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Sample records for involving multiple snps

  1. Multiple ant colony algorithm method for selecting tag SNPs.

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    Liao, Bo; Li, Xiong; Zhu, Wen; Li, Renfa; Wang, Shulin

    2012-10-01

    The search for the association between complex disease and single nucleotide polymorphisms (SNPs) or haplotypes has recently received great attention. Finding a set of tag SNPs for haplotyping in a great number of samples is an important step to reduce cost for association study. Therefore, it is essential to select tag SNPs with more efficient algorithms. In this paper, we model problem of selection tag SNPs by MINIMUM TEST SET and use multiple ant colony algorithm (MACA) to search a smaller set of tag SNPs for haplotyping. The various experimental results on various datasets show that the running time of our method is less than GTagger and MLR. And MACA can find the most representative SNPs for haplotyping, so that MACA is more stable and the number of tag SNPs is also smaller than other evolutionary methods (like GTagger and NSGA-II). Our software is available upon request to the corresponding author.

  2. A Bayesian Hierarchical Model for Relating Multiple SNPs within Multiple Genes to Disease Risk

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    Lewei Duan

    2013-01-01

    Full Text Available A variety of methods have been proposed for studying the association of multiple genes thought to be involved in a common pathway for a particular disease. Here, we present an extension of a Bayesian hierarchical modeling strategy that allows for multiple SNPs within each gene, with external prior information at either the SNP or gene level. The model involves variable selection at the SNP level through latent indicator variables and Bayesian shrinkage at the gene level towards a prior mean vector and covariance matrix that depend on external information. The entire model is fitted using Markov chain Monte Carlo methods. Simulation studies show that the approach is capable of recovering many of the truly causal SNPs and genes, depending upon their frequency and size of their effects. The method is applied to data on 504 SNPs in 38 candidate genes involved in DNA damage response in the WECARE study of second breast cancers in relation to radiotherapy exposure.

  3. Joint effect of multiple common SNPs predicts melanoma susceptibility.

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    Shenying Fang

    Full Text Available Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive value for the model using a polygenic risk score (PRS comprised of 11 SNPs was 0.07(95% CI, 0.05-0.07. The overall predictive value of the PRS together with conventional phenotypic factors in the MDACC population was 0.69 (95% CI, 0.64-0.69. PRS significantly improved the risk prediction and reclassification in melanoma as compared with the conventional model. Our study suggests that a polygenic profile can improve the predictive value of an individual gene polymorphism and may be able to significantly improve the predictive value beyond conventional phenotypic melanoma risk factors.

  4. Bioinformatics Analysis for Coding SNPs of the HLADQA1 Gene Involved in Susceptibility to Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    Yanyun Li; Jun Xing; Linsheng Zhao; Yanni Li; Yuchuan Wang; Weiming Zhang

    2006-01-01

    OBJECTIVE To analyze coding SNPs of the HLA-DQA1 gene involved in susceptibility for cervical cancer by a bioinformatics approach, and to choose some SNPs that may have an association with cervical cancer.METHODS By a SNPper tool we extracted SNPs from a public database (dbSNP), exporting them in FASTA formats suitable for subsequent use.Then we used PARSESNP as a tool for the analysis of the cSNPs.RESULTS In the cSNPs of the HLA-DQA1 gene, we find that rs9272693and rs9272703, are made up of missense mutations which convert a codon for one amino acid into a codon for a different amino acid. We chose a PSSM Difference >10 as a lower level for the scores of changes predicted to be deldterious.CONCLUSION We used a bioinformatics approach for cSNPs analysis of the HLA-DQA1 gene. This method can select the variants in a conserved region, and give a PSSM Difference score. But the results need to be verified in cervical cancer patients and a control population.

  5. Estimating the proportion of variation in susceptibility to multiple sclerosis captured by common SNPs

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    Watson, Corey T.; Disanto, Giulio; Breden, Felix; Giovannoni, Gavin; Ramagopalan, Sreeram V.

    2012-10-01

    Multiple sclerosis (MS) is a complex disease with underlying genetic and environmental factors. Although the contribution of alleles within the major histocompatibility complex (MHC) are known to exert strong effects on MS risk, much remains to be learned about the contributions of loci with more modest effects identified by genome-wide association studies (GWASs), as well as loci that remain undiscovered. We use a recently developed method to estimate the proportion of variance in disease liability explained by 475,806 single nucleotide polymorphisms (SNPs) genotyped in 1,854 MS cases and 5,164 controls. We reveal that ~30% of MS genetic liability is explained by SNPs in this dataset, the majority of which is accounted for by common variants. These results suggest that the unaccounted for proportion could be explained by variants that are in imperfect linkage disequilibrium with common GWAS SNPs, highlighting the potential importance of rare variants in the susceptibility to MS.

  6. Analysis of multiple SNPs in genetic association studies: comparison of three multi-locus methods to prioritize and select SNPs

    NARCIS (Netherlands)

    Heidema, A.G.; Feskens, E.J.M.; Doevendans, P.A.F.M.; Ruven, H.J.T.; Houwelingen, H.C.; Mariman, E.C.M.; Boer, J.M.A.

    2007-01-01

    Nonparametric approaches have been developed that are able to analyze large numbers of single nucleotide polymorphisms (SNPs) in modest sample sizes. These approaches have different selection features and may not provide similar results when applied to the same dataset. Therefore, we compared the re

  7. Seq4SNPs: new software for retrieval of multiple, accurately annotated DNA sequences, ready formatted for SNP assay design

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    Dunning Alison M

    2009-06-01

    Full Text Available Abstract Background In moderate-throughput SNP genotyping there was a gap in the workflow, between choosing a set of SNPs and submitting their sequences to proprietary assay design software, which was not met by existing software. Retrieval and formatting of sequences flanking each SNP, prior to assay design, becomes rate-limiting for more than about ten SNPs, especially if annotated for repetitive regions and adjacent variations. We routinely process up to 50 SNPs at once. Implementation We created Seq4SNPs, a web-based, walk-away software that can process one to several hundred SNPs given rs numbers as input. It outputs a file of fully annotated sequences formatted for one of three proprietary design softwares: TaqMan's Primer-By-Design FileBuilder, Sequenom's iPLEX or SNPstream's Autoprimer, as well as unannotated fasta sequences. We found genotyping assays to be inhibited by repetitive sequences or the presence of additional variations flanking the SNP under test, and in multiplexes, repetitive sequence flanking one SNP adversely affects multiple assays. Assay design software programs avoid such regions if the input sequences are appropriately annotated, so we used Seq4SNPs to provide suitably annotated input sequences, and improved our genotyping success rate. Adjacent SNPs can also be avoided, by annotating sequences used as input for primer design. Conclusion The accuracy of annotation by Seq4SNPs is significantly better than manual annotation (P Using Seq4SNPs to incorporate all annotation for additional SNPs and repetitive elements into sequences, for genotyping assay designer software, minimizes assay failure at the design stage, reducing the cost of genotyping. Seq4SNPs provides a rapid route for replacement of poor test SNP sequences. We routinely use this software for assay sequence preparation. Seq4SNPs is available as a service at http://moya.srl.cam.ac.uk/oncology/bio/s4shome.html and http://moya.srl

  8. Laryngeal Involvement of Multiple Myeloma

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    Ariel B. Grobman

    2012-01-01

    Full Text Available The objectives of this paper are to discuss a rare cause of laryngeal multiple myeloma, to review unique pathologic findings associated with plasma cell neoplasms, to discuss epidemiology, differential diagnosis, and treatment options for plasma cell neoplasms of the larynx. Laryngeal multiple myeloma, also noted in the literature as “metastatic” multiple myeloma, presenting as a de novo laryngeal mass is extremely rare with few reported cases. Laryngeal involvement of extramedullary tumors is reported to be between 6% and 18% with the epiglottis, glottis, false vocal folds, aryepiglottic folds, and subglottis involved in decreasing the order of frequency. We present the case of a 58-year-old male with a history of IgA smoldering myeloma who presented to a tertiary care laryngological practice with a two-month history of dysphonia, which was found to be laryngeal involvement of multiple myeloma. We review the classification of and differentiation between different plasma cell neoplasms, disease workups, pathologic findings, and treatment options.

  9. Lymphoblastic lymphoma involving multiple vertebrae.

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    Li, Da; Xu, Yu-Lun; Wu, Zhen

    2017-09-26

    Acute lymphoblastic lymphoma (ALL) was a malignant hematological disease in childhood but rarely, initially involved epidural compartment in adult. A 20-year-old male presented with progressive osphyalgia for 2 months and left lower motor weakness for 2 weeks with constipation. Physical examination revealed decreased muscle strength and numbness of left lower limb, and abnormal gait. Contrasted MRI showed multiple vertebrae of hypointense T1 signals (C2/C4/C7/T5/T8/T9/T12/L2/L4) and an intraspinal epidural lesion (L2-4). Subtotal resection was achieved. Histopathology suggested malignant B-cell lymphoma with Ki-67 of 90% and positivity of leukocyte common antigen (LCA). A bone marrow biopsy was unequivocally diagnostic of B-cell ALL followed by chemotherapy (Methotrexate) and partial recovery was observed. The present case was the oldest patient with epidural ALL. The radiographic changes in multiple vertebrae suggested metabolic, hematological, or granulomatous disease. The marrow biopsy was necessary if without hypercalcemia and abnormal peripheral blood examination. Accurate pathological diagnosis was essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Multiple SNPs in intron 41 of thyroglobulin gene are associated with autoimmune thyroid disease in the Japanese population.

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    Yoshiyuki Ban

    Full Text Available BACKGROUND: The etiology of the autoimmune thyroid diseases (AITDs, Graves' disease (GD and Hashimoto's thyroiditis (HT, is largely unknown. However, genetic susceptibility is believed to play a major role. Two whole genome scans from Japan and from the US identified a locus on chromosome 8q24 that showed evidence for linkage with AITD and HT. Recent studies have demonstrated an association between thyroglobulin (Tg polymorphisms and AITD in Caucasians, suggesting that Tg is a susceptibility gene on 8q24. OBJECTIVES: The objective of the study was to refine Tg association with AITD, by analyzing a panel of 25 SNPs across an extended 260 kb region of the Tg. METHODS: We studied 458 Japanese AITD patients (287 GD and 171 HT patients and 221 matched Japanese control subjects in association studies. Case-control association studies were performed using 25 Tg single nucleotide polymorphisms (SNPs chosen from a database of the Single Nucleotide Polymorphism Database (dbSNP. Haplotype analysis was undertaken using the computer program SNPAlyze version 7.0. PRINCIPAL FINDINGS AND CONCLUSIONS: In total, 5 SNPs revealed association with GD (P<0.05, with the strongest SNP associations at rs2256366 (P = 0.002 and rs2687836 (P = 0.0077, both located in intron 41 of the Tg gene. Because of the strong LD between these two strongest associated variants, we performed the haplotype analysis, and identified a major protective haplotype for GD (P = 0.001. These results suggested that the Tg gene is involved in susceptibility for GD and AITD in the Japanese.

  11. Single nucleotide polymorphisms (SNPs) involved in insulin resistance, weight regulation, lipid metabolism and inflammation in relation to metabolic syndrome: an epidemiological study

    NARCIS (Netherlands)

    Povel, C.M.; Boer, J.M.A.; Onland-Moret, N.; Dolle, M.E.; Feskens, E.J.M.; Schouw, van der Y.T.

    2012-01-01

    Background: Mechanisms involved in metabolic syndrome (MetS) development include insulin resistance, weight regulation, inflammation and lipid metabolism. Aim of this study is to investigate the association of single nucleotide polymorphisms (SNPs) involved in these mechanisms with MetS. Methods: In

  12. Understanding of Multiplicative Contexts Involving Fractions.

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    Hardiman, Pamela Thibodeau; Mestre, Jose P.

    Numerous studies indicate that performance in solving single step multiplicative word problems is influenced by both problem structure and the types of numbers involved in the problem. For example, including numbers less than one often increases the difficulty of a problem. What remains unclear is how problem structure and number type interact in…

  13. in silico identification of genetic variants in glucocerebrosidase (GBA gene involved in Gaucher’s disease using multiple software tools.

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    Madhumathi eManickam

    2014-05-01

    Full Text Available Gaucher’s disease is an autosomal recessive disorder caused by the deficiency of glucocerebrosidase, a lysosomal enzyme that catalysis the hydrolysis of the glycolipid glucocerebroside to ceramide and glucose. Polymorphisms in GBA gene have been associated with the development of Gaucher disease. We hypothesize that prediction of SNPs using multiple state of the art software tools will help in increasing the confidence in identification of SNPs involved in Gaucher's disease. Enzyme replacement therapy is the only option for GD. Our goal is to use several state of art SNP algorithms to predict/address harmful SNPs using comparative studies. In this study seven different algorithms (SIFT, MutPred, nsSNP Analyzer, PANTHER, PMUT, PROVEAN and SNPs&GO were used to predict the harmful polymorphisms. Among the 7 programs, SIFT found 47 nsSNPs as deleterious, MutPred found 46 nsSNPs as harmful. nsSNP Analyzer program found 43 out of 47 nsSNPs are disease causing SNPs whereas PANTHER found 32 out of 47 as highly deleterious, 22 out of 47 are classified as pathological mutations by PMUT, 44 out of 47 were predicted to be deleterious by PROVEAN server, all 47 shows the disease related mutations by SNPs&GO. Twenty two nsSNPs were commonly predicted by all the seven different algorithms. The common 22 targeted mutations are F251L, C342G, W312C, P415R, R463C, D127V, A309V, G46E, G202E, P391L, Y363C, Y205C, W378C, I402T, S366R, F397S, Y418C, P401L, G195E, W184R, R48W and T43R.

  14. Acute multiple infarction involving the anterior circulation.

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    Bogousslavsky, J; Bernasconi, A; Kumral, E

    1996-01-01

    To evaluate the frequency and clinical, topographic, and etiologic patterns of acute multiple infarction involving the anterior circulation. Data analysis from a prospective acute stroke registry in a community-based primary care center. Among 751 patients with first ischemic stroke in the anterior circulation over a 4-year period, 40 patients (5%) had acute multiple infarcts involving the anterior circulation. On computed tomography and magnetic resonance imaging with gadolinium enhancement, there were four topographic patterns of infarction: (1) superficial infarcts (11 patients [28%]); (2) superficial and deep infarcts (12 patients [30%]); (3) deep infarcts (three patients [8%]); and (4) infarcts involving the anterior and the posterior circulation (14 patients [35%]). Both cerebral hemispheres were involved in one fourth of the cases. A specific clinical picture was found in up to 20% of the patients. This included global aphasia with left hemianopia, hemisensory loss or hemiparesis (in right-handed patients), transcortical mixed aphasia with hemianopia, and acute pure cognitive impairment ("dementia"). Large-artery disease was found in 13 patients (33%); a cardiac source of embolism was found in 11 patients (28%); and both were found in three patients (8%). Bilateral infarcts were related to cardioembolism (four patients) and bilateral large-artery disease (three patients). One month after stroke, one fourth of the patients were independent, one third had some disability, and 40% were either dead or completely dependent. Acute multiple infarcts involving the anterior circulation may be bilateral more frequently than is currently thought, and they are often associated with posterior circulation infarcts. They mainly involve the pial hemispheral territories, commonly being caused by cardioembolism or bilateral carotid atheroma. They may be associated with a specific neurologic-neuropsychological dysfunction pattern in up to one fifth of the patients, allowing

  15. Central nervous system involvement by multiple myeloma

    DEFF Research Database (Denmark)

    Jurczyszyn, Artur; Grzasko, Norbert; Gozzetti, Alessandro

    2016-01-01

    The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate......, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated...... untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. This article is protected by copyright. All rights reserved....

  16. Central Nervous System Involvement by Multiple Myeloma

    DEFF Research Database (Denmark)

    Jurczyszyn, A.; Gozzetti, A.; Cerase, A.

    2015-01-01

    Introduction: Central nervous system (CNS) involvement by multiple myeloma (MM) is a rare occurrence and is found in approximately 1% of MM patients at some time during the course of their disease. At the time of diagnosis, extramedullary MM is found in 7% of patients, and another 6% may develop....... Results: The median time from MM diagnosis to CNS MM diagnosis was 3 years. Upon diagnosis, 97% patients with CNS MM received frontline therapy, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. The most common symptoms at presentation were visual changes (36...... history of chemotherapy and unfavorable cytogenetic profile, survival of individuals free from these negative prognostic factors can be prolonged due to administration of systemic treatment and/or radiotherapy. Prospective multi-institutional studies are warranted to improve the outcome of patients...

  17. Peculiar chondroblastoma involving multiple tarsal bones

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    Fukunaga, Masaharu [Jikei University School of Medicine, Department of Pathology, Tokyo (Japan); the Jikei University Daisan Hospital, Department of Pathology, Tokyo (Japan); Asanuma, Kazuo [Jikei University School of Medicine, Department of Orthopedic Surgery, Tokyo (Japan); Irie, Takeo [Jikei University School of Medicine, Department of Radiology, Tokyo (Japan)

    2010-07-15

    A case of peculiar chondroblastoma involving multiple tarsal bones in a 49-year-old woman is described. The patient presented with pain and swelling of the right foot. Radiographs revealed a lytic expansile lesion of medial, intermediate, and lateral cuneiform bones, navicular, cuboid, and tarsal bones of the right foot, indicating a malignant tumor. Biopsies demonstrated a diffuse proliferation of round cells with eccentric and indented nuclei with longitudinal grooves and eosinophilic cytoplasm. Atypia was prominent, but mitotic figures were rare. The stroma was chondroid with focal chicken-wire calcification. On electron microscopy, the tumor exhibited chondroblastic features. The patient is alive with the tumor 7 years after radiotherapy. The tumor is considered a chondroblastoma with low malignant potential. (orig.)

  18. A closer look at evolution: Variants (SNPs) of genes involved in skin pigmentation, including EXOC2, TYR, TYRP1, and DCT, are associated with 25(OH)D serum concentration.

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    Saternus, Roman; Pilz, Stefan; Gräber, Stefan; Kleber, Marcus; März, Winfried; Vogt, Thomas; Reichrath, Jörg

    2015-01-01

    cohort (median, 15.5 ng/mL). Although 1 SNP in the EXOC2 gene reached the aimed significance level after correction for multiple comparisons (false discovery rate) and was associated with a Δ25(OH)D value more than 5.00 ng/mL, 11 SNPs located in the TYR (n = 4), PRKACG (n = 1), EDN1 (n = 3), TYRP1 (n = 1), and microphthalmia-associated transcription factor (n = 2) genes reached the aimed significance level after false discovery rate correction but were not associated with Δ25(OH)D value more than 5.00 ng/mL. We conclude that variants of genes involved in skin pigmentation are predictive of serum 25(OH)D levels in the Caucasian population. Our data indicate that out of the variants in 29 different genes analyzed, variants of 11 genes, including EXOC2, TYR, and TYRP1, have the highest impact on vitamin D status. Our results have a fundamental importance to understand the role of sunlight, skin pigmentation, and vitamin D for the human evolution.

  19. Involvement of multiple cell lineages in atherogenesis | Ogeng'o ...

    African Journals Online (AJOL)

    Involvement of multiple cell lineages in atherogenesis. ... PROMOTING ACCESS TO AFRICAN RESEARCH ... smooth muscle cells, fibroblasts, stem cells, pericytes, mast cells, dendritic cells, macrophages and immigrant cells usually found in ...

  20. SNPs & indels Schizophyllum commune

    NARCIS (Netherlands)

    Nieuwenhuis, B.P.S.; Aanen, D.K.

    2013-01-01

    This description accompanies four files containing SNPs and indels found in two sets of isolates of Schizophyllum commune. This dataset was created for and used in Nieuwenhuis, Nieuwhof and Aanen (2013) On the asymmetry of mating in natural populations of the mushroom fungus Schizophyllum commune. F

  1. Analysis of bilinear stochastic systems. [involving multiplicative noise processes

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    Willsky, A. S.; Marcus, S. I.; Martin, D. N.

    1974-01-01

    Analysis of stochastic dynamical systems that involve multiplicative (bilinear) noise processes is considered. After defining the systems of interest, the evolution of the moments of such systems, the question of stochastic stability, and estimation for bilinear stochastic systems are discussed. Both exact and approximate methods of analysis are introduced, and, in particular, the uses of Lie-theoretic concepts and harmonic analysis are discussed.

  2. Parent involvement and student academic performance: a multiple mediational analysis.

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    Topor, David R; Keane, Susan P; Shelton, Terri L; Calkins, Susan D

    2010-01-01

    Parent involvement in a child's education is consistently found to be positively associated with a child's academic performance. However, there has been little investigation of the mechanisms that explain this association. The present study examines two potential mechanisms of this association: the child's perception of cognitive competence and the quality of the student-teacher relationship. This study used a sample of 158 seven-year-old participants, their mothers, and their teachers. Results indicated a statistically significant association between parent involvement and a child's academic performance, over and above the impact of the child's intelligence. A multiple mediation model indicated that the child's perception of cognitive competence fully mediated the relation between parent involvement and the child's performance on a standardized achievement test. The quality of the student-teacher relationship fully mediated the relation between parent involvement and teacher ratings of the child's classroom academic performance. Limitations, future research directions, and implications for public policy initiatives are discussed.

  3. Typhoid Fever Complicated By Multiple Organ Involvement In A Child

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    Mustafa Taskesen

    2008-12-01

    Full Text Available A 12-year old girl was admitted to our clinic because of fever, headache, diarrhea and weakness for 10 days. Dyspne, tachycardia, hypotension, fever and letargy were determined in physical examination. The levels of urea, creatinine, aspartate aminotransferase, alanine aminotransferase were found to be increased. In echocardiography, myocardial dysfunction and low systolic functions were detected. Blood culture was positive for S.typhi. We report multiple organ involvement in a patient with typhoid fever and review the literature.

  4. A Case of Multiple Myeloma with Lung Involvement

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    Kaushik Saha

    2012-04-01

    Full Text Available Plasmacytoma are extramedullary accumulations of plasma cells. Mostextramedullary plasmacytomas are associated with the upper respiratory tract. The lung is rarely involved. We report a rare case of lung plasmacytoma with multiple myeloma. The patient is a 60-year-old male who presented with chest pain and a lung mass visualized on CT scan. A preliminary diagnosis of occult lung cancer with widespread skeletal metastasis was made. The diagnosis of lung plasmacytoma with multiplemyeloma was made after extensive investigations.

  5. Intracranial involvement in plasmacytomas and multiple myeloma: a pictorial essay

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    Cerase, Alfonso; Gennari, Paola; Monti, Lucia; Venturi, Carlo [Azienda Ospedaliera Universitaria Senese, Unit of Diagnostic and Therapeutic Neuroradiology, and InterDepartmental Center of Nuclear Magnetic Resonance, Policlinico ' Santa Maria alle Scotte' , Siena (Italy); Tarantino, Annachiara; Muccio, Carmine Franco [Azienda Ospedaliera ' G. Rummo' , Unit of Neuroradiology, Department of Neurosciences, Benevento (Italy); Gozzetti, Alessandro [University of Siena, Unit of Hematology and Transplants, Policlinico ' Santa Maria alle Scotte' , Siena (Italy); Di Blasi, Arturo [Azienda Ospedaliera ' G. Rummo' , Unit of Pathology, Department of Oncology, Benevento (Italy)

    2008-08-15

    The purpose of this pictorial essay is to increase awareness of the clinical presentation, neuroradiological findings, treatment options, and neuroradiological follow-up of plasmacytomas and multiple myeloma with intracranial growth. This pictorial essay reviews the clinical features and neuroradiological findings in seven patients (four women, three men; age range at diagnosis 62-82 years) followed in two institutions. Six patients, one with IgG-{kappa} plasmacytoma, and five with IgG-{kappa}(n=3), IgG-{lambda}(n=1), and nonsecretory (n=1) multiple myeloma, had been seen over a period of 9 years in one institution, and the other patient with IgG-{kappa} plasmacytoma had been seen over a period of 3.5 years in the other. Intracranial involvement is rare, most frequently resulting from osseous lesions in the cranial vault, skull base, nose, or paranasal sinuses. Primary dural or leptomeningeal involvement is rarer. Some typical findings of a dural and/or osseous plasmacytoma include iso- to hyperdensity on CT scan, T1 equal to high signal intensity and T2 markedly hypointense signal on MRI, and high vascularity possibly documented on intraarterial digital subtraction angiography. However, the neuroradiological findings generally lack specificity, since they are generally no different from those of meningioma, metastasis, lymphoma, dural sarcoma, plasma cell granuloma, infectious meningitis, and leptomeningeal carcinomatosis. The spectrum of clinical and neuroradiological evaluation shows that intracranial involvement from plasmacytoma and multiple myeloma must be taken into account in the differential diagnosis of cranial osseous and meningeal disease. (orig.)

  6. Multiple vascular anomalies involving renal, testicular and suprarenal arteries

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    Suresh Rao

    2015-09-01

    Full Text Available Knowledge of variations of blood vessels of the abdomen is important during operative, diagnostic and endovascular pro- cedures. During routine dissection of the abdominal cavity, we came across multiple vascular anomalies involving renal, suprarenal and testicular arteries. The left kidney was supplied by two renal arteries originating together from the abdomi- nal aorta, and the right kidney was supplied by two accessory renal arteries, one of which was arising from the right renal artery and the other one from the aorta (about 2 inches below the origin of the renal artery. Accessory renal veins were present on both sides. The right testicular artery was arising from the lower accessory renal artery. The left testicular artery was looping around the inferior tributary of the left renal vein, whereby forming a sharp kink. The left middle suprarenal artery was diving into three small branches; the upper two branches were supplying the left suprarenal gland, whereas the lower branch was supplying the left kidney. Furthermore, detailed literature and the clinical and surgical importance of the case are discussed. [Arch Clin Exp Surg 2015; 4(3.000: 168-171

  7. Performance of random forest when SNPs are in linkage disequilibrium

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    Cupples L Adrienne

    2009-03-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs may be correlated due to linkage disequilibrium (LD. Association studies look for both direct and indirect associations with disease loci. In a Random Forest (RF analysis, correlation between a true risk SNP and SNPs in LD may lead to diminished variable importance for the true risk SNP. One approach to address this problem is to select SNPs in linkage equilibrium (LE for analysis. Here, we explore alternative methods for dealing with SNPs in LD: change the tree-building algorithm by building each tree in an RF only with SNPs in LE, modify the importance measure (IM, and use haplotypes instead of SNPs to build a RF. Results We evaluated the performance of our alternative methods by simulation of a spectrum of complex genetics models. When a haplotype rather than an individual SNP is the risk factor, we find that the original Random Forest method performed on SNPs provides good performance. When individual, genotyped SNPs are the risk factors, we find that the stronger the genetic effect, the stronger the effect LD has on the performance of the original RF. A revised importance measure used with the original RF is relatively robust to LD among SNPs; this revised importance measure used with the revised RF is sometimes inflated. Overall, we find that the revised importance measure used with the original RF is the best choice when the genetic model and the number of SNPs in LD with risk SNPs are unknown. For the haplotype-based method, under a multiplicative heterogeneity model, we observed a decrease in the performance of RF with increasing LD among the SNPs in the haplotype. Conclusion Our results suggest that by strategically revising the Random Forest method tree-building or importance measure calculation, power can increase when LD exists between SNPs. We conclude that the revised Random Forest method performed on SNPs offers an advantage of not requiring genotype phase, making it a

  8. The distribution of SNPs in human gene regulatory regions

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    Guo Yongjian

    2005-10-01

    Full Text Available Abstract Background As a result of high-throughput genotyping methods, millions of human genetic variants have been reported in recent years. To efficiently identify those with significant biological functions, a practical strategy is to concentrate on variants located in important sequence regions such as gene regulatory regions. Results Analysis of the most common type of variant, single nucleotide polymorphisms (SNPs, shows that in gene promoter regions more SNPs occur in close proximity to transcriptional start sites than in regions further upstream, and a disproportionate number of those SNPs represent nucleotide transversions. Additionally, the number of SNPs found in the predicted transcription factor binding sites is higher than in non-binding site sequences. Conclusion Current information about transcription factor binding site sequence patterns may not be exhaustive, and SNPs may be actively involved in influencing gene expression by affecting the transcription factor binding sites.

  9. Coding SNPs as intrinsic markers for sample tracking in large-scale transcriptome studies.

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    Xu, Weihong; Gao, Hong; Seok, Junhee; Wilhelmy, Julie; Mindrinos, Michael N; Davis, Ronald W; Xiao, Wenzhong

    2012-06-01

    Large-scale transcriptome profiling in clinical studies often involves assaying multiple samples of a patient to monitor disease progression, treatment effect, and host response in multiple tissues. Such profiling is prone to human error, which often results in mislabeled samples. Here, we present a method to detect mislabeled sample outliers using coding single nucleotide polymorphisms (cSNPs) specifically designed on the microarray and demonstrate that the mislabeled samples can be efficiently identified by either simple clustering of allele-specific expression scores or Mahalanobis distance-based outlier detection method. Based on our results, we recommend the incorporation of cSNPs into future transcriptome array designs as intrinsic markers for sample tracking.

  10. Restriction enzyme mining for SNPs in genomes.

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    Chuang, Li-Yeh; Yang, Cheng-Hong; Tsui, Ke-Hung; Cheng, Yu-Huei; Chang, Phei-Lang; Wen, Cheng-Hao; Chang, Hsueh-Wei

    2008-01-01

    Many different single nucleotide polymorphisms (SNPs) genotyping methods have been developed recently. However, most of them are expensive. Using restriction enzymes for SNP genotyping is a cost-effective method. However, restriction enzyme mining for SNPs in a genome sequence is still challenging for researchers who do not have a background in genomics and bioinformatics. In this review, the basic bioinformatics tools used for restriction enzyme mining for SNP genotyping are summarized and described. The objectives of this paper include: i) the introduction of SNPs, genotyping and PCR-restriction fragment length polymorphism (RFLP); ii) a review of components for genotyping software, including tools for primer design only or restriction enzyme mining only; iii) a review of software providing the flanking sequence for primer design; iv) recent advances in PCR-RFLP tools and natural and mutagenic PCR-RFLP; v) highlighting the strategy for restriction enzyme mining for SNP genotyping; vi) a discussion of potential problems for multiple PCR-RFLP. The different implications for restriction enzymes on sense and antisense strands are also discussed. Our PCR-RFLP freeware, SNP-RFLPing, is included in this review to illustrate many characteristics of PCR-RFLP software design. Future developments will include further sophistication of PCR-RFLP software in order to provide better visualization and a more interactive environment for SNP genotyping and to integrate the software with other tools used in association studies.

  11. Multiple osseous involvements in a case of disseminated cryptococcosis

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    Singh Rakesh

    2010-01-01

    Full Text Available Osseous involvement occurs in 5-10% of patients with disseminated cryptococcosis. We are reporting an unusual case of disseminated cryptococcosis involving the sternum and lumbar vertebra with the formation of psoas abscess with pulmonary tuberculosis. The patient presented with fever for 3 months. A diagnosis of pulmonary tuberculosis was made on thoracic contrast-enhanced computerized tomography and she was put on antituberculosis treatment. She was immunocompetent with negative human immunodeficiency virus. She conceived subsequently and had complaints of backache and swelling over the sternum. Magnetic resonance imaging showed destruction of L5 vertebra with psoas abscess. Vertebral cryptococcosis may mimic tuberculosis and malignancy. She had a bad obstetric history and experienced five, first-trimester spontaneous abortions in each successive year since 2001. This pregnancy again resulted in spontaneous abortion. Cryptococcus neoformans was isolated from two different sites: pus-involving the sternum and ultrasound-guided psoas abscess aspirate. Serum latex agglutination test for cryptococcal capsular polysaccharide antigen was positive. The diagnosis of cryptococcosis was delayed because the patient was diagnosed as a case of pulmonary tuberculosis, wherein clinical signs, symptoms and radiological findings in both the conditions are similar. Amphotericin B was started but she developed varicella infection and expired due to cardiac failure.

  12. OBSTACLE DETECTION SYSTEM INVOLVING FUSION OF MULTIPLE SENSOR TECHNOLOGIES

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    C. Giannì

    2017-08-01

    Full Text Available Obstacle detection is a fundamental task for Unmanned Aerial Vehicles (UAV as a part of a Sense and Avoid system. In this study, we present a method of multi-sensor obstacle detection that demonstrated good results on different kind of obstacles. This method can be implemented on low-cost platforms involving a DSP or small FPGA. In this paper, we also present a study on the typical targets that can be tough to detect because of their characteristics of reflectivity, form factor, heterogeneity and show how data fusion can often overcome the limitations of each technology.

  13. Identification of Type 2 Diabetes-associated combination of SNPs using Support Vector Machine

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    Park Keun-Joon

    2010-04-01

    Full Text Available Abstract Background Type 2 diabetes mellitus (T2D, a metabolic disorder characterized by insulin resistance and relative insulin deficiency, is a complex disease of major public health importance. Its incidence is rapidly increasing in the developed countries. Complex diseases are caused by interactions between multiple genes and environmental factors. Most association studies aim to identify individual susceptibility single markers using a simple disease model. Recent studies are trying to estimate the effects of multiple genes and multi-locus in genome-wide association. However, estimating the effects of association is very difficult. We aim to assess the rules for classifying diseased and normal subjects by evaluating potential gene-gene interactions in the same or distinct biological pathways. Results We analyzed the importance of gene-gene interactions in T2D susceptibility by investigating 408 single nucleotide polymorphisms (SNPs in 87 genes involved in major T2D-related pathways in 462 T2D patients and 456 healthy controls from the Korean cohort studies. We evaluated the support vector machine (SVM method to differentiate between cases and controls using SNP information in a 10-fold cross-validation test. We achieved a 65.3% prediction rate with a combination of 14 SNPs in 12 genes by using the radial basis function (RBF-kernel SVM. Similarly, we investigated subpopulation data sets of men and women and identified different SNP combinations with the prediction rates of 70.9% and 70.6%, respectively. As the high-throughput technology for genome-wide SNPs improves, it is likely that a much higher prediction rate with biologically more interesting combination of SNPs can be acquired by using this method. Conclusions Support Vector Machine based feature selection method in this research found novel association between combinations of SNPs and T2D in a Korean population.

  14. An Isolated Bee Sting Involving Multiple Cranial Nerves

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    Hassan Motamed

    2013-01-01

    Full Text Available Hymenoptera stings are self-limiting events or due to allergic reactions. Sometimes envenomation with Hymenoptera can cause rare complications such as acute encephalopathy, peripheral neuritis, acute renal failure, nephrotic syndrome, silent myocardial infarction, rhabdomyolysis, conjunctivitis, corneal infiltration, lens subluxation, and optic neuropathy. The mechanism of peripheral nervous system damage is not clearly known. In our studied case after bee sting on face between the eyebrows with little erythema and  cm in size, bilateral blindness developed and gradually improved. Lateral movement of eyes was restricted with no pain. Involvement of cranial nerves including II, V, and VI was found. With conservative therapy after a year significant improvement has been achieved.

  15. Management of Klippel-Trenauny syndrome with multiple organ involvement

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    Nassiri Javad

    2007-01-01

    Full Text Available Klippel-Trenauny syndrome is a disturbance in the development of the mesodermal and ectodermal tissues occurring in utero, which is characterized by vascular nevi, varicose veins, soft tissue, and occasionally, bone hyperplasia. Our patient is a 6-year-old boy with presentation of left lower extremity over growth, abdominal mass, abdominal pain, bilateral buttock mass, rectal bleeding, and skin hemangiomatosis. The major problems of this case were involvement of the levator ani, external anal sphincter, and encasement of the sciatic nerves within the buttock mass. We concluded that the use of muscle and nerve stimulator for detection and saving sphincters and the nerves in these cases could improve the results of surgical resection.

  16. High-throughput mining of E-genome-specific SNPs for characterizing Thinopyrum elongatum introgressions in common wheat.

    Science.gov (United States)

    Lou, Haijuan; Dong, Lingli; Zhang, Kunpu; Wang, Da-Wei; Zhao, Maolin; Li, Yiwen; Rong, Chaowu; Qin, Huanju; Zhang, Aimin; Dong, Zhenying; Wang, Daowen

    2017-02-09

    Diploid Thinopyrum elongatum (EE, 2n = 2x = 14) and related polyploid species constitute an important gene pool for improving Triticeae grain and forage crops. However, the genomic and molecular marker resources are generally poor for these species. To aid the genetic, molecular, breeding and ecological studies involving Thinopyrum species, we developed a strategy for mining and validating E-genome-specific SNPs using Th. elongatum and common wheat (Triticum aestivum, AABBDD, 2n = 6x = 42) as experimental materials. By comparing the transcriptomes between Chinese Spring (CS, a common wheat variety) and the CS-Th. elongatum octoploid, 35,193 candidate SNPs between E genome genes and their common wheat orthologs were computed. Through comparative genomic analysis, these SNPs were putatively assigned to the seven individual E genome chromosomes. Among 420 randomly selected SNPs, 373 could be validated. Thus, approximately 89% of the mined SNPs may be authentic with respect to their polymorphism and chromosomal location. Using 14 such SNPs as molecular markers, complex E genome introgressions were reliably identified in 78 common wheat-Th. elongatum hybrids, and the structural feature of a novel recombinant chromosome formed by 6E and 7E was revealed. Finally, based on testing 33 SNPs assigned to chromosome 3E in multiple genotypes of Th. elongatum, Pseudoroegneria stipifolia (carrying the St genome related to E) and common wheat, we suggest that some of the SNP markers may also be applicable for genetic studies within and among the Thinopyrum species (populations) carrying E and/or St genomes in the future. © 2017 John Wiley & Sons Ltd.

  17. Testing SNPs and sets of SNPs for importance in association studies

    OpenAIRE

    Schwender, Holger; Ruczinski, Ingo; Ickstadt, Katja

    2010-01-01

    A major goal of genetic association studies concerned with single nucleotide polymorphisms (SNPs) is the detection of SNPs exhibiting an impact on the risk of developing a disease. Typically, this problem is approached by testing each of the SNPs individually. This, however, can lead to an inaccurate measurement of the influence of the SNPs on the disease risk, in particular, if SNPs only show an effect when interacting with other SNPs, as the multivariate structure of the data is ignored. In...

  18. Myelomatous ascites as an initial manifestation of extramedullary involvement of multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo Youn; Lee, Hae Kyung; Yi, Boem Ha; Lee, Min Hee; Kim, Hee Kyung; Park, Seong Kyu [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

    2017-03-15

    Multiple myeloma is a common hematological malignancy. Aggressive myeloma invades the organs outside the bone marrow, lymph, or reticuloendothelial systems. Among the extramedullary involvements of multiple myeloma, myelomatous ascites are extremely rare and are associated with a poor prognosis. We describe a case of myelomatous ascites as an initial manifestation of extramedullary involvement of multiple myeloma in 39-year-old patient. The patient was treated with high-dose chemotherapy, but extensive extramedullary involvement progressed, and the patient expired approximately five months after the initial detection of ascites.

  19. Association of the Three Common SNPs of Cyclooxygenase-2 Gene (rs20417, rs689466, and rs5275 with the Susceptibility of Breast Cancer: An Updated Meta-Analysis Involving 34,590 Subjects

    Directory of Open Access Journals (Sweden)

    Zhi-Jun Dai

    2014-01-01

    Full Text Available Several single nucleotide polymorphisms have been identified in cyclooxygenase-2 (COX-2 genes (e.g., −765 G>C (rs20417, −1195G>A (rs689466, and 8473 C>T (rs5275. The association of these SNPs with the risk of different cancer types is still controversial. This study aims to evaluate the correlation between these SNPs and breast cancer risk in different ethnic groups. We have searched PubMed, Web of Knowledge, and Embase for relevant studies. Odds ratios (ORs with 95% confidence intervals (CIs were used to estimate the strength of the associations. A total of 13 studies (15,330 cases and 19,260 controls were eligible for meta-analysis. This meta-analysis showed that COX-2 rs20417 polymorphism was correlated with an increased risk of breast cancer in Caucasians, while rs689466 was associated with a decreased risk of breast cancer in Caucasians. The rs5275 polymorphism had no association with breast cancer risk.

  20. Cinnamon polyphenols regulate multiple metabolic pathways involved in intestinal lipid metabolism of primary small intestinal enterocytes

    Science.gov (United States)

    Increasing evidence suggests that dietary factors may affect the expression of multiple genes and signaling pathways including those that regulate intestinal lipoprotein metabolism. The small intestine is actively involved in the regulation of dietary lipid absorption, intracellular transport and me...

  1. Benign Paroxysmal Positional Vertigo with Simultaneous Involvement of Multiple Semicircular Canals

    OpenAIRE

    Shim, Dae Bo; Song, Chang Eun; Jung, Eun Jung; Ko, Kyung Min; Park, Jin Woo; Song, Mee Hyun

    2014-01-01

    Background and Objectives Benign paroxysmal positional vertigo (BPPV) generally involves a single semicircular canal (single canal BPPV) but it has been reported that more than one semicircular canal on either the same or the opposite side can be involved in 6.8-20% of the cases (multiple canal BPPV). In this study, the clinical characteristics of multiple canal BPPV were analyzed and compared to those of single canal BPPV. Materials and Methods Retrospective analysis was performed on 1054 co...

  2. Neural fuzzy digital filtering: multivariate identifier filters involving multiple inputs and multiple outputs (MIMO

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    Juan Carlos García Infante

    2011-01-01

    Full Text Available  Multivariate identifier filters (multiple inputs and multiple outputs - MIMO are adaptive digital systems having a loop in accordance with an objective function to adjust matrix parameter convergence to observable reference system dynamics. One way of complying with this condition is to use fuzzy logic inference mechanisms which interpret and select the best matrix parameter from a knowledge base. Such selection mechanisms with neural networks can provide a response from the best operational level for each change in state (Shannon, 1948. This paper considers the MIMO digital filter model using neuro fuzzy digital filtering to find an adaptive  parameter matrix which is integrated into the Kalman filter by the transition matrix. The filter uses the neural network as back-propagation into the fuzzy mechanism to do this, interpreting its variables and its respective levels and selecting the best values for automatically adjusting transition matrix values. The Matlab simulation describes the neural fuzzy digital filter giving an approximation of exponential convergence seen in functional error. 

  3. Role of DISC1 interacting proteins in schizophrenia risk from genome-wide analysis of missense SNPs.

    Science.gov (United States)

    Costas, Javier; Suárez-Rama, Jose Javier; Carrera, Noa; Paz, Eduardo; Páramo, Mario; Agra, Santiago; Brenlla, Julio; Ramos-Ríos, Ramón; Arrojo, Manuel

    2013-11-01

    A balanced translocation affecting DISC1 cosegregates with several psychiatric disorders, including schizophrenia, in a Scottish family. DISC1 is a hub protein of a network of protein-protein interactions involved in multiple developmental pathways within the brain. Gene set-based analysis has been proposed as an alternative to individual analysis of single nucleotide polymorphisms (SNPs) to get information from genome-wide association studies. In this work, we tested for an overrepresentation of the DISC1 interacting proteins within the top results of our ranked list of genes based on our previous genome-wide association study of missense SNPs in schizophrenia. Our data set consisted of 5100 common missense SNPs genotyped in 476 schizophrenic patients and 447 control subjects from Galicia, NW Spain. We used a modification of the Gene Set Enrichment Analysis adapted for SNPs, as implemented in the GenGen software. The analysis detected an overrepresentation of the DISC1 interacting proteins (permuted P-value=0.0158), indicative of the role of this gene set in schizophrenia risk. We identified seven leading-edge genes, MACF1, UTRN, DST, DISC1, KIF3A, SYNE1, and AKAP9, responsible for the overrepresentation. These genes are involved in neuronal cytoskeleton organization and intracellular transport through the microtubule cytoskeleton, suggesting that these processes may be impaired in schizophrenia.

  4. Ramsay Hunt syndrome and zoster laryngitis with multiple cranial nerve involvement.

    Science.gov (United States)

    Shinha, Takashi; Krishna, Pasala

    2015-01-01

    Ramsay Hunt syndrome is characterized by varicella zoster virus infection affecting the geniculate ganglion of the facial nerve. It typically presents with vesicles in the external auditory canal associated with auricular pain and peripheral facial nerve paralysis. Although vestibulocochlear nerve is frequently co-involved during the course of Ramsay Hunt syndrome, multiple lower cranial nerve involvement has rarely been described in the literature. In addition, laryngitis due to varicella zoster virus is a diagnostic challenge due to its unfamiliarity among clinicians. We report a case of Ramsay Hunt syndrome with laryngitis involving multiple lower cranial nerves.

  5. Ramsay Hunt syndrome and zoster laryngitis with multiple cranial nerve involvement

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    Takashi Shinha

    2015-01-01

    Full Text Available Ramsay Hunt syndrome is characterized by varicella zoster virus infection affecting the geniculate ganglion of the facial nerve. It typically presents with vesicles in the external auditory canal associated with auricular pain and peripheral facial nerve paralysis. Although vestibulocochlear nerve is frequently co-involved during the course of Ramsay Hunt syndrome, multiple lower cranial nerve involvement has rarely been described in the literature. In addition, laryngitis due to varicella zoster virus is a diagnostic challenge due to its unfamiliarity among clinicians. We report a case of Ramsay Hunt syndrome with laryngitis involving multiple lower cranial nerves.

  6. Trigeminal root entry zone involvement in neuromyelitis optica and multiple sclerosis.

    Science.gov (United States)

    Sugiyama, Atsuhiko; Mori, Masahiro; Masuda, Hiroki; Uchida, Tomohiko; Muto, Mayumi; Uzawa, Akiyuki; Ito, Shoichi; Kuwabara, Satoshi

    2015-08-15

    Trigeminal root entry zone abnormality on brain magnetic resonance imaging has been frequently reported in multiple sclerosis patients, but it has not been investigated in neuromyelitis optica patients. Brain magnetic resonance imaging of 128 consecutive multiple sclerosis patients and 46 neuromyelitis optica patients was evaluated. Trigeminal root entry zone abnormality was present in 11 (8.6%) of the multiple sclerosis patients and two (4.3%) of the neuromyelitis optica patients. The pontine trigeminal root entry zone may be involved in both multiple sclerosis and neuromyelitis optica.

  7. Mission concepts and operations for asteroid mitigation involving multiple gravity tractors

    Science.gov (United States)

    Foster, Cyrus; Bellerose, Julie; Mauro, David; Jaroux, Belgacem

    2013-09-01

    The gravity tractor concept is a proposed method to deflect an imminent asteroid impact through gravitational tugging over a time scale of years. In this study, we present mission scenarios and operational considerations for asteroid mitigation efforts involving multiple gravity tractors. We quantify the deflection performance improvement provided by a multiple gravity tractor campaign and assess its sensitivity to staggered launches. We next explore several proximity operation strategies to accommodate multiple gravity tractors at a single asteroid including formation-flying and mechanically-docked configurations. Finally, we utilize 99942 Apophis as an illustrative example to assess the performance of a multiple gravity tractor campaign.

  8. Percutaneous Release of Trigger Fingers: Comparing Multiple Digits with Single Digit Involvement

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    Hossein Saremi

    2016-07-01

    Full Text Available Background: To evaluate safety and efficacy of percutaneous release of trigger finger in multiple digits involvement in comparison with  single digit involvement.   Method: A number of 100 patients (131 fingers were treated by percutaneous release and divided into two groups: single digit (group A and multiple digits (group B. They were followed up for one year. Success rate, pain, complications and duration of analgesic use were studied and then compared in both groups. Results: All patients in both groups were treated successfully without any recurrence in a one-year follow-up. No complication was observed, but postoperative duration of pain was significantly different between the two groups. Period of painkiller use was also different between the two groups. Conclusion: Percutaneous release is a safe and effective treatment for trigger fingers even if multiple digits are involved. It is also safe in thumb and index finger involvement and diabetic patients.

  9. Kinship Testing Based on SNPs Using Microarray System

    Science.gov (United States)

    Cho, Sohee; Seo, Hee Jin; Lee, Jihyun; Yu, Hyung Jin; Lee, Soong Deok

    2016-01-01

    Background Kinship testing using biallelic SNP markers has been demonstrated to be a promising approach as a supplement to standard STR typing, and several systems, such as pyrosequencing and microarray, have been introduced and utilized in real forensic cases. The Affymetrix microarray containing 169 autosomal SNPs developed for forensic application was applied to our practical case for kinship analysis that had remained inconclusive due to partial STR profiles of degraded DNA and possibility of inbreeding within the population. Case Report 169 autosomal SNPs were typed on array with severely degraded DNA of two bone samples, and the kinship compared to genotypes in a reference database of their putative family members. Results Two bone samples remained unidentified through traditional STR typing with partial profiles of 10 or 14 of 16 alleles. Because these samples originated from a geographically isolated population, a cautious approach was required when analyzing and declaring true paternity only based on PI values. In a supplementary SNP typing, 106 and 78 SNPs were obtained, and the match candidates were found in each case with improved PI values than using only STRs and with no discrepant SNPs in comparison. Conclusion Our case showed that the utility of multiple SNPs on array is expected in practical forensic caseworks with an establishment of reference database. PMID:27994531

  10. Kinship Testing Based on SNPs Using Microarray System.

    Science.gov (United States)

    Cho, Sohee; Seo, Hee Jin; Lee, Jihyun; Yu, Hyung Jin; Lee, Soong Deok

    2016-11-01

    Kinship testing using biallelic SNP markers has been demonstrated to be a promising approach as a supplement to standard STR typing, and several systems, such as pyrosequencing and microarray, have been introduced and utilized in real forensic cases. The Affymetrix microarray containing 169 autosomal SNPs developed for forensic application was applied to our practical case for kinship analysis that had remained inconclusive due to partial STR profiles of degraded DNA and possibility of inbreeding within the population. 169 autosomal SNPs were typed on array with severely degraded DNA of two bone samples, and the kinship compared to genotypes in a reference database of their putative family members. Two bone samples remained unidentified through traditional STR typing with partial profiles of 10 or 14 of 16 alleles. Because these samples originated from a geographically isolated population, a cautious approach was required when analyzing and declaring true paternity only based on PI values. In a supplementary SNP typing, 106 and 78 SNPs were obtained, and the match candidates were found in each case with improved PI values than using only STRs and with no discrepant SNPs in comparison. Our case showed that the utility of multiple SNPs on array is expected in practical forensic caseworks with an establishment of reference database.

  11. The Multiple Factors and Multiple Stages Involved in Sedimentary Ore Genesis

    Institute of Scientific and Technical Information of China (English)

    叶连俊; 陈其英

    1990-01-01

    Sedimentary mineral deposits cannot be formed by any kind of simple chemical reactions,but are products of a complex multi-episodic process depending on multiple factors,The whole process is governed by a combination of sedimentary,geochemical,biogeochemical,organic geochemical,paleoclimatical,mechanical agents as well as by the properties of relevant earth crust segment and its structural making up and tectonic mobility A Sedimentary ore deposit is nothing but a special kind of sedimentary facies,characterized by definite sedimentary assemblages,Different genetic types of ore deposit and different ore associations characterize different sedimentary assemblages in different ore-forming belts.Crustal movement,including orogenic,epeirogenic and,oparticularly eustatic events,controls the formation and distribution of all kinds of sedimentary mineral deposits,most of which occur within the transgression front in the lower part of marine transpressive series.Mineral deposits of economic importance cannot be precipitated directly from sea water,but are products of terrestrial imbibition,biological enrichment and pore water concentration instead,Deposits formed above the wave base in the inner continental shelf under strong dynamic condition of sea water are often large and predominantly clastic in texture with commercial grade.Below the wave base in the outer continental shelf environment,where it is more or less dynamically stagnant and oxygen-deficient,the resulted in dustrial ore deposits are mostly of diagenetic or strata-bound type,formed through deep-burying diagenesis.The theory of multi-factor and multi-episodic metallogenesis includes three major aspects:the ore-forming process,the sedimentary environment and the geological background.The study of the forma tion process itself and the sources of ore-forming elements would provide useful clues to further prospectiong Whereas,invstigations of the sedimentary environments should shed light on the spacial

  12. How well do HapMap SNPs capture the untyped SNPs?

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    Yang Yuchen

    2006-09-01

    Full Text Available Abstract Background The recent advancement in human genome sequencing and genotyping has revealed millions of single nucleotide polymorphisms (SNP which determine the variation among human beings. One of the particular important projects is The International HapMap Project which provides the catalogue of human genetic variation for disease association studies. In this paper, we analyzed the genotype data in HapMap project by using National Institute of Environmental Health Sciences Environmental Genome Project (NIEHS EGP SNPs. We first determine whether the HapMap data are transferable to the NIEHS data. Then, we study how well the HapMap SNPs capture the untyped SNPs in the region. Finally, we provide general guidelines for determining whether the SNPs chosen from HapMap may be able to capture most of the untyped SNPs. Results Our analysis shows that HapMap data are not robust enough to capture the untyped variants for most of the human genes. The performance of SNPs for European and Asian samples are marginal in capturing the untyped variants, i.e. approximately 55%. Expectedly, the SNPs from HapMap YRI panel can only capture approximately 30% of the variants. Although the overall performance is low, however, the SNPs for some genes perform very well and are able to capture most of the variants along the gene. This is observed in the European and Asian panel, but not in African panel. Through observation, we concluded that in order to have a well covered SNPs reference panel, the SNPs density and the association among reference SNPs are important to estimate the robustness of the chosen SNPs. Conclusion We have analyzed the coverage of HapMap SNPs using NIEHS EGP data. The results show that HapMap SNPs are transferable to the NIEHS SNPs. However, HapMap SNPs cannot capture some of the untyped SNPs and therefore resequencing may be needed to uncover more SNPs in the missing region.

  13. Detection of regulatory SNPs in human genome using ChIP-seq ENCODE data.

    Science.gov (United States)

    Bryzgalov, Leonid O; Antontseva, Elena V; Matveeva, Marina Yu; Shilov, Alexander G; Kashina, Elena V; Mordvinov, Viatcheslav A; Merkulova, Tatyana I

    2013-01-01

    A vast amount of SNPs derived from genome-wide association studies are represented by non-coding ones, therefore exacerbating the need for effective identification of regulatory SNPs (rSNPs) among them. However, this task remains challenging since the regulatory part of the human genome is annotated much poorly as opposed to coding regions. Here we describe an approach aggregating the whole set of ENCODE ChIP-seq data in order to search for rSNPs, and provide the experimental evidence of its efficiency. Its algorithm is based on the assumption that the enrichment of a genomic region with transcription factor binding loci (ChIP-seq peaks) indicates its regulatory function, and thereby SNPs located in this region are more likely to influence transcription regulation. To ensure that the approach preferably selects functionally meaningful SNPs, we performed enrichment analysis of several human SNP datasets associated with phenotypic manifestations. It was shown that all samples are significantly enriched with SNPs falling into the regions of multiple ChIP-seq peaks as compared with the randomly selected SNPs. For experimental verification, 40 SNPs falling into overlapping regions of at least 7 TF binding loci were selected from OMIM. The effect of SNPs on the binding of the DNA fragments containing them to the nuclear proteins from four human cell lines (HepG2, HeLaS3, HCT-116, and K562) has been tested by EMSA. A radical change in the binding pattern has been observed for 29 SNPs, besides, 6 more SNPs also demonstrated less pronounced changes. Taken together, the results demonstrate the effective way to search for potential rSNPs with the aid of ChIP-seq data provided by ENCODE project.

  14. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data

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    Tianjiao Zhang

    2016-01-01

    Full Text Available Many disease-related single nucleotide polymorphisms (SNPs have been inferred from genome-wide association studies (GWAS in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important role in regulating gene expression. The SNPs located in enhancer elements may affect gene expression and lead to disease. We presented a method for identifying liver cancer-related enhancer SNPs through integrating GWAS and histone modification ChIP-seq data. We identified 22 liver cancer-related enhancer SNPs, 9 of which were regulatory SNPs involved in distal transcriptional regulation. The results highlight that these enhancer SNPs may play important roles in liver cancer.

  15. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data

    Science.gov (United States)

    Hu, Yang; Wu, Xiaoliang; Ma, Rui

    2016-01-01

    Many disease-related single nucleotide polymorphisms (SNPs) have been inferred from genome-wide association studies (GWAS) in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important role in regulating gene expression. The SNPs located in enhancer elements may affect gene expression and lead to disease. We presented a method for identifying liver cancer-related enhancer SNPs through integrating GWAS and histone modification ChIP-seq data. We identified 22 liver cancer-related enhancer SNPs, 9 of which were regulatory SNPs involved in distal transcriptional regulation. The results highlight that these enhancer SNPs may play important roles in liver cancer. PMID:27429976

  16. SNPs in Multi-Species Conserved Sequences (MCS as useful markers in association studies: a practical approach

    Directory of Open Access Journals (Sweden)

    Pericak-Vance Margaret A

    2007-08-01

    Full Text Available Abstract Background Although genes play a key role in many complex diseases, the specific genes involved in most complex diseases remain largely unidentified. Their discovery will hinge on the identification of key sequence variants that are conclusively associated with disease. While much attention has been focused on variants in protein-coding DNA, variants in noncoding regions may also play many important roles in complex disease by altering gene regulation. Since the vast majority of noncoding genomic sequence is of unknown function, this increases the challenge of identifying "functional" variants that cause disease. However, evolutionary conservation can be used as a guide to indicate regions of noncoding or coding DNA that are likely to have biological function, and thus may be more likely to harbor SNP variants with functional consequences. To help bias marker selection in favor of such variants, we devised a process that prioritizes annotated SNPs for genotyping studies based on their location within Multi-species Conserved Sequences (MCSs and used this process to select SNPs in a region of linkage to a complex disease. This allowed us to evaluate the utility of the chosen SNPs for further association studies. Previously, a region of chromosome 1q43 was linked to Multiple Sclerosis (MS in a genome-wide screen. We chose annotated SNPs in the region based on location within MCSs (termed MCS-SNPs. We then obtained genotypes for 478 MCS-SNPs in 989 individuals from MS families. Results Analysis of our MCS-SNP genotypes from the 1q43 region and comparison to HapMap data confirmed that annotated SNPs in MCS regions are frequently polymorphic and show subtle signatures of selective pressure, consistent with previous reports of genome-wide variation in conserved regions. We also present an online tool that allows MCS data to be directly exported to the UCSC genome browser so that MCS-SNPs can be easily identified within genomic regions of

  17. "Running a Train": Adolescent Boys' Accounts of Sexual Intercourse Involving Multiple Males and One Female

    Science.gov (United States)

    Rothman, Emily F.; Decker, Michele R.; Reed, Elizabeth; Raj, Anita; Silverman, Jay G.; Miller, Elizabeth

    2008-01-01

    The authors used qualitative research methods to explore the context and sexual risk behavior associated with sexual intercourse involving multiple males and one female, commonly called "running a train." Participants were 20 adolescent males aged 14 to 22 years who were either perpetrators of dating violence or perceived by teachers to…

  18. Multiple infections by the anther smut pathogen are frequent and involve related strains.

    Directory of Open Access Journals (Sweden)

    Manuela López-Villavicencio

    2007-11-01

    Full Text Available Population models of host-parasite interactions predict that when different parasite genotypes compete within a host for limited resources, those that exploit the host faster will be selected, leading to an increase in parasite virulence. When parasites sharing a host are related, however, kin selection should lead to more cooperative host exploitation that may involve slower rates of parasite reproduction. Despite their potential importance, studies that assess the prevalence of multiple genotype infections in natural populations remain rare, and studies quantifying the relatedness of parasites occurring together as natural multiple infections are particularly scarce. We investigated multiple infections in natural populations of the systemic fungal plant parasite Microbotryum violaceum, the anther smut of Caryophyllaceae, on its host, Silene latifolia. We found that multiple infections can be extremely frequent, with different fungal genotypes found in different stems of single plants. Multiple infections involved parasite genotypes more closely related than would be expected based upon their genetic diversity or due to spatial substructuring within the parasite populations. Together with previous sequential inoculation experiments, our results suggest that M. violaceum actively excludes divergent competitors while tolerating closely related genotypes. Such an exclusion mechanism might explain why multiple infections were less frequent in populations with the highest genetic diversity, which is at odds with intuitive expectations. Thus, these results demonstrate that genetic diversity can influence the prevalence of multiple infections in nature, which will have important consequences for their optimal levels of virulence. Measuring the occurrence of multiple infections and the relatedness among parasites within hosts in natural populations may be important for understanding the evolutionary dynamics of disease, the consequences of vaccine use

  19. The multiple imputation method: a case study involving secondary data analysis.

    Science.gov (United States)

    Walani, Salimah R; Cleland, Charles M

    2015-05-01

    To illustrate with the example of a secondary data analysis study the use of the multiple imputation method to replace missing data. Most large public datasets have missing data, which need to be handled by researchers conducting secondary data analysis studies. Multiple imputation is a technique widely used to replace missing values while preserving the sample size and sampling variability of the data. The 2004 National Sample Survey of Registered Nurses. The authors created a model to impute missing values using the chained equation method. They used imputation diagnostics procedures and conducted regression analysis of imputed data to determine the differences between the log hourly wages of internationally educated and US-educated registered nurses. The authors used multiple imputation procedures to replace missing values in a large dataset with 29,059 observations. Five multiple imputed datasets were created. Imputation diagnostics using time series and density plots showed that imputation was successful. The authors also present an example of the use of multiple imputed datasets to conduct regression analysis to answer a substantive research question. Multiple imputation is a powerful technique for imputing missing values in large datasets while preserving the sample size and variance of the data. Even though the chained equation method involves complex statistical computations, recent innovations in software and computation have made it possible for researchers to conduct this technique on large datasets. The authors recommend nurse researchers use multiple imputation methods for handling missing data to improve the statistical power and external validity of their studies.

  20. First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene.

    Science.gov (United States)

    Mohamoud, Hussein Sheikh Ali; Hussain, Muhammad Ramzan Manwar; El-Harouni, Ashraf A; Shaik, Noor Ahmad; Qasmi, Zaheer Ulhaq; Merican, Amir Feisal; Baig, Mukhtiar; Anwar, Yasir; Asfour, Hani; Bondagji, Nabeel; Al-Aama, Jumana Yousuf

    2014-01-01

    GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases.

  1. First Comprehensive In Silico Analysis of the Functional and Structural Consequences of SNPs in Human GalNAc-T1 Gene

    Directory of Open Access Journals (Sweden)

    Hussein Sheikh Ali Mohamoud

    2014-01-01

    Full Text Available GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants from 18 nsSNPs of GalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568 were also identified in GalNAc-T1 by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases.

  2. Multiple myeloma with pleural involvement after pelvic radiotherapy for endometrial carcinoma

    Directory of Open Access Journals (Sweden)

    Bulent Karagoz

    2013-08-01

    Full Text Available Although ionizing radiation is strongest factor linked to multiple myeloma, increased myeloma risk has not been fully explained after pelvic radiation. Pleural involvement of MM is also rare. We present a MM case with pleural involvement as an unusual presentation diagnosed in fifth years of pelvic radiotherapy. A sixty-two-year-old woman with dyspnea and a mass in forehead was admitted to our clinic. Before five year, the patient had received pelvic external beam radiotherapy (RT with dose of 40 Gy for endometrial adenocarcinoma. PET/CT scan detected FDG uptakes in frontal bone, right pleura, and sacrum. Lambda light chain type multiple myeloma with pleural involvement was diagnosed with histopathological examinations of frontal bone mass, bone marrow, and pleural fluid and with serum/urine electroforesis. The patient died in second course of VAD chemotherapy. Although relation between increased myeloma risk and pelvic radiation is not clear and pleural involvement is rare, multiple myeloma should be included to the differential diagnosis in patients received pelvic radiotherapy or in unexplained pleural effusion. [Dis Mol Med 2013; 1(4.000: 87-89

  3. Central nervous system involvement in primary Sjogren`s syndrome manifesting as multiple sclerosis.

    Science.gov (United States)

    Liu, Jing-Yao; Zhao, Teng; Zhou, Chun-Kui

    2014-04-01

    Central nervous system symptoms in patients with primary Sjogren`s syndrome are rare. They can present as extraglandular manifestations and require a differential diagnosis from multiple sclerosis. Due to a variety of presentations, Sjogren`s syndrome with neurologic involvement may be difficult to diagnose. Here, we report a case of a 75-year-old woman who was first diagnosed with multiple sclerosis in 2010, but who was subsequently diagnosed with primary Sjogren`s syndrome 2 years later after showing signs of atypical neurologic manifestations. Therefore, primary Sjogren`s syndrome should be suspected in patients who present with atypical clinical and radiologic neurologic manifestations.

  4. Virtual reality and claustrophobia: multiple components therapy involving game editor virtual environments exposure.

    Science.gov (United States)

    Malbos, E; Mestre, D R; Note, I D; Gellato, C

    2008-12-01

    The effectiveness of a multiple components therapy regarding claustrophobia and involving virtual reality (VR) will be demonstrated through a trial which immersed six claustrophobic patients in multiple context-graded enclosed virtual environments (VE) using affordable VR apparatus and software. The results of the questionnaires and behavior tests exhibited a significant reduction in fear towards the enclosed space and quality of life improvement. Such gains were maintained at 6-month follow-up. Presence score indicated the patients felt immersed and present inside the game editor VE.

  5. Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility

    Institute of Scientific and Technical Information of China (English)

    Anatoly SHMYGOL; Joanna GULLAM; Andrew BLANKS; Steven THORNTON

    2006-01-01

    Oxytocin is a small peptide hormone with multiple sites of action in human body.It regulates a large number of reproduction-related processes in all species.Particularly important is its ability to stimulate uterine contractility.This is achieved by multiple mechanisms involving sarcoplasmic reticulum Ca2+ release and sensitization of the contractile apparatus to Ca2+.In this paper,we review the data published by US and other groups on oxytocin-induced modulation of uterine contractility.We conclude that sensitization of contractile apparatus to Ca2+ is the most relevant physiological effect of oxytocin on human myometrium.

  6. Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves

    Institute of Scientific and Technical Information of China (English)

    Soo Ryang Kim; Fumio Kanda; Hiroshi Kobessho; Koji Sugimoto; Toshiyuki Matsuoka; Masatoshi Kudo; Yoshitake Hayashi

    2006-01-01

    We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-yearold woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI)disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement.The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

  7. A case of disseminated hydatid disease by surgery involving multiple organs

    Directory of Open Access Journals (Sweden)

    Asli Tanrivermis Sayit

    2014-09-01

    Full Text Available Hydatid disease is the most common parasitic infection in the world, and is caused by the parasite Echinococcus granulosus. The most common site of this disease is the liver (75%, followed by the lungs, kidney, bones, and brain. Multiple abdominal organ and peritoneal involvement can also be seen in some cases. The dissemination of hydatid cyst disease can develop spontaneously or secondary to trauma or surgery. Here, we present the case of a 69-year-old man with multiple cyst hydatidosis, who underwent surgery for acute appendicitis approximately 20 years previously. Computed tomography of the abdomen shows the multiple active and inactive cystic lesions in the liver, spleen, right kidney, and mesentery. This patient required surgery several times, as well as medical treatment, after the rupture of a mesenteric hydatid cyst during the appendectomy. Combined anthelmintic treatment was recommended to the patient who refused further surgical treatment.

  8. Diagnosis and Treatment of Bone Disease in Multiple Myeloma: Spotlight on Spinal Involvement

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2013-01-01

    Full Text Available Bone disease is observed in almost 80% of newly diagnosed symptomatic multiple myeloma patients, and spine is the bone site that is more frequently affected by myeloma-induced osteoporosis, osteolyses, or compression fractures. In almost 20% of the cases, spinal cord compression may occur; diagnosis and treatment must be carried out rapidly in order to avoid a permanent sensitive or motor defect. Although whole body skeletal X-ray is considered mandatory for multiple myeloma staging, magnetic resonance imaging is presently considered the most appropriate diagnostic technique for the evaluation of vertebral alterations, as it allows to detect not only the exact morphology of the lesions, but also the pattern of bone marrow infiltration by the disease. Multiple treatment modalities can be used to manage multiple myeloma-related vertebral lesions. Surgery or radiotherapy is mainly employed in case of spinal cord compression, impending fractures, or intractable pain. Percutaneous vertebroplasty or balloon kyphoplasty can reduce local pain in a significant fraction of treated patients, without interfering with subsequent therapeutic programs. Systemic antimyeloma therapy with conventional chemotherapy or, more appropriately, with combinations of conventional chemotherapy and compounds acting on both neoplastic plasma cells and bone marrow microenvironment must be soon initiated in order to reduce bone resorption and, possibly, promote bone formation. Bisphosphonates should also be used in combination with antimyeloma therapy as they reduce bone resorption and prolong patients survival. A multidisciplinary approach is thus needed in order to properly manage spinal involvement in multiple myeloma.

  9. Development of a multiplex PCR assay detecting 52 autosomal SNPs

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Phillips, C.; Børsting, Claus

    2006-01-01

    be performed. The SNPforID consortium (www.snpforid.org) was established in 2003 with the principal goal of developing a SNP-based system of DNA analysis that would have comparable discrimination power and ease of use to those of existing short tandem repeat (STR) based techniques. Here, we describe a strategy...... for amplifying 52 genomic DNA fragments, each containing one SNP, in a single tube, and accurately genotyping the PCR product mixture using two single base extension reactions. This multiplex approach reduces the cost of SNP genotyping and requires as little as 0.5 ng of genomic DNA to detect 52 SNPs. We used...... a multiple injection approach for DNA sequencers that can effectively detect all the SNPs amplified in a single electrophoretic run. We present SNP data for 700 unrelated individuals from 9 populations...

  10. Description and interpretation of various SNPs identified by BRCA2 gene sequencing

    Directory of Open Access Journals (Sweden)

    Anca Negura

    2011-12-01

    Full Text Available Molecular diagnosis for hereditary breast and ovarian cancer (HBOC involves systematic DNA sequencing of predisposition genes like BRCA1 or BRCA2. Deleterious mutations within such genes are responsible for developing the disease, but other sequence variants can also be identified. Common Single Nucleotide Polymorphisms (SNPs are usually present in human genome, defining alleles whose frequencies widely vary in different populations. Either intragenic or intronic, silent or generating aminoacid substitutions, SNPs cannot be afforded themselves a predisposition status. However, prevalent SNPs can be used to define gene haplotypes, with also various frequencies. Since some mutation can easily be assigned to haplotypes (such is the case for BRCA1 gene, SNPs can therefore provide usual information in interpreting gene mutations effects on hereditary predisposition to cancer. Here we describe 10 BRCA2 SNPs identified by complete gene sequencing

  11. Association between SNPs within candidate genes and compounds related to boar taint and reproduction

    DEFF Research Database (Denmark)

    Moe, Maren; Lien, Sigbjørn; Aasmundstad, Torunn

    2009-01-01

    understanding of the complex regulation of the trait and for the purpose of identifying markers that can be used to improve the gain of breeding. The beneficial SNPs to be used in breeding would have the combinational effects of reducing levels of boar taint without affecting fertility of the animals. The aim...... of this study was to detect SNPs in boar taint candidate genes and to perform association studies for both single SNPs and haplotypes with levels of boar taint compounds and phenotypes related to reproduction. RESULTS: An association study involving 275 SNPs in 121 genes and compounds related to boar taint...... and reproduction were carried out in Duroc and Norwegian Landrace boars. Phenotypes investigated were levels of androstenone, skatole and indole in adipose tissue, levels of androstenone, testosterone, estrone sulphate and 17beta-estradiol in plasma, and length of bulbo urethralis gland. The SNPs were genotyped...

  12. Multiple Family Groups for Child Behavior Difficulties Retention Among Child Welfare-Involved Caregivers.

    Science.gov (United States)

    Gopalan, Geetha; Fuss, Ashley; Wisdom, Jennifer P

    2015-09-01

    Among children who remain at home with their permanent caregivers following a child welfare investigation, few who manifest emotional and behavioral difficulties actually engage in mental health treatment. The Multiple Family Group service delivery model to reduce childhood disruptive behavior disorders (MFG) has shown promise in engaging child welfare-involved families. This qualitative study examines caregiver perceptions of factors that influence retention in MFGs among child welfare-involved families. Twenty-five predominantly Black and Hispanic adult (ages 26-57) female caregivers with child welfare services involvement participated in individual, in-depth interviews about their experience with MFGs. Transcribed interview data were thematically coded guided by grounded theory methodology. Emergent themes were subsequently organized into a conceptual framework. Within the overarching influence of child welfare services involvement, specific components of MFGs influencing retention included the quality of interaction among group members, group facilitators' attentive approach with caregivers, supports designed to overcome logistical barriers (i.e., child care, transportation expenses, meals), and perceptions of MFG content and activities as fun and helpful. Caregiver factors, including their mental health and personal characteristics, as well as children's behavior, (i.e., observed changes in behavioral difficulties) were also associated with retention. High acceptability suggest utility for implementing MFGs within settings serving child welfare involved families, with additional modifications to tailor to setting and client features.

  13. Multiple Family Groups for Child Behavior Difficulties Retention Among Child Welfare–Involved Caregivers

    Science.gov (United States)

    Gopalan, Geetha; Fuss, Ashley; Wisdom, Jennifer P.

    2013-01-01

    Among children who remain at home with their permanent caregivers following a child welfare investigation, few who manifest emotional and behavioral difficulties actually engage in mental health treatment. The Multiple Family Group service delivery model to reduce childhood disruptive behavior disorders (MFG) has shown promise in engaging child welfare-involved families. This qualitative study examines caregiver perceptions of factors that influence retention in MFGs among child welfare-involved families. Methods Twenty-five predominantly Black and Hispanic adult (ages 26–57) female caregivers with child welfare services involvement participated in individual, in-depth interviews about their experience with MFGs. Transcribed interview data were thematically coded guided by grounded theory methodology. Emergent themes were subsequently organized into a conceptual framework. Results Within the overarching influence of child welfare services involvement, specific components of MFGs influencing retention included the quality of interaction among group members, group facilitators’ attentive approach with caregivers, supports designed to overcome logistical barriers (i.e., child care, transportation expenses, meals), and perceptions of MFG content and activities as fun and helpful. Caregiver factors, including their mental health and personal characteristics, as well as children’s behavior, (i.e., observed changes in behavioral difficulties) were also associated with retention. Conclusions High acceptability suggest utility for implementing MFGs within settings serving child welfare involved families, with additional modifications to tailor to setting and client features. PMID:26527856

  14. A phenomenographic analysis of first-year engineering students' experiences with problems involving multiple possible solutions

    Science.gov (United States)

    Dringenberg, Emily A.

    Engineers are expected to solve problems that are ill-structured. These problems are presented with a lack of necessary information and allow for different ways of engaging with the problem; they are open-ended and involve multiple possible solutions with multiple means of evaluation. In order to allow maximum time for students to develop skills for solving such problems, undergraduate engineering programs can introduce such problems during the first year of students' education, in the form of cornerstone design tasks. This provides students with more opportunities to develop their ability to engage with ill-structured problems, which are characteristic of engineering work. Researchers have documented variation within both the behavior and perceptions of students' early experiences with design problems. General themes include novice-like design behavior, discomfort with lack of information, difficulty with problem scoping, and resistance to ambiguity. To build on these generalizations of students' experiences, a more thorough understanding of the variation in how students experience this phenomenon of engaging with ill-structured problems is needed to design effective learning environments. This work presents the qualitatively different ways that engineering students experience problems with multiple possible solutions during their first year of engineering studies. Using phenomenography as the methodological framework, data were collected through in-depth, semi-structured interviews with 27 first-year engineering students. The iterative, phenomenographic analysis resulted in seven descriptive categories for the ways participants experienced problems involving multiple possible solutions. The names of these categories represent the different foci of the students' experiences: completion, transition, iteration, organization, collaboration, reasoning, and growth. These categories are organized along two crucial dimensions of variation: reaction to ambiguity and role

  15. Identification of SNPs in Goats (Capra hircus using RNA-Seq Analysis

    Directory of Open Access Journals (Sweden)

    Upasna Sharma

    2012-08-01

    Full Text Available Single Nucleotide Polymorphisms (SNPs have become the marker of choice for genome-wide association studies. In order to provide the best genome coverage for the analysis of performance and production traits, a large number of relatively evenly distributed SNPs are needed. Gene-associated SNPs may fulfill these requirements of large numbers and genome wide distribution. In addition, gene-associated SNPs could themselves be causative SNPs for traits. The main objective of our work was to identify large numbers of gene-associated SNPs using high-throughput next generation sequencing. Transcriptome sequencing was conducted on 2 tissues viz. liver and kidney for 5 breeds of goat (Kanniadu, Osmanabadi, Black Bengal, Changthangi and Sirohi using Illumina next generation sequencing technology. Approximately 46.4 million reads for Black Bengal, 61.9 from Kanniadu, 58.2 from Changthangi, 47.3 from Osmanabadi, 73.2 from Sirohi were obtained by sequencing gene transcripts derived from kidney while 37, 27.2, 19.4, 56.9 and 80.7 million reads were obtained by gene transcripts derived from liver. The analysis of total number of SNPs in liver and kidney revealed that out of a total of 68597 SNPs in liver, the total number of transversions was 21300 and the number of transitions was 47297. A total of 1574 SNPs of liver were complex. Similarly for kidney the total number of 72047 SNPs were categorised into 22774 transversions and 49273 transitions. The total number of complex SNPs in kidney was 1597. The number of transitions is more than double the number of transversions in both the tissues. Further analysis of transversion revealed a preponderance of cytosine and guanine change compared to other nucleotides. 12863 and 11319 transversions out of 21300 and 22774 transversions respectively for liver and kidney revealed this bias. When multiple individuals with different genetic backgrounds were used, RNA-Seq was very effective for the identification of SNPs. The

  16. Novel and efficient tag SNPs selection algorithms.

    Science.gov (United States)

    Chen, Wen-Pei; Hung, Che-Lun; Tsai, Suh-Jen Jane; Lin, Yaw-Ling

    2014-01-01

    SNPs are the most abundant forms of genetic variations amongst species; the association studies between complex diseases and SNPs or haplotypes have received great attention. However, these studies are restricted by the cost of genotyping all SNPs; thus, it is necessary to find smaller subsets, or tag SNPs, representing the rest of the SNPs. In fact, the existing tag SNP selection algorithms are notoriously time-consuming. An efficient algorithm for tag SNP selection was presented, which was applied to analyze the HapMap YRI data. The experimental results show that the proposed algorithm can achieve better performance than the existing tag SNP selection algorithms; in most cases, this proposed algorithm is at least ten times faster than the existing methods. In many cases, when the redundant ratio of the block is high, the proposed algorithm can even be thousands times faster than the previously known methods. Tools and web services for haplotype block analysis integrated by hadoop MapReduce framework are also developed using the proposed algorithm as computation kernels.

  17. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects

    Directory of Open Access Journals (Sweden)

    Shaw Gary M

    2009-06-01

    Full Text Available Abstract Background Folic acid taken in early pregnancy reduces risks for delivering offspring with several congenital anomalies. The mechanism by which folic acid reduces risk is unknown. Investigations into genetic variation that influences transport and metabolism of folate will help fill this data gap. We focused on 118 SNPs involved in folate transport and metabolism. Methods Using data from a California population-based registry, we investigated whether risks of spina bifida or conotruncal heart defects were influenced by 118 single nucleotide polymorphisms (SNPs associated with the complex folate pathway. This case-control study included 259 infants with spina bifida and a random sample of 359 nonmalformed control infants born during 1983–86 or 1994–95. It also included 214 infants with conotruncal heart defects born during 1983–86. Infant genotyping was performed blinded to case or control status using a designed SNPlex assay. We examined single SNP effects for each of the 118 SNPs, as well as haplotypes, for each of the two outcomes. Results Few odds ratios (ORs revealed sizable departures from 1.0. With respect to spina bifida, we observed ORs with 95% confidence intervals that did not include 1.0 for the following SNPs (heterozygous or homozygous relative to the reference genotype: BHMT (rs3733890 OR = 1.8 (1.1–3.1, CBS (rs2851391 OR = 2.0 (1.2–3.1; CBS (rs234713 OR = 2.9 (1.3–6.7; MTHFD1 (rs2236224 OR = 1.7 (1.1–2.7; MTHFD1 (hcv11462908 OR = 0.2 (0–0.9; MTHFD2 (rs702465 OR = 0.6 (0.4–0.9; MTHFD2 (rs7571842 OR = 0.6 (0.4–0.9; MTHFR (rs1801133 OR = 2.0 (1.2–3.1; MTRR (rs162036 OR = 3.0 (1.5–5.9; MTRR (rs10380 OR = 3.4 (1.6–7.1; MTRR (rs1801394 OR = 0.7 (0.5–0.9; MTRR (rs9332 OR = 2.7 (1.3–5.3; TYMS (rs2847149 OR = 2.2 (1.4–3.5; TYMS (rs1001761 OR = 2.4 (1.5–3.8; and TYMS (rs502396 OR = 2.1 (1.3–3.3. However, multiple SNPs observed for a given gene showed evidence of linkage disequilibrium indicating

  18. Utilizing HapMap and tagging SNPs.

    Science.gov (United States)

    Haiman, Christopher A; Stram, Daniel O

    2008-01-01

    Advancements in our understanding of variation in the human genome and rapid improvements in high-throughput genotyping technology have made it feasible to study most of the human genetic diversity that is due to common variations in relation to observable phenotypes. Over the past few years, public SNP databases have matured and empirical genome-wide SNP data, such as that generated by the International HapMap Project, have shown the utility and efficiency of selecting and testing informative markers ("tag SNPs") that exploit redundancies among nearby polymorphisms due to linkage disequilibrium (LD). In this chapter, we will demonstrate how to use the HapMap resource and the Haploview program to process and analyze genetic data from HapMap, to evaluate LD relations between SNPs, and to select tagging SNPs to be examined in disease association studies.

  19. Gray matter involvement in patients with multiple sclerosis as shown by magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Reshiana Rumzan; CHEN Xuan; LI Yong-mei

    2012-01-01

    Objective To summarize the main findings seen on conventional and advanced magnetic resonance imaging (MRI)used to assess gray matter (GM) involvement in patients with multiple sclerosis (MS).Data sources The data used in this review were obtained mainly from studies reported in the PubMed database using the terms of multiple sclerosis,gray matter,magnetic resonance imaging.Study selection Relevant literatures on studies of GM involvement in MS patients were identified,retrieved and reviewed.Results MS is the most common chronic,disabling central nervous system disease in young adults.Although traditional thinking has considered MS to be a chronic inflammatory demyelinating condition affecting solely the white matter (WM) of the central nervous system,over the last few years it has been shown that GM pathology is also common and extensive.GM demyelinating lesions can not only be found in the cerebral cortex but also in the deep gray nuclei.Apart from focal demyelinatad lesions,diffuse neuronal loss and atrophy is also present in the GM of MS patients.Conclusions The widespread use of conventional and quantitative MRI based techniques in MS has led to an improved understanding of the mechanisms underlying the inflammatory and neurodegenerative processes of the disease.However,more researches are needed to unravel GM pathology in MS patients,which at present remains enigmatic.

  20. MicroRNA399 is involved in multiple nutrients starvation responses in rice

    Directory of Open Access Journals (Sweden)

    Bin eHu

    2015-03-01

    Full Text Available The increasing evidences have revealed that microRNAs (miRNAs play significant role in nutrient stress response. Previously, miR399 was documented to be induced by phosphorus (P starvation and involved in regulating P starvation responses. To further investigate the function of miR399 in rice (Oryza sativa L., we performed GeneChip analysis with OsmiR399 over-expressing plants. Interestingly, our results showed that, besides P starvation responsive genes, the expression of a number of genes involved in iron (Fe, potassium (K, sodium (Na, and calcium (Ca absorption was dramatically up-regulated in OsmiR399 over-expressing plants. Consistently, the concentrations of Fe, K, Na, and Ca were also increased in OsmiR399 over-expressing plants. The expression of OsmiR399 was also up-regulated by these nutrient starvations, respectively. Moreover, the loss-of-function of LTN1, the down-stream target of OsmiR399, also resulted in the increase of multiple metal elements and the up-regulation of the absorption related genes. These results indicated that OsmiR399 participates in the regulation of multiple nutrient starvation responses, which also gives new view on understanding the interaction among different nutrients mediated by miR399.

  1. Acceleration of multiple solution of a boundary value problem involving a linear algebraic system

    Science.gov (United States)

    Gazizov, Talgat R.; Kuksenko, Sergey P.; Surovtsev, Roman S.

    2016-06-01

    Multiple solution of a boundary value problem that involves a linear algebraic system is considered. New approach to acceleration of the solution is proposed. The approach uses the structure of the linear system matrix. Particularly, location of entries in the right columns and low rows of the matrix, which undergo variation due to the computing in the range of parameters, is used to apply block LU decomposition. Application of the approach is considered on the example of multiple computing of the capacitance matrix by method of moments used in numerical electromagnetics. Expressions for analytic estimation of the acceleration are presented. Results of the numerical experiments for solution of 100 linear systems with matrix orders of 1000, 2000, 3000 and different relations of variated and constant entries of the matrix show that block LU decomposition can be effective for multiple solution of linear systems. The speed up compared to pointwise LU factorization increases (up to 15) for larger number and order of considered systems with lower number of variated entries.

  2. Tool for rapid annotation of microbial SNPs (TRAMS): a simple program for rapid annotation of genomic variation in prokaryotes.

    Science.gov (United States)

    Reumerman, Richard A; Tucker, Nicholas P; Herron, Paul R; Hoskisson, Paul A; Sangal, Vartul

    2013-09-01

    Next generation sequencing (NGS) has been widely used to study genomic variation in a variety of prokaryotes. Single nucleotide polymorphisms (SNPs) resulting from genomic comparisons need to be annotated for their functional impact on the coding sequences. We have developed a program, TRAMS, for functional annotation of genomic SNPs which is available to download as a single file executable for WINDOWS users with limited computational experience and as a Python script for Mac OS and Linux users. TRAMS needs a tab delimited text file containing SNP locations, reference nucleotide and SNPs in variant strains along with a reference genome sequence in GenBank or EMBL format. SNPs are annotated as synonymous, nonsynonymous or nonsense. Nonsynonymous SNPs in start and stop codons are separated as non-start and non-stop SNPs, respectively. SNPs in multiple overlapping features are annotated separately for each feature and multiple nucleotide polymorphisms within a codon are combined before annotation. We have also developed a workflow for Galaxy, a highly used tool for analysing NGS data, to map short reads to a reference genome and extract and annotate the SNPs. TRAMS is a simple program for rapid and accurate annotation of SNPs that will be very useful for microbiologists in analysing genomic diversity in microbial populations.

  3. Multiple proteins of White spot syndrome virus involved in recognition of -integrin

    Indian Academy of Sciences (India)

    Jing-Yan Zhang; Qing-Hui Liu; Jie Huang

    2014-06-01

    The recognition and attachment of virus to its host cell surface is a critical step for viral infection. Recent research revealed that -integrin was involved in White spot syndrome virus (WSSV) infection. In this study, the interaction of -integrin with structure proteins of WSSV and motifs involved in WSSV infection was examined. The results showed that envelope proteins VP26, VP31, VP37, VP90 and nucleocapsid protein VP136 interacted with LvInt. RGD-, YGL- and LDV-related peptide functioned as motifs of WSSV proteins binding with -integrin. The -integrin ligand of RGDT had better blocking effect compared with that of YGL- and LDV-related peptides. In vivo assay indicated that RGD-, LDV- and YGL-related peptides could partially block WSSV infection. These data collectively indicate that multiple proteins were involved in recognition of -integrin. Identification of proteins in WSSV that are associated with -integrin will assist development of new agents for effective control of the white spot syndrome.

  4. Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio [University ' ' Federico II' ' , Department of Public Health, Nephrology Unit, Naples (Italy); Russo, Camilla [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Feriozzi, Sandro [Belcolle Hospital, Nephrology and Dialysis Department, Viterbo (Italy); Veroux, Massimiliano [University Hospital of Catania, Department of Medical and Surgical Sciences and Advanced Technologies, Catania (Italy); Battaglia, Yuri [St. Anna Hospital-University, Department of Specialized Medicine, Division of Nephrology and Dialysis, Ferrara (Italy); Concolino, Daniela [University Magna Graecia, Department of Pediatrics, Catanzaro (Italy); Pieruzzi, Federico [University of Milano-Bicocca, Nephrology Unit, Milan (Italy); Tuttolomondo, Antonino [University of Palermo, Internal Medicine, DiBiMIS, Palermo (Italy); Caronia, Aurelio [Triolo Zancia Care Home, Palermo (Italy); Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo [University ' ' Federico II' ' , Department of Neurosciences and Reproductive and Odontostomatological Sciences, Naples (Italy)

    2017-06-15

    Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

  5. An unusual presentation of brucellosis, involving multiple organ systems, with low agglutinating titers: a case report

    Directory of Open Access Journals (Sweden)

    Khorvash Farzin

    2007-07-01

    Full Text Available Abstract Background Brucellosis is a multi-system disease that may present with a broad spectrum of clinical manifestations. While hepatic involvement in brucellosis is not rare, it may rarely involve the kidney or display with cardiac manifestations. Central nervous system involvement in brucellosis sometimes can cause demyelinating syndromes. Here we present a case of brucella hepatitis, myocarditis, acute disseminated encephalomyelitis, and renal failure. Case presentation A 26-year-old man presented with fever, ataxia, and dysarthria. He was a shepherd and gave a history of low grade fever, chilly sensation, cold sweating, loss of appetite, arthralgia and 10 Kg weight loss during the previous 3 months. He had a body temperature of 39°C at the time of admission. On laboratory tests he had elevated level of liver enzymes, blood urea nitrogen, Creatinine, Creatine phosphokinase (MB, and moderate proteinuria. He also had abnormal echocardiography and brain MRI. Enzyme-linked immunosorbent assay for IgG and IgM was negative. Standard tube agglutination test (STAT and 2-mercaptoethanol (2-ME titers were 1:80 and 1:40 respectively. Finally he was diagnosed with brucellosis by positive blood culture and the polymerase chain reaction for Brucella mellitensis. Conclusion In endemic areas clinicians should consider brucellosis in any unusual presentation involving multiple organ systems, even if serology is inconclusive. In endemic areas low STAT and 2-ME titers should be considered as an indication of brucellosis and in these cases additional testing is recommended to rule out brucellosis.

  6. Evaluating GWAS-identified SNPs for age at natural menopause among chinese women.

    Directory of Open Access Journals (Sweden)

    Chong Shen

    Full Text Available BACKGROUND: Age at natural menopause (ANM is a complex trait with high heritability and is associated with several major hormonal-related diseases. Recently, several genome-wide association studies (GWAS, conducted exclusively among women of European ancestry, have discovered dozens of genetic loci influencing ANM. No study has been conducted to evaluate whether these findings can be generalized to Chinese women. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the index single nucleotide polymorphisms (SNPs in 19 GWAS-identified genetic susceptibility loci for ANM among 3,533 Chinese women who had natural menopause. We also investigated 3 additional SNPs which were in LD with the index SNP in European-ancestry but not in Asian-ancestry populations. Two genetic risk scores (GRS were calculated to summarize SNPs across multiple loci one for all SNPs tested (GRSall, and one for SNPs which showed association in our study (GRSsel. All 22 SNPs showed the same association direction as previously reported. Eight SNPs were nominally statistically significant with P≤0.05: rs4246511 (RHBDL2, rs12461110 (NLRP11, rs2307449 (POLG, rs12611091 (BRSK1, rs1172822 (BRSK1, rs365132 (UIMC1, rs2720044 (ASH2L, and rs7246479 (TMEM150B. Especially, SNPs rs4246511, rs365132, rs1172822, and rs7246479 remained significant even after Bonferroni correction. Significant associations were observed for GRS. Women in the highest quartile began menopause 0.7 years (P = 3.24×10(-9 and 0.9 years (P = 4.61×10(-11 later than those in the lowest quartile for GRSsel and GRSall, respectively. CONCLUSIONS: Among the 22 investigated SNPs, eight showed associations with ANM (P<0.05 in our Chinese population. Results from this study extend some recent GWAS findings to the Asian-ancestry population and may guide future efforts to identify genetic determination of menopause.

  7. Involvement of Multiple Transporters-mediated Transports in Mizoribine and Methotrexate Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Teruo Murakami

    2012-08-01

    Full Text Available Mizoribine is administered orally and excreted into urine without being metabolized. Many research groups have reported a linear relationship between the dose and peak serum concentration, between the dose and AUC, and between AUC and cumulative urinary excretion of mizoribine. In contrast, a significant interindividual variability, with a small intraindividual variability, in oral bioavailability of mizoribine is also reported. The interindividual variability is mostly considered to be due to the polymophisms of transporter genes. Methotrexate (MTX is administered orally and/or by parenteral routes, depending on the dose. Metabolic enzymes and multiple transporters are involved in the pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked interindividual variability and saturation with increase in the dose of MTX, with a small intraindividual variability, where the contribution of gene polymophisms of transporters and enzymes is suggested. Therapeutic drug monitoring of both mizoribine and MTX is expected to improve their clinical efficacy in the treatment of rheumatoid arthritis.

  8. Florigen is involved in axillary bud development at multiple stages in Arabidopsis.

    Science.gov (United States)

    Niwa, Masaki; Endo, Motomu; Araki, Takashi

    2013-11-01

    The wide variety of plant architectures is largely based on diverse and flexible modes of axillary shoot development. In Arabidopsis, floral transition (flowering) stimulates axillary bud development. The mechanism that links flowering and axillary bud development is, however, largely unknown. We recently showed that FLOWERING LOCUS T (FT) protein, which acts as florigen, promotes the phase transition of axillary meristems, whereas BRANCHED1 (BRC1) antagonizes the florigen action in axillary buds. Here, we present evidences for another possible role of florigen in axillary bud development. Ectopic overexpression of FT or another florigen gene TWIN SISTER OF FT (TSF) with LEAFY (LFY) induces ectopic buds at cotyledonary axils, confirming the previous proposal that these genes are involved in formation of axillary buds. Taken together with our previous report that florigen promotes axillary shoot elongation, we propose that florigen regulates axillary bud development at multiple stages to coordinate it with flowering in Arabidopsis.

  9. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jun [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Pharmacology, College of Medicine, Wuhan University of Science and Technology, Wuhan (China); Cao, Hui [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Hongjie [Section of Neurobiology, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL (United States); Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xiang, Ming, E-mail: xiangming@mails.tjmu.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2015-06-15

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation.

  10. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    Science.gov (United States)

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  11. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    DEFF Research Database (Denmark)

    Wong, Jaslyn E M M; Midtgaard, Søren Roi; Gysel, Kira

    2015-01-01

    LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multi......LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement...... of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering...... solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers...

  12. Identification of gene expression patterns crucially involved in experimental autoimmune encephalomyelitis and multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Martin M. Herrmann

    2016-10-01

    Full Text Available After encounter with a central nervous system (CNS-derived autoantigen, lymphocytes leave the lymph nodes and enter the CNS. This event leads only rarely to subsequent tissue damage. Genes relevant to CNS pathology after cell infiltration are largely undefined. Myelin-oligodendrocyte-glycoprotein (MOG-induced experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a chronic autoimmune disease of the CNS that results in disability. To assess genes that are involved in encephalitogenicity and subsequent tissue damage mediated by CNS-infiltrating cells, we performed a DNA microarray analysis from cells derived from lymph nodes and eluted from CNS in LEW.1AV1 (RT1av1 rats immunized with MOG 91-108. The data was compared to immunizations with adjuvant alone or naive rats and to immunizations with the immunogenic but not encephalitogenic MOG 73-90 peptide. Here, we show involvement of Cd38, Cxcr4 and Akt and confirm these findings by the use of Cd38-knockout (B6.129P2-Cd38tm1Lnd/J mice, S1P-receptor modulation during EAE and quantitative expression analysis in individuals with MS. The hereby-defined underlying pathways indicate cellular activation and migration pathways mediated by G-protein-coupled receptors as crucial events in CNS tissue damage. These pathways can be further explored for novel therapeutic interventions.

  13. Effect of fluoxetine on learning and memory involves multiple 5-HT systems.

    Science.gov (United States)

    Meneses, A; Hong, E

    1995-10-01

    Diverse evidence suggests that 5-HT uptake blockers enhance learning and memory. However, there is no information about the mechanisms of action involved in such effects. The aim of the present work was to investigate the nature of the receptors involved in the effects of fluoxetine on learning. Therefore, a dose-response curve of posttraining injection (intraperitoneal) of fluoxetine was carried out in an associative learning task (auto-shaping). Fluoxetine or the vehicle was injected 10 min after 5-HT antagonists: (+/-)-pindolol, (+/-)-propanolol, NAN-190, ketanserin, ritanserin, mesulergine, MDL 72222, or SDZ 205-557. Presynaptic activity was eliminated by means of chloroamphetamine pretreatment. Scopolamine (an anticholinergic) and dizocilpine (a noncompetitive NMDA receptor antagonist) were also used. Results showed that fluoxetine enhanced learning of the conditioned response (CR) in a dose-dependent fashion. All 5-HT antagonists had no effects by themselves but inhibited the effects of fluoxetine at different degrees. Decrement of CR produced by scopolamine was reversed by fluoxetine. Dizocilpine did not affect CR but prevented the effects of fluoxetine. The present findings suggest that the actions of fluoxetine on learning are due to an interaction with multiple receptors of postsynaptic nature.

  14. Involvement of Multiple Gene-Silencing Pathways in a Paramutation-like Phenomenon in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Zhimin Zheng

    2015-05-01

    Full Text Available Paramutation is an epigenetic phenomenon that has been observed in a number of multicellular organisms. The epigenetically silenced state of paramutated alleles is not only meiotically stable but also “infectious” to active homologous alleles. The molecular mechanism of paramutation remains unclear, but components involved in RNA-directed DNA methylation (RdDM are required. Here, we report a multi-copy pRD29A-LUC transgene in Arabidopsis thaliana that behaves like a paramutation locus. The silent state of LUC is induced by mutations in the DNA glycosylase gene ROS1. The silent alleles of LUC are not only meiotically stable but also able to transform active LUC alleles into silent ones, in the absence of ros1 mutations. Maintaining silencing at the LUC gene requires action of multiple pathways besides RdDM. Our study identified specific factors that are involved in the paramutation-like phenomenon and established a model system for the study of paramutation in Arabidopsis.

  15. Involvement of multiple elements in FXR-mediated transcriptional activation of FGF19.

    Science.gov (United States)

    Miyata, Masaaki; Hata, Tatsuya; Yamakawa, Hiroki; Kagawa, Tatehiro; Yoshinari, Kouichi; Yamazoe, Yasushi

    2012-10-01

    The intestinal endocrine hormone human fibroblast growth factor 19 (FGF19) is involved in the regulation of not only hepatic bile acid metabolism but also carbohydrate and lipid metabolism. In the present study, bile acid/farnesoid X receptor (FXR) responsiveness in the FGF19 promoter region was investigated by a reporter assay using the human colon carcinoma cell line LS174T. The assay revealed the presence of bile acid/FXR-responsive elements in the 5'-flanking region up to 8.8 kb of FGF19. Deletion analysis indicated that regions from -1866 to -1833, from -1427 to -1353, and from -75 to +262 were involved in FXR responsiveness. Four, four, and two consecutive half-sites of nuclear receptors were observed in the three regions, respectively. An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay revealed FXR/retinoid X receptor α (RXRα) heterodimer binding in these three regions. EMSA and reporter assays using mutated constructs indicated that the nuclear receptor IR1, ER2, and DR8 motifs in the 5'-flanking region were involved in FXR responsiveness of FGF19. Lithocholic acid (LCA) (10 μM), chenodeoxycholic acid (CDCA) (10 μM), or GW4064 (0.1 μM) treatment increased reporter activity in a construct including the three motifs under FXR-expressing conditions whereas LCA and not CDCA or GW4064 treatment increased the reporter activity under pregnane X receptor (PXR)-expressing conditions. These results suggest that FGF19 is transcriptionally activated through multiple FXR-responsive elements in the promoter region.

  16. Ca2+ sparks evoked by depolarization of rat ventricular myocytes involve multiple release sites

    Institute of Scientific and Technical Information of China (English)

    ZANGWei-Jin; YUXiao-Jiang; ZANGYi-Min

    2003-01-01

    AIM:To investigate the fundamental nature of calcium release events (Ca2+‘sparks’) evoked in rat ventricular myocytes during excitation-contraction (E-C) coupling. METHODS: High-resolution line-scan confocal imaging with the fluorescent calcium indicator and patch-clamp techniques were used to study the spontaneous Ca2+ sparks and sparks evoked by depolarization. RESULTS: 1)Line scans oriented along the length of the cell showed that both spontaneous sparks and sparks evoked by depolarization to -35mV appeared to arise at single sites spacing about 1.80μm apart (ie, the sarcomere length), and measurements of their longitudinal spread (full-width at halfmaximal amplitude:FWHM) followed single Gaussian distributions with means of 2.6μm. 2)Different to this,transverse line scans often revealed spontaneous and evoked sparks that appeared to arise near-synchronously from paired sites. Measurements of transverse FWHM of both spontaneous and evoked sparks showed bimodal distributions, which were fit well by the sums of two Gaussian curves with means of 1.8 and 2.9μm for spontaneous sparks and ith means of 1.9 and 3.1 μm for evoked sparks. Relative areas under the two Gaussian curves were 1.73:1 and 1.85:1, respectively, for spontaneous and evoked sparks. CONCLUSIONS: Ca2+ sparks evoked by depolarization are not ′unitary′ events, but often involve multiple sites of origin along Z-lines, as previously shown for spontaneous sparks. Thus, Ca2+ released during sparks directly triggered by influx through L-type Ca2+ channels may, in turn, trigger neighboring sites. The restricted involvement of only a few transverse release sites preserves the essential feature of the ‘local control’ theory of E-C coupling.

  17. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

    2015-03-01

    The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

  18. Planning paths to multiple targets: memory involvement and planning heuristics in spatial problem solving.

    Science.gov (United States)

    Wiener, J M; Ehbauer, N N; Mallot, H A

    2009-09-01

    For large numbers of targets, path planning is a complex and computationally expensive task. Humans, however, usually solve such tasks quickly and efficiently. We present experiments studying human path planning performance and the cognitive processes and heuristics involved. Twenty-five places were arranged on a regular grid in a large room. Participants were repeatedly asked to solve traveling salesman problems (TSP), i.e., to find the shortest closed loop connecting a start location with multiple target locations. In Experiment 1, we tested whether humans employed the nearest neighbor (NN) strategy when solving the TSP. Results showed that subjects outperform the NN-strategy, suggesting that it is not sufficient to explain human route planning behavior. As a second possible strategy we tested a hierarchical planning heuristic in Experiment 2, demonstrating that participants first plan a coarse route on the region level that is refined during navigation. To test for the relevance of spatial working memory (SWM) and spatial long-term memory (LTM) for planning performance and the planning heuristics applied, we varied the memory demands between conditions in Experiment 2. In one condition the target locations were directly marked, such that no memory was required; a second condition required participants to memorize the target locations during path planning (SWM); in a third condition, additionally, the locations of targets had to retrieved from LTM (SWM and LTM). Results showed that navigation performance decreased with increasing memory demands while the dependence on the hierarchical planning heuristic increased.

  19. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase.

    Science.gov (United States)

    Wong, Jaslyn E M M; Midtgaard, Søren Roi; Gysel, Kira; Thygesen, Mikkel B; Sørensen, Kasper K; Jensen, Knud J; Stougaard, Jens; Thirup, Søren; Blaise, Mickaël

    2015-03-01

    LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

  20. Visualization of a City Sustainability Index (CSI: Towards Transdisciplinary Approaches Involving Multiple Stakeholders

    Directory of Open Access Journals (Sweden)

    Koichiro Mori

    2015-09-01

    Full Text Available We have developed a visualized 3-D model of a City Sustainability Index (CSI based on our original concept of city sustainability in which a sustainable city is defined as one that maximizes socio-economic benefits while meeting constraint conditions of the environment and socio-economic equity on a permanent basis. The CSI is based on constraint and maximization indicators. Constraint indicators assess whether a city meets the necessary minimum conditions for city sustainability. Maximization indicators measure the benefits that a city generates in socio-economic aspects. When used in the policy-making process, the choice of constraint indicators should be implemented using a top-down approach. In contrast, a bottom-up approach is more suitable for defining maximization indicators because this technique involves multiple stakeholders (in a transdisciplinary approach. Using different materials of various colors, shapes, sizes, we designed and constructed the visualized physical model of the CSI to help people evaluate and compare the performance of different cities in terms of sustainability. The visualized model of the CSI can convey complicated information in a simple and straightforward manner to diverse stakeholders so that the sustainability analysis can be understood intuitively by ordinary citizens as well as experts. Thus, the CSI model helps stakeholders to develop critical thinking about city sustainability and enables policymakers to make informed decisions for sustainability through a transdisciplinary approach.

  1. W55a Encodes a Novel Protein Kinase That Is Involved in Multiple Stress Responses

    Institute of Scientific and Technical Information of China (English)

    Zhao-Shi Xu; Li Liu; Zhi-Yong Ni; Pei Liu; Ming Chen; Lian-Cheng Li; Yao-Feng Chen; You-Zhi Ma

    2009-01-01

    Protein kinases play crucial roles In response to external environment stress signals. A putative protein kinase, W55a, belonging to SNF1-related protein kinase 2 (SnRK2) subfamily, was isolated from a cDNA library of drought-treated wheat seedlings. The entire length of W55a was obtained using rapid amplification of 5' cDNA ends (5'-RACE) and reverse transcription-polymerase chain reaction(RT-PCR). It contains a 1029-bp open reading frame (ORF) encoding 342 amino acids. The deduced amino acid sequence of W55a had eleven conserved catalytic subdomains and one Ser/Thr protein kinase active-site that characterize Ser/Thr protein kinases. Phylogenetic analysis showed that W55a was 90.38% homologous with rice SAPK1, a member of the SnRK2 family. Using nullisomic-tetrasomic and ditelocentric lines of Chinese Spring, W55a was located on chromosome 2BS. Expression pattern analysis revealed that W55a was upregulated by drought and salt, exogenous abscisic acid, salicylic acid, ethylene and methyl jasmonata, but was not responsive to cold stress. In addition, W55a transcripts were abundant in leaves, but not in roots or stems, under environmental stresses. Transgenic Arabidopsis plants overexprassing W55a exhibited higher tolerance to drought. Based on these findings, W55a encodes a novel dehydration-responsive protein kinase that is involved in multiple stress signal transductions.

  2. Human SNPs resulting in premature stop codons and protein truncation

    OpenAIRE

    Savas Sevtap; Tuzmen Sukru; Ozcelik Hilmi

    2006-01-01

    Abstract Single nucleotide polymorphisms (SNPs) constitute the most common type of genetic variation in humans. SNPs introducing premature termination codons (PTCs), herein called X-SNPs, can alter the stability and function of transcripts and proteins and thus are considered to be biologically important. Initial studies suggested a strong selection against such variations/mutations. In this study, we undertook a genome-wide systematic screening to identify human X-SNPs using the dbSNP databa...

  3. Selecting additional tag SNPs for tolerating missing data in genotyping

    Directory of Open Access Journals (Sweden)

    Chen Ting

    2005-11-01

    Full Text Available Abstract Background Recent studies have shown that the patterns of linkage disequilibrium observed in human populations have a block-like structure, and a small subset of SNPs (called tag SNPs is sufficient to distinguish each pair of haplotype patterns in the block. In reality, some tag SNPs may be missing, and we may fail to distinguish two distinct haplotypes due to the ambiguity caused by missing data. Results We show there exists a subset of SNPs (referred to as robust tag SNPs which can still distinguish all distinct haplotypes even when some SNPs are missing. The problem of finding minimum robust tag SNPs is shown to be NP-hard. To find robust tag SNPs efficiently, we propose two greedy algorithms and one linear programming relaxation algorithm. The experimental results indicate that (1 the solutions found by these algorithms are quite close to the optimal solution; (2 the genotyping cost saved by using tag SNPs can be as high as 80%; and (3 genotyping additional tag SNPs for tolerating missing data is still cost-effective. Conclusion Genotyping robust tag SNPs is more practical than just genotyping the minimum tag SNPs if we can not avoid the occurrence of missing data. Our theoretical analysis and experimental results show that the performance of our algorithms is not only efficient but the solution found is also close to the optimal solution.

  4. Multiple functional involvement of thymosin beta-4 in tooth germ development.

    Science.gov (United States)

    Ookuma, Yukiko F; Kiyoshima, Tamotsu; Kobayashi, Ieyoshi; Nagata, Kengo; Wada, Hiroko; Fujiwara, Hiroaki; Yamaza, Haruyoshi; Nonaka, Kazuaki; Sakai, Hidetaka

    2013-02-01

    Thymosin beta-4 (Tβ4) is known to be ubiquitously involved in the actin monomer sequestering on the cytoskeleton. Our previous study showed specific temporal and special in situ expression pattern of Tβ4 mRNA in dental epithelial and mesenchymal cells in the developing tooth germ of the mouse lower first molar. In this study, we examined the functional implications of Tβ4 in the developmental course of the mouse lower first molar. An inhibition assay using Tβ4 antisense sulfur-substituted oligodeoxynucleotide (AS S-ODN) in cultured embryonic day 11.0 (E11.0) mandibles showed a significant growth inhibition of the tooth germ. However, no growth arrest of the cultured E15.0 tooth germ was observed by using Tβ4 AS S-ODN. The Tβ4 knockdown led to significantly decreased expression levels of type II/III runt-related transcription factor 2 (Runx2) and nucleolin (Ncl) in the cultured E11.0 mandibles. Since our previous studies proved that the inhibition of type II/III Runx2 and Ncl translations resulted in the developmental arrest of the tooth germ in the cultured E11.0 mandible, Tβ4 appears to play roles in tooth germ development via the regulation of the type II/III Runx2 and Ncl expressions. Tβ4 knockdown also resulted in decreased secretion of matrix metalloproteinase (Mmp)-2, a reduced cell motility activity and upregulation of E-cadherin in dental epithelial mDE6 cells. These results suggest that Tβ4 plays multiple functional roles in odontogenic epithelial cells in the early stages of tooth germ development by regulating the expression of odontogenesis-related genes.

  5. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

    Directory of Open Access Journals (Sweden)

    Yee Suan Poo

    2014-12-01

    Full Text Available The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.

  6. The Persistence of Asthma requires Multiple Feedback Circuits Involving ILC2 and IL33

    Science.gov (United States)

    Christianson, Christina A.; Goplen, Nicholas P.; Zafar, Iram; Irvin, Chaoyu; Good, James T.; Rollins, Donald R.; Gorentla, Balachandra; Liu, Weimin; Gorska, Magdalena M.; Chu, HongWei; Martin, Richard J.; Alam, Rafeul

    2015-01-01

    Background Asthma in the mouse model spontaneously resolves after cessation of allergen exposure. We developed a mouse model where asthma features persisted for 6 months after cessation of allergen exposure. Objective To elucidate factors contributing to the persistence of asthma. Methods We utilized a combination of immunologic, genetic, microarray and pharmacologic approaches to dissect the mechanism of persistence of asthma. Results Elimination of T cells though antibody-mediated depletion or lethal irradiation and transplantation of Rag1−/− bone marrow in mice with chronic asthma resulted in resolution of airway inflammation but not airway hyperreactivity or remodeling. Elimination of T cells and ILC2 through lethal irradiation and transplantation of Rag2−/−γc−/− bone marrow or blockade of IL33 resulted in resolution of airway inflammation and hyperreactivity. Persistence of asthma required multiple interconnected feedback and feed forward circuits between ILC2 and epithelial cells. Epithelial IL33 induced ILC2, a rich source of IL13. The latter directly induced epithelial IL33 establishing a positive feedback circuit. IL33 auto-induced, generating another feedback circuit. IL13 upregulated IL33 receptors and facilitated IL33 auto-induction, thus establishing a feed forward circuit. Elimination of any component of these circuits resulted in resolution of chronic asthma. In agreement with the foregoing, IL33 and ILC2 were increased in the airways from asthmatic patients. IL33 correlated with disease severity. Conclusions We present a critical network of feedback and feed forward interactions between epithelial cells and ILC2 involved in maintaining chronic asthma. Although T cells contributed to the severity of chronic asthma they were redundant in maintaining airway hyperreactivity and remodeling. PMID:25617223

  7. Genome bioinformatic analysis of nonsynonymous SNPs

    Directory of Open Access Journals (Sweden)

    Todd John A

    2007-08-01

    Full Text Available Abstract Background Genome-wide association studies of common diseases for common, low penetrance causal variants are underway. A proportion of these will alter protein sequences, the most common of which is the non-synonymous single nucleotide polymorphism (nsSNP. It would be an advantage if the functional effects of an nsSNP on protein structure and function could be predicted, both for the final identification process of a causal variant in a disease-associated chromosome region, and in further functional analyses of the nsSNP and its disease-associated protein. Results In the present report we have compared and contrasted structure- and sequence-based methods of prediction to over 5500 genes carrying nearly 24,000 nsSNPs, by employing an automatic comparative modelling procedure to build models for the genes. The nsSNP information came from two sources, the OMIM database which are rare (minor allele frequency, MAF, 0.05, have no known link to a disease. For over 40% of the nsSNPs, structure-based methods predicted which of these sequence changes are likely to either disrupt the structure of the protein or interfere with the function or interactions of the protein. For the remaining 60%, we generated sequence-based predictions. Conclusion We show that, in general, the prediction tools are able distinguish disease causing mutations from those mutations which are thought to have a neutral affect. We give examples of mutations in genes that are predicted to be deleterious and may have a role in disease. Contrary to previous reports, we also show that rare mutations are consistently predicted to be deleterious as often as commonly occurring nsSNPs.

  8. Multiplex PCR and minisequencing of SNPs--a model with 35 Y chromosome SNPs

    DEFF Research Database (Denmark)

    Sanchez, Juan J; Børsting, Claus; Hallenberg, Charlotte

    2003-01-01

    We have developed a robust single nucleotide polymorphism (SNPs) typing assay with co-amplification of 25 DNA-fragments and the detection of 35 human Y chromosome SNPs. The sizes of the PCR products ranged from 79 to 186 base pairs. PCR primers were designed to have a theoretical Tm of 60 +/- 5...... degrees C at a salt concentration of 180 mM. The sizes of the primers ranged from 19 to 34 nucleotides. The concentration of amplification primers was adjusted to obtain balanced amounts of PCR products in 8mM MgCl2. For routine purposes, 1 ng of genomic DNA was amplified and the lower limit...... was approximately 100 pg DNA. The minisequencing reactions were performed simultaneously for all 35 SNPs with fluorescently labelled dideoxynucleotides. The size of the minisequencing primers ranged from 19 to 106 nucleotides. The minisequencing reactions were analysed by capillary electrophoresis and multicolour...

  9. The Development of Ciprofloxacin Resistance in Pseudomonas aeruginosa Involves Multiple Response Stages and Multiple Proteins ▿ † ‡

    Science.gov (United States)

    Su, Hsun-Cheng; Ramkissoon, Kevin; Doolittle, Janet; Clark, Martha; Khatun, Jainab; Secrest, Ashley; Wolfgang, Matthew C.; Giddings, Morgan C.

    2010-01-01

    Microbes have developed resistance to nearly every antibiotic, yet the steps leading to drug resistance remain unclear. Here we report a multistage process by which Pseudomonas aeruginosa acquires drug resistance following exposure to ciprofloxacin at levels ranging from 0.5× to 8× the initial MIC. In stage I, susceptible cells are killed en masse by the exposure. In stage II, a small, slow to nongrowing population survives antibiotic exposure that does not exhibit significantly increased resistance according to the MIC measure. In stage III, exhibited at 0.5× to 4× the MIC, a growing population emerges to reconstitute the population, and these cells display heritable increases in drug resistance of up to 50 times the original level. We studied the stage III cells by proteomic methods to uncover differences in the regulatory pathways that are involved in this phenotype, revealing upregulation of phosphorylation on two proteins, succinate-semialdehyde dehydrogenase (SSADH) and methylmalonate-semialdehyde dehydrogenase (MMSADH), and also revealing upregulation of a highly conserved protein of unknown function. Transposon disruption in the encoding genes for each of these targets substantially dampened the ability of cells to develop the stage III phenotype. Considering these results in combination with computational models of resistance and genomic sequencing results, we postulate that stage III heritable resistance develops from a combination of both genomic mutations and modulation of one or more preexisting cellular pathways. PMID:20696867

  10. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants.

    Science.gov (United States)

    Burton, Paul R; Clayton, David G; Cardon, Lon R; Craddock, Nick; Deloukas, Panos; Duncanson, Audrey; Kwiatkowski, Dominic P; McCarthy, Mark I; Ouwehand, Willem H; Samani, Nilesh J; Todd, John A; Donnelly, Peter; Barrett, Jeffrey C; Davison, Dan; Easton, Doug; Evans, David M; Leung, Hin-Tak; Marchini, Jonathan L; Morris, Andrew P; Spencer, Chris C A; Tobin, Martin D; Attwood, Antony P; Boorman, James P; Cant, Barbara; Everson, Ursula; Hussey, Judith M; Jolley, Jennifer D; Knight, Alexandra S; Koch, Kerstin; Meech, Elizabeth; Nutland, Sarah; Prowse, Christopher V; Stevens, Helen E; Taylor, Niall C; Walters, Graham R; Walker, Neil M; Watkins, Nicholas A; Winzer, Thilo; Jones, Richard W; McArdle, Wendy L; Ring, Susan M; Strachan, David P; Pembrey, Marcus; Breen, Gerome; St Clair, David; Caesar, Sian; Gordon-Smith, Katharine; Jones, Lisa; Fraser, Christine; Green, Elaine K; Grozeva, Detelina; Hamshere, Marian L; Holmans, Peter A; Jones, Ian R; Kirov, George; Moskivina, Valentina; Nikolov, Ivan; O'Donovan, Michael C; Owen, Michael J; Collier, David A; Elkin, Amanda; Farmer, Anne; Williamson, Richard; McGuffin, Peter; Young, Allan H; Ferrier, I Nicol; Ball, Stephen G; Balmforth, Anthony J; Barrett, Jennifer H; Bishop, Timothy D; Iles, Mark M; Maqbool, Azhar; Yuldasheva, Nadira; Hall, Alistair S; Braund, Peter S; Dixon, Richard J; Mangino, Massimo; Stevens, Suzanne; Thompson, John R; Bredin, Francesca; Tremelling, Mark; Parkes, Miles; Drummond, Hazel; Lees, Charles W; Nimmo, Elaine R; Satsangi, Jack; Fisher, Sheila A; Forbes, Alastair; Lewis, Cathryn M; Onnie, Clive M; Prescott, Natalie J; Sanderson, Jeremy; Matthew, Christopher G; Barbour, Jamie; Mohiuddin, M Khalid; Todhunter, Catherine E; Mansfield, John C; Ahmad, Tariq; Cummings, Fraser R; Jewell, Derek P; Webster, John; Brown, Morris J; Lathrop, Mark G; Connell, John; Dominiczak, Anna; Marcano, Carolina A Braga; Burke, Beverley; Dobson, Richard; Gungadoo, Johannie; Lee, Kate L; Munroe, Patricia B; Newhouse, Stephen J; Onipinla, Abiodun; Wallace, Chris; Xue, Mingzhan; Caulfield, Mark; Farrall, Martin; Barton, Anne; Bruce, Ian N; Donovan, Hannah; Eyre, Steve; Gilbert, Paul D; Hilder, Samantha L; Hinks, Anne M; John, Sally L; Potter, Catherine; Silman, Alan J; Symmons, Deborah P M; Thomson, Wendy; Worthington, Jane; Dunger, David B; Widmer, Barry; Frayling, Timothy M; Freathy, Rachel M; Lango, Hana; Perry, John R B; Shields, Beverley M; Weedon, Michael N; Hattersley, Andrew T; Hitman, Graham A; Walker, Mark; Elliott, Kate S; Groves, Christopher J; Lindgren, Cecilia M; Rayner, Nigel W; Timpson, Nicolas J; Zeggini, Eleftheria; Newport, Melanie; Sirugo, Giorgio; Lyons, Emily; Vannberg, Fredrik; Hill, Adrian V S; Bradbury, Linda A; Farrar, Claire; Pointon, Jennifer J; Wordsworth, Paul; Brown, Matthew A; Franklyn, Jayne A; Heward, Joanne M; Simmonds, Matthew J; Gough, Stephen C L; Seal, Sheila; Stratton, Michael R; Rahman, Nazneen; Ban, Maria; Goris, An; Sawcer, Stephen J; Compston, Alastair; Conway, David; Jallow, Muminatou; Newport, Melanie; Sirugo, Giorgio; Rockett, Kirk A; Bumpstead, Suzannah J; Chaney, Amy; Downes, Kate; Ghori, Mohammed J R; Gwilliam, Rhian; Hunt, Sarah E; Inouye, Michael; Keniry, Andrew; King, Emma; McGinnis, Ralph; Potter, Simon; Ravindrarajah, Rathi; Whittaker, Pamela; Widden, Claire; Withers, David; Cardin, Niall J; Davison, Dan; Ferreira, Teresa; Pereira-Gale, Joanne; Hallgrimsdo'ttir, Ingeleif B; Howie, Bryan N; Su, Zhan; Teo, Yik Ying; Vukcevic, Damjan; Bentley, David; Brown, Matthew A; Compston, Alastair; Farrall, Martin; Hall, Alistair S; Hattersley, Andrew T; Hill, Adrian V S; Parkes, Miles; Pembrey, Marcus; Stratton, Michael R; Mitchell, Sarah L; Newby, Paul R; Brand, Oliver J; Carr-Smith, Jackie; Pearce, Simon H S; McGinnis, R; Keniry, A; Deloukas, P; Reveille, John D; Zhou, Xiaodong; Sims, Anne-Marie; Dowling, Alison; Taylor, Jacqueline; Doan, Tracy; Davis, John C; Savage, Laurie; Ward, Michael M; Learch, Thomas L; Weisman, Michael H; Brown, Mathew

    2007-11-01

    We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

  11. Filtrado digital neuronal difuso: caso MIMO Neural fuzzy digital filtering: multivariate identifier filters involving multiple inputs and multiple outputs (MIMO

    Directory of Open Access Journals (Sweden)

    Medel Juárez José de J.

    2011-05-01

    Full Text Available  

    Los filtros identificadores multivariables (MIMO son sistemas digitales adaptivos que cuentan con retroalimentación para que, de acuerdo a una función objetivo, ajusten su matriz de parámetros con la que se aproximan a la di-námica observable del sistema de referencia. Una forma de que un identificador cumpla con esas condiciones, es la de la lógica difusa por medio de sus mecanismos de in-ferencia que interpretan y seleccionan en una base de co-nocimiento la mejor matriz de parámetros. Estos mecanismos de selección mediante las redes neuronales permiten encontrar la respuesta con el mejor nivel de operación para cada cambio de estado (Shannon, 1948. En este artículo se considera en el modelo MIMO del filtrado digital, el proceso neuronal difuso para la estimación matricial de parámetros adaptiva, que se integra en el filtro de Kalman a través de la matriz de transición. Para ello se utilizó la red neuronal del tipo retropropagación en el mecanismo difuso, interpretando sus variables y sus respectivos niveles, seleccionando los mejores valores para ajustar automáticamente los valores de la matriz de transición. La simulación en Matlab presenta al filtrado digital neuronal difuso dando el seguimiento, observándose un funcional de error decreciente exponencialmente.

     

     

    Multivariate identifier filters (multiple inputs and multiple outputs - MIMO are adaptive digital systems having a loop in accordance with an objective function to adjust matrix parameter

  12. Generation of genome-scale gene-associated SNPs in catfish for the construction of a high-density SNP array

    Directory of Open Access Journals (Sweden)

    Kaltenboeck Ludmilla

    2011-01-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs have become the marker of choice for genome-wide association studies. In order to provide the best genome coverage for the analysis of performance and production traits, a large number of relatively evenly distributed SNPs are needed. Gene-associated SNPs may fulfill these requirements of large numbers and genome wide distribution. In addition, gene-associated SNPs could themselves be causative SNPs for traits. The objective of this project was to identify large numbers of gene-associated SNPs using high-throughput next generation sequencing. Results Transcriptome sequencing was conducted for channel catfish and blue catfish using Illumina next generation sequencing technology. Approximately 220 million reads (15.6 Gb for channel catfish and 280 million reads (19.6 Gb for blue catfish were obtained by sequencing gene transcripts derived from various tissues of multiple individuals from a diverse genetic background. A total of over 35 billion base pairs of expressed short read sequences were generated. Over two million putative SNPs were identified from channel catfish and almost 2.5 million putative SNPs were identified from blue catfish. Of these putative SNPs, a set of filtered SNPs were identified including 342,104 intra-specific SNPs for channel catfish, 366,269 intra-specific SNPs for blue catfish, and 420,727 inter-specific SNPs between channel catfish and blue catfish. These filtered SNPs are distributed within 16,562 unique genes in channel catfish and 17,423 unique genes in blue catfish. Conclusions For aquaculture species, transcriptome analysis of pooled RNA samples from multiple individuals using Illumina sequencing technology is both technically efficient and cost-effective for generating expressed sequences. Such an approach is most effective when coupled to existing EST resources generated using traditional sequencing approaches because the reference ESTs facilitate

  13. Accuracy of effect size estimates from published psychological experiments involving multiple trials.

    Science.gov (United States)

    Brand, Andrew; Bradley, M T; Best, Lisa A; Stoica, George

    2011-01-01

    The reporting of exaggerated effect size estimates may occur either through researchers accepting statistically significant results when power is inadequate and/or from repeated measures approaches aggregating, averaging multiple items, or multiple trials. Monte-Carlo simulations with input of a small, medium, or large effect size were conducted on multiple items or trials that were either averaged or aggregated to create a single dependent measure. Alpha was set at the .05 level, and the trials were assessed over item or trial correlations ranging from 0 to 1. Simulations showed a large increase in observed effect size averages and the power to accept these estimates as statistically significant increased over numbers of trials or items. Overestimation effects were mitigated as correlations between trials increased but still remained substantial in some cases. The implications of these findings for meta-analyses and different research scenarios are discussed.

  14. The vestibular evoked myogenic potentials (VEMP) score: a promising tool for evaluation of brainstem involvement in multiple sclerosis.

    Science.gov (United States)

    Gabelić, T; Krbot Skorić, M; Adamec, I; Barun, B; Zadro, I; Habek, M

    2015-02-01

    Concerning the great importance of brainstem involvement in multiple sclerosis (MS), the aim of this study was to explore the role of the newly developed vestibular evoked myogenic potentials (VEMP) score as a possible marker of brainstem involvement in MS patients. This was a prospective case-control study which included 100 MS patients divided into two groups (without and with clinical signs of brainstem involvement) and 50 healthy controls. Ocular VEMP (oVEMP) and cervical VEMP (cVEMP) measurements were performed in all participants and analyzed for latencies, conduction block and amplitude asymmetry ratio. Based on this the VEMP score was calculated and compared with Expanded Disability Status Scale (EDSS), disease duration and magnetic resonance imaging data. Multiple sclerosis patients with clinical signs of brainstem involvement (group 2) had a statistically significant higher percentage of VEMP conduction blocks compared with patients without clinical signs of brainstem involvement (group 1) and healthy controls (P = 0.027 and P VEMP score was significantly higher in group 2 compared with group 1 (P = 0.018) and correlated with EDSS and disease duration (P = 0.011 and P = 0.032, respectively). Multivariate linear regression analysis showed that the VEMP score has a statistically significant influence on the EDSS score (P VEMP score enables better evaluation of brainstem involvement than either of these evoked potentials alone and correlates well with disability. © 2014 EAN.

  15. Targeted Metabolic Engineering Guided by Computational Analysis of Single-Nucleotide Polymorphisms (SNPs)

    DEFF Research Database (Denmark)

    Udatha, D B R K Gupta; Rasmussen, Simon; Sicheritz-Pontén, Thomas

    2013-01-01

    The non-synonymous SNPs, the so-called non-silent SNPs, which are single-nucleotide variations in the coding regions that give "birth" to amino acid mutations, are often involved in the modulation of protein function. Understanding the effect of individual amino acid mutations on a protein....../enzyme function or stability is useful for altering its properties for a wide variety of engineering studies. Since measuring the effects of amino acid mutations experimentally is a laborious process, a variety of computational methods have been discussed here that aid to extract direct genotype to phenotype...

  16. HLA-DP antigens are involved in the susceptibility to multiple sclerosis

    DEFF Research Database (Denmark)

    Ødum, Niels; Hyldig-Nielsen, J J; Morling, N;

    1988-01-01

    Forty-five unrelated patients with multiple sclerosis (MS) from Sweden and 166 Danish controls were typed for HLA-DP using Primed Lymphocyte Typing. Thirty-nine MS-patients and 63 controls were also DNA-typed with the Restriction Fragment Length Polymorphism (RFLP) technique for HLA-DP and -DR ge...

  17. Recurrent, multiple, calcified soft tissue metastases from osteogenic sarcoma without pulmonary involvement

    NARCIS (Netherlands)

    Wolf, R; Wolf, RFE; Hoekstra, HJ

    1999-01-01

    Osteosarcoma (osteogenic sarcoma) metastasizes primarily to the lung. With the introduction of neoadjuvant chemotherapy as part of the treatment, the overall and disease-free survival rates have dramatically improved. In this case report, a young man with multiple soft tissue and bone metastases,

  18. Recurrent, multiple, calcified soft tissue metastases from osteogenic sarcoma without pulmonary involvement

    NARCIS (Netherlands)

    Wolf, R; Wolf, RFE; Hoekstra, HJ

    1999-01-01

    Osteosarcoma (osteogenic sarcoma) metastasizes primarily to the lung. With the introduction of neoadjuvant chemotherapy as part of the treatment, the overall and disease-free survival rates have dramatically improved. In this case report, a young man with multiple soft tissue and bone metastases, in

  19. Influence of SNPs in nutrient-sensitive candidate genes and gene-diet interactions on blood lipids

    DEFF Research Database (Denmark)

    Brahe, Lena Kirchner; Angquist, Lars; Larsen, Lesli Hingstrup

    2013-01-01

    -cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect), and a 6-month ad libitum weight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP-dietary protein interaction effect on TAG was identified for lipin 1...... (LPIN1) rs4315495, with a decrease in TAG of - 0·26 mmol/l per A-allele/protein unit (95 % CI - 0·38, - 0·14, P= 0·000043). In conclusion, we investigated SNP-diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism...... pathways, and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration....

  20. A functional link between FOXA1 and breast cancer SNPs

    OpenAIRE

    Katika, Madhumohan R; Hurtado, Antoni

    2013-01-01

    Genome-wide association studies have revealed a multitude of breast cancer-associated SNPs. The majority of these SNPs are located in noncoding regions of the genome. Yet how they contribute to breast cancer development is unknown. Recently, a groundbreaking study by the Lupien group has shown that risk-associated SNPs of breast cancer are enriched for FOXA1 binding sites, which influences the function of this transcription factor.

  1. The molecular marker for new type--SNPs%新型的分子标记--SNPs

    Institute of Scientific and Technical Information of China (English)

    吴春太; 叶水英; 李雄; 方团

    2003-01-01

    SNPs(Single nucleotide polymorphisms)是近年来发展起来的最有效的新一代分子标记.本文对SNPs的发展、基本原理、检测,以及在确定疾病相关基因研究中的应用进行了介绍和评述.

  2. Multiple positive solutions for Kirchhoff type problems involving concave and convex nonlinearities in R^3

    Directory of Open Access Journals (Sweden)

    Xiaofei Cao

    2016-11-01

    Full Text Available In this article, we consider the multiplicity of positive solutions for a class of Kirchhoff type problems with concave and convex nonlinearities. Under appropriate assumptions, we prove that the problem has at least two positive solutions, moreover, one of which is a positive ground state solution. Our approach is mainly based on the Nehari manifold, Ekeland variational principle and the theory of Lagrange multipliers.

  3. Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, T.L.; Sellebjerg, F; Jensen, C.V.;

    2001-01-01

    . The levels of CXCL10 were higher in the patient group than in controls but two outliers in the control group also had high CSF concentrations of CXCL10. The CSF concentrations of CXCL10 did not change over time or after treatment. The CSF concentration of CXCL10 was positively correlated with the CSF...... and IgG synthesis levels. CXCL10 may be involved in the maintenance of intrathecal inflammation whereas CCL2 correlates negatively with measures of inflammation, suggesting differential involvement of CXCL10 and CCL2 in CNS inflammation...

  4. Biomarker Detection in Association Studies: Modeling SNPs Simultaneously via Logistic ANOVA

    KAUST Repository

    Jung, Yoonsuh

    2014-10-02

    In genome-wide association studies, the primary task is to detect biomarkers in the form of Single Nucleotide Polymorphisms (SNPs) that have nontrivial associations with a disease phenotype and some other important clinical/environmental factors. However, the extremely large number of SNPs comparing to the sample size inhibits application of classical methods such as the multiple logistic regression. Currently the most commonly used approach is still to analyze one SNP at a time. In this paper, we propose to consider the genotypes of the SNPs simultaneously via a logistic analysis of variance (ANOVA) model, which expresses the logit transformed mean of SNP genotypes as the summation of the SNP effects, effects of the disease phenotype and/or other clinical variables, and the interaction effects. We use a reduced-rank representation of the interaction-effect matrix for dimensionality reduction, and employ the L 1-penalty in a penalized likelihood framework to filter out the SNPs that have no associations. We develop a Majorization-Minimization algorithm for computational implementation. In addition, we propose a modified BIC criterion to select the penalty parameters and determine the rank number. The proposed method is applied to a Multiple Sclerosis data set and simulated data sets and shows promise in biomarker detection.

  5. From Corrections to Community: The Juvenile Reentry Experience as Characterized by Multiple Systems Involvement

    Science.gov (United States)

    Cusick, Gretchen Ruth; Goerge, Robert M.; Bell, Katie Claussen

    2009-01-01

    This Chapin Hall report describes findings on the extent of system involvement among Illinois youth released from correctional facilities, tracking a population of youth under age 18 in Illinois following their release. Using administrative records, researchers develop profiles of reentry experiences across the many systems that serve youth and…

  6. Facilitating evaluations of innovative, competence-based assessments: creating understanding and involving multiple stakeholders.

    NARCIS (Netherlands)

    Gulikers, J.T.M.; Baartman, L.; Biemans, H.J.A.

    2010-01-01

    Schools are held more responsible for evaluating, quality assuring and improving their student assessments. Teachers’ lack of understanding of new, competence-based assessments as well as the lack of key stakeholders’ involvement, hamper effective and efficient self-evaluations by teachers of innova

  7. Managing Supplier Involvement in New Product Development: A Multiple-Case Study

    NARCIS (Netherlands)

    F.E.A. van Echtelt (Ferrie); J.Y.F. Wynstra (Finn); A.J. van Weele (Arjan); G.M. Duysters (Geert)

    2006-01-01

    textabstractExisting studies of supplier involvement in new product development have mainly focused on project-related short-term processes and success-factors. This study validates and extends an existing exploratory framework, which comprises both long-term strategic processes and short-term opera

  8. The Floating Upper Limb: Multiple Injuries Involving Ipsilateral, Proximal, Humeral, Supracondylar, and Distal Radial Limb

    Science.gov (United States)

    Manaan, Qazi; Bashir, Adil; Zahoor, Adnan; Mokhdomi, Taseem A.

    2016-01-01

    Floating arm injury represents a common yet complicated injury of the childhood severely associated with limb deformation and even morbidity, if not precisely addressed and credibly operated. Here, we report a rare floating upper limb case of a 9-year-old boy with multiple injuries of ipsilateral proximal humeral, supracondylar and distal radial limb. This is the first report to document such a combined floating elbow and floating arm injury in the same limb. In this report, we discuss the surgical procedures used and recovery of the patient monitored to ascertain the effectiveness of the method in limb reorganisation. PMID:27583121

  9. 3D hydrodynamics involving multiple eccentric impellers in unbaffled cylindrical tank

    Institute of Scientific and Technical Information of China (English)

    Houari Ameur

    2016-01-01

    In this paper, the numerical predictions of 3D hydrodynamics and power consumption in a vessel stirred by mul-tiple eccentrical y located impel ers are presented. The vessel is a flat-bottomed cylindrical one equipped with six-curved bladed impel ers. Aqueous solutions of xanthan gum are used, which have a shear thinning behavior with yield stress. The influence of several parameters on the mixing efficiency has been investigated, namely:the stirring rate, fluid rheology, impeller number and impeller clearance from the tank bottom. Our predicted results are compared with other experimental data and a satisfactory agreement is found.

  10. The Floating Upper Limb: Multiple Injuries Involving Ipsilateral, Proximal, Humeral, Supracondylar, and Distal Radial Limb.

    Science.gov (United States)

    Manaan, Qazi; Bashir, Adil; Zahoor, Adnan; Mokhdomi, Taseem A; Danish, Qazi

    2016-09-01

    Floating arm injury represents a common yet complicated injury of the childhood severely associated with limb deformation and even morbidity, if not precisely addressed and credibly operated. Here, we report a rare floating upper limb case of a 9-year-old boy with multiple injuries of ipsilateral proximal humeral, supracondylar and distal radial limb. This is the first report to document such a combined floating elbow and floating arm injury in the same limb. In this report, we discuss the surgical procedures used and recovery of the patient monitored to ascertain the effectiveness of the method in limb reorganisation.

  11. Functional Neuroanatomy Involved in Automatic order Mental Arithmetic and Recitation of the Multiplication Table

    Science.gov (United States)

    Wang, Li-Qun; Saito, Masao

    We used 1.5T functional magnetic resonance imaging (fMRI) to explore that which brain areas contribute uniquely to numeric computation. The BOLD effect activation pattern of metal arithmetic task (successive subtraction: actual calculation task) was compared with multiplication tables repetition task (rote verbal arithmetic memory task) response. The activation found in right parietal lobule during metal arithmetic task suggested that quantitative cognition or numeric computation may need the assistance of sensuous convert, such as spatial imagination and spatial sensuous convert. In addition, this mechanism may be an ’analog algorithm’ in the simple mental arithmetic processing.

  12. Roles, authority and involvement of the management accounting function: a multiple case-study perspective

    OpenAIRE

    Lambert, Caroline; Sponem, Samuel

    2010-01-01

    Recent techniques and shifts in the environment are often foreseen as leading management accountants to adopt a business orientation. However, empirical evidence pointing to fundamental shifts in the roles played by management accountants remains relatively scarce. The authors explore this paradox and give sense to the various roles played by the management accounting function by focusing on how management accountants are involved in and endowed with authority in decision-making situations.

  13. Langerhans Cell Histiocytosis of the Thyroid with Multiple Cervical Lymph Node Involvement Accompanying Metastatic Thyroid Papillary Carcinoma

    Science.gov (United States)

    Ceyran, A. Bahar; Şenol, Serkan; Bayraktar, Barış; Özkanlı, Şeyma; Cinel, Z. Leyla; Aydın, Abdullah

    2014-01-01

    A 37-year-old male case was admitted with goiter. Ultrasonography of thyroid showed a 5 cm cystic nodule in the left lobe with a 1.5 cm solid component. Fine needle aspiration biopsy revealed atypia of undetermined significance or follicular lesion. The patient was operated on. The pathological diagnosis was reported as papillary thyroid carcinoma. The immunohistochemical examination showed multiple foci of Langerhans cell histiocytosis involving both lobes. The patient died due to cardiac arrest with respiratory causes in the early postoperative period. Langerhans cell histiocytosis is a rare primary condition which involves abnormal clonal proliferation of Langerhans cells in various tissues and organs. Thyroid involvement is infrequently seen. Although the etiology is unknown, genetic components may be linked to the disease. It is also associated with a family history of thyroid disease. Papillary thyroid carcinoma is the most common malignant epithelial tumor of the thyroid gland. Langerhans cell histiocytosis presenting with papillary thyroid carcinoma is rare. The privilege of our case is langerhans cell histiocytosis of the thyroid with multiple cervical lymph node involvement accompanying cervical lymph node metastatic thyroid papillary carcinoma. PMID:25349760

  14. Involvement of the choroid plexus in multiple sclerosis autoimmune inflammation: a neuropathological study.

    Science.gov (United States)

    Vercellino, Marco; Votta, Barbara; Condello, Cecilia; Piacentino, Chiara; Romagnolo, Alberto; Merola, Aristide; Capello, Elisabetta; Mancardi, Giovanni Luigi; Mutani, Roberto; Giordana, Maria Teresa; Cavalla, Paola

    2008-08-13

    An immunological function has been proposed for the choroid plexus (CP). In multiple sclerosis (MS) brains, CPs show (immunohistochemistry to HLA-DR, CD3, CD20, CD68, VCAM-1, CD138) T lymphocytes in vessels and stroma, VCAM-1 expression on endothelia, intense HLA-DR immunostaining on cells in CP stroma, among CP epithelium and on epiplexus cells. CPs in control or amyotrophic lateral sclerosis brains do not show such inflammatory changes. Intense CP inflammation is observed in viral encephalitis. Changes in MS CPs suggest persisting immune activation, with intensity similar to acute encephalitis, even in MS phases in which neurodegeneration prevails. In MS, CPs could represent a site for lymphocyte entry in the CSF and for CSF antigens presentation.

  15. Involvement of Leishmania donovani major surface glycoprotein gp63 in promastigote multiplication

    Indian Academy of Sciences (India)

    Sanjeev Pandey; Phuljhuri Chakraborti; Rakhi Sharma; Santu Bandyopadhyay; Dwijen Sarkar; Samit Adhya

    2004-03-01

    The major surface glycoprotein gp63 of the kinetoplastid protozoal parasite Leishmania is implicated as a ligand mediating uptake of the parasite into, and survival within, the host macrophage. By expressing gp63 antisense RNA from an episomal vector in L. donovani promastigotes, gp63-deficient transfectants were obtained. Reduction of the gp63 level resulted in increased generation times, altered cell morphology, accumulation of cells in the G2/M phase of the cell cycle, and increased numbers of binucleate cells with one or two kinetoplasts. Growth was stimulated, and the number of binucleate cells reduced, by addition to the culture of a bacterially expressed fusion protein containing the fibronectin-like SRYD motif and the zinc-binding (metalloprotease) domain of gp63. These observations support an additional role of gp63 in promastigote multiplication; the fibronectin-like properties of gp63 may be important in this process.

  16. Service user involvement enhanced the research quality in a study using interpretative phenomenological analysis - the power of multiple perspectives.

    Science.gov (United States)

    Mjøsund, Nina Helen; Eriksson, Monica; Espnes, Geir Arild; Haaland-Øverby, Mette; Jensen, Sven Liang; Norheim, Irene; Kjus, Solveig Helene Høymork; Portaasen, Inger-Lill; Vinje, Hege Forbech

    2017-01-01

    The aim of this study was to examine how service user involvement can contribute to the development of interpretative phenomenological analysis methodology and enhance research quality. Interpretative phenomenological analysis is a qualitative methodology used in nursing research internationally to understand human experiences that are essential to the participants. Service user involvement is requested in nursing research. We share experiences from 4 years of collaboration (2012-2015) on a mental health promotion project, which involved an advisory team. Five research advisors either with a diagnosis or related to a person with severe mental illness constituted the team. They collaborated with the research fellow throughout the entire research process and have co-authored this article. We examined the joint process of analysing the empirical data from interviews. Our analytical discussions were audiotaped, transcribed and subsequently interpreted following the guidelines for good qualitative analysis in interpretative phenomenological analysis studies. The advisory team became 'the researcher's helping hand'. Multiple perspectives influenced the qualitative analysis, which gave more insightful interpretations of nuances, complexity, richness or ambiguity in the interviewed participants' accounts. The outcome of the service user involvement was increased breadth and depth in findings. Service user involvement improved the research quality in a nursing research project on mental health promotion. The interpretative element of interpretative phenomenological analysis was enhanced by the emergence of multiple perspectives in the qualitative analysis of the empirical data. We argue that service user involvement and interpretative phenomenological analysis methodology can mutually reinforce each other and strengthen qualitative methodology. © 2016 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.

  17. Consortium analysis of 7 candidate SNPs for ovarian cancer

    DEFF Research Database (Denmark)

    Ramus, S.J.; Vierkant, R.A.; Johnatty, S.E.

    2008-01-01

    The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H...

  18. A pilot study on factors involved with work participation in the early stages of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Karin Van der Hiele

    Full Text Available Up to 30% of recently diagnosed MS patients lose their jobs in the first four years after diagnosis. Taking into account the personal and socio-economic importance of sustaining employment, it is of the utmost importance to examine factors involved with work participation.To investigate differences in self-reported functioning in recently diagnosed MS patients with and without a paid job.Self-reports of physical and cognitive functioning, depression, anxiety and fatigue were gathered from 44 relapsing-remitting MS patients diagnosed within 3 years.Patients with a paid job (57% reported better physical functioning (p<0.001, better memory functioning (p = 0.01 and a lower physical impact of fatigue (p = 0.018 than patients without a paid job. Physical functioning was the main predictor of employment status in a logistic regression model. In those with a paid job better memory functioning (r = 0.54, p = 0.005 and a lower social impact of fatigue (r =  -0.46, p = 0.029 correlated with an increased number of working hours.Better physical functioning is the primary factor involved with increased work participation in early MS. Better self-reported memory functioning and less social fatigue were associated with increased working hours. These findings highlight the importance of battling these symptoms in the early stages of MS.

  19. Assessing SNPs in coat colour genes for cattle breed traceability

    Directory of Open Access Journals (Sweden)

    Paola Crepaldi

    2010-01-01

    Full Text Available Aim of this research was to identify a panel of SNPs in coat colour genes useful for breed traceability in Rendena, an autochthonous cattle breed raised in the province of Trento, and other 4 Italian cattle breeds. First, we sequenced some regions of several coat colour genes in 10 animals belonging to 5 breeds characterised by different coat colour phenotypes (Rendena, Italian Brown, Grey Alpine, Italian Friesian, and Italian Red Pied, and we detected 21 SNPs in 13 genes. These markers and 6 additional SNPs were used to genotype 180 animals of the same 5 breeds obtaining useful genotyping data for a total of 22 SNPs in 13 genes. Five out of the 22 SNP markers in the MC1R, KIT, MLPH, and SILV genes had the highest discriminating power. The panel of 22 SNPs is useful to trace Rendena particularly from Red Italian Pied and Italian Friesian.

  20. Investigation of SNPs in the porcine desmoglein 1 gene

    DEFF Research Database (Denmark)

    Daugaard, L.; Andresen, Lars Ole; Fredholm, M.

    2007-01-01

    epidermitis were diagnosed clinically as affected or unaffected. Two regions of the desmoglein I gene were sequenced and genotypes of the SNPs were established. Seven SNPs (823T>C, 828A>G, 829A>G, 830A>T, 831A>T, 838A>C and 1139C>T) were found in the analysed sequences and the allele frequencies were...... the location of single nucleotide polymorphisms (SNPs) in the porcine desmoglein I gene (PIG)DSGI in correlation to the cleavage site as well as if the genotype of the SNPs is correlated to susceptibility or resistance to the disease. Results: DNA from 32 affected and 32 unaffected piglets with exudative...... determined for the SNPs resulting in amino acid change. Four of the seven polymorphisms wre situated in the motif known to be important for toxin cleavage. The distribution of the genotypes between affected and unaffected animals was analysed. Conclusion: The study indicated a possible correlation between...

  1. Operator identities involving the bivariate Rogers-Szegö polynomials and their applications to the multiple q-series identities

    Science.gov (United States)

    Zhang, Zhizheng; Wang, Tianze

    2008-07-01

    In this paper, we first give several operator identities involving the bivariate Rogers-Szegö polynomials. By applying the technique of parameter augmentation to the multiple q-binomial theorems given by Milne [S.C. Milne, Balanced summation theorems for U(n) basic hypergeometric series, AdvE Math. 131 (1997) 93-187], we obtain several new multiple q-series identities involving the bivariate Rogers-Szegö polynomials. These include multiple extensions of Mehler's formula and Rogers's formula. Our U(n+1) generalizations are quite natural as they are also a direct and immediate consequence of their (often classical) known one-variable cases and Milne's fundamental theorem for An or U(n+1) basic hypergeometric series in Theorem 1E49 of [S.C. Milne, An elementary proof of the Macdonald identities for , Adv. Math. 57 (1985) 34-70], as rewritten in Lemma 7.3 on p. 163 of [S.C. Milne, Balanced summation theorems for U(n) basic hypergeometric series, Adv. Math. 131 (1997) 93-187] or Corollary 4.4 on pp. 768-769 of [S.C. Milne, M. Schlosser, A new An extension of Ramanujan's summation with applications to multilateral An series, Rocky Mountain J. Math. 32 (2002) 759-792].

  2. Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

    Science.gov (United States)

    Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

    2017-02-01

    Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas

  3. Recurrent malignant otitis externa with multiple cranial nerve involvement: A case report

    Directory of Open Access Journals (Sweden)

    Đerić Dragoslava

    2016-01-01

    Full Text Available Introduction. Necrotizing otitis externa is a rare but conditionally fatal infection of external auditory canal with extension to deep soft tissue and bones, resulting in necrosis and osteomyelitis of the temporal bone and scull base. This condition is also known as malignant otitis due to an aggressive behavior and poor treatment response. Early diagnosis of malignant otitis is a difficult challenge. We present an illustrative case of necrotizing otitis externa and suggest some strategies to avoid diagnostic and treatment pitfalls. Case Outline. A 70-year-old patient presented with signs of malignant otitis externa, complicated by peripheral facial palsy. Adequate diagnostic and treatment procedures were performed with clinical signs of resolution. The recurrence of malignant infection had presented three months after previous infection with multiple cranial nerve neuropathies and signs of jugular vein and lateral sinus thrombosis. An aggressive antibiotic treatment and surgery were carried out, followed by substantial recovery of the patient and complete restoration of cranial nerves’ functions. Conclusion. Necrotizing otitis externa is a serious condition with uncertain prognosis. The suspicion of malignant external otitis should be raised in cases of resistance to topical treatment, especially in patient with predisposing factors. Evidence-based guideline for necrotizing otitis externa still doesn’t exist and treatment protocol should be adjusted to individual presentation of each patient.

  4. Involvement of multiple transcription factors for metal-induced spy gene expression in Escherichia coli.

    Science.gov (United States)

    Yamamoto, Kaneyoshi; Ogasawara, Hiroshi; Ishihama, Akira

    2008-01-20

    Bacteria are directly exposed to metals in environment. To maintain the intracellular metal homeostasis, Escherichia coli contain a number of gene regulation systems, each for response to a specific metal. A periplasmic protein Spy of E. coli was found to be induced upon short-exposure to copper ion in CpxAR-dependent manner. Transcription of the spy gene was also induced by long-exposure to zinc ion. This induction, however, depended on another two-component system BaeSR. Using DNase-I footprinting assay, we identified two BaeR-binding regions on the spy promoter with a direct repeat of the BaeR-box sequence, TCTNCANAA. The zinc-responsive BaeR-binding sites were separated from copper-responsive CpxR-binding site, implying that the spy promoter responds to two species of metal independently through different using sensor-response regulator systems. Since BaeSR-dependent zinc response requires longer time, the induction of spy gene transcription by external zinc may include multiple steps such as through sensing the zinc-induced envelope disorder by BaeSR.

  5. Multiplicity of solutions for a class of quasilinear Kirchhoff system involving the fractional p-Laplacian

    Science.gov (United States)

    Xiang, Mingqi; Zhang, Binlin; Rădulescu, Vicenţiu D.

    2016-10-01

    In this paper, we investigate the multiplicity of solutions for a p-Kirchhoff system driven by a nonlocal integro-differential operator with zero Dirichlet boundary data. As a special case, we consider the following fractional p-Kirchhoff system {(∑i=1k[ui]s,pp)θ-1(-Δ)psuj(x)=λj|uj|q-2uj+∑i≠jβij|ui|m|uj|m-2ujin  Ω,uj=0in  RN\\Ω, where {≤ft[{{u}j}\\right]}s,p}={{≤ft({\\int}{\\int}{{{R}2N}}\\frac{|{{u}j}(x)-{{u}j}( y){{|}p}}{|x-y{{|}N+ps}}\\text{d}x\\text{d}y\\right)}1/p} , j=1,2,\\ldots,k , k≥slant 2 , θ ≥slant 1 , Ω is an open bounded subset of {{{R}}N} with Lipschitz boundary \\partial Ω , N  >  ps with s\\in (0,1) , (- Δ )ps is the fractional p-Laplacian, {{λj}>0 and {βij}={βji} for i\

  6. Esperance: Multiple episodes of aqueous alteration involving fracture fills and coatings at Matijevic Hill, Mars

    Science.gov (United States)

    Clark, Benton C.; Morris, Richard V.; Herkenhoff, Kenneth E.; Farrand, William H.; Gellert, Ralf; Jolliff, Bradley L.; Arvidson, Raymond E.; Squyres, Steven W.; Mittelfehldt, David W.; Ming, Douglas W.; Yen, Albert S.

    2016-01-01

    In the search for evidence of past aqueous activity by the Mars Exploration Rover Opportunity, fracture-filling veins and rock coatings are prime candidates for exploration. At one location within a segment of remaining rim material surrounding Endeavour Crater, a set of “boxwork” fractures in an outcrop called Esperance are filled by a bright, hydrated, and highly siliceous (SiO2 ~ 66 wt%) material, which has overall a montmorillonite-like chemical composition. This material is partially covered by patches of a thin, dark coating that is sulfate-rich (SO3 ~ 21 wt%) but also contains significant levels of Si, Fe, Ca, and Mg. The simultaneous presence of abundant S, Si, and Fe indicates significant mineralogical complexity within the coating. This combination of vein and coating compositions is unlike previous analyses on Mars. Both materials are heterogeneously eroded, presumably by eolian abrasion. The evidence indicates at least two separate episodes of solute precipitation from aqueous fluids at this location, possibly widely separated in time. In addition to the implications for multiple episodes of alteration at the surface of the planet, aqueous chemical environments such as these would have been habitable at the time of their formation and are also favorable for preservation of organic material.

  7. Angiogenic, neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity.

    Science.gov (United States)

    Smith, Taylor F; Anastopoulos, Arthur D; Garrett, Melanie E; Arias-Vasquez, Alejandro; Franke, Barbara; Oades, Robert D; Sonuga-Barke, Edmund; Asherson, Philip; Gill, Michael; Buitelaar, Jan K; Sergeant, Joseph A; Kollins, Scott H; Faraone, Stephen V; Ashley-Koch, Allison

    2014-12-01

    Low birth weight is associated with increased risk for Attention-Deficit/Hyperactivity Disorder (ADHD); however, the etiological underpinnings of this relationship remain unclear. This study investigated if genetic variants in angiogenic, dopaminergic, neurotrophic, kynurenine, and cytokine-related biological pathways moderate the relationship between birth weight and ADHD symptom severity. A total of 398 youth from two multi-site, family-based studies of ADHD were included in the analysis. The sample consisted of 360 ADHD probands, 21 affected siblings, and 17 unaffected siblings. A set of 164 SNPs from 31 candidate genes, representing five biological pathways, were included in our analyses. Birth weight and gestational age data were collected from a state birth registry, medical records, and parent report. Generalized Estimating Equations tested for main effects and interactions between individual SNPs and birth weight centile in predicting ADHD symptom severity. SNPs within neurotrophic (NTRK3) and cytokine genes (CNTFR) were associated with ADHD inattentive symptom severity. There was no main effect of birth weight centile on ADHD symptom severity. SNPs within angiogenic (NRP1 & NRP2), neurotrophic (NTRK1 & NTRK3), cytokine (IL16 & S100B), and kynurenine (CCBL1 & CCBL2) genes moderate the association between birth weight centile and ADHD symptom severity. The SNP main effects and SNP × birth weight centile interactions remained significant after adjusting for multiple testing. Genetic variability in angiogenic, neurotrophic, and inflammatory systems may moderate the association between restricted prenatal growth, a proxy for an adverse prenatal environment, and risk to develop ADHD.

  8. Multiple Evolutionary Events Involved in Maintaining Homologs of Resistance to Powdery Mildew 8 in Brassica napus

    Science.gov (United States)

    Li, Qin; Li, Jing; Sun, Jin-Long; Ma, Xian-Feng; Wang, Ting-Ting; Berkey, Robert; Yang, Hui; Niu, Ying-Ze; Fan, Jing; Li, Yan; Xiao, Shunyuan; Wang, Wen-Ming

    2016-01-01

    The Resistance to Powdery Mildew 8 (RPW8) locus confers broad-spectrum resistance to powdery mildew in Arabidopsis thaliana. There are four Homologous to RPW8s (BrHRs) in Brassica rapa and three in Brassica oleracea (BoHRs). Brassica napus (Bn) is derived from diploidization of a hybrid between B. rapa and B. oleracea, thus should have seven homologs of RPW8 (BnHRs). It is unclear whether these genes are still maintained or lost in B. napus after diploidization and how they might have been evolved. Here, we reported the identification and sequence polymorphisms of BnHRs from a set of B. napus accessions. Our data indicated that while the BoHR copy from B. oleracea is highly conserved, the BrHR copy from B. rapa is relatively variable in the B. napus genome owing to multiple evolutionary events, such as gene loss, point mutation, insertion, deletion, and intragenic recombination. Given the overall high sequence homology of BnHR genes, it is not surprising that both intragenic recombination between two orthologs and two paralogs were detected in B. napus, which may explain the loss of BoHR genes in some B. napus accessions. When ectopically expressed in Arabidopsis, a C-terminally truncated version of BnHRa and BnHRb, as well as the full length BnHRd fused with YFP at their C-termini could trigger cell death in the absence of pathogens and enhanced resistance to powdery mildew disease. Moreover, subcellular localization analysis showed that both BnHRa-YFP and BnHRb-YFP were mainly localized to the extra-haustorial membrane encasing the haustorium of powdery mildew. Taken together, our data suggest that the duplicated BnHR genes might have been subjected to differential selection and at least some may play a role in defense and could serve as resistance resource in engineering disease-resistant plants. PMID:27493652

  9. Multiple Evolutionary Events Involved in Maintaining Homologs of Resistance to Powdery Mildew 8 in Brassica napus.

    Science.gov (United States)

    Li, Qin; Li, Jing; Sun, Jin-Long; Ma, Xian-Feng; Wang, Ting-Ting; Berkey, Robert; Yang, Hui; Niu, Ying-Ze; Fan, Jing; Li, Yan; Xiao, Shunyuan; Wang, Wen-Ming

    2016-01-01

    The Resistance to Powdery Mildew 8 (RPW8) locus confers broad-spectrum resistance to powdery mildew in Arabidopsis thaliana. There are four Homologous to RPW8s (BrHRs) in Brassica rapa and three in Brassica oleracea (BoHRs). Brassica napus (Bn) is derived from diploidization of a hybrid between B. rapa and B. oleracea, thus should have seven homologs of RPW8 (BnHRs). It is unclear whether these genes are still maintained or lost in B. napus after diploidization and how they might have been evolved. Here, we reported the identification and sequence polymorphisms of BnHRs from a set of B. napus accessions. Our data indicated that while the BoHR copy from B. oleracea is highly conserved, the BrHR copy from B. rapa is relatively variable in the B. napus genome owing to multiple evolutionary events, such as gene loss, point mutation, insertion, deletion, and intragenic recombination. Given the overall high sequence homology of BnHR genes, it is not surprising that both intragenic recombination between two orthologs and two paralogs were detected in B. napus, which may explain the loss of BoHR genes in some B. napus accessions. When ectopically expressed in Arabidopsis, a C-terminally truncated version of BnHRa and BnHRb, as well as the full length BnHRd fused with YFP at their C-termini could trigger cell death in the absence of pathogens and enhanced resistance to powdery mildew disease. Moreover, subcellular localization analysis showed that both BnHRa-YFP and BnHRb-YFP were mainly localized to the extra-haustorial membrane encasing the haustorium of powdery mildew. Taken together, our data suggest that the duplicated BnHR genes might have been subjected to differential selection and at least some may play a role in defense and could serve as resistance resource in engineering disease-resistant plants.

  10. Multiple Evolutionary Selections Involved in Synonymous Codon Usages in the Streptococcus agalactiae Genome.

    Science.gov (United States)

    Ma, Yan-Ping; Ke, Hao; Liang, Zhi-Ling; Liu, Zhen-Xing; Hao, Le; Ma, Jiang-Yao; Li, Yu-Gu

    2016-02-24

    Streptococcus agalactiae is an important human and animal pathogen. To better understand the genetic features and evolution of S. agalactiae, multiple factors influencing synonymous codon usage patterns in S. agalactiae were analyzed in this study. A- and U-ending rich codons were used in S. agalactiae function genes through the overall codon usage analysis, indicating that Adenine (A)/Thymine (T) compositional constraints might contribute an important role to the synonymous codon usage pattern. The GC3% against the effective number of codon (ENC) value suggested that translational selection was the important factor for codon bias in the microorganism. Principal component analysis (PCA) showed that (i) mutational pressure was the most important factor in shaping codon usage of all open reading frames (ORFs) in the S. agalactiae genome; (ii) strand specific mutational bias was not capable of influencing the codon usage bias in the leading and lagging strands; and (iii) gene length was not the important factor in synonymous codon usage pattern in this organism. Additionally, the high correlation between tRNA adaptation index (tAI) value and codon adaptation index (CAI), frequency of optimal codons (Fop) value, reinforced the role of natural selection for efficient translation in S. agalactiae. Comparison of synonymous codon usage pattern between S. agalactiae and susceptible hosts (human and tilapia) showed that synonymous codon usage of S. agalactiae was independent of the synonymous codon usage of susceptible hosts. The study of codon usage in S. agalactiae may provide evidence about the molecular evolution of the bacterium and a greater understanding of evolutionary relationships between S. agalactiae and its hosts.

  11. Multiple evolutionary events involved in maintaining homologs of Resistance to Powdery Mildew 8 in Brassica napus

    Directory of Open Access Journals (Sweden)

    Qin Li

    2016-07-01

    Full Text Available The Resistance to Powdery Mildew 8 (RPW8 locus confers broad-spectrum resistance to powdery mildew in Arabidopsis thaliana. There are four Homologous to RPW8s (BrHRs in Brassica rapa and three in B. oleracea (BoHRs. B. napus (Bn is derived from diploidization of a hybrid between B. rapa and B. oleracea, thus should have seven homologs of RPW8 (BnHRs. It is unclear whether these genes are still maintained or lost in B. napus after diploidization and how they might have been evolved. Here we reported the identification and sequence polymorphisms of BnHRs from a set of B. napus accessions. Our data indicated that while the BoHR copy from B. oleracea is highly conserved, the BrHR copy from B. rapa is relatively variable in the B. napus genome owing to multiple evolutionary events, such as gene loss, point mutation, insertion, deletion and intragenic recombination. Given the overall high sequence homology of BnHR genes, it is not surprising that both intragenic recombination between two orthologs and two paralogs were detected in B. napus, which may explain the loss of BoHR genes in some B. napus accessions. When ectopically expressed in Arabidopsis, a C-terminally truncated version of BnHRa and BnHRb, as well as the full length BnHRd fused with YFP at their C-termini could trigger cell death in the absence of pathogens and enhanced resistance to powdery mildew disease. Moreover, subcellular localization analysis showed that both BnHRa-YFP and BnHRb-YFP were mainly localized to the extra-haustorial membrane (EHM encasing the haustorium of powdery mildew. Taken together, our data suggest that the duplicated BnHR genes might have been subjected to differential selection and at least some may play a role in defense and could serve as resistance resource in engineering disease-resistant plants.

  12. 宫颈癌相关基因HLA-DRB1编码区SNPs的生物信息学分析%Bioinformatic analysis for coding single nucleotide polymorphisms (SNPs) of HLA-DRB1 gene involved in susceptibility for cervical cancer

    Institute of Scientific and Technical Information of China (English)

    李艳芸; 邢军; 徐垚; 赵林胜; 李燕妮; 王玉川; 张维铭

    2006-01-01

    目的用生物信息学的方法建立筛选宫颈癌相关基因HLA-DRB1编码区SNPs的技术平台,筛选出与宫颈癌发病相关联的SNPs.方法使用SNPper软件从公共数据库dbSNP获得HLA-DRB1编码区的SNPs数据,在dbSNP数据库获取相应的FASTA序列,使用PARSESNP软件进行分析.结果在HLA-DRB1基因的编码区发现2个SNPs(rs1059576和rs1059582),其单核苷酸的变化会引发错义突变,PSSM Difference大于10,该突变为有害突变.另外rs9269958变异则引发终止密码子的产生.结论建立的生物信息学的方法可以对基因编码区的SNPs进行分析,在众多的SNPs中搜寻出序列保守区的变异,并给出评价标准,但是所得结果需要在宫颈癌与对照人群中进行试验验证.

  13. Computation of haplotypes on SNPs subsets: advantage of the "global method"

    Directory of Open Access Journals (Sweden)

    Do Hervé

    2006-10-01

    Full Text Available Abstract Background Genetic association studies aim at finding correlations between a disease state and genetic variations such as SNPs or combinations of SNPs, termed haplotypes. Some haplotypes have a particular biological meaning such as the ones derived from SNPs located in the promoters, or the ones derived from non synonymous SNPs. All these haplotypes are "subhaplotypes" because they refer only to a part of the SNPs found in the gene. Until now, subhaplotypes were directly computed from the very SNPs chosen to constitute them, without taking into account the rest of the information corresponding to the other SNPs located in the gene. In the present work, we describe an alternative approach, called the "global method", which takes into account all the SNPs known in the region and compare the efficacy of the two "direct" and "global" methods. Results We used empirical haplotypes data sets from the GH1 promoter and the APOE gene, and 10 simulated datasets, and randomly introduced in them missing information (from 0% up to 20% to compare the 2 methods. For each method, we used the PHASE haplotyping software since it was described to be the best. We showed that the use of the "global method" for subhaplotyping leads always to a better error rate than the classical direct haplotyping. The advantage provided by this alternative method increases with the percentage of missing genotyping data (diminution of the average error rate from 25% to less than 10%. We applied the global method software on the GRIV cohort for AIDS genetic associations and some associations previously identified through direct subhaplotyping were found to be erroneous. Conclusion The global method for subhaplotyping can reduce, sometimes dramatically, the error rate on patient resolutions and haplotypes frequencies. One should thus use this method in order to minimise the risk of a false interpretation in genetic studies involving subhaplotypes. In practice the global method

  14. Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

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    Georgios Koutsis

    2015-01-01

    Full Text Available We report a patient with relapsing remitting multiple sclerosis (MS and X-linked Charcot-Marie-Tooth disease (CMTX, carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars. Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

  15. Color vision versus pattern visual evoked potentials in the assessment of subclinical optic pathway involvement in multiple sclerosis

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    Fatih C Gundogan

    2013-01-01

    Full Text Available Background: Optic pathway involvement in multiple sclerosis is frequently the initial sign in the disease process. In most clinical applications, pattern visual evoked potential (PVEP is used in the assessment of optic pathway involvement. Objective: To question the value of PVEP against color vision assessment in the diagnosis of subclinical optic pathway involvement. Materials and Methods: This prospective, cross-sectional study included 20 multiple sclerosis patients without a history of optic neuritis, and 20 healthy control subjects. Farnsworth-Munsell (FM 100-Hue testing and PVEPs to 60-min arc and 15-min arc checks by using Roland-Consult RetiScan® system were performed. P 100 amplitude, P 100 latency in PVEP and total error scores (TES in FM 100-Hue test were assessed. Results: Expanded Disability Status Scale score and the time from diagnosis were 2.21 ± 2.53 (ranging from 0 to 7 and 4.1 ± 4.4 years. MS group showed significantly delayed P 100 latency for both checks (P 0.05 for all. 14 MS patients (70% had an increased TESs in FM-100 Hue, 11 (55% MS patients had delayed P 100 latency and 9 (45% had reduced P 100 amplitude. The areas under the ROC curves were 0.944 for FM-100 Hue test, 0.753 for P 100 latency, and 0.173 for P 100 amplitude. Conclusions: Color vision testing seems to be more sensitive than PVEP in detecting subclinical visual pathway involvement in MS.

  16. In Silico Analysis of FMR1 Gene Missense SNPs.

    Science.gov (United States)

    Tekcan, Akin

    2016-06-01

    The FMR1 gene, a member of the fragile X-related gene family, is responsible for fragile X syndrome (FXS). Missense single-nucleotide polymorphisms (SNPs) are responsible for many complex diseases. The effect of FMR1 gene missense SNPs is unknown. The aim of this study, using in silico techniques, was to analyze all known missense mutations that can affect the functionality of the FMR1 gene, leading to mental retardation (MR) and FXS. Data on the human FMR1 gene were collected from the Ensembl database (release 81), National Centre for Biological Information dbSNP Short Genetic Variations database, 1000 Genomes Browser, and NHLBI Exome Sequencing Project Exome Variant Server. In silico analysis was then performed. One hundred-twenty different missense SNPs of the FMR1 gene were determined. Of these, 11.66 % of the FMR1 gene missense SNPs were in highly conserved domains, and 83.33 % were in domains with high variety. The results of the in silico prediction analysis showed that 31.66 % of the FMR1 gene SNPs were disease related and that 50 % of SNPs had a pathogenic effect. The results of the structural and functional analysis revealed that although the R138Q mutation did not seem to have a damaging effect on the protein, the G266E and I304N SNPs appeared to disturb the interaction between the domains and affect the function of the protein. This is the first study to analyze all missense SNPs of the FMR1 gene. The results indicate the applicability of a bioinformatics approach to FXS and other FMR1-related diseases. I think that the analysis of FMR1 gene missense SNPs using bioinformatics methods would help diagnosis of FXS and other FMR1-related diseases.

  17. Utility of X-chromosome SNPs in relationship testing

    DEFF Research Database (Denmark)

    2008-01-01

    (SNPs) in relationship testing have been published. We selected 25 highly polymorphic biallelic SNPs distributed through the human X-chromosome. One 25-plex PCR reaction and one 25-plex single base extension (SNaPshot) reaction were developed. The maximum size of the PCR products was 120ábp and the size...... of the SBE primers varied between 18 and 85 nucleotides. We analyzed the allele and haplotype frequencies in 1078 unrelated males. All the SNPs were polymorphic and the lowest minor allele frequency was 0.103. All the haplotypes were unique. The forensic parameters were calculated in the Danish and Somali...

  18. Multiple and variable NHEJ-like genes are involved in resistance to DNA damage in Streptomyces ambofaciens

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    Grégory Hoff

    2016-11-01

    Full Text Available Non homologous end-joining (NHEJ is a double strand break (DSB repair pathway which does not require any homologous template and can ligate two DNA ends together. The basic bacterial NHEJ machinery involves two partners: the Ku protein, a DNA end binding protein for DSB recognition and the multifunctional LigD protein composed a ligase, a nuclease and a polymerase domain, for end processing and ligation of the broken ends. In silico analyses performed in the 38 sequenced genomes of Streptomyces species revealed the existence of a large panel of NHEJ-like genes. Indeed, ku genes or ligD domain homologues are scattered throughout the genome in multiple copies and can be distinguished in two categories: the core NHEJ gene set constituted of conserved loci and the variable NHEJ gene set constituted of NHEJ-like genes present in only a part of the species. In Streptomyces ambofaciens ATCC 23877, not only the deletion of core genes but also that of variable genes led to an increased sensitivity to DNA damage induced by electron beam irradiation. Multiple mutants of ku, ligase or polymerase encoding genes showed an aggravated phenotype compared to single mutants. Biochemical assays revealed the ability of Ku-like proteins to protect and to stimulate ligation of DNA ends. RT-qPCR and GFP fusion experiments suggested that ku-like genes show a growth phase dependent expression profile consistent with their involvement in DNA repair during spores formation and/or germination.

  19. SNPs analysis of ABCA4 gene in Han Chinese in Beijing%中国北京汉族人群 ABCA4基因的 SNPs 研究

    Institute of Scientific and Technical Information of China (English)

    张小龙; 王红

    2015-01-01

    Objective:To provide the basis of single nucleotide polymorphism(SNPs)for identification and analysis of ABCA4 gene related etiologic studies in Han Chinese in Beijing(CHB).Methods:SNPs of ABCA4 gene were analyzed for minor allele frequencies (MAFs),haplotype frequencies,linkage disequilibrium patterns,and tag SNPs by Haploview program using the HapMap data.Re-sults:129(37.6%)of 343 SNPs were monotonic.95 tagging SNPs were identified in 214 eligible SNPs with 3 haplotype blocks identi-fied.The frequencies of the top 2 haplotypes among each of the 3 haplotype blocks were between 91.1% and 94.0%.Conclusion:SNPs in ABCA4 gene were analyzed by Haploview program.The analysis provides clues for future studies involving this gene.%目的:研究北京汉族人群中 ABCA4基因单核苷酸多态性,为病因学研究提供依据。方法:选取国际人类基因组单体型图计划(HapMap)公布的北京汉族人群(Han Chinese in Beijing,China,CHB)ABCA4基因 SNPs 基因型数据,利用 Haploview 4.2软件对其进行分析。结果:Hapmap 提供的343个 ABCA4基因的 SNPs 中,有129个(37.6%)纯合基因型 SNPs 和214个(62.39%)合格 SNPs。本研究共确定95个标签 SNPs,构建了 3个单体域,各单体域均以前2种单体型为主,累计频率在91.1%~94.0%之间。结论:通过分析北京汉族人群 ABCA4基因 SNPs 数据,得到了标签 SNPs、单体域和主要单体型,为进一步的病因学研究打下了基础。

  20. Screening and Analysis of Coding SNPs of HLA-DQA1 Gene Involved in Susceptibility for Cervical Cancer%宫颈癌易感基因 HLA-DQA1编码区SNPs的筛选和分析

    Institute of Scientific and Technical Information of China (English)

    李艳芸; 邢军; 赵林胜; 李燕妮; 王玉川; 张维铭

    2006-01-01

    背景与目的:人类白细胞抗原(human leukocyte antigen,HLA)基因多态性的差异在宫颈癌发病过程中发挥重要作用,本研究用生物信息学的方法筛选宫颈癌易感基因HLA-DQA1编码区的单核苷酸多态性(single nucleotide polymorphisms,SNPs),并对其多态性的变异所引发的氨基酸变化是否会导致基因的功能异常进行筛选和分析.方法:使用SNPper软件从公共数据库dbSNP获得HLA-DQA1编码区的SNPs数据,在dbSNP数据库获取相应的FASTA序列,使用PARSESNP软件进行筛选和分析.结果:在HLA-DQA1基因的编码区发现2个SNPs(rs9272693和rs9272703),其单核苷酸的变化会引发错义突变,PSSMDifference大于10,预测该突变为有害突变.结论:建立的生物信息学方法可以对基因编码区的SNPs进行分析,在众多的SNPs中搜寻出序列保守区的变异,并给出评价标准,但是所得结果需要在宫颈癌患者与对照人群中进行实验验证.

  1. Potentially functional SNPs (pfSNPs as novel genomic predictors of 5-FU response in metastatic colorectal cancer patients.

    Directory of Open Access Journals (Sweden)

    Jingbo Wang

    Full Text Available 5-Fluorouracil (5-FU and its pro-drug Capecitabine have been widely used in treating colorectal cancer. However, not all patients will respond to the drug, hence there is a need to develop reliable early predictive biomarkers for 5-FU response. Here, we report a novel potentially functional Single Nucleotide Polymorphism (pfSNP approach to identify SNPs that may serve as predictive biomarkers of response to 5-FU in Chinese metastatic colorectal cancer (CRC patients. 1547 pfSNPs and one variable number tandem repeat (VNTR in 139 genes in 5-FU drug (both PK and PD pathway and colorectal cancer disease pathways were examined in 2 groups of CRC patients. Shrinkage of liver metastasis measured by RECIST criteria was used as the clinical end point. Four non-responder-specific pfSNPs were found to account for 37.5% of all non-responders (P<0.0003. Five additional pfSNPs were identified from a multivariate model (AUC under ROC = 0.875 that was applied for all other pfSNPs, excluding the non-responder-specific pfSNPs. These pfSNPs, which can differentiate the other non-responders from responders, mainly reside in tumor suppressor genes or genes implicated in colorectal cancer risk. Hence, a total of 9 novel SNPs with potential functional significance may be able to distinguish non-responders from responders to 5-FU. These pfSNPs may be useful biomarkers for predicting response to 5-FU.

  2. An Ehrlichia chaffeensis tandem repeat protein interacts with multiple host targets involved in cell signaling, transcriptional regulation, and vesicle trafficking.

    Science.gov (United States)

    Wakeel, Abdul; Kuriakose, Jeeba A; McBride, Jere W

    2009-05-01

    Ehrlichia chaffeensis is an obligately intracellular bacterium that exhibits tropism for mononuclear phagocytes forming cytoplasmic membrane-bound microcolonies called morulae. To survive and replicate within phagocytes, E. chaffeensis exploits the host cell by modulating a number of host cell processes, but the ehrlichial effector proteins involved are unknown. In this study, we determined that p47, a secreted, differentially expressed, tandem repeat (TR) protein, interacts with multiple host proteins associated with cell signaling, transcriptional regulation, and vesicle trafficking. Yeast two-hybrid analysis revealed that p47 interacts with polycomb group ring finger 5 (PCGF5) protein, Src protein tyrosine kinase FYN (FYN), protein tyrosine phosphatase non-receptor type 2 (PTPN2), and adenylate cyclase-associated protein 1 (CAP1). p47 interaction with these proteins was further confirmed by coimmunoprecipitation assays and colocalization in HeLa cells transfected with p47-green fluorescent fusion protein (AcGFP1-p47). Moreover, confocal microscopy demonstrated p47-expressing dense-cored (DC) ehrlichiae colocalized with PCGF5, FYN, PTPN2, and CAP1. An amino-terminally truncated form of p47 containing TRs interacted only with PCGF5 and not with FYN, PTPN2, and CAP1, indicating differences in p47 domains that are involved in these interactions. These results demonstrate that p47 is involved in a complex network of interactions involving numerous host cell proteins. Furthermore, this study provides a new insight into the molecular and functional distinction of DC ehrlichiae, as well as the effector proteins involved in facilitating ehrlichial survival in mononuclear phagocytes.

  3. Linking SNPs to CAG repeat length in Huntington's disease patients.

    Science.gov (United States)

    Liu, Wanzhao; Kennington, Lori A; Rosas, H Diana; Hersch, Steven; Cha, Jang-Ho; Zamore, Phillip D; Aronin, Neil

    2008-11-01

    Allele-specific silencing using small interfering RNAs targeting heterozygous single-nucleotide polymorphisms (SNPs) is a promising therapy for human trinucleotide repeat diseases such as Huntington's disease. Linking SNP identities to the two HTT alleles, normal and disease-causing, is a prerequisite for allele-specific RNA interference. Here we describe a method, SNP linkage by circularization (SLiC), to identify linkage between CAG repeat length and nucleotide identity of heterozygous SNPs using Huntington's disease patient peripheral blood samples.

  4. Investigation of SNPs in the porcine desmoglein 1 gene

    Directory of Open Access Journals (Sweden)

    Andresen Lars

    2007-03-01

    Full Text Available Abstract Background Desmoglein 1 (DSG1 is the target protein in the skin disease exudative epidermitis in pigs caused by virulent strains of Staphylococcus hyicus. The exfoliative toxins produced by S. hyicus digest the porcine desmoglein 1 (PIGDSG1 by a very specific reaction. This study investigated the location of single nucleotide polymorphisms (SNPs in the porcine desmoglein 1 gene (PIGDSG1 in correlation to the cleavage site as well as if the genotype of the SNPs is correlated to susceptibility or resistance to the disease. Results DNA from 32 affected and 32 unaffected piglets with exudative epidermitis were diagnosed clinically as affected or unaffected. Two regions of the desmoglein 1 gene were sequenced and genotypes of the SNPs were established. Seven SNPs (823T>C, 828A>G, 829A>G, 830A>T, 831A>T, 838A>C and 1139C>T were found in the analysed sequences and the allele frequencies were determined for the SNPs resulting in amino acid change. Four of the seven polymorphisms were situated in the motif known to be important for toxin cleavage. The distribution of the genotypes between affected and unaffected animals was analysed. Conclusion The study indicated a possible correlation between the genotypes of two out of seven SNPs found in the porcine desmoglein 1 gene and the susceptibility to exudative epidermitis.

  5. Endothelial nitric oxide synthase tagSNPs influence the effects of enalapril in essential hypertension.

    Science.gov (United States)

    Oliveira-Paula, Gustavo H; Lacchini, Riccardo; Luizon, Marcelo R; Fontana, Vanessa; Silva, Pamela S; Biagi, Celso; Tanus-Santos, Jose E

    2016-05-01

    The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are associated with up-regulation of endothelial nitric oxide synthase (NOS3) activity. This mechanism may explain how polymorphisms in NOS3 gene affect the antihypertensive responses to ACEi. While clinically relevant NOS3 polymorphisms were previously shown to affect the antihypertensive responses to enalapril, no study has tested the hypothesis that NOS3 tagSNPs influence the antihypertensive effects of this drug. We examined whether the NOS3 tagSNPs rs3918226, rs3918188, and rs743506, and their haplotypes, affect the antihypertensive responses to enalapril in 101 patients with essential hypertension. Subjects were prospectively treated only with enalapril for 8 weeks. Genotypes were determined by Taqman(®) allele discrimination assay and real-time polymerase chain reaction (PCR) and haplotype frequencies were estimated. We compared the effects of NOS3 tagSNPs on changes in blood pressure after enalapril treatment. To confirm our findings, multiple linear regression analysis was performed adjusting for age, gender, ethnicity, and alcohol consumption. We found that hypertensive patients carrying the AA genotype for the tagSNP rs3918188 showed lower decreases in blood pressure in response to enalapril. Moreover, the TCA haplotype was associated with improved decreases in blood pressure in response to enalapril compared with the CAG haplotype. Adjustment for covariates in multiple linear regression analysis did not change these effects. In addition, when patients were stratified according to the dose of enalapril used, we found that the carries of the T allele for the functional tagSNP rs3918226 showed more intense decreases in blood pressure in response to enalapril 20 mg/day. Our findings suggest that NOS3 tagSNPs influence the effects of enalapril in essential hypertension.

  6. A calmodulin-binding/CGCG box DNA-binding protein family involved in multiple signaling pathways in plants

    Science.gov (United States)

    Yang, Tianbao; Poovaiah, B. W.

    2002-01-01

    We reported earlier that the tobacco early ethylene-responsive gene NtER1 encodes a calmodulin-binding protein (Yang, T., and Poovaiah, B. W. (2000) J. Biol. Chem. 275, 38467-38473). Here we demonstrate that there is one NtER1 homolog as well as five related genes in Arabidopsis. These six genes are rapidly and differentially induced by environmental signals such as temperature extremes, UVB, salt, and wounding; hormones such as ethylene and abscisic acid; and signal molecules such as methyl jasmonate, H(2)O(2), and salicylic acid. Hence, they were designated as AtSR1-6 (Arabidopsis thaliana signal-responsive genes). Ca(2+)/calmodulin binds to all AtSRs, and their calmodulin-binding regions are located on a conserved basic amphiphilic alpha-helical motif in the C terminus. AtSR1 targets the nucleus and specifically recognizes a novel 6-bp CGCG box (A/C/G)CGCG(G/T/C). The multiple CGCG cis-elements are found in promoters of genes such as those involved in ethylene signaling, abscisic acid signaling, and light signal perception. The DNA-binding domain in AtSR1 is located on the N-terminal 146 bp where all AtSR1-related proteins share high similarity but have no similarity to other known DNA-binding proteins. The calmodulin-binding nuclear proteins isolated from wounded leaves exhibit specific CGCG box DNA binding activities. These results suggest that the AtSR gene family encodes a family of calmodulin-binding/DNA-binding proteins involved in multiple signal transduction pathways in plants.

  7. Multiple and substitute addictions involving prescription drugs misuse among 12th graders: gateway theory revisited with Market Basket Analysis.

    Science.gov (United States)

    Jayawardene, Wasantha Parakrama; YoussefAgha, Ahmed Hassan

    2014-01-01

    This study aimed to identify the sequential patterns of drug use initiation, which included prescription drugs misuse (PDM), among 12th-grade students in Indiana. The study also tested the suitability of the data mining method Market Basket Analysis (MBA) to detect common drug use initiation sequences in large-scale surveys. Data from 2007 to 2009 Annual Surveys of Alcohol, Tobacco, and Other Drug Use by Indiana Children and Adolescents were used for this study. A close-ended, self-administered questionnaire was used to ask adolescents about the use of 21 substance categories and the age of first use. "Support%" and "confidence%" statistics of Market Basket Analysis detected multiple and substitute addictions, respectively. The lifetime prevalence of using any addictive substance was 73.3%, and it has been decreasing during past few years. Although the lifetime prevalence of PDM was 19.2%, it has been increasing. Males and whites were more likely to use drugs and engage in multiple addictions. Market Basket Analysis identified common drug use initiation sequences that involved 11 drugs. High levels of support existed for associations among alcohol, cigarettes, and marijuana, whereas associations that included prescription drugs had medium levels of support. Market Basket Analysis is useful for the detection of common substance use initiation sequences in large-scale surveys. Before initiation of prescription drugs, physicians should consider the adolescents' risk of addiction. Prevention programs should address multiple addictions, substitute addictions, common sequences in drug use initiation, sex and racial differences in PDM, and normative beliefs of parents and adolescents in relation to PDM.

  8. Fluorescence excitation involving multiple electron transition states of N{sub 2} and CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C.Y.R.; Chen, F.Z.; Hung, T.; Judge, D.L. [Univ. of Southern California, Los Angeles, CA (United States)

    1997-04-01

    The electronic states and electronic structures of N{sub 2} and CO{sub 2} in the 8-50 eV energy region have been studied extensively both experimentally and theoretically. In the energy region higher than 25 eV there exists many electronic states including multiple electron transition (MET) states which are responsible for producing most of the dissociative photoionization products. The electronic states at energies higher than 50 eV have been mainly determined by Auger spectroscopy, double charge transfer, photofragment spectroscopy and ion-ion coincidence spectroscopy. The absorption and ionization spectra of these molecules at energies higher than 50 eV mainly show a monotonic decrease in cross section values and exhibit structureless features. The decay channels of MET and Rydberg (or superexcited) states include autoionization, ionization, dissociative ionization, predissociation, and dissociation while those of single ion and multiple ion states may involve predissociation. and dissociation processes. The study of fluorescence specifically probes electronically excited species resulting from the above-mentioned decay channels and provides information for understanding the competition among these channels.

  9. Cost-effective multiplexing before capture allows screening of 25 000 clinically relevant SNPs in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Dalgaard, M. D.; Borst, L.;

    2011-01-01

    a model disease for exploring the impact of genetic variation due to well-characterized cytogenetics, drug response pathways and precise monitoring of minimal residual disease. Here, we have selected clinically relevant genes and SNPs through literature screening, and on the basis of associations with key...... designed a cost-effective, high-throughput capture assay of â¼25â000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows...

  10. "GenotypeColour™": colour visualisation of SNPs and CNVs

    Directory of Open Access Journals (Sweden)

    Magri Chiara

    2009-02-01

    Full Text Available Abstract Background The volume of data available on genetic variations has increased considerably with the recent development of high-density, single-nucleotide polymorphism (SNP arrays. Several software programs have been developed to assist researchers in the analysis of this huge amount of data, but few can rely upon a whole genome variability visualisation system that could help data interpretation. Results We have developed GenotypeColour™ as a rapid user-friendly tool able to upload, visualise and compare the huge amounts of data produced by Affymetrix Human Mapping GeneChips without losing the overall view of the data. Some features of GenotypeColour™ include visualising the entire genome variability in a single screenshot for one or more samples, the simultaneous display of the genotype and Copy Number state for thousands of SNPs, and the comparison of large amounts of samples by producing "consensus" images displaying regions of complete or partial identity. The software is also useful for genotype analysis of trios and to show regions of potential uniparental disomy (UPD. All information can then be exported in a tabular format for analysis with dedicated software. At present, the software can handle data from 10 K, 100 K, 250 K, 5.0 and 6.0 Affymetrix chips. Conclusion We have created a software that offers a new way of displaying and comparing SNP and CNV genomic data. The software is available free at http://www.med.unibs.it/~barlati/GenotypeColour and is especially useful for the analysis of multiple samples.

  11. Identification of protein networks involved in the disease course of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Annelies Vanheel

    Full Text Available A more detailed insight into disease mechanisms of multiple sclerosis (MS is crucial for the development of new and more effective therapies. MS is a chronic inflammatory autoimmune disease of the central nervous system. The aim of this study is to identify novel disease associated proteins involved in the development of inflammatory brain lesions, to help unravel underlying disease processes. Brainstem proteins were obtained from rats with MBP induced acute experimental autoimmune encephalomyelitis (EAE, a well characterized disease model of MS. Samples were collected at different time points: just before onset of symptoms, at the top of the disease and following recovery. To analyze changes in the brainstem proteome during the disease course, a quantitative proteomics study was performed using two-dimensional difference in-gel electrophoresis (2D-DIGE followed by mass spectrometry. We identified 75 unique proteins in 92 spots with a significant abundance difference between the experimental groups. To find disease-related networks, these regulated proteins were mapped to existing biological networks by Ingenuity Pathway Analysis (IPA. The analysis revealed that 70% of these proteins have been described to take part in neurological disease. Furthermore, some focus networks were created by IPA. These networks suggest an integrated regulation of the identified proteins with the addition of some putative regulators. Post-synaptic density protein 95 (DLG4, a key player in neuronal signalling and calcium-activated potassium channel alpha 1 (KCNMA1, involved in neurotransmitter release, are 2 putative regulators connecting 64% of the identified proteins. Functional blocking of the KCNMA1 in macrophages was able to alter myelin phagocytosis, a disease mechanism highly involved in EAE and MS pathology. Quantitative analysis of differentially expressed brainstem proteins in an animal model of MS is a first step to identify disease-associated proteins and

  12. Association between SNPs in defined functional pathways and risk of early or late toxicity as well as individual radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Reuther, Sebastian; Raabe, Annette; Borgmann, Kerstin; Dikomey, Ekkehard [University Medical Center Hamburg-Eppendorf, Laboratory of Radiobiology and Experimental Radiooncology, Department of Radiotherapy and Radiooncology, Hamburg (Germany); Szymczak, Silke [University at Luebeck, Institute of Medical Biometry and Statistics, University Medical Center Schleswig-Holstein (Germany); Christian-Albrechts-University Kiel, Institute of Clinical Molecular Biology, Kiel (Germany); Ziegler, Andreas [University at Luebeck, Institute of Medical Biometry and Statistics, University Medical Center Schleswig-Holstein (Germany); University of Luebeck, Center for Clinical Trials, Luebeck (Germany); Petersen, Cordula [University Medical Center Hamburg-Eppendorf, Clinic of Radiotherapy and Radiooncology, Hamburg (Germany); Hoeller, Ulrike [Charite Universitaetsmedizin Berlin, Department of Radiotherapy, Berlin (Germany)

    2014-08-26

    The aim of this study was to determine the impact of functional single nucleotide polymorphism (SNP) pathways involved in the ROS pathway, DNA repair, or TGFB1 signaling on acute or late normal toxicity as well as individual radiosensitivity. Patients receiving breast-conserving surgery and radiotherapy were examined either for erythema (n = 83), fibrosis (n = 123), or individual radiosensitivity (n = 123). The 17 SNPs analyzed are involved in the ROS pathway (GSTP1, SOD2, NQO1, NOS3, XDH), DNA repair (XRCC1, XRCC3, XRCC6, ERCC2, LIG4, ATM) or TGFB signaling (SKIL, EP300, APC, AXIN1, TGFB1). Associations with biological and clinical endpoints were studied for single SNPs but especially for combinations of SNPs assuming that a SNP is either beneficial or deleterious and needs to be weighted. With one exception, no significant association was seen between a single SNP and the three endpoints studied. No significant associations were also observed when applying a multi-SNP model assuming that each SNP was deleterious. In contrast, significant associations were obtained when SNPs were suggested to be either beneficial or deleterious. These associations increased, when each SNP was weighted individually. Detailed analysis revealed that both erythema and individual radiosensitivity especially depend on SNPs affecting DNA repair and TGFB1 signaling, while SNPs in ROS pathway were of minor importance. Functional pathways of SNPs may be used to form a risk score allowing to predict acute and late radiation-induced toxicity but also to unravel the underlying biological mechanisms. (orig.) [German] Fuer ein SNP-Netzwerk (''single nucleotide polymorphism'', Einzelnukleotidpolymorphismus), welches im ROS-Signalweg, an der DNA-Reparatur und im TGFB1-Signalweg involviert ist, sollen die Bedeutung fuer die akute und spaete Toxizitaet sowie die individuelle Strahlenempfindlichkeit bestimmt werden. Nach Strahlentherapie wurden Brustkrebspatientinnen entweder

  13. A model-based approach to selection of tag SNPs

    Directory of Open Access Journals (Sweden)

    Sun Fengzhu

    2006-06-01

    Full Text Available Abstract Background Single Nucleotide Polymorphisms (SNPs are the most common type of polymorphisms found in the human genome. Effective genetic association studies require the identification of sets of tag SNPs that capture as much haplotype information as possible. Tag SNP selection is analogous to the problem of data compression in information theory. According to Shannon's framework, the optimal tag set maximizes the entropy of the tag SNPs subject to constraints on the number of SNPs. This approach requires an appropriate probabilistic model. Compared to simple measures of Linkage Disequilibrium (LD, a good model of haplotype sequences can more accurately account for LD structure. It also provides a machinery for the prediction of tagged SNPs and thereby to assess the performances of tag sets through their ability to predict larger SNP sets. Results Here, we compute the description code-lengths of SNP data for an array of models and we develop tag SNP selection methods based on these models and the strategy of entropy maximization. Using data sets from the HapMap and ENCODE projects, we show that the hidden Markov model introduced by Li and Stephens outperforms the other models in several aspects: description code-length of SNP data, information content of tag sets, and prediction of tagged SNPs. This is the first use of this model in the context of tag SNP selection. Conclusion Our study provides strong evidence that the tag sets selected by our best method, based on Li and Stephens model, outperform those chosen by several existing methods. The results also suggest that information content evaluated with a good model is more sensitive for assessing the quality of a tagging set than the correct prediction rate of tagged SNPs. Besides, we show that haplotype phase uncertainty has an almost negligible impact on the ability of good tag sets to predict tagged SNPs. This justifies the selection of tag SNPs on the basis of haplotype

  14. Genetic variation and recent positive selection in worldwide human populations: evidence from nearly 1 million SNPs.

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    David López Herráez

    Full Text Available BACKGROUND: Genome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world. METHODOLOGY: We genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations from the Human Genome Diversity Panel (HGDP-CEPH. When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental level. CONCLUSIONS: Our analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature.

  15. Investigation of SNPs in the porcine desmoglein 1 gene

    DEFF Research Database (Denmark)

    Daugaard, L.; Andresen, Lars Ole; Fredholm, M.

    2007-01-01

    Background: Desmoglein I (DSGI) is the target protein in the skin disease exudative epidermitis in pigs caused by virulent strains of Staphylococcus hyicus. The exfoliative toxins produced by S. hyicus digest the porcine desmoglein I (PIG)DSGI by a very specific reaction. This study investigated...... epidermitis were diagnosed clinically as affected or unaffected. Two regions of the desmoglein I gene were sequenced and genotypes of the SNPs were established. Seven SNPs (823T>C, 828A>G, 829A>G, 830A>T, 831A>T, 838A>C and 1139C>T) were found in the analysed sequences and the allele frequencies were...... the genotypes of two out of seven SNPs found in the porcine desmoglein I gene and the susceptibility to exudative epidermitis....

  16. A periodic pattern of SNPs in the human genome

    DEFF Research Database (Denmark)

    Madsen, Bo Eskerod; Villesen, Palle; Wiuf, Carsten

    2007-01-01

    or alignment errors, for example, transposable elements (SINE, LINE, and LTR), tandem repeats, and large duplicated regions. However, we found that the pattern is almost entirely confined to what we define as "periodic DNA." Periodic DNA is a genomic region with a high degree of periodicity in nucleotide usage...... periodic DNA. Our results suggest that not all SNPs in the human genome are created by independent single nucleotide mutations, and that care should be taken in analysis of SNPs from periodic DNA. The latter may have important consequences for SNP and association studies....

  17. Association of Five SNPs at the PARK16 locus as a Susceptibility Locus with Parkinson's Disease for Forensic Application

    Institute of Scientific and Technical Information of China (English)

    CUI Hong-gang; TIAN Xiao-fei; LUO Xiao-guang; LI Feng-rui; ZHU Lan-hui; ZHOU Yi-shu; REN Yan

    2013-01-01

    To investigate the association of five SNPs (rs823083,rs708723,rs4951261,rs823076 and rs16856110) at the PARK16 locus with Parkinson's disease (PD),and to potentiate its forensic application.The genomic DNAs of 215 PD patients and 212 matched controls from the northern Han Chinese population were amplified in two independent PCR systems and subsequently genotyped by digestion with the three endonucleases (Hinf Ⅰ,Nco Ⅰ and Msp Ⅰ).The genetic parameters and association studies were carried out with SPSS 13.0,Haploview version 4.2 and PLINK 1.07 sofiwares.We detected accurately all genotypes in the five SNPs with multiplex PCR-RFLP and mismatched multiplex PCR-RFLP techniques.The genotypes of four SNPs,except for rs823083,were in Hardy-Weinberg equilibrium.The four SNPs,rs16856110,rs4951261,rs708723 and rs823076,which were in linkage equilibrium,should not be associated with PD (P-values ranging from 0.077 to 0.544).The SNPs investigated at the PARK16 locus were not found to be involved in PD-associated blocks in the northern Han Chinese population.The allele distributions of rs708723,rs4951261,rs823076 and rs16856110 in the northern Han Chinese population can be highly polymorphic,which can be applied to genetic analvsis and forensic practices.

  18. Nonreciprocal chromosomal translocations in renal cancer involve multiple DSBs and NHEJ associated with breakpoint inversion but not necessarily with transcription.

    Science.gov (United States)

    Ali, Hanif; Daser, Angelika; Dear, Paul; Wood, Henry; Rabbitts, Pamela; Rabbitts, Terence

    2013-04-01

    Chromosomal translocations and other abnormalities are central to the initiation of cancer in all cell types. Understanding the mechanism is therefore important to evaluate the evolution of cancer from the cancer initiating events to overt disease. Recent work has concentrated on model systems to develop an understanding of the molecular mechanisms of translocations but naturally occurring events are more ideal case studies since biological selection is absent from model systems. In solid tumours, nonreciprocal translocations are most commonly found, and accordingly we have investigated the recurrent nonreciprocal t(3;5) chromosomal translocations in renal carcinoma to better understand the mechanism of these naturally occurring translocations in cancer. Unexpectedly, the junctions of these translocations can be associated with site-specific, intrachromosomal inversion involving at least two double strand breaks (DSB) in cis and rejoining by nonhomologous end joining or micro-homology end joining. However, these translocations are not necessarily associated with transcribed regions questioning accessibility per se in controlling these events. In addition, intrachromosomal deletions also occur. We conclude these naturally occurring, nonreciprocal t(3;5) chromosomal translocations occur after complex and multiple unresolved intrachromosomal DSBs leading to aberrant joining with concurrent interstitial inversion and that clonal selection of cells is the critical element in cancer development emerging from a plethora of DSBs that may not always be pathogenic.

  19. Elder Care, Multiple Role Involvement, and Well-Being Among Middle-Aged Men and Women in Japan.

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    Kikuzawa, Saeko

    2015-12-01

    Japan's population is aging at an unprecedented rate. Combined with the tradition of family responsibility for elder care, this rapid population aging has resulted in middle-aged Japanese people being much more likely today than in past decades to face the responsibility of caring for their elderly parents alongside their other major roles. Using nationally representative Japanese data, this study assessed the individual and combined implications of caregiving and other role involvements for the well-being of middle-aged men and women. Some evidence was found for deleterious psychological consequences of the caregiver role. However, in contrast to expectations, the interaction between the roles of caregiver and worker was positively associated with well-being among both men and women. The results suggest the importance of middle-aged adults being able to keep working when they have to care for their aging parents. Another important finding was significant gender differences in the psychological consequences of holding multiple family- and work-related roles and in combining these with the caregiver role. Further analysis showed that the spousal role was also negatively associated with depressive symptoms and positively associated with satisfaction for men but not for women. Gender differences in the findings appear to reflect the significant gender asymmetry in role experiences in Japan.

  20. Establishment of a pipeline to analyse non-synonymous SNPs in Bos taurus

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    Schreiber Mark

    2006-11-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are an abundant form of genetic variation in the genome of every species and are useful for gene mapping and association studies. Of particular interest are non-synonymous SNPs, which may alter protein function and phenotype. We therefore examined bovine expressed sequences for non-synonymous SNPs and validated and tested selected SNPs for their association with measured traits. Results Over 500,000 public bovine expressed sequence tagged (EST sequences were used to search for coding SNPs (cSNPs. A total of 15,353 SNPs were detected in the transcribed sequences studied, of which 6,325 were predicted to be coding SNPs with the remaining 9,028 SNPs presumed to be in untranslated regions. Of the cSNPs detected, 2,868 were predicted to result in a change in the amino acid encoded. In order to determine the actual number of non-synonymous polymorphic SNPs we designed assays for 920 of the putative SNPs. These SNPs were then genotyped through a panel of cattle DNA pools using chip-based MALDI-TOF mass spectrometry. Of the SNPs tested, 29% were found to be polymorphic with a minor allele frequency >10%. A subset of the SNPs was genotyped through animal resources in order to look for association with age of puberty, facial eczema resistance or meat yield. Three SNPs were nominally associated with resistance to the disease facial eczema (P Conclusion We have identified 15,353 putative SNPs in or close to bovine genes and 2,868 of these SNPs were predicted to be non-synonymous. Approximately 29% of the non-synonymous SNPs were polymorphic and common with a minor allele frequency >10%. Of the SNPs detected in this study, 99% have not been previously reported. These novel SNPs will be useful for association studies or gene mapping.

  1. Ratio of involved/uninvolved immunoglobulin quantification by Hevylite™ assay: clinical and prognostic impact in multiple myeloma

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    Koulieris Efstathios

    2012-04-01

    Full Text Available Abstract Background HevyLite™ is a new, recently developed method that facilitates separate quantification of the kappa- and lambda-bounded amounts of a given immunoglobulin (Ig. Using this method, we measured intact immunoglobulin (heavy/light chain; HLC IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda individually, as well as their deriving ratios (HLCR in a series of IgG or IgA multiple myeloma (MM patients, to investigate and assess the contribution of these tests to disease evaluation. Patients and methods HevyLite™ assays were used in sera from 130 healthy individuals (HI and 103 MM patients, at time of diagnosis. In patients, the level of paraprotein was IgG in 78 (52 IgG-kappa, 26 IgG-lambda and IgΑ in 25 (13 IgΑ-kappa, 12 IgΑ-lambda. Durie-Salmon and International Staging System stages were evenly distributed. Symptomatic patients (n = 77 received treatment while asymptomatic ones (n = 26 were followed. Patients' median follow-up was at 32.6 months. HLCR was calculated with the involved Ig (either G or A as numerator. Results In HI, median IgG-kappa was 6.85, IgG-lambda 3.81, IgA-kappa 1.19 and IgA-lambda 0.98 g/L. The corresponding median involving HLC values in MM patients were 25.8, 23.45, 28.9 and 36.4 g/L. HLC-IgG related to anemia, high serum free light chain ratio and extensive bone marrow infiltration, while high HLCR correlated with the same plus increased β2-microglobulin. In addition, increased HLCR and the presence of immunoparesis correlated with time to treatment. Patients with high HLCR had a significantly shorter survival (p = 0.022; HLCR retained its prognostic value in multivariate analysis. Conclusions HLC and HLCR quantify the precise amount of the involved immunoglobulin more accurately than other methods; moreover, they carry prognostic information regarding survival in MM patients.

  2. Concordant gene expression in leukemia cells and normal leukocytes is associated with germline cis-SNPs.

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    Deborah French

    Full Text Available The degree to which gene expression covaries between different primary tissues within an individual is not well defined. We hypothesized that expression that is concordant across tissues is more likely influenced by genetic variability than gene expression which is discordant between tissues. We quantified expression of 11,873 genes in paired samples of primary leukemia cells and normal leukocytes from 92 patients with acute lymphoblastic leukemia (ALL. Genetic variation at >500,000 single nucleotide polymorphisms (SNPs was also assessed. The expression of only 176/11,783 (1.5% genes was correlated (p<0.008, FDR = 25% in the two tissue types, but expression of a high proportion (20 of these 176 genes was significantly related to cis-SNP genotypes (adjusted p<0.05. In an independent set of 134 patients with ALL, 14 of these 20 genes were validated as having expression related to cis-SNPs, as were 9 of 20 genes in a second validation set of HapMap cell lines. Genes whose expression was concordant among tissue types were more likely to be associated with germline cis-SNPs than genes with discordant expression in these tissues; genes affected were involved in housekeeping functions (GSTM2, GAPDH and NCOR1 and purine metabolism.

  3. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

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    Apalasamy, Y.D. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Ming, M.F.; Rampal, S.; Bulgiba, A. [Julius Centre University of Malaya, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Mohamed, Z. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia)

    2012-08-24

    The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

  4. Enrichment of risk SNPs in regulatory regions implicate diverse tissues in Parkinson's disease etiology.

    Science.gov (United States)

    Coetzee, Simon G; Pierce, Steven; Brundin, Patrik; Brundin, Lena; Hazelett, Dennis J; Coetzee, Gerhard A

    2016-07-27

    Recent genome-wide association studies (GWAS) of Parkinson's disease (PD) revealed at least 26 risk loci, with associated single nucleotide polymorphisms (SNPs) located in non-coding DNA having unknown functions in risk. In order to explore in which cell types these SNPs (and their correlated surrogates at r(2) ≥ 0.8) could alter cellular function, we assessed their location overlap with histone modification regions that indicate transcription regulation in 77 diverse cell types. We found statistically significant enrichment of risk SNPs at 12 loci in active enhancers or promoters. We investigated 4 risk loci in depth that were most significantly enriched (-logeP > 14) and contained 8 putative enhancers in the different cell types. These enriched loci, along with eQTL associations, were unexpectedly present in non-neuronal cell types. These included lymphocytes, mesendoderm, liver- and fat-cells, indicating that cell types outside the brain are involved in the genetic predisposition to PD. Annotating regulatory risk regions within specific cell types may unravel new putative risk mechanisms and molecular pathways that contribute to PD development.

  5. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

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    Y.D. Apalasamy

    2012-12-01

    Full Text Available The common variants in the fat mass- and obesity-associated (FTO gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs and linkage disequilibrium (LD blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D’ = 1.0. In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

  6. Scanning the genome for gene SNPs related to climate adaptation and estimating selection at the molecular level in boreal black spruce.

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    Prunier, Julien; Laroche, Jérôme; Beaulieu, Jean; Bousquet, Jean

    2011-04-01

    Outlier detection methods were used to scan the genome of the boreal conifer black spruce (Picea mariana [Mill.] B.S.P.) for gene single-nucleotide polymorphisms (SNPs) potentially involved in adaptations to temperature and precipitation variations. The scan involved 583 SNPs from 313 genes potentially playing adaptive roles. Differentiation estimates among population groups defined following variation in temperature and precipitation were moderately high for adaptive quantitative characters such as the timing of budset or tree height (Q(ST) = 0.189-0.314). Average differentiation estimates for gene SNPs were null, with F(ST) values of 0.005 and 0.006, respectively, among temperature and precipitation population groups. Using two detection approaches, a total of 26 SNPs from 25 genes distributed among 11 of the 12 linkage groups of black spruce were detected as outliers with F(ST) as high as 0.078. Nearly half of the outlier SNPs were located in exons and half of those were nonsynonymous. The functional annotations of genes carrying outlier SNPs and regression analyses between the frequencies of these SNPs and climatic variables supported their implication in adaptive processes. Several genes carrying outlier SNPs belonged to gene families previously found to harbour outlier SNPs in a reproductively isolated but largely sympatric congeneric species, suggesting differential subfunctionalization of gene duplicates. Selection coefficient estimates (S) were moderate but well above the magnitude of drift (>1/N(e)), indicating that the signature of natural selection could be detected at the nucleotide level despite the recent establishment of these populations during the Holocene. © 2011 Blackwell Publishing Ltd.

  7. Study of 25 X-chromosome SNPs in the Portuguese

    DEFF Research Database (Denmark)

    Pereira, Vania; Tomas Mas, Carmen; Amorim, António

    2011-01-01

    The importance of X-chromosome markers in individual identifications, population genetics, forensics and kinship testing is getting wide recognition. In this work, we studied the distributions of 25 X-chromosome single nucleotide polymorphisms (X-SNPs) in population samples from Northern, Central...

  8. Nitric oxide-induced murine hematopoietic stem cell fate involves multiple signaling proteins, gene expression, and redox modulation.

    Science.gov (United States)

    Nogueira-Pedro, Amanda; Dias, Carolina C; Regina, Helena; Segreto, C; Addios, Priscilla C; Lungato, Lisandro; D'Almeida, Vania; Barros, Carlos C; Higa, Elisa M S; Buri, Marcus V; Ferreira, Alice T; Paredes-Gamero, Edgar Julian

    2014-11-01

    There are a growing number of reports showing the influence of redox modulation in cellular signaling. Although the regulation of hematopoiesis by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been described, their direct participation in the differentiation of hematopoietic stem cells (HSCs) remains unclear. In this work, the direct role of nitric oxide (NO(•)), a RNS, in the modulation of hematopoiesis was investigated using two sources of NO(•) , one produced by endothelial cells stimulated with carbachol in vitro and another using the NO(•)-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) in vivo. Two main NO(•) effects were observed: proliferation of HSCs-especially of the short-term HSCs-and its commitment and terminal differentiation to the myeloid lineage. NO(•)-induced proliferation was characterized by the increase in the number of cycling HSCs and hematopoietic progenitor cells positive to BrdU and Ki-67, upregulation of Notch-1, Cx43, PECAM-1, CaR, ERK1/2, Akt, p38, PKC, and c-Myc. NO(•)-induced HSCs differentiation was characterized by the increase in granulocytic-macrophage progenitors, granulocyte-macrophage colony forming units, mature myeloid cells, upregulation of PU.1, and C/EBPα genes concomitantly to the downregulation of GATA-3 and Ikz-3 genes, activation of Stat5 and downregulation of the other analyzed proteins mentioned above. Also, redox status modulation differed between proliferation and differentiation responses, which is likely associated with the transition of the proliferative to differentiation status. Our findings provide evidence of the role of NO(•) in inducing HSCs proliferation and myeloid differentiation involving multiple signaling. © 2014 AlphaMed Press.

  9. The Etiology of Multiple Sclerosis: Genetic Evidence for the Involvement of the Human Endogenous Retrovirus HERV-Fc1

    DEFF Research Database (Denmark)

    Nexø, Bjørn Andersen; Christensen, Tove; Frederiksen, Jette;

    2011-01-01

    We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact...

  10. LD2SNPing: linkage disequilibrium plotter and RFLP enzyme mining for tag SNPs

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    Cheng Yu-Huei

    2009-06-01

    Full Text Available Abstract Background Linkage disequilibrium (LD mapping is commonly used to evaluate markers for genome-wide association studies. Most types of LD software focus strictly on LD analysis and visualization, but lack supporting services for genotyping. Results We developed a freeware called LD2SNPing, which provides a complete package of mining tools for genotyping and LD analysis environments. The software provides SNP ID- and gene-centric online retrievals for SNP information and tag SNP selection from dbSNP/NCBI and HapMap, respectively. Restriction fragment length polymorphism (RFLP enzyme information for SNP genotype is available to all SNP IDs and tag SNPs. Single and multiple SNP inputs are possible in order to perform LD analysis by online retrieval from HapMap and NCBI. An LD statistics section provides D, D', r2, δQ, ρ, and the P values of the Hardy-Weinberg Equilibrium for each SNP marker, and Chi-square and likelihood-ratio tests for the pair-wise association of two SNPs in LD calculation. Finally, 2D and 3D plots, as well as plain-text output of the results, can be selected. Conclusion LD2SNPing thus provides a novel visualization environment for multiple SNP input, which facilitates SNP association studies. The software, user manual, and tutorial are freely available at http://bio.kuas.edu.tw/LD2NPing.

  11. Genome-wide SNPs and re-sequencing of growth habit and inflorescence genes in barley: implications for association mapping in germplasm arrays varying in size and structure

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    Muehlbauer Gary J

    2010-12-01

    Full Text Available Abstract Background Considerations in applying association mapping (AM to plant breeding are population structure and size: not accounting for structure and/or using small populations can lead to elevated false-positive rates. The principal determinants of population structure in cultivated barley are growth habit and inflorescence type. Both are under complex genetic control: growth habit is controlled by the epistatic interactions of several genes. For inflorescence type, multiple loss-of-function alleles in one gene lead to the same phenotype. We used these two traits as models for assessing the effectiveness of AM. This research was initiated using the CAP Core germplasm array (n = 102 assembled at the start of the Barley Coordinated Agricultural Project (CAP. This array was genotyped with 4,608 SNPs and we re-sequenced genes involved in morphology, growth and development. Larger arrays of breeding germplasm were subsequently genotyped and phenotyped under the auspices of the CAP project. This provided sets of 247 accessions phenotyped for growth habit and 2,473 accessions phenotyped for inflorescence type. Each of the larger populations was genotyped with 3,072 SNPs derived from the original set of 4,608. Results Significant associations with SNPs located in the vicinity of the loci involved in growth habit and inflorescence type were found in the CAP Core. Differentiation of true and spurious associations was not possible without a priori knowledge of the candidate genes, based on re-sequencing. The re-sequencing data were used to define allele types of the determinant genes based on functional polymorphisms. In a second round of association mapping, these synthetic markers based on allele types gave the most significant associations. When the synthetic markers were used as anchor points for analysis of interactions, we detected other known-function genes and candidate loci involved in the control of growth habit and inflorescence type. We

  12. Identification of candidate genes for prostate cancer-risk SNPs utilizing a normal prostate tissue eQTL data set

    Science.gov (United States)

    Thibodeau, S. N.; French, A. J.; McDonnell, S. K.; Cheville, J.; Middha, S.; Tillmans, L.; Riska, S.; Baheti, S.; Larson, M. C.; Fogarty, Z.; Zhang, Y.; Larson, N.; Nair, A.; O'Brien, D.; Wang, L.; Schaid, D J.

    2015-01-01

    Multiple studies have identified loci associated with the risk of developing prostate cancer but the associated genes are not well studied. Here we create a normal prostate tissue-specific eQTL data set and apply this data set to previously identified prostate cancer (PrCa)-risk SNPs in an effort to identify candidate target genes. The eQTL data set is constructed by the genotyping and RNA sequencing of 471 samples. We focus on 146 PrCa-risk SNPs, including all SNPs in linkage disequilibrium with each risk SNP, resulting in 100 unique risk intervals. We analyse cis-acting associations where the transcript is located within 2 Mb (±1 Mb) of the risk SNP interval. Of all SNP–gene combinations tested, 41.7% of SNPs demonstrate a significant eQTL signal after adjustment for sample histology and 14 expression principal component covariates. Of the 100 PrCa-risk intervals, 51 have a significant eQTL signal and these are associated with 88 genes. This study provides a rich resource to study biological mechanisms underlying genetic risk to PrCa. PMID:26611117

  13. SNPs and Hox gene mapping in Ciona intestinalis

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    Biffali Elio

    2008-01-01

    Full Text Available Abstract Background The tunicate Ciona intestinalis (Enterogona, Ascidiacea, a major model system for evolutionary and developmental genetics of chordates, harbours two cryptic species. To assess the degree of intra- and inter-specific genetic variability, we report the identification and analysis of C. intestinalis SNP (Single Nucleotide Polymorphism markers. A SNP subset was used to determine the genetic distance between Hox-5 and -10 genes. Results DNA fragments were amplified from 12 regions of C. intestinalis sp. A. In total, 128 SNPs and 32 one bp indels have been identified within 8 Kb DNA. SNPs in coding regions cause 4 synonymous and 12 non-synonymous substitutions. The highest SNP frequency was detected in the Hox5 and Hox10 intragenic regions. In C. intestinalis, these two genes have lost their archetypal topology within the cluster, such that Hox10 is located between Hox4 and Hox5. A subset of the above primers was used to perform successful amplification in C. intestinalis sp. B. In this cryptic species, 62 SNPs were identified within 3614 bp: 41 in non-coding and 21 in coding regions. The genetic distance of the Hox-5 and -10 loci, computed combining a classical backcross approach with the application of SNP markers, was found to be 8.4 cM (Haldane's function. Based on the physical distance, 1 cM corresponds to 39.5 Kb. Linkage disequilibrium between the aforementioned loci was calculated in the backcross generation. Conclusion SNPs here described allow analysis and comparisons within and between C. intestinalis cryptic species. We provide the first reliable computation of genetic distance in this important model chordate. This latter result represents an important platform for future studies on Hox genes showing deviations from the archetypal topology.

  14. In vitro vs in silico detected SNPs for the development of a genotyping array: what can we learn from a non-model species?

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    Camille Lepoittevin

    Full Text Available BACKGROUND: There is considerable interest in the high-throughput discovery and genotyping of single nucleotide polymorphisms (SNPs to accelerate genetic mapping and enable association studies. This study provides an assessment of EST-derived and resequencing-derived SNP quality in maritime pine (Pinus pinaster Ait., a conifer characterized by a huge genome size ( approximately 23.8 Gb/C. METHODOLOGY/PRINCIPAL FINDINGS: A 384-SNPs GoldenGate genotyping array was built from i/ 184 SNPs originally detected in a set of 40 re-sequenced candidate genes (in vitro SNPs, chosen on the basis of functionality scores, presence of neighboring polymorphisms, minor allele frequencies and linkage disequilibrium and ii/ 200 SNPs screened from ESTs (in silico SNPs selected based on the number of ESTs used for SNP detection, the SNP minor allele frequency and the quality of SNP flanking sequences. The global success rate of the assay was 66.9%, and a conversion rate (considering only polymorphic SNPs of 51% was achieved. In vitro SNPs showed significantly higher genotyping-success and conversion rates than in silico SNPs (+11.5% and +18.5%, respectively. The reproducibility was 100%, and the genotyping error rate very low (0.54%, dropping down to 0.06% when removing four SNPs showing elevated error rates. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that ESTs provide a resource for SNP identification in non-model species, which do not require any additional bench work and little bio-informatics analysis. However, the time and cost benefits of in silico SNPs are counterbalanced by a lower conversion rate than in vitro SNPs. This drawback is acceptable for population-based experiments, but could be dramatic in experiments involving samples from narrow genetic backgrounds. In addition, we showed that both the visual inspection of genotyping clusters and the estimation of a per SNP error rate should help identify markers that are not suitable to the Golden

  15. V-MitoSNP: visualization of human mitochondrial SNPs

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    Tsui Ke-Hung

    2006-08-01

    Full Text Available Abstract Background Mitochondrial single nucleotide polymorphisms (mtSNPs constitute important data when trying to shed some light on human diseases and cancers. Unfortunately, providing relevant mtSNP genotyping information in mtDNA databases in a neatly organized and transparent visual manner still remains a challenge. Amongst the many methods reported for SNP genotyping, determining the restriction fragment length polymorphisms (RFLPs is still one of the most convenient and cost-saving methods. In this study, we prepared the visualization of the mtDNA genome in a way, which integrates the RFLP genotyping information with mitochondria related cancers and diseases in a user-friendly, intuitive and interactive manner. The inherent problem associated with mtDNA sequences in BLAST of the NCBI database was also solved. Description V-MitoSNP provides complete mtSNP information for four different kinds of inputs: (1 color-coded visual input by selecting genes of interest on the genome graph, (2 keyword search by locus, disease and mtSNP rs# ID, (3 visualized input of nucleotide range by clicking the selected region of the mtDNA sequence, and (4 sequences mtBLAST. The V-MitoSNP output provides 500 bp (base pairs flanking sequences for each SNP coupled with the RFLP enzyme and the corresponding natural or mismatched primer sets. The output format enables users to see the SNP genotype pattern of the RFLP by virtual electrophoresis of each mtSNP. The rate of successful design of enzymes and primers for RFLPs in all mtSNPs was 99.1%. The RFLP information was validated by actual agarose electrophoresis and showed successful results for all mtSNPs tested. The mtBLAST function in V-MitoSNP provides the gene information within the input sequence rather than providing the complete mitochondrial chromosome as in the NCBI BLAST database. All mtSNPs with rs number entries in NCBI are integrated in the corresponding SNP in V-MitoSNP. Conclusion V-MitoSNP is a web

  16. Differences in allele frequencies of autosomal dominant hypercholesterolemia SNPs in the Malaysian population.

    Science.gov (United States)

    Alex, Livy; Chahil, Jagdish Kaur; Lye, Say Hean; Bagali, Pramod; Ler, Lian Wee

    2012-06-01

    Hypercholesterolemia is caused by different interactions of lifestyle and genetic determinants. At the genetic level, it can be attributed to the interactions of multiple polymorphisms, or as in the example of familial hypercholesterolemia (FH), it can be the result of a single mutation. A large number of genetic markers, mostly single nucleotide polymorphisms (SNP) or mutations in three genes, implicated in autosomal dominant hypercholesterolemia (ADH), viz APOB (apolipoprotein B), LDLR (low density lipoprotein receptor) and PCSK9 (proprotein convertase subtilisin/kexin type-9), have been identified and characterized. However, such studies have been insufficiently undertaken specifically in Malaysia and Southeast Asia in general. The main objective of this study was to identify ADH variants, specifically ADH-causing mutations and hypercholesterolemia-associated polymorphisms in multiethnic Malaysian population. We aimed to evaluate published SNPs in ADH causing genes, in this population and to report any unusual trends. We examined a large number of selected SNPs from previous studies of APOB, LDLR, PCSK9 and other genes, in clinically diagnosed ADH patients (n=141) and healthy control subjects (n=111). Selection of SNPs was initiated by searching within genes reported to be associated with ADH from known databases. The important finding was 137 mono-allelic markers (44.1%) and 173 polymorphic markers (55.8%) in both subject groups. By comparing to publicly available data, out of the 137 mono-allelic markers, 23 markers showed significant differences in allele frequency among Malaysians, European Whites, Han Chinese, Yoruba and Gujarati Indians. Our data can serve as reference for others in related fields of study during the planning of their experiments.

  17. Simultaneous analysis of all SNPs in genome-wide and re-sequencing association studies.

    Directory of Open Access Journals (Sweden)

    Clive J Hoggart

    2008-07-01

    Full Text Available Testing one SNP at a time does not fully realise the potential of genome-wide association studies to identify multiple causal variants, which is a plausible scenario for many complex diseases. We show that simultaneous analysis of the entire set of SNPs from a genome-wide study to identify the subset that best predicts disease outcome is now feasible, thanks to developments in stochastic search methods. We used a Bayesian-inspired penalised maximum likelihood approach in which every SNP can be considered for additive, dominant, and recessive contributions to disease risk. Posterior mode estimates were obtained for regression coefficients that were each assigned a prior with a sharp mode at zero. A non-zero coefficient estimate was interpreted as corresponding to a significant SNP. We investigated two prior distributions and show that the normal-exponential-gamma prior leads to improved SNP selection in comparison with single-SNP tests. We also derived an explicit approximation for type-I error that avoids the need to use permutation procedures. As well as genome-wide analyses, our method is well-suited to fine mapping with very dense SNP sets obtained from re-sequencing and/or imputation. It can accommodate quantitative as well as case-control phenotypes, covariate adjustment, and can be extended to search for interactions. Here, we demonstrate the power and empirical type-I error of our approach using simulated case-control data sets of up to 500 K SNPs, a real genome-wide data set of 300 K SNPs, and a sequence-based dataset, each of which can be analysed in a few hours on a desktop workstation.

  18. Multiple Dimensions of Parental Involvement and Its Links to Young Adolescent Self-Evaluation and Academic Achievement

    Science.gov (United States)

    Kaplan Toren, Nurit

    2013-01-01

    Drawing on early research on parental involvement and its effect on children's school functioning, it was hypothesized in this study that parents' educational involvement is positively related to two indicators of school functioning: academic self-competence and academic achievement. However, in light of research on the distinction between…

  19. Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population.

    Science.gov (United States)

    Shen, Gong-Qing; Rao, Shaoqi; Martinelli, Nicola; Li, Lin; Olivieri, Oliviero; Corrocher, Roberto; Abdullah, Kalil G; Hazen, Stanley L; Smith, Jonathan; Barnard, John; Plow, Edward F; Girelli, Domenico; Wang, Qing K

    2008-01-01

    Genome-wide single nucleotide polymorphism (SNP) association studies recently identified four SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) on chromosome 9p21 that were associated with coronary artery disease (CAD) and myocardial infarction (MI) in Caucasian populations from northern Europe and North America. Our aim was to determine whether these SNPs were associated with MI in a southern Europe/Mediterranean population. We employed a case-control association design involving 416 MI patients and 308 non-MI controls from Italy. Significant allelic association was identified between all four SNPs and MI. The association remained significant after adjusting for covariates for MI (P=0.007-0.029). One risk haplotype (GGGG; P=0.028) and one protective haplotype (AAAA; P=0.047) were identified. Genotypic association analysis demonstrated that the SNPs conferred susceptibility to MI most likely in a dominant model (P=0.0007-0.013). When the case cohort was divided into a group of MI patients with a family history (n=248) and one group without it (n=168), the positive, significant association was identified only in the group with the family history. These results indicate that chromosome 9p21 confers risk for development of MI in an Italian population.

  20. SNPs genotyping technologies and their applications in farm animals breeding programs: review

    Directory of Open Access Journals (Sweden)

    Hamed Kharrati Koopaee

    2014-02-01

    Full Text Available Single nucleotide polymorphisms (SNPs are DNA sequence variations that occur when a single nucleotide: adenine (A, thymine (T, cytosine (C or guanine (G in the genome sequence is altered. Traditional and high throughput methods are two main strategies for SNPs genotyping. The SNPs genotyping technologies provide powerful resources for animal breeding programs.Genomic selection using SNPs is a new tool for choosing the best breeding animals. In addition, the high density maps using SNPs can provide useful genetic tools to study quantitative traits genetic variations. There are many sources of SNPs and exhaustive numbers of methods of SNP detection to be considered. For many traits in farm animals, the rate of genetic improvement can be nearly doubled when SNPs information is used compared to the current methods of genetic evaluation. The goal of this review is to characterize the SNPs genotyping methods and their applications in farm animals breeding.

  1. SNPs in the SCGB3A2 promoter are associated with susceptibility to Graves’ disease

    Institute of Scientific and Technical Information of China (English)

    梁军

    2013-01-01

    Objective To investigate the association of single nucleotide polymorphisms(SNPs) in the SCGB3A2(secretoglobin family 3A member 2) gene promoter with susceptibility of Graves’ disease. Methods One-hundred and seventy-nine SNPs within

  2. Establishment of a pipeline to analyse non-synonymous SNPs in Bos taurus

    OpenAIRE

    Schreiber Mark; Morris Chris A; McCulloch Alan F; Dodds Ken G; Cullen Neil G; Manley Tim R; Glass Belinda C; Keane Orla M; Lee Michael A; Warren Jonathan; Zadissa Amonida; Wilson Theresa; McEwan John C

    2006-01-01

    Abstract Background Single nucleotide polymorphisms (SNPs) are an abundant form of genetic variation in the genome of every species and are useful for gene mapping and association studies. Of particular interest are non-synonymous SNPs, which may alter protein function and phenotype. We therefore examined bovine expressed sequences for non-synonymous SNPs and validated and tested selected SNPs for their association with measured traits. Results Over 500,000 public bovine expressed sequence ta...

  3. The Effects of Multiple Exemplar Training on a Working Memory Task Involving Sequential Responding in Children with Autism

    Science.gov (United States)

    Baltruschat, Lisa; Hasselhorn, Marcus; Tarbox, Jonathan; Dixon, Dennis R.; Najdowski, Adel; Mullins, Ryan David; Gould, Evelyn

    2012-01-01

    This study is part of a programmatic line of research into the use of basic positive reinforcement procedures for improving working memory in children with autism spectrum disorders. The authors evaluated the effects of multiple exemplar training, utilizing positive reinforcement, on performance of a "digit span backwards" task--a test of working…

  4. A genome-wide association study of heat stress-associated SNPs in catfish.

    Science.gov (United States)

    Jin, Y; Zhou, T; Geng, X; Liu, S; Chen, A; Yao, J; Jiang, C; Tan, S; Su, B; Liu, Z

    2017-04-01

    Heat tolerance is a complex and economically important trait for catfish genetic breeding programs. With global climate change, it is becoming an increasingly important trait. To better understand the molecular basis of heat stress, a genome-wide association study (GWAS) was carried out using the 250 K catfish SNP array with interspecific backcross progenies, which derived from crossing female channel catfish with male F1 hybrid catfish (female channel catfish × male blue catfish). Three significant associated SNPs were detected by performing an EMMAX approach for GWAS. The SNP located on linkage group 14 explained 12.1% of phenotypical variation. The other two SNPs, located on linkage group 16, explained 11.3 and 11.5% of phenotypical variation respectively. A total of 14 genes with heat stress related functions were detected within the significant associated regions. Among them, five genes-TRAF2, FBXW5, ANAPC2, UBR1 and KLHL29- have known functions in the protein degradation process through the ubiquitination pathway. Other genes related to heat stress include genes involved in protein biosynthesis (PRPF4 and SYNCRIP), protein folding (DNAJC25), molecule and iron transport (SLC25A46 and CLIC5), cytoskeletal reorganization (COL12A1) and energy metabolism (COX7A2, PLCB1 and PLCB4) processes. The results provide fundamental information about genes and pathways that is useful for further investigation into the molecular mechanisms of heat stress. The associated SNPs could be promising candidates for selecting heat-tolerant catfish lines after validating their effects on larger and various catfish populations.

  5. The evolutionary history of Afrocanarian blue tits inferred from genomewide SNPs.

    Science.gov (United States)

    Gohli, Jostein; Leder, Erica H; Garcia-Del-Rey, Eduardo; Johannessen, Lars Erik; Johnsen, Arild; Laskemoen, Terje; Popp, Magnus; Lifjeld, Jan T

    2015-01-01

    A common challenge in phylogenetic reconstruction is to find enough suitable genomic markers to reliably trace splitting events with short internodes. Here, we present phylogenetic analyses based on genomewide single-nucleotide polymorphisms (SNPs) of an enigmatic avian radiation, the subspecies complex of Afrocanarian blue tits (Cyanistes teneriffae). The two sister species, the Eurasian blue tit (Cyanistes caeruleus) and the azure tit (Cyanistes cyanus), constituted the out-group. We generated a large data set of SNPs for analysis of population structure and phylogeny. We also adapted our protocol to utilize degraded DNA from old museum skins from Libya. We found strong population structuring that largely confirmed subspecies monophyly and constructed a coalescent-based phylogeny with full support at all major nodes. The results are consistent with a recent hypothesis that La Palma and Libya are relic populations of an ancient Afrocanarian blue tit, although a small data set for Libya could not resolve its position relative to La Palma. The birds on the eastern islands of Fuerteventura and Lanzarote are similar to those in Morocco. Together they constitute the sister group to the clade containing the other Canary Islands (except La Palma), in which El Hierro is sister to the three central islands. Hence, extant Canary Islands populations seem to originate from multiple independent colonization events. We also found population divergences in a key reproductive trait, viz. sperm length, which may constitute reproductive barriers between certain populations. We recommend a taxonomic revision of this polytypic species, where several subspecies should qualify for species rank.

  6. SNPs Selection using Gravitational Search Algorithm and Exhaustive Search for Association Mapping

    Science.gov (United States)

    Kusuma, W. A.; Hasibuan, L. S.; Istiadi, M. A.

    2016-01-01

    Single Nucleotide Polymorphisms (SNPs) are known having association to phenotipic variations. The study of linking SNPs to interest phenotype is refer to Association Mapping (AM), which is classified as a combinatorial problem. Exhaustive Search (ES) approach is able to be implemented to select targeted SNPs exactly since it evaluate all possible combinations of SNPs, but it is not efficient in terms of computer resources and computation time. Heuristic Search (HS) approach is an alternative to improve the performance of ES in those terms, but it still suffers high false positive SNPs in each combinations. Gravitational Search Algorithm (GSA) is a new HS algorithm that yields better performance than other nature inspired HS. This paper proposed a new method which combined GSA and ES to identify the most appropriate combination of SNPs linked to interest phenotype. Testing was conducted using dataset without epistasis and dataset with epistasis. Using dataset without epistasis with 7 targeted SNPs, the proposed method identified 7 SNPs - 6 True Positive (TP) SNPs and 1 False Positive (FP) SNP- with association value of 0.83. In addition, the proposed method could identified 3 SNPs- 2 TP SNP and 1 FP SNP with association value of 0.87 by using dataset with epistases and 5 targeted SNPs. The results showed that the method is robust in reducing redundant SNPs and identifying main markers.

  7. Comparison of information content for microsatellites and SNPs in poultry and cattle

    NARCIS (Netherlands)

    Schopen, G.C.B.; Bovenhuis, H.; Visker, M.H.P.W.; Arendonk, van J.A.M.

    2008-01-01

    Data were available for 12 poultry microsatellites and 29 poultry single nucleotide polymorphisms (SNPs), and for 34 cattle microsatellites and 36 cattle SNPs. Stochastic permutation was used to determine the number of SNPs needed to obtain the same average information content as a given number of m

  8. Tracing cattle breeds with principal components analysis ancestry informative SNPs.

    Directory of Open Access Journals (Sweden)

    Jamey Lewis

    Full Text Available The recent release of the Bovine HapMap dataset represents the most detailed survey of bovine genetic diversity to date, providing an important resource for the design and development of livestock production. We studied this dataset, comprising more than 30,000 Single Nucleotide Polymorphisms (SNPs for 19 breeds (13 taurine, three zebu, and three hybrid breeds, seeking to identify small panels of genetic markers that can be used to trace the breed of unknown cattle samples. Taking advantage of the power of Principal Components Analysis and algorithms that we have recently described for the selection of Ancestry Informative Markers from genomewide datasets, we present a decision-tree which can be used to accurately infer the origin of individual cattle. In doing so, we present a thorough examination of population genetic structure in modern bovine breeds. Performing extensive cross-validation experiments, we demonstrate that 250-500 carefully selected SNPs suffice in order to achieve close to 100% prediction accuracy of individual ancestry, when this particular set of 19 breeds is considered. Our methods, coupled with the dense genotypic data that is becoming increasingly available, have the potential to become a valuable tool and have considerable impact in worldwide livestock production. They can be used to inform the design of studies of the genetic basis of economically important traits in cattle, as well as breeding programs and efforts to conserve biodiversity. Furthermore, the SNPs that we have identified can provide a reliable solution for the traceability of breed-specific branded products.

  9. Genotyping of Brucella species using clade specific SNPs

    Directory of Open Access Journals (Sweden)

    Foster Jeffrey T

    2012-06-01

    Full Text Available Abstract Background Brucellosis is a worldwide disease of mammals caused by Alphaproteobacteria in the genus Brucella. The genus is genetically monomorphic, requiring extensive genotyping to differentiate isolates. We utilized two different genotyping strategies to characterize isolates. First, we developed a microarray-based assay based on 1000 single nucleotide polymorphisms (SNPs that were identified from whole genome comparisons of two B. abortus isolates , one B. melitensis, and one B. suis. We then genotyped a diverse collection of 85 Brucella strains at these SNP loci and generated a phylogenetic tree of relationships. Second, we developed a selective primer-extension assay system using capillary electrophoresis that targeted 17 high value SNPs across 8 major branches of the phylogeny and determined their genotypes in a large collection ( n = 340 of diverse isolates. Results Our 1000 SNP microarray readily distinguished B. abortus, B. melitensis, and B. suis, differentiating B. melitensis and B. suis into two clades each. Brucella abortus was divided into four major clades. Our capillary-based SNP genotyping confirmed all major branches from the microarray assay and assigned all samples to defined lineages. Isolates from these lineages and closely related isolates, among the most commonly encountered lineages worldwide, can now be quickly and easily identified and genetically characterized. Conclusions We have identified clade-specific SNPs in Brucella that can be used for rapid assignment into major groups below the species level in the three main Brucella species. Our assays represent SNP genotyping approaches that can reliably determine the evolutionary relationships of bacterial isolates without the need for whole genome sequencing of all isolates.

  10. Altofrequency SNPs of mitochondrial DNA in 26 Han Chinese

    Institute of Scientific and Technical Information of China (English)

    LUO Yong-jun; GAO Wen-xiang; GAO Yu-qi; CHEN Jian; TAN Xiao-ling; LIU Xin; CHEN Hai-hua

    2007-01-01

    Objective:To explore the possible mitochondrial DNA (mtDNA) polymorphism in Han Chinese.Methods:The complete mitochondrial genome of 26 unrelated healthy Han Chinese were extracted and sequenced.Results:The mtDNA nucleotide sites (2 706,7 028,8 860,11 719,and 15 326)were found totally different from the Revised Cambridge Reference Sequence (rCRS).These single nucleotide polymorphisms (SNPs) were 2 706 A→G,7 028 C→T,8 860 A→G,11 719 G→A,15 326 A→G.Conclusion:These findings provide new insights into the characteristics of Han Chinese mitochondrial genetic diversity.

  11. Combinations of SNPs related to signal transduction in bipolar disorder

    DEFF Research Database (Denmark)

    Koefoed, Pernille; Andreassen, Ole A; Bennike, Bente

    2011-01-01

    of complex diseases, it may be useful to look at combinations of genotypes. Genes related to signal transmission, e.g., ion channel genes, may be of interest in this respect in the context of bipolar disorder. In the present study, we analysed 803 SNPs in 55 genes related to aspects of signal transmission...... and calculated all combinations of three genotypes from the 3×803 SNP genotypes for 1355 controls and 607 patients with bipolar disorder. Four clusters of patient-specific combinations were identified. Permutation tests indicated that some of these combinations might be related to bipolar disorder. The WTCCC...

  12. Typing of Y chromosome SNPs with multiplex PCR methods

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Børsting, Claus; Morling, Niels

    2005-01-01

    We describe a method for the simultaneous typing of Y-chromosome single nucleotide polymorphism (SNP) markers by means of multiplex polymerase chain reaction (PCR) strategies that allow the detection of 35 Y chromosome SNPs on 25 amplicons from 100 to 200 pg of chromosomal deoxyribonucleic acid...... factors for the creation of larger SNP typing PCR multiplexes include careful selection of primers for the primary amplification and the SBE reaction, use of DNA primers with homogenous composition, and balancing the primer concentrations for both the amplification and the SBE reactions....

  13. SNPs Array Karyotyping in Non-Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Maryam Etebari

    2015-11-01

    Full Text Available The traditional methods for detection of chromosomal aberrations, which included cytogenetic or gene candidate solutions, suffered from low sensitivity or the need for previous knowledge of the target regions of the genome. With the advent of single nucleotide polymorphism (SNP arrays, genome screening at global level in order to find chromosomal aberrations like copy number variants, DNA amplifications, deletions, and also loss of heterozygosity became feasible. In this review, we present an update of the knowledge, gained by SNPs arrays, of the genomic complexity of the most important subtypes of non-Hodgkin lymphomas.

  14. ASSESSMENT OF CHAROLAIS BULLS POPULATION STRUCTURE BASED ON SNPs ANALYSES

    OpenAIRE

    Nina Moravčíková; Tomáš Minarovič; Anna Trakovická

    2014-01-01

    The aim of this study was identification of SNPs in leptin (LEP), leptin receptor (LEPR), growth hormone (GH) and specific pituitary transcription factor (Pit-1) genes in order to analyze genetic structure of Charolais bulls’ population. The total numbers of genomic DNA samples were taken from 52 breeding bulls and analyzed by PCR-RFLP method. After digestion with restriction enzymes were detected in bulls’ population alleles with frequency: LEP/Sau3AI A 0.83 and B 0.17 (±0.037); LEPR/BseGI C...

  15. Molecular Beacon CNT-based Detection of SNPs

    Science.gov (United States)

    Egorova, V. P.; Krylova, H. V.; Lipnevich, I. V.; Veligura, A. A.; Shulitsky, B. G.; Y Fedotenkova, L.

    2015-11-01

    An fluorescence quenching effect due to few-walled carbon nanotubes chemically modified by carboxyl groups has been utilized to discriminate Single Nucleotide Polymorphism (SNP). It was shown that the complex obtained from these nanotube and singlestranded primer DNA is formed due to stacking interactions between the hexagons of the nanotubes and aromatic rings of nucleotide bases as well as due to establishing of hydrogen bonds between acceptor amine groups of nucleotide bases and donor carboxyl groups of the nanotubes. It has been demonstrated that these complexes may be used to make highly effective DNA biosensors detecting SNPs which operate as molecular beacons.

  16. SNPs, linkage disequilibrium, and chronic mountain sickness in Tibetan Chinese

    Directory of Open Access Journals (Sweden)

    Buroker NE

    2017-07-01

    Full Text Available Norman E Buroker,1 Xue-Han Ning,1,2,† Zhao-Nian Zhou,3 Kui Li,4 Wei-Jun Cen,4 Xiu-Feng Wu,3 Wei-Zhong Zhu,5 C Ronald Scott,1 Shi-Han Chen1 1Department of Pediatrics, University of Washington, 2Division of Cardiology, Seattle Children’s Hospital Research Foundation, Seattle, WA, USA; 3Laboratory of Hypoxia Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; 4Lhasa People Hospital, Lhasa, Tibet; 5Center for Cardiovascular Biology and Regenerative Medicine, University of Washington, Seattle, WA, USA †Xue-Han Ning passed away on April 20, 2015 Abstract: Chronic mountain sickness (CMS is estimated at 1.2% in Tibetans living at the Qinghai–Tibetan Plateau. Eighteen single-nucleotide polymorphisms (SNPs from nine nuclear genes that have an association with CMS in Tibetans have been analyzed by using pairwise linkage disequilibrium (LD. The SNPs included are the angiotensin-converting enzyme (rs4340, the angiotensinogen (rs699, and the angiotensin II type 1 receptor (AGTR1 (rs5186 from the renin–angiotensin system. A low-density lipoprotein apolipoprotein B (rs693 SNP was also included. From the hypoxia-inducible factor oxygen signaling pathway, the endothetal Per-Arnt-Sim domain protein 1 (EPAS1 and the egl nine homolog 1 (ENGL1 (rs480902 SNPs were included in the study. SNPs from the vascular endothelial growth factor (VEGF signaling pathway included are the v-akt murine thymoma viral oncogene homolog 3 (rs4590656 and rs2291409, the endothelial cell nitric oxide synthase 3 (rs1007311 and rs1799983, and the (VEGFA (rs699947, rs34357231, rs79469752, rs13207351, rs28357093, rs1570360, rs2010963, and rs3025039. An increase in LD occurred in 40 pairwise comparisons, whereas a decrease in LD was found in 55 pairwise comparisons between the controls and CMS patients. These changes were found to occur within and between signaling pathways, which suggests that there is an interaction between SNP

  17. Analysis of 49 autosomal SNPs in an Iraqi population

    DEFF Research Database (Denmark)

    Tomas Mas, Carmen; Diez, Isabel E; Moncada, Enrique;

    2013-01-01

    Forty-nine of the 52 autosomal single nucleotide polymorphisms (SNPs) in the SNPforID 52plex were typed in 101 unrelated Iraqis living in Denmark. No significant deviation from HWE was found in all but one of the 49 SNP systems and no significant pairwise linkage disequilibrium was observed for any...... SNP pair. When 18 worldwide populations were compared (including populations in Iraq, Turkey, Israel, Pakistan, India, China, Taiwan, Japan, Siberia, Algeria, Somalia, Uganda, Mozambique, Angola, Nigeria, Denmark, Portugal, Spain), a significant global F(ST) value was obtained. All but six F...

  18. Involvement of individual subsites and secondary substrate binding sites in multiple attack on amylose by barley alpha-amylase

    DEFF Research Database (Denmark)

    Kramhøft, Birte; Bak-Jensen, Kristian Sass; Mori, Haruhide

    2005-01-01

    Barley alpha-amylase 1 (AMY1) hydrolyzed amylose with a degree of multiple attack (DMA) of 1.9; that is, on average, 2.9 glycoside bonds are cleaved per productive enzyme-substrate encounter. Six AMY1 mutants, spanning the substrate binding cleft from subsites -6 to +4, and a fusion protein, AMY1...... can be manipulated by structural changes in the active site or by introduction of extra substrate binding sites....... translocation of substrate in the binding cleft upon the initial cleavage to produce G6-G10, essentially independent of subsite mutations, and short-distance moves resulting in individually very different rates of release of G1-G4. Accordingly, the degree of multiple attack as well as the profile of products...

  19. NOS3 tagSNPs does not modify the chronic kidney disease progression in autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Ramanathan, Gnanasambandan; Periyasamy, Soundararajan; Lakkakula, Bhaskar Vks

    2014-09-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary and progressive renal disorder. It is also recognised as the most frequent genetic cause of chronic kidney diseases (CKD). In the present study, four tagging SNPs and two more well studied polymorphisms (Intron 4 VNTR and Glu298Asp) the NOS3 gene were investigated to unravel the potential modifier effect of NOS3 gene on the progression of CKD in ADPKD. A total of 102 ADPKD patients and 106 controls were selected for the study. The tagSNPs and Glu298Asp polymorphisms were genotyped using FRET-based KASPar method and intron-4 VNTR by polymerase chain reaction electrophoresis. The genotypes and haplotypes in the controls and ADPKD subjects were analysed by χ(2) tests and haploview software. Mantel-Haenszel stratified and univariate analyses were performed to estimate the influence of different genotypes between different CKD stages and hypertension. The tagSNPs of NOS3 genotypes and haplotypes did not exhibit any significant differences between controls and ADPKD patients. The significant linkage disequilibrium was observed between the rs3918184 and rs2853796 by forming LD block. In univariate analysis, the age and family history of Diabetes mellitus (DM) showed significant association with advancement of CKD, but not with the eNOS polymorphisms. Our data suggests that there is no evidence for the involvement of NOS3 tag SNPs in the progression to CKD in ADPKD patients. A systematic study using well validated functional SNPs is necessary to clarify the role of the NOS3 gene in the development of CKD in ADPKD. © 2014 Asian Pacific Society of Nephrology.

  20. Rapid multiplex high resolution melting method to analyze inflammatory related SNPs in preterm birth

    Directory of Open Access Journals (Sweden)

    Pereyra Silvana

    2012-01-01

    Full Text Available Abstract Background Complex traits like cancer, diabetes, obesity or schizophrenia arise from an intricate interaction between genetic and environmental factors. Complex disorders often cluster in families without a clear-cut pattern of inheritance. Genomic wide association studies focus on the detection of tens or hundreds individual markers contributing to complex diseases. In order to test if a subset of single nucleotide polymorphisms (SNPs from candidate genes are associated to a condition of interest in a particular individual or group of people, new techniques are needed. High-resolution melting (HRM analysis is a new method in which polymerase chain reaction (PCR and mutations scanning are carried out simultaneously in a closed tube, making the procedure fast, inexpensive and easy. Preterm birth (PTB is considered a complex disease, where genetic and environmental factors interact to carry out the delivery of a newborn before 37 weeks of gestation. It is accepted that inflammation plays an important role in pregnancy and PTB. Methods Here, we used real time-PCR followed by HRM analysis to simultaneously identify several gene variations involved in inflammatory pathways on preterm labor. SNPs from TLR4, IL6, IL1 beta and IL12RB genes were analyzed in a case-control study. The results were confirmed either by sequencing or by PCR followed by restriction fragment length polymorphism. Results We were able to simultaneously recognize the variations of four genes with similar accuracy than other methods. In order to obtain non-overlapping melting temperatures, the key step in this strategy was primer design. Genotypic frequencies found for each SNP are in concordance with those previously described in similar populations. None of the studied SNPs were associated with PTB. Conclusions Several gene variations related to the same inflammatory pathway were screened through a new flexible, fast and non expensive method with the purpose of analyzing

  1. Ratio of involved/uninvolved immunoglobulin quantification by Hevylite™ assay: clinical and prognostic impact in multiple myeloma

    OpenAIRE

    2012-01-01

    Abstract Background HevyLite™ is a new, recently developed method that facilitates separate quantification of the kappa- and lambda-bounded amounts of a given immunoglobulin (Ig). Using this method, we measured intact immunoglobulin (heavy/light chain; HLC) IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda individually, as well as their deriving ratios (HLCR) in a series of IgG or IgA multiple myeloma (MM) patients, to investigate and assess the contribution of these tests to disease evaluation. P...

  2. SNPs in genes functional in starch-sugar interconversion associate with natural variation of tuber starch and sugar content of potato (Solanum tuberosum L.).

    Science.gov (United States)

    Schreiber, Lena; Nader-Nieto, Anna Camila; Schönhals, Elske Maria; Walkemeier, Birgit; Gebhardt, Christiane

    2014-07-31

    Starch accumulation and breakdown are vital processes in plant storage organs such as seeds, roots, and tubers. In tubers of potato (Solanum tuberosum L.) a small fraction of starch is converted into the reducing sugars glucose and fructose. Reducing sugars accumulate in response to cold temperatures. Even small quantities of reducing sugars affect negatively the quality of processed products such as chips and French fries. Tuber starch and sugar content are inversely correlated complex traits that are controlled by multiple genetic and environmental factors. Based on in silico annotation of the potato genome sequence, 123 loci are involved in starch-sugar interconversion, approximately half of which have been previously cloned and characterized. By means of candidate gene association mapping, we identified single-nucleotide polymorphisms (SNPs) in eight genes known to have key functions in starch-sugar interconversion, which were diagnostic for increased tuber starch and/or decreased sugar content and vice versa. Most positive or negative effects of SNPs on tuber-reducing sugar content were reproducible in two different collections of potato cultivars. The diagnostic SNP markers are useful for breeding applications. An allele of the plastidic starch phosphorylase PHO1a associated with increased tuber starch content was cloned as full-length cDNA and characterized. The PHO1a-HA allele has several amino acid changes, one of which is unique among all known starch/glycogen phosphorylases. This mutation might cause reduced enzyme activity due to impaired formation of the active dimers, thereby limiting starch breakdown.

  3. SNPs in Genes Functional in Starch-Sugar Interconversion Associate with Natural Variation of Tuber Starch and Sugar Content of Potato (Solanum tuberosum L.)

    Science.gov (United States)

    Schreiber, Lena; Nader-Nieto, Anna Camila; Schönhals, Elske Maria; Walkemeier, Birgit; Gebhardt, Christiane

    2014-01-01

    Starch accumulation and breakdown are vital processes in plant storage organs such as seeds, roots, and tubers. In tubers of potato (Solanum tuberosum L.) a small fraction of starch is converted into the reducing sugars glucose and fructose. Reducing sugars accumulate in response to cold temperatures. Even small quantities of reducing sugars affect negatively the quality of processed products such as chips and French fries. Tuber starch and sugar content are inversely correlated complex traits that are controlled by multiple genetic and environmental factors. Based on in silico annotation of the potato genome sequence, 123 loci are involved in starch-sugar interconversion, approximately half of which have been previously cloned and characterized. By means of candidate gene association mapping, we identified single-nucleotide polymorphisms (SNPs) in eight genes known to have key functions in starch-sugar interconversion, which were diagnostic for increased tuber starch and/or decreased sugar content and vice versa. Most positive or negative effects of SNPs on tuber-reducing sugar content were reproducible in two different collections of potato cultivars. The diagnostic SNP markers are useful for breeding applications. An allele of the plastidic starch phosphorylase PHO1a associated with increased tuber starch content was cloned as full-length cDNA and characterized. The PHO1a-HA allele has several amino acid changes, one of which is unique among all known starch/glycogen phosphorylases. This mutation might cause reduced enzyme activity due to impaired formation of the active dimers, thereby limiting starch breakdown. PMID:25081979

  4. Are genetic variants for tobacco smoking associated with cannabis involvement?

    Science.gov (United States)

    Agrawal, Arpana; Lynskey, Michael T; Kapoor, Manav; Bucholz, Kathleen K; Edenberg, Howard J; Schuckit, Marc; Brooks, Andrew; Hesselbrock, Victor; Kramer, John; Saccone, Nancy; Tischfield, Jay; Bierut, Laura J

    2015-05-01

    Cannabis users are highly likely to also be tobacco cigarette smokers and a proportion of this comorbidity is attributable to shared genetic influences. Three large meta-analyses of genomewide association studies (GWAS) of tobacco smoking have identified multiple genomewide significant (psmoking and with cannabis involvement in an independent sample. Eleven SNPs associated with cigarettes per day (CPD), ever versus never smoking and current smoking/smoking cessation at psmoking measures in 2716 European-American subjects from the Study of Addictions Genes and Environment (SAGE) and with lifetime and current cannabis use and DSM-IV cannabis abuse/dependence. Cannabis use and tobacco smoking correlated at 0.54. Rs16969968 in CHRNA5 (and its proxy, rs1051730 in CHRNA3) and rs1451240, a proxy for rs13280604 in CHRNB3, were associated with CPD after Bonferroni correction (psmoking initiation, as in the original meta-analysis and also with lifetime cannabis use. Associations with cannabis involvement were no longer significant upon adjustment for the tobacco smoking measures. The modest associations between cannabis involvement and SNPs for tobacco smoking were not independent of the comorbidity between tobacco and cannabis involvement. Larger samples of individuals might be required to articulate the specific genetic architecture of cannabis involvement. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Identification of miRSNPs associated with the risk of multiple myeloma

    DEFF Research Database (Denmark)

    Macauda, Angelica; Calvetti, Diego; Maccari, Giuseppe

    2017-01-01

    Multiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the bone marrow, associated with the production of a monoclonal immunoglobulin (M protein) which can be detected in the blood and/or urine. Multiple lines of evidence suggest that genetic factors are involved in MM...... consisted of 1,832 controls and 2,894 MM cases recruited from 7 European countries and Israel in the context of the IMMEnSE (International Multiple Myeloma rESEarch) consortium. In this population two SNPs showed an association with p

  6. CS1, a SLAM family receptor involved in immune regulation, is a therapeutic target in multiple myeloma.

    Science.gov (United States)

    Veillette, André; Guo, Huaijian

    2013-10-01

    Signaling lymphocytic activation molecule (SLAM) family receptors have been implicated in normal immunity, immunodeficiencies and autoimmunity. CS1 (also known as CRACC, CD319 and SLAMF7) is a member of the SLAM family expressed on several normal hematopoietic cell types. It is also highly and nearly universally expressed on multiple myeloma (MM) cells. This review focuses on the biology of CS1, both in normal hematopoietic cells and in MM cells. It also discusses the preclinical and clinical data on the use of a humanized anti-CS1 monoclonal antibody, elotuzumab, for the treatment of MM. Based on current knowledge, CS1 is a compelling new target for the treatment of MM.

  7. Involvement of individual subsites and secondary substrate binding sites in multiple attack on amylose by barley alpha-amylase

    DEFF Research Database (Denmark)

    Kramhøft, Birte; Bak-Jensen, Kristian Sass; Mori, Haruhide;

    2005-01-01

    Barley alpha-amylase 1 (AMY1) hydrolyzed amylose with a degree of multiple attack (DMA) of 1.9; that is, on average, 2.9 glycoside bonds are cleaved per productive enzyme-substrate encounter. Six AMY1 mutants, spanning the substrate binding cleft from subsites -6 to +4, and a fusion protein, AMY1......-SBD, of AMY1 and the starch binding domain (SBD) of Aspergillus niger glucoamylase were also analyzed. DMA of the subsite -6 mutant Y105A and AMY1-SBD increased to 3.3 and 3.0, respectively. M53E, M298S, and T212W at subsites -2, +1/+2, and +4, respectively, and the double mutant Y105A/T212W had...

  8. SNPs in DNA repair or oxidative stress genes and late subcutaneous fibrosis in patients following single shot partial breast irradiation

    Directory of Open Access Journals (Sweden)

    Falvo Elisabetta

    2012-01-01

    Full Text Available Abstract Background The aim of this study was to evaluate the potential association between single nucleotide polymorphisms related response to radiotherapy injury, such as genes related to DNA repair or enzymes involved in anti-oxidative activities. The paper aims to identify marker genes able to predict an increased risk of late toxicity studying our group of patients who underwent a Single Shot 3D-CRT PBI (SSPBI after BCS (breast conserving surgery. Methods A total of 57 breast cancer patients who underwent SSPBI were genotyped for SNPs (single nucleotide polymorphisms in XRCC1, XRCC3, GST and RAD51 by Pyrosequencing technology. Univariate analysis (ORs and 95% CI was performed to correlate SNPs with the risk of developing ≥ G2 fibrosis or fat necrosis. Results A higher significant risk of developing ≥ G2 fibrosis or fat necrosis in patients with: polymorphic variant GSTP1 (Ile105Val (OR = 2.9; 95%CI, 0.88-10.14, p = 0.047. Conclusions The presence of some SNPs involved in DNA repair or response to oxidative stress seem to be able to predict late toxicity. Trial Registration ClinicalTrials.gov: NCT01316328

  9. MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs

    Directory of Open Access Journals (Sweden)

    Liu Chenxing

    2012-11-01

    Full Text Available Abstract Background Numerous single nucleotide polymorphisms (SNPs associated with complex diseases have been identified by genome-wide association studies (GWAS and expression quantitative trait loci (eQTLs studies. However, few of these SNPs have explicit biological functions. Recent studies indicated that the SNPs within the 3’UTR regions of susceptibility genes could affect complex traits/diseases by affecting the function of miRNAs. These 3’UTR SNPs are functional candidates and therefore of interest to GWAS and eQTL researchers. Description We developed a publicly available online database, MirSNP (http://cmbi.bjmu.edu.cn/mirsnp, which is a collection of human SNPs in predicted miRNA-mRNA binding sites. We identified 414,510 SNPs that might affect miRNA-mRNA binding. Annotations were added to these SNPs to predict whether a SNP within the target site would decrease/break or enhance/create an miRNA-mRNA binding site. By applying MirSNP database to three brain eQTL data sets, we identified four unreported SNPs (rs3087822, rs13042, rs1058381, and rs1058398, which might affect miRNA binding and thus affect the expression of their host genes in the brain. We also applied the MirSNP database to our GWAS for schizophrenia: seven predicted miRNA-related SNPs (p  Conclusion MirSNP could identify the putative miRNA-related SNPs from GWAS and eQTLs researches and provide the direction for subsequent functional researches.

  10. Extracting the Beat: An Experience-dependent Complex Integration of Multisensory Information Involving Multiple Levels of the Nervous System

    Directory of Open Access Journals (Sweden)

    Laurel J. Trainor

    2009-04-01

    Full Text Available In a series of studies we have shown that movement (or vestibular stimulation that is synchronized to every second or every third beat of a metrically ambiguous rhythm pattern biases people to perceive the meter as a march or as a waltz, respectively. Riggle (this volume claims that we postulate an "innate", "specialized brain unit" for beat perception that is "directly" influenced by vestibular input. In fact, to the contrary, we argue that experience likely plays a large role in the development of rhythmic auditory-movement interactions, and that rhythmic processing in the brain is widely distributed and includes subcortical and cortical areas involved in sound processing and movement. Further, we argue that vestibular and auditory information are integrated at various subcortical and cortical levels along with input from other sensory modalities, and it is not clear which levels are most important for rhythm processing or, indeed, what a "direct" influence of vestibular input would mean. Finally, we argue that vestibular input to sound location mechanisms may be involved, but likely cannot explain the influence of vestibular input on the perception of auditory rhythm. This remains an empirical question for future research.

  11. Identification of Circular RNAs From the Parental Genes Involved in Multiple Aspects of Cellular Metabolism in Barley

    Directory of Open Access Journals (Sweden)

    Behrooz eDarbani

    2016-06-01

    Full Text Available RNA circularization made by head-to-tail back-splicing events is involved in the regulation of gene expression from transcriptional to post-translational levels. By exploiting RNA-Seq data and down-stream analysis, we shed light on the importance of circular RNAs in plants. The results introduce circular RNAs as novel interactors in the regulation of gene expression in plants and imply the comprehensiveness of this regulatory pathway by identifying circular RNAs for a diverse set of genes. These genes are involved in several aspects of cellular metabolism as hormonal signaling, intracellular protein sorting, carbohydrate metabolism and cell-wall biogenesis, respiration, amino acid biosynthesis, transcription and translation, and protein ubiquitination. Additionally, these parental loci of circular RNAs, from both nuclear and mitochondrial genomes, encode for different transcript classes including protein coding transcripts, microRNA, rRNA, and long non-coding/microprotein coding RNAs. The results shed light on the mitochondrial exonic circular RNAs and imply the importance of circular RNAs for regulation of mitochondrial genes. Importantly, we introduce circular RNAs in barley and elucidate their cellular-level alterations across tissues and in response to micronutrients iron and zinc. In further support of circular RNAs' functional roles in plants, we report several cases where fluctuations of circRNAs do not correlate with the levels of their parental-loci encoded linear transcripts.Keywords: circular RNAs, coding and non-coding transcripts, leaves, seeds, transfer cells, micronutrients, mitochondria

  12. Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test

    Directory of Open Access Journals (Sweden)

    Yun Joo Yoo

    2015-01-01

    Full Text Available Gene-based analysis of multiple single nucleotide polymorphisms (SNPs in a gene region is an alternative to single SNP analysis. The multi-bin linear combination test (MLC proposed in previous studies utilizes the correlation among SNPs within a gene to construct a gene-based global test. SNPs are partitioned into clusters of highly correlated SNPs, and the MLC test statistic quadratically combines linear combination statistics constructed for each cluster. The test has degrees of freedom equal to the number of clusters and can be more powerful than a fully quadratic or fully linear test statistic. In this study, we develop a new SNP clustering algorithm designed to find cliques, which are complete subnetworks of SNPs with all pairwise correlations above a threshold. We evaluate the performance of the MLC test using the clique-based CLQ algorithm versus using the tag-SNP-based LDSelect algorithm. In our numerical power calculations we observed that the two clustering algorithms produce identical clusters about 40~60% of the time, yielding similar power on average. However, because the CLQ algorithm tends to produce smaller clusters with stronger positive correlation, the MLC test is less likely to be affected by the occurrence of opposing signs in the individual SNP effect coefficients.

  13. Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test.

    Science.gov (United States)

    Yoo, Yun Joo; Kim, Sun Ah; Bull, Shelley B

    2015-01-01

    Gene-based analysis of multiple single nucleotide polymorphisms (SNPs) in a gene region is an alternative to single SNP analysis. The multi-bin linear combination test (MLC) proposed in previous studies utilizes the correlation among SNPs within a gene to construct a gene-based global test. SNPs are partitioned into clusters of highly correlated SNPs, and the MLC test statistic quadratically combines linear combination statistics constructed for each cluster. The test has degrees of freedom equal to the number of clusters and can be more powerful than a fully quadratic or fully linear test statistic. In this study, we develop a new SNP clustering algorithm designed to find cliques, which are complete subnetworks of SNPs with all pairwise correlations above a threshold. We evaluate the performance of the MLC test using the clique-based CLQ algorithm versus using the tag-SNP-based LDSelect algorithm. In our numerical power calculations we observed that the two clustering algorithms produce identical clusters about 40~60% of the time, yielding similar power on average. However, because the CLQ algorithm tends to produce smaller clusters with stronger positive correlation, the MLC test is less likely to be affected by the occurrence of opposing signs in the individual SNP effect coefficients.

  14. A SNP Harvester Analysis to Better Detect SNPs of CCDC158 Gene That Are Associated with Carcass Quality Traits in Hanwoo.

    Science.gov (United States)

    Lee, Jea-Young; Lee, Jong-Hyeong; Yeo, Jung-Sou; Kim, Jong-Joo

    2013-06-01

    The purpose of this study was to investigate interaction effects of genes using a Harvester method. A sample of Korean cattle, Hanwoo (n = 476) was chosen from the National Livestock Research Institute of Korea that were sired by 50 Korean proven bulls. The steers were born between the spring of 1998 and the autumn of 2002 and reared under a progeny-testing program at the Daekwanryeong and Namwon branches of NLRI. The steers were slaughtered at approximately 24 months of age and carcass quality traits were measured. A SNP Harvester method was applied with a support vector machine (SVM) to detect significant SNPs in the CCDC158 gene and interaction effects between the SNPs that were associated with average daily gains, cold carcass weight, longissimus dorsi muscle area, and marbling scores. The statistical significance of the major SNP combinations was evaluated with x (2)-statistics. The genotype combinations of three SNPs, g.34425+102 A>T(AA), g.4102636T>G(GT), and g.11614+19G>T(GG) had a greater effect than the rest of SNP combinations, e.g. 0.82 vs. 0.75 kg, 343 vs. 314 kg, 80.4 vs 74.7 cm(2), and 7.35 vs. 5.01, for the four respective traits (pHarvester method is a good option when multiple SNPs and interaction effects are tested. The significant SNPs could be applied to improve meat quality of Hanwoo via marker-assisted selection.

  15. Identification of circular RNAs from the parental genes involved in multiple aspects of cellular metabolism in barley

    DEFF Research Database (Denmark)

    Shirvanehdeh, Behrooz Darbani; Noeparvar, Shahin; Borg, Søren

    2016-01-01

    circular RNAs as novel interactors in the regulation of gene expression in plants and imply the comprehensiveness of this regulatory pathway by identifying circular RNAs for a diverse set of genes. These genes are involved in several aspects of cellular metabolism as hormonal signaling, intracellular...... protein sorting, carbohydrate metabolism and cell-wall biogenesis, respiration, amino acid biosynthesis, transcription and translation, and protein ubiquitination. Additionally, these parental loci of circular RNAs, from both nuclear and mitochondrial genomes, encode for different transcript classes...... and elucidate their cellular-level alterations across tissues and in response to micronutrients iron and zinc. In further support of circular RNAs’ functional roles in plants, we report several cases where fluctuations of circRNAs do not correlate with the levels of their parental-loci encoded linear...

  16. Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model.

    Science.gov (United States)

    Vergo, Sandra; Craner, Matthew J; Etzensperger, Ruth; Attfield, Kathrine; Friese, Manuel A; Newcombe, Jia; Esiri, Margaret; Fugger, Lars

    2011-02-01

    Although there is growing evidence for a role of excess intracellular cations, particularly calcium ions, in neuronal and glial cell injury in multiple sclerosis, as well as in non-inflammatory neurological conditions, the molecular mechanisms involved are not fully determined. We previously showed that the acid-sensing ion channel 1 which, when activated under the acidotic tissue conditions found in inflammatory lesions opens to allow influx of sodium and calcium ions, contributes to axonal injury in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. However, the extent and cellular distribution of acid-sensing ion channel 1 expression in neurons and glia in inflammatory lesions is unknown and, crucially, acid-sensing ion channel 1 expression has not been determined in multiple sclerosis lesions. Here we studied acute and chronic experimental autoimmune encephalomyelitis and multiple sclerosis spinal cord and optic nerve tissues to describe in detail the distribution of acid-sensing ion channel 1 and its relationship with neuronal and glial damage. We also tested the effects of amiloride treatment on tissue damage in the mouse models. We found that acid-sensing ion channel 1 was upregulated in axons and oligodendrocytes within lesions from mice with acute experimental autoimmune encephalomyelitis and from patients with active multiple sclerosis. The expression of acid-sensing ion channel 1 was associated with axonal damage as indicated by co-localization with the axonal injury marker beta amyloid precursor protein. Moreover, blocking acid-sensing ion channel 1 with amiloride protected both myelin and neurons from damage in the acute model, and when given either at disease onset or, more clinically relevant, at first relapse, ameliorated disability in mice with chronic-relapsing experimental autoimmune encephalomyelitis. Together these findings suggest that blockade of acid-sensing ion channel 1 has the potential to provide both neuro

  17. Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds.

    Science.gov (United States)

    Jaganathan, Ganesh K; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

    2017-03-13

    The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h(-1)) suffered significantly higher membrane damage at temperature between -20 °C and -10 °C than slow cooled (3 °Ch(-1)) seeds (P  0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to -20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.

  18. Multiple Kinases Involved in the Nicotinic Modulation of Gamma Oscillations in the Rat Hippocampal CA3 Area

    Science.gov (United States)

    Wang, JianGang; He, XiaoLong; Guo, Fangli; Cheng, XiangLin; Wang, Yali; Wang, XiaoFang; Feng, ZhiWei; Vreugdenhil, Martin; Lu, ChengBiao

    2017-01-01

    Neuronal synchronization at gamma band frequency (20–80 Hz, γ oscillations) is closely associated with higher brain function, such as learning, memory and attention. Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the hippocampus, and modulate hippocampal γ oscillations, but the intracellular mechanism underlying such modulation remains elusive. We explored multiple kinases by which nicotine can modulate γ oscillations induced by kainate in rat hippocampal area CA3 in vitro. We found that inhibitors of cyclic AMP dependent kinase (protein kinase A, PKA), protein kinase C (PKC), N-methyl-D-aspartate receptor (NMDA) receptors, Phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinases (ERK), each individually could prevent the γ oscillation-enhancing effect of 1 μM nicotine, whereas none of them affected baseline γ oscillation strength. Inhibition of the serine/threonine kinase Akt increased baseline γ oscillations and partially blocked its nicotinic enhancement. We propose that the PKA-NMDAR-PI3K-ERK pathway modifies cellular properties required for the nicotinic enhancement of γ oscillations, dependent on a PKC-ERK mediated pathway. These signaling pathways provide clues for restoring γ oscillations in pathological conditions affecting cognition. The suppression of γ oscillations at 100 μM nicotine was only dependent on PKA-NMDAR activation and may be due to very high intracellular calcium levels.

  19. Growth inhibition and apoptosis in cancer cells induced by polyphenolic compounds of Acacia hydaspica: Involvement of multiple signal transduction pathways

    Science.gov (United States)

    Afsar, Tayyaba; Trembley, Janeen H.; Salomon, Christine E.; Razak, Suhail; Khan, Muhammad Rashid; Ahmed, Khalil

    2016-01-01

    Acacia hydaspica R. Parker is known for its medicinal uses in multiple ailments. In this study, we performed bioassay-guided fractionation of cytotoxic compounds from A. hydaspica and investigated their effects on growth and signaling activity in prostate and breast cancer cell lines. Four active polyphenolic compounds were identified as 7-O-galloyl catechin (GC), catechin (C), methyl gallate (MG), and catechin-3-O-gallate (CG). The four compounds inhibited prostate cancer PC-3 cell growth in a dose-dependent manner, whereas CG and MG inhibited breast cancer MDA-MB-231 cell growth. All tested compounds inhibited cell survival and colony growth in both cell lines, and there was evidence of chromatin condensation, cell shrinkage and apoptotic bodies. Further, acridine orange, ethidium bromide, propidium iodide and DAPI staining demonstrated that cell death occurred partly via apoptosis in both PC-3 and MDA-MB-231 cells. In PC-3 cells treatment repressed the expression of anti-apoptotic molecules Bcl-2, Bcl-xL and survivin, coupled with down-regulation of signaling pathways AKT, NFκB, ERK1/2 and JAK/STAT. In MDA-MB-231 cells, treatment induced reduction of CK2α, Bcl-xL, survivin and xIAP protein expression along with suppression of NFκB, JAK/STAT and PI3K pathways. Our findings suggest that certain polyphenolic compounds derived from A. hydaspica may be promising chemopreventive/therapeutic candidates against cancer. PMID:26975752

  20. Vacuolar transport in tobacco leaf epidermis cells involves a single route for soluble cargo and multiple routes for membrane cargo.

    Science.gov (United States)

    Bottanelli, Francesca; Foresti, Ombretta; Hanton, Sally; Denecke, Jürgen

    2011-08-01

    We tested if different classes of vacuolar cargo reach the vacuole via distinct mechanisms by interference at multiple steps along the transport route. We show that nucleotide-free mutants of low molecular weight GTPases, including Rab11, the Rab5 members Rha1 and Ara6, and the tonoplast-resident Rab7, caused induced secretion of both lytic and storage vacuolar cargo. In situ analysis in leaf epidermis cells indicates a sequential action of Rab11, Rab5, and Rab7 GTPases. Compared with Rab5 members, mutant Rab11 mediates an early transport defect interfering with the arrival of cargo at prevacuoles, while mutant Rab7 inhibits the final delivery to the vacuole and increases cargo levels in prevacuoles. In contrast with soluble cargo, membrane cargo may follow different routes. Tonoplast targeting of an α-TIP chimera was impaired by nucleotide-free Rha1, Ara6, and Rab7 similar to soluble cargo. By contrast, the tail-anchored tonoplast SNARE Vam3 shares only the Rab7-mediated vacuolar deposition step. The most marked difference was observed for the calcineurin binding protein CBL6, which was insensitive to all Rab mutants tested. Unlike soluble cargo, α-TIP and Vam3, CBL6 transport to the vacuole was COPII independent. The results indicate that soluble vacuolar proteins follow a single route to vacuoles, while membrane spanning proteins may use at least three different transport mechanisms.

  1. Assembly of ROMK1 (Kir 1.1a) inward rectifier K+ channel subunits involves multiple interaction sites.

    Science.gov (United States)

    Koster, J C; Bentle, K A; Nichols, C G; Ho, K

    1998-04-01

    The ROMK1 (Kir 1.1a) channel is formed by a tetrameric complex of subunits, each characterized by cytoplasmic N- and C-termini and a core region of two transmembrane helices flanking a pore-forming segment. To delineate the general regions mediating the assembly of ROMK1 subunits we constructed epitope-tagged N-terminal, C-terminal, and transmembrane segment deletion mutants. Nonfunctional subunits with N-terminal, core region, and C-terminal deletions had dominant negative effects when coexpressed with wild-type ROMK1 subunits in Xenopus oocytes. In contrast, coexpression of these nonfunctional subunits with Kv 2.1 (DRK1) did not suppress Kv 2.1 currents in control oocytes. Interactions between epitope-tagged mutant and wild-type ROMK1 subunits were studied in parallel by immunoprecipitating [35S]-labeled oocyte membrane proteins. Complexes containing both wild-type and mutant subunits that retained H5, M2, and C-terminal regions were coimmunoprecipitated to a greater extent than complexes consisting of wild-type and mutant subunits with core region and/or C-terminal deletions. The present findings are consistent with the hypothesis that multiple interaction sites located in the core region and cytoplasmic termini of ROMK1 subunits mediate homomultimeric assembly.

  2. Are alpha-blockers involved in lower urinary tract dysfunction in multiple system atrophy? A comparison of prazosin and moxisylyte.

    Science.gov (United States)

    Sakakibara, R; Hattori, T; Uchiyama, T; Suenaga, T; Takahashi, H; Yamanishi, T; Egoshi, K; Sekita, N

    2000-03-15

    Lower urinary tract dysfunction is a major cause of morbidity in patients with multiple system atrophy (MSA). alpha1-Adrenergic receptors are present in the proximal urethra where impaired relaxation may be responsible for voiding difficulty and a large amount of residual urine. An open study was designed to evaluate whether the blockade of these receptors by prazosin (a nonselective alpha1 blocker) and moxisylyte (an alpha1A-selective blocker) would improve bladder emptying in patients with MSA. Post-micturition residual volumes and clinical symptoms of 49 patients with MSA were evaluated at trial entry and after 4 weeks (prazosin; n=21 and moxisylyte; n=28). The respective means for the prazosin and moxisylyte groups were 38.1% and 35.2% reductions in residual urine volume (P<0.05), and there was lessening of urinary symptoms. Side effects due to orthostatic hypotension were seen in 23.8% of the prazosin group but in only 10.7% of the moxisylyte group. These effects were common in patients with postural hypotension of more than -30 mmHg at trial entry (P<0.05). Modulation of alpha1-receptors may function in the management of lower urinary tract dysfunction in MSA.

  3. High irradiance responses involving photoreversible multiple photoreceptors as related to photoperiodic induction of cell division in Euglena.

    Science.gov (United States)

    Bolige, Aoen; Goto, Ken

    2007-02-01

    Little is known about the photoreceptors involved in the photoperiodism of unicellular organisms, which we elucidated by deriving their action spectra. The flagellated alga Euglena gracilis exhibits photoperiodism, with a long-day response in cell reproduction. The underlying clock is a circadian rhythm with photoinductive capability, peaking at subjective dusk and occurring at the 26th hour in continuous darkness (DD) when transferred from continuous light (LL); it regulates photoinduction, a high-irradiance response (HIR), of a dark-capability of progressing through cell division. We derived the action spectra by irradiating E. gracilis with monochromatic light for 3h at around the 26th hour; the action maxima occurred at 380, 450-460, 480, 610, 640, 660, 680, and 740nm. Except for the maximum at 450-460nm, which was always a major maximum, the maxima greatly depended on the red (R)/far-red (FR) ratio of the prior LL. The high R/FR ratio resulted in a dominant major peak at 640nm and minor peaks at 480 and 680nm, whereas the low ratio resulted in dominant major peaks at 610 and 740nm and minor peaks at 380 and 660nm; the critical fluence was minimally about 60mmolm(-2). These HIRs resulted from the accumulation of corresponding low-fluence responses (LFRs) because we found that repetition of a 3-min light/dark cycle, with critical fluences of 1mmolm(-2), lasting for 3h resulted in the same photoinduction as the continuous 3-h irradiation. Moreover, these LFRs expressed photoreversibility. Thus, photoperiodic photoinduction involves Euglena-phytochrome (640 and 740nm) and blue photoreceptor (460nm). Although 380, 480, 610, 660, and 680nm may also represent Euglena-phytochrome, a definite conclusion awaits further study.

  4. ASSESSMENT OF CHAROLAIS BULLS POPULATION STRUCTURE BASED ON SNPs ANALYSES

    Directory of Open Access Journals (Sweden)

    Nina Moravčíková

    2014-02-01

    Full Text Available The aim of this study was identification of SNPs in leptin (LEP, leptin receptor (LEPR, growth hormone (GH and specific pituitary transcription factor (Pit-1 genes in order to analyze genetic structure of Charolais bulls’ population. The total numbers of genomic DNA samples were taken from 52 breeding bulls and analyzed by PCR-RFLP method. After digestion with restriction enzymes were detected in bulls’ population alleles with frequency: LEP/Sau3AI A 0.83 and B 0.17 (±0.037; LEPR/BseGI C 0.95 and T 0.05 (±0.021, GH/AluI L 0.62 and V 0.38 (±0.048 and Pit1/HinfI A 0.40 and B 0.60 (±0.048. Based on the observed vs. expected genotypes frequencies population across loci were in Hardy-Weinberg equilibrium (P>0.05, only in case of Pit-1 locus was detected disequilibrium. Predominant were in analyzed breeding bulls LEP/Sau3AIAA (0.69, LEPR/T945MCC (0.90, GH/AluILL (0.43 and Pit-1/HinfIAB (0.65 genotypes. The observed heterozygosity of SNPs was also transferred to the low (LEP/Sau3AI/0.248 and LEPR/T945M/0.088 or median polymorphic information content (GH/AluI/0.366 and Pit-1/HinfI/0.370. Within genetic variability estimating negative (LEPR/T945M and Pit-1/HinfI and positive values (LEP/Sau3AI and GH/AluI of fixation indexes FIS indicating slight heterozygote excess or deficiency based on analyzed genetic marker were observed.

  5. Central cholinergic involvement in sequential behavior: impairments of performance by atropine in a serial multiple choice task for rats.

    Science.gov (United States)

    Fountain, Stephen B; Rowan, James D; Wollan, Michael O

    2013-11-01

    Two experiments examined whether muscarinic cholinergic systems play a role in rats' ability to perform well-learned highly-structured serial response patterns, particularly focusing on rats' performance on pattern elements learned by encoding rules versus by acquisition of stimulus-response (S-R) associations. Rats performed serial patterns of responses in a serial multiple choice task in an 8-lever circular array for hypothalamic brain-stimulation reward. Two experiments examined the effects of atropine, a centrally-acting muscarinic cholinergic receptor antagonist, on rats' ability to perform pattern elements where responses were controlled by rules versus elements, such as rule-inconsistent "violation elements" and elements following "phrasing cues," where responses were controlled by associative cues. In Experiment 1, 3-element chunks of both patterns were signaled by pauses that served as phrasing cues before chunk-boundary elements, but one pattern also included a violation element that was inconsistent with pattern structure. Once rats reached a high criterion of performance, the drug challenge was intraperitoneal injection of a single dose of 50 mg/kg atropine sulfate. Atropine impaired performance on elements learned by S-R learning, namely, chunk-boundary elements and the violation element, but had no effect on performance of rule-based within-chunk elements. In Experiment 2, patterns were phrased and unphrased perfect patterns (i.e., without violation elements). To control for peripheral effects of atropine, rats were treated with a series of doses of either centrally-acting atropine or peripherally-acting atropine methyl nitrate (AMN), which does not cross the blood-brain barrier. Once rats reached a high criterion, the drug challenges were on alternate days in the order 50, 25, and 100 mg/kg of either atropine sulfate or AMN. Atropine, but not AMN, impaired performance in the phrased perfect pattern for pattern elements where S-R associations were

  6. Multiple intracellular signallings involved in regulation of on channels by GH releasing or inhibitory hormones in pituitary somatotropes

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Influx of Ca2- via Ca2+ channels is the major step triggering exocytosis of pituitary somatotropes to release growth hormone (GH). Voltage-gated Ca2+ and K+ channels, the primary determinants of the influx of Ca2+ in somatotropes, are regulated by GH-releasing hornone (GHRH) and somatostatin (SRIF) through G protein-coupled signalling systems. Using whole-cell patch-clamp techniques, the changes of the Ca2+ and K+ currents in primary cultured somatotropes were recorded and signalling systems were studied using pharmacological reagents and intracellular dialysis of non-permeable molecules including antibodies and antisense oligonucleotides. GHRH increased both L-and T-types Ca2+ currents and decreased transient (I4) and delayed rectified (Ik) K+ currents. The increase in Ca2+ currents by GHRH was mediated by cAMP/protein kinase A system but the decrease in K+ currents required normal function of protein kinase C system. The GHRH-induced alteration of Ca2+ and K+ currents augments the influx of Ca2+ , leading to an increase in the [ Ca2+ ]i and the GH secretion. In contrary, a significant reduction in Ca2+ currents and increase in K currents were obtained in response to SRIF. The ion channel response to SRIF was demonstrated as a membrane delimited pathway and can be recorded by classic whole-cell configuration, Intracellular dialysis of anti-αi3 antibodies attenuated the increase in K + currents by SRIF whereas anti-αo antibodies blocked the reduction in the Ca2+ current by SRIF. Dialysis of antisense oligonucleotides specific for αo2 sub-units also attenuated the inhibition of SRIF on the Ca2+current. The Gi3 protein mediated the increase in K + currents and the Go2 protein mediated the reduction in the Ca2 +current by SRIF. The SRIF-induced alteration of Ca2 + and K + currents diminished the influx of Ca2+ , leading to a decrease in the [ Ca2+ ]i and the GH secretion. It is therefore concluded that multiple signalling systems are employed in the ion channel

  7. Familial ainhum: A case report of multiple toe involvement in a father and son, staging of ainhum with insight into different types of constricting bands

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    B T Priya

    2015-01-01

    Full Text Available Ainhum, also known as dactylolysis spontanea, is a painful constriction of the base of the fifth toe, frequently followed by spontaneous amputation a few years later. The disease is often symmetrical on both the feet, but, occasionally, other toes are also affected and rarely the distal phalanx of the fifth finger. Pseudoainhum is a similar condition that occurs as a secondary event resulting from certain hereditary and nonhereditary diseases that lead to annular constriction of digits. We hereby present a case of familial ainhum in father and son with multiple toes affected, autoamputation, and more involvement of fourth toe than the fifth toe, which is a very rare finding.

  8. Familial ainhum: a case report of multiple toe involvement in a father and son, staging of ainhum with insight into different types of constricting bands.

    Science.gov (United States)

    Priya, Bt; Suganthy, Rajakumari R; Manimegalai, M; Krishnaveni, A

    2015-01-01

    Ainhum, also known as dactylolysis spontanea, is a painful constriction of the base of the fifth toe, frequently followed by spontaneous amputation a few years later. The disease is often symmetrical on both the feet, but, occasionally, other toes are also affected and rarely the distal phalanx of the fifth finger. Pseudoainhum is a similar condition that occurs as a secondary event resulting from certain hereditary and nonhereditary diseases that lead to annular constriction of digits. We hereby present a case of familial ainhum in father and son with multiple toes affected, autoamputation, and more involvement of fourth toe than the fifth toe, which is a very rare finding.

  9. Transcriptional activation of multiple operons involved in para-nitrophenol degradation by Pseudomonas sp. Strain WBC-3.

    Science.gov (United States)

    Zhang, Wen-Mao; Zhang, Jun-Jie; Jiang, Xuan; Chao, Hongjun; Zhou, Ning-Yi

    2015-01-01

    Pseudomonas sp. strain WBC-3 utilizes para-nitrophenol (PNP) as a sole carbon and energy source. The genes involved in PNP degradation are organized in the following three operons: pnpA, pnpB, and pnpCDEFG. How the expression of the genes is regulated is unknown. In this study, an LysR-type transcriptional regulator (LTTR) is identified to activate the expression of the genes in response to the specific inducer PNP. While the LTTR coding gene pnpR was found to be not physically linked to any of the three catabolic operons, it was shown to be essential for the growth of strain WBC-3 on PNP. Furthermore, PnpR positively regulated its own expression, which is different from the function of classical LTTRs. A regulatory binding site (RBS) with a 17-bp imperfect palindromic sequence (GTT-N11-AAC) was identified in all pnpA, pnpB, pnpC, and pnpR promoters. Through electrophoretic mobility shift assays and mutagenic analyses, this motif was proven to be necessary for PnpR binding. This consensus motif is centered at positions approximately -55 bp relative to the four transcriptional start sites (TSSs). RBS integrity was required for both high-affinity PnpR binding and transcriptional activation of pnpA, pnpB, and pnpR. However, this integrity was essential only for high-affinity PnpR binding to the promoter of pnpCDEFG and not for its activation. Intriguingly, unlike other LTTRs studied, no changes in lengths of the PnpR binding regions of the pnpA and pnpB promoters were observed after the addition of the inducer PNP in DNase I footprinting.

  10. Involvement of multiple stressors induced by non-thermal plasma-charged aerosols during inactivation of airborne bacteria

    Science.gov (United States)

    Vaze, Nachiket D.; Park, Sin; Brooks, Ari D.; Fridman, Alexander; Joshi, Suresh G.

    2017-01-01

    A lab-scale, tunable, single-filament, point-to-point nonthermal dieletric-barrier discharge (DBD) plasma device was built to study the mechanisms of inactivation of aerosolized bacterial pathogens. The system inactivates airborne antibiotic-resistant pathogens efficiently. Nebulization mediated pre-optimized (4 log and 7 log) bacterial loads were challenged to plasma-charged aerosols, and lethal and sublethal doses determined using colony assay, and cell viability assay; and the loss of membrane potential and cellular respiration were determined using cell membrane potential assay and XTT assay. Using the strategies of Escherichia coli wildtype, over-expression mutant, deletion mutants, and peroxide and heat stress scavenging, we analyzed activation of intracellular reactive oxygen species (ROS) and heat shock protein (hsp) chaperons. Superoxide dismutase deletion mutants (ΔsodA, ΔsodB, ΔsodAΔsodB) and catalase mutants ΔkatG and ΔkatEΔkatG did not show significant difference from wildtype strain, and ΔkatE and ΔahpC was found significantly more susceptible to cell death than wildtype. The oxyR regulon was found to mediate plasma-charged aerosol-induced oxidative stress in bacteria. Hsp deficient E. coli (ΔhtpG, ΔgroEL, ΔclpX, ΔgrpE) showed complete inactivation of cells at ambient temperature, and the treatment at cold temperature (4°C) significantly protected hsp deletion mutants and wildtype cells, and indicate a direct involvement of hsp in plasma-charged aerosol mediated E. coli cell death. PMID:28166240

  11. The pressor effect of angiotensin-(1-7 in the rat rostral ventrolateral medulla involves multiple peripheral mechanisms

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    Rita C. Oliveira

    2013-01-01

    Full Text Available OBJECTIVE: In the present study, the peripheral mechanism that mediates the pressor effect of angiotensin-(1-7 in the rostral ventrolateral medulla was investigated. METHOD: Angiotensin-(1-7 (25 pmol was bilaterally microinjected in the rostral ventrolateral medulla near the ventral surface in urethane-anesthetized male Wistar rats that were untreated or treated (intravenously with effective doses of selective autonomic receptor antagonists (atenolol, prazosin, methyl-atropine, and hexamethonium or a vasopressin V1 receptor antagonist [d(CH25 -Tyr(Me-AVP] given alone or in combination. RESULTS: Unexpectedly, the pressor response produced by angiotensin-(1-7 (16 ± 2 mmHg, n = 12, which was not associated with significant changes in heart rate, was not significantly altered by peripheral treatment with prazosin, the vasopressin V1 receptor antagonist, hexamethonium or methyl-atropine. Similar results were obtained in experiments that tested the association of prazosin and atenolol; methyl-atropine and the vasopressin V1 antagonist or methyl-atropine and prazosin. Peripheral treatment with the combination of prazosin, atenolol and the vasopressin V1 antagonist abolished the pressor effect of glutamate; however, this treatment produced only a small decrease in the pressor effect of angiotensin-(1-7 at the rostral ventrolateral medulla. The combination of hexamethonium with the vasopressin V1 receptor antagonist or the combination of prazosin, atenolol, the vasopressin V1 receptor antagonist and methyl-atropine was effective in blocking the effect of angiotensin-(1-7 at the rostral ventrolateral medulla. CONCLUSION: These results indicate that angiotensin-(1-7 triggers a complex pressor response at the rostral ventrolateral medulla that involves an increase in sympathetic tonus, release of vasopressin and possibly the inhibition of a vasodilatory mechanism.

  12. Global identification of multiple OsGH9 family members and their involvement in cellulose crystallinity modification in rice.

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    Guosheng Xie

    Full Text Available Plant glycoside hydrolase family 9 (GH9 comprises typical endo-β-1,4-glucanase (EGases, EC3.2.1.4. Although GH9A (KORRIGAN family genes have been reported to be involved in cellulose biosynthesis in plants, much remains unknown about other GH9 subclasses. In this study, we observed a global gene co-expression profiling and conducted a correlation analysis between OsGH9 and OsCESA among 66 tissues covering most periods of life cycles in 2 rice varieties. Our results showed that OsGH9A3 and B5 possessed an extremely high co-expression with OsCESA1, 3, and 8 typical for cellulose biosynthesis in rice. Using two distinct rice non-GH9 mutants and wild type, we performed integrative analysis of gene expression level by qRT-PCR, cellulase activities in situ and in vitro, and lignocellulose crystallinity index (CrI in four internodes of stem tissues. For the first time, OsGH9B1, 3, and 16 were characterized with the potential role in lignocellulose crystallinity alteration in rice, whereas OsGH9A3 and B5 were suggested for cellulose biosynthesis. In addition, phylogenetic analysis and gene co-expression comparison revealed GH9 function similarity in Arabidopsis and rice. Hence, the data can provide insights into GH9 function in plants and offer the potential strategy for genetic manipulation of plant cell wall using the five aforementioned novel OsGH9 genes.

  13. Identification of Multiple Dehalogenase Genes Involved in Tetrachloroethene-to-Ethene Dechlorination in a Dehalococcoides-Dominated Enrichment Culture

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    Mohamed Ismaeil

    2017-01-01

    Full Text Available Chloroethenes (CEs are widespread groundwater toxicants that are reductively dechlorinated to nontoxic ethene (ETH by members of Dehalococcoides. This study established a Dehalococcoides-dominated enrichment culture (designated “YN3” that dechlorinates tetrachloroethene (PCE to ETH with high dechlorination activity, that is, complete dechlorination of 800 μM PCE to ETH within 14 days in the presence of Dehalococcoides species at 5.7±1.9×107 copies of 16S rRNA gene/mL. The metagenome of YN3 harbored 18 rdhA genes (designated YN3rdhA1–18 encoding the catalytic subunit of reductive dehalogenase (RdhA, four of which were suggested to be involved in PCE-to-ETH dechlorination based on significant increases in their transcription in response to CE addition. The predicted proteins for two of these four genes, YN3RdhA8 and YN3RdhA16, showed 94% and 97% of amino acid similarity with PceA and VcrA, which are well known to dechlorinate PCE to trichloroethene (TCE and TCE to ETH, respectively. The other two rdhAs, YN3rdhA6 and YN3rdhA12, which were never proved as rdhA for CEs, showed particularly high transcription upon addition of vinyl chloride (VC, with 75±38 and 16±8.6 mRNA copies per gene, respectively, suggesting their possible functions as novel VC-reductive dehalogenases. Moreover, metagenome data indicated the presence of three coexisting bacterial species, including novel species of the genus Bacteroides, which might promote CE dechlorination by Dehalococcoides.

  14. dbQSNP: a database of SNPs in human promoter regions with allele frequency information determined by single-strand conformation polymorphism-based methods.

    Science.gov (United States)

    Tahira, Tomoko; Baba, Shingo; Higasa, Koichiro; Kukita, Yoji; Suzuki, Yutaka; Sugano, Sumio; Hayashi, Kenshi

    2005-08-01

    We present a database, dbQSNP (http://qsnp.gen.kyushu-u.ac.jp/), that provides sequence and allele frequency information for single-nucleotide polymorphisms (SNPs) located in the promoter regions of human genes, which were defined by the 5' ends of full-length cDNA clones. We searched for the SNPs in these regions by sequencing or single-strand conformation polymorphism (SSCP) analysis. The allele frequencies of the identified SNPs in two ethnic groups were quantified by SSCP analyses of pooled DNA samples. The accuracy of our estimation is supported by strong correlations between the frequencies in our data and those in other databases for the same ethnic groups. The frequencies vary considerably between the two ethnic groups studied, suggesting the need for population-based collections and allele frequency determination of SNPs, in, e.g., association studies of diseases. We show profiles of SNP densities that are characteristic of transcription start site regions. A fraction of the SNPs revealed a significantly different allele frequency between the groups, suggesting differential selection of the genes involved.

  15. Reduced Representation Libraries from DNA Pools Analysed with Next Generation Semiconductor Based-Sequencing to Identify SNPs in Extreme and Divergent Pigs for Back Fat Thickness

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    Samuele Bovo

    2015-01-01

    Full Text Available The aim of this study was to identify single nucleotide polymorphisms (SNPs that could be associated with back fat thickness (BFT in pigs. To achieve this goal, we evaluated the potential and limits of an experimental design that combined several methodologies. DNA samples from two groups of Italian Large White pigs with divergent estimating breeding value (EBV for BFT were separately pooled and sequenced, after preparation of reduced representation libraries (RRLs, on the Ion Torrent technology. Taking advantage from SNAPE for SNPs calling in sequenced DNA pools, 39,165 SNPs were identified; 1/4 of them were novel variants not reported in dbSNP. Combining sequencing data with Illumina PorcineSNP60 BeadChip genotyping results on the same animals, 661 genomic positions overlapped with a good approximation of minor allele frequency estimation. A total of 54 SNPs showing enriched alleles in one or in the other RRLs might be potential markers associated with BFT. Some of these SNPs were close to genes involved in obesity related phenotypes.

  16. Identification of single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of foodborne Bacillus spp.

    Science.gov (United States)

    Fernández-No, I C; Böhme, K; Caamaño-Antelo, S; Barros-Velázquez, J; Calo-Mata, P

    2015-04-01

    The main goal of this work was the identification of single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of foodborne Bacillus spp. that may be useful for typing purposes. These species include, among others, Bacillus cereus, an important pathogenic species involved in food poisoning, and Bacillus licheniformis, Bacillus subtilis and Bacillus pumilus, which are causative agents of food spoilage described as responsible for foodborne disease outbreaks. With this purpose in mind, 52 Bacillus strains isolated from culture collections and fresh and processed food were considered. SNP type "Y" at sites 212 and 476 appeared in the majority of B. licheniformis studied strains. SNP type "R" at site 278 was detected in many strains of the B. subtilis/Bacillus amyloliquefaciens group, while polymorphism "Y" at site 173 was characteristic of the majority of strains of B. cereus/Bacillus thuringiensis group. The analysis of SNPs provided more intra-specific information than phylogenetic analysis in the cases of B. cereus and B. subtilis. Moreover, this study describes novel SNPs that should be considered when designing 16S rRNA-based primers and probes for multiplex-PCR, Real-Time PCR and microarray systems for foodborne Bacillus spp.

  17. Characterization of genome-wide SNPs for the water flea Daphnia pulicaria generated by genotyping-by-sequencing (GBS).

    Science.gov (United States)

    Muñoz, Joaquín; Chaturvedi, Anurag; De Meester, Luc; Weider, Lawrence J

    2016-06-27

    The keystone aquatic herbivore Daphnia has been studied for more than 150 years in the context of evolution, ecology and ecotoxicology. Although it is rapidly becoming an emergent model for environmental and population genomics, there have been limited genome-wide level studies in natural populations. We report a unique resource of novel Single Nucleotide Polymorphic (SNP) markers for Daphnia pulicaria using the reduction in genomic complexity with the restriction enzymes approach, genotyping-by-sequencing. Using the genome of D. pulex as a reference, SNPs were scored for 53 clones from five natural populations that varied in lake trophic status. Our analyses resulted in 32,313 highly confident and bi-allelic SNP markers. 1,364 outlier SNPs were mapped on the annotated D. pulex genome, which identified 2,335 genes, including 565 within functional genes. Out of 885 EuKaryotic Orthologous Groups that we found from outlier SNPs, 294 were involved in three metabolic and four regulatory pathways. Bayesian-clustering analyses showed two distinct population clusters representing the possible combined effects of geography and lake trophic status. Our results provide an invaluable tool for future population genomics surveys in Daphnia targeting informative regions related to physiological processes that can be linked to the ecology of this emerging eco-responsive taxon.

  18. Characterization of genome-wide SNPs for the water flea Daphnia pulicaria generated by genotyping-by-sequencing (GBS)

    Science.gov (United States)

    Muñoz, Joaquín; Chaturvedi, Anurag; De Meester, Luc; Weider, Lawrence J.

    2016-01-01

    The keystone aquatic herbivore Daphnia has been studied for more than 150 years in the context of evolution, ecology and ecotoxicology. Although it is rapidly becoming an emergent model for environmental and population genomics, there have been limited genome-wide level studies in natural populations. We report a unique resource of novel Single Nucleotide Polymorphic (SNP) markers for Daphnia pulicaria using the reduction in genomic complexity with the restriction enzymes approach, genotyping-by-sequencing. Using the genome of D. pulex as a reference, SNPs were scored for 53 clones from five natural populations that varied in lake trophic status. Our analyses resulted in 32,313 highly confident and bi-allelic SNP markers. 1,364 outlier SNPs were mapped on the annotated D. pulex genome, which identified 2,335 genes, including 565 within functional genes. Out of 885 EuKaryotic Orthologous Groups that we found from outlier SNPs, 294 were involved in three metabolic and four regulatory pathways. Bayesian-clustering analyses showed two distinct population clusters representing the possible combined effects of geography and lake trophic status. Our results provide an invaluable tool for future population genomics surveys in Daphnia targeting informative regions related to physiological processes that can be linked to the ecology of this emerging eco-responsive taxon. PMID:27346179

  19. On the path-dependence of the open-cell voltage of a galvanic cell involving a ternary or multinary compound with multiple mobile ionic species under multiple chemical potential gradients.

    Science.gov (United States)

    Yoo, Han-Ill; Martin, Manfred

    2010-11-28

    It is well known that the open-cell voltage (U) of a galvanic cell involving a binary compound, or a multinary compound with a single kind of mobile ionic species, is a state property under a gradient of chemical potential of the mobile component. It is not so transparent, however, whether U is still a state property when involving a ternary or multinary compound with two or more kinds of mobile ions under multiple chemical potential gradients of those mobile components. We clarify this issue with a multinary oxide that conducts oxide ions, protons and electron holes and is exposed to the chemical potential gradients of both water and oxygen. We show that U is path- and history-dependent, and manifests itself along the diffusion paths of the two mobile components H and O under given boundary conditions.

  20. Computational and Structural Investigation of Deleterious Functional SNPs in Breast Cancer BRCA2 Gene

    Institute of Scientific and Technical Information of China (English)

    Rajasekaran R; George Priya Doss; Sudandiradoss C; Ramanathan K; Rituraj Purohit; Rao Sethumadhavan

    2008-01-01

    In this work, we have analyzed the genetic variation that can alter the expression and the function in BRCA2 gene using computational methods. Out of the total 534 SNPs, 101 were found to be non synonymous (nsSNPs). Among the 7 SNPs in the untranslated region, 3 SNPs were found in 5′ and 4 SNPs were found in 3′ un-translated regions (UTR). Of the nsSNPs 20.7% were found to be damaging by both SIFT and PolyPhen server among the 101 nsSNPs investigated. UTR resource tool suggested that 2 SNPs in the 5′ UTR region and 4 SNPs in the 3′ UTR regions might change the protein expression levels. The mutation from asparagine to isoleucine at the position 3124 of the native protein of BRCA2 gene was most deleterious by both SIFT and PolyPhen servers. A structural analysis of this mutated protein and the native protein was made which had an RMSD value of 0.301 nm. Based on this work, we proposed that this most deleterious nsSNP with an SNPid rs28897759 is an important candidate for the cause of breast cancer by BRCA2 gene.

  1. Impact of SNPs on Protein Phosphorylation Status in Rice (Oryza sativa L.

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    Shoukai Lin

    2016-11-01

    Full Text Available Single nucleotide polymorphisms (SNPs are widely used in functional genomics and genetics research work. The high-quality sequence of rice genome has provided a genome-wide SNP and proteome resource. However, the impact of SNPs on protein phosphorylation status in rice is not fully understood. In this paper, we firstly updated rice SNP resource based on the new rice genome Ver. 7.0, then systematically analyzed the potential impact of Non-synonymous SNPs (nsSNPs on the protein phosphorylation status. There were 3,897,312 SNPs in Ver. 7.0 rice genome, among which 9.9% was nsSNPs. Whilst, a total 2,508,261 phosphorylated sites were predicted in rice proteome. Interestingly, we observed that 150,197 (39.1% nsSNPs could influence protein phosphorylation status, among which 52.2% might induce changes of protein kinase (PK types for adjacent phosphorylation sites. We constructed a database, SNP_rice, to deposit the updated rice SNP resource and phosSNPs information. It was freely available to academic researchers at http://bioinformatics.fafu.edu.cn. As a case study, we detected five nsSNPs that potentially influenced heterotrimeric G proteins phosphorylation status in rice, indicating that genetic polymorphisms showed impact on the signal transduction by influencing the phosphorylation status of heterotrimeric G proteins. The results in this work could be a useful resource for future experimental identification and provide interesting information for better rice breeding.

  2. Transcriptome assembly and identification of genes and SNPs associated with growth traits in largemouth bass (Micropterus salmoides).

    Science.gov (United States)

    Li, Shengjie; Liu, Hao; Bai, Junjie; Zhu, Xinping

    2017-04-01

    Growth is one of the most crucial economic traits of all aquaculture species, but the molecular mechanisms involved in growth of largemouth bass (Micropterus salmoides) are poorly understood. The objective of this study was to screen growth-related genes of M. salmoides by RNA sequencing and identify growth-related single-nucleotide polymorphism (SNP) markers through a growth association study. The muscle transcriptomes of fast- and slow-growing largemouth bass were obtained using the RNA-Seq technique. A total of 54,058,178 and 54,742,444 qualified Illumina read pairs were obtained for the fast-growing and slow-growing groups, respectively, giving rise to 4,865,236,020 and 4,926,819,960 total clean bases, respectively. Gene expression profiling showed that 3,530 unigenes were differentially expressed between the fast-growing and slow-growing phenotypes (false discovery rate ≤0.001, the absolute value of log2 (fold change) ≥1), including 1,441 up-regulated and 2,889 down-regulated unigenes in the fast-growing largemouth bass. Analysis of these genes revealed that several signalling pathways, including the growth hormone-insulin-like growth factor 1 axis and signalling pathway, the glycolysis pathway, and the myostatin/transforming growth factor beta signalling pathway, as well as heat shock protein, cytoskeleton, and myofibril component genes might be associated with muscle growth. From these genes, 10 genes with putative SNPs were selected, and 17 SNPs were genotyped successfully. Marker-trait analysis in 340 individuals of Youlu No. 1 largemouth bass revealed three SNPs associated with growth in key genes (phosphoenolpyruvate carboxykinase 1, FOXO3b, and heat shock protein beta-1). This research provides information about key genes and SNPs related to growth, providing new clues to understanding the molecular basis of largemouth bass growth.

  3. Traf2- and Nck-interacting kinase (TNIK) is involved in the anti-cancer mechanism of dovitinib in human multiple myeloma IM-9 cells.

    Science.gov (United States)

    Chon, Hae Jung; Lee, Yura; Bae, Kyoung Jun; Byun, Byung Jin; Kim, Soon Ae; Kim, Jiyeon

    2016-07-01

    Traf2- and Nck-interacting kinase (TNIK) is a member of the germinal center kinase family. TNIK was first identified as a kinase that is involved in regulating cytoskeletal organization in many types of cells, and it was recently proposed as a novel therapeutic target in several types of human cancers. Although previous studies suggest that TNIK plays a pivotal role in cancer cell survival and prognosis, its function in hematological cancer cell survival has not been investigated. Here we investigated the relationship between TNIK function and cell viability in multiple myeloma IM-9 cells using TNIK small interfering RNA (siRNA) transfection and dovitinib treatment. Treatment of IM-9 cells with TNIK siRNA and dovitinib treatment reduced cell proliferation. The ATP competing kinase assay and western blot analysis showed that dovitinib strongly inhibited both the interaction of TNIK with ATP (K i, 13 nM) and the activation of Wnt signaling effectors such as β-catenin and TCF4. Dovitinib also induced caspase-dependent apoptosis in IM-9 cells without significant cytotoxicity in PBMCs. Our results provide new evidence that TNIK may be involved in the proliferation of multiple myeloma IM-9 cells and in the anti-cancer activity of dovitinib via inhibition of the endogenous Wnt signaling pathway.

  4. Treatment of degloving injury involving multiple fingers with combined abdominal superficial fascial flap, dorsalis pedis flap, dorsal toe flap, and toe-web flap.

    Science.gov (United States)

    Han, Fengshan; Wang, Guangnan; Li, Gaoshan; Ping, Juan; Mao, Zhi

    2015-01-01

    Our aim was to summarize the treatment of degloving injury involving multiple fingers using combined abdominal superficial fascial flap, dorsalis pedis flap, dorsal toe flap, and toe-web flap. Each degloved finger was debrided under microscopic guidance and embedded in the superficial layer of the abdominal fascia. The abdominal skin was sutured to the skin on the back and side of the hand to promote circumferential healing. After removal, the only remaining injured region was on the flexor surface, and this was repaired by multiple dorsal toe flaps, toe-web flaps, and dorsalis pedis flaps to provide blood vessels and sensory nerves. All fingers had proper flap thickness 3-6 months after surgery, and required only lateral Z-plasty modification with web deepening and widening to narrow the fingers and extend their relative length. We completed flap-graft and finger narrowing for 25 fingers in eight patients. Abdominal skin flaps and dorsal toe flaps were grafted, and resulted in both firmness and softness, providing finger flexibility. The dorsal toe flap provided good blood circulation and sensory nerves, and was used to cover the finger-flexor surface to regain sensation and stability when holding objects. During the 1-8 years of follow-up, sensation on the finger-flexor side recovered to the S3-4 level, and patient satisfaction based on the Michigan Hand Outcomes Questionnaire was 4-5. Flap ulcers or bone/tendon necrosis were not observed. Treatment of degloving injury involving multiple fingers with combined abdominal superficial fascial flap, dorsalis pedis flap, dorsal toe flap, and toe-web flap was effective and reliable.

  5. Characterization of SNPs associated with prostate cancer in men of Ashkenazic descent from the set of GWAS identified SNPs: impact of cancer family history and cumulative SNP risk prediction.

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    Ilir Agalliu

    Full Text Available BACKGROUND: Genome-wide association studies (GWAS have identified multiple SNPs associated with prostate cancer (PrCa. Population isolates may have different sets of risk alleles for PrCa constituting unique population and individual risk profiles. METHODS: To test this hypothesis, associations between 31 GWAS SNPs of PrCa were examined among 979 PrCa cases and 1,251 controls of Ashkenazic descent using logistic regression. We also investigated risks by age at diagnosis, pathological features of PrCa, and family history of cancer. Moreover, we examined associations between cumulative number of risk alleles and PrCa and assessed the utility of risk alleles in PrCa risk prediction by comparing the area under the curve (AUC for different logistic models. RESULTS: Of the 31 genotyped SNPs, 8 were associated with PrCa at p ≤ 0.002 (corrected p-value threshold with odds ratios (ORs ranging from 1.22 to 1.42 per risk allele. Four SNPs were associated with aggressive PrCa, while three other SNPs showed potential interactions for PrCa by family history of PrCa (rs8102476; 19q13, lung cancer (rs17021918; 4q22, and breast cancer (rs10896449; 11q13. Men in the highest vs. lowest quartile of cumulative number of risk alleles had ORs of 3.70 (95% CI 2.76-4.97; 3.76 (95% CI 2.57-5.50, and 5.20 (95% CI 2.94-9.19 for overall PrCa, aggressive cancer and younger age at diagnosis, respectively. The addition of cumulative risk alleles to the model containing age at diagnosis and family history of PrCa yielded a slightly higher AUC (0.69 vs. 0.64. CONCLUSION: These data define a set of risk alleles associated with PrCa in men of Ashkenazic descent and indicate possible genetic differences for PrCa between populations of European and Ashkenazic ancestry. Use of genetic markers might provide an opportunity to identify men at highest risk for younger age of onset PrCa; however, their clinical utility in identifying men at highest risk for aggressive cancer remains

  6. Computational screening and molecular dynamics simulation of disease associated nsSNPs in CENP-E

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Ambuj [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India); Purohit, Rituraj, E-mail: riturajpurohit@gmail.com [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India)

    2012-10-15

    Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors. Mutations in centroemere proteins have been observed in promoting aneuploidy and tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP-E) is involved in inducing cancers. In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP, MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding affinity of ATP molecule to the CENP-E motor domain. Complementarity scores obtained from docking studies showed significant loss in ATP binding affinity of mutant structure. Molecular dynamics simulation was carried to examine the structural consequences of Y63H mutation. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R{sub g}), solvent accessibility surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector projection, trace of covariance matrix and atom density analysis results showed notable loss in stability for mutant structure. Y63H mutation was also shown to disrupt the native conformation of ATP binding region in CENP-E motor domain. Docking studies for remaining 18 mutations at 63rd residue position as well as other two computationally predicted disease associated mutations S22L and P69S were also carried to investigate their affect on ATP binding affinity of CENP-E motor domain. Our study provided a promising computational methodology to study the tumorigenic consequences of nsSNPs that have not been characterized and clear clue to the wet lab scientist.

  7. DNA chip-based expression profile analysis indicates involvement of the phosphatidylinositol signaling pathway in multiple plant responses to hormone and abiotic treatments

    Institute of Scientific and Technical Information of China (English)

    Wen Hui LIN; Rui YE; Hui MA; Zhi Hong XU; Hong Wei XUE

    2004-01-01

    The phosphatidylinositol (PI) metabolic pathway is considered critical in plant responses to many environmental factors,and previous studies have indicated the involvement of multiple PI-related gene families during cellular responses.Through a detailed analysis of the Arabidopsis thaliana genome,82 polypeptides were identified as being involved in PI signaling. These could be grouped into different families including PI synthases (PIS),PI-phosphate kinases (PIPK),phospholipases (PL),inositol polyphosphate phosphatases (IPPase),inositol polyphosphate kinases (IPK),PI transfer proteins and putative inositol polyphosphate receptors. The presence of more than 10 isoforms of PIPK,PLC,PLD and IPPase suggested that these genes might be differentially expressed during plant cellular responses or growth and development. Accordingly,DNA chip technology was employed to study the expression patterns of various isoforms.In total,79 mRNA clones were amplified and used for DNA chip generation. Expression profile analysis was performed using samples that represented multiple tissues or cellular responses. Tested samples included normal leaf,stem and flower tissues,and leaves from plants treated with various hormones (auxin,cytokinin,gibberellin,abscisic acid and brassinosteroid) or environmental factors (temperature,calcium,sodium,drought,salicylic acid and jasmonic acid).Results showed that many PI pathway-related genes were differentially expressed under these experimental conditions.In particular,the different isoforms of each family were specifically expressed in many cases,suggesting their involvement in tissue specificity and cellular responses to environmental conditions. This work provides a starting point for functional studies of the relevant PI-related proteins and may help shed light onto the role of PI pathways in development and cellular responses.

  8. Linking neuroscientific research on decision making to the educational context of novice students assigned to a multiple-choice scientific task involving common misconceptions about electrical circuits

    Directory of Open Access Journals (Sweden)

    Patrice ePotvin

    2014-01-01

    Full Text Available Functional magnetic resonance imaging was used to identify the brain-based mechanisms of uncertainty and certainty associated with answers to multiple-choice questions involving common misconceptions about electric circuits. Twenty-two (22 scientifically novice participants (humanities and arts college students were asked, in an fMRI study, whether or not they thought the light bulbs in images presenting electric circuits were lighted up correctly, and if they were certain or uncertain of their answers. When participants reported that they were unsure of their responses, analyses revealed significant activations in brain areas typically involved in uncertainty (anterior cingulate cortex, anterior insula cortex, and superior/dorsomedial frontal cortex and in the left middle/superior temporal lobe. Certainty was associated with large bilateral activations in the occipital and parietal regions usually involved in visuospatial processing. Correct-and-certain answers were associated with activations that suggest a stronger mobilization of visual attention resources when compared to incorrect-and-certain answers. These findings provide insights into brain-based mechanisms of uncertainty that are activated when common misconceptions, identified as such by science education research literature, interfere in decision making in a school-like task. We also discuss the implications of these results from an educational perspective.

  9. Linking neuroscientific research on decision making to the educational context of novice students assigned to a multiple-choice scientific task involving common misconceptions about electrical circuits.

    Science.gov (United States)

    Potvin, Patrice; Turmel, Elaine; Masson, Steve

    2014-01-01

    Functional magnetic resonance imaging was used to identify the brain-based mechanisms of uncertainty and certainty associated with answers to multiple-choice questions involving common misconceptions about electric circuits. Twenty-two scientifically novice participants (humanities and arts college students) were asked, in an fMRI study, whether or not they thought the light bulbs in images presenting electric circuits were lighted up correctly, and if they were certain or uncertain of their answers. When participants reported that they were unsure of their responses, analyses revealed significant activations in brain areas typically involved in uncertainty (anterior cingulate cortex, anterior insula cortex, and superior/dorsomedial frontal cortex) and in the left middle/superior temporal lobe. Certainty was associated with large bilateral activations in the occipital and parietal regions usually involved in visuospatial processing. Correct-and-certain answers were associated with activations that suggest a stronger mobilization of visual attention resources when compared to incorrect-and-certain answers. These findings provide insights into brain-based mechanisms of uncertainty that are activated when common misconceptions, identified as such by science education research literature, interfere in decision making in a school-like task. We also discuss the implications of these results from an educational perspective.

  10. IL2RA/CD25 gene polymorphisms: uneven association with multiple sclerosis (MS and type 1 diabetes (T1D.

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    Antonio Alcina

    Full Text Available BACKGROUND: IL-2 receptor (IL2R alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. METHODS AND RESULTS: Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS and 5 SNPs associated with type 1 diabetes (T1D in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3'- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032. The most associated T1D SNP (rs41295061 was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286 of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. CONCLUSIONS: These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases.

  11. IL2RA/CD25 Gene Polymorphisms: Uneven Association with Multiple Sclerosis (MS) and Type 1 Diabetes (T1D)

    Science.gov (United States)

    Alcina, Antonio; Fedetz, María; Ndagire, Dorothy; Fernández, Oscar; Leyva, Laura; Guerrero, Miguel; Abad-Grau, María M.; Arnal, Carmen; Delgado, Concepción; Lucas, Miguel; Izquierdo, Guillermo; Matesanz, Fuencisla

    2009-01-01

    Background IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. Methods and Results Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3′- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. Conclusions These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases. PMID:19125193

  12. Multiple Solutions Involving Geoboard Problems.

    Science.gov (United States)

    Smith, Lyle R.

    1993-01-01

    Illustrates various methods to determine the perimeter and area of triangles and polygons formed on the geoboard. Methods utilize algebraic techniques, trigonometry, geometric theorems, and analytic geometry to solve problems and connect a variety of mathematical concepts. (MDH)

  13. Application of SNPs for population genetics of nonmodel organisms: new opportunities and challenges

    DEFF Research Database (Denmark)

    Helyar, S.J.; Hansen, Jakob Hemmer; Bekkevold, Dorte

    2011-01-01

    Recent improvements in the speed, cost and accuracy of next generation sequencing are revolutionizing the discovery of single nucleotide polymorphisms (SNPs). SNPs are increasingly being used as an addition to the molecular ecology toolkit in nonmodel organisms, but their efficient use remains ch...

  14. SNPs in PPARG associate with type 2 diabetes and interact with physical activity

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas; Lakka, Timo A; Laaksonen, David E

    2008-01-01

    To study the associations of seven single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor gamma (PPARG) gene with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D), and the interactions of the SNPs with physical activity (PA)....

  15. CsSNP: A Web-Based Tool for the Detecting of Comparative Segments SNPs.

    Science.gov (United States)

    Wang, Yi; Wang, Shuangshuang; Zhou, Dongjie; Yang, Shuai; Xu, Yongchao; Yang, Chao; Yang, Long

    2016-07-01

    SNP (single nucleotide polymorphism) is a popular tool for the study of genetic diversity, evolution, and other areas. Therefore, it is necessary to develop a convenient, utility, robust, rapid, and open source detecting-SNP tool for all researchers. Since the detection of SNPs needs special software and series steps including alignment, detection, analysis and present, the study of SNPs is limited for nonprofessional users. CsSNP (Comparative segments SNP, http://biodb.sdau.edu.cn/cssnp/ ) is a freely available web tool based on the Blat, Blast, and Perl programs to detect comparative segments SNPs and to show the detail information of SNPs. The results are filtered and presented in the statistics figure and a Gbrowse map. This platform contains the reference genomic sequences and coding sequences of 60 plant species, and also provides new opportunities for the users to detect SNPs easily. CsSNP is provided a convenient tool for nonprofessional users to find comparative segments SNPs in their own sequences, and give the users the information and the analysis of SNPs, and display these data in a dynamic map. It provides a new method to detect SNPs and may accelerate related studies.

  16. Data mining of public SNP databases for the selection of intragenic SNPs

    NARCIS (Netherlands)

    Aerts, J.; Wetzels, Y.; Cohen, N.; Aerssens, J.

    2002-01-01

    Different strategies to search public single nucleotide polymorphism (SNP) databases for intragenic SNPs were evaluated. First, we assembled a strategy to annotate SNPs onto candidate genes based on a BLAST search of public SNP databases (Intragenic SNP Annotation by BLAST, ISAB). Only BLAST hits th

  17. Association analysis of IL10, TNF-α and IL23R-IL12RB2 SNPs with Behçet's disease risk in Western Algeria

    Directory of Open Access Journals (Sweden)

    Ouahiba eKhaib Dit Naib

    2013-10-01

    Full Text Available Objective: We have conducted the first study of the association of interleukin (IL-10, tumor necrosis factor alpha (TNF-α and IL23R-IL12RB2 regionSNPswith Behçet's disease (BD in Western Algeria. Methods: A total of 51 BD patients and 96 unrelated controls from West region of Algeria were genotyped by direct sequencing for 11 SNPs including 2 SNPsfrom the IL10 promoter [c.-819T>C (rs1800871, c.-592A>C (rs1800872], 6 SNPs from the TNF-α promoter [c.-1211T>C (rs1799964, c.-1043C>A (rs1800630, c.-1037C>T (rs1799724, c.-556G>A (rs1800750, c.-488G>A (rs1800629 and c.-418G>A (rs361525], and 3 SNPs from the IL23R-IL12RB2 region [g.67747415A>C (rs12119179, g.67740092G>A (rs11209032 and g.67760140T>C (rs924080]. Results: The minor alleles c.-819T and c.-592A were significantly associated with BD (OR= 2.18; 95% CI 1.28-3.73, p = 0.003; whereas, there was weaker association between TNF-αpromoter SNPs or IL23R-IL12RB2 region and disease risk.Conclusion: Unlike the TNF-αand the IL23R-IL12RB2 region SNPs, the two IL10 SNPs were strongly associated with BD. The -819T, and -592A alleles and the -819TT, -819CT, and -592AA and -592CA genotypes seem to be highly involved in the risk of developing of BD in the population of Western Algeria.

  18. 丘脑枕核参与情绪信息加工的多条通路%Pulvinar Involves in Multiple Pathways of Emotion Processing

    Institute of Scientific and Technical Information of China (English)

    陈珊珊; 蔡厚德

    2015-01-01

    丘脑枕核参与多条加工情绪信息的神经通路因而在情绪信息加工中具有重要作用。第一:丘脑枕核参与到上丘−丘脑枕核−杏仁核通路。该通路可以在没有初级视觉皮层参与情况下对情绪信息进行快速加工;第二:丘脑枕核以皮层−丘脑枕核−皮层环路和上丘−丘脑枕核−皮层通路两种形式参与到丘脑枕核−皮层通路。该通路通过控制皮层间同步化水平促进信息传递的效率;同时通过整合皮层和皮层下情绪信号扩大其在行为输出方面的影响力。%The pulvinar complex plays an important role in emotion processing by involving in multiple pathways. First, pulvinar involves in superior colliculus-pulvinar-amygdala pathway, which can process the emotional stimuli rapidly without the involvement of visual cortex. Second, pulvinar involves in pulvinar- cortical pathway in two different forms—cortico-pulvino-cortico circuits and colliculo-pulvinar-cortical pathway. This neural mechanism can increase the efficacy of information exchange by controlling the degree of synchrony between cortical regions, and can amplify signals in a manner that enhances their behavioral impact by coordinating the signals between cortical and subcortical regions.

  19. Inferring Alcoholism SNPs and Regulatory Chemical Compounds Based on Ensemble Bayesian Network.

    Science.gov (United States)

    Chen, Huan; Sun, Jiatong; Jiang, Hong; Wang, Xianyue; Wu, Lingxiang; Wu, Wei; Wang, Qh

    2016-12-20

    The disturbance of consciousness is one of the most common symptoms of those have alcoholism and may cause disability and mortality. Previous studies indicated that several single nucleotide polymorphisms (SNP) increase the susceptibility of alcoholism. In this study, we utilized the Ensemble Bayesian Network (EBN) method to identify causal SNPs of alcoholism based on the verified GAW14 data. Thirteen out of eighteen SNPs directly connected with alcoholism were found concordance with potential risk regions of alcoholism in OMIM database. As a number of SNPs were found contributing to alteration on gene expression, known as expression quantitative trait loci (eQTLs), we further sought to identify chemical compounds acting as regulators of alcoholism genes captured by causal SNPs. Chloroprene and valproic acid were identified as the expression regulators for genes C11orf66 and SALL3 which were captured by alcoholism SNPs, respectively.

  20. Effect of SNPs in protein kinase Czgene on gene expression in the reporter gene detection system

    Institute of Scientific and Technical Information of China (English)

    Zhuo Liu; Hong-Xia Sun; Yong-Wei Zhang; Yun-Feng Li; Jin Zuo; Yan Meng; Fu-De Fang

    2004-01-01

    AIM: To investigated the effects of the SNPs (rs411021,rs436045, rs427811, rs385039 and rs809912) on gene expression and further identify the susceptibility genes of type 2 diabetes.METHODS: Ten allele fragments (49 bp each) were synthesized according to the 5 SNPs mentioned above.These fragments were cloned into luciferase reporter gene vector and then transfected into HepG2 cells. The activity of the luciferase was assayed. Effects of the SNPs on RNA splicing were analyzed by bioinformatics.RESULTS: rs427811T allele and rs809912G allele enhanced the activity of the reporter gene expression. None of the 5 SNPs affected RNA splicing.CONCLUSION: SNPs in protein kinase Cz (PKCZ) gene probably play a role in the susceptibility to type 2 diabetes by affecting the expression level of the relevant genes.

  1. Apolipoprotein gene involved in lipid metabolism

    Science.gov (United States)

    Rubin, Edward; Pennacchio, Len A.

    2007-07-03

    Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

  2. Two benzimidazole resistance-associated SNPs in the isotype-1 β-tubulin gene predominate in Haemonchus contortus populations from eight regions in China

    Directory of Open Access Journals (Sweden)

    Zongze Zhang

    2016-12-01

    Full Text Available Haemonchus contortus is one of the most important parasitic nematodes of small ruminants around the world, particularly in tropical and subtropical regions. The control of haemonchosis relies mainly on anthelmintics, but the excessive and prolonged use of anthelmintics is causing serious drug resistance issues in many countries. As benzimidazole (BZ anthelmintics have been broadly used in China, we hypothesized that resistance is widespread. Given the link between three known single nucleotide polymorphisms (SNPs, designated F167Y, E198A and F200Y in the isotype-1 β-tubulin gene and BZ resistance, our goal here was to explore the presence of these mutations in H. contortus from small ruminants (sheep and goats from eight provinces in China using PCR-coupled sequencing. In addition, the genetic diversity and genetic relationship of isotype-1 β-tubulin sequence haplotypes were also investigated. Among 192 H. contortus adult individuals representing the eight populations, we identified six distinct sequence types, five of which had SNP E198A (GCA and/or F200Y (TAC. Sequence analysis showed that the frequencies of SNPs E198A and F200Y were 0–70% and 0–31%, respectively. SNP F167Y (TAC was not detected in any population. In addition, high haplotype diversities (0.455–0.939 and nucleotide diversities (0.018–0.039 were calculated. A network analysis of the isotype-1 β-tubulin gene sequences showed that SNPs E198A and F200Y occurred in multiple distinct groupings, suggesting multiple independent origins of these SNPs. The findings of this first study of SNPs in the isotype-1 β-tubulin gene of H. contortus populations suggest that BZ resistance is prevalent in some regions of China, and that any control strategy might focus on monitoring BZ resistance in this country.

  3. High-risk human papillomavirus infection involving multiple anatomic sites of the female lower genital tract: a multiplex real-time polymerase chain reaction-based study.

    Science.gov (United States)

    Hui, Yiang; Manna, Pradip; Ou, Joyce J; Kerley, Spencer; Zhang, Cunxian; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul

    2015-09-01

    High-risk human papillomavirus infection usually is seen at one anatomic site in an individual. Rarely, infection at multiple anatomic sites of the female lower genital tract in the same individual is encountered either simultaneously and/or at a later date. The current study identifies the various subtypes of high-risk human papillomavirus infection in these scenarios and analyzes the potential significance of these findings. High-risk human papillomavirus infection involving 22 anatomic sites from 7 individuals was identified after institutional review board approval. Residual paraffin-embedded tissue samples were retrieved, and all 15 high-risk human papillomavirus were identified and viral load quantified using multiplex real-time polymerase chain reaction-based method. Multiple high-risk human papillomavirus subtypes were identified in 32% of the samples and as many as 5 different subtypes of high-risk human papillomavirus infection in a single anatomic site. In general, each anatomic site has unique combination of viral subtypes, although one individual showed overlapping subtypes in the vagina, cervix, and vulvar samples. Higher viral load and rare subtypes are more frequent in younger patients and in dysplasia compared with carcinoma. Follow-up ranging from 3 to 84 months revealed persistent high-risk human papillomavirus infection in 60% of cases. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Genotyping of 75 SNPs using arrays for individual identification in five population groups.

    Science.gov (United States)

    Hwa, Hsiao-Lin; Wu, Lawrence Shih Hsin; Lin, Chun-Yen; Huang, Tsun-Ying; Yin, Hsiang-I; Tseng, Li-Hui; Lee, James Chun-I

    2016-01-01

    Single nucleotide polymorphism (SNP) typing offers promise to forensic genetics. Various strategies and panels for analyzing SNP markers for individual identification have been published. However, the best panels with fewer identity SNPs for all major population groups are still under discussion. This study aimed to find more autosomal SNPs with high heterozygosity for individual identification among Asian populations. Ninety-six autosomal SNPs of 502 DNA samples from unrelated individuals of five population groups (208 Taiwanese Han, 83 Filipinos, 62 Thais, 69 Indonesians, and 80 individuals with European, Near Eastern, or South Asian ancestry) were analyzed using arrays in an initial screening, and 75 SNPs (group A, 46 newly selected SNPs; groups B, 29 SNPs based on a previous SNP panel) were selected for further statistical analyses. Some SNPs with high heterozygosity from Asian populations were identified. The combined random match probability of the best 40 and 45 SNPs was between 3.16 × 10(-17) and 7.75 × 10(-17) and between 2.33 × 10(-19) and 7.00 × 10(-19), respectively, in all five populations. These loci offer comparable power to short tandem repeats (STRs) for routine forensic profiling. In this study, we demonstrated the population genetic characteristics and forensic parameters of 75 SNPs with high heterozygosity from five population groups. This SNPs panel can provide valuable genotypic information and can be helpful in forensic casework for individual identification among these populations.

  5. Longer epilepsy duration and multiple lobe involvement predict worse seizure outcomes for patients with refractory temporal lobe epilepsy associated with neurocysticercosis

    Directory of Open Access Journals (Sweden)

    Lucas Crociati Meguins

    2015-12-01

    Full Text Available ABSTRACT Objective To investigate the surgical outcomes of temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS and neurocysticercosis (NCC. Methods A retrospective investigation of patients with TLE-HS was conducted in a tertiary center. Results Seventy-nine (62.2%, 37 (29.1%, 6 (4.7%, and 5 (3.9% patients were Engel class I, II, III, and IV, respectively. Fifty-two (71.2% patients with epilepsy durations ≤ 10 years prior to surgery were seizure-free 1 year after the operation compared to 27 (50.0% patients with epilepsy durations > 10 years (p = 0.0121. Forty-three (72.9% patients with three or fewer lobes affected by NCC were seizure-free one year after the operation, and 36 (52.9% patients with more than three involved lobes were seizure-free after surgery (p = 0.0163. Conclusions Longer epilepsy durations and multiple lobe involvement predicted worse seizure outcomes in TLE-HS plus NCC patients.

  6. SNPs ANALYSIS AS A TOOL IN MOLECULAR GENETICS DIAGNOSTICS

    Directory of Open Access Journals (Sweden)

    Dewi Rusnita

    2015-05-01

    Full Text Available AbstrakSingle Nucleotide Polymorphism (SNP merupakan variasi genetik yang ditemukan pada lebih dari 1% populasi. Haplotipe, yang merupakan sekelompok SNP atau alel dalam satu kromosom, dapat di turunkan ke generasi selanjutnya dan dapat digunakan untuk menelusuri gen penyebab penyakit (marker genetik. Artikel ini bertujuan menjelaskan aplikasi analisis SNP dalam diagnosis beberapa sindrom yang disebabkan gangguan genetik. Berdasarkan laporan studi terdahulu, sindrom yang disebabkan oleh UPD (uniparental disomy maupun penyakit autosomal resesif yang muncul sebagai akibat perkawinan sedarah dapat dideteksi dengan SNP array melalui analisis block of homozygosity dalam kromosom. Kelebihan lain SNP array adalah kemampuannya dalam mendeteksi mosaicism level rendah yang tidak terdeteksi dengan pemeriksaan sitogenetik konvensional. Bahkan saat ini, SNP array sedang diujicobakan dalam IVF untuk mendapatkan bayi yang sehat. Hal ini dapat dilakukan dengan mendeteksi ada atau tidaknya gen tunggal penyebab penyakit pada embrio hasil bayi tabung sebelum embrio ditanamkan ke uterus. Analisis SNP dengan SNP array mempunyai banyak kelebihan dibanding metode pemeriksaan SNP lainnya dan diharapkan dapat digunakan secara luas dalam bidang diagnostik molekuler genetik di masa mendatang.AbstractSingle Nucleotide Polymorphism (SNP is a genetic variant with a frequency of >1% of a large population. Haplotypes, a combination of a set of SNPs/alleles that appear as “associated blocks” on one chromosome, tend to be inherited together to the next offspring and can be used as genetic markers to trace particular diseases. This article aimed at explaining of SNP analysis application in diagnosis of genetic-disorder related syndrome. Previous studies showed that syndromes caused by UPD or autosomal recessive disorder as a result of consanguineous marriage can be identified by SNP array through analysing block of homozygosity region in a chromosome. Another advantage of SNP

  7. Transcriptome Analysis of an Insecticide Resistant Housefly Strain: Insights about SNPs and Regulatory Elements in Cytochrome P450 Genes.

    Directory of Open Access Journals (Sweden)

    Khalid Mahmood

    Full Text Available Insecticide resistance in the housefly, Musca domestica, has been investigated for more than 60 years. It will enter a new era after the recent publication of the housefly genome and the development of multiple next generation sequencing technologies. The genetic background of the xenobiotic response can now be investigated in greater detail. Here, we investigate the 454-pyrosequencing transcriptome of the spinosad-resistant 791spin strain in relation to the housefly genome with focus on P450 genes.The de novo assembly of clean reads gave 35,834 contigs consisting of 21,780 sequences of the spinosad resistant strain. The 3,648 sequences were annotated with an enzyme code EC number and were mapped to 124 KEGG pathways with metabolic processes as most highly represented pathway. One hundred and twenty contigs were annotated as P450s covering 44 different P450 genes of housefly. Eight differentially expressed P450s genes were identified and investigated for SNPs, CpG islands and common regulatory motifs in promoter and coding regions. Functional annotation clustering of metabolic related genes and motif analysis of P450s revealed their association with epigenetic, transcription and gene expression related functions. The sequence variation analysis resulted in 12 SNPs and eight of them found in cyp6d1. There is variation in location, size and frequency of CpG islands and specific motifs were also identified in these P450s. Moreover, identified motifs were associated to GO terms and transcription factors using bioinformatic tools.Transcriptome data of a spinosad resistant strain provide together with genome data fundamental support for future research to understand evolution of resistance in houseflies. Here, we report for the first time the SNPs, CpG islands and common regulatory motifs in differentially expressed P450s. Taken together our findings will serve as a stepping stone to advance understanding of the mechanism and role of P450s in

  8. Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Kullo Iftikhar J

    2011-04-01

    Full Text Available Abstract Background We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants. Methods From the database of genome-wide association studies (GWAS, we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels. We identified 292 SNPs in 270 genes associated with a disease or trait at P -8. As part of the Human Genome-Diversity Project (HGDP, 158 (54.1% of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, FST, was calculated to quantify differences in risk allele frequencies (RAFs among populations and geographic areas. Results Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global FST (0.1042 for 158 SNPs among the populations was not significantly higher than the mean global FST of 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global FST (P FST of 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score. Conclusion Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.

  9. Screening and Evaluation of Deleterious SNPs in APOE Gene of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Tariq Ahmad Masoodi

    2012-01-01

    Full Text Available Introduction. Apolipoprotein E (APOE is an important risk factor for Alzheimer’s disease (AD and is present in 30–50% of patients who develop late-onset AD. Several single-nucleotide polymorphisms (SNPs are present in APOE gene which act as the biomarkers for exploring the genetic basis of this disease. The objective of this study is to identify deleterious nsSNPs associated with APOE gene. Methods. The SNPs were retrieved from dbSNP. Using I-Mutant, protein stability change was calculated. The potentially functional nonsynonymous (ns SNPs and their effect on protein was predicted by PolyPhen and SIFT, respectively. FASTSNP was used for functional analysis and estimation of risk score. The functional impact on the APOE protein was evaluated by using Swiss PDB viewer and NOMAD-Ref server. Results. Six nsSNPs were found to be least stable by I-Mutant 2.0 with DDG value of >−1.0. Four nsSNPs showed a highly deleterious tolerance index score of 0.00. Nine nsSNPs were found to be probably damaging with position-specific independent counts (PSICs score of ≥2.0. Seven nsSNPs were found to be highly polymorphic with a risk score of 3-4. The total energies and root-mean-square deviation (RMSD values were higher for three mutant-type structures compared to the native modeled structure. Conclusion. We concluded that three nsSNPs, namely, rs11542041, rs11542040, and rs11542034, to be potentially functional polymorphic.

  10. Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs

    OpenAIRE

    Adoue, Veronique; Schiavi, Alicia; Light, Nicholas; Carlsson Almlöf, Jonas; Lundmark, Per; Ge, Bing; Kwan, Tony; Caron, Maxime; Rönnblom, Lars; Wang, Chuan; Chen, Shu-Huang; Goodall, Alison H; Cambien, Francois; Deloukas, Panos; Ouwehand, Willem H.

    2014-01-01

    Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified ...

  11. Association of SNPs and haplotypes in GABA(A) receptor beta(2) gene with schizophrenia

    Institute of Scientific and Technical Information of China (English)

    WSLau; CFXuan; ZChan; CFFeng; GYHe; LCao; ZCLiu; HLuan; QMXue

    2005-01-01

    Disturbances in GABAergic system have been observed in schizophrenics.(1-3) In the present study, population association analysis was performed on 19 SNPs in the alpha(l), beta(2), gamma(2), epsilon and pi subunit genes of GABA(A) receptor. Five SNPs in GABRB2, namely B217G1584T, rs1816071, rs194072, rs252944 and rs187269,were found to be significantly associated, and their haplotypes in linkage disequilibrium, with schizophrenia. This represents the first report on any disease association of SNPs in the human GABA(A) receptor genes, and focuses attention on the GABAergic hypothesis of schizophrenia etiology.(3,4)

  12. Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

    DEFF Research Database (Denmark)

    Darabi, Hatef; Beesley, Jonathan; Droit, Arnaud

    2016-01-01

    Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (i......COGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates...... for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10(-09), r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10(-11), r(2...

  13. Mieloma múltiplo: invasão leptomeníngea difusa Diffuse leptomeningeal involvement in multiple myelomatosis: a case report

    Directory of Open Access Journals (Sweden)

    N. O. Facure

    1971-03-01

    Full Text Available Registro de caso de paciente com infiltração leptomeníngea por metás-tase de mieloma múltiplo. A infiltração neoplásica ocorria nas leptomeninges da base do encéfalo e, em especial, nas do canal raqueano. O tecido tumoral formava manguito no espaço sub-aracnóideo que envolvia os segmentos cervical e torácico da medula espinhal. A partir dos segmentos lombares a medula se achava infiltrada pelo tumor; as raízes da cauda equina achavam-se também invadidas pelo tecido neoplásico. Não foi feito o diagnóstico em vida. O quadro clínico caracterizava-se por sinais de irritação meníngea e de sofrimento radículo-medular a partir dos segmentos lombares altos e o quadro liquórico, por reação inflamatória de tipo sub-agudo que determinava bloqueio do canal raqueano. Os autores chamam a atenção para a raridade da invasão leptomeníngea por mieloma múltiplo e para a dificuldade diagnostica do caso. Neste último sentido discutem os dados do quadro liquórico bem como salientam não ter sido possível completar o estudo histoquímico das células plasmocitárias.A case of a patient with multiple myelomatosis that presented diffuse leptomeningeal involvement by metastatic tissue is reported. The diagnosis was based upon necroscopic examination. The leptomeninges were infiltrated by neoplastic cells, the infiltration being more evident in the leptomeninges of the spinal canal. In this region the subarachnoid space was filled by neoplastic tissue that surrounded the spinal cord and cauda equina. The lumbal and sacral portions of spinal cord were invaded by tumor cells. Fever, congestion of left eye and signs of leptomeningeal irritation appeared at first and were followed by crural paraplegia about two months later. At this occasion a CSF examination showed changes proper to subacute inflammatory process and the manometric test of Stookey suggested the occurence of blockage in the spinal canal. The unusual leptomeningeal involvement

  14. MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium.

    Directory of Open Access Journals (Sweden)

    Matthew F Buas

    Full Text Available Incidence of esophageal adenocarcinoma (EA has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett's esophagus (BE, such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON genome-wide association study (GWAS of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs that potentially affect the biogenesis or biological activity of microRNAs (miRNAs, small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes; miRNA gene loci (234 SNPs, 210 genes; and miRNA-targeted mRNAs (177 SNPs, 158 genes. Nominal associations (P0.50, and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity. This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.

  15. Tomato LeTHIC is an Fe-requiring HMP-P synthase involved in thiamine synthesis and regulated by multiple factors.

    Science.gov (United States)

    Zhao, Weina; Cheng, Xudong; Huang, Zongan; Fan, Huajie; Wu, Huilan; Ling, Hong-Qing

    2011-06-01

    Thiamine is a key primary metabolite which is necessary for the viability of all organisms. It is a dietary requirement for mammals because only prokaryotes, fungi and plants are thiamine prototrophs. In contrast to the well documented biosynthetic mechanism in bacteria, much remains to be deciphered in plants. In this work, a tomato thiamine-auxotrophic (thiamineless, tl) mutant was characterized. The tl mutant occurs due to inactivation of LeTHIC transcription as a result of insertion of a large unknown DNA fragment in its 5'-untranslated region. Expression of wild-type LeTHIC in tl plants was able to complement the mutant to wild type. LeTHIC possessed the same function as E.cTHIC [an Escherichia coli 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase involved in synthesis of the pyrimidine moiety of thiamine] because expression of LeTHIC rescued THIC-deficient strains of E. coli under culture conditions without thiamine supplementation, suggesting that plants employ a bacteria-like route of pyrimidine moiety synthesis. LeTHIC is an Fe-S cluster protein localized in chloroplasts, and Fe is required for maintenance of its enzyme activity because Fe deficiency resulted in a significant reduction of thiamine content in tomato leaves. Further, we also showed that the expression of LeTHIC is tightly regulated at the transcriptional and post-transcriptional level by multiple factors, such as light, Fe status and thiamine pyrophosphate (TPP)-riboswitch. The results clearly demonstrated that a feedback regulation mechanism is involved in synthesis of the pyrimidine moiety for controlling thiamine synthesis in tomato. Our results provide a new insight into understanding the molecular mechanism of thiamine biosynthesis in plants.

  16. FGFR2 risk SNPs confer breast cancer risk by augmenting oestrogen responsiveness.

    Science.gov (United States)

    Campbell, Thomas M; Castro, Mauro A A; de Santiago, Ines; Fletcher, Michael N C; Halim, Silvia; Prathalingam, Radhika; Ponder, Bruce A J; Meyer, Kerstin B

    2016-08-01

    The fibroblast growth factor receptor 2 (FGFR2) locus is consistently the top hit in genome-wide association studies for oestrogen receptor-positive (ER(+)) breast cancer. Yet, its mode of action continues to be controversial. Here, we employ a systems biology approach to demonstrate that signalling via FGFR2 counteracts cell activation by oestrogen. In the presence of oestrogen, the oestrogen receptor (ESR1) regulon (set of ESR1 target genes) is in an active state. However, signalling by FGFR2 is able to reverse the activity of the ESR1 regulon. This effect is seen in multiple distinct FGFR2 signalling model systems, across multiple cells lines and is dependent on the presence of FGFR2. Increased oestrogen exposure has long been associated with an increased risk of breast cancer. We therefore hypothesized that risk variants should reduce FGFR2 expression and subsequent signalling. Indeed, transient transfection experiments assaying the three independent variants of the FGFR2 risk locus (rs2981578, rs35054928 and rs45631563) in their normal chromosomal context show that these single-nucleotide polymorphisms (SNPs) map to transcriptional silencer elements and that, compared with wild type, the risk alleles augment silencer activity. The presence of risk variants results in lower FGFR2 expression and increased oestrogen responsiveness. We thus propose a molecular mechanism by which FGFR2 can confer increased breast cancer risk that is consistent with oestrogen exposure as a major driver of breast cancer risk. Our findings may have implications for the clinical use of FGFR2 inhibitors.

  17. Transcriptome characterization and high throughput SSRs and SNPs discovery in Cucurbita pepo (Cucurbitaceae

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    Nuez Fernando

    2011-02-01

    Full Text Available Abstract Background Cucurbita pepo belongs to the Cucurbitaceae family. The "Zucchini" types rank among the highest-valued vegetables worldwide, and other C. pepo and related Cucurbita spp., are food staples and rich sources of fat and vitamins. A broad range of genomic tools are today available for other cucurbits that have become models for the study of different metabolic processes. However, these tools are still lacking in the Cucurbita genus, thus limiting gene discovery and the process of breeding. Results We report the generation of a total of 512,751 C. pepo EST sequences, using 454 GS FLX Titanium technology. ESTs were obtained from normalized cDNA libraries (root, leaves, and flower tissue prepared using two varieties with contrasting phenotypes for plant, flowering and fruit traits, representing the two C. pepo subspecies: subsp. pepo cv. Zucchini and subsp. ovifera cv Scallop. De novo assembling was performed to generate a collection of 49,610 Cucurbita unigenes (average length of 626 bp that represent the first transcriptome of the species. Over 60% of the unigenes were functionally annotated and assigned to one or more Gene Ontology terms. The distributions of Cucurbita unigenes followed similar tendencies than that reported for Arabidopsis or melon, suggesting that the dataset may represent the whole Cucurbita transcriptome. About 34% unigenes were detected to have known orthologs of Arabidopsis or melon, including genes potentially involved in disease resistance, flowering and fruit quality. Furthermore, a set of 1,882 unigenes with SSR motifs and 9,043 high confidence SNPs between Zucchini and Scallop were identified, of which 3,538 SNPs met criteria for use with high throughput genotyping platforms, and 144 could be detected as CAPS. A set of markers were validated, being 80% of them polymorphic in a set of variable C. pepo and C. moschata accessions. Conclusion We present the first broad survey of gene sequences and allelic

  18. Association of tag SNPs of GPx-3 with essential hypertension in rural Han Chinese in Fuxin, Liaoning, China

    Institute of Scientific and Technical Information of China (English)

    HAO Ying; LI Hong; SUN Ying-xian; WU Bao-gang; SHI Jin; CHEN Yan-li; SUN Zhao-qing; ZHENG Li-qiang; ZHANG Xin-gang; GENG Ning; LI Tie-jun

    2011-01-01

    Background Genetic mechanisms contribute to blood pressure regulation. This study investigated whether glutathione peroxidase (GPx-3) tag single nucleotide polymorphisms (SNPs) are associated with hypertension in the rural areas of Fuxin county, Liaoning province, China.Methods Indigenous Fuxin Han people participated, 523 unrelated hypertensives and 547 controls were recruited. All tag SNPs of GPx-3 gene were selected. We estimated SNP allele frequency in DNA pools with pyrosequencing.Results Before Bonferroni correction, C allele frequency for rs8177417 was significantly higher in hypertensives than those in controls (23.4% vs. 19.3%, P=0.014); T allele frequency for rs3828599 was significantly lower in hypertensives than those in controls (35.6% vs. 40.8%,P=0.009). However, when a Bonferroni correction for multiple testing was applied, only the polymorphisms rs3828599 of GPx-3 gene was associated with hypertension (P=0.045, OR: 0.833, 95%CI: 0.695-0.998).Conclusion The polymorphism of rs3828599 of GPx-3 gene might be associated with hypertension in rural Han Chinese from Fuxin, Liaoning.

  19. Inter-observer agreement for the evaluation of bone involvement on Whole Body Low Dose Computed Tomography (WBLDCT) in Multiple Myeloma (MM)

    Energy Technology Data Exchange (ETDEWEB)

    Zacchino, M.; Minetti, V.; Dore, R.; Calliada, F. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Institute of Radiology, Pavia (Italy); Bonaffini, P.A.; Nasatti, A.; Sironi, S. [University of Milano Bicocca, San Gerardo Hospital, Department of Diagnostic Radiology, Monza (Italy); Corso, A. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Division of Hematology, Pavia (Italy); Tinelli, C. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Service of Biometry and Statistics, Pavia (Italy)

    2015-11-15

    We aimed to assess inter-observer agreement in bone involvement evaluation and define accuracy and reproducibility of MDCT images analysis in Multiple Myeloma (MM), by comparing two acquisition protocols at two different institutions. A total of 100 MM patients underwent whole body low-dose computed tomography (WB-LDCT), with two protocols: Group I (50 patients), 80 kV and 200-230 mAs; Group II, 120 kV-40 mAs. Four readers (two experts) retrospectively reviewed 22 anatomical districts, reporting the following for each patient: 1) osteolytic lesions; 2) cortical bone integrity; 3) fractures; 4) risk of vertebral collapse; 5) hyperattenuating bone lesions; and 6) extraosseous extension. Inter-observer agreement (by all readers, expert and young observers and comparison of the two protocols) was then statistically analyzed. According to Cohen's criteria, inter-observer agreement among the four readers and between experts and residents was good for the detection of bone lesions and extra-medullary extension, and for the evaluation of risk of collapse and cortical integrity. There was good agreement when comparing the two protocols. A greater variability was found for the evaluation of hyperattenuating lesions and the presence of fractures. WB-LDCT represents a reproducible and reliable technique that is helpful for defining bone disease in MM patients, with partial influence of readers' experience. (orig.)

  20. The rice OsNAC6 transcription factor orchestrates multiple molecular mechanisms involving root structural adaptions and nicotianamine biosynthesis for drought tolerance.

    Science.gov (United States)

    Lee, Dong-Keun; Chung, Pil Joong; Jeong, Jin Seo; Jang, Geupil; Bang, Seung Woon; Jung, Harin; Kim, Youn Shic; Ha, Sun-Hwa; Choi, Yang Do; Kim, Ju-Kon

    2016-11-28

    Drought has a serious impact on agriculture worldwide. A plant's ability to adapt to rhizosphere drought stress requires reprogramming of root growth and development. Although physiological studies have documented the root adaption for tolerance to the drought stress, underlying molecular mechanisms is still incomplete, which is essential for crop engineering. Here, we identified OsNAC6-mediated root structural adaptations, including increased root number and root diameter, which enhanced drought tolerance. Multiyear drought field tests demonstrated that the grain yield of OsNAC6 root-specific overexpressing transgenic rice lines was less affected by drought stress than were nontransgenic controls. Genome-wide analyses of loss- and gain-of-function mutants revealed that OsNAC6 up-regulates the expression of direct target genes involved in membrane modification, nicotianamine (NA) biosynthesis, glutathione relocation, 3'-phophoadenosine 5'-phosphosulphate accumulation and glycosylation, which represent multiple drought tolerance pathways. Moreover, overexpression of NICOTIANAMINE SYNTHASE genes, direct targets of OsNAC6, promoted the accumulation of the metal chelator NA and, consequently, drought tolerance. Collectively, OsNAC6 orchestrates novel molecular drought tolerance mechanisms and has potential for the biotechnological development of high-yielding crops under water-limiting conditions.

  1. Optimisation and validation of methods to assess single nucleotide polymorphisms (SNPs) in archival histological material

    DEFF Research Database (Denmark)

    Andreassen, Christian Nicolaj; Sørensen, Flemming Brandt; Overgaard, J.;

    2004-01-01

    only archival specimens are available. This study was conducted to validate protocols optimised for assessment of SNPs based on paraffin embedded, formalin fixed tissue samples. PATIENTS AND METHODS: In 137 breast cancer patients, three TGFB1 SNPs were assessed based on archival histological specimens...... TGFB1 SNPs was used to provide an indirect validation of the genotyping results. Furthermore, two different methods for DNA extraction were compared (semi-automatic DNA extraction using the ABI Prism 6100 Nucleic Acid PrepStation versus Proteinase K digestion for 5 days followed by boiling and DNA...... precipitation). RESULTS: Assessment of SNPs based on archival histological material is encumbered by a number of obstacles and pitfalls. However, these can be widely overcome by careful optimisation of the methods used for sample selection, DNA extraction and PCR. Within 130 samples that fulfil the criteria...

  2. High-throughput SNP genotyping: combining tag SNPs and molecular beacons

    CSIR Research Space (South Africa)

    Barreiro, LB

    2009-10-01

    Full Text Available In the last decade, molecular beacons have emerged to become a widely used tool in the multiplex typing of single nucleotide polymorphisms (SNPs). Improvements in detection technologies in instrumentation and chemistries to label these probes have...

  3. SNP uniqueness problem: a proof-of-principle in HapMap SNPs.

    Science.gov (United States)

    Doron, Shany; Shweiki, Dorit

    2011-04-01

    SNP-based research strongly affects our biomedical and clinically associated knowledge. Nonunique and false-positive SNP existence in commonly used datasets may thus lead to biased, inaccurate clinically associated conclusions. We designed a computational study to reveal the degree of nonunique/false-positive SNPs in the HapMap dataset. Two sets of SNP flanking sequences were used as queries for BLAT analysis against the human genome. 4.2% and 11.9% of HapMap SNPs align to the genome nonuniquely (long and short, respectively). Furthermore, an average of 7.9% nonunique SNPs are included in common commercial genotyping arrays (according to our designed probes). Nonunique SNPs identified in this study are represented to various degrees in clinically associated databases, stressing the consequence of inaccurate SNP annotation and hence SNP utilization. Unfortunately, our results question some disease-related genotyping analyses, raising a worrisome concern on their validity.

  4. No Association of SNPs in One-Carbon Metabolism Genes with Prostate Cancer Risk

    OpenAIRE

    Stevens, Victoria L.; Rodriguez, Carmen; Sun, Juzhong; Talbot, Jeffrey T.; Thun, Michael J.; Calle, Eugenia E.

    2008-01-01

    One-carbon metabolism mediates the inter-conversion of folates for the synthesis of precursors used in DNA synthesis, repair and methylation. Inadequate folate nutrition or compromised metabolism can disrupt these processes and facilitate carcinogenesis. In this study, we investigated associations of 39 candidate SNPs in nine one-carbon metabolism genes with risk of prostate cancer using 1,144 cases and 1,144 controls from the Cancer Prevention Study-II Nutrition Cohort. None of these SNPs we...

  5. AB048. X-chromosomal SNPs variation in populations of Russia

    OpenAIRE

    Stepanov, Vadim; Vagaitseva, Kseniya; Kharkov, Vladimir

    2015-01-01

    X-chromosome markers are informative tool for studying a genetic diversity in human populations and have become a useful in DNA identification when certain complex kinship cases need to be unravelled. In this work we present population genetic data on X-chromosome-wide SNPs in North Eurasian populations and report XSNP multiplex system for forensic genetics. A total of 2,867 X-chromosomal SNPs were genotyped in 12 populations using Illumina microarray platform. Twelve populations under study ...

  6. All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs

    DEFF Research Database (Denmark)

    Schork, Andrew J; Thompson, Wesley K; Pham, Phillip;

    2013-01-01

    (TDR = 1-FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment...

  7. Verification of SNPs Associated with Growth Traits in Two Populations of Farmed Atlantic Salmon

    Directory of Open Access Journals (Sweden)

    Hsin Y. Tsai

    2015-12-01

    Full Text Available Understanding the relationship between genetic variants and traits of economic importance in aquaculture species is pertinent to selective breeding programmes. High-throughput sequencing technologies have enabled the discovery of large numbers of SNPs in Atlantic salmon, and high density SNP arrays now exist. A previous genome-wide association study (GWAS using a high density SNP array (132K SNPs has revealed the polygenic nature of early growth traits in salmon, but has also identified candidate SNPs showing suggestive associations with these traits. The aim of this study was to test the association of the candidate growth-associated SNPs in a separate population of farmed Atlantic salmon to verify their effects. Identifying SNP-trait associations in two populations provides evidence that the associations are true and robust. Using a large cohort (N = 1152, we successfully genotyped eight candidate SNPs from the previous GWAS, two of which were significantly associated with several growth and fillet traits measured at harvest. The genes proximal to these SNPs were identified by alignment to the salmon reference genome and are discussed in the context of their potential role in underpinning genetic variation in salmon growth.

  8. SNPs and MALDI-TOF MS: tools for DNA typing in forensic paternity testing and anthropology.

    Science.gov (United States)

    Petkovski, Elizabet; Keyser-Tracqui, Christine; Hienne, Rémi; Ludes, Bertrand

    2005-05-01

    DNA markers used for individual identification in forensic sciences are based on repeat sequences in nuclear DNA and the mitochondrial DNA hypervariable regions 1 and 2. An alternative to these markers is the use of single nucleotide polymorphisms (SNPs). These have a particular advantage in the analysis of degraded or poor samples, which are often all that is available in forensics or anthropology. In order to study the potential of SNP analysis in these fields, 41 SNPs were selected on the basis of following criteria: conservation, lack of phenotypic expression, and frequency of occurrence in populations. Thirty-six autosomal SNPs were used for genotyping 21 inclusionary and 3 exclusionary paternity cases. The behavior of 5 X-chromosome SNPs was analyzed in a French representative population. Our approach to SNP typing is a multiplex PCR based amplification followed by simultaneous detection by primer extension (PEX) analyzed by Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). The selected autosomal SNPs showed independent inheritance and gave clear results in paternity investigation. All X-SNPs were useful as both paternity and identification markers. PEX and MALDI-TOF MS, with their high sensitivity, precision and speed, gave a powerful method for forensic and anthropological exploitation of biallelic markers.

  9. Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Dov Shiffman

    Full Text Available Myocardial infarction (MI is a common complex disease with a genetic component. While several single nucleotide polymorphisms (SNPs have been reported to be associated with risk of MI, they do not fully explain the observed genetic component of MI. We have been investigating the association between MI and SNPs that are located in genes and have the potential to affect gene function or expression. We have previously published studies that tested about 12,000 SNPs for association with risk of MI, early-onset MI, or coronary stenosis. In the current study we tested 17,576 SNPs that could affect gene function or expression. In order to use genotyping resources efficiently, we staged the testing of these SNPs in three case-control studies of MI. In the first study (762 cases, 857 controls we tested 17,576 SNPs and found 1,949 SNPs that were associated with MI (P<0.05. We tested these 1,949 SNPs in a second study (579 cases and 1159 controls and found that 24 SNPs were associated with MI (1-sided P<0.05 and had the same risk alleles in the first and second study. Finally, we tested these 24 SNPs in a third study (475 cases and 619 controls and found that 5 SNPs in 4 genes (ENO1, FXN (2 SNPs, HLA-DPB2, and LPA were associated with MI in the third study (1-sided P<0.05, and had the same risk alleles in all three studies. The false discovery rate for this group of 5 SNPs was 0.23. Thus, we have identified 5 SNPs that merit further examination for their potential association with MI. One of these SNPs (in LPA, has been previously shown to be associated with risk of cardiovascular disease in other studies.

  10. Preparing for Multiple Births

    Science.gov (United States)

    ... Video Games, and the Internet Preparing for Multiple Births KidsHealth > For Parents > Preparing for Multiple Births Print ... a combination of both. The Risks of Multiple Births The most common risk involved with multiple births ...

  11. In vitro human keratinocyte migration rates are associated with SNPs in the KRT1 interval.

    Directory of Open Access Journals (Sweden)

    Heng Tao

    Full Text Available Efforts to develop effective therapeutic treatments for promoting fast wound healing after injury to the epidermis are hindered by a lack of understanding of the factors involved. Re-epithelialization is an essential step of wound healing involving the migration of epidermal keratinocytes over the wound site. Here, we examine genetic variants in the keratin-1 (KRT1 locus for association with migration rates of human epidermal keratinocytes (HEK isolated from different individuals. Although the role of intermediate filament genes, including KRT1, in wound activated keratinocytes is well established, this is the first study to examine if genetic variants in humans contribute to differences in the migration rates of these cells. Using an in vitro scratch wound assay we observe quantifiable variation in HEK migration rates in two independent sets of samples; 24 samples in the first set and 17 samples in the second set. We analyze genetic variants in the KRT1 interval and identify SNPs significantly associated with HEK migration rates in both samples sets. Additionally, we show in the first set of samples that the average migration rate of HEK cells homozygous for one common haplotype pattern in the KRT1 interval is significantly faster than that of HEK cells homozygous for a second common haplotype pattern. Our study demonstrates that genetic variants in the KRT1 interval contribute to quantifiable differences in the migration rates of keratinocytes isolated from different individuals. Furthermore we show that in vitro cell assays can successfully be used to deconstruct complex traits into simple biological model systems for genetic association studies.

  12. A reduced number of mtSNPs saturates mitochondrial DNA haplotype diversity of worldwide population groups.

    Science.gov (United States)

    Salas, Antonio; Amigo, Jorge

    2010-05-03

    The high levels of variation characterising the mitochondrial DNA (mtDNA) molecule are due ultimately to its high average mutation rate; moreover, mtDNA variation is deeply structured in different populations and ethnic groups. There is growing interest in selecting a reduced number of mtDNA single nucleotide polymorphisms (mtSNPs) that account for the maximum level of discrimination power in a given population. Applications of the selected mtSNP panel range from anthropologic and medical studies to forensic genetic casework. This study proposes a new simulation-based method that explores the ability of different mtSNP panels to yield the maximum levels of discrimination power. The method explores subsets of mtSNPs of different sizes randomly chosen from a preselected panel of mtSNPs based on frequency. More than 2,000 complete genomes representing three main continental human population groups (Africa, Europe, and Asia) and two admixed populations ("African-Americans" and "Hispanics") were collected from GenBank and the literature, and were used as training sets. Haplotype diversity was measured for each combination of mtSNP and compared with existing mtSNP panels available in the literature. The data indicates that only a reduced number of mtSNPs ranging from six to 22 are needed to account for 95% of the maximum haplotype diversity of a given population sample. However, only a small proportion of the best mtSNPs are shared between populations, indicating that there is not a perfect set of "universal" mtSNPs suitable for all population contexts. The discrimination power provided by these mtSNPs is much higher than the power of the mtSNP panels proposed in the literature to date. Some mtSNP combinations also yield high diversity values in admixed populations. The proposed computational approach for exploring combinations of mtSNPs that optimise the discrimination power of a given set of mtSNPs is more efficient than previous empirical approaches. In contrast to

  13. Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation.

    Science.gov (United States)

    Du, QiaoLing; Pan, YouDong; Zhang, YouHua; Zhang, HaiLong; Zheng, YaJuan; Lu, Ling; Wang, JunLei; Duan, Tao; Chen, JianFeng

    2014-07-07

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP. Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10-40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining. The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas. Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis.

  14. Identification and analysis of Single Nucleotide Polymorphisms (SNPs in the mosquito Anopheles funestus, malaria vector

    Directory of Open Access Journals (Sweden)

    Hemingway Janet

    2007-01-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the most common source of genetic variation in eukaryotic species and have become an important marker for genetic studies. The mosquito Anopheles funestus is one of the major malaria vectors in Africa and yet, prior to this study, no SNPs have been described for this species. Here we report a genome-wide set of SNP markers for use in genetic studies on this important human disease vector. Results DNA fragments from 50 genes were amplified and sequenced from 21 specimens of An. funestus. A third of specimens were field collected in Malawi, a third from a colony of Mozambican origin and a third form a colony of Angolan origin. A total of 494 SNPs including 303 within the coding regions of genes and 5 indels were identified. The physical positions of these SNPs in the genome are known. There were on average 7 SNPs per kilobase similar to that observed in An. gambiae and Drosophila melanogaster. Transitions outnumbered transversions, at a ratio of 2:1. The increased frequency of transition substitutions in coding regions is likely due to the structure of the genetic code and selective constraints. Synonymous sites within coding regions showed a higher polymorphism rate than non-coding introns or 3' and 5'flanking DNA with most of the substitutions in coding regions being observed at the 3rd codon position. A positive correlation in the level of polymorphism was observed between coding and non-coding regions within a gene. By genotyping a subset of 30 SNPs, we confirmed the validity of the SNPs identified during this study. Conclusion This set of SNP markers represents a useful tool for genetic studies in An. funestus, and will be useful in identifying candidate genes that affect diverse ranges of phenotypes that impact on vector control, such as resistance insecticide, mosquito behavior and vector competence.

  15. Presence of SNPs in GDF9 mRNA of Iranian Afshari Sheep

    Directory of Open Access Journals (Sweden)

    Talat Saiedi

    2012-01-01

    Full Text Available Background: Multiple births occur frequently in some Iranian sheep breeds, while infertilityscarcely occurs. Mutation detection in major fecundity genes has been explored in most of Iraniansheep flocks over the last decade. However, previously reported single nucleotide polymorphisms(SNPs for bone morphogenetic protein receptor-(BMPR-1B and growth differentiation factor GDF9( known to affect fertility have not been detected. This study was conducted to assess whetherany significant mutations in GDF9 were extracted from slaughtered ewe ovaries of Iranian Afsharisheep breed.Materials and Methods: Ovaries defined as poor, fair, and excellent quality based on externalvisual appearance of follicles were used for histology and RNA extraction processes. High qualityRNAs underwent reverse transcriptase-polymerase chain reaction (RT-PCR from GDF9 mRNA,and the products sequenced.Results: No streak ovaries, which are considered indicators of infertility due to homozygocity forsome mutations in GDF9 and BMP15, were found. Sequencing results from GDF9 cDNA showedthat G2 (C471T, G3 (G477A, and G4 (G721A mutations were observed from 1, 4, and 1 out of12 ewes, respectively. Though all 3 mutations were previously reported, this is the first report ontheir presence in Iranian breeds. The first and second mutations do not alter the amino acids, whileG4 is a non-conservative mutation leading to E241K in the prohormone.Conclusion: As the G4 mutation was observed only in ovaries defined superficially as top quality,it could be considered as one of reasons for higher ovulation rate in some sheep. Furthermore sincemultiple mutations were observed in some cases, it might be possible that combinations of minormutations in GDF9 and BMP15 interact to affect fecundity in some Iranian sheep breeds.

  16. A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia

    Science.gov (United States)

    Ferrari, Raffaele; Grassi, Mario; Salvi, Erika; Borroni, Barbara; Palluzzi, Fernando; Pepe, Daniele; D'Avila, Francesca; Padovani, Alessandro; Archetti, Silvana; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Galimberti, Daniela; Scarpini, Elio; Serpente, Maria; Rossi, Giacomina; Giaccone, Giorgio; Tagliavini, Fabrizio; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Bruni, Amalia C.; Maletta, Raffaele G.; Bernardi, Livia; Postiglione, Alfredo; Milan, Graziella; Franceschi, Massimo; Puca, Annibale A.; Novelli, Valeria; Barlassina, Cristina; Glorioso, Nicola; Manunta, Paolo; Singleton, Andrew; Cusi, Daniele; Hardy, John; Momeni, Parastoo

    2015-01-01

    Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10−7 and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of –cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD–genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis. PMID:26154020

  17. A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia.

    Science.gov (United States)

    Ferrari, Raffaele; Grassi, Mario; Salvi, Erika; Borroni, Barbara; Palluzzi, Fernando; Pepe, Daniele; D'Avila, Francesca; Padovani, Alessandro; Archetti, Silvana; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Galimberti, Daniela; Scarpini, Elio; Serpente, Maria; Rossi, Giacomina; Giaccone, Giorgio; Tagliavini, Fabrizio; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Bruni, Amalia C; Maletta, Raffaele G; Bernardi, Livia; Postiglione, Alfredo; Milan, Graziella; Franceschi, Massimo; Puca, Annibale A; Novelli, Valeria; Barlassina, Cristina; Glorioso, Nicola; Manunta, Paolo; Singleton, Andrew; Cusi, Daniele; Hardy, John; Momeni, Parastoo

    2015-10-01

    Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10(-7) and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of -cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD-genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis.

  18. Association analysis identifies Melampsora ×columbiana poplar leaf rust resistance SNPs.

    Directory of Open Access Journals (Sweden)

    Jonathan La Mantia

    Full Text Available Populus species are currently being domesticated through intensive time- and resource-dependent programs for utilization in phytoremediation, wood and paper products, and conversion to biofuels. Poplar leaf rust disease can greatly reduce wood volume. Genetic resistance is effective in reducing economic losses but major resistance loci have been race-specific and can be readily defeated by the pathogen. Developing durable disease resistance requires the identification of non-race-specific loci. In the presented study, area under the disease progress curve was calculated from natural infection of Melampsora ×columbiana in three consecutive years. Association analysis was performed using 412 P. trichocarpa clones genotyped with 29,355 SNPs covering 3,543 genes. We found 40 SNPs within 26 unique genes significantly associated (permutated P<0.05 with poplar rust severity. Moreover, two SNPs were repeated in all three years suggesting non-race-specificity and three additional SNPs were differentially expressed in other poplar rust interactions. These five SNPs were found in genes that have orthologs in Arabidopsis with functionality in pathogen induced transcriptome reprogramming, Ca²⁺/calmodulin and salicylic acid signaling, and tolerance to reactive oxygen species. The additive effect of non-R gene functional variants may constitute high levels of durable poplar leaf rust resistance. Therefore, these findings are of significance for speeding the genetic improvement of this long-lived, economically important organism.

  19. Studies on interaction of colloidal silver nanoparticles (SNPs) with five different bacterial species.

    Science.gov (United States)

    Khan, S Sudheer; Mukherjee, Amitava; Chandrasekaran, N

    2011-10-01

    Silver nanoparticles (SNPs) are being increasingly used in many consumer products like textile fabrics, cosmetics, washing machines, food and drug products owing to its excellent antimicrobial properties. Here we have studied the adsorption and toxicity of SNPs on bacterial species such as Pseudomonas aeruginosa, Micrococcus luteus, Bacillus subtilis, Bacillus barbaricus and Klebsiella pneumoniae. The influence of zeta potential on the adsorption of SNPs on bacterial cell surface was investigated at acidic, neutral and alkaline pH and with varying salt (NaCl) concentrations (0.05, 0.1, 0.5, 1 and 1.5 M). The survival rate of bacterial species decreased with increase in adsorption of SNPs. Maximum adsorption and toxicity was observed at pH 5, and NaCl concentration of 0.5 M, there by resulting in less toxicity. The zeta potential study suggests that, the adsorption of SNPs on the cell surface was related to electrostatic force of attraction. The equilibrium and kinetics of the adsorption process were also studied. The adsorption equilibrium isotherms fitted well to the Langmuir model. The kinetics of adsorption fitted best to pseudo-first-order. These findings form a basis for interpreting the interaction of nanoparticles with environmental bacterial species.

  20. Single nucleotide polymorphisms (SNPs) in key cytokines may modulate food allergy phenotypes

    Science.gov (United States)

    Brown, Paula; Nair, Bindukumar; Sykes, Donald E.; Rich, Gary; Reynolds, Jessica L.; Aalinkeel, Ravikumar; Wheeler, John; Schwartz, Stanley A.

    2012-01-01

    Single nucleotide polymorphisms (SNPs) can play a direct or indirect role in phenotypic expression in food allergy pathogenesis. Our goal was to quantitate the expression of SNPs in relevant cytokines that were expressed in food allergic patients. SNPs in cytokine genes IL-4 and IL-10 are known to be important in IgE generation and regulation. We examined IL-4 (C-590T), IL-4Rα (1652A/G) and IL-10 (C-627A) SNPs using real-time PCR followed by restriction fragment length polymorphism (RFLP) analysis. Our results show that the AA, AG and GG genotypes for IL-4Rα (1652A/G) polymorphisms were statistically different in radioallergosorbent test (RAST) positive versus negative patients, and although no statistically significant differences were observed between genotypes in the IL-4 (C-590T) and IL-10 (C-627A) SNPs, we observed a significant decrease in IL-4 (C-590T) gene expression and increase in IL-4Rα (1652A/G) and IL-10 (C-627A) gene expression between RAST+ versus RAST− patients, respectively. We also observed significant modulation in the protein expression of IL-4 and IL-10 in the serum samples of the RAST+ patients as compared to the RAST− patients indicating that changes in SNP expression resulted in altered phenotypic response in these patients. PMID:23230389

  1. Mining the 30UTR of Autism-implicated Genes for SNPs Perturbing MicroRNA Regulation

    Institute of Scientific and Technical Information of China (English)

    Varadharajan Vaishnavi; Mayakannan Manikandan; Arasambattu Kannan Munirajan

    2014-01-01

    Autism spectrum disorder (ASD) refers to a group of childhood neurodevelopmental dis-orders with polygenic etiology. The expression of many genes implicated in ASD is tightly regulated by various factors including microRNAs (miRNAs), a class of noncoding RNAs 22 nucleotides in length that function to suppress translation by pairing with‘miRNA recognition elements’ (MREs) present in the 30untranslated region (30UTR) of target mRNAs. This emphasizes the role played by miRNAs in regulating neurogenesis, brain development and differentiation and hence any perturba-tions in this regulatory mechanism might affect these processes as well. Recently, single nucleotide polymorphisms (SNPs) present within 30UTRs of mRNAs have been shown to modulate existing MREs or even create new MREs. Therefore, we hypothesized that SNPs perturbing miRNA-medi-ated gene regulation might lead to aberrant expression of autism-implicated genes, thus resulting in disease predisposition or pathogenesis in at least a subpopulation of ASD individuals. We developed a systematic computational pipeline that integrates data from well-established databases. By following a stringent selection criterion, we identified 9 MRE-modulating SNPs and another 12 MRE-creating SNPs in the 30UTR of autism-implicated genes. These high-confidence candidate SNPs may play roles in ASD and hence would be valuable for further functional validation.

  2. Mining the 3'UTR of autism-implicated genes for SNPs perturbing microRNA regulation.

    Science.gov (United States)

    Vaishnavi, Varadharajan; Manikandan, Mayakannan; Munirajan, Arasambattu Kannan

    2014-04-01

    Autism spectrum disorder (ASD) refers to a group of childhood neurodevelopmental disorders with polygenic etiology. The expression of many genes implicated in ASD is tightly regulated by various factors including microRNAs (miRNAs), a class of noncoding RNAs ~22 nucleotides in length that function to suppress translation by pairing with 'miRNA recognition elements' (MREs) present in the 3'untranslated region (3'UTR) of target mRNAs. This emphasizes the role played by miRNAs in regulating neurogenesis, brain development and differentiation and hence any perturbations in this regulatory mechanism might affect these processes as well. Recently, single nucleotide polymorphisms (SNPs) present within 3'UTRs of mRNAs have been shown to modulate existing MREs or even create new MREs. Therefore, we hypothesized that SNPs perturbing miRNA-mediated gene regulation might lead to aberrant expression of autism-implicated genes, thus resulting in disease predisposition or pathogenesis in at least a subpopulation of ASD individuals. We developed a systematic computational pipeline that integrates data from well-established databases. By following a stringent selection criterion, we identified 9 MRE-modulating SNPs and another 12 MRE-creating SNPs in the 3'UTR of autism-implicated genes. These high-confidence candidate SNPs may play roles in ASD and hence would be valuable for further functional validation. Copyright © 2014. Production and hosting by Elsevier Ltd.

  3. Partition dataset according to amino acid type improves the prediction of deleterious non-synonymous SNPs

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jing; Li, Yuan-Yuan [School of Biotechnology, East China University of Science and Technology, Shanghai 200237 (China); Shanghai Center for Bioinformation Technology, Shanghai 200235 (China); Li, Yi-Xue, E-mail: yxli@sibs.ac.cn [School of Biotechnology, East China University of Science and Technology, Shanghai 200237 (China); Shanghai Center for Bioinformation Technology, Shanghai 200235 (China); Ye, Zhi-Qiang, E-mail: yezq@pkusz.edu.cn [Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055 (China); Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer Proper dataset partition can improve the prediction of deleterious nsSNPs. Black-Right-Pointing-Pointer Partition according to original residue type at nsSNP is a good criterion. Black-Right-Pointing-Pointer Similar strategy is supposed promising in other machine learning problems. -- Abstract: Many non-synonymous SNPs (nsSNPs) are associated with diseases, and numerous machine learning methods have been applied to train classifiers for sorting disease-associated nsSNPs from neutral ones. The continuously accumulated nsSNP data allows us to further explore better prediction approaches. In this work, we partitioned the training data into 20 subsets according to either original or substituted amino acid type at the nsSNP site. Using support vector machine (SVM), training classification models on each subset resulted in an overall accuracy of 76.3% or 74.9% depending on the two different partition criteria, while training on the whole dataset obtained an accuracy of only 72.6%. Moreover, the dataset was also randomly divided into 20 subsets, but the corresponding accuracy was only 73.2%. Our results demonstrated that partitioning the whole training dataset into subsets properly, i.e., according to the residue type at the nsSNP site, will improve the performance of the trained classifiers significantly, which should be valuable in developing better tools for predicting the disease-association of nsSNPs.

  4. Clustering of SNPs along a chromosome can the neutral model be rejected?

    CERN Document Server

    Eriksson, A; Mehlig, B

    2002-01-01

    Single nucleotide polymorphisms (SNPs) often appear in clusters along the length of a chromosome. This is due to variation in local coalescent times caused by,for example, selection or recombination. Here we investigate whether recombination alone (within a neutral model) can cause statistically significant SNP clustering. We measure the extent of SNP clustering as the ratio between the variance of SNPs found in bins of length $l$, and the mean number of SNPs in such bins, $\\sigma^2_l/\\mu_l$. For a uniform SNP distribution $\\sigma^2_l/\\mu_l=1$, for clustered SNPs $\\sigma^2_l/\\mu_l > 1$. Apart from the bin length, three length scales are important when accounting for SNP clustering: The mean distance between neighboring SNPs, $\\Delta$, the mean length of chromosome segments with constant time to the most recent common ancestor, $\\el$, and the total length of the chromosome, $L$. We show that SNP clustering is observed if $\\Delta < \\el \\ll L$. Moreover, if $l\\ll \\el \\ll L$, clustering becomes independent of ...

  5. Finding a Needle in a Haystack: Distinguishing Mexican Maize Landraces Using a Small Number of SNPs

    Science.gov (United States)

    Caldu-Primo, Jose L.; Mastretta-Yanes, Alicia; Wegier, Ana; Piñero, Daniel

    2017-01-01

    In Mexico's territory, the center of origin and domestication of maize (Zea mays), there is a large phenotypic diversity of this crop. This diversity has been classified into “landraces.” Previous studies have reported that genomic variation in Mexican maize is better explained by environmental factors, particularly those related with altitude, than by landrace. Still, landraces are extensively used by agronomists, who recognize them as stable and discriminatory categories for the classification of samples. In order to investigate the genomic foundation of maize landraces, we analyzed genomic data (35,909 SNPs from Illumina MaizeSNP50 BeadChip) obtained from 50 samples representing five maize landraces (Comiteco, Conejo, Tehua, Zapalote Grande, and Zapalote Chico), and searched for markers suitable for landrace assignment. Landrace clusters could not be identified taking all the genomic information, but they become manifest taking only a subset of SNPs with high FST among landraces. Discriminant analysis of principal components was conducted to classify samples using SNP data. Two classification analyses were done, first classifying samples by landrace and then by altitude category. Through this classification method, we identified 20 landrace-informative SNPs and 14 altitude-informative SNPs, with only 6 SNPs in common for both analyses. These results show that Mexican maize phenotypic diversity can be classified in landraces using a small number of genomic markers, given the fact that landrace genomic diversity is influenced by environmental factors as well as artificial selection due to bio-cultural practices. PMID:28458682

  6. Single Nucleotide Polymorphisms (SNPs) Discovery and Linkage Disequilibrium (LD) in Forest Trees

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    With completion of the Populus genome sequencing project and the availability of many expressed sequence tags (ESTs) databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms (SNPs), which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium (LD) rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.

  7. 11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma

    Directory of Open Access Journals (Sweden)

    Ambrosini Valentina

    2007-06-01

    Full Text Available Abstract Background Multiple Myeloma (MM is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS, Magnetic resonance (MR and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40% had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20% had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40% had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042. Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8. Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.

  8. The icmF3 locus is involved in multiple adaptation- and virulence-related characteristics in Pseudomonas aeruginosa PAO1

    Directory of Open Access Journals (Sweden)

    Jinshui eLin

    2015-10-01

    Full Text Available The type VI secretion system (T6SS is widely distributed in Gram-negative bacteria. Three separate T6SSs called H1-, H2-, and H3-T6SS have been discovered in Pseudomonas aeruginosa PAO1. Recent studies suggest that, in contrast to the H1-T6SS that targets prokaryotic cells, H2-T6SS and H3-T6SS are involved in interactions with both prokaryotic and eukaryotic cells. However, the detailed functions of T6SS components are still uncharacterized. The intracellular multiplication factor (IcmF protein is conserved in type VI secretion systems (T6SS of all different bacterial pathogens. Bioinformatic analysis revealed that IcmF3 in P. aeruginosa PAO1 is different from other IcmF homologues and may represent a new branch of these proteins with distinct functions. Herein, we have investigated the function of IcmF3 in this strain. We have shown that deletion of the icmF3 gene in P. aeruginosa PAO1 is associated with pleiotropic phenotypes. The icmF3 mutant has variant colony morphology and an hypergrowth phenotype in iron-limiting medium. Surprisingly, this mutant is also defective for the production of pyoverdine, as well as defects in swimming motility and virulence in a C. elegans worm model. The icmF3 mutant exhibits higher conjugation frequency than the wild type and increased biofilm formation on abiotic surfaces. Additionally, expression of two phenazine biosynthetic loci is increased in the icmF3 mutant, leading to the overproduction of pyocyanin. Finally, the mutant exhibits decreased susceptibility to aminoglycosides such as tobramycin and gentamicin. And the detected phenotypes can be restored completely or partially by trans complementation of wild type icmF3 gene. The pleiotropic effects observed upon icmF3 deletion demonstrate that icmF3 plays critical roles in both pathogenesis and environmental adaptation in P. aeruginosa PAO1.

  9. Systemic inflammation in progressive multiple sclerosis involves follicular T-helper, Th17- and activated B-cells and correlates with progression.

    Directory of Open Access Journals (Sweden)

    Jeppe Romme Christensen

    Full Text Available Pathology studies of progressive multiple sclerosis (MS indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship with disease progression, using flow cytometry and gene expression analysis of CD4(+ and CD8(+T-cells, B-cells, monocytes and dendritic cells. Furthermore, gene expression of cerebrospinal fluid cells was studied. Flow cytometry studies revealed increased frequencies of ICOS(+TFH-cells in peripheral blood from relapsing-remitting (RRMS and secondary progressive (SPMS MS patients. All MS subtypes had decreased frequencies of Th1 TFH-cells, while primary progressive (PPMS MS patients had increased frequency of Th17 TFH-cells. The Th17-subset, interleukin-23-receptor(+CD4(+T-cells, was significantly increased in PPMS and SPMS. In the analysis of B-cells, we found a significant increase of plasmablasts and DC-SIGN(+ and CD83(+B-cells in SPMS. ICOS(+TFH-cells and DC-SIGN(+B-cells correlated with disease progression in SPMS patients. Gene expression analysis of peripheral blood cell subsets substantiated the flow cytometry findings by demonstrating increased expression of IL21, IL21R and ICOS in CD4(+T-cells in progressive MS. Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and PPMS patients had increased expression of TFH-cell and plasmablast markers. In conclusion, this study is the first to demonstrate the potential involvement of activated TFH-cells in MS. The increased frequencies of Th17-cells, activated TFH- and B-cells parallel findings

  10. Role of {sup 18}F-FDG PET/CT in the assessment of bone involvement in newly diagnosed multiple myeloma: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Nanni, Cristina; Farsad, Mohsen; Castellucci, Paolo; Fanti, Stefano [Policlinico S.Orsola-Malpighi, UO Medicina Nucleare, Bologna (Italy); Zamagni, Elena; Tosi, Patrizia; Cangini, Delia; Cavo, Michele [Policlinico S.Orsola-Malpighi, Istituto di Ematologia, Bologna (Italy); Salizzoni, Eugenio; Canini, Romeo [Policlinico S.Orsola-Malpighi, Istituto di Radiologia, Bologna (Italy)

    2006-05-15

    Purpose Multiple myeloma (MM) is a malignant B cell and plasma cell disorder which involves the skeleton in more than 80% of patients at diagnosis. The aim of this study was to compare whole-body X-ray (WBXR), MRI and {sup 18}F-FDG PET/CT in patients with MM. Methods The study population comprised 28 newly diagnosed MM patients. Findings of {sup 18}F-FDG PET/CT were compared with those of WBXR and MRI with regard to the number and site of lesions detected. Results Comparing 18F-FDG PET/CT and WBXR, it was found that in 16/28 pts (57%) {sup 18}F-FDG PET/CT detected more lesions, all of which were located in the skeleton. Nine of these 16 patients had a completely negative WBXR survey. In 12/28 pts (43%) the two methods yielded equivalent findings. Comparing {sup 18}F-FDG PET/CT and MRI, it was found that in 7/28 pts (25%), {sup 18}F-FDG PET/CT detected more lytic bone lesions, all of which were located outside the field of view of MRI (bone lesions in six cases and a soft tissue lesion in one). In 14/28 pts (50%), {sup 18}F-FDG PET/CT and MRI detected the same number of lesions in the spine and pelvis, while in 7/28 pts (25%) MRI detected an infiltrative pattern in the spine whereas {sup 18}F-FDG PET/CT was negative. Conclusion {sup 18}F-FDG PET/CT appears to be more sensitive than WBXR for the detection of small lytic bone lesions, whereas it has the same sensitivity as MRI in detecting bone disease of the spine and pelvis. On the other hand, MRI may be superior to 18F-FDG PET/CT in diagnosing an infiltrative pattern in the spine. Therefore, careful evaluation of MM bone disease at diagnosis should include both MRI of the spine and {sup 18}F-FDG PET/CT.

  11. ASSOCIATIONS BETWEEN SNPs IN BOVINE ESTROGEN RECEPTOR GENE AND PRODUCTION TRAITS IN HOLSTEIN CATTLE

    Directory of Open Access Journals (Sweden)

    Nina Moravčíková

    2015-02-01

    Full Text Available aim of this study was to determine allelic and genotypic frequency of two SNPs in ERα gene and evaluate the associations between ERα genetic variants and milk production traits in Holstein cattle. Analysis of the molecular mechanisms involved in the regulation of reproduction in connection with milk production and followed genotyping of the individuals with optimal genetic potential may facilitate the animal selection in dairy cattle farms. Genomic DNA was obtained in total from 150 hair root samples of Holstein cows. Two polymorphic sites in 5´region on ERα gene (BTA6 were analysed. Genotyping of animals was carried out by PCR-RFLP method using SnaBI and BglI restriction endonucleases. After restriction analyses was detected in population the presence of two ERα/SnaBI (GG, AG, and three ERα/BglI genotypes (GG, AG, AA. The highest proportion was found for individuals with ERα/SnaBI GG (85% and ERα/BglI AA (83% genotypes. The missing of ERα/SnaBI AA genotype was reflected to the higher distribution of G allele (0.92± 0.02. For the ERα/BglI polymorphism was observed the higher frequency of A allele (0.91±0.02. The differences between observed and expected genotype frequencies caused the deviations from HWE in locus ERα/SnaBI. The statistical analyses of ERα genotypes effect on milk production traits was performed with linear models (GLM procedure. Based on the selected effect we were able to estimate the variability of analyzed traits on 80%. The ERα/SnaBI and ERα/BglI genotypes affected the variability of milk, protein and fat yield only non-significant (P > 0.05.

  12. A Comprehensive In Silico Analysis of the Functional and Structural Impact of SNPs in the IGF1R Gene

    Directory of Open Access Journals (Sweden)

    S. A. de Alencar

    2010-01-01

    Full Text Available Insulin-like growth factor 1 receptor (IGF1R acts as a critical mediator of cell proliferation and survival. Many single nucleotide polymorphisms (SNPs found in the IGF1R gene have been associated with various diseases, including both breast and prostate cancer. The genetics of these diseases could be better understood by knowing the functions of these SNPs. In this study, we performed a comprehensive analysis of the functional and structural impact of all known SNPs in this gene using publicly available computational prediction tools. Out of a total of 2412 SNPs in IGF1R retrieved from dbSNP, we found 32 nsSNPs, 58 sSNPs, 83 mRNA 3′ UTR SNPs, and 2225 intronic SNPs. Among the nsSNPs, a total of six missense nsSNPs were found to be damaging by both a sequence homology-based tool (SIFT and a structural homology-based method (PolyPhen, and one nonsense nsSNP was found. Further, we modeled mutant proteins and compared the total energy values with the native IGF1R protein, and showed that a mutation from arginine to cysteine at position 1216 (rs61740868 on the surface of the protein caused the greatest impact on stability. Also, the FASTSNP tool suggested that 31 sSNPs and 3 intronic SNPs might affect splicing regulation. Based on our investigation, we report potential candidate SNPs for future studies on IGF1R mutations.

  13. SNPs selected by information content outperform randomly selected microsatellite loci for delineating genetic identification and introgression in the endangered dark European honeybee (Apis mellifera mellifera).

    Science.gov (United States)

    Muñoz, Irene; Henriques, Dora; Jara, Laura; Johnston, J Spencer; Chávez-Galarza, Julio; De La Rúa, Pilar; Pinto, M Alice

    2016-11-14

    The honeybee (Apis mellifera) has been threatened by multiple factors including pests and pathogens, pesticides and loss of locally adapted gene complexes due to replacement and introgression. In western Europe, the genetic integrity of the native A. m. mellifera (M-lineage) is endangered due to trading and intensive queen breeding with commercial subspecies of eastern European ancestry (C-lineage). Effective conservation actions require reliable molecular tools to identify pure-bred A. m. mellifera colonies. Microsatellites have been preferred for identification of A. m. mellifera stocks across conservation centres. However, owing to high throughput, easy transferability between laboratories and low genotyping error, SNPs promise to become popular. Here, we compared the resolving power of a widely utilized microsatellite set to detect structure and introgression with that of different sets that combine a variable number of SNPs selected for their information content and genomic proximity to the microsatellite loci. Contrary to every SNP data set, microsatellites did not discriminate between the two lineages in the PCA space. Mean introgression proportions were identical across the two marker types, although at the individual level, microsatellites' performance was relatively poor at the upper range of Q-values, a result reflected by their lower precision. Our results suggest that SNPs are more accurate and powerful than microsatellites for identification of A. m. mellifera colonies, especially when they are selected by information content.

  14. Investigation of multiple organ involvement in Fabry disease%法布里病患者多器官病变的临床特点分析

    Institute of Scientific and Technical Information of China (English)

    张巍; 康曼德; 赵亚雯; 李凡; 舒俊龙; 左越焕; 刘靖; 黄一宁; 袁云

    2015-01-01

    Objective To investigate incidence and clinical features of multiple organ involvement in Chinese patients with Fabry disease.Methods We collected 151 patients of 31 families with Fabry disease,all of whom were confirmed by classic pathology,decreased α-galactosidase A activity or GLA mutation from the year of 2011 to 2014 in Department of Neurology,Peking University First Hospital.The clinical data included incidence and onset of neuralgia,renal dysfunction,heart disease,hypertension and cerebral stroke.We calculate the incidence of these symptoms and analyze their gender difference using chisquare with SPSS 17.0 software.Results Among 31 families with Fabry disease,151 patients (82 males and 69 females) were affected,including 91 patients (60.26%) with neuralgia,62 patients (41.06%) with renal disease,33 patients (21.85%) with heart disease,33 patients (21.85%) with hypertension,and 21 patients (13.91%) with cerebral stroke.The peak incidence of neuralgia was from 10 to 20 years old,followed by renal disease from 30 to 40 years old,heart disease and stroke from 40 to 50 years old.There is no peak period for hypertension.Except for males with higher incidence of renal dysfunction than females (P < 0.05),there were no gender difference in the incidence of other organ involvement.Conclusion The incidence and onset of multiple organ dysfunction in Chinese patients with Fabry disease displayed special regularity.Gender difference appeared only in renal disease.%目的 总结我国法布里病患者多器官病变的发生率和临床表现特点.方法 收集北京大学第一医院神经内科2001-2014年依据病理改变、α-半乳糖苷酶活性A测定和GLA基因突变检查确诊的31个法布里病家系发病者的临床资料,统计其神经痛、肾脏病变、心脏病变、高血压病和脑卒中的发生率和起病时间,使用SPSS 17.0统计软件对男女患者不同器官损害的发生率进行x2检验,比较男女患者上述

  15. A robust linkage map of the porcine autosome based on gene-associated SNPs

    DEFF Research Database (Denmark)

    Vingborg, Rikke K K; Gregersen, Vivi R; Zhan, Bujie;

    2009-01-01

    Background Genetic linkage maps are necessary for mapping of mendelian traits and quantitative trait loci (QTLs). To identify the actual genes, which control these traits, a map based on gene-associated single nucleotide polymorphism (SNP) markers is highly valuable. In this study, the SNPs were...... genotyped in a large family material comprising more than 5,000 piglets derived from 12 Duroc boars crossed with 236 Danish Landrace/Danish Large White sows. The SNPs were identified in sequence alignments of 4,600 different amplicons obtained from the 12 boars and containing coding regions of genes derived...... from expressed sequence tags (ESTs) and genomic shotgun sequences. Results Linkage maps of all 18 porcine autosomes were constructed based on 456 gene-associated and six porcine EST-based SNPs. The total length of the averaged-sex whole porcine autosome was estimated to 1,711.8 cM resulting...

  16. Observed Changes in the Alertness and Communicative Involvement of Students with Multiple and Severe Disability Following In-Class Mentor Modelling for Staff in Segregated and General Education Classrooms

    Science.gov (United States)

    Foreman, P.; Arthur-Kelly, M.; Bennett, D.; Neilands, J.; Colyvas, K.

    2014-01-01

    Background: The improvement of engagement and involvement in communicative and socially centred exchanges for individuals with multiple and severe disability (MSD) presents complex and urgent challenges to educators. This paper reports the findings of an intervention study designed to enhance the interactive skills of students with MSD using an…

  17. Identifying Causal Genes at the Multiple Sclerosis Associated Region 6q23 Using Capture Hi-C.

    Science.gov (United States)

    Martin, Paul; McGovern, Amanda; Massey, Jonathan; Schoenfelder, Stefan; Duffus, Kate; Yarwood, Annie; Barton, Anne; Worthington, Jane; Fraser, Peter; Eyre, Stephen; Orozco, Gisela

    2016-01-01

    The chromosomal region 6q23 has been found to be associated with multiple sclerosis (MS) predisposition through genome wide association studies (GWAS). There are four independent single nucleotide polymorphisms (SNPs) associated with MS in this region, which spans around 2.5 Mb. Most GWAS variants associated with complex traits, including these four MS associated SNPs, are non-coding and their function is currently unknown. However, GWAS variants have been found to be enriched in enhancers and there is evidence that they may be involved in transcriptional regulation of their distant target genes through long range chromatin looping. The aim of this work is to identify causal disease genes in the 6q23 locus by studying long range chromatin interactions, using the recently developed Capture Hi-C method in human T and B-cell lines. Interactions involving four independent associations unique to MS, tagged by rs11154801, rs17066096, rs7769192 and rs67297943 were analysed using Capture Hi-C Analysis of Genomic Organisation (CHiCAGO). We found that the pattern of chromatin looping interactions in the MS 6q23 associated region is complex. Interactions cluster in two regions, the first involving the rs11154801 region and a second containing the rs17066096, rs7769192 and rs67297943 SNPs. Firstly, SNPs located within the AHI1 gene, tagged by rs11154801, are correlated with expression of AHI1 and interact with its promoter. These SNPs also interact with other potential candidate genes such as SGK1 and BCLAF1. Secondly, the rs17066096, rs7769192 and rs67297943 SNPs interact with each other and with immune-related genes such as IL20RA, IL22RA2, IFNGR1 and TNFAIP3. Finally, the above-mentioned regions interact with each other and therefore, may co-regulate these target genes. These results suggest that the four 6q23 variants, independently associated with MS, are involved in the regulation of several genes, including immune genes. These findings could help understand mechanisms

  18. SNPs in stress-responsive rice genes: validation, genotyping, functional relevance and population structure

    Directory of Open Access Journals (Sweden)

    Parida Swarup K

    2012-08-01

    Full Text Available Abstract Background Single nucleotide polymorphism (SNP validation and large-scale genotyping are required to maximize the use of DNA sequence variation and determine the functional relevance of candidate genes for complex stress tolerance traits through genetic association in rice. We used the bead array platform-based Illumina GoldenGate assay to validate and genotype SNPs in a select set of stress-responsive genes to understand their functional relevance and study the population structure in rice. Results Of the 384 putative SNPs assayed, we successfully validated and genotyped 362 (94.3%. Of these 325 (84.6% showed polymorphism among the 91 rice genotypes examined. Physical distribution, degree of allele sharing, admixtures and introgression, and amino acid replacement of SNPs in 263 abiotic and 62 biotic stress-responsive genes provided clues for identification and targeted mapping of trait-associated genomic regions. We assessed the functional and adaptive significance of validated SNPs in a set of contrasting drought tolerant upland and sensitive lowland rice genotypes by correlating their allelic variation with amino acid sequence alterations in catalytic domains and three-dimensional secondary protein structure encoded by stress-responsive genes. We found a strong genetic association among SNPs in the nine stress-responsive genes with upland and lowland ecological adaptation. Higher nucleotide diversity was observed in indica accessions compared with other rice sub-populations based on different population genetic parameters. The inferred ancestry of 16% among rice genotypes was derived from admixed populations with the maximum between upland aus and wild Oryza species. Conclusions SNPs validated in biotic and abiotic stress-responsive rice genes can be used in association analyses to identify candidate genes and develop functional markers for stress tolerance in rice.

  19. Computational identification and structural analysis of deleterious functional SNPs in MLL gene causing acute leukemia.

    Science.gov (United States)

    George Priya Doss, C; Rajasekaran, R; Sethumadhavan, Rao

    2010-09-01

    A promising application of the huge amounts of data from the Human Genome Project currently available offers new opportunities for identifying the genetic predisposition and developing a better understanding of complex diseases such as cancers. The main focus of cancer genetics is the study of mutations that are causally implicated in tumorigenesis. The identification of such causal mutations does not only provide insight into cancer biology but also presents anticancer therapeutic targets and diagnostic markers. In this study, we evaluated the Single Nucleotide Polymorphisms (SNPs) that can alter the expression and the function in MLL gene through computational methods. We applied an evolutionary perspective to screen the SNPs using a sequence homologybased SIFT tool, suggested that 10 non-synonymous SNPs (nsSNPs) (50%) were found to be deleterious. Structure based approach PolyPhen server suggested that 5 nsSNPS (25%) may disrupt protein function and structure. PupaSuite tool predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Structure analysis was carried out with the major mutations that occurred in the native protein coded by MLL gene is at amino acid positions Q1198P and K1203Q. The solvent accessibility results showed that 7 residues changed from exposed state in the native type protein to buried state in Q1198P mutant protein and remained unchanged in the case of K1203Q. From the overall results obtained, nsSNP with id (rs1784246) at the amino acid position Q1198P could be considered as deleterious mutation in the acute leukemia caused by MLL gene.

  20. Identification of novel drought-tolerant-associated SNPs in common bean (Phaseolus vulgaris).

    Science.gov (United States)

    Villordo-Pineda, Emiliano; González-Chavira, Mario M; Giraldo-Carbajo, Patricia; Acosta-Gallegos, Jorge A; Caballero-Pérez, Juan

    2015-01-01

    Common bean (Phaseolus vulgaris L.) is a leguminous in high demand for human nutrition and a very important agricultural product. Production of common bean is constrained by environmental stresses such as drought. Although conventional plant selection has been used to increase production yield and stress tolerance, drought tolerance selection based on phenotype is complicated by associated physiological, anatomical, cellular, biochemical, and molecular changes. These changes are modulated by differential gene expression. A common method to identify genes associated with phenotypes of interest is the characterization of Single Nucleotide Polymorphims (SNPs) to link them to specific functions. In this work, we selected two drought-tolerant parental lines from Mesoamerica, Pinto Villa, and Pinto Saltillo. The parental lines were used to generate a population of 282 families (F3:5) and characterized by 169 SNPs. We associated the segregation of the molecular markers in our population with phenotypes including flowering time, physiological maturity, reproductive period, plant, seed and total biomass, reuse index, seed yield, weight of 100 seeds, and harvest index in three cultivation cycles. We observed 83 SNPs with significant association (p < 0.0003 after Bonferroni correction) with our quantified phenotypes. Phenotypes most associated were days to flowering and seed biomass with 58 and 44 associated SNPs, respectively. Thirty-seven out of the 83 SNPs were annotated to a gene with a potential function related to drought tolerance or relevant molecular/biochemical functions. Some SNPs such as SNP28 and SNP128 are related to starch biosynthesis, a common osmotic protector; and SNP18 is related to proline biosynthesis, another well-known osmotic protector.

  1. A custom correlation coefficient (CCC) approach for fast identification of multi-SNP association patterns in genome-wide SNPs data.

    Science.gov (United States)

    Climer, Sharlee; Yang, Wei; de las Fuentes, Lisa; Dávila-Román, Victor G; Gu, C Charles

    2014-11-01

    Complex diseases are often associated with sets of multiple interacting genetic factors and possibly with unique sets of the genetic factors in different groups of individuals (genetic heterogeneity). We introduce a novel concept of custom correlation coefficient (CCC) between single nucleotide polymorphisms (SNPs) that address genetic heterogeneity by measuring subset correlations autonomously. It is used to develop a 3-step process to identify candidate multi-SNP patterns: (1) pairwise (SNP-SNP) correlations are computed using CCC; (2) clusters of so-correlated SNPs identified; and (3) frequencies of these clusters in disease cases and controls compared to identify disease-associated multi-SNP patterns. This method identified 42 candidate multi-SNP associations with hypertensive heart disease (HHD), among which one cluster of 22 SNPs (six genes) included 13 in SLC8A1 (aka NCX1, an essential component of cardiac excitation-contraction coupling) and another of 32 SNPs had 29 from a different segment of SLC8A1. While allele frequencies show little difference between cases and controls, the cluster of 22 associated alleles were found in 20% of controls but no cases and the other in 3% of controls but 20% of cases. These suggest that both protective and risk effects on HHD could be exerted by combinations of variants in different regions of SLC8A1, modified by variants from other genes. The results demonstrate that this new correlation metric identifies disease-associated multi-SNP patterns overlooked by commonly used correlation measures. Furthermore, computation time using CCC is a small fraction of that required by other methods, thereby enabling the analyses of large GWAS datasets.

  2. Typing of 49 autosomal SNPs by single base extension and capillary electrophoresis for forensic genetic testing

    DEFF Research Database (Denmark)

    Børsting, Claus; Tomas Mas, Carmen; Morling, Niels

    2012-01-01

    We describe a method for simultaneous amplification of 49 autosomal single nucleotide polymorphisms (SNPs) by multiplex PCR and detection of the SNP alleles by single base extension (SBE) and capillary electrophoresis. All the SNPs may be amplified from only 100 pg of genomic DNA and the length o...... victim identifications, where the DNA from the victims may be highly degraded and the victims are identified via investigation of their relatives. The assay was validated according to the ISO 17025 standard and used for routine case work in our laboratory....

  3. Typing of 24 mtDNA SNPs in a Chinese Population Using SNaPshot Minisequencing

    Institute of Scientific and Technical Information of China (English)

    黄代新; 桂程; 易少华; 杨庆恩; 杨荣芝; 梅焜

    2010-01-01

    Three SNaPshot multiplex assays were developed to test 23 coding region single nucleotide polymorphisms(SNPs) and one control region SNP outside hypervariable regions(HVR)Ⅰand Ⅱ,which was aimed at increasing the discrimination power of the mitochondrial DNA(mtDNA) typing in forensic casework,and confirming haplogroup assignments of mtDNA profiles in both human population studies and medical research.The selected SNPs targeted the East Asian phylogeny.These multiplex assays were validated by comparing with t...

  4. MAF and haplotype frequencies of 404 SNPs in ROR2 gone in Han Chinese in Beijing%北京汉族人群ROR2基因SNPs等位基因及单体型频率研究

    Institute of Scientific and Technical Information of China (English)

    赵凯平; 袁长征; 王红

    2011-01-01

    Objective: SNPs screening for etiologic studies involving ROR2 gene. Methods: SNPs in ROR2 gene were analyzed using CHB data from HapMap by Haploview program. Results and Discussion: Among the 404 SNPs genotyped in ROR2 gene, a total of 263 SNPs have passed our quality control criteria ( Genotyping call rate > 80%, MAF > 1%, HWE test P >0. 01 and gender difference P > 0. 05 ). The number of SNPs dropped due to MAF = 0 were 103 (25.5%) and these SNPs should be avoided in SNPs selection in ROR2 gene related studies that will be conducted in Chinese population. Seventy two percent (189) of the 263 eligible SNPs have MAF greater than 10% providing a rich resource for etiologic studies. Seventy seven tagging SNPs were identified in 263 eligible SNPs with five haplotype blocks identified. The frequencies for the top two haplotypes among each of the five haplotype blocks were between 68. 1% and 92. 3%. Conclusion: Our analysis of SNPs in ROR2 gene provided clues for future studies involving this gene and primary method for studying other genes as well.%目的 为病因学研究中ROR2基因SNPs的确定和分析提供依据.方法 利用Haploview软件对HapMap数据库中北京汉族人群(CHB)ROR2基因SNPs基因型数据进行分析.结果 和讨论 ROR2基因404个SNPs中,103个(25.5%)SNPs为纯合基因型,在中国人群中进行研究时,应避免选择这些SNPs作为遗传标记.263个合格SNPs中,MAF高于10%的SNPs为189个,占71.9%,有足够的标记可供选择.利用263个合格SNPs.本研究共确定77个标签SNPs,构建了5个单体域,各单体域均以前两种单体型为主,累计频率在68.1%-92.3%之间.结论 对北京汉族人群ROR2基因SNPs数据进行的全面分析,为该人群中基因与相关痰病的病因学研究打下了基础,也为其它基因的初步研究提供了方法.

  5. Genetic variants in urinary bladder cancer: collective power of the "wimp SNPs".

    Science.gov (United States)

    Golka, Klaus; Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Marchan, Rosemarie; Ickstadt, Katja; Schwender, Holger; Bolt, Hermann M; Hengstler, Jan G

    2011-06-01

    In recent years, genome-wide association studies (GWAS) have identified more than 300 validated associations between genetic variants and risk of approximately 70 common diseases. A small number of rare variants with a frequency of usually less than 1% are associated with a strongly enhanced risk, such as genetic variants of TP53, RB1, BRCA1, and BRCA2. Only a very small number of SNPs (with a frequency of more that 1% of the rare allele) have effects of a factor of two or higher. Examples include APOE4 in Alzheimer's disease, LOXL1 in exfoliative glaucoma, and CFH in age-related macular degeneration. However, the majority of all identified SNPs have odds ratios between 1.1 and 1.5. In the case of urinary bladder cancer, all known SNPs that have been validated in sufficiently large populations are associated with odds ratios smaller than 1.5. These SNPs are located next to the following genes: MYC, TP63, PSCA, the TERT-CLPTM1L locus, FGFR3, TACC3, NAT2, CBX6, APOBEC3A, CCNE1, and UGT1A. It is likely that these moderate risk or "wimp SNPs" interact, and because of their high number, collectively have a strong influence on whether an individual will develop cancer or not. It should be considered that variants identified so far explain only approximately 5-10% of the overall inherited risk. Possibly, the remaining variance is due to an even higher number of SNPs with odds ratios smaller than 1.1. Recent studies have provided the following information: (1) The functions of genes identified as relevant for bladder cancer focus on detoxification of carcinogens, control of the cell cycle and apoptosis, as well as maintenance of DNA integrity. (2) Many novel SNPs are far away from the protein coding regions, suggesting that these SNPs are located on distant-acting transcriptional enhancers. (3) The low odds ratio of each individual bladder cancer-associated SNP is too low to justify reasonable preventive measures. However, if the recently identified SNPs interact, they may

  6. Cellular prion protein is required for neuritogenesis: fine-tuning of multiple signaling pathways involved in focal adhesions and actin cytoskeleton dynamics

    Directory of Open Access Journals (Sweden)

    Alleaume-Butaux A

    2013-07-01

    Full Text Available Aurélie Alleaume-Butaux,1,2 Caroline Dakowski,1,2 Mathéa Pietri,1,2 Sophie Mouillet-Richard,1,2 Jean-Marie Launay,3,4 Odile Kellermann,1,2 Benoit Schneider1,2 1INSERM, UMR-S 747, 2Paris Descartes University, Sorbonne Paris Cité, UMR-S 747, 3Public Hospital of Paris, Department of Biochemistry, INSERM UMR-S 942, Lariboisière Hospital, Paris, France; 4Pharma Research Department, Hoffmann La Roche Ltd, Basel, Switzerland Abstract: Neuritogenesis is a dynamic phenomenon associated with neuronal differentiation that allows a rather spherical neuronal stem cell to develop dendrites and axon, a prerequisite for the integration and transmission of signals. The acquisition of neuronal polarity occurs in three steps: (1 neurite sprouting, which consists of the formation of buds emerging from the postmitotic neuronal soma; (2 neurite outgrowth, which represents the conversion of buds into neurites, their elongation and evolution into axon or dendrites; and (3 the stability and plasticity of neuronal polarity. In neuronal stem cells, remodeling and activation of focal adhesions (FAs associated with deep modifications of the actin cytoskeleton is a prerequisite for neurite sprouting and subsequent neurite outgrowth. A multiple set of growth factors and interactors located in the extracellular matrix and the plasma membrane orchestrate neuritogenesis by acting on intracellular signaling effectors, notably small G proteins such as RhoA, Rac, and Cdc42, which are involved in actin turnover and the dynamics of FAs. The cellular prion protein (PrPC, a glycosylphosphatidylinositol (GPI-anchored membrane protein mainly known for its role in a group of fatal neurodegenerative diseases, has emerged as a central player in neuritogenesis. Here, we review the contribution of PrPC to neuronal polarization and detail the current knowledge on the signaling pathways fine-tuned by PrPC to promote neurite sprouting, outgrowth, and maintenance. We emphasize that Pr

  7. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data

    OpenAIRE

    Zhang, Tianjiao; Hu, Yang; Wu, Xiaoliang; Ma, Rui; Jiang, Qinghua; Wang, Yadong

    2016-01-01

    Many disease-related single nucleotide polymorphisms (SNPs) have been inferred from genome-wide association studies (GWAS) in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important ...

  8. PupasView: a visual tool for selecting suitable SNPs, with putative pathological effect in genes, for genotyping purposes

    OpenAIRE

    Conde, Lucía; Vaquerizas, Juan M; Ferrer-Costa, Carles; de la Cruz, Xavier; Orozco, Modesto; Dopazo, Joaquín

    2005-01-01

    We have developed a web tool, PupasView, for the selection of single nucleotide polymorphisms (SNPs) with potential phenotypic effect. PupasView constitutes an interactive environment in which functional information and population frequency data can be used as sequential filters over linkage disequilibrium parameters to obtain a final list of SNPs optimal for genotyping purposes. PupasView is the first resource that integrates phenotypic effects caused by SNPs at both the translational and th...

  9. Role of HIF1A, VEGFA and VEGFR2 SNPs in the Susceptibility and Progression of COPD in a Spanish Population

    Science.gov (United States)

    Baz-Dávila, Rebeca; Espinoza-Jiménez, Adriana; Rodríguez-Pérez, María del Cristo; Zulueta, Javier; Varo, Nerea; Montejo, Ángela; Almeida-González, Delia; Aguirre-Jaime, Armando; Córdoba-Lanús, Elizabeth; Casanova, Ciro

    2016-01-01

    Hypoxia is involved in the development of chronic inflammatory processes. Under hypoxic conditions HIF1A, VEGF and VEGFR2 are expressed and mediate the course of the resultant disease. The aim of the present study was to define the associations between tSNPs in these genes and COPD susceptibility and progression in a Spanish cohort. The T alleles in rs3025020 and rs833070 SNPs (VEGFA gene) were less frequent in the group of COPD cases and were associated with a lower risk of developing the disease (OR = 0.60; 95% CI = 0. 39–0.93; p = 0.023 and OR = 0.60; 95% CI = 0.38–0.96; p = 0.034, respectively) under a dominant model of inheritance. The haplotype in which both SNPs presented the T allele confirmed the association found (OR = 0.02; 95% CI = 0.00 to 0.66; p = 0.03). Moreover, patients with COPD carrying the T allele in homozygosis in rs3025020 SNP showed higher lung function values and this association remained constant during 3 years of follow-up. In conclusion, T allele in rs833070 and rs3025020 may confer a protective effect to COPD susceptibility in a Spanish population and the association of the SNP rs3025020 with lung function may be suggesting a role for VEGF in the progression of the disease. PMID:27163696

  10. Genetic variants in lipid metabolism are independently associated with multiple features of the metabolic syndrome

    NARCIS (Netherlands)

    Povel, C.M.; Boer, J.M.; Imholz, S.; Dolle, M.E.; Feskens, E.J.M.

    2011-01-01

    Background Our objective was to find single nucleotide polymorphisms (SNPs), within transcriptional pathways of glucose and lipid metabolism, which are related to multiple features of the metabolic syndrome (MetS). Methods 373 SNPs were measured in 3575 subjects of the Doetinchem cohort. Prevalence

  11. Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

    Science.gov (United States)

    Darabi, Hatef; Beesley, Jonathan; Droit, Arnaud; Kar, Siddhartha; Nord, Silje; Moradi Marjaneh, Mahdi; Soucy, Penny; Michailidou, Kyriaki; Ghoussaini, Maya; Fues Wahl, Hanna; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Alonso, M. Rosario; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W.; Benitez, Javier; Bogdanova, Natalia V.; Bojesen, Stig E.; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Choi, Ji-Yeob; Conroy, Don M.; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Devilee, Peter; Dörk, Thilo; Easton, Douglas F.; Fasching, Peter A.; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G.; Goldberg, Mark S.; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A.; Hallberg, Emily; Hamann, Ute; Hartman, Mikael; Hollestelle, Antoinette; Hopper, John L.; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Kang, Daehee; Khan, Sofia; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Lambrechts, Diether; Le Marchand, Loic; Lee, Soo Chin; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Mayes, Rebecca; McKay, James; Meindl, Alfons; Milne, Roger L.; Muir, Kenneth; Neuhausen, Susan L.; Nevanlinna, Heli; Olswold, Curtis; Orr, Nick; Peterlongo, Paolo; Pita, Guillermo; Pylkäs, Katri; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C.; Stram, Daniel O.; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H.; Tessier, Daniel C.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine M.; Vincent, Daniel; Winqvist, Robert; Wu, Anna H.; Wu, Pei-Ei; Yip, Cheng Har; Zheng, Wei; Pharoah, Paul D. P.; Hall, Per; Edwards, Stacey L.; Simard, Jacques; French, Juliet D.; Chenevix-Trench, Georgia; Dunning, Alison M.

    2016-01-01

    Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90–0.94; P = 8.96 × 10−15)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10−09, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10−11, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus. PMID:27600471

  12. Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs).

    Science.gov (United States)

    Darabi, Hatef; Beesley, Jonathan; Droit, Arnaud; Kar, Siddhartha; Nord, Silje; Moradi Marjaneh, Mahdi; Soucy, Penny; Michailidou, Kyriaki; Ghoussaini, Maya; Fues Wahl, Hanna; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Alonso, M Rosario; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Benitez, Javier; Bogdanova, Natalia V; Bojesen, Stig E; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Choi, Ji-Yeob; Conroy, Don M; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Devilee, Peter; Dörk, Thilo; Easton, Douglas F; Fasching, Peter A; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G; Goldberg, Mark S; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A; Hallberg, Emily; Hamann, Ute; Hartman, Mikael; Hollestelle, Antoinette; Hopper, John L; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Kang, Daehee; Khan, Sofia; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Lambrechts, Diether; Le Marchand, Loic; Lee, Soo Chin; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Mayes, Rebecca; McKay, James; Meindl, Alfons; Milne, Roger L; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Olswold, Curtis; Orr, Nick; Peterlongo, Paolo; Pita, Guillermo; Pylkäs, Katri; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C; Stram, Daniel O; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H; Tessier, Daniel C; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine M; Vincent, Daniel; Winqvist, Robert; Wu, Anna H; Wu, Pei-Ei; Yip, Cheng Har; Zheng, Wei; Pharoah, Paul D P; Hall, Per; Edwards, Stacey L; Simard, Jacques; French, Juliet D; Chenevix-Trench, Georgia; Dunning, Alison M

    2016-09-07

    Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10(-09), r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10(-11), r(2) = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

  13. Novel SNPs in HSPB8 gene and their association with heat tolerance traits in Sahiwal indigenous cattle.

    Science.gov (United States)

    Verma, Nishant; Gupta, Ishwar Dayal; Verma, Archana; Kumar, Rakesh; Das, Ramendra; Vineeth, M R

    2016-01-01

    Heat shock proteins (HSPs) are expressed in response to heat stress, and the polymorphism in HSP genes at single-nucleotide level has been reported to be associated with heat tolerance and production performance traits in cattle. HSPB8 gene has been mapped on Bos taurus autosome 17 (BTA-17) spanning nearly 13,252 bp and comprising three exons and two introns. The present study was conducted in Sahiwal cows (n = 108) reared in subtropical climate with the objectives to identify SNPs in all three exons and part of intron 1 of HSPB8 gene and to analyze their association with heat tolerance traits in Sahiwal cows. Respiration rate (RR) and rectal temperature (RT) were recorded once during probable extreme hours in different seasons or Temperature-Humidity Index (THI), i.e., winter, spring, and summer. Heat tolerance coefficient (HTC) was also calculated to check the adaptability of the animals during the period of heat stress. The comparative sequence analysis revealed a total two single-nucleotide polymorphisms (SNPs), i.e., g.507G>A in exon 1 and g.881T>C in intron 1 of HSPB8 gene. Out of these two identified SNPs, only one SNP, i.e., g.507G>A, was found to be significantly associated with heat tolerance indicator traits (RR, RT, and HTC) in Sahiwal cows. The perusal of results across different seasons showed the significant (P A SNP of HSPB8 gene. However, in case of another SNP, i.e., g.881T>C, located on intron 1, the RR, RT, and HTC were having non-significant association with the different genotypes, i.e., TT and TC. These findings may partly suggest that GA genotype of SNP g.507G>A of HSPB8 gene has a probable role in heat tolerance in Sahiwal cattle and can therefore be utilized as a marker in propagation of thermo-tolerance cattle in hot tropical and subtropical climate. Nevertheless, the involvement of other regulatory mechanisms cannot be overruled.

  14. Association of ESR1 gene tagging SNPs with breast cancer risk

    DEFF Research Database (Denmark)

    Dunning, Alison M; Healey, Catherine S; Baynes, Caroline

    2009-01-01

    We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55,000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant...

  15. Hansa: an automated method for discriminating disease and neutral human nsSNPs.

    Science.gov (United States)

    Acharya, Vishal; Nagarajaram, Hampapathalu A

    2012-02-01

    Variations are mostly due to nonsynonymous single nucleotide polymorphisms (nsSNPs), some of which are associated with certain diseases. Phenotypic effects of a large number of nsSNPs have not been characterized. Although several methods have been developed to predict the effects of nsSNPs as "disease" or "neutral," there is still a need for development of methods with improved prediction accuracies. We, therefore, developed a support vector machine (SVM) based method named Hansa which uses a novel set of discriminatory features to classify nsSNPs into disease (pathogenic) and benign (neutral) types. Validation studies on a benchmark dataset and further on an independent dataset of well-characterized known disease and neutral mutations show that Hansa outperforms the other known methods. For example, fivefold cross-validation studies using the benchmark HumVar dataset reveal that at the false positive rate (FPR) of 20% Hansa yields a true positive rate (TPR) of 82% that is about 10% higher than the best-known method. Hansa is available in the form of a web server at http://hansa.cdfd.org.in:8080.

  16. SNPsnap: a Web-based tool for identification and annotation of matched SNPs

    DEFF Research Database (Denmark)

    Pers, Tune Hannes; Timshel, Pascal; Hirschhorn, Joel N.

    2015-01-01

    Summary : An important computational step following genome-wide association studies (GWAS) is to assess whether disease or trait-associated single-nucleotide polymorphisms (SNPs) enrich for particular biological annotations. SNP-based enrichment analysis needs to account for biases such as co......@broadinstitute.org Supplementary information : Supplementary data are available at Bioinformatics online....

  17. SNPs at 3'-UTR of the bovine CDIPT gene associated with Qinchuan cattle meat quality traits.

    Science.gov (United States)

    Fu, C Z; Wang, H; Mei, C G; Wang, J L; Jiang, B J; Ma, X H; Wang, H B; Cheng, G; Zan, L S

    2013-03-13

    The CDIPT is crucial to the fatty acid metabolic pathway, intracellular signal transduction and energy metabolism in eukaryotic cells. We detected three SNPs at 3'-untranslated regions (UTR), named 3'-UTR_108 A > G, 3'-UTR_448 G > A and 3'-UTR_477 C > G, of the CDIPT gene in 618 Qinchuan cattle using PCR-RFLP and DNA sequencing methods. At each of the three SNPs, we found three genotypes named as follows: AA, AB, BB (3'-UTR_108 A > G), CC, CD, DD (3'-UTR_448 G > A) and EE, EF, FF (3'-UTR_477 C > G.). Based on association analysis of these SNPs with ultrasound measurement traits, individuals of genotype BB had a significantly larger loin muscle area than genotype AA. Individuals of genotype CC had significantly thicker back fat than individuals of genotype DD. Individuals of genotype EE also had significantly thicker back fat than did individuals of genotype FF. We conclude that these SNPs of the CDIPT gene could be used as molecular markers for selecting and breeding beef cattle with superior body traits, depending on breeding goals.

  18. RNAsnp: efficient detection of local RNA secondary structure changes induced by SNPs

    DEFF Research Database (Denmark)

    Radhakrishnan, Sabarinathan; Tafer, Hakim; Seemann, Ernst Stefan

    2013-01-01

    precomputed tables of the distribution of SNP effects as function of length and GC content. RNAsnp thus achieves both a noise reduction and speed-up of several orders of magnitude over shuffling-based approaches. On a data set comprising 501 SNPs associated with human-inherited diseases, we predict 54 to have...

  19. Identification of pummelo cultivars by using a panel of 25 selected SNPs and 12 DNA segments.

    Directory of Open Access Journals (Sweden)

    Bo Wu

    Full Text Available Pummelo cultivars are usually difficult to identify morphologically, especially when fruits are unavailable. The problem was addressed in this study with the use of two methods: high resolution melting analysis of SNPs and sequencing of DNA segments. In the first method, a set of 25 SNPs with high polymorphic information content were selected from SNPs predicted by analyzing ESTs and sequenced DNA segments. High resolution melting analysis was then used to genotype 260 accessions including 55 from Myanmar, and 178 different genotypes were thus identified. A total of 99 cultivars were assigned to 86 different genotypes since the known somatic mutants were identical to their original genotypes at the analyzed SNP loci. The Myanmar samples were genotypically different from each other and from all other samples, indicating they were derived from sexual propagation. Statistical analysis showed that the set of SNPs was powerful enough for identifying at least 1000 pummelo genotypes, though the discrimination power varied in different pummelo groups and populations. In the second method, 12 genomic DNA segments of 24 representative pummelo accessions were sequenced. Analysis of the sequences revealed the existence of a high haplotype polymorphism in pummelo, and statistical analysis showed that the segments could be used as genetic barcodes that should be informative enough to allow reliable identification of 1200 pummelo cultivars. The high level of haplotype diversity and an apparent population structure shown by DNA segments and by SNP genotypes, respectively, were discussed in relation to the origin and domestication of the pummelo species.

  20. Cross-amplification and validation of SNPs conserved over 44 million years between seals and dogs.

    Directory of Open Access Journals (Sweden)

    Joseph I Hoffman

    Full Text Available High-density SNP arrays developed for humans and their companion species provide a rapid and convenient tool for generating SNP data in closely-related non-model organisms, but have not yet been widely applied to phylogenetically divergent taxa. Consequently, we used the CanineHD BeadChip to genotype 24 Antarctic fur seal (Arctocephalus gazella individuals. Despite seals and dogs having diverged around 44 million years ago, 33,324 out of 173,662 loci (19.2% could be genotyped, of which 173 were polymorphic and clearly interpretable. Two SNPs were validated using KASP genotyping assays, with the resulting genotypes being 100% concordant with those obtained from the high-density array. Two loci were also confirmed through in silico visualisation after mapping them to the fur seal transcriptome. Polymorphic SNPs were distributed broadly throughout the dog genome and did not differ significantly in proximity to genes from either monomorphic SNPs or those that failed to cross-amplify in seals. However, the nearest genes to polymorphic SNPs were significantly enriched for functional annotations relating to energy metabolism, suggesting a possible bias towards conserved regions of the genome.

  1. Known susceptibility SNPs for sporadic prostate cancer show a similar association with "hereditary" prostate cancer

    NARCIS (Netherlands)

    Cremers, R.G.H.M.; Galesloot, T.E.; Aben, K.K.H.; Oort, I.M. van; Vasen, H.F.A.; Vermeulen, S.; Kiemeney, L.A.L.M.

    2015-01-01

    BACKGROUND: More than 70 single nucleotide polymorphisms (SNPs) have been reported to be associated with prostate cancer (PC) risk; these were mainly identified in the general population with predominantly sporadic PC (SPC). Previous studies have suggested similar associations between a selection of

  2. Typing of 49 autosomal SNPs by SNaPshot in the Slovenian population

    DEFF Research Database (Denmark)

    Drobnic, Katja; Børsting, Claus; Rockenbauer, Eszter

    2010-01-01

    A total of 157 unrelated individuals residing in Slovenia were typed for 49 of the autosomal single nucleotide polymorphisms (SNPs) in the SNPforID 52plex with the SNaPshot assay. We obtained full SNP profiles in all but one individual and perfect concordance was obtained in duplicated analyses...

  3. SNP2TFBS – a database of regulatory SNPs affecting predicted transcription factor binding site affinity

    Science.gov (United States)

    Kumar, Sunil; Ambrosini, Giovanna; Bucher, Philipp

    2017-01-01

    SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/. PMID:27899579

  4. SNPs selection using support vector regression and genetic algorithms in GWAS.

    Science.gov (United States)

    de Oliveira, Fabrízzio Condé; Borges, Carlos Cristiano Hasenclever; Almeida, Fernanda Nascimento; e Silva, Fabyano Fonseca; da Silva Verneque, Rui; da Silva, Marcos Vinicius G B; Arbex, Wagner

    2014-01-01

    This paper proposes a new methodology to simultaneously select the most relevant SNPs markers for the characterization of any measurable phenotype described by a continuous variable using Support Vector Regression with Pearson Universal kernel as fitness function of a binary genetic algorithm. The proposed methodology is multi-attribute towards considering several markers simultaneously to explain the phenotype and is based jointly on statistical tools, machine learning and computational intelligence. The suggested method has shown potential in the simulated database 1, with additive effects only, and real database. In this simulated database, with a total of 1,000 markers, and 7 with major effect on the phenotype and the other 993 SNPs representing the noise, the method identified 21 markers. Of this total, 5 are relevant SNPs between the 7 but 16 are false positives. In real database, initially with 50,752 SNPs, we have reduced to 3,073 markers, increasing the accuracy of the model. In the simulated database 2, with additive effects and interactions (epistasis), the proposed method matched to the methodology most commonly used in GWAS. The method suggested in this paper demonstrates the effectiveness in explaining the real phenotype (PTA for milk), because with the application of the wrapper based on genetic algorithm and Support Vector Regression with Pearson Universal, many redundant markers were eliminated, increasing the prediction and accuracy of the model on the real database without quality control filters. The PUK demonstrated that it can replicate the performance of linear and RBF kernels.

  5. Comprehensive survey of SNPs in the Affymetrix exon array using the 1000 Genomes dataset.

    Directory of Open Access Journals (Sweden)

    Eric R Gamazon

    Full Text Available Microarray gene expression data has been used in genome-wide association studies to allow researchers to study gene regulation as well as other complex phenotypes including disease risks and drug response. To reach scientifically sound conclusions from these studies, however, it is necessary to get reliable summarization of gene expression intensities. Among various factors that could affect expression profiling using a microarray platform, single nucleotide polymorphisms (SNPs in target mRNA may lead to reduced signal intensity measurements and result in spurious results. The recently released 1000 Genomes Project dataset provides an opportunity to evaluate the distribution of both known and novel SNPs in the International HapMap Project lymphoblastoid cell lines (LCLs. We mapped the 1000 Genomes Project genotypic data to the Affymetrix GeneChip Human Exon 1.0ST array (exon array, which had been used in our previous studies and for which gene expression data had been made publicly available. We also evaluated the potential impact of these SNPs on the differentially spliced probesets we had identified previously. Though the 1000 Genomes Project data allowed a comprehensive survey of the SNPs in this particular array, the same approach can certainly be applied to other microarray platforms. Furthermore, we present a detailed catalogue of SNP-containing probesets (exon-level and transcript clusters (gene-level, which can be considered in evaluating findings using the exon array as well as benefit the design of follow-up experiments and data re-analysis.

  6. LD-Spline: Mapping SNPs on genotyping platforms to genomic regions using patterns of linkage disequilibrium

    Directory of Open Access Journals (Sweden)

    Bush William S

    2009-12-01

    Full Text Available Abstract Background Gene-centric analysis tools for genome-wide association study data are being developed both to annotate single locus statistics and to prioritize or group single nucleotide polymorphisms (SNPs prior to analysis. These approaches require knowledge about the relationships between SNPs on a genotyping platform and genes in the human genome. SNPs in the genome can represent broader genomic regions via linkage disequilibrium (LD, and population-specific patterns of LD can be exploited to generate a data-driven map of SNPs to genes. Methods In this study, we implemented LD-Spline, a database routine that defines the genomic boundaries a particular SNP represents using linkage disequilibrium statistics from the International HapMap Project. We compared the LD-Spline haplotype block partitioning approach to that of the four gamete rule and the Gabriel et al. approach using simulated data; in addition, we processed two commonly used genome-wide association study platforms. Results We illustrate that LD-Spline performs comparably to the four-gamete rule and the Gabriel et al. approach; however as a SNP-centric approach LD-Spline has the added benefit of systematically identifying a genomic boundary for each SNP, where the global block partitioning approaches may falter due to sampling variation in LD statistics. Conclusion LD-Spline is an integrated database routine that quickly and effectively defines the genomic region marked by a SNP using linkage disequilibrium, with a SNP-centric block definition algorithm.

  7. The MS@Work study : a 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis

    NARCIS (Netherlands)

    van der Hiele, Karin; van Gorp, Dennis A. M.; Heerings, Marco A. P.; van Lieshout, Irma; Jongen, Peter J.; Reneman, Michiel F.; van der Klink, Jac J. L.; Vosman, Frans; Middelkoop, Huub A. M.; Visser, Leo H.

    2015-01-01

    Background: Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading

  8. Genetic analysis of reelin gene (RELN) SNPs: no association with autism spectrum disorder in the Indian population.

    Science.gov (United States)

    Dutta, Shruti; Sinha, Swagata; Ghosh, Saurabh; Chatterjee, Anindita; Ahmed, Shabina; Usha, Rajamma

    2008-08-15

    Involvement of reelin with Autism spectrum disorder (ASD) has been implicated through several biochemical as well as genetic studies. Reelin is an extracellular signaling protein, which plays a significant role in cytoarchitectonic pattern formation of different brain areas during development. Reelin gene (RELN) is located on chromosome 7q22; an important autism critical region identified through several genome-wide scans. A number of genetic studies have been carried out to investigate the association of reelin with autism. Recently we reported possible paternal effect in the transmission of CGG repeat alleles of RELN in the susceptibility towards autism. Further analysis on other polymorphisms is warranted to validate the status of RELN as a candidate for autism. Therefore in the present study, we have investigated six more SNPs (rs727531, rs2072403, rs2072402, rs362691, rs362719, rs736707) in 102 patients, 182 parents and 101 healthy controls. We have followed DSM-IV criteria and the screening for autism was carried out using CARS. Genomic DNA isolated from blood was used for PCR and subsequent RFLP analysis. Finally, case-control and family-based association studies were carried out to examine the genetic association of these SNP markers with ASD in the Indian population. But, we failed to detect either preferential parental transmission of any alleles of the markers to affected offspring or any biased allelic or genotypic distribution between the cases and controls. Thus the present study suggests that these SNPs of RELN are unlikely to be associated with ASD in the Indian population.

  9. Genomic Selection for Drought Tolerance Using Genome-Wide SNPs in Maize

    Directory of Open Access Journals (Sweden)

    Thirunavukkarasu Nepolean

    2017-04-01

    Full Text Available Traditional breeding strategies for selecting superior genotypes depending on phenotypic traits have proven to be of limited success, as this direct selection is hindered by low heritability, genetic interactions such as epistasis, environmental-genotype interactions, and polygenic effects. With the advent of new genomic tools, breeders have paved a way for selecting superior breeds. Genomic selection (GS has emerged as one of the most important approaches for predicting genotype performance. Here, we tested the breeding values of 240 maize subtropical lines phenotyped for drought at different environments using 29,619 cured SNPs. Prediction accuracies of seven genomic selection models (ridge regression, LASSO, elastic net, random forest, reproducing kernel Hilbert space, Bayes A and Bayes B were tested for their agronomic traits. Though prediction accuracies of Bayes B, Bayes A and RKHS were comparable, Bayes B outperformed the other models by predicting highest Pearson correlation coefficient in all three environments. From Bayes B, a set of the top 1053 significant SNPs with higher marker effects was selected across all datasets to validate the genes and QTLs. Out of these 1053 SNPs, 77 SNPs associated with 10 drought-responsive transcription factors. These transcription factors were associated with different physiological and molecular functions (stomatal closure, root development, hormonal signaling and photosynthesis. Of several models, Bayes B has been shown to have the highest level of prediction accuracy for our data sets. Our experiments also highlighted several SNPs based on their performance and relative importance to drought tolerance. The result of our experiments is important for the selection of superior genotypes and candidate genes for breeding drought-tolerant maize hybrids.

  10. Altered transmission of HOX and apoptotic SNPs identify a potential common pathway for clubfoot.

    Science.gov (United States)

    Ester, Audrey R; Weymouth, Katelyn S; Burt, Amber; Wise, Carol A; Scott, Allison; Gurnett, Christina A; Dobbs, Matthew B; Blanton, Susan H; Hecht, Jacqueline T

    2009-12-01

    Clubfoot is a common birth defect that affects 135,000 newborns each year worldwide. It is characterized by equinus deformity of one or both feet and hypoplastic calf muscles. Despite numerous study approaches, the cause(s) remains poorly understood although a multifactorial etiology is generally accepted. We considered the HOXA and HOXD gene clusters and insulin-like growth factor binding protein 3 (IGFBP3) as candidate genes because of their important roles in limb and muscle morphogenesis. Twenty SNPs from the HOXA and HOXD gene clusters and 12 SNPs in IGFBP3 were genotyped in a sample composed of non-Hispanic white and Hispanic multiplex and simplex families (discovery samples) and a second sample of non-Hispanic white simplex trios (validation sample). Four SNPs (rs6668, rs2428431, rs3801776, and rs3779456) in the HOXA cluster demonstrated altered transmission in the discovery sample, but only rs3801776, located in the HOXA basal promoter region, showed altered transmission in both the discovery and validation samples (P = 0.004 and 0.028). Interestingly, HOXA9 is expressed in muscle during development. An SNP in IGFBP3, rs13223993, also showed altered transmission (P = 0.003) in the discovery sample. Gene-gene interactions were identified between variants in HOXA, HOXD, and IGFBP3 and with previously associated SNPs in mitochondrial-mediated apoptotic genes. The most significant interactions were found between CASP3 SNPS and variants in HOXA, HOXD, and IGFBP3. These results suggest a biologic model for clubfoot in which perturbation of HOX and apoptotic genes together affect muscle and limb development, which may cause the downstream failure of limb rotation into a plantar grade position.

  11. Predicting deleterious nsSNPs: an analysis of sequence and structural attributes

    Directory of Open Access Journals (Sweden)

    Saqi Mansoor AS

    2006-04-01

    Full Text Available Abstract Background There has been an explosion in the number of single nucleotide polymorphisms (SNPs within public databases. In this study we focused on non-synonymous protein coding single nucleotide polymorphisms (nsSNPs, some associated with disease and others which are thought to be neutral. We describe the distribution of both types of nsSNPs using structural and sequence based features and assess the relative value of these attributes as predictors of function using machine learning methods. We also address the common problem of balance within machine learning methods and show the effect of imbalance on nsSNP function prediction. We show that nsSNP function prediction can be significantly improved by 100% undersampling of the majority class. The learnt rules were then applied to make predictions of function on all nsSNPs within Ensembl. Results The measure of prediction success is greatly affected by the level of imbalance in the training dataset. We found the balanced dataset that included all attributes produced the best prediction. The performance as measured by the Matthews correlation coefficient (MCC varied between 0.49 and 0.25 depending on the imbalance. As previously observed, the degree of sequence conservation at the nsSNP position is the single most useful attribute. In addition to conservation, structural predictions made using a balanced dataset can be of value. Conclusion The predictions for all nsSNPs within Ensembl, based on a balanced dataset using all attributes, are available as a DAS annotation. Instructions for adding the track to Ensembl are at http://www.brightstudy.ac.uk/das_help.html

  12. Identification of novel drought-tolerant-associated SNPs in common bean (Phaseolus vulgaris

    Directory of Open Access Journals (Sweden)

    Emiliano eVillordo-Pineda

    2015-07-01

    Full Text Available Common bean (Phaseolus vulgaris L. is a leguminous in high demand for human nutrition and a veryimportant agricultural product. Production of common bean is constrained by environmental stressessuch as drought. Although conventional plant selection has been used to increase production yield andstress tolerance, drought tolerance selection based on phenotype is complicated by associatedphysiological, anatomical, cellular, biochemical and molecular changes. These changes are modulatedby differential gene expression. A common method to identify genes associated with phenotypes ofinterest is the characterization of Single Nucleotide Polymorphims (SNPs to link them to specificfunctions.In this work, we selected two drought-tolerant parental lines from Mesoamerica, Pinto Villa and PintoSaltillo. The parental lines were used to generate a population of 282 families (F 3:5 and characterizedby 169 SNPs . We associated the segregation of the molecular markers in our population withphenotypes including flowering time, physiological maturity, reproductive period, plant, seed and totalbiomass, reuse index, seed yield, weight of 100 seeds and harvest index in three cultivation cycles.We observed 83 SNPs with significant association (p < 0.0003 after Bonferroni correction with ourquantified phenotypes. Phenotypes most associated were days to flowering and seed biomass with 58and 44 associated SNPs respectively. Thirty-seven out of the 83 SNPs were annotated to a gene with apotential function related to drought tolerance or relevant molecular/biochemical functions. Some SNPssuch as SNP28 and SNP128 are related to starch biosynthesis, a common osmotic protector; andSNP18 is related to proline biosynthesis, another well-known osmotic protector.

  13. Antipsychotic-induced movement disorders in long-stay psychiatric patients and 45 tag SNPs in 7 candidate genes: a prospective study.

    Directory of Open Access Journals (Sweden)

    P Roberto Bakker

    Full Text Available OBJECTIVE: Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD, parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia, subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia, as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 7 candidate genes (GRIN2B, GRIN2A, HSPG2, DRD3, DRD4, HTR2C, and NQO1. METHODS: Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. The authors genotyped 45 tag SNPs in 7 candidate genes, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders. RESULTS: Various tag SNPs reached nominal significance; TD with rs1345423, rs7192557, rs1650420, as well as rs11644461; orofacial dyskinesia with rs7192557, rs1650420, as well as rs4911871; limb truncal dyskinesia with rs1345423, rs7192557, rs1650420, as well as rs11866328; bradykinesia with rs2192970; akathisia with rs324035; and the principal-factor with rs10772715. After controlling for multiple testing, no significant results remained. CONCLUSIONS: The findings suggest that selected tag SNPs are not associated with a susceptibility to movement disorders. However, as the sample size was small and previous studies show inconsistent results, definite conclusions cannot be made. Replication is needed in larger study samples, preferably in longitudinal studies which take the fluctuating course of movement disorders and gene-environment interactions into account.

  14. Sequence diversity in three tomato species: SNPs, markers, and molecular evolution.

    Science.gov (United States)

    Jiménez-Gómez, José M; Maloof, Julin N

    2009-07-03

    available that represents the most comprehensive survey of sequence diversity across Solanum species to date. These SNPs, plus thousands of molecular makers designed to detect the polymorphisms are available to the community via a website. Evolutionary analyses on these polymorphism uncovered sets of genes potentially important for the evolution and domestication of tomato; interestingly these sets were enriched for genes involved in response to the environment.

  15. Fine Mapping and Functional Analysis of the Multiple Sclerosis Risk Gene CD6

    Science.gov (United States)

    Swaminathan, Bhairavi; Cuapio, Angélica; Alloza, Iraide; Matesanz, Fuencisla; Alcina, Antonio; García-Barcina, Maria; Fedetz, Maria; Fernández, Óscar; Lucas, Miguel; Órpez, Teresa; Pinto-Medel, Mª Jesus; Otaegui, David; Olascoaga, Javier; Urcelay, Elena; Ortiz, Miguel A.; Arroyo, Rafael; Oksenberg, Jorge R.; Antigüedad, Alfredo; Tolosa, Eva; Vandenbroeck, Koen

    2013-01-01

    CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (Pmax(T) permutation = 1×10−4). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naïve cells, P = 0.0001; CD8+ naïve cells, P<0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells. PMID:23638056

  16. GENIE: a software package for gene-gene interaction analysis in genetic association studies using multiple GPU or CPU cores.

    Science.gov (United States)

    Chikkagoudar, Satish; Wang, Kai; Li, Mingyao

    2011-05-26

    Gene-gene interaction in genetic association studies is computationally intensive when a large number of SNPs are involved. Most of the latest Central Processing Units (CPUs) have multiple cores, whereas Graphics Processing Units (GPUs) also have hundreds of cores and have been recently used to implement faster scientific software. However, currently there are no genetic analysis software packages that allow users to fully utilize the computing power of these multi-core devices for genetic interaction analysis for binary traits. Here we present a novel software package GENIE, which utilizes the power of multiple GPU or CPU processor cores to parallelize the interaction analysis. GENIE reads an entire genetic association study dataset into memory and partitions the dataset into fragments with non-overlapping sets of SNPs. For each fragment, GENIE analyzes: 1) the interaction of SNPs within it in parallel, and 2) the interaction between the SNPs of the current fragment and other fragments in parallel. We tested GENIE on a large-scale candidate gene study on high-density lipoprotein cholesterol. Using an NVIDIA Tesla C1060 graphics card, the GPU mode of GENIE achieves a speedup of 27 times over its single-core CPU mode run. GENIE is open-source, economical, user-friendly, and scalable. Since the computing power and memory capacity of graphics cards are increasing rapidly while their cost is going down, we anticipate that GENIE will achieve greater speedups with faster GPU cards. Documentation, source code, and precompiled binaries can be downloaded from http://www.cceb.upenn.edu/~mli/software/GENIE/.

  17. High throughput sequencing in mice: a platform comparison identifies a preponderance of cryptic SNPs

    Directory of Open Access Journals (Sweden)

    Darakjian Priscila

    2009-08-01

    Full Text Available Abstract Background Allelic variation is the cornerstone of genetically determined differences in gene expression, gene product structure, physiology, and behavior. However, allelic variation, particularly cryptic (unknown or not annotated variation, is problematic for follow up analyses. Polymorphisms result in a high incidence of false positive and false negative results in hybridization based analyses and hinder the identification of the true variation underlying genetically determined differences in physiology and behavior. Given the proliferation of mouse genetic models (e.g., knockout models, selectively bred lines, heterogeneous stocks derived from standard inbred strains and wild mice and the wealth of gene expression microarray and phenotypic studies using genetic models, the impact of naturally-occurring polymorphisms on these data is critical. With the advent of next-generation, high-throughput sequencing, we are now in a position to determine to what extent polymorphisms are currently cryptic in such models and their impact on downstream analyses. Results We sequenced the two most commonly used inbred mouse strains, DBA/2J and C57BL/6J, across a region of chromosome 1 (171.6 – 174.6 megabases using two next generation high-throughput sequencing platforms: Applied Biosystems (SOLiD and Illumina (Genome Analyzer. Using the same templates on both platforms, we compared realignments and single nucleotide polymorphism (SNP detection with an 80 fold average read depth across platforms and samples. While public datasets currently annotate 4,527 SNPs between the two strains in this interval, thorough high-throughput sequencing identified a total of 11,824 SNPs in the interval, including 7,663 new SNPs. Furthermore, we confirmed 40 missense SNPs and discovered 36 new missense SNPs. Conclusion Comparisons utilizing even two of the best characterized mouse genetic models, DBA/2J and C57BL/6J, indicate that more than half of naturally

  18. Quick, “Imputation-free” meta-analysis with proxy-SNPs

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    Meesters Christian

    2012-09-01

    Full Text Available Abstract Background Meta-analysis (MA is widely used to pool genome-wide association studies (GWASes in order to a increase the power to detect strong or weak genotype effects or b as a result verification method. As a consequence of differing SNP panels among genotyping chips, imputation is the method of choice within GWAS consortia to avoid losing too many SNPs in a MA. YAMAS (Yet Another Meta Analysis Software, however, enables cross-GWAS conclusions prior to finished and polished imputation runs, which eventually are time-consuming. Results Here we present a fast method to avoid forfeiting SNPs present in only a subset of studies, without relying on imputation. This is accomplished by using reference linkage disequilibrium data from 1,000 Genomes/HapMap projects to find proxy-SNPs together with in-phase alleles for SNPs missing in at least one study. MA is conducted by combining association effect estimates of a SNP and those of its proxy-SNPs. Our algorithm is implemented in the MA software YAMAS. Association results from GWAS analysis applications can be used as input files for MA, tremendously speeding up MA compared to the conventional imputation approach. We show that our proxy algorithm is well-powered and yields valuable ad hoc results, possibly providing an incentive for follow-up studies. We propose our method as a quick screening step prior to imputation-based MA, as well as an additional main approach for studies without available reference data matching the ethnicities of study participants. As a proof of principle, we analyzed six dbGaP Type II Diabetes GWAS and found that the proxy algorithm clearly outperforms naïve MA on the p-value level: for 17 out of 23 we observe an improvement on the p-value level by a factor of more than two, and a maximum improvement by a factor of 2127. Conclusions YAMAS is an efficient and fast meta-analysis program which offers various methods, including conventional MA as well as inserting proxy-SNPs

  19. Organ heterogeneity of host-derived matrix metalloproteinase expression and its involvement in multiple-organ metastasis by lung cancer cell lines.

    Science.gov (United States)

    Shiraga, Minoru; Yano, Seiji; Yamamoto, Akihiko; Ogawa, Hirohisa; Goto, Hisatsugu; Miki, Toyokazu; Miki, Keisuke; Zhang, Helong; Sone, Saburo

    2002-10-15

    Cancer metastasis is tightly regulated by the interaction of tumor cells and host organ microenvironments. Matrix metalloproteinases (MMPs), produced by both tumor cells and host stromal cells, play a central role in tumor invasion and angiogenesis. We determined whether metastatic potential of lung cancer to multiple organs is dependent solely on the expression of MMPs by tumor cells, using two metastasis models of human lung cancer cell lines expressing various levels of MMPs and a MMP inhibitor (ONO-4817). In the lung metastasis model, tumor cells (PC14, PC14PE6, H226, A549) inoculated i.v. into nude or SCID mice metastasized only in the lung. In the multiple-organ metastasis model, tumor cells (RERF-LC-AI, SBC-3/DOX, H69/VP, which express low levels of MMPs) inoculated i.v. into natural killer cell-depleted SCID mice metastasized into the liver, kidneys, and systemic lymph nodes. Film in situ zymography analysis revealed that the nontumor parenchyma of the lung had no gelatinolytic activity, whereas gelatinolytic activity of the liver and kidney was high and low, respectively. In the lung metastasis model, gelatinolytic activity of lung nodules directly correlated with the in vitro expression of MMP-2 and MMP-9 by tumor cells. Inhibition of MMP activity by ONO-4817 suppressed lung metastasis by the cell lines that expressed MMPs, but not those that did not express MMP, via the inhibition of MMP activity of lung tumors. In the multiple-organ metastasis model, liver parenchyma, but not liver nodules, showed gelatinolytic activity. The MMP inhibition reduced metastasis to the liver, but not to the kidney or lymph nodes, via inhibition of MMP activity of liver parenchyma. These findings suggest that MMP expression varies among the host organ microenvironments and that stromal MMPs may promote metastasis of lung cancer. Therefore, antimetastatic effects based on MMP inhibition may be dependent on MMPs derived not only from tumor cells but also from organ

  20. Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

    DEFF Research Database (Denmark)

    Romme Christensen, Jeppe; Börnsen, Lars; Ratzer, Rikke

    2013-01-01

    Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH......) cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship...... a pathogenic role of systemic inflammation in progressive MS. These observations may have implications for the treatment of progressive MS....

  1. Polymorphisms in the genes involved in the arachidonic acid-pathway, fish consumption and the risk of colorectal cancer.

    NARCIS (Netherlands)

    Siezen, Christine L E; Bueno-de-Mesquita, H Bas; Peeters, Petra H M; Kram, Nicolien R; Doeselaar, Marina van; Kranen, Henk J van

    2006-01-01

    The objective of this study on colorectal cancer was to investigate the associations between SNPs in the genes involved in the arachidonic acid (AA)-pathway, their haplotypes and colorectal cancer. Moreover, interactions between SNPs and fish consumption were considered. In this study, a total of 50

  2. Multiple solutions and numerical analysis to the dynamic and stationary models coupling a delayed energy balance model involving latent heat and discontinuous albedo with a deep ocean.

    Science.gov (United States)

    Díaz, J I; Hidalgo, A; Tello, L

    2014-10-08

    We study a climatologically important interaction of two of the main components of the geophysical system by adding an energy balance model for the averaged atmospheric temperature as dynamic boundary condition to a diagnostic ocean model having an additional spatial dimension. In this work, we give deeper insight than previous papers in the literature, mainly with respect to the 1990 pioneering model by Watts and Morantine. We are taking into consideration the latent heat for the two phase ocean as well as a possible delayed term. Non-uniqueness for the initial boundary value problem, uniqueness under a non-degeneracy condition and the existence of multiple stationary solutions are proved here. These multiplicity results suggest that an S-shaped bifurcation diagram should be expected to occur in this class of models generalizing previous energy balance models. The numerical method applied to the model is based on a finite volume scheme with nonlinear weighted essentially non-oscillatory reconstruction and Runge-Kutta total variation diminishing for time integration.

  3. Multiple solutions and numerical analysis to the dynamic and stationary models coupling a delayed energy balance model involving latent heat and discontinuous albedo with a deep ocean

    Science.gov (United States)

    Díaz, J. I.; Hidalgo, A.; Tello, L.

    2014-01-01

    We study a climatologically important interaction of two of the main components of the geophysical system by adding an energy balance model for the averaged atmospheric temperature as dynamic boundary condition to a diagnostic ocean model having an additional spatial dimension. In this work, we give deeper insight than previous papers in the literature, mainly with respect to the 1990 pioneering model by Watts and Morantine. We are taking into consideration the latent heat for the two phase ocean as well as a possible delayed term. Non-uniqueness for the initial boundary value problem, uniqueness under a non-degeneracy condition and the existence of multiple stationary solutions are proved here. These multiplicity results suggest that an S-shaped bifurcation diagram should be expected to occur in this class of models generalizing previous energy balance models. The numerical method applied to the model is based on a finite volume scheme with nonlinear weighted essentially non-oscillatory reconstruction and Runge–Kutta total variation diminishing for time integration. PMID:25294969

  4. MYO9B polymorphisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Kemppinen, A.; Suvela, M.; Tienari, P.J.

    2009-01-01

    Single-nucleotide polymorphisms (SNPs) in the 3' region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First...

  5. MYO9B polymorphisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Kemppinen, A.; Suvela, M.; Tienari, P.J.

    2009-01-01

    Single-nucleotide polymorphisms (SNPs) in the 3' region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. Firs...

  6. Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs

    DEFF Research Database (Denmark)

    Lee, S Hong; DeCandia, Teresa R; Ripke, Stephan;

    2012-01-01

    of schizophrenia is the same in males and females, and that a disproportionate proportion of variation is attributable to a set of 2,725 genes expressed in the central nervous system (CNS; P = 7.6 × 10(-8)). These results are consistent with a polygenic genetic architecture and imply more individual SNP......Schizophrenia is a complex disorder caused by both genetic and environmental factors. Using 9,087 affected individuals, 12,171 controls and 915,354 imputed SNPs from the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC-SCZ), we estimate that 23% (s.e. = 1......%) of variation in liability to schizophrenia is captured by SNPs. We show that a substantial proportion of this variation must be the result of common causal variants, that the variance explained by each chromosome is linearly related to its length (r = 0.89, P = 2.6 × 10(-8)), that the genetic basis...

  7. Multiple homicides.

    Science.gov (United States)

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  8. Impact of five SNPs in dopamine-related genes on executive function.

    Science.gov (United States)

    Mitaki, S; Isomura, M; Maniwa, K; Yamasaki, M; Nagai, A; Nabika, T; Yamaguchi, S

    2013-01-01

    Dopamine neurotransmission is a critical factor for executive function, which is controlled by the prefrontal cortex in humans. Although the contribution of genetic factors to the regulation of brain dopaminergic activity is widely acknowledged, identification of a genotype-phenotype association has not yet been clearly established. In this study, we therefore evaluated the effects of five functional single-nucleotide polymorphisms (SNPs) in specific genes related to dopamine neurotransmission on executive function in a general population. Participants of the health examination at the Shimane Institute of Health Science were recruited for this study (n = 964). To evaluate executive function, the Frontal Assessment Battery (FAB) was administered. SNPs were genotyped using the TaqMan method. A significant association was found between an SNP in the catechol-O-methyltransferase (COMT) gene (rs4680) encoding the low-activity Met allele and FAB score (P = 0.003). Of note, the flexibility subset of the FAB was associated with the SNP in COMT (P = 0.003) after adjustment for confounding factors. The generalized multifactor dimensionality reduction method identified that the combination of two SNPs in the COMT gene (rs4680) and the dopamine D4 receptor gene (rs1800955) had a significant effect on FAB score. Our study indicates a contribution of rs4680 in the COMT gene to the variability in executive function, as assessed by the FAB. In addition, we have indicated that a complex gene-gene interaction between SNPs in the genes related to dopamine neurotransmission may influence executive function in a general population. © 2012 John Wiley & Sons A/S.

  9. Investigation on the role of nsSNPs in HNPCC genes – a bioinformatics approach

    Directory of Open Access Journals (Sweden)

    Sethumadhavan Rao

    2009-04-01

    Full Text Available Abstract Background A central focus of cancer genetics is the study of mutations that are causally implicated in tumorigenesis. The identification of such causal mutations not only provides insight into cancer biology but also presents anticancer therapeutic targets and diagnostic markers. Missense mutations are nucleotide substitutions that change an amino acid in a protein, the deleterious effects of these mutations are commonly attributed to their impact on primary amino acid sequence and protein structure. Methods The method to identify functional SNPs from a pool, containing both functional and neutral SNPs is challenging by experimental protocols. To explore possible relationships between genetic mutation and phenotypic variation, we employed different bioinformatics algorithms like Sorting Intolerant from Tolerant (SIFT, Polymorphism Phenotyping (PolyPhen, and PupaSuite to predict the impact of these amino acid substitutions on protein activity of mismatch repair (MMR genes causing hereditary nonpolyposis colorectal cancer (HNPCC. Results SIFT classified 22 of 125 variants (18% as 'Intolerant." PolyPhen classified 40 of 125 amino acid substitutions (32% as "Probably or possibly damaging". The PupaSuite predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Based on the PolyPhen scores and availability of three-dimensional structures, structure analysis was carried out with the major mutations that occurred in the native protein coded by MSH2 and MSH6 genes. The amino acid residues in the native and mutant model protein were further analyzed for solvent accessibility and secondary structure to check the stability of the proteins. Conclusion Based on this approach, we have shown that four nsSNPs, which were predicted to have functional consequences (MSH2-Y43C, MSH6-Y538S, MSH6-S580L, and MSH6-K854M, were already found to be associated with cancer risk. Our study demonstrates the presence of other

  10. Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs.

    Directory of Open Access Journals (Sweden)

    Andrea G Nackley

    Full Text Available Catechol-O-methyltransferase (COMT is an enzyme that plays a key role in the modulation of catechol-dependent functions such as cognition, cardiovascular function, and pain processing. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous (val(158met position, designated as low (LPS, average (APS, and high pain sensitive (HPS, are associated with experimental pain sensitivity and risk of developing chronic musculoskeletal pain conditions. APS and HPS haplotypes produce significant functional effects, coding for 3- and 20-fold reductions in COMT enzymatic activity, respectively. In the present study, we investigated whether additional minor single nucleotide polymorphisms (SNPs, accruing in 1 to 5% of the population, situated in the COMT transcript region contribute to haplotype-dependent enzymatic activity. Computer analysis of COMT ESTs showed that one synonymous minor SNP (rs769224 is linked to the APS haplotype and three minor SNPs (two synonymous: rs6267, rs740602 and one nonsynonymous: rs8192488 are linked to the HPS haplotype. Results from in silico and in vitro experiments revealed that inclusion of allelic variants of these minor SNPs in APS or HPS haplotypes did not modify COMT function at the level of mRNA folding, RNA transcription, protein translation, or enzymatic activity. These data suggest that neutral variants are carried with APS and HPS haplotypes, while the high activity LPS haplotype displays less linked variation. Thus, both minor synonymous and nonsynonymous SNPs in the coding region are markers of functional APS and HPS haplotypes rather than independent contributors to COMT activity.

  11. AB048. X-chromosomal SNPs variation in populations of Russia

    Science.gov (United States)

    Stepanov, Vadim; Vagaitseva, Kseniya; Kharkov, Vladimir

    2015-01-01

    X-chromosome markers are informative tool for studying a genetic diversity in human populations and have become a useful in DNA identification when certain complex kinship cases need to be unravelled. In this work we present population genetic data on X-chromosome-wide SNPs in North Eurasian populations and report XSNP multiplex system for forensic genetics. A total of 2,867 X-chromosomal SNPs were genotyped in 12 populations using Illumina microarray platform. Twelve populations under study (Komi, Mordva, Russians, Kirghiz, Kazakh, Uzbek, Buryat, Yakut, Evenk, Tuva, Khanty, Ket) represent various language families and geographic regions of North Eurasia (Eastern Europe, Central Asia, Siberia and North Asia). North Eurasian populations are highly genetically differentiated with respect to XSNPs allele frequencies. Average level of genetic differentiation (Gst) for 12 populations is 6.03% and ranged from 1.05% to 30.05% per individual SNP. Principal component analysis of allele frequencies demonstrated geographic pattern of population clustering, as well as longitudinal gradient in genetic diversity. The 66 XSNPs characterized by high expected heterozygosity and linkage equilibrium in populations under study were selected for constructing a panel for forensic genetic applications. Average heterozygosity of selected SNPs varied from 0.4925 to 0.4958. Overall values of power of discrimination for males and females (PDm and PDf) obtained with these XSNPs set are several magnitude higher than those for standard forensic STR panels. Protocol for multiplex amplification of 66 XSNPs in two separate multiplex PCR reactions and MALDI-TOF mass spectrometry genotyping was developed. North Eurasian populations demonstrate high level of genetic diversity and differentiation for X-chromosome-wide SNPs. Based on obtained population genetic data, highly informative multiplex XSNPs panel for forensic genetics was developed.

  12. Evaluating the transferability of Hapmap SNPs to a Singapore Chinese population

    Directory of Open Access Journals (Sweden)

    Wang De Yun

    2010-05-01

    Full Text Available Abstract Background The International Hapmap project serves as a valuable resource for human genome variation data, however its applicability to other populations has yet to be exhaustively investigated. In this paper, we use high density genotyping chips and resequencing strategies to compare the Singapore Chinese population with the Hapmap populations. First we compared 1028 and 114 unrelated Singapore Chinese samples genotyped using the Illumina Human Hapmap 550 k chip and Affymetrix 500 k array respectively against the 270 samples from Hapmap. Secondly, data from 20 candidate genes on 5q31-33 resequenced for an asthma candidate gene based study was also used for the analysis. Results A total of 237 SNPs were identified through resequencing of which only 95 SNPs (40% were in Hapmap; however an additional 56 SNPs (24% were not genotyped directly but had a proxy SNP in the Hapmap. At the genome-wide level, Singapore Chinese were highly correlated with Hapmap Han Chinese with correlation of 0.954 and 0.947 for the Illumina and Affymetrix platforms respectively with deviant SNPs randomly distributed within and across all chromosomes. Conclusions The high correlation between our population and Hapmap Han Chinese reaffirms the applicability of Hapmap based genome-wide chips for GWA studies. There is a clear population signature for the Singapore Chinese samples and they predominantly resemble the southern Han Chinese population; however when new migrants particularly those with northern Han Chinese background were included, population stratification issues may arise. Future studies needs to address population stratification within the sample collection while designing and interpreting GWAS in the Chinese population.

  13. Application of CRISPRi for prokaryotic metabolic engineering involving multiple genes, a case study: Controllable P(3HB-co-4HB) biosynthesis.

    Science.gov (United States)

    Lv, Li; Ren, Yi-Lin; Chen, Jin-Chun; Wu, Qiong; Chen, Guo-Qiang

    2015-05-01

    Clustered regularly interspaced short palindromic repeats interference (CRISPRi) is used to edit eukaryotic genomes. Here, we show that CRISPRi can also be used for fine-tuning prokaryotic gene expression while simultaneously regulating multiple essential gene expression with less labor and time consumption. As a case study, CRISPRi was used to control polyhydroxyalkanoate (PHA) biosynthesis pathway flux and to adjust PHA composition. A pathway was constructed in Escherichia coli for the production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] from glucose. The native gene sad encoding E. coli succinate semi-aldehyde dehydrogenase was expressed under the control of CRISPRi using five specially designed single guide RNAs (sgRNAs) for regulating carbon flux to 4-hydroxybutyrate (4HB) biosynthesis. The system allowed formation of P(3HB-co-4HB) consisting of 1-9mol% 4HB. Additionally, succinate, generated by succinyl-coA synthetase and succinate dehydrogenase (respectively encoded by genes sucC, sucD and sdhA, sdhB) was channeled preferentially to the 4HB precursor by using selected sgRNAs such as sucC2, sucD2, sdhB2 and sdhA1 via CRISPRi. The resulting 4HB content in P(3HB-co-4HB) was found to range from 1.4 to 18.4mol% depending on the expression levels of down-regulated genes. The results show that CRISPRi is a feasible method to simultaneously manipulate multiple genes in E. coli.

  14. Integration of regulatory signals through involvement of multiple global regulators: control of the Escherichia coli gltBDF operon by Lrp, IHF, Crp, and ArgR

    Directory of Open Access Journals (Sweden)

    Mishra Pankaj K

    2007-01-01

    Full Text Available Abstract Background The glutamate synthase operon (gltBDF contributes to one of the two main pathways of ammonia assimilation in Escherichia coli. Of the seven most-global regulators, together affecting expression of about half of all E. coli genes, two were previously shown to exert direct, positive control on gltBDF transcription: Lrp and IHF. The involvement of Lrp is unusual in two respects: first, it is insensitive to the usual coregulator leucine, and second, Lrp binds more than 150 bp upstream of the transcription starting point. There was indirect evidence for involvement of a third global regulator, Crp. Given the physiological importance of gltBDF, and the potential opportunity to learn about integration of global regulatory signals, a combination of in vivo and in vitro approaches was used to investigate the involvement of additional regulatory proteins, and to determine their relative binding positions and potential interactions with one another and with RNA polymerase (RNAP. Results Crp and a more local regulator, ArgR, directly control gltBDF transcription, both acting negatively. Crp-cAMP binds a sequence centered at -65.5 relative to the transcript start. Mutation of conserved nucleotides in the Crp binding site abolishes the Crp-dependent repression. ArgR also binds to the gltBDF promoter region, upstream of the Lrp binding sites, and decreases transcription. RNAP only yields a defined DNAse I footprint under two tested conditions: in the presence of both Lrp and IHF, or in the presence of Crp-cAMP. The DNAse I footprint of RNAP in the presence of Lrp and IHF is altered by ArgR. Conclusion The involvement of nearly half of E. coli's most-global regulatory proteins in the control of gltBDF transcription is striking, but seems consistent with the central metabolic role of this operon. Determining the mechanisms of activation and repression for gltBDF was beyond the scope of this study. However the results are consistent with a

  15. Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation

    Science.gov (United States)

    Ruiz, Jesus; Herrero, María José; Bosó, Virginia; Megías, Juan Eduardo; Hervás, David; Poveda, Jose Luis; Escrivá, Juan; Pastor, Amparo; Solé, Amparo; Aliño, Salvador Francisco

    2015-01-01

    Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc). The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC). In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%). Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation. PMID:26307985

  16. FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs

    Directory of Open Access Journals (Sweden)

    Zhao Hongyu

    2008-01-01

    Full Text Available Abstract Background FTO is a gene located in chromosome region 16q12.2. Recently two studies have found associations of several single nucleotide polymorphisms (SNPs in FTO with body mass index (BMI and obesity, particularly rs1421085, rs17817449, and rs9939609. Methods We examined these three SNPs in 583 extremely obese women with current BMI greater than 35 kg/m2 and lifetime BMI greater than 40 kg/m2, and 544 controls who were currently normal weight (BMI2 and had never been overweight during their lifetimes. Results We detected highly significant associations of obesity with alleles in all three SNPs (p -9. The strongest association was with rs1421085 (p = 3.04 × 10-10, OR = 1.75, CI = 1.47–2.08. A subset of 99 cases had extremely discordant sisters with BMI2. The discordant sisters differed in allele and genotype frequencies in parallel with the overall case and control sample. The strongest association was with rs17817449 (z = 3.57, p = 3.6 × 10-4. Conclusion These results suggest common variability in FTO is associated with increased obesity risk or resistance and may in part account for differences between closely related individuals.

  17. Impact of Single Nucleotide Polymorphisms (SNPs on Immunosuppressive Therapy in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Jesus Ruiz

    2015-08-01

    Full Text Available Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA, during the first six months after lung transplantation (51 patients. The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc. The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC. In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%. Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation.

  18. Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds.

    Science.gov (United States)

    Schaefer, Robert J; Schubert, Mikkel; Bailey, Ernest; Bannasch, Danika L; Barrey, Eric; Bar-Gal, Gila Kahila; Brem, Gottfried; Brooks, Samantha A; Distl, Ottmar; Fries, Ruedi; Finno, Carrie J; Gerber, Vinzenz; Haase, Bianca; Jagannathan, Vidhya; Kalbfleisch, Ted; Leeb, Tosso; Lindgren, Gabriella; Lopes, Maria Susana; Mach, Núria; da Câmara Machado, Artur; MacLeod, James N; McCoy, Annette; Metzger, Julia; Penedo, Cecilia; Polani, Sagi; Rieder, Stefan; Tammen, Imke; Tetens, Jens; Thaller, Georg; Verini-Supplizi, Andrea; Wade, Claire M; Wallner, Barbara; Orlando, Ludovic; Mickelson, James R; McCue, Molly E

    2017-07-27

    To date, genome-scale analyses in the domestic horse have been limited by suboptimal single nucleotide polymorphism (SNP) density and uneven genomic coverage of the current SNP genotyping arrays. The recent availability of whole genome sequences has created the opportunity to develop a next generation, high-density equine SNP array. Using whole genome sequence from 153 individuals representing 24 distinct breeds collated by the equine genomics community, we cataloged over 23 million de novo discovered genetic variants. Leveraging genotype data from individuals with both whole genome sequence, and genotypes from lower-density, legacy SNP arrays, a subset of ~5 million high-quality, high-density array candidate SNPs were selected based on breed representation and uniform spacing across the genome. Considering probe design recommendations from a commercial vendor (Affymetrix, now Thermo Fisher Scientific) a set of ~2 million SNPs were selected for a next-generation high-density SNP chip (MNEc2M). Genotype data were generated using the MNEc2M array from a cohort of 332 horses from 20 breeds and a lower-density array, consisting of ~670 thousand SNPs (MNEc670k), was designed for genotype imputation. Here, we document the steps taken to design both the MNEc2M and MNEc670k arrays, report genomic and technical properties of these genotyping platforms, and demonstrate the imputation capabilities of these tools for the domestic horse.

  19. SNPs of melanocortin 4 receptor (MC4R) associated with body weight in Beagle dogs.

    Science.gov (United States)

    Zeng, Ruixia; Zhang, Yibo; Du, Peng

    2014-01-01

    Melanocortin 4 receptor (MC4R), which is associated with inherited human obesity, is involoved in food intake and body weight of mammals. To study the relationships between MC4R gene polymorphism and body weight in Beagle dogs, we detected and compared the nucleotide sequence of the whole coding region and 3'- and 5'- flanking regions of the dog MC4R gene (1214 bp). In 120 Beagle dogs, two SNPs (A420C, C895T) were identified and their relation with body weight was analyzed with RFLP-PCR method. The results showed that the SNP at A420C was significantly associated with canine body weight trait when it changed amino acid 101 of the MC4R protein from asparagine to threonine, while canine body weight variations were significant in female dogs when MC4R nonsense mutation at C895T. It suggested that the two SNPs might affect the MC4R gene's function which was relative to body weight in Beagle dogs. Therefore, MC4R was a candidate gene for selecting different size dogs with the MC4R SNPs (A420C, C895T) being potentially valuable as a genetic marker.

  20. HapMap SNP Scanner: an online program to mine SNPs responsible for cell phenotype.

    Science.gov (United States)

    Yamamura, T; Hikita, J; Bleakley, M; Hirosawa, T; Sato-Otsubo, A; Torikai, H; Hamajima, T; Nannya, Y; Demachi-Okamura, A; Maruya, E; Saji, H; Yamamoto, Y; Takahashi, T; Emi, N; Morishima, Y; Kodera, Y; Kuzushima, K; Riddell, S R; Ogawa, S; Akatsuka, Y

    2012-08-01

    Minor histocompatibility (H) antigens are targets of graft-vs-host disease and graft-vs-tumor responses after human leukocyte antigen matched allogeneic hematopoietic stem cell transplantation. Recently, we reported a strategy for genetic mapping of linkage disequilibrium blocks that encoded novel minor H antigens using the large dataset from the International HapMap Project combined with conventional immunologic assays to assess recognition of HapMap B-lymphoid cell line by minor H antigen-specific T cells. In this study, we have constructed and provide an online interactive program and demonstrate its utility for searching for single-nucleotide polymorphisms (SNPs) responsible for minor H antigen generation. The website is available as 'HapMap SNP Scanner', and can incorporate T-cell recognition and other data with genotyping datasets from CEU, JPT, CHB, and YRI to provide a list of candidate SNPs that correlate with observed phenotypes. This method should substantially facilitate discovery of novel SNPs responsible for minor H antigens and be applicable for assaying of other specific cell phenotypes (e.g. drug sensitivity) to identify individuals who may benefit from SNP-based customized therapies.

  1. Comparison of ENCODE region SNPs between Cebu Filipino and Asian HapMap samples.

    Science.gov (United States)

    Marvelle, Amanda F; Lange, Leslie A; Qin, Li; Wang, Yunfei; Lange, Ethan M; Adair, Linda S; Mohlke, Karen L

    2007-01-01

    Patterns of linkage disequilibrium (LD) act as the framework for designing efficient association studies; these patterns are being studied and catalogued by The International HapMap Project. The current study assessed the transferability of tag SNPs chosen from HapMap panels to a cohort of 80 individuals from metro Cebu, Philippines, who participated in the Cebu Longitudinal Health and Nutrition Survey (CLHNS). The analyses focused on 627 single nucleotide polymorphisms (SNPs) in the central 40 kb within each of the 10 HapMap ENCODE regions. The similarity between the genetic variants in Cebu Filipino samples and HapMap panels was examined using allele frequency estimates, measures of pairwise linkage disequilibrium (LD), and haplotype frequency estimates. For these measures, strong correlations were observed between the Cebu Filipino samples and the Asian panels from HapMap, with the strongest correlations observed with the Han Chinese from Beijing (CHB) panel. Tag SNPs selected using the HapMap CHB panel were particularly effective at representing the genetic variation in Cebu Filipino samples. These results suggest that the HapMap data will be an effective resource for future studies in Cebu Filipino samples.

  2. Identification of SNPs in the promoter of β-lactoglobulin gene in three Sicilian goat breeds

    Directory of Open Access Journals (Sweden)

    Baldassare Portolano

    2010-01-01

    Full Text Available The aim of this work was to sequence the full-length promoter region of the caprine β-lactoglobulin (β-lg gene in three Sicilian goat breeds (Girgentana, Maltese, and Derivata di Siria, in order to identify polymorphisms, to search for transcription factors (TFs sites, and to check if polymorphisms found lay within TFs binding sites. The promoter region of β-lg gene in Sicilian goat breeds showed high level of polymorphism due to the presence of 31 SNPs. Binding sites for several TFs were found within the goat β-lg promoter and within regions conserved between ovine and caprine species. Two SNPs were detected within TFs binding sites, such as MPBF and NF-I. Further studies are in progress to confirm polymorphic sites, to evaluate the possible effect of these mutations on binding affinity of TFs, their relationship with β-lg gene expression, and the functional role of SNPs within the TFs sites of the promoter region on milk traits.

  3. Evidence of Multiple Treponema Phylotypes Involved in Bovine Digital Dermatitis as Shown by 16S rRNA Gene Analysis and Fluorescence In Situ Hybridization

    DEFF Research Database (Denmark)

    Klitgaard, Kirstine; Boye, Mette; Capion, Nynne

    2008-01-01

    The etiopathogenesis of the skin disease digital dermatitis (DD), an important cause of lameness in cattle, remains uncertain. Microscopically, the disease appears to be polymicrobial, with spirochetes as the predominant bacteria. The objective of this study was to identify the main part of the b......The etiopathogenesis of the skin disease digital dermatitis (DD), an important cause of lameness in cattle, remains uncertain. Microscopically, the disease appears to be polymicrobial, with spirochetes as the predominant bacteria. The objective of this study was to identify the main part...... of the bacteria involved in DD lesions of cattle by using culture-independent molecular methods. Ten different phylotypes of Treponema were identified either by 16S rRNA gene sequencing of bacteria from DD lesions or by fluorescence in situ hybridization (FISH) analysis using phylotype-specific 16S r...... that Treponema accounted for more than 90% of the total bacterial population in the biopsy specimens. These data strongly suggest that a group of apparently symbiotic Treponema species are involved as primary bacterial pathogens in DD....

  4. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    NARCIS (Netherlands)

    Bojesen, Stig E.; Pooley, Karen A.; Johnatty, Sharon E.; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P.; Edwards, Stacey L.; Pickett, Hilda A.; Shen, Howard C.; Smart, Chanel E.; Hillman, Kristine M.; Mai, Phuong L.; Lawrenson, Kate; Stutz, Michael D.; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnstonw, Rebecca L.; French, Juliet D.; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F.; Maranian, Melanie J.; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A.; Gonzalez-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A.; Alvarez, Nuria; Larson, Melissa C.; Fridley, Brooke L.; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S.; Peto, Julian; Kalli, Kimberly R.; Broeks, Annegien; Armasu, Sebastian M.; Schmidt, Marjanka K.; Braaf, Linde M.; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E.; Lambrechts, Diether; Rogmann, Lisa; Guenel, Pascal; Teoman, Attila; Milne, Roger L.; Garcia, Joaquin J.; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J.; Haiman, Christopher A.; Wang-Gohrke, Shan; Andrulis, Irene L.; Moysich, Kirsten B.; Hopper, John L.; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G.; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A.; Carney, Michael E.; Radice, Paolo; Wilkens, Lynne R.; Swerdlow, Anthony; Goodman, Marc T.; Brauch, Hiltrud; Garcia-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Durst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V.; Doerk, Thilo; Pelttari, Liisa M.; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H.; Kristensen, Vessela; Ness, Roberta B.; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H.; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y.; Sangrajrang, Suleeporn; Kjaer, Susanne Kruger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Hogdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A.; Nordestgaard, Borge G.; Flyger, Henrik; Vachon, Celine; Olson, Janet E.; Wang, Xianshu; Levine, Douglas A.; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M.; Silva, Isabel Dos Santos; Cramer, Daniel W.; Gibson, Lorna; Terry, Kathryn L.; Fletcher, Olivia; Vitonis, Allison F.; van der Schoot, C. Ellen; Poole, Elizabeth M.; Hogervorst, Frans B. L.; Tworoger, Shelley S.; Liu, Jianjun; Bandera, Elisa V.; Li, Jingmei; Olson, Sara H.; Humphreys, Keith; Row, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomaki, Kristiina; Salvesen, Helga B.; Muranen, Taru A.; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K.; Wildiers, Hans; Kiemeney, Lambertus A.; Mulot, Claire; Aben, Katja K.; Laurent-Puig, Pierre; Altena, Anne Mvan; Therese Truong, [No Value; Massuger, Leon F. A. G.; Benitez, Javier; Pejovic, Tanja; Arias Perez, Jose Ignacio; Hoatlin, Maureen; Zamora, M. Pilar; Cook, Linda S.; Balasubramanian, Sabapathy P.; Kelemen, Linda E.; Schneeweiss, Andreas; Le, Nhu D.; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E.; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Marchand, Loic Le; Yang, Hannah P.; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A.; Hogdall, Claus K.; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C.; Jager, Agnes; den Ouweland, Ans M. Wvan; Brown, Robert; Martens, John W. M.; Flanagan, James M.; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S.; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Mueller, Heiko; Arndt, Volker; Labreche, France; Gao, Yu-Tang; Goldberg, Mark S.; Yang, Gong; Dumont, Martine; McLaughlin, John R.; Hartmann, Arndt; Ekici, Arif B.; Beckmann, Matthias W.; Phelan, Catherine M.; Lux, Michael P.; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A.; Ficarazzi, Filomena

    TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer

  5. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    DEFF Research Database (Denmark)

    Bojesen, Stig Egil; Pooley, Karen A; Johnatty, Sharon E

    2013-01-01

    TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases an...

  6. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    NARCIS (Netherlands)

    Bojesen, Stig E.; Pooley, Karen A.; Johnatty, Sharon E.; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P.; Edwards, Stacey L.; Pickett, Hilda A.; Shen, Howard C.; Smart, Chanel E.; Hillman, Kristine M.; Mai, Phuong L.; Lawrenson, Kate; Stutz, Michael D.; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnstonw, Rebecca L.; French, Juliet D.; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F.; Maranian, Melanie J.; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A.; Gonzalez-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A.; Alvarez, Nuria; Larson, Melissa C.; Fridley, Brooke L.; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S.; Peto, Julian; Kalli, Kimberly R.; Broeks, Annegien; Armasu, Sebastian M.; Schmidt, Marjanka K.; Braaf, Linde M.; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E.; Lambrechts, Diether; Rogmann, Lisa; Guenel, Pascal; Teoman, Attila; Milne, Roger L.; Garcia, Joaquin J.; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J.; Haiman, Christopher A.; Wang-Gohrke, Shan; Andrulis, Irene L.; Moysich, Kirsten B.; Hopper, John L.; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G.; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A.; Carney, Michael E.; Radice, Paolo; Wilkens, Lynne R.; Swerdlow, Anthony; Goodman, Marc T.; Brauch, Hiltrud; Garcia-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Durst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V.; Doerk, Thilo; Pelttari, Liisa M.; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H.; Kristensen, Vessela; Ness, Roberta B.; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H.; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y.; Sangrajrang, Suleeporn; Kjaer, Susanne Kruger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Hogdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A.; Nordestgaard, Borge G.; Flyger, Henrik; Vachon, Celine; Olson, Janet E.; Wang, Xianshu; Levine, Douglas A.; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M.; Silva, Isabel Dos Santos; Cramer, Daniel W.; Gibson, Lorna; Terry, Kathryn L.; Fletcher, Olivia; Vitonis, Allison F.; van der Schoot, C. Ellen; Poole, Elizabeth M.; Hogervorst, Frans B. L.; Tworoger, Shelley S.; Liu, Jianjun; Bandera, Elisa V.; Li, Jingmei; Olson, Sara H.; Humphreys, Keith; Row, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomaki, Kristiina; Salvesen, Helga B.; Muranen, Taru A.; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K.; Wildiers, Hans; Kiemeney, Lambertus A.; Mulot, Claire; Aben, Katja K.; Laurent-Puig, Pierre; Altena, Anne Mvan; Therese Truong, [No Value; Massuger, Leon F. A. G.; Benitez, Javier; Pejovic, Tanja; Arias Perez, Jose Ignacio; Hoatlin, Maureen; Zamora, M. Pilar; Cook, Linda S.; Balasubramanian, Sabapathy P.; Kelemen, Linda E.; Schneeweiss, Andreas; Le, Nhu D.; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E.; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Marchand, Loic Le; Yang, Hannah P.; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A.; Hogdall, Claus K.; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C.; Jager, Agnes; den Ouweland, Ans M. Wvan; Brown, Robert; Martens, John W. M.; Flanagan, James M.; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S.; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Mueller, Heiko; Arndt, Volker; Labreche, France; Gao, Yu-Tang; Goldberg, Mark S.; Yang, Gong; Dumont, Martine; McLaughlin, John R.; Hartmann, Arndt; Ekici, Arif B.; Beckmann, Matthias W.; Phelan, Catherine M.; Lux, Michael P.; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A.; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J.; Orr, Nick; Menon, Usha; Pearce, Celeste L.; Bruening, Thomas; Pike, Malcolm C.; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J.; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K.; Pylkas, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A. E. M.; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M.; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N.; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K.; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O.; van den Berg, David; Yip, Cheng Har; Ikrarn, M. Kamran; Teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B.; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; Teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S.; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Garber, Judy; Narod, Steven A.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Imyanitov, Evgeny N.; Tihomirova, Laima; Arun, Banu K.; Campbell, Ian; Mensenkamp, Arjen R.; van Asperen, Christi J.; van Roozendaa, Kees E. P.; Meijers-Heijboer, Hanne; Collee, J. Margriet; Oosterwijk, Jan C.; Hooning, Maartje J.; Rookus, Matti A.; van der Luijt, Rob B.; Os, Theo A. Mvan; Evans, D. Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M. John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D.; Cole, Trevor; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M.; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valerie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B.; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Pendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Ake; Mein, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L.; Domchek, Susan M.; Rodriguez, Gustavo C.; Salani, Ritu; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A.; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A.; Lesterm, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B.; Olswold, Curtis; Cunningham, Julie M.; Slager, Susan; Pankratz, Vernon S.; Dicks, Ed; Lakhani, Sunil R.; Couch, Fergus J.; Hall, Per; Monteiro, Alvaro N. A.; Gayther, Simon A.; Pharoah, Paul D. P.; Reddel, Roger R.; Goode, Ellen L.; Greene, Mark H.; Easton, Douglas F.; Berchuck, Andrew; Antoniou, Antonis C.; Chenevix-Trench, Georgia; Dunning, Alison M.

    2013-01-01

    TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer ca

  7. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    NARCIS (Netherlands)

    Bojesen, Stig E.; Pooley, Karen A.; Johnatty, Sharon E.; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P.; Edwards, Stacey L.; Pickett, Hilda A.; Shen, Howard C.; Smart, Chanel E.; Hillman, Kristine M.; Mai, Phuong L.; Lawrenson, Kate; Stutz, Michael D.; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnstonw, Rebecca L.; French, Juliet D.; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F.; Maranian, Melanie J.; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A.; Gonzalez-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A.; Alvarez, Nuria; Larson, Melissa C.; Fridley, Brooke L.; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S.; Peto, Julian; Kalli, Kimberly R.; Broeks, Annegien; Armasu, Sebastian M.; Schmidt, Marjanka K.; Braaf, Linde M.; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E.; Lambrechts, Diether; Rogmann, Lisa; Guenel, Pascal; Teoman, Attila; Milne, Roger L.; Garcia, Joaquin J.; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J.; Haiman, Christopher A.; Wang-Gohrke, Shan; Andrulis, Irene L.; Moysich, Kirsten B.; Hopper, John L.; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G.; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A.; Carney, Michael E.; Radice, Paolo; Wilkens, Lynne R.; Swerdlow, Anthony; Goodman, Marc T.; Brauch, Hiltrud; Garcia-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Durst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V.; Doerk, Thilo; Pelttari, Liisa M.; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H.; Kristensen, Vessela; Ness, Roberta B.; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H.; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y.; Sangrajrang, Suleeporn; Kjaer, Susanne Kruger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Hogdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A.; Nordestgaard, Borge G.; Flyger, Henrik; Vachon, Celine; Olson, Janet E.; Wang, Xianshu; Levine, Douglas A.; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M.; Silva, Isabel Dos Santos; Cramer, Daniel W.; Gibson, Lorna; Terry, Kathryn L.; Fletcher, Olivia; Vitonis, Allison F.; van der Schoot, C. Ellen; Poole, Elizabeth M.; Hogervorst, Frans B. L.; Tworoger, Shelley S.; Liu, Jianjun; Bandera, Elisa V.; Li, Jingmei; Olson, Sara H.; Humphreys, Keith; Row, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomaki, Kristiina; Salvesen, Helga B.; Muranen, Taru A.; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K.; Wildiers, Hans; Kiemeney, Lambertus A.; Mulot, Claire; Aben, Katja K.; Laurent-Puig, Pierre; Altena, Anne Mvan; Therese Truong, [No Value; Massuger, Leon F. A. G.; Benitez, Javier; Pejovic, Tanja; Arias Perez, Jose Ignacio; Hoatlin, Maureen; Zamora, M. Pilar; Cook, Linda S.; Balasubramanian, Sabapathy P.; Kelemen, Linda E.; Schneeweiss, Andreas; Le, Nhu D.; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E.; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Marchand, Loic Le; Yang, Hannah P.; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A.; Hogdall, Claus K.; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C.; Jager, Agnes; den Ouweland, Ans M. Wvan; Brown, Robert; Martens, John W. M.; Flanagan, James M.; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S.; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Mueller, Heiko; Arndt, Volker; Labreche, France; Gao, Yu-Tang; Goldberg, Mark S.; Yang, Gong; Dumont, Martine; McLaughlin, John R.; Hartmann, Arndt; Ekici, Arif B.; Beckmann, Matthias W.; Phelan, Catherine M.; Lux, Michael P.; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A.; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J.; Orr, Nick; Menon, Usha; Pearce, Celeste L.; Bruening, Thomas; Pike, Malcolm C.; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J.; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K.; Pylkas, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A. E. M.; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M.; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N.; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K.; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O.; van den Berg, David; Yip, Cheng Har; Ikrarn, M. Kamran; Teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B.; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; Teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S.; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Garber, Judy; Narod, Steven A.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Imyanitov, Evgeny N.; Tihomirova, Laima; Arun, Banu K.; Campbell, Ian; Mensenkamp, Arjen R.; van Asperen, Christi J.; van Roozendaa, Kees E. P.; Meijers-Heijboer, Hanne; Collee, J. Margriet; Oosterwijk, Jan C.; Hooning, Maartje J.; Rookus, Matti A.; van der Luijt, Rob B.; Os, Theo A. Mvan; Evans, D. Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M. John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D.; Cole, Trevor; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M.; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valerie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B.; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Pendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Ake; Mein, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L.; Domchek, Susan M.; Rodriguez, Gustavo C.; Salani, Ritu; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A.; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A.; Lesterm, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B.; Olswold, Curtis; Cunningham, Julie M.; Slager, Susan; Pankratz, Vernon S.; Dicks, Ed; Lakhani, Sunil R.; Couch, Fergus J.; Hall, Per; Monteiro, Alvaro N. A.; Gayther, Simon A.; Pharoah, Paul D. P.; Reddel, Roger R.; Goode, Ellen L.; Greene, Mark H.; Easton, Douglas F.; Berchuck, Andrew; Antoniou, Antonis C.; Chenevix-Trench, Georgia; Dunning, Alison M.

    2013-01-01

    TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer ca

  8. Statistical epistasis and progressive brain change in schizophrenia: an approach for examining the relationships between multiple genes.

    Science.gov (United States)

    Andreasen, N C; Wilcox, M A; Ho, B-C; Epping, E; Ziebell, S; Zeien, E; Weiss, B; Wassink, T

    2012-11-01

    Although schizophrenia is generally considered to occur as a consequence of multiple genes that interact with one another, very few methods have been developed to model epistasis. Phenotype definition has also been a major challenge for research on the genetics of schizophrenia. In this report, we use novel statistical techniques to address the high dimensionality of genomic data, and we apply a refinement in phenotype definition by basing it on the occurrence of brain changes during the early course of the illness, as measured by repeated magnetic resonance scans (i.e., an 'intermediate phenotype.') The method combines a machine-learning algorithm, the ensemble method using stochastic gradient boosting, with traditional general linear model statistics. We began with 14 genes that are relevant to schizophrenia, based on association studies or their role in neurodevelopment, and then used statistical techniques to reduce them to five genes and 17 single nucleotide polymorphisms (SNPs) that had a significant statistical interaction: five for PDE4B, four for RELN, four for ERBB4, three for DISC1 and one for NRG1. Five of the SNPs involved in these interactions replicate previous research in that, these five SNPs have previously been identified as schizophrenia vulnerability markers or implicate cognitive processes relevant to schizophrenia. This ability to replicate previous work suggests that our method has potential for detecting a meaningful epistatic relationship among the genes that influence brain abnormalities in schizophrenia.

  9. The IASLC Lung Cancer Staging Project: Summary of Proposals for Revisions of the Classification of Lung Cancers with Multiple Pulmonary Sites of Involvement in the Forthcoming Eighth Edition of the TNM Classification.

    Science.gov (United States)

    Detterbeck, Frank C; Nicholson, Andrew G; Franklin, Wilbur A; Marom, Edith M; Travis, William D; Girard, Nicolas; Arenberg, Douglas A; Bolejack, Vanessa; Donington, Jessica S; Mazzone, Peter J; Tanoue, Lynn T; Rusch, Valerie W; Crowley, John; Asamura, Hisao; Rami-Porta, Ramón

    2016-05-01

    Patients with lung cancer who harbor multiple pulmonary sites of disease have been challenging to classify; a subcommittee of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee was charged with developing proposals for the eighth edition of the tumor, node, and metastasis (TNM) classification to address this issue. A systematic literature review and analysis of the International Association for the Study of Lung Cancer database was performed to develop proposals for revision in an iterative process involving multispecialty international input and review. Details of the evidence base are summarized in other articles. Four patterns of disease are recognized; the clinical presentation, pathologic correlates, and biologic behavior of these suggest specific applications of the TNM classification rules. First, it is proposed that second primary lung cancers be designated with a T, N, and M category for each tumor. Second, tumors with a separate tumor nodule of the same histologic type (either suspected or proved) should be classified according to the location of the separate nodule relative to the index tumor-T3 for a same-lobe, T4 for a same-side (different lobe), and M1a for an other-side location-with a single N and M category. Third, multiple tumors with prominent ground glass (imaging) or lepidic (histologic) features should be designated by the T category of the highest T lesion, the number or m in parentheses (#/m) to indicate the multiplicity, and a collective N and M category for all. Finally, it is proposed that diffuse pneumonic-type lung cancers be designated by size (or T3) if in one lobe, T4 if involving multiple same-side lobes, and M1a if involving both lungs with a single N and M category for all areas of involvement. We propose to tailor TNM classification of multiple pulmonary sites of lung cancer to reflect the unique aspects of four different patterns of presentation. We hope that this will lead to

  10. Study on the Effect of γ-Irradiation on Gadolinium Oxysulfide Nanophosphors (Gd2O2S-NPs

    Directory of Open Access Journals (Sweden)

    Muhammad Hassyakirin Hasim

    2017-01-01

    Full Text Available Gadolinium oxysulfide nanophosphors (Gd2O2S-NPs have been successfully synthesized using γ-irradiation and hydrogenation treatment. The primary stage of Gd2O2S-NPs synthesis was carried out using various doses of γ-irradiation to form diverse sizes of Gd2(SO43 precursor, followed by hydrogenation treatment at 900°C for 2 hours to form Gd2O2S-NPs. Then, the nanophosphors were characterized for the structure, morphology, and luminescence properties through X-ray diffraction (XRD, field emission scanning electron microscopy (FESEM, and photoluminescence spectrometer (PL. Pure hexagonal phase of Gd2O2S-NPs was obtained with high crystallinity and without any impurities. The morphologies were observed from grain-like nanostructures transformed to spherical shape as the irradiation dose reached 40 kGy. Besides, Gd2O2S-NPs which were prepared at highest irradiation dose of 40 kGy show highest intensity of emission peak at 548 nm and corresponded to Stark level transition from the GJ6 state of Gd3+ ion. It can be emphasized that the different doses of γ-irradiation influenced the nucleation event of Gd2(SO43 precursor thus affecting the morphology and size particles of Gd2O2S-NPs. Hence, from the results, it can be suggested that Gd2O2S-NPs can be a promising host for optical applications.

  11. Comparing genetic variants detected in the 1000 genomes project with SNPs determined by the International HapMap Consortium

    Indian Academy of Sciences (India)

    Wenqian Zhang; Hui Wen Ng; Mao Shu; Heng Luo; Zhenqiang Su; Weigong Ge; Roger Perkins; Weida Tong; Huixiao Hong

    2015-12-01

    Single-nucleotide polymorphisms (SNPs) determined based on SNP arrays from the international HapMap consortium (HapMap) and the genetic variants detected in the 1000 genomes project (1KGP) can serve as two references for genomewide association studies (GWAS). We conducted comparative analyses to provide a means for assessing concerns regarding SNP array-based GWAS findings as well as for realistically bounding expectations for next generation sequencing (NGS)-based GWAS. We calculated and compared base composition, transitions to transversions ratio, minor allele frequency and heterozygous rate for SNPs from HapMap and 1KGP for the 622 common individuals. We analysed the genotype discordance between HapMap and 1KGP to assess consistency in the SNPs from the two references. In 1KGP, 90.58% of 36,817,799 SNPs detected were not measured in HapMap. More SNPs with minor allele frequencies less than 0.01 were found in 1KGP than HapMap. The two references have low discordance (generally smaller than 0.02) in genotypes of common SNPs, with most discordance from heterozygous SNPs. Our study demonstrated that SNP array-based GWAS findings were reliable and useful, although only a small portion of genetic variances were explained. NGS can detect not only common but also rare variants, supporting the expectation that NGS-based GWAS will be able to incorporate a much larger portion of genetic variance than SNP arrays-based GWAS.

  12. Comparing genetic variants detected in the 1000 genomes project with SNPs determined by the International HapMap Consortium.

    Science.gov (United States)

    Zhang, Wenqian; Ng, Hui Wen; Shu, Mao; Luo, Heng; Su, ZhenQiang; Ge, Weigong; Perkins, Roger; Tong, Weida; Hong, Huixiao

    2015-12-01

    Single-nucleotide polymorphisms (SNPs) determined based on SNP arrays from the international HapMap consortium (HapMap) and the genetic variants detected in the 1000 genomes project (1KGP) can serve as two references for genomewide association studies (GWAS). We conducted comparative analyses to provide a means for assessing concerns regarding SNP array-based GWAS findings as well as for realistically bounding expectations for next generation sequencing (NGS)-based GWAS. We calculated and compared base composition, transitions to transversions ratio, minor allele frequency and heterozygous rate for SNPs from HapMap and 1KGP for the 622 common individuals. We analysed the genotype discordance between HapMap and 1KGP to assess consistency in the SNPs from the two references. In 1KGP, 90.58% of 36,817,799 SNPs detected were not measured in HapMap. More SNPs with minor allele frequencies less than 0.01 were found in 1KGP than HapMap. The two references have low disc ordance (generally smaller than 0.02) in genotypes of common SNPs, with most discordance from heterozygous SNPs. Our study demonstrated that SNP array-based GWAS findings were reliable and useful, although only a small portion of genetic variances were explained. NGS can detect not only common but also rare variants, supporting the expectation that NGS-based GWAS will be able to incorporate a much larger portion of genetic variance than SNP arrays-based GWAS.

  13. Candidate SNPs for carcass and meat traits in Nelore animals and in their crosses with Bos taurus

    Directory of Open Access Journals (Sweden)

    Rogério Abdallah Curi

    2012-02-01

    Full Text Available The objective of this work was to evaluate the effects of single-nucleotide polymorphisms (SNPs in the genes IGF1 (AF_017143.1:g.198C>T, MSTN (AF_320998.1:g.433C>A, MYOD1 (NC_007313:g.1274A>G and MYF5 (NC_007303:g.1911A>G on carcass and meat traits in Nelore (Bos indicus and Nelore x B. taurus. A total of 300 animals were genotyped and phenotyped for rib eye area (REA, backfat thickness (BT, intramuscular fat (IF, shear force (SF and myofibrillar fragmentation index (MFI. The effects of allele substitution for each SNP were estimated by regression of the evaluated phenotypes on the number of copies of a particular allele using the general linear model. The polymorphism at IGF1 was non-informative in Nelore animals. In crossbred animals, the IGF1 C allele was associated with greater REA. However, this relation was not significant after Bonferroni correction for multiple testing. The A allele of the MSTN polymorphism was absent in Nelore cattle and was only found in two crossbred animals. The polymorphisms of MYOD1 and MYF5 were little informative in Nelore animals with G allele frequency of 0.097 and A allele frequency of 0.031, respectively. These markers show no association with the analyzed traits in the total sample of evaluated animals.

  14. Family-Based Association Testing of OCD-associated SNPs of SLC1A1 in an autism sample.

    Science.gov (United States)

    Brune, Camille W; Kim, Soo-Jeong; Hanna, Gregory L; Courchesne, Eric; Lord, Catherine; Leventhal, Bennett L; Cook, Edwin H

    2008-04-01

    Reports identified the neuronal glutamate transporter gene, SLC1A1 (OMIM 133550, chromosome 9p24), as a positional and functional candidate gene for obsessive-compulsive disorder (OCD). The presence of obsessions and compulsions similar to OCD in autism, the identification of this region in a genome-wide linkage analysis of individuals with autism spectrum disorders (ASDs), and the hypothesized role of glutamate in ASDs make SLC1A1 a candidate gene for ASD as well. To test for association between SLC1A1 and autism, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with autism. Family-Based Association Tests (FBAT) with additive and recessive models were used to check for association. Additionally, an rs301430-rs301979 haplotype identified for OCD was investigated. FBAT revealed nominally significant association between autism and one SNP under a recessive model. The G allele of rs301979 was undertransmitted (equivalent to overtransmission of the C allele under a dominant model) to individuals with autism (Z=-2.47, P=0.01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons.

  15. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs.

    Science.gov (United States)

    Saccone, Scott F; Hinrichs, Anthony L; Saccone, Nancy L; Chase, Gary A; Konvicka, Karel; Madden, Pamela A F; Breslau, Naomi; Johnson, Eric O; Hatsukami, Dorothy; Pomerleau, Ovide; Swan, Gary E; Goate, Alison M; Rutter, Joni; Bertelsen, Sarah; Fox, Louis; Fugman, Douglas; Martin, Nicholas G; Montgomery, Grant W; Wang, Jen C; Ballinger, Dennis G; Rice, John P; Bierut, Laura Jean

    2007-01-01

    Nicotine dependence is one of the world's leading causes of preventable death. To discover genetic variants that influence risk for nicotine dependence, we targeted over 300 candidate genes and analyzed 3713 single nucleotide polymorphisms (SNPs) in 1050 cases and 879 controls. The Fagerström test for nicotine dependence (FTND) was used to assess dependence, in which cases were required to have an FTND of 4 or more. The control criterion was strict: control subjects must have smoked at least 100 cigarettes in their lifetimes and had an FTND of 0 during the heaviest period of smoking. After correcting for multiple testing by controlling the false discovery rate, several cholinergic nicotinic receptor genes dominated the top signals. The strongest association was from an SNP representing CHRNB3, the beta3 nicotinic receptor subunit gene (P = 9.4 x 10(-5)). Biologically, the most compelling evidence for a risk variant came from a non-synonymous SNP in the alpha5 nicotinic receptor subunit gene CHRNA5 (P = 6.4 x 10(-4)). This SNP exhibited evidence of a recessive mode of inheritance, resulting in individuals having a 2-fold increase in risk of developing nicotine dependence once exposed to cigarette smoking. Other genes among the top signals were KCNJ6 and GABRA4. This study represents one of the most powerful and extensive studies of nicotine dependence to date and has found novel risk loci that require confirmation by replication studies.

  16. MegaSNPHunter: a learning approach to detect disease predisposition SNPs and high level interactions in genome wide association study

    Directory of Open Access Journals (Sweden)

    Xue Hong

    2009-01-01

    Full Text Available Abstract Background The interactions of multiple single nucleotide polymorphisms (SNPs are highly hypothesized to affect an individual's susceptibility to complex diseases. Although many works have been done to identify and quantify the importance of multi-SNP interactions, few of them could handle the genome wide data due to the combinatorial explosive search space and the difficulty to statistically evaluate the high-order interactions given limited samples. Results Three comparative experiments are designed to evaluate the performance of MegaSNPHunter. The first experiment uses synthetic data generated on the basis of epistasis models. The second one uses a genome wide study on Parkinson disease (data acquired by using Illumina HumanHap300 SNP chips. The third one chooses the rheumatoid arthritis study from Wellcome Trust Case Control Consortium (WTCCC using Affymetrix GeneChip 500K Mapping Array Set. MegaSNPHunter outperforms the best solution in this area and reports many potential interactions for the two real studies. Conclusion The experimental results on both synthetic data and two real data sets demonstrate that our proposed approach outperforms the best solution that is currently available in handling large-scale SNP data both in terms of speed and in terms of detection of potential interactions that were not identified before. To our knowledge, MegaSNPHunter is the first approach that is capable of identifying the disease-associated SNP interactions from WTCCC studies and is promising for practical disease prognosis.

  17. High allelic burden of four obesity SNPs is associated with poorer weight loss outcomes following gastric bypass surgery.

    Science.gov (United States)

    Still, Christopher D; Wood, G Craig; Chu, Xin; Erdman, Robert; Manney, Christina H; Benotti, Peter N; Petrick, Anthony T; Strodel, William E; Mirshahi, Uyenlinh L; Mirshahi, Tooraj; Carey, David J; Gerhard, Glenn S

    2011-08-01

    Genome-wide association and linkage studies have identified multiple susceptibility loci for obesity. We hypothesized that such loci may affect weight loss outcomes following dietary or surgical weight loss interventions. A total of 1,001 white individuals with extreme obesity (BMI >35 kg/m(2)) who underwent a preoperative diet/behavioral weight loss intervention and Roux-en-Y gastric bypass surgery were genotyped for single-nucleotide polymorphisms (SNPs) in or near the fat mass and obesity-associated (FTO), insulin induced gene 2 (INSIG2), melanocortin 4 receptor (MC4R), and proprotein convertase subtilisin/kexin type 1 (PCSK1) obesity genes. Association analysis was performed using recessive and additive models with pre- and postoperative weight loss data. An increasing number of obesity SNP alleles or homozygous SNP genotypes was associated with increased BMI (P weight (P weight lost from a short-term dietary intervention and any individual obesity SNP or cumulative number of obesity SNP alleles or homozygous SNP genotypes was observed. Linear mixed regression analysis revealed significant differences in postoperative weight loss trajectories across groups with low, intermediate, and high numbers of obesity SNP alleles or numbers of homozygous SNP genotypes (P weight loss with initial BMI metabolic rate, binge eating behavior, and other clinical parameters were not associated with genotype. These data suggest that response to a surgical weight loss intervention is influenced by genetic susceptibility and BMI.

  18. A set of EST-SNPs for map saturation and cultivar identification in melon

    Directory of Open Access Journals (Sweden)

    Monforte Antonio J

    2009-07-01

    Full Text Available Abstract Background There are few genomic tools available in melon (Cucumis melo L., a member of the Cucurbitaceae, despite its importance as a crop. Among these tools, genetic maps have been constructed mainly using marker types such as simple sequence repeats (SSR, restriction fragment length polymorphisms (RFLP and amplified fragment length polymorphisms (AFLP in different mapping populations. There is a growing need for saturating the genetic map with single nucleotide polymorphisms (SNP, more amenable for high throughput analysis, especially if these markers are located in gene coding regions, to provide functional markers. Expressed sequence tags (ESTs from melon are available in public databases, and resequencing ESTs or validating SNPs detected in silico are excellent ways to discover SNPs. Results EST-based SNPs were discovered after resequencing ESTs between the parental lines of the PI 161375 (SC × 'Piel de sapo' (PS genetic map or using in silico SNP information from EST databases. In total 200 EST-based SNPs were mapped in the melon genetic map using a bin-mapping strategy, increasing the map density to 2.35 cM/marker. A subset of 45 SNPs was used to study variation in a panel of 48 melon accessions covering a wide range of the genetic diversity of the species. SNP analysis correctly reflected the genetic relationships compared with other marker systems, being able to distinguish all the accessions and cultivars. Conclusion This is the first example of a genetic map in a cucurbit species that includes a major set of SNP markers discovered using ESTs. The PI 161375 × 'Piel de sapo' melon genetic map has around 700 markers, of which more than 500 are gene-based markers (SNP, RFLP and SSR. This genetic map will be a central tool for the construction of the melon physical map, the step prior to sequencing the complete genome. Using the set of SNP markers, it was possible to define the genetic relationships within a collection of forty

  19. Gene expression analysis of overwintering mountain pine beetle larvae suggests multiple systems involved in overwintering stress, cold hardiness, and preparation for spring development

    Directory of Open Access Journals (Sweden)

    Jeanne A. Robert

    2016-07-01

    Full Text Available Cold-induced mortality has historically been a key aspect of mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae, population control, but little is known about the molecular basis for cold tolerance in this insect. We used RNA-seq analysis to monitor gene expression patterns of mountain pine beetle larvae at four time points during their overwintering period—early-autumn, late-autumn, early-spring, and late-spring. Changing transcript profiles over the winter indicates a multipronged physiological response from larvae that is broadly characterized by gene transcripts involved in insect immune responses and detoxification during the autumn. In the spring, although transcripts associated with developmental process are present, there was no particular biological process dominating the transcriptome.

  20. The complex clinical issues involved in an athlete's decision to retire from collision sport due to multiple concussions: a case study of a professional athlete

    Directory of Open Access Journals (Sweden)

    Andrew eGardner

    2013-09-01

    Full Text Available The issue of retirement from athletic participation due to repetitive concussive injuries remains controversial. The complexity of providing recommendations to elite athletes is highlighted by the prospect that offering inappropriate advice may foreseeably lead to engagement in a medico-legal challenge. Currently no evidenced-based, scientifically validated guidelines for forming the basis of such a decision exist. The current paper discusses the complexities of this challenge in addition to presenting a case study of a professional athlete. A number of central issues to consider when discussing athlete retirement revolve around the player’s medical and concussion histories, the current clinical profile, the athlete’s long-term life goals and understanding of the potential long-terms risks. Ensuring that thorough investigations of all possible differential diagnosis, that may explain the presenting symptoms, are conducted is also essential. Discussion pertaining to recommendations for guiding the clinical approach to the retirement issue for athletes with a history of multiple concussions is presented.

  1. Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition.

    Science.gov (United States)

    Yang, Tai; Li, Min-Hui; Liu, Jin; Huang, Ning; Li, Ning; Liu, Si-Nian; Liu, Yang; Zhang, Tao; Zou, Qiang; Li, Hua

    2014-06-01

    2-(1H-benzimidazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (BMT-1), a bicyclic compound, belongs to the benzimidazole group and consists of the fusion of benzene and imidazole. The objective of the present study was to assess the effect of BMT-1 on the proliferation of multiple myeloma (MM) cells and identify whether BMT-1 induces apoptosis in MM cells. Our results showed a dose- and time-dependent decrease in the proliferation of MM cells treated with BMT-1. Further studies revealed that the antiproliferative effects of BMT-1 were caused by induction of apoptosis with activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in MM cells. In addition, BMT-1 induced the loss of mitochondrial membrane potential resulting in the activation of caspase-8 and -9. Furthermore, the MM cells treated with BMT-1 showed a more acidic intracellular pH (pHi) as indicated by a lower FL1/FL2 ratio caused by inhibition of H+/K+-ATPase. Collectively, these findings demonstrated that a decrease in pHi, caused by H+/K+-ATPase inhibition induced by BMT-1, triggered the dysfunction of the mitochondria resulting in the apoptosis of MM cells. Therefore, BMT-1 may be used as a lead compound for the design and development of new agents with which to treat MM and other forms of cancer.

  2. Sensory neuronopathy involves the spinal cord and brachial plexus: a quantitative study employing multiple-echo data image combination (MEDIC) and turbo inversion recovery magnitude (TIRM)

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Yi-Fang; Tang, Wei-Jun; Li, Yu-Xin; Geng, Dao-Ying [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Zhu, Dong-Qing; Chen, Xiang-Jun [Fudan University, Department of Neurology, Huashan Hospital, Shanghai (China); Zee, Chi-Shing [University of Southern California Keck School of Medicine, Department of Radiology, Los Angeles, CA (United States)

    2013-01-15

    Sensory neuronopathy (SNN) is a distinctive subtype of peripheral neuropathies, specifically targeting dorsal root ganglion (DRG). We utilized MRI to demonstrate the imaging characteristics of DRG, spinal cord (SC), and brachial plexus at C7 level in SNN. We attempted multiple-echo data image combination (MEDIC) and turbo inversion recovery magnitude (TIRM) methods in nine patients with sensory neuronopathy and compared with those in 16 disease controls and 20 healthy volunteers. All participants underwent MRI for the measurement of DRG, posterior column (PC), lateral column, and spinal cord area (SCA) at C7 level. DRG diameters were obtained through its largest cross section, standardized by dividing sagittal diameter of mid-C7 vertebral canal. We also made comparisons of standardized anteroposterior diameter (APD) and left-right diameters of SC and PC in these groups. Signal intensity and diameter of C7 spinal nerve were assessed on TIRM. Compared to control groups, signal intensities of DRG and PC were higher in SNN patients when using MEDIC, but the standardized diameters were shorter in either DRG or PC. Abnormal PC signal intensities were identified in eight out of nine SNN patients (89 %) with MEDIC and five out of nine (56 %) with T2-weighted images. SCA, assessed with MEDIC, was smaller in SNN patients than in the other groups, with significant reduction of its standardized APD. C7 nerve root diameters, assessed with TIRM, were decreased in SNN patients. MEDIC and TIRM sequences demonstrate increased signal intensities and decreased area of DRG and PC, and decreased diameter of nerve roots in patients with SNN, which can play a significant role in early diagnosis. (orig.)

  3. The Heparan and Heparin Metabolism Pathway is Involved in Regulation of Fatty Acid Composition

    Directory of Open Access Journals (Sweden)

    Zhihua Jiang, Jennifer J. Michal, Xiao-Lin Wu, Zengxiang Pan, Michael D. MacNeil

    2011-01-01

    Full Text Available Six genes involved in the heparan sulfate and heparin metabolism pathway, DSEL (dermatan sulfate epimerase-like, EXTL1 (exostoses (multiple-like 1, HS6ST1 (heparan sulfate 6-O-sulfotransferase 1, HS6ST3 (heparan sulfate 6-O-sulfotransferase 3, NDST3 (N-deacetylase/N-sulfotransferase (heparan glucosaminyl 3, and SULT1A1 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1, were investigated for their associations with muscle lipid composition using cattle as a model organism. Nineteen single nucleotide polymorphisms (SNPs/multiple nucleotide length polymorphisms (MNLPs were identified in five of these six genes. Six of these mutations were then genotyped on 246 Wagyu x Limousin F2 animals, which were measured for 5 carcass, 6 eating quality and 8 fatty acid composition traits. Association analysis revealed that DSEL, EXTL1 and HS6ST1 significantly affected two stearoyl-CoA desaturase activity indices, the amount of conjugated linoleic acid (CLA, and the relative amount of saturated fatty acids (SFA and monounsaturated fatty acids (MUFA in skeletal muscle (P<0.05. In particular, HS6ST1 joined our previously reported SCD1 and UQCRC1 genes to form a three gene network for one of the stearoyl-CoA desaturase activity indices. These results provide evidence that genes involved in heparan sulfate and heparin metabolism are also involved in regulation of lipid metabolism in bovine muscle. Whether the SNPs affected heparan sulfate proteoglycan structure is unknown and warrants further investigation.

  4. O custo que envolve a retirada de múltiplos órgãos Cost that involves the retriet of multiple organs

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    CÍCERA IZABEL C. DE OLIVEIRA GUERRA

    2002-06-01

    Full Text Available O processo que envolve a doação e retirada de órgãos é complexo e tem um custo elevado para os hospitais que o realizam. Neste artigo é estimado o custo médio total envolvido nesse processo, comparando-o com a remuneração paga pelo Sistema Único de Saúde. OBJETIVO: Levantar os gastos com captação, manutenção do doador e retirada de órgãos para transplante. MÉTODOS: É um estudo retrospectivo, baseado no levantamento dos prontuários de 32 doadores admitidos na Organização de Procura de Órgãos do Instituto Dante Pazzanese de Cardiologia, São Paulo, no período de janeiro a dezembro de 1999. Os gastos levantados foram em relação aos seguinte itens: recursos humanos, material de consumo, utilidade pública, exames complementares, depreciação de equipamentos, material permanente e transporte. RESULTADOS: O estudo realizado encontrou o custo médio de R$ 2.883,34 para o processo de doação, captação e retirada de órgãos, desde a avaliação até a entrega do corpo a família. O valor pago pelo SUS é de R$ 1. 853,71. Este custo cobre 65% do custo médio real. CONCLUSÃO: O artigo demonstra a importância da realização de estudos de custos, de procedimentos, com o objetivo de orientar a definição/atualização das tabelas de remuneração de serviços.The process of organ donation and retreat is complex and involves a high cost for hospitals that do it.PURPOSE: to survey the expenses with the process of donation and retreat of organs.METHODS: retrospective study based on medical records of 32 donors, admitted in the Search Organs Organisation do Instituto Dante Pazzanese de Cardiologia, during the period from January to December of 1999.RESULTS: the process is complex and involves a special structure as well as 24 hours of activities, making it costly. Expenses were related with the following items: human resources, permanent material, public utilities, complementary examinations, depreciation of equipment and

  5. Molecular cloning and functional characterization of a novel apple MdCIPK6L gene reveals its involvement in multiple abiotic stress tolerance in transgenic plants.

    Science.gov (United States)

    Wang, Rong-Kai; Li, Ling-Li; Cao, Zhong-Hui; Zhao, Qiang; Li, Ming; Zhang, Ling-Yun; Hao, Yu-Jin

    2012-05-01

    CBL-interacting protein kinases (CIPKs) are involved in many aspects of plant responses to abiotic stresses. However, their functions are poorly understood in fruit trees. In this study, a salt-induced MdCIPK6L gene was isolated from apple. Its expression was positively induced by abiotic stresses, stress-related hormones and exogenous Ca(2+). MdCIPK6L was not homologous to AtSOS2, however, its ectopic expression functionally complemented Arabidopsis sos2 mutant. Furthermore, yeast two-hybrid assay showed that MdCIPK6L protein interacted with AtSOS3, indicating that it functions in salt tolerance partially like AtSOS2 through SOS pathway. As a result, the overexpression of both MdCIPK6L and MdCIPK6LT175D remarkably enhanced the tolerance to salt, osmotic/drought and chilling stresses, but did not affect root growth, in transgenic Arabidopsis and apple. Also, T-to-D mutation to MdCIPK6L at Thr175 did not affect its function. These differences between MdCIPK6L and other CIPKs, especially CIPK6s, indicate that MdCIPK6L encodes a novel CIPK in apple. Finally, MdCIPK6L overexpression also conferred tolerance to salt, drought and chilling stresses in transgenic tomatoes. Therefore, MdCIPK6L functions in stress tolerance crossing the species barriers, and is supposed to be a potential candidate gene to improve stress tolerance by genetic manipulation in apple and other crops.

  6. Genetic differences in the two main groups of the Japanese population based on autosomal SNPs and haplotypes.

    Science.gov (United States)

    Yamaguchi-Kabata, Yumi; Tsunoda, Tatsuhiko; Kumasaka, Natsuhiko; Takahashi, Atsushi; Hosono, Naoya; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki

    2012-05-01

    Although the Japanese population has a rather low genetic diversity, we recently confirmed the presence of two main clusters (the Hondo and Ryukyu clusters) through principal component analysis of genome-wide single-nucleotide polymorphism (SNP) genotypes. Understanding the genetic differences between the two main clusters requires further genome-wide analyses based on a dense SNP set and comparison of haplotype frequencies. In the present study, we determined haplotypes for the Hondo cluster of the Japanese population by detecting SNP homozygotes with 388,591 autosomal SNPs from 18,379 individuals and estimated the haplotype frequencies. Haplotypes for the Ryukyu cluster were inferred by a statistical approach using the genotype data from 504 individuals. We then compared the haplotype frequencies between the Hondo and Ryukyu clusters. In most genomic regions, the haplotype frequencies in the Hondo and Ryukyu clusters were very similar. However, in addition to the human leukocyte antigen region on chromosome 6, other genomic regions (chromosomes 3, 4, 5, 7, 10 and 12) showed dissimilarities in haplotype frequency. These regions were enriched for genes involved in the immune system, cell-cell adhesion and the intracellular signaling cascade. These differentiated genomic regions between the Hondo and Ryukyu clusters are of interest because they (1) should be examined carefully in association studies and (2) likely contain genes responsible for morphological or physiological differences between the two groups.

  7. Lack of association between SNPs in the NEUROD2 gene and alcohol dependence in a German patient sample.

    Science.gov (United States)

    Zill, Peter; Preuss, Ulrich W; Koller, Gabrielle; Bondy, Brigitta; Soyka, Michael

    2011-05-15

    Results of a human post mortem study performed by our own group have suggested that the transcription factor NEUROD2, which plays a role in neuronal development, as well as in the development of anxiety and risk behavior in mice, might be a susceptibility factor for addictive disorders. Therefore the aim of the present study was to analyze a possible relation between genetic variants in the NEUROD2 gene and alcohol dependence in a sample of the Munich Gene Bank of Alcoholism (MGBA). We performed single SNP (single nucleotide polymorphism) and haplotype studies in 430 alcohol-dependent patients and 365 healthy controls with four SNPs covering the gene region of NEUROD2. Neither single SNP nor haplotype analysis could detect significant associations with alcohol dependence. Additionally we could not detect any relation of the analyzed genetic variants to Cloninger's Type 1/2 or Babor's Type A/B classification, to the age of onset or to the amount of alcohol intake. Our results do not provide evidence for an involvement of NEUROD2 polymorphisms in the pathophysiology of alcohol dependence. Further association studies are needed to confirm our findings.

  8. Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough.

    Science.gov (United States)

    McMahon, George; Ring, Susan M; Davey-Smith, George; Timpson, Nicholas J

    2015-10-15

    Whooping cough is currently seeing resurgence in countries despite high vaccine coverage. There is considerable variation in subject-specific response to infection and vaccine efficacy, but little is known about the role of human genetics. We carried out a case-control genome-wide association study of adult or parent-reported history of whooping cough in two cohorts from the UK: the ALSPAC cohort and the 1958 British Birth Cohort (815/758 cases and 6341/4308 controls, respectively). We also imputed HLA alleles using dense SNP data in the MHC region and carried out gene-based and gene-set tests of association and estimated the amount of additive genetic variation explained by common SNPs. We observed a novel association at SNPs in the MHC class II region in both cohorts [lead SNP rs9271768 after meta-analysis, odds ratio [95% confidence intervals (CIs)] 1.47 (1.35, 1.6), P-value 1.21E - 18]. Multiple strong associations were also observed at alleles at the HLA class II loci. The majority of these associations were explained by the lead SNP rs9271768. Gene-based and gene-set tests and estimates of explainable common genetic variation could not establish the presence of additional associations in our sample. Genetic variation at the MHC class II region plays a role in susceptibility to whooping cough. These findings provide additional perspective on mechanisms of whooping cough infection and vaccine efficacy.

  9. Diagnostic SNPs for inferring population structure in American mink (Neovison vison) identified through RAD sequencing

    DEFF Research Database (Denmark)

    2015-01-01

    Data from: "Diagnostic SNPs for inferring population structure in American mink (Neovison vison) identified through RAD sequencing" in Genomic Resources Notes accepted 1 October 2014 to 30 November 2014....

  10. Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals.

    Science.gov (United States)

    Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Stevnsner, Tinna; Bohr, Vilhelm A; Christensen, Kaare; Christiansen, Lene

    2015-02-01

    FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 oldest-old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3A variation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture risk for carriers of the minor alleles of 8 and 10 SNPs, respectively. These positive directions of effects are in agreement with the positive effects on longevity previously reported for these SNPs. However, when correcting for the test of 9 phenotypes by Bonferroni correction, bone fracture showed borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94-100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis of both study populations displayed similar or decreased sized P-values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed.

  11. Proteasome Modulator 9 SNPs are linked to hypertension in type 2 diabetes families

    Directory of Open Access Journals (Sweden)

    Gragnoli Claudia

    2011-08-01

    Full Text Available Abstract Background Chromosome 12q24 was recently associated with hypertension. Proteasome Modulator 9 (PSMD9 lies in the 12q24 locus and is in linkage with MODY3, type 2 diabetes (T2D, microvascular and macrovascular pathology, carpal tunnel syndrome, and hypercholesterolemia in Italian families. Aims Our goal was to determine whether PSMD9 is linked to elevated blood pressure/hypertension in T2D families. Methods We characterized the Italian T2D families' members for presence and/or absence of elevated blood pressure (≥ 130/80 and/or hypertension. The phenotypes were described as unknown in all cases in which the diagnosis was either unclear or the data were not available for the subject studied. We tested in the 200 Italians families for the presence of the linkage of the PSMD9 T2D risk single nucleotide polymorphisms (SNPs IVS3+nt460 A > G, IVS3+nt437 T > C and E197G A > G with elevated blood pressure/hypertension. The non-parametric linkage analysis was performed for this qualitative phenotype by using the Merlin software; the Lod score and correspondent P-value were calculated. Parametric linkage analysis was also performed. For the significant linkage score, 1000 replicates were run to calculate the empirical P-value. Results The PSMD9 gene SNPs studied are in linkage with elevated blood pressure/hypertension in our Italian families. Conclusions We conclude that the PSMD9 gene and/or any variant in linkage disequilibrium with the SNPs studied contribute to the linkage to hypertension within our family dataset. This is the first report of PSMD9 linkage to hypertension within the 12q24 locus.

  12. VnD: a structure-centric database of disease-related SNPs and drugs.

    Science.gov (United States)

    Yang, Jin Ok; Oh, Sangho; Ko, Gunhwan; Park, Seong-Jin; Kim, Woo-Yeon; Lee, Byungwook; Lee, Sanghyuk

    2011-01-01

    Numerous genetic variations have been found to be related to human diseases. Significant portion of those affect the drug response as well by changing the protein structure and function. Therefore, it is crucial to understand the trilateral relationship among genomic variations, diseases and drugs. We present the variations and drugs (VnD), a consolidated database containing information on diseases, related genes and genetic variations, protein structures and drug information. VnD was built in three steps. First, we integrated various resources systematically to deduce catalogs of disease-related genes, single nucleotide polymorphisms (SNPs), protein mutations and relevant drugs. VnD contains 137,195 disease-related gene records (13,940 distinct genes) and 16,586 genetic variation records (1790 distinct variations). Next, we carried out structure modeling and docking simulation for wild-type and mutant proteins to examine the structural and functional consequences of non-synonymous SNPs in the drug-related genes. Conformational changes in 590 wild-type and 4437 mutant proteins from drug-related genes were included in our database. Finally, we investigated the structural and biochemical properties relevant to drug binding such as the distribution of SNPs in proximal protein pockets, thermo-chemical stability, interactions with drugs and physico-chemical properties. The VnD database, available at http://vnd.kobic.re.kr:8080/VnD/ or vandd.org, would be a useful platform for researchers studying the underlying mechanism for association among genetic variations, diseases and drugs.

  13. Use of SNPs to determine the breakpoints of complex deficiencies, facilitating gene mapping in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Hoffmann Melissa

    2005-05-01

    Full Text Available Abstract Background Genetic deletions or deficiencies have been used for gene mapping and discovery in various organisms, ranging from the nematode Caenorhabditis elegans all the way to humans. One problem with large deletions is the determination of the location of their breakpoints. This is exacerbated in the case of complex deficiencies that delete a region of the genome, while retaining some of the intervening sequence. Previous methods, using genetic complementation or cytology were hampered by low marker density and were consequently not very precise at positioning the breakpoints of complex deficiencies. The identification of increasing numbers of Single Nucleotide Polymorphisms (SNPs has resulted in the use of these as genetic markers, and consequently in their utilization for defining the breakpoints of deletions using molecular biology methods. Results Here, we show that SNPs can be used to help position the breakpoints of a complex deficiency in C. elegans. The technique uses a combination of genetic crosses and molecular biology to generate robust and highly reproducible results with strong internal controls when trying to determine the breakpoints of deficiencies. The combined use of this technique and standard genetic mapping allowed us to rapidly narrow down the region of interest in our attempts to clone a gene. Conclusion Unlike previous methods used to locate deficiency breakpoints, our technique has the advantage of not being limited by the amount of starting material. It also incorporates internal controls to eliminate false positives and negatives. The technique can also easily be adapted for use in other organisms in which both genetic deficiencies and SNPs are available, thereby aiding gene discovery in these other models.

  14. Discovering Genome-Wide Tag SNPs Based on the Mutual Information of the Variants

    Science.gov (United States)

    Elmas, Abdulkadir; Ou Yang, Tai-Hsien; Wang, Xiaodong

    2016-01-01

    Exploring linkage disequilibrium (LD) patterns among the single nucleotide polymorphism (SNP) sites can improve the accuracy and cost-effectiveness of genomic association studies, whereby representative (tag) SNPs are identified to sufficiently represent the genomic diversity in populations. There has been considerable amount of effort in developing efficient algorithms to select tag SNPs from the growing large-scale data sets. Methods using the classical pairwise-LD and multi-locus LD measures have been proposed that aim to reduce the computational complexity and to increase the accuracy, respectively. The present work solves the tag SNP selection problem by efficiently balancing the computational complexity and accuracy, and improves the coverage in genomic diversity in a cost-effective manner. The employed algorithm makes use of mutual information to explore the multi-locus association between SNPs and can handle different data types and conditions. Experiments with benchmark HapMap data sets show comparable or better performance against the state-of-the-art algorithms. In particular, as a novel application, the genome-wide SNP tagging is performed in the 1000 Genomes Project data sets, and produced a well-annotated database of tagging variants that capture the common genotype diversity in 2,504 samples from 26 human populations. Compared to conventional methods, the algorithm requires as input only the genotype (or haplotype) sequences, can scale up to genome-wide analyses, and produces accurate solutions with more information-rich output, providing an improved platform for researchers towards the subsequent association studies. PMID:27992465

  15. Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression.

    Directory of Open Access Journals (Sweden)

    Jonas Carlsson Almlöf

    Full Text Available A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs by genome-wide allele-specific gene expression (ASE analysis with that of traditional expression quantitative trait locus (eQTL mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.

  16. An evaluation of the performance of tag SNPs derived from HapMap in a Caucasian population.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available The Haplotype Map (HapMap project recently generated genotype data for more than 1 million single-nucleotide polymorphisms (SNPs in four population samples. The main application of the data is in the selection of tag single-nucleotide polymorphisms (tSNPs to use in association studies. The usefulness of this selection process needs to be verified in populations outside those used for the HapMap project. In addition, it is not known how well the data represent the general population, as only 90-120 chromosomes were used for each population and since the genotyped SNPs were selected so as to have high frequencies. In this study, we analyzed more than 1,000 individuals from Estonia. The population of this northern European country has been influenced by many different waves of migrations from Europe and Russia. We genotyped 1,536 randomly selected SNPs from two 500-kbp ENCODE regions on Chromosome 2. We observed that the tSNPs selected from the CEPH (Centre d'Etude du Polymorphisme Humain from Utah (CEU HapMap samples (derived from US residents with northern and western European ancestry captured most of the variation in the Estonia sample. (Between 90% and 95% of the SNPs with a minor allele frequency of more than 5% have an r2 of at least 0.8 with one of the CEU tSNPs. Using the reverse approach, tags selected from the Estonia sample could almost equally well describe the CEU sample. Finally, we observed that the sample size, the allelic frequency, and the SNP density in the dataset used to select the tags each have important effects on the tagging performance. Overall, our study supports the use of HapMap data in other Caucasian populations, but the SNP density and the bias towards high-frequency SNPs have to be taken into account when designing association studies.

  17. An evaluation of the performance of tag SNPs derived from HapMap in a Caucasian population.

    Science.gov (United States)

    Montpetit, Alexandre; Nelis, Mari; Laflamme, Philippe; Magi, Reedik; Ke, Xiayi; Remm, Maido; Cardon, Lon; Hudson, Thomas J; Metspalu, Andres

    2006-03-01

    The Haplotype Map (HapMap) project recently generated genotype data for more than 1 million single-nucleotide polymorphisms (SNPs) in four population samples. The main application of the data is in the selection of tag single-nucleotide polymorphisms (tSNPs) to use in association studies. The usefulness of this selection process needs to be verified in populations outside those used for the HapMap project. In addition, it is not known how well the data represent the general population, as only 90-120 chromosomes were used for each population and since the genotyped SNPs were selected so as to have high frequencies. In this study, we analyzed more than 1,000 individuals from Estonia. The population of this northern European country has been influenced by many different waves of migrations from Europe and Russia. We genotyped 1,536 randomly selected SNPs from two 500-kbp ENCODE regions on Chromosome 2. We observed that the tSNPs selected from the CEPH (Centre d'Etude du Polymorphisme Humain) from Utah (CEU) HapMap samples (derived from US residents with northern and western European ancestry) captured most of the variation in the Estonia sample. (Between 90% and 95% of the SNPs with a minor allele frequency of more than 5% have an r2 of at least 0.8 with one of the CEU tSNPs.) Using the reverse approach, tags selected from the Estonia sample could almost equally well describe the CEU sample. Finally, we observed that the sample size, the allelic frequency, and the SNP density in the dataset used to select the tags each have important effects on the tagging performance. Overall, our study supports the use of HapMap data in other Caucasian populations, but the SNP density and the bias towards high-frequency SNPs have to be taken into account when designing association studies.

  18. Analysis of 49 autosomal SNPs in three ethnic groups from Iran

    DEFF Research Database (Denmark)

    Sharafi Farzad, M; Tomas Mas, Carmen; Børsting, C

    2013-01-01

    A total number of 149 individuals from Iran (Persians, Lurs and Kurds) were analyzed for 49 autosomal SNPs using PCR, SBE and capillary electrophoresis. No deviation from Hardy-Weinberg expectations was observed. One SNP pair (rs1015250-rs251934) showed significant linkage disequilibrium in Kurds....... However, this was most likely due to chance. High intrapopulation variability and no significant population structure were observed among the three ethnic groups from Iran. Pairwise FST values obtained from the mean numbers of pairwise differences between SNP profiles were calculated for Persians, Lurs...

  19. Phosphorylation states of cell cycle and DNA repair proteins can be altered by the nsSNPs

    Directory of Open Access Journals (Sweden)

    Savas Sevtap

    2005-08-01

    Full Text Available Abstract Background Phosphorylation is a reversible post-translational modification that affects the intrinsic properties of proteins, such as structure and function. Non-synonymous single nucleotide polymorphisms (nsSNPs result in the substitution of the encoded amino acids and thus are likely to alter the phosphorylation motifs in the proteins. Methods In this study, we used the web-based NetPhos tool to predict candidate nsSNPs that either introduce or remove putative phosphorylation sites in proteins that act in DNA repair and cell cycle pathways. Results Our results demonstrated that a total of 15 nsSNPs (16.9% were likely to alter the putative phosphorylation patterns of 14 proteins. Three of these SNPs (CDKN1A-S31R, OGG1-S326C, and XRCC3-T241M have already found to be associated with altered cancer risk. We believe that this set of nsSNPs constitutes an excellent resource for further molecular and genetic analyses. Conclusion The novel systematic approach used in this study will accelerate the understanding of how naturally occurring human SNPs may alter protein function through the modification of phosphorylation mechanisms and contribute to disease susceptibility.

  20. Association of Genome-Wide Association Study (GWAS) Identified SNPs and Risk of Breast Cancer in an Indian Population

    Science.gov (United States)

    Nagrani, Rajini; Mhatre, Sharayu; Rajaraman, Preetha; Chatterjee, Nilanjan; Akbari, Mohammad R.; Boffetta, Paolo; Brennan, Paul; Badwe, Rajendra; Gupta, Sudeep; Dikshit, Rajesh

    2017-01-01

    To date, no studies have investigated the association of the GWAS-identified SNPs with BC risk in Indian population. We investigated the association of 30 previously reported and replicated BC susceptibility SNPs in 1,204 cases and 1,212 controls from a hospital based case-control study conducted at the Tata Memorial Hospital, Mumbai. As a measure of total susceptibility burden, the polygenic risk score (PRS) for each individual was defined by the weighted sum of genotypes from 21 independent SNPs with weights derived from previously published estimates of association odds-ratios. Logistic regression models were used to assess risk associated with individual SNPs and overall PRS, and stratified by menopausal and receptor status. A total of 11 SNPs from eight genomic regions (FGFR2, 9q31.2, MAP3K, CCND1, ZM1Z1, RAD51L11, ESR1 and UST) showed statistically significant (p-value ≤ 0.05) evidence of association, either overall or when stratified by menopausal status or hormone receptor status. BC SNPs previously identified in Caucasian population showed evidence of replication in the Indian population mainly with respect to risk of postmenopausal and hormone receptor positive BC. PMID:28098224

  1. Improvement of diagnostic confidence for detection of multiple myeloma involvement of the ribs by a new CT software generating rib unfolded images: Comparison with 5- and 1-mm axial images

    Energy Technology Data Exchange (ETDEWEB)

    Homann, Georg; Mustafa, Deedar Farhad; Nikolaou, Konstantin; Horger, Marius [Eberhard Karls University Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Weisel, Katja [Eberhard Karls University Tuebingen, Department of Internal Medicine II, Tuebingen (Germany); Ditt, Hendrik [Healthcare Sector Imaging and Therapy Division, Siemens AG, Forchheim (Germany)

    2015-04-02

    To investigate the performance of a new CT software generating rib unfolded images for improved detection of rib osteolyses in patients with multiple myeloma. One hundred sixteen patients who underwent whole-body reduced-dose multidetector computed tomography (WBRD-MDCT) for multiple myeloma diagnosis and during follow-up were retrospectively evaluated. Nonenhanced CT scans with 5- and 1-mm slice thickness were interpreted by two readers with focus on detection of rib involvement (location, number, fracture). Image analysis of ''unfolded,'' 1-mm-based CT rib images was subsequently undertaken. We classified the number of lytic bone lesions into 0, 1, 2, <5, <10 and ≥10. For all three data sets the reading time was registered. An approximated sum of 6,727 myeloma-related rib lesions was found. On a patient-based analysis, CT (5 mm), CT (1 mm) and CT (1 mm ''unfolded rib'') yielded a sensitivity, specificity and accuracy of 79.7/94.7/87.1, 88.1/93/90.5 and 98.3/96.5/97.4, respectively. In a lesion-based analysis, the sensitivity, specificity and accuracy of the three evaluations were 69.7/87.2/70.5, 79.8/55.9/78 and 96.5/89.7/96.1. Mean reading time for 5 mm/1 mm axial images and unfolded images was 178.7/215.1/90.8 s, respectively. The generation of ''unfolded rib'' images improves detection of rib involvement in patients with multiple myeloma and significantly reduces reading time. (orig.)

  2. Alternative splicing, promoter methylation, and functional SNPs of sperm flagella 2 gene in testis and mature spermatozoa of Holstein bulls.

    Science.gov (United States)

    Guo, F; Yang, B; Ju, Z H; Wang, X G; Qi, C; Zhang, Y; Wang, C F; Liu, H D; Feng, M Y; Chen, Y; Xu, Y X; Zhong, J F; Huang, J M

    2014-02-01

    The sperm flagella 2 (SPEF2) gene is essential for development of normal sperm tail and male fertility. In this study, we characterized first the splice variants, promoter and its methylation, and functional single-nucleotide polymorphisms (SNPs) of the SPEF2 gene in newborn and adult Holstein bulls. Four splice variants were identified in the testes, epididymis, sperm, heart, spleen, lungs, kidneys, and liver tissues through RT-PCR, clone sequencing, and western blot analysis. Immunohistochemistry revealed that the SPEF2 was specifically expressed in the primary spermatocytes, elongated spermatids, and round spermatids in the testes and epididymis. SPEF2-SV1 was differentially expressed in the sperms of high-performance and low-performance adult bulls; SPEF2-SV2 presents the highest expression in testis and epididymis; SPEF2-SV3 was only detected in testis and epididymis. An SNP (c.2851G>T) in exon 20 of SPEF2, located within a putative exonic splice enhancer, potentially produced SPEF2-SV3 and was involved in semen deformity rate and post-thaw cryopreserved sperm motility. The luciferase reporter and bisulfite sequencing analysis suggested that the methylation pattern of the core promoter did not significantly differ between the full-sib bulls that presented hypomethylation in the ejaculated semen and testis. This finding indicates that sperm quality is unrelated to SPEF2 methylation pattern. Our data suggest that alternative splicing, rather than methylation, is involved in the regulation of SPEF2 expression in the testes and sperm and is one of the determinants of sperm motility during bull spermatogenesis. The exonic SNP (c.2851G>T) produces aberrant splice variants, which can be used as a candidate marker for semen traits selection breeding of Holstein bulls.

  3. An approach to identify SNPs in the gene encoding acetyl-CoA acetyltransferase-2 (ACAT-2 and their proposed role in metabolic processes in pig.

    Directory of Open Access Journals (Sweden)

    Simrinder Singh Sodhi

    Full Text Available The novel liver protein acetyl-CoA acetyltransferase-2 (ACAT2 is involved in the beta-oxidation and lipid metabolism. Its comprehensive relative expression, in silico non-synonymous single nucleotide polymorphism (nsSNP analysis, as well as its annotation in terms of metabolic process with another protein from the same family, namely, acetyl-CoA acyltransferase-2 (ACAA2 was performed in Sus scrofa. This investigation was conducted to understand the most important nsSNPs of ACAT2 in terms of their effects on metabolic activities and protein conformation. The two most deleterious mutations at residues 122 (I to V and 281 (R to H were found in ACAT2. Validation of expression of genes in the laboratory also supported the idea of differential expression of ACAT2 and ACAA2 conceived through the in silico analysis. Analysis of the relative expression of ACAT2 and ACAA2 in the liver tissue of Jeju native pig showed that the former expressed significantly higher (P<0.05. Overall, the computational prediction supported by wet laboratory analysis suggests that ACAT2 might contribute more to metabolic processes than ACAA2 in swine. Further associations of SNPs in ACAT2 with production traits might guide efforts to improve growth performance in Jeju native pigs.

  4. Genetic Mapping of Millions of SNPs in Safflower (Carthamus tinctorius L. via Whole-Genome Resequencing

    Directory of Open Access Journals (Sweden)

    John E. Bowers

    2016-07-01

    Full Text Available Accurate assembly of complete genomes is facilitated by very high density genetic maps. We performed low-coverage, whole-genome shotgun sequencing on 96 F6 recombinant inbred lines (RILs of a cross between safflower (Carthamus tinctorius L. and its wild progenitor (C. palaestinus Eig. We also produced a draft genome assembly of C. tinctorius covering 866 million bp (∼two-thirds of the expected 1.35 Gbp genome after sequencing a single, short insert library to ∼21 × depth. Sequence reads from the RILs were mapped to this genome assembly to facilitate SNP identification, and the resulting polymorphisms were used to construct a genetic map. The resulting map included 2,008,196 genetically located SNPs in 1178 unique positions. A total of 57,270 scaffolds, each containing five or more mapped SNPs, were anchored to the map. This resulted in the assignment of sequence covering 14% of the expected genome length to a genetic position. Comparison of this safflower map to genetic maps of sunflower and lettuce revealed numerous chromosomal rearrangements, and the resulting patterns were consistent with a whole-genome duplication event in the lineage leading to sunflower. This sequence-based genetic map provides a powerful tool for the assembly of a low-cost draft genome of safflower, and the same general approach is expected to work for other species.

  5. Genetic Mapping of Millions of SNPs in Safflower (Carthamus tinctorius L.) via Whole-Genome Resequencing.

    Science.gov (United States)

    Bowers, John E; Pearl, Stephanie A; Burke, John M

    2016-07-07

    Accurate assembly of complete genomes is facilitated by very high density genetic maps. We performed low-coverage, whole-genome shotgun sequencing on 96 F6 recombinant inbred lines (RILs) of a cross between safflower (Carthamus tinctorius L.) and its wild progenitor (C. palaestinus Eig). We also produced a draft genome assembly of C. tinctorius covering 866 million bp (∼two-thirds) of the expected 1.35 Gbp genome after sequencing a single, short insert library to ∼21 × depth. Sequence reads from the RILs were mapped to this genome assembly to facilitate SNP identification, and the resulting polymorphisms were used to construct a genetic map. The resulting map included 2,008,196 genetically located SNPs in 1178 unique positions. A total of 57,270 scaffolds, each containing five or more mapped SNPs, were anchored to the map. This resulted in the assignment of sequence covering 14% of the expected genome length to a genetic position. Comparison of this safflower map to genetic maps of sunflower and lettuce revealed numerous chromosomal rearrangements, and the resulting patterns were consistent with a whole-genome duplication event in the lineage leading to sunflower. This sequence-based genetic map provides a powerful tool for the assembly of a low-cost draft genome of safflower, and the same general approach is expected to work for other species.

  6. VEGF-A and VEGFR1 SNPs associate with preeclampsia in a Philippine population.

    Science.gov (United States)

    Amosco, Melissa D; Villar, Van Anthony M; Naniong, Justin Michael A; David-Bustamante, Lara Marie G; Jose, Pedro A; Palmes-Saloma, Cynthia P

    The vascular endothelial growth factor (VEGF) family is important for establishing normal pregnancy, and related single nucleotide polymorphisms (SNPs) are implicated in abnormal placentation and preeclampsia. We evaluated the association between preeclampsia and several VEGF SNPs among Filipinos, an ethnically distinct group with high prevalence of preeclampsia. The genotypes and allelic variants were determined in a case-control study (191 controls and 165 preeclampsia patients) through SNP analysis of VEGF-A (rs2010963, rs3025039) and VEGF-C (rs7664413) and their corresponding receptors VEGFR1 (rs722503, rs12584067, rs7335588) and VEGFR3 (rs307826) from venous blood DNA. VEGF-A rs3025039 C allele has been shown to associate with preeclampsia (odds ratio of 1.648 (1.03-2.62)), while the T allele bestowed an additive effect for the maintenance of normal, uncomplicated pregnancy and against the development of preeclampsia (odds ratio of 0.62 (0.39-0.98)). VEGFR1 rs722503 is associated with preeclampsia occurring at or after the age of 40 years. The results showed that genetic variability of VEGF-A and VEGFR1 are important in the etiology of preeclampsia among Filipinos.

  7. Genomics and introgression: discovery and mapping of thousands of species-diagnostic SNPs using RAD sequencing

    Science.gov (United States)

    Hand, Brian K; Hether, Tyler D; Kovach, Ryan P.; Muhlfeld, Clint C.; Amish, Stephen J.; Boyer, Matthew C.; O’Rourke, Sean M.; Miller, Michael R.; Lowe, Winsor H.; Hohenlohe, Paul A.; Luikart, Gordon

    2015-01-01

    Invasive hybridization and introgression pose a serious threat to the persistence of many native species. Understanding the effects of hybridization on native populations (e.g., fitness consequences) requires numerous species-diagnostic loci distributed genome-wide. Here we used RAD sequencing to discover thousands of single-nucleotide polymorphisms (SNPs) that are diagnostic between rainbow trout (RBT, Oncorhynchus mykiss), the world’s most widely introduced fish, and native westslope cutthroat trout (WCT, O. clarkii lewisi) in the northern Rocky Mountains, USA. We advanced previous work that identified 4,914 species-diagnostic loci by using longer sequence reads (100 bp vs. 60 bp) and a larger set of individuals (n = 84). We sequenced RAD libraries for individuals from diverse sampling sources, including native populations of WCT and hatchery broodstocks of WCT and RBT. We also took advantage of a newly released reference genome assembly for RBT to align our RAD loci. In total, we discovered 16,788 putatively diagnostic SNPs, 10,267 of which we mapped to anchored chromosome locations on the RBT genome. A small portion of previously discovered putative diagnostic loci (325 of 4,914) were no longer diagnostic (i.e., fixed between species) based on our wider survey of non-hybridized RBT and WCT individuals. Our study suggests that RAD loci mapped to a draft genome assembly could provide the marker density required to identify genes and chromosomal regions influencing selection in admixed populations of conservation concern and evolutionary interest.

  8. Evaluation of random forest regression for prediction of breeding value from genomewide SNPs

    Indian Academy of Sciences (India)

    Rupam Kumar Sarkar; A. R. Rao; Prabina Kumar Meher; T. Nepolean; T. Mohapatra

    2015-06-01

    Genomic prediction is meant for estimating the breeding value using molecular marker data which has turned out to be a powerful tool for efficient utilization of germplasm resources and rapid improvement of cultivars. Model-based techniques have been widely used for prediction of breeding values of genotypes from genomewide association studies. However, application of the random forest (RF), a model-free ensemble learning method, is not widely used for prediction. In this study, the optimum values of tuning parameters of RF have been identified and applied to predict the breeding value of genotypes based on genomewide single-nucleotide polymorphisms (SNPs), where the number of SNPs ($P$ variables) is much higher than the number of genotypes ($n$ observations) ($P >> n$). Further, a comparison was made with the model-based genomic prediction methods, namely, least absolute shrinkage and selection operator (LASSO), ridge regression (RR) and elastic net (EN) under $P >> n$. It was found that the correlations between the predicted and observed trait response were 0.591, 0.539, 0.431 and 0.587 for RF, LASSO, RR and EN, respectively, which implies superiority of the RF over the model-based techniques in genomic prediction. Hence, we suggest that the RF methodology can be used as an alternative to the model-based techniques for the prediction of breeding value at genome level with higher accuracy.

  9. Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes

    KAUST Repository

    Chatterjee, Nilanjan

    2009-11-01

    Although prospective logistic regression is the standard method of analysis for case-control data, it has been recently noted that in genetic epidemiologic studies one can use the "retrospective" likelihood to gain major power by incorporating various population genetics model assumptions such as Hardy-Weinberg-Equilibrium (HWE), gene-gene and gene-environment independence. In this article we review these modern methods and contrast them with the more classical approaches through two types of applications (i) association tests for typed and untyped single nucleotide polymorphisms (SNPs) and (ii) estimation of haplotype effects and haplotype-environment interactions in the presence of haplotype-phase ambiguity. We provide novel insights to existing methods by construction of various score-tests and pseudo-likelihoods. In addition, we describe a novel two-stage method for analysis of untyped SNPs that can use any flexible external algorithm for genotype imputation followed by a powerful association test based on the retrospective likelihood. We illustrate applications of the methods using simulated and real data. © Institute of Mathematical Statistics, 2009.

  10. Transposon Insertions, Structural Variations, and SNPs Contribute to the Evolution of the Melon Genome.

    Science.gov (United States)

    Sanseverino, Walter; Hénaff, Elizabeth; Vives, Cristina; Pinosio, Sara; Burgos-Paz, William; Morgante, Michele; Ramos-Onsins, Sebastián E; Garcia-Mas, Jordi; Casacuberta, Josep Maria

    2015-10-01

    The availability of extensive databases of crop genome sequences should allow analysis of crop variability at an unprecedented scale, which should have an important impact in plant breeding. However, up to now the analysis of genetic variability at the whole-genome scale has been mainly restricted to single nucleotide polymorphisms (SNPs). This is a strong limitation as structural variation (SV) and transposon insertion polymorphisms are frequent in plant species and have had an important mutational role in crop domestication and breeding. Here, we present the first comprehensive analysis of melon genetic diversity, which includes a detailed analysis of SNPs, SV, and transposon insertion polymorphisms. The variability found among seven melon varieties representing the species diversity and including wild accessions and highly breed lines, is relatively high due in part to the marked divergence of some lineages. The diversity is distributed nonuniformly across the genome, being lower at the extremes of the chromosomes and higher in the pericentromeric regions, which is compatible with the effect of purifying selection and recombination forces over functional regions. Additionally, this variability is greatly reduced among elite varieties, probably due to selection during breeding. We have found some chromosomal regions showing a high differentiation of the elite varieties versus the rest, which could be considered as strongly selected candidate regions. Our data also suggest that transposons and SV may be at the origin of an important fraction of the variability in melon, which highlights the importance of analyzing all types of genetic variability to understand crop genome evolution.

  11. Optimization of heteroduplex analysis for the detection of BRCA mutations and SNPs

    Directory of Open Access Journals (Sweden)

    Lucian Negura

    2011-02-01

    Full Text Available BRCA1 and BRCA2 are tumour suppressor genes whose mutant phenotypes predispose to breast and ovarian cancer. Screening for mutations in these genes is now standard practice for hereditary breast and ovarian cancer (HBOC cases in Europe, and permits medical follow-up and genetic counselling adapted to the needs of individuals in such families. Currently, most laboratories performing diagnostic analysis of the BRCA genes use PCR of exons and intron-exon boundaries coupled to a pre-screening step to identify anomalous amplicons. The techniques employed for the detection of mutations and SNPs have evolved over time and vary in sensitivity, specificity and cost-effectiveness. As a variant for pre-screening techniques, we chose the recently developed Surveyor® heteroduplex cleavage method as a sensitive and specific technique to reveal anomalous amplicons of the BRCA genes, using only basic laboratory equipment and agarose gel electrophoresis. Here we present the detection of either mutations or SNPs within the BRCA1 exon 7, using heteroduplex analysis (HA by mismatch-specific endonuclease, confirmed by dideoxy sequencing.

  12. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

    Science.gov (United States)

    Lee, S Hong; Ripke, Stephan; Neale, Benjamin M; Faraone, Stephen V; Purcell, Shaun M; Perlis, Roy H; Mowry, Bryan J; Thapar, Anita; Goddard, Michael E; Witte, John S; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E; Asherson, Philip; Azevedo, Maria H; Backlund, Lena; Badner, Judith A; Bailey, Anthony J; Banaschewski, Tobias; Barchas, Jack D; Barnes, Michael R; Barrett, Thomas B; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B; Black, Donald W; Blackwood, Douglas H R; Bloss, Cinnamon S; Boehnke, Michael; Boomsma, Dorret I; Breen, Gerome; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G; Buitelaar, Jan K; Bunney, William E; Buxbaum, Joseph D; Byerley, William F; Byrne, Enda M; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Cloninger, C Robert; Collier, David A; Cook, Edwin H; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H; Craig, David W; Craig, Ian W; Crosbie, Jennifer; Cuccaro, Michael L; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J; Doyle, Alysa E; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P; Edenberg, Howard J; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E; Ferrier, I Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B; Freitag, Christine M; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V; Georgieva, Lyudmila; Gershon, Elliot S; Geschwind, Daniel H; Giegling, Ina; Gill, Michael; Gordon, Scott D; Gordon-Smith, Katherine; Green, Elaine K; Greenwood, Tiffany A; Grice, Dorothy E; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P; Hamshere, Marian L; Hansen, Thomas F; Hartmann, Annette M; Hautzinger, Martin; Heath, Andrew C; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hipolito, Maria; Hoefels, Susanne; Holmans, Peter A; Holsboer, Florian; Hoogendijk, Witte J; Hottenga, Jouke-Jan; Hultman, Christina M; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Edward G; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kähler, Anna K; Kahn, René S; Kandaswamy, Radhika; Keller, Matthew C; Kennedy, James L; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K; Klauck, Sabine M; Klei, Lambertus; Knowles, James A; Kohli, Martin A; Koller, Daniel L; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Långström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B; Leboyer, Marion; Ledbetter, David H; Lee, Phil H; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F; Lewis, Cathryn M; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A; Lin, Dan-Yu; Linszen, Don H; Liu, Chunyu; Lohoff, Falk W; Loo, Sandra K; Lord, Catherine; Lowe, Jennifer K; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela A F; Maestrini, Elena; Magnusson, Patrik K E; Mahon, Pamela B; Maier, Wolfgang; Malhotra, Anil K; Mane, Shrikant M; Martin, Christa L; Martin, Nicholas G; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A; McGhee, Kevin A; McGough, James J; McGrath, Patrick J; McGuffin, Peter; McInnis, Melvin G; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W; McMahon, Francis J; McMahon, William M; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P; Montgomery, Grant W; Moran, Jennifer L; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W; Morrow, Eric M; Moskvina, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W; Muir, Walter J; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M; Myin-Germeys, Inez; Neale, Michael C; Nelson, Stan F; Nievergelt, Caroline M; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A; Nöthen, Markus M; Nurnberger, John I; Nwulia, Evaristus A; Nyholt, Dale R; O'Dushlaine, Colm; Oades, Robert D; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A; Osby, Urban; Owen, Michael J; Palotie, Aarno; Parr, Jeremy R; Paterson, Andrew D; Pato, Carlos N; Pato, Michele T; Penninx, Brenda W; Pergadia, Michele L; Pericak-Vance, Margaret A; Pickard, Benjamin S; Pimm, Jonathan; Piven, Joseph; Posthuma, Danielle; Potash, James B; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J; Quinn, Emma M; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B; Raychaudhuri, Soumya; Rehnström, Karola; Reif, Andreas; Ribasés, Marta; Rice, John P; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rossin, Lizzy; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R; Sanders, Stephan J; Santangelo, Susan L; Sergeant, Joseph A; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F; Scheftner, William A; Schellenberg, Gerard D; Scherer, Stephen W; Schork, Nicholas J; Schulze, Thomas G; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J; Shi, Jianxin; Shilling, Paul D; Shyn, Stanley I; Silverman, Jeremy M; Slager, Susan L; Smalley, Susan L; Smit, Johannes H; Smith, Erin N; Sonuga-Barke, Edmund J S; St Clair, David; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S; Strohmaier, Jana; Stroup, T Scott; Sutcliffe, James S; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C; Todorov, Alexandre A; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M; Vieland, Veronica J; Vincent, John B; Visscher, Peter M; Walsh, Christopher A; Wassink, Thomas H; Watson, Stanley J; Weissman, Myrna M; Werge, Thomas; Wienker, Thomas F; Wijsman, Ellen M; Willemsen, Gonneke; Williams, Nigel; Willsey, A Jeremy; Witt, Stephanie H; Xu, Wei; Young, Allan H; Yu, Timothy W; Zammit, Stanley; Zandi, Peter P; Zhang, Peng; Zitman, Frans G; Zöllner, Sebastian; Devlin, Bernie; Kelsoe, John R; Sklar, Pamela; Daly, Mark J; O'Donovan, Michael C; Craddock, Nicholas; Sullivan, Patrick F; Smoller, Jordan W; Kendler, Kenneth S; Wray, Naomi R

    2013-09-01

    Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

  13. Assignment of chromosomal locations for unassigned SNPs/scaffolds based on pair-wise linkage disequilibrium estimates.

    Science.gov (United States)

    Khatkar, Mehar S; Hobbs, Matthew; Neuditschko, Markus; Sölkner, Johann; Nicholas, Frank W; Raadsma, Herman W

    2010-04-07

    Recent developments of high-density SNP chips across a number of species require accurate genetic maps. Despite rapid advances in genome sequence assembly and availability of a number of tools for creating genetic maps, the exact genome location for a number of SNPs from these SNP chips still remains unknown. We have developed a locus ordering procedure based on linkage disequilibrium (LODE) which provides estimation of the chromosomal positions of unaligned SNPs and scaffolds. It also provides an alternative means for verification of genetic maps. We exemplified LODE in cattle. The utility of the LODE procedure was demonstrated using data from 1,943 bulls genotyped for 73,569 SNPs across three different SNP chips. First, the utility of the procedure was tested by analysing the masked positions of 1,500 randomly-chosen SNPs with known locations (50 from each chromosome), representing three classes of minor allele frequencies (MAF), namely >0.05, 0.01assigned a location) was 96.7%, 30.6% and 2.0%; with an accuracy (the percentage of SNPs assigned correctly) of 99.9%, 98.9% and 33.3% in the three classes of MAF, respectively. The average precision for placement of the SNPs was 914, 3,137 and 6,853 kb, respectively. Secondly, 4,688 of 5,314 SNPs unpositioned in the Btau4.0 assembly were positioned using the LODE procedure. Based on these results, the positions of 485 unordered scaffolds were determined. The procedure was also used to validate the genome positions of 53,068 SNPs placed on Btau4.0 bovine assembly, resulting in identification of problem areas in the assembly. Finally, the accuracy of the LODE procedure was independently validated by comparative mapping on the hg18 human assembly. The LODE procedure described in this study is an efficient and accurate method for positioning SNPs (MAF>0.05), for validating and checking the quality of a genome assembly, and offers a means for positioning of unordered scaffolds containing SNPs. The LODE procedure will be

  14. SNPs in the bovine IL-10 receptor are associated with somatic cell score in Canadian dairy bulls.

    Science.gov (United States)

    Verschoor, Chris P; Pant, Sameer D; Schenkel, Flavio S; Sharma, Bhawani S; Karrow, Niel A

    2009-07-01

    Altering the balance between pro- and anti-inflammatory responses can influence an animal's susceptibility to acute or chronic inflammatory disease; bovine mastitis is no exception. Genetic variation in the form of single nucleotide polymorphisms (SNPs) may alter the function and expression of genes that regulate inflammation, making them important candidates for defining an animal's risk of developing acute or chronic mastitis. The objective of the present study was to identify SNPs in genes that regulate anti-inflammatory responses and test their association with estimated breeding values (EBVs) for somatic cell score (SCS), a trait highly correlated with the incidence of mastitis. These genes included bovine interleukin-10 (IL-10) and its receptor (IL-10R), and transforming growth factor beta1 (TGF-beta1) and its receptor (TGF-betaR). Sequencing-pooled DNA allowed for the identification of SNPs in IL-10 (n = 2), IL-10Ralpha (n = 6) and beta (n = 2), and TGF-beta1 (n = 1). These SNPs were subsequently genotyped in a cohort of Holstein (n = 500), Jersey (n = 83), and Guernsey (n = 50) bulls. Linear regression analysis identified significant SNP effects for IL-10Ralpha 1185C>T with SCS. Haplotype IL-10Ralpha AAT showed a significant effect on increasing SCS compared to the most common haplotype. The results presented here indicate that SNPs in IL-10Ralpha may contribute to variation in the SCS of dairy cattle. Although functional studies are necessary to ascertain whether these SNPs are causal polymorphisms or merely in linkage with the true causal SNP(s), a selection program incorporating these markers could have a beneficial influence on the average SCS and productivity of a dairy herd.

  15. Natural functional SNPs in miR-155 alter its expression level, blood cell counts and immune responses

    Directory of Open Access Journals (Sweden)

    Congcong Li

    2016-08-01

    Full Text Available miR-155 has been confirmed to be a key factor in immune responses in humans and other mammals. Therefore, investigation of variations in miR-155 could be useful for understanding the differences in immunity between individuals. In this study, four SNPs in miR-155 were identified in mice (Mus musculus and humans (Homo sapiens. In mice, the four SNPs were closely linked and formed two miR-155 haplotypes (A and B. Ten distinct types of blood parameters were associated with miR-155 expression under normal conditions. Additionally, 4 and 14 blood parameters were significantly different between these two genotypes under normal and lipopolysaccharide (LPS stimulation conditions, respectively. Moreover, the expression levels of miR-155, the inflammatory response to LPS stimulation and the lethal ratio following Salmonella typhimurium infection were significantly increased in mice harboring the AA genotype. Further, two SNPs, one in the loop region and the other near the 3' terminal of pre-miR-155, were confirmed to be responsible for the differential expression of miR-155 in mice. Interestingly, two additional SNPs, one in the loop region and the other in the middle of miR-155*, modulated the function of miR-155 in humans. Predictions of secondary RNA structure using RNAfold showed that these SNPs affected the structure of miR-155 in both mice and humans. Our results provide novel evidence of the natural functional SNPs of miR-155 in both mice and humans, which may affect the expression levels of mature miR-155 by modulating its secondary structure. The SNPs of human miR-155 may be considered as causal mutations for some immune-related diseases in the clinic. The two genotypes of mice could be used as natural models for studying the mechanisms of immune diseases caused by abnormal expression of miR-155 in humans.

  16. Analysis of copy loss and gain variations in Holstein cattle autosomes using BeadChip SNPs

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    Weller Joel I

    2010-11-01

    Full Text Available Abstract Background Copy number variation (CNV has been recently identified in human and other mammalian genomes, and there is a growing awareness of CNV's potential as a major source for heritable variation in complex traits. Genomic selection is a newly developed tool based on the estimation of breeding values for quantitative traits through the use of genome-wide genotyping of SNPs. Over 30,000 Holstein bulls have been genotyped with the Illumina BovineSNP50 BeadChip, which includes 54,001 SNPs (~SNP/50,000 bp, some of which fall within CNV regions. Results We used the BeadChip data obtained for 912 Israeli bulls to investigate the effects of CNV on SNP calls. For each of the SNPs, we estimated the frequencies of occurrence of loss of heterozygosity (LOH and of gain, based either on deviation from the expected Hardy-Weinberg equilibrium (HWE or on signal intensity (SI using the PennCNV "detect" option. Correlations between LOH/CNV frequencies predicted by the two methods were low (up to r = 0.08. Nevertheless, 418 locations displayed significantly high frequencies by both methods. Efficiency of designating large genomic clusters of olfactory receptors as CNVs was 29%. Frequency values for copy loss were distinguishable in non-autosomal regions, indicating misplacement of a region in the current BTA7 map. Analysis of BTA18 placed major quantitative trait loci affecting net merit in the US Holstein population in regions rich in segmental duplications and CNVs. Enrichment of transporters in CNV loci suggested their potential effect on milk-production traits. Conclusions Expansion of HWE and PennCNV analyses allowed estimating LOH/CNV frequencies, and combining the two methods yielded more sensitive detection of inherited CNVs and better estimation of their possible effects on cattle genetics. Although this approach was more effective than methodologies previously applied in cattle, it has severe limitations. Thus the number of CNVs reported here

  17. Mining the 3′UTR of Autism-implicated Genes for SNPs Perturbing MicroRNA Regulation

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    Varadharajan Vaishnavi

    2014-04-01

    Full Text Available Autism spectrum disorder (ASD refers to a group of childhood neurodevelopmental disorders with polygenic etiology. The expression of many genes implicated in ASD is tightly regulated by various factors including microRNAs (miRNAs, a class of noncoding RNAs ∼22 nucleotides in length that function to suppress translation by pairing with ‘miRNA recognition elements’ (MREs present in the 3′untranslated region (3′UTR of target mRNAs. This emphasizes the role played by miRNAs in regulating neurogenesis, brain development and differentiation and hence any perturbations in this regulatory mechanism might affect these processes as well. Recently, single nucleotide polymorphisms (SNPs present within 3′UTRs of mRNAs have been shown to modulate existing MREs or even create new MREs. Therefore, we hypothesized that SNPs perturbing miRNA-mediated gene regulation might lead to aberrant expression of autism-implicated genes, thus resulting in disease predisposition or pathogenesis in at least a subpopulation of ASD individuals. We developed a systematic computational pipeline that integrates data from well-established databases. By following a stringent selection criterion, we identified 9 MRE-modulating SNPs and another 12 MRE-creating SNPs in the 3′UTR of autism-implicated genes. These high-confidence candidate SNPs may play roles in ASD and hence would be valuable for further functional validation.

  18. Theodore E. Woodward Award: lactase persistence SNPs in African populations regulate promoter activity in intestinal cell culture.

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    Sibley, Eric; Ahn, Jong Kun

    2011-01-01

    Lactase-phlorizin hydrolase, lactase, is the intestinal enzyme responsible for the digestion of the milk sugar lactose. The majority of the world's human population experiences a decline in expression of the lactase gene by late childhood (lactase non-persistence). Individuals with lactase persistence, however, continue to express high levels of the lactase gene throughout adulthood. Lactase persistence is a heritable autosomal dominant condition and has been strongly correlated with several single nucleotide polymorphisms (SNPs) located ∼14 kb upstream of the lactase gene in different ethnic populations: -13910*T in Europeans and -13907*G, -13915*G, and -14010*C in several African populations. The coincidence of the four SNPs clustering within 100 bp strongly suggests that this region mediates the lactase non-persistence/persistence phenotype. Having previously characterized the European SNP, we aimed to determine whether the African SNPs similarly mediate a functional role in regulating the lactase promoter. Human intestinal Caco-2 cells were transfected with lactase SNP/promoter-reporter constructs and assayed for promoter activity. The -13907*G and -13915*G SNPs result in a significant enhancement of lactase promoter activity relative to the ancestral lactase non-persistence genotype. Such differential regulation by the SNPs is consistent with a causative role in the mechanism specifying the lactase persistence phenotype.

  19. Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression

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    Cowper-Sal·lari, Richard; Zhang, Xiaoyang; Wright, Jason B.; Bailey, Swneke D.; Cole, Michael D.; Eeckhoute, Jerome; Moore, Jason H.; Lupien, Mathieu

    2012-01-01

    Genome-wide association studies (GWASs) have identified thousands of single nucleotide polymorphisms (SNPs) associated with human traits and diseases. But because the vast majority of these SNPs are located in the noncoding regions of the genome their risk promoting mechanisms are elusive. Employing a new methodology combining cistromics, epigenomics and genotype imputation we annotate the noncoding regions of the genome in breast cancer cells and systematically identify the functional nature of SNPs associated with breast cancer risk. Our results demonstrate that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of H3K4me1 in a cancer and cell-type-specific manner. Furthermore, the majority of these risk-associated SNPs modulate the affinity of chromatin for FOXA1 at distal regulatory elements, which results in allele-specific gene expression, exemplified by the effect of the rs4784227 SNP on the TOX3 gene found within the 16q12.1 risk locus. PMID:23001124

  20. High density linkage mapping of genomic and transcriptomic SNPs for synteny analysis and anchoring the genome sequence of chickpea

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    Gaur, Rashmi; Jeena, Ganga; Shah, Niraj; Gupta, Shefali; Pradhan, Seema; Tyagi, Akhilesh K; Jain, Mukesh; Chattopadhyay, Debasis; Bhatia, Sabhyata

    2015-01-01

    This study presents genome-wide discovery of SNPs through next generation sequencing of the genome of Cicer reticulatum. Mapping of the C. reticulatum sequenced reads onto the draft genome assembly of C. arietinum (desi chickpea) resulted in identification of 842,104 genomic SNPs which were utilized along with an additional 36,446 genic SNPs identified from transcriptome sequences of the aforementioned varieties. Two new chickpea Oligo Pool All (OPAs) each having 3,072 SNPs were designed and utilized for SNP genotyping of 129 Recombinant Inbred Lines (RILs). Using Illumina GoldenGate Technology genotyping data of 5,041 SNPs were generated and combined with the 1,673 marker data from previously published studies, to generate a high resolution linkage map. The map comprised of 6698 markers distributed on eight linkage groups spanning 1083.93 cM with an average inter-marker distance of 0.16 cM. Utility of the present map was demonstrated for improving the anchoring of the earlier reported draft genome sequence of desi chickpea by ~30% and that of kabuli chickpea by 18%. The genetic map reported in this study represents the most dense linkage map of chickpea , with the potential to facilitate efficient anchoring of the draft genome sequences of desi as well as kabuli chickpea varieties. PMID:26303721

  1. A Mismatch EndoNuclease Array-Based Methodology (MENA for Identifying Known SNPs or Novel Point Mutations

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    Josep M. Comeron

    2016-04-01

    Full Text Available Accurate and rapid identification or confirmation of single nucleotide polymorphisms (SNPs, point mutations and other human genomic variation facilitates understanding the genetic basis of disease. We have developed a new methodology (called MENA (Mismatch EndoNuclease Array pairing DNA mismatch endonuclease enzymology with tiling microarray hybridization in order to genotype both known point mutations (such as SNPs as well as identify previously undiscovered point mutations and small indels. We show that our assay can rapidly genotype known SNPs in a human genomic DNA sample with 99% accuracy, in addition to identifying novel point mutations and small indels with a false discovery rate as low as 10%. Our technology provides a platform for a variety of applications, including: (1 genotyping known SNPs as well as confirming newly discovered SNPs from whole genome sequencing analyses; (2 identifying novel point mutations and indels in any genomic region from any organism for which genome sequence information is available; and (3 screening panels of genes associated with particular diseases and disorders in patient samples to identify causative mutations. As a proof of principle for using MENA to discover novel mutations, we report identification of a novel allele of the beethoven (btv gene in Drosophila, which encodes a ciliary cytoplasmic dynein motor protein important for auditory mechanosensation.

  2. A Mismatch EndoNuclease Array-Based Methodology (MENA) for Identifying Known SNPs or Novel Point Mutations

    Science.gov (United States)

    Comeron, Josep M.; Reed, Jordan; Christie, Matthew; Jacobs, Julia S.; Dierdorff, Jason; Eberl, Daniel F.; Manak, J. Robert

    2016-01-01

    Accurate and rapid identification or confirmation of single nucleotide polymorphisms (SNPs), point mutations and other human genomic variation facilitates understanding the genetic basis of disease. We have developed a new methodology (called MENA (Mismatch EndoNuclease Array)) pairing DNA mismatch endonuclease enzymology with tiling microarray hybridization in order to genotype both known point mutations (such as SNPs) as well as identify previously undiscovered point mutations and small indels. We show that our assay can rapidly genotype known SNPs in a human genomic DNA sample with 99% accuracy, in addition to identifying novel point mutations and small indels with a false discovery rate as low as 10%. Our technology provides a platform for a variety of applications, including: (1) genotyping known SNPs as well as confirming newly discovered SNPs from whole genome sequencing analyses; (2) identifying novel point mutations and indels in any genomic region from any organism for which genome sequence information is available; and (3) screening panels of genes associated with particular diseases and disorders in patient samples to identify causative mutations. As a proof of principle for using MENA to discover novel mutations, we report identification of a novel allele of the beethoven (btv) gene in Drosophila, which encodes a ciliary cytoplasmic dynein motor protein important for auditory mechanosensation. PMID:27600073