions did not deviate from Hardy–Weinberg equilibrium and the major allele frequencies were 83% and 77%, respectively. The cardiovascular risk factors were equally distributed in terms of the different genotypes and haplotypes associated with the two polymorphisms. The five-year mortality rate did not differ among the different EDN1 T-1370G and K198N genotypes and haplotypes. Haplotype analysis revealed that carriers of the G-T (compound EDN1 T-1370G G/K198N T) haplotype had a higher cardiac index than did non-carriers (p = 0.0008); however, this difference did not reach significance after adjusting for multiple testing. The results indicate that common variations in EDN1 do not act as prognostic markers for long-term survival in patients undergoing on-pump cardiac surgery. PMID:26121692

  11. Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups

    PubMed Central

    da Costa, Kerry-Ann; Corbin, Karen D.; Niculescu, Mihai D.; Galanko, Joseph A.; Zeisel, Steven H.

    2014-01-01

    Effect alleles (alleles with a polymorphism that is associated with the effect being measured) in a small number of single-nucleotide polymorphisms (SNPs) are known to influence the dietary requirement for choline. In this study, we examined a much larger number of SNPs (n=200) in 10 genes related to choline metabolism for associations with development of organ dysfunction (liver or muscle) when 79 humans were fed a low-choline diet. We confirmed that effect alleles in SNPs such as the C allele of PEMT rs12325817 increase the risk of developing organ dysfunction in women when they consume a diet low in choline, and we identified novel effect alleles, such as the C allele of CHKA SNP rs7928739, that alter dietary choline requirements. When fed a low-choline diet, some people presented with muscle damage rather than liver damage; several effect alleles in SLC44A1 (rs7873937, G allele; rs2771040, G; rs6479313, G; rs16924529, A; and rs3199966, C) and one in CHKB (rs1557502, A) were more common in these individuals. This suggests that pathways related to choline metabolism are more important for normal muscle function than previously thought. In European, Mexican, and Asian Americans, and in individuals of African descent, we examined the prevalence of the effect alleles in SNPs that alter choline requirement and found that they are differentially distributed among people of different ethnic and racial backgrounds. Overall, our study has identified novel genetic variants that modulate choline requirements and suggests that the dietary requirement for choline may be different across racial and ethnic groups.—Da Costa, K.-A., Corbin, K. D., Niculescu, M. D., Galanko, J. A., Zeisel, S. H. Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups. PMID:24671709

  12. Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups.

    PubMed

    da Costa, Kerry-Ann; Corbin, Karen D; Niculescu, Mihai D; Galanko, Joseph A; Zeisel, Steven H

    2014-07-01

    Effect alleles (alleles with a polymorphism that is associated with the effect being measured) in a small number of single-nucleotide polymorphisms (SNPs) are known to influence the dietary requirement for choline. In this study, we examined a much larger number of SNPs (n=200) in 10 genes related to choline metabolism for associations with development of organ dysfunction (liver or muscle) when 79 humans were fed a low-choline diet. We confirmed that effect alleles in SNPs such as the C allele of PEMT rs12325817 increase the risk of developing organ dysfunction in women when they consume a diet low in choline, and we identified novel effect alleles, such as the C allele of CHKA SNP rs7928739, that alter dietary choline requirements. When fed a low-choline diet, some people presented with muscle damage rather than liver damage; several effect alleles in SLC44A1 (rs7873937, G allele; rs2771040, G; rs6479313, G; rs16924529, A; and rs3199966, C) and one in CHKB (rs1557502, A) were more common in these individuals. This suggests that pathways related to choline metabolism are more important for normal muscle function than previously thought. In European, Mexican, and Asian Americans, and in individuals of African descent, we examined the prevalence of the effect alleles in SNPs that alter choline requirement and found that they are differentially distributed among people of different ethnic and racial backgrounds. Overall, our study has identified novel genetic variants that modulate choline requirements and suggests that the dietary requirement for choline may be different across racial and ethnic groups.-Da Costa, K.-A., Corbin, K. D., Niculescu, M. D., Galanko, J. A., Zeisel, S. H. Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups. PMID:24671709

  13. Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: complement component C1q and Prnp polymorphisms

    USGS Publications Warehouse

    Blanchong, Julie A.; Heisey, Dennis M.; Scribner, Kim T.; Libants, Scot V.; Johnson, Chad; Aiken, Judd M.; Langenberg, Julia A.; Samuel, Michael D.

    2009-01-01

    The genetic basis of susceptibility to chronic wasting disease (CWD) in free-ranging cervids is of great interest. Association studies of disease susceptibility in free-ranging populations, however, face considerable challenges including: the need for large sample sizes when disease is rare, animals of unknown pedigree create a risk of spurious results due to population admixture, and the inability to control disease exposure or dose. We used an innovative matched case–control design and conditional logistic regression to evaluate associations between polymorphisms of complement C1q and prion protein (Prnp) genes and CWD infection in white-tailed deer from the CWD endemic area in south-central Wisconsin. To reduce problems due to admixture or disease-risk confounding, we used neutral genetic (microsatellite) data to identify closely related CWD-positive (n = 68) and CWD-negative (n = 91) female deer to serve as matched cases and controls. Cases and controls were also matched on factors (sex, location, age) previously demonstrated to affect CWD infection risk. For Prnp, deer with at least one Serine (S) at amino acid 96 were significantly less likely to be CWD-positive relative to deer homozygous for Glycine (G). This is the first characterization of genes associated with the complement system in white-tailed deer. No tests for association between any C1q polymorphism and CWD infection were significant at p < 0.05. After controlling for Prnp, we found weak support for an elevated risk of CWD infection in deer with at least one Glycine (G) at amino acid 56 of the C1qC gene. While we documented numerous amino acid polymorphisms in C1q genes none appear to be strongly associated with CWD susceptibility.

  14. A Panel of Genetic Polymorphism for the Prediction of Prognosis in Patients with Early Stage Non-Small Cell Lung Cancer after Surgical Resection

    PubMed Central

    Jeon, Hyo-Sung; Choi, Yi-Young; Lee, Won Kee; Lee, Eung Bae; Lee, Hyun Cheol; Kang, Hyo-Gyoung; Yoo, Seung Soo; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Lee, Myung Hoon; Kim, Young Tae; Jheon, Sanghoon; Park, Jae Yong

    2015-01-01

    Background This study was conducted to investigate whether a panel of eight genetic polymorphisms can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC) after surgical resection. Materials and Methods We selected eight single nucleotide polymorphisms (SNPs) which have been associated with the prognosis of lung cancer patients after surgery in our previous studies. A total of 814 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the eight SNPs with overall survival (OS) and disease-free survival (DFS) was analyzed. Results The eight SNPs (CD3EAP rs967591, TNFRSF10B rs1047266, AKT1 rs3803300, C3 rs2287845, HOMER2 rs1256428, GNB2L1 rs3756585, ADAMTSL3 rs11259927, and CD3D rs3181259) were significantly associated with OS and/or DFS. Combining those eight SNPs, we designed a prognostic index to predict the prognosis of patients. According to relative risk of death, a score value was assigned to each genotype of the SNPs. A worse prognosis corresponded to a higher score value, and the sum of score values of eight SNPs defined the prognostic index of a patient. When we categorized the patients into two groups based on the prognostic index, high risk group was significantly associated with worse OS and DFS compared to low risk group (aHR for OS = 2.21, 95% CI = 1.69–2.88, P = 8.0 x 10?9, and aHR for DFS = 1.58, 95% CI = 1.29–1.94, P = 1.0 x 10?5). Conclusions Prognostic index using eight genetic polymorphisms may be useful for the prognostication of patients with surgically resected NSCLC. PMID:26462029

  15. Genetic polymorphism study at four minisatellite loci (D1S80, D17S5, D19S20, and APOB) among five Indian population groups.

    PubMed

    Das, Birajalaxmi; Ghosh, Anu; Chauhan, P S; Seshadri, M

    2002-06-01

    The present study reports the genetic variation observed among five anthropologically distinct population groups of India, using four highly polymorphic minisatellite loci (D1S80, D17S5, D19S20, and APOB 3' VNTR) in order to examine the effect of geographical and linguistic affiliations on the genetic affinities among these groups. Random individuals from five ethnic groups were studied; the sample size ranged from 235 to 364. The population groups belong to two geographically separated regions of India, the state of Maharashtra (western India) and the state of Kerala (southern India). The two Maharashtrian groups (Konkanastha Brahmins and Marathas) speak "Marathi," an Indo-European language, whereas the three Kerala population groups (Nairs, Ezhavas, and Muslims) speak "Malayalam," an Indo-Dravidian language. Genomic DNA was extracted from peripheral blood samples and analyzed using amplified fragment length polymorphism (Amp-FLP) technique. All four loci displayed high heterozygosity with average heterozygosity in the range of 0.82 to 0.84. The Polymorphic Information Content and Power of Discrimination were > or = 0.75 and > or = 0.80, respectively. The coefficient of gene differentiation was found to be low (average G(ST) = 1.2%; range between 0.6% at D1S80 locus to 1.6% at APOB 3' VNTR locus) across the loci, indicating close affinity among the population groups. The neighbor-joining tree revealed two clear clusters, one for the two Maharashtrian population groups and the other for the three Kerala population groups. The results obtained are in conformity with the geographical and linguistic backgrounds of the studied populations. PMID:12180760

  16. Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity in Chinese rectal cancer patients treated with pelvic radiotherapy

    PubMed Central

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Zhu, Ji; Sun, Menghong; Deng, Yun; Liang, Liping; Li, Guichao; Wu, Yongxin; Fan, Ming; Wei, Qingyi; Zhang, Zhen

    2015-01-01

    Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ?2 and grade 0–1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ?2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ?3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients that developed grade ?2 toxicities for diarrhea and fecal incontinence, respectively. The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated with the risk of diarrhea and incontinence (P<0.05), whereas the AG and GG genotypes of rs2227631 in PAI-1 were associated with an increased risk of incontinence. The CT genotype of PAR-1 rs32934 was associated with an increased risk of total toxicity compared with the CC allele. Our results demonstrated that SNPs in the PAI-1 and PAR-1 genes were associated with acute injury in rectal cancer patients treated with pelvic irradiation. These SNPs may be useful biomarkers for predicting acute radiotoxicity in patients with rectal cancer if validated in future studies. PMID:26347502

  17. Polymorphisms and Plasma Levels of Tissue Inhibitor of Metalloproteinase-3: Impact on Genetic Susceptibility and Clinical Outcome of Oral Cancer

    PubMed Central

    Su, Chun-Wen; Huang, Yi-Wen; Chen, Mu-Kuan; Su, Shih-Chi; Yang, Shun-Fa; Lin, Chiao-Wen

    2015-01-01

    Abstract Oral cancer, the fourth most common cancer among men in Taiwan, is associated with environmental carcinogens. Tissue inhibitor of metalloproteinase-3 (TIMP3), a member of the TIMP family, is the only protein that binds to the extracellular matrix for suppressing cancer cell growth, angiogenesis, migration, and invasion. The association of TIMP3 polymorphism with oral cancer susceptibility, however, has not yet been reported. In this study, 1947 participants—1200 healthy male controls and 747 male patients with oral cancer—were recruited. Allelic discrimination of TIMP3 ?1296 T?>?C (rs9619311), TIMP3 C?>?T (rs9862), and TIMP3 C?>?T (rs11547635) polymorphisms were assessed through real-time polymerase chain reaction. The authors discovered that individuals carrying the polymorphic rs9862 allele are more susceptible to oral cancer [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.2-1.9; adjusted OR (AOR), 1.6; 95% CI, 1.2–2.1] after adjustment for betel quid chewing, alcohol, and tobacco consumption. Among 601 betel quid chewers, the TIMP3 polymorphism rs9862?T/T carriers had a 32.2-fold (95% CI, 20.2–51.3) increased oral cancer risk compared with those carrying C/C and not chewing betel quid. In addition, the authors observed a significant association between rs9862 variants and large tumors (OR, 1.5; 95% CI, 1.0–2.3) development. Moreover, TIMP3 plasma levels significantly increased in oral cancer patients who have large tumor or carry T allele rs9862 polymorphism. In conclusion, these results suggest that gene-environment interactions between the TIMP3 rs9862 polymorphisms and betel quid may alter oral cancer susceptibility and tumor growth in Taiwanese men. PMID:26579821

  18. Genetic correlation of SOCS3 polymorphisms with infantile asthma: an evidence based on a case-control study

    PubMed Central

    Fang, Ying; Ren, Xiaoxia; Feng, Zhanwei

    2015-01-01

    Objective: In order to explore the relevance of SOCS3 gene polymorphisms with infantile asthma and provide evidence for the ethology of infantile asthma, we conducted this case-control study. Methods: A total of 273 children were enrolled for study in this article, including 119 children with asthma and 154 healthy controls frequency-matched with the former in sex and age. The genotyping of SOCS3 rs4969170, rs4969168 polymorphisms in all subjects were performed using TaqMan probe method. Odds ratio (OR) with 95% confidence interval (CI) was used to represent the association strength between SOCS3 polymorphisms and infantile asthma and calculated by ?² test which was conducted to check the Hardy-Weinberg equilibrium (HWE) in the control group. Results: The genotypes distributions of SOCS3 polymorphisms in controls conformed to HWE. Compared with GG/GA genotype in SOCS3 rs4969170, AA genotype obviously increased the susceptibility to asthma in children (OR=2.556, 95% CI=1.377-4.744) and A allele also made the same conclusion (OR=2.287, 95% CI=1.311-3.991). Differently in rs4969168, AG and AG/GG genotypes distributions had significant differences in two groups (P=0.036, 0.043). This two polymorphisms existed the linkage disequilibrium and the haplotype analysis showed that A-G and A-A haplotypes in rs4969170-rs4969168 increased 1.855 and 0.863 times risk of asthma development in children, respectively. Conclusions: A significant relevance involved in SOCS3 gene polymorphisms and infantile asthma development based on a Chinese Han population. PMID:26464723

  19. Genetic polymorphisms in the Rb-binding zinc finger gene RIZ and the risk of lung cancer.

    PubMed

    Yoon, Kyong-Ah; Park, Sohee; Hwangbo, Bin; Shin, Hyoung Doo; Cheong, Hyun Sub; Shin, Hai-Rim; Lee, Jin Soo

    2007-09-01

    Histone methyltransferase (HMT) enzymes that methylate the lysine of histones are involved in chromatin-mediated gene expression. Previously, we reported that a novel polymorphism of SUV39H2, the HMT that is required for the methylation of H3-K9, was associated with an increased risk of lung cancer in Koreans. The retinoblastoma protein-interacting zinc finger gene RIZ (PRDM2) is also a member of a histone/protein-methyltransferase superfamily, and the inactivation of RIZ in many cancers was detected as frameshift mutations, hypermethylation and missense mutations. In this study, we show the association of RIZ polymorphisms with the risk of lung cancer. In a hospital-based study of 335 lung cancer patients and 335 age- and gender-matched healthy controls, 120 polymorphisms of RIZ were screened. Of the 120 genotyped single nucleotide polymorphisms (SNPs), 42 SNPs were selected for the statistical analysis based on their frequency (>5%) and linkage disequilibrium [LD; only a representative SNP was analyzed if there were absolute LDs (r2 = 1)]; this resulted in three LD blocks. The +92337G>A and +95701C>A polymorphisms showed a statistically significant association with the reduced risk of lung adenocarcinomas after correcting the P values for multiple testing [for carrying one variant allele versus none, adjusted odds ratio (aOR) = 0.55 (95% CI = 0.38-0.78), corrected P = 0.04; aOR = 0.54 (95% CI = 0.38-0.77), corrected P = 0.02, respectively]. One haplotype (Ht5) in LD block 3 of RIZ was significantly associated with the reduced risk of lung adenocarcinomas (aOR = 0.28, 95% CI = 0.13-0.58) as well as overall lung cancer (aOR = 0.50, 95% CI = 0.30-0.82). This study suggested that RIZ polymorphisms may be important predictive markers for lung cancer susceptibility. PMID:17693662

  20. Genetic polymorphisms of interleukin-6 gene and susceptibility to coronary artery disease in Chinese population: Evidence based on 4582 subjects.

    PubMed

    Liu, Shun-Lin; Yin, Yan-Wei; Sun, Qian-Qian; Hu, Ai-Min; Zhang, Shi-Jie

    2015-07-01

    The aim of this study was to explore whether interleukin-6 (IL-6) gene (-174 G/C and -572 C/G) polymorphisms are associated with susceptibility to coronary artery disease (CAD) risk in Chinese population. All the statistical tests were performed using Stata version 11.0. Twelve articles involving 16 studies were included in this meta-analysis, covering a total of 2309 CAD cases and 2273 controls. For IL-6 gene -572 C/G polymorphism, the results showed evidence for significant association between IL-6 gene -572 C/G polymorphism and CAD risk (for G allele vs. C allele: OR=1.48, 95% CI=1.26-1.74, p<0.001; for G/G vs. C/C: OR=2.60, 95% CI=1.54-4.39, p<0.001; for G/G vs. G/C+C/C: OR=2.15, 95% CI=1.35-3.42, p=0.001; for G/G+G/C vs. C/C: OR=1.55, 95% CI=1.29-1.85, p<0.001). However, for IL-6 gene -174 G/C polymorphism, no significant association was found between this variation and CAD risk. In summary, our meta-analysis showed evidence that IL-6 gene -572 C/G polymorphism may be a risk factor for CAD susceptibility. For IL-6 gene -174 G/C polymorphism, no significant association was found between this variation and CAD risk. PMID:26079504

  1. Neurological toxicity after phenytoin infusion in a pediatric patient with epilepsy: influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms.

    PubMed

    Dorado, P; López-Torres, E; Peñas-Lledó, E M; Martínez-Antón, J; Llerena, A

    2013-08-01

    Pharmacogenetic studies have shown that genetic defects in drug-metabolizing enzymes encoded by CYP2C9, CYP2C19 genes and by the transporter ABCB1 gene can influence phenytoin (PTH) plasma levels and toxicity. The patient reported here is a 2-year-old girl with a medical history of cryptogenic (probably symptomatic) epilepsy, who had her first focal seizure with secondary generalization at 13 months of age. She initially received oral valproate treatment and three months later, she was prescribed an oral oxcarbazepine treatment. At 20 months of age, she was admitted to the Emergency Department because of generalized convulsive Status Epilepticus needing to be immediately treated with rectal diazepam (0.5?mg?kg(-1)), intravenous diazepam (0.3?mg?kg(-1)), and intravenous phenytoin with an initial-loading dose of 15?mg?kg(-1). However, two hours after the initial-loading dose of PTH, the patient developed dizziness, nystagmus, ataxia and excessive sedation. Other potential causes of PTH toxicity were excluded such as drug interactions, decreased albumin or lab error. Therefore, to explain the neurological toxicity, PTH plasma levels and CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms were analyzed. Initial plasma PTH levels were higher than expected (69?mg?l(-1); normal range: 10-20?mg?l(-1)), and the patient was homozygous for the CYP2C9*2 allele, heterozygous for the CYP2C19*4 allele and homozygous for the 3435C and 1236C ABCB1 alleles. Present findings support the previously established relationship between CYP2C9 and CYP2C19 genetic polymorphisms and the increased risk to develop PTH toxicity owing to high plasma concentrations. Nevertheless, although the association of these genes with PTH-induced adverse effects has been well-documented in adult populations, this is the first report examining the influence of these genetic polymorphisms on PTH plasma levels and toxicity in a pediatric patient. PMID:22641027

  2. MULTILOCUS SIMPLE SEQUENCE REPEATS AND SINGLE NUCLEOTIDE POLYMORPHISM MARKERS FOR GENOTYPING AND ASSESSING GENETIC DIVERSITY OF XYLELLA FASTIDIOSA IN CALIFORNIA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To develop effective disease management strategies, we need to understand population structure and genetic diversity of pathogens in agricultural ecosystems. Current information regarding population structure and genetic diversity of Xylella fastidiosa (Xf) in California is insufficient to adequate...

  3. MORPHOMETRIC ANALYSIS OF GENETIC VARIATION IN HIPPOCAMPAL SHAPE IN MILD COGNITIVE IMPAIRMENT: ROLE OF AN IL-6 PROMOTER POLYMORPHISM

    E-print Network

    Chung, Moo K.

    .harker.rhodes}@dartmouth.edu We study the connection between genotype and imaging phenotype in order to detect possible genetic phenotypes and genetic profiles has the potential to elucidate biological pathways for better understanding1 MORPHOMETRIC ANALYSIS OF GENETIC VARIATION IN HIPPOCAMPAL SHAPE IN MILD COGNITIVE IMPAIRMENT

  4. A Genetic Susceptibility Mechanism for Major Depression: Combinations of polymorphisms Defined the Risk of Major Depression and Subpopulations.

    PubMed

    Wang, Yanfang; Sun, Ning; Li, Suping; Du, Qiaorong; Xu, Yong; Liu, Zhifeng; Zhang, Kerang

    2015-06-01

    Major Depression (MD) is a highly inherited psychiatric disorder. The norepinephrine transporter (NET) gene plays important role in pathophysiology of MD. This study attempted to examine the relationship between polymorphisms of NET gene and MD. Patients with MD and healthy controls were recruited and subgrouped. The T-182C and G1287A polymorphisms of NET gene were genotyped by direct sequencing. The genotypic and allelic frequencies were compared using the Pearson ?2 analysis. The linkage disequilibrium was analyzed using the UNPHASED program. Significant differences in genotypic and allelic frequencies of T-182C polymorphism were observed between MD subgroups and controls. When referenced by TT genotype, the OR value increased gradient from TC to CC genotype; when referenced by T allele, the odds ratio value of C allele also increased. Compared with those having both -182?T/T and 1287?G/G genotypes, in patients with MD, early-onset MD, and MD with suicide concept group, the -182?C/C and 1287?G/A combinatorial genotype has significant risk; yet in patients with MD family history, the -182?C/C and 1287?A/A combinatorial genotype has significant risk. Different combinations of T-182C and the G1287A polymorphisms of NET gene might increase morbidity risk of MD subpopulations. PMID:26061302

  5. Association of Genetic Polymorphisms of IFNGR1 with the Risk of Pulmonary Tuberculosis in Zahedan, Southeast Iran

    PubMed Central

    Naderi, Mohammad; Hashemi, Mohammad; Rezaei, Maryam; Safdari, Abolhassan

    2015-01-01

    Aim. The present study was undertaken to find out the possible association between interferon-gamma (IFN-?) receptor 1 (IFNGR1) gene polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. Methods. Polymorphisms of IFNGR1 rs1327474 (?611 A/G), rs11914 (+189 T/G), rs7749390 (+95 C/T), and rs137854905 (27-bp ins/del) were determined in 173 PTB patients and 164 healthy subjects. Results. Our findings showed that rs11914 TG genotypes decreased the risk of PTB in comparison with TT (OR = 0.36, 95% CI = 0.21–0.62, and p = 0.0002). The rs11914 G allele decreased the risk of PTB compared with T allele (OR = 0.41, 95% CI = 0.25–0.68, and p = 0.0006). IFNGR1 rs7749390 CT genotype decreased the risk of PTB in comparison with CC genotype (OR = 0.55, 95% CI = 0.32–0.95, and p = 0.038). No significant association was found between IFNGR1 rs1327474 A/G polymorphism and risk/protective of PTB. The rs137854905 (27-bp I/D) variant was not polymorphic in our population. Conclusion. Our findings showed that IFNGR1 rs11914 and rs7749390 variants decreased the risk of PTB susceptibility in our population. PMID:26649196

  6. EST-PCR Markers Representing Watermelon Fruit Genes are Polymorphic among Watermelon Heirloom Cultivars Sharing a Narrow Genetic Base

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To date there are only a few sequenced-tagged site (STS) markers associated with genes controlling fruit quality in watermelon. In this study, we examined polymorphism in coding regions of genes expressed in watermelon fruit. A normalized cDNA library was constructed for watermelon fruit (Citrullu...

  7. DETECTION OF GENETIC VARIATION IN WILD POPULATIONS OF THREE ALLIUM SPECIES USING AMPLIFIED FRAGMENT LENGTH POLYMORPHISMS (AFLP)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Allium is distributed worldwide and includes about 80 North American species, with at least 13 occurring in Utah. This study examines amplified fragment length polymorphism (AFLP) variation within and among wild populations of three Allium species varying in abundance and distribution, na...

  8. Effects of genetic polymorphisms on antioxidant status and concentrations of the metals in the blood of riverside Amazonian communities co-exposed to Hg and Pb.

    PubMed

    Barcelos, Gustavo Rafael Mazzaron; Souza, Marilesia Ferreira de; Oliveira, Andréia Ávila Soares de; Lengert, André van Helvoort; Oliveira, Marcelo Tempesta de; Camargo, Rossana Batista de Oliveira Godoy; Grotto, Denise; Valentini, Juliana; Garcia, Solange Cristina; Braga, Gilberto Úbida Leite; Cólus, Ilce Mara de Syllos; Adeyemi, Joseph; Barbosa, Fernando

    2015-04-01

    There have been reports of genetic effects affecting the metabolism of Hg and Pb individually, and thus modulating their toxicities. However, there is still a knowledge gap with respect to how genetics may influence the toxicities of these toxic metals during a co-exposure scenario. This present study is therefore aimed at investigating the effects of polymorphisms in genes (GSTM1, GSTT1, GSTP1, GCLM, GCLC, GPx1, ALAD, VDR and MDR1) that have been implicated in Hg and Pb metabolisms affects the kinetics of these metals, as well as various blood antioxidant status parameters: MDA and GSH, and the activities of CAT, GPx and ALAD among populations that have been co-exposed to both Hg and Pb. Study subjects (207 men; 188 women) were from an Amazonian population in Brazil, exposed to Hg and Pb from diet. The blood levels of Hg and Pb were determined by ICP-MS while genotyping were performed by PCR assays. The median values of Hg and Pb in blood were 39.8µg/L and 11.0µg/dL, respectively. GSTM1, ALAD and VDR polymorphisms influenced Hg in blood (?=0.17; 0.37 and 0.17; respectively, p<0.050) while variations on GCLM, GSTT1 and MDR1 (TT) modulated the concentrations of Pb among the subjects (?=-0.14; 0.13 and -0.22; re-spectively, p<0.050). GSTT1 and GCLM polymorphisms also are associated to changes of MDA concentrations. Persons with null GSTM1 genotype had higher activity of the antioxidant enzyme CAT than carries of the allele. Individuals with deletion of both GSTM1 and GSTT1 had a decreased expression of GPx compared to those that expressed at least, one of the enzymes. ALAD 1/2 subjects had lower ALAD activity than individuals with the non-variant genotype. Our findings give further support that polymorphisms related to Hg and Pb metabolism may modulate Hg and Pb body burden and, consequently metals-induced toxicity. PMID:25728017

  9. Influence of genetic polymorphisms on the pharmacokinetics of celecoxib and its two main metabolites in healthy Chinese subjects.

    PubMed

    Liu, Ruijuan; Gong, Chuting; Tao, Lei; Yang, Wen; Zheng, Xiaohong; Ma, Pengcheng; Ding, Li

    2015-11-15

    Celecoxib is a selective cyclooxygenase-2 inhibitor used extensively for the treatment of rheumatism and osteoarthritis. The aim of this study was to evaluate the influence of the genetic polymorphisms of CYP2C9, CYP2D6 and CYP3A4 on the pharmacokinetics (PK) of celecoxib and its two main metabolites, hydroxyl-celecoxib and carboxy-celecoxib, in healthy Chinese subjects, based on a bioequivalence study of celecoxib. This study was an open-label, two-period, crossover study. 52 healthy Chinese male subjects were recruited and were genotyped for CYP2C9*3, CYP2C9*13, CYP2D6*10 and CYP3A4*18 by using polymerase chain reactions (PCR). They were randomly divided into two groups and each group received either 200mg test formulation followed by reference formulation or vice versa with a one-week washout period. Safety and tolerability were monitored throughout the study and no severe adverse events were observed. Genotyping using PCR revealed that none of the subjects carried the CYP3A4*18 and CYP2C9*13. Therefore, the influence of the CYP2C9*3 and CYP2D6*10 on the PK of celecoxib and its metabolites in Chinese was studied. Compared with CYP2C9*1/*1 group, pharmacokinetic parameters of celecoxib such as AUC0-48 and Cmax was increased by 90.6% and 45.8%, the t1/2 was extended by 21.8% and the CL/F was decreased by 51.1% in CYP2C9*1/*3 group. In terms of hydroxy-celecoxib, compared with CYP2C9*1/*1 group, the Cmax was decreased by 17.2%, the t1/2 prolonged 42.1% in CYP2C9*1/*3 group. In terms of carboxy-celecoxib, the AUC0-48 was increased by 25.2%, the t1/2 prolonged 16.1% and the CL/F was decreased by 21.2% in CYP2C9*1/*3 group. Except for the t1/2 of hydroxy-celecoxib, no statistically significant difference was observed in other pharmacokinetic parameters of hydroxy-celecoxib and carboxy-celecoxib between the two CYP2C9 genotypic groups. This study revealed that there was no significant influence of CYP2D6*10 on the metabolism of celecoxib, and the expression of CYP2C9*3 led to increased drug exposure and slowed drug disposition in healthy Chinese male subjects. PMID:26360837

  10. Genetic association of the ApoB and ApoA1 gene polymorphisms with the risk for alcohol-induced osteonecrosis of femoral head

    PubMed Central

    Wang, Yuan; Cao, Yuju; Li, Yizhou; Guo, Yongchang; Wang, Quanjian; Yang, Min; Zhang, Ning; Jin, Tianbo; Wang, Jianzhong

    2015-01-01

    Polymorphisms of apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1) gene and ApoB/ApoA1 Ratio were associated with lipid metabolism disorders in previous reports. The aim of this study assess whether variation of ApoB, ApoA1 gene are associated or not with alcohol-induced osteonecrosis of femoral head (ONFH). In a case-control study, we genotyped 4 single-nucleotide polymorphisms (SNPs) in ApoB and ApoA1 genes in 209 alcohol-induced ONFH patients and 300 healthy control subjects in Han Chinese population using ?2 test and genetic model analysis. The analysis revealed that the frequencies of ApoB and ApoA1 genotypes were significantly different in alcohol-induced ONFH patients than in controls. We identified rs1042034, rs676210 and rs673548 in ApoB gene were associated with decreased risk of alcohol-induced ONFH using recessive model analysis (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.19-0.99; P = 0.042), the OR, CI, P value of three SNPs were the same after adjusted for gender + age. We also identified rs632153 in ApoA1 gene was associated with increased risk of alcohol-induced ONFH using allele model (OR, 1.83; 95% CI, 1.16-2.88; P = 0.008) and log-additive model (adjusted OR, 1.77; 95% CI, 1.00-3.14; P = 0.046), analysis respectively. Haplotype analysis demonstrated no difference between ApoB and alcohol-induced ONFH. Polymorphisms of the ApoB and ApoA1 gene are associated with alcohol-induced ONFH in the Han Chinese population. PMID:26617857

  11. The Influence of C3435T Polymorphism of the ABCB1 Gene on Genetic Susceptibility to Depression and Treatment Response in Polish Population - Preliminary Report

    PubMed Central

    Jele?, Agnieszka Maria; Sa?agacka, Aleksandra; ?ebrowska, Marta Karolina; Mirowski, Marek; Talarowska, Monika; Ga?ecki, Piotr; Balcerczak, Ewa Izabela

    2015-01-01

    Background: Despite the high prevalence of depression, the mechanism of the origin of this disease as well as the causes of resistance to therapy in some patients are still not fully understood. Increasingly, the possible role of genetic factors is considered. One of them is polymorphisms in the ABCB1 (MDR1) gene which encodes P-glycoprotein, responsible for the transport of xenobiotics, including antidepressant drugs, through the blood-brain barrier. Methods: C3435T was evaluated in 90 patients with recurrent depressive disorders (rDD). Genotyping was performed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: The obtained results indicate that the TT genotype occurred more frequently among patients with rDD than in healthy volunteers (p=0.0441). Also, at least one C allele was present significantly less frequent in the study group than in healthy individuals (p=0.0300). The severity of depressive symptoms was higher among patient with the CC genotype in comparison with the other genotypes (p=0.0106) but treatment response to antidepressants was better in this group than among patients with CT or TT genotypes (p=0.0301). Likewise, patients with the T allele have a significantly lower severity of symptoms (p=0.0026) and decreased therapy effectiveness (p=0.0142) than C allele carriers. Conclusions: This study suggests that C3435T polymorphisms in the ABCB1 gene are strongly associated with a predisposition to depression development, the severity of depressive symptoms and the effectiveness of therapy with using different groups of antidepressant agents. PMID:26664259

  12. Role of XPC, XPD, XRCC1, GSTP genetic polymorphisms and Barrett’s esophagus in a cohort of Italian subjects. A neural network analysis

    PubMed Central

    Tarlarini, Claudia; Penco, Silvana; Conio, Massimo; Grossi, Enzo

    2012-01-01

    Background Barrett’s esophagus (BE), a metaplastic premalignant disorder, represents the primary risk factor for the development of esophageal adenocarcinoma. Chronic gastroesophageal reflux disease and central obesity have been associated with BE and esophageal adenocarcinoma, but relatively little is known about the specific genes that confer susceptibility to BE carcinogenesis. Methods A total of 74 patients with BE and 67 controls coming from six gastrointestinal Italian units were evaluated for six polymorphisms in four genes: XPC, XPD nucleotide excision repair (NER) genes, XRCC1 (BER gene), and glutathione S-transferase P1. Smoking status was analyzed together with the genetic data. Statistical analysis was performed through Artificial Neural Networks. Results Distributions of sex, smoking history, and polymorphisms among BE cases and controls did not show statistically significant differences. The r-value from linear correlation allowed us to identify possible protective factors as well as possible risk factors. The application of advanced intelligent systems allowed for the selection of a subgroup of nine variables. Artificial Neural Networks applied on the final data set reached mean global accuracy of 60%, reaching as high as 65.88%. Conclusion We report here results from an exploratory study. Results from this study failed to find an association among the tested single nucleotide polymorphisms and BE phenotype through classical statistical methods. On the contrary, advanced intelligent systems are really able to handle the disease complexity, not treating the data with reductionist approaches unable to detect multiple genes of smaller effect in predisposing to the disease. Impact To detect multiple genes of smaller effects in predisposing individuals to Barrett’s esophagus. PMID:22893750

  13. Association of Methylenetetrahydrofolate Reductase (MTHFR-677 and MTHFR-1298) Genetic Polymorphisms with Occlusive Artery Disease and Deep Venous Thrombosis in Macedonians

    PubMed Central

    Spiroski, Igor; Kedev, Sashko; Antov, Slobodan; Arsov, Todor; Krstevska, Marija; Dzhekova-Stojkova, Sloboda; Kostovska, Stojanka; Trajkov, Dejan; Petlichkovski, Aleksandar; Strezova, Ana; Efinska-Mladenovska, Olivija; Spiroski, Mirko

    2008-01-01

    Aim To analyze the association of methylenetetrahydrofolate reductase polymorphisms (MTHFR-677 and MTHFR-1298) with occlusive artery disease and deep venous thrombosis in Macedonians. Methods We examined 83 healthy respondents, 76 patients with occlusive artery disease, and 67 patients with deep venous thrombosis. Blood samples were collected and DNA was isolated from peripheral blood leukocytes. Identification of MTHFR mutations was done with CVD StripAssay (ViennaLab, Labordiagnostika GmbH, Vienna, Austria) and the population genetics analysis package, PyPop, was used for the analysis. Pearson P values, crude odds ratio, and Wald’s 95% confidence intervals were calculated. Results The frequency of C alleles of MTHFR-677 was 0.575 in patients with deep venous thrombosis, 0.612 in patients with occlusive artery disease, and 0.645 in healthy participants. The frequency of T allele of MTHFR-677 was lower in healthy participants (0.355) than in patients with occlusive artery disease (0.388) and deep venous thrombosis (0.425). The frequency of A allele for MTHFR-1298 was 0.729 in healthy participants, 0.770 in patients with occlusive artery disease, and 0.746 in patients with deep venous thrombosis. The frequency of C allele of MTHFR-1298 was 0.271 in healthy participants, 0.230 in patients with occlusive artery disease, and 0.425 in patients with deep venous thrombosis. No association of MTHFR-677 and MTHFR-1289 polymorphisms with occlusive artery disease and deep venous thrombosis was found, except for the protective effect of MTHFR/CA:CC diplotype for occlusive artery disease. Conclusion We could not confirm a significant association of MTHFR-677 and MTHFR-1289 polymorphisms with occlusive artery disease or deep venous thrombosis in Macedonians, except for the protective effect of MTHFR/CA:CC diplotype against occlusive artery disease. PMID:18293456

  14. Significant correlation between a set of genetic polymorphisms and a functional brain network revealed by feature selection and sparse Partial Least Squares.

    PubMed

    Le Floch, Edith; Guillemot, Vincent; Frouin, Vincent; Pinel, Philippe; Lalanne, Christophe; Trinchera, Laura; Tenenhaus, Arthur; Moreno, Antonio; Zilbovicius, Monica; Bourgeron, Thomas; Dehaene, Stanislas; Thirion, Bertrand; Poline, Jean-Baptiste; Duchesnay, Edouard

    2012-10-15

    Brain imaging is increasingly recognised as an intermediate phenotype to understand the complex path between genetics and behavioural or clinical phenotypes. In this context, a first goal is to propose methods to identify the part of genetic variability that explains some neuroimaging variability. Classical univariate approaches often ignore the potential joint effects that may exist between genes or the potential covariations between brain regions. In this paper, we propose instead to investigate an exploratory multivariate method in order to identify a set of Single Nucleotide Polymorphisms (SNPs) covarying with a set of neuroimaging phenotypes derived from functional Magnetic Resonance Imaging (fMRI). Recently, Partial Least Squares (PLS) regression or Canonical Correlation Analysis (CCA) have been proposed to analyse DNA and transcriptomics. Here, we propose to transpose this idea to the DNA vs. imaging context. However, in very high-dimensional settings like in imaging genetics studies, such multivariate methods may encounter overfitting issues. Thus we investigate the use of different strategies of regularisation and dimension reduction techniques combined with PLS or CCA to face the very high dimensionality of imaging genetics studies. We propose a comparison study of the different strategies on a simulated dataset first and then on a real dataset composed of 94 subjects, around 600,000 SNPs and 34 functional MRI lateralisation indexes computed from reading and speech comprehension contrast maps. We estimate the generalisability of the multivariate association with a cross-validation scheme and demonstrate the significance of this link, using a permutation procedure. Univariate selection appears to be necessary to reduce the dimensionality. However, the significant association uncovered by this two-step approach combining univariate filtering and L1-regularised PLS suggests that discovering meaningful genetic associations calls for a multivariate approach. PMID:22781162

  15. Genetic diversity of maternal lineage in the endangered Kiso horse based on polymorphism of the mitochondrial DNA D-loop region.

    PubMed

    Takasu, Masaki; Ishihara, Namiko; Tozaki, Teruaki; Kakoi, Hironaga; Maeda, Masami; Mukoyama, Harutaka

    2014-11-01

    To determine genetic characteristics of the maternal lineage of the Kiso horse based on polymorphisms of the mitochondrial DNA D-loop region, we collected blood samples from 136 Kiso horses, 91% of the entire population, and sequenced 411 bp from 15,437 to 15,847 in the region. First of all, we estimated the demographic history; by searching homology between the obtained and known sequences using Basic Local Alignment Search Tool, by mismatch analysis to evaluate the mutation processes using Arlequin, and by building a phylogenetic tree showing the relationship of the mtDNA haplotypes for 24 horse breeds around the world using Molecular Evolutionary Genetics Analysis softwear. The results suggested that various horses that came to Japan stayed at Kiso region and became ancestors of Kiso horse and also genetically supported the theory that the Kiso horse was historically improved by other Japanese native horse breeds. Next, we analyzed the diversity of current maternal lineage by classifying the resulting sequences, and by calculating the haplotype diversity and nucleotide diversity using Arlequin. Then, we visualized the relationship among haplotypes by a median-joining network using NETWORK 4.6.0.0. The results suggested the diversity of maternal lineage in the Kiso horse was reasonably maintained. Lastly, we predicted future change of the diversity of maternal lineage in Kiso horse by assessing the regional distribution of the acquired haplotypes. The distribution suggested that diversity of maternal lineage would possibly be reducing. PMID:25056676

  16. Genetic Diversity of Maternal Lineage in the Endangered Kiso Horse Based on Polymorphism of the Mitochondrial DNA D-Loop Region

    PubMed Central

    TAKASU, Masaki; ISHIHARA, Namiko; TOZAKI, Teruaki; KAKOI, Hironaga; MAEDA, Masami; MUKOYAMA, Harutaka

    2014-01-01

    ABSTRACT To determine genetic characteristics of the maternal lineage of the Kiso horse based on polymorphisms of the mitochondrial DNA D-loop region, we collected blood samples from 136 Kiso horses, 91% of the entire population, and sequenced 411 bp from 15,437 to 15,847 in the region. First of all, we estimated the demographic history; by searching homology between the obtained and known sequences using Basic Local Alignment Search Tool, by mismatch analysis to evaluate the mutation processes using Arlequin, and by building a phylogenetic tree showing the relationship of the mtDNA haplotypes for 24 horse breeds around the world using Molecular Evolutionary Genetics Analysis softwear. The results suggested that various horses that came to Japan stayed at Kiso region and became ancestors of Kiso horse and also genetically supported the theory that the Kiso horse was historically improved by other Japanese native horse breeds. Next, we analyzed the diversity of current maternal lineage by classifying the resulting sequences, and by calculating the haplotype diversity and nucleotide diversity using Arlequin. Then, we visualized the relationship among haplotypes by a median-joining network using NETWORK 4.6.0.0. The results suggested the diversity of maternal lineage in the Kiso horse was reasonably maintained. Lastly, we predicted future change of the diversity of maternal lineage in Kiso horse by assessing the regional distribution of the acquired haplotypes. The distribution suggested that diversity of maternal lineage would possibly be reducing. PMID:25056676

  17. Single Nucleotide Polymorphisms Reveal Genetic Structuring of the Carpathian Newt and Provide Evidence of Interspecific Gene Flow in the Nuclear Genome

    PubMed Central

    Zieli?ski, Piotr; Dudek, Katarzyna; Stuglik, Micha? Tadeusz; Liana, Marcin; Babik, Wies?aw

    2014-01-01

    Genetic variation within species is commonly structured in a hierarchical manner which may result from superimposition of processes acting at different spatial and temporal scales. In organisms of limited dispersal ability, signatures of past subdivision are detectable for a long time. Studies of contemporary genetic structure in such taxa inform about the history of isolation, range changes and local admixture resulting from geographically restricted hybridization with related species. Here we use a set of 139 transcriptome-derived, unlinked nuclear single nucleotide polymorphisms (SNP) to assess the genetic structure of the Carpathian newt (Lissotriton montandoni, Lm) and introgression from its congener, the smooth newt (L. vulgaris, Lv). Two substantially differentiated groups of Lm populations likely originated from separate refugia, both located in the Eastern Carpathians. The colonization of the present range in north-western and south-western directions was accompanied by a modest loss of variation; admixture between the two groups has occurred in the middle of the Eastern Carpathians. Local, apparently recent introgression of Lv alleles into several Lm populations was detected, demonstrating increased power for admixture detection in comparison to a previous study based on a limited number of microsatellite markers. The level of introgression was higher in Lm populations classified as admixed than in syntopic populations. We discuss the possible causes and propose further tests to distinguish between alternatives. Several outlier loci were identified in tests of interspecific differentiation, suggesting genomic heterogeneity of gene flow between species. PMID:24820116

  18. Single nucleotide polymorphisms reveal genetic structuring of the carpathian newt and provide evidence of interspecific gene flow in the nuclear genome.

    PubMed

    Zieli?ski, Piotr; Dudek, Katarzyna; Stuglik, Micha? Tadeusz; Liana, Marcin; Babik, Wies?aw

    2014-01-01

    Genetic variation within species is commonly structured in a hierarchical manner which may result from superimposition of processes acting at different spatial and temporal scales. In organisms of limited dispersal ability, signatures of past subdivision are detectable for a long time. Studies of contemporary genetic structure in such taxa inform about the history of isolation, range changes and local admixture resulting from geographically restricted hybridization with related species. Here we use a set of 139 transcriptome-derived, unlinked nuclear single nucleotide polymorphisms (SNP) to assess the genetic structure of the Carpathian newt (Lissotriton montandoni, Lm) and introgression from its congener, the smooth newt (L. vulgaris, Lv). Two substantially differentiated groups of Lm populations likely originated from separate refugia, both located in the Eastern Carpathians. The colonization of the present range in north-western and south-western directions was accompanied by a modest loss of variation; admixture between the two groups has occurred in the middle of the Eastern Carpathians. Local, apparently recent introgression of Lv alleles into several Lm populations was detected, demonstrating increased power for admixture detection in comparison to a previous study based on a limited number of microsatellite markers. The level of introgression was higher in Lm populations classified as admixed than in syntopic populations. We discuss the possible causes and propose further tests to distinguish between alternatives. Several outlier loci were identified in tests of interspecific differentiation, suggesting genomic heterogeneity of gene flow between species. PMID:24820116

  19. Genetic Relatedness among Environmental, Clinical, and Diseased-Eel Vibrio vulnificus Isolates from Different Geographic Regions by Ribotyping and Randomly Amplified Polymorphic DNA PCR

    PubMed Central

    Arias, Covadonga R.; Pujalte, María Jesús; Garay, Esperanza; Aznar, Rosa

    1998-01-01

    Genetic relationships among 132 strains of Vibrio vulnificus (clinical, environmental, and diseased-eel isolates from different geographic origins, as well as seawater and shellfish isolates from the western Mediterranean coast, including reference strains) were analyzed by random amplified polymorphic DNA (RAPD) PCR. Results were validated by ribotyping. For ribotyping, DNAs were digested with KpnI and hybridized with an oligonucleotide probe complementary to a highly conserved sequence in the 23S rRNA gene. Random amplification of DNA was performed with M13 and T3 universal primers. The comparison between ribotyping and RAPD PCR revealed an overall agreement regarding the high level of homogeneity of diseased-eel isolates in contrast to the genetic heterogeneity of Mediterranean isolates. The latter suggests the existence of autochthonous clones present in Mediterranean coastal waters. Both techniques have revealed a genetic proximity among Spanish fish farm isolates and a close relationship between four Spanish eel farm isolates and some Mediterranean isolates. Whereas the differentiation within diseased-eel isolates was only possible by ribotyping, RAPD PCR was able to differentiate phenotypically atypical isolates of V. vulnificus. On the basis of our results, RAPD PCR is proposed as a better technique than ribotyping for rapid typing in the routine analysis of new V. vulnificus isolates. PMID:9726889

  20. Cognitive control and the COMT Val¹??Met polymorphism: genetic modulation of videogame training and transfer to task-switching efficiency.

    PubMed

    Colzato, Lorenza S; van den Wildenberg, Wery P M; Hommel, Bernhard

    2014-09-01

    The study investigated whether successful transfer of game-based cognitive improvements to untrained tasks might be modulated by preexisting neuro-developmental factors, such as genetic variability related to the catechol-O-methyltransferase (COMT)-an enzyme responsible for the degradation of dopamine. The COMT Val(158)Met genotype may differentially affect cognitive stability and flexibility, and we hypothesized that Val/Val homozygous individuals (who possess low prefrontal dopamine levels) show more pronounced cognitive flexibility than Met/-carriers (who possess high prefrontal dopamine levels). We trained participants, genotyped for the COMT Val(158)Met polymorphism on playing "Half-Life 2", a first-person shooter game which has been shown to improve cognitive flexibility. Pre-training (baseline) and post-training measures of cognitive flexibility were acquired by means of a task-switching paradigm. As expected, Val/Val homozygous individuals showed larger beneficial transfer effects than Met/-carriers. Our findings support the idea that genetic predisposition modulates transfer effects and that playing first-person shooter games promotes cognitive flexibility in individuals with a suitable genetic predisposition. PMID:24030137

  1. Prediction of retrotransposons and assessment of genetic variability based on developed retrotransposon-based insertion polymorphism (RBIP) markers in Pyrus L.

    PubMed

    Jiang, Shuang; Zong, Yu; Yue, Xiaoyan; Postman, Joseph; Teng, Yuanwen; Cai, Danying

    2015-02-01

    Interspecific hybridization has been considered the major mode of evolution in Pyrus (pear), and thus, the genetic relationships within this genus have not been well documented. Retrotransposons are ubiquitous components of plant genomes and 42.4 % of the pear genome was reported to be long terminal repeat (LTR) retrotransposons, implying that retrotransposons might be significant in the evolution of Pyrus. In this study, 1,836 putative full-length LTR retrotransposons were isolated and 196 retrotransposon-based insertion polymorphism (RBIP) primers were developed, of which 24 pairs to the Ppcr1 subfamily of copia retrotransposons were used to analyze genetic diversity among 110 Pyrus accessions from Eurasia. Our results showed that Ppcr1 replicated many times in the development of cultivated Asian pears. The genetic structure analysis and the unweighted pair group method with arithmetic mean (UPGMA) dendrogram indicated that all accessions could be divided into Oriental and Occidental groups. In Oriental pears, wild pea pears clustered separately into independent groups in accordance with their morphological classifications. Cultivars of P. ussuriensis Maxim, P. pyrifolia Nakai, and P. pyrifolia Chinese white pear were mingled together, which inferred that hybridization events occurred during the development of the cultivated Asian pears. In Occidental pears, two clades were obtained in the UPGMA dendrogram in accordance with their geographical distribution; one contained the European species and the other included species from North Africa and West Asia. New findings in this study will be important to further understand the phylogeny of Pyrus and origins of cultivated pears. PMID:25216935

  2. Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: Application for diagnosis, genetic counseling, and therapy

    SciTech Connect

    Hiort, O. Tufts-New England Medical Center, Boston, MA ); Huang, Q. ); Sinnecker, G.H.G.; Kruse, K. ); Sadeghi-Nejad, A.; Wolfe, H.J. ); Yandell, D.W. ) Harvard School of Public Health, Boston, MA )

    1993-07-01

    Recent studies indicate that mutations in the androgen receptor gene are associated with androgen insensitivity syndromes, a heterogeneous group of related disorders involving defective sexual differentiation in karyotypic males. In this report, the authors address the possibility of rapid mutational analysis of the androgen receptor gene for initial diagnosis, genetic counseling, and molecular subclassification of affected patients and their families. DNA from peripheral blood leukocytes of six patients from five families with various degrees of androgen insensitivity was studied. Exons 2 to 8 of the androgen receptor gene were analyzed using a combination of single strand conformation polymorphism analysis and direct DNA sequencing. Female family members were also studied to identify heterozygote carriers. Point mutations in the AR gene were identified in all six patients, and all mutations caused amino acid substitutions. One patient with incomplete androgen insensitivity was a mosaic for the mutation. Four of the five mothers, as well as a young sister of one patient, were carriers of the mutation present in the affected child. The data show that new mutations may occur in the androgen receptor gene leading to sporadic androgen insensitivity syndrome. Molecular genetic characterization of the variant allele can serve as a primary tool for diagnosis and subsequent therapy, and can provide a basis for distinguishing heterozygous carriers in familial androgen resistance. The identification of carriers is of substantial clinical importance for genetic counseling. 29 refs., 2 figs., 1 tab.

  3. Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism | Office of Cancer Genomics

    Cancer.gov

    Neuroblastoma is a paediatric malignancy that typically arises in early childhood, and is derived from the developing sympathetic nervous system. Clinical phenotypes range from localized tumours with excellent outcomes to widely metastatic disease in which long-term survival is approximately 40% despite intensive therapy. A previous genome-wide association study identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility and oncogenic addiction to LMO1 in the tumour cells.

  4. Genetic polymorphisms of the AMPD1 gene and their correlations with IMP contents in Fast Partridge and Lingshan chickens.

    PubMed

    Hu, Jin; Yu, Ping; Ding, Xiaoling; Xu, Minglong; Guo, Baoping; Xu, Yinxue

    2015-12-15

    The object of this study was to evaluate associations between the adenosine monophosphate deaminase 1 (AMPD1) gene polymorphisms and inosine monophosphate acid (IMP) contents of chicken to provide a molecular marker for breeding. Three single nucleotide polymorphisms (SNPs), g.4064G/A, g.5573A/G and g.6805G/A were detected in exons IV, VI, and VIII of the AMPD1 gene in Fast Partridge and Lingshan chickens, respectively. All were purine conversion and caused no alteration in amino acid sequence. Statistical analysis revealed that Lingshan chicken with the homozygous genotype AA at position 4064 and 6805 had a significantly greater IMP content than those with the GG genotype (P<0.05). Fast Partridge chicken with the genotype GG at position 6805 had a significantly greater IMP content compared with those with the AA genotype (P<0.05). In conclusion, the polymorphism at g.6805A/G was correlated with IMP content (P<0.05) in both Fast Partridge and Lingshan chickens. The results in our study suggest that SNP 6805A/G can be used as a possible candidate marker of IMP content of chicken. PMID:26275943

  5. Norwalk Harbor Report Card

    E-print Network

    Boynton, Walter R.

    , such as parking lots, streets, and roofs, water from storms and even light rain can flow quickly and directly into a storm drain system. This water flow, called runoff, transports a wide variety of pollutants (such, and the Harbor. This type of pollution, often difficult to control, is called Nonpoint Source Pollution (NSP

  6. [Characteristic of the Genetic Variability of Four Polymorphic Variants (rs2069705, rs17880053, rs11126176, and rs804271) in Representative Samples of Indigenous and Alien Populations of Siberia].

    PubMed

    Kucher, A N; Babushkina, N P; Kulish, E V; Makeeva, O A; Bragina, E Yu; Goncharova, I A; Eremina, E R; Puzyrev, V P

    2015-08-01

    The variability of potentially important functional polymorphic variants rs2069705 (5'UTR of the IFNG gene), rs17880053 (near 5'UTR of the IFNGR2), rs11126176 (LOC100287361 pseudogene), and rs804271 (near 5'UTR of the NEIL2 gene) was characterized in representatives of four ethnic groups living in the Siberian region. These ethnic groups included three indigenous Mongoloid ethnic groups (Yakuts, the residents of the Republic of Sakha (Yakutia), Tuvinians from the Republic of Tuva, and Buryats from the Republic Buryatia) and the alien Russian population. All of the examined variants were polymorphic. The frequency of the rs2069705 allele C in Russians was 0.5833, while it was in a range from 0.7842 to 0.8967 in representatives of the indigenous populations. The frequency of rs17880053 deletion was 0.8073 in Russians and from 0.4474 to 0.5521 in the indigenous ethnic groups. The frequency of the rs11126176 allele A was equal to 0.5398 in Russians but was recorded with lower frequencies in indigenous ethnic groups (from 0.2722 to 0.4551). The frequency of the rs804271 allele Gwas 0.5215 in Russians and from 0.2527 to 0.4022 indigenous ethnic groups. With respect to the genotype structure, the alien Russian population was considerably distanced from indigenous Mongoloid populations. Specifically, the genetic distance was 0.0742 between Russians and Yakuts, 0.1365 between Russians and Tuvinians, and 0.1433 between Russians and Buryats. Among the Mongoloid indigenous ethnic groups of Siberia, Tuvinians and Yakuts were the most distant from each other (0.0262). The genetic distance was equal to 0.0151 between Yakuts and Buryats and 0.0127 between Buryats and Tuvinians. PMID:26601495

  7. Interactions between Paraoxonase 1 Genetic Polymorphisms and Smoking and Their Effects on Oxidative Stress and Lung Cancer Risk in a Korean Population

    PubMed Central

    Eom, Sang-Yong; Yim, Dong-Hyuk; Lee, Chul-Ho; Choe, Kang-Hyeon; An, Jin Young; Lee, Kye Young; Kim, Yong-Dae; Kim, Heon

    2015-01-01

    Background Few studies in epidemiology have evaluated the effects of gene-environment interaction on oxidative stress, even though this interaction is an important etiologic factor in lung carcinogenesis. We investigated the effects of the genetic polymorphisms of paraoxonase 1 (PON1), smoking, and the interaction between the two on lung cancer risk and oxidative stress. Methods This study’s subjects consisted of 416 newly diagnosed lung cancer patients and an equal number of matched controls. The GoldenGate assay was used for genotypic analyses of the PON1 gene. Urinary 8-hydroxydeoxyguanosine (8-OHdG) and thiobarbituric acid reactive substances levels were measured as indicators of oxidative stress. Results The PON1 rs662 AA genotype showed a significantly lower risk of lung cancer than the GG genotype (OR = 0.60, 95% CI: 0.36–0.99). The protective effect of the PON1 rs662 AA genotype on lung cancer risk was limited to non-smokers. Lung cancer patients who had the rs662 A allele showed a dose-dependent association between smoking status and oxidative stress markers. Among non-smoking lung cancer patients, urinary 8-OHdG levels were significantly lower in individuals with the rs662 GA and AA genotypes than in those with the GG genotype. Furthermore, we found a significant interaction effect between PON1 rs662 and smoking status on urinary 8-OHdG levels in lung cancer patients. Conclusions Our results suggest that the protective effect of PON1 rs662 SNP against lung carcinogenesis and the induction of oxidative stress might be modulated by the interaction between PON1 genetic polymorphisms and tobacco smoking. PMID:25741997

  8. Genetic Polymorphisms at HLA-A, -B, and -DRB1 Loci in Han Population of Xi’an City in China

    PubMed Central

    Shen, Chunmei; Zhu, Bofeng; Liu, Mengli; Li, Shengbin

    2008-01-01

    Aim To determine genetic polymorphisms at human leukocyte antigen (HLA)-A, -B, and -DRB1 loci in Han population of Xi’an city in China. Methods Polymerase chain reaction-based reverse line-strip sequence specific oligonucleotide hybridization was used to determine the alleles of HLA-A, -B, and -DRB1 in 516 unrelated, healthy individuals of Han population in Xi’an. Allele frequencies at HLA-A, -B, and -DRB1 loci were estimated by direct counting method. Haplotype frequencies were calculated from genotype data by expectation maximization. Results A total of 14 alleles of HLA-A, 33 alleles of HLA-B, and 13 alleles of HLA-DRB1 were found. The most common alleles were HLA-A*02 (28.39%), A*11 (19.19%), and A*24 (16.28%); HLA-B*13 (11.05%), B*15 (B62: 9.30%), and B*51 (8.53%); and HLA-DRB1*15 (17.15%), DRB1*09 (13.18%), and DRB1*04 (10.85%). The most common haplotypes of HLA-A-B-DRB1 haplotype were HLA-A*30-B*13-DRB1*07 (3.93%), HLA-A*02-B*46-DRB1*09 (3.20%), and HLA-A*33-B*58-DRB1*17 (1.63%). Conclusion The finding that the HLA loci are highly polymorphic in Han population of Xi’an City may be useful for population genetics, HLA-related studies, human identification, and paternity tests in forensic sciences. PMID:18716994

  9. Assessment of interactions between PAH exposure and genetic polymorphisms on PAH-DNA adducts in African American, Dominican, and Caucasian mothers and newborns.

    PubMed

    Wang, Shuang; Chanock, Stephen; Tang, Deliang; Li, Zhigang; Jedrychowski, Wieslaw; Perera, Frederica P

    2008-02-01

    Polycyclic aromatic hydrocarbons (PAH) are widespread pollutants commonly found in air, food, and drinking water. Benzo[a]pyrene is a well-studied representative PAH found in air from fossil fuel combustion and a transplacental carcinogen experimentally. PAHs bind covalently to DNA to form DNA adducts, an indicator of DNA damage, and an informative biomarker of potential cancer risk. Associations between PAH-DNA adduct levels and both cancer risk and developmental deficits have been seen in previous experimental and epidemiologic studies. Several genes have been shown to play an important role in the metabolic activation or detoxification of PAHs, including the cytochrome P450 genes CYP1A1 and CYP1B1 and the glutathione S-transferase (GST) genes GSTM1, and GSTT2. Genetic variation in these genes could influence susceptibility to adverse effects of PAHs in polluted air. Here, we have explored interactions between prenatal PAH exposure and 17 polymorphisms in these genes (rs2198843, rs1456432, rs4646903, rs4646421, rs2606345, rs7495708, rs2472299, rs162549, rs1056837, rs1056836, rs162560, rs10012, rs2617266, rs2719, rs1622002, rs140194, and gene deletion GSTM1-02) and haplotypes on PAH-DNA adducts in cord blood of 547 newborns and in maternal blood of 806 mothers from three different self-described ethnic groups: African Americans, Dominicans, and Caucasians. PAHs were measured by personal air monitoring of mothers during pregnancy. Significant interactions (p < 0.05) were observed between certain genetic polymorphisms and CYP1A1 haplotype and PAHs in mothers and their newborns in the three ethnic groups. However, with our limited sample size, the current findings are suggestive only, warranting further study. PMID:18268125

  10. The role of the immunological background of mice in the genetic variability of Schistosoma mansoni as detected by random amplification of polymorphic DNA.

    PubMed

    Cossa-Moiane, I L; Mendes, T; Ferreira, T M; Mauricio, I; Calado, M; Afonso, A; Belo, S

    2015-11-01

    Schistosomiasis is a parasitic disease caused by flatworms of the genus Schistosoma. Among the Schistosoma species known to infect humans, S. mansoni is the most frequent cause of intestinal schistosomiasis in sub-Saharan Africa and South America: the World Health Organization estimates that about 200,000 deaths per year result from schistosomiasis in sub-Saharan Africa alone. The Schistosoma life cycle requires two different hosts: a snail as intermediate host and a mammal as definitive host. People become infected when they come into contact with water contaminated with free-living larvae (e.g. when swimming, fishing, washing). Although S. mansoni has mechanisms for escaping the host immune system, only a minority of infecting larvae develop into adults, suggesting that strain selection occurs at the host level. To test this hypothesis, we compared the Belo Horizonte (BH) strain of S. mansoni recovered from definitive hosts with different immunological backgrounds using random amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR). Schistosoma mansoni DNA profiles of worms obtained from wild-type (CD1 and C57BL/6J) and mutant (J?18- / - and TGF?RIIdn) mice were analysed. Four primers produced polymorphic profiles, which can therefore potentially be used as reference biomarkers. All male worms were genetically distinct from females isolated from the same host, with female worms showing more specific fragments than males. Of the four host-derived schistosome populations, female and male adults recovered from TGF?RIIdn mice showed RAPD-PCR profiles that were most similar to each other. Altogether, these data indicate that host immunological backgrounds can influence the genetic diversity of parasite populations. PMID:24991919

  11. Genetic polymorphism of 12S rRNA gene among Dermacentor reticulatus Fabricius ticks in the Chernobyl Nuclear Power Plant Exclusion Zone.

    PubMed

    Movila, Alexandru; Morozov, Alexandr; Sitnicova, Natalia

    2013-02-01

    The molecular genetic variability of the 12S rRNA gene, on the basis of partial primary sequence and in silico-predicted secondary structures among Dermacentor reticulatus (Fabricius 1794) ticks, was studied in the Chernobyl Nuclear Power Plant (ChNPP) Exclusion Zone. In total, 20, 20, and 25 ethanol-preserved specimens, previously collected at 3 sites with 0.76, 1.91, and 4.5 millisievert (mSv)/hr ionizing radiation background, were examined. The primary sequence analysis generated 4 haplotypes defined by 3 polymorphic sites. The most common haplotype 1 was found in all 3 locations, representing 86.2% of all sampled individuals. Haplotype 4 (10.8%) was detected at the 1.91 and 4.50 mSv/hr sites. The unique haplotypes 2 (1.5%) and 3 (1.5%) were detected only at the 1.91 and 4.50 mSv/hr sites, respectively. The haplotype diversity, nucleotide diversity, and pairwise nucleotide differences for 2 tick populations at the 1.90 and 4.50 mSv/hr sites were 0.279, 0.00085, and 0.289, and 0.397, 0.00122, 0.413, respectively. No polymorphism was detected in ticks collected at the 0.76 mSv/hr site. The primary sequences of 12S rRNA were folded into the secondary structures and the free energy of haplotypes was calculated. The free energy at 37 C (?G) of the nonmutant haplotype 1 and the mutant haplotypes 2, 3, and 4 were -45.79, -44.17, -39.56, and -45.79 kcal/mol, respectively. Considering the correlation between the structural profile similarity of 12S rRNA and point mutations, haplotypes 1 and 4 have similar secondary structure profiles and have received a 0.999219 similarity score in the cluster tree. The unique haplotypes 2 and 3 have differences in the secondary structure in comparison with haplotypes 1 and 4; the similarity scores were 0.914747 and 0.169431, respectively. Further studies using more genetic markers are warranted to ascertain the genetic variability and population genetic structure within D. reticulatus tick populations in the ChNPP Exclusion Zone and to resolve their vector capacity. PMID:22924906

  12. Effects of the Interactions between Dust Exposure and Genetic Polymorphisms in Nalp3, Caspase-1, and IL-1? on the Risk of Silicosis: A Case-Control Study

    PubMed Central

    Rong, Yi; Liu, Yuewei; Wang, Xin; Guan, Hongyu; Chen, Weihong

    2015-01-01

    Objectives To evaluate the effects of the interactions between polymorphisms in Nalp3, caspase-1, and interleukin(IL)-1? genes and occupational dust exposure on the risk of silicosis. Methods We conducted a population-based case-control study in a large iron mine in China. Between January 2006 and December 2009, we identified 179 patients with silicosis to evaluate as cases and 201 individuals without silicosis to evaluate as controls. We estimated cumulative dust exposure (CDE) for all subjects and we genotyped polymorphisms in Nalp3, caspase-1, and IL-1? genes. We estimated odds ratios(ORs), 95% confidence intervals(95%CIs), and p-values using logistic regression models adjusted for selected confounders. Results After adjusting for age, smoking status, and CDE, subjects with the CT genotype of Ex4-849C>T in Nalp3 and the GA genotype of Ex2+37G>A in caspase-1 had increased risks of silicosis (adjusted ORs[95%CIs] = 2.40 [1.12–5.12] and 3.62 [1.63–8.02], respectively). Among subjects younger than 70 years old, those with the CC genotype of IVS8-7652A>C in Nalp3 had a lower risk of silicosis than those with other genotypes (adjusted OR[95%CI] = 0.24[0.06–0.88]). Among subjects aged 70 years and older, those with the CT genotype of Ex4-849C>T in Nalp3 and those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs [95%CI] = 2.52[1.04–6.12] and 5.19[1.88–14.35], respectively). Among subjects with CDE greater than 120 mg/m3×year and among smokers, those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs[95%CIs] = 26.37[3.35–207.39] and 3.47[1.40–8.64], respectively). Conclusions Genetic polymorphisms in Nalp3 and caspase-1 may be associated with individual susceptibility to silicosis, especially when the polymorphisms interact with age, CDE, or smoking status. PMID:26496436

  13. Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients.

    PubMed

    Umamaheswaran, Gurusamy; Praveen, Ramakrishnan Geethakumari; Damodaran, Solai Elango; Das, Ashok Kumar; Adithan, Chandrasekaran

    2015-11-01

    Metformin is an oral antidiabetic drug, commonly used for treating type 2 diabetes mellitus (T2DM) patients. It is transported into the hepatocytes by polyspecific organic cation transporter 1, which is encoded by the gene SLC22A1. It has been hypothesized that genetic variations of SLC22A1 gene will influence inter-individual variation in glucose lowering efficacy of metformin. Previous studies have demonstrated this in other populations with conflicting results, but it remains to be elucidated in Indian population. Henceforth, the objective of the study was to evaluate the impact of SLC22A1 rs622342 gene polymorphism on the clinical efficacy of metformin in South Indian T2DM patients. A total of 122 newly detected, treatment naive T2DM patients of either sex were included in this study. The patients were started on metformin monotherapy and followed up for 12 weeks. Genotype was determined using qRT-PCR. Before and after treatment with metformin, body mass index (BMI), serum lipid profile, glycated hemoglobin (HbA1c), fasting and postprandial glucose level, and blood pressure (BP) were measured. The study cohort mean age was 49.57 ± 9.88 years. Of the 122 T2DM patients, 93 were classified as responders and 29 as non-responders based on fall in HbA1c levels. Interestingly, carriers of one variant allele 'C' (AC) of rs622342 polymorphism were less among the responders than those who did not (44.8 vs. 22.6 %). The response was even lesser (13.8 vs. 4.3 %) in carriers of two copies of "C" allele (CC). On the contrary, patients with two copies of allele 'A' (AA) had 5.6 times greater chance of responding to metformin treatment. A similar trend was observed when the proportion was analyzed under different genetic models (OR 3.85, 95 % CI 1.61-9.19 for dominant; OR 3.56, 95 % CI 0.83-15.26 for recessive; OR 0.35, 95 % CI 0.14-0.86 for over-dominant; and OR 4.10, 95 % CI 1.78-9.43 for additive). Further, metformin showed significant beneficial effects on BMI, HbA1c, FPG, PPG, lipid parameters and BP. These data suggest that the allele and genotypes of SLC22A1 rs622342 gene polymorphism were associated with the therapeutic efficacy of metformin in South Indian patients with T2DM. PMID:25492374

  14. Single-nucleotide Polymorphisms in the p53 Signaling Pathway

    PubMed Central

    Grochola, Lukasz F.; Zeron-Medina, Jorge; Mériaux, Sophie; Bond, Gareth L.

    2010-01-01

    The p53 tumor suppressor pathway is central both in reducing cancer frequency in vertebrates and in mediating the response of commonly used cancer therapies. This article aims to summarize and discuss a large body of evidence suggesting that the p53 pathway harbors functional inherited single-nucleotide polymorphisms (SNPs) that affect p53 signaling in cells, resulting in differences in cancer risk and clinical outcome in humans. The insights gained through these studies into how the functional p53 pathway SNPs could help in the tailoring of cancer therapies to the individual are discussed. Moreover, recent work is discussed that suggests that many more functional p53 pathway SNPs are yet to be fully characterized and that a thorough analysis of the functional human genetics of this important tumor suppressor pathway is required. PMID:20452958

  15. New polymorphic mitochondrial markers for sponge phylogeography

    E-print Network

    Solé-Cava, Antonio M.

    and population genetic studies in the Porifera have been limited by the lack of available polymorphic DNA markers-level systematics, phylogeography and population genetics studies. Keywords: DNA markers, Porifera, population

  16. Common SSRI side-effects in older adults associated with genetic polymorphisms in the serotonin transporter and receptors: Data from a randomized controlled trial

    PubMed Central

    Garfield, Lauren D.; Dixon, David; Nowotny, Petra; Lotrich, Francis E.; Pollock, Bruce G.; Kristjansson, Sean D.; Doré, Peter M.; Lenze, Eric J.

    2013-01-01

    Objective Antidepressant side-effects are a significant public health issue, associated with poor adherence, premature treatment discontinuation and in rare cases significant harm. This is especially relevant for older adults, who assume the largest and most serious burden of medication side-effects. We investigated the association between antidepressant side-effects and genetic variation in the serotonin system in anxious, older adults participating in a randomized, placebo-controlled trial of the SSRI escitalopram. Method Adults (n=177) aged ? 60 years were randomized to active treatment or placebo for 12-weeks. Side-effects were assessed using the UKU side effect rating scale. Genetic polymorphisms were putative functional variants in the promoters of the serotonin transporter and 1A and 2A receptors (5-HTTLPR (L/S + rs25531), HTR1A rs6295, HTR2A rs6311, respectively). Results Four significant drug-placebo side-effect differences were found, including increased duration of sleep, dry mouth, diarrhea and diminished sexual desire. Analyses using putative high- vs low-transcription genotype groupings revealed 6 pharmacogenetic effects: greater dry mouth and decreased sexual desire for the low- and high-expressing genotypes of the serotonin transporter, respectively, and greater diarrhea with the low-transcription genotype of the 1A receptor. Diminished sexual desire was experienced significantly more in those with high-expressing genotype and either the serotonin transporter, 1A or 2A receptors. There was not a significant relationship between drug concentration and side-effects nor a mean difference in drug concentration between low- and high-expressing genotypes. Conclusion Genetic variation in the 5HT system may predict who develops common SSRI side-effects and why. More work is needed to further characterize this genetic modulation and to translate research findings into strategies useful for more personalized patient care. PMID:24021217

  17. Genetic diversity patterns in five protist species occurring in lakes.

    PubMed

    Logares, Ramiro; Boltovskoy, Andrés; Bensch, Staffan; Laybourn-Parry, Johanna; Rengefors, Karin

    2009-05-01

    Little is known about the extent of the genetic diversity and its structuring patterns in protist species living in lakes. Here, we have investigated the genetic diversity patterns within five dinoflagellate species (Peridinium aciculiferum, Peridinium cinctum, Peridiniopsis borgei, Polarella glacialis, Scrippsiella aff. hangoei) that are present in lakes and sometimes, in marine habitats located in polar and temperate regions. A total of 68 clonal strains were investigated using Amplified Fragment Length Polymorphism (AFLP), a sensitive genetic fingerprinting technique. All used strains within each species had identical ITS nuclear ribosomal DNA sequences, a characteristic that indicates that they likely belong to the same species. We found a wide variability in the genetic diversity among species (between 20% and 90% of polymorphic loci; Nei's gene diversity between 0.08 and 0.37). In some cases, our analyses suggested the presence of different genetically homogeneous subgroups (genetic populations) within the same water body. Thus, it appears that different genetic populations can coexist within the same lake despite the likely occurrence of recombination that tends to homogenize the gene pool. Overall, our results indicated that a large number of dinoflagellate genotypes are present in lake populations, instead of a few dominating ones. In addition, our study shows that protists with identical ITS sequences can harbor considerable amounts of genetic diversity. PMID:19162540

  18. Effects of functional genetic polymorphisms in the CYP19A1 gene on prostate cancer risk and survival.

    PubMed

    Kanda, Sohei; Tsuchiya, Norihiko; Narita, Shintaro; Inoue, Takamitsu; Huang, Mingguo; Chiba, Syuji; Akihama, Susumu; Saito, Mitsuru; Numakura, Kazuyuki; Tsuruta, Hiroshi; Satoh, Shigeru; Saito, Seiichi; Ohyama, Chikara; Arai, Yoichi; Ogawa, Osamu; Habuchi, Tomonori

    2015-01-01

    CYP19 catalyzes the conversion of androgens to estrogens and is a critical enzyme affecting the sex hormone milieu. In this study, we investigated the functions of CYP19A1 polymorphisms and their associations with prostate cancer risk and clinical outcome. This case-control study evaluated the effects of three single nucleotide polymorphisms (SNPs) in CYP19A1 on the risk of prostate cancer in 330 prostate cancer patients and 354 normal controls. The associations between each SNP and sex hormone levels were evaluated in 164 healthy male patients. The functions of the SNPs were determined by reporter gene assays in PC3 and DU145 cell lines. Prostate-specific antigen nadir was evaluated in 142 patients with metastatic prostate cancer treated with androgen deprivation therapy. Cancer-specific survival (CSS) was determined in 166 patients with metastatic prostate cancer, to evaluate the influence of the three SNPs. Each variant allele of the three SNPs significantly decreased the risk of prostate cancer. Haplotype analysis showed that the T-A-G haplotype (corresponding to rs2470152-rs10459592-rs4775936) increased the risk of prostate cancer, while the C-C-A haplotype decreased the risk. The estrone/androstenedione ratio was significantly higher in men with the C allele of rs2470152, the C allele of rs10459592, and the A allele of rs4775936 in a gene-dosage-dependent manner. Patients with the variant allele at rs4775936 had significantly shorter CSS. These results indicate that CYP19A1 polymorphisms may influence prostate cancer risk and survival by modifying promoter activity, with subsequent effects on the sex hormone milieu. PMID:24803183

  19. Associations between Genetic Polymorphisms in IL-33, IL1R1 and Risk for Inflammatory Bowel Disease

    PubMed Central

    Latiano, Anna; Palmieri, Orazio; Pastorelli, Luca; Vecchi, Maurizio; Pizarro, Theresa T.; Bossa, Fabrizio; Merla, Giuseppe; Augello, Bartolomeo; Latiano, Tiziana; Corritore, Giuseppe; Settesoldi, Alessia; Valvano, Maria Rosa; D’Incà, Renata; Stronati, Laura; Annese, Vito; Andriulli, Angelo

    2013-01-01

    Background Recent evidence suggests that the IL-33/IL1RL1 axis plays a critical role in several autoimmune and inflammatory disorders; however, its mechanistic role in inflammatory bowel disease (IBD) has not been clearly defined. We investigated the contribution of IL-33 and IL1RL1 polymorphisms to IBD risk, and possible correlations with phenotype in an Italian cohort of adult and pediatric patients. Methods We evaluated the association of six SNPs in IL-33 and IL1RL1 genes, in 805 Crohn’s disease (CD), 816 ulcerative colitis (UC), and 752 controls, using Taqman. IL-33 and IL1RL1 mRNA expression was also analyzed. Results Significant allele and genotype associations with IL-33 rs3939286 were found in CD (P?=?0.004; P?=?0.035) and UC patients (P?=?0.002; P?=?0.038). After stratifying the cohort for age at diagnosis, the differences remained significant only in the IBD adult-onset. Significant associations were also obtained in CD patients with two IL1RL1 polymorphisms (rs13015714 and rs2058660, P<0.015). By combining homo- and heterozygous carriers of the rs13015714 risk allele, differences were still significant for both CD adult- and pediatric-onset. Upon genotype-phenotype evaluation, an increased frequency of extensive colitis in adult UC (P?=?0.019) and in steroid-responsive pediatric patients (P?=?0.024) carrying the IL-33 rs3939286 risk genotype, was observed. mRNA expression of IL-33 and IL1RL1 in inflamed IBD biopsy samples was significantly increased. Conclusions Common IL-33 and IL1RL1 polymorphisms contribute to the risk of IBD in an Italian cohort of adult and pediatric patients, with some influence on sub-phenotypes. PMID:23634226

  20. Association Between Genetic Polymorphisms in the XRCC1, XRCC3, XPD, GSTM1, GSTT1, MSH2, MLH1, MSH3, and MGMT Genes and Radiosensitivity in Breast Cancer Patients

    SciTech Connect

    Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca; Sani, Cristina; Biti, Giampaolo; Livi, Lorenzo; Barletta, Emanuela; Costantini, Adele Seniori; Gorini, Giuseppe

    2011-09-01

    Purpose: Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Methods and Materials: Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results: Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR = 53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR = 38.26; 95% CI, 1.19-1232.52). Conclusions: To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be involved in cellular response to radiotherapy. Genetic polymorphisms may be promising candidates for predicting acute radiosensitivity, but further studies are necessary to confirm our findings.

  1. Genetic markers of cholesterol transport and gray matter diffusion: a preliminary study of the CETP I405V polymorphism.

    PubMed

    Salminen, Lauren E; Schofield, Peter R; Pierce, Kerrie D; Luo, Xi; Zhao, Yi; Laidlaw, David H; Cabeen, Ryan P; Conturo, Thomas E; Lane, Elizabeth M; Heaps, Jodi M; Bolzenius, Jacob D; Baker, Laurie M; Cooley, Sarah A; Scott, Staci; Cagle, Lee M; Paul, Robert H

    2015-11-01

    Variations of the cholesteryl ester transfer protein polymorphism (CETP I405V/rs5882) have been associated with an increased risk for neurodegeneration, particularly when examined in conjunction with the epsilon 4 isoform of apolipoprotein E (ApoE4). Despite these identified relationships, the impact of I405V on gray matter microstructure remains unknown. The present study examined the impact of the CETP I405V polymorphism on gray matter integrity among 52 healthy adults between ages 51 and 85. Gray matter was measured bilaterally using diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Participants were grouped according to a dominant statistical model (II genotype vs. IV/VV genotypes) and secondary analyses were completed to examine the interactive effects of CETP and ApoE4 on DTI metrics. Compared to individuals with the IV/VV genotypes, II homozygotes demonstrated significantly higher MD in bilateral temporal, parietal, and occipital gray matter. Secondary analyses revealed higher FA and AD in the left temporal lobe of IV/VV genotypes with an ApoE4 allele. Our results provide preliminary evidence that CETP II homozygosity is a predisposing risk factor for gray matter abnormalities in posterior brain regions in healthy older adults, independent of an ApoE4 allele. PMID:26253899

  2. Metacercarial polymorphism and genetic variation of Paragonimus heterotremus (Digenea: Paragonimidae), and a re-appraisal of the taxonomic status of Paragonimus pseudoheterotremus.

    PubMed

    Doanh, P N; Thaenkham, U; An, P T; Hien, H V; Horii, Y; Nawa, Y

    2015-03-01

    Paragonimus heterotremus, which is an important pathogen for human paragonimiasis in Asia, is recognized as having the smallest metacercariae (maximum diameter < 300 ?m) of any previously reported Paragonimus species. Recently, P. pseudoheterotremus has been described from Thailand as a new species having metacercariae (about 200 ?m) slightly smaller than those of Thai P. heterotremus. In fact, the small size of P. pseudoheterotremus metacercariae is compatible with those of P. heterotremus from India and China. In this study in Vietnam, we found variably sized small metacercariae which are expected to consist of both P. heterotremus and P. pseudoheterotremus. Contrary to expectation, the adult flukes obtained by separate infection of experimental cats with different sized metacercariae were all identified as P. heterotremus, using both morphological and molecular characteristics. The molecular analyses of an extensive collection of P. heterotremus/P. pseudoheterotremus isolates from Asian countries also indicated that genetic distances between different populations of P. heterotremus are even larger than that between P. pseudoheterotremus and P. heterotremus. The haplotype network showed that all P. heterotremus and P. pseudoheterotremus isolates formed a P. heterotremus complex consisting of three groups with strong geographical origins. In addition, the Indian P. heterotremus group is the root of the other P. heterotremus and P. pseudoheterotremus populations. Based on the observed metacercarial polymorphisms and genetic variation in P. heterotremus, P. pseudoheterotremus should be considered a geographically isolated population of the P. heterotremus complex. PMID:24229574

  3. Interaction between Arsenic Exposure from Drinking Water and Genetic Polymorphisms on Cardiovascular Disease in Bangladesh: A Prospective Case-Cohort Study

    PubMed Central

    Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G.; Liu, Mengling; Cheng, Xin; Parvez, Faruque; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Jiang, Jieying; Roy, Shantanu; Paul-Brutus, Rachelle; Slavkovich, Vesna; Islam, Tariqul; Levy, Diane; VanderWeele, Tyler J.; Pierce, Brandon L.; Graziano, Joseph H.; Ahsan, Habibul

    2015-01-01

    Background: Epidemiologic data on genetic susceptibility to cardiovascular effects of arsenic exposure from drinking water are limited. Objective: We investigated whether the association between well-water arsenic and cardiovascular disease (CVD) differed by 170 single nucleotide polymorphisms (SNPs) in 17 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Method: We conducted a prospective case-cohort study nested in the Health Effects of Arsenic Longitudinal Study, with a random subcohort of 1,375 subjects and 447 incident fatal and nonfatal cases of CVD. Well-water arsenic was measured in 2000 at baseline. The CVD cases, 56 of which occurred in the subcohort, included 238 coronary heart disease cases, 165 stroke cases, and 44 deaths due to other CVD identified during follow-up from 2000 to 2012. Results: Of the 170 SNPs tested, multiplicative interactions between well-water arsenic and two SNPs, rs281432 in ICAM1 (padj = 0.0002) and rs3176867 in VCAM1 (padj = 0.035), were significant for CVD after adjustment for multiple testing. Compared with those with GC or CC genotype in rs281432 and lower well-water arsenic, the adjusted hazard ratio (aHR) for CVD was 1.82 (95% CI: 1.31, 2.54) for a 1-SD increase in well-water arsenic combined with the GG genotype, which was greater than expected given aHRs of 1.08 and 0.96 for separate effects of arsenic and the genotype alone, respectively. Similarly, the joint aHR for arsenic and the rs3176867 CC genotype was 1.34 (95% CI: 0.95, 1.87), greater than expected given aHRs for their separate effects of 1.02 and 0.84, respectively. Conclusions: Associations between CVD and arsenic exposure may be modified by genetic variants related to endothelial dysfunction. Citation: Wu F, Jasmine F, Kibriya MG, Liu M, Cheng X, Parvez F, Islam T, Ahmed A, Rakibuz-Zaman M, Jiang J, Roy S, Paul-Brutus R, Slavkovich V, Islam T, Levy D, VanderWeele TJ, Pierce BL, Graziano JH, Ahsan H, Chen Y. 2015. Interaction between arsenic exposure from drinking water and genetic polymorphisms on cardiovascular disease in Bangladesh: a prospective case-cohort study. Environ Health Perspect 123:451–457;?http://dx.doi.org/10.1289/ehp.1307883 PMID:25575156

  4. Genetic deficiency and polymorphisms of cyclophilin A reveal its essential role for Human Coronavirus 229E replication.

    PubMed

    von Brunn, Albrecht; Ciesek, Sandra; von Brunn, Brigitte; Carbajo-Lozoya, Javier

    2015-10-01

    Replication of coronaviruses is inhibited in vitro by cyclosporin A, a well-known immunosuppressive drug which binds to cellular cyclophilins thus inactivating their enzymatic cis-trans peptidyl-prolyl isomerase function. Latter is required for proper folding of cellular proteins and of proteins of several viruses. Here, we summarize present knowledge on the role of cyclophilin A during coronavirus replication. We present data on the effect of cyclophilin A single nucleotide polymorphism mutants on the replication of human CoV-229E demonstrating the requirement of proper cyclophilin A function for virus propagation. Results define cellular cyclophilin A as a host target for inhibition of coronaviruses ranging from relatively mild common cold to highly pathogenic SARS-CoV and MERS-CoV viruses with the perspective of disclosing non-immunosuppressive cyclosporin A analogs to broadly inactivate the coronavirus family. PMID:26318518

  5. Genetic polymorphism of ten MiniSTR loci in the population of Punjab Pakistan for forensic application.

    PubMed

    Shafique, Muhammad; Shahzad, Muhammad Saqib; Shan, Muhammad Adnan; Ali, Azam; Rahman, Ziaur; Husnain, Tayyab

    2015-09-01

    Ten MiniSTR loci were analyzed on 250 unrelated individuals of Punjabi population from Punjab province of Pakistan. The product amplification range is from 65 to 280 bp. Allele frequency for a total of 98 observed alleles is from 0.002 to 0.41. Forensic and paternity statistical parameters were investigated including combined power of discrimination (PD), combined power of exclusion (PE), and cumulative probability of matching (PM) equaled to 0.99999999999824, 0.999824, and 1.75931?×?10(-12), respectively. These MiniSTRs on the basis of high degree polymorphism and fragment size reduction will be highly informative in most of the forensic cases where DNA of the samples is degraded, mass disasters, and dead body identification. Significant differences were observed in all loci when comparing with same STR loci in previously published different world populations. PMID:25422056

  6. Genetic Association Study of Putative Functional Single Nucleotide Polymorphisms of Genes in Folate Metabolism and Spina Bifida

    PubMed Central

    Martinez, Carla A.; Northrup, Hope; Lin, Jone-Ing; Morrison, Alanna C.; Fletcher, Jack M.; Tyerman, Gayle H.; Au, Kit Sing

    2009-01-01

    OBJECTIVE We tested putative functional single nucleotide polymorphisms (SNPs) in genes which regulate the folate/homocysteine metabolism pathway for their contribution to spina bifida (SB) susceptibility. STUDY DESIGN The study consisted of 610 unrelated simplex SB patient families. Genotypes of 46 SNPs located in the coding sequence or promoter region of 11 genes were investigated. Associations between transmission of alleles and SB in the offspring were examined using the reconstruction-combined transmission disequilibrium test. RESULTS Significant association of SNP rs5742905 in cystathionine-?-synthase (CBS), rs1643649 in dihydrofolate reductase (DHFR), rs2853533 in thymidylate synthetase (TYMS), and rs3737965 in methylene-tetrahydrofolate-reductase (MTHFR) was found (p= 0.015, 0.041, 0.021, and 0.007 respectively). CONCLUSION Transmission disequilibrium of SNP alleles in CBS, DHFR, MTHFR and TYMS confers an increased susceptibility to SB. PMID:19683694

  7. Genetic polymorphisms in paraoxonase 1 and G protein-coupled receptor 77, and the risk of glucose-6-phosphate dehydrogenase deficiency in a Saudi population

    PubMed Central

    Alharbi, Khalid K.

    2015-01-01

    Objectives: To investigate the role of amino acid substitution variants Q192R and C698T in the development of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a Saudi male population. Methods: This case-control study was carried out in 200 Saudi male individuals: 100 patients with G6PD deficiency, and 100 control subjects collected between July and August 2011 in the Taif region of Saudi Arabia. A total of 2100 male Saudi individuals were screened by a fluorescence spot test, and 100 with G6PD deficiency were selected. Two common variants PON1 (rs662) and C5L2 (rs149572881) were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results: The results showed that the R allele and QR genotype were associated with the Q192R polymorphism in PON1 (R versus Q odds ratio [OR], 1.72; 95% confidence interval [95% CI], 1.1-2.6; p=0.01; and QR versus QQ: OR, 1.98; 95% CI, 1.1-3.6; p=0.02). All the C698T genotypes and allele frequencies in C5L2 were almost similar in both the cases and controls (CT versus CC: OR, 2.04; 95% CI, 0.3-11.4; p=0.40; and T versus C: OR, 2.02; 95% CI, 0.3-11.1; p=0.41). Conclusions: These findings suggest the association of PON1 with G6PD deficiency in the Saudi male population studied herein. Future studies, including correlation analyses between the clinical features and genotypes in populations of different ethnicities, are warranted to confirm the disease association with these genetic mutations. PMID:25935173

  8. Genetic polymorphisms of glutathione S-transferase M1, T1, and P1, and the assessment of oxidative damage in infertile men with varicoceles from northwestern China.

    PubMed

    Tang, Kaifa; Xue, Wei; Xing, Yao; Xu, Shaoyuan; Wu, Qifei; Liu, Ruizhe; Wang, Xinyang; Xing, Junping

    2012-01-01

    Our objective was to investigate the genetic polymorphisms of the glutathione S-transferase M1, T1, and P1 genes (GSTM1, GSTT1, and GSTP1) and to assess the oxidative damage in infertile men with varicoceles from northwestern China. A total of 65 infertile men with varicoceles and 30 controls were included in the study. Multiplex polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism analyses were used to identify the genotypes. Sperm DNA damage was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). The levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) were measured by high-performance liquid chromatography with electrochemical detection. The activities of malondialdehyde (MDA) and nitric oxide (NO), and the total antioxidant capacity (TAC) were detected by spectroscopic analysis, and sperm characteristics were measured using computer-assisted semen analysis. The frequencies of the GSTM1, GSTT1, and GSTP1 genotypes were not significantly different between the control and patient groups (P > .05). The percentage of TUNEL-positive sperm and the levels of 8-OH-dG, MDA, and NO were higher but the sperm concentration and motility and the TAC were lower in the patients with the GSTM1, GSTT1, and GSTM1/T1 null genotypes than those in the patients with the GSTM1, GSTT1, and GSTM1/T1 present genotypes (P < .05). However, no significant differences were observed between the GSTP1 A/A and A/G+G/G genotypes (P > .05). Our results suggest that the GSTM1 and GSTT1 null genotypes may predispose sperm to increased oxidative damage in infertile men with varicoceles; however, GSTP1 allelic variation was not significantly different between the patient and control groups in this study. PMID:21546615

  9. Single-nucleotide polymorphism discovery and validation in high-density SNP array for genetic analysis in European white oaks.

    PubMed

    Lepoittevin, C; Bodénès, C; Chancerel, E; Villate, L; Lang, T; Lesur, I; Boury, C; Ehrenmann, F; Zelenica, D; Boland, A; Besse, C; Garnier-Géré, P; Plomion, C; Kremer, A

    2015-11-01

    An Illumina Infinium SNP genotyping array was constructed for European white oaks. Six individuals of Quercus petraea and Q. robur were considered for SNP discovery using both previously obtained Sanger sequences across 676 gene regions (1371 in vitro SNPs) and Roche 454 technology sequences from 5112 contigs (6542 putative in silico SNPs). The 7913 SNPs were genotyped across the six parental individuals, full-sib progenies (one within each species and two interspecific crosses between Q. petraea and Q. robur) and three natural populations from south-western France that included two additional interfertile white oak species (Q. pubescens and Q. pyrenaica). The genotyping success rate in mapping populations was 80.4% overall and 72.4% for polymorphic SNPs. In natural populations, these figures were lower (54.8% and 51.9%, respectively). Illumina genotype clusters with compression (shift of clusters on the normalized x-axis) were detected in ~25% of the successfully genotyped SNPs and may be due to the presence of paralogues. Compressed clusters were significantly more frequent for SNPs showing a priori incorrect Illumina genotypes, suggesting that they should be considered with caution or discarded. Altogether, these results show a high experimental error rate for the Infinium array (between 15% and 20% of SNPs potentially unreliable and 10% when excluding all compressed clusters), and recommendations are proposed when applying this type of high-throughput technique. Finally, results on diversity levels and shared polymorphisms across targeted white oaks and more distant species of the Quercus genus are discussed, and perspectives for future comparative studies are proposed. PMID:25818027

  10. Four genetic polymorphisms of lymphotoxin-alpha gene and cancer risk: a systematic review and meta-analysis.

    PubMed

    Huang, Yi; Yu, Xi; Wang, Lingyan; Zhou, Shengjun; Sun, Jie; Feng, Nan; Nie, Sheng; Wu, Jingmi; Gao, Feng; Fei, Bing; Wang, Jianyong; Lin, Zhiqing; Li, Xianru; Xu, Leiting; Gao, Xiang; Ye, Meng; Duan, Shiwei

    2013-01-01

    Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine that plays an important role in the inflammatory and immunologic response. Numerous studies have shown LTA polymorphisms as risk factors for cancers, but the results remain inconclusive. The goal of the present meta-analyses is to establish the associations between cancers and four LTA variants (rs1041981, rs2239704, rs2229094 and rs746868). A total of 30 case-control studies involving 58,649 participants were included in the current meta-analyses. Our results showed significant associations with increased cancer risk for rs1041981 (odd ratio (OR) = 1.15, 99% confidential interval (CI) = 1.07-1.25, P < 0.0001, I(2) = 12.2%), rs2239704 (OR = 1.08, 99% CI = 1.01-1.16, P = 0.021, I(2) = 0.0%) and rs2229094 (OR = 1.28, 99% CI = 1.09-1.50, P = 0.003, I(2) = 0.0%). No evidence was found for the association between rs746868 and cancer risk (OR = 1.01, 99% CI = 0.93-1.10, P = 0.771, I(2) = 0.0%). Subgroup meta-analysis suggested that rs2239704 was likely to increase the risk of hematological malignancy (OR = 1.10, 99% CI = 1.01-1.20, P = 0.023, I(2) = 0.0%), and rs2229094 was specific for the increased risk of adenocarcinoma (OR = 1.33, 99% CI = 1.11-1.59, P = 0.002, I(2) = 0.0%). In conclusion, our meta-analyses suggested that the LTA rs1041981, rs2239704 and rs2229094 polymorphisms contributed to the increased risk of cancers. Future functional studies were needed to clarify the mechanistic roles of the three variants in the cancer risk. PMID:24349304

  11. Genetic association between low-density lipoprotein receptor-related protein gene polymorphisms and Alzheimer's disease in Chinese Han population.

    PubMed

    Zhou, Yong-Tao; Zhang, Zhen-Xin; Chan, Piu; He, Xiao-Ming; Tang, Mou-Ni; Wu, Cheng-Bin; Hong, Zhen

    2008-10-17

    Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. Low-density lipoprotein receptor-related protein (LRP), as a receptor of apolipoprotein E (APOE), APP, and alpha2 macroglobulin (alpha2-M), keeps the balance between degeneration and production of beta-amyloid protein (Abeta) clearance. Its gene had been defined as a candidate gene for AD, but the results were not universal. Total 496 AD patients and 478 controls were recruited in Chinese Han population and real-time PCR was used to detect the polymorphism of LRP C766T. Multiple logistic regression, Chi-square test and survival analysis were performed to explore the association. The distribution of LRP genotypes and alleles was significantly different between cases and controls, and T allele could reduce the risk for developing AD (OR of CT genotype: 0.57; 95% CI: 0.38-0.85, rho=0.003; OR of T allele: 0.57; 95% CI: 0.39-0.83, rho=0.003). TT genotype carriers had 5 years later for developing AD compared with CC genotype carriers, but survival analysis did not conform this (LRP TT vs. CT and CC log rank chi(2)=2.71, rho=0.26). The distribution of LRP C766T genotypes and alleles was different among different severity stratified by MMSE yet (rho=0.26). Our data suggested that the polymorphism of LRP C766T was strongly associated with AD and T allele might be a protective factor for AD in Chinese Han population. PMID:18706476

  12. Influence of genetic polymorphisms of styrene-metabolizing enzymes on the levels of urinary biomarkers of styrene exposure.

    PubMed

    Carbonari, Damiano; Mansi, Antonella; Proietto, Anna Rita; Paci, Enrico; Bonanni, Rossana Claudia; Gherardi, Monica; Gatto, Maria Pia; Sisto, Renata; Tranfo, Giovanna

    2015-03-01

    Styrene exposure is still present in different occupational settings including manufacture of synthetic rubber, resins, polyesters and plastic. The aim of this work was to investigate the effects of polymorphic genes CYP2E1, EPHX1, GSTT1, and GSTM1 on the urinary concentrations of the styrene metabolites mandelic acid (MA), phenylglyoxylic acid (PGA) and on the concentration ratios between (MA+PGA) and urinary styrene (U-Sty) and airborne styrene (A-Sty), in 30 workers from two fiberglass-reinforced plastic manufacturing plants and 26 unexposed controls. Personal air sampling and biological monitoring results revealed that sometimes exposure levels exceeded both the threshold limit value (TLV) and the biological exposure index (BEI) suggested by the American Conference of Governmental Industrial Hygienists. A significantly reduced excretion of styrene metabolites (MA+PGA) in individuals carrying the CYP2E1*5B and CYP2E1*6 heterozygote alleles, with respect to the homozygote wild type, was observed only in the exposed group. A reduction was also detected, in the same group, in subjects carrying the slow allele EPHX1 (codon 113), through the lowering of (MA+PGA)/urinary styrene concentration ratio. In addition, the ratio between MA+PGA and the personal airborne styrene concentration appeared to be modulated by the predicted mEH activity, in the exposed group, as evidenced by univariate linear regression analysis. Our results confirm some previous hypotheses about the role of the polymorphism of genes coding for enzymes involved in the styrene detoxification pathway: this may significantly reduce the levels of excreted metabolites and therefore it must be taken into account in the interpretation of the biological monitoring results for occupational exposure. PMID:25562543

  13. Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes.

    PubMed

    Fang, Shenying; Wang, Yuling; Chun, Yun S; Liu, Huey; Ross, Merrick I; Gershenwald, Jeffrey E; Cormier, Janice N; Royal, Richard E; Lucci, Anthony; Schacherer, Christopher W; Reveille, John D; Chen, Wei; Sui, Dawen; Bassett, Roland L; Wang, Li-E; Wei, Qingyi; Amos, Christopher I; Lee, Jeffrey E

    2015-09-01

    Recent investigation has identified association of IL-12p40 blood levels with melanoma recurrence and patient survival. No studies have investigated associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL-12p40 blood levels or their potential contributions to melanoma susceptibility or patient outcome. In the current study, 818,237 SNPs were available for 1,804 melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573 cases (discovery), 249 cases (case validation), and 299 controls (control validation). SNPs were evaluated for association with log[IL-12p40] levels in the discovery data set and replicated in two validation data sets, and significant SNPs were assessed for association with melanoma susceptibility and patient outcomes. The most significant SNP associated with log[IL-12p40] was in the IL-12B gene region (rs6897260, combined P=9.26 × 10(-38)); this single variant explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1 was rs6895454 (combined P=2.24 × 10(-9)). A marker in IL12B was associated with melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00-2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11-3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40 polymorphisms may contribute to melanoma susceptibility and influence patient outcome. PMID:25848976

  14. Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes

    PubMed Central

    Fang, Shenying; Wang, Yuling; Chun, Yun S; Liu, Huey; Ross, Merrick I; Gershenwald, Jeffrey E; Cormier, Janice N; Royal, Richard E; Lucci, Anthony; Schacherer, Christopher W; Reveille, John D; Chen, Wei; Sui, Dawen; Bassett, Roland L; Wang, Li-E; Wei, Qingyi; Amos, Christopher I; Lee, Jeffrey E

    2015-01-01

    Recent investigation has identified association of IL-12p40 blood levels with melanoma recurrence and patient survival. No studies have investigated associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL-12p40 blood levels or their potential contributions to melanoma susceptibility or patient outcome. In the current study, 818,237 SNPs were available for 1,804 melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573 cases (discovery), 249 cases (case validation), and 299 controls (control validation). SNPs were evaluated for association with log[IL-12p40] levels in the discovery data set and replicated in two validation data sets, and significant SNPs were assessed for association with melanoma susceptibility and patient outcomes. The most significant SNP associated with log[IL-12p40] was in the IL-12B gene region (rs6897260, combined P=9.26 × 10?38); this single variant explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1 was rs6895454 (combined P=2.24 × 10?9). A marker in IL12B was associated with melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00–2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11–3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40 polymorphisms may contribute to melanoma susceptibility and influence patient outcome. PMID:25848976

  15. Molecular population genetics of the melanic plumage polymorphism in Arctic skuas (Stercorarius parasiticus): evidence for divergent selection on plumage colour.

    PubMed

    Janssen, Kirstin; Mundy, Nicholas I

    2013-09-01

    The Arctic skua (Stercorarius parasiticus) is a classic example of an avian plumage polymorphism, with variation in melanin-based ventral plumage coloration defining pale, intermediate and dark morphs in adults of both sexes. However, despite several decades of field research, there is an incomplete understanding of how the polymorphism in ventral plumage colour is maintained and the selective forces involved. Here, we investigate selection on a locus (MC1R) that is strongly associated with plumage colour variation in Arctic skuas using patterns of nucleotide variation and comparison to neutral loci (nuclear introns and mtDNA). We find that three linked nonsynonymous mutations in MC1R, including the single mutation described previously, are associated with plumage colour in the Arctic skua. The position of nonsynonymous mutations on a MC1R haplotype network implies that divergent selection drove the initial evolution of the colour morphs. Comparisons of F(ST)s of MC1R vs. nuclear introns among five skua populations differing in proportion of dark morphs along an approximate north-south cline reveal a signature of divergent selection on MC1R. In contrast, we find limited evidence for balancing selection on MC1R within populations, although the power is low. Our results provide strong evidence for both past and ongoing selection on MC1R, and, by implication, plumage colour in Arctic skuas. The results suggest that a fruitful avenue for future ecological studies will be analysis of selection on morphs in colonies at the extremes along the morph ratio cline. PMID:23980902

  16. Am. J. Hum. Genet. 64:13711377, 1999 Modification of BRCA1-Associated Breast Cancer Risk by the Polymorphic

    E-print Network

    Brown, Myles

    Am. J. Hum. Genet. 64:1371­1377, 1999 1371 Modification of BRCA1-Associated Breast Cancer Risk gene have a greatly increased risk of developing breast cancer. However, there is also substantial interindividual vari- ability in the occurrence of breast cancer among BRCA1 mutation carriers. We hypothesize

  17. Genetic identity, ancestry and parentage in farmer selections of cacao from Aceh, Indonesia revealed by single nucleotide polymorphism (SNP) markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cacao (Theobroma cacao L.) is the source of cocoa powder and butter used for chocolate and this species originated in the rainforests of South America. Indonesia is the 3rd largest cacao producer in the world with an annual cacao output of 0.55 million tons. Knowledge of on-farm genetic diversity is...

  18. Associations between genetic polymorphisms of insulin-like growth factor axis genes and risk for age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: Our objective was to investigate if insulin-like growth factor (IGF) axis genes affect the risk for age-related macular degeneration (AMD). Methods: 864 Caucasian non-diabetic participants from the Age-Related Eye Disease Study (AREDS) Genetic Repository were used in this case control st...

  19. Single nucleotide polymorphism-specific regulation of matrix metalloproteinase-9 by multiple miRNAs targeting the coding exon

    PubMed Central

    Duellman, Tyler; Warren, Christopher; Yang, Jay

    2014-01-01

    Microribonucleic acids (miRNAs) work with exquisite specificity and are able to distinguish a target from a non-target based on a single nucleotide mismatch in the core nucleotide domain. We questioned whether miRNA regulation of gene expression could occur in a single nucleotide polymorphism (SNP)-specific manner, manifesting as a post-transcriptional control of expression of genetic polymorphisms. In our recent study of the functional consequences of matrix metalloproteinase (MMP)-9 SNPs, we discovered that expression of a coding exon SNP in the pro-domain of the protein resulted in a profound decrease in the secreted protein. This missense SNP results in the N38S amino acid change and a loss of an N-glycosylation site. A systematic study demonstrated that the loss of secreted protein was due not to the loss of an N-glycosylation site, but rather an SNP-specific targeting by miR-671-3p and miR-657. Bioinformatics analysis identified 41 SNP-specific miRNA targeting MMP-9 SNPs, mostly in the coding exon and an extension of the analysis to chromosome 20, where the MMP-9 gene is located, suggesting that SNP-specific miRNAs targeting the coding exon are prevalent. This selective post-transcriptional regulation of a target messenger RNA harboring genetic polymorphisms by miRNAs offers an SNP-dependent post-transcriptional regulatory mechanism, allowing for polymorphic-specific differential gene regulation. PMID:24627221

  20. Breast cancer screening for Korean women must consider traditional risks as well as two genetic risk factors: genetic polymorphisms and inheritable gene mutations.

    PubMed

    Anderson, Gwen; Jun, Myunghee; Choi, Kyungsook

    2007-01-01

    Asian women worldwide have increasing rates of breast cancer due to acculturation which may be altering, gene to gene and/or, genetic and environmental interactions at the cellular level. The purpose of this integrative review is to alert nurses and physicians to rising rates of breast cancer among Korean women and to a need for breast health screening programs in the United States that are more culturally responsive and attentive to the effects of acculturation and genetic risk factors. A comprehensive review of the English and Korean literature pertaining to rising incidence of breast cancer among Korean women in their homeland and in the United States is retraced since 1983. Korean women in Korea and in the United States face similar barriers to cancer screening services. Korean women need knowledge about the effect of acculturation on breast cancer risk and patterns of familial inheritance of breast cancer. Screening is especially important among younger women (younger than age 35), those with a strong family history, and women in community settings where acculturation has its greatest impact. Nurse clinicians and researchers who aim to improve breast cancer screening among minority women must pay closer attention to these risk factors and design culturally competent services and evaluation research. In the United States and Korea, Korean nurses are needed to specialize in breast cancer screening as well as cancer genetic risk assessment and genetic counseling. PMID:17510585

  1. Genetic polymorphisms in the one-carbon metabolism pathway genes and susceptibility to non-Hodgkin lymphoma.

    PubMed

    Suthandiram, Sujatha; Gan, Gin-Gin; Mohd Zain, Shamsul; Bee, Ping-Chong; Lian, Lay-Hoong; Chang, Kian-Meng; Ong, Tee-Chuan; Mohamed, Zahurin

    2015-03-01

    Corroborating evidence related to the role of aberrations on one-carbon metabolism (OCM) genes has been inconsistent. We evaluated the association between polymorphisms in 12 single nucleotide polymorphisms (SNPs) in 8 OCM genes (CBS, FPGS, FTHFD, MTRR, SHMT1, SLC19A1, TCN1, and TYMS), and non-Hodgkin lymphoma (NHL) risk in a multi-ethnic population which includes Malay, Chinese and Indian ethnic subgroups. Cases (N?=?372) and controls (N?=?722) were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects showed a significantly enhanced NHL risk for CBS Ex9?+?33C?>?T (T versus C: OR 1.55, 95% CI 1.22-1.96, P?=?0.0003), CBS Ex18-319G?>?A (A versus G: OR 1.15, 95% CI 1.14-1.83; P?=?0.002), SHMT1 Ex12?+?236 T?>?C (T versus C: OR 1.44, 95% CI 1.15-1.81, P?=?0.002), and TYMS Ex8?+?157C?>?T (T versus C: OR 1.29, 95% CI 1.06-1.57, P?=?0.01). Haplotype analysis for CBS SNPs showed a significantly decreased risk of NHL in subjects with haplotype CG (OR 0.69, 95% CI 0.56-0.86, P?=?<0.001). The GG haplotype for the FTHFD SNPs showed a significant increased risk of NHL (OR 1.40, 95% CI 1.12-1.76, P?=?0.002). For the TYMS gene, haplotype CAT at TYMS (OR 0.67, 95% CI 0.49-0.90, P?=?0.007) was associated with decreased risk of NHL, while haplotype TAC (OR 1.29, 95% CI 1.05-1.58, P?=?0.01) was found to confer increased risk of NHL. Our study suggests that variation in several OCM genes (CBS, FTHFD, SHMT1, TCN1, and TYMS) may influence susceptibility to NHL. PMID:25384508

  2. Gene number determination and genetic polymorphism of the gamma delta T cell co-receptor WC1 genes

    PubMed Central

    2012-01-01

    Background WC1 co-receptors belong to the scavenger receptor cysteine-rich (SRCR) superfamily and are encoded by a multi-gene family. Expression of particular WC1 genes defines functional subpopulations of WC1+ ?? T cells. We have previously identified partial or complete genomic sequences for thirteen different WC1 genes through annotation of the bovine genome Btau_3.1 build. We also identified two WC1 cDNA sequences from other cattle that did not correspond to sequences in the Btau_3.1 build. Their absence in the Btau_3.1 build may have reflected gaps in the genome assembly or polymorphisms among animals. Since the response of ?? T cells to bacterial challenge is determined by WC1 gene expression, it was critical to understand whether individual cattle or breeds differ in the number of WC1 genes or display polymorphisms. Results Real-time quantitative PCR using DNA from the animal whose genome was sequenced (“Dominette”) and sixteen other animals representing ten breeds of cattle, showed that the number of genes coding for WC1 co-receptors is thirteen. The complete coding sequences of those thirteen WC1 genes is presented, including the correction of an error in the WC1-2 gene due to mis-assembly in the Btau_3.1 build. All other cDNA sequences were found to agree with the previous annotation of complete or partial WC1 genes. PCR amplification and sequencing of the most variable N-terminal SRCR domain (domain 1 which has the SRCR “a” pattern) of each of the thirteen WC1 genes showed that the sequences are highly conserved among individuals and breeds. Of 160 sequences of domain 1 from three breeds of cattle, no additional sequences beyond the thirteen described WC1 genes were found. Analysis of the complete WC1 cDNA sequences indicated that the thirteen WC1 genes code for three distinct WC1 molecular forms. Conclusion The bovine WC1 multi-gene family is composed of thirteen genes coding for three structural forms whose sequences are highly conserved among individual cattle and breeds. The sequence diversity necessary for WC1 genes to function as a multi-genic pattern recognition receptor array is encoded in the genome, rather than generated by recombinatorial diversity or hypermutation. PMID:23072335

  3. A comparison of genetic map distance and linkage disequilibrium between 15 polymorphic dinucleotide repeat loci in two populations

    SciTech Connect

    Urbanek, M.; Goldman, D.; Long, J.C.

    1994-09-01

    Linkage disequilibrium has recently been used to map the diastrophic dysplasia gene in a Finnish sample. One advantage of this method is that the large pedigrees required by some other methods are unnecessary. Another advantage is that linkage disequilibrium mapping capitalizes on the cumulative history of recombination events, rather than those occurring within the sampled individuals. A potential limitation of linkage disequilibrium mapping is that linkage equilibrium is likely to prevail in all but the most isolated populations, e.g., those which have recently experienced founder effects or severe population bottlenecks. In order to test the method`s generality, we examined patterns of linkage disequilibrium between pairs of loci within a known genetic map. Two populations were analyzed. The first population, Navajo Indians (N=45), is an isolate that experienced a severe bottleneck in the 1860`s. The second population, Maryland Caucasians (N=45), is cosmopolitan. We expected the Navajo sample to display more linkage disequilibrium than the Caucasian sample, and possibly that the Navajo disequilibrium pattern would reflect the genetic map. Linkage disequilibrium coefficients were estimated between pairs of alleles at different loci using maximum likelihood. The genetic isolate structure of Navajo Indians is confirmed by the DNA typings. Heterozygosity is lower than in the Caucasians, and fewer different alleles are observed. However, a relationship between genetic map distance and linkage disequilibrium could be discerned in neither the Navajo nor the Maryland samples. Slightly more linkage disequilibrium was observed in the Navajos, but both data sets were characterized by very low disequilibrium levels. We tentatively conclude that linkage disequilibrium mapping with dinucleotide repeats will only be useful with close linkage between markers and diseases, even in very isolated populations.

  4. Integrating mechanistic and polymorphism data to characterize human genetic susceptibility for environmental chemical risk assessment in the 21st century

    SciTech Connect

    Mortensen, Holly M.; Euling, Susan Y.

    2013-09-15

    Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from high-throughput/high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization of drug target and disease loci, and have been successfully utilized to inform the mechanism of action for numerous environmental chemicals. Large-scale population genotyping studies may help to characterize levels of variability across human populations at identified target loci implicated in response to environmental chemicals. By combining mechanistic data for a given environmental chemical with next generation sequencing data that provides human population variation information, one can begin to characterize differential susceptibility due to genetic variability to environmental chemicals within and across genetically heterogeneous human populations. The integration of such data sources will be informative to human health risk assessment.

  5. Integrating mechanistic and polymorphism data to characterize human genetic susceptibility for environmental chemical risk assessment in the 21st century.

    PubMed

    Mortensen, Holly M; Euling, Susan Y

    2013-09-15

    Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from high-throughput/high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization of drug target and disease loci, and have been successfully utilized to inform the mechanism of action for numerous environmental chemicals. Large-scale population genotyping studies may help to characterize levels of variability across human populations at identified target loci implicated in response to environmental chemicals. By combining mechanistic data for a given environmental chemical with next generation sequencing data that provides human population variation information, one can begin to characterize differential susceptibility due to genetic variability to environmental chemicals within and across genetically heterogeneous human populations. The integration of such data sources will be informative to human health risk assessment. PMID:21291902

  6. Population genetics of dinucleotide (dC-dA)n.(dG-dT)n polymorphisms in world populations.

    PubMed Central

    Deka, R; Jin, L; Shriver, M D; Yu, L M; DeCroo, S; Hundrieser, J; Bunker, C H; Ferrell, R E; Chakraborty, R

    1995-01-01

    We have characterized eight dinucleotide (dC-dA)n.(dG-dT)n repeat loci located on human chromosome 13q in eight human populations and in a sample of chimpanzees. Even though there is substantial variation in allele frequencies at each locus, at a given locus the most frequent alleles are shared by all human populations. The level of heterozygosity is reduced in isolated or small populations, such as the Pehuenche Indians of Chile, the Dogrib of Canada, and the New Guinea highlanders. On the other hand, larger average heterozygosities are observed in large and cosmopolitan populations, such as the Sokoto population from Nigeria and German Caucasians. Conformity with Hardy-Weinberg equilibrium is generally observed at these loci, unless (a) a population is isolated or small or (b) the repeat motif of the locus is not perfect (e.g., D13S197). Multilocus genotype probabilities at these microsatellite loci do not show departure from the independence rule, unless the loci are closely linked. The allele size distributions at these (CA)n loci do not follow a strict single-step stepwise-mutation model. However, this features does not compromise the ability to detect population affinities, when these loci are used simultaneously. The microsatellite loci examined here are present and, with the exception of the locus D13S197, are polymorphic in the chimpanzees, showing an overlapping distribution of allele sizes with those observed in human populations. Images Figure 1 PMID:7847383

  7. Biological features of an early-maturity mutant of sweet sorghum induced by carbon ions irradiation and its genetic polymorphism

    NASA Astrophysics Data System (ADS)

    Dong, Xicun; Li, Wenjian

    2012-08-01

    It is well known that heavy ions irradiation is characterized by a high linear energy transfer (LET) and relative biological effectiveness (RBE). These characters are believed to increase mutation frequency and mutation spectrum of plants or mammalian cells irradiated by heavy ions. Here we describe an early-maturity mutant of sweet sorghum induced by carbon ion irradiation. The growth period of this mutant was shortened by about 20 days compared to the wild type. The proline content of the mutant was increased by 11.05% while the malondialdehyde content was significantly lower than that of wild type. In addition, the RAPD analysis indicated that the percentage of polymorphism between the mutant KFJT-1 and the control KFJT-CK reached 5.26%. The gain of early-maturity might solve the problem in the northwest region of China where seeds of sweet sorghum cannot be mature because of early frost. The early-maturity mutant may be important for future space cultivation.

  8. Assessment of the genetic polymorphism and physiological characterization of indigenous Oenococcus oeni strains isolated from Aglianico del Vulture red wine.

    PubMed

    Cafaro, Caterina; Bonomo, Maria Grazia; Guerrieri, Antonio; Crispo, Fabiana; Ciriello, Rosanna; Salzano, Giovanni

    2016-01-01

    The aim of this study was a reliable intra-species discrimination and strain biodiversity in Oenococcus oeni populations of two different Aglianico wineries by molecular, biochemical, and physiological characterization. Pulsed field gel electrophoresis (PFGE) analysis revealed a high polymorphism related to the origin (winery) of strains, while differential display PCR (DD-PCR) allowed a further discrimination of strains from the same winery. Moreover, the heterogeneity of these natural populations was investigated by capillary electrophoresis and enzymatic assays. A variability related to a different surface charge distribution was observed among strains, linked to their origin. Malolactic activity study evidenced strain-specific differences in malic acid degradation, and then, only the presence of L(-)-malic acid in the medium induced the mle gene. This study provided evidences on the importance of intra-species biodiversity of malolactic bacterial populations in wine ecosystems, as each wine possess peculiar winemaking conditions and physical-chemical properties which make specific the bacterial survival and growth. This study highlighted a great biodiversity among O. oeni strains that can be also winery specific. Such biodiversity within a certain winery and winemaking area is important for selecting malolactic starters, and strain-specific trait identification is especially important to match individual strains to specific industrial process. PMID:26016849

  9. A genetic map of chromosome 20q12-q13. 1: Multiple highly polymorphic microsatellite and RFLP markers linked to the maturity-onset diabetes of the Young (MODY) locus

    SciTech Connect

    Rothschild, C.B.; Akots, G.; Hayworth, R.; Pettenati, M.J.; Rao, P.N.; Wood, P. ); Stolz, F.M.; Hansmann, I. ); Serino, K.; Keith, T.P. ); Fajans, S.S. )

    1993-01-01

    Multiple highly polymorphic markers have been used to construct a genetic map of the q12-q13.1 region of chromosome 20 and to map the location of the maturity-onset diabetes of the young (MODY) locus. The genetic map encompasses 23 cM and includes 11 loci with PIC values >.50, seven of which have PICs >.70. New dinucleotide repeat polymorphisms associated with the D20S17, PPGB, and ADA loci have been identified and mapped. The dinucleotide repeat polymorphisms have increased the PIC of the ADA locus to .89 and, with an additional RFLP at the D20S17 locus, the PIC of the D20S17 locus to .88. The order of the D20S17 and ADA loci determined genetically (cen-ADA-D20S17-qter) was confirmed by multicolor fluorescence in situ hybridization. The previously unmapped PPGB marker is closely linked to D20S17, with a two-point lod score of 50.53 at [cflx [theta

  10. Population genetic variation of the Southern Ocean krill, Euphausia superba, in the Western Antarctic Peninsula region based on mitochondrial single nucleotide polymorphisms (SNPs)

    NASA Astrophysics Data System (ADS)

    Batta-Lona, Paola G.; Bucklin, Ann; Wiebe, Peter H.; Patarnello, Tomaso; Copley, Nancy J.

    2011-07-01

    The Southern Ocean krill, Euphausia superba, is one of the best-studied marine zooplankton species in terms of population genetic diversity and structure; with few exceptions, previous studies have shown the species to be genetically homogeneous at larger spatial scales. The goals of this study are to examine sub-regional scale population genetic diversity and structure of E. superba using molecular characters selected with this goal in mind, and to thereby examine hypotheses of the source(s) of recruitment for krill populations of the Western Antarctic Peninsula (WAP). Collections were made throughout the WAP region during US GLOBEC cruises in austral fall, 2001 and 2002. A total of 585 E. superba (including all 6 furcilia larval stages, juveniles, and adults) was analyzed after confirmation of species identification using a competitive multiplexed species-specific PCR (SS-PCR) reaction based on mitochondrial cytochrome oxidase I (mtCOI) sequences. The molecular markers used were allele frequencies at single nucleotide polymorphism (SNP) sites in the gene encoding mitochondrial Cytochrome b (cyt b). Four SNP sites that showed desirable patterns of allelic variation were selected; alleles were detected using a multiplexed single-base extension PCR protocol. A total of 22 SNP haplotypes (i.e., strings of polymorphisms at the four SNP sites) was observed; haplotype diversity (Hd)=0.811 (s.d.=0.008). Analysis of molecular variation within and among samples, areas (i.e., Marguerite Bay, Crystal Sound, shelf, and offshore) and collection years revealed no difference between 2001 and 2002 collections overall, although differences between 2001 and 2002 collections from Marguerite Bay explained 7.4% of the variance ( FST=0.072; p=0.002±0.001). Most of the variation (96.3%) occurred within samples each year, with no significant differentiation among areas. There was small, but significant differentiation among samples within areas in 2001 (4.6%; FST=0.045; p=0.015±0.003) and 2002 (6.3%; FST=0.062; p=0.000±0.000). There was evidence of life stage-specific spatial differentiation for furcilia in 2002 for F1 (18.1%, p=0.000±0.000) and F2 (9.2%, p=0.001±0.001). The significant differentiation among samples for E. superba within areas was interpreted as evidence of multiple sources of recruitment of E. superba in the WAP region, consistent with advective transport in observed circulation patterns and reproduction and spawning in both offshore and shelf habitats. Further population genetic analysis at sub-regional scales is needed to understand and eventually predict population dynamic processes (e.g., recruitment, migration, retention, and over-wintering) of Southern Ocean krill.

  11. Association of Fc gamma-receptors IIa, IIIa, and IIIb genetic polymorphism with susceptibility to chronic periodontitis in South Indian population

    PubMed Central

    Hans, Veenu Madaan; Mehta, Dhoom Singh; Hans, Mayank

    2015-01-01

    Background and Objective: Fc gamma receptors (Fc?Rs) are the members of the immunoglobulin superfamily and may play a role in the pathogenesis of periodontitis. Genetic variation in these receptors and its link with various forms of periodontitis is being studied in different populations. The aim of the present study is to determine whether specific Fc?RIIa, Fc?RIIIa, and Fc?RIIIb alleles and/or genotypes are associated with risk for susceptibility to generalized chronic periodontitis (GCP) in South Indian population. Materials and Methods: The study population consisted of 120 South Indian subjects; 60 with GCP and 60 periodontally healthy. Deoxyribonucleic acid (DNA) was extracted from samples collected by scrapping buccal epithelium. Fc?RIIa and Fc?RIIIa genotyping were performed by polymerase chain reaction (PCR) amplification of DNA with allele-specific primers followed by allele-specific restriction digestion of the products. However, Fc?RIIIb genotyping was done by allele-specific PCR. Results: No significant difference in the distribution of Fc?RIIa H/R and Fc?RIIIa NA1/NA2 genotypes or their respective alleles was observed in GCP patients and healthy subjects. For Fc?RIIIa F/V genetic polymorphism, the homozygous V/V genotype and V allele were significantly overrepresented in GCP patients while F/F genotype and F allele in controls. Conclusion: The present study demonstrates that Fc?RIIIa V/V genotype, as well as V allele, could be a possible risk factor for chronic periodontitis in South Indian population. PMID:26604564

  12. Discovery and mapping of a new expressed sequence tag-single nucleotide polymorphism and simple sequence repeat panel for large-scale genetic studies and breeding of Theobroma cacao L.

    PubMed Central

    Allegre, Mathilde; Argout, Xavier; Boccara, Michel; Fouet, Olivier; Roguet, Yolande; Bérard, Aurélie; Thévenin, Jean Marc; Chauveau, Aurélie; Rivallan, Ronan; Clement, Didier; Courtois, Brigitte; Gramacho, Karina; Boland-Augé, Anne; Tahi, Mathias; Umaharan, Pathmanathan; Brunel, Dominique; Lanaud, Claire

    2012-01-01

    Theobroma cacao is an economically important tree of several tropical countries. Its genetic improvement is essential to provide protection against major diseases and improve chocolate quality. We discovered and mapped new expressed sequence tag-single nucleotide polymorphism (EST-SNP) and simple sequence repeat (SSR) markers and constructed a high-density genetic map. By screening 149 650 ESTs, 5246 SNPs were detected in silico, of which 1536 corresponded to genes with a putative function, while 851 had a clear polymorphic pattern across a collection of genetic resources. In addition, 409 new SSR markers were detected on the Criollo genome. Lastly, 681 new EST-SNPs and 163 new SSRs were added to the pre-existing 418 co-dominant markers to construct a large consensus genetic map. This high-density map and the set of new genetic markers identified in this study are a milestone in cocoa genomics and for marker-assisted breeding. The data are available at http://tropgenedb.cirad.fr. PMID:22210604

  13. Genetics

    MedlinePLUS

    Homozygous; Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  14. Mycobacterium tuberculosis Type II Toxin-Antitoxin Systems: Genetic Polymorphisms and Functional Properties and the Possibility of Their Use for Genotyping.

    PubMed

    Zaychikova, Marina V; Zakharevich, Natalia V; Sagaidak, Maria O; Bogolubova, Nadezhda A; Smirnova, Tatiana G; Andreevskaya, Sofya N; Larionova, Elena E; Alekseeva, Maria G; Chernousova, Larisa N; Danilenko, Valery N

    2015-01-01

    Various genetic markers such as IS-elements, DR-elements, variable number tandem repeats (VNTR), single nucleotide polymorphisms (SNPs) in housekeeping genes and other groups of genes are being used for genotyping. We propose a different approach. We suggest the type II toxin-antitoxin (TA) systems, which play a significant role in the formation of pathogenicity, tolerance and persistence phenotypes, and thus in the survival of Mycobacterium tuberculosis in the host organism at various developmental stages (colonization, infection of macrophages, etc.), as the marker genes. Most genes of TA systems function together, forming a single network: an antitoxin from one pair may interact with toxins from other pairs and even from other families. In this work a bioinformatics analysis of genes of the type II TA systems from 173 sequenced genomes of M. tuberculosis was performed. A number of genes of type II TA systems were found to carry SNPs that correlate with specific genotypes. We propose a minimally sufficient set of genes of TA systems for separation of M. tuberculosis strains at nine basic genotype and for further division into subtypes. Using this set of genes, we genotyped a collection consisting of 62 clinical isolates of M. tuberculosis. The possibility of using our set of genes for genotyping using PCR is also demonstrated. PMID:26658274

  15. A single-nucleotide polymorphism-based approach for rapid and cost-effective genetic wolf monitoring in Europe based on noninvasively collected samples.