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Sample records for cag repeat polymorphism

  1. Positive association of the androgen receptor CAG repeat length polymorphism with the risk of prostate cancer.

    Science.gov (United States)

    Paz-Y-Miño, César; Robles, Paulo; Salazar, Carolina; Leone, Paola E; García-Cárdenas, Jennyfer M; Naranjo, Manuel; López-Cortés, Andrés

    2016-08-01

    Prostate cancer (PC) is the most frequently diagnosed cancer in Ecuador (15.6%). The androgen receptor gene codes for a protein that has an androgen‑binding domain, DNA‑binding domain and N‑terminal domain, which contains two polymorphic trinucleotide repeats (CAG and GGC). The aim of the present study was to determine whether variations in the number of repetitions of CAG and GGC are associated with the pathological features and the risk of developing PC. The polymorphic CAG and GGC repeat lengths in 108 mestizo patients with PC, 148 healthy mestizo individuals, and 78 healthy indigenous individuals were examined via a retrospective case‑control study. Genotypes were determined by genomic sequencing. The results demonstrated that patients with ≤21 CAG repeats have an increased risk of developing PC [odds ratio (OR)=2.99, 95% confidence interval (CI) =1.79‑5.01; P<0.001]. The presence of ≤21 CAG repeats was also associated with a tumor stage ≥T2c (OR=4.75; 95% CI=1.77‑12.72; P<0.005) and a Gleason score ≥7 (OR=2.9; 95% CI=1.1‑7.66; P=0.03). In addition, the combination of ≤21 CAG and ≥17 GGC repeats was associated with the risk of developing PC (OR=2.42; 95% CI=1.38‑4.25; P=0.002) and with tumor stage ≥T2c (OR=2.77; 95% CI=1.13‑6.79; P=0.02). In conclusion, the histopathological characteristics and PC risk in Ecuadorian indigenous and mestizo populations differs in association with the CAG repeats, and the combination of CAG and GGC repeats. PMID:27357524

  2. Androgen Receptor CAG Repeat Polymorphism and Epigenetic Influence among the South Indian Women with Polycystic Ovary Syndrome

    OpenAIRE

    Shilpi Dasgupta; Pisapati V S Sirisha; Kudugunti Neelaveni; Kathragadda Anuradha; Alla G Reddy; Kumarasamy Thangaraj; B Mohan Reddy

    2010-01-01

    The present study was carried out to assess the role of androgen receptor CAG repeat polymorphism and X chromosome inactivation (XCI) pattern among Indian PCOS women and controls which has not been hitherto explored and also to test the hypothesis that shorter CAG alleles would be preferentially activated in PCOS. CAG repeat polymorphism and X chromosome methylation patterns were compared between PCOS and non-PCOS women. 250 PCOS women and 299 controls were included for this study. Androgen r...

  3. MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington's disease mice.

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    Stéphanie Tomé

    Full Text Available Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD (CAG∼100 transgene, when present in a congenic C57BL/6J (B6 background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with

  4. The impact of the CAG repeat polymorphism of the androgen receptor gene on muscle and adipose tissues in 20-29-year-old Danish men: Odense Androgen Study

    DEFF Research Database (Denmark)

    Nielsen, Torben Leo; Hagen, Claus; Wraae, Kristian;

    2010-01-01

    The number of CAG repeats (CAG(n)) within the CAG repeat polymorphism of the androgen receptor gene correlates inversely with the transactivation of the receptor.......The number of CAG repeats (CAG(n)) within the CAG repeat polymorphism of the androgen receptor gene correlates inversely with the transactivation of the receptor....

  5. Relationships among androgen receptor CAG repeat polymorphism, sex hormones and penile length in Han adult men from China:a cross-sectional study

    Institute of Scientific and Technical Information of China (English)

    YanMin Ma; DaLin He; KaiJie Wu; Liang Ning; Jin Zeng; Bo Kou; HongJun Xie; ZhenKun Ma; XinYang Wang; YongGuang Gong

    2014-01-01

    This study aimed to investigate the correlations among androgen receptor (AR) CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and iffty-three healthy men (aged 22.8 ± 3.1 years) were enrolled. The individuals were grouped as CAG short (CAGS) if they harbored repeat length of≤20 or as CAG long (CAGL) if their CAG repeat length was>20. Body height/weight, penile length and other parameters were examined and recorded by the speciifed physicians;CAG repeat polymorphism was determined by the polymerase chain reaction (PCR) method;and the serum levels of the sex hormones were detected by radioimmunoassay. Student’s t-test or linear regression analysis was used to assess the associations among AR CAG repeat polymorphism, sex hormones and penile length. This investigation showed that the serum total testosterone (T) level was positively associated with the AR CAG repeat length (P= 0.01); whereas, no signiifcant correlation of T or AR CAG repeat polymorphism with the penile length was found (P= 0.593). Interestingly, an inverse association was observed between serum prolactin (PRL) levels and penile length by linear regression analyses (b=-0.024, P= 0.039, 95%conifdence interval (CI):-0.047, 0). Collectively, this study provides the ifrst evidence that serum PRL, but not T or AR CAG repeat polymorphism, is correlated with penile length in the Han adult population from northwestern China.

  6. Association analysis of a highly polymorphic CAG Repeat in the human potassium channel gene KCNN3 and migraine susceptibility

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    Ovcaric Mick

    2005-09-01

    Full Text Available Abstract Background Migraine is a polygenic multifactorial disease, possessing environmental and genetic causative factors with multiple involved genes. Mutations in various ion channel genes are responsible for a number of neurological disorders. KCNN3 is a neuronal small conductance calcium-activated potassium channel gene that contains two polyglutamine tracts, encoded by polymorphic CAG repeats in the gene. This gene plays a critical role in determining the firing pattern of neurons and acts to regulate intracellular calcium channels. Methods The present association study tested whether length variations in the second (more 3' polymorphic CAG repeat in exon 1 of the KCNN3 gene, are involved in susceptibility to migraine with and without aura (MA and MO. In total 423 DNA samples from unrelated individuals, of which 202 consisted of migraine patients and 221 non-migraine controls, were genotyped and analysed using a fluorescence labelled primer set on an ABI310 Genetic Analyzer. Allele frequencies were calculated from observed genotype counts for the KCNN3 polymorphism. Analysis was performed using standard contingency table analysis, incorporating the chi-squared test of independence and CLUMP analysis. Results Overall, there was no convincing evidence that KCNN3 CAG lengths differ between Caucasian migraineurs and controls, with no significant difference in the allelic length distribution of CAG repeats between the population groups (P = 0.090. Also the MA and MO subtypes did not differ significantly between control allelic distributions (P > 0.05. The prevalence of the long CAG repeat (>19 repeats did not reach statistical significance in migraineurs (P = 0.15, nor was there a significant difference between the MA and MO subgroups observed compared to controls (P = 0.46 and P = 0.09, respectively, or between MA vs MO (P = 0.40. Conclusion This association study provides no evidence that length variations of the second polyglutamine array in

  7. CAG repeat polymorphisms in the androgen receptor and breast cancer risk in women: a meta-analysis of 17 studies

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    Mao Q

    2015-08-01

    Full Text Available Qixing Mao,1–3,* Mantang Qiu,1–3,* Gaochao Dong,3 Wenjie Xia,1–3 Shuai Zhang,1,3 Youtao Xu,1,3 Jie Wang,3 Yin Rong,1,3 Lin Xu,1,3 Feng Jiang1,3 1Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Institute of Jiangsu Province, 2Fourth Clinical College of Nanjing Medical University, 3Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: The association between polymorphic CAG repeats in the androgen receptor gene in women and breast cancer susceptibility has been studied extensively. However, the conclusions regarding this relationship remain conflicting. The purpose of this meta-analysis was to identify whether androgen receptor CAG repeat lengths were related to breast cancer susceptibility. The MEDLINE, PubMed, and EMBASE databases were searched through to December 2014 to identify eligible studies. Data and study quality were rigorously assessed by two investigators according to the Newcastle-Ottawa Quality Assessment Scale. The publication bias was assessed by the Begg’s test. Seventeen eligible studies were included in this meta-analysis. The overall analysis suggested no association between CAG polymorphisms and breast cancer risk (odds ratio [OR] 1.031, 95% confidence interval [CI] 0.855–1.245. However, in the subgroup analysis, we observed that long CAG repeats significantly increased the risk of breast cancer in the Caucasian population (OR 1.447, 95% CI 1.089–1.992. Additionally, the risk was significantly increased in Caucasian women carrying two alleles with CAG repeats ≥22 units compared with those with two shorter alleles (OR 1.315, 95% CI 1.014–1.707. These findings suggest that long CAG repeats increase the risk of breast cancer in Caucasian women. However, larger scale case-control studies are needed to validate our results. Keywords: androgen, CAG repeat polymorphism, women

  8. Androgen receptor CAG repeats length polymorphism and the risk of polycystic ovarian syndrome (PCOS.

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    Singh Rajender

    Full Text Available OBJECTIVE: Polycystic ovarian syndrome (PCOS refers to an inheritable androgen excess disorder characterized by multiple small follicles located at the ovarian periphery. Hyperandrogenism in PCOS, and inverse correlation between androgen receptor (AR CAG numbers and AR function, led us to hypothesize that CAG length variations may affect PCOS risk. METHODS: CAG repeat region of 169 patients recruited following strictly defined Rotterdam (2003 inclusion criteria and that of 175 ethnically similar control samples, were analyzed. We also conducted a meta-analysis on the data taken from published studies, to generate a pooled estimate on 2194 cases and 2242 controls. RESULTS: CAG bi-allelic mean length was between 8.5 and 24.5 (mean = 17.43, SD = 2.43 repeats in the controls and between 11 and 24 (mean = 17.39, SD = 2.29 repeats in the cases, without any significant difference between the two groups. Further, comparison of bi-allelic mean and its frequency distribution in three categories (short, moderate and long alleles did not show any significant difference between controls and various case subgroups. Frequency distribution of bi-allelic mean in two categories (extreme and moderate alleles showed over-representation of extreme sized alleles in the cases with marginally significant value (50.3% vs. 61.5%, χ(2 = 4.41; P = 0.036, which turned insignificant upon applying Bonferroni correction for multiple comparisons. X-chromosome inactivation analysis showed no significant difference in the inactivation pattern of CAG alleles or in the comparison of weighed bi-allelic mean between cases and controls. Meta-analysis also showed no significant correlation between CAG length and PCOS risk, except a minor over-representation of short CAG alleles in the cases. CONCLUSION: CAG bi-allelic mean length did not differ between controls and cases/case sub-groups nor did the allele distribution. Over-representation of short

  9. ANDROGEN RECEPTOR CAG AND GGN REPEAT POLYMORPHISMS AND BONE MASS IN BOYS AND GIRLS.

    Science.gov (United States)

    Rodríguez-Garcia, Lorena; Ponce-Gonzalez, Jesus G; González-Henriquez, Juan J; Rodriguez-Gonzalez, Francisco G; Díaz-Chico, Bonifacio N; Calbet, Jose A L; Serrano-Sanchez, José A; Dorado, Cecilia; Guadalupe-Grau, Amelia

    2015-12-01

    Introducción: el gen humano del receptor de androgenos (AR) posee dos repeticiones polimorficas de trinucleotidos (CAG y GGN) que afectan a la cantidad de proteina AR traducida. En este estudio, genotipamos esos tractos polimorficos en una muestra representativa de ninos caucasicos espanoles (Tanner ≤ 5), compuesta por 152 ninos (11.5 } 2.6 anos) y 116 ninas (10.1 } 3.2 anos) e investigamos su asociacion con la masa osea. Métodos: la longitud de las repeticiones CAG y GGN se determino mediante PCR y analisis de fragmentos. La composicion corporal se midio mediante absorciometria dual de rayos X (DXA). Los participantes fueron agrupados como CAG cortos (CAGS) si poseian una longitud de repeticiones ≤ 21 y CAG largos si esta era > 21. Ademas, los participantes se agruparon como GGN cortos (GGNS) si poseian una longitud de repeticiones ≤ 23 y GGN largos (GGNL) si esta era > 23. Resultados: en los ninos se encontraron diferencias en talla, peso corporal, densidad mineral osea (BMD) y contenido mineral oseo (BMC) del cuerpo entero, BMC de las extremidades superiores e inferiores, BMD del cuello del femur, BMC y BMD del triangulo de Ward’s y BMD de la espina lumbar entre los grupos CAGS y CAGL (P < 0,05). Ademas, el BMD de las extremidades superiores fue significativamente diferente entre los grupos GGNS y GGNL. Tras ajustar por variables confusoras, la unica diferencia que se mantuvo significativa fue la del BMD en las extremidades superiores entre los grupos GGNS y GGNL (P < 0,05). No se observaron diferencias entre los grupos CAG y GGN y la masa osea en las ninas. Conclusiones: nuestros resultados apoyan la hipotesis de que los alelos largos de los polimorfismos CAG y GGN del AR estan asociados con una mayor masa osea en ninos prepuberes.

  10. Association of the polymorphism of the CAG repeat in the mitochondrial DNA polymerase gamma gene (POLG) with testicular germ-cell cancer

    DEFF Research Database (Denmark)

    Blomberg Jensen, M; Leffers, H; Petersen, J H;

    2008-01-01

    BACKGROUND: A possible association between the polymorphic CAG repeat in the DNA polymerase gamma (POLG) gene and the risk of testicular germ-cell tumours (TGCT) was investigated in this study. The hypothesis was prompted by an earlier preliminary study proposing an association of the absence of ...

  11. 男乳癌与 AR 基因 CAG 重复多态性的相关性研究%Related research of male breast cancer and CAG repeat polymorphism of AR gene

    Institute of Scientific and Technical Information of China (English)

    崔佳琳; 黄睿; 姜永冬; 韩继广; 牛明; 魏巍; 郑伟; 宋燕妮

    2015-01-01

    目的:探讨雄激素受体( AR)基因外显子CAG重复频数多态性与男性乳腺癌(男乳癌)发病风险的关系。方法研究对象为40例男性乳腺癌患者和40例男性健康者,从外周血提取DNA,对AR基因外显子CAG编码序列进行PCR扩增、测序和计算CAG重复频数,用χ2检验和Logistic回归分析AR基因CAG重复频数长度对男乳癌发病风险的影响。结果男性乳腺癌病例组和对照组CAG重复频数长度存在差异,其差异具有统计学意义,CAG重复频数长度超过22男性乳腺癌发病风险是重复频数长度少于21的3.52倍(OR=3.52,P=0.036)。结论 AR基因CAG重复频数长度是预测男性乳腺癌发病风险的指标,较长(超过22)的CAG重复序列可增加男乳癌的发病风险。%Objectiv e To investigate the correlation between ( CAG) n repeat polymorphism of androgen receptor(AR)geneandmalebreastcancer.Methods 40casesofmalebreastcancerand40controlswerecol-lected.DNA was extracted from peripheral blood and the AR gene CAG coding exon sequences for PCR amplifica -tion,sequencing and calculated the number of CAG repeats frquency .χ2 test and Logistic regression analysis were used assess the AR gene CAG repeat length frequency affect the number of male breast cancer risk .Results There was statistically significant difference in male breast cancer cases and controls the number of CAG repeat length frequency.Man for whom the(CAG)n≥22 repeat sequence had 3.52 times risk of male breast compared (CAG)n≤22(OR=3.52,P=0.036).Conclusion AR gene CAG repeat length is a predictor of the frequency of male breast cancer risk .Longer CAG repeats can increase the risk of male breast cancer .

  12. No effects of androgen receptor gene CAG and GGC repeat polymorphisms on digit ratio (2D:4D): Meta-analysis

    OpenAIRE

    Voracek, Martin

    2013-01-01

    Objectives: A series of meta-analyses assessed whether differentially efficacious variants (CAG and GGC repeat-length polymorphisms) of the human androgen receptor gene are associated with digit ratio (2D:4D), a widely investigated putative pointer to prenatal androgen action. Methods: Extensive literature search strategies identified a maximum of 16 samples (total N = 2157) eligible for meta-analysis. Results: In contrast to a small-sample (N = 50) initial report, widely cited affirmatively ...

  13. Contributions by the CAG-repeat Polymorphism of the Androgen Receptor Gene and Circulating Androgens to Muscle Size. Odense Androgen Study - A Population-based Study of 20-29 Year-old Danish Men

    DEFF Research Database (Denmark)

    Nielsen, Torben Leo; Hagen, Claus; Wraae, Kristian;

    2007-01-01

    -29 years, who matched the background population as regards body mass index, chronic disease, medication, physical activity, smoking, and sociodemographic parameters. Genotyping was performed in 767 men, whole body DXA in 783 men, and MRI in 406 consecutively included men. Main Outcome Measures: Six......-repeat number correlated inversely with thigh and axial muscle area and with lower and upper extremity lean body mass. Except for upper extremity lean body mass, these findings remained significant in multivariate analyses controlling for circulating androgens, physical activity, smoking, alcohol intake......Context: The number of CAG-repeats within the CAG-repeat polymorphism of the androgen receptor gene is inversely correlated with the transcriptional activity of the androgen receptor. Objective: To study the effect of the CAG-repeat number and circulating androgens on muscle size, to examine...

  14. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

    DEFF Research Database (Denmark)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty;

    2011-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

  15. How strong is the association between CAG and GGN repeat length polymorphisms in the androgen receptor gene and prostate cancer risk?

    NARCIS (Netherlands)

    Zeegers, M.P.; Kiemeney, L.A.L.M.; Nieder, A.M.; Ostrer, H.

    2004-01-01

    OBJECTIVE: Although narrative reviews have suggested an association between (CAG)n and (GGN)n polymorphisms in the AR gene and prostate cancer, it has never been quantified systematically. The purpose of this meta-analysis was to provide relative and absolute quantitative summary estimates with suff

  16. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten;

    2013-01-01

    on an infantile SCA2 patient who, due to germ-line CAG repeat instability in her father, inherited an extremely expanded CAG repeat in the SCA2 locus. Surprisingly, the expanded allele of the father was an interrupted CAG repeat sequence. Furthermore, analyses of single spermatozoa showed a high frequency...

  17. Androgen receptor CAG polymorphism and the risk of benign prostatic hyperplasia in a Brazilian population

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    Vanderlei Biolchi

    2012-06-01

    Full Text Available Benign prostatic hyperplasia (BPH is a very frequent age-related proliferative abnormality in men. Polymorphic CAG repeat in the androgen receptor (AR can alter transactivation of androgen-responsive genes and potentially influence BPH risk. We investigated the association between CAG repeat length and risk of BPH in a case-control study of a Brazilian population. We evaluated 214 patients; 126 with BPH and 88 healthy controls. DNA was extracted from peripheral leucocytes and the AR gene was analyzed using fragment analysis. Hazard ratio (HR and 95% confidence interval were estimated using logistic regression models. Mean CAG length was not different between patients with BPH and controls. The CAG repeat length was examined as a categorical variable (CAG 21 and CAG 22 and did not differ between the control vs. the BPH group. We found no evidence for an association between AR CAG repeat length in BPH risk in a population-based sample of Brazilians.

  18. The relationship between anogenital distance and the androgen receptor CAG repeat length

    Institute of Scientific and Technical Information of China (English)

    Michael L Eisenberg; Tung-Chin Hsieh; Alexander W Pastuszak; Matthew G McIntyre; Rustin C Walters; Dolores J Lamb; Larry I Lipshultz

    2013-01-01

    Anogenital distance (AGD) is used to define degree of virilization of genital development,with shorter length being associated with feminization and male infertility.The first exon of the androgen receptor (AR) consists of a polymorphic sequence of cytosine-adenine-guanine (CAG) repeats,with longer CAG repeat lengths being associated with decreased receptor function.We sought to determine if there is an association between AGD and AR CAG repeat length.A cross-sectional,prospective cohort of men evaluated at a urology clinic at a single institution was recruited.AGD (the distance from the posterior scrotum to the anal verge) and penile length (PL) were measured.Sanger DNA sequence analysis was used to define CAG repeat length.AGD and CAG repeat lengths in 195 men were determined.On unadjusted analysis,there was no linear relationship between CAG repeat length and PL (P=0.17) or AGD (P=0.31).However,on sub-population analyses,those men with longer CAG repeat lengths (>26) had significantly shorter AGDs compared to men with shorter CAG repeat lengths.For example,the mean AGD was 41.9 vs.32.4 mm with a CAG repeat length ≤ 26 vs.>26 (P=0.01).In addition,when stratifying the cohort based on AGD,those with AGD less than the median (i.e.40 mm) had a longer CAG repeat length compared to men with an AGD >40 mm (P=0.02).In summary,no linear relationship was found between AGD and AR CAG repeat length overall.

  19. An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting.

    Science.gov (United States)

    Saffert, Paul; Adamla, Frauke; Schieweck, Rico; Atkins, John F; Ignatova, Zoya

    2016-08-26

    Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the -1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5' end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1. PMID:27382061

  20. In Vitro Expansion of CAG, CAA, and Mixed CAG/CAA Repeats

    OpenAIRE

    Grzegorz Figura; Edyta Koscianska; Krzyzosiak, Wlodzimierz J.

    2015-01-01

    Polyglutamine diseases, including Huntington’s disease and a number of spinocerebellar ataxias, are caused by expanded CAG repeats that are located in translated sequences of individual, functionally-unrelated genes. Only mutant proteins containing polyglutamine expansions have long been thought to be pathogenic, but recent evidence has implicated mutant transcripts containing long CAG repeats in pathogenic processes. The presence of two pathogenic factors prompted us to attempt to distinguis...

  1. Counting CAG repeats in the Huntington’s disease gene by restriction endonuclease EcoP15I cleavage

    OpenAIRE

    Moencke-Buchner, E.; Reich, S.; Muecke, M.; M. Reuter; Messer, W; Wanker, E E; Krueger, D.H.

    2002-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder with autosomal-dominant inheritance. The disease is caused by a CAG trinucleotide repeat expansion located in the first exon of the HD gene. The CAG repeat is highly polymorphic and varies from 6 to 37 repeats on chromosomes of unaffected individuals and from more than 30 to 180 repeats on chromosomes of HD patients. In this study, we show that the number of CAG repeats in the HD gene can be determined by restriction of the...

  2. The impact of the CAG repeat polymorphism of the androgen receptor gene on muscle and adipose tissues in 20-29-year-old Danish men: Odense Androgen Study

    DEFF Research Database (Denmark)

    Nielsen, Torben Leo; Hagen, Claus; Wraae, Kristian;

    2010-01-01

    .m. and visceral) were measured in 393 men by magnetic resonance imaging (MRI). Lean body mass (LBM) and fat mass (FM) were measured in all men by whole body dual-energy X-ray absorptiometry (DEXA). The absolute areas acquired by MRI were the main outcomes. The absolute DEXA measurements and relative assessments.......108), and relative LBMtotal (r=–0.082), and positively with relative SATthigh (r=0.137), relative SATlower trunk (r=0.188), relative FMlower extremity (r=0.107), and relative FMtotal (r=0.082). These relationships remained significant, controlling for physical activity, smoking, chronic disease, and age. CAGn did...... not correlate with any circulating androgen. Conclusions: The CAG repeat polymorphism affects body composition in young men: absolute musclethigh and absolute musclelower trunk increase as CAGn decreases. Expressed relatively, muscle areas and LBM increase, while SAT and FM decrease as CAGn decreases...

  3. Study on relationship between polymorphism of Har gene (CAG)n micro-satellite and prostate cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Gang; WANG Xiao-hui; XIA Bing; CHEN Guang-chun; LU Jian

    2002-01-01

    Objective: To study the relationship between the polymorphic (CAG)n micro-satellite of human androgen receptor (bAR) gene and prostate cancer (Pca). Methods: The number of (CAG)n repeats in 107 normal males were measured by a two-step [α-32P]-dCTP incorporated asymmetric polymeric chain reaction (PCR), and the (CAG)n repeats of both malignant and nonmalignant prostate cells in fixed paraffin-embedded tissue (PET) specimen from 36 case of Pca were determined by sequence analysis. Results: The repeats of polymorphic (CAG) n among normal men ranged from 11 to 29, and the most frequent repeat was 22(18. 69%), with 23(14. 02%), 24(10. 28%) and 21(10. 28%) being less frequent. The (CAG)n repeats of malignant prostate cells equaled to that of nonmalignant adjacent prostate tissue cells from the same PET specimen in all 36 Pca, and the (CAG)n repeats in 36 Pca which ranged from 16 to 22 were shorter than that in normal males significantly (P<0. 05), while no significant difference in (CAG)n repeats among various grade of tumor's differentiation(well-differentiated, intermediate-differentiated and poor-differentiated) was found (P> 0. 05). Conclusion: The present study suggest that short hAR gene (CAG)n micro-satellite might be associated with the occurrence of Pca, but not with the differentiation of Pca.

  4. Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men

    DEFF Research Database (Denmark)

    Brokken, L J S; Rylander, L; Jönsson, B A;

    2013-01-01

    Recently the dogma that there is an inverse linear association between androgen receptor (AR) CAG and GGN polymorphisms and receptor activity has been challenged. We analysed the pattern of association between 21 male reproductive phenotypes and AR CAG/GGN repeat lengths in 557 proven-fertile men...

  5. Androgen Receptor CAG Repeat Length Is Associated With Body Fat and Serum SHBG in Boys

    DEFF Research Database (Denmark)

    Mouritsen, Annette; Hagen, Casper P; Sørensen, Kaspar;

    2013-01-01

    Background: Longer androgen receptor gene CAG trinucleotide repeats, AR (CAG)n, have been associated with reduced sensitivity of the androgen receptor (AR) in vitro as well as in humans. Furthermore, short AR (CAG)n have been associated with premature adrenarche. Objective: The aim of the study w...

  6. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    DEFF Research Database (Denmark)

    Lee, J-M; Ramos, E M; Lee, J-H;

    2012-01-01

    Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound...

  7. GFP-based fluorescence assay for CAG repeat instability in cultured human cells.

    Directory of Open Access Journals (Sweden)

    Beatriz A Santillan

    Full Text Available Trinucleotide repeats can be highly unstable, mutating far more frequently than point mutations. Repeats typically mutate by addition or loss of units of the repeat. CAG repeat expansions in humans trigger neurological diseases that include myotonic dystrophy, Huntington disease, and several spinocerebellar ataxias. In human cells, diverse mechanisms promote CAG repeat instability, and in mice, the mechanisms of instability are varied and tissue-dependent. Dissection of mechanistic complexity and discovery of potential therapeutics necessitates quantitative and scalable screens for repeat mutation. We describe a GFP-based assay for screening modifiers of CAG repeat instability in human cells. The assay exploits an engineered intronic CAG repeat tract that interferes with expression of an inducible GFP minigene. Like the phenotypes of many trinucleotide repeat disorders, we find that GFP function is impaired by repeat expansion, in a length-dependent manner. The intensity of fluorescence varies inversely with repeat length, allowing estimates of repeat tract changes in live cells. We validate the assay using transcription through the repeat and engineered CAG-specific nucleases, which have previously been reported to induce CAG repeat instability. The assay is relatively fast and should be adaptable to large-scale screens of chemical and shRNA libraries.

  8. CAG repeat expansions in bipolar and unipolar disorders

    Energy Technology Data Exchange (ETDEWEB)

    Oruc, L.; Verheyen, G.R.; Raeymaekers, P.; Van Broeckhoven, C. [Univ. of Antwerp (Belgium)] [and others

    1997-03-01

    Family, twin, and adoption studies consistently have indicated that the familial aggregation of bipolar (BP) disorder and unipolar recurrent major depression (UPR) is accounted for largely by genetic factors. However, the mode of inheritance is complex. One of the possible explanations could be that a gene with variable penetrance and variable expression is involved. Recently there have been reports on a new class of genetic diseases caused by an abnormal trinucleotide-repeat expansion (TRE). In a number of genetic disorders, these dynamic mutations were proved to be the biological basis for the clinically observed phenomenon of anticipation. DNA consisting of repeated triplets of nucleotides becomes unstable and increases in size over generations within families, giving rise to an increased severity and/or an earlier onset of the disorder. It has been recognized for a long time that anticipation occurs in multiplex families transmitting mental illness. More recent studies also suggest that both BP disorder and UPR show features that are compatible with anticipation. Although the findings of anticipation in BP disorders and in UPR must be interpreted with caution because of the possible presence of numerous ascertainment biases, they support the hypothesis that pathological TREs are implicated in the transmission of these disorders. TRE combined with variable penetrance of expression could explain the complex transmission pattern observed in BP disorder. In view of this, the recent reports of an association between CAG-repeat length and BP disorder in a Belgian, Swedish, and British population are promising. 14 refs., 1 fig., 1 tab.

  9. A pathogenic mechanism in Huntington's disease involves small CAG-repeated RNAs with neurotoxic activity.

    Directory of Open Access Journals (Sweden)

    Mónica Bañez-Coronel

    Full Text Available Huntington's disease (HD is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater induced cell death and increased levels of small CAG-repeated RNAs (sCAGs, of ≈21 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approaches.

  10. Unusual structures are present in DNA fragments containing super-long Huntingtin CAG repeats.

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    Daniel Duzdevich

    Full Text Available BACKGROUND: In the R6/2 mouse model of Huntington's disease (HD, expansion of the CAG trinucleotide repeat length beyond about 300 repeats induces a novel phenotype associated with a reduction in transcription of the transgene. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the structure of polymerase chain reaction (PCR-generated DNA containing up to 585 CAG repeats using atomic force microscopy (AFM. As the number of CAG repeats increased, an increasing proportion of the DNA molecules exhibited unusual structural features, including convolutions and multiple protrusions. At least some of these features are hairpin loops, as judged by cross-sectional analysis and sensitivity to cleavage by mung bean nuclease. Single-molecule force measurements showed that the convoluted DNA was very resistant to untangling. In vitro replication by PCR was markedly reduced, and TseI restriction enzyme digestion was also hindered by the abnormal DNA structures. However, significantly, the DNA gained sensitivity to cleavage by the Type III restriction-modification enzyme, EcoP15I. CONCLUSIONS/SIGNIFICANCE: "Super-long" CAG repeats are found in a number of neurological diseases and may also appear through CAG repeat instability. We suggest that unusual DNA structures associated with super-long CAG repeats decrease transcriptional efficiency in vitro. We also raise the possibility that if these structures occur in vivo, they may play a role in the aetiology of CAG repeat diseases such as HD.

  11. Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Nicole; Acosta; Andrés; Quiroga; Pilar; Delgado; María; Mercedes; Bravo; Carlos; Jaramillo

    2010-01-01

    AIM: To investigate Helicobacter pylori (H. pylori) CagA diversity and to evaluate the association between protein polymorphisms and the occurrence of gastric pathologies. METHODS: One hundred and twenty-two clinical isolates of H. pylori cultured from gastric biopsies obtained from Colombian patients with dyspepsia were included as study material. DNA extracted from isolates was used to determine cagA status, amplifying the C-terminal cagA gene region by polymerase chain reaction. One hundred and six strai...

  12. Assessment of Correlation between Androgen Receptor CAG Repeat Length and Infertility in Infertile Men Living in Khuzestan, Iran

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    Saeid Reza Khatami

    2015-02-01

    Full Text Available Background: The androgen receptor (AR gene contains a polymorphic trinucleotide repeat that encodes a polyglutamine tract in its N-terminal transactivation domain (NTAD. We aimed to find a correlation between the length of this polymorphic tract and azoospermia or oligozoospermia in infertile men living in Khuzestan, Iran. Materials and Methods: In this case-control study during two years till 2010, we searched for microdeletions in the Y chromosome in 84 infertile male patients with normal karyotype who lived in Khuzestan Province, Southwest of Iran. All cases (n=12 of azoospermia or oligozoospermia resulting from Y chromosome microdeletions were excluded from our study. The number of CAG repeats in exon 1 of the AR gene was determined in 72 patients with azoospermia or oligozoospermia and in 72 fertile controls, using the polymerase chain reaction (PCR and polyacrylamide gel electrophoresis. Results: Microdeletions were detected in 14.3% (n=12 patients suffering severe oligozoospermia. The mean CAG repeat length was 18.99 ± 0.35 (range, 11-26 and 19.96 ± 0.54 (range, 12-25 in infertile males and controls, respectively. Also in the infertile group, the most common allele was 19 (26.38%, while in controls, it was 25 (22.22%. Conclusion: Y chromosome microdeletions could be one of the main reasons of male infertility living in Khuzestan Province, while there was no correlation between CAG length in AR gene with azoospermia or oligozoospermia in infertile men living in Khuzestan, Iran.

  13. Helicobacter pylori cagL amino acid polymorphisms and its association with gastroduodenal diseases.

    Science.gov (United States)

    Shukla, Sanket Kumar; Prasad, Kashi Nath; Tripathi, Aparna; Jaiswal, Virendra; Khatoon, Jahanarah; Ghsohal, Uday Chand; Krishnani, Narendra; Husain, Nuzhat

    2013-07-01

    CagL is a pilus protein of Helicobacter pylori that interacts with host cellular α5β1 integrins through its arginine-glycine-aspartate (RGD) motif, guiding proper positioning of the T4SS and translocation of CagA. Deletion or sequence variations of cagL significantly diminished the ability of H. pylori to induce secretion of IL-8 by the host cell. Therefore, this study was undertaken to investigate the association of cagL and its amino acid sequence polymorphisms with gastric cancer (GC), peptic ulcer disease (PUD), and non-ulcer dyspepsia (NUD) as there are no such studies from India. In total, 200 adult patients (NUD 120, PUD 30, GC 50) who underwent an upper gastrointestinal endoscopy were enrolled. H. pylori infection was diagnosed by rapid urease test, culture, histopathology, and PCR. The collected isolates were screened for cagL genotype by PCR and assessed for amino acid sequence polymorphisms using sequence translation. The prevalence of H. pylori infection in study population was 52.5%. Most of the isolates were cagL genopositive (86.6%), and all had RGD motif in their amino acid sequences. D58 and K59 polymorphisms in cagL-genopositive strains were significantly higher in GC patients (P < 0.05). Combined D58K59 polymorphism was associated with higher risk of GC (3.8-fold) when compared to NUD. In conclusion, H. pylori cagL amino acid polymorphisms such as D58K59 are correlated with a higher risk of GC in the Indian population. Further studies are required to know the exact role of particular cagL amino acid polymorphisms in the pathogenicity of H. pylori infection. PMID:22941498

  14. Positive selection of a pre-expansion CAG repeat of the human SCA2 gene.

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    Fuli Yu

    2005-09-01

    Full Text Available A region of approximately one megabase of human Chromosome 12 shows extensive linkage disequilibrium in Utah residents with ancestry from northern and western Europe. This strikingly large linkage disequilibrium block was analyzed with statistical and experimental methods to determine whether natural selection could be implicated in shaping the current genome structure. Extended Haplotype Homozygosity and Relative Extended Haplotype Homozygosity analyses on this region mapped a core region of the strongest conserved haplotype to the exon 1 of the Spinocerebellar ataxia type 2 gene (SCA2. Direct DNA sequencing of this region of the SCA2 gene revealed a significant association between a pre-expanded allele [(CAG8CAA(CAG4CAA(CAG8] of CAG repeats within exon 1 and the selected haplotype of the SCA2 gene. A significantly negative Tajima's D value (-2.20, p < 0.01 on this site consistently suggested selection on the CAG repeat. This region was also investigated in the three other populations, none of which showed signs of selection. These results suggest that a recent positive selection of the pre-expansion SCA2 CAG repeat has occurred in Utah residents with European ancestry.

  15. Androgen receptor CAG polymorphism and sporadic and early-onset prostate cancer among Mexican men.

    Science.gov (United States)

    Gómez, Rocío; Torres-Sánchez, Luisa; Camacho-Mejorado, Rafael; Burguete-García, Ana I; Vázquez-Salas, Ruth Argelia; Martínez-Nava, Gabriela A; Santana, Carla; Noris, Gino

    2016-09-01

    A short CAG repeat length in the gene encoding for the androgen receptor (AR) has been associated with prostate cancer (PC) risk and aggressiveness. In Latino men, information on this association is scarce. Hence, the aim of this study was to evaluate this association in Mexican males. Using fragment analysis by capillary electrophoresis, we determined the number of CAG repeats-(CAG)n-in AR gene from 158 incident PC cases and 326 age-matched healthy controls (±5 years), residing in Mexico City, Mexico. According to Gleason scale and age at diagnosis, cases were classified as high (⩾7) and low grade (<7), as well as early onset (<60 years) or late onset PC (⩾60 years). At diagnosis, 78% of cases were classified as high-grade and 26.6% as early onset. Men with sporadic (no family history of PC) and early-onset PC presented shorter CAG repeat length than controls (18.6±2.2 vs 19.5±2.5; P=0.02). Lower number of CAG repeats (CAG)⩽19 were associated with a greater risk for early-onset PC (odds ratio: 2.31; 95% confidence interval: 1.14-4.69). CAG repeat length could increase the risk for sporadic and early-onset PC. The best cutoff point for identifying at-risk subjects was (CAG)19. However, further studies are necessary to replicate our findings in subjects with a family history of PC and also to evaluate the association between CAG repeats length and disease progression.

  16. Nuclear speckles are detention centers for transcripts containing expanded CAG repeats.

    Science.gov (United States)

    Urbanek, Martyna O; Jazurek, Magdalena; Switonski, Pawel M; Figura, Grzegorz; Krzyzosiak, Wlodzimierz J

    2016-09-01

    The human genetic disorders caused by CAG repeat expansions in the translated sequences of various genes are called polyglutamine (polyQ) diseases because of the cellular "toxicity" of the mutant proteins. The contribution of mutant transcripts to the pathogenesis of these diseases is supported by several observations obtained from cellular models of these disorders. Here, we show that the common feature of cell lines modeling polyQ diseases is the formation of nuclear CAG RNA foci. We performed qualitative and quantitative analyses of these foci in numerous cellular models endogenously and exogenously expressing mutant transcripts by fluorescence in situ hybridization (FISH). We compared the CAG RNA foci of polyQ diseases with the CUG foci of myotonic dystrophy type 1 and found substantial differences in their number and morphology. Smaller differences within the polyQ disease group were also revealed and included a positive correlation between the foci number and the CAG repeat length. We show that expanded CAA repeats, also encoding glutamine, did not trigger RNA foci formation and foci formation is independent of the presence of mutant polyglutamine protein. Using FISH combined with immunofluorescence, we demonstrated partial co-localization of CAG repeat foci with MBNL1 alternative splicing factor, which explains the mild deregulation of MBNL1-dependent genes. We also showed that foci reside within nuclear speckles in diverse cell types: fibroblasts, lymphoblasts, iPS cells and neuronal progenitors and remain dependent on integrity of these nuclear structures. PMID:27239700

  17. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    Science.gov (United States)

    Lee, J.-M.; Ramos, E.M.; Lee, J.-H.; Gillis, T.; Mysore, J.S.; Hayden, M.R.; Warby, S.C.; Morrison, P.; Nance, M.; Ross, C.A.; Margolis, R.L.; Squitieri, F.; Orobello, S.; Di Donato, S.; Gomez-Tortosa, E.; Ayuso, C.; Suchowersky, O.; Trent, R.J.A.; McCusker, E.; Novelletto, A.; Frontali, M.; Jones, R.; Ashizawa, T.; Frank, S.; Saint-Hilaire, M.H.; Hersch, S.M.; Rosas, H.D.; Lucente, D.; Harrison, M.B.; Zanko, A.; Abramson, R.K.; Marder, K.; Sequeiros, J.; Paulsen, J.S.; Landwehrmeyer, G.B.; Myers, R.H.; MacDonald, M.E.; Durr, Alexandra; Rosenblatt, Adam; Frati, Luigi; Perlman, Susan; Conneally, Patrick M.; Klimek, Mary Lou; Diggin, Melissa; Hadzi, Tiffany; Duckett, Ayana; Ahmed, Anwar; Allen, Paul; Ames, David; Anderson, Christine; Anderson, Karla; Anderson, Karen; Andrews, Thomasin; Ashburner, John; Axelson, Eric; Aylward, Elizabeth; Barker, Roger A.; Barth, Katrin; Barton, Stacey; Baynes, Kathleen; Bea, Alexandra; Beall, Erik; Beg, Mirza Faisal; Beglinger, Leigh J.; Biglan, Kevin; Bjork, Kristine; Blanchard, Steve; Bockholt, Jeremy; Bommu, Sudharshan Reddy; Brossman, Bradley; Burrows, Maggie; Calhoun, Vince; Carlozzi, Noelle; Chesire, Amy; Chiu, Edmond; Chua, Phyllis; Connell, R.J.; Connor, Carmela; Corey-Bloom, Jody; Craufurd, David; Cross, Stephen; Cysique, Lucette; Santos, Rachelle Dar; Davis, Jennifer; Decolongon, Joji; DiPietro, Anna; Doucette, Nicholas; Downing, Nancy; Dudler, Ann; Dunn, Steve; Ecker, Daniel; Epping, Eric A.; Erickson, Diane; Erwin, Cheryl; Evans, Ken; Factor, Stewart A.; Farias, Sarah; Fatas, Marta; Fiedorowicz, Jess; Fullam, Ruth; Furtado, Sarah; Garde, Monica Bascunana; Gehl, Carissa; Geschwind, Michael D.; Goh, Anita; Gooblar, Jon; Goodman, Anna; Griffith, Jane; Groves, Mark; Guttman, Mark; Hamilton, Joanne; Harrington, Deborah; Harris, Greg; Heaton, Robert K.; Helmer, Karl; Henneberry, Machelle; Hershey, Tamara; Herwig, Kelly; Howard, Elizabeth; Hunter, Christine; Jankovic, Joseph; Johnson, Hans; Johnson, Arik; Jones, Kathy; Juhl, Andrew; Kim, Eun Young; Kimble, Mycah; King, Pamela; Klimek, Mary Lou; Klöppel, Stefan; Koenig, Katherine; Komiti, Angela; Kumar, Rajeev; Langbehn, Douglas; Leavitt, Blair; Leserman, Anne; Lim, Kelvin; Lipe, Hillary; Lowe, Mark; Magnotta, Vincent A.; Mallonee, William M.; Mans, Nicole; Marietta, Jacquie; Marshall, Frederick; Martin, Wayne; Mason, Sarah; Matheson, Kirsty; Matson, Wayne; Mazzoni, Pietro; McDowell, William; Miedzybrodzka, Zosia; Miller, Michael; Mills, James; Miracle, Dawn; Montross, Kelsey; Moore, David; Mori, Sasumu; Moser, David J.; Moskowitz, Carol; Newman, Emily; Nopoulos, Peg; Novak, Marianne; O'Rourke, Justin; Oakes, David; Ondo, William; Orth, Michael; Panegyres, Peter; Pease, Karen; Perlman, Susan; Perlmutter, Joel; Peterson, Asa; Phillips, Michael; Pierson, Ron; Potkin, Steve; Preston, Joy; Quaid, Kimberly; Radtke, Dawn; Rae, Daniela; Rao, Stephen; Raymond, Lynn; Reading, Sarah; Ready, Rebecca; Reece, Christine; Reilmann, Ralf; Reynolds, Norm; Richardson, Kylie; Rickards, Hugh; Ro, Eunyoe; Robinson, Robert; Rodnitzky, Robert; Rogers, Ben; Rosenblatt, Adam; Rosser, Elisabeth; Rosser, Anne; Price, Kathy; Price, Kathy; Ryan, Pat; Salmon, David; Samii, Ali; Schumacher, Jamy; Schumacher, Jessica; Sendon, Jose Luis Lópenz; Shear, Paula; Sheinberg, Alanna; Shpritz, Barnett; Siedlecki, Karen; Simpson, Sheila A.; Singer, Adam; Smith, Jim; Smith, Megan; Smith, Glenn; Snyder, Pete; Song, Allen; Sran, Satwinder; Stephan, Klaas; Stober, Janice; Sü?muth, Sigurd; Suter, Greg; Tabrizi, Sarah; Tempkin, Terry; Testa, Claudia; Thompson, Sean; Thomsen, Teri; Thumma, Kelli; Toga, Arthur; Trautmann, Sonja; Tremont, Geoff; Turner, Jessica; Uc, Ergun; Vaccarino, Anthony; van Duijn, Eric; Van Walsem, Marleen; Vik, Stacie; Vonsattel, Jean Paul; Vuletich, Elizabeth; Warner, Tom; Wasserman, Paula; Wassink, Thomas; Waterman, Elijah; Weaver, Kurt; Weir, David; Welsh, Claire; Werling-Witkoske, Chris; Wesson, Melissa; Westervelt, Holly; Weydt, Patrick; Wheelock, Vicki; Williams, Kent; Williams, Janet; Wodarski, Mary; Wojcieszek, Joanne; Wood, Jessica; Wood-Siverio, Cathy; Wu, Shuhua; Yastrubetskaya, Olga; de Yebenes, Justo Garcia; Zhao, Yong Qiang; Zimbelman, Janice; Zschiegner, Roland; Aaserud, Olaf; Abbruzzese, Giovanni; Andrews, Thomasin; Andrich, Jurgin; Antczak, Jakub; Arran, Natalie; Artiga, Maria J. Saiz; Bachoud-Lévi, Anne-Catherine; Banaszkiewicz, Krysztof; di Poggio, Monica Bandettini; Bandmann, Oliver; Barbera, Miguel A.; Barker, Roger A.; Barrero, Francisco; Barth, Katrin; Bas, Jordi; Beister, Antoine; Bentivoglio, Anna Rita; Bertini, Elisabetta; Biunno, Ida; Bjørgo, Kathrine; Bjørnevoll, Inga; Bohlen, Stefan; Bonelli, Raphael M.; Bos, Reineke; Bourne, Colin; Bradbury, Alyson; Brockie, Peter; Brown, Felicity; Bruno, Stefania; Bryl, Anna; Buck, Andrea; Burg, Sabrina; Burgunder, Jean-Marc; Burns, Peter; Burrows, Liz; Busquets, Nuria; Busse, Monica; Calopa, Matilde; Carruesco, Gemma T.; Casado, Ana Gonzalez; Catena, Judit López; Chu, Carol; Ciesielska, Anna; Clapton, Jackie; Clayton, Carole; Clenaghan, Catherine; Coelho, Miguel; Connemann, Julia; Craufurd, David; Crooks, Jenny; Cubillo, Patricia Trigo; Cubo, Esther; Curtis, Adrienne; De Michele, Giuseppe; De Nicola, A.; de Souza, Jenny; de Weert, A. Marit; de Yébenes, Justo Garcia; Dekker, M.; Descals, A. Martínez; Di Maio, Luigi; Di Pietro, Anna; Dipple, Heather; Dose, Matthias; Dumas, Eve M.; Dunnett, Stephen; Ecker, Daniel; Elifani, F.; Ellison-Rose, Lynda; Elorza, Marina D.; Eschenbach, Carolin; Evans, Carole; Fairtlough, Helen; Fannemel, Madelein; Fasano, Alfonso; Fenollar, Maria; Ferrandes, Giovanna; Ferreira, Jaoquim J.; Fillingham, Kay; Finisterra, Ana Maria; Fisher, K.; Fletcher, Amy; Foster, Jillian; Foustanos, Isabella; Frech, Fernando A.; Fullam, Robert; Fullham, Ruth; Gago, Miguel; García, RocioGarcía-Ramos; García, Socorro S.; Garrett, Carolina; Gellera, Cinzia; Gill, Paul; Ginestroni, Andrea; Golding, Charlotte; Goodman, Anna; Gørvell, Per; Grant, Janet; Griguoli, A.; Gross, Diana; Guedes, Leonor; BascuñanaGuerra, Monica; Guerra, Maria Rosalia; Guerrero, Rosa; Guia, Dolores B.; Guidubaldi, Arianna; Hallam, Caroline; Hamer, Stephanie; Hammer, Kathrin; Handley, Olivia J.; Harding, Alison; Hasholt, Lis; Hedge, Reikha; Heiberg, Arvid; Heinicke, Walburgis; Held, Christine; Hernanz, Laura Casas; Herranhof, Briggitte; Herrera, Carmen Durán; Hidding, Ute; Hiivola, Heli; Hill, Susan; Hjermind, Lena. E.; Hobson, Emma; Hoffmann, Rainer; Holl, Anna Hödl; Howard, Liz; Hunt, Sarah; Huson, Susan; Ialongo, Tamara; Idiago, Jesus Miguel R.; Illmann, Torsten; Jachinska, Katarzyna; Jacopini, Gioia; Jakobsen, Oda; Jamieson, Stuart; Jamrozik, Zygmunt; Janik, Piotr; Johns, Nicola; Jones, Lesley; Jones, Una; Jurgens, Caroline K.; Kaelin, Alain; Kalbarczyk, Anna; Kershaw, Ann; Khalil, Hanan; Kieni, Janina; Klimberg, Aneta; Koivisto, Susana P.; Koppers, Kerstin; Kosinski, Christoph Michael; Krawczyk, Malgorzata; Kremer, Berry; Krysa, Wioletta; Kwiecinski, Hubert; Lahiri, Nayana; Lambeck, Johann; Lange, Herwig; Laver, Fiona; Leenders, K.L.; Levey, Jamie; Leythaeuser, Gabriele; Lezius, Franziska; Llesoy, Joan Roig; Löhle, Matthias; López, Cristobal Diez-Aja; Lorenza, Fortuna; Loria, Giovanna; Magnet, Markus; Mandich, Paola; Marchese, Roberta; Marcinkowski, Jerzy; Mariotti, Caterina; Mariscal, Natividad; Markova, Ivana; Marquard, Ralf; Martikainen, Kirsti; Martínez, Isabel Haro; Martínez-Descals, Asuncion; Martino, T.; Mason, Sarah; McKenzie, Sue; Mechi, Claudia; Mendes, Tiago; Mestre, Tiago; Middleton, Julia; Milkereit, Eva; Miller, Joanne; Miller, Julie; Minster, Sara; Möller, Jens Carsten; Monza, Daniela; Morales, Blas; Moreau, Laura V.; Moreno, Jose L. López-Sendón; Münchau, Alexander; Murch, Ann; Nielsen, Jørgen E.; Niess, Anke; Nørremølle, Anne; Novak, Marianne; O'Donovan, Kristy; Orth, Michael; Otti, Daniela; Owen, Michael; Padieu, Helene; Paganini, Marco; Painold, Annamaria; Päivärinta, Markku; Partington-Jones, Lucy; Paterski, Laurent; Paterson, Nicole; Patino, Dawn; Patton, Michael; Peinemann, Alexander; Peppa, Nadia; Perea, Maria Fuensanta Noguera; Peterson, Maria; Piacentini, Silvia; Piano, Carla; Càrdenas, Regina Pons i; Prehn, Christian; Price, Kathleen; Probst, Daniela; Quarrell, Oliver; Quiroga, Purificacion Pin; Raab, Tina; Rakowicz, Maryla; Raman, Ashok; Raymond, Lucy; Reilmann, Ralf; Reinante, Gema; Reisinger, Karin; Retterstol, Lars; Ribaï, Pascale; Riballo, Antonio V.; Ribas, Guillermo G.; Richter, Sven; Rickards, Hugh; Rinaldi, Carlo; Rissling, Ida; Ritchie, Stuart; Rivera, Susana Vázquez; Robert, Misericordia Floriach; Roca, Elvira; Romano, Silvia; Romoli, Anna Maria; Roos, Raymond A.C.; Røren, Niini; Rose, Sarah; Rosser, Elisabeth; Rosser, Anne; Rossi, Fabiana; Rothery, Jean; Rudzinska, Monika; Ruíz, Pedro J. García; Ruíz, Belan Garzon; Russo, Cinzia Valeria; Ryglewicz, Danuta; Saft, Carston; Salvatore, Elena; Sánchez, Vicenta; Sando, Sigrid Botne; Šašinková, Pavla; Sass, Christian; Scheibl, Monika; Schiefer, Johannes; Schlangen, Christiane; Schmidt, Simone; Schöggl, Helmut; Schrenk, Caroline; Schüpbach, Michael; Schuierer, Michele; Sebastián, Ana Rojo; Selimbegovic-Turkovic, Amina; Sempolowicz, Justyna; Silva, Mark; Sitek, Emilia; Slawek, Jaroslaw; Snowden, Julie; Soleti, Francesco; Soliveri, Paola; Sollom, Andrea; Soltan, Witold; Sorbi, Sandro; Sorensen, Sven Asger; Spadaro, Maria; Städtler, Michael; Stamm, Christiane; Steiner, Tanja; Stokholm, Jette; Stokke, Bodil; Stopford, Cheryl; Storch, Alexander; Straßburger, Katrin; Stubbe, Lars; Sulek, Anna; Szczudlik, Andrzej; Tabrizi, Sarah; Taylor, Rachel; Terol, Santiago Duran-Sindreu; Thomas, Gareth; Thompson, Jennifer; Thomson, Aileen; Tidswell, Katherine; Torres, Maria M. Antequera; Toscano, Jean; Townhill, Jenny; Trautmann, Sonja; Tucci, Tecla; Tuuha, Katri; Uhrova, Tereza; Valadas, Anabela; van Hout, Monique S.E.; van Oostrom, J.C.H.; van Vugt, Jeroen P.P.; vanm, Walsem Marleen R.; Vandenberghe, Wim; Verellen-Dumoulin, Christine; Vergara, Mar Ruiz; Verstappen, C.C.P.; Verstraelen, Nichola; Viladrich, Celia Mareca; Villanueva, Clara; Wahlström, Jan; Warner, Thomas; Wehus, Raghild; Weindl, Adolf; Werner, Cornelius J.; Westmoreland, Leann; Weydt, Patrick; Wiedemann, Alexandra; Wild, Edward; Wild, Sue; Witjes-Ané, Marie-Noelle; Witkowski, Grzegorz; Wójcik, Magdalena; Wolz, Martin; Wolz, Annett; Wright, Jan; Yardumian, Pam; Yates, Shona; Yudina, Elizaveta; Zaremba, Jacek; Zaugg, Sabine W.; Zdzienicka, Elzbieta; Zielonka, Daniel; Zielonka, Euginiusz; Zinzi, Paola; Zittel, Simone; Zucker, Birgrit; Adams, John; Agarwal, Pinky; Antonijevic, Irina; Beck, Christopher; Chiu, Edmond; Churchyard, Andrew; Colcher, Amy; Corey-Bloom, Jody; Dorsey, Ray; Drazinic, Carolyn; Dubinsky, Richard; Duff, Kevin; Factor, Stewart; Foroud, Tatiana; Furtado, Sarah; Giuliano, Joe; Greenamyre, Timothy; Higgins, Don; Jankovic, Joseph; Jennings, Dana; Kang, Un Jung; Kostyk, Sandra; Kumar, Rajeev; Leavitt, Blair; LeDoux, Mark; Mallonee, William; Marshall, Frederick; Mohlo, Eric; Morgan, John; Oakes, David; Panegyres, Peter; Panisset, Michel; Perlman, Susan; Perlmutter, Joel; Quaid, Kimberly; Raymond, Lynn; Revilla, Fredy; Robertson, Suzanne; Robottom, Bradley; Sanchez-Ramos, Juan; Scott, Burton; Shannon, Kathleen; Shoulson, Ira; Singer, Carlos; Tabbal, Samer; Testa, Claudia; van, Kammen Dan; Vetter, Louise; Walker, Francis; Warner, John; Weiner, illiam; Wheelock, Vicki; Yastrubetskaya, Olga; Barton, Stacey; Broyles, Janice; Clouse, Ronda; Coleman, Allison; Davis, Robert; Decolongon, Joji; DeLaRosa, Jeanene; Deuel, Lisa; Dietrich, Susan; Dubinsky, Hilary; Eaton, Ken; Erickson, Diane; Fitzpatrick, Mary Jane; Frucht, Steven; Gartner, Maureen; Goldstein, Jody; Griffith, Jane; Hickey, Charlyne; Hunt, Victoria; Jaglin, Jeana; Klimek, Mary Lou; Lindsay, Pat; Louis, Elan; Loy, Clemet; Lucarelli, Nancy; Malarick, Keith; Martin, Amanda; McInnis, Robert; Moskowitz, Carol; Muratori, Lisa; Nucifora, Frederick; O'Neill, Christine; Palao, Alicia; Peavy, Guerry; Quesada, Monica; Schmidt, Amy; Segro, Vicki; Sperin, Elaine; Suter, Greg; Tanev, Kalo; Tempkin, Teresa; Thiede, Curtis; Wasserman, Paula; Welsh, Claire; Wesson, Melissa; Zauber, Elizabeth

    2012-01-01

    Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology® 2012;78:690–695 PMID:22323755

  18. Single cell analysis reveals gametic and tissue-specific instability of the SCA1 CAG repeat

    Energy Technology Data Exchange (ETDEWEB)

    Chong, S.S.; McCall, A.E.; Cota, J. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Spinocerebellar ataxia type 1 is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat within the SCA1 gene on chromosome 6p22-23. We performed a comparative analysis of the SCA1 CAG repeat from blood and sperm of an affected male. Genomic amplification revealed a broader smear of the SCA1 allele product from sperm compared to that from peripheral blood leukocytes (PBL). To resolve this observed difference, we analyzed single sperm directly and demonstrate that the SCA1 allele in PBL is also heterogeneous, although the range of variability in allele sizes is much less than that observed in sperm. Limited genome analysis was also performed on PBL DNA from an unaffected individual with an upper normal allele of 36 repeats in parallel with an affected individual with an expanded allele of 40 repeats. The 36 repeat normal allele, which contains a CAT interruption, was completely stable compared to the uninterrupted repeat of the SCA1 allele, demonstrating a direct correlation between absence of a CAT interruption and somatic instability of the repeat. We also analyzed the size of the CAG repeat in tissues derived from various brain regions from a patient with juvenile-onset disease to determine if the size of the expansion correlated with the site of neuropathology. The results clearly show tissue-specific differences in mosaicism of repeat length. More importantly, the pattern of tissue-specific differences in repeat-length mosaicism in SCA1 within the brain parallels those seen in Huntington disease. In both disorders the expanded alleles are smaller in cerebellar tissue. These results suggest that the observed tissue-specific differences in instability of the SCA1 CAG repeat, either within the brain or between blood and sperm, are a function of the intracellular milieu or the intrinsic replicative potential of the various celltypes.

  19. Twisting right to left: A…A mismatch in a CAG trinucleotide repeat overexpansion provokes left-handed Z-DNA conformation.

    Directory of Open Access Journals (Sweden)

    Noorain Khan

    2015-04-01

    Full Text Available Conformational polymorphism of DNA is a major causative factor behind several incurable trinucleotide repeat expansion disorders that arise from overexpansion of trinucleotide repeats located in coding/non-coding regions of specific genes. Hairpin DNA structures that are formed due to overexpansion of CAG repeat lead to Huntington's disorder and spinocerebellar ataxias. Nonetheless, DNA hairpin stem structure that generally embraces B-form with canonical base pairs is poorly understood in the context of periodic noncanonical A…A mismatch as found in CAG repeat overexpansion. Molecular dynamics simulations on DNA hairpin stems containing A…A mismatches in a CAG repeat overexpansion show that A…A dictates local Z-form irrespective of starting glycosyl conformation, in sharp contrast to canonical DNA duplex. Transition from B-to-Z is due to the mechanistic effect that originates from its pronounced nonisostericity with flanking canonical base pairs facilitated by base extrusion, backbone and/or base flipping. Based on these structural insights we envisage that such an unusual DNA structure of the CAG hairpin stem may have a role in disease pathogenesis. As this is the first study that delineates the influence of a single A…A mismatch in reversing DNA helicity, it would further have an impact on understanding DNA mismatch repair.

  20. Relation of atrophic gastritis with Helicobacter pylori-CagA+and interleukin-1 gene polymorphisms

    Institute of Scientific and Technical Information of China (English)

    Rafaela Sierra; Francis Mégraud; Clas Une; Vanessa Ramírez; Warner Alpízar-Alpízar; María I González; José A Ramírez; Antoine de Mascarel; Patricia Cuenca; Guillermo Pérez-Pérez

    2008-01-01

    AIM: To determine the association of Helicobacter pylori (H pylon) CagA+ infection and pro-inflammatory poly-morphisms of the genes interleukin (IL)-IRN and IL-1B with the risk of gastric atrophy and peptic ulcers in a dyspeptic population in Costa Rica, a country with high incidence and mortality of gastric cancer. METHODS: Seven biopsy specimens, a fasting blood sample and a questionnaire concerning nutritional and sociodemographic factors were obtained from 501 con-secutive patients who had undergone endoscopy for dyspeptic symptoms. A histopathological diagnosis was made. Pepsinogen concentrations were analyzed by enzyme linked immunosorbent assay (ELISA). Infection with H pylori CagA* was determined by serology and polymerase chain reaction (PCR). IL-1B and IL-1RN polymorphisms genotyping was performed by PCR-restriction fragment length polymorphism (PCR-RFLP) and PCR respectively. RESULTS: In this dyspeptic population, 86% wereHpy/ori positive and of these, 67.8% were positive forCagA. Atrophic antral gastritis (AAG) was associatedwith CagA+ status [odd ratio (OR) = 4.1; P < 0.000]and fruit consumption (OR = 0.3; P < 0.00). Atrophicbody gastritis (ABG) was associated with pepsinogenPGI/PGII < 3.4 (OR = 4.9; P < 0.04) and alcoholconsumption (OR = 7.3; P < 0.02). Duodenal ulcerwas associated with CagA+ (OR = 2.9; P < 0.04) andsmoking (OR = 2.4; P < 0.04). PGI < 60 μg/L as wellas PGI/PGII < 3.4 were associated with CagA+. CONCLUSION: In a dyspeptic population in Costa Rica,H pylori CagA+ is not associated with ABG, but it is arisk factor for AAG. The pro-inflammatory cytokine poly-morphisms IL-1B + 3945 and IL-1RN are not associatedwith the atrophic lesions of this dyspeptic population.

  1. Meta-analysis of relationship between androgen receptor CAG repeats length polymorphism and the polycystic ovary syndrome%雄激素受体(CAG)n基因多态性与多囊卵巢综合征相关性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    余瑞梅; 邱娜璇; 陈春敏

    2015-01-01

    目的 评价雄激素受体(androgen receptor,AR) (CAG)n基因多态性与多囊卵巢综合征(polycystic ovary syndrome,PCOS)易感性的相关性.方法 检索Pubmed、Embase、CNKI、VIP、万方数据库,英文检索词为androgen receptor,polycystic ovarian syndrome,中文检索词为雄激素受体和多囊卵巢综合征,收集有关AR (CAG)n基因多态性与PCOS易感性的病例对照研究,进行Meta分析.结果 共纳入12篇文献,PCOS组1 697例,对照组(健康女性)1 984例.Meta分析结果显示,PCOS组与对照组间AR (CAG)n重复序列长度比较,差异无统计学意义[标准化均数差(SMD)=-0.05,95%CI:-0.19~0.08,P=0.440].PCOS患者中,高雄激素血症(hyperandrogenism,HA)患者与非HA患者间AR (CAG)n重复序列长度比较,差异无统计学意义(SMD=0.56,95%CI:-0.13~1.25,P=0.110).结论 AR (CAG)n基因多态性可能与P-COS及其并发的高雄激素血症的发生无关联.

  2. Continuous and periodic expansion of CAG repeats in Huntington's disease R6/1 mice.

    Directory of Open Access Journals (Sweden)

    Linda Møllersen

    Full Text Available Huntington's disease (HD is one of several neurodegenerative disorders caused by expansion of CAG repeats in a coding gene. Somatic CAG expansion rates in HD vary between organs, and the greatest instability is observed in the brain, correlating with neuropathology. The fundamental mechanisms of somatic CAG repeat instability are poorly understood, but locally formed secondary DNA structures generated during replication and/or repair are believed to underlie triplet repeat expansion. Recent studies in HD mice have demonstrated that mismatch repair (MMR and base excision repair (BER proteins are expansion inducing components in brain tissues. This study was designed to simultaneously investigate the rates and modes of expansion in different tissues of HD R6/1 mice in order to further understand the expansion mechanisms in vivo. We demonstrate continuous small expansions in most somatic tissues (exemplified by tail, which bear the signature of many short, probably single-repeat expansions and contractions occurring over time. In contrast, striatum and cortex display a dramatic--and apparently irreversible--periodic expansion. Expansion profiles displaying this kind of periodicity in the expansion process have not previously been reported. These in vivo findings imply that mechanistically distinct expansion processes occur in different tissues.

  3. Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

    KAUST Repository

    Viterbo, David

    2016-03-16

    Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

  4. Serum testosterone levels and androgen receptor CAG polymorphism correlate with hepatitis B virus (HBV-related acute liver failure in male HBV carriers.

    Directory of Open Access Journals (Sweden)

    Bao-Yan Xu

    Full Text Available BACKGROUND: Augmentation of androgen/androgen receptor (AR pathway may influence chronic hepatitis B (CHB more likely in males. AR activity is modulated by a polymorphic CAG repeat sequence in AR exon 1. This study aimed to investigate the relationship between serum testosterone levels, CAG repeat numbers and hepatitis B virus (HBV-related acute liver failure (ALF. METHODS: Three hundred and seventy eight male CHB patients with ALF and 441 asymptomatic HBV carriers (AsCs were recruited. AR CAG repeats numbers were analyzed. The serum testosterone levels of AsCs, ALFs and patients with hepatitis B flare groups, and sequential serum samples, were assessed quantitatively. RESULTS: The median CAG repeat (M-CAG frequency was significantly higher in ALF patients than AsCs (P<0.001. Patients with M-CAG alleles (P<0.001, OR 3.0, 95% CI 2.1-4.2 had the highest risk for ALF. Serum testosterone levels were significantly higher (P<0.001 at hepatitis flare point (8.2 ± 3.0 ng/mL than inactive phase (6.4 ± 2.0 ng/mL. CHB (8.30 ± 2.71 ng/mL, P = 7.6 × 10(-6 and ALF group (2.61 ± 1.83 ng/mL, P = 1.7 × 10(-17 had significantly different levels of testosterone in comparison with AsCs group (6.56 ± 2.36 ng/mL. The serum testosterone levels sharply decreased from hepatitis flare phase to liver failure phase, and tended to be normal at the recovery phase. Male AsCs with M-CAG alleles had significantly lower serum testosterone levels (P<0.05. CONCLUSIONS: There was a serum testosterone fluctuation during hepatitis B flare and HBV-related ALF, and the median CAG repeats in AR gene exon 1 were associated with lower serum testosterone levels in asymptomatic HBV carriers and an increased susceptibility to HBV-related ALF.

  5. Corepressor effect on androgen receptor activity varies with the length of the CAG encoded polyglutamine repeat and is dependent on receptor/corepressor ratio in prostate cancer cells.

    Science.gov (United States)

    Buchanan, Grant; Need, Eleanor F; Barrett, Jeffrey M; Bianco-Miotto, Tina; Thompson, Vanessa C; Butler, Lisa M; Marshall, Villis R; Tilley, Wayne D; Coetzee, Gerhard A

    2011-08-01

    The response of prostate cells to androgens reflects a combination of androgen receptor (AR) transactivation and transrepression, but how these two processes differ mechanistically and influence prostate cancer risk and disease outcome remain elusive. Given recent interest in targeting AR transrepressive processes, a better understanding of AR/corepressor interaction and responses is warranted. Here, we used transactivation and interaction assays with wild-type and mutant ARs, and deletion AR fragments, to dissect the relationship between AR and the corepressor, silencing mediator for retinoic acid and thyroid hormone receptors (SMRT). We additionally tested how these processes are influenced by AR agonist and antagonist ligands, as well as by variation in the polyglutamine tract in the AR amino terminal domain (NTD), which is encoded by a polymorphic CAG repeat in the gene. SMRT was recruited to the AR ligand binding domain by agonist ligand, and as determined by the effect of strategic mutations in activation function 2 (AF-2), requires a precise conformation of that domain. A distinct region of SMRT also mediated interaction with the AR-NTD via the transactivation unit 5 (TAU5; residues 315-538) region. The degree to which SMRT was able to repress AR increased from 17% to 56% as the AR polyglutamine repeat length was increased from 9 to 42 residues, but critically this effect could be abolished by increasing the SMRT:AR molar ratio. These data suggest that the extent to which the CAG encoded polyglutamine repeat influences AR activity represents a balance between corepressor and coactivator occupancy of the same ligand-dependent and independent AR interaction surfaces. Changes in the homeostatic relationship of AR to these molecules, including SMRT, may explain the variable penetrance of the CAG repeat and the loss of AR signaling flexibility in prostate cancer progression.

  6. Mutant CAG repeats of Huntingtin transcript fold into hairpins, form nuclear foci and are targets for RNA interference

    OpenAIRE

    de Mezer, Mateusz; Wojciechowska, Marzena; Napierala, Marek; Sobczak, Krzysztof; Krzyzosiak, Wlodzimierz J.

    2011-01-01

    The CAG repeat expansions that occur in translated regions of specific genes can cause human genetic disorders known as polyglutamine (poly-Q)-triggered diseases. Huntington’s disease and spinobulbar muscular atrophy (SBMA) are examples of these diseases in which underlying mutations are localized near other trinucleotide repeats in the huntingtin (HTT) and androgen receptor (AR) genes, respectively. Mutant proteins that contain expanded polyglutamine tracts are well-known triggers of pathoge...

  7. Effects of Anthocyanins on CAG Repeat Instability and Behaviour in Huntington’s Disease R6/1 Mice

    Science.gov (United States)

    Møllersen, Linda; Moldestad, Olve; Rowe, Alexander D.; Bjølgerud, Anja; Holm, Ingunn; Tveterås, Linda; Klungland, Arne; Retterstøl, Lars

    2016-01-01

    Background: Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by CAG repeat expansions in the HTT gene. Somatic repeat expansion in the R6/1 mouse model of HD depends on mismatch repair and is worsened by base excision repair initiated by the 7,8-dihydroxy-8-oxoguanine-DNA glycosylase (Ogg1) or Nei-like 1 (Neil1). Ogg1 and Neil1 repairs common oxidative lesions. Methods: We investigated whether anthocyanin antioxidants added daily to the drinking water could affect CAG repeat instability in several organs and behaviour in R6/1 HD mice. In addition, anthocyanin-treated and untreated R6/1 HD mice at 22 weeks of age were tested in the open field test and on the rotarod. Results: Anthocyanin-treated R6/1 HD mice showed reduced instability index in the ears and in the cortex compared to untreated R6/1 mice, and no difference in liver and kidney. There were no significant differences in any of the parameters tested in the behavioural tests among anthocyanin-treated and untreated R6/1 HD mice. Conclusions: Our results indicate that continuous anthocyanin-treatment may have modest effects on CAG repeat instability in the ears and the cortex of R6/1 mice. More studies are required to investigate if anthocyanin-treatment could affect behaviour earlier in the disease course. PMID:27540492

  8. A unified rapid PCR method for detection of normal and expanded trinucleotide alleles of CAG repeats in huntington chorea and CGG repeats in fragile X syndrome.

    Science.gov (United States)

    Todorov, Tihomir; Todorova, Albena; Georgieva, Bilyana; Mitev, Vanyo

    2010-06-01

    We report on a unified rapid betaine-based-PCR protocol for amplification of the (CAG)n region in Huntington disease (HD) and the (CGG)n region in Fragile X syndrome (FXS), followed by an electrophoretic separation on automated sequencer for precise determination of the triplet numbers. The high betaine concentration (2.5 M betaine) permits precise amplification of the CAG and CGG repeats. Ten HD affected patients and 10 healthy individuals from HD families were re-evaluated. For FXS the CGG region in normal individuals and premutations of about 100 repeats were precisely amplified by this protocol. Ten unrelated FXS premutation carriers and 24 mentally retarded non-FXS affected boys were re-examined by this method. The results totally coincided with the previous ones. This protocol is a good choice as a fast screening test. Within 24 h we can have preliminary information on the patient's genetic status. Normal individuals, CGG premutation carriers up to 100 repeats, as well as HD patients carrying an expansion up to 50 CAG repeats can be easily clarified. This accounts for a relatively large proportion (about 90%) of the suspected HD and FXS patients, referred to our laboratory for genetic analysis. The calculation of the repeat's number is more accurate for the correct interpretation of the results, screening tests and genetic counselling.

  9. Three Huntington's Disease Specific Mutation-Carrying Human Embryonic Stem Cell Lines Have Stable Number of CAG Repeats upon In Vitro Differentiation into Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Laureen Jacquet

    Full Text Available Huntington disease (HD; OMIM 143100, a progressive neurodegenerative disorder, is caused by an expanded trinucleotide CAG (polyQ motif in the HTT gene. Cardiovascular symptoms, often present in early stage HD patients, are, in general, ascribed to dysautonomia. However, cardio-specific expression of polyQ peptides caused pathological response in murine models, suggesting the presence of a nervous system-independent heart phenotype in HD patients. A positive correlation between the CAG repeat size and severity of symptoms observed in HD patients has also been observed in in vitro HD cellular models. Here, we test the suitability of human embryonic stem cell (hESC lines carrying HD-specific mutation as in vitro models for understanding molecular mechanisms of cardiac pathology seen in HD patients. We have differentiated three HD-hESC lines into cardiomyocytes and investigated CAG stability up to 60 days after starting differentiation. To assess CAG stability in other tissues, the lines were also subjected to in vivo differentiation into teratomas for 10 weeks. Neither directed differentiation into cardiomyocytes in vitro nor in vivo differentiation into teratomas, rich in immature neuronal tissue, led to an increase in the number of CAG repeats. Although the CAG stability might be cell line-dependent, induced pluripotent stem cells generated from patients with larger numbers of CAG repeats could have an advantage as a research tool for understanding cardiac symptoms of HD patients.

  10. Structural Insights Reveal the Dynamics of the Repeating r(CAG Transcript Found in Huntington's Disease (HD and Spinocerebellar Ataxias (SCAs.

    Directory of Open Access Journals (Sweden)

    Arpita Tawani

    Full Text Available In humans, neurodegenerative disorders such as Huntington's disease (HD and many spinocerebellar ataxias (SCAs have been found to be associated with CAG trinucleotide repeat expansion. An important RNA-mediated mechanism that causes these diseases involves the binding of the splicing regulator protein MBNL1 (Muscleblind-like 1 protein to expanded r(CAG repeats. Moreover, mutant huntingtin protein translated from expanded r(CAG also yields toxic effects. To discern the role of mutant RNA in these diseases, it is essential to gather information about its structure. Detailed insight into the different structures and conformations adopted by these mutant transcripts is vital for developing therapeutics targeting them. Here, we report the crystal structure of an RNA model with a r(CAG motif, which is complemented by an NMR-based solution structure obtained from restrained Molecular Dynamics (rMD simulation studies. Crystal structure data of the RNA model resolved at 2.3 Å reveals non-canonical pairing of adenine in 5´-CAG/3´-GAC motif samples in different syn and anti conformations. The overall RNA structure has helical parameters intermediate to the A- and B-forms of nucleic acids due to the global widening of major grooves and base-pair preferences near internal AA loops. The comprehension of structural behaviour by studying the spectral features and the dynamics also supports the flexible nature of the r(CAG motif.

  11. Presence of terminal EPIYA phosphorylation motifs in Helicobacter pylori CagA contributes to IL-8 secretion, irrespective of the number of repeats.

    Directory of Open Access Journals (Sweden)

    Konstantinos S Papadakos

    Full Text Available CagA protein contributes to pro-inflammatory responses during H. pylori infection, following its intracellular delivery to gastric epithelial cells. Here, we report for the first time in an isogenic background, on the subtle role of CagA phosphorylation on terminal EPIYA-C motifs in the transcriptional activation and expression of IL-8. We utilized isogenic H. pylori mutants of P12 reference strain, expressing CagA with varying number of EPIYA-C motifs and the corresponding phosphorylation defective EPIFA-C motifs while preserving intact the CM multimerization motifs. These mutants had been previously closely scrutinized in terms of type IV secretion system functionality, CagA translocation and its subsequent phosphorylation. Following infection of gastric epithelial cell lines, transcriptional activation of IL-8 gene and secreted IL-8 levels were found to be strictly dependent upon the functionality of the EPIYA-C phosphorylation motifs, as EPIFA-C phosphorylation-deficient CagA expression failed to induce full IL-8 transcriptional activity. Interestingly, levels of IL-8 gene activation and of secreted IL-8 were the same, irrespective of the number of EPIYA-C terminal repeats. We monitored IkBα phosphorylation and confirmed CagA involvement in NF-kB activation. Furthermore, we observed that presence of EPIYA-C functional phosphorylation motifs contributed to NF-kB activation. NF-kB upstream signaling events, such as early ERK1/2 and AKT activation were confirmed to be independent of EPIYA-C phosphorylation. On the contrary, use of TAK1 specific inhibitor 5Z-7-Oxozeaenol resulted in complete arrest of IL-8 secretion, in a dose-dependent manner, irrespective of CagA status. H. pylori-infected TAK1(-/- mouse embryonic fibroblasts (MEFs failed to induce NF-kB activity, unlike the respective control MEFs. CagA and TAK1 were found to immunoprecipitate together, irrespective of CagA EPIYA-C status, thus confirming earlier reports of TAK1 and Cag

  12. The Presence of Clitoromegaly in the Nonclassical Form of 21-Hydroxylase Deficiency Could Be Partially Modulated by the CAG Polymorphic Tract of the Androgen Receptor Gene

    Science.gov (United States)

    Garcia Gomes, Larissa; Bugano Diniz Gomes, Diogo; Marcondes, José Antônio Miguel; Madureira, Guiomar; de Mendonca, Berenice Bilharinho; Bachega, Tânia A. Sartori Sanchez

    2016-01-01

    Background In the nonclassical form (NC), good correlation has been observed between genotypes and 17OH-progesterone (17-OHP) levels. However, this correlation was not identified with regard to the severity of hyperandrogenic manifestations, which could depend on interindividual variability in peripheral androgen sensitivity. Androgen action is modulated by the polymorphic CAG tract (nCAG) of the androgen receptor (AR) gene and by polymorphisms in 5α-reductase type 2 (SRD5A2) enzyme, both of which are involved in the severity of hyperandrogenic disorders. Objectives To analyze whether nCAG-AR and SRD5A2 polymorphisms influence the severity of the nonclassical phenotype. Patients NC patients (n = 114) diagnosed by stimulated-17OHP ≥10 ng/mL were divided into groups according to the beginning of hyperandrogenic manifestations (pediatric and adolescent/adult) and CYP21A2 genotypes (C/C: homozygosis for mild mutations; A/C: compound heterozygosis for severe/mild mutations). Methods CYP21A2 mutations were screened by allelic-specific PCR, MLPA and/or sequencing. HpaII-digested and HpaII-undigested DNA samples underwent GeneScan analysis to study nCAG, and the SRD5A2 polymorphisms were screened by RLFP. Results Mean nCAG did not differ among pediatric, adolescent/adult and asymptomatic subjects. In the C/C genotype, we observed a significantly lower frequency of longer CAG alleles in pediatric patients than in adolescent/adults (p = 0.01). In patients carrying the A/C genotype, the frequencies of shorter and longer CAG alleles did not differ between pediatric patients and adolescent/adults (p>0.05). Patients with clitoromegaly had significantly lower weighted CAG biallelic mean than those without it: 19.1±2.7 and 21.6±2.5, respectively (p = 0.007), independent of the CYP21A2 genotype's severity. The SRD5A2 polymorphisms were not associated with the variability of hyperandrogenic NC phenotypes. Conclusions In this series, we observed a modulatory effect of the CAG

  13. Association of H pylori cagA and vacA genotypes and IL-8 gene polymorphisms with clinical outcome of infection in Iranian patients with gastrointestinal diseases

    Institute of Scientific and Technical Information of China (English)

    Eskandar Kamali-Sarvestani; Abdulah Bazargani; Malihe Masoudian; Kamran Lankarani; Ali-Reza Taghavi; Mehdi Saberifiroozi

    2006-01-01

    AIM: To find out if a functional promoter polymorphism in the IL-8 gene along with cagA status and polymorphisms in vac4 gene influence the type of diseases in Iranian patients infected by H pylori.METHODS: IL-8 -251 A/T polymorphism was genotypedby oligonucleotide allele specific PCR (ASO-PCR) in a sample of 233 patients with H pylori infection undergoing upper gastrointestinal endoscopy. The presence of cagA gene and polymorphisms in vacA gene was also determined by PCR. Association of these genetic polymorphisms with the development of gastritis, peptic ulcers as well as gastric cancer was tested. RESULTS: When the patients with different clinical manifestations were compared according to the presence of cagA gene or various vacA genotypes, only the vacA genotypes were significantly different among gastritis, peptic ulcer and gastric cancer patients (x2= 17.8; P =0.001). Furthermore, there was a significant difference in the frequency of IL-8 -251 A/T genotypes between patients with gastric cancer and benign diseases (x2=10.47; P = 0.005).CONCLUSION: The IL-8 -251 A/T polymorphism and the polymorphisms in H pylori vacA gene are involved in limiting the infection outcome to gastritis and peptic ulcer or in favoring cancer onset in Iranian patients.

  14. Bovine proteins containing poly-glutamine repeats are often polymorphic and enriched for components of transcriptional regulatory complexes

    LENUS (Irish Health Repository)

    Whan, Vicki

    2010-11-23

    Abstract Background About forty human diseases are caused by repeat instability mutations. A distinct subset of these diseases is the result of extreme expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding poly-glutamine (poly-Q) tracts in proteins. Polymorphic repeat length variation is also apparent in human poly-Q encoding genes from normal individuals. As these coding sequence repeats are subject to selection in mammals, it has been suggested that normal variations in some of these typically highly conserved genes are implicated in morphological differences between species and phenotypic variations within species. At present, poly-Q encoding genes in non-human mammalian species are poorly documented, as are their functions and propensities for polymorphic variation. Results The current investigation identified 178 bovine poly-Q encoding genes (Q ≥ 5) and within this group, 26 genes with orthologs in both human and mouse that did not contain poly-Q repeats. The bovine poly-Q encoding genes typically had ubiquitous expression patterns although there was bias towards expression in epithelia, brain and testes. They were also characterised by unusually large sizes. Analysis of gene ontology terms revealed that the encoded proteins were strongly enriched for functions associated with transcriptional regulation and many contributed to physical interaction networks in the nucleus where they presumably act cooperatively in transcriptional regulatory complexes. In addition, the coding sequence CAG repeats in some bovine genes impacted mRNA splicing thereby generating unusual transcriptional diversity, which in at least one instance was tissue-specific. The poly-Q encoding genes were prioritised using multiple criteria for their likelihood of being polymorphic and then the highest ranking group was experimentally tested for polymorphic variation within a cattle diversity panel. Extensive and meiotically stable variation was identified

  15. A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions.

    Science.gov (United States)

    Zhang, Xue-Song; Tegtmeyer, Nicole; Traube, Leah; Jindal, Shawn; Perez-Perez, Guillermo; Sticht, Heinrich; Backert, Steffen; Blaser, Martin J

    2015-02-01

    Helicobacter pylori persistently colonizes the human stomach, with mixed roles in human health. The CagA protein, a key host-interaction factor, is translocated by a type IV secretion system into host epithelial cells, where its EPIYA tyrosine phosphorylation motifs (TPMs) are recognized by host cell kinases, leading to multiple host cell signaling cascades. The CagA TPMs have been described as type A, B, C or D, each with a specific conserved amino acid sequence surrounding EPIYA. Database searching revealed strong non-random distribution of the B-motifs (including EPIYA and EPIYT) in Western H. pylori isolates. In silico analysis of Western H. pylori CagA sequences provided evidence that the EPIYT B-TPMs are significantly less associated with gastric cancer than the EPIYA B-TPMs. By generating and using a phosphorylated CagA B-TPM-specific antibody, we demonstrated the phosphorylated state of the CagA B-TPM EPIYT during H. pylori co-culture with host cells. We also showed that within host cells, CagA interaction with phosphoinositol 3-kinase (PI3-kinase) was B-TPM tyrosine-phosphorylation-dependent, and the recombinant CagA with EPIYT B-TPM had higher affinity to PI3-kinase and enhanced induction of AKT than the isogenic CagA with EPIYA B-TPM. Structural modeling of the CagA B-TPM motif bound to PI3-kinase indicated that the threonine residue at the pY+1 position forms a side-chain hydrogen bond to N-417 of PI3-kinase, which cannot be formed by alanine. During co-culture with AGS cells, an H. pylori strain with a CagA EPIYT B-TPM had significantly attenuated induction of interleukin-8 and hummingbird phenotype, compared to the isogenic strain with B-TPM EPIYA. These results suggest that the A/T polymorphisms could regulate CagA activity through interfering with host signaling pathways related to carcinogenesis, thus influencing cancer risk.

  16. A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions.

    Directory of Open Access Journals (Sweden)

    Xue-Song Zhang

    2015-02-01

    Full Text Available Helicobacter pylori persistently colonizes the human stomach, with mixed roles in human health. The CagA protein, a key host-interaction factor, is translocated by a type IV secretion system into host epithelial cells, where its EPIYA tyrosine phosphorylation motifs (TPMs are recognized by host cell kinases, leading to multiple host cell signaling cascades. The CagA TPMs have been described as type A, B, C or D, each with a specific conserved amino acid sequence surrounding EPIYA. Database searching revealed strong non-random distribution of the B-motifs (including EPIYA and EPIYT in Western H. pylori isolates. In silico analysis of Western H. pylori CagA sequences provided evidence that the EPIYT B-TPMs are significantly less associated with gastric cancer than the EPIYA B-TPMs. By generating and using a phosphorylated CagA B-TPM-specific antibody, we demonstrated the phosphorylated state of the CagA B-TPM EPIYT during H. pylori co-culture with host cells. We also showed that within host cells, CagA interaction with phosphoinositol 3-kinase (PI3-kinase was B-TPM tyrosine-phosphorylation-dependent, and the recombinant CagA with EPIYT B-TPM had higher affinity to PI3-kinase and enhanced induction of AKT than the isogenic CagA with EPIYA B-TPM. Structural modeling of the CagA B-TPM motif bound to PI3-kinase indicated that the threonine residue at the pY+1 position forms a side-chain hydrogen bond to N-417 of PI3-kinase, which cannot be formed by alanine. During co-culture with AGS cells, an H. pylori strain with a CagA EPIYT B-TPM had significantly attenuated induction of interleukin-8 and hummingbird phenotype, compared to the isogenic strain with B-TPM EPIYA. These results suggest that the A/T polymorphisms could regulate CagA activity through interfering with host signaling pathways related to carcinogenesis, thus influencing cancer risk.

  17. Random rapid amplification of cDNA ends (RRACE) allows for cloning of multiple novel human cDNA fragments containing (CAG)n repeats.

    Science.gov (United States)

    Carney, J P; McKnight, C; VanEpps, S; Kelley, M R

    1995-04-01

    We describe a new technique for isolating cDNA fragments in which (i) either a partial sequence of the cDNA is known or (ii) a repeat sequence is utilized. We have used this technique, termed random rapid amplification of cDNA ends (random RACE), to isolate a number of trinucleotide repeat (CAG)n-containing genes. Using the random RACE (RRACE) technique, we have isolated over a hundred (CAG)n-containing genes. The results of our initial analysis of ten clones indicate that three are identical to previously cloned (CAG)n-containing genes. Three of our clones matched with expressed sequence tags, one of which contained a CA repeat. The remaining four clones did not match with any sequence in GenBank. These results indicate that this approach provides a rapid and efficient method for isolating trinucleotide repeat-containing cDNA fragments. Finally, this technique may be used for purposes other than cloning repeat-containing cDNA fragments. If only a partial sequence of a gene is known, our system, described here, provides a rapid and efficient method for isolating a fragment of the gene of interest. PMID:7536696

  18. Novel BAC mouse model of Huntington’s disease with 225 CAG repeats exhibits an early widespread and stable degenerative phenotype

    Science.gov (United States)

    Wegrzynowicz, Michal; Bichell, Terry Jo; Soares, Barbara D.; Loth, Meredith K.; McGlothan, Jennifer L.; Alikhan, Fatima S.; Hua, Kegang; Coughlin, Jennifer M.; Holt, Hunter K.; Jetter, Christopher S.; Mori, Susumu; Pomper, Martin G.; Osmand, Alexander P.; Guilarte, Tomás R.; Bowman, Aaron B.

    2015-01-01

    BACKGROUND Unusually large CAG repeat expansions (>60) in exon one of Huntingtin (HTT) are invariably associated with a juvenile-onset form of Huntington’s disease (HD), characterized by a more extensive and rapidly progressing neuropathology than the more prevalent adult-onset form. However, existing mouse models of HD that express the full-length Htt gene with CAG repeat lengths associated with juvenile HD (ranging between ~75 to ~150 repeats in published models) exhibit selective neurodegenerative phenotypes more consistent with adult-onset HD. OBJECTIVE To determine if a very large CAG repeat (>200) in full-length Htt elicits neurodegenerative phenotypes consistent with juvenile HD. METHODS Using a bacterial artificial chromosome (BAC) system, we generated mice expressing full-length mouse Htt with ~225 CAG repeats under control of the mouse Htt promoter. Mice were characterized using behavioral, neuropathological, biochemical and brain imaging methods. RESULTS BAC-225Q mice exhibit phenotypes consistent with a subset of features seen in juvenile-onset HD: very early motor behavior abnormalities, reduced body weight, widespread and progressive increase in Htt aggregates, gliosis, and neurodegeneration. Early striatal pathology was observed, including reactive gliosis and loss of dopamine receptors, prior to detectable volume loss. HD-related blood markers of impaired energy metabolism and systemic inflammation were also increased. Aside from an age-dependent progression of diffuse nuclear aggregates at 6 months of age to abundant neuropil aggregates at 12 months of age, other pathological and motor phenotypes showed little to no progression. CONCLUSIONS The HD phenotypes present in animals 3 to 12 months of age make the BAC-225Q mice a unique and stable model of full-length mutant Htt associated phenotypes, including body weight loss, behavioral impairment and HD-like neurodegenerative phenotypes characteristic of juvenile-onset HD and/or late-stage adult

  19. No evidence that 2D:4D is related to the number of CAG repeats in the androgen receptor gene

    Directory of Open Access Journals (Sweden)

    Johannes eHönekopp

    2013-12-01

    Full Text Available The length ratio of the second to the fourth digit (2D:4D is a putative marker of prenatal testosterone (T effects. The number of CAG repeats (CAGn in the AR gene is negatively correlated with T sensitivity in vitro. Results regarding the relationship between 2D:4D and CAGn are mixed but have featured prominently in arguments for and against the validity of 2D:4D. Here, I present random-effects meta-analyses on 14 relevant samples with altogether 1,904 subjects. Results were homogeneous across studies. Even liberal estimates (upper limit of the 95% CI were close to zero and therefore suggested no substantial relationship of CAGn with either right-hand 2D:4D, left-hand 2D:4D, or the difference between the two. However, closer analysis of the effects of CAGn on T dependent gene activation in vitro and of relationships between CAGn and T dependent phenotypic characteristics suggest that normal variability of CAGn has mostly no, very small, or inconsistent effects. Therefore, the lack of a clear association between CAGn and 2D:4D has no negative implications for the latter’s validity as a marker of prenatal T effects.

  20. Multiple repeats of Helicobacter pylori CagA EPIYA-C phosphorylation sites predict risk of gastric ulcer in Iran.

    Science.gov (United States)

    Honarmand-Jahromy, Sahar; Siavoshi, Farideh; Malekzadeh, Reza; Sattari, Taher Nejad; Latifi-Navid, Saeid

    2015-12-01

    Biological activity of Helicobacter pylori oncoprotein CagA is determined by a diversity in the tyrosine phosphorylation motif sites. In the present study, the diversity and the type of the H. pylori CagA EPIYA motifs and their association with gastric ulcer (GU) and duodenal ulcer (DU) in Iranian dyspeptic patients were assessed. PCR amplification, sequencing, and bioinformatic analysis were performed to determine the pattern of CagA EPIYA motifs. Of 168 H. pylori cagA(+) strains, the frequency of ABC was 93.50%, ABCCC 5.40%, ABC + ABCCC 0.6% and ABCC 0.6%. There was no EPIYA-D segment. The ABCCC pattern of EPIYA motif was more frequent in the H. pylori isolates from GU (8/50, 16%) than in those from chronic gastritis (CG) (0/81, 0%) (P = 0). In contrast, The ABC pattern of EPIYA motif was less frequent in the H. pylori isolates from GU (41/50, 82%) than in those from CG (80/81, 98.80%) (Age-sex-adjusted odds ratio (OR) = 0.020, 95% CI = 0.002-0.259; P = 0.003). The distribution of the ABC motif was almost the same in H. pylori isolates from CG (98.80%) and DU diseases (97.30%). There was no significant association between the number of CagA EPIYA-C segment and DU (P > 0.05). We have proposed that CagA from Iranian H. pylori strains were Western type and all strains had active phosphorylation sites. The three EPIYA-C motifs of CagA were more frequently observed in the H. pylori strains from GU; thus it might be an important biomarker for predicting the GU risk in Iran.

  1. Marked phenotypic heterogeneity associated with expansion of a CAG repeat sequence at the spinocerebellar ataxia 3/Machado-Joseph disease locus

    Energy Technology Data Exchange (ETDEWEB)

    Cancel, G.; Abbas, N.; Stevanin, G. [Hopital de la Salpetriere, Paris (France)] [and others

    1995-10-01

    The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group of neurodegenerative disorders, has been mapped to chromosome 14q32.1. ADCA type I patients from families segregating SCA3 share clinical features in common with those with Machado-Joseph disease (MJD), the gene of which maps to the same region. We show here that the disease gene segregating in each of three French ADCA type I kindreds and in a French family with neuropathological findings suggesting the ataxochoreic form of dentatorubropallidoluysian atrophy carries an expanded CAG repeat sequence located at the same locus as that for MJD. Analysis of the mutation in these families shows a strong negative correlation between size of the expanded CAG repeat and age at onset of clinical disease. Instability of the expanded triplet repeat was not found to be affected by sex of the parent transmitting the mutation. Evidence was found for somatic and gonadal mosaicism for alleles carrying expanded trinucleotide repeats. 36 refs., 5 figs., 2 tabs.

  2. 家族性亨廷顿病临床和(CAG)n多态性分析%The polymorphism analysis of (CAG)n gene in Huntington's disease

    Institute of Scientific and Technical Information of China (English)

    初海鹰; 王剑锋; 杨佩满; 黄尚志

    2003-01-01

    @@ 亨廷顿病(Huntington's disease, HD)是一种常染色体显性遗传的基底节和大脑皮层变性疾病,临床特征为慢性进行性的舞蹈样动作和痴呆.1993年,分离获得HD相关基因IT15,并确定其开放阅读框架5'端多态性CAG三核苷酸重复序列的过度扩展为致病的突变[1],正常人群(CAG)n拷贝数为11-34个.通过检测CAG拷贝数,可从基因水平确诊HD.基于此,我们对一个家族性HD家系两个病例进行了基因分析.

  3. Distribution of Polymorphic and Non-Polymorphic Microsatellite Repeats in Xenopus tropicalis

    Directory of Open Access Journals (Sweden)

    Amy K. Sater

    2008-01-01

    Full Text Available The results of our bioinformatics analysis have found over 91,000 di-, tri-, and tetranucleotide microsatellites in our survey of 25% of the X. tropicalis genome, suggesting there may be over 360,000 within the entire genome. Within the X. tropicalis genome, dinucleotide (78.7% microsatellites vastly out numbered tri- and tetranucleotide microsatellites. Similarly, AT-rich repeats are overwhelmingly dominant. The four AT-only motifs (AT, AAT, AAAT, and AATT account for 51,858 out of 91,304 microsatellites found. Individually, AT microsatellites were the most common repeat found, representing over half of all di-, tri-, and tetranucleotide microsatellites. This contrasts with data from other studies, which show that AC is the most frequent microsatellite in vertebrate genomes (Toth et al. 2000. In addition, we have determined the rate of polymorphism for 5,128 non-redundant microsatellites, embedded in unique sequences. Interestingly, this subgroup of microsatellites was determined to have significantly longer repeats than genomic microsatellites as a whole. In addition, microsatellite loci with tandem repeat lengths more than 30 bp exhibited a significantly higher degree of polymorphism than other loci. Pairwise comparisons show that tetranucleotide microsatellites have the highest polymorphic rates. In addition, AAT and ATC showed significant higher polymorphism than other trinucleotide microsatellites, while AGAT and AAAG were significantly more polymorphic than other tetranucleotide microsatellites.

  4. ATXN2 with intermediate-length CAG/CAA repeats does not seem to be a risk factor in hereditary spastic paraplegia

    DEFF Research Database (Denmark)

    Nielsen, Troels Tolstrup; Svenstrup, Kirsten; Budtz-Jørgensen, Esben;

    2012-01-01

    Hereditary spastic paraplegia (HSP) confines a group of heterogeneous neurodegenerative disorders characterized by progressive spasticity and lower limb weakness. Age of onset is highly variable even in familial cases with known mutations suggesting that the disease is modulated by other yet...... unknown parameters. Although progressive gait disturbances, lower limb spasticity and extensor plantar responses are hallmarks of HSP these characteristics are also found in other neurodegenerative disorders, e.g. amytrophic lateral sclerosis (ALS). HSP has been linked to ALS and frontotemporal...... in spinocerebellar ataxia type 2, has been shown to be a modulator of TDP-43 induced toxicity in ALS animal and cell models. Finally, it has been shown that ATXN2 with non-pathogenic intermediate-length CAG/CAA repeat elongations (encoding the polyglutamine tract) is a genetic risk factor of ALS. Considering...

  5. Modelling studies on neurodegenerative disease-causing triplet repeat sequences d(GGC/GCC)n and d(CAG/CTG)n

    Indian Academy of Sciences (India)

    Shibasish Chowdhury; Manju Bansal

    2001-12-01

    Model building and molecular mechanics studies have been carried out to examine the potential structures for d(GGC/GCC)5 and d(CAG/CTG)5 that might relate to their biological function and association with triplet repeat expansion diseases. Model building studies suggested that hairpin and quadruplex structures could be formed with these repeat sequences. Molecular mechanics studies have demonstrated that the hairpin and hairpin dimer structures of triplet repeat sequences formed by looping out of the two strands are as favourable as the corresponding B-DNA type hetero duplex structures. Further, at high salt condition, Greek key type quadruplex structures are energetically comparable with hairpin dimer and B-DNA type duplex structures. All tetrads in the quadruplex structures are well stacked and provide favourable stacking energy values. Interestingly, in the energy minimized hairpin dimer and Greek key type quadruplex structures, all the bases even in the non-G tetrads are cyclically hydrogen bonded, even though the A, C and T-tetrads were not hydrogen bonded in the starting structures.

  6. Improved set of short-tandem-repeat polymorphisms for screening the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Bo; Vaske, D.; Weber, J.L. [Marshfield Medical Research Foundation, WI (United States)] [and others

    1997-02-01

    Short-tandem-repeat (microsatellite) DNA polymorphisms are widely used for screening the human and other genomes in initial linkage mapping. Since the average spacing between polymorphisms in genome screens is usually {ge}10 cM and since many thousands of human short-tandem-repeat polymorphisms (STRPs) are now available, optimal subsets of STRPs must be selected for screening. Two screening sets of STRPs for humans have been described in the literature, both of which are based primarily on dinucleotide-repeat polymorphisms. Here we describe our eighth and most recent human screening set, which is based almost entirely on trinucleotide-and tetranucleotide-repeat polymorphisms. 7 refs., 1 tab.

  7. Size of the exon 1-CAG repeats of the androgen receptor gene employed as a molecular marker in the diagnosis of Turner syndrome in girls with short stature.

    Science.gov (United States)

    Figueiredo, C C; Kochi, C; Longui, C A; Rocha, M N; Richeti, F; Evangelista, N M A; Calliari, L E P; Monte, O

    2008-01-01

    Turner syndrome (TS) is one of the most common chromosomal abnormalities among girls. Complete monosomy of X chromosome is responsible for almost 50% of all cases of TS, and mosaicism and X anomaly are detected in the other half. It has already been demonstrated that early diagnosis of these children allows appropriate growth hormone treatment with better final height prognosis and introduction of estrogen at an ideal chronological age. Sixty-four short-stature girls were selected and the clinical data obtained were birth weight and height, weight and height at the first medical visit and target height. Other clinical data including cardiac and renal abnormalities, otitis, Hashimoto thyroiditis, cubitus valgus, short neck, widely separated nipples, and pigmented nevi were obtained from the patients' medical records. The aim of the present study was to evaluate the screening of a group of short-stature girls for TS based on the number of CAG repeats of the androgen receptor gene analyzed by GeneScan software. Patient samples with two alleles (heterozygous) were 49/64 (76.5%) and with one allele (homozygous) were 15/64 (23.5%). A karyotype was determined in 30 patients, 9 homozygous and 21 heterozygous. In the homozygous group, 6/9 were 45,X and 3/9 were 46,XX. In the heterozygous group, 17/21 were 46,XX, and 4/21 were TS patients with mosaicism (45,X/46,XX; 45,X/46XiXq; 46XdelXp). The pattern obtained by GeneScan in two patients with mosaicism in the karyotype was an imbalance between the peak heights of the two alleles, suggesting that this imbalance could be present when there is a mosaicism. The frequency of TS abnormalities (18.7%) did not differ between TS and 46,XX girls. Thus, it is important to accurately assess the incidence of TS in growth-retarded girls, even in the absence of other dysmorphisms. In this study, we diagnosed 6 cases of TS 45,X (9.4%) by molecular analysis, with a 100% sensitivity and 85% specificity. This molecular analysis was able to

  8. Neil1 is a genetic modifier of somatic and germline CAG trinucleotide repeat instability in R6/1 mice

    OpenAIRE

    Møllersen, Linda; Rowe, Alexander D; Illuzzi, Jennifer L.; Hildrestrand, Gunn A; Gerhold, Katharina J.; Tveterås, Linda; Bjølgerud, Anja; Wilson, David M.; Bjørås, Magnar; Klungland, Arne

    2012-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder caused by trinucleotide repeat (TNR) expansions. We show here that somatic TNR expansions are significantly reduced in several organs of R6/1 mice lacking exon 2 of Nei-like 1 (Neil1) (R6/1/Neil1 −/−), when compared with R6/1/Neil1 +/+ mice. Somatic TNR expansion is measured by two different methods, namely mean repeat change and instability index. Reduced somatic expansions are more pronounced in male R6/1/Neil1 −/− mice, ...

  9. Intermediate CAG repeat lengths (53,54) for MJD/SCA3 are associated with an abnormal phenotype

    NARCIS (Netherlands)

    van Alfen, N; Sinke, R J; Zwarts, M J; Gabreëls-Festen, A; Praamstra, P; Kremer, B P; Horstink, M W

    2001-01-01

    We report on a Dutch family in which 4 members in 2 generations have intermediate repeat lengths (53 and 54) for Machado-Joseph Disease/Spinocerebellar Ataxia (MJD/SCA3). All but the youngest have a restless legs syndrome with fasciculations and a sensorimotor axonal polyneuropathy. Central neurolog

  10. Presence of terminal EPIYA phosphorylation motifs in Helicobacter pylori CagA contributes to IL-8 secretion, irrespective of the number of repeats.

    OpenAIRE

    Papadakos, Konstantinos S.; Sougleri, Ioanna S; Mentis, Andreas F; Efstathios Hatziloukas; Sgouras, Dionyssios N.

    2013-01-01

    CagA protein contributes to pro-inflammatory responses during H. pylori infection, following its intracellular delivery to gastric epithelial cells. Here, we report for the first time in an isogenic background, on the subtle role of CagA phosphorylation on terminal EPIYA-C motifs in the transcriptional activation and expression of IL-8. We utilized isogenic H. pylori mutants of P12 reference strain, expressing CagA with varying number of EPIYA-C motifs and the corresponding phosphorylation de...

  11. Oxidized dNTPs and the OGG1 and MUTYH DNA glycosylases combine to induce CAG/CTG repeat instability.

    Science.gov (United States)

    Cilli, Piera; Ventura, Ilenia; Minoprio, Anna; Meccia, Ettore; Martire, Alberto; Wilson, Samuel H; Bignami, Margherita; Mazzei, Filomena

    2016-06-20

    DNA trinucleotide repeat (TNR) expansion underlies several neurodegenerative disorders including Huntington's disease (HD). Accumulation of oxidized DNA bases and their inefficient processing by base excision repair (BER) are among the factors suggested to contribute to TNR expansion. In this study, we have examined whether oxidation of the purine dNTPs in the dNTP pool provides a source of DNA damage that promotes TNR expansion. We demonstrate that during BER of 8-oxoguanine (8-oxodG) in TNR sequences, DNA polymerase β (POL β) can incorporate 8-oxodGMP with the formation of 8-oxodG:C and 8-oxodG:A mispairs. Their processing by the OGG1 and MUTYH DNA glycosylases generates closely spaced incisions on opposite DNA strands that are permissive for TNR expansion. Evidence in HD model R6/2 mice indicates that these DNA glycosylases are present in brain areas affected by neurodegeneration. Consistent with prevailing oxidative stress, the same brain areas contained increased DNA 8-oxodG levels and expression of the p53-inducible ribonucleotide reductase. Our in vitro and in vivo data support a model where an oxidized dNTPs pool together with aberrant BER processing contribute to TNR expansion in non-replicating cells. PMID:26980281

  12. Severe and rapidly progressing cognitive phenotype in a SCA17-family with only marginally expanded CAG/CAA repeats in the TATA-box binding protein gene: A case report

    Directory of Open Access Journals (Sweden)

    Nielsen Troels

    2012-08-01

    Full Text Available Abstract Background The autosomal dominant spinocerebellar ataxias (SCAs confine a group of rare and heterogeneous disorders, which present with progressive ataxia and numerous other features e.g. peripheral neuropathy, macular degeneration and cognitive impairment, and a subset of these disorders is caused by CAG-repeat expansions in their respective genes. The diagnosing of the SCAs is often difficult due to the phenotypic overlap among several of the subtypes and with other neurodegenerative disorders e.g. Huntington’s disease. Case presentation We report a family in which the proband had rapidly progressing cognitive decline and only subtle cerebellar symptoms from age 42. Sequencing of the TATA-box binding protein gene revealed a modest elongation of the CAG/CAA-repeat of only two repeats above the non-pathogenic threshold of 41, confirming a diagnosis of SCA17. Normally, repeats within this range show reduced penetrance and result in a milder disease course with slower progression and later age of onset. Thus, this case presented with an unusual phenotype. Conclusions The current case highlights the diagnostic challenge of neurodegenerative disorders and the need for a thorough clinical and paraclinical examination of patients presenting with rapid cognitive decline to make a precise diagnosis on which further genetic counseling and initiation of treatment modalities can be based.

  13. Polymorphic repeat in AIB1 does not alter breast cancer risk

    International Nuclear Information System (INIS)

    We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor characteristics. These findings suggest that AIB1 repeat genotype does not influence postmenopausal breast cancer risk among Caucasian women in the general population. A causal association between endogenous and exogenous estrogens and breast cancer has been established. Steroid hormones regulate the expression of proteins that are involved in breast cell proliferation and development after binding to their respective steroid hormone receptors. Coactivator and corepressor proteins have recently been identified that interact with steroid hormone receptors and modulate transcriptional activation [1]. AIB1 (amplified in breast 1) is a member of the steroid receptor coactivator (SRC) family that interacts with estrogen receptor (ER)α in a ligand-dependent manner, and increases estrogen-dependent transcription [2]. Amplification and overexpression of AIB1 has been observed in breast and ovarian cancer cell lines and in breast tumors [2,3]. A polymorphic stretch of glutamine amino acids, with unknown biologic function, has recently been described in the carboxyl-terminal region of AIB1 [4]. Among women with germline BRCA1 mutations, significant positive associations were observed between AIB1 alleles with 26 or fewer glutamine repeats and breast cancer risk [5] To establish whether AIB1 repeat alleles are associated with breast cancer risk and specific tumor characteristics among Caucasian women. We evaluated associations prospectively between AIB1 alleles and breast cancer risk in the Nurses' Health Study using a nested case-control design. The Nurses' Health Study was initiated in 1976, when 121 700 US-registered nurses between the ages of 30 and 55 years returned an

  14. Progress study on the mechanism of CAG repeats dynamic mutation in polyQ disease%多聚谷氨酰胺病CAG重复序列动态突变机制研究进展

    Institute of Scientific and Technical Information of China (English)

    王春荣; 江泓

    2012-01-01

    多聚谷氨酰胺病是一类中枢神经系统退行性疾病.由致病基因外显子内胞嘧啶-腺嘌呤-鸟嘌呤(CAG)三核苷酸重复序列拷贝数异常扩增导致其编码的多聚谷氨酰胺链异常延长,引起多聚谷氨酰胺扩展突变蛋白积聚而致病.迄今为止,共发现9种因多聚谷氨酰胺扩展突变型蛋白积聚引起的遗传性神经退行性疾病.CAG重复序列在代间传递过程中发生动态突变(拷贝数不断扩增),进而导致发病年龄提前和疾病严重程度增加.%Polyglutamine (polyQ) disease is a group of neurodegenerative disorders caused by abnormal expansion of CAG repeats within coding regions of certain causative genes, which are translated into a series of abnormally expanded polyQ tracts causing cytotoxicity. So far, nine diseases caused by expanded polyQ tracts have been demonstrated including Huntington's disease (HD), spinobulbar muscular atrophy (SBMA), dentatorubral-pallidoluysian atrophy (DRPLA) and several spinocerebellar ataxias subtypes (SCA). In human, long CAG repeats tend to expand during transmissions from parent to offspring, named as dynamic mutation, leading to an earlier age of disease onset and more severe symptoms in subsequent generations. The review presents some novel mechanisms based on dynamic mutation.

  15. Clinical characteristics of Huntington disease in two pedigrees and analysis of expanded CAG trinucleotide repeat%2个Huntington病家系临床特征及CAG重复性分析

    Institute of Scientific and Technical Information of China (English)

    曹广娜; 包新华; 卢红梅; 张晶晶; 马一楠; 顾卫红; 熊晖; 秦炯; 吴希如

    2011-01-01

    目的:探讨Huntington病(Huntington disease,HD)的临床和遗传特征.方法:对收集的2个中国汉族HD家系患者的临床资料进行综合分析,应用聚合酶链式反应及基因扫描方法对其中9例家系成员的IT15基因的三核苷酸重复序列进行分析.结果:在两个家系中确诊了6例患者(男女均有发病),患者IT15基因的基因型均为杂合子,致病CAG重复拷贝数介于40~78次.两个家系中子代较父代发病年龄提前,家系2中可见发病年龄与CAG重复拷贝数呈负相关.6例患者中有1例为少年型HD,其临床表现明显不同于成人型,以肌张力障碍为主要表现.结论:HD是一种由CAG重复序列异常扩增所致的神经变性病,存在遗传早现现象;少年型HD的临床表现不同于成人型,CAG重复拷贝数与发病年龄及疾病严重程度有关.%Objective: To understand the clinical and genetic features of Huntington disease ( HD) . Methods: The clinical data of HD cases from 2 Chinese families were analyzed and trinucleotide repeat in the IT15 gene were investigated in 9 of the two families by polymerase chain reaction and GeneScan. Results : Among the two pedigrees, 6 cases were ascertained as HD by genetic test. Genotypes of IT15 were heterozygous in these HD patients. CAG repeat of the patients in the HD chromosome were 40 -78. In the two pedigrees, the onset age was earlier in the subsequent generations than that of their fathers. In pedigree 2, the onset age was inversely correlated with CAG repeat number. One out of the 6 cases was juvenile-onset type of Huntington disease, whose clinical symptoms were different from those of the adultonset cases, especially the hypertonic manifestation. Conclusion: HD is an autosomal dominant neurodegenerative disorder with genetic anticipation caused by enlargement of CAG repeat in IT15 gene. The clinical manifestation is different between the juvenile-onset and the adult-onset. The number of CAG repeat is inversely

  16. EGFR CA repeat polymorphism predict clinical outcome in EGFR mutation positive NSCLC patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther Larsen, Anne; Nissen, Peter Henrik; Meldgaard, Peter;

    2014-01-01

    OBJECTIVES: Somatic mutations in the epidermal growth factor receptor (EGFR) are predictors of efficacy for treatment with the EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer (NSCLC). A CA repeat polymorphism in intron 1 of the EGFR gene influences the transcription...... of the EGFR gene. This study evaluates the association between the CA repeat polymorphism and outcome in NSCLC patients treated with erlotinib.MATERIALS AND METHODS: Number of CA repeats in the EGFR gene was evaluated with PCR-fragment length analysis by capillary electrophoresis in 432 advanced NSCLC...... patients treated with erlotinib irrespective of EGFR mutation status. Patients were dichotomized into harboring short allele (CA≤16 in any allele) or long alleles (CA>16 in both alleles). Number of repeats was correlated with clinical characteristic and outcome. A subgroup analysis was performed based...

  17. Association between a Tetranucleotide Repeat Polymorphism of SPAG16 Gene and Cataract in Male Children

    Directory of Open Access Journals (Sweden)

    Shipra Mehra

    2013-01-01

    Full Text Available Purpose. Studies involving genotyping of STR markers at 2q34 have repeatedly found the region to host the disease haplotype for pediatric cataract. Present study investigated the association of D2S2944 marker, in sperm associated antigen 16 (SPAG16 gene and rs2289917 polymorphism, in γ-crystallin B gene, with childhood cataract. Methods. 97 pediatric cataract cases and 110 children with no ocular defects were examined for tetranucleotide repeat marker/SNP using PCR-SSLP/RFLP techniques. Polymorphisms were assessed for association using contingency tables and linkage disequilibrium among alleles of the markers was estimated. Energy-optimization program predicted the secondary structure models of repeats of D2S2944. Results. Seven alleles of D2S2944, with 9–15 “GATA” repeats, were observed. Frequency of the longer allele of D2S2944, ≥(GATA13 repeats, was 0.73 in cases and 0.56 in controls (P=0.0123. Male children bearing ≥(GATA13 repeats showed >3-fold higher risk for cataract (CI95% = 1.43–7.00, P=0.0043, Pc=0.0086 as compared to female children (OR=1.19, CI95% = 0.49–2.92, P=0.70. Cases with haplotype—≥(GATA13 of D2S2944 and “C” allele rs2289917—have a higher risk for pediatric cataract (OR=2.952, CI95% = 1.595~5.463, P=0.000453. >(GATA13 repeats formed energetically more favorable stem-loop structure. Conclusion. Intragenic microsatellite repeat expansion in SPAG16 gene increases predisposition to pediatric cataract by probably interfering posttranscriptional events and affecting the expression of adjacent lens transparency gene/s in a gender bias manner.

  18. Isolation and molecular characterization of a highly polymorphic centromeric tandem repeat in the family Falconidae.

    Science.gov (United States)

    Longmire, J L; Lewis, A K; Brown, N C; Buckingham, J M; Clark, L M; Jones, M D; Meincke, L J; Meyne, J; Ratliff, R L; Ray, F A

    1988-01-01

    An abundant tandem repeat has been cloned from genomic DNA of the merlin (Falco columbarius). The cloned sequence is 174 bp in length, and maps by in situ hybridization to the centromeric regions of several of the large chromosomes within the merlin karyotype. Complementary sequences have been identified within a variety of falcon species; these sequences are either absent or in very low copy number in the family Accipitridae. The cloned merlin repeat reveals highly polymorphic restriction patterns in the peregrine falcon (Falco peregrinus). These polymorphisms, which have been shown to be stably inherited within a family of captive peregrines, can be used to differentiate the Greenland and Argentina populations of this endangered raptor species.

  19. Biological activity of the virulence factor cagA of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    朱永良; 郑树; 钱可大; 方平楚

    2004-01-01

    Background China is one of the countries with the highest incidence of H. Pylori and more than 9090 isolates possessed the cagA gene. This study was to evaluate the biological activity of the H.pylori virulence factor cagA isolated from Chinese patients. Methods cagA DNA fragments were amplified from the genomic DNA and subsequently cloned into the mammalian expression vector for cell transfection and DNA sequencing. cagA protein, phosphorylated-tyrosine cagA and the complex of cagA precipitated with SHP-2 were identified respectively by western blot in the crude cell lysate from conditionally immortalized gastric epithelial cells at 48 hours after transfection with cagA DNA. In addition, the ability of induction of scattering phenotype was examined after transient expression of cagA in AGS cells. Results The C-terminal half of cagA contained only one repeated sequence and three tandem five-amino-acid motifs glutamic acid-proline-isoleucine-tyrosine-alanine (EPIYA). Moreover, the amino acid sequence of D2 region in repeated sequence was aspartic acid-phenylanaline-aspartic acid (D-F-D) which was significantly distinguished from the three repeated sequences and aspartic acid-aspartic adid-leucine (D-D-L) in the western standard strain NCTC11637. Western blot revealed that cagA became phosphorylated in tyrosine site and bound with SHP-2 after transient expression of cagA DNA in gastric epithelial cells. Transient expression of cagA in AGS cells showed that cagA was able to induce the elongation phenotype although to a lesser extent than western strains. Conclusions cagA perturbs cell signaling pathways by binding with SHP-2. However, significant difference exists in amino acid sequence and biological function of cagA in Chinese compared with those of western countries.

  20. Fen1 does not control somatic hypermutability of the (CTG)(n)*(CAG)(n) repeat in a knock-in mouse model for DM1.

    NARCIS (Netherlands)

    Broek, W.J.A.A. van den; Nelen, M.R.; Heijden, G.W. van der; Wansink, D.G.; Wieringa, B.

    2006-01-01

    The mechanism of trinucleotide repeat expansion, an important cause of neuromuscular and neurodegenerative diseases, is poorly understood. We report here on the study of the role of flap endonuclease 1 (Fen1), a structure-specific nuclease with both 5' flap endonuclease and 5'-3' exonuclease activit

  1. A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Katherine A Bolton

    2016-06-01

    Full Text Available Due to the lack of high-throughput genetic assays for tandem repeats, there is a paucity of knowledge about the role they may play in disease. A polymorphic CA repeat in the promoter region of the insulin-like growth factor 1 gene (IGF1 has been studied extensively over the past 10 years for association with the risk of developing breast cancer, among other cancers, with variable results. The aim of this study was to determine if this CA repeat is associated with the risk of developing breast cancer and endometrial cancer. Using a case–control design, we analysed the length of this CA repeat in a series of breast cancer and endometrial cancer cases and compared this with a control population. Our results showed an association when both alleles were considered in breast and endometrial cancers (P=0.029 and 0.011, respectively, but this did not pass our corrected threshold for significance due to multiple testing. When the allele lengths were analysed categorically against the most common allele length of 19 CA repeats, an association was observed with the risk of endometrial cancer due to a reduction in the number of long alleles (P=0.013. This was confirmed in an analysis of the long alleles separately for endometrial cancer risk (P=0.0012. Our study found no association between the length of this polymorphic CA repeat and breast cancer risk. The significant association observed between the CA repeat length and the risk of developing endometrial cancer has not been previously reported.

  2. A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer

    Science.gov (United States)

    Bolton, Katherine A; Avery-Kiejda, Kelly A; Holliday, Elizabeth G; Attia, John; Bowden, Nikola A

    2016-01-01

    Due to the lack of high-throughput genetic assays for tandem repeats, there is a paucity of knowledge about the role they may play in disease. A polymorphic CA repeat in the promoter region of the insulin-like growth factor 1 gene (IGF1 has been studied extensively over the past 10 years for association with the risk of developing breast cancer, among other cancers, with variable results. The aim of this study was to determine if this CA repeat is associated with the risk of developing breast cancer and endometrial cancer. Using a case–control design, we analysed the length of this CA repeat in a series of breast cancer and endometrial cancer cases and compared this with a control population. Our results showed an association when both alleles were considered in breast and endometrial cancers (P=0.029 and 0.011, respectively), but this did not pass our corrected threshold for significance due to multiple testing. When the allele lengths were analysed categorically against the most common allele length of 19 CA repeats, an association was observed with the risk of endometrial cancer due to a reduction in the number of long alleles (P=0.013). This was confirmed in an analysis of the long alleles separately for endometrial cancer risk (P=0.0012). Our study found no association between the length of this polymorphic CA repeat and breast cancer risk. The significant association observed between the CA repeat length and the risk of developing endometrial cancer has not been previously reported. PMID:27090263

  3. A study of allelic polymorphism of four short tandem repeats in the population of northwestern Russia

    Energy Technology Data Exchange (ETDEWEB)

    Aseev, M.V.; Skakun, V.N.; Baranov, V.S. [Ott Institute of Obstetrics and Gynecology, St. Petersburg (Russian Federation)

    1995-06-01

    Characteristics of the allelic polymorphisms of the trimeric AGC repeat of the androgen receptor gene (Xq11-12), exon 1 (AR); the tetrameric ATCT repeat of the von Willebrand factor gene (12p12), intron 40 (vWF); the AGAT repeat of the hypoxanthine phosphoribosyltransferase gene (Xq26) (HPRT); and the AGAT repeat of anonymous DNA sequences of the short arm of chromosome X (STRX1) were studied in 160 DNA samples from unrelated inhabitants of northwestern Russia using the method of polymerase chain reaction. Seventeen, ten, eight, and nine alleles were revealed electrophoretically for short tandem repeats of AR, vWF, HPRT, and STRX1, respectively. The heterozygosity indices for these repeats were 0.80, 0.70, 0.54, and 0.58, respectively. The values for AR and vWF correlated with those expected according to the Hardy-Weinberg equilibrium, whereas the values for HPRT and STRX1 differed significantly from those theoretically expected. The individualization potentials were 0.045, 0.135, 0.095, and 0.061 for the short tandem repeats of AR, vWF, HPRT, and STRX1, respectively. The distribution of genotypes for the set of these four loci in the population studied was determined. The possibilities of using the studied polymorphic marker systems in molecular diagnosis of the corresponding monogenic diseases - spinal and bulbar muscle atrophy (AR), Lesch-Nyhan disease (HPRT), and von Willebrand disease (vWF) - as well as in population human genetics, testing of personal identity, and molecular approaches to the estimation of mutagenic activity are discussed. 17 refs., 2 figs., 6 tabs.

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

    Directory of Open Access Journals (Sweden)

    Macedo Selma E

    2012-02-01

    Full Text Available Abstract 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.

  5. Analysis of Y-chromosomal short tandem repeat (STR) polymorphism in an Iranian Sadat population.

    Science.gov (United States)

    Rafiee, M R; Sokhansanj, A; Naghizadeh, M A; Farazmand, A

    2009-08-01

    The molecular genotyping of individuals and reconstruction of kinship through short and highly polymorphic DNA markers, so called short tandem repeats (STR), has become one of the important and efficient methods in anthropology studies and forensic science. Although many populations have been analyzed, no study has yet been carried out on Sadat populations who are putative descendents of Prophet Mohammad (peace be upon him). Polymorphisms of 6 Y-STR loci (DYS19, DYS385a/b, DYS389II, DYS390, DYS392, and DYS393) have been studied in an unrelated population of Sadat males. The aim of this study was to find possible similarities within Sadat males, resided in Iran. Among Sadat, DYS385b was proved to be the most polymorphic (GD = 0.8588), and DYS392 showed the lowest polymorphism (GD = 0.3527). In 50 samples, 45 different haplotypes were found, of which 39 haplotypes were unique. In the study, three samples had multi-allelic patterns. Haplotype diversity, in regard to these 7 markers was 0.9942. PMID:19769300

  6. Chromosomal abnormalities and polymorphic variants in couples with repeated miscarriage in Mexico.

    Science.gov (United States)

    De la Fuente-Cortés, Beatriz E; Cerda-Flores, Ricardo M; Dávila-Rodríguez, Martha I; García-Vielma, Catalina; De la Rosa Alvarado, Rosa M; Cortés-Gutiérrez, Elva I

    2009-04-01

    Cytogenetic studies have an important role in the evaluation of couples with repeated miscarriages and poor obstetric history. To estimate the prevalence of chromosomal abnormalities and polymorphic variants in 158 couples with repeated miscarriages, a cross-sectional study was conducted in Monterrey, Mexico from 1995 to 2003. Peripheral blood lymphocytes were cultured for chromosomal studies using standard methods. Twelve couples showed chromosomal abnormalities (7.60%), two Robertsonian translocations (1.27%), two balanced translocations (1.27%), one inversion (0.63%), and one a novel insertion (0.63%). This insertion [46, XX, ins (15;8) (q26;p11p23)] is unique, and is the third reported in association with repeated abortion. Mosaicism was observed in six couples (3.80%, three with structural abnormalities and three with numerical abnormalities). A female to male ratio of 1.4:1 was observed. In addition to these chromosomal abnormalities, polymorphic variants in constitutive heterochromatin of the 1qh+, 9qh+, and 16qh+ chromosomes were observed in 25 couples (15.82%), of the Yqh+ chromosome in 21 couples (13.29%), and of satellite in 35 couples (22.15%). In conclusion, chromosome analysis is necessary for appropriate clinical management of these patients.

  7. Androgen receptor gene polymorphisms are associated with aggression in Japanese Akita Inu

    OpenAIRE

    Konno, Akitsugu; Inoue-Murayama, Miho; Hasegawa, Toshikazu

    2011-01-01

    We tested for an association between variable number of tandem repeats in the canine androgen receptor (AR) gene and personality differences in Japanese Akita Inu dogs. The polymorphic trinucleotide (CAG) repeat region coding for glutamine in exon 1 of the AR gene was genotyped using genomic DNA obtained from 171 dogs. Three alleles (23, 24 and 26 repeats) were detected, and the allele frequency differed with the coat colour. We assessed the personality profiles of 100 fawn-coloured dogs (54 ...

  8. γA gene repeats polymorphism for the analysis of haplotypes of abnormal hemoglobins

    Directory of Open Access Journals (Sweden)

    Nejat Akar

    2014-09-01

    Full Text Available Aim of this study was to analyze γ A gene repeat polymorphism for the analysis of haplotypes of hemoglobin (Hb variants such as Hb S, Hb D-Punjab, Hb O-Arab. Sickle cell cases had mainly Benin and Arab/Indian haplotype. We found three different haplotypes among Hb S, Hb O Arab and Hb D-Punjab cases. We named these three variants as Anatolian-1 and Anatolian-2 and Asian. Our data revealed that Hb O Arab may arise twice one from Asia and the other from Europe.

  9. Efficacy Improvement of PCR Amplification of CAG Trinucleotide Repeats in the Coding Sequence of Spinocerebellar Ataxia Type II Gene%提高SCA2编码区CAG三核苷酸重复的PCR扩增效率

    Institute of Scientific and Technical Information of China (English)

    汤熙翔; 夏家辉

    2000-01-01

    To improve the efficacy of PCR amplification of CAG trinucleotide repeats in the coding sequence of spinocerebellar ataxia type II gene(69.2% G+C), hot-start PCR, base-replacement PCR, and the addition of enhancers(1%~12.5% DMSO , 1%~25% glycerol ,1%~12.5% formamide) were performed and compared with normal PCR . The results showed that hot-start PCR, base-replacement PCR and the addition of enhancers(1%~10% DMSO , 5%~20% glycerol , 1%~10% formamide) improved the amplification efficacy of the GC rich region. Gene diagnosis in 70 SCA pedgrees and 60 spontaneous SCA patients were also conducted.%以遗传性脊髓小脑共济失调II型基因(spinocerebellar ataxia type II gene SCA2)编码区内的CAG三核苷酸重复为研究对象(G+C含量为69.2%),比较了热启动PCR、碱基替代PCR、添加增效剂(1%~12.5%二甲亚砜、1%~25%甘油、1%~12.5%甲酰胺)与常规PCR的扩增效率,发现热启动PCR、碱基替代PCR及添加增效剂(1%~10%二甲亚砜、5%~20%甘油、1%~10%甲酰胺)能提高该GC富集区的扩增效率,并对70个SCA家系及60个散发SCA患者进行了SCA2的基因诊断。

  10. Identification of polymorphic tandem repeats by direct comparison of genome sequence from different bacterial strains : a web-based resource

    Directory of Open Access Journals (Sweden)

    Vergnaud Gilles

    2004-01-01

    Full Text Available Abstract Background Polymorphic tandem repeat typing is a new generic technology which has been proved to be very efficient for bacterial pathogens such as B. anthracis, M. tuberculosis, P. aeruginosa, L. pneumophila, Y. pestis. The previously developed tandem repeats database takes advantage of the release of genome sequence data for a growing number of bacteria to facilitate the identification of tandem repeats. The development of an assay then requires the evaluation of tandem repeat polymorphism on well-selected sets of isolates. In the case of major human pathogens, such as S. aureus, more than one strain is being sequenced, so that tandem repeats most likely to be polymorphic can now be selected in silico based on genome sequence comparison. Results In addition to the previously described general Tandem Repeats Database, we have developed a tool to automatically identify tandem repeats of a different length in the genome sequence of two (or more closely related bacterial strains. Genome comparisons are pre-computed. The results of the comparisons are parsed in a database, which can be conveniently queried over the internet according to criteria of practical value, including repeat unit length, predicted size difference, etc. Comparisons are available for 16 bacterial species, and the orthopox viruses, including the variola virus and three of its close neighbors. Conclusions We are presenting an internet-based resource to help develop and perform tandem repeats based bacterial strain typing. The tools accessible at http://minisatellites.u-psud.fr now comprise four parts. The Tandem Repeats Database enables the identification of tandem repeats across entire genomes. The Strain Comparison Page identifies tandem repeats differing between different genome sequences from the same species. The "Blast in the Tandem Repeats Database" facilitates the search for a known tandem repeat and the prediction of amplification product sizes. The "Bacterial

  11. Simple sequence repeats in Neurospora crassa: distribution, polymorphism and evolutionary inference

    Directory of Open Access Journals (Sweden)

    Park Jongsun

    2008-01-01

    Full Text Available Abstract Background Simple sequence repeats (SSRs have been successfully used for various genetic and evolutionary studies in eukaryotic systems. The eukaryotic model organism Neurospora crassa is an excellent system to study evolution and biological function of SSRs. Results We identified and characterized 2749 SSRs of 963 SSR types in the genome of N. crassa. The distribution of tri-nucleotide (nt SSRs, the most common SSRs in N. crassa, was significantly biased in exons. We further characterized the distribution of 19 abundant SSR types (AST, which account for 71% of total SSRs in the N. crassa genome, using a Poisson log-linear model. We also characterized the size variation of SSRs among natural accessions using Polymorphic Index Content (PIC and ANOVA analyses and found that there are genome-wide, chromosome-dependent and local-specific variations. Using polymorphic SSRs, we have built linkage maps from three line-cross populations. Conclusion Taking our computational, statistical and experimental data together, we conclude that 1 the distributions of the SSRs in the sequenced N. crassa genome differ systematically between chromosomes as well as between SSR types, 2 the size variation of tri-nt SSRs in exons might be an important mechanism in generating functional variation of proteins in N. crassa, 3 there are different levels of evolutionary forces in variation of amino acid repeats, and 4 SSRs are stable molecular markers for genetic studies in N. crassa.

  12. Polymorphism in the HASPB repeat region of East African Leishmania donovani strains.

    Directory of Open Access Journals (Sweden)

    Arie Zackay

    Full Text Available BACKGROUND/OBJECTIVES: Visceral leishmaniasis (VL caused by Leishmania donovani is a major health problem in Ethiopia. Parasites in disparate regions are transmitted by different vectors, and cluster in distinctive genotypes. Recently isolated strains from VL and HIV-VL co-infected patients in north and south Ethiopia were characterized as part of a longitudinal study on VL transmission. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-three L. donovani strains were examined by polymerase chain reaction (PCR targeting three regions: internal transcribed spacer 1 (ITS1, cysteine protease B (cpb, and HASPB (k26. ITS1- and cpb--PCR identified these strains as L. donovani. Interestingly, the k26--PCR amplicon size varied depending on the patient's geographic origin. Most strains from northwestern Ethiopia (36/40 produced a 290 bp product with a minority (4/40 giving a 410 bp amplicon. All of the latter strains were isolated from patients with HIV-VL co-infections, while the former group contained both VL and HIV-VL co-infected patients. Almost all the strains (20/23 from southwestern Ethiopia produced a 450 bp amplicon with smaller products (290 or 360 bp only observed for three strains. Sudanese strains produced amplicons identical (290 bp to those found in northwestern Ethiopia; while Kenyan strains gave larger PCR products (500 and 650 bp. High-resolution melt (HRM analysis distinguished the different PCR products. Sequence analysis showed that the k26 repeat region in L. donovani is comprised of polymorphic 13 and 14 amino acid motifs. The 13 amino acid peptide motifs, prevalent in L. donovani, are rare in L. infantum. The number and order of the repeats in L. donovani varies between geographic regions. CONCLUSIONS/SIGNIFICANCE: HASPB repeat region (k26 shows considerable polymorphism among L. donovani strains from different regions in East Africa. This should be taken into account when designing diagnostic assays and vaccines based on this antigen.

  13. The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated with peptic ulcer and gastric cancer in Mexican population

    OpenAIRE

    Beltrán-Anaya, Fredy Omar; Poblete, Tomás Manuel; Román-Román, Adolfo; Reyes, Salomón; de Sampedro, José; Peralta-Zaragoza, Oscar; Rodríguez, Miguel Ángel; del Moral-Hernández, Oscar; ILLADES-AGUIAR, BERENICE; Fernández-Tilapa, Gloria

    2014-01-01

    Background Helicobacter pylori chronic infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. Cytotoxin-associated gene A (cagA)-positive H. pylori strains increase the risk of gastric pathology. The carcinogenic potential of CagA is linked to its polymorphic EPIYA motif variants. The goals of this study were to investigate the frequency of cagA-positive Helicobacter pylori in Mexican patients with gastric pathologies and to assess the association of cagA EPIYA moti...

  14. Helicobacter pylori CagL Hypervariable Motif: A Global Analysis of Geographical Diversity and Association With Gastric Cancer.

    Science.gov (United States)

    Gorrell, Rebecca J; Zwickel, Nicolas; Reynolds, John; Bulach, Dieter; Kwok, Terry

    2016-06-15

    Previous studies suggest overrepresentation of particular polymorphisms within the Helicobacter pylori CagL hypervariable motif (CagLHM) in gastric cancer-associated isolates. However, these disease correlations were geographically variable and ambiguous. We compared the disease correlation of several hundred geographically diverse CagL sequences and identified 33 CagLHM sequence combinations with disparate geographical distribution, revealing substantial worldwide CagLHM diversity, particularly within Asian countries. Notably, polymorphisms E59 and I60 were significantly overrepresented, whereas D58 and E62 were underrepresented, in gastric cancer-associated H. pylori isolates worldwide. Thus, CagLHM regional diversity may contribute to the varied prevalence of H. pylori-related gastric cancer observed in diverse populations. PMID:26908724

  15. 直接检测IT15基因(CAG)n重复对亨廷顿氏病进行基因诊断%Direct Detection of the Expanded CAG Repeat in IT15 Gene for Molecular Diagnosis of Huntington's Disease

    Institute of Scientific and Technical Information of China (English)

    毛跃华; 周刚; 陈美珏; 任兆瑞; 曾溢滔; 王秀英; 许志大

    1995-01-01

    应用巢式PCR和变性聚丙烯酰胺凝胶电泳放射自显影鉴定IT15基因(CAG)n串联重复序列拷贝数的技术,对40名正常中国人以及徐州和浙江两大亨廷顿氏病(HD病)家系46名家庭成员进行了分析.结果表明,正常中国人IT15基因(CAG)n拷贝数为16左右,而HD患者的突变基因(CAG)n拷贝数均大于40,两者之间不重叠.对38名HD病高风险者进行症状前分子诊断,揭示11名家庭成员为HD基因的携带者,与家系调查和临床分析的结果相吻合.本文结果不仅证明IT15基因的动态突变也是导致中国人HD病的遗传学基础,而且为HD病的基因诊断、遗传咨询和遗传保健提供了科学资料.

  16. Normal ATXN3 allele but not CHIP polymorphisms modulates age at onset in Machado-Joseph Disease

    Directory of Open Access Journals (Sweden)

    Marcondes C. França Jr

    2012-11-01

    Full Text Available Background: Age at onset (AO in Machado-Joseph disease (MJD is closely associated with the length of the CAG repeat at the mutant ATXN3 allele, but there are other intervening factors. Experimental evidence indicates that the normal ATXN3 allele and the C-terminal heat shock protein 70 (Hsp70-interacting protein (CHIP may be genetic modifiers of AO in MJD. Methods: To investigate this hypothesis, we determined the length of normal and expanded CAG repeats at the ATXN3 gene in 210 unrelated patients with MJD. In addition, we genotyped five single nucleotide polymorphisms (SNPs within the CHIP gene. We first compared the frequencies of the different genotypes in two subgroups of patients who were highly discordant for AO after correction for the length of the expanded CAG allele. The possible modifier effect of each gene was then evaluated in a stepwise multiple linear regression model. Results: AO was associated with the length of the expanded CAG allele (r2 = 0.596, p<0.001. Frequencies of the normal CAG repeats at the ATXN3 gene and of CHIP polymorphisms did not differ significantly between groups with highly discordant ages at onset. However, addition of the normal allele improved the model fit for prediction of AO (r2 = 0.604, p=0.014. Indeed, we found that the normal CAG allele at ATXN3 had a positive independent effect on AO. Conclusion: The normal CAG repeat at the ATXN3 gene has a small but significant influence on AO of MJD.

  17. Allelic polymorphisms in the repeat and promoter regions of the interleukin-4 gene and malaria severity in Ghanaian children

    DEFF Research Database (Denmark)

    Gyan, B A; Goka, B; Cvetkovic, J T;

    2004-01-01

    Immunoglobulin E has been associated with severe malaria suggesting a regulatory role for interleukin (IL)-4 and/or IgE in the pathogenesis of severe malaria. We have investigated possible associations between polymorphisms in the IL-4 repeat region (intron 3) and promoter regions (IL-4 +33CT and...

  18. A high-density simple sequence repeat and single nucleotide polymorphism genetic map of the tetraploid cotton genome

    Science.gov (United States)

    Cotton genome complexity was investigated with a saturated molecular genetic map that combined several sets of microsatellites or simple sequence repeats (SSR) and the first major public set of single nucleotide polymorphism (SNP) markers in cotton genomes (Gossypium spp.), and that was constructed ...

  19. Psychiatric symptoms and CAG expansion in Huntington`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Weber, M.W.; Schmid, W.; Spiegel, R. [Univ. of Zuerich (Switzerland)

    1996-02-16

    The mutation responsible for Huntington`s disease (HD) is an elongated CAG repeat in the coding region of the IT15 gene. A PCR-based test with high sensitivity and accuracy is now available to identify asymptomatic gene carriers and patients. An inverse correlation between CAG copy number and age at disease onset has been found in a large number of affected individuals. The influence of the CAG repeat expansion on other phenotypic manifestations, especially specific psychiatric symptoms has not been studied intensively. In order to elucidate this situation we investigated the relation between CAG copy number and distinct psychiatric phenotypes found in 79 HD-patients. None of the four differentiated categories (personality change, psychosis, depression, and nonspecific alterations) showed significant differences in respect to size of the CAG expansion. In addition, no influence of individual sex on psychiatric presentation could be found. On the other hand in patients with personality changes maternal transmission was significantly more frequent compared with all other groups. Therefore we suggest that clinical severity of psychiatric features in HD is not directly dependent on the size of the dynamic mutation involved. The complex pathogenetic mechanisms leading to psychiatric alterations are still unknown and thus genotyping does not provide information about expected psychiatric symptoms in HD gene carriers. 40 refs., 1 fig., 2 tabs.

  20. Intraspecific differentiation of Hancornia speciosa revealed by simple sequence repeat and random amplified polymorphic DNA markers.

    Science.gov (United States)

    Nogueira, C A; Stafuzza, N B; Ribeiro, T P; Prado, A D L; Menezes, I P P; Peixoto, N; Gonçalves, P J; Almeida, L M

    2015-01-01

    Hancornia speciosa, popularly known as mangabeira, is a fruit tree native to the Brazilian Cerrado that shows great economic potential, due to its multiple uses. Intraspecific classification of this species is difficult because it shows high morphological diversity. An early study of the species reported that there are six botanic varieties that differ morphologically mainly in the shapes of their leaves and flowers. Except to note the wide morphological variation and economic potential of this species, few studies have been published about the genetic diversity of mangabeira. Knowledge of the genetic variability of this species among populations would be useful for genetic conservation and breeding programs. Therefore, we tested the transferability of 12 simple sequence repeats from expressed sequence tags (EST-SSRs) from Catharanthus roseus to H. speciosa and used 10 random amplified polymorphic DNA markers to evaluate the genetic variability among botanical varieties of H. speciosa. We obtained a high transferability frequency of EST-SSR markers from C. roseus to H. speciosa (75%). However, EST-SSR markers showed low heterozygosity and locus variability (two or three alleles by locus), which suggest low genetic diversity in the mangabeira samples. The Jaccard dissimilarity index and an examination of geographic distances indicated a non-spatial structuring of the genetic variability. Our markers were unable to distinguish H. speciosa botanical varieties. PMID:26662392

  1. Abundance and length polymorphism of microsatellite repeats in Beta vulgaris L.

    Science.gov (United States)

    Mörchen, M; Cuguen, J; Michaelis, G; Hänni, C; Saumitou-Laprade, P

    1996-03-01

    Simple sequence repeats (SSRs) are known to exhibit high degrees of variability even among closely related individuals. Their usage as nuclear genetic markers requires their conversion into sequence-tagged sites (STSs). In this paper we present the development of simple sequences as STSs for Beta vulgaris. This species comprises wild, cultivated, and weedy forms; the latter are thought to originate from accidental hybridisation between the other two. Two partial genomic libraries were screened with simple sequence motifs (AT, CA, CT, ATT, GTG, and CA, CT, respectively). Clones of 22 CA, nine CT, eight ATT, and one GTG sequence were obtained. AT micro satellites were present in compound motifs, not recognised by the probe. Sequence comparisons revealed that 20 CA clones containing short motifs (800 bp). Genetic variability was high among wild beets, lower among cultivated beets, and intermediate among weed beets. One allele of each locus was found at high frequencies in cultivated beets and, to a lower extent, in weed beets. The combination of three polymorphic loci allowed the individual identification of 17/17 wild and 15/15 weed beets, and 21/32, mostly homozygous, cultivated beets.

  2. Androgen Receptor Gene Polymorphism and Breast Cancer Risk%AR基因外显子1的CAG重复多态性与乳腺癌发生的关系

    Institute of Scientific and Technical Information of China (English)

    孟洁; 付丽

    2012-01-01

    Objective To assess the association between AR ( Androgen Receptor ) gene polymorphism[ CAG ]n in exon 1 and breast cancer. Methods 50 cases of breast cancer and 50 controls were collected. DNA was extracted from peripheral blood leukocytes. The encoding sequence of AR gene exonl was amplified by PCR. After direct sequencing of PCR products,the CAG repeats were calculated. The Wilcoxon rank test was used to compare the distributions of the [ CAG ]n. Breast cancer risk was assessed using multivariate logistic regression. Results The [ CAG ]n was 15 ~26 for cases and was 16 ~26 for controls. The distribution of [ CAG ]n for cases and controls was different P =0.015 ). Women for whom the [ CAG ]n was ≥24 units had approximately 5. 6 risk of breast cancer compared [ CAG ]n ≤20 ( P =0. 04,OR =5. 6 ). Conclusion These data suggest that AR gene exonl[ CAG ]n has influence on breast cancer, and longer AR [ CAG ]n may increase breast cancer risk.%目的 探讨AR(雄激素受体)基因外显子1的CAG重复多态性与乳腺癌发生的关系.方法 研究对象为50例乳腺癌患者和50例健康者,从外周血淋巴细胞中提取基因组DNA,对AR基因外显子1的编码序列进行PCR扩增,扩增产物进行DNA序列测定,计算CAG重复频率.Wilcoxon rank test 比较病例组和对照组的[CAG]n分布,采用多因素log回归分析[CAG]n对乳腺癌发病风险的影响.结果 病例组[CAG]n为15~26,对照组为16~26;两组重复频率分布有差异(P=0.015),[CAG]n≥24时乳腺癌发病风险为[CAG]n≤20的5.6倍(P=0.04,OR=5.6).结论 AR基因外显子1的CAG重复频率对乳腺癌风险发病有影响,长[CAG]n可增大乳腺癌发病风险.

  3. (AC)n dinucleotide repeat polymorphism in 5' beta-globin gene in native and Mestizo Mexican populations.

    Science.gov (United States)

    Peñaloza, R; Delgado, P; Arenas, D; Barrientos, C; Buentello, L; Loeza, F; Salamanca, F

    2001-12-01

    Repeated sequences are dispersed along the human genome. These sequences are useful as markers in diagnosis of inherited diseases, in forensic medicine, and in tracking the origin and evolution of human populations. The (AC)n repeated element is the most frequent in the human genome. In this paper, the (AC)n repeated element located in the 5' flanking region of the beta-globin gene was studied by single-strand conformation polymorphism (SSCP). Four ethnic Mexican groups (Mixteca, Nahua, Otomí, Purépecha) and a Mestizo population were analyzed. We observed three alleles, A [(AC)16, B [(AC)14], and C [(AC)18], with a frequency of between 68.2% and 86.9%, 13.1% and 18.2%, and 6.7% and 13.7%, respectively. Allele C was present only in Purépecha and Mestizo groups. The absence of this allele in the other ethnic groups studied suggests that there is low genetic admixture of Purépecha and that this is a relatively isolated population. However, it could be that the C allele occurs in low frequencies in the other groups as a result of small sample sizes. The (AC)n repeat polymorphism in the beta-globin gene has not been previously studied in Amerindian populations.

  4. Characterization of CagA variable region of Helicobacter pylori isolates from Chinese patients

    Institute of Scientific and Technical Information of China (English)

    Yong-Liang Zhu; Shu Zheng; Qin Du; Ke-Da Qian; Ping-Chu Fang

    2005-01-01

    AIM: To characterize the CagA variable region of Helicobacter pylori isolates from Chinese patients.METHODS: DNA fragments in CagA variable region were amplified and sequenced respectively from genomic DNA of 19 isolates from patients with gastric cancer and 20isolates from patients with chronic gastritis. The tendency of phosphorylation in tyrosine(s) of CagA proteins was evaluated subsequently by phosphorylation assay in vivo and in vitro respectively.RESULTS: About 97.44% (38/39) H pylori isolates possessed CagA gene. CagA+ strains contained 2-4tandem five-amino-acid motifs EPIYA but only one EPIYA had repeated sequence in CagA variable region in different isolates. There was no significant difference between the number of EPIYA motifs in H pylori from patients with different diseases. However, only tyrosine site in EPIYA within repeated sequence could be phosphorylated by AGS cells in vivo although all tyrosine sites in EPIYA could be phosphorylated in vitro.CONCLUSION: CagA in Chinese has no functional difference in perturbing cellular signal pathway among different H pylori isolates.

  5. Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Kyllo, J.H.; Collins, M.M.; Vetter, K.L. [Univ. of Iowa College of Medicine, Iowa City, IA (United States)] [and others

    1996-03-29

    Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene of chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes. 25 refs., 5 figs., 2 tabs.

  6. CTG repeats distribution and Alu insertion polymorphism at myotonic dystrophy (DM) gene in Amhara and Oromo populations of Ethiopia.

    Science.gov (United States)

    Gennarelli, M; Pavoni, M; Cruciani, F; De Stefano, G; Dallapiccola, B; Novelli, G

    1999-01-01

    Myotonic dystrophy (DM) is a dominantly inherited neuromuscular disease, highly variable and multisystemic, which is caused by the expansion of a CTG repeat located in the 3' untranslated region of the DMPK gene. Normal alleles show a copy number of 5-37 repeats on normal chromosomes, amplified to 50-3000 copies on DM chromosomes. The trinucleotide repeat shows a trimodal allele distribution in the majority of the examined population. The first class includes alleles carrying (CTG)5, the second class, alleles in the range 7-18 repeats, and the third class, alleles (CTG) > or =19. The frequency of this third class is directly related to the prevalence of DM in different populations, suggesting that normal large-sized alleles predispose toward DM. We studied CTG repeat allele distribution and Alu insertion and/or deletion polymorphism at the myotonic dystrophy locus in two major Ethiopian populations, the Amhara and Oromo. CTG allele distribution and haplotype analysis on a total of 224 normal chromosomes showed significant differences between the two ethnic groups. These differences have a bearing on the out-of-Africa hypothesis for the origin of the DM mutation. In addition, (CTG) > or =19 were exclusively detected in the Amhara population, confirming the predisposing role of these alleles compared with the DM expansion-mutation.

  7. Prenatal diagnosis of familial dysautonomia by analysis of linked CA-repeat polymorphisms on chromosome 9q31-q33

    Energy Technology Data Exchange (ETDEWEB)

    Eng, C.M.; Desnick, R.J. [Mount Sinai School of Medicine, New York, NY (United States); Slaugenhaupt, S.A.; Gusella, J.F. [Harvard Medical School, Boston, MA (United States)] [and others

    1995-11-20

    Familial dysautonomia (FD) is an autosomal recessive sensory neuropathy that affects about 1 in 3,700 individuals of Ashkenazi Jewish ancestry. The underlying biochemical and genetic defects are unknown, thereby precluding prenatal diagnosis in at-risk families. Recently, the FD gene (DYS) was mapped with strong linkage disequilibrium to polymorphic markers in the chromosome 9 region q31-q33. In this report, the use of these markers for the prenatal diagnosis of FD by linkage analysis in families with a previously affected child was evaluated. Genomic DNA from appropriate family members was analyzed to construct haplotypes using informative CA repeat polymorphisms closely linked to and flanking the FD locus. The calculation of risk for the prenatal diagnoses was performed by linkage analysis. All seven FD families were informative for the closely linked polymorphic markers and fetal diagnoses were made in eight pregnancies. Six fetal diagnoses were predicted with >98% accuracy, while two with recombinations were predicted with at least 88% and 92% accuracy. Use of these closely linked markers permitted the reliable prenatal diagnosis of FD in families with a previously affected child. 14 refs., 3 figs.

  8. Endothelial Nitric Oxide Synthase Gene Intron 4, 27 bp Repeat Polymorphism and Essential Hypertension in the Kazakh Chinese Population

    Institute of Scientific and Technical Information of China (English)

    Fengmei DENG; Huimin ZHANG; Juan ZHAO; Hua ZHONG; Ling HE; Jun LI; Le ZHANG; Shuren WANG; Qinghua HU; Bin TANG; Fang HE; Shuxia GUO; Jiang CHEN; Feng LI; Xuehua WU; Jun ZHANG

    2007-01-01

    To investigate the relationship between 27 bp repeat polymorphism in intron 4 in the endothelial nitric oxide synthase (eNOS4) gene and essential hypertension in the Kazakh Chinese population, 151 patients with essential hypertension and 138 healthy people were selected from the Boertonggu countryside of Shawan region in the Xinjiang Uygur Autonomous Region of China in 2006. The polymorphism of eNOS in the two groups was detected with polymerase chain reaction assays and the genotype frequencies in each group were calculated following the Hardy-Weinberg law. Four and five tandem 27 bp repeats were designated as "a" and "b", respectively. It was found that the frequencies of b/b, b/a and a/a genotypes of the eNOS4 gene were 84.06%, 15.22% and 0.72% in the control group, and 81.46%, 15.89% and 2.65% in the hypertension group, respectively. The frequencies of gene "b" and "a" were 91.67% and 8.33% in the control group and 89.40% and 10.60% in the hypertension group, respectively. It was found that plasma eNOS activity was not associated with genotypes and alleles of eNOS gene. Plasma eNOS activity in the hypertension group was significantly decreased compared with the control group (P<0.01). The results suggest that eNOS4 gene polymorphisms are unlikely to be the major genetic susceptibility factors for essential hypertension in the Xinjiang Kazakh population. However, a positive association between plasma eNOS activity and essential hypertension has been revealed.

  9. [Tissue-specific Changes in the Polymorphism of Simple Repeats in DNA of the Offspring of Different Sex Born from Irradiated Male or Female Mice].

    Science.gov (United States)

    Lomaeva, M G; Fomenko, L A; Vasil'eva, G V; Bezlepkin, V G

    2016-01-01

    Evidence is presented indicating the differences in the polymorphism of microsatellite (MCS) repeats in DNA of somatic tissues in the offspring of BALB/c mice of different sex born from preconceptionally irradiated males or females. Brother-sister groups of the offspring born by non-irradiated parental pairs were compared with the offspring obtained after the irradiation of one parent in the same pairs. The number of MCS repeats in DNA of somatic tissues of the offspring from irradiated males or females was compared by a polymerase chain reaction using an arbitrary primer. It was found that changes in the polymorphism of the number of MCS repeats in the offspring from the males irradiated at a dose of 2 Gy was insignificant as compared with the offspring from control animals. In the offspring born by the females irradiated at a dose of 2 Gy (which does not impair the reproductive capacity), a statistically significant increase in the polymorphism was observed. Changes in the polymorphism were different in the offspring of different sex. A higher level of polymorphism was revealed in the female offspring born from the females of the F0 generation after their irradiation at a dose of 2 Gy. The increase in the polymorphism of the number of MCS repeats in DNA was more pronounced in postmitotic tissues compared with proliferating tissues. PMID:27534065

  10. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Spink, Barbara C. [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Bloom, Michael S. [Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Wu, Susan [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Sell, Stewart; Schneider, Erasmus [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Ding, Xinxin [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Spink, David C., E-mail: spink@wadsworth.org [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States)

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung

  11. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    International Nuclear Information System (INIS)

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC)n, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC)2 alleles were observed; however, in western gorilla, (GGGGC)n alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC)n was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC)n alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC)2 was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC)n short tandem repeats are inherited, and that the (GGGGC)2 allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC)n, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC)n microsatellite instability • AHR promoter activity of a construct with (GGGGC)2 was lower than that of (GGGGC)4 • The frequency of (GGGGC)2 in lung cancer patients was 8-fold higher than in neonates • The (GGGGC)2 allele may

  12. Evolution of cagA oncogene of Helicobacter pylori through recombination.

    Directory of Open Access Journals (Sweden)

    Yoshikazu Furuta

    Full Text Available Helicobacter pylori is a gastric pathogen that infects half the human population and causes gastritis, ulcers, and cancer. The cagA gene product is a major virulence factor associated with gastric cancer. It is injected into epithelial cells, undergoes phosphorylation by host cell kinases, and perturbs host signaling pathways. CagA is known for its geographical, structural, and functional diversity in the C-terminal half, where an EPIYA host-interacting motif is repeated. The Western version of CagA carries the EPIYA segment types A, B, and C, while the East Asian CagA carries types A, B, and D and shows higher virulence. Many structural variants such as duplications and deletions are reported. In this study, we gained insight into the relationships of CagA variants through various modes of recombination, by analyzing all known cagA variants at the DNA sequence level with the single nucleotide resolution. Processes that occurred were: (i homologous recombination between DNA sequences for CagA multimerization (CM sequence; (ii recombination between DNA sequences for the EPIYA motif; and (iii recombination between short similar DNA sequences. The left half of the EPIYA-D segment characteristic of East Asian CagA was derived from Western type EPIYA, with Amerind type EPIYA as the intermediate, through rearrangements of specific sequences within the gene. Adaptive amino acid changes were detected in the variable region as well as in the conserved region at sites to which no specific function has yet been assigned. Each showed a unique evolutionary distribution. These results clarify recombination-mediated routes of cagA evolution and provide a solid basis for a deeper understanding of its function in pathogenesis.

  13. Association Between Interleukin 4 Gene Seventy-Base-Pair Variable Number of Tandem Repeats Polymorphism and Uterine Leiomyoma

    Directory of Open Access Journals (Sweden)

    Salimi

    2014-06-01

    Full Text Available Background Uterine Leiomyoma (UL is the most common gynecological tumor and a public health problem. Higher serum interleukin 4 (IL-4 level, as an anti-inflammatory cytokine that regulates TH1/TH2 cells balance, has been observed in the uterine cavity. Objectives The aim of this study was to investigate the association between IL4 gene variable number of tandem repeats (VNTR polymorphism and the risk of UL in southeast of Iran. Patients and Methods We compared of 99 patients with UL with that of 102 healthy controls. The IL4 VNTR polymorphism was genotyped by gel electrophoresis after PCR amplification. Results There was no significant association between RP*1/RP*2 and RP*2/RP*2 genotypes and UL; however, a significant association between RP*2/RP*2 genotype and UL was found after adjustment for age (OR, 4; 95% CI, 1.3-12.4; and P = 0.015. The frequency of RP*2 allele was significantly higher in women with UL (OR, 1.9; 95% CI, 1.1-3.5; and P = 0.03. Conclusions The IL4 VNTR RP*2/RP*2 genotype could be an age-related risk factor for UL. Moreover, the frequency of RP*2 allele was significantly higher in women with UL.

  14. Mapping of a Wheat Resistance Gene to Yellow Mosaic Disease by Amplified Fragment Length Polymorphism and Simple Sequence Repeat Markers

    Institute of Scientific and Technical Information of China (English)

    Wei-Hua LIU; Huan NIE; Zhen-Tian HE; Xiu-Lan CHEN; Yue-Peng HAN; Jin-Rong WANG; Xin LI; Cheng-Gui HAN; Jia-Lin YU

    2005-01-01

    Wheat (Triticum aestivum L.) yellow mosaic virus (WYMV) is transmitted by a fungal vector through soil and causes serious wheat yield losses due to yellow mosaic disease, with yellow-streaked leaves and stunted plants. In the present study, the amplified fragment length polymorphisms (AFLP) and simple sequence repeat (SSR) were used to identify the molecular linkages with the resistance gene against WYMV. Bulked segregant analysis was performed with an F2 population derived from the cross of cultivar Ningmai 9 (resistant) × cultivar Yangmai 10 (susceptible). By screening among the resistant or susceptible parents, the F2 pools and the individuals in the F2 population with 64 combined selective AFLP primers(EcoRI/MseI) or 290 reported SSR primers, a polymorphic DNA segment (approximately 120 bp) was amplified using the primer pair E2/M5, and an SSR marker (approximately 180 bp) was located on wheat chromosome 2A using the primer Xgwm328. Analysis with MAPMAKER/Exp Version 3.0b (Whitehead institute for Biomedical Research, Cambridge, MA, USA) indicated that these two markers were dominantly associated with the resistance gene at distances of 5.4 cM or 17.6 cM, respectively. The resistance gene to WYMV derived from Ningmai 9, is temporarily named YmNM, and was mapped to wheat chromosome 2A.

  15. CagI is an essential component of the Helicobacter pylori Cag type IV secretion system and forms a complex with CagL.

    Directory of Open Access Journals (Sweden)

    Kieu Thuy Pham

    Full Text Available Helicobacter pylori, the causative agent of type B gastritis, peptic ulcers, gastric adenocarcinoma and MALT lymphoma, uses the Cag type IV secretion system to induce a strong proinflammatory response in the gastric mucosa and to inject its effector protein CagA into gastric cells. CagA translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it is considered as a major bacterial virulence trait. Recently, it has been shown that binding of the type IV secretion apparatus to integrin receptors on target cells is a crucial step in the translocation process. Several bacterial proteins, including the Cag-specific components CagL and CagI, have been involved in this interaction. Here, we have examined the localization and interactions of CagI in the bacterial cell. Since the cagI gene overlaps and is co-transcribed with the cagL gene, the role of CagI for type IV secretion system function has been difficult to assess, and conflicting results have been reported regarding its involvement in the proinflammatory response. Using a marker-free gene deletion approach and genetic complementation, we show now that CagI is an essential component of the Cag type IV secretion apparatus for both CagA translocation and interleukin-8 induction. CagI is distributed over soluble and membrane-associated pools and seems to be partly surface-exposed. Deletion of several genes encoding essential Cag components has an impact on protein levels of CagI and CagL, suggesting that both proteins require partial assembly of the secretion apparatus. Finally, we show by co-immunoprecipitation that CagI and CagL interact with each other. Taken together, our results indicate that CagI and CagL form a functional complex which is formed at a late stage of secretion apparatus assembly.

  16. CAG tract of MJD-1 may be prone to frameshifts causing polyalanine accumulation.

    Science.gov (United States)

    Gaspar, C; Jannatipour, M; Dion, P; Laganière, J; Sequeiros, J; Brais, B; Rouleau, G A

    2000-08-12

    Machado-Joseph disease (MJD) is one of several disorders caused by the expansion of a coding CAG repeat (exp-CAG). The presence of intranuclear inclusions (INIs) in patients and cellular models of exp-CAG-associated diseases has lead to a nuclear toxicity model. Similar INIs are found in oculopharyngeal muscular dystrophy, which is caused by a short expansion of an alanine-encoding GCG repeat. Here we propose that transcriptional or translational frameshifts occurring within expanded CAG tracts result in the production and accumulation of polyalanine-containing mutant proteins. We hypothesize that these alanine polymers deposit in cells forming INIs and may contribute to nuclear toxicity. We show evidence that supports our hypothesis in lymphoblast cells from MJD patients, as well as in pontine neurons of MJD brain and in in vitro cell culture models of the disease. We also provide evidence that alanine polymers alone are harmful to cells and predict that a similar pathogenic mechanism may occur in the other CAG repeat disorders. PMID:10942424

  17. CAG tract of MJD-1 may be prone to frameshifts causing polyalanine accumulation.

    Science.gov (United States)

    Gaspar, C; Jannatipour, M; Dion, P; Laganière, J; Sequeiros, J; Brais, B; Rouleau, G A

    2000-08-12

    Machado-Joseph disease (MJD) is one of several disorders caused by the expansion of a coding CAG repeat (exp-CAG). The presence of intranuclear inclusions (INIs) in patients and cellular models of exp-CAG-associated diseases has lead to a nuclear toxicity model. Similar INIs are found in oculopharyngeal muscular dystrophy, which is caused by a short expansion of an alanine-encoding GCG repeat. Here we propose that transcriptional or translational frameshifts occurring within expanded CAG tracts result in the production and accumulation of polyalanine-containing mutant proteins. We hypothesize that these alanine polymers deposit in cells forming INIs and may contribute to nuclear toxicity. We show evidence that supports our hypothesis in lymphoblast cells from MJD patients, as well as in pontine neurons of MJD brain and in in vitro cell culture models of the disease. We also provide evidence that alanine polymers alone are harmful to cells and predict that a similar pathogenic mechanism may occur in the other CAG repeat disorders.

  18. Improving global and regional resolution of male lineage differentiation by simple single-copy Y-chromosomal short tandem repeat polymorphisms

    NARCIS (Netherlands)

    M. Vermeulen (Mark); A. Wollstein (Andreas); K. van der Gaag (Kristiaan); O. Lao Grueso (Oscar); Y. Xue (Yali); Q. Wang (Qiuju); L. Roewer (Lutz); H. Knoblauch (Hans); C. Tyler-Smith (Chris); P. de Knijff (Peter); M.H. Kayser (Manfred)

    2009-01-01

    textabstractWe analyzed 67 short tandem repeat polymorphisms from the non-recombining part of the Y-chromosome (Y-STRs), including 49 rarely studied simple single-copy (ss)Y-STRs and 18 widely used Y-STRs, in 590 males from 51 populations belonging to 8 worldwide regions (HGDP-CEPH panel). Although

  19. Clustering of Beijing genotype Mycobacterium tuberculosis isolates from the Mekong delta in Vietnam on the basis of variable number of tandem repeat versus restriction fragment length polymorphism typing.

    NARCIS (Netherlands)

    Huyen, M.N.; Kremer, K.; Lan, N.T.; Buu, T.N.; Cobelens, F.G.; Tiemersma, E.W.; Haas, P. de; Soolingen, D. van

    2013-01-01

    BACKGROUND: In comparison to restriction fragment length polymorphism (RFLP) typing, variable number of tandem repeat (VNTR) typing is easier to perform, faster and yields results in a simple, numerical format. Therefore, this technique has gained recognition as the new international gold standard i

  20. Development of Single Nucleotide Polymorphism markers in Theobroma cacao and comparison to Simple Sequence Repeat markers for genotyping of Cameroon clones.

    Science.gov (United States)

    Single Nucleotide Polymorphism (SNP) markers are increasingly being used in crop breeding programs, slowly replacing Simple Sequence Repeats (SSR) and other markers. SNPs provide many benefits over SSRs, including ease of analysis and unambiguous results across various platforms. We have identifie...

  1. Size polymorphism of chicken major histocompatibility complex-encoded B-G molecules is due to length variation in the cytoplasmic heptad repeat region

    DEFF Research Database (Denmark)

    Kaufman, J; Salomonsen, J; Skjødt, K;

    1990-01-01

    that the extracellular regions of these molecules are very similar and that the length polymorphism is due to variations in the cytoplasmic regions. Inspection of the cDNA-derived protein sequence in this region shows many heptad repeats, which may allow variation in length by step deletion and alternative splicing...

  2. Anthropometry in Klinefelter syndrome - multifactorial influences due to CAG length, testosterone treatment and possibly intrauterine hypogonadism

    DEFF Research Database (Denmark)

    Chang, Simon; Skakkebæk, Anne; Trolle, Christian;

    2015-01-01

    .47)(p<0.02 for all), as well as total fat mass (0.74), abdominal fat mass (0.67) and total body fat percentage (0.84) was increased in KS males (p<0.001 for all), while bitesticular volume was reduced (4.6). AR CAG repeat length was comparable in KS and controls, and among KS CAG correlated to arm...... body composition in KS and relate findings to biochemistry and X-chromosome related genetic markers. Design, setting and participants: 73 KS males referred to our clinic and 73 age-matched controls underwent comprehensive measurements of anthropometry and body composition in a cross-sectional, case......-controlled study. Furthermore, genetic analysis for parental origin of the supernumerary X-chromosome, skewed X-chromosome inactivation and androgen receptor (AR) CAG repeat length was done. Main outcome measure: Anthropometry and body composition in KS and the effect of genotype hereon. Results: KS males were...

  3. COMT Val158Met Polymorphism Modulates Huntington's Disease Progression

    Science.gov (United States)

    Rebeix, Isabelle; Dupoux, Emmanuel; Durr, Alexandra; Brice, Alexis; Charles, Perrine; Cleret de Langavant, Laurent; Youssov, Katia; Verny, Christophe; Damotte, Vincent; Azulay, Jean-Philippe; Goizet, Cyril; Simonin, Clémence; Tranchant, Christine; Maison, Patrick; Rialland, Amandine; Schmitz, David; Jacquemot, Charlotte; Fontaine, Bertrand; Bachoud-Lévi, Anne-Catherine

    2016-01-01

    Little is known about the genetic factors modulating the progression of Huntington’s disease (HD). Dopamine levels are affected in HD and modulate executive functions, the main cognitive disorder of HD. We investigated whether the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which influences dopamine (DA) degradation, affects clinical progression in HD. We carried out a prospective longitudinal multicenter study from 1994 to 2011, on 438 HD gene carriers at different stages of the disease (34 pre-manifest; 172 stage 1; 130 stage 2; 80 stage 3; 17 stage 4; and 5 stage 5), according to Total Functional Capacity (TFC) score. We used the Unified Huntington’s Disease Rating Scale to evaluate motor, cognitive, behavioral and functional decline. We genotyped participants for COMT polymorphism (107 Met-homozygous, 114 Val-homozygous and 217 heterozygous). 367 controls of similar ancestry were also genotyped. We compared clinical progression, on each domain, between groups of COMT polymorphisms, using latent-class mixed models accounting for disease duration and number of CAG (cytosine adenine guanine) repeats. We show that HD gene carriers with fewer CAG repeats and with the Val allele in COMT polymorphism displayed slower cognitive decline. The rate of cognitive decline was greater for Met/Met homozygotes, which displayed a better maintenance of cognitive capacity in earlier stages of the disease, but had a worse performance than Val allele carriers later on. COMT polymorphism did not significantly impact functional and behavioral performance. Since COMT polymorphism influences progression in HD, it could be used for stratification in future clinical trials. Moreover, DA treatments based on the specific COMT polymorphism and adapted according to disease duration could potentially slow HD progression. PMID:27657697

  4. Association between monoamine oxidase A gene promoter 30 bp repeat polymorphism and tardive dyskinesia in Chinese schizophrenics

    Institute of Scientific and Technical Information of China (English)

    Changhe Fan; Lihua Li; Yan Fu; Hehuang Deng; Xiangjiao Liao; Youcai Zhou

    2006-01-01

    BACKGROUND: The pathophysiology of tardive dyskinesia (TD) is not yet fully understood. With the hypothesis of altered dopaminergic neurotransmission, altered activities of dopamine degrading enzymes such as monoamine oxidase A (MAOA) and their coding genes are supposed to be related to the pathophysiology of TD.OBJECTIVE: To investigate possible association between 30 bp variable number tandem repeat (VNTR) polymorphism in the promoter of MAOA gene and susceptibility, severity of neuroleptic induced TD in Chinese Han people in Guandong Province.DESIGN: Non-randomization-synchronization controlled study. SETTING: Guangdong Mental Health Institute, Guangdong Provincial People's Hospital; Guangzhou Psychiatric Hospital; Affiliated Psychiatric Hospital of Guangzhou Municipal Bureau of Civil Administration. PARTICIPANTS: A total of 179 subjects were enrolled in the study. All subjects were sporadic and genetically unrelated Chinese schizophrenic patients who were hospitalizing in Guangzhou Psychiatric Hospital or Affiliated Psychiatric Hospital of Guangzhou Municipal Bureau of Civil Administration during January to April 2005. The diagnosis of schizophrenia was made according to the criteria of Diagnostic and Statistic Manual of Mental Disorder-the third edition-revised (DSM-Ⅲ-R). Among all patients, 88 were diagnosed as with TD and 91 without TD according to the research diagnostic criteria described by Schooler-Kane. Informed consent was obtained from all subjects or their relatives.METHODS: ① TD severity was assessed with the AIMS which was a 5-degree rating scale from 0 to 4 (corresponding to none, minimal, mild, moderate and severe, respectively). The study was approved by the Ethics Committees of the two hospitals and informed consent was obtained from all subjects or their relatives. ② The polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) techniques were used to detect MAOA gene 30 bp VNTR polymorphism in schizophrenic patients

  5. Polymorphism Profile of Nine Short Tandem Repeat Loci in the Han Chinese

    Institute of Scientific and Technical Information of China (English)

    Shuangding Li; Chunxia Yan; Yajun Deng; Ruilin Wang; Jian Wang; Huanming Yang; Shengbin Li

    2003-01-01

    Nine short tandem repeat (STR) markers (D3S1358, VWA, FGA, THO1, TPOX,CSFIPO, D5S818, D13S317, and D7S820) and a sex-identification marker (Amel-ogenin locus) were amplified with multiplex PCR and were genotyped with afour-color fluorescence method in samples from 174 unrelated Han individuals inNorth China. The allele frequencies, genotype frequencies, heterozygosity, prob-ability of discrimination powers, probability of paternity exclusion and Hardy-Weinberg equilibrium expectations were determined. The results demonstratedthat the genotypes at all these STR loci in Han population conform to Hardy-Weinberg equilibrium expectations. The combined discrimination power (DP) was1.05 × 10-10 within nine STR loci analyzed and the probability of paternity exclusion(EPP) was 0.9998. The results indicate that these nine STR loci and the Amelo-genin locus are useful markers for human identification, paternity and maternitytesting and sex determination in forensic sciences.

  6. Genetic polymorphisms of 17 short tandem repeat loci on Y chromosome in central Croatian population.

    Science.gov (United States)

    Gršković, Branka; Mršić, Gordan; Polašek, Ozren; Vrdoljak, Andro; Merkaš, Siniša; Anđelinović, Simun

    2011-06-01

    In forensic casework, Y-chromosome short tandem repeat (STR) haplotyping is used in human identification, paternity testing and sexual assault cases where Y-STRs provide a male-specific DNA profile. The aim of this study was to describe the genetic structure of Y chromosome in a central Croatian population. We carried out a statistical analysis of the data from previously performed genetic analyses collected during routine forensic work by the Forensic Science Centre "Ivan Vučetić". A total of 220 unrelated healthy men from central Croatia were selected for the purpose of this study. Genomic DNA was extracted using a Chelex procedure from FTA(®) cards. Y-chromosomal STRs were determined using the AmpFISTR Yfiler PCR amplification kit. The haplotype frequencies were determined by direct counting and analyzed using Arlequin 3.1 and analysis of molecular variance calculated with the Y chromosome haplotype reference database online analysis tool. A total of 212 haplotypes were identified, 204 of which were unique. Total haplotype diversity was 0.993. Locus diversity varied from 0.325 for DYS392 to 0.786 for DYS385. Discrimination capacity was 92.7%. Allele frequencies diversity was 0.615. Intermediate alleles 17.2, 18.2 and 19.2 were found at DYS458 locus. A comparison with published data for the European minimal haplotype set showed the closest relationship to the Croatian capital of Zagreb and Bosnia and Herzegovina with significant genetic distance from Slovenia and Austria. The central Croatian population is now well characterized in terms of Y-chromosome STRs, thus providing a solid basis for further forensic and genetic epidemiology studies. PMID:21279707

  7. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Directory of Open Access Journals (Sweden)

    Ricardo Mouro Pinto

    2013-10-01

    Full Text Available The Huntington's disease gene (HTT CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111 mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111 than on a 129 background (129.Hdh(Q111 . Linkage mapping in (B6x129.Hdh(Q111 F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111 mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111 somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3 complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3. The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest

  8. Genetic polymorphism of the 26 short tandem repeat loci in the Chinese Hebei Han population using two commercial forensic kits.

    Science.gov (United States)

    Lei, Liang; Xu, Jie; Du, Qingqing; Fu, Lihong; Zhang, Xiaojing; Yu, Feng; Ma, Chunling; Cong, Bin; Li, Shujin

    2015-01-01

    We determined the allele frequencies and forensic parameters for the 26 short tandem repeat (STR) autosomal markers in two commercial kits (the Investigator HDplex and AmpFLSTR(®) Identifiler(®) systems) for 183 unrelated individuals from the Han population of the Hebei Province of China. The 26 STRs were all in Hardy-Weinberg equilibrium. No linkage disequilibrium was detected between any pair of loci. The combined power of discrimination and the combined power of exclusion for the 26 STR loci were 1-7.74E-31 and 1-1.21E-11, respectively. Six rare alleles of D10S2325 were identified and named 20, 21, 22, 23, 24, and 31. All the length of the six rare alleles were out of the range of allelic ladder. We calculated the population pairwise genetic distance based on the allele frequencies, using published population data including German, central Polish, south Dutch, northeastern Polish, south Brazilian, Korean, Sichuan Han of China, and Shanghai Han of China. Also we examined the population pairwise genetic distance of loci included in Identifiler system between Hebei Han and other ethnic population of China. These 26 autosomal STR loci could provide highly informative polymorphic data for paternity testing and forensic identification in the Hebei Han population in China. Because they are all in linkage equilibrium, they could be used together to solve deficient kinship cases or cases with mutations. PMID:25262358

  9. Assessment of genetic diversity in Mucuna species of India using randomly amplified polymorphic DNA and inter simple sequence repeat markers.

    Science.gov (United States)

    Patil, Ravishankar R; Pawar, Kiran D; Rane, Manali R; Yadav, Shrirang R; Bapat, Vishwas A; Jadhav, Jyoti P

    2016-04-01

    Genus Mucuna which is native to China and Eastern India comprises of perennial climbing legume with long slender branches, trifoliate leaves and bear green or brown pod covered with soft or rigid hairs that cause intense irritation. The plants of this genus are agronomically and economically important and commercially cultivated in India, China and other regions of the world. The high degrees of taxonomical confusions exist in Mucuna species that make authentic identification and classification difficult. In the present study, the genetic diversity among the 59 accessions of six species and three varieties of M. pruriens has been assessed using DNA fingerprinting based molecular markers techniques namely randomly amplified polymorphic DNA (RAPD), inter simple sequence repeats (ISSR) and combined dataset of RAPD and ISSR. Also, genetic relationship among two endemic species of Mucuna namely M. imbricata and M. macrocarpa and two varieties namely IIHR hybrid (MHR) and Dhanwantari (MD) with other species under study was investigated by using cluster analysis and principal coordinate analysis. The cluster analysis of RAPD, ISSR and combined dataset of RAPD and ISSR clearly demonstrated the existence of high interspecific variation than intra-specific variation in genus Mucuna. The utility and efficacy of RAPD and ISSR for the study of intra species and interspecies genetic diversity was evident from AMOVA and PCoA analysis. This study demonstrates the genetic diversity in Mucuna species and indicates that these markers could be successfully used to assess genetic variation among the accessions of Mucuna species. PMID:27436912

  10. Selection pressure on human STR loci and its relevance in repeat expansion disease

    KAUST Repository

    Shimada, Makoto K.

    2016-06-11

    Short Tandem Repeats (STRs) comprise repeats of one to several base pairs. Because of the high mutability due to strand slippage during DNA synthesis, rapid evolutionary change in the number of repeating units directly shapes the range of repeat-number variation according to selection pressure. However, the remaining questions include: Why are STRs causing repeat expansion diseases maintained in the human population; and why are these limited to neurodegenerative diseases? By evaluating the genome-wide selection pressure on STRs using the database we constructed, we identified two different patterns of relationship in repeat-number polymorphisms between DNA and amino-acid sequences, although both patterns are evolutionary consequences of avoiding the formation of harmful long STRs. First, a mixture of degenerate codons is represented in poly-proline (poly-P) repeats. Second, long poly-glutamine (poly-Q) repeats are favored at the protein level; however, at the DNA level, STRs encoding long poly-Qs are frequently divided by synonymous SNPs. Furthermore, significant enrichments of apoptosis and neurodevelopment were biological processes found specifically in genes encoding poly-Qs with repeat polymorphism. This suggests the existence of a specific molecular function for polymorphic and/or long poly-Q stretches. Given that the poly-Qs causing expansion diseases were longer than other poly-Qs, even in healthy subjects, our results indicate that the evolutionary benefits of long and/or polymorphic poly-Q stretches outweigh the risks of long CAG repeats predisposing to pathological hyper-expansions. Molecular pathways in neurodevelopment requiring long and polymorphic poly-Q stretches may provide a clue to understanding why poly-Q expansion diseases are limited to neurodegenerative diseases. © 2016, Springer-Verlag Berlin Heidelberg.

  11. Genetic polymorphisms of short tandem repeat loci D13S305, D13S631 and D13S634 in the Han population of Tianjin, China

    OpenAIRE

    SHI, YUNFANG; LI, XIAOZHOU; JU, DUAN; Li, Yan; Zhang, Xiuling; Zhang, Ying

    2015-01-01

    Short tandem repeat (STR) markers, also known as microsatellites, are extensively used in mapping studies, forensics and disease diagnosis due to their small dimension and low mutation and high polymorphism rates. In recent years quantitative fluorescence polymerase chain reaction (QF-PCR) has been successfully used to amplify STR markers in the prenatal diagnosis of common chromosomal abnormalities. This method provides a diagnosis of common aneuploidies 24–48 h after sampling with low error...

  12. Genotyping of the Helicobacter pylori cagA Gene Isolated From Gastric Biopsies in Shiraz, Southern Iran: A PCR-RFLP and Sequence Analysis Approach

    OpenAIRE

    Moaddeb, Afsaneh; Fattahi, Mohammad Reza; Firouzi, Roya; Derakhshandeh, Abdollah; Farshad, Shohreh

    2016-01-01

    Background Cytotoxin-associated gene A (cagA) is an important virulence factor in the pathogenesis of Helicobacter pylori. Objectives The aim of this study was to genotype the H. pylori cagA gene isolated from antral biopsies of patients with stomach symptoms, using a PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. Patients and Methods A total of 161 gastric biopsies were collected from patients with stomach symptoms. After isolation of H. pylori from the biopsy culture, the...

  13. Hsp90 modulates CAG repeat instability in human cells

    OpenAIRE

    Mittelman, David; Sykoudis, Kristen; Hersh, Megan; Lin, Yunfu; Wilson, John H.

    2010-01-01

    The Hsp90 molecular chaperone has been implicated as a contributor to evolution in several organisms by revealing cryptic variation that can yield dramatic phenotypes when the chaperone is diverted from its normal functions by environmental stress. In addition, as a cancer drug target, Hsp90 inhibition has been documented to sensitize cells to DNA-damaging agents, suggesting a function for Hsp90 in DNA repair. Here we explore the potential role of Hsp90 in modulating the stability of nucleoti...

  14. Endothelial nitric oxide synthase gene intron 4 variable number tandem repeat polymorphism in β-thalassemia major: relation to cardiovascular complications.

    Science.gov (United States)

    Tantawy, Azza A G; Adly, Amira A M; Ismail, Eman A; Aly, Shereen H

    2015-06-01

    Endothelial nitric oxide synthase (eNOS), an enzyme that generates nitric oxide, is a major determinant of endothelial function. Several eNOS gene polymorphisms have been reported as 'susceptibility genes' in various human diseases states, including cardiovascular, pulmonary and renal diseases. We studied the 27-base pair tandem repeat polymorphism in intron 4 of eNOS gene in 60 β-thalassemia major (β-TM) patients compared with 60 healthy controls and assessed its role in subclinical atherosclerosis and vascular complications. Patients were evaluated stressing on transfusion history, splenectomy, thrombotic events, echocardiography and carotid intima-media thickness (CIMT). Analysis of eNOS intron 4 gene polymorphism was performed by PCR. No significant difference was found between β-TM patients and controls with regard to the distribution of eNOS4 alleles or genotypes. The frequency of eNOS4a allele (aa and ab genotypes) was significantly higher in β-TM patients with pulmonary hypertension or cardiomyopathy. Logistic regression analysis revealed that eNOS4a allele was an independent risk factor for pulmonary hypertension in β-TM patients [odds ratio (OR) 2.2, 95% confidence interval (95% CI) 1.19-5.6; P polymorphism is related to endothelial dysfunction and subclinical atherosclerosis and could be a possible genetic marker for prediction of increased susceptibility to cardiovascular complications. PMID:25699607

  15. Endothelial nitric oxide synthase gene intron 4 variable number tandem repeat polymorphism in β-thalassemia major: relation to cardiovascular complications.

    Science.gov (United States)

    Tantawy, Azza A G; Adly, Amira A M; Ismail, Eman A; Aly, Shereen H

    2015-06-01

    Endothelial nitric oxide synthase (eNOS), an enzyme that generates nitric oxide, is a major determinant of endothelial function. Several eNOS gene polymorphisms have been reported as 'susceptibility genes' in various human diseases states, including cardiovascular, pulmonary and renal diseases. We studied the 27-base pair tandem repeat polymorphism in intron 4 of eNOS gene in 60 β-thalassemia major (β-TM) patients compared with 60 healthy controls and assessed its role in subclinical atherosclerosis and vascular complications. Patients were evaluated stressing on transfusion history, splenectomy, thrombotic events, echocardiography and carotid intima-media thickness (CIMT). Analysis of eNOS intron 4 gene polymorphism was performed by PCR. No significant difference was found between β-TM patients and controls with regard to the distribution of eNOS4 alleles or genotypes. The frequency of eNOS4a allele (aa and ab genotypes) was significantly higher in β-TM patients with pulmonary hypertension or cardiomyopathy. Logistic regression analysis revealed that eNOS4a allele was an independent risk factor for pulmonary hypertension in β-TM patients [odds ratio (OR) 2.2, 95% confidence interval (95% CI) 1.19-5.6; P < 0.001]. We suggest that eNOS intron 4 gene polymorphism is related to endothelial dysfunction and subclinical atherosclerosis and could be a possible genetic marker for prediction of increased susceptibility to cardiovascular complications.

  16. The CFTR polymorphisms poly-T, TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens

    Institute of Scientific and Technical Information of China (English)

    Wu-Hua Ni; Lei Jiang; Qian-Jin Fei; Jian-Yuan Jin; Xu Yang; Xue-Feng Huang

    2012-01-01

    Congenital bilateral absence of the vas deferens (CBAVD) is a frequent cause of obstructive azoospermia,and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene have also been frequently identified in patients with CBAVD.However,the distribution of the CFTR polymorphisms M470V,poly-T,TG-repeats and F508del mutation in the Chinese CBAVD population with presumed low cystic fibrosis (CF) frequency remains to be evaluated.Samples obtained from 109 Chinese infertile males with CBAVD and 104 normal controls were analyzed for the presence of CFTR (TG)m(T)n,M470V and F508del by PCR amplification followed by direct sequencing.Our study showed that the F508del mutation was not found in our patients.The 5T mutation was present with high frequency in Chinese CBAVD patients and IVS8-5T linked to either 12 or 13 TG repeats was highly prevalent among CBAVD patients (97.22% of 72 cases and 96.91% of 97 alleles with IVS8-5T).Moreover,a statistically significant relationship between TG12-5T-V470 haplotype and CBAVD was detected.This study indicated that the CFTR polymorphisms poly-T,TG-repeats and M470V might affect the process of CBAVD in the Chinese population.

  17. Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population

    Institute of Scientific and Technical Information of China (English)

    Qin Huang; Wei Ding; Mu-Xin Wei

    2008-01-01

    AIM: To investigate the three important cystic fibrosis transmembrane conductance regulator (CFTR) haplotypes po!y-T, TG-repeats and the M470V polymorphisms in the Chinese population, and to compare their distribution with that in Caucasians and other Asian populations.METHODS: Genomic DNA was extracted from blood leukocytes. Exons 9 and 10 of the CFTR gene were obtained through polymerase chain reaction (PCR). Exon 9 DNA sequences were directly detected by an automated sequencer and poly-T and TG-repeats were identified by direct sequence analysis. Pure exon 10 PCR-amplified products were digested by Hph I restriction enzyme and the M470V mutation was detected by the AGE photos of digestion products.RESULTS: T7 was the most common (93.6%) haplotype and the (TG)ll frequency of 57.2% and (TG)12 frequency of 40.9% were dominant haplotypes in the junction of intron 8 (IVS-8) and exon 9. The frequency of T5 was 3.8% and all T5 allele tracts (10 alleles) were joined with (TG)12. Four new alleles of T6 (1.5%) were found in three healthy individuals. In exon 10, the V allele (56.1%) was slightly more frequent than the M allele (43.9%), and the M/V (45.5%) was the dominant genotype in these individuals. The three major haplotypes T7-(TG)ll-V470, T7-(TG)12-M470 and T7-TG11-M470 were related to nearly 86.0% of the population.CONCLUSION: The polymorphisms of poly-T, TG-repeats, and M470V distribution were similar to those in other East Asians, but they had marked differences in frequency from those single haplotype polymorphisms or linkage haplotypes in Caucasians. Thus, they may be able to explain the low incidence of CF and CF-like diseases in Asians.

  18. Association of STin2 Variable Number of Tandem Repeat (VNTR) Polymorphism of Serotonin Transporter Gene with Lifelong Premature Ejaculation: A Case-Control Study in Han Chinese Subjects

    Science.gov (United States)

    Huang, Yuanyuan; Zhang, Xiansheng; Gao, Jingjing; Tang, Dongdong; Gao, Pan; Peng, Dangwei; Liang, Chaozhao

    2016-01-01

    Background The STin2 VNTR polymorphism has a variable number of tandem repeats in intron 2 of the serotonin transporter gene. We aimed to explore the relationship between STin2 VNTR polymorphism and lifelong premature ejaculation (LPE). Material/Methods We recruited a total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as LPE, and 101 controls without PE complaint. Allelic variations of STin2 VNTR were genotyped using PCR-based technology. We evaluated the associations between STin2 VNTR allelic and genotypic frequencies and LPE, as well as the intravaginal ejaculation latency time (IELT) of different STin2 VNTR genotypes among LPE patients. Results The patients and controls did not differ significantly in terms of any characteristic except age. A significantly higher frequency of STin2.12/12 genotype was found among LPE patients versus controls (P=0.026). Frequency of patients carrying at least 1 copy of the 10-repeat allele was significantly lower compared to the control group (28.3% vs. 41.8%, OR=0.55; 95%CI=0.31–0.97, P=0.040). In the LPE group, the mean IELT showed significant difference in STin2.12/12 genotype when compared to those with STin2.12/10 and STin2.10/10 genotypes. The mean IELT in10-repeat allele carriers was 50% longer compared to homozygous carriers of the STin2.12 allele. Conclusions Our results indicate the presence of STin2.10 allele is a protective factor for LPE. Men carrying the higher expression genotype STin2. 12/12 have shorter IELT than 10-repeat allele carriers. PMID:27713390

  19. Variable number of tandem repeat polymorphisms of the interleukin-1 receptor antagonist gene IL-1RN: a novel association with the athlete status

    Directory of Open Access Journals (Sweden)

    Ryckman Kelli K

    2010-02-01

    Full Text Available Abstract Background The interleukin-1 (IL-1 family of cytokines is involved in the inflammatory and repair reactions of skeletal muscle during and after exercise. Specifically, plasma levels of the IL-1 receptor antagonist (IL-1ra increase dramatically after intense exercise, and accumulating evidence points to an effect of genetic polymorphisms on athletic phenotypes. Therefore, the IL-1 family cytokine genes are plausible candidate genes for athleticism. We explored whether IL-1 polymorphisms are associated with athlete status in European subjects. Methods Genomic DNA was obtained from 205 (53 professional and 152 competitive non-professional Italian athletes and 458 non-athlete controls. Two diallelic polymorphisms in the IL-1β gene (IL-1B at -511 and +3954 positions, and a variable number tandem repeats (VNTR in intron 2 of the IL-1ra gene (IL-1RN were assessed. Results We found a 2-fold higher frequency of the IL-1RN 1/2 genotype in athletes compared to non-athlete controls (OR = 1.93, 95% CI = 1.37-2.74, 41.0% vs. 26.4%, and a lower frequency of the 1/1 genotype (OR = 0.55, 95% CI = 0.40-0.77, 43.9% vs. 58.5%. Frequency of the IL-1RN 2/2 genotype did not differ between groups. No significant differences between athletes and controls were found for either -511 or +3954 IL-1B polymorphisms. However, the haplotype (-511C-(+3954T-(VNTR2 was 3-fold more frequent in athletes than in non-athletes (OR = 3.02, 95% CI = 1.16-7.87. Interestingly, the IL-1RN 1/2 genotype was more frequent in professional than in non-professional athletes (OR = 1.92, 95% CI = 1.02-3.61, 52.8% vs. 36.8%. Conclusions Our study found that variants at the IL-1ra gene associate with athletic status. This confirms the crucial role that cytokine IL-1ra plays in human physical exercise. The VNTR IL-1RN polymorphism may have implications for muscle health, performance, and/or recovery capacities. Further studies are needed to assess these specific issues. As VNTR IL-1RN

  20. 雄激素受体基因第一外显子CAG重复多态与POF的关联性%The association of androgen receptor gene first exon CAG repeat polymorphism and POF

    Institute of Scientific and Technical Information of China (English)

    刘丹; 赵君利; 刘丽; 成洁; 袁莹莹; 杜娟; 程方

    2013-01-01

    目的 探讨雄激素受体基因第一外显子CAG重复多态与卵巢早衰(POF)的关联性.方法 应用聚合酶链反应及变性聚丙烯酰胺凝胶分离技术检测40例POF患者及52例卵巢功能正常的对照女性雄激素受体(AR)基因第一外显子CAG多态,比较并分析其在2组中的分布情况.结果 POF组和对照组的AR基因第一外显子CAG重复次数范围分别为15~30次和14~35次,双等位基因均值分别为22.91±1.94和23±2.17,差异无统计学意义(P>0.05).AR基因CAG短重复多态(n<23)在POF组和对照组中的分布分别为47.5%和51.92%,AR基因CAG长重复多态(n≥23)在POF组和对照组分布分别为52.5%和48.1%,差异均无统计学意义(P>0.05).结论 AR基因第一外显子CAG多态与POF无明显相关性,不是POF的主要致病因素.

  1. Glycoprotein I of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region

    DEFF Research Database (Denmark)

    Norberg, Peter; Olofsson, Sigvard; Tarp, Mads Agervig;

    2007-01-01

    -glycosylation not only for the two most commonly expressed N-acetyl-d-galactosamine (GalNAc)-T1 and -T2 transferases, but also for the GalNAc-T3, -T4 and -T11 transferases. Immunoblotting of virus-infected cells showed that gI was exclusively O-glycosylated with GalNAc monosaccharides (Tn antigen). A polymorphic mucin...

  2. A codon-usage variant in the (GGN){sub n} trinucleotide polymorphism of the androgen receptor gene as an aid in the prenatal diagnosis of ambiguous genitalia due to partial androgen insensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Lumbroso, R.; Vasiliou, M.; Beitel, L.K. [McGill Univ., Montreal, Quebec (Canada)] [and others

    1994-09-01

    Exon 1 at the X-linked androgen receptor (AR) locus encodes an N-terminal modulatory domain that contains two large homopolyamino acid tracts: (CAG;glutamine;Gln){sub 11-33} and (GGN;Glycine;Cly){sub 15-27}. Certain AR mutations cause partial androgen insensitivity (PAI) with frank genital ambiguity that may engender appreciable parental anxiety and patient morbidity. If the AR mutation in a PAI family is unknown, the AR`s intragenic trinucleotide repeat polymorphisms may be used for prenatal diagnosis. However, intergenerational instability of repeat-size may be worrisome, particularly when the information alleles differ by only a few repeats. Here, we report the discovery of a codon-usage (silent substitution) variant in the GGN repeat, and describe its use as a source of complementary information for prenatal diagnosis. The standard sense sequence of the (GGN){sub n} tract is (GGT){sub 3} GGG(GGT){sub 2} (GGC){sub 9-21}. On 4 of 27 X chromosomes we noted that the internal GGT sequence was expanded to 3 or 4 repeats. We used an internal (GGT){sub 4} repeat in a total (GGN){sub 24} tract together with a (CAG){sub 20} tract to distinguish an X chromosome with a mutant AR allele from another X chromosome, bearing a normal allele, that had an internal (GGT){sub 2} repeat in a total (GGN){sub 23} tract together with a (CAG){sub 21} tract. Subsequently, we found the base change leading to a pathogenic amino acid substitution (M779I) in codon 6 of the mutant AR gene in an affected maternal aunt and the fetus at risk. This confirmed the prenatal diagnosis based on the intragenic trinucleotide repeat polymorphisms, and it strengthened the prediction of external genital ambiguity using our previous experience with M779I in another family.

  3. Effect of variable number of tandem repeats polymorphism in the human dopamine transporter gene on conflict information processing according to event-related potential

    Institute of Scientific and Technical Information of China (English)

    Chunyu Han; Yuping Wang; Xin Wang; Ying Liu

    2010-01-01

    The dopamine transporter(DAT)is responsible for dopamine reuptake from the synaptic cleft.A variable number of tandem repeats polymorphism in the DAT gene is related to DAT availability and has been associated with cognition.With the advantage of high-time resolution,event-related potential is an important method to study the time course of human information processing.Previous results have suggested that dopamine exhibits a close relationship with conflicting information processing.Therefore,the present study assumed that conflicting information processing could be influenced by DAT variable number of tandem repeats polymorphism.To confirm this,the present study analyzed the influence of DAT genotypes on N270,which is presumed to reflect neural activity of conflict information processing in young healthy adults.A S1-S2 matching task was performed in healthy adults with 10/10 genotype(n = 14)and 10/9genotypes(n = 14),respectively,when event-related potentials were recorded.Results demonstrated that subjects with the 10/10 genotype exhibited shorter N270 latency and quicker reaction times compared with subjects with the 10/9 genotype.There were no differences in N270amplitude between the two genotypes.These results suggested that 10/10 genotype subjects more efficiently processed conflict information.

  4. Helicobacter pylori cagA Promoter Region Sequences Influence CagA Expression and Interleukin 8 Secretion.

    Science.gov (United States)

    Ferreira, Rui M; Pinto-Ribeiro, Ines; Wen, Xiaogang; Marcos-Pinto, Ricardo; Dinis-Ribeiro, Mário; Carneiro, Fátima; Figueiredo, Ceu

    2016-02-15

    Heterogeneity at the Helicobacter pylori cagA gene promoter region has been linked to variation in CagA expression and gastric histopathology. Here, we characterized the cagA promoter and expression in 46 H. pylori strains from Portugal. Our results confirm the relationship between cagA promoter region variation and protein expression originally observed in strains from Colombia. We observed that individuals with intestinal metaplasia were all infected with H. pylori strains containing a specific cagA motif. Additionally, we provided novel functional evidence that strain-specific sequences in the cagA promoter region and CagA expression levels influence interleukin 8 secretion by the host gastric epithelial cells.

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

    OpenAIRE

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

    2011-01-01

    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 fo...

  6. DNA polymorphisms in cuban varieties of avocado (persea americana mill.) as detected by inverse sequence tagged repeat (ISTR) analysis

    International Nuclear Information System (INIS)

    A survey of the genetic diversity among commercial Cuban avocado varieties was initiated using ISTR analysis. ISTR markers were efficient in detecting polymorphisms among the genotypes. The obtained dissimilarities values ranged from 0.24 between var. Suardia and Hass to 1.00 between Lula and Los Moros or CHI-3 with an average dissimilarity of 0.78. A cluster analysis was performed based on dissimilarity using UPGMA as the clustering method. The efficiency of UPGMA in estimating genetic relationships between varieties was corroborated by the cophenetic correlation coefficients, which indicated that the distortion degree in the relationship of the estimated dissimilarities was minimal. Ecological groups were not adequately represented in the dendrogram. Thus, West Indians, Guatemalan and Mexican genotypes were positioned across the dendrogram. The utility of ISTR for genotype identification and assessment of genetic diversity in commercial avocado varieties is discussed

  7. 2003 CAG Educational Needs Assessment Report

    Directory of Open Access Journals (Sweden)

    Desmond Leddin

    2003-01-01

    Full Text Available The annual survey of Canadian Association of Gastroenterology (CAG members’ educational needs was conducted online this past April. One hundred eightyseven individuals (one fifth of the membership completed the needs assessment. The topic most in demand for future educational events was inflammatory bowel disease, both from the clinical and basic science perspectives. Other highly rated topics were endoscopy, pharmacological therapeutics, celiac disease and pancreatitis/pancreatic disease. Educational materials were judged to be the most valuable component of exhibit areas. Results of the needs assessment were used to shape the 2004 Canadian Digestive Diseases Week (CDDW program.

  8. The (CAG)n tract of Machado–Joseph Disease gene (ATXN3): a comparison between DNA and mRNA in patients and controls

    Science.gov (United States)

    Bettencourt, Conceição; Santos, Cristina; Montiel, Rafael; Kay, Teresa; Vasconcelos, João; Maciel, Patrícia; Lima, Manuela

    2010-01-01

    Machado–Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder of late onset (occurring at a mean age of 40.2 years). The clinical manifestation of MJD is dependent on the presence of an expansion of the (CAG)n motif within exon 10 of the ATXN3 gene, located at 14q32.1. The variance in onset of MJD is only partially correlated (∼50–80%) with the extension of the CAG tract in genomic DNA (gDNA). The main aim of this work was to determine whether there are discrepancies in the size of the (CAG)n tract between gDNA and mRNA, and to establish whether there is a better association between age at onset and repeat size at the mRNA level. We typed gDNA and cDNA samples for the (CAG)n tract totalizing 108 wild-type and 52 expanded ATXN3 alleles. In wild-type alleles no differences were found between gDNA and cDNA. In expanded alleles, the CAG repeat size in gDNA was not always directly transcribed into the mRNA; on average there were differences of +1 repeat at the cDNA level. The slight discrepancies obtained were insufficient to cause significant differences in the distribution of the expanded alleles, and therefore no improvement in onset variance explanation was obtained with mRNA. PMID:19935829

  9. Summary of the 2002 CAG Strategic Planning Survey

    Directory of Open Access Journals (Sweden)

    Philip M Sherman

    2004-01-01

    Full Text Available In this Journal, we have recently highlighted the progress of the Canadian Association of Gastroenterology (CAG in meeting the goals and objectives outlined in the first Strategic Plan developed in 1993 (1. In September 2002, a Strategic Planning survey was mailed to all members of the CAG (a copy of the cover letter and survey are present for viewing on the CAG Web site www.cag-acg.org/whatsnew/strat_plann_surv.htm. The results of the responses to this survey were collated and presented to the Past Presidents of the CAG at a retreat held during the summer of 2003. These findings were then employed to develop a Strategic Plan for the CAG to guide its progress and development over the next five to ten years. A subsequent issue of this Journal will include a presentation of the CAG 2004 Strategic Plan, which was finalized and approved by the CAG Governing Board during the annual fall meeting in October 2003.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Celec, Peter; Tretinárová, Denisa; Minárik, Gabriel; Ficek, Andrej; Szemes, Tomáš; Lakatošová, Silvia; Schmidtová, Eva; Turňa, Ján; Kádaši, Ľudevít; 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

  12. Genetic polymorphisms related to testosterone metabolism in intellectually gifted boys.

    Science.gov (United States)

    Celec, Peter; Tretinárová, Denisa; Minárik, Gabriel; Ficek, Andrej; Szemes, Tomáš; Lakatošová, Silvia; Schmidtová, Eva; Turňa, Ján; Kádaši, Ľudevít; 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.

  13. DNA polymorphism among Fusarium oxysporum f.sp. elaeidis populations from oil palm, using a repeated and dispersed sequence "Palm".

    Science.gov (United States)

    Mouyna, I; Renard, J L; Brygoo, Y

    1996-07-31

    A worldwide collection, of 76 F. oxysporum f.sp. elaeidis isolates (Foe), and of 21 F. oxysporum isolates from the soil of several palm grove was analysed by RFLP. As a probe, we used a random DNA fragment (probe 46) from a genomic library of a Foe isolate. This probe contains two different types of sequence, one being repeated and dispersed in the genome "Palm", the other being a single-copy sequence. All F. oxysporum isolates from the palm-grove soils were non-pathogenic to oil palm. They all had a simple restriction pattern with one band homologous to the single-copy sequence of probe 46. All Foe isolates were pathogenic to oil palm and they all had complex patterns due to hybridization with "Palm". This repetitive sequence reveals that Foe isolates are distinct from the other F. oxysporum palm-grove soils isolates. The sequence can reliably discriminate pathogenic from non-pathogenic oil palm isolates. Based on DNA fingerprint similarities, Foe populations were divided into ten groups consisting of isolates with the same geographic origin. Isolates from Brazil and Ecuador were an exception to that rule as they had the same restriction pattern as a few isolates from the Ivory Coast, suggesting they may originated from Africa.

  14. Relevance of MUC1 mucin variable number of tandem repeats polymorphism in H pylori adhesion to gastric epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Natália R Costa; Nuno Mendes; Nuno T Marcos; Celso A Reis; Thomas Caffrey; Michael A Hollingsworth; Filipe Santos-Silva

    2008-01-01

    AIM:To evaluate the influence of MUC1 mucin variable number of tandem repeats (VNTR) variability on H pylori adhesion to gastric cells.METHODS:Enzyme linked immunosorbent assay (ELISA)-based adhesion assays were performed to measure the adhesion of different H pylori strains (HP26695 and HPTx30a) to gastric carcinoma cell lines (GP202 and MKN45) and GP202 clones expressing recombinant MUC1 with different VNTR lengths.RESULTS:Evaluation of adhesion results shows that H pylori pathogenic strain HP26695 has a significantly higher (P<0.05) adhesion to all the cell lines and clones tested,when compared to the non-pathogenic strain HPTx30a.Bacteria showed a significantly higher (P<0.05)adhesion to the GP202 cell line,when compared to the MKN45 cell line.Furthermore,both strains showed a significantly higher (P<0.05) adhesion to GP202 clones with larger MUC1 VNTR domains.CONCLUSION:This work shows that MUC1 mucin variability conditions H pylori binding to gastric cells.The extent of bacterial adhesion depends on the size of the MUC1 VNTR domain.The adhesion is further dependent on bacterial pathogenicity and the gastric cell line.MUC1 mucin variability may contribute to determine H pylori colonization of the gastric mucosa.

  15. [open quotes]Cryptic[close quotes] repeating triplets of purines and pyrimidines (cRRY(i)) are frequent and polymorphic: Analysis of coding cRRY(i) in the proopiomelanocortin (POMC) and TATA-binding protein (TBP) genes

    Energy Technology Data Exchange (ETDEWEB)

    Gostout, B.; Qiang Liu; Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

    1993-06-01

    Triplets of the form of purine, purine, pyrimidine (RRY(i)) are enhanced in frequency in the genomes of primates, rodents, and bacteria. Some RRY(i) are [open quotes]cryptic[close quotes] repeats (cRRY(i)) in which no one tandem run of a trinucleotide predominates. A search of human GenBank sequence revealed that the sequences of cRRY(i) are highly nonrandom. Three randomly chosen human cRRY(i) were sequenced in search of polymorphic alleles. Multiple polymorphic alleles were found in cRRY(i) in the coding regions of the genes for proopiomelanocortin (POMC) and TATA-binding protein (TBP). The highly polymorphic TBP cRRY(i) was characterized in detail. Direct sequencing of 157 unrelated human alleles demonstrated the presence of 20 different alleles which resulted in 29--40 consecutive glutamines in the amino-terminal region of TBP. These alleles are differently distributed among the races. PCR was used to screen 1,846 additional alleles in order to characterize more fully the range of variation in the population. Three additional alleles were discovered, but there was no example of a substantial sequence amplification as is seen in the repeat sequences associated with X-linked spinal and bulbar muscular atrophy, myotonic dystrophy, or the fragile-X syndrome. The structure of the TBP cRRY(i) is conserved in the five monkey species examined. In the chimpanzee, examination of four individuals revealed that the cRRY(i) was highly polymorphic, but the pattern of polymorphism differed from that in humans. The TBP cRRY(i) displays both similarities with and differences from the previously described RRY(i) in the coding sequence of the androgen receptor. The data suggest how simple tandem repeats could evolve from cryptic repeats. 18 refs., 3 figs., 6 tabs.

  16. Amplification of a single-locus variable-number direct repeats with restriction fragment length polymorphism (DR-PCR/RFLP) for genetic typing of Acinetobacter baumannii strains.

    Science.gov (United States)

    Nowak-Zaleska, Alicja; Krawczyk, Beata; Kotłowski, Roman; Mikucka, Agnieszka; Gospodarek, Eugenia

    2008-01-01

    In search of an effective DNA typing technique for Acinetobacter baumannii strains for hospital epidemiology use, the performance and convenience of a new target sequence was evaluated. Using known genomic sequences of Acinetobacter baumannii strains AR 319754 and ATCC 17978, we developed single-locus variable-number direct-repeat analysis using polymerase chain reaction-restriction fragment length polymorphism (DR-PCR/RFLP) method. A total of 90 Acinetobacter baumannii strains isolated from patients of the Clinical Hospital in Bydgoszcz, Poland, were examined. Initially, all strains were typed using macrorestriction analysis of the chromosomal DNA by pulsed-field gel electrophoresis (REA-PFGE). Digestion of the chromosomal DNA with the ApaI endonuclease and separation of the fragments by PFGE revealed 21 unique types. Application of DR-PCR/RFLP resulted in recognition of 12 clusters. The results showed that the DR-PCR/RFLP method is less discriminatory than REA-PFGE, however, the novel genotyping method can be used as an alternative technique for generating DNA profiles in epidemiological studies of intra-species genetic relatedness of Acinetobacter baumannii strains.

  17. Genetic and physical mapping of 2q35 in the region of NRAMP and IL8R genes: Identification of a polymorphic repeat in exon 2 of NRAMP

    Energy Technology Data Exchange (ETDEWEB)

    White, J.K.; Shaw, M.A.; Barton, C.H. [Addenbrooke`s Hospital, Cambridge (United Kingdom)] [and others

    1994-11-15

    Recent interest has focused on the region of conserved synteny between mouse chromosome 1 and human 2q33-q37, particularly over the region encoding the murine macrophage resistance gene Ity/Lsh/Bcg (candidate Nramp) and members of the Il8r interleukin-8 (IL8) receptor gene cluster. In this paper, identification of a restriction fragment length polymorphism in the Il8RB gene in 35 pedigrees previously typed for markers in the 2q33-37 interval provided evidence (lod scores > 3) for linkage between Il8RB and the 2q34-135 markers FN1, TNP1, VIL1, and DES. Physical mapping, using yeast artificial chromosomes isolated with VIL1, confirmed that IL8RA, IL8RB and the IL8RB pseudogene map within the NRAMP-VIL1 interval, with the physical distance (155 kb) from 5{prime} LSH to 3{prime} VIL1 representing {approx}3-fold that observed in the mouse. Partial sequencing of NRAMP confirmed the presence of the N-terminal proline/serine-rich putative SH3 binding domain in exon 2 of the human gene. Further analysis of Brazilian leprosy and visceral leishmaniasis pedigrees identified a rare second allele varying in a 9-nucleotide repeat motif of the exon 2 sequence but segregating independently of the disease phenotype. 38 refs., 4 figs., 3 tabs.

  18. Clustering of Beijing genotype Mycobacterium tuberculosis isolates from the Mekong delta in Vietnam on the basis of variable number of tandem repeat versus restriction fragment length polymorphism typing

    Directory of Open Access Journals (Sweden)

    Huyen Mai NT

    2013-02-01

    Full Text Available Abstract Background In comparison to restriction fragment length polymorphism (RFLP typing, variable number of tandem repeat (VNTR typing is easier to perform, faster and yields results in a simple, numerical format. Therefore, this technique has gained recognition as the new international gold standard in typing of Mycobacterium tuberculosis. However, some reports indicated that VNTR typing may be less suitable for Beijing genotype isolates. We therefore compared the performance of internationally standardized RFLP and 24 loci VNTR typing to discriminate among 100 Beijing genotype isolates from the Southern Vietnam. Methods Hundred Beijing genotype strains defined by spoligotyping were randomly selected and typed by RFLP and VNTR typing. The discriminatory power of VNTR and RFLP typing was compared using the Bionumerics software. Results Among 95 Beijing strains available for analysis, 14 clusters were identified comprising 34 strains and 61 unique profiles in 24 loci VNTR typing ((Hunter Gaston Discrimination Index (HGDI = 0.994. 13 clusters containing 31 strains and 64 unique patterns in RFLP typing (HGDI = 0.994 were found. Nine RFLP clusters were subdivided by VNTR typing and 12 VNTR clusters were split by RFLP. Five isolates (5% revealing double alleles or no signal in two or more loci in VNTR typing could not be analyzed. Conclusions Overall, 24 loci VNTR typing and RFLP typing had similar high-level of discrimination among 95 Beijing strains from Southern Vietnam. However, loci VNTR 154, VNTR 2461 and VNTR 3171 had hardly added any value to the level of discrimination.

  19. Genetic diversity in domesticated soybean (Glycine max) and its wild progenitor (Glycine soja) for simple sequence repeat and single-nucleotide polymorphism loci.

    Science.gov (United States)

    Li, Ying-Hui; Li, Wei; Zhang, Chen; Yang, Liang; Chang, Ru-Zhen; Gaut, Brandon S; Qiu, Li-Juan

    2010-10-01

    • The study of genetic diversity between a crop and its wild relatives may yield fundamental insights into evolutionary history and the process of domestication. • In this study, we genotyped a sample of 303 accessions of domesticated soybean (Glycine max) and its wild progenitor Glycine soja with 99 microsatellite markers and 554 single-nucleotide polymorphism (SNP) markers. • The simple sequence repeat (SSR) loci averaged 21.5 alleles per locus and overall Nei's gene diversity of 0.77. The SNPs had substantially lower genetic diversity (0.35) than SSRs. A SSR analyses indicated that G. soja exhibited higher diversity than G. max, but SNPs provided a slightly different snapshot of diversity between the two taxa. For both marker types, the primary division of genetic diversity was between the wild and domesticated accessions. Within taxa, G. max consisted of four geographic regions in China. G. soja formed six subgroups. Genealogical analyses indicated that cultivated soybean tended to form a monophyletic clade with respect to G. soja. • G. soja and G. max represent distinct germplasm pools. Limited evidence of admixture was discovered between these two species. Overall, our analyses are consistent with the origin of G. max from regions along the Yellow River of China.

  20. Androgen insensitivity syndrome: do trinucleotide repeats in androgen receptor gene have any role?

    Institute of Scientific and Technical Information of China (English)

    Singh Rajender; Nalini J. Gupta; Baidyanath Chakravarty; Lalji Singh; Kumarasamy Thangaraj

    2008-01-01

    Aim: To investigate the role of CAG and GGN repeats as genetic background affecting androgen insensitivity syn- drome (AIS) phenotype. Methods: We analyzed lengths of androgen receptor (AR)-CAG and GGN repeats in 69 AIS cases, along with 136 unrelated normal male individuals. The lengths of repeats were analyzed using polymerase chain reaction (PCR) amplification followed by allelic genotyping to determine allele length. Results: Our study revealed significantly shorter mean lengths of CAG repeats in patients (mean 18.25 repeats, range 14-26 repeats) in comparison to the controls (mean 22.57 repeats, range 12-39 repeats) (two-tailed P < 0.0001). GGN repeats, however, did not differ significantly between patients (mean 21.48 repeats) and controls (mean 21.21 repeats) (two- tailed P = 0.474). Among patients' groups, the mean number of CAG repeats in partial androgen insensitivity cases (mean 15.83 repeats) was significantly less than in complete androgen insensitivity cases (mean 19.46 repeats) (two- tailed P < 0.0001). Conclusion: The findings suggest that shorter lengths of repeats in the AR gene might act as low penetrance genetic background in varying manifestation of androgen insensitivity. (Asian J Androl 2008 Jul; 10: 616-624)

  1. Failure to confirm influence of Methyltetrahydrofolate reductase (MTHFR polymorphisms on age at onset of Huntington disease

    Directory of Open Access Journals (Sweden)

    Wieczorek Stefan

    2005-12-01

    Full Text Available Abstract Background Huntington disease (HD is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Recently, suggestive association has been reported between a single nucleotide polymorphism (SNP; rs1801131, also known as A1298C in the methyltetrahydrofolate reductase (MTHFR gene and AO of HD. 5,10-MTHFR is a key enzyme in the folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using part of a previously established study cohort plus additional patients and appropriate statistical methods, we reinvestigated two polymorphisms in the MTHFR gene, C677T and A1298C, as well as their association with AO in 167 HD patients. Results There was no statistically significant impact on AO for HD patients, neither of MTHFR SNPs nor of the combinations thereof. Conclusion Contrary to previously described evidence the A1298C polymorphism in the MTHFR gene does not appear to modulate AO of HD patients.

  2. The 27-bp repeat polymorphism in intron 4 (27 bp-VNTR) of endothelial nitric oxide synthase (eNOS) gene is associated with albumin to creatinine ratio in Mexican Americans

    OpenAIRE

    Nath, Subrata D.; He, Xin; Voruganti, V. Saroja; Blangero, John; MacCluer, Jean W.; Comuzzie, Anthony G.; Arar, Nedal H; Abboud, Hanna E.; Thameem, Farook

    2009-01-01

    The T-786C, Glu298Asp, and 27 bp variable number of tandem repeats (27 bp-VNTR-a/b) polymorphsims of the endothelial nitric oxide synthase (eNOS) gene are thought to alter nitric oxide production and contribute to the development of vascular and renal disease risk. The objective of this study is to investigate whether these three polymorphisms examined previously by others are associated with cardiovascular and renal disease risk in Mexican Americans. Study participants (N = 848; 21 families)...

  3. Infection with cagA-positive and cagA-negative types of Helicobacter pylori among children and adolescents with gastrointestinal symptoms in Latvia.

    Science.gov (United States)

    Daugule, I; Rumba, I; Engstrand, L; Ejderhamn, J

    2003-10-01

    In order to determine the prevalence of concomitant cagA-positive and cagA-negative Helicobacter pylori genotypes in individual subjects, a group of 56 symptomatic patients (aged 8-18 years) was studied. Among 31 patients culture-positive for Helicobacter pylori, only cagA-positive colonies were isolated from 18 patients, both cagA-positive and cagA-negative genotypes were isolated from 4 patients, and in 9 patients all of the individual colonies isolated were cagA-negative, but in seven of them a pool of colonies was positive for cagA. Thus, the presence of both cagA-positive and cagA-negative genotypes in the same individual was identified in 11 of the 31 culture-positive patients tested, and most of the patients predominantly colonized by cagA-negative strains also harbored a small amount of cagA-positive strains. Previous or current infection with cagA-positive strains of Helicobacter pylori was observed in 50 of the 56 patients studied.

  4. Interactions between CagA and smoking in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Xiao-Qin Wang; Hong Yan; Paul D Terry; Jian-Sheng Wang; Li Cheng; Wen-An Wu; Sen-Ke Hu

    2011-01-01

    AIM: To examine the interactions between cytotoxinassociated gene (CagA ) positive Helicobacter pylori infection and smoking in non-cardiac gastric cancer. METHODS: A case-control study (257 cases and 514 frequency-matched controls) was conducted from September 2008 to July 2010 in Xi'an, China. Cases were newly diagnosed, histologically confirmed non-cardiac cancer. Controls were randomly selected from similar communities to the cases and were further matched by sex and age (± 5 years). A face-to-face interview was performed by the investigators for each participant. Data were obtained using a standardized questionnaire that included questions regarding known or suspected lifestyle and environmental risk factors of gastric cancer. A 5 mL sample of fasting venous blood was taken. CagA infection was serologically detected by enzymelinked immunosorbent assays. RESULTS: Smoking and CagA infection were statistically significant risk factors of non-cardiac cancer. CagA was categorized in tertiles, and the odds ratio (OR) was 12.4 (95% CI: 6.1-20.3, P = 0.003) for CagA after being adjusted for confounding factors when the highexposure category was compared with the low-exposure category. Smokers had an OR of 5.4 compared with subjects who never smoked (95% CI: 2.3-9.0, P = 0.002). The OR of non-cardiac cancer was 3.5 (95% CI: 1.8-5.3) for non-smokers with CagA infection, 3.5 (95% CI: 1.9-5.1) for smokers without CagA infection, and 8.7 (95% CI: 5.1-11.9) for smokers with CagA infection compared with subjects without these risk factors. After adjusting for confounding factors, the corresponding ORs of non-cardiac cancer were 3.2 (95% CI: 1.5-6.8), 2.7 (95% CI: 1.3-4.9) and 19.5 (95% CI: 10.3-42.2), respectively. There was a multiplicative interaction between smoking and CagA , with a synergistic factor of 2.257 (Z = 2.315, P = 0.021). CONCLUSION: These findings support a meaningful interaction between CagA and smoking for the risk of gastric cancer which may have

  5. 5meCpG epigenetic marks neighboring a primate-conserved core promoter short tandem repeat indicate X-chromosome inactivation.

    Directory of Open Access Journals (Sweden)

    Filipe Brum Machado

    Full Text Available X-chromosome inactivation (XCI is the epigenetic transcriptional silencing of an X-chromosome during the early stages of embryonic development in female eutherian mammals. XCI assures monoallelic expression in each cell and compensation for dosage-sensitive X-linked genes between females (XX and males (XY. DNA methylation at the carbon-5 position of the cytosine pyrimidine ring in the context of a CpG dinucleotide sequence (5meCpG in promoter regions is a key epigenetic marker for transcriptional gene silencing. Using computational analysis, we revealed an extragenic tandem GAAA repeat 230-bp from the landmark CpG island of the human X-linked retinitis pigmentosa 2 RP2 promoter whose 5meCpG status correlates with XCI. We used this RP2 onshore tandem GAAA repeat to develop an allele-specific 5meCpG-based PCR assay that is highly concordant with the human androgen receptor (AR exonic tandem CAG repeat-based standard HUMARA assay in discriminating active (Xa from inactive (Xi X-chromosomes. The RP2 onshore tandem GAAA repeat contains neutral features that are lacking in the AR disease-linked tandem CAG repeat, is highly polymorphic (heterozygosity rates approximately 0.8 and shows minimal variation in the Xa/Xi ratio. The combined informativeness of RP2/AR is approximately 0.97, and this assay excels at determining the 5meCpG status of alleles at the Xp (RP2 and Xq (AR chromosome arms in a single reaction. These findings are relevant and directly translatable to nonhuman primate models of XCI in which the AR CAG-repeat is monomorphic. We conducted the RP2 onshore tandem GAAA repeat assay in the naturally occurring chimeric New World monkey marmoset (Callitrichidae and found it to be informative. The RP2 onshore tandem GAAA repeat will facilitate studies on the variable phenotypic expression of dominant and recessive X-linked diseases, epigenetic changes in twins, the physiology of aging hematopoiesis, the pathogenesis of age-related hematopoietic

  6. Effects of Recent Stress and Variation in the Serotonin Transporter Polymorphism (5-HTTLPR) on Depressive Symptoms: A Repeated-Measures Study of Adults Age 50 and Older.

    Science.gov (United States)

    Arpawong, Thalida E; Lee, Jinkook; Phillips, Drystan F; Crimmins, Eileen M; Levine, Morgan E; Prescott, Carol A

    2016-01-01

    Depending on genetic sensitivity to it, stress may affect depressive symptomatology differentially. Applying the stress-diathesis hypothesis to older adults, we postulate: (1) recent stress will associate with increased depressive symptom levels and (2) this effect will be greater for individuals with at least one short allele of the serotonin transporter gene promoter region (5-HTTLPR). Further, we employ a design that addresses specific limitations of many prior studies that have examined the 5-HTTLPR × SLE relation, by: (a) using a within-person repeated-measures design to address fluctuations that occur within individuals over time, increase power for detecting G × E, and address GE correlation; (b) studying reports of exogenous stressful events (those unlikely to be caused by depression) to help rule out reverse causation and negativity bias, and in order to assess stressors that are more etiologically relevant to depressive symptomatology in older adults. The sample is drawn from the Health and Retirement Study, a U.S. population-based study of older individuals (N = 28,248; mean age = 67.5; 57.3 % female; 80.7 % Non-Hispanic White, 14.9 % Hispanic/Latino, 4.5 % African American; genetic subsample = 12,332), from whom measures of depressive symptoms and exogenous stressors were collected biannually (1994-2010). Variation in the 5-HTTLPR was characterized via haplotype, using two single nucleotide polymorphisms (SNPs). Ordered logit models were constructed to predict levels of depressive symptoms from 5-HTTLPR and stressors, comparing results of the most commonly applied statistical approaches (i.e., comparing allelic and genotypic models, and continuous and categorical predictors) used in the literature. All models were stratified by race/ethnicity. Overall, results show a main effect of recent stress for all ethnic groups, and mixed results for the variation in 5-HTTLPR × stress interaction, contingent upon statistical model used. Findings

  7. [Production of a recombinant CagA protein for the detection of Helicobacter pylori CagA antibodies].

    Science.gov (United States)

    Akgüç, Miray; Karatayli, Ersin; Çelik, Esra; Koyuncu, Duygu; Çelik, İnci; Karatayli, Senem Ceren; Özden, Ali; Bozdayi, A Mithat

    2014-07-01

    At present, Helicobacter pylori infections affect approximately 50% of the world population. It is known that H.pylori is related with several gastric diseases including chronic atrophic gastritis, peptic and gastric ulcers as well as gastric carcinomas. CagA (Cytotoxin-associated gene A) protein which is one of the most important virulence factors of H.pylori, is thought to be responsible for the development of gastric cancer. CagA is a 128 kDa hydrophilic protein which binds to the epitelial stomach cells and is known to be phosphorylated on its EPIYA regions. The EPIYA regions are highly variable and carry a higher risk of developing gastric cancer than CagA negative strains. The aim of this study was to construct a prokaryotic expression system expressing a recombinant CagA protein, which can be used for the detection of anti-CagA antibodies. For the isolation of H.pylori genomic DNA, a total of 112 gastric biopsy samples obtained from patients who were previously found positive for rapid urease (CLO) test, were used. H.pylori DNAs were amplified from 57 of those samples by polymerase chain reaction (PCR) and of them 35 were found positive in terms of cagA gene. Different EPIYA motifs were detected in 25 out of 35 cagA positive samples, and one of those samples that contained the highest number of EPIYA motif, was chosen for the cloning procedure. Molecular cloning and expression of the recombinant fragment were performed with Champion Pet151/D expression vector (Invitrogen, USA), the expression of which was induced by the addition of IPTG (Isopropyl-beta-D-thiogalactopyranoside) into the E.coli culture medium. Expression was observed with anti-histidin HRP (Horse Radish Peroxidase) antibodies by SDS-PAGE and Western Blot (WB) analysis. In our study, two clones possessing different fragments from the same H.pylori strain with three different EPIYA motifs were succesfully expressed. Since CagA antigen plays a signicant role in the pathogenesis of H

  8. The human [gamma]-aminobutyric acid receptor subunit [beta]3 and [alpha]5 gene cluster in chromosome 15q11-q13 is rich in highly polymorphic (CA)[sub n] repeats

    Energy Technology Data Exchange (ETDEWEB)

    Glatt, K.; Lalande, M. (Howard Hughes Medical Institute, Boston, MA (United States)); Sinnett, D. (Harvard Medical School, Boston, MA (United States))

    1994-01-01

    The [gamma]-aminobutyric acid (GABA[sub A]) receptor [beta]33 (GABRB3) and [alpha]5 (GABRA5) subunit genes have been localized to the Angelman and Prader-Willi syndrome region of chromosome 15q11-q13. GABRB3, which encompasses 250 kb, is located 100 kb proximal of GABRA5, with the two genes arranged in head-to-head transcriptional orientation. In screening 135 kb of cloned DNA within a 260-kb interval extending from within GABRB3 to the 5[prime] end of GABRA5, 10 new (CA), repeats have been identified. Five of these have been analyzed in detail and found to be highly polymorphic, with the polymorphism information content (PIC) ranging from 0.7 to 0.85 and with heterozygosities of 67 to 94%. In the clones from GABRB3/GABRA5 region, therefore, the frequency of (CA)[sub n] with PICs [ge] 0.7 is 1 per 27 kb. Previous estimates of the density of (CA)[sub n] with PICs [ge] 0.7 in the human genome have been approximately 10-fold lower. The GABRB3/GABRA5 region appears, therefore, to be enriched for highly informative (CA)[sub n]. This set of closely spaced, short tandem repeat polymorphisms will be useful in the molecular analyses of Prader-Willi and Angelman syndromes and in high-resolution studies of genetic recombination within this region. 21 refs., 2 figs., 1 tab.

  9. Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes

    DEFF Research Database (Denmark)

    Vinther-Jensen, T; Nielsen, Troels Tolstrup; Budtz-Jørgensen, E;

    2016-01-01

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has...

  10. Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation.

    Science.gov (United States)

    Stein, M; Rappuoli, R; Covacci, A

    2000-02-01

    Helicobacter pylori strains associated with severe tissue damage and inflammation possess a unique genetic locus, cag, containing 31 genes originating from a distant event of horizontal transfer and retained as a pathogenicity island. The cag system is an Helicobacter-specific type IV secretion engine involved in cellular responses like induction of pedestals, secretion of IL-8, and phosphorylation of proteic targets. It has previously been reported that cocultivation of epithelial cells with Helicobacter pylori triggers signal transduction and tyrosine phosphorylation of a 145-kDa putative host cell protein. Herein, we demonstrate that this protein is not derived from the host but rather is the bacterial immunodominant antigen CagA, a virulence factor commonly expressed in peptic ulcer disease and thought to be an orphan of a specific biological function. Thus, CagA is delivered into the epithelial cells by the cag type IV secretion system where it is phosphorylated on tyrosine residues by an as yet unidentified host cell kinase and wired to eukaryotic signal transduction pathways and cytoskeletal plasticity. PMID:10655519

  11. Molecular analysis of the (CAGN repeat causing Huntington′s disease in 34 Iranian families

    Directory of Open Access Journals (Sweden)

    Hormozian F

    2004-01-01

    Full Text Available Huntington′s disease (HD is an inherited neurodegenerative disorder characterized by chorea and progressive dementia. The mutation causing the disease has been identified as an unstable expansion of a trinucleotide (CAG n at the 5′ end of the IT 15 gene on chromosome 4. We have analyzed the distribution of CAG repeats in 71 Iranian individuals (34 patients and 37 unaffected family members belonging to 31 unrelated families thought to segregate HD. We found one expanded CAG allele in 22 individuals (65% belonging to 21 unrelated families. In these HD patients, expanded alleles varied from 40 to 83 CAG units and normal alleles varied from 13 to 36 CAGs. A significant negative correlation between age at onset of symptoms and size of the expanded CAG allele was found (r= - 0.51; P=0. 1. In addition, we genotyped 25 unrelated control individuals (total of 50 alleles and found normal CAG repeats varying from 10 to 34 units. In conclusion, our results showed that molecular confirmation of the clinical diagnosis in HD should be sought in all suspected patients, making it possible for adequate genetic counseling. This Study is the first report of molecular diagnosis of Huntington disease among Iranian population and ever in Middle East and with regard to high frequency of consanguinity marriage in this region.

  12. Polymorphisms in the AR and PSA genes as markers of susceptibility and aggressiveness in prostate cancer

    DEFF Research Database (Denmark)

    Kuasne, Hellen; Rodrigues, Iara Sant'Ana; Fuganti, Paulo Emílio;

    2010-01-01

    The study of genes involved in androgen pathway can contribute to a better knowledge of prostate cancer. Our aim was to examine if polymorphisms in prostate-specific antigen (PSA) and androgen receptor (AR) genes were involved in prostate cancer risk and aggressiveness. Genotypes were determined...... by PCR-RFLP (PSA) or using a 377 ABI DNA Sequencer (AR). PSA(G/G) genotype (OR = 1.78, 95% CI = 1.06–2.99) and AR short CAG repeats (OR = 1.89, 95% CI = 1.21–2.96) increased risk for prostate cancer and were related with tumor aggressiveness. About 38.3% of tumors showed microsatellite instability...

  13. Construction of prokaryotic expression system of 2 148-bp fragment from cagA gene and detection of cagA gene, CagA protein in Helicobacter pyloriisolates and its antibody in sera of patients

    Institute of Scientific and Technical Information of China (English)

    Jie Yan; Yuan Wang; Shi-He Shao; Ya-Fei Mao; Hua-Wen Li; Yi-Hui Luo

    2004-01-01

    AIM: To construct a prokaryotic expression system of a Helicobacter pylori ( H pylori) cagA gene fragment and establish enzyme-linked immunosorbent assays (ELISA) for detecting CagA and its antibody, so as to understand the manner in which the infection of CagA-expressing H pylori (CagA+ H pylori) isolates cause diseases.METHODS: H pylori strains in gastric biopsy specimens from 156 patients with positive results in rapid urease test were isolated. PCR was used to detect the frequency of cagA gene in the 109 H pylori isolates and to amplify a 2 148-bp fragment (cagA1) of cagA gene from a clinical strain Y06. A prokaryotic expression system of cagA1 gene was constructed,and the expression of the target recombinant protein (rCagA1) was examined by SDS-PAGE. Western blotting and immunodiffusion assay were employed to determine the immunoreactivity and antigenicity of rCagA1, respectively.Two ELISAs were established to detect CagA expression in 109 H pylori isolates and the presence of CagA antibody in the corresponding patients′ sera, and the correlations between infection with CagA+ H pylori and gastritis as well as peptic ulcer were analyzed.RESULTS: Of all the clinical specimens obtained, 80.8%(126/156) were found to have H pylori isolates and 97.2%of the isolates (106/109) were positive for caaA gene. In comparison with the reported data, the cloned cagA1fragment possessed 94.83% and 93.30% homologies with the nucleotide and putative amino acid sequences,respectively. The output of rCagA1 produced by the constructed recombinant prokaryotic expression system was approximately 30% of the total bacterial protein, rCagA1was able to bind to the commercial antibody against the whole-cells of H pylori and to induce the immunized rabbits to produce antibody with an immunodiffusion titer of 1:4. A proportion as high as 92.6% of the H pylori isolates (101/109)expressed CagA and 88.1% of the patients′ serum samples (96/109) were CagA antibody-positive. The percentage of

  14. Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA

    OpenAIRE

    Asako Shimoda; Koji Ueda; Shin Nishiumi; Naoko Murata-Kamiya; Sada-atsu Mukai; Shin-ichi Sawada; Takeshi Azuma; Masanori Hatakeyama; Kazunari Akiyoshi

    2016-01-01

    CagA, encoded by cytotoxin-associated gene A (cagA), is a major virulence factor of Helicobacter pylori, a gastric pathogen involved in the development of upper gastrointestinal diseases. Infection with cagA-positive H. pylori may also be associated with diseases outside the stomach, although the mechanisms through which H. pylori infection promotes extragastric diseases remain unknown. Here, we report that CagA is present in serum-derived extracellular vesicles, known as exosomes, in patient...

  15. Based Upon Repeat Pattern (BURP): an algorithm to characterize the long-term evolution of Staphylococcus aureus populations based on spa polymorphisms

    OpenAIRE

    Sammeth Michael; Rothgänger Jörg; Berssenbrügge Christoph; Weniger Thomas; Mellmann Alexander; Stoye Jens; Harmsen Dag

    2007-01-01

    Abstract Background For typing of Staphylococcus aureus, DNA sequencing of the repeat region of the protein A (spa) gene is a well established discriminatory method for outbreak investigations. Recently, it was hypothesized that this region also reflects long-term epidemiology. However, no automated and objective algorithm existed to cluster different repeat regions. In this study, the Based Upon Repeat Pattern (BURP) implementation that is a heuristic variant of the newly described EDSI algo...

  16. Mixed Infection with cagA Positive and cagA Negative Strains of Helicobacter pylori Lowers Disease Burden in The Gambia

    Science.gov (United States)

    Secka, Ousman; Antonio, Martin; Berg, Douglas E.; Tapgun, Mary; Bottomley, Christian; Thomas, Vivat; Walton, Robert; Corrah, Tumani; Thomas, Julian E.; Adegbola, Richard A.

    2011-01-01

    Background The prevalence of Helicobacter pylori including strains with putatively virulent genotypes is high, whereas the H. pylori-associated disease burden is low, in Africa compared to developed countries. In this study, we investigated the prevalence of virulence-related H. pylori genotypes and their association with gastroduodenal diseases in The Gambia. Methods and Findings DNA extracted from biopsies and H. pylori cultures from 169 subjects with abdominal pain, dyspepsia or other gastroduodenal diseases were tested by PCR for H. pylori. The H. pylori positive samples were further tested for the cagA oncogene and vacA toxin gene. One hundred and twenty one subjects (71.6%) were H. pylori positive. The cagA gene and more toxigenic s1 and m1 alleles of the vacA gene were found in 61.2%, 76.9% and 45.5% respectively of Gambian patients harbouring H. pylori. There was a high prevalence of cagA positive strains in patients with overt gastric diseases than those with non-ulcerative dyspepsia (NUD) (p = 0.05); however, mixed infection by cagA positive and cagA negative strains was more common in patients with NUD compared to patients with gastric disease (24.5% versus 0%; p = 0.002). Conclusion This study shows that the prevalence of H. pylori is high in dyspeptic patients in The Gambia and that many strains are of the putatively more virulent cagA+, vacAs1 and vacAm1 genotypes. This study has also shown significantly lower disease burden in Gambians infected with a mixture of cag-positive and cag-negative strains, relative to those containing only cag-positive or only cag-negative strains, which suggests that harbouring both cag-positive and cag-negative strains is protective. PMID:22140492

  17. Mixed infection with cagA positive and cagA negative strains of Helicobacter pylori lowers disease burden in The Gambia.

    Directory of Open Access Journals (Sweden)

    Ousman Secka

    Full Text Available BACKGROUND: The prevalence of Helicobacter pylori including strains with putatively virulent genotypes is high, whereas the H. pylori-associated disease burden is low, in Africa compared to developed countries. In this study, we investigated the prevalence of virulence-related H. pylori genotypes and their association with gastroduodenal diseases in The Gambia. METHODS AND FINDINGS: DNA extracted from biopsies and H. pylori cultures from 169 subjects with abdominal pain, dyspepsia or other gastroduodenal diseases were tested by PCR for H. pylori. The H. pylori positive samples were further tested for the cagA oncogene and vacA toxin gene. One hundred and twenty one subjects (71.6% were H. pylori positive. The cagA gene and more toxigenic s1 and m1 alleles of the vacA gene were found in 61.2%, 76.9% and 45.5% respectively of Gambian patients harbouring H. pylori. There was a high prevalence of cagA positive strains in patients with overt gastric diseases than those with non-ulcerative dyspepsia (NUD (p = 0.05; however, mixed infection by cagA positive and cagA negative strains was more common in patients with NUD compared to patients with gastric disease (24.5% versus 0%; p = 0.002. CONCLUSION: This study shows that the prevalence of H. pylori is high in dyspeptic patients in The Gambia and that many strains are of the putatively more virulent cagA+, vacAs1 and vacAm1 genotypes. This study has also shown significantly lower disease burden in Gambians infected with a mixture of cag-positive and cag-negative strains, relative to those containing only cag-positive or only cag-negative strains, which suggests that harbouring both cag-positive and cag-negative strains is protective.

  18. Repetições CAG: candidatos na gênese das psicoses funcionais

    Directory of Open Access Journals (Sweden)

    Lima Ivanor Velloso Meira

    1999-01-01

    Full Text Available O autor discorre sobre a instabilidade do DNA em regiões de repetições CAG e sua associação com doenças que afetam o SNC e apresentam o fenômeno da antecipação genética. Revisa também os achados de antecipação em famílias com transtorno bipolar e esquizofrenia, assim como as investigações com o método RED (Repeat Expansion Detection e com o anticorpo 1C2, que apontam para uma participação desse mecanismo mutacional na determinação genética das psicoses funcionais.

  19. Heterogeneity of cag genotypes of Helicobacter pylori in the esophageal mucosa of dyspeptic patients and its relation to histopathological outcomes

    Directory of Open Access Journals (Sweden)

    Monica Contreras

    2014-09-01

    Conclusions: H. pylori may coexist in similar proportions without dominance of one cag genotype, suggesting a heterogeneous distribution in the esophagus. The cagE and virB11 genes can be used as markers of cag-PAI in the esophagus. The single cag-PAI genotype in both mucosae confers an increased risk of developing histological damage.

  20. The 27-bp repeat polymorphism in intron 4 (27 bp-VNTR) of endothelial nitric oxide synthase (eNOS) gene is associated with albumin to creatinine ratio in Mexican Americans.

    Science.gov (United States)

    Nath, Subrata D; He, Xin; Voruganti, V Saroja; Blangero, John; MacCluer, Jean W; Comuzzie, Anthony G; Arar, Nedal H; Abboud, Hanna E; Thameem, Farook

    2009-11-01

    The T-786C, Glu298Asp, and 27 bp variable number of tandem repeats (27 bp-VNTR-a/b) polymorphsims of the endothelial nitric oxide synthase (eNOS) gene are thought to alter nitric oxide production and contribute to the development of vascular and renal disease risk. The objective of this study is to investigate whether these three polymorphisms examined previously by others are associated with cardiovascular and renal disease risk in Mexican Americans. Study participants (N = 848; 21 families) were genotyped for T-786C, Glu298Asp, and 27 bp-VNTR-a/b polymorphisms by PCR followed by restriction digestion. Association analyses were performed by a measured genotype approach implemented in the program SOLAR. Of the phenotypes (type 2 diabetes, hypertension, body mass index, waist circumference, total cholesterol, high density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure, albumin to creatinine ratio (ACR), and estimated glomerular filtration rate) examined for association, the 27 bp-VNTR-a/b variant exhibited statistically significant association with ACR (P = 0.047) after accounting for the trait specific covariate effects. In addition, the promoter variant (T-786C) showed a significant association with triglycerides (P = 0.034) after accounting for covariate influences. In conclusion, the present study adds evidence to the role of eNOS candidate gene polymorphisms in modulating the risk factors related to cardiovascular-renal disease in Mexican Americans although the magnitude of the genetic effect is small. PMID:19468830

  1. Evaluation of the Pattern of EPIYA Motifs in the Helicobacter pylori cagA Gene of Patients with Gastritis and Gastric Adenocarcinoma from the Brazilian Amazon Region.

    Science.gov (United States)

    Vilar E Silva, Adenielson; Junior, Mario Ribeiro da Silva; Vinagre, Ruth Maria Dias Ferreira; Santos, Kemper Nunes; da Costa, Renata Aparecida Andrade; Fecury, Amanda Alves; Quaresma, Juarez Antônio Simões; Martins, Luisa Caricio

    2014-01-01

    The Helicobacter pylori is associated with the development of different diseases. The clinical outcome of infection may be associated with the cagA bacterial genotype. The aim of this study was to determine the EPIYA patterns of strains isolated from patients with gastritis and gastric adenocarcinoma and correlate these patterns with the histopathological features. Gastric biopsy samples were selected from 384 patients infected with H. pylori, including 194 with chronic gastritis and 190 with gastric adenocarcinoma. The presence of the cagA gene and the EPIYA motif was determined by PCR. The cagA gene was more prevalent in patients with gastric cancer and was associated with a higher degree of inflammation, neutrophil activity, and development of intestinal metaplasia. The number of EPIYA-C repeats showed a significant association with an increased risk of gastric carcinoma (OR = 3.79, 95% CI = 1.92-7.46, and P = 0.002). A larger number of EPIYA-C motifs were also associated with intestinal metaplasia. In the present study, infection with H. pylori strains harboring more than one EPIYA-C motif in the cagA gene was associated with the development of intestinal metaplasia and gastric adenocarcinoma but not with neutrophil activity or degree of inflammation. PMID:26904732

  2. Evaluation of the Pattern of EPIYA Motifs in the Helicobacter pylori cagA Gene of Patients with Gastritis and Gastric Adenocarcinoma from the Brazilian Amazon Region

    Directory of Open Access Journals (Sweden)

    Adenielson Vilar e Silva

    2014-01-01

    Full Text Available The Helicobacter pylori is associated with the development of different diseases. The clinical outcome of infection may be associated with the cagA bacterial genotype. The aim of this study was to determine the EPIYA patterns of strains isolated from patients with gastritis and gastric adenocarcinoma and correlate these patterns with the histopathological features. Gastric biopsy samples were selected from 384 patients infected with H. pylori, including 194 with chronic gastritis and 190 with gastric adenocarcinoma. The presence of the cagA gene and the EPIYA motif was determined by PCR. The cagA gene was more prevalent in patients with gastric cancer and was associated with a higher degree of inflammation, neutrophil activity, and development of intestinal metaplasia. The number of EPIYA-C repeats showed a significant association with an increased risk of gastric carcinoma (OR = 3.79, 95% CI = 1.92–7.46, and P=0.002. A larger number of EPIYA-C motifs were also associated with intestinal metaplasia. In the present study, infection with H. pylori strains harboring more than one EPIYA-C motif in the cagA gene was associated with the development of intestinal metaplasia and gastric adenocarcinoma but not with neutrophil activity or degree of inflammation.

  3. Genome-Wide Analysis of Simple Sequence Repeats and Efficient Development of Polymorphic SSR Markers Based on Whole Genome Re-Sequencing of Multiple Isolates of the Wheat Stripe Rust Fungus.

    Directory of Open Access Journals (Sweden)

    Huaiyong Luo

    Full Text Available The biotrophic parasitic fungus Puccinia striiformis f. sp. tritici (Pst causes stripe rust, a devastating disease of wheat, endangering global food security. Because the Pst population is highly dynamic, it is difficult to develop wheat cultivars with durable and highly effective resistance. Simple sequence repeats (SSRs are widely used as molecular markers in genetic studies to determine population structure in many organisms. However, only a small number of SSR markers have been developed for Pst. In this study, a total of 4,792 SSR loci were identified using the whole genome sequences of six isolates from different regions of the world, with a marker density of one SSR per 22.95 kb. The majority of the SSRs were di- and tri-nucleotide repeats. A database containing 1,113 SSR markers were established. Through in silico comparison, the previously reported SSR markers were found mainly in exons, whereas the SSR markers in the database were mostly in intergenic regions. Furthermore, 105 polymorphic SSR markers were confirmed in silico by their identical positions and nucleotide variations with INDELs identified among the six isolates. When 104 in silico polymorphic SSR markers were used to genotype 21 Pst isolates, 84 produced the target bands, and 82 of them were polymorphic and revealed the genetic relationships among the isolates. The results show that whole genome re-sequencing of multiple isolates provides an ideal resource for developing SSR markers, and the newly developed SSR markers are useful for genetic and population studies of the wheat stripe rust fungus.

  4. Development and Characterization of Simple Sequence Repeat Markers Providing Genome-Wide Coverage and High Resolution in Maize

    Science.gov (United States)

    Xu, Jie; Liu, Ling; Xu, Yunbi; Chen, Churun; Rong, Tingzhao; Ali, Farhan; Zhou, Shufeng; Wu, Fengkai; Liu, Yaxi; Wang, Jing; Cao, Moju; Lu, Yanli

    2013-01-01

    Simple sequence repeats (SSRs) have been widely used in maize genetics and breeding, because they are co-dominant, easy to score, and highly abundant. In this study, we used whole-genome sequences from 16 maize inbreds and 1 wild relative to determine SSR abundance and to develop a set of high-density polymorphic SSR markers. A total of 264 658 SSRs were identified across the 17 genomes, with an average of 135 693 SSRs per genome. Marker density was one SSR every of 15.48 kb. (C/G)n, (AT)n, (CAG/CTG)n, and (AAAT/ATTT)n were the most frequent motifs for mono, di-, tri-, and tetra-nucleotide SSRs, respectively. SSRs were most abundant in intergenic region and least frequent in untranslated regions, as revealed by comparing SSR distributions of three representative resequenced genomes. Comparing SSR sequences and e-polymerase chain reaction analysis among the 17 tested genomes created a new database, including 111 887 SSRs, that could be develop as polymorphic markers in silico. Among these markers, 58.00, 26.09, 7.20, 3.00, 3.93, and 1.78% of them had mono, di-, tri-, tetra-, penta-, and hexa-nucleotide motifs, respectively. Polymorphic information content for 35 573 polymorphic SSRs out of 111 887 loci varied from 0.05 to 0.83, with an average of 0.31 in the 17 tested genomes. Experimental validation of polymorphic SSR markers showed that over 70% of the primer pairs could generate the target bands with length polymorphism, and these markers would be very powerful when they are used for genetic populations derived from various types of maize germplasms that were sampled for this study. PMID:23804557

  5. Helicobacter pylori CagA disrupts epithelial patterning by activating myosin light chain.

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    Jonathan B Muyskens

    Full Text Available Helicobacter pylori infection is a leading cause of ulcers and gastric cancer. We show that expression of the H. pylori virulence factor CagA in a model Drosophila melanogaster epithelium induces morphological disruptions including ectopic furrowing. We find that CagA alters the distribution and increases the levels of activated myosin regulatory light chain (MLC, a key regulator of epithelial integrity. Reducing MLC activity suppresses CagA-induced disruptions. A CagA mutant lacking EPIYA motifs (CagA(EPISA induces less epithelial disruption and is not targeted to apical foci like wild-type CagA. In a cell culture model in which CagA(EPISA and CagA have equivalent subcellular localization, CagA(EPISA is equally potent in activating MLC. Therefore, in our transgenic system, CagA is targeted by EPIYA motifs to a specific apical region of the epithelium where it efficiently activates MLC to disrupt epithelial integrity.

  6. Burden of Hospital Admission and Repeat Angiography in Angina Pectoris Patients with and without Coronary Artery Disease

    DEFF Research Database (Denmark)

    Jespersen, Lasse; Abildstrom, Steen Z; Hvelplund, Anders;

    2014-01-01

    AIMS: To evaluate risk of hospitalization due to cardiovascular disease (CVD) and repeat coronary angiography (CAG) in stable angina pectoris (SAP) with no obstructive coronary artery disease (CAD) versus obstructive CAD, and asymptomatic reference individuals. METHODS AND RESULTS: We followed 11......-, and 3-vessel disease, respectively (all Prepeat CAG with multivariable adjusted hazard ratios for patients with angiographically normal coronary arteries being 2.3(1.9-2.9), for angiographically diffuse non-obstructive CAD 5.5(4.4-6.8) and for obstructive CAD...... 6.6-9.4(range)(all Prepeat CAG compared with asymptomatic reference...

  7. Outcomes of CAG Regimen for Refractory Biphenotypic Acute Leukemia Patients

    Institute of Scientific and Technical Information of China (English)

    Guang-sheng He; Xiang Zhang; De-pei Wu; Ai-ning Sun; Zheng-ming Jin; Hui-ying Qiu; Miao Miao; Xiao-wen Tang; Zheng-zheng Fu; Yue Han

    2009-01-01

    Objective To evaluated the efficiency of low-dose cytosine arabinoside plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor(CAG)regimen for refractory biphenotypic acute leukemia(BAL).Methods We treated 5 refractory BAL patients by CAG regimen(10 mg·m 2 cytosine arabinoside subcutaneously administrated every 12 hours,day 1-14;5-7 mg·m2 aclarubicin intravenously administrated daily,day 1-8;and concurrently used 200 μg.m-2·d-1 granulocyte colony-stimulating factor subcutaneously)from November 2002 to April 2007.The efficacy of the regimen was evaluated by response rate,and the side effects were also measured.Results The complete remission rate was 80% ,median duration of absolute neutrophil count<5.0×108/L and platelet count<2.0×1010/L was day 13 and day 1,respectively;and the infection rate was low(Ⅲ-Ⅳ infection rate,20.00% ).Conclusion CAG regimen as remission induction chemotherapy for BAL patients is effective with a high remission rate and low toxicity.

  8. Based Upon Repeat Pattern (BURP: an algorithm to characterize the long-term evolution of Staphylococcus aureus populations based on spa polymorphisms

    Directory of Open Access Journals (Sweden)

    Sammeth Michael

    2007-10-01

    Full Text Available Abstract Background For typing of Staphylococcus aureus, DNA sequencing of the repeat region of the protein A (spa gene is a well established discriminatory method for outbreak investigations. Recently, it was hypothesized that this region also reflects long-term epidemiology. However, no automated and objective algorithm existed to cluster different repeat regions. In this study, the Based Upon Repeat Pattern (BURP implementation that is a heuristic variant of the newly described EDSI algorithm was investigated to infer the clonal relatedness of different spa types. For calibration of BURP parameters, 400 representative S. aureus strains with different spa types were characterized by MLST and clustered using eBURST as "gold standard" for their phylogeny. Typing concordance analysis between eBURST and BURP clustering (spa-CC were performed using all possible BURP parameters to determine their optimal combination. BURP was subsequently evaluated with a strain collection reflecting the breadth of diversity of S. aureus (JCM 2002; 40:4544. Results In total, the 400 strains exhibited 122 different MLST types. eBURST grouped them into 23 clonal complexes (CC; 354 isolates and 33 singletons (46 isolates. BURP clustering of spa types using all possible parameter combinations and subsequent comparison with eBURST CCs resulted in concordances ranging from 8.2 to 96.2%. However, 96.2% concordance was reached only if spa types shorter than 8 repeats were excluded, which resulted in 37% excluded spa types. Therefore, the optimal combination of the BURP parameters was "exclude spa types shorter than 5 repeats" and "cluster spa types into spa-CC if cost distances are less than 4" exhibiting 95.3% concordance to eBURST. This algorithm identified 24 spa-CCs, 40 singletons, and excluded only 7.8% spa types. Analyzing the natural population with these parameters, the comparison of whole-genome micro-array groupings (at the level of 0.31 Pearson correlation index

  9. Neutral Polymorphisms in Putative Housekeeping Genes and Tandem Repeats Unravels the Population Genetics and Evolutionary History of Plasmodium vivax in India

    OpenAIRE

    Prajapati, Surendra K.; Joshi, Hema; Carlton, Jane M.; Rizvi, M. Alam

    2013-01-01

    The evolutionary history and age of Plasmodium vivax has been inferred as both recent and ancient by several studies, mainly using mitochondrial genome diversity. Here we address the age of P. vivax on the Indian subcontinent using selectively neutral housekeeping genes and tandem repeat loci. Analysis of ten housekeeping genes revealed a substantial number of SNPs (n = 75) from 100 P. vivax isolates collected from five geographical regions of India. Neutrality tests showed a majority of the ...

  10. Helicobacter pylori CagA Inhibits PAR1-MARK Family Kinases by Mimicking Host Substrates

    Energy Technology Data Exchange (ETDEWEB)

    Nesic, D.; Miller, M; Quinkert, Z; Stein, M; Chait, B; Stebbins, C

    2010-01-01

    The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2.

  11. Roles of the nucleolus in the CAG RNA-mediated toxicity.

    Science.gov (United States)

    Tsoi, Ho; Chan, Ho Yin Edwin

    2014-06-01

    The nucleolus is a subnuclear compartment within the cell nucleus that serves as the site for ribosomal RNA (rRNA) transcription and the assembly of ribosome subunits. Apart from its classical role in ribosomal biogenesis, a number of cellular regulatory roles have recently been assigned to the nucleolus, including governing the induction of apoptosis. "Nucleolar stress" is a term that is used to describe a signaling pathway through which the nucleolus communicates with other subcellular compartments, including the mitochondria, to induce apoptosis. It is an effective mechanism for eliminating cells that are incapable of performing protein synthesis efficiently due to ribosome biogenesis defects. The down-regulation of rRNA transcription is a common cause of nucleolar function disruption that subsequently triggers nucleolar stress, and has been associated with the pathogenesis of neurological disorders such as spinocerebellar ataxias (SCAs) and Huntington's diseases (HD). This article discusses recent advances in mechanistic studies of how expanded CAG trinucleotide repeat RNA transcripts trigger nucleolar stress in SCAs, HD and other trinucleotide repeat disorders. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.

  12. Genetic polymorphism and forensic parameters of nine short tandem repeat loci in Ngöbé and Emberá Amerindians of Panama.

    Science.gov (United States)

    Castro, Edgardo A; Trejos, Diomedes E; Berovides-Alvarez, Vicente; Arias, Tomás D; Ramos, Carlos W

    2007-10-01

    Nine STR loci (CSF1PO, TPOX, TH01, F13A01, FESFPS, VWA, D16S539, D7S820, and D13S317) were analyzed in unrelated Ngöbé and Emberá Amerindians of Panama. The chi-square test demonstrated statistically significant differences (P shared their alleles with the highest frequencies in seven loci. However, there were also noticeable differences at the TPOX locus, which showed its highest frequencies at alleles 11 (0.48) and 6 (0.54) for the Ngöé and Emberá, respectively. Interestingly, these alleles are present in one population and are absent in the other, suggesting that they could be distinctive for each population. These results demonstrate that, despite the fact that each population belongs to a different linguistic stock [Chibchan (Ngöbé) and Chocoan (Emberá)], both retain strong similarities in their allele-frequency distributions. Three loci (TPOX, VWA, and F13A01) in the Ngöbé and two loci (TH01 and TPOX) in the Emberá departed from Hardy-Weinberg equilibrium. The analysis of the STR markers demonstrates that, despite their low levels of genetic polymorphisms, most of them could be informative for forensic purposes, showing a combined power of discrimination of 0.9999 for both Amerindian populations. However, powers of exclusion in the Ngöbé were very low, particularly at the TH01 (0.04) and FESFPS (0.08) loci. The combined powers of exclusion were 0.9338 and 0.9890 for the Ngöbé and the Emberá, respectively. Furthermore, the combined typical paternity index in the Ngöbé was considerably low (2.58), and in the Emberá it was 40.44, which is also very low. The low genetic polymorphism levels suggest that theuse of additional loci supplementing the battery of the nine loci is recommended for paternity and forensic tests in both populations, particularly for the Ngöbé.

  13. An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA

    Directory of Open Access Journals (Sweden)

    Jens eConradi

    2012-05-01

    Full Text Available Helicobacter pylori is a specific gastric pathogen that colonizes the stomach in more than 50% of the world’s human population. Infection with this bacterium can induce several types of gastric pathology, ranging from chronic gastritis to peptic ulcers and even adenocarcinoma. Virulent H. pylori isolates encode components of a type IV secretion system (T4SS, which form a pilus for the injection of virulence proteins such as CagA into host target cells. This is accomplished by a specialized adhesin on the pilus surface, the protein CagL, a putative VirB5 ortholog, which binds to host cell β1 integrin, triggering subsequent delivery of CagA across the host cell membrane. Like the human extracellular matrix protein fibronectin, CagL contains an RGD (Arg-Gly-Asp motif and is able to trigger intracellular signaling pathways by RGD-dependent binding to integrins. While CagL binding to host cells is mediated primarily by the RGD motif, we identified an auxiliary binding motif for CagL-integrin interaction. Here, we report on a surface-exposed FEANE (Phe-Glu-Ala-Asn-Glu interaction motif in spatial proximity to the RGD sequence, which enhances the interactions of CagL with integrins. It will be referred to as RGD helper sequence (RHS. Competitive cell adhesion assays with recombinant wild type CagL and point mutants, competition experiments with synthetic cyclic and linear peptides, and peptide array experiments revealed amino acids essential for the interaction of the RHS motif with integrins. Infection experiments indicate that the RHS motif plays a role in the early interaction of H. pylori T4SS with integrin, to trigger signaling and to inject CagA into host cells. We thus postulate that CagL is a versatile T4SS surface protein equipped with at least two motifs to promote binding to integrins, thereby causing aberrant signaling within host cells and facilitating translocation of CagA into host cells, thus contributing directly to H. pylori

  14. Repeated Miscarriage

    Science.gov (United States)

    f AQ FREQUENTLY ASKED QUESTIONS FAQ100 PREGNANCY Repeated Miscarriages • What is recurrent pregnancy loss? • What is the likelihood of having repeated miscarriages? • What is the most common cause of miscarriage? • ...

  15. Helicobacter pylori and CagA under conditions of iron deficiency.

    Science.gov (United States)

    Noto, Jennifer M; Peek, Richard M

    2015-01-01

    Iron deficiency is the most common nutritional deficiency worldwide and compelling evidence has demonstrated that this condition heightens the risk of gastric cancer. Infection with Helicobacter pylori is the strongest known risk factor for the development of gastric adenocarcinoma. Recent work has demonstrated that, under conditions of iron deficiency, H. pylori-induced gastric carcinogenesis is augmented through increased formation of the strain-specific cag type IV secretion system and enhanced delivery of the bacterial oncoprotein CagA into host cells. Although CagA is a potent virulence factor that promotes oncogenic responses, additional studies have now demonstrated that CagA modulates host cell iron homeostasis in vitro and fundamental metabolic functions of the bacterial cell in vivo. Here we discuss these findings and describe working models by which CagA exerts its effects on gastric epithelial cells, with particular emphasis on its potential role in modulation of host iron homeostasis.

  16. 幽门螺杆菌cagA基因和血清CagA抗体与VacA表达关系的研究

    Institute of Scientific and Technical Information of China (English)

    张尤历; 刘厚钰; 等

    1999-01-01

    目的;探讨幽门螺杆菌cagA基因和血清CagA抗体与VacA表达的关系。方法:用聚合酶链反应法(PCR)测定由62例慢性胃炎、消化性溃疡和胃癌患者胃罕粘膜分离获得Hp菌株:用酶免疫技术测定患者血清HpCagA抗体;用Hela细胞培养法测定Hp菌株VacA活性。结果:cagA基因阳性和阴性Hp菌株表达VacA阳必班组分别为40.00%和33.33%(P>0.05);血清CagA抗体阳性和阴性患者感染Hp菌株体外产生VacA阳性率分别为33.33%和42.11%(P>0.05)。结论:HpcagA基因和血清CagA抗体与VacA表达之间无相互依赖关系,vacA基因是一个独立的标志物。

  17. Infrared fluorescent automated detection of thirteen short tandem repeat polymorphisms and one gender-determining system of the CODIS core system.

    Science.gov (United States)

    Ricci, U; Sani, I; Guarducci, S; Biondi, C; Pelagatti, S; Lazzerini, V; Brusaferri, A; Lapini, M; Andreucci, E; Giunti, L; Giovannucci Uzielli, M L

    2000-11-01

    We used an infrared (IR) automated fluorescence monolaser sequencer for the analysis of 13 autosomal short tandem repeat (STR) systems (TPOX, D3S1358, FGA, CSF1PO, D5S818, D7S820, D8S1179, TH01, vWA, D13S317, D16S359, D18S51, D21S11) and the X-Y homologous gene amelogenin system. These two systems represent the core of the combined DNA index systems (CODIS). Four independent multiplex reactions, based on the polymerase chain reaction (PCR) technique and on the direct labeling of the forward primer of every primer pair, with a new molecule (IRDye800), were set up, permitting the exact characterization of the alleles by comparison with ladders of specific sequenced alleles. This is the first report of the whole analysis of the STRs of the CODIS core using an IR automated DNA sequencer. The protocol was used to solve paternity/maternity tests and for population studies. The electrophoretic system also proved useful for the correct typing of those loci differing in size by only 2 bp. A sensibility study demonstrated that the test can detect an average of 10 pg of undegraded human DNA. We also performed a preliminary study analyzing some forensic samples and mixed stains, which suggested the usefulness of using this analytical system for human identification as well as for forensic purposes.

  18. Comparison of a PCR-restriction fragment length polymorphism (PCR-RFLP) assay to pulsed-field gel electrophoresis to determine the effect of repeated subculture and prolonged storage on RFLP patterns of Shiga toxin-producing Escherichia coli O157:H7.

    Science.gov (United States)

    Shima, Kensuke; Wu, Yuluo; Sugimoto, Norihiko; Asakura, Masahiro; Nishimura, Kazuhiko; Yamasaki, Shinji

    2006-11-01

    In this study, we compared a recently developed PCR-restriction fragment length polymorphism (PCR-RFLP) assay with pulsed-field gel electrophoresis (PFGE) using three different Shiga toxin-producing Escherichia coli (STEC) strains to understand whether repeated subculture in vitro and prolonged storage at room temperature affect the RFLP patterns of STEC. The PFGE profiles of the STEC strains changed by 1 to 8 fragments after repeated subculture and prolonged storage; one strain was no longer clonal after repeated subculture compared to the original isolate according to the Tenover criteria. In contrast, RFLP patterns obtained by PCR-RFLP were identical after repeated subculture and prolonged storage. These data clearly indicate that the PCR-RFLP assay which is based on the diversity of region V, a regulatory region of Stx-phage, was not affected by repeated subculture and prolonged storage and is a more practical and reliable method for molecular typing of STEC strains.

  19. Cloning and sequencing of cagA gene fragment of Helicobacter pylori with coccoid form

    Institute of Scientific and Technical Information of China (English)

    Ke-Xia Wang; Xue-Feng Wang

    2004-01-01

    AIM: To clone and sequence the cagA gene fragment of Helicobacter pylori ( H pylori) with coccoid form.METHODS: H pylori strain NCTC11637 were transformed to coccoid form by exposure to antibiotics in subinhibitory concentrations. The coccoid H pyloriwas collected. cagA gene of the coccoid H pylori strain was amplified by PCR.After purified, the target fragment was cloned into plasmid pMD-18T. The recombinant plasmid pMD-18T-cagA was transformed into E. coli JM109. Positive clones were screened and identified by PCR and digestion with restriction endonucleases. The sequence of inserted fragment was then analysed.RESULTS: cagA gene of 3 444 bp was obtained from the coccoid H pylori genome DNA. The recombinant plasmid pMD-18T-cagA was constructed, then it was digested by BamH Ⅰ+Sac Ⅰ, and the product of digestion was identical with the predicted one. Sequence analysis showed that the homology of coccoid and the reported original sequence H pylori was 99.7%.CONCLUSION: The recombinant plasmid containing cagA gene from coccoid H pylori has been constructed successfully.The coccoid H pylori contain completed cagA gene, which may be related to pathogenicity of them.

  20. Expression of the CagA gene of H. pylori and application of its product

    Institute of Scientific and Technical Information of China (English)

    Feng Chan Han; Xiao Jun Yan; Cheng Zhi Su

    2000-01-01

    @@ INTRODUCTION Helicobacter pylori (Hp) plays an important role in the upper digestive tract diseases. It can be divided into two main groups (toxic and non-toxic Hp )according to the production of vacuolating cytotoxin (VacA). The toxic bacteria also produce cytotoxin associated protein A (CagA) which might have something to do with the transcription, folding,transportation or the function of VacA. Studies showed that CagA positive Hp ( CagA+ Hp )accounted for more than 50% of all kinds of Hp,and peptic ulcer and gastric cancer were closely related to their infection[1-7].

  1. [Comparison of clinical efficacy between decitabine combined with CAG regimen and CAG regimen alone in patients with intermediate to high-risk myelodysplastic syndromes].

    Science.gov (United States)

    Zhang, Yun-Ping; Wu, Wen-Zhong; Cui, Guo-Xing

    2014-10-01

    This study was purposed to compare the clinical efficacy and adverse reactions of low-dose decitabine combined with CAG regimen (aclarubicin, Ara-C, and G-CSF) and CAG regimen alone in intermediate to high-risk myelodysplastic syndromes (MDS), and evaluate the validity and efficacy of the former regimen as new treatment method of intermediate to high-risk myelodysplastic syndromes. A total of 12 patients with intermediate (IR) to high-risk (HR) MDS treated by low-dose decitabine combined with CAG regimen and 10 patients with IR to HR MDS treated by CAG regimen alone were evaluated after treatment of 1 cycle and at least after 2 cycles. The complete remission (CR) after 1 cycle, overall remission rate (ORR), progression free survival (PFS) and overall survival (OS) between them were analyzed. The results showed that 9 patients treated by low-dose decitabine combined with CAG regimen achieved complete remission after 1 cycle, 2 patients achieved partial remission, 1 patient did not show reaction. The complete remission rate was 75.0% and overall response rate was 91.7%. The median time of disease free survival was 9 months (0-27 months). The median overall survival time was 16 months (3-28 months). 4 patients suffered from pulmonary infection after treatment and then were all cured after treatment with anti-infective therapy. The 5 patients treated by CAG regimen alone achieved complete remission,3 patients achieved partial remission, 2 patients showed non-reaction. The complete remission rate was 50.0% and overall response rate was 80.0%. The median time of disease free survival was 6 months(0-18 months). The median overall survival time was 13 months(3-31 months), 4 patients suffered from pulmonary infection, 1 patient suffered from enteric infection and 1 patient suffered from Escherichia coli septicemia after treatment, all of them becomed better after active treatment. Two groups of patients all had no serious adverse reactions, All patients could tolerate, no

  2. PSA and androgen-related gene (AR, CYP17, and CYP19) polymorphisms and the risk of adenocarcinoma at prostate biopsy

    DEFF Research Database (Denmark)

    dos Santos, Rodrigo Mattos; de Jesus, Carlos Márcio Nóbrega; Trindade Filho, José Carlos Souza;

    2008-01-01

    The aim of the present study was to examine the impact of polymorphisms in prostate-specific antigen (PSA) and androgen-related genes (AR, CYP17, and CYP19) on prostate cancer (PCa) risk in selected high-risk patients who underwent prostate biopsy. Blood samples and prostate tissues were obtained...... for DNA analysis. Single-nucleotide polymorphisms in the 50-untranslated regions (UTRs) of the PSA (substitution A>G at position-158) and CYP17 (substitution T>C at 50-UTR) genes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism assays. The CAG and TTTA repeats...... in the AR and CYP19 genes, respectively, were genotyped by PCR-based GeneScan analysis. Patients with the GG genotype of the PSA gene had a higher risk of PCa than those with the AG or AA genotype (OR=3.79, p=0.00138). The AA genotype was associated with lower PSA levels (6.44 +/- 1.64 ng=mL) compared...

  3. Prevalence of Helicobacter pylori cagA genotype among dyspeptic patients in Southern Thailand

    Institute of Scientific and Technical Information of China (English)

    Sueptrakool Wisessombat; Chatruthai Meethai

    2014-01-01

    Objective: To investigate the prevalence of Helicobacter pylori (H. pylori) infection in dyspepsia patients and its relation to virulence factor cagA gene. Methods: In total, 110 gastric biopsies from dyspeptic patients were comparatively studied using rapid urease test and multiplex polymerase chain reaction (PCR). Results: Multiplex PCR detected three genes of 16S rRNA, cagA, and ureC. H. pylori was detected in 14 gastric biopsies (13%). Significantly higher numbers of female were infected. Furthermore,cag A gene was found in all H. pylori-positive specimens. In addition, the result indicated that the multiplex PCR with annealing temperature at 57 oC was able to effectively amplify specific products. Conclusions:The results confirmed high prevalence of cagA gene in H. pylori among dyspeptic patients in Southern Thailand.

  4. What exists beyond cagA and vacA? Helicobacter pylori genes in gastric diseases.

    Science.gov (United States)

    da Costa, Débora Menezes; Pereira, Eliane dos Santos; Rabenhorst, Silvia Helena Barem

    2015-10-01

    Helicobacter pylori (H. pylori) infection is present in more than half the world's population and has been associated with several gastric disorders, such as gastritis, peptic ulceration, and gastric adenocarcinoma. The clinical outcome of this infection depends on host and bacterial factors where H. pylori virulence genes seem to play a relevant role. Studies of cagA and vacA genes established that they were determining factors in gastric pathogenesis. However, there are gastric cancer cases that are cagA-negative. Several other virulence genes have been searched for, but these genes remain less well known that cagA and vacA. Thus, this review aimed to establish which genes have been suggested as potentially relevant virulence factors for H. pylori-associated gastrointestinal diseases. We focused on the cag-pathogenicity island, genes with adherence and motility functions, and iceA based on the relevance shown in several studies in the literature.

  5. Diagnostic value of CagA IgG in the process to eradicate Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Zhi Bang Yang; Pi Long Wang; Ming Ming Gu; Li Hao Chen; Quan Chen; Lin Zhan

    2000-01-01

    AIM To investigate the diagnostic value of CagA IgG in serum.METHODS Seventy three patients with peptic ulcer infected with HP were eradicated by antibioticstherapy. At pretreatment, wk9 and wk20 after treatment, the detection of Hp in gastric muscosa bybacteriologic method were performed, and CagA and whole-cell antigen of HP igG in serum by ELISAmethod were also performed at the same time.RESULTS The IgG titres of Hp CagA and whole-cell antigen changes in accordance with the efficacy ofHp eradicated. The former with an earlier appearance and a greater number of cases decreased to normallevel in comparison with the latter.CONCLUSION CagA IgG is a better index for observing the effectiveness of the eradication of Hp.

  6. Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori

    LENUS (Irish Health Repository)

    Backert, Steffen

    2011-11-01

    Abstract Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA\\/B, SabA, AlpA\\/B, OipA and HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a type IV secretion system (T4SS). The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA\\/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed.

  7. Association of cyclooxygenase-2 expression with Hp-cagA infection in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Xiao-Lin Guo; Li-Er Wang; Shu-Yan Du; Chen-Ling Fan; Li Li; Peng Wang; Yuan Yuan

    2003-01-01

    AIM: To observe the expression of cyclooxygenase-2 (COX-2) and to investigate the association between COX-2expression and infection with cytotoxic-associated gene A( cagA) positive strair Helicobacter pylori ( Hp) in humangastric cancer, and subsequently to provide fresh ideas forthe early prevention of gastric cancer.METHODS: 32 Specimens of gastric cancer andcorresponding adjacent normal gastric mucosa were obtainedfrom patients who had undergone surgical operations ofgastric cancer. All the samples including 1 case of stomachmalignant lymphoma and 31 cases of gastric adenocarcinomawere confirmed by pathology diagnosis. The expression ofCOX-2 in 32 specimens of gastric cancer and correspondingadjacent normal gastric mucosa was quantitativelydetermined and analyzed with Flow Cytometry, and the levelsof COX-2 protein were compared between specimens withcagA+ Hp infection and those without cagA+ Hp infection.The cagA gene in 32 specimens of gastric cancer wasdetected bypolymerase chain reaction (PCR) method.RESULTS: Twenty-seven of 32 (84 %) specimens of gastriccancer showed over-expression of COX-2, compared withthe adjacent normal gastric mucosa. cagA+ gene weredetected from 19 specimens of gastric cancer, but not fromthe other 13 specimens. The levels of COX-2 protein in 19specimens of gastric cancer with cagA+ Hp infection (thenumber of positive cells was 73.82±18.2) were significantlyhigher than those in the 13 specimens without cagA+ Hpinfection (the number of positive cells was 35.92±22.1).CONCLUSION: COX-2 is overexpressed in gastric cancerand cagA+Hp infection could up-regulate the expression ofCOX-2 in gastric cancer in human. There may also existanother way or channel to regulate the expression of COX-2 in gastric cancer in addition to cagA+Hp infection.Therefore, applying COX-2 selective inhibitors could be aneffective and promising way to prevent gastric cancer.

  8. Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Backert Steffen

    2011-11-01

    Full Text Available Abstract Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA/B, SabA, AlpA/B, OipA and HopZ and the cag (cytotoxin-associated genes pathogenicity island encoding a type IV secretion system (T4SS. The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed.

  9. Pathogenicty and immune prophylaxis of cag pathogenicity island gene knockout homogenic mutants

    Institute of Scientific and Technical Information of China (English)

    Huan-Jian Lin; Jing Xue; Yang Bai; Ji-De Wang; Ya-Li Zhang; Dian-Yuan Zhou

    2004-01-01

    AIM: To clarify the role of cag pathogenicity island (cagPAI)of Helicobacter pylori(H pylori) in the pathogenicity and immune prophylaxis of H pyloriinfection.METHODS: Three pairs of H pylori including 3 strains of cagPAI positive wildtype bacteria and their cagPAI knockout homogenic mutants were utilized. H pylori binding to the gastric epithelial cells was analyzed by flow cytometry assays.Apoptosis of gastric epithelial cells induced by H pylori was determined by ELISA assay. Prophylaxis effect of the wildtype and mutant strains was compared by immunization with the sonicate of the bacteria into mice model.RESULTS: No difference was found in the apoptasis between cagPAI positive and knockout H pylori strains in respective of the ability in the binding to gastric epithelial cells as well as the induction of apoptosis. Both types of the bacteria were able to protect the mice from the infection of H pylori after immunization, with no difference between them regarding to the protection rate as well as the stimulation of the proliferation of splenocytes of the mice.CONCLUSION: The role of cagPAI in the pathogenicity and prophylaxis of H pylori infection remains to be cleared.

  10. Deletion of cagA gene of Helicobacter pylori by PCR products

    Institute of Scientific and Technical Information of China (English)

    Xun Zeng; Li-Hua He; Yan Yin; Mao-Jun Zhang; Jian-Zhong Zhang

    2005-01-01

    AIM: Cytotoxin-associated protein (antigen) A (CagA)plays an important role in Helicobacter pylori(H pylori)pathogenesis. Our aim was to obtain cagA mutant strains by a new mutation method so as to better understand the mechanism of CagA in epithelial cells. METHODS: In contrast with the traditional method using suicide plasmid, we constructed cagA- mutant strains directly with PCR products. The constructed mutant clones grew on selective media and allelic exchange was confirmed by Southern blot. Furthermore, two different transformation methods, electroporation, and natural transformation, were compared with regard to the efficiency of recombination.RESULTS: The mutation by PCR products could be completed within 3-5 d, and the recombination rate by electroporation and natural transformation was 4.02×10-8 and 1.03x 10-9 respectively. Mutation rate by electroporation (4.02× 10-8) was far higher than by natural transformation (1.03× 10-9) (P = 0.000<0.005).CONCLUSION: cagA- mutant strains have been constructed,which is important for further study on the function of CagA in epithelial cells. A mutation method by directly using PCR products has been proved successful with a much higher mutation rate, and is easier, especially when in combination with electroporation. This method could be widely used in gene deletion of H pylori.

  11. Study on Effect of ANTI-VacA + CagA + Helicobacter pylori-IgY Against VacA + CagA + Hp%抗VacA+CagA+幽门螺杆菌IgY的抗感染作用研究

    Institute of Scientific and Technical Information of China (English)

    傅颖媛; 黎健; 李娟; 曾小平; 况南珍

    2006-01-01

    为研究抗VacA+CagA+幽门螺杆菌(Hp)IgY的抗感染作用,以VacA+CagA+Hp为抗原免疫蛋鸡,聚乙二醇法和水稀释法从鸡卵黄中提取抗-VacA+CagA+Hp-lgY,酶联免疫吸附实验(ELISA)测定IgY抗体效价.建立胃腔感染VacA+CagA Hp的昆明系小鼠模型,观察抗-VacA+CagA+Hp-IgY对小鼠胃腔感染VacA+CagA+Hp的防治效果.ELISA法测定IgY效价均为1:20,480;抗-VacA+CagA+Hp-IgY防治小鼠胃腔感染VacA+CagA Hp效果较理想,IgY高、中剂量组效果优于阳性对照组(P<0.05);低剂量组效果等同于阳性对照组(P>0.05).抗-VacA+CagA+Hp-IgY较好的体内抗感染作用,提示该IgY有望成为较理想的治疗VacA+CagA+Hp感染的生物制剂.

  12. Repeat associated non-ATG translation initiation: one DNA, two transcripts, seven reading frames, potentially nine toxic entities!

    Directory of Open Access Journals (Sweden)

    Christopher E Pearson

    2011-03-01

    Full Text Available Diseases associated with unstable repetitive elements in the DNA, RNA, and amino acids have consistently revealed scientific surprises. Most diseases are caused by expansions of trinucleotide repeats, which ultimately lead to diseases like Huntington's disease, myotonic dystrophy, fragile X syndrome, and a series of spinocerebellar ataxias. These repeat mutations are dynamic, changing through generations and within an individual, and the repeats can be bi-directionally transcribed. Unsuspected modes of pathogenesis involve aberrant loss of protein expression; aberrant over-expression of non-mutant proteins; toxic-gain-of-protein function through expanded polyglutamine tracts that are encoded by expanded CAG tracts; and RNA-toxic-gain-of-function caused by transcripts harboring expanded CUG, CAG, or CGG tracts. A recent advance reveals that RNA transcripts with expanded CAG repeats can be translated in the complete absence of a starting ATG, and this Repeat Associated Non-ATG translation (RAN-translation occurs across expanded CAG repeats in all reading frames (CAG, AGC, and GCA to produce homopolymeric proteins of long polyglutamine, polyserine, and polyalanine tracts. Expanded CTG tracts expressing CUG transcripts also show RAN-translation occurring in all three frames (CUG, UGC, and GCU, to produce polyleucine, polycysteine, and polyalanine. These RAN-translation products can be toxic. Thus, one unstable (CAG•(CTG DNA can produce two expanded repeat transcripts and homopolymeric proteins with reading frames (the AUG-directed polyGln and six RAN-translation proteins, yielding a total of potentially nine toxic entities. The occurrence of RAN-translation in patient tissues expands our horizons of modes of disease pathogenesis. Moreover, since RAN-translation counters the canonical requirements of translation initiation, many new questions are now posed that must be addressed. This review covers RAN-translation and some of the pertinent

  13. ProtRepeatsDB: a database of amino acid repeats in genomes

    Directory of Open Access Journals (Sweden)

    Chauhan Virander S

    2006-07-01

    Full Text Available Abstract Background Genome wide and cross species comparisons of amino acid repeats is an intriguing problem in biology mainly due to the highly polymorphic nature and diverse functions of amino acid repeats. Innate protein repeats constitute vital functional and structural regions in proteins. Repeats are of great consequence in evolution of proteins, as evident from analysis of repeats in different organisms. In the post genomic era, availability of protein sequences encoded in different genomes provides a unique opportunity to perform large scale comparative studies of amino acid repeats. ProtRepeatsDB http://bioinfo.icgeb.res.in/repeats/ is a relational database of perfect and mismatch repeats, access to which is designed as a resource and collection of tools for detection and cross species comparisons of different types of amino acid repeats. Description ProtRepeatsDB (v1.2 consists of perfect as well as mismatch amino acid repeats in the protein sequences of 141 organisms, the genomes of which are now available. The web interface of ProtRepeatsDB consists of different tools to perform repeat s; based on protein IDs, organism name, repeat sequences, and keywords as in FASTA headers, size, frequency, gene ontology (GO annotation IDs and regular expressions (REGEXP describing repeats. These tools also allow formulation of a variety of simple, complex and logical queries to facilitate mining and large-scale cross-species comparisons of amino acid repeats. In addition to this, the database also contains sequence analysis tools to determine repeats in user input sequences. Conclusion ProtRepeatsDB is a multi-organism database of different types of amino acid repeats present in proteins. It integrates useful tools to perform genome wide queries for rapid screening and identification of amino acid repeats and facilitates comparative and evolutionary studies of the repeats. The database is useful for identification of species or organism specific

  14. Association of Helicobacter pylori cagA Gene with Gastric Cancer and Peptic Ulcer in Saudi Patients.

    Science.gov (United States)

    Saber, Taisir; Ghonaim, Mabrouk M; Yousef, Amany R; Khalifa, Amany; Al Qurashi, Hesham; Shaqhan, Mohammad; Samaha, Mohammad

    2015-07-01

    This study was conducted to assess the relationship between occurrence of gastric cancer and peptic ulcer, and the presence of H. pylori cagA gene and anti-CagA IgG, and to estimate the value of these antibodies in detecting infection by cagA gene-positive H. pylori strains in Saudi patients. The study included 180 patients who were subjected to upper gastrointestinal endoscopy in Taif province and Western region of Saudi Arabia (60 gastric cancer, 60 peptic ulcer, and 60 with non-ulcer dyspepsia). Gastric biopsy specimens were obtained and tested for H. pylori infection by rapid urease test and culture. PCR was performed on the isolated strains and biopsy specimens for detection of the cagA gene. Blood samples were collected and tested for CagA IgG by ELISA. H. pylori infection was detected among 72.8% of patients. The cagA gene and anti-CagA IgG were found in 63.4% and 61.8% of H. pylori-infected patients, respectively. They were significantly (p ulcer compared with those with non-ulcer dyspepsia. Detection of the CagA IgG was 91.6% sensitive, 89.6% specific, and 90.8% accurate compared with detection of the cagA gene. Its positive and negative predictive values were 93.8% and 86%, respectively. The study showed a significant association between the presence of the cagA gene and gastric cancer and peptic ulcer disease, and between anti-CagA IgG and the cagA gene in Saudi patients. However, a further larger study is required to confirm this finding.

  15. cagE as a biomarker of the pathogenicity of Helicobacter pylori

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    Ivy Bastos Ramis

    2013-04-01

    Full Text Available Introduction Helicobacter pylori infection is associated with gastro-duodenal diseases. Genes related to pathogenicity have been described for H. pylori and some of them appear to be associated with more severe clinical outcomes of the infection. The present study investigates the role of cagE as a pathogenicity biomarker of H. pylori compare it to cagA, vacA, iceA and babA2 genes and correlate with endoscopic diagnoses. Methods Were collected biopsy samples of 144 dyspeptic patients at the Hospital of the Federal University of Rio Grande, Rio Grande do Sul, Brazil. After collection, the samples were sent for histological examination, DNA extraction and detection of all putative pathogenicity genes by PCR. Results Of the 144 patients undergoing endoscopy, 57 (39.6% presented H. pylori by histological examination and PCR by detection of the ureA gene. Based on the endoscopic diagnoses, 45.6% (26/57 of the patients had erosive gastritis, while 54.4% (31/57 had enanthematous gastritis. The genes cagA, cagE, vacAs1/m1, vacAs1/m2 and iceA1 were related to erosive gastritis, while the genes vacAs2/m2, iceA2 and babA2 were associated to enanthematous gastritis. We found a statistically significant association between the presence of cagE and the endoscopic diagnosis. However, we detect no statistically significant association between the endoscopic diagnosis and the presence of cagA, vacA, iceA and babA2, although a biological association has been suggested. Conclusions Thus, cagE could be a risk biomarker for gastric lesions and may contribute to a better evaluation of the H. pylori pathogenic potential and to the prognosis of infection evolution in the gastric mucosa.

  16. Helicobacter pylori cagA and vacA genotypes in Cuban and Venezuelan populations

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    Diana Ortiz-Princz

    2010-05-01

    Full Text Available The aim of this study was to determine the presence of Helicobacter pylori cytotoxin-associated gene (cagA/vacuolating cytotoxin gene (vacA among patients with chronic gastritis in Cuba and Venezuela. Gastric antrum biopsies were taken for culture, DNA extraction and PCR analysis. Amplification of vacA and cagA segments was performed using two regions of cagA: 349 bp were amplified with the F1/B1 primers and the remaining 335 bp were amplified with the B7629/B7628 primers. The VA1-F/VA1-R set of primers was used to amplify the 259-bp (s1 or 286-bp (s2 product and the VAG-R/VAG-F set of primers was used to amplify the 567-bp (m1 or 642-bp (m2 regions of vacA. cagA was detected in 87% of the antral samples from Cuban patients and 80.3% of those from Venezuelan patients. All possible combinations of vacA regions were found, with the exception of s2/m1. The predominant combination found in both countries was s1/m1. The percentage of cagA+ strains was increased by the use of a second set of primers and a greater number of strains was amplified with the B7629/B7628 primers in the Cuban patients (p = 0.0001. There was no significant difference between the presence of the allelic variants of vacA and cagA in both populations. The predominant genotype was cagA+/s1m1 in both countries. The results support the necessary investigation of isolates circulating among the human population in each region.

  17. Prevalence of helicobacter pylori CagE genotypes, in patients with non-ulcer dyspepsia,

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    M.R. Haghshenas

    2008-01-01

    Full Text Available Prevalence of helicobacter pylori CagE genotypes, in patients with non-ulcer dyspepsia, peptic ulcer and gastric carcinomaM.H. Shirazi, M.R. Pourmand ,M.R. Haghshenas, V.A. Rezaee, AbstractBackground and Purpose: Helicobacter pylori are a bacterial pathogen evolved to chronically colonize the gastric epithelium and causes gastritis, peptic ulcers, and even gastric malignancies in few infected humans. More recently, a pathogenicity island has been identified within the H. pylori genome that contains a cluster of genes, including cagE. The aim of the current study was to investigate the prevalence of cagE genotypes of H. pylori isolates from patients with NUD(Non Ulcer Dyspepsia, peptic ulcer and cancer.Materials and Methods: 150 Gastric biopsy specimens obtained from patients were inoculated onto a Brucella Columbia Agar containing 5% sheep for 3 to 5 days at 37°C under micro aerobic conditions (5% O2, 5% CO2, and 90% N2. After DNA extraction, genotyping of the cagE gene was performed by PCR amplification using the primers. PCR products were separated by 1% agarose gel electrophoresis and examined under UV illumination.Results: Of 92 positive cultures, 34, 28, 20, and 10 isolations were obtained from patients with NUD, duodenal ulcers (DU, gastric ulcers (GU and gastric cancer (GC, respectively. The frequency of cagE gene was 88/24%, 100% , 85% , 100% and within isolates of patients with NUD, DU, GU and GC, respectively.Conclusion: The presence of cagE in patients with Helicobacter pylori infection is not a marker for predicting or diagnosing the resultant diseases.Key words: Helicobacter pylori, CagE, NUD, CancerJ Mazand Univ Med Sci 2008; 18(64: 37-43 (Persian

  18. 四川省夹江县人群18个STR位点的遗传多态性%Genetic Polymorphism of 18 Short Tandem Repeat Loci in Jiajiang County of Sichuan Province

    Institute of Scientific and Technical Information of China (English)

    王乐; 赵兴春; 张建; 陈婷; 王邦义; 白雪; 叶健

    2015-01-01

    loci showed the heterozygosity ≥ 0.633,the matching probability ≥ 0.018,the discrimination power ≥ 0.790,the polymorphic information content ≥ 0.56,the probability of paternity exclusion ≥ 0.332,and the typical paternity index ≥ 1.36.Conclusion:This work studied the genetic polymorphism of 18 short tandem repeat loci in Jiajiang county of Sichuan province providing pronounced basic data for subsequent human population genetic and forensic DNA research work.The cumulative matching probability of the DNATyperTM1 9 kit reaches 3.477 × 10-22,while its cumulative excluding probability of paternity is 0.999999974.

  19. Interleukin-1 and TNF-α polymorphisms and Helicobacter pylori in a Brazilian Amazon population

    Institute of Scientific and Technical Information of China (English)

    Hivana Patricia Melo Barbosa; Luisa Caricio Martins; Sidney Emanuel Batista dos Santos; Samia Demachki; Monica Baraúna Assumpcao; Charliana Damasceno Aragao; Tereza Cristina de Oliveira Corvelo

    2009-01-01

    AIM:To study the association between Interleukin-1 (IL-1) and tumor necrosis factor (TNF)-α polymorphisms, infection by Helicobacter pylori ( H pylori) and the development of gastrointestinal diseases. METHODS:Genomic DNA was ext racted f rom the peripheral blood of 177 patients with various gastrointestinal diseases and from 100 healthy volunteers. The polymorphisms in IL-1β and TNF-α genes were analyzed using the polymerase chain reactionrestriction fragment length polymorphism method PCRRFLP) and those from IL-1RN with PCR. The presence of infection due to H pylori and the presence of the CagA toxin were detected by serology. The histopathological parameters in the gastric biopsies of the patients were according to the Sydney classification. RESULTS:A comparison of the frequencies of the different polymorphisms studied among the patients and the control group demonstrated that the allele IL- 1RN*2 was more frequent among patients with gastric ulcers and adenocarcinoma. Carriers of the allele ILRN* 2 and those with reactive serology for anti-CagA IgG had a greater risk of developing peptic ulcer and gastric adenocarcinoma, as well as a higher degree of inflammation and neutrophilic activity in the gastric mucosa. CONCLUSION:Our results indicate a positive association between IL-1RN gene polymorphism and infection by positive H pylori CagA strains and the development of gastric ulcers and adenocarcinoma.

  20. 中国人诱导型一氧化氮合酶基因STR多态性研究%A Short Tandem Repeat Polymorphism in the Inducible Nitric Oxide Synthase Gene in Chinese Population

    Institute of Scientific and Technical Information of China (English)

    吕星; 路萍; 邢瑞云; 孙琪云; 邱泽武; 韩莉; 周绪斌; 郑晓飞

    2002-01-01

    一氧化氮(nitric oxide, NO)作为一种可在细胞间自由扩散的信使分子在神经递质传递和血管舒张调节等生理与病理过程中起重要作用.NO通过一氧化氮合酶(nitric oxide synthase, NOS)催化L-精氨酸的氧化反应而生成.目前在哺乳动物中已发现细胞来源、表达方式和活性调节不同的3种NOS同工酶,分别为神经原型NOS(neuronal NOS, nNOS)、诱导型NOS(inducible NOS, iNOS)和内皮细胞型NOS(endothelial NOS, eNOS).3种NOS由位于不同染色体上的基因所编码.人iNOS基因位于第17号染色体长臂(17q11.2~17q12),全长约37kb,含有26个外显子.iNOS可在多种类型的细胞中通过IL-1、IFN-α、TNF-γ等细胞因子和其他介质的刺激作用而诱导表达.iNOS基因5′-端调控区内存在一个CCTTT串联重复的多态性位点,这一多态性基因座已在北爱尔兰的糖尿病患者中证实与微血管病变有关.另有实验表明,CCTTT串联重复序列的变化对iNOS基因的转录将产生不同影响.目前在东方种族中有关iNOS基因CCTTT串联重复多态性尚未见报道.将303名中国汉族人基因组DNA用于iNOS基因CCTTT串联重复多态性分析,鉴定出了12种等位基因和49种基因型,其中重复17次、18次和19次的等位基因是在人类中首次发现的新等位基因.统计学检验和比较表明,中国汉族人iNOS基因CCTTT串联重复序列的6个等位基因频率与来自英格兰的高加索人差异显著,说明这一多态性位点的等位基因频率分布存在种族差异.在中国正常人群中获得的有关iNOS基因STR多态性的统计资料,对于进一步研究这一多态性基因座与心脑血管疾病的相关性将有重要应用价值.%Polymorphism of the (CCTTT)n repeat, a short tandem repeats (STR) located in promoter region of the inducible nitric oxide synthase (iNOS) gene, was analyzed in a total of 316 Chinese healthy subjects. Twelve alleles and forty-nine genotypes were identified

  1. Intergeneration CAG expansion in a Wuhan juvenile-onset Huntingto ndisease family%武汉地区CAG扩增突变致青少年发病的亨廷顿舞蹈病的家系分析

    Institute of Scientific and Technical Information of China (English)

    刘媛; 沈滟; 李和; 王慧; 杨真荣; 陈燕; 唐艳平

    2007-01-01

    目的 对青少年发病的亨廷顿舞蹈病(Huntington disease)家系进行致病IT15基因早期诊断分析,为家系成员提供遗传咨询,并为后续的HD发病机制及实验治疗研究提供依据.方法 按照知情同意原则抽取家系成员外周血,提取基因组DNA,采用改良的降落PCR方法扩增IT15基因致病区域,DNA测序检测异常等位基因(CAG)n三核苷酸重复次数.结果 在该家系三代25名成员中,共发现8名致病IT15基因携带者,其中,Ⅲ10、Ⅲ12、Ⅲ14、Ⅳ3和Ⅴ2 CAG三核苷酸的拷贝数均为48,Ⅳ11和Ⅳ12均为(CAG)67,Ⅳ14为(CAG)63,而对照组35名正常人的CAG三核苷酸的拷贝数为8-25,两者之间没有重叠.结论 家系中第四代致病基因携带者Ⅳ14与第三代患者Ⅲ10比较,CAG三核苷酸重复次数增加15次,即本家系IT15基因在传递过程中发生了扩增突变.同时,扩增突变导致该家系出现青少年发病及遗传早现现象.%Objective To make early diagnosis of IT15 gene mutation in a Wuhan juvenile-onset Huntington disease (HD)family, for providing them with genetic counseling, and making preparation for the further research on pathogenesis and experimental therapy of HD. Methods According to the principle of informed consent, we extracted genomic DNA from peripheral blood samples and carried genetic diagnosis of pathogenic exon 1 of IT15 gene by modified touchdown PCR and DNA sequencing methods. Results Eight of twenty-five family members carried abnormal allele: Ⅲ10, Ⅲ12, Ⅲ14, Ⅳ3,and Ⅴ2 carried (CAG) 48, Ⅳ11 and Ⅳ12 carried (CAG) 67, and Ⅳ14 carried (CAG) 63, in contrast with the 8-25 CAG trinucleotides in the members of control group. Ⅳ14 carried 15 more CAG trinucleotides than her father Ⅲ10. Conclusion The results definitely confirm the diagnosis of HD and indicate the CAG trinucleotide repeat expansion of IT15 gene in this HD family.In addition, CAG expansion results in juvenile-onset and anticipation (characterized

  2. Spinocerebellar ataxia type 2 (SCA2) in an Egyptian family presenting with polyphagia and marked CAG expansion in infancy.

    Science.gov (United States)

    Abdel-Aleem, Alice; Zaki, Maha S

    2008-03-01

    We describe an Egyptian family having SCA2 affecting three generations with marked molecular and clinical anticipation observed in the index case. Our proband was a male child starting as early as 2 years old with progressive extrapyramidal manifestations, slow eye movements and cognitive impairment. A history of nonspecific mild developmental delay was recorded. The patient lost all cognitive functions, had persistent dystonic posture, trophic changes, vasomotor instability, dysphagia and died at the age of 7 years. The age at presentation among other affected family members varied between 11 and 45 years old across three generations. The early common neurological symptoms were choreoathetotic movements, myoclonic jerk, gait difficulty, expressionless face and emotional liability. Later, overt ataxia, incoordination, dysarthria, mild dementia and slow eye saccades predominated. Brisk tendon reflexes were detected in three cases. Peripheral nerve affection was a late manifestation. Interestingly, polyphagia and obesity were striking manifestations in the middle stage of the disease; an observation that might support a previously suggested relation between the ataxin-2 gene and body weight. The proband showed an amplified allele with marked CAG expansion in the form of a smear sized 69-75 repeats resulted from maternal transmission. To our knowledge, our index case is the second report in the literature presenting with infantile onset SCA2 and intermediate repeat expansion. This family expands the phenotypic spectrum of early onset SCA2 and points out the importance of considering SCA2 gene analysis in children with progressive neurological impairment and abnormal movements with or without polyphagia. PMID:18297329

  3. Synthesis and characterization of Fe 3 O 4 @C@Ag nanocomposites and their antibacterial performance

    Science.gov (United States)

    Xia, Haiqing; Cui, Bin; Zhou, Junhong; Zhang, Lulu; Zhang, Ji; Guo, Xiaohui; Guo, Huilin

    2011-09-01

    We synthesized Fe 3O 4@C@Ag nanocomposites through a combination of solvothermal, hydrothermal, and chemical redox reactions. Characterization of the resulting samples by X-ray diffraction, Fourier-transform infrared spectroscopy, field-emission scanning and transmission electron microscopy, and magnetic measurement is reported. Compared to Fe 3O 4@Ag nanocomposites, the Fe 3O 4@C@Ag nanocomposites showed enhanced antibacterial activity. The Fe 3O 4@C@Ag nanocomposites were able to almost entirely prevent growth of Escherichia coli when the concentration of Ag nanoparticles was 10 μg/mL. Antibacterial activity of the Fe 3O 4@C@Ag nanocomposites was maintained for more than 40 h at 37 °C. The intermediate carbon layer not only protects magnetic core, but also improves the dispersion and antibacterial activity of the silver nanoparticles. The magnetic core can be used to control the specific location of the antibacterial agent (via external magnetic field) and to recycle the residual silver nanoparticles. The Fe 3O 4@C@Ag nanocomposites will have potential uses in many fields as catalysts, absorbents, and bifunctional magnetic-optical materials.

  4. ABO blood groups and Helicobacter pylori cagA infection: evidence of an association

    Directory of Open Access Journals (Sweden)

    DE Mattos

    2010-01-01

    Full Text Available Diseases resulting from Helicobacter pylori infection appear to be dependent on a host of genetic traits and virulence factors possessed by this microorganism. This paper aimed to investigate the association between the ABO histo-blood groups and H. pylori cagA infections. Genomic DNA samples (n = 110 of gastric biopsies obtained from patients with endoscopic diagnosis of peptic ulcers (n = 25 and chronic active gastritis (n = 85 were analyzed by PCR using specific primers for the cagA gene. Of the samples, 66.4% (n = 73 tested positive and 33.6% (n = 37 negative for the gene. The cagA strain was predominant in peptic ulcers (n = 21; 84.0% compared with chronic active gastritis (n = 52; 61.2% (p = 0.05; OR 3.332; 95% CI: 1.050-10.576. Additionally, the cagA strain was prevalent in the type O blood (48/63; 76.2% compared with other ABO phenotypes (25/47; 53.2% (p = 0.01; OR 2.816; 95% CI: 1.246-6.364. These results suggest that H. pylori cagA infection is associated with the O blood group in Brazilian patients suffering from chronic active gastritis and peptic ulcers.

  5. A Semiparametric Bayesian Model for Repeatedly Repeated Binary Outcomes

    OpenAIRE

    Quintana, Fernando A.; Müller, Peter; Rosner, Gary L.; Mary V Relling

    2008-01-01

    We discuss the analysis of data from single nucleotide polymorphism (SNP) arrays comparing tumor and normal tissues. The data consist of sequences of indicators for loss of heterozygosity (LOH) and involve three nested levels of repetition: chromosomes for a given patient, regions within chromosomes, and SNPs nested within regions. We propose to analyze these data using a semiparametric model for multi-level repeated binary data. At the top level of the hierarchy we assume a sampling model fo...

  6. 幽门螺杆菌VacA和CagA的研究进展

    Institute of Scientific and Technical Information of China (English)

    龙敏; 别平华; 俞守义; 凌贤龙; 房殿春

    2001-01-01

    幽门螺杆菌(Hp)感染呈全球性分布,多数地区感染达50%,细胞空泡毒素(VacA)及细胞毒相关蛋白(CagA)在Hp致病过程中起重要作用.不同Hp菌株的VacA和CagA存在基因型和表型的差异.研究Hp的vacA和cagA基因及其产物对于进一步阐明与临床的关系、Hp感染疾病的防治都有十分重要的意义.

  7. Helicobacter pylori cag-Pathogenicity island-dependent early immunological response triggers later precancerous gastric changes in Mongolian gerbils.

    Directory of Open Access Journals (Sweden)

    Tobias Wiedemann

    Full Text Available Infection with Helicobacter pylori, carrying a functional cag type IV secretion system (cag-T4SS to inject the Cytotoxin associated antigen (CagA into gastric cells, is associated with an increased risk for severe gastric diseases in humans. Here we studied the pathomechanism of H. pylori and the role of the cag-pathogenicity island (cag-PAI for the induction of gastric ulcer and precancerous conditions over time (2-64 weeks using the Mongolian gerbil model. Animals were challenged with H. pylori B128 (WT, or an isogenic B128DeltacagY mutant-strain that produces CagA, but is unable to translocate it into gastric cells. H. pylori colonization density was quantified in antrum and corpus mucosa separately. Paraffin sections were graded for inflammation and histological changes verified by immunohistochemistry. Physiological and inflammatory markers were quantitated by RIA and RT-PCR, respectively. An early cag-T4SS-dependent inflammation of the corpus mucosa (4-8 weeks occurred only in WT-infected animals, resulting in a severe active and chronic gastritis with a significant increase of proinflammatory cytokines, mucous gland metaplasia, and atrophy of the parietal cells. At late time points only WT-infected animals developed hypochlorhydria and hypergastrinemia in parallel to gastric ulcers, gastritis cystica profunda, and focal dysplasia. The early cag-PAI-dependent immunological response triggers later physiological and histopathological alterations towards gastric malignancies.

  8. 反复胚胎种植失败患者HLA-Cw基因多态性的研究%Study on polymorphism of HLA-Cw in patients with repeated implantation failure

    Institute of Scientific and Technical Information of China (English)

    王丽娟; 梁佩燕; 吴彤华; 李观贵; 陈晓燕; 尹彪; 曾勇

    2013-01-01

    目的 初探HLA-Cw基因多态性与反复胚胎种植失败的关系.方法 采用聚合酶链反应-直接碱基序列分析基因分型技术的方法对研究组50例反复胚胎种植失败患者和对照组17例一次体外受精-胚胎移植即获得妊娠并分娩活婴的患者进行HLA-Cw基因多态性检测,并采用SPSS17.0软件进行分析.结果 (1)在HLA-Cw01、HLA-Cw03、HLA-Cw07基因位点中,研究组和对照组均有较高的频率;(2)研究组HLA-Cw06基因频率较对照组高,HLA-Cw07基因频率低于对照组;(3)研究组和对照组的HLA-Cwasn频率远高于HLA-Cwlys;(4)研究组的HLA-Cwasn频率略低于对照组,HLA-Cwlys频率略高于对照组;(5)研究组夫妇双方均未检出HLA-Cwlys等位基因的比例较对照组低,而至少一方检出至少一个HLA-Cwlys等位基因的比例则较高.上述各观察指标两组间均无显著性差异(P>0.05).结论 HLA-Cwlys频率在反复胚胎种植失败患者中有增加趋势,虽无显著性差异,但有待扩大样本量进行进一步统计分析.%Objective: To investigate the correlation between the HLA-Cw gene polymorphism and the repeated implantation failure.Methods: Fifty patients with repeated implantation failure(study group)were matched to 17 patients who got pregnancy and had living birth from the first in vitro fertilization embryo transfer cycle (control group) . The genotyping of HLA-Cw gene detected by a polymerase chain reaction-sequence based genotyping(PCR-SBT)method. The data of the two groups was analyzed by the SPSS17. 0 software.Results: The results of both groups showed a high gene frequency in HLA-Cw * 01, HLA-Cw * 03 and HLA-Cw * 07. The gene frequency of HLA-Cw * 06 in the study group was higher than that in the control group. The gene frequency of HLA-Cw * 07 in the study group was lower than that in the control group. In both groups,their HLA-Cw asn frequency was much higher than HLA-Cw lys frequency. The study group had less HLA-Cw asn gene frequency

  9. L'erbario del Prof. Manlio Chiappini (1924-1998) in Herbarium CAG

    OpenAIRE

    Curreli, Federica; Fogu, Maria Caterina

    2000-01-01

    The herbarium of Chiappini, held in Herbarium CAG of Cagliari University, is presented. Prof. Manlio Chiappini, who dead the 4th of january 1998, teached Botany at the Athenaeum of Cagliari from 1965 to 1987 and from 1965 to 1986 he was director of Botanical Institute and Botanical gardens of Cagliari University. From a research carried out in Herbarium CAG is shown that Chiappini’s herbarium is compound of 1262 exsiccata, referred to 630 specific and subspecific entities (about the 30% of Sa...

  10. CagA and VacA Helicobacter pylori antibodies in gastric cancer

    OpenAIRE

    Suriani, Renzo; Colozza, Maurilio; Cardesi, Enrico; Mazzucco, Dario; Marino, Maria; Grosso, Silvia; Sanseverinati, Sabina; Venturini, Ivo; Borghi, Athos; Zeneroli, Maria Luisa

    2008-01-01

    BACKGROUND: Infection with different genotypes of virulent Helicobacter pylori strains (cytotoxin-associated gene A [CagA]-and/or vacuolating cytotoxin A [VacA]-positive) can play a role in the development of atrophic gastritis, duodenal ulcer (DU) and gastric cancer (GC).OBJECTIVE: To determine whether patients with GC and H pylori-negative histological staining had previously been infected with H pylori CagA- and/or VacA-positive virulent strains.METHODS: Twenty-three GC patients with a mea...

  11. A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

    Directory of Open Access Journals (Sweden)

    Sabine M Hölter

    Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

  12. 西安地区幽门螺杆菌cagA、cagE、vacA基因型与上消化道疾病的关系

    Institute of Scientific and Technical Information of China (English)

    庄坤; 宋瑛; 张玲霞; 张沥; 张欣; 张宁霞; 方雅丽

    2014-01-01

    目的:探讨西安地区就医人群幽门螺杆菌(HP)菌株vacA、cagA、cagE基因型与上消化道疾病的关系。方法:选取胃粘膜活检组织中分离培养到幽门螺杆菌的消化性溃疡58例,慢性胃炎30例,采用标准酚-氯仿抽提法提取 HP基因组DNA ,检测幽门螺杆菌cagA、cagE、vacA在消化性溃疡及慢性胃炎患者胃组织中的表达。结果:88株幽门螺杆菌中cag A 的阳性率为100%, cagE的阳性率为100%,vacA s1/m-的阳性率为17.0%,vacA s1/m1a的阳性率为2.3%,vacA s1/m1a+m1b的阳性率为1.1%,vacA s1/m1a+ m2的阳性率为1.1%,vacA s1/m2的阳性率为55.7%,vacA s1/m1b+m2的阳性率为1.1%,vacA s1/m1b的阳性率为17.0%,vacA s2/m2的阳性率为2.3%。结论:西安地区就医人群培养分离的 H P菌株中,cag A 和cag E阳性率均为100%,与本地区疾病类型和严重程度不相关,不能作为西安地区HP毒力强弱的标志。西安地区就医人群幽门螺杆菌菌株的vacA基因型以s1/m2为主,但vacA各基因亚型均与临床结局无相关性。

  13. 短串联重复序列基因座与冲动暴力行为的关联研究%Association study of the genetic polymorphism of fifteen short tandem repeats loci and aggressive violent behavior

    Institute of Scientific and Technical Information of China (English)

    杨春; 巴华杰; 高志勤; 赵汉清; 余海鹰; 施建安; 过伟

    2012-01-01

    目的 探讨冲动暴力行为与相关短串联重复序列基因座的关联情况.方法 运用AmpFISTR IdentifilerTM荧光标记复合扩增体系,对203例冲动暴力行为罪犯(研究组)与207名非暴力行为健康个体(对照组)样本进行聚合酶链反应复合扩增,然后应用ABI3100型基因分析系统对扩增产物进行电泳和基因检测,观察2组15个STR基因座等位基因及基因型频率的差异.结果 15个STR基因座均符合遗传平衡定律(Hardy-Weinberg定律);研究组与对照组THO1和TPOX基因座的等位基因频率分布的差异有统计学意义(P<0.05);研究组和对照组THO1-10频率分别为0.0172和0.0580,差异有统计学意义(P=0.002,OR=0.29,95% CI:0.12 ~0.67);研究组和对照组TPOX-11频率分别为0.3621和0.2391,差异有统计学意义(P=0.000,OR=1.81,95% CI:1.33 ~ 2.45);其他STR基因座等位基因频率及所有基因型频率2组差异均无统计学意义(P>0.05).结论 THO1和TPOX基因座多态性与冲动暴力行为可能存在关联,等位基因THO1-10、TPOX-11与冲动暴力行为的发生可能有一定关系.%Objective To investigate the association of aggressive violent behavior and related short tandem repeats (STRs) loci by the analysis of 15 STRs loci genetic polymorphism.Methods The biological samples of 203 persons with aggressive violent behaviors and 207 healthy persons without violent behavior were collected.Then the DNA sample was amplified by AmpFISTR IdentifilerTM system and separated by electrophoresis to compare the genotypes and alleles of 15 STRs gene frequencies in the two groups.Results All the 15 STRs loci in people with aggressive violent behavior and healthy people were found to coincide with Hardy-Weinberg equilibrium ( P > 0.05 ).There was a significant difference in distributing of allele frequency of THO1 and TPOX between people with aggressive violent behaviors and healthy people ( P < 0.05 ).The frequency of allele 10 of THO1

  14. Clinical significance of infection with cag A and vac A positive helicobacter pylori strains

    Directory of Open Access Journals (Sweden)

    Sokić-Milutinović Aleksandra

    2004-01-01

    Full Text Available Clinical relevance of infection with different Helicobacter pylori strains was reviewed in this paper. Helicobacter pylori (H. pylori infection plays a role in pathogenesis of chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. Extragastric manifestations of H. pylori infection most probably include acne rosacea and chronic urticaria, while the importance of H. pylori infection for pathogenesis of growth retardation in children, iron deficiency anemia, coronary heart disease, stroke and idiopathic thrombocytopenic purpura remains vague. The expression of two H. pylori proteins, cytotoxin associated protein (cag A and vacuolization cytotoxin (vac A is considered to be related with pathogenicity of the bacterium. It is clear that presence of cag A+ strains is important for development of peptic ulcer; nevertheless, it is also protective against esophageal reflux disease. On the other hand, cag A+ strains are common in gastric adenocarcinoma and MALT lymphoma patients, but it seems that certain subtypes of vac A cytotoxin are more important risk factors. Infection with cag A+ strains is more common in patients with acne rosacea, stroke and coronary heart disease.

  15. CagA and VacA Helicobacter Pylori Antibodies in Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Renzo Suriani

    2008-01-01

    Full Text Available BACKGROUND: Infection with different genotypes of virulent Helicobacter pylori strains (cytotoxin-associated gene A [CagA]-and/or vacuolating cytotoxin A [VacA]-positive can play a role in the development of atrophic gastritis, duodenal ulcer (DU and gastric cancer (GC.

  16. Induction of CD69 expression by cagPAI-positive Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Naoki Mori; Chie Ishikawa; Masachika Senba

    2011-01-01

    AIM: To investigate and elucidate the molecular mech-anism that regulates inducible expression of CD69 by Helicobacter pylori (H. pylori ) infection.METHODS: The expression levels of CD69 in a T-cell line, Jurkat, primary human peripheral blood mononu-clear cells (PBMCs), and CD4+T cells, were assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and flow cytometry. Activation of CD69 promoter was detected by reporter gene. Nuclear factor (NF)-κB activation in Jurkat cells infected with H. pylori was evaluated by electrophoretic mobility shift assay. The role of NF-κB signaling in H. pylori -induced CD69 expression was analyzed using inhibitors of NF-κB and dominant-negative mutants. The isogenic mutants with disrupted cag pathogenicity island ( cagPAI) and virD4 were used to elucidate the role of cagPAI-encoding type Ⅳ secretion system and CagA in CD69 expression.RESULTS: CD69 staining was detected in mucosal lymphocytes and macrophages in specimens of pa-tients with H. pylori -positive gastritis. Although cagPAI-positive H. pylori and an isogenic mutant of virD4 induced CD69 expression, an isogenic mutant of cag-PAI failed to induce this in Jurkat cells. H. pylori also induced CD69 expression in PBMCs and CD4+T cells. The activation of the CD69 promoter by H. pylori was mediated through NF-κB. Transfection of dominant-negative mutants of IκBs, IκB kinases, and NF-κB-inducing kinase inhibited H. pylori -induced CD69 activation. Inhibitors of NF-κB suppressed H. pylori -induced CD69 mRNA expression.CONCLUSION: The results suggest that H. pylori in-duces CD69 expression through the activation of NF-κB. cagPAI might be relevant in the induction of CD69 expression in T cells. CD69 in T cells may play a role in H. pylori -induced gastritis.

  17. A transgenic Drosophila model demonstrates that the Helicobacter pylori CagA protein functions as a eukaryotic Gab adaptor.

    Directory of Open Access Journals (Sweden)

    Crystal M Botham

    2008-05-01

    Full Text Available Infection with the human gastric pathogen Helicobacter pylori is associated with a spectrum of diseases including gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. The cytotoxin-associated gene A (CagA protein of H. pylori, which is translocated into host cells via a type IV secretion system, is a major risk factor for disease development. Experiments in gastric tissue culture cells have shown that once translocated, CagA activates the phosphatase SHP-2, which is a component of receptor tyrosine kinase (RTK pathways whose over-activation is associated with cancer formation. Based on CagA's ability to activate SHP-2, it has been proposed that CagA functions as a prokaryotic mimic of the eukaryotic Grb2-associated binder (Gab adaptor protein, which normally activates SHP-2. We have developed a transgenic Drosophila model to test this hypothesis by investigating whether CagA can function in a well-characterized Gab-dependent process: the specification of photoreceptors cells in the Drosophila eye. We demonstrate that CagA expression is sufficient to rescue photoreceptor development in the absence of the Drosophila Gab homologue, Daughter of Sevenless (DOS. Furthermore, CagA's ability to promote photoreceptor development requires the SHP-2 phosphatase Corkscrew (CSW. These results provide the first demonstration that CagA functions as a Gab protein within the tissue of an organism and provide insight into CagA's oncogenic potential. Since many translocated bacterial proteins target highly conserved eukaryotic cellular processes, such as the RTK signaling pathway, the transgenic Drosophila model should be of general use for testing the in vivo function of bacterial effector proteins and for identifying the host genes through which they function.

  18. Variation in number of cagA EPIYA-C phosphorylation motifs between cultured Helicobacter pylori and biopsy strain DNA

    OpenAIRE

    Karlsson, Anneli; Ryberg, Anna; Nosouhi Dehnoei, Marjan; Borch, Kurt; Monstein, Hans-Jürg

    2012-01-01

    The Helicobacter pylori cagA gene encodes a cytotoxin which is activated by phosphorylation after entering the host epithelial cell. Phosphorylation occurs on specific tyrosine residues within EPIYA motifs in the variable 3'-region. Four different cagA EPIYA motifs have been defined according to the surrounding amino acid sequence; EPIYA-A, -B, -C and -D. Commonly, EPIYA-A and -B are followed by one or more EPIYA-C or -D motif. Due to observed discrepancies in cagA genotypes in cultured H. py...

  19. The repetitive sequence genotype research of Helicobacter pylori with VacA+ or CagA+%VacA+和CagA+的幽门螺杆菌重复序列基因分型研究

    Institute of Scientific and Technical Information of China (English)

    李晓华; 黄赞松; 黄衍强; 周喜汉; 韦鹏涯; 岑朝; 黄小凤

    2013-01-01

    Objective To investigate the correlation between Helicobacter pylori ( Hp ) with VacA + or CagA + and repetitive sequence genotype. Methods The amplification of VacA and CagA gene fragments were conducted with PCR. Strains were genotyped with REP - PCR and further clustered with NTsys_2 software. Results The 26 VacA and CagA gene positive strains were divided into six genotype groups according to homology, both with 3,3,8,4,6,2 strains in each Hp group, respectively. Conclusion The VacA and CagA positive strains could be divided into six genotype groups, and the repetitive sequence genotype is not associated with VacA and CagA gene.%目的 探索VacA+和CagA+与幽门螺杆菌(Hp)重复序列基因分型的关系.方法 采用PCR方法确定VacA+或CagA+ Hp菌株,重复序列基因分型方法分别对26株VacA+和CagA+的菌株进行基因分型,并运用NTsys_2软件,根据相似性78%进行聚类分型.结果 VacA+和CagA+的26株Hp均被分为6个基因型,分别是Group Ⅰ、Group Ⅱ、Group Ⅲ、Group Ⅳ、Group Ⅴ和Group Ⅵ,且每类聚集的菌株数相同,分别是3、3、8、4、6、2株.结论 VacA+和CagA+的Hp可以分成6大类基因型,VacA+和CagA+与Hp重复序列基因分型无密切关系.

  20. Differentiation of Strains of Xylella fastidiosa by a Variable Number of Tandem Repeat Analysis

    OpenAIRE

    Coletta-Filho, Helvécio Della; Takita, Marco Aurélio; de Souza, Alessandra Alves; Aguilar-Vildoso, Carlos Ivan; Machado, Marcos Antonio

    2001-01-01

    Short sequence repeats (SSRs) with a potential variable number of tandem repeat (VNTR) loci were identified in the genome of the citrus pathogen Xylella fastidiosa and used for typing studies. Although mono- and dinucleotide repeats were absent, we found several intermediate-length 7-, 8-, and 9-nucleotide repeats, which we examined for allelic polymorphisms using PCR. Five genuine VNTR loci were highly polymorphic within a set of 27 X. fastidiosa strains from different hosts. The highest ave...

  1. Relationship between idiopathic thrombocytopenic purpura and helicobacter pylori CagA protein in adults%成人特发性血小板减少性紫癜与幽门螺杆菌CagA蛋白的关系

    Institute of Scientific and Technical Information of China (English)

    张晋琳; 李慧; 王晓冬; 王春森; 吴良华

    2011-01-01

    目的了解成人特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)与幽门螺杆菌(helicobacter pylori,Hp)CagA蛋白的关系.方法 采用14C尿素呼吸试验对正常成人和ITP患者进行Hp检测后,对Hp阳性的ITP患者进行CagA蛋白抗体检测.依据急性ITP,慢性ITP,难治性ITP对ITP患者进行分类.结果 223例正常患者中123例Hp阳性,感染率为55.2%,而CagA蛋白抗体阳性为42例,占34.1%.278例ITP患者中Hp阳性176例,感染率63.3%,其中CagA蛋白抗体阳性83例,占47.2%,ITP患者的Hp感染率与正常人相似,但CagA蛋白抗体阳性率显著高于正常人(P0.05).结论 纳入研究的ITP患者的Hp感染率与正常人相似,但CagA蛋白抗体阳性率明显高于正常人,提示CagA蛋白在成人ITP的发生发展中具有一定作用.进一步分析也显示不同类型的ITP患者Hp感染率及CagA蛋白阳性率差异无统计学意义.

  2. 淮南地区学生幽门螺杆菌vacA和cagA基因分布特征%Distribution Characteristics of vacA and cagA from Helicobacter Pylori Among Students in Huainan

    Institute of Scientific and Technical Information of China (English)

    汪雪峰; 崔玉宝; 王克霞; 陈琳; 吴静; 胡友莹

    2006-01-01

    目的研究淮南地区学生幽门螺杆菌(Helicobacter pylori,H.pylori)cagA和vacA基因分布特征,为防治工作提供理论依据.方法对74例有消化道症状,年龄在7~24岁的在校学生进行胃镜检查,并在胃窦部取活检粘膜作H.pylori的分离培养,利用聚合酶链反应技术(PCR)测定分离培养出的H.pylori菌株的cagA和vacA基因并进行分型.结果74例学生中,分离培养出H.pylori菌株24例,基因测定结果显示,24株H.pylori临床分离株中,94.7%(23/24)含vacA基因,70.8%(17/24)含cagA基因;其中慢性胃炎vacA和cagA基因检出率分别为94.7%(18/19),70.6%(12/17);2例胃溃疡及3例十二指肠球部溃疡均全部为vacA和cagA阳性;进一步分型发现89.5%(17/19)的慢性胃炎为vacA+和cagA+,而5例溃疡患者均为vacA+和cagA+.结论淮南地区学生H.pylori感染多为vacA+和cagA+菌株,应充分重视H.pylori毒力因子的监测.

  3. Short QTc Interval in Males with Klinefelter Syndrome-Influence of CAG Repeat Length, Body Composition, and Testosterone Replacement Therapy

    DEFF Research Database (Denmark)

    Jørgensen, Inger Norlyk; Skakkebaek, Anne; Andersen, Niels Holmark;

    2015-01-01

    BackgroundKlinefelter syndrome (KS) is a sex chromosomal aneuploidy (47,XXY) affecting 1/660 males. Based on findings in Turner syndrome, we hypothesized that electrocardiogram (ECG) abnormalities would be present in males with KS. ObjectiveTo investigate ECGs in males with KS and compare...... teach-the-tangent method excluding the U-wave. QTc was calculated using Bazett's equation, Hodges' equation, and a linear regression model. Body mass index, abdominal fat, and muscle mass as well as sex hormone levels were secondary parameters. The prevalence of mutations in genes related to short QT...... interval comparable to controls. No mutations in genes related to short QT syndrome were found. ConclusionWe found short QTc interval in males with KS, with further shortening of the QTc interval by T. These results suggest that genes on the X chromosome could be involved in regulation of the QTc interval...

  4. Androgen receptor gene CAG repeat length as modifier of the association between Persistent Organohalogen Pollutant exposure markers and semen characteristics

    DEFF Research Database (Denmark)

    Giwercman, Aleksander; Rylander, Lars; Rignell-Hydbom, Anna;

    2007-01-01

    OBJECTIVES: Exposure to persistent organohalogen pollutants was suggested to impair male reproductive function. A gene-environment interaction has been proposed. No genes modifying the effect of persistent organohalogen pollutants on reproductive organs have yet been identified. We aimed to inves...

  5. HA novel approach to investigate tissue-specific trinucleotide repeat instability

    Directory of Open Access Journals (Sweden)

    Boily Marie-Josee

    2010-03-01

    Full Text Available Abstract Background In Huntington's disease (HD, an expanded CAG repeat produces characteristic striatal neurodegeneration. Interestingly, the HD CAG repeat, whose length determines age at onset, undergoes tissue-specific somatic instability, predominant in the striatum, suggesting that tissue-specific CAG length changes could modify the disease process. Therefore, understanding the mechanisms underlying the tissue specificity of somatic instability may provide novel routes to therapies. However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors. Results Here we describe a novel approach to gain insight into the factors responsible for the tissue specificity of somatic instability. Using accurate genetic knock-in mouse models of HD, we developed a reliable, high-throughput method to quantify tissue HD CAG repeat instability and integrated this with genome-wide bioinformatic approaches. Using tissue instability quantified in 16 tissues as a phenotype and tissue microarray gene expression as a predictor, we built a mathematical model and identified a gene expression signature that accurately predicted tissue instability. Using the predictive ability of this signature we found that somatic instability was not a consequence of pathogenesis. In support of this, genetic crosses with models of accelerated neuropathology failed to induce somatic instability. In addition, we searched for genes and pathways that correlated with tissue instability. We found that expression levels of DNA repair genes did not explain the tissue specificity of somatic instability. Instead, our data implicate other pathways, particularly cell cycle, metabolism and neurotransmitter pathways, acting in combination to generate tissue-specific patterns of instability. Conclusion Our study clearly demonstrates that multiple tissue factors reflect the level of

  6. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    This paper takes polymorphism to the multi-object level. Traditional inheritance, polymorphism, and late binding interact nicely to provide both flexibility and safety — when a method is invoked on an object via a polymorphic reference, late binding ensures that we get the appropriate...... implementation of that method for the actual object. We are granted the flexibility of using different kinds of objects and different method implementations, and we are guaranteed the safety of the combination. Nested classes, polymorphism, and late binding of nested classes interact similarly to provide both...... safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...

  7. CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Shu-Kui Wang; Hui-Fang Zhu; Bang-Shun He; Zhen-Yu Zhang; Zhi-Tan Chen; Zi-Zheng Wang; Guan-Ling Wu

    2007-01-01

    AIM: To characterize the immune responses including local and systemic immunity induced by infection with H pylori, especially with CagA+ H pylori strains and the underlying immunopathogenesis.METHODS: A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA), the presence of T helper (Th) cells and regulatory T (Treg)cells in peripheral blood mononuclear cells (PBMCs),expression of plasma cytokines, and RNA and protein expression of IFN-γ and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test, urea [14C]breath test, immunoblotting test, flow cytometry, real time RT-PCR and immunohistochemistry.RESULTS: Of the patients, 629 (88.47%) were infected with H pylori; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains, Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis, while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However,there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection,CONCLUSION: Polarization of Th cell immune responses occurs in patients with CagA+ H pylori infection, which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.

  8. Association between cag-pathogenicity island in Helicobacter pylori isolates from peptic ulcer, gastric carcinoma, and nonulcer dyspepsia subjects with histological changes

    Institute of Scientific and Technical Information of China (English)

    Mahaboob Ali; Aleem A Khan; Santosh K Tiwari; Niyaz Ahmed; L Venkateswar Rao; CM Habibullah

    2005-01-01

    AIM: To investigate the presence of the cay-pathogenicity island and the associated histological damage caused by strains with complete cay-PAI and with partial deletions in correlation to the disease status.METHODS: We analyzed the complete cag-PAI of 174representative Helicobacter pylori (H pylori ) clinical isolates obtained from patients with duodenal ulcer,gastric ulcer, gastric cancer, and non-ulcer dyspepsia using eight different oligonucleotide primers viz cagA1,cagA2, cagAP1, cagAP2, cagE, cagT, LEC-1, LEC-2spanning five different loci of the whole cag-PAI by polymerase chain reaction (PCR).RESULTS: The complete screening of the genes comprising the cag-PAI showed that larger proportions of subjects with gastric ulcer (97.8%) inhabited strains with complete cag-PAI, followed by gastric cancer (85.7%),non-ulcer dyspepsia (7.1%), and duodenal ulcer (6.9%),significant differences were found in the percentagedistribution of the genes in all the clinical groups studied.It was found that strains with complete cag-PAI were able to cause severe histological damage than with the partially deleted ones.CONCLUSION: The cay-PAI is a strong virulent marker in the disease pathogenesis as it is shown that a large number of those infected with strain with complete cag-PAI had one or the other of the irreversible gastric pathologies and interestingly 18.5% of them developed gastric carcinoma. The presence of an intact cayPAI correlates with the development of more severe pathology, and such strains were found more frequently in patients with severe gastroduodenal disease. Partial deletions of the cag-PAI appear to be sufficient to render the organism less pathogenic.

  9. Antibiotic resistance and cagA gene correlation: A looming crisis of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Adnan Khan; Amber Farooqui; Hamid Manzoor; Syed Shakeel Akhtar; Muhammad Saeed Quraishy; Shahana Urooj Kazmi

    2012-01-01

    AIM:To determine antibiotic resistance of Helicobacter pylori (H.pylori) in Pakistan and its correlation with host and pathogen associated factors.METHODS:A total of 178 strains of H.pylori were isolated from gastric biopsies of dyspeptic patients.Susceptibility patterns against first and second-line antibiotics were determined and trends of resistance were analyzed in relation to the sampling period,gastric conditions and cagA gene carriage.The effect of cagA gene on the acquisition of resistance was investigated by mutant selection assay.RESULTS:The observations showed that monoresistant strains were prevalent with rates of 89% for metronidazole,36% for clarithromycin,37% for amoxicillin,18.5% for ofloxacin and 12% for tetracycline.Furthermore,clarithromycin resistance was on the rise from 2005 to 2008 (32% vs 38%,P =0.004) and it is significantly observed in non ulcerative dyspeptic patients compared to gastritis,gastric ulcer and duodenal ulcer cases (53% vs 20%,18% and 19%,P =0.000).On the contrary,metronidazole and ofloxacin resistance were more common in gastritis and gastric ulcer cases.Distribution analysis and frequencies of resistant mutants in vitro correlated with the absence of cagA gene with metronidazole and ofloxacin resistance.CONCLUSION:The study confirms the alarming levels of antibiotic resistance associated with the degree of gastric inflammation and cagA gene carriage in H.pylori strains.

  10. P53 codon 11, 72, and 248 gene polymorphisms in endometriosis

    OpenAIRE

    Hsieh, Yao-Yuan; Lin, Chich-Sheng

    2006-01-01

    Objective: Mutated p53 gene is related to the instability of cell growth and cell cycle progression. We aimed to evaluate the association between endometriosis and p53 codon 11, 72 and 248 gene polymorphisms. Patients and methods: Women were divided into two groups: (1) moderate/severe endometriosis (n=148), and (2) non-endometriosis groups (n=150). P53 gene polymorphisms include codon11 Glu/Gln or Lys (GAG->CAG or AAG), codon 72 Arg/Pro (CGC->CCC), and codon 248 Arg/Thr (CGG->TCG). These gen...

  11. Determination of strains of Helicobacter pylori and of polymorphism in the interleukin-8 gene in patients with stomach cancer

    Directory of Open Access Journals (Sweden)

    Ruth Maria Dias Ferreira Vinagre

    2011-03-01

    Full Text Available CONTEXT: Gastric neoplasia is the second most common cause of death by cancer in the world and H. pylori is classified as a type I human carcinogen by the World Health Organization. However, despite the high prevalence of infection by H. pylori around the world, less than 3% of individuals carrying the bacteria develop gastric neoplasias. Such a fact indicates that evolution towards malignancy may be associated with bacterial factors in the host and the environment. OBJECTIVES: To investigate the association between polymorphism in the region promoting the IL-8 (-251 gene and the H. pylori genotype, based on the vacA alleles and the presence of the cagA gene, using clinical and histopathological data. METHODS: In a prospective study, a total of 102 patients with stomach cancer and 103 healthy volunteers were analysed. Polymorphism in interleukin 8 (-251 was determined by the PCR-restriction fragment length polymorphism reaction and sequencing. PCR was used for genotyping the vacA alleles and the cagA in the bacterial strains PCR. Gastric biopsies were histologically assessed. RESULTS: The H. pylori serology was positive for 101 (99% of all patients analysed, and 98 (97% of them were colonized by only one strain. In patients with monoinfection, 82 (84% of the bacterial strains observed had the s1b/m1 genotype. The cagA gene was detected in 74 (73% of patients infected by H. pylori. The presence of the cagA gene was demonstrated as associated with the presence of the s1b/m1 genotype of the vacA gene (P = 0.002. As for polymorphism in the interleukin 8 (-251 gene we observed that the AA (P = 0.026 and AT (P = 0.005 genotypes were most frequent in the group of patients with gastric adenocarcinoma. By comparing the different types of isolated bacterial strains with the interleukin -8 (-251 and the histopathological data we observed that carriers of the A allele (AT and AA infected by virulent strains (m1s1 cagA+ demonstrated a greater risk of

  12. Triplet repeat DNA structures and human genetic disease: dynamic mutations from dynamic DNA

    Indian Academy of Sciences (India)

    Richard R Sinden; Vladimir N Potaman; Elena A Oussatcheva; Christopher E Pearson; Yuri L Lyubchenko; Luda S Shlyakhtenko

    2002-02-01

    Fourteen genetic neurodegenerative diseases and three fragile sites have been associated with the expansion of (CTG)n•(CAG)n, (CGG)n•(CCG)n, or (GAA)n•(TTC)n repeat tracts. Different models have been proposed for the expansion of triplet repeats, most of which presume the formation of alternative DNA structures in repeat tracts. One of the most likely structures, slipped strand DNA, may stably and reproducibly form within triplet repeat sequences. The propensity to form slipped strand DNA is proportional to the length and homogeneity of the repeat tract. The remarkable stability of slipped strand DNA may, in part, be due to loop-loop interactions facilitated by the sequence complementarity of the loops and the dynamic structure of three-way junctions formed at the loop-outs.

  13. A method for the analysis of 32 X chromosome insertion deletion polymorphisms in a single PCR

    DEFF Research Database (Denmark)

    Pereira, Rui; Pereira, Vania; Gomes, Iva;

    2012-01-01

    Studies of human genetic variation predominantly use short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) but Insertion deletion polymorphisms (Indels) are being increasingly explored. They combine desirable characteristics of other genetic markers, especially the possibility of...

  14. Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates

    Institute of Scientific and Technical Information of China (English)

    Lino E Torres; Karelia Melián; Arlenis Moreno; Jordis Alonso; Carlos A Sabatier; Mayrín Hernández; Ludisleydis Bermúdez; Boris L Rodríguez

    2009-01-01

    AIM: To investigate the prevalence of vacuolating cytotoxin ( vacA), cytotoxin associated gene A ( cagA) and blood adhesion binding antigen ( babA2) genotypes of Helicobacter pylori ( H pylori) isolates from Cuban dyspeptic patients. METHODS: DNA was extracted from H pylori-positive cultures taken from 130 dyspeptic patients. Genotyping was performed by PCR, using specific primers for vacA ( s1, s2, m1, m2), cagA and babA2 genes. Endoscopic observations and histological examinations were used to determine patient pathologies. RESULTS: vacA alleles s1, s2, m1 and m2 were detected in 96 (73.8%), 34 (26.2%), 75 (57.7%) and 52 isolates (40%), respectively, while the cagA gene was detected in 95 isolates (73.2%). One hundred and seven isolates (82.3%) were babA2-positive. A significant correlation was observed between vacAs1m1 and cagA and between vacAs1m1 and babA2 genotypes ( P < 0.001 and P < 0.05, respectively) and between babA2 genotype and cagA status ( P < 0.05); but, no correlation was observed between vacAs1 and babA2 genotypes. Eighty five (65.4%) and 73 (56.2%) strains were type 1 ( vacAs1- cagA-positive) and "triplepositive" ( vacAs1- cagA- babA2-positive), respectively, and their presence was significantly associated with duodenal ulcer ( P < 0.01 and P < 0.001, respectively). CONCLUSION: The distribution of the main virulence factors in the Cuban strains in this study resembled that of the Western-type strains, and the more virulent H pylori isolates were significantly associated with duodenal ulcer, ulcer disease being the worst pathology observed in the group studied.

  15. Helicobacter pylori with stronger intensity of CagA phosphorylation lead to an increased risk of gastric intestinal metaplasia and cancer

    Directory of Open Access Journals (Sweden)

    Cheng Hsiu-Chi

    2011-05-01

    Full Text Available Abstract Background Nearly all Taiwanese H. pylori stains are cagA-genopositive and encode CagA protein. In this study, we evaluated whether different intensity of tyrosine phosphorylated-CagA (p-CagA had an impact on the clinical diseases and histological outcomes in this area. Results We enrolled 469 dyspeptic patients and prospectively obtained the gastric biopsy specimens and the H. pylori isolates. These patients were categorized according to the clinical diseases, such as duodenal ulcer, gastric ulcer, gastric cancer, and gastritis with or without intestinal metaplasia. Their gastric specimens were reviewed by the updated Sydney's system. Furthermore, a total of 146 patients were randomly selected from each clinical category for evaluation of their isolates' p-CagA intensity by in vitro AGS cells co-culture. The p-CagA was sparse in 30 (20.5%, weak in 59 (40.5%, and strong in 57 (39% isolates. The isolates from the patients of gastric cancer or gastritis with intestinal metaplasia had stronger p-CagA intensity than those of gastritis without intestinal metaplasia (p ≤ 0.002. Moreover, the patients infected with isolates with strong or weak p-CagA intensity had a higher risk of gastric intestinal metaplasia (p Conclusions Infection with H. pylori stains with stronger p-CagA intensity may lead to an increased risk of gastric intestinal metaplasia and cancer.

  16. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Man [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Li, Fu-gang [Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China); Xie, Xi-sheng [Department of Nephrology, Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), Nanchong City 637400 (China); Wang, Shao-qing [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Fan, Jun-ming, E-mail: junmingfan@163.com [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China)

    2014-02-07

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.

  17. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    International Nuclear Information System (INIS)

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells

  18. Triplet repeat length bias and variation in the human transcriptome

    OpenAIRE

    Molla, Michael; Delcher, Arthur; Sunyaev, Shamil; Cantor, Charles; Kasif, Simon

    2009-01-01

    Length variation in short tandem repeats (STRs) is an important family of DNA polymorphisms with numerous applications in genetics, medicine, forensics, and evolutionary analysis. Several major diseases have been associated with length variation of trinucleotide (triplet) repeats including Huntington's disease, hereditary ataxias and spinobulbar muscular atrophy. Using the reference human genome, we have catalogued all triplet repeats in genic regions. This data revealed a bias in noncoding D...

  19. PCR Method for Measuring vacA Genotype and cagA Gene of Helicobacter Pylori%PCR方法测定幽门螺杆菌vacA基因型和cagA基因

    Institute of Scientific and Technical Information of China (English)

    谢啸东; 张尤历

    2001-01-01

    目的:建立幽门螺杆菌vacA基因型和cagA基因的PCR测定方法.方法:应用多聚酶链反应方法对62例慢性胃炎、消化性溃疡和胃癌患者分离获得幽门螺杆菌菌株的vacA基因型和cagA基因进行测定.结果:62株幽门螺杆菌菌株均具有vacA基因,所有菌株的vacA基因型均为sla/m2型.cagA基因的总阳性率为56.45%;慢性胃炎、消化性溃疡和胃癌患者分离获得幽门螺杆菌的cagA基因阳性率分别为55.56%、54.17%和63.64%(P>0.05).结论:本研究建立的PCR测定幽门螺杆菌vacA基因型和cagA基因方法敏感性高、特异性强.

  20. Repeat-until-success quantum repeaters

    Science.gov (United States)

    Bruschi, David Edward; Barlow, Thomas M.; Razavi, Mohsen; Beige, Almut

    2014-09-01

    We propose a repeat-until-success protocol to improve the performance of probabilistic quantum repeaters. Conventionally, these rely on passive static linear-optics elements and photodetectors to perform Bell-state measurements (BSMs) with a maximum success rate of 50%. This is a strong impediment for entanglement swapping between distant quantum memories. Every time a BSM fails, entanglement needs to be redistributed between the corresponding memories in the repeater link. The key ingredients of our scheme are repeatable BSMs. Under ideal conditions, these turn probabilistic quantum repeaters into deterministic ones. Under realistic conditions, our protocol too might fail. However, using additional threshold detectors now allows us to improve the entanglement generation rate by almost orders of magnitude, at a nominal distance of 1000 km, compared to schemes that rely on conventional BSMs. This improvement is sufficient to make the performance of our scheme comparable to the expected performance of some deterministic quantum repeaters.

  1. How valid is single nucleotide polymorphism (SNP) diagnosis for the individual risk assessment of breast cancer?

    Science.gov (United States)

    Tempfer, Clemens B; Hefler, Lukas A; Schneeberger, Christian; Huber, Johannes C

    2006-03-01

    The number of reports investigating disease susceptibility based on the carriage of low-penetrance, high-frequency single nucleotide polymorphisms (SNPs) has increased in recent years. Evidence is accumulating defining specific individual variations in breast cancer susceptibility. Genetic variations of estradiol and xenobiotics metabolisms as well as genes involved in cell-cycle control have been described as significant contributors to breast cancer susceptibility, with variations depending on ethnic background and co-factors such as smoking and family history of breast cancer. In sum, the highest level of evidence to date linking SNPs and breast cancer comes from nested case-control studies within the prospective Nurses' Health Study. These data establish seven SNPs - hPRB +331G/A, AR CAG repeat, CYP19 (TTTA)10, CYP1A1 MspI, VDR FOK1, XRCC1 Arg194Trp and XRCC2 Arg188His - as small but significant risk factors for spontaneous, non-hereditary breast cancer. In addition, meta-analysis of data in the literature establishes the TGFBR1*6A, HRAS1, GSTP Ile105Val and GSTM1 SNPs as low-penetrance genetic risk factors of sporadic breast cancer. The clinical consequences of such a risk elevation may be detailed instruction of the patient as to general measures of breast cancer prevention such as a low-fat diet, optimization of body mass index, physical exercise, avoidance of alcohol and long-term hormone replacement therapy, and participation in a breast cancer screening program between the ages of 50 and 70 years. Specific surgical or drug interventions such as prophylactic mastectomy and oophorectomy or prophylactic intake of tamoxifen are not indicated based on SNP analysis at this time. PMID:16835078

  2. A yeast tRNA mutant that causes pseudohyphal growth exhibits reduced rates of CAG codon translation.

    Science.gov (United States)

    Kemp, Alain J; Betney, Russell; Ciandrini, Luca; Schwenger, Alexandra C M; Romano, M Carmen; Stansfield, Ian

    2013-01-01

    In Saccharomyces cerevisiae, the SUP70 gene encodes the CAG-decoding tRNA(Gln)(CUG). A mutant allele, sup70-65, induces pseudohyphal growth on rich medium, an inappropriate nitrogen starvation response. This mutant tRNA is also a UAG nonsense suppressor via first base wobble. To investigate the basis of the pseudohyphal phenotype, 10 novel sup70 UAG suppressor alleles were identified, defining positions in the tRNA(Gln)(CUG) anticodon stem that restrict first base wobble. However, none conferred pseudohyphal growth, showing altered CUG anticodon presentation cannot itself induce pseudohyphal growth. Northern blot analysis revealed the sup70-65 tRNA(Gln)(CUG) is unstable, inefficiently charged, and 80% reduced in its effective concentration. A stochastic model simulation of translation predicted compromised expression of CAG-rich ORFs in the tRNA(Gln)(CUG)-depleted sup70-65 mutant. This prediction was validated by demonstrating that luciferase expression in the mutant was 60% reduced by introducing multiple tandem CAG (but not CAA) codons into this ORF. In addition, the sup70-65 pseudohyphal phenotype was partly complemented by overexpressing CAA-decoding tRNA(Gln)(UUG), an inefficient wobble-decoder of CAG. We thus show that introducing codons decoded by a rare tRNA near the 5' end of an ORF can reduce eukaryote translational expression, and that the mutant tRNA(CUG)(Gln) constitutive pseudohyphal differentiation phenotype correlates strongly with reduced CAG decoding efficiency. PMID:23146061

  3. The frequency of Helicobacter pylor infection and cagA expression in the Korean patients with gastric carcinoma

    International Nuclear Information System (INIS)

    Helicobacter pylori infection had been approved as a group 1 carcinogen by the international agency for research on cancer. However the association between H.pylori infection and gastric carcinoma was not so definite in South Asia including Korea, and the role of cagA gene of H.pylori in gastric carcinogenesis was a controversial issue. The aims of this study were firstly to study in vivo expression frequency of 16S rRNA and cagA gene of H.pylori, secondly to study the association between H.pylori infection and gastric cancer, the association between cagA expression and gastric cancer in Korean patients. In vivo expression rate of 16S rRNA was 74 % of gastric carcinoma patients and cagA expression rate was 51 % of gastric carcinoma patients with H.pylori infection. Although 90 % of gastric carcinoma patients had H.pylori infection, the association between H.pylori infection and gastric carcinoma was not significant. And there was no significant association between cagA expression and gastric carcinoma. (author). 37 refs., 2 tabs., 1 fig

  4. An inverse relationship between CagA+ strains of Helicobacter pylori infection and risk of erosive GERD

    International Nuclear Information System (INIS)

    The aim of this study is investigating the association of Helicobacter pylori (H. pylori) infection and its cytogenetic-associated gene A (cag A) strain with reflux esophagitis. In a case-control setting (May 2005-2006), patients with reflux esophagitis (case group) were compared with age and gender matched people suffering from symptoms of gastroesophageal reflux disease with normal upper gastrointestinal endoscopic findings (control group) in Imam Khomeini Hospital, Tabriz, Iran. The rates of H. pylori and its cagA positive infections were separately compared between the 2 groups and the subgroups with different severity of reflux esophagitis. Ninety-two and 93 patients were enrolled in the case and control groups. The rate of H.pylori infection was significantly lower in case group (81.5%versus 87.10%, p=0.29, odd ratio 0.654, 95% confidence interval [CI] 0.293 to 1.495). The CagA positive infections were found significantly more frequent in the control group (59.1% versus 40.2%, p=0.01, odd ratio 0.465, 95% CI 0.258 to 0.836). There was no significant difference between the severity subgroups of the disease for H. pylori (p=0.30) or cagA positive infection rates (p=0.40). The cagA positive strains might have a protective effect against reflux esophagitis. (author)

  5. Purification and relationship with gastric disease of a 130 kDa(CagA) protein of Helicobacter pylorl

    Institute of Scientific and Technical Information of China (English)

    叶少菁; 方平楚; 毛国根; 厉朝龙; 丘翔; 陈海洋

    2003-01-01

    Objective:The aims of this research were to purify and identify the 130 kDa(CagA) protein of H.pylori clinical isolate HP97002 and evaluate the relationships between the purified 130 kDa(CagA) pro-tein and gastric diseases.Methods:The procedure for isolating the protein included 6 mol/L guanidine ex-tract,size exclusion chromatography and elusion from gel.Sera of 68 patients with gastric diseases(44 with chronic gastritis,15 with atrophic gastritis,7 with peptic ulcer disease,2 with gastric cancer) were obtained,and the serological response to CagA was studied by Westem-blot using the purified protein,Results;The pu-rified protein was 130 kDa and preserved good antigenicity and revealed basic isoelectric point about of 8.1. Among 68 sera,43 sera could recognize the purified protein associated with chronic agastritis 47.7%(21/44),atrophic gastritis 86.7%(13/15),peptic ulcer disease 100%(7/7),gastric cancer 100%(2/2).Compared with each other,the difference was significant(x2=13.327,P=0.004),and 130 kDa(CagA) protein was associated with severe gastric diseases(rs=0.442,P=0.001).Conclusion:The 130 kDa(CagA) protein was associated wih severe gastric diseases.

  6. The frequency of Helicobacter pylor infection and cagA expression in the Korean patients with gastric carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Sook Hyang; Kim, Yoo Chul [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1997-12-01

    Helicobacter pylori infection had been approved as a group 1 carcinogen by the international agency for research on cancer. However the association between H.pylori infection and gastric carcinoma was not so definite in South Asia including Korea, and the role of cagA gene of H.pylori in gastric carcinogenesis was a controversial issue. The aims of this study were firstly to study in vivo expression frequency of 16S rRNA and cagA gene of H.pylori, secondly to study the association between H.pylori infection and gastric cancer, the association between cagA expression and gastric cancer in Korean patients. In vivo expression rate of 16S rRNA was 74 % of gastric carcinoma patients and cagA expression rate was 51 % of gastric carcinoma patients with H.pylori infection. Although 90 % of gastric carcinoma patients had H.pylori infection, the association between H.pylori infection and gastric carcinoma was not significant. And there was no significant association between cagA expression and gastric carcinoma. (author). 37 refs., 2 tabs., 1 fig.

  7. Study on detecting of Helicobacter pylori cagA and vacA gene and typing of vacA genotypes%幽门螺杆菌vacA基因分型和cagA基因检测

    Institute of Scientific and Technical Information of China (English)

    杨学文; 王礼文; 陈云峰; 缪界平; 陈亚军

    2000-01-01

    [目的]建立检测幽门螺杆菌(Hp)的cagA、vacA基因及其基因型的方法,观察vacA基因型与cagA状态的相关性.[方法]应用聚合酶链反应(PCR)对172份Hp阳性标本进行Hp cagA和vacA基因检测及其基因型分析.[结果]172份Hp阳性标本中,vacA阳性数172(100%),cagA阳性数93(54.07%);49例萎缩性胃炎患者中,cagA阳性菌株感染47例(95.92%),64例浅表性胃炎患者中,vacA阳性菌株感染28例(43.75%),两者有显著差异(p<0.05);vacA中间区域型m1和m2分别为80和92例,两者无明显差异(p>0.05),信号序列型sla、slb、s2分别为82、68、22例,sla与slb无明显差异(P>0.05),sla、slb、sl(sla+slb)均显著多于s2型(p<0.05).检出所有的6种信号序列/中间区域组合型,slb/ml和sla/m2分别为48和52例,明显多于其它基因型(p<0.05),s2/ml仅为2列,明显少于其它基因型(p<0.01).对Hp vacA基因型与cagA状态相关性分析,s1/m1、s1/m2、s2/m1、s2/m2型的cagA阳性数为分别为45、48、0、0,93份cagA阳性标本均为s1(s1/m1+s1/m2).[结论]vacA基因存在于所有Hp中,而cagA基因仅存在于50%~60%的Hp中,vacA s1型与cagA密切相关,cagA阳性菌株感染与萎缩性胃炎十分相关.因此,对Hp cagA基因和vacA基因型的检测,有助于加深对Hp致病机理的认识,为Hp的分型和Hp感染患者的治疗提供有力的帮助.

  8. Integrin engagement by the helical RGD motif of the Helicobacter pylori CagL protein is regulated by pH-induced displacement of a neighboring helix.

    Science.gov (United States)

    Bonsor, Daniel A; Pham, Kieu T; Beadenkopf, Robert; Diederichs, Kay; Haas, Rainer; Beckett, Dorothy; Fischer, Wolfgang; Sundberg, Eric J

    2015-05-15

    Arginine-aspartate-glycine (RGD) motifs are recognized by integrins to bridge cells to one another and the extracellular matrix. RGD motifs typically reside in exposed loop conformations. X-ray crystal structures of the Helicobacter pylori protein CagL revealed that RGD motifs can also exist in helical regions of proteins. Interactions between CagL and host gastric epithelial cell via integrins are required for the translocation of the bacterial oncoprotein CagA. Here, we have investigated the molecular basis of the CagL-host cell interactions using structural, biophysical, and functional analyses. We solved an x-ray crystal structure of CagL that revealed conformational changes induced by low pH not present in previous structures. Using analytical ultracentrifugation, we found that pH-induced conformational changes in CagL occur in solution and not just in the crystalline environment. By designing numerous CagL mutants based on all available crystal structures, we probed the functional roles of CagL conformational changes on cell surface integrin engagement. Together, our data indicate that the helical RGD motif in CagL is buried by a neighboring helix at low pH to inhibit CagL binding to integrin, whereas at neutral pH the neighboring helix is displaced to allow integrin access to the CagL RGD motif. This novel molecular mechanism of regulating integrin-RGD motif interactions by changes in the chemical environment provides new insight to H. pylori-mediated oncogenesis.

  9. Clinical significance of Helicobacter pylori cagA and iceA genotype status

    Institute of Scientific and Technical Information of China (English)

    Nasser; Amjad; Hussain; Ali; Osman; Najibah; Abdul; Razak; Junaini; Kassian; Jeffri; Din; Nasuruddin; bin; Abdullah

    2010-01-01

    AIM:To study the presence of Helicobacter pylori(H.pylori) virulence factors and clinical outcome in H.pylori infected patients.METHODS:A prospective analysis of ninety nine H.pylori-positive patients who underwent endoscopy in our Endoscopy suite were included in this study.DNA was isolated from antral biopsy samples and the presence of cagA,iceA,and iceA2 genotypes were determined by polymerase chain reaction and a reverse hybridization technique.Screening for H.pylori infection was performed in all patie...

  10. 多巴胺转运体基因多态性与异常体液型乳腺癌的相关性%Association analysis between polymorphism of dopamine transporter variable number tandem repeat and breast cancer with abnormal Hilit

    Institute of Scientific and Technical Information of China (English)

    彭晓梅; 哈木拉提·吾甫尔; 多力坤·买买提玉素甫; 代文成; 吐尔逊·买买提

    2010-01-01

    目的 探讨多巴胺转运体基因(DATl)3'端40 bp VNTR多态性与新疆维吾尔自治区汉族人群异常体液型乳腺癌的相关性.方法 按维吾尔医学将乳腺癌患者分为4种体液型,采用聚合酶链式反应(PCR)和VNTR多态性分析技术对新疆汉族144例乳腺癌患者和104名正常对照组DAT1多态性进行检测,比较各组间等位基因和基因型频率分布的差异.结果 所测人群中,DAT1VNTR多态性表现出7、9-11倍重复的4种等位基因,其中最常见的等位基因为10倍重复的480 bp片段,其基因频率为90.9%;共检出7种基因型,其中最常见的基因型为10/10倍重复,占83.1%.异常黏液质型乳腺癌患者的DAT1 VNTR 10倍重复等位基因和10/10倍重复基因型频率显著高于正常对照组(OR=0.127,95%CI为0.016~0.988,P=0.026;OR=0.134,95%CI为0.018-1.016,P=0.020)和异常胆液质型乳腺癌患者组(OR=0.132,95%CI为0.016~1.075,P=0.049;OR=0.132,95%CI为0.017-1.042,P=0.033).结论 多巴胺转运体基冈(DAT1)3'端40 bp VNTR10倍重复等位基因和10/10倍重复基因型可能增加新疆汉族维吾尔医异常黏液质型乳腺癌的发病风险,可能与异常胆液质型乳腺癌易感件无关.%Objective To explore the association between polymorphism of dopamine 1 transporter variable number tandem repeat ( DAT1 VNTR) and breast cancer with abnormal Hilit in Chinese Han population from Xinjiang. Methods The breast caner patients were divided into four body fluids according to Uighur medicine theory. And polymerase chain reaction and VNTR polymorphism technique were employed to detect genotypie and allelie frequencies of a 40 bp VNTR polymorphism situated in 3'untranslated region of DAT1 gene in 144 breast cancer patients with abnormal Hilit and 104 normal control subjects in Han population of Xinjiang province. Results In our sample, the repeat numbers of 40 bp were 7 and 9-11 (PCR product length of 360 bp and 440 bp to 520 bp) and 10-repeat allele (480 bp

  11. 人类短串联重复D21S1409的遗传多态性研究%Genetic polymorphisms of human short tandem repeat D21S1409

    Institute of Scientific and Technical Information of China (English)

    郝冰涛; 王应太; 李怡; 杨艳丽; 朱文玉; 司艳梅

    2001-01-01

    Objective: We researched the genetic polymorphisms of D21S1409 in Henan population and its using in forensic science. Methods: Collecting not-relative persons in Henan population and getting the DNA with Chelex.Using polymerase chain reaction and nondenaturing polyacrylamide gel electrophoresis silver staining to type the persons. Results: A total of 6 alleles and 12 genotypes was found in Henan population,its heterozygosity is high and the locus can be used in forensic genetics. Conclusion: We get the frequency of the locus D21S1409 in Henan population.The results of amniotic fluid,villus,blood stain mean D21S1409 is a good locus for forensic.%目的: 研究人类短串联重复序列D21S1409在河南汉族人群中的遗传多态性,并探讨该基因座在法医学的应用可能性。方法: 采集河南无血缘关系汉族个体血样,应用Chelex法提取DNA,聚合酶链式反应扩增,非变性聚丙烯酰胺凝胶电泳分型。结果: 得到D21S1409在河南汉族群体中的基因频率,有6个等位基因,12个基因型,杂合度为0.65,个体识别库为0.81,非父排除率为0.37。结论: 该基因座多态性较好,分布符合Hardy-Weinberg平衡,可以用于个体识别和亲权鉴定。

  12. Specific serum immunoglobulin G to Hpylori and CagA in healthy children and adults (south-east of Iran)

    Institute of Scientific and Technical Information of China (English)

    A Jafarzadeh; MT Rezayati; M Nemati

    2007-01-01

    AIM: To evaluate the serologic IgG response to H pylori and CagA across age groups and in healthy children and adults.METHODS: Totally, 386 children aged 1-15 years and 200 adults aged 20-60 years, were enrolled to study. The serum samples of participant were tested for presence of anti-//pylori and anti-CagA IgG by using ELJSA method.RESULTS: The seroprevalence of H pylori in adults was significantly higher than that observed in children (67.5% vs 46.6%; P < 0.000003). In children, the seropositivity rate in males (51.9%) was significantly (P < 0.05) higher than that observed in females (41.7%). The prevalence of serum anti-CagA antibody was 72.8% and 67.4% in infected children and adults, respectively. The mean titer of serum anti-CagA antibodies was significantly higher among children in comparison to adults (64.1 Uarb/mL vs 30.7; P < 0.03). In infected children and adults the prevalence of serum anti-CagA antibody was higher in males compared to females (78.4% vs 66.3%; P = 0.07 and 75.6% vs 54.71%; P < 0.04, respectively). The age-specific prevalence of anti-H pylori and anti-CagA antibody (in infected subjects) was 37.6% and 59.57% at age 1-5 years, 46.9% and 75% at age 6-10 years, 54.9% and 79.45% at age 11-15, 59.01% and 83.33% at age 20-30 years, 66.6% and 60.52% at age 31-40 years, 73.46% and 63.88% at age 41-50 years and 75.75% and 60% at age 51-60 years with mean titer of anti-CagA antibody of 75.94, 63.32, 57.11, 52.06, 23.62, 21.52 and 21.80 Uarb/mL, respectively. There was significant difference between mean serum anti-CagA antibody in age subgroups (P < 0.001).CONCLUSION: These results showed that anti-//pylori and anti-CagA antibodies were common in the children and adults. The///7y/0//-specific antibodies influenced by age and sex of subjects. Moreover, it seems that males are more susceptible to infection with CagA+ strains compared to females. The seroprevalence of anti-CagA antibody was increased with age, up to 30 years and then decreased. It

  13. Novel effects of Helicobacter pylori CagA on key genes of gastric cancer signal transduction: a comparative transfection study.

    Science.gov (United States)

    Vaziri, Farzam; Peerayeh, Shahin N; Alebouyeh, Masoud; Maghsoudi, Nader; Azimzadeh, Pedram; Siadat, Seyed D; Zali, Mohammad R

    2015-04-01

    Helicobacter pylori (H. pylori) infection is now recognized as a worldwide problem. Helicobacter pylori CagA is the first bacterial oncoprotein to be identified in relation to human cancer. Helicobacter pylori CagA is noted for structural diversity in its C-terminal region (contains EPIYA motifs), with which CagA interacts with numerous host cell proteins. Deregulation of host signaling by translocated bacterial proteins provides a new aspect of microbial-host cell interaction. The aim of this study is to compare the cellular effects of two different CagA EPIYA motifs on identified signaling pathways involve in gastric carcinogenesis. To investigate the effects of CagA protein carboxyl region variations on the transcription of genes involved in gastric epithelial carcinogenesis pathways, the eukaryotic vector carrying the cagA gene (ABC and ABCCC types) was transfected into gastric cancer cell line. The 42 identified key genes of signal transduction involved in gastric cancer were analyzed at the transcription level by real-time PCR. The results of real-time PCR provide us important clue that the ABCCC oncoprotein variant can change the fate of the cell completely different from ABC type. In fact, these result proposed that the ABCCC type can induce the intestinal metaplasia, IL-8, perturbation of Crk adaptor proteins, anti-apoptotic effect and carcinogenic effect more significantly than ABC type. These data support our hypothesis of a complex interaction of host cell and these two different H. pylori effector variants that determines host cellular fate.

  14. Helicobacter pylori CagA and IL-1β Promote the Epithelial-to-Mesenchymal Transition in a Nontransformed Epithelial Cell Model

    Directory of Open Access Journals (Sweden)

    Haruki Arévalo-Romero

    2016-01-01

    Full Text Available Gastric cancer is the third cause of cancer death worldwide and infection by Helicobacter pylori (H. pylori is considered the most important risk factor, mainly by the activity of its virulence factor CagA. H. pylori/CagA-induced chronic inflammation triggers a series of gastric lesions of increased severity, starting with gastritis and ending with cancer. IL-1β has been associated with tumor development and invasiveness in different types of cancer, including gastric cancer. Currently, it is not clear if there is an association between CagA and IL-1β at a cellular level. In this study, we analyzed the effects of IL-1β and CagA on MCF-10A nontransformed cells. We found evidence that both CagA and IL-1β trigger the initiation of the epithelial-to-mesenchymal transition characterized by β-catenin nuclear translocation, increased expression of Snail1 and ZEB1, downregulation of CDH1, and morphological changes during MCF-10A acini formation. However, only CagA induced MMP9 activity and cell invasion. Our data support that IL-1β and CagA target the β-catenin pathway, with CagA leading to acquisition of a stage related to aggressive tumors.

  15. Helicobacter pylori CagA Suppresses Apoptosis through Activation of AKT in a Nontransformed Epithelial Cell Model of Glandular Acini Formation

    Directory of Open Access Journals (Sweden)

    Gabriela Vallejo-Flores

    2015-01-01

    Full Text Available H. pylori infection is the most important environmental risk to develop gastric cancer, mainly through its virulence factor CagA. In vitro models of CagA function have demonstrated a phosphoprotein activity targeting multiple cellular signaling pathways, while cagA transgenic mice develop carcinomas of the gastrointestinal tract, supporting oncogenic functions. However, it is still not completely clear how CagA alters cellular processes associated with carcinogenic events. In this study, we evaluated the capacity of H. pylori CagA positive and negative strains to alter nontransformed MCF-10A glandular acini formation. We found that CagA positive strains inhibited lumen formation arguing for an evasion of apoptosis activity of central acini cells. In agreement, CagA positive strains induced a cell survival activity that correlated with phosphorylation of AKT and of proapoptotic proteins BIM and BAD. Anoikis is a specific type of apoptosis characterized by AKT and BIM activation and it is the mechanism responsible for lumen formation of MCF-10A acini in vitro and mammary glands in vivo. Anoikis resistance is also a common mechanism of invading tumor cells. Our data support that CagA positive strains signaling function targets the AKT and BIM signaling pathway and this could contribute to its oncogenic activity through anoikis evasion.

  16. Helicobacter pylori CagA Suppresses Apoptosis through Activation of AKT in a Nontransformed Epithelial Cell Model of Glandular Acini Formation

    Science.gov (United States)

    Vallejo-Flores, Gabriela; Torres, Javier; Sandoval-Montes, Claudia; Arévalo-Romero, Haruki; Meza, Isaura; Camorlinga-Ponce, Margarita; Torres-Morales, Julián; Chávez-Rueda, Adriana Karina; Legorreta-Haquet, María Victoria; Fuentes-Pananá, Ezequiel M.

    2015-01-01

    H. pylori infection is the most important environmental risk to develop gastric cancer, mainly through its virulence factor CagA. In vitro models of CagA function have demonstrated a phosphoprotein activity targeting multiple cellular signaling pathways, while cagA transgenic mice develop carcinomas of the gastrointestinal tract, supporting oncogenic functions. However, it is still not completely clear how CagA alters cellular processes associated with carcinogenic events. In this study, we evaluated the capacity of H. pylori CagA positive and negative strains to alter nontransformed MCF-10A glandular acini formation. We found that CagA positive strains inhibited lumen formation arguing for an evasion of apoptosis activity of central acini cells. In agreement, CagA positive strains induced a cell survival activity that correlated with phosphorylation of AKT and of proapoptotic proteins BIM and BAD. Anoikis is a specific type of apoptosis characterized by AKT and BIM activation and it is the mechanism responsible for lumen formation of MCF-10A acini in vitro and mammary glands in vivo. Anoikis resistance is also a common mechanism of invading tumor cells. Our data support that CagA positive strains signaling function targets the AKT and BIM signaling pathway and this could contribute to its oncogenic activity through anoikis evasion. PMID:26557697

  17. Helicobacter pylori CagA and IL-1β Promote the Epithelial-to-Mesenchymal Transition in a Nontransformed Epithelial Cell Model

    Science.gov (United States)

    Arévalo-Romero, Haruki; Meza, Isaura; Vallejo-Flores, Gabriela

    2016-01-01

    Gastric cancer is the third cause of cancer death worldwide and infection by Helicobacter pylori (H. pylori) is considered the most important risk factor, mainly by the activity of its virulence factor CagA. H. pylori/CagA-induced chronic inflammation triggers a series of gastric lesions of increased severity, starting with gastritis and ending with cancer. IL-1β has been associated with tumor development and invasiveness in different types of cancer, including gastric cancer. Currently, it is not clear if there is an association between CagA and IL-1β at a cellular level. In this study, we analyzed the effects of IL-1β and CagA on MCF-10A nontransformed cells. We found evidence that both CagA and IL-1β trigger the initiation of the epithelial-to-mesenchymal transition characterized by β-catenin nuclear translocation, increased expression of Snail1 and ZEB1, downregulation of CDH1, and morphological changes during MCF-10A acini formation. However, only CagA induced MMP9 activity and cell invasion. Our data support that IL-1β and CagA target the β-catenin pathway, with CagA leading to acquisition of a stage related to aggressive tumors. PMID:27525003

  18. Analysis of the intactness of Helicobacter pylori cag pathogenicity island in Iranian strains by a new PCR-based strategy and its relationship with virulence genotypes and EPIYA motifs.

    Science.gov (United States)

    Yadegar, Abbas; Alebouyeh, Masoud; Zali, Mohammad Reza

    2015-10-01

    Variants of the Helicobacter pylori cag pathogenicity island (cagPAI) and certain virulence genotypes have been proposed to be associated with different gastric disorders. In the present study, we designed a new PCR-based strategy to investigate the intactness of cagPAI in Iranian patients using highly specific primer sets spanning the cagPAI region. The possible relationship between the cagPAI status of the strains and clinical outcomes was also determined. We also characterized virulence genotypes (cagL, cagA, vacA, babA2 and sabA) and variants of CagA EPIYA motifs in these strains. H. pylori was detected in 61 out of 126 patients with various gastroduodenal diseases. The cagL, cagA, vacA s1m1, vacA s1m2, vacA s2m2, babA2, and sabA genotypes were detected in 96.7%, 85.2%, 29.5%, 45.9%, 24.6%, 96.7%, and 83.6% of the strains, respectively. Among the 52 cagA-positive strains, EPIYA motifs ABC, ABCC, ABCCC, and mixed types were orderly detected in the 39, 7, 1, and 5 strains. The cagPAI positivity included both intact and partially deleted, with the overall frequencies of 70.5% and 26.2%, respectively. The majority of the strains from patients with PUD (87.5%), gastric erosion (83.3%) and cancer (80%) presented an intact cagPAI, while a lower frequency of cagPAI intactness was detected in gastritis patients (61.1%). However, no significant relationship was found between the possession of intact cagPAI and clinical outcomes. Furthermore, we found that cagA and vacA s1m1 genotypes were significantly correlated with intact cagPAI (P=0.015 and P=0.012). A significant correlation was also found between EPIYA-ABC and intact cagPAI (P=0.010). The proposed PCR-based scheme was found to be useful for determining the intactness of cagPAI. Our findings also indicate that the cagPAI appears to be intact and rather conserved in majority of Iranian strains. Finally, our study proposed that H. pylori strains with partially deleted cagPAI were less likely to cause severe diseases

  19. 基因多态性与复发性自然流产的相关性研究%Study on the relationship between gene polymorphism and repeated spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    李静益; 傅萍

    2012-01-01

    Repeated spontaneous abortion ( RSA) refers to abortions that occurred in succession two or more than two. The causes of RSA are complicated, including chromosomal abnormality of embryos, abnormal immune functions, luteal insufficiency, infection, genitourinary tract anomaly and so on. But now there are still some etiology and pathogenesis of RSA which are not clear, changes in genetic background and other facters may cause part of populations prone to RSA. Rerrent years some new points are put forward from the perspective of Immunology and Genetics, considering the causes of RSA are related with hereditary. Trying to find out susceptibility gene or pathogenic gene and clarifying the pathogenesis of RSA fundamentally, is important to the RSA treatment and prevention.%复发性自然流产(recurrent spontaneous abortions,RSA)是指连续发生2次或2次以上流产者.RSA的病因复杂,包括胚胎染色体异常、免疫功能异常、黄体功能不足、感染、生殖道异常等.但目前仍有部分RSA患者病因及发病机制尚不清楚,遗传背景等因素的改变可能使部分人群易发生RSA[1].近年来从免疫遗传角度提出了一些新的观点,认为RSA的发生与遗传有关.寻找RSA的易感基因或致病基因,从根本上阐明RSA的发病机理,是RSA治疗和预防的重要途径.

  20. Distribution of cagG gene in Helicobacter pylori isolates from Chinese patients with different gastroduodenal diseases and its clinical and pathological significance

    Institute of Scientific and Technical Information of China (English)

    Can Xu; Zhao-Shen Li; Zhen-Xing Tu; Guo-Ming Xu; Yan-Fang Gong; Xiao-Hua Man

    2003-01-01

    AIM: To determine the distribution of cagG gene of Helicobacter pylori(Hpylori) isolates cultured from patients with various digestive diseases and its relationship with gastroduodenal diseases.METHODS: cagG was amplified by polymerase chain reaction in 145 H pylori isolates cultured from patients with chronic gastritis (n=72), duodenal ulcer (n=48), gastric ulcer (n=17), or gastric and duodenal ulcer (n=8), and the relationship between cagGstatus and the grade of gastric mucosal inflammation was determined.RESULTS: cagG was present in 91.7% of the 145 H pylori isolates, with the rates were 90.3%, 93.8%, 88.2% and 100.0%, respectively, in those from patients with chronic gastritis, duodenal ulcer, gastric ulcer, and gastric and duodenal ulcer. There was no significant difference among the four groups (P>0.05). The average grade of gastric mucosal inflammation in the antrum and corpus was 1.819±0.325and 1.768±0.312, respectively in cagG positive patients,whereas the average inflammation grade was 1.649±0.297,1.598±0.278 respectively in cagG negative cases (P>0.05).CONCLUSION: cagG gene of H pylori was quite conservative,and most H pylori strains in Chinese patients were cagG positive.cagG status was not related to clinical outcome or the degree of gastric mucosal inflammation. Therefore, cagG can notbe used as a single marker for discrimination of H pylori strains with respect to a specific digestive disease.

  1. TPR repeats and ELTR pattern: length variation as a function evolution mechanism.

    Science.gov (United States)

    Yang, Ke-Qian

    2007-12-01

    TPR repeat was originally defined as a 34 amino acid structural repeat (TPR-34). Equal length tandem repeats (ELTR) was proposed to represent the ancestral repeat pattern. Length polymorphism of TPR repeats was analyzed using PATTINPROT, two new versions of TPR repeat of 40 and 42 amino acids were identified. These 'long' TPRs endow new functional capacities to the resulting proteins. A strong correlation between varied lengths and new functions supports the hypothesis that length variation is an underlying mechanism for the function evolution of repeat containing proteins.

  2. Prognostic significance of genetic polymorphisms in disease progression and survival in prostate cancer after androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Tsung-Yi Huang

    2015-06-01

    Full Text Available It is believed that androgens and their receptors regulate normal prostate growth and mediate prostate cancer development. Androgen deprivation therapy is the most commonly used treatment for advanced prostate cancer. Although the therapy is initially effective, progression of the disease to castration-resistant prostate cancer is almost inevitable, leading to treatment failure. Despite the existence of current clinical parameters, new biomarkers are urgently needed to improve the prognosis. Some molecules and DNA-based genetic biomarkers are under investigation as potential prognostic factors. The advancement in molecular cytogenetic research, such as genome-wide association for single-nucleotide polymorphisms, has made possible the detection of genetic mutations. In this study, a literature search from August 1985 to April 2013 was performed through the PubMed database using the keywords “genetic polymorphisms”, “prostate cancer” and “androgen deprivation therapy”. The results revealed that several genome-wide association studies (such as rs16901979, rs7931342, HSD17B4, rs6162 in the CYP17A1, rs4243229 and rs7201637 in the HSD17B2, rs1062577 in the ESR1, SLCO1B3, SLCO2B1, rs2939244 in the ARRDC3, rs9508016 in the FLT1, rs6504145 in the SKAP1, rs7830611 in the FBXO32, rs9508016 in the FLT1, rs12529 in the AKR1C3, rs16934641 in the BNC2, rs3763763 in the TACC2, rs2051778 in the ALPK1, and rs3763763 in the TACC2, AR, ESR1, and ESR2 and single-nucleotide polymorphisms in important pathways (such as androgen signal, biosynthesis, metabolism, androgen receptor binding site, response element, androgen receptor CAG repeat polymorphism length, and estrogen receptor-binding sites involved in prostate cancer occurrence and mechanism could serve as candidate biomarkers for the early detection of castration-resistant prostate cancer after androgen deprivation therapy. Additional investigations are required to decipher precisely the gene

  3. Helicobacter pylori vacA genotypes and cagA status and their relationship to associated diseases

    Institute of Scientific and Technical Information of China (English)

    Peng Hou; Zhen Xing Tu; Guo Ming Xu; Yan Fang Gong; Xu Hui Ji; Zhao Shen Li

    2000-01-01

    Helicobacter pylori (H. pylori ) is a major causativebacterium of chronic gastritis, peptic ulcer and mucosaassociated lymphoid tissue lymphoma in humans, and associated with an increased risk of gastric cancer[1 -8]. An important virulant factor of H. pylori is the vacuolating cytotoxin ( VacA ) encoded by vacA that induces cytoplasmic vacuolation in target cells both in vitro and in vivo[9-11]. VacA is produced as a 140 kDa precursor which contains an N-terminal signal peptide and an approximately 33 kDa C-terminal outer membrance exporter. The precursor is cleaved at both N-terminal and C-terminal and secreted into the extracellular milieu as a 95 kDa mature protein. The mature protein futher undergoes specific cleavage to yield 37 kDa and 58 kDa subunits[12-14] Although vacA is present in all H. pylori strains, only about 50% to 60% of strains can induce vacuolation of epithelial cells as assessed by the HeLa cell assay. vacA shows considerable genetic variation in H. pylori isolated from all over the world and contains at least two variable regions. The s region exists as sl or s2 allelic types. Among type sl strains, subtypes sla and slb have been identified. The m region occurs as ml or m2 allelic types. Specific vacA genotype of H. pylori strains are associated with the production of the cytotoxin in vitro, epithelial damage in vivo, and clinical consequences[15-27]. The other virulant factor is the cytotoxin-associated protein (CagA) encoded by the cytotoxin-associated gene (cagA). The cagA gene is present in about 60% to 70% of strains and all of these strains express the cagA. The presence of cagA is also associated with the production of the cytotoxin in vitro, and clinical outcome[24-30]. The aim of this study was (i) to identify vacA genotypes and cagA status of H. pylori isolated from Chinese patients; (ii) to evaluation the relatioship beween vacA genotypes, cagA status and related gastroenterological disorders.

  4. Polymorphism of 17 Short Tandem Repeat Loci of Tibetan Minority Ethnic Group from Lhasa%拉萨地区藏族人群17个短串联重复序列基因座的遗传多态性

    Institute of Scientific and Technical Information of China (English)

    马骏; 巴华杰; 张文杰; 李开

    2011-01-01

    目的 调查拉萨地区藏族人群17个短串联重复序列(STR)基因座的遗传多态性分布.方法 采用国产AGCU17+1荧光标记复合扩增试剂盒,结合AB9700扩增仪和3130XL遗传分析仪,对拉萨地区132名藏族无关个体的静脉血进行基因组多态性检测,并用GeneMapper 3.2软件进行基因分型.结果 17个STR基因座在132名藏族无关个体中的等位基因频率介于0.0038~0.5720,个体识别能力介于0.779 ~0.979,非父排除率值介于0.327 ~0.737,多态信息含量介于0.538~0.910,杂合度介于0.629~0.871.累积耦合概率为3.93×10-20,累积非父排除率为0.9999995234.17个STR基因座中,Penta E与D6S1043的各项多态性指标均为最高,TPOX基因座的各项指标值均为最低.结论 17个STR基因座在藏族人群的多态性研究中具有较高的应用价值,可用于该地区的群体学研究、法医学个体识别等领域.%Objective To investigate the polymorphism of 17 short tandem repeat (STR) loci of Tibetan minority ethnic group from Lhasa. Methods Blood samples were obtained from 132 unrelated Tibetan individuals from Lhasa. DNA templates were screened by home-made AGCU17 + 1 kit and 3130XL genetic analyzer. Genotyping was performed using GeneMapper software (version 3. 2). Results The allele frequencies of 17 STR loci ranged 0. 0038-0. 5720, and the power of discrimination ranged 0. 779-0. 979, the power of exclusion ranged 0.327-0.737, the polymorphism information contents ranged 0.538-0.910, and the het-erozygosity ranged 0. 629-0. 871. The cumulative coupling probability was 3. 93 x 10"20, and the cumulative power of exclusion was 0. 9999995234. Of 17 STR loci, Penta E and D6S1043 had the highest polymorphism indicators, while TPOX had the lowest Conclusion The 17 STR loci used in this study are highly polymorphism in Tibetan minority ethnic group from Lhasa and fit for the population genetic study and forensic cases.

  5. Helicobacter pylori cagA and iceA genotypes status and risk of peptic ulcer in Saudi patients

    International Nuclear Information System (INIS)

    Objective was to determine the prevalence of cagA+ and iceA genotypes among Helicobacter pylori (H. pylori) isolates from a group of Saudi patients with gastric complaints, and to find out any significant correlation between these strains and severe gastric clinical outcomes such as peptic ulcer and gastric cancer in Saudi population. A total of 1104 gastric biopsies from 368 patients who presented with symptoms suggestive of chronic gastritis, peptic ulcer disease, or gastric carcinoma were taken from the main hospitals in the Western region of Saudi Arabia from July 2004 to July 2005. We cultured the samples for H. pylori and a polymerase chain reaction was carried out to check for the presence or absence of cagA gene and the status of iceA genotypes. Among the 368 suspected patients to be infected with H. pylori by means of clinical features and endoscopic findings; 103 (28%) were positive using culture technique. The relation of the presence of cagA and the development of cases to gastritis and ulcer was statistically significant (p=0.0001). Furthermore, this study revealed that 100% of ulcer cases were infected with iceA1 with a statistically significant correlation (p=0.0001), while 94.6% of gastritis and 90.9% of normal were infected with iceA2 (p=0.0001). Moreover cagA+/iceA1 combined genotypes was statistically correlated with peptic ulcer (100%) but not cagA-/iceA1 (0%; p=0.0001).Certain H. pylori genotypes were more virulent than others. Multiple clinical implications based on these finding might be studied further.(author)

  6. Molecular interactions between MUC1 epithelial mucin, β-catenin, and CagA proteins

    Directory of Open Access Journals (Sweden)

    Wei eGuang

    2012-05-01

    Full Text Available Interleukin (IL-8-driven neutrophil infiltration of the gastric mucosa is pathognomonic of persistent Helicobacter pylori infection. Our prior study showed that ectopic over-expression of MUC1 in human AGS gastric epithelial cells reduced H. pylori-stimulated IL-8 production compared with cells expressing MUC1 endogenously. Conversely, Muc1 knockout (Muc1-/- mice displayed an increased level of transcripts encoding the keratinocyte chemoattractant (KC, the murine equivalent of human IL-8, in gastric mucosa compared with Muc1(+/+ mice during experimental H. pylori infection. The current study tested the hypothesis that a decreased IL-8 level observed following MUC1 over-expression is mediated through the ability of MUC1 to associate with β-catenin, thereby inhibiting H. pylori-induced β-catenin nuclear translocation. Increased neutrophil infiltration of the gastric mucosa of H. pylori-infected Muc1(-/- mice was observed compared with Muc1(+/+ wild type littermates, thus defining the functional consequences of increased KC expression in the Muc1-null animals. Protein co-immunoprecipitation (coIP studies using lysates of untreated or H. pylori-treated AGS cells demonstrated that (a MUC1 formed a coIP complex with β-catenin and CagA, (b MUC1 over-expression reduced CagA/β-catenin coIP, and (c in the absence of MUC1 over-expression, H. pylori infection increased the nuclear level of β-catenin, (d whereas MUC1 over-expression decreased bacteria-driven β-catenin nuclear localization. These results suggest that manipulation of MUC1 expression in gastric epithelia may be an effective therapeutic strategy to inhibit H. pylori-dependent IL-8 production, neutrophil infiltration, and stomach inflammation.

  7. New polymorphic variants of human blood clotting factor IX

    Energy Technology Data Exchange (ETDEWEB)

    Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V. [Hematological Research Center, Moscow (Russian Federation); Plutalov, O.V.; Berlin, Yu.A. [Shemyakin Institute of Bioorganic Chemistry, Moscow (Russian Federation)

    1995-04-01

    The polymorphism of Alu-repeats, which are located in the introns of the human factor IX gene (copies 1-3), was studied. To identify polymorphic variants, direct sequencing of PCR products that contained appropriate repeats was used. In each case, 20 unrelated X chromosomes were studied. A polymorphic Dra I site was found near the 3{prime}-end of Alu copy 3 within the region of the polyA tract. A PCR-based testing system with internal control of restriction hydrolysis was suggested. Testing 81 unrelated X chromosomes revealed that the frequency of the polymorphic Dra I site is 0.23. Taq I polymorphism, which was revealed in Alu copy 4 of factor IX gene in our previous work, was found to be closely linked to Dra I polymorphism. Studies in linkage between different types of polymorphisms of the factor IX gene revealed the presence of a rare polymorphism in intron a that was located within the same minisatellite region as the known polymorphic insertion 50 bp/Dde I. However, the size of the insertion in our case was 26 bp. Only one polymorphic variant was found among over 150 unrelated X chromosomes derived from humans from Moscow and its vicinity. 10 refs., 4 figs., 1 tab.

  8. Gene conversion homogenizes the CMT1A paralogous repeats

    OpenAIRE

    Hurles Matthew E

    2001-01-01

    Abstract Background Non-allelic homologous recombination between paralogous repeats is increasingly being recognized as a major mechanism causing both pathogenic microdeletions and duplications, and structural polymorphism in the human genome. It has recently been shown empirically that gene conversion can homogenize such repeats, resulting in longer stretches of absolute identity that may increase the rate of non-allelic homologous recombination. Results Here, a statistical test to detect ge...

  9. A novel multiplex analysis of filaggrin polymorphisms

    DEFF Research Database (Denmark)

    Meldgaard, Michael; Szecsi, Pal B; Carlsen, Berit C;

    2012-01-01

    The filaggrin protein is expressed as profilaggrin mainly in stratum granulosum cells of the epidermis. The profilaggrin gene codes for 10-12 filaggrin repeats. The filaggrin protein is important for skin barrier function. Filaggrin deficiency due to functional null-polymorphisms affects 8-10% of...

  10. Morphological and pathologic changes of experimental chronic atrophic gastritis (CAG) and the regulating mechanism of protein expression in rats

    Institute of Scientific and Technical Information of China (English)

    WANG Liang-jing; CHEN Shu-jie; CHEN Zhe; CAI Jian-ting; SI Jian-min

    2006-01-01

    Objective: To study the pathologic change and molecular regulation in cell proliferation and apoptosis of gastric mucosa in rats with chronic atrophic gastritis (CAG), and evaluate the possible mechanisms. Methods: Rats were administered with 60% alcohol or 2% salicylate sodium, 20 mmol/L deoxycholate sodium and 0.1% ammonia water to establish chronic atrophic gastritis (CAG) models. The gastric specimens were prepared for microscopic view with hematoxylin and eosin (H-E)and alcian blue (A-B) stain. The number of infiltrated inflammatory cells, the thickness of the mucosa gland layer (μm) and the number of gastric glands were calculated. The damage of barrier in mucosa with erosion or ulceration, and the thickness of mucin were examined by scanned electron microscope (SEM). The levels of PGE2, EGF (epiderminal growth factor) and gastrin in the serum were measured with radioimmunoassay or ELISA method. The immunohistochemistry method was used to observe the number of G cells, the expression of protein of EGFR (EGF receptor), C-erbB-2, p53, p16 and bcl-2 in gastric tissue. Results:Under SEM observation, the gastric mucosa was diffused erosion or ulceration and the thickness of mucin was decreased. Compared with normal rats, the grade of inflammatory cell infiltration in CAG rats was elevated, whereas the thickness and number of gastric gland were significantly lower (P<0.05). Compared with normal level of (0.61+0.28) μg/L, EGF in CAG (2.2±0.83) μg/L was significantly higher (P<0.05). The levels of PGE2 and gastrin in serum were significantly lower in CAG rats than that in normal rats (P<0.05). Immunohistochemistry detection showed that the number of G cell in antrum was lower in CAG group (P<0.05). Immuno-stain showed EGFR protein expression in the basal and bilateral membrane, and the cytoplasma in atrophic gastric gland, while negative expression was observed in normal gastric epithelial cells. Positive staining of p53 and p16 protein was localized in

  11. Genotype and Allele Frequency of the 27-bp Tandem RepeatPolymorphism in the Endothelial Nitric Oxide SynthaseGene in Chinese Population%中国人eNOS基因VNTR多态性的基因型与等位基因频率

    Institute of Scientific and Technical Information of China (English)

    路萍; 郑晓飞; 吕星; 吴苏华; 邢瑞云; 孙琪云; 韩莉; 蓝红

    2001-01-01

    一氧化氮合酶(nitric oxide synthase,NOS)催化L-精氨酸的氧化反应生成L-瓜氨酸和一氧化氮(nitric oxide,NO).NO可通过cGMP依赖的信号传导途径介导平滑肌细胞舒张,是调节血管张力的重要信使分子.NO尚可抑制血小板凝集,对血栓形成起重要调节作用.目前在哺乳动物中已发现细胞来源、表达方式和活性调节不同的3种NOS同工酶,分别为神经元型NOS(neuronal NOS,nNOS)、诱导型NOS(inducible NOS,iNOS)和内皮细胞型NOS(endothelial NOS,eNOS).人的eNOS基因位于第7号染色体长臂(7q36),全长约21kb,含有26个外显子和25个内含子.eNOS基因存在多个与心脑血管疾病相关的基因多态性位点.其中位于第4内含子的一个以27bp为核心的数目可变性串联重复序列(variable number of tandem repeat,VNTR)多态性位点,已被证实与原发性高血压、心肌梗死和静脉血栓形成有关.目前在我国尚缺乏NOS基因多态性在正常人群中基因型及等位基因频率分布的统计资料.为此,我们从316名健康中国人的基因组DNA检测了eNOS基因第4内含子VNTR多态性的基因型和等位基因,鉴定出重复6次、5次和4次的3种等位基因,以及6/5杂合、5/5纯合、5/4杂合和4/4纯合的4种基因型.同时我们将正常中国人eNOS 基因VNTR 多态性的基因型和等位基因频率与其他种族的相关资料进行了统计对比.结果表明,中国人eNOS基因VNTR的各种基因型和等位基因频率与日本人相似,4/4纯合基因型频率与高加索人差异显著,各种基因型和等位基因频率与非裔美国人均存在显著差异.%Genotype and allele frequency of the polymorphic 27-bp repeat, a variable number of tandem repeats (VNTR) located in intron 4 of the endothelial nitric oxide synthase gene, were analyzed in 316 healthy Chinese individuals. Four genotypes, namely 6/5-repeats heterozygous, 5/5-repeats homozygous,5/4-repeats heterozygous and 4/4-repeats homozygous

  12. High Diversity of vacA and cagA Helicobacter pylori Genotypes in Patients with and without Gastric Cancer

    Science.gov (United States)

    López-Vidal, Yolanda; Ponce-de-León, Sergio; Castillo-Rojas, Gonzalo; Barreto-Zúñiga, Rafael; Torre-Delgadillo, Aldo

    2008-01-01

    Background Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. Methodology/Principal Findings Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008), and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003). A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036). A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003). Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins. Conclusion/Significance High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work. PMID:19050763

  13. cagA and vacA genotype of Helicobacter pylori associated with gastric diseases in Xi'an area

    Institute of Scientific and Technical Information of China (English)

    Wen Qiao; Jia-Lu Hu; Bing Xiao; Kai-Chun Wu; Dao-Rong Peng; John C Atherton; Hui Xue

    2003-01-01

    AIM: To establish stock of clinical Helicobacter pylori (H.pylon) isolates, to perform cagA and vacA typing of these isolates, to evaluate the relationship between genotypes of cagA and vacA and upper gastrointestinal diseases and to assess the association of vacA genotypes with presence of the pathogenicity marker-cagA.METHODS: Clinical H.pylori strains were isolated from the antrum of 259 patients in Clumbia agar. The isolated H.pylori strains were identified by histology, and16SrRNA PCR.CagA genotypes were detected by colony hybridization, the probe was derived from the cloned plasmid PcagA, and digested by EcoRI-HindⅢ and the isolated PcagA DNA fragment was radioactively labelled by the random priming method. vacA genes types (s,m)and subtypes (s1a, s1b,s2) were typed by PCR. Vacuolating toxin was detected with neutral red absorb test. The results were treated statistically by χ2test, ttest, and rank sum test.RESULTS: A total of 192 clinical H. pylori strains were isolated and the stock of Helicobacter pylori was established. The total positive rate of cagA was 87 % in all gastric diseases,and 95 % in gastric cancer group. There was a difference between gastric cancer group and the other groups (P<0.05)except duodenal ulcer group. The expression of type s1 of vacA was more than type s2 (P<0.05), and, the expression of type m1 was equal to type m2. In gastric cancer group,there was a difference between s1a and s1b (P<0.05), and s1a was more than s1b. Vacuolating toxins were more in Xi′an area isolates.CONCLUSION: The cagA+ vacA type s1 clinical isolates are more in Xi′an area, but this can not serve as an index to predict gastric cancer.

  14. High diversity of vacA and cagA Helicobacter pylori genotypes in patients with and without gastric cancer.

    Directory of Open Access Journals (Sweden)

    Yolanda López-Vidal

    Full Text Available BACKGROUND: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008, and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003. A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036. A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003. Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins. CONCLUSION/SIGNIFICANCE: High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work.

  15. Genetic polymorphisms of 9 non-combined of DNA index system short tandem repeat loci in Guangdong Han population%九个非DNA联合索引系统核心短串联重复序列基因座在广东汉族人群的遗传多态性

    Institute of Scientific and Technical Information of China (English)

    张晋湘; 薛天羽; 李海霞; 孙宏钰; 成建定

    2009-01-01

    目的 调查D7S3048等9个非DNA联合索引系统(combined of DNA index system,CODIS)指定的核心短串联重复序列(short tandem repeat,STR)基因座在广东汉族人群的遗传多态性.方法 采用荧光标记复合扩增和毛细管电泳技术,对广东汉族500名无关个体的DNA进行9个STR基因座分型.结果 500名无关个体在D7S3048等9个非CODIS核心STR基因座共检出115个等位基因,160种基因型,各基因座杂合度为0.824~0.884,个人识别能力为0.925~0.969,多态信息总量为0.77~0.86,均符合Hardy-Weinberg平衡(P>0.05),9个STR基因座的累计个体识别力达1.00×10~(-13),三联体累计非父排除率为0.999989488,二联体累计非父排除率为0.873436.结论 D7S3048等9个STR基因座在个体识别及亲子鉴定中是一个高效的检测系统,在二联体亲子鉴定中可作为补充基因座满足疑难、单亲和突变案件的需求.%Objective To investigate the genetic polymorphisms and their forensic application of 9 non-combined of DNA index system (CODIS) short tandem repeat (STR) loci in Guangdong Han population. Methods DNA samples from 500 unrelated individuals were extracted and amplified with fluorescence labeled multiplex PCR system. PCR products were separated and genotyped with capillary electrophoresis. Results One hundred and fifteen alleles and 160 genotypes were observed in the 9 STR loci, respectively. The heterozygosity was 0. 824-0. 884, the discrimination power (DP) was 0. 925-0. 969 and the polymorphism information content (PIC) was 0. 77-0. 86, respectively. The distribution met the Hardy-Weinberg equilibrium (P>0.05). The total discrimination power was 1.00×10~(-13), the combined probability of exclusion for trio-paternity testing was 0. 999989488. The combined probability of exclusion for duo-paternity testing was 0. 873436. Conclusion The 9 STR loci are powerful and reliable for personal identification and paternity testing. They can be used as supplementary loci

  16. Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease: a registry-based cohort study.

    Directory of Open Access Journals (Sweden)

    Lasse Jespersen

    Full Text Available AIMS: To evaluate risk of hospitalization due to cardiovascular disease (CVD and repeat coronary angiography (CAG in stable angina pectoris (SAP with no obstructive coronary artery disease (CAD versus obstructive CAD, and asymptomatic reference individuals. METHODS AND RESULTS: We followed 11,223 patients with no prior CVD having a first-time CAG in 1998-2009 due to SAP symptoms and 5,695 asymptomatic reference individuals from the Copenhagen City Heart Study through registry linkage for 7.8 years (median. In recurrent event survival analysis, patients with SAP had 3-4-fold higher risk of hospitalization for CVD irrespective of CAG findings and cardiovascular comorbidity. Multivariable adjusted hazard ratios(95%CI for patients with angiographically normal coronary arteries was 3.0(2.5-3.5, for angiographically diffuse non-obstructive CAD 3.9(3.3-4.6 and for 1-3-vessel disease 3.6-4.1(range(all P<0.001. Mean accumulated hospitalization time was 3.5(3.0-4.0(days/10 years follow-up in reference individuals and 4.5(3.8-5.2/7.0(5.4-8.6/6.7(5.2-8.1/6.1(5.2-7.4/8.6(6.6-10.7 in patients with angiographically normal coronary arteries/angiographically diffuse non-obstructive CAD/1-, 2-, and 3-vessel disease, respectively (all P<0.05, age-adjusted. SAP symptoms predicted repeat CAG with multivariable adjusted hazard ratios for patients with angiographically normal coronary arteries being 2.3(1.9-2.9, for angiographically diffuse non-obstructive CAD 5.5(4.4-6.8 and for obstructive CAD 6.6-9.4(range(all P<0.001. CONCLUSIONS: Patients with SAP symptoms and angiographically normal coronary arteries or angiographically diffuse non-obstructive CAD suffer from considerably greater CVD burdens in terms of hospitalization for CVD and repeat CAG compared with asymptomatic reference individuals even after adjustment for cardiac risk factors and exclusion of cardiovascular comorbidity as cause. Contrary to common perception, excluding obstructive CAD by CAG in such

  17. Helicobacter pylori-induced IL-1β secretion in innate immune cells is regulated by the NLRP3 inflammasome and requires the cag pathogenicity island.

    Science.gov (United States)

    Semper, Raphaela P; Mejías-Luque, Raquel; Groß, Christina; Anderl, Florian; Müller, Anne; Vieth, Michael; Busch, Dirk H; Prazeres da Costa, Clarissa; Ruland, Jürgen; Groß, Olaf; Gerhard, Markus

    2014-10-01

    Infection with the gram-negative bacterium Helicobacter pylori is the most prevalent chronic bacterial infection, affecting ∼50% of the world's population, and is the main risk factor of gastric cancer. The proinflammatory cytokine IL-1β plays a crucial role in the development of gastric tumors and polymorphisms in the IL-1 gene cluster leading to increased IL-1β production have been associated with increased risk for gastric cancer. To be active, pro-IL-1β must be cleaved by the inflammasome, an intracellular multiprotein complex implicated in physiological and pathological inflammation. Recently, H. pylori was postulated to activate the inflammasome in murine bone marrow-derived dendritic cells; however, the molecular mechanisms as well as the bacterial virulence factor acting as signal 2 activating the inflammasome remain elusive. In this study, we analyzed the inflammasome complex regulating IL-1β upon H. pylori infection as well as the molecular mechanisms involved. Our results indicate that H. pylori-induced IL-1β secretion is mediated by activation of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 inflammasome. We also show that reactive oxygen species, potassium efflux, and lysosomal destabilization are the main cellular mechanisms responsible of nucleotide-binding oligomerization domain family, pyrin domain-containing 3 inflammasome activation upon H. pylori infection, and identify vacuolating cytotoxin A and cag pathogenicity island as the bacterial virulence determinants involved. Moreover, in vivo experiments indicate an important role for the inflammasome in the onset and establishment of H. pylori infection and in the subsequent inflammatory response of the host. PMID:25172489

  18. IGF-1基因启动子区CA重复序列多态性与代谢综合征关系研究%Association of CA repeats polymorphism in the promoter region of IGF-1 gene with metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    杨敏; 向红丁; 陈伟; 凌伟

    2011-01-01

    目的 探讨胰岛素样生长因子1(IGF-1)基因启动子区CA重复序列多态性与代谢综合征(MS)的关系.方法 收集北京市东城区常住人口1047例,采用2005年国际糖尿病联盟标准诊断代谢综合征.将受试者的基因组DNA应用聚合酶链反应扩增,再通过选择不同长度的纯合子样本测序确定CA重复的次数,以确定等位基因.同时测量身高、体重、腰围、血糖、血脂、胰岛素及血IGF-1.结果 (CA)19纯合组MS患病率显著低于不携带(CA)19组(9.1% vs 24.0%,x2=18.05,P<0.01)及(CA)19杂合组(9.1% vs 18.3%,x2=8.55,P<0.01);三组间血IGF-1水平差异有统计学意义[(114.0±52.6)μg/L vs(136.6±80.5)μg/L vs(129.2±49.1)μg/L,F=3.16,P<0.05],(CA)19纯合组血IGF-1水平低于不携带(CA)19组及(CA)19杂合组.三组间体重指数(BMI)、腰围(WC)、甘油三酯(TG)、空腹胰岛素(Fins)、2hIns及胰岛素敏感性指数(ISI)差异均有统计学意义(P<0.05),(CA)19纯合组的BMI、WC、TG、FIns、2hIns均低于另两组,而ISI高于另两组.结论 IGF-1基因启动子区CA重复序列多态性与汉族人群MS发病有关.%Objective To explore the relationship between CA repeats polymorphism in the promoter region of IGF-1 gene and MS in the Han nationality.Methods 1047 subjects were recruited from general population of Dongcheng District in Beijing.MS was diagnosed based on the criteria for MS in 2005 by IDF.Genomic DNA was extracted by standard methods.PCR,Genescan,Genotyper and direct sequencing were conducted to screen CA repeats polymorphism in the promoter region of the human IGF-1 gene.Levels of plasma glucose,lipids,serum insulin and IGF-1 were determined.BMI and ISI were calculated.Results The prevalence of MS in (CA) 19 homozygote was lower than that in (CA) 19 heterozygote (9.1% vs 18.3%,x2 = 8.55,P < 0.01) and without (CA) 19 (9.1% vs 24.0%,x2 = 18.05,P < 0.01).The level of serum IGF-1 had differences among the three groups [ (114.0 ± 52.6) μg/L vs

  19. Helicobacter pylori CagA induces tumor suppressor gene hypermethylation by upregulating DNMT1 via AKT-NFκB pathway in gastric cancer development.

    Science.gov (United States)

    Zhang, Bao-Gui; Hu, Lei; Zang, Ming De; Wang, He-Xiao; Zhao, Wei; Li, Jian-Fang; Su, Li-Ping; Shao, Zhifeng; Zhao, Xiaodong; Zhu, Zheng-Gang; Yan, Min; Liu, Bingya

    2016-03-01

    Methylation of CpG islands in tumor suppressor gene prompter is one of the most characteristic abnormalities in Helicobacter pylori (HP)-associated gastric carcinoma (GC). Here, we investigated the pathogenic and molecular mechanisms underlying hypermethylation of tumor suppressor genes in HP induced GC development. We found that tumor suppressor genes hypermethylation, represented by MGMT, positively correlated with CagA in clinical specimens, gastric tissues from HP infected C57 mice and GC cell lines transfected by CagA or treated by HP infection. CagA enhanced PDK1 and AKT interaction and increased AKT phosphorylation. The P-AKT subsequent activated NFκB, which then bound to DNMT1 promoter and increased its expression. Finally, the upregulated DNMT1 promoted tumor suppressor genes hypermethylation with MGMT as a representative. In conclusion, CagA increased tumor suppressor genes hypermethylation via stimulating DNMT1 expression through the AKT-NFκB pathway. PMID:26848521

  20. Helicobacter pylori counteracts the apoptotic action of its VacA toxin by injecting the CagA protein into gastric epithelial cells.

    Directory of Open Access Journals (Sweden)

    Amanda Oldani

    2009-10-01

    Full Text Available Infection with Helicobacter pylori is responsible for gastritis and gastroduodenal ulcers but is also a high risk factor for the development of gastric adenocarcinoma and lymphoma. The most pathogenic H. pylori strains (i.e., the so-called type I strains associate the CagA virulence protein with an active VacA cytotoxin but the rationale for this association is unknown. CagA, directly injected by the bacterium into colonized epithelium via a type IV secretion system, leads to cellular morphological, anti-apoptotic and proinflammatory effects responsible in the long-term (years or decades for ulcer and cancer. VacA, via pinocytosis and intracellular trafficking, induces epithelial cell apoptosis and vacuolation. Using human gastric epithelial cells in culture transfected with cDNA encoding for either the wild-type 38 kDa C-terminal signaling domain of CagA or its non-tyrosine-phosphorylatable mutant form, we found that, depending on tyrosine-phosphorylation by host kinases, CagA inhibited VacA-induced apoptosis by two complementary mechanisms. Tyrosine-phosphorylated CagA prevented pinocytosed VacA to reach its target intracellular compartments. Unphosphorylated CagA triggered an anti-apoptotic activity blocking VacA-induced apoptosis at the mitochondrial level without affecting the intracellular trafficking of the toxin. Assaying the level of apoptosis of gastric epithelial cells infected with wild-type CagA(+/VacA(+H. pylori or isogenic mutants lacking of either CagA or VacA, we confirmed the results obtained in cells transfected with the CagA C-ter constructions showing that CagA antagonizes VacA-induced apoptosis. VacA toxin plays a role during H. pylori stomach colonization. However, once bacteria have colonized the gastric niche, the apoptotic action of VacA might be detrimental for the survival of H. pylori adherent to the mucosa. CagA association with VacA is thus a novel, highly ingenious microbial strategy to locally protect its

  1. Association of smoking, alcohol and NSAIDs use with expression of cag A and cag T genes of Helicobacter pylori in salivary samples of asymptomatic subjects

    Institute of Scientific and Technical Information of China (English)

    Pinaki Ghosh; Subhash Laxmanrao Bodhankar

    2012-01-01

    Objective:To determine the association of smoking, alcohol and nonsteroidal anti-inflammatory drugs (NSAIDs) use with presence and virulence of Helicobacter pylori (H. pylori) infection in a representative sample of a random adult population of asymptomatic subjects. Methods:Non virulent 16S rRNA and virulent cag A and T genes from salivary samples of 854 asymptomatic subjects were determined using polymerase chain reaction. The presence and absence of virulent and non virulent infection was statistically compared with consumption of smoking, alcohol and NSAIDs. Results:The prevalence of infection in male and female subjects was found to be 69.25%and 66.90%, respectively. The prevalence of infection in the population of asymptomatic subjects with respect to consumption of alcohol was as follows:current (31.22%), former (52.20%) and never (43.58%). The prevalence of infection in the population of asymptomatic subjects with respect to smoking of cigarettes was as follows:current (88.80%), former (57.14%) and never (33.33%). The prevalence of infection in the subject population consuming NSAIDs and not consuming NSAIDs frequently was found to be 82.75%and 21.16%, respectively. Virulence in male and female subjects was found to be 60.00%and 50.00%, respectively. The presence of virulent infection in the population of asymptomatic subjects with respect to consumption of alcohol was as follows:current (28.57%), former (40.15%) and never (50.00%). The prevalence of virulent infection in the population of asymptomatic subjects with respect to smoking of cigarettes was as follows:current (79.32%), former (75.00%) and never (50.00%). The prevalence of virulent infection in the subject population consuming NSAIDs and not consuming NSAIDs frequently was found to be 88.23%and 66.66%, respectively. Conclusions:It can be concluded that smoking and NSAIDs consumption are aggravating factors for virulence of H. pylori and alcohol can inhibit H. pylori infection in asymptomatic

  2. 幽门螺杆菌耐药性与cagA、VacA基因相关分析%Relationship between cagA and VacA genotypes of helicobacter pylori and drug resistance

    Institute of Scientific and Technical Information of China (English)

    许俊; 谢国艳

    2010-01-01

    目的 分析幽门螺杆菌的耐药性与cagA、VacA基因的关系.方法 将上消化道疾病患者胃窦部组织接种后培养,并进行药敏试验,PCR聚合酶链反应技术测定幽门螺杆菌的cagA、VacA基因,同时测患者血清抗体.结果81株敏感菌株cagA基因检出率77.8%,VacA基因检出率95.1%,58株耐药菌株cagA基因检出率38.8%,VacA基因检出率94.8%.结论 VacA基因与耐药性无关,耐药菌株中以不含cagA基因的HP菌株为主.

  3. An analysis of patients receiving emergency CAG without PCI and the value of GRACE score in predicting PCI possibilities in NSTE-ACS patients

    OpenAIRE

    Zhou, Bo-Da; Zu, Ling-Yun; Mi, Lin; WANG, GUI-SONG; Guo, Li-Jun; Gao, Wei

    2015-01-01

    Background There are patients who underwent emergency coronary angiography (CAG) but did not receive percutaneous coronary intervention (PCI). The aim of this study was to analyze these reasons. Methods This is a single-center retrospective study. We recruited 201 consecutive patients who received emergency CAG but did not receive PCI. To investigate the value of the Global Registry of Acute Coronary Events (GRACE) score in predicting PCI possibilities in non-ST segment elevation acute corona...

  4. Lower Circulating Levels of Chemokine CXCL10 In Helicobacter Pylori-Infected Patients with Peptic Ulcer: Influence of the Bacterial Virulence Factor CagA

    Directory of Open Access Journals (Sweden)

    Abdollah Jafarzadeh

    2013-03-01

    Full Text Available Background and objectives: Alterations in CXCL10 (a Th1 chemokine expression have been associated with various diseases. The aim of this study was to evaluate the serum CXCL10 levels in H. pylori-infected patients with peptic ulcer (PU and to determine its association with bacterial virulence factor cytotoxin-associated gene A (CagA. Materials and Methods: Serum samples from 90 H. pylori infected patients (70 were anti-CagA+, 20 were anti-CagA-, 65 asymptomatic (AS carriers (40 were anti-CagA+, 25 were anti-CagA- and 30 healthy H. pylori-negative subjects (as a control were tested for the concentrations of CXCL10 by using ELISA method. Results: The mean serum levels of CXCL10 in PU patients (96.64 ± 20.85 Pg/mL was significantly lower than those observed in AS subjects (162.16 ± 53.31 Pg/mL, P < 0.01 and control group (193.93 ± 42.14 Pg/mL, P < 0.02. In the PU group, the levels of CXCL10 in anti-CagA+ subjects was significantly higher in comparison to anti-CagA- patients (P<0.04. Conclusion: These results showed that the mean concentrations of CXCL10 in H. pylori-infected-PU patients was lower than AS carriers and control group. In the PU group, the serum levels of CXCL10 were affected by bacterial factor CagA.

  5. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  6. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  7. Construction and Expression of Helicobacter Pylori Virulence Factor CagA Prokaryotic Expression Vector%幽门螺杆菌细胞毒素相关蛋白CagA原核表达载体的构建及诱导表达

    Institute of Scientific and Technical Information of China (English)

    杨贵珍; 王易

    2012-01-01

    目的 构建幽门螺杆菌细胞毒素相关蛋白CagA的原核表达载体并诱导表达,为进一步利用此表达载体研究中药的抗幽门螺杆菌的机制提供物质条件.方法 以幽门螺杆菌基因组为模板,通过PCR体外扩增cagA基因,将cagA基因插入带绿色荧光蛋白标签的原核表达载体PET34b,利用含氨苄青霉素的LB平皿筛选阳性克隆子,以IPTG诱导含重组子PET34b-cagA的E.coli DH5α表达CagA蛋白.结果 PCR扩增出3 400 bp的DNA片段,SDS-PAGE电泳显示出有分子量128 kD的蛋白条带.结论 成功克隆并表达了幽门螺杆菌毒力因子CagA,为后续研究中药抗幽门螺杆菌奠定了物质基础.%Objective To construct the prokaryotic expression vector PET34b-cagA of H. pylori virulence factor CagA and induce the expression in order to further study the mechanism of Chinese medicines against H. pyloriMethods cagA gene of H. pylori was amplified by PCR. the cagA gene was inserted into expression vector PET34b, and LB plate containing ampicillin was used to screen positive clones. E. coli DH5α containing the positive recombinant PET34b-cagA was induced by IPTG to express CagA protein. Results 3 400 bp DNA fragment was amplified by PCR, and a 128 kDa protein band was displayed by SDS-PAGE electrophoresis. Conclusion The H. pylori virulence factor CagA was successfully cloned and expressed, which may provide a foundation for the study on Chinese medicines against H. pylori.

  8. Hydrogen Metabolism in Helicobacter pylori Plays a Role in Gastric Carcinogenesis through Facilitating CagA Translocation

    Science.gov (United States)

    Wang, Ge; Romero-Gallo, Judith; Benoit, Stéphane L.; Piazuelo, M. Blanca; Dominguez, Ricardo L.; Morgan, Douglas R.; Peek, Richard M.

    2016-01-01

    ABSTRACT A known virulence factor of Helicobacter pylori that augments gastric cancer risk is the CagA cytotoxin. A carcinogenic derivative strain, 7.13, that has a greater ability to translocate CagA exhibits much higher hydrogenase activity than its parent noncarcinogenic strain, B128. A Δhyd mutant strain with deletion of hydrogenase genes was ineffective in CagA translocation into human gastric epithelial AGS cells, while no significant attenuation of cell adhesion was observed. The quinone reductase inhibitor 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO) was used to specifically inhibit the H2-utilizing respiratory chain of outer membrane-permeabilized bacterial cells; that level of inhibitor also greatly attenuated CagA translocation into AGS cells, indicating the H2-generated transmembrane potential is a contributor to toxin translocation. The Δhyd strain showed a decreased frequency of DNA transformation, suggesting that H. pylori hydrogenase is also involved in energizing the DNA uptake apparatus. In a gerbil model of infection, the ability of the Δhyd strain to induce inflammation was significantly attenuated (at 12 weeks postinoculation), while all of the gerbils infected with the parent strain (7.13) exhibited a high level of inflammation. Gastric cancer developed in 50% of gerbils infected with the wild-type strain 7.13 but in none of the animals infected with the Δhyd strain. By examining the hydrogenase activities from well-defined clinical H. pylori isolates, we observed that strains isolated from cancer patients (n = 6) have a significantly higher hydrogenase (H2/O2) activity than the strains isolated from gastritis patients (n = 6), further supporting an association between H. pylori hydrogenase activity and gastric carcinogenesis in humans. PMID:27531909

  9. Helicobacter pylori vacA and cagA genotypes in patients from northeastern Brazil with upper gastrointestinal diseases

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    Meyssa Quezado de Figueiredo Cavalcante

    2012-06-01

    Full Text Available Helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. In this study, we evaluated the Helicobacter pylori vacA and cagA genotypes in patients from a Brazilian region where there is a high prevalence of gastric cancer. Polymerase chain reaction (PCR was used to investigate vacA mosaicism and cagA status in the gastric mucosa of 134 H. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. The s1m1 variant was the predominant vacA genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with H. pylori infection [p = 0.03, odds ratio (OR = 5.72, 95% confidence interval (CI = 1.15-38.60]. Furthermore, all of the s1 alleles were s1b. Mixed vacA m1/m2 strains were found more frequently in patients with gastric cancer and a cagA-positive status was significantly associated with gastric cancer (p = 0.016, OR = 10.36, 95% CI = 1.35-217.31. Patients with gastric cancer (21/21, 100%, p = 0.006 or peptic ulcers (20/21, 95%, p = 0.02 were more frequently colonised by more virulent H. pylori strains compared to gastritis patients (41/61, 67.2%. In conclusion, in the northeastern of Brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent H. pylori strains, carrying the cagA gene and s1m1 vacA alleles, predominates and is correlated with more severe H. pylori-associated diseases.

  10. Intragenic tandem repeats in Daphnia magna: structure, function and distribution

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    Du Pasquier Louis

    2009-10-01

    Full Text Available Abstract Background Expressed sequence tag (EST databases provide a valuable source of genetic data in organisms whose genome sequence information is not yet compiled. We used a published EST database for the waterflea Daphnia magna (Crustacea:Cladocera to isolate variable number of tandem repeat (VNTR markers for linkage mapping, Quantitative Trait Loci (QTL, and functional studies. Findings Seventy-four polymorphic markers were isolated and characterised. Analyses of repeat structure, putative gene function and polymorphism indicated that intragenic tandem repeats are not distributed randomly in the mRNA sequences; instead, dinucleotides are more frequent in non-coding regions, whereas trinucleotides (and longer motifs involving multiple-of-three nucleotide repeats are preferentially situated in coding regions. We also observed differential distribution of repeat motifs across putative genetic functions. This indicates differential selective constraints and possible functional significance of VNTR polymorphism in at least some genes. Conclusion Databases of VNTR markers situated in genes whose putative function can be inferred from homology searches will be a valuable resource for the genetic study of functional variation and selection.

  11. Recursive quantum repeater networks

    CERN Document Server

    Van Meter, Rodney; Horsman, Clare

    2011-01-01

    Internet-scale quantum repeater networks will be heterogeneous in physical technology, repeater functionality, and management. The classical control necessary to use the network will therefore face similar issues as Internet data transmission. Many scalability and management problems that arose during the development of the Internet might have been solved in a more uniform fashion, improving flexibility and reducing redundant engineering effort. Quantum repeater network development is currently at the stage where we risk similar duplication when separate systems are combined. We propose a unifying framework that can be used with all existing repeater designs. We introduce the notion of a Quantum Recursive Network Architecture, developed from the emerging classical concept of 'recursive networks', extending recursive mechanisms from a focus on data forwarding to a more general distributed computing request framework. Recursion abstracts independent transit networks as single relay nodes, unifies software layer...

  12. American College of Medical Genetics and Genomics Standards and Guidelines for Clinical Genetics Laboratories, 2014 edition: technical standards and guidelines for Huntington disease.

    Science.gov (United States)

    Bean, Lora; Bayrak-Toydemir, Pinar

    2014-12-01

    Huntington disease is an autosomal-dominant neurodegenerative disease of mid-life onset caused by expansion of a polymorphic trinucleotide (CAG) repeat. Variable penetrance for alleles carrying 36-39 repeats has been noted, but the disease appears fully penetrant when the repeat numbers are >40. An abnormal CAG repeat may expand, contract, or be stably transmitted when passed from parent to child. Assays used to diagnose Huntington disease must be optimized to ensure the accurate and unambiguous quantitation of CAG repeat length. This document provides an overview of Huntington disease and methodological considerations for Huntington disease testing. Examples of laboratory reports are also included.

  13. Alu repeats as markers for forensic DNA analyses

    Energy Technology Data Exchange (ETDEWEB)

    Batzer, M.A.; Alegria-Hartman, M. [Lawrence Livermore National Lab., CA (United States); Kass, D.H. [Louisiana State Univ., New Orleans, LA (United States)] [and others

    1994-01-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 98.9% nucleotide identity with the HS subfamily consensus sequence, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 inch and 3 inch unique flanking DNA sequences from each HS Alu that allow the locus to be assayed for the presence or absence of the Alu repeat. The dimorphic HS Alu sequences probably inserted in the human genome after the radiation of modem humans (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project. HS Alu family member insertions differ from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) in that polymorphisms due to Alu insertions arise as a result of a unique event which has occurred only one time in the human population and spread through the population from that point. Therefore, individuals that share HS Alu repeats inherited these elements from a common ancestor. Most VNTR and RFLP polymorphisms may arise multiple times in parallel within a population.

  14. The polymorphism of a variable number of tandem repeats in the endothelial nitric oxide synthase gene is associated with portal hypertension of liver cirrhosis in Chinese population%内皮型一氧化氮合酶基因VNTR多态性与肝硬化门脉高压症的相关性研究

    Institute of Scientific and Technical Information of China (English)

    程元桥; 王文琦; 林菊生; 熊平

    2004-01-01

    目的探讨内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)基因第4内含子数目可变性串联重复序列(variable number 0ftandem repeats polymorphism,VNTR)多态性与肝硬化门脉高压症的相关性.方法采用病例对照和聚合酶链反应(PCR)及非变性聚丙烯酰胺凝胶电泳的方法,检测106例乙肝后肝硬化患者和108名健康对照者eNOS基因第4内含子的VNTR多态性及外周血NO-2/NO3含量,并进行统计分析.结果乙肝后肝硬化患者a等位基因频率高于对照组(13.21%VS 8.8%),但差异无显著性意义;然而,在门脉高压a等位基因频率明显高于对照组,差异有显著性意义(14.62%VS 8.8,P<0.05),相关分析呈正相关(r=0.16).携带a等位基因者发生门脉高压症的危险性高于非a等位基因携带者1.2倍(OR=2.2).结论eNOS基因第4内含子的VNTR多态性与肝硬化门脉高压症形成相关,a等位基因可能是中国人群门脉高压症的遗传易感性的基因标志之一.

  15. Intragenic tandem repeat variation between Legionella pneumophila strains

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    Jarraud Sophie

    2008-12-01

    Full Text Available Abstract Background Bacterial genomes harbour a large number of tandem repeats, yet the possible phenotypic effects of those found within the coding region of genes are only beginning to be examined. Evidence exists from other organisms that these repeats can be involved in the evolution of new genes, gene regulation, adaptation, resistance to environmental stresses, and avoidance of the immune system. Results In this study, we have investigated the presence and variability in copy number of intragenic tandemly repeated sequences in the genome of Legionella pneumophila, the etiological agent of a severe pneumonia known as Legionnaires' disease. Within the genome of the Philadelphia strain, we have identified 26 intragenic tandem repeat sequences using conservative selection criteria. Of these, seven were "polymorphic" in terms of repeat copy number between a large number of L. pneumophila serogroup 1 strains. These strains were collected from a wide variety of environments and patients in several geographical regions. Within this panel of strains, all but one of these seven genes exhibited statistically different patterns in repeat copy number between samples from different origins (environmental, clinical, and hot springs. Conclusion These results support the hypothesis that intragenic tandem repeats could play a role in virulence and adaptation to different environments. While tandem repeats are an increasingly popular focus of molecular typing studies in prokaryotes, including in L. pneumophila, this study is the first examining the difference in tandem repeat distribution as a function of clinical or environmental origin.

  16. H pylori infection and systemic antibodies to CagA and heat shock protein 60 in patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    Cristina Lenzi; Fabio Rollo; Ranuccio Nuti; Natale Figura; Alberto Palazzuoli; Nicola Giordano; Giuliano Alegente; Catia Gonnelli; Maria Stella Campagna; Annalisa Santucci; Michele Sozzi; Panagiotis Papakostas

    2006-01-01

    AIM: To determine the overall prevalence of H pylori and CagA positive H pylori infection and the prevalence of other bacterial and viral causes of chronic infection in patients with coronary heart disease (CHD), and the potential role of anti-heat-shock protein 60 (Hsp60) antibody response to these proteins in increasing the risk of CHD development.METHODS: Eighty patients with CHD and 160 controls were employed. We also compared the levels of antiheat-shock protein 60 (Hsp60) antibodies in the two groups. The H pylori infection and the CagA status were determined serologically, using commercially available enzyme-linked immunosorbent assays (ELISA), and a Western blotting method developed in our laboratory.Systemic antibodies to Hsp60 were determined by a sandwich ELISA, using a polyclonal antibody to Hsp60 to sensitise polystyrene plates and a commercially available human Hsp60 as an antigen.RESULTS: The overall prevalence of H pylori infection was 78.7% (n = 63) in patients and 76.2% (n =122) in controls (P = 0.07). Patients infected by CagApositive (CagA+) H pylori strains were 71.4% (n = 45) vs 52.4% of infected controls (P = 0.030, OR = 2.27). Systemic levels of IgG to Hsp60 were increased in H pylorinegative patients compared with uninfected controls (P< 0.001) and CagA-positive infected patients compared with CagA-positive infected controls (P = 0.007).CONCLUSION: CagA positive H pylori infection may concur to the development of CHD; high levels of antiHsp60 antibodies may constitute a marker and/or a concomitant pathogenic factor of the disease.

  17. Prevalence and Correlation with Clinical Diseases of Helicobacter pylori cagA and vacA Genotype among Gastric Patients from Northeast China

    Directory of Open Access Journals (Sweden)

    Faisal Aziz

    2014-01-01

    Full Text Available Helicobacter pylori vacA and cagA genes have significant genetic heterogenicity, resulting in different clinical outcomes. Northeast part of China has reported high prevalence of H. pylori infections and gastric cancer. Hence, we investigated the H. pylori cagA and vacA genotypes with clinical outcomes in Northeast China. Gastric tissue samples (n=169, chronic gastritis (GIs, gastric ulcer (GU, and gastric cancer (GC were analysed for 16S rRNA ureA, cagA, and cagA genotypes by PCR. A total of 141 (84% cases were found positive for H. pylori by 16S rRNA and ureA. GC showed high H. pylori infection (93% compared with GIs (72% and GU (84%. The vacAs1am1 was highly found in GC (40% and GU (36%, vacAs1am2 in GIs (33%, vacAs1bm1 (14% and vacAs1bm2 (8% in GU cases, and s2m1 in normal cases (33%, while vacAs1cm1 showed low frequency in GIs (2% and GU (3% and GC showed negative result. The East-Asian cagA strain was highly observed in GC (43%, as compared to GIs (41% and GU (20%. The East-Asian cagA/vacAs1am1 was significantly higher in GC (23% than in GU (22% and GIs (145 patients. The East-Asian type cagA with vacAs1a and vacAm1 is the most predominant genotype in H. pylori strains of Northeast China.

  18. Prevalence of cagA and vacA among Helicobacter pylori-infected patients in Iran: a systematic review and meta-analysis.

    Science.gov (United States)

    Sayehmiri, Fatemeh; Kiani, Faezeh; Sayehmiri, Kourosh; Soroush, Setareh; Asadollahi, Khairollah; Alikhani, Mohammad Yousef; Delpisheh, Ali; Emaneini, Mohammad; Bogdanović, Lidija; Varzi, Ali Mohammad; Zarrilli, Raffaele; Taherikalani, Morovat

    2015-07-30

    The varieties of infections caused by Helicobacter pylori may be due to differences in bacterial genotypes and virulence factors as well as environmental and host-related factors. This study aimed to investigate the prevalence of cagA and vacA genes among H. pylori-infected patients in Iran and analyze their relevance to the disease status between two clinical groups via a meta-analysis method. Different databases including PubMed, ISI, Scopus, SID, Magiran, Science Direct, and Medlib were investigated, and 23 relevant articles from the period between 2001 and 2012 were finally analyzed. The relevant data obtained from these papers were analyzed by a random-effects model. Data were analyzed using R software and STATA. The prevalence of cagA and vacA genes among H. pylori-infected patients was 70% (95% CI, 64-75) and 41% (95% CI, 24.3-57.7), respectively. The prevalence of duodenal ulcers, peptic ulcers, and gastritis among cagA+ individuals was 53% (95% CI, 20-86), 65% (95% CI, 34-97), and 71% (95% CI, 59-84), respectively. Odds ratio (OR) between cagA-positive compared with cagA-negative patients showed a 1.89 (95% CI, 1.38-2.57) risk of ulcers. In conclusion, the frequency of cagA gene among H. pylori strains is elevated in Iran and it seems to be more frequently associated with gastritis. Therefore, any information about cagA and vacA prevalence among different H. pylori-infected clinical groups in the country can help public health authorities to plan preventive policies to reduce the prevalence of diseases associated with H. pylori infection.

  19. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  20. Honesty through repeated interactions.

    Science.gov (United States)

    Rich, Patricia; Zollman, Kevin J S

    2016-04-21

    In the study of signaling, it is well known that the cost of deception is an essential element for stable honest signaling in nature. In this paper, we show how costs for deception can arise endogenously from repeated interactions between individuals. Utilizing the Sir Philip Sidney game as an illustrative case, we show that repeated interactions can sustain honesty with no observable signal costs, even when deception cannot be directly observed. We provide a number of potential experimental tests for this theory which distinguish it from the available alternatives. PMID:26869213

  1. All-optical repeater.

    Science.gov (United States)

    Silberberg, Y

    1986-06-01

    An all-optical device containing saturable gain, saturable loss, and unsaturable loss is shown to transform weak, distorted optical pulses into uniform standard-shape pulses. The proposed device performs thresholding, amplification, and pulse shaping as required from an optical repeater. It is shown that such a device could be realized by existing semiconductor technology.

  2. Bidirectional Manchester repeater

    Science.gov (United States)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  3. Induction of TLR-2 and TLR-5 expression by Helicobacter pylori switches cagPAI-dependent signalling leading to the secretion of IL-8 and TNF-α.

    Directory of Open Access Journals (Sweden)

    Suneesh Kumar Pachathundikandi

    Full Text Available Helicobacter pylori is the causative agent for developing gastritis, gastric ulcer, and even gastric cancer. Virulent strains carry the cag pathogenicity island (cagPAI encoding a type-IV secretion system (T4SS for injecting the CagA protein. However, mechanisms of sensing this pathogen through Toll-like receptors (TLRs and downstream signalling pathways in the development of different pathologies are widely unclear. Here, we explored the involvement of TLR-2 and TLR-5 in THP-1 cells and HEK293 cell lines (stably transfected with TLR-2 or TLR-5 during infection with wild-type H. pylori and isogenic cagPAI mutants. H. pylori triggered enhanced TLR-2 and TLR-5 expression in THP-1, HEK293-TLR2 and HEK293-TLR5 cells, but not in the HEK293 control. In addition, IL-8 and TNF-α cytokine secretion in THP-1 cells was induced in a cagPAI-dependent manner. Furthermore, we show that HEK293 cells are not competent for the uptake of T4SS-delivered CagA, and are therefore ideally suited for studying TLR signalling in the absence of T4SS functions. HEK293 control cells, which do not induce TLR-2 and TLR-5 expression during infection, only secreted cytokines in small amounts, in agreement with T4SS functions being absent. In contrast, HEK293-TLR2 and HEK293-TLR5 cells were highly competent for inducing the secretion of IL-8 and TNF-α cytokines in a cagPAI-independent manner, suggesting that the expression of TLR-2 or TLR-5 has profoundly changed the capability to trigger pro-inflammatory signalling upon infection. Using phospho-specific antibodies and luciferase reporter assays, we further demonstrate that H. pylori induces IRAK-1 and IκB phosphorylation in a TLR-dependent manner, and this was required for activation of transcription factor NF-κB. Finally, NF-κB activation in HEK293-TLR2 and HEK293-TLR5 cells was confirmed by expressing p65-GFP which was translocated from the cytoplasm into the nucleus. These data indicate that H. pylori-induced expression

  4. Clinical and pathological importance of vacA allele heterogeneity and cagA status in peptic ulcer disease in patients from North Brazil

    Directory of Open Access Journals (Sweden)

    Luisa Caricio Martins

    2005-12-01

    Full Text Available We have examined the prevalence of gene cagA and vacA alleles in 129 patients, 69 with gastritis and 60 with peptic ulcer diseases from North Brazil and their relation with histopathological data. vacA and cagA genotype were determined by polymerase chain reaction. Hematoxylin-eosin staining was used for histological diagnosis. 96.6% of the patients were colonized by Helicobacter pylori strains harboring single vacA genotype (nont-mixed infection. Among them, 11.8% had subtype s1a, 67.8% had subtype s1b, and 17% subtype s2. In regard to the middle region analysis, m1 alleles were found in 75.4% and m2 in 21.2% of patients. The cagA gene was detected in 78% patients infected with H. pylori and was associated with the s1-m1 vacA genotype. The H. pylori strains, vacA s1b m1/cagA-positive, were associated with increased risk of peptic ulcer disease and higher amounts of lymphocytic and neutrophilic infiltrates and the presence of intestinal metaplasia. These findings show that cagA and vacA genotyping may have clinical relevance in Brazil.

  5. Detection of H pylori infection by ELISA and Western blot techniques and evaluation of anti CagA seropositivity in adult Turkish dyspeptic patients

    Institute of Scientific and Technical Information of China (English)

    (O)zlem Yilmaz; Nazime (S)en; Ahmet Ali Küpelio(g)lu; (I)lkay (S)im(s)ek

    2006-01-01

    AIM: To detect H pylori infection and to evaluate the anti CagA seropositivity in adult Turkish dyspeptic patients. METHODS: We evaluated anti-H pylori IgA, IgG and anti-CagA antibodies using commercial enzyme-linked immunoassay (ELISA) and Western blot in dyspeptic Turkish patients. H pylori status was determined by histology and rapid urease testing.RESULTS: Fifty-six patients were entered. Forty-eight (85.7%) out of the 56 patients were positive for H pylori.H pylori IgG seropositivity was 82.1%, IgA seropositivity 48.2%. CagA ELISA showed that IgG was positive in 50% and IgA in 30.4% of those with H pylori infections.Western blot showed that IgG seropositivity was 80.4%and IgA seropositivity 33.9%. Western blot detected IgG antibodies with reactivity to CagA in 50%, VacA in 62.5%, UreB in 87.5%, UreA in 80.4%, and OMP in 57.1%. None of the tests had a sensitivity and specificity above 80%.CONCLUSION: None of these commercial tests seems clinically useful for H pylori detection in adult dyspeptic patients, while Western blot can give seropositivity and determine anti-CagA, VacA virulence factor status of Turkish dyspeptic patients in the Izmir region.

  6. UreA and cagA genes of Helicobacter pylori in Egyptian patients with laryngeal squamous cell carcinoma and benign laryngeal polyps: a cohort study.

    Science.gov (United States)

    Barakat, Ghada; Nabiel, Yasmin; Ali, Omima; El-Nady, Ghada; Musaad, Ahmed; El-Sharkawy, Asser

    2016-10-01

    This work aims to estimate the prevalence of Helicobacter pylori ureA gene and evaluate cagA gene-positive strains in both patients of laryngeal squamous cell carcinoma (LSCC) and those with benign laryngeal polyps. This study included 49 patients confirmed pathologically to have LSCC and 15 patients with benign laryngeal polyps over a period from June 2013 to March 2015. Samples of laryngeal tissue were collected during direct laryngoscope under general anesthesia to be pathologically evaluated followed by analysis for H. pylori detection. Each laryngeal tissue sample was divided into three parts; one for bacteriological examination, the second for pathological examination and the third for PCR to detect both ureA and cagA genes. Out of 49 LSCC samples, 31 (64.6 %) was positive for ureA by PCR. Out of them, 29 samples (93.5 %) were cagA positive. Only three cases (20 %) of the benign laryngeal polyp were ureA positive by PCR and one of them was cagA positive by PCR. By the bacteriological culture, only eight samples (25.8 %) gave growth. All of them were ureA positive and only seven of them were cagA positive. There was a significant association between presence of H. pylori and LSCC as compared to benign laryngeal polyp which may contribute in the pathogenesis of laryngeal carcinoma. These results should be confirmed by further studies over larger number of cases.

  7. A yeast tRNA mutant that causes pseudohyphal growth exhibits reduced rates of CAG codon translation

    OpenAIRE

    Kemp, Alain J; Betney, Russell; Ciandrini, Luca; Schwenger, Alexandra C M; Romano, M. Carmen; Stansfield, Ian

    2012-01-01

    In Saccharomyces cerevisiae, the SUP70 gene encodes the CAG-decoding tRNAGln CUG. A mutant allele, sup70-65 , induces pseudohyphal growth on rich medium, an inappropriate nitrogen starvation response. This mutant tRNA is also a UAG nonsense suppressor via first base wobble. To investigate the basis of the pseudohyphal phenotype, 10 novel sup70 UAG suppressor alleles were identified, defining positions in the tRNAGln CUG anticodon stem that restrict first base wobble. However, none conferred p...

  8. cagA, vacA and iceA virulence genes of Helicobacter pylori isolates of children in Finland.

    Science.gov (United States)

    Karhukorpi, J; Yan, Y; Kolho, K L; Rautelin, H; Lahti, M; Sirviö, A; Riipinen, K; Lindahl, H; Verkasalo, M; Fagerholm, R; Karttunen, R

    2000-10-01

    cagA, vacA s and m genotypes and iceA alleles were analyzed from Helicobacter pylori strains isolated from 17 Finnish children and 32 children of non-Finnish origin living in Finland. Twelve children in the latter group were eastern European and 15 were of African origin. Only three children of non-Finnish origin were born in Finland. The vacA sla subtype was more prevalent in the isolates from Finnish children than African children (76% vs. 7%, Pchildren originating from different geographic regions, but the geographic variation of s1 subtypes resembled that described in other reports.

  9. P53 codon 11, 72, and 248 gene polymorphisms in endometriosis

    Directory of Open Access Journals (Sweden)

    Yao-Yuan Hsieh , Chich-Sheng Lin

    2006-01-01

    Full Text Available Objective: Mutated p53 gene is related to the instability of cell growth and cell cycle progression. We aimed to evaluate the association between endometriosis and p53 codon 11, 72 and 248 gene polymorphisms. Patients and methods: Women were divided into two groups: (1 moderate/severe endometriosis (n=148, and (2 non-endometriosis groups (n=150. P53 gene polymorphisms include codon11 Glu/Gln or Lys (GAG->CAG or AAG, codon 72 Arg/Pro (CGC->CCC, and codon 248 Arg/Thr (CGG->TCG. These gene polymorphisms were amplified by polymerase chain reaction and detected by electrophoresis after restriction enzyme (Taq I, BstU I, Hap II digestions. Associations between the endometriosis and p53 polymorphisms were evaluated. Results: The distributions of p53 codon 72 polymorphisms in both groups were significantly different. The proportions of Arg homozygotes/heterozygotes/Pro homozygotes in both groups were 9.5/66.2/24.3% and 30.7/50/19.3%. The proportions of Arg/Pro alleles were 42.6/57.4% and 56/44%. The distributions of p53 codon 11 and 248 polymorphisms in both groups were non-significantly different. All individuals appeared the wild genotypes (Glu11 and Arg248 homozygotes. Conclusion: Association between endometriosis and p53 codon 72 polymorphism exists. P53 codon 72*Pro-related genotype and allele are related with higher susceptibility of endometriosis. P53 codon 11 and 248 polymorphisms are not related with endometriosis susceptibility.

  10. Role of vacuolating cytotoxin VacA and cytotoxin-associated antigen CagA of Helicobacter pylori in the progression of gastric cancer.

    Science.gov (United States)

    Ki, Mi-Ran; Hwang, Meeyul; Kim, Ah-Young; Lee, Eun-Mi; Lee, Eun-Joo; Lee, Myeong-Mi; Sung, Soo-Eun; Kim, Sang-Hyeob; Lee, Hye Seung; Jeong, Kyu-Shik

    2014-11-01

    Helicobacter (H.) pylori strains that express the cagA and s1a vacA genes are associated with an increased risk for gastric cancer. Here, we examined the association between the products of these virulence genes with the development of gastric cancer by immunohistochemical staining of gastric biopsy specimens taken from 208 routine gastroscopies and 43 gastric cancer patients. The correlation was analyzed by multivariate logistic regression. CagA and VacA expressions in gastric mucosa were significantly associated with chronic gastritis (CG) and intestinal metaplasia (IM), respectively, accompanying CG independent of age. The association of CagA expression with IM accompanying CG was increased in patients over 50-year old (p subsequent progression of IM from CG with an increasing age. PMID:25038872

  11. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  12. High Frequency of cagA and vacA s1a/m2 Genotype among Helicobacter pylori Infected Gastric Biopsies of Pakistani Children

    Directory of Open Access Journals (Sweden)

    Ahmed, S.

    2011-01-01

    Full Text Available The vacuolating cytotoxin VacA and cytotoxin associated gene product CagA, encoded by vacA and cagA are major virulence determinants associated with pathogenesis of Helicobacter pylori. The presence and prevalence of two major H. pylori virulence associated genes among gastric biopsies of Pakistani children were investigated in the current study. Fifty one gastric biopsy specimens of children were analysed for 16S rRNA, vacA and cagA genes using PCR. The results showed that 21 (41.2% biopsies were positive for H. pylori as determined by 16S rRNA PCR. In the 21 H. pylori positive gastric biopsies, 19 (90.5% showed vacA s1a, 1 (4.75% was vacA s1b and 1 (4.75% was vacA s2 whereas, 5 (23.8% were vacA m1 and 16 (76.2% were vacA m2. None of the H. pylori positive biopsies carried vacA s1c subtype. The cagA gene was found in 13 (61.9% of H. pylori infected biopsies and different vacA combinations were found with or without cagA gene. H. pylori was detected with high frequency of cagA while vacA s1a and vacA m2 regions with vacA s1a/m2 genotype were predominant in H. pylori infected gastric biopsies of children.

  13. Effect observation and mechanism of low - dose decitabine combined with modified CAG therapeutic regimen in the treatment of patients with myelodysplastic syndrome(MDS)%低剂量地西他滨序贯改良 CAG 方案对治疗骨髓增生异常综合征的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    陈喜填; 夏维林; 林东; 王楚林; 张淳嘉; 吴桂香

    2016-01-01

    目的:探究低剂量地西他滨序贯改良 CAG 方案对治疗中高危骨髓增生异常综合征(Myelodysplastic syn-drome,MDS)的临床疗效。方法:随机抽取收治的中高危 MDS 患者96例,分为观察组46例及对照组患者50例,其中观察组患者采用低剂量地西他滨序贯 CAG 方案进行治疗,而对照组患者均采用 CAG 方案进行治疗,观察两组患者的临床疗效、不良反应的发生情况及处理结果。结果:观察组比对照组患者的疾病缓解率更高、疗效更显著,且两组比较差异具有统计学意义(P ﹤0.05)。结论:低剂量地西他滨序贯改良 CAG 方案治疗高危 MDS 比单用 CAG 方案疗效更明显、确切。%Objective The objection of the study was to investigate the clinical efficiencies and adverse reactions of treating the myelodysplastic syndrome(MDS)by using low - does decitabine combined with modified CAG therapeutic regimen. Method 96 high - risk MDS patients were randomly selected,they were divided into observation group with 46 cases and control group with 50 cases. The observation group was treated with low - dose decitabine combined with modified CAG therapeutic regimen, while the control group was treated with CAG therapeutic regimen. Clinical efficacy,adverse reactions and treatment results of each group were observed and analyzed. Results The remission rate was higher and the curative effect was more significant of ob-servation group when compared with control group,the difference between two groups has statistical significance( P ﹤ 0. 05) . Conclusion The effect of high risk MDS in treatment with low dose of decitabine combined with modified CAG therapeutic regi-ment is more significance than treated with CAG therapeutic regimen.

  14. Genetic polymorphisms of short tandem repeat D21S1411 and D21S1413 loci in the fetuses of Tianjin%天津市汉族胎儿D21S1411和D21S1413STR基因座遗传多态性的研究

    Institute of Scientific and Technical Information of China (English)

    孙立娟; 李晓洲; 史云芳; 李岩; 岳天孚; 张颖

    2011-01-01

    目的:调查天津市汉族胎儿21号染色体上D21S1411和D21S1413短串联重复序列(STR)的遗传多态性,获取群体遗传学数据,为其应用于产前诊断提供依据.方法:选取211例产前诊断样本,提取DNA,复合扩增D21S1411和D21S1413 STR基因座,非变性聚丙烯酰胺凝胶电泳,分析扩增产物.用PowerState V12软件分析群体遗传学指标.结果:D21S1411 STR基因座共发现9种等位基因,45种基因型.D21S1413 STR基因座共发现7种等位基因,28种基因型.D21S1411基因座的观察杂合度(Ho)、多态信息含量(PIC)、个体识别率(DP)和非父排除率(PE)分别为75.4%、0.85%、0.967%、0.516%.D21S1413基因座的Ho、PIC、DP、PE分别为87.2%、0.82%、0.947%、0.739%.D21S1411和D21S1413 2个STR基因座累计PIC为0.973,累计DP为0.998,累计PE为0.874.结论:D21S1411和D21S1413 STR基因座均符合Hardy-Weinberg平衡定律,在天津市汉族胎儿群体中具有较高的杂合度和多态信息含量,可用于唐氏综合征的基因诊断和产前基因诊断.%Objective: To investigate the genetic polymorphism distribution of D21S1411 and D21S1413 located on chromosome 21 in the fetuses of Tianjin and provided a preliminary database for prenatal diagnosis. Methods: A total of 211 samples with prenatal diagnosis from unrelated fetuses were collected. Multiplex polymerase chain reaction involving D21S1411 and D21S1413 loci was conducted. Non- degeneration polyacrlamide gel electrophoresis was performed to detect the amplification products. Data of population genetics was obtained by using PowerStatsV12 software. Result: Nine alleles and 45 genotypes of D21S1411 loci and 7 alleles and 28 genotypes of D21S1413 loci were observed. The values of Ho, PIC, DP, PE of D21S1411 were 0.75, 0.85, 0.967 and 0.516, respectively. The values of Ho, PIC, DP, PE of D21S1413 were 0.87, 0.82, 0.947,0. 739, respectively. The cumulative PIC, DP, PE of ID21S1411 and D21S1413 loci were 0. 973, 0. 998, 0

  15. Genetic polymorphisms of seventeen Y-chromosomal short tandem repeats loci in She nationality of Fujian province%福建畲族17个染色体短串联重复序列基因座遗传多态性

    Institute of Scientific and Technical Information of China (English)

    滕少康; 曹林枝; 林燕燕; 陈桐君; 郭月丽

    2012-01-01

    目的:调查Y染色体17个短串联重复序列(Y-STR)基因座的多态性及其单倍型在福建畲族人群的分布情况.方法:应用AmpFlSTR(@)YfilerTM荧光标记复合扩增系统,对福建畲族152名无关男性个体血液样本进行17个Y-STR位点的复合扩增,应用ABI PRISM 310遗传分析仪对扩增产物进行检测分析.结果:DYS456、DYS389 Ⅰ、DYS390、DYS389Ⅱ、DYS458、DYS19、DYS385a\\b、DYS393、DYS391、DYS439、DYS635、DYS392、Y-GATA-H4、DYS437、DYS438、DYS448各位点遗传多样性(gene diversity,GD值)分布在0.419 6~0.944 7之间.17个Y-STR位点共同构成的单倍型150种,其单倍型多样性为0.999 825 7.结论:福建畲族17个Y-STR位点具有丰富的遗传多样性,可为父权鉴定和父系进化研究提供有价值的遗传学资料.%Objective: To investigate the Allelic and haplotype frequency distribution of seventeen short tandem repeat (STR) loci of Y chromosome in She nationality in Fujian province. Methods: Seventeen Y-STR loci, of which the template DNAs were extracted from blood samples of 152 unrelated male individuals in She population of Fujian province, were amplified by using the AmpFlSTR(R) Yfiler TM. The PCR products were genotyped with ABI PRISM 310 genetic analyzer. Results: The Gene diversity ranged from 0. 419 6-0. 944 7 at DYS456, DYS389 Ⅰ , DYS390, DYS389 Ⅱ , DYS458, DYS19, DYS385a\\b, DYS393, DYS391, DYS439, DYS635, DYS392, Y-GATA-H4, DYS437, DYS438, DYS448. A total of 150 different hap-lotypes were observed. The haplotype diversity value calculated from all 17 loci combined was 0. 999 825 7. Conclusion: The 17 Y-STR loci in She population of Fujian province are highly affluent genetic polymorphic and can offer valuable genetic data for paternity testing and paternal genetic lineages evolution.

  16. 成都地区汉族人群17个Y短串联重复序列基因座遗传多态性分析%Analysis of the genetic polymorphism of 17 Y-chromosomal short tandem repeat loci in the Han population in Chengdu

    Institute of Scientific and Technical Information of China (English)

    宋兴勃; 范红; 应斌武; 陆小军; 王军; 叶远馨

    2009-01-01

    Objective To obtain the population genetic data of 17 Y-chromosomal short tandem repeat (Y-STR) in the Han population in Chengdu of Sichuan Province. Methods The 17 Y-STR loci were amplified from the blood samples of 111 unrelated Chengdu Han individuals using the AmpF1STR~(R)Yfiler~(TM) system. The PCR products were genotyped with an ABI 3130 genetic analyzer. Results In the loci of in DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635, DYS392, Y-GATA-H4, DYS437, DYS438, and DYS448, 3 to 8 alleles were detected in the Han population in Chengdu, and 36 alleles were detected in the locus DYS385a/b, with the minimal gene diversity (GD) value of 0.3970 (DYS391) and maximal value of 0.9561 (DYS385a/b). The DNA samples of 16 women and 7 different species of animals were amplified, but no specific products were found for the 17 Y-STR loci. No mutations of the 17 Y-STR alleles were observed in 20 father-son pairs as confirmed by autosomal STR analysis. Conclusion The 17 Y-STR loci are highly polymorphic and are suitable for personal identification, paternity testing, population genetics and anthropology studies.%目的 获得17个Y染色体短串联重复序列(Y-STR)基因座在成都汉族人群中的群体遗传学数据.方法 应用AmpFISTR(R)Yfiler~(TM)荧光标记复合扩增系统,对成都地区111名无关男性个体血样进行17个Y-STR基因座的复合扩增,用ABl3130遗传分析仪对扩增产物进行检测分析.结果 DYS456、DYS389 Ⅰ、DYS390、DYS389 Ⅱ、DYS458、DYS19、DYS385a/b、DYS393、DYS391、DYS439、DYS635、DYS392、Y-GATA-H4、DYS437、DYS438、DYS448基因座在成都地区汉族群体分别检出3~8个等位基因,DYS385a/b检出36个等位基因组,各基因座基因多样性最低为0.3970(DYS391),最高为0.9561(DYS385a/b).检测16例女性血样和7种动物血样,17个Y-STR基因座均无扩增产物.另对20个二代父性家系调查显示同一家系成员17个Y-STR基因座单倍

  17. 广西毛南族17个Y染色体短串联重复序列基因座遗传多态性%Genetic polymorphisms of seventeen Y-chromosomeal short tandem repeats loci in Maonan nationality in Guangxi province

    Institute of Scientific and Technical Information of China (English)

    滕少康; 曹林枝; 黄世宁; 黄昌盛; 侯一平

    2009-01-01

    目的:调查17个Y染色体短串联重复序列(Y-STR)基因座及其单倍型在广西毛南族人群中的分布情况.方法:应用AmpFlSTR~((R)) Yfiler~(TM)荧光标记复合扩增系统,对毛南族208名无关男性个体血样进行17个Y-STR位点的复合扩增,用ABI PRISM310遗传分析仪对扩增产物进行检测分析.结果:DYS456、 DYS389Ⅰ、 DYS390、 DYS389Ⅱ、 DYS458、 DYS19、 DYS385a\\b、 DYS393、 DYS391、 DYS439、 DYS635、 DYS392、 Y-GATA-H4、 DYS437、 DYS438、 DYS448各位点遗传多样性(GD值)分布在0 5852~0 9770之间.17个Y-STR位点共同构成的单倍型205种,其单倍型多样性为0 999785.广西毛南族与其他群体的Y-STR位点等位基因分布差异具有统计学意义.结论:广西毛南族17个Y-STR位点具有丰富的遗传多样性,可为父权鉴定和父系进化研究提供有价值的遗传学资料.%Objective:To investigate the Allelic and haplotype frequency distribution of seventeen short tandem repeat loci of Y chromosome in Maonan nationality in Guangxi province. Methods:Seventeen Y-STR loci, of which the template DNAs were extracted from blood samples of 184 unrelated male individuals in Maonan population, were amplified by using the AmpFISTR~((R)) Yfiler~(TM) The PCR products were genotyped with ABI PRISM 310 genetic analyzer. Results:The gene diversity ranged from 0.585 2 to 0.977 0 at DYS456, DYS389 Ⅰ , DYS390, DYS389 Ⅱ , DYS458, DYS19, DYS385a\\b, DYS393, DYS391, DYS439, DYS635, DYS392, Y-GATA-H4, DYS437, DYS438 and DYS448. A total of 205 different haplotypes were observed. The haplotype diversity value calculated from all 17 loci combined was 0. 999 785. The significant difference of the allelic frequency distribution in Y-STR loci was observed between Maonan population and other observed populations. Conclusion:The 17 Y-STR loci in Maonan population of Guangxi province are highly affluent genetic polymorphic and can offer valuable genetic data for paternity testing and

  18. Analysis of Polymorphism in 54 bp Variable Number Tandem Repeat of Period3 Gene of Children with Attention Deficit Hyperactivity Disorder%注意缺陷多动障碍患儿Period3基因可变数目串联重复序列多态性分析

    Institute of Scientific and Technical Information of China (English)

    曹银利; 石太新; 唐成和; 常晓

    2012-01-01

    Objective To investigate the association between polymorphism in 54 bp - variable number tandem repeat( VNTR) of Period3 (Per3) gene exon 18 and the susceptibility of attention deficit hyperactivity disorder (ADHD) and related sleep disturbances in Chinese Han children. Methods From Aug. 2005 to May 2010,166 unrelated children with ADHD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders IV criteria were recruited from the First Affiliated Hospital of Xinxiang Medical University. One hundred and fifty healthy children were selected as healthy control group. The Sleep Disturbance Scale for Children (SDSC) was used to assess the sleep disturbance in ADHD group. Fifty - four bp - VNTR genotyping results were obtained through polymerase chain reaction method in the both groups. The children in ADHD group were divided into ADHD with sleep disturbance group and ADHD without sleep disturbance group according SDSC. And the genotype and allele frequencies were analyzed. Results The genotype distribution in 54 bp - VNTR between ADHD group and healthy control group was not different (P, >0. 05). However, there was significant difference between ADHD with sleep disturbance group and ADHD without sleep disturbance group,and the Per33 allele frequency was significantly higher in ADHD patients with obvious sleep disturbance compared that in ADHD patients without sleep disturbance (x2 = 15. 028, P < 0. 001; OR = 2.760,95% CI; 1. 635 - 4. 658). Conclusions There is no association between the Per3 gene 54 bp - VNTR polymorphism and ADHD susceptibility, but the ADHD children with Per3 allele are susceptible to sleep disturbance.%目的 探讨Period3 (Per3)基因18号外显子54 bp可变数目串联重复(VNTR)序列多态性与中国汉族儿童注意缺陷多动障碍(ADHD)伴睡眠障碍的相关性.方法 选取2005年8月-2010年5月在本科就诊、符合美国《精神障碍诊断与统计手册(第4版)》诊断标准的166

  19. Serotonin transporter gene polymorphisms in irritable bowel syndrome and their impact on tegaserod treatment

    Institute of Scientific and Technical Information of China (English)

    李瑜元

    2006-01-01

    Objective To investigate the serotonin reuptake transporter (SERT) genetic polymorphisms in the 5 -hydroxytryptamine (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) and the variable number tandem repeats (VNTRs) in intron 2 among Chinese people, and their relationship to the pathogenesis of irritable bowel syndrome (IBS);and to investigate the im-

  20. 慢性胃炎和消化性溃疡中幽门螺杆菌babA2和cagA及vacA基因型分析%Analysis of babA2,cagA and vacA genotypes of Helicobacter pylori in chronic gastritis and peptic ulcer

    Institute of Scientific and Technical Information of China (English)

    茅海燕; 方平楚; 叶少菁; 尤建飞; 朱永良; 俞建国

    2003-01-01

    目的:研究慢性胃炎和消化性溃疡中幽门螺杆菌(Hp)babA2、cagA、vacA基因型的分布,探讨Hp babA2、cagA、vacA基因型与慢性胃炎和消化性溃疡的关系.方法:用聚合酶链反应测定58株从浙江省慢性胃炎和消化性溃疡患者中分离的Hp babA2基因、cagA基因和vacA基因亚型.结果:58株Hp中babA2、cagA、vacA s1a、vacA m1、vacA m2基因的阳性率分别为87.9%、100%、93.1%、1.7%、65.5%.慢性胃炎和消化性溃疡患者感染的Hp babA2、vacA s1a、vacA m2基因阳性率差异无显著性(P>0.05).结论:从浙江地区慢性胃炎和消化性溃疡患者中分离的Hp babA2、cagA、vacA基因型均以babA2阳性、cagA阳性和vacA s1a/m2型为主,未发现Hp babA2、cagA和vacA基因型与慢性胃炎和消化性溃疡的关系.

  1. Intensional Effect Polymorphism

    OpenAIRE

    Long, Yuheng; Liu, Yu David; Rajan, Hridesh

    2015-01-01

    Type-and-effect systems are a powerful tool for program construction and verification. We describe intensional effect polymorphism, a new foundation for effect systems that integrates static and dynamic effect checking. Our system allows the effect of polymorphic code to be intensionally inspected through a lightweight notion of dynamic typing. When coupled with parametric polymorphism, the powerful system utilizes runtime information to enable precise effect reasoning, while at the same time...

  2. Polymorphous computing fabric

    Science.gov (United States)

    Wolinski, Christophe Czeslaw; Gokhale, Maya B.; McCabe, Kevin Peter

    2011-01-18

    Fabric-based computing systems and methods are disclosed. A fabric-based computing system can include a polymorphous computing fabric that can be customized on a per application basis and a host processor in communication with said polymorphous computing fabric. The polymorphous computing fabric includes a cellular architecture that can be highly parameterized to enable a customized synthesis of fabric instances for a variety of enhanced application performances thereof. A global memory concept can also be included that provides the host processor random access to all variables and instructions associated with the polymorphous computing fabric.

  3. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-08-01

    The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques for duct leakage using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards. The three duct leak measurement methods assessed in this report are the two duct pressurization methods that are commonly used by many practitioners and the DeltaQ technique. These are methods B, C and A, respectively of the ASTM E1554 standard. Although it would be useful to evaluate other duct leak test methods, this study focused on those test methods that are commonly used and are required in various test standards, such as BPI (2010), RESNET (2014), ASHRAE 62.2 (2013), California Title 24 (CEC 2012), DOE Weatherization and many other energy efficiency programs.

  4. Molecular phylogeny analysis of full-length vacA and cagA genesfrom Helicobacter pylori%幽门螺杆菌vacA 和cagA 基因全长分子系统发育分析

    Institute of Scientific and Technical Information of China (English)

    杨泽民; 陈蔚文

    2012-01-01

    All amino acid full-length sequences of VacA and CagA proteins from Helicobacter pylori strains including vacA and cagA genes were downloaded from GenBank. Molecular phylogenic trees of VacA and CagA were constructed by ClastalX 2.0 and MEGA 5.05 software to understand phylogenetic relationships of vacA and cagA genes, clinical infection effects, and genotype characteristics of different clustering groups. The results showed that the phylogenetic trees of VacA and CagA recapitulated the same three-clustering groups, i.e., East Asia group 1 and 2 and Western group, and all H. pylori strains had similar distribution. The strains of East Asia group 1 were significantly higher in patients with atrophic gastritis. Genotype vacA contained mainly s1c/m1b ands1a/m1b, while genotype cagA was mostly EPIYA-ABD. The strains of East Asia group 2 were higher in patients with duodenal ulcer. Genotype vacA was mainly slc/m2 and sla/m2, while genotype cagA was mostly EPIYA-AB'C. The strains of Western group were higher in patients with duodenal ulcer and chronic gastritis than with atrophic gastritis. Genotype vacA was mainly s1a/m1a and s1b/m1a, while genotype cagA was mostly EPIYA-AB/B'CC. All of these results illustrated that there might be inheritant relationship of coevolution between vacA and cagA genes; East Asia group 1 and 2 and Western group had different vacA and cagA sub-genotypes, which had close relationship to its clinical infection effects. It might be necessary to deeply analyze vacA and cagA sub-genotypes in the research of H. pylori-related diseases.%文章从GenBank 中下载所有含有vacA 和cagA 基因的H.pylori 菌株的VacA 和CagA全长氨基酸序列,利用ClastalX 2.0 和MEGA 5.05 软件构建VacA 和CagA 分子系统发育树,探讨两基因之间的分子系统发育关系和不同聚类群的临床感染结果与基因型特征.结果显示,VacA 和CagA 具有高度相似的分子系统发育树,并且所有H.pylori 菌株在系统发育树中具

  5. Repeat Customer Success in Extension

    Science.gov (United States)

    Bess, Melissa M.; Traub, Sarah M.

    2013-01-01

    Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

  6. The importance of vacA, cagA, and iceA genotypes of Helicobacter pylori infection in peptic ulcer disease and gastroesophageal reflux disease

    NARCIS (Netherlands)

    Arents, NLA; van Zwet, AA; Thijs, JC; Kooistra-Smid, AMD; van Slochteren, KR; Degener, JE; Kleibeuker, JH; van Doorn, LJ

    2001-01-01

    OBJECTIVE: To study the relationship between the presence of H. pylori virulence factors and clinical outcome in H. pylori infected patients. METHODS: DNA was isolated from an antral biopsy sample and vacA, cagA, and iceA genotype were determined by PCR and a reverse hybridization technique in 183 p

  7. Lack of correlation of vacA genotype, cagA gene of Helicobacter pylori and their expresson products with various gastroduodenal diseases%幽门螺杆菌vacA基因型、cagA基因及其表达产物与不同类型胃十二指肠疾病的关系

    Institute of Scientific and Technical Information of China (English)

    张尤历; 刘厚钰; 周康

    2001-01-01

    Abstract:Objective To investigate the correlation among vacA genotypes, cagA gene, VacA, serum CagA antibodies of Helicobacter pylori (H. pylori) and gastroduodenal diseases. Methods vacA genotypes and cagA gene of 62 H. pylori strains isolated from patients with chronic gastritis, peptic ulcer and gastric cancer were tested by polymerase chain reaction, and Hela cell assay for VacA activity in vitro. Serum CagA antibodies were measured by EIA method in the same patients.Results All 62 H. pylori strains possessed the vacA gene and vacA genotypes of all strains were type s1a/m2. Total positive rate of cagA gene was 56.45%; the positive rates of cagA gene of H. pylori strains isolated from patients with chronic gastritis, peptic ulcer and gastric cancer were 55.56%, 54.17% and 63.64%, respectively (P>0.05). The total positive rate of VacA was 37.10%; the positive rates of VacA produced by H. pylori strains isolated from patients with chronic gastritis, peptic ulcer and gastric cancer were 33.33%, 29.17% and 63.64%, respectively (P>0.05). The positive rates of CagA antibodies in patients with chronic gastritis, peptic ulcer and gastric cancer were 70.37%, 79.17% and 40.00%, respectively (P>0.05). The total positive rate of CagA antibodies was 68.85%.Conclusion There was no correlation among cagA gene and vacA genotypes of H. pylori, VacA, serum CagA antibodies and various gastroduodenal diseases.%目的研究幽门螺杆菌vacA基因型、cagA基因,空泡形成细胞毒素和血清CagA抗体与胃十二指肠疾病的关系.方法应用多聚酶链反应方法对62例慢性胃炎、消化性溃疡和胃癌患者分离获得幽门螺杆菌菌株的vacA基因型和cagA基因进行测定;应用Hela细胞方法测定体外空泡形成细胞毒素活性;应用酶免疫测定方法检测同一患者的血清CagA抗体.结果 62株幽门螺杆菌菌株均具有vacA基因,所有菌株的vacA基因型均为sla/m2型.cagA基因的总阳性率为56.45%;慢性胃炎、消化

  8. Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of Western-type Helicobacter pylori strains.

    Directory of Open Access Journals (Sweden)

    Judith Lind

    Full Text Available The clinical outcome of Helicobacter pylori infections is determined by multiple host-pathogen interactions that may develop to chronic gastritis, and sometimes peptic ulcers or gastric cancer. Highly virulent strains encode a type IV secretion system (T4SS that delivers the effector protein CagA into gastric epithelial cells. Translocated CagA undergoes tyrosine phosphorylation at EPIYA-sequence motifs, called A, B and C in Western-type strains, by members of the oncogenic Src and Abl host kinases. Phosphorylated EPIYA-motifs mediate interactions of CagA with host signaling factors--in particular various SH2-domain containing human proteins--thereby hijacking multiple downstream signaling cascades. Observations of tyrosine-phosphorylated CagA are mainly based on the use of commercial phosphotyrosine antibodies, which originally were selected to detect phosphotyrosines in mammalian proteins. Systematic studies of phosphorylated EPIYA-motif detection by the different antibodies would be very useful, but are not yet available. To address this issue, we synthesized phospho- and non-phosphopeptides representing each predominant Western CagA EPIYA-motif, and determined the recognition patterns of seven different phosphotyrosine antibodies in Western blots, and also performed infection studies with diverse representative Western H. pylori strains. Our results show that a total of 9-11 amino acids containing the phosphorylated EPIYA-motifs are necessary and sufficient for specific detection by these antibodies, but revealed great variability in sequence recognition. Three of the antibodies recognized phosphorylated EPIYA-motifs A, B and C similarly well; whereas preferential binding to phosphorylated motif A and motifs A and C was found with two and one antibodies, respectively, and the seventh anti-phosphotyrosine antibody did not recognize any phosphorylated EPIYA-motif. Controls showed that none of the antibodies recognized the corresponding non

  9. A Brief Review of Short Tandem Repeat Mutation

    Institute of Scientific and Technical Information of China (English)

    Hao Fan; Jia-You Chu

    2007-01-01

    Short tandem repeats (STRs) are short tandemly repeated DNA sequences that involve a repetitive unit of 1-6 bp. Because of their polymorphisms and high mutation rates, STRs are widely used in biological research. Strand-slippage replication is the predominant mutation mechanism of STRs, and the stepwise mutation model is regarded as the main mutation model. STR mutation rates can be influenced by many factors. Moreover, some trinucleotide repeats are associated with human neurodegenerative diseases. In order to deepen our knowledge of these diseases and broaden STR application, it is essential to understand the STR mutation process in detail. In this review, we focus on the current known information about STR mutation.

  10. Comparison of three PCR methods for detection of Helicobacter pylori DNA and detection of cagA gene in gastric biopsy specimens

    Institute of Scientific and Technical Information of China (English)

    SI Smith; AO Coker; KS Oyedeji; AO Arigbabu; F Cantet; F Megraud; OO Ojo; AO Uwaifo; JA Otegbayo; SO Ola

    2004-01-01

    AIM: To comparatively evaluate PCR and other diagnostic methods (the rapid urease test and / or culture) in order to determine which of the three PCR methods (ureA, glmM and 26-kDa, SSA gene) was most appropriate in the diagnosis of Helicobacter pylori (Hpylori) infection and also to evaluate the detection of a putative virulence marker of H pylori, the cagA gene, by PCR in biopsy specimens.METHODS: One hundred and eighty-nine biopsy specimens were collected from 63 patients (three biopsies each)undergoing upper gastroduodenal endoscopy for various dyspeptic symptoms. The PCR methods used to detect H pylori DNA directly from biopsies were the glmM, 26-kDa,ureA and then cagA was used to compare the culture technique and CLO for urease with the culture technique being used as the gold standard.RESULTS: Thirty-five percent of the biopsies were positive for Hpylori DNA using the 3 PCR methods, while 68% of these were positive for the cagA gene. Twenty-four percent of the biopsies were negative for H pylori DNA in all PCR methods screened. The remaining 41% were either positive for ureA gene only, glmMonly, 26-kDa only, or ureA + glmM,ureA + 26-kDa, glmM + 26-kDa. Out of the 35% positive biopsies, 41% and 82% were positive by culture and CLO respectively, while all negative biopsies were also negative by culture and cagA. Cag A+ infection was also predominantly found in Hpylori DNA of the biopsies irrespective of the clinical diagnosis.CONCLUSION: This method is useful for correctly identifying infections caused by H pylori and can be easily applied in our laboratory for diagnostic purposes.

  11. Disruption of cagA, the apoprotein gene of chromoprotein antibiotic C-1027, eliminates holo-antibiotic production, but not the cytotoxic chromophore.

    Science.gov (United States)

    Cui, Zhihui; Wang, Lifei; Wang, Songmei; Li, Guangwei; Hong, Bin

    2009-11-01

    C-1027 is a chromoprotein of the nine-membered enediyne antitumour antibiotic family, comprising apoprotein to stabilize and transport the enediyne chromophore. The disruption of apoprotein gene cagA within the C-1027 biosynthetic gene cluster abolished C-1027 holo-antibiotic production detected by an antibacterial assay, as well as the expression of the apoprotein and C-1027 chromophore extracted following protein precipitation of the culture supernatant. Complementation of the cagA-disrupted mutant AKO with the intact cagA gene restored C-1027 production, suggesting that cagA is indispensable for holo-antibiotic production. Overexpression of cagA in the wild-type strain resulted in a significant increase in C-1027 production as expected. Surprisingly, electrospray ionization (ESI)-MS and ESI-MS/MS analyses suggested that the AKO mutant still produced the C-1027 enediyne chromophore [m/z=844 (M+H)(+)] and its aromatized product [m/z=846 (M+H)(+)]. Consistent with this, the results from gene expression analysis using real-time reverse transcriptase-PCR showed that transcripts of the positive regulator sgcR3 and the structural genes sgcA1, sgcC4, sgcD6 and sgcE were readily detected in the AKO mutant as well as in the wild-type and the complementation strain. These results provided, for the first time, evidence suggesting that the apoprotein of C-1027 is not essential in the self-resistance mechanism for the enediyne chromophore. PMID:19845765

  12. Expression of cytokeratins in Helicobacter pylori-associated chronic gastritis of adult patients infected with cagA + strains: An immunohistochemical study

    Institute of Scientific and Technical Information of China (English)

    Vera Todorovic; Aleksandra Sokic-Milutinovic; Neda Drndarevic; Marjan Micev; Olivera Mlitrovic; Ivan Nikolic; Thomas Wex; Tomica Milosavljevic; Peter Malfertheiner

    2006-01-01

    AIM: To investigate the expression of different cytokeratins (CKs) in gastric epithelium of adult patients with chronic gastritis infected with Helicobacter pylori(H pylori) cagA + strains.METHODS: The expression of CK 7, 8, 18, 19 and 20 was studied immunohistochemically in antral gastric biopsies of 84 patients. All the CKs were immunostained in cagA +H pylori gastritis (57 cases), non-Hpylori gastritis (17 cases) and normal gastric mucosa (10 cases).RESULTS: In cagA+ Hpylori gastritis, CK8 was expressed comparably to the normal antral mucosa from surface epithelium to deep glands. Distribution of CK18 and CK 19 was unchanged, i.e. transmucosal,but intensity of the expression was different in foveolar region in comparison to normal gastric mucosa. Cytokeratin 18 immunoreactivity was significantly higher in the foveolar epithelium of H pylori-positive gastritis compared to both Hpylori-negative gastritis and controls.On the contrary, decrease in CK19 immunoreactivity occurred in foveolar epithelium of H pylori-positive gastritis. In both normal and inflamed antral mucosa without H pylori infection, CK20 was expressed strongly/ moderately and homogenously in surface epithelium and upper foveolar region, but in H pylori-induced gastritis significant decrease of expression in foveolar region was noted. Generally, in both normal antral mucosa and H pylori-negative gastritis, expression of CK7 was not observed, while in about half cagA+ H pylori-infected patients, moderate focal CK7 immunoreactivity of the neck and coiled gland areas was registered, especially in areas with more severe inflammatory infiltrate.CONCLUSION: Alterations in expression of CK 7, 18,19 and 20 together with normal expression of CK8 occur in antral mucosa of H pylori-associated chronic gastritis in adult patients infected with cagA+ strains. Alterations in different cytokeratins expression might contribute to weakening of epithelial tight junctions observed in H pylori-infected gastric mucosa.

  13. Helicobacter pylori iceA, clinical outcomes, and correlation with cagA: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Seiji Shiota

    Full Text Available BACKGROUND: Although the iceA (induced by contact with epithelium allelic types of Helicobacter pylori have been reported to be associated with peptic ulcer, the importance of iceA on clinical outcomes based on subsequent studies is controversial. The aim of this study was to estimate the magnitude of the risk for clinical outcomes associated with iceA. METHODS: A literature search was performed using the PubMed and EMBASE databases for articles published through April 2011. Published case-control studies examining the relationship between iceA and clinical outcomes (gastritis, peptic ulcer, including gastric ulcer and duodenal ulcer, and gastric cancer were included. RESULTS: Fifty studies with a total of 5,357 patients were identified in the search. Infection with iceA1-positive H. pylori increased the overall risk for peptic ulcer by 1.26-fold (95% confidence interval [CI], 1.09-1.45. However, the test for heterogeneity was significant among these studies. Sensitivity analysis showed that the presence of iceA1 was significantly associated with peptic ulcer (odds ratio [OR] = 1.25, 95% CI = 1.08-1.44. The presence of iceA2 was inversely associated with peptic ulcer (OR = 0.76, 95% CI = 0.65-0.89. The presence of iceA was not associated with gastric cancer. Most studies examined the cagA status; however, only 15 studies examined the correlation and only 2 showed a positive correlation between the presence of cagA and iceA1. CONCLUSION: Our meta-analysis confirmed the importance of the presence of iceA for peptic ulcer, although the significance was marginal.

  14. Oncogenic CagA promotes gastric cancer risk via activating ERK signaling pathways: a nested case-control study.

    Directory of Open Access Journals (Sweden)

    Jae Jeong Yang

    Full Text Available BACKGROUND: CagA cellular interaction via activation of the ERK signaling pathway may be a starting point in the development of gastric cancer. This study aimed to evaluate whether genes involved in ERK downstream signaling pathways activated by CagA are susceptible genetic markers for gastric cancer. METHODS: In the discovery phase, a total of 580 SNPs within +/-5 kbp of 30 candidate genes were genotyped to examine an association with gastric cancer risk in the Korean Multi-center Cancer Cohort (100 incident gastric cancer case-control sets. The most significant SNPs (raw or permutated p value<0.02 identified in the discovery analysis were re-evaluated in the extension phase using unconditional logistic regression model (400 gastric cancer case-control sets. Combined analyses including pooled- and meta-analysis were conducted to summarize all the results. RESULTS: 24 SNPs in eight genes (ERK, Dock180, C3G, Rap1, Src, CrkL, Mek and Crk were significantly associated with gastric cancer risk in the individual SNP analyses in the discovery phase (p<0.05. In the extension analyses, ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 showed marginally significant gene-dose effects for gastric cancer. Consistently, final combined analysis presented the SNPs as significantly associated with gastric cancer risk (OR = 1.56, [95% CI: 1.19-2.06], OR = 0.61, [95% CI: 0.43-0.87], OR = 0.59, [95% CI: 0.54-0.76], respectively. CONCLUSIONS: Our findings suggest that ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 are genetic determinants in gastric carcinogenesis.

  15. The association of eNOS gene polymorphism with avascular necrosis of femoral head.

    Directory of Open Access Journals (Sweden)

    Liwen Zheng

    Full Text Available OBJECTIVES: Necrosis of femoral head is a severe pathological state with multiple etiologies. This study investigated the association of the 27-bp repeat polymorphism in intron 4 and G894T polymorphism in exon 7 of the endothelial nitric oxide synthase (eNOS gene with the pathogenesis of avascular necrosis of femoral head (ANFH. METHODS: A total of 125 non-traumatic ANFH patients and 126 healthy controls were recruited for this study. The 27-bp repeat polymorphisms in intron 4 were analyzed by polymerase chain reaction (PCR and sequencing. The G894T polymorphisms in exon 7 were analyzed by PCR- restriction fragment length polymorphism (PCR-RFLP analysis. RESULTS: All alleles were observed in non-traumatic ANFH patients and control subjects. Both ANFH patients and idiopathic subgroup of ANFH patients showed higher frequency of the 4a/b genotype than controls (p = 0.001 and p = 0.020, respectively. Significantly higher frequency of G/T genotype was observed in ANFH patients and idiopathic subgroup of ANFH patients compared to controls (p = 0.009 and p = 0.035, respectively. CONCLUSION: eNOS gene polymorphisms may be a risk factor for ANFH. The 27-bp repeat polymorphism in intron 4, G894T polymorphism in exon 7, and subsequently reduced eNOS activity may be involved in the etiology of idiopathic ANFH.

  16. Androgen receptor gene polymorphism in zebra species

    Directory of Open Access Journals (Sweden)

    Hideyuki Ito

    2015-09-01

    Full Text Available Androgen receptor genes (AR have been found to have associations with reproductive development, behavioral traits, and disorders in humans. However, the influence of similar genetic effects on the behavior of other animals is scarce. We examined the loci AR glutamine repeat (ARQ in 44 Grevy's zebras, 23 plains zebras, and three mountain zebras, and compared them with those of domesticated horses. We observed polymorphism among zebra species and between zebra and horse. As androgens such as testosterone influence aggressiveness, AR polymorphism among equid species may be associated with differences in levels of aggression and tameness. Our findings indicate that it would be useful to conduct further studies focusing on the potential association between AR and personality traits, and to understand domestication of equid species.

  17. Detection of Helicobacter pylori virulence factors and interleukin-1 polymorphisms in patients with abdominal complaint

    International Nuclear Information System (INIS)

    Full text: Gastric Cancer is the second leading cause of cancer related death in Mongolia (National Cancer Center, report-2006). Chronic infection with Helicobacter pylori affects approximately half the world and results in malignancy in a small subset of this population. There was sufficient evidence that the Working Group of the International Agency for Research on Cancer (IARC-1994) classified it as a class I carcinogen, the only bacterial agent on this list. The aim of the study is to detect and define the role of H.pylori virulence factors and host IL-1 polymorphisms to prevent further gastric cancer. In the future, this combined bacterial/host genotyping may provide an important opportunity to identify patients who are at high risk for the development of gastric carcinoma long before malignancy occurs. Patients and biopsy specimens. Two biopsy specimens and 5ml of blood samples were collected from each of 59 patients who had abdominal complaint, after informed consent was obtained. All patients lived in Ulaanbaatar, Mongolia, 100% were of Mongolian nationality. Their mean age was 40.33 years (range, 1575 years). One biopsy specimen was used to test urease, and another was stored for molecular testing. DNA isolation from blood and tissue sample was performed with ''Promega'' kit, according to the manufacturer's instruction. Tissue samples were homogenized treated with proteinase K prior to DNA extraction. H. pylori detection and genotyping. For H.pylori, detection was by UreC primer. For virulence gene typing of H.pylori cagA and vacA, gene specific primer were used. Genotyping of IL-1 polymorphisms. IL-1B polymorphisms were distinguished by 2 methods, 5-nuclease PCR assay and restriction fragment length polymorphism analysis (RFLP). Result. Strain characteristics of H. pylori were investigated in all 59 patients. 66,7% (40/59) and 76,3% (29/36) of the patients were infected with H. pylori by UreC PCR and by urea test, respectively. The vacAs1 genotype was

  18. Saturation of repeated quantum measurements

    Science.gov (United States)

    Haapasalo, Erkka; Heinosaari, Teiko; Kuramochi, Yui

    2016-08-01

    We study sequential measurement scenarios where the system is repeatedly subjected to the same measurement process. We first provide examples of such repeated measurements where further repetitions of the measurement do not increase our knowledge on the system after some finite number of measurement steps. We also prove, however, that repeating the Lüders measurement of an unsharp two-outcome observable never saturates in this sense, and we characterize the observable measured in the limit of infinitely many repetitions. Our result implies that a repeated measurement can be used to correct the inherent noise of an unsharp observable.

  19. Androgen receptor polyglutamine repeat number: models of selection and disease susceptibility.

    Science.gov (United States)

    Ryan, Calen P; Crespi, Bernard J

    2013-02-01

    Variation in polyglutamine repeat number in the androgen receptor (AR CAGn) is negatively correlated with the transcription of androgen-responsive genes and is associated with susceptibility to an extensive list of human disease. Only a small portion of the heritability for many of these diseases is explained by conventional SNP-based genome-wide association studies, and the forces shaping AR CAGn among humans remains largely unexplored. Here, we propose evolutionary models for understanding selection at the AR CAG locus, namely balancing selection, sexual conflict, accumulation-selection, and antagonistic pleiotropy. We evaluate these models by examining AR CAGn-linked susceptibility to eight extensively studied diseases representing the diverse physiological roles of androgens, and consider the costs of these diseases by their frequency and fitness effects. Five diseases could contribute to the distribution of AR CAGn observed among contemporary human populations. With support for disease susceptibilities associated with long and short AR CAGn, balancing selection provides a useful model for studying selection at this locus. Gender-specific differences AR CAGn health effects also support this locus as a candidate for sexual conflict over repeat number. Accompanied by the accumulation of AR CAGn in humans, these models help explain the distribution of repeat number in contemporary human populations. PMID:23467468

  20. DWI Repeaters and Non-Repeaters: A Comparison.

    Science.gov (United States)

    Weeber, Stan

    1981-01-01

    Discussed how driving-while-intoxicated (DWI) repeaters differed signigicantly from nonrepeaters on 4 of 23 variables tested. Repeaters were more likely to have zero or two dependent children, attend church frequently, drink occasionally and have one or more arrests for public intoxication. (Author)

  1. To Repeat or Not to Repeat a Course

    Science.gov (United States)

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  2. Expressions and Effects of CagA and IL-9 in Helicobacter pylori Infected Patients with Peptic Ulcer and Gastric Polyps%CagA和IL-9在幽门螺杆菌感染伴消化性溃疡和胃息肉患者中的表达及其作用研究

    Institute of Scientific and Technical Information of China (English)

    陈周利

    2015-01-01

    背景:研究表明幽门螺杆菌(Hp)感染与消化性溃疡(PU)和胃息肉(GP)的发生相关.细胞毒素相关蛋白A(CagA)是Hp致病的重要毒力因子,而白细胞介素-9(IL-9)是具有抗炎效应的细胞因子.目的:探讨CagA、IL-9在Hp感染伴PU和GP患者中的表达及其作用.方法:纳入2013年1月-2014年3月于惠东县人民医院就诊的Hp感染伴PU(Hp+ PU组)或Hp感染伴PU和GP患者(Hp+ PU+ GP组),无Hp感染的慢性胃炎患者作为对照组.采用ELISA法检测血清CagA、IL-9水平;采用免疫组化法检测胃黏膜组织CagA、IL-9表达.结果:Hp+ PU组、Hp+PU+ GP组血清CagA水平均显著高于对照组(P<0.01),血清IL-9水平均显著低于对照组(P<0.01),且Hp+ PU+ GP组血清IL-9水平显著低于Hp+ PU组(P<0.05).Hp+ PU组、Hp+ PU+ GP组CagA+患者比例均显著高于对照组(P<0.05);三组患者中,CagA+患者血清IL-9水平均显著低于CagA-患者(P<0.01),Hp+ PU+ GP组C舭+患者血清IL-9水平显著低于Hp+ PU组和对照组CagA+患者(P<0.05).Hp+ PU组、Hp+ PU+ GP组胃黏膜CagA阳性面积比值显著高于对照组(P<0.01),Hp+ PU+ GP组又显著高于Hp+ PU组(P<0.05).Hp+ PU组、Hp+ PU+ GP组胃黏膜IL-9阳性面积比值显著低于对照组(P<0.05),Hp+ PU+ GP组又显著低于Hp+ PU组(P<0.01).结论:CagA+ Hp感染可能与PU和GP的发生有关.IL-9参与了Hp感染诱导的免疫应答,且可能对Hp感染所致的PU和GP具有抑制作用.

  3. 78 FR 65594 - Vehicular Repeaters

    Science.gov (United States)

    2013-11-01

    ... Proceedings, 63 FR 24121 (May 1, 1998). Electronic Filers: Comments may be filed electronically using the... COMMISSION 47 CFR Part 90 Vehicular Repeaters AGENCY: Federal Communications Commission. ACTION: Proposed... the Commission's rules to allow the licensing and operation of vehicular repeater systems and...

  4. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  5. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

    OpenAIRE

    Robarts, Daniel W. H.; Wolfe, Andrea D.

    2014-01-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open readin...

  6. New source of genetic polymorphisms in Lepidoptera?

    Science.gov (United States)

    Hundsdoerfer, Anna K; Wink, Michael

    2005-01-01

    The variability level of the ISSR (inter-simple sequences repeat) primer (GACA)4 was examined in the three Lepidoptera families Pyralidae, Sphingidae and Pieridae. Our study shows that the tetra-repeat (GACA)n is evidently present in sufficient numbers in these butterflies to provide informative DNA fingerprints. The variability is mostly rather high, but within a comparable range to other ISSR studies. Although less polymorphisms may be encountered in some butterfly families, this study indicates that high variability of this marker may be a common characteristic of Lepidoptera genomes. An appeal for a minimal level of standardization of ISSR-PCR data analysis is formulated to enable an exact comparison between the groups of organisms studied with this fingerprint technique. PMID:16163839

  7. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  8. Tandem repeat markers as novel diagnostic tools for high resolution fingerprinting of Wolbachia

    Directory of Open Access Journals (Sweden)

    Riegler Markus

    2012-01-01

    Full Text Available Abstract Background Strains of the endosymbiotic bacterium Wolbachia pipientis are extremely diverse both genotypically and in terms of their induced phenotypes in invertebrate hosts. Despite extensive molecular characterisation of Wolbachia diversity, little is known about the actual genomic diversity within or between closely related strains that group tightly on the basis of existing gene marker systems, including Multiple Locus Sequence Typing (MLST. There is an urgent need for higher resolution fingerprinting markers of Wolbachia for studies of population genetics, horizontal transmission and experimental evolution. Results The genome of the wMel Wolbachia strain that infects Drosophila melanogaster contains inter- and intragenic tandem repeats that may evolve through expansion or contraction. We identified hypervariable regions in wMel, including intergenic Variable Number Tandem Repeats (VNTRs, and genes encoding ankyrin (ANK repeat domains. We amplified these markers from 14 related Wolbachia strains belonging to supergroup A and were successful in differentiating size polymorphic alleles. Because of their tandemly repeated structure and length polymorphism, the markers can be used in a PCR-diagnostic multilocus typing approach, analogous to the Multiple Locus VNTR Analysis (MLVA established for many other bacteria and organisms. The isolated markers are highly specific for supergroup A and not informative for other supergroups. However, in silico analysis of completed genomes from other supergroups revealed the presence of tandem repeats that are variable and could therefore be useful for typing target strains. Conclusions Wolbachia genomes contain inter- and intragenic tandem repeats that evolve through expansion or contraction. A selection of polymorphic tandem repeats is a novel and useful PCR diagnostic extension to the existing MLST typing system of Wolbachia, as it allows rapid and inexpensive high-throughput fingerprinting of

  9. 胰岛素样生长因子Ⅰ基因第1内含子微卫星多态性对山西白猪体重和体尺性状的影响%Association of CA Repeat Polymorphism at Intron 1 of Insulin-like Growth Factor Ⅰ Gene with Body Weight and Body Size in Shanxi White Pig

    Institute of Scientific and Technical Information of China (English)

    王效京; 王松柏; 石建中; 杨晓奋; 贾静敏; 高鹏飞; 郭晓红; 李步高; 曹果清

    2012-01-01

    A total of 174 pigs from Shanxi White pig were used to investigate associations between the polymorphic (CA)n sequence repeat located at the first intron of the insulin-like growth factor (IGF- I ) gene and the traits of body weights at different growth stages and body sizes at six-month age by unvariate animal model. There were six alieles, which were 198,202, 204,206,208 and 210 bp,were detected in Shanxi White population. The frequencies of alleles of 198 and 202 bp,with less CA repeat number, were 0. 2759 and 0. 2385, respectively, which were greater than those of alleles with more CA repeat number, such as the allele of 208 bp, whose frequency was 0. 0747. Twelve genotypes were found in Shanxi White population, the frequencies of homozygotes were greater than 0. 010 apart from 208/208 bp,and the frequencies of heterozygotes were 0. 017. The associations of IGF- I genotype with the traits of birth weight, weaning weight, body weight, body height, body length, chest girth,back fat thickness alive at six-month age were significant (P<0. 05). Individuals with genotype of 204/204 bp has greater body weight and thinner back fat thickness than those of others, which was in accordance with the pig breeding direction in China,should be selected as boars or sows in the selection and breeding programme.%试验检测了山西白猪174个个体胰岛素样生长因子-Ⅰ (insulin-like growth factor Ⅰ,IGF-Ⅰ)基因第1内含子以CA为核心重复序列的微卫星座位的多态性,并利用单变量动物模型分析了多态位点对山西白猪不同阶段体重和体尺性状的影响.结果表明,在该座位上,共检测到6个等位基因,分别为198、202、204、206、208和210 bp,表现出CA重复数较低的等位基因198和202 bp频率较高,分别为0.2759和0.2385;CA重复数较高的等位基因208 bp频率较低,为0.0747;共检测到12种基因型,纯合子频率较高,均大于0.010(208/208 bp类型除外);而杂合子个体频率都较低,为0

  10. A pilot study of Helicobacter pylori genotypes and cytokine gene polymorphisms in reflux oesophagitis and peptic ulcer disease.

    Science.gov (United States)

    Akdogan, R A; Ozgur, O; Gucuyeter, S; Kaklikkaya, N; Cobanoglu, U; Aydin, F

    2014-01-01

    Helicobacter pylori causes various diseases such as chronic gastritis, peptic ulcer and gastric cancer. While majority of the people infected with H. pylori is asymptomatic, 15-20 % of them develop such diseases. The main factors, which determine the development of H. pylori related diseases might be bacterial virulence, host genetic and environmental factors.The aim of this study was to reveal the factors that play a role in the disease development in patients with reflux esophagitis and peptic ulcer, infected with Helicobacter pylori. Environmental factors such as medical agents, smoking and body mass index were evaluated. The factors specific to bacteria such as vacA, CagA, babA and iceA virulence genotypes and the host factors such as IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, interferon-γ, TNF-α, ve TGF-β1 gene polymorphisms were compared between the two groups.H. pylori infected twenty five patients with reflux esophagitis and peptic ulcer were enrolled in the study. There was no statistical difference between the two groups regarding environmental factors. IL-2 -330T +166T (p=0.037) and IL10 -1082A; -819C (p=0.049) gene polymorphisms were significantly more common in the group of patients with peptic ulcer compared to the group with reflux esophagitis. In both groups of patients, either with reflux esophagitis or peptic ulcer, multiple H. pylori virulence genotypes (cagA, vacA, babA) (mean values 74 %, 78 %, 54 % respectively) were observed.In this study, we revealed that cytokine gene polymorphisms may play a role in the development peptic ulcer while H. pylori virulence genotypes seem to be crucial for the development of associated diseases (Tab. 4, Ref. 51).

  11. Alu repeats as markers for human population genetics

    Energy Technology Data Exchange (ETDEWEB)

    Batzer, M.A.; Alegria-Hartman, M. [Lawrence Livermore National Lab., CA (United States); Bazan, H. [Louisiana State Univ., New Orleans, LA (United States). Medical Center] [and others

    1993-09-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 97.9% nucleotide identity with each other and an average of 98.9% nucleotide identity with the HS subfamily consensus sequence. HS Alu family members are thought to be derived from a single source ``master`` gene, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 in. and 3 in. unique flanking DNA sequences from each HS Alu that allows the locus to be assayed for the presence or absence of an Alu repeat. Individual HS Alu sequences were found to be either monomorphic or dimorphic for the presence or absence of each repeat. The monomorphic HS Alu family members inserted in the human genome after the human/great ape divergence (which is thought to have occurred 4--6 million years ago), but before the radiation of modem man. The dimorphic HS Alu sequences inserted in the human genome after the radiation of modem man (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project as well. HS Alu family member insertion dimorphism differs from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) because individuals share HS Alu family member insertions based upon identity by descent from a common ancestor as a result of a single event which occurred one time within the human population. The VNTR and RFLP polymorphisms may arise multiple times within a population and are identical by state only.

  12. Detection of an unstable non-coding tandem repeat in the ZNF291 gene.

    Science.gov (United States)

    Laura, Vallo; Emanuela, Bonifazi; Corrado, Angelini; Giuseppe, Novelli; Annalisa, Botta

    2007-01-01

    Repeat instability is an important form of mutation that is responsible for several neurological, neurodegenerative and neuromuscular disorders. In this study we identified an unstable [CCTG](n) repeat in the second intron of the ZNF291 gene, on chromosome 15q21-24. The repeat number is polymorphic in normal population and the ZNF291 transcript is expressed in different areas of human brain, skeletal muscle and heart. These findings suggest that ZNF291 gene should be taken in consideration as an attractive candidate for neuromuscular expansion related diseases mapping in this locus.

  13. Clustered regularly interspaced short palindromic repeats (CRISPRs) for the genotyping of bacterial pathogens.

    Science.gov (United States)

    Grissa, Ibtissem; Vergnaud, Gilles; Pourcel, Christine

    2009-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPRs) are DNA sequences composed of a succession of repeats (23- to 47-bp long) separated by unique sequences called spacers. Polymorphism can be observed in different strains of a species and may be used for genotyping. We describe protocols and bioinformatics tools that allow the identification of CRISPRs from sequenced genomes, their comparison, and their component determination (the direct repeats and the spacers). A schematic representation of the spacer organization can be produced, allowing an easy comparison between strains.

  14. [Clinical efficacy of decitabine combined with modified CAG regimen for relapsed-refractory acute myeloid leukemia with AML1-ETO⁺].

    Science.gov (United States)

    Jing, Yu; Zhu, Cheng-Ying; Zhang, Qi; Niu, Jian-Hua; Yang, Hua; Liu, Shi-Yan; Zhu, Hai-Yan; Yu, Li

    2014-10-01

    This study was aimed to investigate the clinical characteristics of relapsed-refractory acute myeloid leukemia (AML) with AML1-ETO⁺, and its therapeutic efficacy and side effects when decitabine combined with modified CAG regimen was used. Clinical data of 5 cases of AML with AML1-ETO⁺ from January 2013 to Agust 2013 were analyzed retrospectively. The analyzed data included age, sex, initial symptoms, peripheral blood and bone marrow characteristics. Meanwhile, the therapeutic effecacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 5 patients were with median age of 35 (17-43) years. Among these 5 patients, 2 patients were relapsed and other 3 patients were relapsed-refractory patients, their median white blood cell count was 12.55 (7.8-66.55) × 10⁹/L, median platelets count was 44 (20-72) × 10⁹/L, median hemoglobin level was 110 (77-128) g/L, median lactate dehydrogenase level was 312.9 U/L (123.6-877.8) at the initial diagnosis. The results showed that after decitabine combined with modified CAG regimen was administered, 4 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 80% (4/5). The main side effects of this regimen was myelosuppression, these were no new lung infection and other serious complications, one case without complete remission treated with FLAG once again died of heart failure when being mobilized for transplantation. It is concluded that according to preliminary results of decitabine combined with modified CAG regimen for relapsed and refractory AML patients with AML1-ETO⁺ displays higher remission rate and lower side effects, which worthy to further explore for clinal application. PMID:25338566

  15. Association of CagA and VacA presence with ulcer and non-ulcer dyspepsia in a Turkish population

    Institute of Scientific and Technical Information of China (English)

    Kantarceken Bulent; Hilmioglu Fatih; Aladag Murat; Atik Esin; Koksal Fatih; Harputluoglu MMMurat; Harputluoglu Hakan; Karincaoglu Melih; Ates Mehmet; Yildirim Bulent

    2003-01-01

    AIM: The mostly known genotypic virulence features, of H. pyloriare cytotoxin associated gene A (ragA) and Vacuolating cytotoxin gene A (VacA). We investigated the association of these major virulence factors with ulcer and non-ulcer dyspepsia in our region.METHODS: One hundred and forty two dyspeptic patients were studied (average age 44.8±15.9 years, range 15-87years, 64 males and 78 females). Antral and corpus biopsies were taken for detecting and genotyping of H. pylori. 107patients who were H. pylori positive by histological assessment were divided into three groups according to endoscopic findings: Duodenal ulcer (DU), gastric ulcer (GU)and non-ulcer dyspepsia (NUD). The polymerase chain reaction (PCR) was used to detect CagA and VacA genes of H.pylori using specific primers.RESULTS: H.pyloriwas isolated from 75.4 % (107/142) of the patients. Of the 107 patients, 66 (61.7 %) were cagApositive and 82 (76.6 %) were Vacl-positive. CagA gene was positively associated with DU and GU (P<0.01, P<0.02),but not with NUD (P>0.05). Although VacA positivity in ulcer patients was higher than that in NUD group, the difference was not statistically significant (P>0.05).CONCLUSION: There is a significantly positive association between CagA genes and DU and GU. The presence of VacA is not a predictive marker for DU, GU, and NUD in our patients.

  16. Analysis of serum antibody profile against H pylori VacA and CagA antigens in Turkish patients with duodenal ulcer

    Institute of Scientific and Technical Information of China (English)

    Yusuf Erzin; Sibel Altun; Ahmet Dobrucali; Mustafa Aslan; Sibel Erdamar; Ahmet Dirican; Murat Tuncer; Bekir Kocazeybek

    2006-01-01

    AIM:To investigate the frequency of seropositivity against CagA, VacA proteins and to determine their independent effects on the development of duodenal ulcer (DU) in Turkish patients.METHODS:The study was designed as a prospective one from a tertiary referral hospital. Dyspeptic patients who were referred to our endoscopy unit for upper gastrointestinal endoscopy between June 2003 and March 2004 and diagnosed to have DU or nonulcer dyspepsia (NUD) were included. Biopsies from the antrum and body of the stomach were taken in order to assess the current H pylori status by histology, rapid urease test and culture.Fasting sera were obtained from all patients and H pylori status of all sera was determined by IgG antibodies using an enzyme-linked immunosorbent assay (ELISA) kit. All seropositive patients were further analysed using Western blot assays detecting IgG antibodies against CagA and VacA proteins. The x2 test was used for statistical comparison of the values and age-sex adjusted multiple regression analysis was used to determine the independent effects of CagA and VacA seropositivities on the development of DU.RESULTS:Sixty-three patients with DU and 62 patients with NUD were eligible for the final analysis. Seropositivity for anti-CagA was detected in 51 of 62 (82%), and in 55 of 63 (87%) patients with NUD and DU, respectively (P = no significance), and seropositivity for antiVacA was found in 25 of 62 (40%) and in 16 of 63 (25%) patients, with NUD and DU, respectively.CONCLUTSION: These findings suggest that none of these virulence factors is associated with the development of DU in the studied Turkish patients with dyspepsia.

  17. A C-Terminal Coiled-Coil Region of CagL is Responsible for Helicobacter Pylori-Induced Il-8 Expression

    Science.gov (United States)

    Wiedemann, Tobias; Hofbaur, Stefan; Loell, Eva; Rieder, Gabriele

    2016-01-01

    Interleukin-8 (IL-8) is a potent neutrophil-activating chemokine which triggers the infiltration and migration of neutrophils into areas of bacterial infection. Helicobacter pylori-infected patient studies as well as animal models have revealed that H. pylori type I strains carrying an intact cytotoxin-associated gene pathogenicity island (cag-PAI) with a functional type IV secretion system (T4SS) induce IL-8 expression and secretion in gastric mucosa. This gastric mucosal IL-8 expression correlates with severe histological changes due to H. pylori infection. In the present study, we explored a new recognition pattern on the bacterial adhesion protein CagL inducing IL-8 expression in H. pylori-infected host cells. To analyze the secreted IL-8 concentration, we performed IL-8 enzyme-linked immunosorbent assay (ELISA). To investigate the H. pylori-induced IL-8 expression on the transcriptional level, we transiently transfected gastric epithelial cells (AGS) with a human IL-8 luciferase reporter construct. The results of this study demonstrate that specifically the C-terminal coiled-coil region of the H. pylori CagL protein, a protein described to be located on the tip of the T4SS-pilus, is responsible for several in vitro observations: 1) H. pylori-induced IL-8 secretion via the transforming growth factor (TGF)-α activated epidermal growth factor-receptor (EGF-R) signaling pathway; 2) H. pylori-induced elongation of the cells, a typical CagA-induced phenotype; and 3) the bridging of the T4SS to its human target cells. This novel bacterial-host recognition sequence allows a new insight into how H. pylori induces the inflammatory response in gastric epithelial cells and facilitates the development of precancerous conditions. PMID:27766167

  18. [Clinical efficacy of decitabine combined with modified CAG regimen for relapsed-refractory acute myeloid leukemia with AML1-ETO⁺].

    Science.gov (United States)

    Jing, Yu; Zhu, Cheng-Ying; Zhang, Qi; Niu, Jian-Hua; Yang, Hua; Liu, Shi-Yan; Zhu, Hai-Yan; Yu, Li

    2014-10-01

    This study was aimed to investigate the clinical characteristics of relapsed-refractory acute myeloid leukemia (AML) with AML1-ETO⁺, and its therapeutic efficacy and side effects when decitabine combined with modified CAG regimen was used. Clinical data of 5 cases of AML with AML1-ETO⁺ from January 2013 to Agust 2013 were analyzed retrospectively. The analyzed data included age, sex, initial symptoms, peripheral blood and bone marrow characteristics. Meanwhile, the therapeutic effecacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 5 patients were with median age of 35 (17-43) years. Among these 5 patients, 2 patients were relapsed and other 3 patients were relapsed-refractory patients, their median white blood cell count was 12.55 (7.8-66.55) × 10⁹/L, median platelets count was 44 (20-72) × 10⁹/L, median hemoglobin level was 110 (77-128) g/L, median lactate dehydrogenase level was 312.9 U/L (123.6-877.8) at the initial diagnosis. The results showed that after decitabine combined with modified CAG regimen was administered, 4 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 80% (4/5). The main side effects of this regimen was myelosuppression, these were no new lung infection and other serious complications, one case without complete remission treated with FLAG once again died of heart failure when being mobilized for transplantation. It is concluded that according to preliminary results of decitabine combined with modified CAG regimen for relapsed and refractory AML patients with AML1-ETO⁺ displays higher remission rate and lower side effects, which worthy to further explore for clinal application.

  19. The study of the relationship between Helicobacter pylori CagA and VacA genotype and IL-6, IL-8%幽门螺杆菌CagA和VacA基因型与IL-6、IL-8的关系研究

    Institute of Scientific and Technical Information of China (English)

    郭皓; 戚艳丽; 张世同; 李慧; 金建军

    2016-01-01

    目的 观察幽门螺杆菌(Helicobacter pylori,H.pylori)的不同基因型与IL-6、IL-8之间的关系,了解H.pylori的致病机制.方法 采集91例经14C尿素呼气试验检测为H.pylori(+)患者血清,采用酶联免疫吸附试验(ELISA)对CagA、VacA进行定性分析,对IL-6、IL-8进行定量分析.结果 CagA(+)与CagA(-)中所含IL-6、IL-8含量差异有统计学意义(=6.55、t=7.348,P<0.001);VacA(+)与VacA(-)中所含IL-6、IL-8含量差异有统计学意义(t=6.418、t=6.977,P<0.001);CagA、VacA均阳性中所含IL-6、IL-8的含量较CagA、VacA均阴性差异有统计学意义(=6.438、t=7.231,P<0.001);CagA阳性患者血清中IL-6与IL-8含量呈正相关(r=0.672,P<0.01),VacA阳性患者血清中IL-6与IL-8含量呈正相关(r=0.664,P<0.01).结论 CagA、VacA基因型与IL-6、IL-8之间有密切关系,IL-6、IL-8在H.pylori的致病机制中起重要作用,细胞因子在H.pylori感染诱导的炎症反应涉及多种细胞及多种细胞因子的相互作用.

  20. Simple sequence repeats in mycobacterial genomes

    Indian Academy of Sciences (India)

    Vattipally B Sreenu; Pankaj Kumar; Javaregowda Nagaraju; Hampapathalu A Nagarajaram

    2007-01-01

    Simple sequence repeats (SSRs) or microsatellites are the repetitive nucleotide sequences of motifs of length 1–6 bp. They are scattered throughout the genomes of all the known organisms ranging from viruses to eukaryotes. Microsatellites undergo mutations in the form of insertions and deletions (INDELS) of their repeat units with some bias towards insertions that lead to microsatellite tract expansion. Although prokaryotic genomes derive some plasticity due to microsatellite mutations they have in-built mechanisms to arrest undue expansions of microsatellites and one such mechanism is constituted by post-replicative DNA repair enzymes MutL, MutH and MutS. The mycobacterial genomes lack these enzymes and as a null hypothesis one could expect these genomes to harbour many long tracts. It is therefore interesting to analyse the mycobacterial genomes for distribution and abundance of microsatellites tracts and to look for potentially polymorphic microsatellites. Available mycobacterial genomes, Mycobacterium avium, M. leprae, M. bovis and the two strains of M. tuberculosis (CDC1551 and H37Rv) were analysed for frequencies and abundance of SSRs. Our analysis revealed that the SSRs are distributed throughout the mycobacterial genomes at an average of 220–230 SSR tracts per kb. All the mycobacterial genomes contain few regions that are conspicuously denser or poorer in microsatellites compared to their expected genome averages. The genomes distinctly show scarcity of long microsatellites despite the absence of a post-replicative DNA repair system. Such severe scarcity of long microsatellites could arise as a result of strong selection pressures operating against long and unstable sequences although influence of GC-content and role of point mutations in arresting microsatellite expansions can not be ruled out. Nonetheless, the long tracts occasionally found in coding as well as non-coding regions may account for limited genome plasticity in these genomes.

  1. Prevalence of cagA and vacA genes in isolates from patients with Helicobacter pylori-associated gastroduodenal diseases in Recife, Pernambuco, Brazil

    Directory of Open Access Journals (Sweden)

    Brito Carlos AA

    2003-01-01

    Full Text Available Geographical differences in the prevalence of Helicobacter pylori genes and their association with disease severity have been identified. This study analyzes the prevalences of the cagA gene and alleles of the vacA gene in H. pylori-associated gastroduodenal diseases in isolates from Recife, PE, Brazil. Gastric biopsy of 61 H. pylori-positive patients were submitted to DNA extraction and gene amplification by polymerase chain reaction. Among the 61 patients, 21 suffered from duodenal ulcer (DU and 40 from gastritis (GT. The prevalence of H. pylori strains harbouring the cagA gene was higher in the DU group (90.5% than in the GT group (60% (p = 0.02. The vacA gene was amplified in 56 out of 61 biopsies, of which 43 (76.8% contained bacteria carrying the s1 allele and 13 (23.2% the s2. However, the prevalence of the vacA s1 genotying was the same in either DU or GT group. The majority of the s1-typed strains, 39 (90.7% out of 43, were subtype s1b. In resume there was a strong association between the H. pylori cagA+ gene and DU. However, there were no differences between the DU and GT groups in relation to the vacA s1 and s2 alleles distribution, albeit the subtype s1b was predominat.

  2. A CCD-based reader combined with CdS quantum dot-labeled lateral flow strips for ultrasensitive quantitative detection of CagA

    Science.gov (United States)

    Gui, Chen; Wang, Kan; Li, Chao; Dai, Xuan; Cui, Daxiang

    2014-02-01

    Immunochromatographic assays are widely used to detect many analytes. CagA is proved to be associated closely with initiation of gastric carcinoma. Here, we reported that a charge-coupled device (CCD)-based test strip reader combined with CdS quantum dot-labeled lateral flow strips for quantitative detection of CagA was developed, which used 365-nm ultraviolet LED as the excitation light source, and captured the test strip images through an acquisition module. Then, the captured image was transferred to the computer and was processed by a software system. A revised weighted threshold histogram equalization (WTHE) image processing algorithm was applied to analyze the result. CdS quantum dot-labeled lateral flow strips for detection of CagA were prepared. One hundred sera samples from clinical patients with gastric cancer and healthy people were prepared for detection, which demonstrated that the device could realize rapid, stable, and point-of-care detection, with a sensitivity of 20 pg/mL.

  3. Identification of conserved and polymorphic STRs for personal genomes

    Science.gov (United States)

    2014-01-01

    Background Short tandem repeats (STRs) are abundant in human genomes. Numerous STRs have been shown to be associated with genetic diseases and gene regulatory functions, and have been selected as genetic markers for evolutionary and forensic analyses. High-throughput next generation sequencers have fostered new cutting-edge computing techniques for genome-scale analyses, and cross-genome comparisons have facilitated the efficient identification of polymorphic STR markers for various applications. Results An automated and efficient system for detecting human polymorphic STRs at the genome scale is proposed in this study. Assembled contigs from next generation sequencing data were aligned and calibrated according to selected reference sequences. To verify identified polymorphic STRs, human genomes from the 1000 Genomes Project were employed for comprehensive analyses, and STR markers from the Combined DNA Index System (CODIS) and disease-related STR motifs were also applied as cases for evaluation. In addition, we analyzed STR variations for highly conserved homologous genes and human-unique genes. In total 477 polymorphic STRs were identified from 492 human-unique genes, among which 26 STRs were retrieved and clustered into three different groups for efficient comparison. Conclusions We have developed an online system that efficiently identifies polymorphic STRs and provides novel distinguishable STR biomarkers for different levels of specificity. Candidate polymorphic STRs within a personal genome could be easily retrieved and compared to the constructed STR profile through query keywords, gene names, or assembled contigs. PMID:25560225

  4. Spinocerebellar ataxia type 3/Machado-Joseph disease: segregation patterns and factors influencing instability of expanded CAG transmissions.

    Science.gov (United States)

    Souza, G N; Kersting, N; Krum-Santos, A C; Santos, A S P; Furtado, G V; Pacheco, D; Gonçalves, T A; Saute, J A; Schuler-Faccini, L; Mattos, E P; Saraiva-Pereira, M L; Jardim, L B

    2016-08-01

    Controversies about Mendelian segregation and CAG expansion (CAGexp) instabilities during meiosis in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) need clarification. Additional evidence about these issues was obtained from the cohort of all SCA3/MJD individuals living in South Brazil. A survey was carried out to update information registered since 2001. Deaths were checked with the Public Information System, and data was made anonymous. Anticipation and delta-CAGexp from parent-offspring pairs, and delta-CAGexp between siblings were obtained. One hundred and fifty-nine families (94% of the entire registry) were retrieved, comprising 3725 living individuals as of 2015, 625 of these being symptomatic. Minimal prevalence was 6:100,000. Carriers of a CAGexp represented 65.6% of sibs in the genotyped offspring (p r = 0.38; p = 0.001). Age of the parent correlated to delta-CAGexp among 115 direct parent-offspring CAGexp transmissions (ρ = 0.23, p = 0.014). In 98 additional kindreds, the delta-CAGexp between 269 siblings correlated with their delta-of-age (ρ = 0.27, p meiosis was weakly influenced by the age of the transmitting parent at the time of conception. PMID:26693702

  5. Optimizing reproducibility evaluation for random amplified polymorphic DNA markers.

    Science.gov (United States)

    Ramos, J R; Telles, M P C; Diniz-Filho, J A F; Soares, T N; Melo, D B; Oliveira, G

    2008-01-01

    The random amplified polymorphic DNA (RAPD) technique is often criticized because it usually shows low levels of repeatability; thus it can generate spurious bands. These problems can be partially overcome by rigid laboratory protocols and by performing repeatability tests. However, because it is expensive and time-consuming to obtain genetic data twice for all individuals, a few randomly chosen individuals are usually selected for a priori repeatability analysis, introducing a potential bias in genetic parameter estimates. We developed a procedure to optimize repeatability analysis based on RAPD data, which was applied to evaluate genetic variability in three local populations of Tibochina papyrus, an endemic Cerrado plant found in elevated rocky fields in Brazil. We used a simulated annealing procedure to select the smallest number of individuals that contain all bands and repeated the analyses only for those bands that were reproduced in these individuals. We compared genetic parameter estimates using HICKORY and POPGENE softwares on an unreduced data set and on data sets in which we eliminated bands based on repeatability of individuals selected by simulated annealing and based on three randomly selected individuals. Genetic parameter estimates were very similar when we used the optimization procedure to reduce the number of bands analyzed, but as expected, selecting only three individuals to evaluate the repeatability of bands produced very different estimates. We conclude that the problems of repeatability attributed to RAPD markers could be due to bias in the selection of loci and primers and not necessarily to the RAPD technique per se. PMID:19065774

  6. DNA Commission of the International Society of Forensic Genetics: recommendations on forensic analysis using Y-chromosome short tandem repeats

    DEFF Research Database (Denmark)

    Gill, P.; Brenner, C.; Brinkmann, B.;

    2001-01-01

    During the past few years the DNA commission of the International Society of Forensic Genetics has published a series of documents providing guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. This latest report addresses a relat...... a relatively new area, namely Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). This report addresses nomenclature, use of allelic ladders, population genetics and reporting methods Udgivelsesdato: 2001/12...

  7. An analysis of patients receiving emergency CAG without PCI and the value of GRACE score in predicting PCI possibilities in NSTE-ACS patients

    Institute of Scientific and Technical Information of China (English)

    Bo-Da ZHOU; Ling-Yun ZU; Lin MI; Gui-Song WANG; Li-Jun GUO; Wei GAO

    2015-01-01

    Background There are patients who underwent emergency coronary angiography (CAG) but did not receive percutaneous coronary intervention (PCI). The aim of this study was to analyze these reasons. Methods This is a single-center retrospective study. We recruited 201 consecutive patients who received emergency CAG but did not receive PCI. To investigate the value of the Global Registry of Acute Coronary Events (GRACE) score in predicting PCI possibilities in non-ST segment elevation acute coronary syndrome (NSTE-ACS) pa-tients, we recruited 80 consecutive patients who presented with NSTE-ACS and received emergency CAG as well as emergency PCI. Re-sults Among the 201 patients who received emergency CAG but did not receive PCI, 26%patients had final diagnosis other than coronary heart disease. In the patients with significant coronary artery stenosis, 23 patients (11.5%) were recommended to coronary artery bypass grafting (CABG), one patient (0.5%) refused PCI; 13 patients (6.5%) with significant thrombus burden were treated with glycoprotein IIb/IIIa receptor antagonist;74 patients (36.8%) were treated with drug therapy because no severe stenosis (>70%) was present in the crime vessel. Moreover, 80 of the 201 patients were presented with NSTE-ACS (excluding those patients with final diagnosis other than coronary heart disease, excluding those patients planned for CABG treatment), referred as non PCI NSTE-ACS. When comparing their GRACE scores with 80 consecutive patients presented with NSTE-ACS who received emergency CAG as well as emergency PCI (referred as PCI NSTE-ACS), we found that PCI NSTE-ACS patients had significantly higher GRACE scores compared with non PCI NSTE-ACS patients. We then used Receiver Operator Characteristic Curve (ROC) to test whether the GRACE score is good at evaluating the possibilities of PCI in NSTE-ACS patients. The area under the curve was 0.854 ± 0.030 (P<0.001), indicating good predictive value. Furthermore, we analyzed results derived

  8. Gene polymorphisms in chronic periodontitis

    OpenAIRE

    Laine, Marja L; Loos, Bruno G.; Crielaard, W.

    2010-01-01

    We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polymorphism. Candidate gene polymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in ...

  9. Genetically unstable CXG repeats are structurally dynamic and have a high propensity for folding. An NMR and UV spectroscopic study.

    Science.gov (United States)

    Zheng, M; Huang, X; Smith, G K; Yang, X; Gao, X

    1996-11-29

    Recent molecular genetics studies have revealed a correlation between spontaneous, progressive expansion of several DNA trinucleotide repeats and certain hereditary neurodegenerative diseases. Triplet repeat (TR) sequences may be present in structured forms that can mediate the processes interrupting normal cellular replication, transcription, or repair activities, eventually leading to gene mutation. Using high resolution NMR spectroscopy and other biophysical methods, we probed the solution structures and properties of single-stranded TR sequences. These studies have led to the discovery of a new duplex motif (e-motif), present in CCG repeats, and to the elucidation of the structure of the (CTG)3 duplex. In this paper we provide a global picture of the solution behavior of the human disease-related CXG (X = A, C, G, or T) and the comparison GXC (X = A, or T) TR sequences. All six triplet repeats form antiparallel duplexes. The mismatched bases in CAG and CGG repeat duplexes are rather flexible and they do not appear to form stable, paired conformations. By comparison, GAC repeat duplexes and their mismatched A residues are well-structured. Most interestingly, the structures of the disease-related CXG repeats exhibit a propensity for folding at chain lengths as short as 12 residues. Furthermore, the energy barrier for the formation of homo-duplexes from the corresponding complementary hetero-duplexes are much lower for the CXG TR sequences than for the GAC or GTC TR sequences. These results provide insights into the conformation and physiochemical properties of TR sequences. Thus, a basis is provided for further studies of the behavior of long TR sequences in an effort to elucidate the molecular mechanisms of in vivo expansion and function of TR sequences. PMID:8951379

  10. Investigation into the Distribution of vacA and cagA Genes of Helicobacter Pylori in Miners of Huainan City%淮南地区矿工幽门螺杆菌vacA、cagA基因分布特征

    Institute of Scientific and Technical Information of China (English)

    汪雪峰; 崔玉宝; 王钧; 王克霞; 陈琳; 吴静; 胡友莹

    2006-01-01

    [目的]研究淮南地区煤矿工人幽门螺杆菌(Helicobacter pylori,H.pylori)vacA、cagA基因分布特征.[方法]选择经胃镜及病理组织检查诊断证实有相关胃、十二指肠疾病的349名矿工为研究对象,取其胃窦部活检黏膜作H.pylori的分离培养,利用聚合酶链反应技术(PCR)测定分离培养出H.pylori菌株的vacA、cagA基因,并进行分型.[结果]349份样本中共分离培养出244株H.pylori菌株,其中慢性胃炎、萎缩性胃炎、胃溃疡及十二指肠溃疡幽门螺杆菌培养阳性率分别为61.61%(69/112)、61.54%(48/78)、75%(72/96)及87.30%(55/63);基因测定结果显示,244株H.pylori菌株临床分离株中,84.84%(207/244)含vacA基因,73.36%(179/244)含cagA基因;其中慢性胃炎、萎缩性胃炎、胃溃疡及十二指肠溃疡cagA、vacA基因检出率分别为66.67%(46/69)、50.72%(35/69)、85.42%(41/48)和70.83%(34/48)与93.06%(67/72)、84.72%(61/72)、96.36%(53/55)和89.09%(49/55),4种疾病间差异均具显著性(P<0.01).进一步分型发现,慢性胃炎、萎缩性胃炎,胃溃疡及十二指肠溃疡患者中vacA+、cagA+分别为44.93%(31/69)、66.67%(32/48)、79.17%(57/72)、87.27%(48/55),差异具显著性(χ2=30.80,P<0.01).vacA+、cagA+菌株主要多见于损害较严重的胃黏膜表面,如萎缩性炎症、炎性坏死等,23例腺体不典型增生的胃黏膜表面均为vacA+、cagA+菌株.[结论]淮南地区矿工H.pylori感染多为vacA+、cagA+菌株,vacA+、cagA+H.pylori菌株为高毒力菌株,且与较严重的胃黏膜病理改变有关,可能是导致矿工慢性胃炎、消化性溃疡的重要因素,临床应充分重视H.pylori菌株毒力因子的监测.

  11. Teaching polymorphism early

    DEFF Research Database (Denmark)

    2005-01-01

    Is it possible to teach dynamic polymorphism early? What techniques could facilitate teaching it in Java. This panel will bring together people who have considered this question and attempted to implement it in various ways, some more completely than others. It will also give participants...

  12. Polymorphism of sorbitol

    Science.gov (United States)

    Nezzal, Amale; Aerts, Luc; Verspaille, Marleen; Henderickx, Geert; Redl, Andreas

    2009-07-01

    The polymorphism of sorbitol was investigated, confirming the existence of four anhydrous crystalline phases plus the hydrate. The crystallised melt (CM), the alpha form, and the gamma form were obtained via a dry route. The CM was confirmed to be a crystalline state with a spherulite morphology. The alpha form was obtained via direct conversion from the CM, in contrast to more complicated routes previously reported, and was found to have a very high crystallinity. Gamma crystals were obtained by seeding the melt at high temperature; however, crystallinity was clearly less than for alpha crystals. Despite its lower crystallinity, the gamma polymorph was found to be the most stable of the anhydrous crystalline forms; this was confirmed by its high melting point and low hygroscopicity. In contrast, the alpha polymorph has a relatively high melting point but lacks moisture stability at high relative humidity. The hydrate form has the same resistance to moisture as the gamma form, but melts at a lower temperature. The combination of both a high melting point and high stability in the presence of water makes the gamma polymorph best suited for confectionary applications.

  13. Single Nucleotide Polymorphism

    DEFF Research Database (Denmark)

    Børsting, Claus; Pereira, Vania; Andersen, Jeppe Dyrberg;

    2014-01-01

    Single nucleotide polymorphisms (SNPs) are the most frequent DNA sequence variations in the genome. They have been studied extensively in the last decade with various purposes in mind. In this chapter, we will discuss the advantages and disadvantages of using SNPs for human identification...

  14. Investigation of Uranium Polymorphs

    Energy Technology Data Exchange (ETDEWEB)

    Sweet, Lucas E.; Henager, Charles H.; Hu, Shenyang Y.; Johnson, Timothy J.; Meier, David E.; Peper, Shane M.; Schwantes, Jon M.

    2011-08-01

    The UO3-water system is complex and has not been fully characterized, even though these species are common throughout the nuclear fuel cycle. As an example, most production schemes for UO3 result in a mixture of up to six or more different polymorphic phases, and small differences in these conditions will affect phase genesis that ultimately result in measureable changes to the end product. As a result, this feature of the UO3-water system may be useful as a means for determining process history. This research effort attempts to better characterize the UO3-water system with a variety of optical techniques for the purpose of developing some predictive capability for estimating process history in polymorphic phases of unknown origin. Three commercially relevant preparation methods for the production of UO3 were explored. Previously unreported low temperature routes to β- and γ-UO3 were discovered. Raman and fluorescence spectroscopic libraries were established for pure and mixed polymorphic forms of UO3 in addition to the common hydrolysis products of UO3. An advantage of the sensitivity of optical fluorescence microscopy over XRD has been demonstrated. Preliminary aging studies of the α and γ forms of UO3 have been conducted. In addition, development of a 3-D phase field model used to predict phase genesis of the system was initiated. Thermodynamic and structural constants that will feed the model have been gathered from the literature for most of the UO3 polymorphic phases.

  15. Polymorphous Perversity in Texts

    Science.gov (United States)

    Johnson-Eilola, Johndan

    2012-01-01

    Here's the tricky part: If we teach ourselves and our students that texts are made to be broken apart, remixed, remade, do we lose the polymorphous perversity that brought us pleasure in the first place? Does the pleasure of transgression evaporate when the borders are opened?

  16. Enzyme polymorphisms in Canarium

    Science.gov (United States)

    Fifty-two accessions of Canarium involving seven species, C. ovatum, C. album, C. megalanthum, C. harveyi, C. indicum, C. mehenbethene, and C. odontophyllum were studied for isozyme polymorphisms. Starch gel electrophoresis with a histidine-citrate buffer system (pH 6.5) was employed to assay six en...

  17. A new polymorph of Lu(PO3)3

    OpenAIRE

    Anis Bejaoui; Karima Horchani-Naifer; Mokhtar Férid

    2008-01-01

    A new polymorph of lutetium polyphosphate, Lu(PO3)3, was found to be isotypic with the trigonal form of Yb(PO3)3. Two of the three Lu atoms occupy special positions (Wyckoff positions 3a and 3b, site symmetry overline{3}). The atomic arrangement consists of infinite helical polyphosphate chains running along the c axis, with a repeat period of 12 PO4 tetrahedra, joined with LuO6 octahedra.

  18. Association between amygdala reactivity and a dopamine transporter gene polymorphism

    OpenAIRE

    Bergman, O.; Åhs, F; Furmark, T; Appel, L; Linnman, C; Faria, V; Bani, M; Pich, E M; Bettica, P; Henningsson, S; Manuck, S B; Ferrell, R E; Nikolova, Y S; Hariri, A R; Fredrikson, M.

    2014-01-01

    Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3′ untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotio...

  19. A new polymorph of Lu(PO33

    Directory of Open Access Journals (Sweden)

    Anis Bejaoui

    2008-08-01

    Full Text Available A new polymorph of lutetium polyphosphate, Lu(PO33, was found to be isotypic with the trigonal form of Yb(PO33. Two of the three Lu atoms occupy special positions (Wyckoff positions 3a and 3b, site symmetry overline{3}. The atomic arrangement consists of infinite helical polyphosphate chains running along the c axis, with a repeat period of 12 PO4 tetrahedra, joined with LuO6 octahedra.

  20. Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

    International Nuclear Information System (INIS)

    It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA+ was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the X2 test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals

  1. Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

    Energy Technology Data Exchange (ETDEWEB)

    Santos, J.C. [Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Bragança Paulista, SP (Brazil); Ladeira, M.S.P. [Departamento de Patologia, Universidade Estadual Paulista, Botucatu, SP (Brazil); Pedrazzoli, J. Jr.; Ribeiro, M.L. [Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Bragança Paulista, SP (Brazil)

    2012-06-22

    It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA{sup +} was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the X{sup 2} test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.

  2. 九个非DNA联合索引系统短串联重复序列基因座在河北汉族群体的遗传学调查及在亲子鉴定中的应用%Genetic polymorphisms of nine non-DNA combined index system short tandem repeat loci in Hebei Han population and application in paternity testing

    Institute of Scientific and Technical Information of China (English)

    关亚卿; 付丽红; 张晓静; 李淑瑾; 丛斌; 马春玲

    2011-01-01

    Objective To investigate the polymorphisms of 9 non-DNA combined index system(CODIS) short tandem repeats (STRs), i. e., D7S3048, D8S1132, D11S2368, D2S1772, D6S1043,D13S325, D12S391, GATA198B05, D18S1364 in Hebei Han population, and evaluate the usage of them in paternity testing. Methods One hundred and forty-seven unrelated healthy individuals from the Han population of Hebei province were genotyped using STRtyper10G kit including 9 STR loci on ABI 3130 Genetic Analyzer. Hardy-Weinberg equilibrium and population genetic parameters were calculated. Fourteen cases of motherless paternity testing and 2 cases of standard trios with mutation in 1 locus were detected using STRtyper 10G. Results (1) Ninety-nine alleles and 336 genotypes were observed in the 9 STR loci in the population. The cumulative discrimination power(DP) was higher than 0. 999 999 999. The cumulative probability of exclusion(PE) for trios and duos were 0. 999 974 and 0. 998 759 respectively. Departure from Hardy-Weinberg equilibrium was not observed in any of the 9 loci. (2) The combined paternity index (PI)of the 14 cases of motherless paternity testing ranged from 103-104 for 15 STR loci in ID, whereas it reached 105-109 for 22 independent STR loci included in ID and STRtyper 10G. Possible mutation in FGA and vWA was observed in 2 cases of trios, and the combined PI was 5945 and 1840 respectively for 15 STR loci in ID.Adding STRtyper 10G to detect these 2 cases, the combined PI reached 2. 76 × 107 and 4. 88 × 107respectively. Conclusion The genetic polymorphism of the 9 non-CODIS STR loci included in STRtyper 10G was quite high in Chinese Hebei Han population, indicating the 9 STR loci are valuable as complement markers for ID and PP16 kit in motherless paternity testing, paternity testing with mutation and other kinds of complicated paternity testing.%目的 调查9个非DNA联合索引系统(DNA combined index system,CODIS)的短串联重复序列(short tandem repeat,STR)基因座在河北

  3. Always look on both sides: phylogenetic information conveyed by simple sequence repeat allele sequences.

    Directory of Open Access Journals (Sweden)

    Stéphanie Barthe

    Full Text Available Simple sequence repeat (SSR markers are widely used tools for inferences about genetic diversity, phylogeography and spatial genetic structure. Their applications assume that variation among alleles is essentially caused by an expansion or contraction of the number of repeats and that, accessorily, mutations in the target sequences follow the stepwise mutation model (SMM. Generally speaking, PCR amplicon sizes are used as direct indicators of the number of SSR repeats composing an allele with the data analysis either ignoring the extent of allele size differences or assuming that there is a direct correlation between differences in amplicon size and evolutionary distance. However, without precisely knowing the kind and distribution of polymorphism within an allele (SSR and the associated flanking region (FR sequences, it is hard to say what kind of evolutionary message is conveyed by such a synthetic descriptor of polymorphism as DNA amplicon size. In this study, we sequenced several SSR alleles in multiple populations of three divergent tree genera and disentangled the types of polymorphisms contained in each portion of the DNA amplicon containing an SSR. The patterns of diversity provided by amplicon size variation, SSR variation itself, insertions/deletions (indels, and single nucleotide polymorphisms (SNPs observed in the FRs were compared. Amplicon size variation largely reflected SSR repeat number. The amount of variation was as large in FRs as in the SSR itself. The former contributed significantly to the phylogenetic information and sometimes was the main source of differentiation among individuals and populations contained by FR and SSR regions of SSR markers. The presence of mutations occurring at different rates within a marker's sequence offers the opportunity to analyse evolutionary events occurring on various timescales, but at the same time calls for caution in the interpretation of SSR marker data when the distribution of within

  4. Limitations on quantum key repeaters.

    Science.gov (United States)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  5. Antibacterial activities of almond skins on cagA-positive and-negative clinical isolates of Helicobacter pylori

    Science.gov (United States)

    2013-01-01

    Background Helicobacter pylori is known to be a gastric pathogen of humans. Eradication regimens for H. pylori infection have some side effects, compliance problems, relapses, and antibiotic resistance. Therefore, the need for alternative therapies for H. pylori infections is of special interest. We have previously shown that polyphenols from almond skins are active against a range of food-borne pathogens. The aim of this study was to evaluate the antibacterial effects of natural almond skins before and after simulated human digestion and the pure flavonoid compounds epicatechin, naringenin and protocatechuic acid against H. pylori. Results H. pylori strains were isolated from gastric biopsy samples following standard microbiology procedures. Also, cagA and vacA genes were identified using PCR. Susceptibility studies on 34 strains of H. pylori, including two reference strains (ATCC 43504, ATCC 49503), were performed by the standard agar dilution method. Natural almond skin was the most effective compound against H. pylori (MIC range, 64 to 128 μg/ml), followed by natural skin post gastric digestion (MIC range, 128 to 512 μg/ml), and natural almond skin post gastric plus duodenal digestion (MIC range, 256 to 512 μg/ml). Amongst the pure flavonoid compounds, protocatechuic acid showed the greatest activity (MIC range, 128 to 512 μg/ml) against H. pylori strains. Conclusions Polyphenols from almond skins were effective in vitro against H. pylori, irrespective of genotype status and could therefore be used in combination with antibiotics as a novel strategy for antibiotic resistance. PMID:23659287

  6. Polymorphisms in the Haem Oxygenase-1 promoter are not associated with severity of Plasmodium falciparum malaria in Ghanaian children

    DEFF Research Database (Denmark)

    Hansson, Helle H; Sørensen, Lasse Maretty; Balle, Christina;

    2015-01-01

    the allele and genotype frequencies of two single nucleotide polymorphisms; A(-413)T and G(-1135)A, and a (GT)n repeat length polymorphism in the HMOX1 promoter in paediatric malaria patients and controls to determine possible associations with malaria disease severity. METHODS: Study participants were......-specific PCR, restriction fragment length analysis and microsatellite analysis. RESULTS: The number of (GT)n repeats in the study participants varied between 21 and 46 with the majority of alleles having lengths of 26 (8.1%), 29/30 (13.2/17.9%) and 39/40 (8.0/13.8%) repeats, and was categorized into short...... distribution of the A(-413)T and (GT)n repeat polymorphisms were found between the controls and the malaria patients, or between the disease groups, for any of the analysed polymorphisms and no associations with malaria severity were found. CONCLUSION: These results contribute to the understanding of the role...

  7. Development of novel polymorphic microsatellite markers in Siganus fuscescens.

    Science.gov (United States)

    Mao, X Q; Li, Z B; Ning, Y F; Shangguan, J B; Yuan, Y; Huang, Y S; Li, B B

    2016-01-01

    Rabbitfish, Siganus fuscescens, is widely distributed in the Indo-Pacific regions and eastern Mediterranean. Its dwelling place includes reef flats, coral reef regions, and seagrass meadows in tropical area and reef areas or shallow waters in locations at high latitudes. In the present study, 10 new polymorphic microsatellite markers were screened from 30 wild S. fuscescens individuals, using a method of fast isolation protocol and amplified fragment length polymorphism of sequences containing repeats. The number of polymorphic alleles per locus was 3 to 5 with a mean of 4.3, while the value of polymorphic information content ranged from 0.283 to 0.680. The values of the observed and expected heterozygosities were in the range 0.3333-0.8462 and 0.3011-0.7424, respectively. Deviation from Hardy-Weinberg equilibrium was not observed in this study. These polymorphic loci are expected to be effective in evaluating the genetic diversity, population structure, and gene flow and in determining the paternity in S. fuscescens, as well as for conservation management. PMID:27525874

  8. Development of novel polymorphic microsatellite markers in Siganus fuscescens.

    Science.gov (United States)

    Mao, X Q; Li, Z B; Ning, Y F; Shangguan, J B; Yuan, Y; Huang, Y S; Li, B B

    2016-07-29

    Rabbitfish, Siganus fuscescens, is widely distributed in the Indo-Pacific regions and eastern Mediterranean. Its dwelling place includes reef flats, coral reef regions, and seagrass meadows in tropical area and reef areas or shallow waters in locations at high latitudes. In the present study, 10 new polymorphic microsatellite markers were screened from 30 wild S. fuscescens individuals, using a method of fast isolation protocol and amplified fragment length polymorphism of sequences containing repeats. The number of polymorphic alleles per locus was 3 to 5 with a mean of 4.3, while the value of polymorphic information content ranged from 0.283 to 0.680. The values of the observed and expected heterozygosities were in the range 0.3333-0.8462 and 0.3011-0.7424, respectively. Deviation from Hardy-Weinberg equilibrium was not observed in this study. These polymorphic loci are expected to be effective in evaluating the genetic diversity, population structure, and gene flow and in determining the paternity in S. fuscescens, as well as for conservation management.

  9. Sequencing Games with Repeated Players

    NARCIS (Netherlands)

    Estevez Fernandez, M.A.; Borm, P.E.M.; Calleja, P.; Hamers, H.J.M.

    2004-01-01

    Two classes of one machine sequencing situations are considered in which each job corresponds to exactly one player but a player may have more than one job to be processed, so called RP(repeated player) sequencing situations.In max-RP sequencing situations it is assumed that each player's cost funct

  10. Relationship between Helicobacter Pylori strains possessing cagA and vacA and gastroduodenal disease%具有cagA、vacA基因的幽门螺杆菌感染及其与胃十二指肠疾病的关系

    Institute of Scientific and Technical Information of China (English)

    许春娣; 郑洁; 奚容平; 陈舜年; 徐家裕

    2002-01-01

    目的研究上海地区儿童慢性胃炎及消化性溃疡患者中具有cagA、vacA基因幽门螺杆菌感染(HP)的感染状况以及cagA、vacA基因的存在与不同种类胃十二指肠疾病发生的关系. 方法对124例有消化道症状,年龄在4~13岁的儿童行胃镜检查,并在胃窦部取活检粘膜作HP的分离培养.利用聚合酶链反应技术(PCR)测定分离培养出的HP菌株的cagA、vacA基因进行分型.扩增所用引物:cagA1:5′-CCGGAGAATTCGATAACAGGCAAGCTTTTGAGG-3′, cagA2:5′-GCCTGCAGTTATCGAAAA-GATTGTTTGGCAG-3′, vacA1:5′-GTCAGCATCACACCGCAAC-3′, vacA2:5′-CTGCTTGAATGCGCCAAAC-3′. 结果 124例患儿中,分离培养出的HP菌株61株,平均检出率为50.0%,其中慢性胃炎培养阳性率为48.45%(47/97例),十二指肠球部溃疡为62.30%(14/26例),基因测定结果显示,61株HP中62.30%含有cagA基因,42.62%含有vacA基因.慢性胃炎和十二指肠球部溃疡cagA基因检出率相似(分别为61.70%和64.28%),而vacA基因检出率十二指肠球部溃疡明显高于慢性胃炎组(71.43%和34.04%,χ2=6.166, P<0.05).进一步分型发现感染Hp菌株的十二指肠球部溃疡患儿中,50%(7/14)为cagA+、 vacA+型,慢性胃炎患儿中38.30%(18/47)为cagA+、 vacA-型Hp菌株,统计学检查差异有显著意义(χ2=13.48, P<0.05),提示vacA与十二指肠球部溃疡的发生密切相关. 结论十二指肠球部溃疡患儿感染的HP多为cagA+、 vacA+的I型菌,vacA是致小儿十二指肠溃疡的重要因素,cagA与慢性胃炎、十二指肠溃疡的发生有关,但不能作为区分HP感染致不同胃肠道疾病的单一指标.

  11. 联合检测幽门螺杆菌CagA、VacA、Ure、Hsp60及RdxA的临床价值%Clinical value of combined detection of CagA, VacA, Ure,Hsp60 and RdxA in Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    陈海潮; 单平囡; 许德顺

    2012-01-01

    目的 探讨联合检测幽门螺杆菌细胞毒素相关蛋白(CagA)、空泡毒素相关蛋白(VacA)、尿素酶(Ure)、热休克蛋白60(Hsp60)和氮素还原酶(RdxA)在胃、十二指肠疾病中的临床价值.方法 对486例患者以免疫斑点试验(蛋白芯片)检测幽门螺杆菌CagA、VacA、Ure、Hsp60及RdxA抗体,对照组106例为健康体检人员.结果 患者组中CagA、VacA、Ure、Hsp60的总阳性率分别为65.02%、52.67%、71.40%、11.74%,均明显高于对照组(P<0.01);CagA、VacA和Ure检测对萎缩性胃炎、胃癌的阳性率为80.00%~90.00%,对胃、十二指肠溃疡的阳性率为70.00%~78.00%,其余的阳性率均<74.00%,但VacA、Ure、Hsp60检测对胃癌的阳性率均为89.47%.结论 5种Hp抗体检测对表浅性胃炎、萎缩性胃炎、胃,十二指肠溃疡及胃癌诊治有较高参考价值.%OBJECTIVE To study the clinical value of combined detection of CagA, VacA, Ure, Hsp60 ,and RdxA in Helicobacter pylori in the diagnosis and treatment of the gaster-duodenum disease. METHODS The antibodies of CagA, VacA, Ure, Hsp60 and RdxA of H. pylori for 486 patients and 106 personnel of health-examination were detected by the immunospot test (protein array). RESULTS The total positive rates of CagA, VacA, Ure, Hsp60 and RdxA (65.02%. 52.67%, 71.40%, 11. 73% .respectively ) in the patient group were significantly higher than those in the control group(P<0. 001) ; the positive rates of CagA, VacA, and Ure for the detection of atrophic gastritis and gastric cancer varied from 80. 00% to 90. 00%, gaster-duodenum ulcer varied from 70.00% to 78. 00% ,others less than 74. 00% , but the positive rates of VacA, Ure and Hsp60 for the detection of gastric cancer were 89. 47% all. CONCLUSION The detection of 5 Hp antibodies has significant value in diagnosis and treatment of superficial gastritis, atrophic gastritis, gaster-duodenum ulcer, and gastric cancer.

  12. 幽门螺杆菌毒素相关蛋白A的EPIYA多态性对胃上皮细胞AGS形态及IL-8表达的影响%Effects of the Patterns of Helicobacter pylori CagA EPIYA Motifs on AGF Cell Morphology and IL-8 Secretion Levels

    Institute of Scientific and Technical Information of China (English)

    刘鹿; 王艳春; 陶好霞; 袁盛凌; 王令春; 刘纯杰

    2015-01-01

    Objective: To investigate the effects of the patterns of EPIYA motifs of Helicobacter pylori cytotoxin-associated gene A(CagA) on the cell morphology and the IL-8 secretion levels of AGS cells. Methods: The differ⁃ent genotypes of EPIYA motifs of cagA were designed and the codons were humanized, then the synthetic frag⁃ments were assembled and constructed into pcDNA3.1 vector. The recombinants were transfected into AGS cells and the effects of patterns of EPIYA motifs of CagA on cell morphology and the IL-8 secretion levels were ob⁃served. Results: Cellular morphological observation was conducted every 6 h after the transfection, and the num⁃bers of hummingbird-like cells were counted at 24 and 36 h respectively. The statistical results showed that all CagA genotypes could increase the number of cells with hummingbird-like change. Compared with the mock-vehi⁃cle controls, all the six CagA types showed a remarkably significant differences; compared with CagA ABCCC, the five CagA types left showed a remarkably significant differences. In addition, IL-8 secreted by these cells 12 and 36 h after transfection was detected respectively. The statistical analysis revealed that, at 12 h after transfection, the secretion of IL-8 began to appear difference among the six CagA types; at 36 h after transfection, compared with the mock-vehicle controls, CagA ABD, CagA J-Western, CagA ABDD and CagA ABCCC showed a remark⁃ably significant differences. Although both CagA ABD and CagA ABDD belonged to East Asian type, they had sig⁃nificantly different effects on the IL-8 secretion levels of AGS cells. Meanwhile, both CagA ABC and CagA ABCCC which belonged to Western type had significantly different effects on the IL-8 secretion levels too. Con⁃clusion: CagA virulent factor of H.pylori caused cell hummingbird phenotype and increased the IL-8 secretion lev⁃els of AGS cells. The number of EPIYA-C motif was positively correlated with hummingbird-cell formation, and the

  13. Facts and fictions about polymorphism.

    Science.gov (United States)

    Cruz-Cabeza, Aurora J; Reutzel-Edens, Susan M; Bernstein, Joel

    2015-12-01

    We present new facts about polymorphism based on (i) crystallographic data from the Cambridge Structural Database (CSD, a database built over 50 years of community effort), (ii) 229 solid form screens conducted at Hoffmann-La Roche and Eli Lilly and Company over the course of 8+ and 15+ years respectively and (iii) a dataset of 446 polymorphic crystals with energies and properties computed with modern DFT-d methods. We found that molecular flexibility or size has no correlation with the ability of a compound to be polymorphic. Chiral molecules, however, were found to be less prone to polymorphism than their achiral counterparts and compounds able to hydrogen bond exhibit only a slightly higher propensity to polymorphism than those which do not. Whilst the energy difference between polymorphs is usually less than 1 kcal mol(-1), conformational polymorphs are capable of differing by larger values (up to 2.5 kcal mol(-1) in our dataset). As overall statistics, we found that one in three compounds in the CSD are polymorphic whilst at least one in two compounds from the Roche and Lilly set display polymorphism with a higher estimate of up to three in four when compounds are screened intensively. Whilst the statistics provide some guidance of expectations, each compound constitutes a new challenge and prediction and realization of targeted polymorphism still remains a holy grail of materials sciences.

  14. Tiled Polymorphic Temporal Media

    OpenAIRE

    Hudak, Paul; Janin, David

    2014-01-01

    International audience Tiled Polymorphic Temporal Media (Tiled PTM) is an algebraic approach to specifying the composition of multimedia values having an inherent temporal quality --- for example sound clips, musical scores, computer animations, and video clips. Mathematically, one can think of a tiled PTM as a tiling in the one dimension of time. A tiled PTM value has two synchronization marks that specify, via an effective notion of tiled product, how the tiled PTMs are positioned in tim...

  15. Optimization of sequence alignment for simple sequence repeat regions

    Directory of Open Access Journals (Sweden)

    Ogbonnaya Francis C

    2011-07-01

    Full Text Available Abstract Background Microsatellites, or simple sequence repeats (SSRs, are tandemly repeated DNA sequences, including tandem copies of specific sequences no longer than six bases, that are distributed in the genome. SSR has been used as a molecular marker because it is easy to detect and is used in a range of applications, including genetic diversity, genome mapping, and marker assisted selection. It is also very mutable because of slipping in the DNA polymerase during DNA replication. This unique mutation increases the insertion/deletion (INDELs mutation frequency to a high ratio - more than other types of molecular markers such as single nucleotide polymorphism (SNPs. SNPs are more frequent than INDELs. Therefore, all designed algorithms for sequence alignment fit the vast majority of the genomic sequence without considering microsatellite regions, as unique sequences that require special consideration. The old algorithm is limited in its application because there are many overlaps between different repeat units which result in false evolutionary relationships. Findings To overcome the limitation of the aligning algorithm when dealing with SSR loci, a new algorithm was developed using PERL script with a Tk graphical interface. This program is based on aligning sequences after determining the repeated units first, and the last SSR nucleotides positions. This results in a shifting process according to the inserted repeated unit type. When studying the phylogenic relations before and after applying the new algorithm, many differences in the trees were obtained by increasing the SSR length and complexity. However, less distance between different linage had been observed after applying the new algorithm. Conclusions The new algorithm produces better estimates for aligning SSR loci because it reflects more reliable evolutionary relations between different linages. It reduces overlapping during SSR alignment, which results in a more realistic

  16. Analysis of Human Bradykinin Receptor Gene and Endothelial Nitric Oxide Synthase Gene Polymorphisms in End-Stage Renal Disease Among Malaysians

    Directory of Open Access Journals (Sweden)

    R. Vasudevan

    2014-06-01

    Full Text Available The aim of this study was to determine the association of the c.894G>T; p.Glu298Asp polymorphism and the variable number tandem repeat (VNTR polymorphism of the endothelial nitric oxide synthase (eNOS gene and c.181C>T polymorphism of the bradykinin type 2 receptor gene (B2R in Malaysian end-stage renal disease (ESRD subjects.

  17. Polymorphism, monomorphism, and sequences in conserved microsatellites in primate species.

    Science.gov (United States)

    Blanquer-Maumont, A; Crouau-Roy, B

    1995-10-01

    Dimeric short tandem repeats are a source of highly polymorphic markers in the mammalian genome. Genetic variation at these hypervariable loci is extensively used for linkage analysis, for the identification of individuals, and may be useful for interpopulation and interspecies studies. In this paper, we analyze the variability and the sequences of a segment including three microsatellites, first described in man, in several species of primates (chimpanzee, orangutan, gibbon, and macaque) using the heterologous primers (man primers). This region is located on the human chromosome 6p, near the tumor necrosis factor genes, in the major histocompatibility complex. The fact that these primers work in all species studied indicates that they are conserved throughout the different lineages of the two superfamilies, the Hominoidea and the Cercopithecidea, represented by the macaques. However, the intervening sequence displays intraspecific and interspecific variability. The sites of base substitutions and the insertion/deletion events are not evenly distributed within this region. The data suggest that it is necessary to have a minimal number of repeats to increase the rate of mutation sufficiently to allow the development of polymorphism. In some species, the microsatellites present single base variations which reduce the number of contiguous repeats, thus apparently slowing the rate of additional slippage events. Species with such variations or a low number of repeats are monomorphic. These microsatellite sequences are informative in the comparison of closely related species and reflect the phylogeny of the Old World monkeys, apes, and man. PMID:7563137

  18. Directionality switchable gain stabilized linear repeater

    Science.gov (United States)

    Ota, Takayuki; Ohmachi, Tadashi; Aida, Kazuo

    2004-10-01

    We propose a new approach to realize a bidirectional linear repeater suitable for future optical internet networks and fault location in repeater chain with OTDR. The proposed approach is the linear repeater of simple configuration whose directionality is rearranged dynamically by electrical control signal. The repeater is composed of a magneto-optical switch, a circulator, a dynamically gain stabilized unidirectional EDFA, and control circuits. The repeater directionality is rearranged as fast as 0.1ms by an electrical control pulse. It is experimentally confirmed that OTDR with the directionality switchable repeater is feasible for repeater chain. The detailed design and performance of the repeater are also discussed, including the multi-pass interference (MPI) which may arise in the proposed repeater, the effect of the MPI on SNR degradation of the repeater chain and the feed-forward EDFA gain control circuit.

  19. Genetic polymorphism of twelve Y chromosomal short tandem repeat loci in Chinese Hui ethnic group%宁夏回族群体12个Y染色体短串联重复序列基因座多态性研究

    Institute of Scientific and Technical Information of China (English)

    朱永生; 霍正浩; 余兵; 张洪波; 王玉炯; 赵巍; 焦海燕; 党洁; 李生斌

    2007-01-01

    目的 获得12个Y染色体短串联重复序列(Y chromosome short tandem repeat,Y-STR)位点(DYS19、DYS389Ⅰ、DYS389Ⅱ、DYS390、DYS391、DYS392、DYS393、DYS385a、DYS385b、DYS437、DYS438、DYS439)在宁夏回族群体的多态性分布.方法 应用PowerPlex(R)Y荧光标记复合扩增试剂盒,对宁夏回族群体150名无关健康男性个体基因组DNA进行复合扩增,用ABI377测序仪对扩增产物进行检测,统计12个Y-STRs位点群体遗传学参数.结果 12个基因座共检测出75个等位基因,频率分布在0.0067~0.7067之间,基因多样性(gene diversity,GD)分布在0.4446~0.8877之间.在150名无关个体中,共有148种不同的单倍型,其中只有两种单倍型分别为两名个体共有,12个Y-STRs位点联合构成的单倍型多样性为0.9864.结论 12个Y-STRs基因座在宁夏回族群体具有较强的个体识别能力,可应用于群体遗传学及法医学研究.

  20. Large-scale identification of polymorphic microsatellites using an in silico approach

    Directory of Open Access Journals (Sweden)

    Linden C Gerard

    2008-09-01

    Full Text Available Abstract Background Simple Sequence Repeat (SSR or microsatellite markers are valuable for genetic research. Experimental methods to develop SSR markers are laborious, time consuming and expensive. In silico approaches have become a practicable and relatively inexpensive alternative during the last decade, although testing putative SSR markers still is time consuming and expensive. In many species only a relatively small percentage of SSR markers turn out to be polymorphic. This is particularly true for markers derived from expressed sequence tags (ESTs. In EST databases a large redundancy of sequences is present, which may contain information on length-polymorphisms in the SSR they contain, and whether they have been derived from heterozygotes or from different genotypes. Up to now, although a number of programs have been developed to identify SSRs in EST sequences, no software can detect putatively polymorphic SSRs. Results We have developed PolySSR, a new pipeline to identify polymorphic SSRs rather than just SSRs. Sequence information is obtained from public EST databases derived from heterozygous individuals and/or at least two different genotypes. The pipeline includes PCR-primer design for the putatively polymorphic SSR markers, taking into account Single Nucleotide Polymorphisms (SNPs in the flanking regions, thereby improving the success rate of the potential markers. A large number of polymorphic SSRs were identified using publicly available EST sequences of potato, tomato, rice, Arabidopsis, Brassica and chicken. The SSRs obtained were divided into long and short based on the number of times the motif was repeated. Surprisingly, the frequency of polymorphic SSRs was much higher in the short SSRs. Conclusion PolySSR is a very effective tool to identify polymorphic SSRs. Using PolySSR, several hundred putative markers were developed and stored in a searchable database. Validation experiments showed that almost all markers that were

  1. A Repeating Fast Radio Burst

    CERN Document Server

    Spitler, L G; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-01-01

    Fast Radio Bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measures (i.e. integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of the fast radio bursts has led several authors to hypothesise that they originate in cataclysmic astrophysical events. Here we report the detection of ten additional bursts from the direction of FRB121102, using the 305-m Arecibo telescope. These new bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and wh...

  2. Repeatability of Harris Corner Detector

    Institute of Scientific and Technical Information of China (English)

    HU Lili

    2003-01-01

    Interest point detectors are commonly employed to reduce the amount of data to be processed. The ideal interest point detector would robustly select those features which are most appropriate or salient for the application and data at hand. This paper shows that interest points are geometrically stable under different transformations.This property makes interest points very successful in the context of image matching. To measure this property quantatively, we introduce a evaluation criterion: repeatability rate.

  3. Crystallization and Polymorphism of Felodipine

    DEFF Research Database (Denmark)

    Surov, A. O.; Solanko, K. A.; Bond, A. D.;

    2012-01-01

    Two previously known polymorphs (forms I and II) and two new polymorphs (forms III and IV) of the calcium-channel blocker felodipine were obtained during attempts to cocrystallize the compound with a variety of potential cocrystal formers. A correlation was observed between the polymorphic outcome...... and the effective pH value in the presence of the cocrystal former, and it was possible subsequently to produce the four polymorphs by pH adjustment using H2SO4(aq) or NaOH(aq). This suggests that there is no distinct "structure-directing" role for the molecular additives present during the cocrystallization trials...

  4. Nonneutral evolution of tandem repeats in the mitochondrial DNA control region of lagomorphs.

    Science.gov (United States)

    Casane, D; Dennebouy, N; de Rochambeau, H; Mounolou, J C; Monnerot, M

    1997-08-01

    The mitochondrial DNA of the European rabbit (Oryctolagus cuniculus) contains a tandem array of 153-bp repeats in the vicinity of the replication origin of the H-stand. Variation among molecules in the number of these repeats results in inter- and intraindividual length polymorphism (heteroplasmy). Generally, in an individual, one predominant molecular type is observed, the others representing a low percentage of the mtDNA content. At the tissue level, we observe a particular distribution of this polymorphism in the gonads compared with liver, kidneys, or brain, implying a relationship between the differentiation status of the cells and the types of new mtDNA molecules which appear and accumulate during lifetime. Similar tandem repeats were also found in the mtDNA noncoding region of European hares (Lepus europaeus), a cottontail (Sylvilagus floridanus), and a pika (Ochotona rufescens). The lengths and the sequences of these units evolve rapidly and in a concerted way, but the number of repeats is maintained in a narrow range, and an internal 20-bp segment is highly conserved. Constraints restrict the evolution of the primary sequence of these repeated units, the number of which is probably controlled by a stabilizing selection. PMID:9254915

  5. A repeating fast radio burst

    Science.gov (United States)

    Spitler, L. G.; Scholz, P.; Hessels, J. W. T.; Bogdanov, S.; Brazier, A.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J.; Ferdman, R. D.; Freire, P. C. C.; Kaspi, V. M.; Lazarus, P.; Lynch, R.; Madsen, E. C.; McLaughlin, M. A.; Patel, C.; Ransom, S. M.; Seymour, A.; Stairs, I. H.; Stappers, B. W.; van Leeuwen, J.; Zhu, W. W.

    2016-03-01

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  6. 慢性萎缩性胃炎胃黏膜病理改变与CagA VacA的关系%The research on the relationship between the pathological changes of gastric mucosa in chronic atrophic gastritis and the virulence factors CagA, VacA in Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    孟祥军; 吴建新; 李定国; 陆汉明

    2003-01-01

    目的研究慢性萎缩性胃炎时胃黏膜不同的病理变化与幽门螺杆菌(Helicobaterpylori,Hp)致病因子CagA VacA之间的关系.方法120例Hp阳性的慢性萎缩性胃炎患者按黏膜炎症和黏膜萎缩的程度及肠化的有无进行分组,并抽取血清,通过Westernblot法测定血清中特异性抗体CagA(116KD)和VacA(89KD).结果①慢性萎缩性胃炎黏膜炎症的程度与CagA检出的阳性率显著相关,炎症程度严重的病例CagA抗体阳性率显著高于轻度炎症病例(85.1%vs 53.28%,P<0.005);②胃黏膜重度萎缩者VacA抗体阳性率显著高于胃黏膜轻度萎缩者(77.8%vs 38.7%,P<0.005);③慢性萎缩性胃炎患者VacA抗体阳性者多有肠化生,其肠化生的发生率显著高于VacA抗体阴性患者(84.1%vs 30.3%,P<0.005).结论CagA的表达同慢性萎缩性胃炎的严重程度密切相关,其表达的阳性率愈高胃黏膜炎症程度愈重,而VacA的表达则同胃黏膜的萎缩及肠化密切相关,胃黏膜重度萎缩与肠化患者VacA的表达率显著高于胃黏膜轻度萎缩与肠化的患者.

  7. Specialized avian predators repeatedly attack novel color morphs of Heliconius butterflies.

    Science.gov (United States)

    Langham, Gary M

    2004-12-01

    The persistence of Müllerian mimicry and geographically distinct wing patterns, as observed in many Heliconius species (Lepidoptera: Nymphalidae), is difficult to explain from a predator's perspective: predator selection against locally rare patterns must persist despite avoidance learning. Maintaining spatial color-pattern polymorphism requires local pattern avoidance, fine-scale discrimination among similar wing patterns, and repeated attacks on novel color patterns. I tested for these behaviors by presenting 80 adult rufous-tailed jacamars (Galbula ruficauda) with three morphs of Heliconius butterflies, and then presenting the same suite of butterflies to 46 of these jacamars between four and 429 days later. These trials offer the first direct evidence of the selective predator behavior required to maintain aposematic polymorphism: jacamars avoid local aposematic morphs while repeatedly attacking similar but novel morphs over time.

  8. TP53 gene polymorphisms at codons 11, 72, and 248 and association with endometriosis in a Brazilian population.

    Science.gov (United States)

    Camargo-Kosugi, C M; D'Amora, P; Kleine, J P F O; Carvalho, C V; Sato, H; Schor, E; Silva, I D C G

    2014-01-01

    We evaluated the association between TP53 gene polymorphisms and endometriosis in Brazilian women. Genomic DNA was extracted from swabs of buccal cells collected from hospital patients. TP53 gene polymorphisms were investigated at three codons: TP53 11 Glu/Gln or Lys (GAG->CAG or AAG), TP53 72 Arg/Pro (CCG->CCC), and TP53 248 Arg/Thr (CGG->TCG) using the polymerase chain reaction-restriction fragment length polymorphism method. TP53 11 presented the following genotypic distribution: the control group was 98.28% homozygous wild-type (Glu) and 1.72% homozygous variant (Gln/Lys), and the heterozygous genotype was not identified. The genotypic distribution in the endometriosis group was 96% homozygous wild-type (Glu) and 4% heterozygous (Glu-Gln/Lys); the homozygous variant genotype was not identified (P = 0.02). TP53 72 showed the following genotypic distribution: the control group was 29.75% homozygous wild-type (Arg), 47.11% heterozygous (Arg-Pro), and 23.14% homozygous variant (Pro). The genotypic distribution in the endometriosis group was 16.15% homozygous wild-type (Arg), 51.54% heterozygous (Arg-Pro), and 32.31% homozygous variant (Pro) (odds ratio = 2.26; 95% confidence interval = 1.19-4.03; P = 0.02). Only one patient had the homozygous TP53 248 genotype (Arg-Trp/Gln); all other patients were homozygous wild-type in both the control and endometriosis groups (P = 0.51; NS). We found that TP53 72 polymorphism may be associated with susceptibility to endometriosis; the presence of at least 1 polymorphic allele increased the chance of disease development by 2.26-fold. Hence, this genetic variant is a potential candidate marker for endometriosis. PMID:25177931

  9. Detection of Helicobacter pylori in gastric biopsies, saliva and dental plaques of dyspeptic patients from Marília, São Paulo, Brazil: presence of vacA and cagA genes

    OpenAIRE

    LT Rasmussen; RW de Labio; Neto, A. C.; LC Silva; VF Queiroz; MAC Smith; SLM Payão

    2012-01-01

    Helicobacter pylori, a gram-negative bacterium, possesses two important virulence factors: the vacuolating toxin (vacA), and the cytotoxin-associated gene product (cagA). The aim of the present study was to evaluate the presence of H. pylori in the stomach and oral cavity of humans and compare the cagA and vacA genotypes of H. pylori found in different samples (stomach, saliva and dental plaque) from the same patient. Gastric biopsies, saliva and dental plaques were obtained from 62 dyspeptic...

  10. 内皮细胞型一氧化氮合酶基因多态性与高血压病的相关性研究%The polymorphism of a variable number of tandem repeats in the endothelial nitri c oxide synthase gene is associated with essential hypertension in Chinese popul ation

    Institute of Scientific and Technical Information of China (English)

    路萍; 吕星; 邢瑞云; 周绪斌; 郑晓飞; 韩莉; 汪毅荣; 孙琪云

    2002-01-01

    目的探讨内皮细胞型一氧化氮合酶(endothelial nitric oxide synthase,e NOS)基因第4内含子数目可变性串联重复序列(variable number of tandem repeats poly morphism,VNTR)多态性与高血压病(essential hypertension,EH)的相关性. 方法依据VNTR位点侧翼序列设计引物,PCR方法分别自血压正常(normotension,NT)和EH人群基因组DNA扩增VNTR片段,琼脂糖凝胶电泳分析VNTR基因型,对两组VNTR的基因型与等位基因频率进行统计对比. 结果 NT和EH人群eNOS基因VNTR均存在重复4次、5次和6次3种等位基因,以及4/4纯合、4/5杂合、5/5纯合和5/6杂合4种VNTR基因型,但等位基因与基因型的分布频率存在差异.EH人群重复4次的等位基因频率(χ2=30.80,P<0.000 1 ),4/5杂合 (χ2=21.45,P<0.000·1)和4/4纯合(χ2=4.06,P<0.05)的基因型频率明显高于NT人群. 结论 eNOS基因VNTR重复4次的等位基因与EH相关,携带重复4次等位基因的人具有罹患EH 的一定危险性(χ2=33.96,P<0.000·1,OR=3.2,95%可信区间为2.0 97~4.495).

  11. Capsaicin consumption, Helicobacter pylori CagA status and IL1B-31C>T genotypes: a host and environment interaction in gastric cancer.

    Science.gov (United States)

    López-Carrillo, Lizbeth; Camargo, M Constanza; Schneider, Barbara G; Sicinschi, Liviu A; Hernández-Ramírez, Raúl U; Correa, Pelayo; Cebrian, Mariano E

    2012-06-01

    Gastric cancer (GC) has been associated with a complex combination of genetic and environmental factors. In contrast to most countries, available information on GC mortality trends showed a gradual increase in Mexico. Our aim was to explore potential interactions among dietary (chili pepper consumption), infectious (Helicobacter pylori) and genetic factors (IL1B-31 genotypes) on GC risk. The study was performed in three areas of Mexico, with different GC mortality rates. We included 158 GC patients and 317 clinical controls. Consumption of capsaicin (Cap), the pungent active substance of chili peppers, was estimated by food frequency questionnaire. H. pylori CagA status was assessed by ELISA, and IL1B-31 genotypes were determined by TaqMan assays and Pyrosequencing in DNA samples. Multivariate unconditional logistic regression was used to estimate potential interactions. Moderate to high Cap consumption synergistically increased GC risk in genetically susceptible individuals (IL1B-31C allele carriers) infected with the more virulent H. pylori (CagA+) strains. The combined presence of these factors might explain the absence of a decreasing trend for GC in Mexico. However, further research on gene-environment interactions is required to fully understand the factors determining GC patterns in susceptible populations, with the aim of recommending preventive measures for high risk individuals. PMID:22414649

  12. 布鲁氏菌和幽门螺杆菌等6种病原菌16S rRNA和cagA等基因的克隆与鉴定%Cloning and identification of 16S rRNA and cagA genes from six pathogenic bacteria including Brucella and Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    高正琴; 岳秉飞; 贺争鸣

    2010-01-01

    目的 克隆并鉴定布鲁氏菌的16S rRNA、支原体的16S rRNA、泰泽氏菌的16S rRNA、空肠弯曲菌的flaA、肝螺杆菌的flaB和幽门螺杆菌的cagA基因,为建立实时荧光定量PCR检测方法作准备.方法 设计、合成布鲁氏菌的16S rRNA、支原体的16S rRNA、泰泽氏菌的16S rRNA、空肠弯曲菌flaA、肝螺杆菌flaB和幽门螺杆菌的cagA基因的特异性引物;PCR扩增、克隆16S rRNA、flaA、flaB和cagA基因;对重组质粒进行酶切鉴定、PCR鉴定和测序分析.结果 布鲁氏菌的16S rRNA、支原体的16S rRNA、泰泽氏菌的16S rRNA、空肠弯曲杆菌的flaA、肝螺杆菌的flaB和幽门螺杆菌的cagA基因PCR扩增产物分别在612 bp、600 bp、922 bp、637 bp、1 545 bp和1 168 bp处出现特异性目的 条带,结果均与预期扩增的目的 片段大小一致.将PCR产物分别与pMD18-T载体连接并转化感受态细菌大肠埃希菌JM109.对重组质粒pT-BC16S rRNA、pT-MP16S rRNA、pT-CP16S rRNA、pT-CJflaA、pT-HHflaB和pT-HPcagA分别进行酶切鉴定及PCR鉴定,结果均可见特异性目的 条带.测序结果显示,布鲁氏菌的16S rRNA、支原体的16S rRNA、泰泽氏菌的16S rRNA、空肠弯曲菌的flaA、肝螺杆菌的flaB和幽门螺杆菌的cagA基因序列与GenBank中细菌相应序列同源性高达100 %,说明上述6种致病菌的16S rRNA、flaA、flaB和cagA基因已成功克隆.结论 成功克隆了布鲁氏菌16S rRNA、支原体的16S rRNA、泰泽氏菌的16S rRNA、空肠弯曲菌的flaA、肝螺杆菌的flaB和幽门螺杆菌的cagA基因,为建立实时荧光定量PCR检测方法奠定了基础.

  13. 胃癌组织中幽门螺杆菌cagA和vacA的表达及与其感染的相关性%Expression of Helicobacter pylori cagA and vacA and their correlations with Helicobacter pylori infection in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    佟书娟; 陈军; 詹瑧; 杨丹丹; 刘亚平

    2006-01-01

    目的:研究H pylori cagA和H pylori vacA在胃癌、胃黏膜不典型增生和胃炎组织中的表达及与H pylori感染的相关性.方法:采用Warthin-Starry嗜银染色法检测胃癌组织39例,胃黏膜不典型增生组织24例和慢性胃炎组织33例中H pylori感染情况;PCR法检测上述标本H pylori cagA和H pylori vacA的表达.结果:胃癌组织中H pylori,H pylori cagA+株和H pylori vacA+株感染率显著高于慢性胃炎组织(χ2=7.00,P<0.05;χ2=15.20,P<0.05;χ2=12.43,P<0.05);胃黏膜不典型增生组织中H pylori,H pylori cagA+株和H pylori vacA+株感染率显著高于慢性胃炎组织(χ2=6.25,P<0.05;χ2=11.04,P<0.05;χ2=11.61,P<0.05);低分化胃癌组织中H pylori,H pylori cagA+和H pylori vacA+株感染率显著高于高中分化胃癌组织(χ2=8.19,P<0.05;χ2=13.14,P<0.05;χ2=6.62,P<0.05).慢性胃炎、不典型增生和胃癌组织中H pylori与H pylori cagA和H pylori vacA表达均呈正相关(慢性胃炎:r=0.56,P<0.01;r=0.64,P<0.01;不典型增生组织:r=0.64,P<0.01;r=0.92,P<0.01;胃癌:r=0.90,P<0.01;r=0.95,P<0.01).结论:H pylori感染是慢性胃炎向胃黏膜不典型增生及胃癌发展的重要启动因子,H pylori感染可能通过诱导cagA表达促使胃黏膜上皮细胞增殖加快,诱导vacA表达促使胃黏膜上皮细胞损伤;他们的协同作用可能在胃癌发生、发展过程中发挥了重要作用.

  14. Repeated Recovery of Staphylococcus saprophyticus From the Urogenital Tracts of Women: Persistence Vs. Recurrence

    OpenAIRE

    Rupp, M E; J. Han; Goering, R. V.

    1995-01-01

    Objective: The purpose of this study was to determine whether colonization was persistent or recurrent in a small group of women who had repeated recovery of Staphylococcus saprophyticus from their urogenital tracts. Methods: Paired isolates of S. saprophyticus from each of the study subjects were genotypically typed by plasmid fingerprinting and comparison of chromosomal-DNA restriction fragment-length polymorphism patterns by field-inversion gel electrophoresis (FIGE) and contour-clamped ho...

  15. Genetic Diversity Assessment and Identification of New Sour Cherry Genotypes Using Intersimple Sequence Repeat Markers

    OpenAIRE

    Roghayeh Najafzadeh; Kazem Arzani; Naser Bouzari; Ali Saei

    2014-01-01

    Iran is one of the chief origins of subgenus Cerasus germplasm. In this study, the genetic variation of new Iranian sour cherries (which had such superior growth characteristics and fruit quality as to be considered for the introduction of new cultivars) was investigated and identified using 23 intersimple sequence repeat (ISSR) markers. Results indicated a high level of polymorphism of the genotypes based on these markers. According to these results, primers tested in this study specially IS...

  16. A tandem repeats database for bacterial genomes: application to the genotyping of Yersinia pestis and Bacillus anthracis

    Directory of Open Access Journals (Sweden)

    Denoeud France

    2001-03-01

    Full Text Available Abstract Background Some pathogenic bacteria are genetically very homogeneous, making strain discrimination difficult. In the last few years, tandem repeats have been increasingly recognized as markers of choice for genotyping a number of pathogens. The rapid evolution of these structures appears to contribute to the phenotypic flexibility of pathogens. The availability of whole-genome sequences has opened the way to the systematic evaluation of tandem repeats diversity and application to epidemiological studies. Results This report presents a database (http://minisatellites.u-psud.fr of tandem repeats from publicly available bacterial genomes which facilitates the identification and selection of tandem repeats. We illustrate the use of this database by the characterization of minisatellites from two important human pathogens, Yersinia pestis and Bacillus anthracis. In order to avoid simple sequence contingency loci which may be of limited value as epidemiological markers, and to provide genotyping tools amenable to ordinary agarose gel electrophoresis, only tandem repeats with repeat units at least 9 bp long were evaluated. Yersinia pestis contains 64 such minisatellites in which the unit is repeated at least 7 times. An additional collection of 12 loci with at least 6 units, and a high internal conservation were also evaluated. Forty-nine are polymorphic among five Yersinia strains (twenty-five among three Y. pestis strains. Bacillus anthracis contains 30 comparable structures in which the unit is repeated at least 10 times. Half of these tandem repeats show polymorphism among the strains tested. Conclusions Analysis of the currently available bacterial genome sequences classifies Bacillus anthracis and Yersinia pestis as having an average (approximately 30 per Mb density of tandem repeat arrays longer than 100 bp when compared to the other bacterial genomes analysed to date. In both cases, testing a fraction of these sequences for

  17. Polymorphs of Pridopidine Hydrochloride

    DEFF Research Database (Denmark)

    Zimmermann, A.; Frostrup, B.; Bond, A. D.

    2012-01-01

    Pridopidine hydrochloride (Huntexil, Neuro-Search A/S, Ballerup, Denmark) is a dopaminergic stabilizer, currently in development for the treatment of motor symptoms associated with Huntington's disease. In this study, two polymorphic forms are characterized, forms I and II. The crystal structures...... center dot center dot N+-H center dot center dot center dot Cl-center dot center dot center dot N+-H center dot center dot center dot motif between columns. Forms I and II have melting points of 199 and 210 degrees C, respectively. Following melting of form I, a kinetically controlled crystallization...

  18. R497K polymorphism in epidermal growth factor receptor gene is associated with the risk of acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Pan Xin-Min

    2008-07-01

    Full Text Available Abstract Background Previous studies suggested that genetic polymorphisms in the epidermal growth factor receptor (EGFR gene had been implicated in the susceptibility to some tumors and inflammatory diseases. EGFR has been recently implicated in vascular pathophysiological processes associated with excessive remodeling and atherosclerosis. Acute coronary syndrome (ACS is a clinical manifestation of preceding atherosclerosis. Our purpose was to investigate the association of the EGFR polymorphism with the risk of ACS. In this context, we analyzed the HER-1 R497K and EGFR intron 1 (CAn repeat polymorphisms in 191 patients with ACS and 210 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP strategy and direct sequencing. Results There were significant differences in the genotype and allele distribution of R497K polymorphism of the EGFR gene between cases and controls. The Lys allele had a significantly increased risk of ACS compared with the Arg allele (adjusted OR = 1.49, 95% CI: 1.12–1.98, adjusted P = 0.006. However, no significant relationship between the number of (CAn repeats of EGFR intron 1 (both alleles P = 0.911. Considering these two polymorphisms together, there was no statistically significant difference between the two groups. Conclusion R497K polymorphism of the EGFR gene is significantly associated with the risk of ACS. Our data suggests that R497K polymorphism may be used as a genetic susceptibility marker of the ACS.

  19. CAG Report on SEZs

    DEFF Research Database (Denmark)

    Aggarwal, Aradhna

    2014-01-01

    The lack of vision in policy implementation, weak commitment, and lack of spirit of experimentation have jeopardised India’s efforts to industrialise through SEZs…......The lack of vision in policy implementation, weak commitment, and lack of spirit of experimentation have jeopardised India’s efforts to industrialise through SEZs…...

  20. Infección por Helicobacter pylori en la Ciudad de La Habana, Cuba.Prevalencia de las cepas cagA positivas

    Directory of Open Access Journals (Sweden)

    Beatriz Gutiérrez

    2005-12-01

    Full Text Available Existe una gran falta de información acerca de la infección por Helicobacter pylori en los países de la región del Caribe. Nuestros objetivos en este estudio fueron determinar la prevalencia, la resistencia a los antibióticos y los factores de virulencia de la bacteria. La medida de la prevalencia de la infección por H. pylori se determinó en un grupo de pacientes a los que se les practicó una endoscopia en tres centros hospitalarios de La Ciudad de La Habana, lo que nos permitió evaluar la resistencia a la claritromicina y la presencia de cagA + en las cepas obtenidas. De las endoscopias realizadas se obtuvieron 117 biopsias gástricas, procedentes de tres centros hospitalarios de La Ciudad de La Habana, Cuba: Instituto de Oncología, Instituto de Gastroenterología y el Hospital Calixto García. Las biopsias fueron mantenidas a –70 ºC para posterior cultivo en tres medios diferentes (dos selectivos y uno no selectivo y su posterior incubación por 7 días a 37 ºC en una atmósfera de microaerofilia. La presencia de H. pylori fue identificada por la presencia de diferentes enzimas (oxidasa, catalasa, ureasa. Se realizó la extracción del DNA y la PCR, donde se utilizó el primer H2761676 y se amplificó con 397 fragmentos del gen cagA. La susceptibilidad a la claritromicina fue medida por el método de difusión en gel. Diagnóstico endoscópico: (1 cáncer gástrico; (19 úlcera duodenal; (8 úlcera gástrica; (89 dispepsias no ulcerosas, incluyendo (62 gastritis; (9 hernia hiatal; (2 reflujo biliar; (1 pólipo gástrico; (15 panendoscopias normales. Del total de 117 biopsias realizadas, 83 fueron positivas a la infección por H.pylori (70,9% . De las 35 cepas a las que se les realizó presencia de cagA+ resultaron positivas 31 (88,5%. Solo el 3% de las cepas fueron resistentes a la claritromicina. La prevalencia de la infección por H. pylori en la población sintomática de La Ciudad de La Habana es la misma que la reportada en

  1. The role of glutathione S-transferase and claudin-1 gene polymorphisms in contact sensitization

    DEFF Research Database (Denmark)

    Ross-Hansen, K; Linneberg, A; Johansen, J D;

    2013-01-01

    BACKGROUND: Contact sensitization is frequent in the general population and arises from excessive or repeated skin exposure to chemicals and metals. However, little is known about its genetic susceptibility. OBJECTIVES: To determine the role of polymorphisms of glutathione S-transferase (GST) genes...

  2. Human Xq28 Inversion Polymorphism: From Sex Linkage to Genomics--A Genetic Mother Lode

    Science.gov (United States)

    Kirby, Cait S.; Kolber, Natalie; Salih Almohaidi, Asmaa M.; Bierwert, Lou Ann; Saunders, Lori; Williams, Steven; Merritt, Robert

    2016-01-01

    An inversion polymorphism of the filamin and emerin genes at the tip of the long arm of the human X-chromosome serves as the basis of an investigative laboratory in which students learn something new about their own genomes. Long, nearly identical inverted repeats flanking the filamin and emerin genes illustrate how repetitive elements can lead to…

  3. Sequence alignment status and amplicon size difference affecting EST-SSR primer performance and polymorphism

    Science.gov (United States)

    Little attention has been given to failed, poorly-performing, and non-polymorphic expressed sequence tag (EST) simple sequence repeat (SSR) primers. This is due in part to a lack of interest and value in reporting them but also because of the difficulty in addressing the causes of failure on a prime...

  4. Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

    NARCIS (Netherlands)

    E.M. van de Giessen; M.M.L. de Win; M.W.T. Tanck; W. van den Brink; F. Baas; J. Booij

    2009-01-01

    Polymorphisms in the dopamine transporter (DAT) gene SLC6A3 are associated with human striatal DAT expression, but the exact effects on DAT expression are not clear. A variable number of tandem repeats (VNTR) in the 3' untranslated region of the DAT gene was previously investigated in relation to st

  5. CNR1 gene polymorphisms in addictive disorders: a systematic review and a meta-analysis.

    Science.gov (United States)

    Benyamina, Amine; Kebir, Oussama; Blecha, Lisa; Reynaud, Michel; Krebs, Marie-Odile

    2011-01-01

    The aim of the present work was to systematically review all association studies of cannabis receptor 1 (CNR1) polymorphisms with dependence syndrome and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the 'high risk' versus 'low risk' alleles in cases with dependence versus controls. Studies were analyzed by random-effects meta-analysis using pooled OR. Eleven full text articles met our eligibility criteria and nine meta-analyses were performed on three polymorphisms of CNR1: rs1049353, rs806379 and the AAT repeat. Of these, only the AAT polymorphism showed a significant association with illicit substance dependence but only in the Caucasian population samples and using a risk allele definition of ≥ 16 repeats. Our analysis showed a small effect size (OR = 1.55, P = 0.045), with strong heterogeneity (Q = 19.87, P < 0.01 with I² = 85%). In line with the polygenic model, our meta-analysis supports a minor implication for CNR1 AAT polymorphism in illicit substance dependence vulnerability. Further studies in well-phenotyped samples and using more polymorphisms are needed to conclude on the actual influence of cannabinoid receptor polymorphisms. PMID:20192949

  6. Improving repeatability by improving quality

    Energy Technology Data Exchange (ETDEWEB)

    Ronen, Shuki; Ackers, Mark; Schlumberger, Geco-Prakla; Brink, Mundy

    1998-12-31

    Time lapse (4-D) seismic is a promising tool for reservoir characterization and monitoring. The method is apparently simple: to acquire data repeatedly over the same reservoir, process and interpret the data sets, then changes between the data sets indicate changes in the reservoir. A problem with time lapse seismic data is that reservoirs are a relatively small part of the earth and important reservoir changes may cause very small differences to the time lapse data. The challenge is to acquire and process economical time lapse data such that reservoir changes can be detected above the noise of varying acquisition and environment. 7 refs., 9 figs.

  7. Coordinated hybrid automatic repeat request

    KAUST Repository

    Makki, Behrooz

    2014-11-01

    We develop a coordinated hybrid automatic repeat request (HARQ) approach. With the proposed scheme, if a user message is correctly decoded in the first HARQ rounds, its spectrum is allocated to other users, to improve the network outage probability and the users\\' fairness. The results, which are obtained for single- and multiple-antenna setups, demonstrate the efficiency of the proposed approach in different conditions. For instance, with a maximum of M retransmissions and single transmit/receive antennas, the diversity gain of a user increases from M to (J+1)(M-1)+1 where J is the number of users helping that user.

  8. Knob-associated tandem repeats on mitotic chromosomes in maize, Zea diploperennis and their hybrids

    Institute of Scientific and Technical Information of China (English)

    XIONG Zhiyong; GAO Yuan; HE Guanyuan; GU Mingguang; GUO Lequn; SONG Yunchun

    2004-01-01

    Knob-associated tandem repeats, 180-bp repeats and TR-1 elements, together with 45S rDNA were located on mitotic chromosomes of Zea diploperennis (DP),maize inbred line F102 and their hybrid. In DP, knobs on the short arm of chromosomes 1 and 4 and on the long arm of the chromosomes 4 and 5 are composed predominantly of the 180-bp repeats. In addition, 180-bp repeats existed together with TR-1 elements were also detected on the short arm of chromosomes 2 and 5 and on the long arm of the chromosomes 2, 6, 7, 8 and 9. In maize inbred line F102, 180-bp repeats were present in chromosomes 7S and one homologue of chromosomes 8L. TR-1 elements appeared on satellite of chromosome 6 and no detectable hybridization site co-located with 180-bp repeats was observed in maize F102. Polymorphism of size, number, and distribution of 180-bp and TR-1 signals were revealed among different chromosomes in these two species and heteromorphism existed between some homologous chromosomes in the same species.Using these excellent landmarks, the interspecific hybrid of maize and DP were identified. The results suggest that comparative analysis of 180-bp repeats and TR-1 elements may help understand the genome organization and the evolution in Zea.

  9. Toll-like receptor polymorphisms and cerebral malaria: TLR2 Δ22 polymorphism is associated with protection from cerebral malaria in a case control study

    Directory of Open Access Journals (Sweden)

    Greene Jennifer A

    2012-02-01

    Full Text Available Abstract Background In malaria endemic areas, host genetics influence whether a Plasmodium falciparum-infected child develops uncomplicated or severe malaria. TLR2 has been identified as a receptor for P. falciparum-derived glycosylphosphatidylinositol (GPI, and polymorphisms within the TLR2 gene may affect disease pathogenesis. There are two common polymorphisms in the 5' un-translated region (UTR of TLR2, a 22 base pair deletion in the first unstranslated exon (Δ22, and a GT dinucleotide repeat in the second intron (GTn. Methods These polymorphisms were examined in a Ugandan case control study on children with either cerebral malaria or uncomplicated malaria. Serum cytokine levels were analysed by ELISA, according to genotype and disease status. In vitro TLR2 expression was measured according to genotype. Results Both Δ22 and GTn polymorphisms were highly frequent, but only Δ22 heterozygosity was associated with protection from cerebral malaria (OR 0.34, 95% confidence intervals 0.16, 0.73. In vitro, heterozygosity for Δ22 was associated with reduced pam3cys inducible TLR2 expression in human monocyte derived macrophages. In uncomplicated malaria patients, Δ22 homozygosity was associated with elevated serum IL-6 (p = 0.04, and long GT repeat alleles were associated with elevated TNF (p = 0.007. Conclusion Reduced inducible TLR2 expression may lead to attenuated pro-inflammatory responses, a potential mechanism of protection from cerebral malaria present in individuals heterozygous for the TLR2 Δ22 polymorphism.

  10. The CRISPRdb database and tools to display CRISPRs and to generate dictionaries of spacers and repeats

    Directory of Open Access Journals (Sweden)

    Vergnaud Gilles

    2007-05-01

    Full Text Available Abstract Background In Archeae and Bacteria, the repeated elements called CRISPRs for "clustered regularly interspaced short palindromic repeats" are believed to participate in the defence against viruses. Short sequences called spacers are stored in-between repeated elements. In the current model, motifs comprising spacers and repeats may target an invading DNA and lead to its degradation through a proposed mechanism similar to RNA interference. Analysis of intra-species polymorphism shows that new motifs (one spacer and one repeated element are added in a polarised fashion. Although their principal characteristics have been described, a lot remains to be discovered on the way CRISPRs are created and evolve. As new genome sequences become available it appears necessary to develop automated scanning tools to make available CRISPRs related information and to facilitate additional investigations. Description We have produced a program, CRISPRFinder, which identifies CRISPRs and extracts the repeated and unique sequences. Using this software, a database is constructed which is automatically updated monthly from newly released genome sequences. Additional tools were created to allow the alignment of flanking sequences in search for similarities between different loci and to build dictionaries of unique sequences. To date, almost six hundred CRISPRs have been identified in 475 published genomes. Two Archeae out of thirty-seven and about half of Bacteria do not possess a CRISPR. Fine analysis of repeated sequences strongly supports the current view that new motifs are added at one end of the CRISPR adjacent to the putative promoter. Conclusion It is hoped that availability of a public database, regularly updated and which can be queried on the web will help in further dissecting and understanding CRISPR structure and flanking sequences evolution. Subsequent analyses of the intra-species CRISPR polymorphism will be facilitated by CRISPRFinder and the

  11. Concerted evolution of the tandemly repeated genes encoding primate U2 small nuclear RNA (the RNU2 locus) does not prevent rapid diversification of the (CT){sub n} {center_dot} (GA){sub n} microsatellite embedded within the U2 repeat unit

    Energy Technology Data Exchange (ETDEWEB)

    Liao, D.; Weiner, A.M. [Yale Univ., New Haven, CT (United States)

    1995-12-10

    The RNU2 locus encoding human U2 small nuclear RNA (snRNA) is organized as a nearly perfect tandem array containing 5 to 22 copies of a 5.8-kb repeat unit. Just downstream of the U2 snRNA gene in each 5.8-kb repeat unit lies a large (CT){sub n}{center_dot}(GA){sub n} dinucleotide repeat (n {approx} 70). This form of genomic organization, in which one repeat is embedded within another, provides an unusual opportunity to study the balance of forces maintaining the homogeneity of both kinds of repeats. Using a combination of field inversion gel electrophoresis and polymerase chain reaction, we have been able to study the CT microsatellites within individual U2 tandem arrays. We find that the CT microsatellites within an RNU2 allele exhibit significant length polymorphism, despite the remarkable homogeneity of the surrounding U2 repeat units. Length polymorphism is due primarily to loss or gain of CT dinucleotide repeats, but other types of deletions, insertions, and substitutions are also frequent. Polymorphism is greatly reduced in regions where pure (CT){sub n} tracts are interrupted by occasional G residues, suggesting that irregularities stabilize both the length and the sequence of the dinucleotide repeat. We further show that the RNU2 loci of other catarrhine primates (gorilla, chimpanzee, ogangutan, and baboon) contain orthologous CT microsatellites; these also exhibit length polymorphism, but are highly divergent from each other. Thus, although the CT microsatellite is evolving far more rapidly than the rest of the U2 repeat unit, it has persisted through multiple speciation events spanning >35 Myr. The persistence of the CT microsatellite, despite polymorphism and rapid evolution, suggests that it might play a functional role in concerted evolution of the RNU2 loci, perhaps as an initiation site for recombination and/or gene conversion. 70 refs., 5 figs.

  12. Crowding by a repeating pattern.

    Science.gov (United States)

    Rosen, Sarah; Pelli, Denis G

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target-flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker.

  13. CDC Vital Signs: Preventing Repeat Teen Births

    Science.gov (United States)

    ... MB] Read the MMWR Science Clips Preventing Repeat Teen Births Recommend on Facebook Tweet Share Compartir On ... live birth before age 20. Problem Too many teens, ages 15–19, have repeat births. Nearly 1 ...

  14. Automatization and familiarity in repeated checking

    NARCIS (Netherlands)

    Dek, Eliane C P; van den Hout, Marcel A.; Giele, Catharina L.; Engelhard, Iris M.

    2014-01-01

    Repeated checking paradoxically increases memory uncertainty. This study investigated the underlying mechanism of this effect. We hypothesized that as a result of repeated checking, familiarity with stimuli increases, and automatization of the checking procedure occurs, which should result in decrea

  15. 5,10-Methylenetetrahydrofolate Reductase 677 and 1298 Polymorphisms, Folate Intake, and Microsatellite Instability in Colon Cancer

    OpenAIRE

    Eaton, Allison M.; Sandler, Robert; Carethers, John M.; Millikan, Robert C.; Galanko, Joseph; Keku, Temitope O.

    2005-01-01

    The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene plays a critical role in folate metabolism. Studies on the association between MTHFR polymorphisms and length changes in short tandem repeat DNA sequences [microsatellite instability (MSI)] are inconsistent. Using data from colon cancer cases (n = 503) enrolled as part of an existing population-based case-control study, we investigated the association between MTHFR 677 and MTHFR 1298 polymorphisms and MSI. We also examined whether the ...

  16. Essays in the theory of repeated games

    OpenAIRE

    Osório-Costa, António Miguel

    2010-01-01

    This thesis comprises three essays in economic theory. The first two are in the theory of repeated games. The third is also a theoretical contribution, which mixes con- cepts both from repeated games and the theory of incentives. The first chapter is a novel contribution to frequent monitoring in repeated games. The second one, studies for the first time, infinitely repeated games where the repetitions of the stage game are random. The last chapter, studies the provision of incentives in a pr...

  17. Lambda Exonuclease Digestion of CGG Trinucleotide Repeats

    OpenAIRE

    Conroy, R. S.; Koretsky, A P; Moreland, J.

    2009-01-01

    Fragile X syndrome and other triplet repeat diseases are characterized by an elongation of a repeating DNA triplet. The ensemble-averaged lambda exonuclease digestion rate of different substrates, including one with an elongated FMR1 gene containing 120 CGG repeats, was measured using absorption and fluorescence spectroscopy. Using magnetic tweezers sequence-dependent digestion rates and pausing was measured for individual lambda exonucleases. Within the triplet repeats a lower average and na...

  18. Genetic polymorphisms at the leptin receptor gene in three beef cattle breeds

    Directory of Open Access Journals (Sweden)

    Sabrina E.M. Almeida

    2008-01-01

    Full Text Available The genetic diversity of a single nucleotide polymorphism (SNP at the exon 20 (T945M of the leptin receptor gene (LEPR and of three short tandem repeats (STRs BM7225, BMS694, and BMS2145 linked to LEPR was investigated in three beef cattle herds (Brangus Ibagé, Charolais, and Aberdeen Angus. A cheap and effective new method to analyze the T945M polymorphism in cattle populations was developed and the possible role of these polymorphisms in reproduction and weight gain of postpartum cows was evaluated. High levels of genetic diversity were observed with the average heterozygosity of STRs ranging from 0.71 to 0.81. No significant association was detected between LEPR markers and reproductive parameters or daily weight gain. These negative results suggest that the LEPR gene polymorphisms, at least those herein described, do not influence postpartum cows production.

  19. Association between amygdala reactivity and a dopamine transporter gene polymorphism.

    Science.gov (United States)

    Bergman, O; Åhs, F; Furmark, T; Appel, L; Linnman, C; Faria, V; Bani, M; Pich, E M; Bettica, P; Henningsson, S; Manuck, S B; Ferrell, R E; Nikolova, Y S; Hariri, A R; Fredrikson, M; Westberg, L; Eriksson, E

    2014-01-01

    Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [(15)O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity. PMID:25093598

  20. 47 CFR 97.205 - Repeater station.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Repeater station. 97.205 Section 97.205... SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  1. 47 CFR 22.1015 - Repeater operation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Repeater operation. 22.1015 Section 22.1015... Offshore Radiotelephone Service § 22.1015 Repeater operation. Offshore central stations may be used as repeater stations provided that the licensee is able to maintain control of the station, and in...

  2. Topological characteristics of helical repeat proteins

    NARCIS (Netherlands)

    Groves, M R; Barford, D

    1999-01-01

    The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem

  3. Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

    DEFF Research Database (Denmark)

    Andersen, G; Overgaard, J; Albrechtsen, Anders;

    2006-01-01

    The 825C>T polymorphism in the gene encoding the G protein beta3 subunit (GNB3) causes enhanced G protein activation and increased in vitro cell proliferation. This polymorphism is also repeatedly associated with an increased risk of hypertension and has been studied in relation to obesity...... with divergent results. Only a few association studies have investigated whether this polymorphism is related to type 2 diabetes or the metabolic syndrome. We estimated the impact of the GNB3 825C>T polymorphism in relatively large-scale association studies of common phenotypes of the metabolic syndrome....

  4. Hinf I/Tsp509 I and BsoF I polymorphisms in the flanking regions of the human VNTR locus D1S80.

    Science.gov (United States)

    Duncan, G T; Balamurugan, K; Budowle, B; Tracey, M L

    1996-11-01

    The minisatellite locus D1S80 (1p35-p36), is a highly polymorphic VNTR that also contains a Hinf I polymorphism in the 5' flanking region. Our data suggest that the Hinf I polymorphism is a G > T transversion 58 bases downstream from the forward primer. This G > T transversion also creates a Tsp509 I restriction site. Additionally, a G > C transversion polymorphism was identified in the 3' flanking region by the creation of a BsoF I restriction site immediately adjacent to the repeat region. PMID:9021400

  5. Detection of Helicobacter pylori in gastric biopsies, saliva and dental plaques of dyspeptic patients from Marília, São Paulo, Brazil: presence of vacA and cagA genes

    Directory of Open Access Journals (Sweden)

    LT Rasmussen

    2012-01-01

    Full Text Available Helicobacter pylori, a gram-negative bacterium, possesses two important virulence factors: the vacuolating toxin (vacA, and the cytotoxin-associated gene product (cagA. The aim of the present study was to evaluate the presence of H. pylori in the stomach and oral cavity of humans and compare the cagA and vacA genotypes of H. pylori found in different samples (stomach, saliva and dental plaque from the same patient. Gastric biopsies, saliva and dental plaques were obtained from 62 dyspeptic adults. DNA was extracted and evaluated for the presence of H. pylori and the alleles cagA and vacA. Persons with gastritis had a higher frequency of H. pylori -positive samples in the stomach while positive samples from gastric biopsies were significantly correlated with those from the oral cavity. There was a high H. pylori frequency in patients while the cagA gene was associated with vacA s1 alleles in gastric biopsies. Our results suggest a reservoir of the species in the oral cavity and that, in one patient, more than one H. pylori strain may exist in the saliva, dental plaque and stomach. We found a relationship between gastric infection and the bacterium in the oral cavity, with the cytotoxin genotype varying between saliva and dental plaque.

  6. [Clinical efficacy of decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen on elderly patients with high risk myelodysplastic syndrome and acute myeloid leukemia].

    Science.gov (United States)

    Dou, Li-Ping; Jing, Yu; Wang, Quan-Shun; Mei, Jun-Hui; Yu, Li

    2013-06-01

    This study was aimed to observe the clinical efficacy and adverse effects of decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen on elderly patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Five elderly patients with MDS and AML were treated with decitabine plus improved CAG chemotherapy and donor peripheral lymphocyte infusion regimen. Examinations on liver and renal function, electrocardiogram and bone marrow analysis were performed before and after treatment, and adverse effects were observed. The results indicated that after a course of treatment by decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen, the total effective rate was 100%, and 4 patients (80%) achieved complete remission, 1 patient achieved partial remission. The dominant clinical adverse effect was bone marrow depression, the median time of neutrophil>0.5×10(9)/L and platelet>20×10(9)/L was 15 d and 16 d respectively for patients without previous MDS. It is concluded that decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen may be effective with less adverse effects for elderly primary AML and high risk MDS patients, it is a promising therapeutic methods and worthy to deeply study.

  7. Genetic susceptibility on CagA-interacting molecules and gene-environment interaction with phytoestrogens: a putative risk factor for gastric cancer.

    Directory of Open Access Journals (Sweden)

    Jae Jeong Yang

    Full Text Available OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2 are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively. Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05. CONCLUSIONS: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk.

  8. Angiogenin gene polymorphism

    Institute of Scientific and Technical Information of China (English)

    Hongli Wang; Dongsheng Fan; Yingshuang Zhang

    2013-01-01

    Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we se-quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mel itus (129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy pa-tients) and 268 healthy controls. Al subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistical y significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.

  9. Polymorphic Evolutionary Games.

    Science.gov (United States)

    Fishman, Michael A

    2016-06-01

    In this paper, I present an analytical framework for polymorphic evolutionary games suitable for explicitly modeling evolutionary processes in diploid populations with sexual reproduction. The principal aspect of the proposed approach is adding diploid genetics cum sexual recombination to a traditional evolutionary game, and switching from phenotypes to haplotypes as the new game׳s pure strategies. Here, the relevant pure strategy׳s payoffs derived by summing the payoffs of all the phenotypes capable of producing gametes containing that particular haplotype weighted by the pertinent probabilities. The resulting game is structurally identical to the familiar Evolutionary Games with non-linear pure strategy payoffs (Hofbauer and Sigmund, 1998. Cambridge University Press), and can be analyzed in terms of an established analytical framework for such games. And these results can be translated into the terms of genotypic, and whence, phenotypic evolutionary stability pertinent to the original game. PMID:27016340

  10. Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Kayo OSAWA

    2009-01-01

    The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism ofirrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinudeotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity

  11. Gene Polymorphisms in Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Marja L. Laine

    2010-01-01

    Full Text Available We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polymorphism. Candidate gene polymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in the IL1, IL6, IL10, vitamin D receptor, and CD14 genes may be associated with CP in certain populations. However, carriage rates of the rare (-allele of any polymorphism varied considerably among studies and most of the studies appeared under-powered and did not correct for other risk factors. Larger cohorts, well-defined phenotypes, control for other risk factors, and analysis of multiple genes and polymorphisms within the same pathway are needed to get a more comprehensive insight into the contribution of gene polymorphisms in CP.

  12. Analysis of simple sequence repeats markers derived from Phytophthora sojae expressed sequence tags

    Institute of Scientific and Technical Information of China (English)

    ZHU Zhendong; HUO Yunlong; WANG Xiaoming; HUANG Junbin; WU Xiaofei

    2004-01-01

    Five thousand and eight hundred publicly available expressed sequence tags (ESTs) of Phytophthora sojae were electronically searched and 415 simple sequence repeats (SSRs) were identified in 369 ESTs. The average density of SSRs was one SSR per 8.9 kb of EST sequence screened. The most frequent repeats were trinucleotide repeats (50.1%) and the least frequent were tetranucleotide repeats (8.2%). Forty primer pairs were designed and tested on 5 strains of P. sojae. Thirty-three primer pairs had successful PCR amplifications. Of the 33 functional primer pairs, 28 primer pairs produced characteristic SSR bands of the expected size, and 15 primer pairs (45.5%) detected polymorphism among 5 tested strains of P. sojae. Based on the polymorphisms detected with 20 EST-SSR markers, the 5 tested strains of P. sojae were clustered into 3 groups. In this study, the SSR markers of P. sojae were developed for the first time. These markers could be useful for identification, genetic variation study, and molecular mapping of P. sojae and its relative species.

  13. Effect of Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator Polymorphisms on Susceptibility to Type 2 Diabetes in Malaysian Subjects

    Directory of Open Access Journals (Sweden)

    Zaid Al-Hamodi

    2012-01-01

    Full Text Available Elevated activity of plasminogen activator inhibitor-1 (PAI-1 and decreased tissue plasminogen activator (tPA activity are considered to be important risk factors for type 2 diabetes mellitus (T2DM and metabolic syndrome (MetS. The aim of this study was to investigate the association of the PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms with T2DM in Malaysian subjects. Serum insulin, coronary risk panel, plasma glucose, and PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms were studied in 303 T2DM subjects (227 with MetS and 76 without MetS and 131 normal subjects without diabetes and MetS. Statistical analysis showed that the dominant and additive models of PAI-1 4G/5G polymorphism showed a weak association with T2DM without MetS (OR=2.35, P=0.045; OR=1.67, P=0.058. On the other hand, the recessive model of the tPA Alu-repeat I/D polymorphism showed an association with T2DM with MetS (OR=3.32, P=0.013 whereas the dominant and additive models of the tPA Alu-repeat I/D polymorphism were not associated with T2DM either with or without MetS.

  14. General benchmarks for quantum repeaters

    CERN Document Server

    Pirandola, Stefano

    2015-01-01

    Using a technique based on quantum teleportation, we simplify the most general adaptive protocols for key distribution, entanglement distillation and quantum communication over a wide class of quantum channels in arbitrary dimension. Thanks to this method, we bound the ultimate rates for secret key generation and quantum communication through single-mode Gaussian channels and several discrete-variable channels. In particular, we derive exact formulas for the two-way assisted capacities of the bosonic quantum-limited amplifier and the dephasing channel in arbitrary dimension, as well as the secret key capacity of the qubit erasure channel. Our results establish the limits of quantum communication with arbitrary systems and set the most general and precise benchmarks for testing quantum repeaters in both discrete- and continuous-variable settings.

  15. [A feasibility analysis on individualized acupuncture treatment of irritable bowel syndrome under help of genetic polymorphism technique].

    Science.gov (United States)

    Wu, Xiao-Liang; Sun, Jian-Hua; Liu, Lan-Ying; Fu, Hai-Yang; Jiao, Dai-Yan; Shu, Yan-Ye; Chen, Dong; Liu, Cheng-Yong; Zhan, Dao-Wei; Zhang, Wei

    2014-06-01

    Along with the application of genetic polymorphism techniques to individualized treatment of clinical disorders, the screening of polymorphisms markers of serotonin (5-HT) transporter (SERT) is a hot-spot of researches on irritable bowel syndrome (IBS). In the present paper, the authors introduce 1) optimized schemes of diagnosis and treatment of IBS on the basis of syndrome-differentiation for acupuncture in combination with Chinese herbal medicines, and application of 5-HT transporter polymorphism, 2) application of genetic polymorphism to researches on IBS, and 3) feasibility of genetic polymorphism techniques for guiding individualized treatment of IBS. Up to now, serotonin transporter length polymorphic region (5-HTTLPR), serotonin transporter intron 2 variable number of tandem repeat (Stin 2 VNTR) and single nucleotide polymorphism rs 25531 in the long allele of the 5-HTTLPR have been identified. On the basis of the treatment of IBS, we need establishing a set of guide lines for the individualized acupuncture treatment. The genotyping methods for genetic polymorphism should be widely used in this research field. 5-HT TLPR/ Stin 2 VNTR/rs 25531 polymorphisms would have a bright future in the field of IBS research and treatment.

  16. Quality control during repeated fryings

    Directory of Open Access Journals (Sweden)

    Cuesta, C.

    1998-08-01

    Full Text Available Most of the debate ¡s about how the slow or frequent turnover of fresh fat affects the deterioration, of fat used in frying. Then, the modification of different oils used in repeated fryings of potatoes without or with turnover of fresh oil, under similar frying conditions, was evaluated by two criteria: by measuring the total polar component isolated by column chromatography and by the evaluation of the specific compounds related to thermoxidative and hydrolytic alteration by High Performance Size Exclusion Chromatography (HPSEC. The results indicate that with frequent turnover of fresh oil, the critical level of 25% of polar material is rarely reached, and there are fewer problems with fat deterioration because the frying tended to increase the level of polar material and thermoxidative compounds (polymers and dimers of triglycerides and oxidized triglycerides in the fryer oil during the first fryings, followed by minor changes and a tendency to reach a near-steady state in successive fryings. However, in repeated frying of potatoes using a null turnover the alteration rate was higher being linear the relationship found between polar material or the different thermoxidative compounds and the number of fryings. On the other hand chemical reactions produced during deep-fat frying can be minimized by using proper oils. In addition the increased level of consumers awareness toward fat composition and its impact on human health could had an impact on the selection of fats for snacks and for industry. In this way monoenic fats are the most adequate from a nutritional point of view and for its oxidative stability during frying.

  17. Genotyping of PCR-based polymorphisms and linkage-disequilibrium analysis at the NF1 locus

    Energy Technology Data Exchange (ETDEWEB)

    Purandare, S.M.; Viskochil, D.H.; Cawthon, R. [Univ. of Utah, Salt Lake City, UT (United States)] [and others

    1996-07-01

    Six polymorphism across the NF1 gene have been adapted for genotyping through application of PCR-based assays. Three exon-based polymorphisms - at positions 702, 2034, and 10647 in the NF1 cDNA - were genotyped by mutagenically separated PCR (MS-PCR). A fourth polymorphism, DV1.9, is an L1 insertion element in intron 30, and the other two polymorphisms, GXAlu and EVI-20, are short tandem repeats in intron 27b. All the polymorphisms were evaluated in a cohort of 110 CEPH individuals who previously had been analyzed by use of eight RFLPs at the NF1 locus. Pairwise linkage-disequilibrium analyses with the six PCR-based polymorphisms and their flanking markers demonstrated disequilibrium between all tested loci. Genotypes of the four diallelic polymorphisms (702, 2034, 10647, and DV1.9) were also evaluated in cohorts from the CEPH, African, and Japanese populations. The CEPH and Japanese cohorts showed similar heterozygosities and linkage-disequilibrium coefficients. The African cohort showed a higher degree of heterozygosity and lower linkage-disequilibrium values, compared with the CEPH and Japanese cohorts. 36 refs., 2 figs., 3 tabs.

  18. Preliminary study on association of beta2-adrenergic receptor polymorphism with hypertension in hypertensive subjects attending Balok Health Centre, Kuantan.

    Science.gov (United States)

    Atia, A E; Norsidah, K; Nor Zamzila, A; Rafidah Hanim, M; Samsul, D; Aznan, M A M; Rashidah, A R; Norlelawati, A T

    2012-02-01

    Polymorphisms within the beta2-adrenergic receptor (ADRB2) gene have been repeatedly linked to hypertension. Among the ADRB2 polymorphisms detected, Arg16Gly and Gln27Glu codons are considered the two most important variations. The amino acid substitution at these codons may lead to abnormal regulation of ADRB2 activity. The aim of the present study was to assess the association between ADRB2 polymorphisms and hypertension. This case-control study consisted of 100 unrelated subjects (50 hypertensive and 50 matched normal controls). Arg16Gly and the Gln27Glu polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay. There were no significant evidence of association in allelic and genotypes distribution of Arg16Gly and Glu27Gln with blood pressure and hypertension. These findings suggest that the variation within codon 16 and 27 of ADRB2 gene were unlikely to confer genetic susceptibility for hypertension in our population samples. PMID:22582545

  19. Soroprevalência de anticorpos contra o antígeno CagA do Helicobacter pylori em pacientes com úlcera gástrica na região Norte do Brasil Seroprevalence of antibodies against the CagA antigen the Helicobacter pylori in patients with gastric ulcer in the North region of Brazil

    Directory of Open Access Journals (Sweden)

    Luisa Caricio Martins

    2002-08-01

    Full Text Available O Helicobacter pylori é um agente patogênico largamente distribuído no mundo, estando envolvido no desenvolvimento de várias doenças gastrointestinais. Atualmente a infecção pela cepa virulenta (CagA+ do H. pylori é considerado um dos principais fatores etiológicos para o desenvolvimento de ulcerações gástricas. Baseado nessa informação, investigamos a soroprevalência das cepas virulentas entre os pacientes com úlcera gástrica da nossa região, utilizando testes sorológicos para detecção de anticorpos contra o H. pylori e a proteína CagA. Sendo observado que 82% (45/55 dos pacientes estavam infectados pela cepa virulenta, entre esses 89% (40/45 apresentaram grau de inflamação aumentado na mucosa gástrica, com denso infiltrado de leucócitos no tecido, o que provavelmente favoreceu a formação das ulcerações gástricas.Helicobacter pylori is a pathogenic agent with a worldwide distribution and is involved in the development of many gastrointestinal diseases. Nowadays infection with the virulent strain CagA+ of H. pylori is considered one of the main etiological factors in the development of gastric ulcer. Based on this information, we investigated the seroprevalence of virulent strains among patients with gastric ulcer from one region, using serologic tests to detect antibodies against H. pylori and CagA protein. Infection by the virulent strain was found in 82% (40/55 of the patients, and among these, 89% (40/45 presented an increased degree of inflammation in the gastric mucosa, with a dense infiltration of leukocytes in the tissue, which probably favored the formation of gastric ulcer. We concluded that the presence of the virulent strain is related to the development of an increased inflammation in the gastric mucosa.

  20. CagA phosphorylation EPIYA-C motifs and the vacA i genotype in Helicobacter pylori strains of asymptomatic children from a high-risk gastric cancer area in northeastern Brazil

    Science.gov (United States)

    Braga, Lucia Libanez Bessa Campelo; de Oliveira, Maria Aparecida Alves; Gonçalves, Maria Helane Rocha Batista; Chaves, Fernando Kennedy; Benigno, Tiago Gomes da Silva; Gomes, Adriana Dias; Silva, Cícero Igor Simões Moura; Anacleto, Charles; Batista, Sérgio de Assis; Queiroz, Dulciene Maria Magalhães

    2014-01-01

    Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric diseases. Virulence factors such as VacA and CagA have been shown to increase the risk of these diseases. Studies have suggested a causal role of CagA EPIYA-C in gastric carcinogenesis and this factor has been shown to be geographically diverse. We investigated the number of CagA EPIYA motifs and the vacA i genotypes in H. pylori strains from asymptomatic children. We included samples from 40 infected children (18 females and 22 males), extracted DNA directly from the gastric mucus/juice (obtained using the string procedure) and analysed the DNA using polymerase chain reaction and DNA sequencing. The vacA i1 genotype was present in 30 (75%) samples, the i2 allele was present in nine (22.5%) samples and both alleles were present in one (2.5%) sample. The cagA-positive samples showed distinct patterns in the 3’ variable region of cagA and 18 of the 30 (60%) strains contained 1 EPIYA-C motif, whereas 12 (40%) strains contained two EPIYA-C motifs. We confirmed that the studied population was colonised early by the most virulent H. pylori strains, as demonstrated by the high frequency of the vacA i1 allele and the high number of EPIYA-C motifs. Therefore, asymptomatic children from an urban community in Fortaleza in northeastern Brazil are frequently colonised with the most virulent H. pylori strains. PMID:25494468

  1. Identification of the porcine homologous of human disease causing trinucleotide repeat sequences

    DEFF Research Database (Denmark)

    Madsen, Lone Bruhn; Thomsen, Bo; Sølvsten, Christina Ane Elisabeth;

    2007-01-01

    in this paper the identification of porcine noncoding and polyglutamine-encoding TNR regions and the comparison to the homologous TNRs from human, chimpanzee, dog, opossum, rat, and mouse. Several of the porcine TNR regions are highly polymorphic both within and between different breeds. The TNR regions......expansion in the repeat number of intragenic trinucleotide repeats (TNRs) is associated with a variety of inherited human neurodegenerative diseases. To study the compositionof TNRs in a mammalian species representing an evolutionary intermediate between humans and arodents, we describe...... are more conserved in terms of repeat length between humans and pigs than between humans and rodents suggesting that TNR lengths could be implicated in mammalian evolution. The TNRs in the FMR2, SCA6, SCA12, and Huntingtin geenes are comparable in length to alleles naturally occurring in humans, and also...

  2. Typing dinucleotide repeat loci using microplate array diagonal gel electrophoresis: proof of principle.

    Science.gov (United States)

    Rodríguez, Santiago; Chen, Xiao-He; Day, Ian N M

    2004-04-01

    Polymorphic dinucleotide repeat loci ('microsatellite markers') are found in varying abundance throughout the genomes of most organisms. They have been extensively used for genetic studies, but conventional techniques used for their genotyping require sophisticated equipment. Microplate array diagonal gel electrophoresis (MADGE) has previously been extended to economical high-throughput genotyping of trinucleotide and tetranucleotide microsatellite amplicons. However, the capability of this technique to resolve the alleles of dinucleotide repeat loci has not been explored previously. Here we show that a m