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Sample records for phenotype-vana genotype incongruence

  1. Phenotypic and genotypic characterization of vancomycin-resistant Enterococcus faecium clinical isolates from two hospitals in Mexico: First detection of VanB phenotype-vanA genotype.

    Science.gov (United States)

    Bocanegra-Ibarias, Paola; Flores-Treviño, Samantha; Camacho-Ortiz, Adrián; Morfin-Otero, Rayo; Villarreal-Treviño, Licet; Llaca-Díaz, Jorge; Martínez-Landeros, Erik Alan; Rodríguez-Noriega, Eduardo; Calzada-Güereca, Andrés; Maldonado-Garza, Héctor Jesús; Garza-González, Elvira

    2016-01-01

    Enterococcus faecium has emerged as a multidrug-resistant nosocomial pathogen involved in outbreaks worldwide. Our aim was to determine the antimicrobial susceptibility, biofilm production, and clonal relatedness of vancomycin-resistant E. faecium (VREF) clinical isolates from two hospitals in Mexico. Consecutive clinical isolates (n=56) were collected in two tertiary care hospitals in Mexico from 2011 to 2014. VREF isolates were characterized by phenotypic and molecular methods including pulsed-field gel electrophoresis (PFGE). VREF isolates were highly resistant to vancomycin, erythromycin, norfloxacin, high-level streptomycin, and teicoplanin, and showed lower resistance to tetracycline, nitrofurantoin and quinupristin-dalfopristin. None of the isolates were resistant to linezolid. The vanA gene was detected in all isolates. Two VanB phenotype-vanA genotype isolates, highly resistant to vancomycin and susceptible to teicoplanin, were detected. Furthermore, 17.9% of the isolates were classified as biofilm producers, and the espfm gene was found in 98.2% of the isolates. A total of 37 distinct PFGE patterns and 6 clones (25% of the isolates as clone A, 5.4% as clone B, and 3.6% each as clone C, D, E, and F) were detected. Clone A was detected in 5 different wards of the same hospital during 14 months of surveillance. The high resistance to most antimicrobial agents and the moderate cross-transmission of VREF detected accentuates the need for continuous surveillance of E. faecium in the hospital setting. This is also the first reported incidence of the E. faecium VanB phenotype-vanA genotype in the Americas. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  2. The genotype-phenotype map of an evolving digital organism.

    Directory of Open Access Journals (Sweden)

    Miguel A Fortuna

    2017-02-01

    Full Text Available To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes (instruction sequences, which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable.

  3. The genotype-phenotype map of an evolving digital organism.

    Science.gov (United States)

    Fortuna, Miguel A; Zaman, Luis; Ofria, Charles; Wagner, Andreas

    2017-02-01

    To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes (instruction sequences), which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable.

  4. The genotype-phenotype map of an evolving digital organism

    OpenAIRE

    Fortuna, Miguel A.; Zaman, Luis; Ofria, Charles; Wagner, Andreas

    2017-01-01

    To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms fr...

  5. Distribution of genotype network sizes in sequence-to-structure genotype-phenotype maps.

    Science.gov (United States)

    Manrubia, Susanna; Cuesta, José A

    2017-04-01

    An essential quantity to ensure evolvability of populations is the navigability of the genotype space. Navigability, understood as the ease with which alternative phenotypes are reached, relies on the existence of sufficiently large and mutually attainable genotype networks. The size of genotype networks (e.g. the number of RNA sequences folding into a particular secondary structure or the number of DNA sequences coding for the same protein structure) is astronomically large in all functional molecules investigated: an exhaustive experimental or computational study of all RNA folds or all protein structures becomes impossible even for moderately long sequences. Here, we analytically derive the distribution of genotype network sizes for a hierarchy of models which successively incorporate features of increasingly realistic sequence-to-structure genotype-phenotype maps. The main feature of these models relies on the characterization of each phenotype through a prototypical sequence whose sites admit a variable fraction of letters of the alphabet. Our models interpolate between two limit distributions: a power-law distribution, when the ordering of sites in the prototypical sequence is strongly constrained, and a lognormal distribution, as suggested for RNA, when different orderings of the same set of sites yield different phenotypes. Our main result is the qualitative and quantitative identification of those features of sequence-to-structure maps that lead to different distributions of genotype network sizes. © 2017 The Author(s).

  6. Linking genotypes database with locus-specific database and genotype-phenotype correlation in phenylketonuria.

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    Wettstein, Sarah; Underhaug, Jarl; Perez, Belen; Marsden, Brian D; Yue, Wyatt W; Martinez, Aurora; Blau, Nenad

    2015-03-01

    The wide range of metabolic phenotypes in phenylketonuria is due to a large number of variants causing variable impairment in phenylalanine hydroxylase function. A total of 834 phenylalanine hydroxylase gene variants from the locus-specific database PAHvdb and genotypes of 4181 phenylketonuria patients from the BIOPKU database were characterized using FoldX, SIFT Blink, Polyphen-2 and SNPs3D algorithms. Obtained data was correlated with residual enzyme activity, patients' phenotype and tetrahydrobiopterin responsiveness. A descriptive analysis of both databases was compiled and an interactive viewer in PAHvdb database was implemented for structure visualization of missense variants. We found a quantitative relationship between phenylalanine hydroxylase protein stability and enzyme activity (r(s) = 0.479), between protein stability and allelic phenotype (r(s) = -0.458), as well as between enzyme activity and allelic phenotype (r(s) = 0.799). Enzyme stability algorithms (FoldX and SNPs3D), allelic phenotype and enzyme activity were most powerful to predict patients' phenotype and tetrahydrobiopterin response. Phenotype prediction was most accurate in deleterious genotypes (≈ 100%), followed by homozygous (92.9%), hemizygous (94.8%), and compound heterozygous genotypes (77.9%), while tetrahydrobiopterin response was correctly predicted in 71.0% of all cases. To our knowledge this is the largest study using algorithms for the prediction of patients' phenotype and tetrahydrobiopterin responsiveness in phenylketonuria patients, using data from the locus-specific and genotypes database.

  7. Phenotype- and genotype-specific structural alterations in spasmodic dysphonia.

    Science.gov (United States)

    Bianchi, Serena; Battistella, Giovanni; Huddleston, Hailey; Scharf, Rebecca; Fleysher, Lazar; Rumbach, Anna F; Frucht, Steven J; Blitzer, Andrew; Ozelius, Laurie J; Simonyan, Kristina

    2017-04-01

    Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends have been reported in up to 16% of patients, the causative etiology of spasmodic dysphonia is unclear, and the influences of various phenotypes and genotypes on disorder pathophysiology are poorly understood. In this study, we examined structural alterations in cortical gray matter and white matter integrity in relationship to different phenotypes and putative genotypes of spasmodic dysphonia to elucidate the structural component of its complex pathophysiology. Eighty-nine patients with spasmodic dysphonia underwent high-resolution magnetic resonance imaging and diffusion-weighted imaging to examine cortical thickness and white matter fractional anisotropy in adductor versus abductor forms (distinct phenotypes) and in sporadic versus familial cases (distinct genotypes). Phenotype-specific abnormalities were localized in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiata. Genotype-specific alterations were found in the left superior temporal gyrus, supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus. Our findings suggest that phenotypic differences in spasmodic dysphonia arise at the level of the primary and associative areas of motor control, whereas genotype-related pathophysiological mechanisms may be associated with dysfunction of regions regulating phonological and sensory processing. Identification of structural alterations specific to disorder phenotype and putative genotype provides an important step toward future delineation of imaging markers and potential targets for novel therapeutic interventions for spasmodic dysphonia. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  8. The Phenotype/Genotype Correlation of Lactase Persistence among Omani Adults

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    Abdulrahim Al-Abri

    2013-09-01

    Full Text Available Objective: To examine the correlation of lactase persistence phenotype with genotype in Omani adults.Methods: Lactase persistence phenotype was tested by hydrogen breath test in 52 Omani Adults using the Micro H2 analyzer. Results were checked against genotyping using direct DNA sequencing.Results: Forty one individuals with C/C-13910 and T/T-13915 genotypes had positive breath tests (≥20 ppm; while eight of nine individuals with T/C-13910 or T/G-13915 genotypes had negative breath tests (<20 ppm and two subjects were non-hydrogen producers. The agreement between phenotype and genotype using Kappa value was very good (0.93.Conclusion: Genotyping both T/C-13910 and T/G-13915 alleles can be used to assist diagnosis and predict lactose intolerance in the Omani population.

  9. Deep Phenotyping: Deep Learning For Temporal Phenotype/Genotype Classification

    OpenAIRE

    Najafi, Mohammad; Namin, Sarah; Esmaeilzadeh, Mohammad; Brown, Tim; Borevitz, Justin

    2017-01-01

    High resolution and high throughput, genotype to phenotype studies in plants are underway to accelerate breeding of climate ready crops. Complex developmental phenotypes are observed by imaging a variety of accessions in different environment conditions, however extracting the genetically heritable traits is challenging. In the recent years, deep learning techniques and in particular Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs) and Long-Short Term Memories (LSTMs), h...

  10. Primer in Genetics and Genomics, Article 5-Further Defining the Concepts of Genotype and Phenotype and Exploring Genotype-Phenotype Associations.

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    Wright, Fay; Fessele, Kristen

    2017-10-01

    As nurses begin to incorporate genetic and genomic sciences into clinical practice, education, and research, it is essential that they have a working knowledge of the terms foundational to the science. The first article in this primer series provided brief definitions of the basic terms (e.g., genetics and genomics) and introduced the concept of phenotype during the discussion of Mendelian inheritance. These terms, however, are inconsistently used in publications and conversations, and the linkage between genotype and phenotype requires clarification. The goal of this fifth article in the series is to elucidate these terms, provide an overview of the research methods used to determine genotype-phenotype associations, and discuss their significance to nursing through examples from the current nursing literature.

  11. Towards a database for genotype-phenotype association research: mining data from encyclopaedia

    NARCIS (Netherlands)

    Pajić, V.S.; Pavlović-Lažetić, G.M.; Beljanski, M.V.; Brandt, B.W.; Pajić, M.B.

    2013-01-01

    To associate phenotypic characteristics of an organism to molecules encoded by its genome, there is a need for well-structured genotype and phenotype data. We use a novel method for extracting data on phenotype and genotype characteristics of microorganisms from text. As a resource, we use an

  12. Translation of Genotype to Phenotype by a Hierarchy of Cell Subsystems

    OpenAIRE

    Yu, Michael Ku; Kramer, Michael; Dutkowski, Janusz; Srivas, Rohith; Licon, Katherine; Kreisberg, Jason F.; Ng, Cherie T.; Krogan, Nevan; Sharan, Roded; Ideker, Trey

    2016-01-01

    Summary Accurately translating genotype to phenotype requires accounting for the functional impact of genetic variation at many biological scales. Here we present a strategy for genotype-phenotype reasoning based on existing knowledge of cellular subsystems. These subsystems and their hierarchical organization are defined by the Gene Ontology or a complementary ontology inferred directly from previously published datasets. Guided by the ontology?s hierarchical structure, we organize genotype ...

  13. Translation of Genotype to Phenotype by a Hierarchy of Cell Subsystems.

    Science.gov (United States)

    Yu, Michael Ku; Kramer, Michael; Dutkowski, Janusz; Srivas, Rohith; Licon, Katherine; Kreisberg, Jason; Ng, Cherie T; Krogan, Nevan; Sharan, Roded; Ideker, Trey

    2016-02-24

    Accurately translating genotype to phenotype requires accounting for the functional impact of genetic variation at many biological scales. Here we present a strategy for genotype-phenotype reasoning based on existing knowledge of cellular subsystems. These subsystems and their hierarchical organization are defined by the Gene Ontology or a complementary ontology inferred directly from previously published datasets. Guided by the ontology's hierarchical structure, we organize genotype data into an "ontotype," that is, a hierarchy of perturbations representing the effects of genetic variation at multiple cellular scales. The ontotype is then interpreted using logical rules generated by machine learning to predict phenotype. This approach substantially outperforms previous, non-hierarchical methods for translating yeast genotype to cell growth phenotype, and it accurately predicts the growth outcomes of two new screens of 2,503 double gene knockouts impacting DNA repair or nuclear lumen. Ontotypes also generalize to larger knockout combinations, setting the stage for interpreting the complex genetics of disease.

  14. Clustering high-dimensional mixed data to uncover sub-phenotypes: joint analysis of phenotypic and genotypic data.

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    McParland, D; Phillips, C M; Brennan, L; Roche, H M; Gormley, I C

    2017-12-10

    The LIPGENE-SU.VI.MAX study, like many others, recorded high-dimensional continuous phenotypic data and categorical genotypic data. LIPGENE-SU.VI.MAX focuses on the need to account for both phenotypic and genetic factors when studying the metabolic syndrome (MetS), a complex disorder that can lead to higher risk of type 2 diabetes and cardiovascular disease. Interest lies in clustering the LIPGENE-SU.VI.MAX participants into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory. A novel latent variable model that elegantly accommodates high dimensional, mixed data is developed to cluster LIPGENE-SU.VI.MAX participants using a Bayesian finite mixture model. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model. Two clusters or sub-phenotypes ('healthy' and 'at risk') are uncovered. A small subset of variables is deemed discriminatory, which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Further, 7 years after the LIPGENE-SU.VI.MAX data were collected, participants underwent further analysis to diagnose presence or absence of the MetS. The two uncovered sub-phenotypes strongly correspond to the 7-year follow-up disease classification, highlighting the role of phenotypic and genotypic factors in the MetS and emphasising the potential utility of the clustering approach in early screening. Additionally, the ability of the proposed approach to define the uncertainty in sub-phenotype membership at the participant level is synonymous with the concepts of precision medicine and nutrition. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection.

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    Derache, Anne; Wallis, Carole L; Vardhanabhuti, Saran; Bartlett, John; Kumarasamy, Nagalingeswaran; Katzenstein, David

    2016-01-15

    Virologic failure in subtype C is characterized by high resistance to first-line antiretroviral (ARV) drugs, including efavirenz, nevirapine, and lamivudine, with nucleoside resistance including type 2 thymidine analog mutations, K65R, a T69del, and M184V. However, genotypic algorithms predicting resistance are mainly based on subtype B viruses and may under- or overestimate drug resistance in non-B subtypes. To explore potential treatment strategies after first-line failure, we compared genotypic and phenotypic susceptibility of subtype C human immunodeficiency virus 1 (HIV-1) following first-line ARV failure. AIDS Clinical Trials Group 5230 evaluated patients failing an initial nonnucleoside reverse-transcriptase inhibitor (NNRTI) regimen in Africa and Asia, comparing the genotypic drug resistance and phenotypic profile from the PhenoSense (Monogram). Site-directed mutagenesis studies of K65R and T69del assessed the phenotypic impact of these mutations. Genotypic algorithms overestimated resistance to etravirine and rilpivirine, misclassifying 28% and 32%, respectively. Despite K65R with the T69del in 9 samples, tenofovir retained activity in >60%. Reversion of the K65R increased susceptibility to tenofovir and other nucleosides, while reversion of the T69del showed increased resistance to zidovudine, with little impact on other NRTI. Although genotype and phenotype were largely concordant for first-line drugs, estimates of genotypic resistance to etravirine and rilpivirine may misclassify subtype C isolates compared to phenotype. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  16. Relevance and costs of RHD genotyping in women with a weak D phenotype.

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    Laget, L; Izard, C; Durieux-Roussel, E; Gouvitsos, J; Dettori, I; Chiaroni, J; Ferrera-Tourenc, V

    2018-06-01

    For pregnant women, the serologic test results of D antigen will determine the frequency of RBC antibody detection as well as the indication for RhIG prophylaxis. RHD genotyping is the only method that may provide clear guidance on prophylaxis for women with a weak D phenotype. This analysis evaluated the economical implications of using RHD genotyping to guide RhIG prophylaxis among pregnant women with a serological weak D phenotype. We compared the costs of 2 strategies in a cohort of 273 women with weak D phenotype. In the first strategy, we did not perform genotyping and all women with weak D phenotypes were treated as if they were D-, thus considered to be a risk of RhD alloimmunization. These women all received the prophylactic follow up. In the second strategy, RHD genotyping was performed on all women with a serologic weak D phenotype. Then, the follow-up will be determined by phenotype deduced from genotype. On the studied cohort, the additional expense occurred by genotyping is 26,536 €. RHD Genotyping has highlighted 162 weak D Type 1, 2 3, that could safely be managed as D+ and 111 partial D to consider as D-. By comparing the 2 strategies, the savings generated by genotyping the patients of our cohort are € 12,046 for the follow up of one pregnancy. Knowing that in France, a woman has on average 2 pregnancies and that the genotyping is carried out only once, the savings generated for the following pregnancies would be € 38,581. Performing RHD genotyping for pregnant women with a weak D phenotype enables to clearly identify weak D type 1, 2 or 3 from the other variants at risk of alloimmunization. This analysis generates savings in terms of follow-up schedule of pregnant women and RhIG prophylaxis. It also allows saving of D- products for patient with a weak D type 1, 2 or 3 in case of a transfusion need. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. An XML-based interchange format for genotype-phenotype data.

    Science.gov (United States)

    Whirl-Carrillo, M; Woon, M; Thorn, C F; Klein, T E; Altman, R B

    2008-02-01

    Recent advances in high-throughput genotyping and phenotyping have accelerated the creation of pharmacogenomic data. Consequently, the community requires standard formats to exchange large amounts of diverse information. To facilitate the transfer of pharmacogenomics data between databases and analysis packages, we have created a standard XML (eXtensible Markup Language) schema that describes both genotype and phenotype data as well as associated metadata. The schema accommodates information regarding genes, drugs, diseases, experimental methods, genomic/RNA/protein sequences, subjects, subject groups, and literature. The Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB; www.pharmgkb.org) has used this XML schema for more than 5 years to accept and process submissions containing more than 1,814,139 SNPs on 20,797 subjects using 8,975 assays. Although developed in the context of pharmacogenomics, the schema is of general utility for exchange of genotype and phenotype data. We have written syntactic and semantic validators to check documents using this format. The schema and code for validation is available to the community at http://www.pharmgkb.org/schema/index.html (last accessed: 8 October 2007). (c) 2007 Wiley-Liss, Inc.

  18. Integration of curated databases to identify genotype-phenotype associations

    Directory of Open Access Journals (Sweden)

    Li Jianrong

    2006-10-01

    Full Text Available Abstract Background The ability to rapidly characterize an unknown microorganism is critical in both responding to infectious disease and biodefense. To do this, we need some way of anticipating an organism's phenotype based on the molecules encoded by its genome. However, the link between molecular composition (i.e. genotype and phenotype for microbes is not obvious. While there have been several studies that address this challenge, none have yet proposed a large-scale method integrating curated biological information. Here we utilize a systematic approach to discover genotype-phenotype associations that combines phenotypic information from a biomedical informatics database, GIDEON, with the molecular information contained in National Center for Biotechnology Information's Clusters of Orthologous Groups database (NCBI COGs. Results Integrating the information in the two databases, we are able to correlate the presence or absence of a given protein in a microbe with its phenotype as measured by certain morphological characteristics or survival in a particular growth media. With a 0.8 correlation score threshold, 66% of the associations found were confirmed by the literature and at a 0.9 correlation threshold, 86% were positively verified. Conclusion Our results suggest possible phenotypic manifestations for proteins biochemically associated with sugar metabolism and electron transport. Moreover, we believe our approach can be extended to linking pathogenic phenotypes with functionally related proteins.

  19. eCOMPAGT – efficient Combination and Management of Phenotypes and Genotypes for Genetic Epidemiology

    Directory of Open Access Journals (Sweden)

    Specht Günther

    2009-05-01

    Full Text Available Abstract Background High-throughput genotyping and phenotyping projects of large epidemiological study populations require sophisticated laboratory information management systems. Most epidemiological studies include subject-related personal information, which needs to be handled with care by following data privacy protection guidelines. In addition, genotyping core facilities handling cooperative projects require a straightforward solution to monitor the status and financial resources of the different projects. Description We developed a database system for an efficient combination and management of phenotypes and genotypes (eCOMPAGT deriving from genetic epidemiological studies. eCOMPAGT securely stores and manages genotype and phenotype data and enables different user modes with different rights. Special attention was drawn on the import of data deriving from TaqMan and SNPlex genotyping assays. However, the database solution is adjustable to other genotyping systems by programming additional interfaces. Further important features are the scalability of the database and an export interface to statistical software. Conclusion eCOMPAGT can store, administer and connect phenotype data with all kinds of genotype data and is available as a downloadable version at http://dbis-informatik.uibk.ac.at/ecompagt.

  20. Vancomycin-resistant enterococci with vanA gene in treated municipal wastewater and their association with human hospital strains.

    Science.gov (United States)

    Oravcova, Veronika; Mihalcin, Matus; Zakova, Jana; Pospisilova, Lucie; Masarikova, Martina; Literak, Ivan

    2017-12-31

    Vancomycin-resistant enterococci (VRE) are pathogens of increasing medical importance. In Brno, Czech Republic, we collected 37 samples from the effluent of a wastewater treatment plant (WWTP), 21 surface swabs from hospital settings, and 59 fecal samples from hospitalized patients and staff. Moreover, we collected 284 gull cloacal swabs from the colony situated 35km downstream the WWTP. Samples were cultured selectively. Enterococci were identified using MALDI-TOF MS, phenotypically tested for susceptibility to antibiotics, and by PCR for occurrence of resistance and virulence genes. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used to examine genotypic diversity. VRE carrying the vanA gene were found in 32 (86%, n=37) wastewater samples, from which we obtained 49 isolates: Enterococcus faecium (44) and Enterococcus gallinarum (2), Enterococcus casseliflavus (2), and Enterococcus raffinosus (1). From 33 (69%) of 48 inpatient stool samples, we obtained 39 vanA-carrying VRE, which belonged to E. faecium (33 isolates), Enterococcus faecalis (4), and Enterococcus raffinosus (2). Nearly one-third of the samples from hospital surfaces contained VRE with the vanA gene. VRE were not detected among gulls. Sixty-seven (84%, n=80) E. faecium isolates carried virulence genes hyl and/or esp. Virulence of E. faecalis was encoded by gelE, asa1, and cylA genes. A majority of the E. faecium isolates belonged to the clinically important sequence types ST17 (WWTP: 10 isolates; hospital: 4 isolates), ST18 (9;8), and ST78 (5;0). The remaining isolates belonged to ST555 (2;0), ST262 (1;6), ST273 (3;0), ST275 (1;0), ST549 (2;0), ST19 (0;1), ST323 (3;0), and ST884 (7;17). Clinically important enterococci carrying the vanA gene were almost continually detectable in the effluent of the WWTP, indicating insufficient removal of VRE during wastewater treatment and permanent shedding of these antibiotic resistant pathogens into the environment from this

  1. Genotype-phenotype associations in obesity dependent on definition of the obesity phenotype.

    Science.gov (United States)

    Kring, Sofia Inez Iqbal; Larsen, Lesli Hingstrup; Holst, Claus; Toubro, Søren; Hansen, Torben; Astrup, Arne; Pedersen, Oluf; Sørensen, Thorkild I A

    2008-01-01

    In previous studies of associations of variants in the genes UCP2, UCP3, PPARG2, CART, GRL, MC4R, MKKS, SHP, GHRL, and MCHR1 with obesity, we have used a case-control approach with cases defined by a threshold for BMI. In the present study, we assess the association of seven abdominal, peripheral, and overall obesity phenotypes, which were analyzed quantitatively, and thirteen candidate gene polymorphisms in these ten genes in the same cohort. Obese Caucasian men (n = 234, BMI >or= 31.0 kg/m(2)) and a randomly sampled non-obese group (n = 323), originally identified at the draft board examinations, were re-examined at median ages of 47.0 or 49.0 years by anthropometry and DEXA scanning. Obesity phenotypes included BMI, fat body mass index, waist circumference, waist for given BMI, intra-abdominal adipose tissue, hip circumference and lower body fat mass (%). Using logistic regression models, we estimated the odds for defined genotypes (dominant or recessive genetic transmission) in relation to z-scores of the phenotypes. The minor (rare) allele for SHP 512G>C (rs6659176) was associated with increased hip circumference. The minor allele for UCP2 Ins45bp was associated with increased BMI, increased abdominal obesity, and increased hip circumference. The minor allele for UCP2 -866G>A (rs6593669) was associated with borderline increased fat body mass index. The minor allele for MCHR1 100213G>A (rs133072) was associated with reduced abdominal obesity. None of the other genotype-phenotype combinations showed appreciable associations. If replicated in independent studies with focus on the specific phenotypes, our explorative studies suggest significant associations between some candidate gene polymorphisms and distinct obesity phenotypes, predicting beneficial and detrimental effects, depending on compartments for body fat accumulation. Copyright 2008 S. Karger AG, Basel.

  2. Õigus Vanas Testamendis : [bakalaureusetöö] / Haide Rimmel ; Tartu Ülikool, õigusteaduskond ; juhendaja: Peeter Järvelaid

    Index Scriptorium Estoniae

    Rimmel, Haide

    1996-01-01

    Vana Testamendi õiguse üldiseloomustus (kasuistlikud normid, apodiktilised normid), Vana Testamendi õiguse allikad (lepinguraamat, deuteronoomium, Pühadusseadus ja Preestrikoodeks, muud allikad), Vana Testamendi õiguse subjektid (täieõiguslikud kodanikud, võõramaalased, orjad), Vana Testamendi õigusharud (kriminaalõigus, perekonnaõigus, pärimisõigus, võlaõigus, asjaõigus), õigusemõistmine Vanas Testamendis

  3. Vana-Laitsna valla eestlased ja Läti riik / Terje Lõbu

    Index Scriptorium Estoniae

    Lõbu, Terje

    2004-01-01

    Vana-Laitsna valla riiklikust kuuluvusest Vabadussõja ajal ja järel. Vana-Laitsna eestlaste haidusoludest. 1934. aastal sõlmitud Eesti-Läti koolikonventsioonist. Eestilätlaste ja lätieestlaste haridusolude võrdlus 1930ndatel aastatel. Eesti koolide väljasuretamisest Heinastes, Hoomulis, Ipilus ja Läti-Valgas

  4. Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder.

    Science.gov (United States)

    Fu, Rong; Ceballos-Picot, Irene; Torres, Rosa J; Larovere, Laura E; Yamada, Yasukazu; Nguyen, Khue V; Hegde, Madhuri; Visser, Jasper E; Schretlen, David J; Nyhan, William L; Puig, Juan G; O'Neill, Patrick J; Jinnah, H A

    2014-05-01

    Establishing meaningful relationships between genetic variations and clinical disease is a fundamental goal for all human genetic disorders. However, these genotype-phenotype correlations remain incompletely characterized and sometimes conflicting for many diseases. Lesch-Nyhan disease is an X-linked recessive disorder that is caused by a wide variety of mutations in the HPRT1 gene. The gene encodes hypoxanthine-guanine phosphoribosyl transferase, an enzyme involved in purine metabolism. The fine structure of enzyme has been established by crystallography studies, and its function can be measured with very precise biochemical assays. This rich knowledge of genetic alterations in the gene and their functional effect on its protein product provides a powerful model for exploring factors that influence genotype-phenotype correlations. The present study summarizes 615 known genetic mutations, their influence on the gene product, and their relationship to the clinical phenotype. In general, the results are compatible with the concept that the overall severity of the disease depends on how mutations ultimately influence enzyme activity. However, careful evaluation of exceptions to this concept point to several additional genetic and non-genetic factors that influence genotype-phenotype correlations. These factors are not unique to Lesch-Nyhan disease, and are relevant to most other genetic diseases. The disease therefore serves as a valuable model for understanding the challenges associated with establishing genotype-phenotype correlations for other disorders.

  5. Phenotypes in defined genotypes including siblings with Usher syndrome.

    Science.gov (United States)

    Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Andréasson, Sten

    2011-06-01

    To characterize visual function in defined genotypes including siblings with Usher syndrome. Thirteen patients with phenotypically different subtypes of Usher syndrome, including 3 families with affected siblings, were selected. Genetic analysis and ophthalmological examinations including visual fields, full-field electroretinography (ERG), multifocal electroretinography (mf ERG), and optical coherence tomography (OCT) were assessed. The patients' degree of visual handicap was evaluated by a questionnaire (ADL). Twelve of thirteen patients were genotyped as Usher 1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz flickering light response revealed remaining cone function. In 3 of the patients with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp distinction between the area with reduced function and the central area with remaining macular function and normal peak time. OCT demonstrated loss of foveal depression with distortion of the foveal architecture in the macula in all patients. The foveal thickness ranged from 159 to 384 µm and was not correlated to retinal function. Three siblings shared the same mutation for Usher 2C but in contrast to previous reports regarding this genotype, 1 of them diverged in phenotype with substantially normal visual fields, almost normal OCT and mf ERG findings, and only moderately reduced rod and cone function according to ERG. Evaluation of visual function comprising both the severity of the rod cone degeneration and the function in the macular region confirm phenotypical heterogeneity within siblings and between different genotypes of Usher syndrome.

  6. Early-onset stargardt disease: phenotypic and genotypic characteristics

    NARCIS (Netherlands)

    Lambertus, S.; Huet, R.A.C. van; Bax, N.M.; Hoefsloot, L.H.; Cremers, F.P.M.; Boon, C.J.F.; Klevering, B.J.; Hoyng, C.B.

    2015-01-01

    OBJECTIVE: To describe the phenotype and genotype of patients with early-onset Stargardt disease. DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-one Stargardt patients with age at onset

  7. Neuroimaging studies in people with gender incongruence.

    Science.gov (United States)

    Kreukels, Baudewijntje P C; Guillamon, Antonio

    2016-01-01

    The current review gives an overview of brain studies in transgender people. First, we describe studies into the aetiology of feelings of gender incongruence, primarily addressing the sexual differentiation hypothesis: does the brain of transgender individuals resemble that of their natal sex, or that of their experienced gender? Findings from neuroimaging studies focusing on brain structure suggest that the brain phenotypes of trans women (MtF) and trans men (FtM) differ in various ways from control men and women with feminine, masculine, demasculinized and defeminized features. The brain phenotypes of people with feelings of gender incongruence may help us to figure out whether sex differentiation of the brain is atypical in these individuals, and shed light on gender identity development. Task-related imaging studies may show whether brain activation and task performance in transgender people is sex-atypical. Second, we review studies that evaluate the effects of cross-sex hormone treatment on the brain. This type of research provides knowledge on how changes in sex hormone levels may affect brain structure and function.

  8. Kultuuritehas vallutab vana katlamaja / Merit Kask

    Index Scriptorium Estoniae

    Kask, Merit

    2005-01-01

    Kultuuritehase projektijuht Madis Mikkor Tallinna Põhja puiesteel asuva vana elektrijaama tööstusmiljööst ja hoonetest, kuhu kolib kultuuritehas Polymer. Katlamaja plaanitakse avada augustis mitmepäevase festivaliga

  9. FTO genotype is associated with phenotypic variability of body mass index

    NARCIS (Netherlands)

    Yang, J.; Loos, R.J.; Powell, J.E.; Medland, S.E.; Speliotes, E.K.; Chasman, D.I.; Rose, L.M.; Thorleifsson, G.; Steinthorsdottir, V.; Mägi, R.; Waite, L.; Smith, A.V.; Yerges-Armstrong, L.M.; Monda, K.L.; Hadley, D.; Mahajan, A.; Li, G.; Kapur, K.; Vitart, V.; Huffman, J.E.; Wang, S.R.; Palmer, C.; Esko, T.; Fischer, K.; Zhao, J.H.; Demirkan, A.; Isaacs, A.; Feitosa, M.F.; Luan, J.; Heard-Costa, N.L.; White, C.; Jackson, A.U.; Preuss, M; Ziegler, A.; Eriksson, J.; Kutalik, Z.; Frau, F.; Nolte, I.M.; van Vliet-Ostaptchouk, J.V.; Hottenga, J.J.; Jacobs, K.B.; Verweij, N.; Goel, A.; Medina-Gomez, C.; Estrada, K.; Bragg-Gresham, J.L.; Sanna, S.; Sidore, C.; Tyrer, J.; Teumer, A.; Prokopenko, I.; Mangino, M.; Lindgren, C.M.; Assimes, T.L.; Shuldiner, A.R.; Hui, J.; Beilby, J.P.; McArdle, W.L.; Hall, P.; Haritunians, T.; Zgaga, L.; Kolcic, I.; Polasek, O.; Zemunik, T.; Oostra, B.A.; Junttila, M.J.; Grönberg, H.; Schreiber, S; Peters, A.; Hicks, A.A.; Stephens, J.; Foad, N.S.; Laitinen, J.; Pouta, A.; Kaakinen, M.; Willemsen, G.; Vink, J.M.; Wild, S.H.; Navis, G.; Asselbergs, F.W.; Homuth, G.; John, U.; Iribarren, C.; Harris, T.; Launer, L.J.; Gudnason, V.; O'Connell, J.R.; Boerwinkle, E.; Cadby, G.; Palmer, L.J.; James, A.L.; Musk, A.W.; Ingelsson, E.; Psaty, B.M.; Beckmann, J.S.; Waeber, G.; Vollenweider, P.; Hayward, C.; Wright, A.F.; Rudan, I.; Groop, L.C.; Metspalu, A.; Thee Khaw, K.; van Duijn, C.M.; Borecki, I.B.; Province, M.A.; Wareham, N.J.; Tardif, J.C.; Huikuri, H.V.; Cupples, L.A.; Atwood, L.D.; Fox, C.S.; Boehnke, M.; Collins, F.S.; Mohlke, K.L.; Erdmann, J.; Schunkert, H.; Hengstenberg, C.; Stark, K.; Lorentzon, M.; Ohlsson, C.; Cusi, D.; Staessen, J.A.; van der Klauw, M.M.; Pramstaller, P.P.; Kathiresan, S.; Jolley, D.J.; Ripatti, S.; Jarvelin, M.-R.; de Geus, E.J.C.; Boomsma, D.I.; Penninx, B.W.J.H.; Wilson, J.F.; Campbell, H.; Chanock, S.J.; van der Harst, P.; Hamsten, A.; Watkins, H.; Hofman, A.; Witteman, J.C.; Zillikens, M.C.; Uitterlinden, A.G.; Rivadeneira, F.; Kiemeney, L.A.; Vermeulen, S.H.; Abecasis, G.R.; Schlessinger, D.; Schipf, S.; Stumvoll, M.; Tönjes, A.; Spector, T.D.; North, K.E.; Lettre, G.; McCarthy, M.I.; Berndt, S.I.; Heath, A.C.; Madden, P.A.F.; Nyholt, DR; Montgomery, G.W.; Martin, N.G.; McKnight, B.; Strachan, D.P.; Hill, W.G.; Snieder, H.; Ridker, P.M.; Thorsteinsdottir, U.; Stefansson, K.; Frayling, T.M.; Hirschhorn, J.N.; Goddard, M.E.; Visscher, P.M.

    2012-01-01

    There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human

  10. Mining for genotype-phenotype relations in Saccharomyces using partial least squares

    Directory of Open Access Journals (Sweden)

    Sæbø Solve

    2011-08-01

    Full Text Available Abstract Background Multivariate approaches are important due to their versatility and applications in many fields as it provides decisive advantages over univariate analysis in many ways. Genome wide association studies are rapidly emerging, but approaches in hand pay less attention to multivariate relation between genotype and phenotype. We introduce a methodology based on a BLAST approach for extracting information from genomic sequences and Soft- Thresholding Partial Least Squares (ST-PLS for mapping genotype-phenotype relations. Results Applying this methodology to an extensive data set for the model yeast Saccharomyces cerevisiae, we found that the relationship between genotype-phenotype involves surprisingly few genes in the sense that an overwhelmingly large fraction of the phenotypic variation can be explained by variation in less than 1% of the full gene reference set containing 5791 genes. These phenotype influencing genes were evolving 20% faster than non-influential genes and were unevenly distributed over cellular functions, with strong enrichments in functions such as cellular respiration and transposition. These genes were also enriched with known paralogs, stop codon variations and copy number variations, suggesting that such molecular adjustments have had a disproportionate influence on Saccharomyces yeasts recent adaptation to environmental changes in its ecological niche. Conclusions BLAST and PLS based multivariate approach derived results that adhere to the known yeast phylogeny and gene ontology and thus verify that the methodology extracts a set of fast evolving genes that capture the phylogeny of the yeast strains. The approach is worth pursuing, and future investigations should be made to improve the computations of genotype signals as well as variable selection procedure within the PLS framework.

  11. The importance of environment on respiratory genotype/phenotype relationships in the Inuit

    DEFF Research Database (Denmark)

    Candelaria, P V; Backer, V; Khoo, S-K

    2010-01-01

    Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry.......Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry....

  12. Genotype-phenotype associations in children with congenital hyperinsulinism

    DEFF Research Database (Denmark)

    Melikyan, Maria; Brusgaard, Klaus; Petraykina, Elena

    Congenital hyperinsulinism (CHI) is a heterogeneous disease in terms of clinical presentation, genetics and histology. Mutations in eight genes are known to be a cause of CHI, of which ABCC8, KCNJ11 and GCK are among the most common. We investigated genotype-phenotype associations in a cohort...

  13. AMMI analysis to evaluate the adaptability and phenotypic stability of sugarcane genotypes

    Directory of Open Access Journals (Sweden)

    Luís Cláudio Inácio da Silveira

    2013-02-01

    Full Text Available Sugarcane (Saccharum sp. is one of the most important crops in Brazil. The high demand for sugarcane-derived products has stimulated the expansion of sugarcane cultivation in recent years, exploring different environments. The adaptability and the phenotypic stability of sugarcane genotypes in the Minas Gerais state, Brazil, were evaluated based on the additive main effects and multiplicative interaction (AMMI method. We evaluated 15 genotypes (13 clones and two checks: RB867515 and RB72454 in nine environments. The average of two cuttings for the variable tons of pol per hectare (TPH measure was used to discriminate genotypes. Besides the check RB867515 (20.44 t ha-1, the genotype RB987935 showed a high average TPH (20.71 t ha-1, general adaptability and phenotypic stability, and should be suitable for cultivation in the target region. The AMMI method allowed for easy visual identification of superior genotypes for each set of environments.

  14. Prantsuse kunstnikud asustasid vana tehase / Johannes Saar

    Index Scriptorium Estoniae

    Saar, Johannes, 1965-

    2002-01-01

    Prantsuse kunstnike (Delphine Reist, Laurent Faulon, Sebastien Perroud) ja viiuldaja Mathieu Werchowsky Tallinnas valminud installatsiooninäitus "Neli laulu Siivile" vanas Kalinini tehasehoones 7.-12. juunini

  15. The evolution of opsins and color vision: connecting genotype to a complex phenotype

    Directory of Open Access Journals (Sweden)

    Natasha I Bloch

    2016-09-01

    Full Text Available Dissecting the genetic basis of adaptive traits is key to our understanding of evolutionary processes. A major and essential step in the study of evolutionary genetics is drawing link between genotype and phenotype, which depends on the difficult process of defining the phenotype at different levels, from functional to organismal. Visual pigments are a key component of the visual system and their evolution could also provide important clues on the evolution of visual sensory system in response to sexual and natural selection. As a system in which genotype can be linked to phenotype, I will use visual pigments and color vision, particularly in birds, as a case of a complex phenotype. I aim to emphasize the difficulties in drawing the genotype-phenotype relationship for complex phenotypes and to highlight the challenges of doing so for color vision. The use of vision-based receiver models to quantify animal colors and patterns is increasingly important in many fields of evolutionary research, spanning studies of mate choice, predation, camouflage and sensory ecology. Given these models impact on evolution and ecology, it is important to provide other researchers with the opportunity to better understand animal vision and the corresponding advantages and limitations of these models.

  16. New insights into genotype-phenotype correlation for GLI3 mutations.

    Science.gov (United States)

    Démurger, Florence; Ichkou, Amale; Mougou-Zerelli, Soumaya; Le Merrer, Martine; Goudefroye, Géraldine; Delezoide, Anne-Lise; Quélin, Chloé; Manouvrier, Sylvie; Baujat, Geneviève; Fradin, Mélanie; Pasquier, Laurent; Megarbané, André; Faivre, Laurence; Baumann, Clarisse; Nampoothiri, Sheela; Roume, Joëlle; Isidor, Bertrand; Lacombe, Didier; Delrue, Marie-Ange; Mercier, Sandra; Philip, Nicole; Schaefer, Elise; Holder, Muriel; Krause, Amanda; Laffargue, Fanny; Sinico, Martine; Amram, Daniel; André, Gwenaelle; Liquier, Alain; Rossi, Massimiliano; Amiel, Jeanne; Giuliano, Fabienne; Boute, Odile; Dieux-Coeslier, Anne; Jacquemont, Marie-Line; Afenjar, Alexandra; Van Maldergem, Lionel; Lackmy-Port-Lis, Marylin; Vincent-Delorme, Catherine; Chauvet, Marie-Liesse; Cormier-Daire, Valérie; Devisme, Louise; Geneviève, David; Munnich, Arnold; Viot, Géraldine; Raoul, Odile; Romana, Serge; Gonzales, Marie; Encha-Razavi, Ferechte; Odent, Sylvie; Vekemans, Michel; Attie-Bitach, Tania

    2015-01-01

    The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS). PHS was first described as a lethal condition associating hypothalamic hamartoma, postaxial or central polydactyly, anal atresia and bifid epiglottis. Typical GCPS combines polysyndactyly of hands and feet and craniofacial features. Genotype-phenotype correlations have been found both for the location and the nature of GLI3 mutations, highlighting the bifunctional nature of GLI3 during development. Here we report on the molecular and clinical study of 76 cases from 55 families with either a GLI3 mutation (49 GCPS and 21 PHS), or a large deletion encompassing the GLI3 gene (6 GCPS cases). Most of mutations are novel and consistent with the previously reported genotype-phenotype correlation. Our results also show a correlation between the location of the mutation and abnormal corpus callosum observed in some patients with GCPS. Fetal PHS observations emphasize on the possible lethality of GLI3 mutations and extend the phenotypic spectrum of malformations such as agnathia and reductional limbs defects. GLI3 expression studied by in situ hybridization during human development confirms its early expression in target tissues.

  17. Genotypic and phenotypic aspects of primary immunodeficiency diseases of the lymphoid system

    NARCIS (Netherlands)

    J.G. Noordzij

    2002-01-01

    textabstractThis thesis focuses on the immunological phenotype, the mutation analysis, and the residual activity of mutated proteins in patients with PID of the lymphoid system. During this project, we have investigated possible genotype-(immuno)phenotype relationships in patients with antibody

  18. Impact of VANA academic-practice partnership participation on educational mobility decisions and teaching aspirations of nurses.

    Science.gov (United States)

    Wyte-Lake, Tamar; Bowman, Candice; Needleman, Jack; Dougherty, Mary; Scarrott, Diana N; Dobalian, Aram

    2014-01-01

    This study reports findings assessing the influence of the Department of Veterans Affairs Nursing Academy (VANA) academic-practice partnership program on nurse decision making regarding educational mobility and teaching aspirations. We conducted national surveys with nursing faculty from VANA partnership sites in 2011 (N = 133) and 2012 (N = 74). Faculty who spent more hours per week in the VANA role and who reported an increase in satisfaction with their participation in VANA were more likely to have been influenced by their VANA experience in choosing to pursue a higher degree (p academic-practice partnerships grows and their list of benefits is further enumerated, motivating nurses to pursue both higher degrees and faculty roles should be listed among them based on results reported here. Published by Elsevier Inc.

  19. [Mexican phenotype and genotype Vibrio cholerae 01].

    Science.gov (United States)

    Giono, S; Gutiérrez Cogno, L; Rodríguez Angeles, G; del Rio Zolezzi, A; Valdespino González, J L; Sepúlveda Amor, J

    1995-01-01

    This paper presents the phenotypical and genotypical characterization of 26922 Vibrio cholerae 01 strains isolated in Mexico from 1991 to 1993. All strains isolated were El Tor biovar. Strains were sensitive to antibiotics excluding furazolidone, streptomycin and sulfisoxasole to which we found resistance in 97% and we are using this characteristic as epidemiological markers. We detected a marked change in frequency of Inaba serotype from 1991, when it was dominant, with 99.5%, until 1992 when Ogawa serotype turned to be dominant with 95% of isolates. All Vibrio cholerae 01 strains, except one Ogawa strain, were to igenic, and V. choleraeno 01 were not toxigenic by ELISA, PCR and cell culture tests. Dominant ribotype was 5, but we found some strains with 6a pattern and two with ribotype 12. We are searching for ribotype 2 among hemolytic strains in order to learn if there is any relation to Gulf Coast strains prevalent in the USA, but until now we have not found any V. cholerae ribotype 2 in our isolates. Even if rapid tests are recommended for immediate diagnosis of cholera, it is necessary to continue bacterial isolation in order to have strains for phenotyping and genotyping studies that may support epidemiological analysis.

  20. Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

    Science.gov (United States)

    Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

    2016-08-01

    Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

  1. Diagnostic Challenges in Retinitis Pigmentosa: Genotypic Multiplicity and Phenotypic Variability

    Science.gov (United States)

    Chang, Susie; Vaccarella, Leah; Olatunji, Sunday; Cebulla, Colleen; Christoforidis, John

    2011-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders. Diagnosis can be challenging as more than 40 genes are known to cause non-syndromic RP and phenotypic expression can differ significantly resulting in variations in disease severity, age of onset, rate of progression, and clinical findings. We describe the clinical manifestations of RP, the more commonly known causative gene mutations, and the genotypic-phenotypic correlation of RP. PMID:22131872

  2. The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species

    International Nuclear Information System (INIS)

    Mungall, Christopher J.; McMurry, Julie A.; Köhler, Sebastian; Balhoff, James P.; Borromeo, Charles

    2016-01-01

    The correlation of phenotypic outcomes with genetic variation and environmental factors is a core pursuit in biology and biomedicine. Numerous challenges impede our progress: patient phenotypes may not match known diseases, candidate variants may be in genes that have not been characterized, model organisms may not recapitulate human or veterinary diseases, filling evolutionary gaps is difficult, and many resources must be queried to find potentially significant genotype-phenotype associations. Nonhuman organisms have proven instrumental in revealing biological mechanisms. Advanced informatics tools can identify phenotypically relevant disease models in research and diagnostic contexts. Large-scale integration of model organism and clinical research data can provide a breadth of knowledge not available from individual sources and can provide contextualization of data back to these sources. The Monarch Initiative (monarchinitiative.org) is a collaborative, open science effort that aims to semantically integrate genotype-phenotype data from many species and sources in order to support precision medicine, disease modeling, and mechanistic exploration. Our integrated knowledge graph, analytic tools, and web services enable diverse users to explore relationships between phenotypes and genotypes across species.

  3. Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia

    Science.gov (United States)

    Battistella, Giovanni; Fuertinger, Stefan; Fleysher, Lazar; Ozelius, Laurie J.; Simonyan, Kristina

    2017-01-01

    Background Spasmodic dysphonia (SD), or laryngeal dystonia, is a task-specific isolated focal dystonia of unknown causes and pathophysiology. Although functional and structural abnormalities have been described in this disorder, the influence of its different clinical phenotypes and genotypes remains scant, making it difficult to explain SD pathophysiology and to identify potential biomarkers. Methods We used a combination of independent component analysis and linear discriminant analysis of resting-state functional MRI data to investigate brain organization in different SD phenotypes (abductor vs. adductor type) and putative genotypes (familial vs. sporadic cases) and to characterize neural markers for genotype/phenotype categorization. Results We found abnormal functional connectivity within sensorimotor and frontoparietal networks in SD patients compared to healthy individuals as well as phenotype- and genotype-distinct alterations of these networks, involving primary somatosensory, premotor and parietal cortices. The linear discriminant analysis achieved 71% accuracy classifying SD and healthy individuals using connectivity measures in the left inferior parietal and sensorimotor cortex. When categorizing between different forms of SD, the combination of measures from left inferior parietal, premotor and right sensorimotor cortices achieved 81% discriminatory power between familial and sporadic SD cases, whereas the combination of measures from the right superior parietal, primary somatosensory and premotor cortices led to 71% accuracy in the classification of adductor and abductor SD forms. Conclusions Our findings present the first effort to identify and categorize isolated focal dystonia based on its brain functional connectivity profile, which may have a potential impact on the future development of biomarkers for this rare disorder. PMID:27346568

  4. Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia.

    Science.gov (United States)

    Battistella, G; Fuertinger, S; Fleysher, L; Ozelius, L J; Simonyan, K

    2016-10-01

    Spasmodic dysphonia (SD), or laryngeal dystonia, is a task-specific isolated focal dystonia of unknown causes and pathophysiology. Although functional and structural abnormalities have been described in this disorder, the influence of its different clinical phenotypes and genotypes remains scant, making it difficult to explain SD pathophysiology and to identify potential biomarkers. We used a combination of independent component analysis and linear discriminant analysis of resting-state functional magnetic resonance imaging data to investigate brain organization in different SD phenotypes (abductor versus adductor type) and putative genotypes (familial versus sporadic cases) and to characterize neural markers for genotype/phenotype categorization. We found abnormal functional connectivity within sensorimotor and frontoparietal networks in patients with SD compared with healthy individuals as well as phenotype- and genotype-distinct alterations of these networks, involving primary somatosensory, premotor and parietal cortices. The linear discriminant analysis achieved 71% accuracy classifying SD and healthy individuals using connectivity measures in the left inferior parietal and sensorimotor cortices. When categorizing between different forms of SD, the combination of measures from the left inferior parietal, premotor and right sensorimotor cortices achieved 81% discriminatory power between familial and sporadic SD cases, whereas the combination of measures from the right superior parietal, primary somatosensory and premotor cortices led to 71% accuracy in the classification of adductor and abductor SD forms. Our findings present the first effort to identify and categorize isolated focal dystonia based on its brain functional connectivity profile, which may have a potential impact on the future development of biomarkers for this rare disorder. © 2016 EAN.

  5. Genotypic and phenotypic diversity of Alicyclobacillus acidocaldarius isolates.

    Science.gov (United States)

    Félix-Valenzuela, L; Guardiola-Avila, I; Burgara-Estrella, A; Ibarra-Zavala, M; Mata-Haro, V

    2015-10-01

    The fruit juice industry recognizes Alicyclobacillus as a major quality control target micro-organism. In this study, we analysed 19 bacterial isolates to identify Alicyclobacillus species by polymerase chain reaction (PCR) and sequencing analyses. Phenotypic and genomic diversity among isolates were investigated by API 50CHB system and ERIC-PCR (enterobacterial repetitive intergenic consensus-PCR) respectively. All bacterial isolates were identified as Alicyclobacillus acidocaldarius, and almost all showed identical DNA sequences according to their 16S rRNA (rDNA) gene partial sequences. Only few carbohydrates were fermented by A. acidocaldarius isolates, and there was little variability in the biochemical profile. Genotypic fingerprinting of the A. acidocaldarius isolates showed high diversity, and clusters by ERIC-PCR were distinct to those obtained from the 16S rRNA gene phylogenetic tree. There was no correlation between phenotypic and genotypic variability in the A. acidocaldarius isolates analysed in this study. Detection of Alicyclobacillus strains is imperative in fruit concentrates and juices due to the production of guaiacol. Identification of the genera originates rejection of the product by processing industry. However, not all the Alicyclobacillus species are deteriorative and hence the importance to differentiate among them. In this study, partial 16S ribosomal RNA sequence alignment allowed the differentiation of species. In addition, ERIC-PCR was introduced for the genotypic characterization of Alicyclobacillus, as an alternative for differentiation among isolates from the same species. © 2015 The Society for Applied Microbiology.

  6. Genotypic character relationship and phenotypic path coefficient analysis in chili pepper genotypes grown under tropical condition.

    Science.gov (United States)

    Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Oladosu, Yusuff; Kashiani, Pedram

    2017-03-01

    Studies on genotypic and phenotypic correlations among characters of crop plants are useful in planning, evaluating and setting selection criteria for the desired characters in a breeding program. The present study aimed to estimate the phenotypic correlation coefficients among yield and yield attributed characters and to work out the direct and indirect effects of yield-related characters on yield per plant using path coefficient analysis. Twenty-six genotypes of chili pepper were laid out in a randomized complete block design with three replications. Yield per plant showed positive and highly significant (P ≤ 0.01) correlations with most of the characters studied at both the phenotypic and genotypic levels. By contrast, disease incidence and days to flowering showed a significant negative association with yield. Fruit weight and number of fruits exerted positive direct effect on yield and also had a positive and significant (P ≤ 0.01) correlation with yield per plant. However, fruit length showed a low negative direct effect with a strong and positive indirect effect through fruit weight on yield and had a positive and significant association with yield. Longer fruits, heavy fruits and a high number of fruits are variables that are related to higher yields of chili pepper under tropical conditions and hence could be used as a reliable indicator in indirect selection for yield. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  7. Phenotypic and genotypic variability of disc flower corolla length and nectar content in sunflower

    Directory of Open Access Journals (Sweden)

    Joksimović Jovan

    2003-01-01

    Full Text Available The nectar content and disc flower corolla length are the two most important parameters of attractiveness to pollinators in sunflower. The phenotypic and genotypic variability of these two traits was studied in four commercially important hybrids and their parental components in a trial with three fertilizer doses over two years. The results showed that, looking at individual genotypes, the variability of disc flower corolla length was affected the most by year (85.38-97.46%. As the study years were extremely different, the phenotypic variance of the hybrids and parental components was calculated for each year separately. In such conditions, looking at all of the crossing combinations, the largest contribution to phenotypic variance of the corolla length was that of genotype: 57.27-61.11% (NS-H-45 64.51-84.84% (Velja; 96.74-97.20% (NS-H-702 and 13.92-73.17% (NS-H-111. A similar situation was observed for the phenotypic variability of nectar content, where genotype also had the largest influence, namely 39.77-48.25% in NS-H-45; 39.06-42.51% in Velja; 31.97-72.36% in NS-H-702; and 62.13-94.96% in NS-H-111.

  8. Scene incongruity and attention.

    Science.gov (United States)

    Mack, Arien; Clarke, Jason; Erol, Muge; Bert, John

    2017-02-01

    Does scene incongruity, (a mismatch between scene gist and a semantically incongruent object), capture attention and lead to conscious perception? We explored this question using 4 different procedures: Inattention (Experiment 1), Scene description (Experiment 2), Change detection (Experiment 3), and Iconic Memory (Experiment 4). We found no differences between scene incongruity and scene congruity in Experiments 1, 2, and 4, although in Experiment 3 change detection was faster for scenes containing an incongruent object. We offer an explanation for why the change detection results differ from the results of the other three experiments. In all four experiments, participants invariably failed to report the incongruity and routinely mis-described it by normalizing the incongruent object. None of the results supports the claim that semantic incongruity within a scene invariably captures attention and provide strong evidence of the dominant role of scene gist in determining what is perceived. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. A “Forward Genomics” Approach Links Genotype to Phenotype using Independent Phenotypic Losses among Related Species

    Directory of Open Access Journals (Sweden)

    Michael Hiller

    2012-10-01

    Full Text Available Genotype-phenotype mapping is hampered by countless genomic changes between species. We introduce a computational “forward genomics” strategy that—given only an independently lost phenotype and whole genomes—matches genomic and phenotypic loss patterns to associate specific genomic regions with this phenotype. We conducted genome-wide screens for two metabolic phenotypes. First, our approach correctly matches the inactivated Gulo gene exactly with the species that lost the ability to synthesize vitamin C. Second, we attribute naturally low biliary phospholipid levels in guinea pigs and horses to the inactivated phospholipid transporter Abcb4. Human ABCB4 mutations also result in low phospholipid levels but lead to severe liver disease, suggesting compensatory mechanisms in guinea pig and horse. Our simulation studies, counts of independent changes in existing phenotype surveys, and the forthcoming availability of many new genomes all suggest that forward genomics can be applied to many phenotypes, including those relevant for human evolution and disease.

  10. Genotype-Phenotype Correlation of Maternally Inherited Disorders due to Mutations in Mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Peterus Thajeb

    2006-09-01

    Full Text Available Mitochondrial disorders are heterogeneous systemic ailments that are most often caused by maternal inheritance of a variety of mutations of the mitochondrial (mt DNA. Paternal inheritance and somatic mutation are rare. The disorders are well recognized not only for the genotypic heterogeneity, but also the phenotypic variation among the affected members of a single family. The genotype-phenotype correlation of the diversity of the syndromic and non-syndromic features of mitochondrial disorders are discussed. Some aspects of the molecular mechanisms of this heterogeneity, and the histopathologic findings are highlighted.

  11. Phenotype/genotype correlations in Gaucher disease type 1: Clinical and therapeutic implications

    Energy Technology Data Exchange (ETDEWEB)

    Sibille, A.; Eng, C.M.; Kim, S.J.; Pastores, G. (Mount Sinai School of Medicine, New York, NY (United States)); Grabowski, G.A. (Mount Sinai School of Medicine, New York, NY (United States) Univ. of Cincinnati, OH (United States))

    1993-06-01

    Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among Ashkenazi Jews. Gaucher disease type 1 is characterized by marked variability of the phenotype and by the absence of neuronopathic involvement. To test the hypothesis that this phenotypic variability was due to genetic compounds of several different mutant alleles, 161 symptomatic patients with Gaucher disease type 1 (> 90% Ashkenazi Jewish) were analyzed for clinical involvement, and their genotypes were determined. Qualitative and quantitative measures of disease involvement included age at onset of the disease manifestations, hepatic and splenic volumes, age at splenectomy, and severity of bony disease. High statistically significant differences (P < .005) were found in each clinical parameter in patients with the N370S/N370S genotype compared with those patients with the N370S/84GG, N370S/L444P, and N370/ genotypes. The symptomatic N370S homozygotes had onset of their disease two to three decades later than patients with the other genotypes. In addition, patients with the latter genotypes have much more severely involved livers, spleens, and bones and had a higher incidence of splenectomy at an earlier age. These predictive genotype analyses provide the basis for genetic care delivery and therapeutic recommendations in patients affected with Gaucher disease type 1. 38 refs., 1 fig., 4 tabs.

  12. Using Dendritic Heat Maps to Simultaneously Display Genotype Divergence with Phenotype Divergence.

    Science.gov (United States)

    Kellom, Matthew; Raymond, Jason

    2016-01-01

    The advancement of techniques to visualize and analyze large-scale sequencing datasets is an area of active research and is rooted in traditional techniques such as heat maps and dendrograms. We introduce dendritic heat maps that display heat map results over aligned DNA sequence clusters for a range of clustering cutoffs. Dendritic heat maps aid in visualizing the effects of group differences on clustering hierarchy and relative abundance of sampled sequences. Here, we artificially generate two separate datasets with simplified mutation and population growth procedures with GC content group separation to use as example phenotypes. In this work, we use the term phenotype to represent any feature by which groups can be separated. These sequences were clustered in a fractional identity range of 0.75 to 1.0 using agglomerative minimum-, maximum-, and average-linkage algorithms, as well as a divisive centroid-based algorithm. We demonstrate that dendritic heat maps give freedom to scrutinize specific clustering levels across a range of cutoffs, track changes in phenotype inequity across multiple levels of sequence clustering specificity, and easily visualize how deeply rooted changes in phenotype inequity are in a dataset. As genotypes diverge in sample populations, clusters are shown to break apart into smaller clusters at higher identity cutoff levels, similar to a dendrogram. Phenotype divergence, which is shown as a heat map of relative abundance bin response, may or may not follow genotype divergences. This joined view highlights the relationship between genotype and phenotype divergence for treatment groups. We discuss the minimum-, maximum-, average-, and centroid-linkage algorithm approaches to building dendritic heat maps and make a case for the divisive "top-down" centroid-based clustering methodology as being the best option visualize the effects of changing factors on clustering hierarchy and relative abundance.

  13. Using Dendritic Heat Maps to Simultaneously Display Genotype Divergence with Phenotype Divergence.

    Directory of Open Access Journals (Sweden)

    Matthew Kellom

    Full Text Available The advancement of techniques to visualize and analyze large-scale sequencing datasets is an area of active research and is rooted in traditional techniques such as heat maps and dendrograms. We introduce dendritic heat maps that display heat map results over aligned DNA sequence clusters for a range of clustering cutoffs. Dendritic heat maps aid in visualizing the effects of group differences on clustering hierarchy and relative abundance of sampled sequences. Here, we artificially generate two separate datasets with simplified mutation and population growth procedures with GC content group separation to use as example phenotypes. In this work, we use the term phenotype to represent any feature by which groups can be separated. These sequences were clustered in a fractional identity range of 0.75 to 1.0 using agglomerative minimum-, maximum-, and average-linkage algorithms, as well as a divisive centroid-based algorithm. We demonstrate that dendritic heat maps give freedom to scrutinize specific clustering levels across a range of cutoffs, track changes in phenotype inequity across multiple levels of sequence clustering specificity, and easily visualize how deeply rooted changes in phenotype inequity are in a dataset. As genotypes diverge in sample populations, clusters are shown to break apart into smaller clusters at higher identity cutoff levels, similar to a dendrogram. Phenotype divergence, which is shown as a heat map of relative abundance bin response, may or may not follow genotype divergences. This joined view highlights the relationship between genotype and phenotype divergence for treatment groups. We discuss the minimum-, maximum-, average-, and centroid-linkage algorithm approaches to building dendritic heat maps and make a case for the divisive "top-down" centroid-based clustering methodology as being the best option visualize the effects of changing factors on clustering hierarchy and relative abundance.

  14. Genes homologous to glycopeptide resistance vanA are widespread in soil microbial communities

    DEFF Research Database (Denmark)

    Guardabassi, L.; Agersø, Yvonne

    2006-01-01

    -Ala : D-Ala ligase genes unrelated to vanA. In order to enhance detection of vanA-homologous genes, a third PCR step was added using primers targeting vanA in soil Paenibacillus. Sequencing of 25 clones obtained by this method allowed recovery of 23 novel sequences having 86-100% identity with van...

  15. Phenotypic and Genotypic Detection of Campylobacter jejuni at Local Chicken and Chicken Meat

    Directory of Open Access Journals (Sweden)

    A Rosyidi

    2010-05-01

    Full Text Available The Objective of this study was to identify the existence of Campylobacter jejuni based on phenotypic and genotypic characteristic in local chicken and chicken meats. Samples of local chicken intestine and meat were tested for the bacterial existence. Phenotypic examination was carried out by means of cultivation followed by gram staining and biochemical tests. Genotypic examination was conducted by polymerase chain reaction (PCR using genus specific16S rRNA gene at 816 bp and membrane-associated protein A (mapA gene at 589 bp as Campylobacter jejuni species-specific gene. The result of phenotypic detection revealed the existence of Campylobacter spp as gram negative, curved rod shape, oxidase positive, urease negative and motile. Genotypic examination also indicated the existence of bacteria using both primers. However, no Campylobacter jejuni detected from meat of the chickens. The results suggest that the method of PCR using a primer detecting species-specific gene of Campylobacter jejuni gives a rapid and accurate detection of the bacteria as compared to that using phenotypic and biochemical test. Identification of Campylobacter spp from chicken meats should be improved with enrichment method and sample collection. (Animal Production 12(2: 128-134 (2010Key Words: Campylobacter jejuni, mapA gene, local chicken

  16. Phenotype and genotype in 17 patients with Goltz-Gorlin syndrome.

    Science.gov (United States)

    Maas, S M; Lombardi, M P; van Essen, A J; Wakeling, E L; Castle, B; Temple, I K; Kumar, V K A; Writzl, K; Hennekam, Raoul C M

    2009-10-01

    Goltz-Gorlin syndrome or focal dermal hypoplasia is a highly variable, X-linked dominant syndrome with abnormalities of ectodermal and mesodermal origin. In 2007, mutations in the PORCN gene were found to be causative in Goltz-Gorlin syndrome. A series of 17 patients with Goltz-Gorlin syndrome is reported on, and their phenotype and genotype are described. In 14 patients (13 females and one male), a PORCN mutation was found. Mutations included nonsense (n = 5), frameshift (n = 2), aberrant splicing (n = 2) and missense (n = 5) mutations. No genotype-phenotype correlation was found. All patients with the classical features of the syndrome had a detectable mutation. In three females with atypical signs, no mutation was found. The male patient had classical features and showed mosaicism for a PORCN nonsense mutation in fibroblasts. Two affected sisters had a mutation not detectable in their parents, supporting germline mosaicism. Their father had undergone radiation for testicular cancer in the past. Two classically affected females had three severely affected female fetuses which all had midline thoracic and abdominal wall defects, resembling the pentalogy of Cantrell and the limb-body wall complex. Thoracic and abdominal wall defects were also present in two surviving patients. PORCN mutations can possibly cause pentalogy of Cantrell and limb-body wall complexes as well. Therefore, particularly in cases with limb defects, it seems useful to search for these. PORCN mutations can be found in all classically affected cases of Goltz-Gorlin syndrome, including males. Somatic and germline mosaicism occur. There is no evident genotype-phenotype correlation.

  17. Phenotypic and genotypic analysis of anti-tuberculosis drug resistance in Mycobacterium tuberculosis isolates in Myanmar.

    Science.gov (United States)

    Aung, Wah Wah; Ei, Phyu Win; Nyunt, Wint Wint; Swe, Thyn Lei; Lwin, Thandar; Htwe, Mi Mi; Kim, Kyung Jun; Lee, Jong Seok; Kim, Chang Ki; Cho, Sang Nae; Song, Sun Dae; Chang, Chulhun L

    2015-09-01

    Tuberculosis (TB) is one of the most serious health problems in Myanmar. Because TB drug resistance is associated with genetic mutation(s) relevant to responses to each drug, genotypic methods for detecting these mutations have been proposed to overcome the limitations of classic phenotypic drug susceptibility testing (DST). We explored the current estimates of drug-resistant TB and evaluated the usefulness of genotypic DST in Myanmar. We determined the drug susceptibility of Mycobacterium tuberculosis isolated from sputum smear-positive patients with newly diagnosed pulmonary TB at two main TB centers in Myanmar during 2013 by using conventional phenotypic DST and the GenoType MTBDRplus assay (Hain Lifescience, Germany). Discrepant results were confirmed by sequencing the genes relevant to each type of resistance (rpoB for rifampicin; katG and inhA for isoniazid). Of 191 isolates, phenotypic DST showed that 27.7% (n=53) were resistant to at least one first-line drug and 20.9% (n=40) were resistant to two or more, including 18.3% (n=35) multidrug-resistant TB (MDR-TB) strains. Monoresistant strains accounted for 6.8% (n=13) of the samples. Genotypic assay of 189 isolates showed 17.5% (n=33) MDR-TB and 5.3% (n=10) isoniazid-monoresistant strains. Genotypic susceptibility results were 99.5% (n=188) concordant and agreed almost perfectly with phenotypic DST (kappa=0.99; 95% confidence interval 0.96-1.01). The results highlight the burden of TB drug resistance and prove the usefulness of the genotypic DST in Myanmar.

  18. Raimo Pullati XX "Vana Tallinn" / Tõnis Liibek

    Index Scriptorium Estoniae

    Liibek, Tõnis

    2009-01-01

    Ilmus professor Raimo Pullati poolt välja antava linnaajalugu ja -kultuuri tutvustava sarja "Vana Tallinn" XX köide. Tšehhi Teaduste Akadeemia raamatukogus toimus Raimo Pullati poolt välja antud entsüklopeedilise suurteose "Johann Christoph Brotze. Estonica" esitlus

  19. Genetic parameters, phenotypic, genotypic and environmental correlations and genetic variability on sunflower in the Brazilian Savannah

    Directory of Open Access Journals (Sweden)

    Ellen Grippi Lira

    Full Text Available ABSTRACT: Sunflower (Helianthus annuus L. is an annual crop that stands out for its production of high quality oil and for an efficient selection, being necessary to estimate the components of genetic and phenotypic variance. This study aimed to estimate genetic parameters, phenotypic, genotypic and environmental correlations and genetic variability on sunflower in the Brazilian Savannah, evaluating the characters grain yield (YIELD, days to start flowering (DFL based on flowering date in R5, chapter length (CL, weight of a thousand achenes (WTA, plant height (H and oil content (OilC of 16 sunflower genotypes. The experiment was conducted at Embrapa Cerrados, Planaltina, DF, situated at 15º 35’ 30”S latitude, 47º 42’ 30”W longitude and 1.007m above sea level, in soil classified as dystroferric Oxisol. The experimental design used was a complete randomized block with four replicates. The nature for the effects of genotypes and blocks was fixed. Except for the character chapter length, genetic variance was the main component of the phenotypic variance among the genotypes, indicating high genetic variability and experimental efficiency with proper environmental control. In absolute terms, the genetic correlations were superior to phenotypic and environmental. The high values reported for heritability and selective accuracy indicated efficiency of phenotypic selection. Results showed high genetic variability among genotypes, which may contribute to the genetic improvement of sunflower.

  20. Epidemiological markers in Neisseria meningitidis: an estimate of the performance of genotyping vs phenotyping

    DEFF Research Database (Denmark)

    Weis, N; Lind, I

    1998-01-01

    In order to estimate the performance of genotypic vs phenotypic characterization of Neisseria meningitidis, 2 methods, DNA fingerprinting and multilocus enzyme electrophoresis (MEE), were assessed as regards applicability, reproducibility and discriminating capacity. 50 serogroup B and 52 serogro......, and as applied in the study MEE was superior to DNA fingerprinting. Clusters of invasive strains were reliably identified by phenotyping alone, whereas determination of identity of carrier strains and an invasive strain required genotyping.......In order to estimate the performance of genotypic vs phenotypic characterization of Neisseria meningitidis, 2 methods, DNA fingerprinting and multilocus enzyme electrophoresis (MEE), were assessed as regards applicability, reproducibility and discriminating capacity. 50 serogroup B and 52 serogroup...... C Neisseria meningitidis strains from 96 patients with meningococcal disease and 22 serogroup C strains from healthy carriers were investigated. Both methods were 100% applicable to meningococcal strains and results of DNA fingerprinting as well as of MEE were reproducible. The number of types...

  1. Genotype-phenotype correlation in patients suspected of having Sotos syndrome

    NARCIS (Netherlands)

    de Boer, Lonneke; Kant, Sarina G.; Karperien, Marcel; van Beers, Lotte; Tjon, Jennifer; Vink, Geraldine R.; van Tol, Dewy; Dauwerse, Hans; le Cessie, Saskia; Beemer, Frits A.; van der Burgt, Ineke; Hamel, Ben C. J.; Hennekam, Raoul C.; Kuhnle, Ursula; Mathijssen, Inge B.; Veenstra-Knol, Hermine E.; Stumpel, Connie T. Schrander; Breuning, Martijn H.; Wit, Jan M.

    2004-01-01

    Background: Deletions and mutations in the NSD1 gene are the major cause of Sotos syndrome. We wanted to evaluate the genotype-phenotype correlation in patients suspected of having Sotos syndrome and determine the best discriminating parameters for the presence of a NSD1 gene alteration. Methods:

  2. Genotype-phenotype correlation in patients suspected of having sotos syndrome.

    NARCIS (Netherlands)

    Boer, L. de; Kant, S.; Karperien, M.; Beers, L. van; Tjon, J.; Vink, G.R.; Tol, D. van; Dauwerse, H.G.; Cessie, S. le; Beemer, F.A.; Burgt, C.J.A.M. van der; Hamel, B.C.J.; Hennekam, R.C.M.; Kuhnle, U.; Mathijssen, I.B.; Veenstra-Knol, H.E.; Stumpel, C.T.; Breuning, M.H.; Wit, J.M.

    2004-01-01

    BACKGROUND: Deletions and mutations in the NSD1 gene are the major cause of Sotos syndrome. We wanted to evaluate the genotype-phenotype correlation in patients suspected of having Sotos syndrome and determine the best discriminating parameters for the presence of a NSD1 gene alteration. METHODS:

  3. Genotypic and Phenotypic Analysis of Dairy Lactococcus lactis Biodiversity in Milk: Volatile Organic Compounds as Discriminating Markers

    Science.gov (United States)

    Dhaisne, Amandine; Guellerin, Maeva; Laroute, Valérie; Laguerre, Sandrine; Le Bourgeois, Pascal; Loubiere, Pascal

    2013-01-01

    The diversity of nine dairy strains of Lactococcus lactis subsp. lactis in fermented milk was investigated by both genotypic and phenotypic analyses. Pulsed-field gel electrophoresis and multilocus sequence typing were used to establish an integrated genotypic classification. This classification was coherent with discrimination of the L. lactis subsp. lactis bv. diacetylactis lineage and reflected clonal complex phylogeny and the uniqueness of the genomes of these strains. To assess phenotypic diversity, 82 variables were selected as important dairy features; they included physiological descriptors and the production of metabolites and volatile organic compounds (VOCs). Principal-component analysis (PCA) demonstrated the phenotypic uniqueness of each of these genetically closely related strains, allowing strain discrimination. A method of variable selection was developed to reduce the time-consuming experimentation. We therefore identified 20 variables, all associated with VOCs, as phenotypic markers allowing discrimination between strain groups. These markers are representative of the three metabolic pathways involved in flavor: lipolysis, proteolysis, and glycolysis. Despite great phenotypic diversity, the strains could be divided into four robust phenotypic clusters based on their metabolic orientations. Inclusion of genotypic diversity in addition to phenotypic characters in the classification led to five clusters rather than four being defined. However, genotypic characters make a smaller contribution than phenotypic variables (no genetic distances selected among the most contributory variables). This work proposes an original method for the phenotypic differentiation of closely related strains in milk and may be the first step toward a predictive classification for the manufacture of starters. PMID:23709512

  4. Novel EDA mutation in X-linked hypohidrotic ectodermal dysplasia and genotype-phenotype correlation.

    Science.gov (United States)

    Zeng, B; Lu, H; Xiao, X; Zhou, L; Lu, J; Zhu, L; Yu, D; Zhao, W

    2015-11-01

    X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by abnormalities of hair, teeth, and sweat glands, while non-syndromic hypodontia (NSH) affects only teeth. Mutations in Ectodysplasin A (EDA) underlie both XLHED and NSH. This study investigated the genetic causes of six hypohidrotic ectodermal dysplasia (HED) patients and genotype-phenotype correlation. The EDA gene of six patients with HED was sequenced. Bioinformatics analysis and structural modeling for the mutations were performed. The records of 134 patients with XLHED and EDA-related NSH regarding numbers of missing permanent teeth from this study and 20 articles were reviewed. Nonparametric tests were used to analyze genotype-phenotype correlations. In four of the six patients, we identified a novel mutation c.852T>G (p.Phe284Leu) and three reported mutations: c.467G>A (p.Arg156His), c.776C>A (p.Ala259Glu), and c.871G>A (p.Gly291Arg). They were predicted to be pathogenic by bioinformatics analysis and structural modeling. Genotype-phenotype correlation analysis revealed that truncating mutations were associated with more missing teeth. Missense mutations and the mutations affecting the TNF homology domain were correlated with fewer missing teeth. This study extended the mutation spectrum of XLHED and revealed the relationship between genotype and the number of missing permanent teeth. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Muinas-Hellase ja Vana-Egiptuse kultuuriseosed Gustav Teichmülleri nägemuses / Sergei Stadnikov

    Index Scriptorium Estoniae

    Stadnikov, Sergei, 1956-

    2007-01-01

    Vana-Kreeka filosoofia ja vana-egiptuse teoloogia seotusest Teichmülleri käsitluses, mis oli erandlik ja omanäoline, silmas pidades 19. saj. 70ndate aastate ideoloogilist situatsiooni saksa humnitaarteaduses. Herakleitosest kui ida-lääne kommunikatsiooni esindajast.

  6. Same MSH2 Gene Mutation But Variable Phenotypes in 2 Families With Lynch Syndrome: Two Case Reports and Review of Genotype-Phenotype Correlation.

    Science.gov (United States)

    Liccardo, Raffaella; De Rosa, Marina; Duraturo, Francesca

    2018-01-01

    Lynch syndrome is an autosomal dominant syndrome that can be subdivided into Lynch syndrome I, or site-specific colonic cancer, and Lynch syndrome II, or extracolonic cancers, particularly carcinomas of the stomach, endometrium, biliary and pancreatic systems, and urinary tract. Lynch syndrome is associated with point mutations and large rearrangements in DNA MisMatch Repair ( MMR ) genes. This syndrome shows a variable phenotypic expression in people who carry pathogenetic mutations. So far, a correlation in genotype-phenotype has not been definitely established. In this study, we describe 2 Lynch syndrome cases presenting with the same genotype but different phenotypes and discuss possible reasons for this.

  7. Genotypic and phenotypic diversity in populations of plant-probiotic Pseudomonas spp. colonizing roots

    Science.gov (United States)

    Picard, Christine; Bosco, Marco

    2008-01-01

    Several soil microorganisms colonizing roots are known to naturally promote the health of plants by controlling a range of plant pathogens, including bacteria, fungi, and nematodes. The use of theses antagonistic microorganisms, recently named plant-probiotics, to control plant-pathogenic fungi is receiving increasing attention, as they may represent a sustainable alternative to chemical pesticides. Many years of research on plant-probiotic microorganisms (PPM) have indicated that fluorescent pseudomonads producing antimicrobial compounds are largely involved in the suppression of the most widespread soilborne pathogens. Phenotype and genotype analysis of plant-probiotic fluorescent pseudomonads (PFP) have shown considerable genetic variation among these types of strains. Such variability plays an important role in the rhizosphere competence and the biocontrol ability of PFP strains. Understanding the mechanisms by which genotypic and phenotypic diversity occurs in natural populations of PFP could be exploited to choose those agricultural practices which best exploit the indigenous PFP populations, or to isolate new plant-probiotic strains for using them as inoculants. A number of different methods have been used to study diversity within PFP populations. Because different resolutions of the existing microbial diversity can be revealed depending on the approach used, this review first describes the most important methods used for the assessment of fluorescent Pseudomonas diversity. Then, we focus on recent data relating how differences in genotypic and phenotypic diversity within PFP communities can be attributed to geographic location, climate, soil type, soil management regime, and interactions with other soil microorganisms and host plants. It becomes evident that plant-related parameters exert the strongest influence on the genotypic and phenotypic variations in PFP populations.

  8. Phenotypic and genotypic characterization of Flavobacterium psychrophilum from Finnish fish farms

    DEFF Research Database (Denmark)

    Madetoja, J.; Hanninen, M.L.; Hirvela-Koski, V.

    2001-01-01

    Finnish isolates (n = 37) of Flavobacterium psychrophilum isolated from farmed salmonids were studied using phenotypic and genotypic characteristics. The characteristics of isolates were compared with the characteristics of Swedish and Estonian F. psychrophilum isolates and the type strain, F...

  9. Ambient temperature and genotype differentially affect developmental and phenotypic plasticity in Arabidopsis thaliana.

    Science.gov (United States)

    Ibañez, Carla; Poeschl, Yvonne; Peterson, Tom; Bellstädt, Julia; Denk, Kathrin; Gogol-Döring, Andreas; Quint, Marcel; Delker, Carolin

    2017-07-06

    Global increase in ambient temperatures constitute a significant challenge to wild and cultivated plant species. Forward genetic analyses of individual temperature-responsive traits have resulted in the identification of several signaling and response components. However, a comprehensive knowledge about temperature sensitivity of different developmental stages and the contribution of natural variation is still scarce and fragmented at best. Here, we systematically analyze thermomorphogenesis throughout a complete life cycle in ten natural Arabidopsis thaliana accessions grown under long day conditions in four different temperatures ranging from 16 to 28 °C. We used Q 10 , GxE, phenotypic divergence and correlation analyses to assess temperature sensitivity and genotype effects of more than 30 morphometric and developmental traits representing five phenotype classes. We found that genotype and temperature differentially affected plant growth and development with variing strengths. Furthermore, overall correlations among phenotypic temperature responses was relatively low which seems to be caused by differential capacities for temperature adaptations of individual accessions. Genotype-specific temperature responses may be attractive targets for future forward genetic approaches and accession-specific thermomorphogenesis maps may aid the assessment of functional relevance of known and novel regulatory components.

  10. Johani ja Anna-Liisa vana valge / Agneta Land-Koskinen

    Index Scriptorium Estoniae

    Land-Koskinen, Agneta

    2007-01-01

    Renoveeritud vanas majas asuv korter, kus seinad on valged, mis on antiiksetele esemetele ja huvitavatele disainileidudele parimaks taustaks. Kultusobjektideks valgustid, nende hulgas ka Verner Pantoni ja Louis Poulseni loomingut

  11. A rare CYP21A2 mutation in a congenital adrenal hyperplasia kindred displaying genotype-phenotype nonconcordance.

    Science.gov (United States)

    Khattab, Ahmed; Yuen, Tony; Al-Malki, Sultan; Yau, Mabel; Kazmi, Diya; Sun, Li; Harbison, Madeleine; Haider, Shozeb; Zaidi, Mone; New, Maria I

    2016-01-01

    Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is caused by the autosomal recessive inheritance of mutations in the gene CYP21A2. CYP21A2 mutations lead to variable impairment of the 21-hydroxylase enzyme, which, in turn, is associated with three clinical phenotypes, namely, salt wasting, simple virilizing, and nonclassical CAH. However, it is known that a given mutation can associate with different clinical phenotypes, resulting in a high rate of genotype-phenotype nonconcordance. We aimed to study the genotype-phenotype nonconcordance in a family with three siblings affected with nonclassical CAH. All had hormonal evidence of nonclassical CAH, but this phenotype could not be explained by the genotype obtained from commercial CYP21A2 genetic testing, which revealed heterozygosity for the maternal 30 kb deletion mutation. We performed Sanger sequencing of the entire CYP21A2 gene in this family to search for a rare mutation that was not covered by commercial testing and found in the three siblings a second, rare c.1097G>A (p.R366H) mutation in exon 8. Computational modeling confirmed that this was a mild mutation consistent with nonclassical CAH. We recommend that sequencing of entire genes for rare mutations should be carried out when genotype-phenotype nonconcordance is observed in patients with autosomal recessive monogenic disorders, including CAH. © 2015 New York Academy of Sciences.

  12. Assessing the value of phenotypic information from non-genotyped animals for QTL mapping of complex traits in real and simulated populations.

    Science.gov (United States)

    Melo, Thaise P; Takada, Luciana; Baldi, Fernando; Oliveira, Henrique N; Dias, Marina M; Neves, Haroldo H R; Schenkel, Flavio S; Albuquerque, Lucia G; Carvalheiro, Roberto

    2016-06-21

    QTL mapping through genome-wide association studies (GWAS) is challenging, especially in the case of low heritability complex traits and when few animals possess genotypic and phenotypic information. When most of the phenotypic information is from non-genotyped animals, GWAS can be performed using the weighted single-step GBLUP (WssGBLUP) method, which permits to combine all available information, even that of non-genotyped animals. However, it is not clear to what extent phenotypic information from non-genotyped animals increases the power of QTL detection, and whether factors such as the extent of linkage disequilibrium (LD) in the population and weighting SNPs in WssGBLUP affect the importance of using information from non-genotyped animals in GWAS. These questions were investigated in this study using real and simulated data. Analysis of real data showed that the use of phenotypes of non-genotyped animals affected SNP effect estimates and, consequently, QTL mapping. Despite some coincidence, the most important genomic regions identified by the analyses, either using or ignoring phenotypes of non-genotyped animals, were not the same. The simulation results indicated that the inclusion of all available phenotypic information, even that of non-genotyped animals, tends to improve QTL detection for low heritability complex traits. For populations with low levels of LD, this trend of improvement was less pronounced. Stronger shrinkage on SNPs explaining lower variance was not necessarily associated with better QTL mapping. The use of phenotypic information from non-genotyped animals in GWAS may improve the ability to detect QTL for low heritability complex traits, especially in populations in which the level of LD is high.

  13. Emergence of vanA Enterococcus faecium in Denmark, 2005-15

    DEFF Research Database (Denmark)

    Hammerum, Anette M; Baig, Sharmin; Kamel, Yasmin

    2017-01-01

    Objectives: To describe the changing epidemiology of vancomycin-resistant Enterococcus faecium and Enterococcus faecalis in clinical samples in Denmark 2005-15 according to species and van type, and, furthermore, to investigate the genetic relatedness of the clinical E. faecium isolates from 2015...... were detected along with 1 vanA E. faecalis and 1 vanB E. faecalis . cgMLST subdivided the 368 vanA E. faecium isolates into 33 cluster types (CTs), whereas the vanB E. faecium isolate belonged to a different CT. ST203-CT859 was most prevalent (51%), followed by ST80-CT14 (22%), ST117-CT24 (6%), ST80...

  14. Delineation of C12orf65-related phenotypes: a genotype-phenotype relationship.

    Science.gov (United States)

    Spiegel, Ronen; Mandel, Hanna; Saada, Ann; Lerer, Issy; Burger, Ayala; Shaag, Avraham; Shalev, Stavit A; Jabaly-Habib, Haneen; Goldsher, Dorit; Gomori, John M; Lossos, Alex; Elpeleg, Orly; Meiner, Vardiella

    2014-08-01

    C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families. In four family members affected with childhood-onset optic atrophy accompanied by slowly progressive peripheral neuropathy and spastic paraparesis, we identified a homozygous frame shift mutation c.413_417 delAACAA, which predicts a truncated protein lacking the C-terminal portion. In the second family, we studied three affected individuals who presented with early onset optic atrophy, peripheral neuropathy, and spastic gait in addition to moderate intellectual disability. Muscle biopsy in two of the patients revealed decreased activities of the mitochondrial respiratory chain complexes I and IV. In these patients, we identified a homozygous splice mutation, g.21043 T>A (c.282+2 T>A) which leads to skipping of exon 2. Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features. In addition, a clear genotype-phenotype correlation is anticipated in which deleterious mutations which disrupt the GGQ-containing domain in the first coding exon are expected to result in a more severe phenotype, whereas down-stream C-terminal mutations may result in a more favorable phenotype, typically lacking cognitive impairment.

  15. Integrative Genomics: Quantifying significance of phenotype-genotype relationships from multiple sources of high-throughput data

    Directory of Open Access Journals (Sweden)

    Eric eGamazon

    2013-05-01

    Full Text Available Given recent advances in the generation of high-throughput data such as whole genome genetic variation and transcriptome expression, it is critical to come up with novel methods to integrate these heterogeneous datasets and to assess the significance of identified phenotype-genotype relationships. Recent studies show that genome-wide association findings are likely to fall in loci with gene regulatory effects such as expression quantitative trait loci (eQTLs, demonstrating the utility of such integrative approaches. When genotype and gene expression data are available on the same individuals, we developed methods wherein top phenotype-associated genetic variants are prioritized if they are associated, as eQTLs, with gene expression traits that are themselves associated with the phenotype. Yet there has been no method to determine an overall p-value for the findings that arise specifically from the integrative nature of the approach. We propose a computationally feasible permutation method that accounts for the assimilative nature of the method and the correlation structure among gene expression traits and among genotypes. We apply the method to data from a study of cellular sensitivity to etoposide, one of the most widely used chemotherapeutic drugs. To our knowledge, this study is the first statistically sound quantification of the significance of the genotype-phenotype relationships resulting from applying an integrative approach. This method can be easily extended to cases in which gene expression data are replaced by other molecular phenotypes of interest, e.g., microRNA or proteomic data. This study has important implications for studies seeking to expand on genetic association studies by the use of omics data. Finally, we provide an R code to compute the empirical FDR when p-values for the observed and simulated phenotypes are available.

  16. Genetic analyses, phenotypic adaptability and stability in sugarcane genotypes for commercial cultivation in Pernambuco.

    Science.gov (United States)

    Dutra Filho, J A; Junior, T C; Simões Neto, D E

    2015-10-05

    In the present study, we assessed the agro-industrial performance of 22 sugarcane genotypes adaptable to edaphoclimatic conditions in production microregions in the State of Pernambuco, Brazil, and we recommended the commercial cultivation of select genotypes. The variables analyzed were as follows: sucrose percentage in cane juice, tonnage of saccharose per hectare (TPH), sugarcane tonnage per hectare (TCH), fiber, solid soluble contents, total recoverable sugar tonnage (ATR), and total recoverable sugar tonnage per hectare (ATR t/ha). A randomized block design with 4 repeats was used. Combined variance of the experiments, genetic parameter estimates, and environment stratification were analyzed. Phenotypic adaptability and stability were analyzed using the Annicchiarico and Wricke methods and analysis of variance. Genetic gain was estimated using the classic index and sum of ranks. Genotype selection was efficient for TPH, TCH, and ATR t/ha. Genotypes presented a great potential for improvement and a similar response pattern in Litoral Norte and Mata Sul microregions for TPH and TCH and Litoral Norte and Litoral Sul microregions for ATR t/ha. Genotypes SP78-4764, RB813804, and SP79-101 showed better productivity and phenotypic adaptability and stability, according to the Wricke and Annicchiarico methods. These genotypes can be recommended for cultivation in the sugarcane belt in the State of Pernambuco.

  17. The importance of environment on respiratory genotype/phenotype relationships in the Inuit

    DEFF Research Database (Denmark)

    Candelaria, P V; Backer, Vibeke; Khoo, S-K

    2010-01-01

    Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry....

  18. Investigating genotype-phenotype relationships in Rett syndrome using an international data set.

    Science.gov (United States)

    Bebbington, A; Anderson, A; Ravine, D; Fyfe, S; Pineda, M; de Klerk, N; Ben-Zeev, B; Yatawara, N; Percy, A; Kaufmann, W E; Leonard, H

    2008-03-11

    Rett syndrome is an uncommon neurodevelopmental disorder with an incidence of 1:9,000 live female births. The principal genetic cause was first reported in 1999 when the association with mutations in the methyl-CpG-binding protein 2 (or MECP2) gene was identified. This study uses data from a large international database, InterRett, to examine genotype-phenotype relationships and compares these with previous findings in a population-based cohort. The data set for these analyses was derived from a subset of InterRett cases with subject information collected from the family, the clinician, or both. Individual phenotypic characteristics and clinical severity using three scales were compared among those with eight known recurrent pathogenic MECP2 mutations as well as those with C-terminal deletions (n = 272). Overall, p.R270X and p.R255X were the most severe and p.R133C and p.R294X were the mildest mutations. Significant differences by mutation were seen for individual phenotypic characteristics such as hand use, ambulation, and language. This multicenter investigation into the phenotypic correlates of MECP2 mutations in Rett syndrome has provided a greater depth of understanding than hitherto available about the specific phenotypic characteristics associated with commonly occurring mutations. Although the modifying influence of X inactivation on clinical severity could not be included in the analysis, the findings confirm clear genotype-phenotype relationships in Rett syndrome and show the benefits of collaboration crucial to effective research in rare disorders.

  19. Effects of using phenotypic means and genotypic values in GGE biplot analyses on genotype by environment studies on tropical maize (Zea mays).

    Science.gov (United States)

    Granato, I S C; Fritsche-Neto, R; Resende, M D V; Silva, F F

    2016-10-05

    The objective of this study was to examine the effects of the type and intensity of nutritional stress, and of the statistical treatment of the data, on the genotype x environment (G x E) interaction for tropical maize (Zea mays). For this purpose, 39 hybrid combinations were evaluated under low- and high-nitrogen and -phosphorus availability. The plants were harvested at the V6 stage, and the shoot dry mass was estimated. The variance components and genetic values were assessed using the restricted maximum likelihood/best linear unbiased prediction method, and subsequently analyzed using the GGE biplot method. We observed differences in the performances of the hybrids depending on both the type and intensity of nutritional stress. The results of relationship between environments depended on whether genotypic values or phenotypic means were used. The selection of tropical maize genotypes against nutritional stress should be performed for each nutrient availability level within each type of nutritional stress. The use of phenotypic means for this purpose provides greater reliability than do genotypic values for the analysis of the G x E interaction using GGE biplot.

  20. Elucidating the genotype-phenotype map by automatic enumeration and analysis of the phenotypic repertoire.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Starting with a system's relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy.

  1. Stochastic switching in biology: from genotype to phenotype

    International Nuclear Information System (INIS)

    Bressloff, Paul C

    2017-01-01

    There has been a resurgence of interest in non-equilibrium stochastic processes in recent years, driven in part by the observation that the number of molecules (genes, mRNA, proteins) involved in gene expression are often of order 1–1000. This means that deterministic mass-action kinetics tends to break down, and one needs to take into account the discrete, stochastic nature of biochemical reactions. One of the major consequences of molecular noise is the occurrence of stochastic biological switching at both the genotypic and phenotypic levels. For example, individual gene regulatory networks can switch between graded and binary responses, exhibit translational/transcriptional bursting, and support metastability (noise-induced switching between states that are stable in the deterministic limit). If random switching persists at the phenotypic level then this can confer certain advantages to cell populations growing in a changing environment, as exemplified by bacterial persistence in response to antibiotics. Gene expression at the single-cell level can also be regulated by changes in cell density at the population level, a process known as quorum sensing. In contrast to noise-driven phenotypic switching, the switching mechanism in quorum sensing is stimulus-driven and thus noise tends to have a detrimental effect. A common approach to modeling stochastic gene expression is to assume a large but finite system and to approximate the discrete processes by continuous processes using a system-size expansion. However, there is a growing need to have some familiarity with the theory of stochastic processes that goes beyond the standard topics of chemical master equations, the system-size expansion, Langevin equations and the Fokker–Planck equation. Examples include stochastic hybrid systems (piecewise deterministic Markov processes), large deviations and the Wentzel–Kramers–Brillouin (WKB) method, adiabatic reductions, and queuing/renewal theory. The major aim of

  2. Adaptability and phenotypic stability of common bean genotypes through Bayesian inference.

    Science.gov (United States)

    Corrêa, A M; Teodoro, P E; Gonçalves, M C; Barroso, L M A; Nascimento, M; Santos, A; Torres, F E

    2016-04-27

    This study used Bayesian inference to investigate the genotype x environment interaction in common bean grown in Mato Grosso do Sul State, and it also evaluated the efficiency of using informative and minimally informative a priori distributions. Six trials were conducted in randomized blocks, and the grain yield of 13 common bean genotypes was assessed. To represent the minimally informative a priori distributions, a probability distribution with high variance was used, and a meta-analysis concept was adopted to represent the informative a priori distributions. Bayes factors were used to conduct comparisons between the a priori distributions. The Bayesian inference was effective for the selection of upright common bean genotypes with high adaptability and phenotypic stability using the Eberhart and Russell method. Bayes factors indicated that the use of informative a priori distributions provided more accurate results than minimally informative a priori distributions. According to Bayesian inference, the EMGOPA-201, BAMBUÍ, CNF 4999, CNF 4129 A 54, and CNFv 8025 genotypes had specific adaptability to favorable environments, while the IAPAR 14 and IAC CARIOCA ETE genotypes had specific adaptability to unfavorable environments.

  3. Vana Baskini teater mängib suvelavastust / Andris Tammela

    Index Scriptorium Estoniae

    Tammela, Andris

    2009-01-01

    Pärnu Kalevi staadionil ja Kilingi-Nõmme suveaias etenduvast Vana Baskini teatri suvekomöödiast "Hullem kui Hollywoodis". John Patricku näidendi lavastas Ivo Eensalu ja kujundas Kustav-Agu Püüman. Peaosas Helgi Sallo

  4. Genotype-Phenotype Relationship in Patients and Relatives with SHOX Region Anomalies in the French Population.

    Science.gov (United States)

    Auger, Julie; Baptiste, Amandine; Benabbad, Imane; Thierry, Gaëlle; Costa, Jean-Marc; Amouyal, Mélanie; Kottler, Marie-Laure; Leheup, Bruno; Touraine, Renaud; Schmitt, Sébastien; Lebrun, Marine; Cormier Daire, Valérie; Bonnefont, Jean-Paul; de Roux, Nicolas; Elie, Caroline; Rosilio, Myriam

    2016-01-01

    The aim of our study was to describe a large population with anomalies involving the SHOX region, responsible for idiopathic short stature and Léri-Weill dyschondrosteosis (LWD), and to identify a possible genotype/phenotype correlation. We performed a retrospective multicenter study on French subjects with a SHOX region anomaly diagnosed by multiplex ligation-dependent probe amplification or Sanger sequencing. Phenotypes were collected in each of the 7 genetic laboratories practicing this technique for SHOX analysis. Among 205 index cases and 100 related cases, 91.3% had LWD. For index cases, median age at evaluation was 11.7 (9.0; 15.9) years and mean height standard deviation score was -2.3 ± 1.1. A deletion of either SHOX or PAR1 or both was found in 74% of patients. Duplications and point mutations/indels affected 8 and 18% of the population, respectively. Genotype-phenotype correlation showed that deletions were more frequently associated with Madelung deformity and mesomelic shortening in girls, as well as with presence of radiologic anomalies, than duplications. Our results highlight genotype-phenotype relationships in the French population with a SHOX defect and provide new information showing that clinical expression is milder in cases of duplication compared to deletions. © 2016 S. Karger AG, Basel.

  5. CYP2D6 genotype and phenotype relationship in South Indians

    Directory of Open Access Journals (Sweden)

    Naveen A

    2006-01-01

    Full Text Available Background : Genotypes of the drug-metabolizing enzyme CYP2D6 influence plasma levels of 25% of commonlyprescribed drugs. This is the first study in India to investigate the genotype-phenotype relationship of CYP2D6. Aim : To study the influence of some CYP2D6 genotypes on the metabolism of its substrate dextromethorphanin healthy South Indian volunteers and to assess the contribution of the CYP2D6FNx0110 and CYP2D6FNx014 alleles. Materials and Methods : Twenty-six subjects from a previous CYP2D6 genotyping study of healthy volunteerswere included for phenotyping in this study. Selected volunteers belonged to any one of three genotype groups:Group I - two normal activity alleles, Group II - one reduced activity allele and one normal activity allele andGroup III - one loss of function allele along with either a wild type or reduced activity allele. Volunteers werephenotyped for the CYP2D6 enzyme using dextromethorphan as probe drug. Concentrations of the parent drugand metabolite dextrorphan were estimated using high performance liquid chromatography. Metabolic ratioswere calculated as the ratio of parent drug to metabolite in 0-8h urine samples. Statistical Analysis : Metabolic ratios from each genotype group were compared using the Mann-Whitney testat 5% significance, to observe their difference between genotype groups. Results : The mean metabolic ratios±SD in Groups I, II and III were 0.0039±0.0031, 0.0032±0.0017 and0.0391±0.0331 respectively. The mean metabolic ratio of Group III was significantly higher when comparedwith Groups I or II. In heterozygous individuals, the FNx011 or FNx012 alleles compensated for the reduced enzymeactivity due to the FNx0110 allele. However, if a heterozygous individual had a FNx014 allele, the reduced enzyme activitycould not be compensated by the FNx011 or FNx012 alleles. Conclusions : The CYP2D6 enzyme activity was found to be decreased in individuals carrying FNx014 or FNx015 alleles.The FNx011 or FNx

  6. Genotype and Phenotype of 101 Dutch Patients with Congenital Stationary Night Blindness

    NARCIS (Netherlands)

    Bijveld, M.M.C.; Florijn, R.J.; Bergen, A.A.B.; van den Born, L.I.; Kamermans, M.; Prick, L.; Riemslag, F.C.C.; van Schooneveld, M.J.; Kappers, A.M.L.; van Genderen, M.M.

    2013-01-01

    Objective: To investigate the relative frequency of the genetic causes of the Schubert-Bornschein type of congenital stationary night blindness (CSNB) and to determine the genotype-phenotype correlations in CSNB1 and CSNB2. Design: Clinic-based, longitudinal, multicenter study. Participants: A total

  7. Phenotype adaptability and stability of sugarcane genotypes in the sugarcane belt of the state of Pernambuco, Brazil.

    Science.gov (United States)

    Dutra Filho, J A; Junior, T C; Simões Neto, D E

    2014-08-29

    We assessed the agroindustrial performance of 25 sugarcane genotypes adapted to the edaphoclimatic conditions of the State of Pernambuco, Brazil, within the microregions Mata Norte, Mata Sul, Região Central, Litoral Norte, and Litoral Sul. The variables analyzed were POL tonnage per hectare, sugarcane tonnage per hectare, fiber and total recoverable sugar tonnage per hectare, using a randomized block design with four repetitions. Combined variance of experiments, genetic parameter estimates, decomposition of the genotype-environment interaction, and environment stratification were analyzed. Phenotype adaptability and stability were also analyzed. The various genotypes presented great potential for improvement and a similar response pattern to the microregions Centro and Mata Sul of the state of Pernambuco. Genotypes RB863129, RB867515, RB92579, RB953180, SP81-3250, RB75126, and RB942520 were better in productivity and phenotype adaptability and stability compared to genotypes RB892700, RB943365, SP79-1011, Q138, RB943538, SP78-4764, RB953281, RB943066, RB928064, RB93509, RB72454, RB952675, RB952991, RB943161, RB942898, RB872552, RB952900, and RB942849. These genotypes are recommended as cultivation options in the sugarcane belt in the state of Pernambuco, since they stand out in terms of phenotype adaptability and stability as evaluated using the method by Annicchiarico, Lin and Bins, and the method by Eberhart and Russel.

  8. Integrating Evolutionary Game Theory into Mechanistic Genotype-Phenotype Mapping.

    Science.gov (United States)

    Zhu, Xuli; Jiang, Libo; Ye, Meixia; Sun, Lidan; Gragnoli, Claudia; Wu, Rongling

    2016-05-01

    Natural selection has shaped the evolution of organisms toward optimizing their structural and functional design. However, how this universal principle can enhance genotype-phenotype mapping of quantitative traits has remained unexplored. Here we show that the integration of this principle and functional mapping through evolutionary game theory gains new insight into the genetic architecture of complex traits. By viewing phenotype formation as an evolutionary system, we formulate mathematical equations to model the ecological mechanisms that drive the interaction and coordination of its constituent components toward population dynamics and stability. Functional mapping provides a procedure for estimating the genetic parameters that specify the dynamic relationship of competition and cooperation and predicting how genes mediate the evolution of this relationship during trait formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Evaluation of rice genotypes under salt stress at the seedling and reproductive stages using phenotypic and molecular markers

    International Nuclear Information System (INIS)

    Rubel, M.H.; Hassan, L.

    2014-01-01

    Salinity screening for 27 rice genotypes was performed at the seedling and reproductive stages respectively, in the hydroponic system and in sustained water bath. Three selected SSR markers were used to determine salinity tolerance in rice genotypes. Phenotyping of the germplasm was done at EC 12dS/m and 6dS/m at seedling and reproductive stages, respectively. Based on modified standard evaluation score for visual salt injury at seedling stage, eight genotypes were salt tolerant, four were moderately tolerant and the rest fifteen were susceptible. At the reproductive stage, six genotypes were tolerant to EC 6dS/m whereas eleven of them were susceptible. SSR based marker identified seven genotypes as tolerant but ten of them were susceptible for all three markers compared to two checks. Six genotypes were tolerant in both phenotypic and SSR screening. The indentified salt tolerant genotypes can be potential germplasm sources for future breeding program. (author)

  10. Genotypic and phenotypic characterization of Chikungunya virus of different genotypes from Malaysia.

    Directory of Open Access Journals (Sweden)

    I-Ching Sam

    Full Text Available BACKGROUND: Mosquito-borne Chikungunya virus (CHIKV has recently re-emerged globally. The epidemic East/Central/South African (ECSA strains have spread for the first time to Asia, which previously only had endemic Asian strains. In Malaysia, the ECSA strain caused an extensive nationwide outbreak in 2008, while the Asian strains only caused limited outbreaks prior to this. To gain insight into these observed epidemiological differences, we compared genotypic and phenotypic characteristics of CHIKV of Asian and ECSA genotypes isolated in Malaysia. METHODS AND FINDINGS: CHIKV of Asian and ECSA genotypes were isolated from patients during outbreaks in Bagan Panchor in 2006, and Johor in 2008. Sequencing of the CHIKV strains revealed 96.8% amino acid similarity, including an unusual 7 residue deletion in the nsP3 protein of the Asian strain. CHIKV replication in cells and Aedes mosquitoes was measured by virus titration. There were no differences in mammalian cell lines. The ECSA strain reached significantly higher titres in Ae. albopictus cells (C6/36. Both CHIKV strains infected Ae. albopictus mosquitoes at a higher rate than Ae. aegypti, but when compared to each other, the ECSA strain had much higher midgut infection and replication, and salivary gland dissemination, while the Asian strain infected Ae. aegypti at higher rates. CONCLUSIONS: The greater ability of the ECSA strain to replicate in Ae. albopictus may explain why it spread far more quickly and extensively in humans in Malaysia than the Asian strain ever did, particularly in rural areas where Ae. albopictus predominates. Intergenotypic genetic differences were found at E1, E2, and nsP3 sites previously reported to be determinants of host adaptability in alphaviruses. Transmission of CHIKV in humans is influenced by virus strain and vector species, which has implications for regions with more than one circulating CHIKV genotype and Aedes species.

  11. Network Based Integrated Analysis of Phenotype-Genotype Data for Prioritization of Candidate Symptom Genes

    Directory of Open Access Journals (Sweden)

    Xing Li

    2014-01-01

    Full Text Available Background. Symptoms and signs (symptoms in brief are the essential clinical manifestations for individualized diagnosis and treatment in traditional Chinese medicine (TCM. To gain insights into the molecular mechanism of symptoms, we develop a computational approach to identify the candidate genes of symptoms. Methods. This paper presents a network-based approach for the integrated analysis of multiple phenotype-genotype data sources and the prediction of the prioritizing genes for the associated symptoms. The method first calculates the similarities between symptoms and diseases based on the symptom-disease relationships retrieved from the PubMed bibliographic database. Then the disease-gene associations and protein-protein interactions are utilized to construct a phenotype-genotype network. The PRINCE algorithm is finally used to rank the potential genes for the associated symptoms. Results. The proposed method gets reliable gene rank list with AUC (area under curve 0.616 in classification. Some novel genes like CALCA, ESR1, and MTHFR were predicted to be associated with headache symptoms, which are not recorded in the benchmark data set, but have been reported in recent published literatures. Conclusions. Our study demonstrated that by integrating phenotype-genotype relationships into a complex network framework it provides an effective approach to identify candidate genes of symptoms.

  12. Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome

    DEFF Research Database (Denmark)

    Maas, Saskia M; Shaw, Adam C; Bikker, Hennie

    2015-01-01

    it remained uncertain whether TRPS1 was partially or completely deleted. Main features defining the facial phenotype include fine and sparse hair, thick and broad eyebrows, especially the medial portion, a broad nasal ridge and tip, underdeveloped nasal alae, and a broad columella. The facial manifestations......, but haploinsufficiency of RAD21 is also likely to contribute. Genotype-phenotype studies showed that mutations located in exon 6 may have somewhat more pronounced facial characteristics and more marked shortening of hands and feet compared to mutations located elsewhere in TRPS1, but numbers are too small to allow firm...

  13. Plant phenomics and the need for physiological phenotyping across scales to narrow the genotype-to-phenotype knowledge gap

    DEFF Research Database (Denmark)

    Grosskinsky, Dominik Kilian; Svensgaard, Jesper; Christensen, Svend

    2015-01-01

    Plants are affected by complex genome×environment×management interactions which determine phenotypic plasticity as a result of the variability of genetic components. Whereas great advances have been made in the cost-efficient and high-throughput analyses of genetic information and non-invasive ph......Plants are affected by complex genome×environment×management interactions which determine phenotypic plasticity as a result of the variability of genetic components. Whereas great advances have been made in the cost-efficient and high-throughput analyses of genetic information and non......-invasive phenotyping, the large-scale analyses of the underlying physiological mechanisms lag behind. The external phenotype is determined by the sum of the complex interactions of metabolic pathways and intracellular regulatory networks that is reflected in an internal, physiological, and biochemical phenotype......, ultimately enabling the in silico assessment of responses under defined environments with advanced crop models. This will allow generation of robust physiological predictors also for complex traits to bridge the knowledge gap between genotype and phenotype for applications in breeding, precision farming...

  14. GENOTYPE-PHENOTYPE STUDY OF FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS TYPE 3

    OpenAIRE

    Sieni , Elena; Cetica , Valentina; Santoro , Alessandra; Beutel , Karin; Mastrodicasa , Elena; Meeths , Marie; Ciambotti , Benedetta; Brugnolo , Francesca; Zur Stadt , Udo; Pende , Daniela; Moretta , Lorenzo; Griffiths , Gillian M.; Henter , Jan-Inge; Janka , Gritta; Arico , Maurizio

    2011-01-01

    Abstract Background: Mutations of UNC13D are causative for FHL3 (OMIM 608898). We present a genotype-phenotype study of 845 FHL3 patients. Methods: A consortium of 3 countries planned to pool in a common database data on presenting features and mutations from individual patients with biallelic UNC13D mutations. Results: 845 FHL3 patients (median age: 4.1 months) were reported from Florence, Italy (n=54), Hamburg, Germany (n=18), Stockholm, Sweden (n=123). Their ethnic origi...

  15. Human Paraoxonase1 Hydrolysis of Nanomolar Chlorpyrifos-oxon Concentrations is Unaffected by Phenotype or Q192R Genotype

    Science.gov (United States)

    Coombes, R. Hunter; Meek, Edward C.; Dail, Mary Beth; Chambers, Howard W.; Chambers, Janice E.

    2016-01-01

    The organophosphorus insecticide chlorpyrifos has been widely used. Its active metabolite chlorpyrifos-oxon (CPO) is a potent anticholinesterase and is detoxified by paraoxonase-1 (PON1). PON1 activity is influenced by numerous factors including a Q192R polymorphism. Using forty human blood samples bearing homozygous genotypes and either high or low activity phenotypes (as determined by high concentration assays of paraoxon and diazoxon hydrolysis) the serum PON1 hydrolysis of high (320 μM) and low (178 nM) CPO concentrations was assessed using direct or indirect spectrophotometric methods, respectively. PON1 activity at high CPO concentration reflected the phenotype and genotype differences; subjects with the high activity phenotype and homozygous for the PON1R192 alloform hydrolyzed significantly more CPO than subjects with the low activity phenotype and/or PON1Q192 alloform (High RR=11023±722, Low RR=9467±798, High QQ=8809±672, Low QQ=6030±1015 μmoles CPO hydrolyzed/min/L serum). However, PON1 hydrolysis of CPO at the lower, more environmentally relevant concentration showed no significant differences between the PON1192 genotypes and/or between high and low activity phenotypes (High RR=231±27, Low RR=219±52, High QQ=193±59, Low QQ=185±43 nmoles CPO/min/L serum). Low CPO concentrations were probably not saturating, so PON1 did not display maximal velocity and the PON1 genotype/phenotype might not influence the extent of metabolism at environmental exposures. PMID:25093614

  16. A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry.

    Science.gov (United States)

    Papa, Riccardo; Doglio, Matteo; Lachmann, Helen J; Ozen, Seza; Frenkel, Joost; Simon, Anna; Neven, Bénédicte; Kuemmerle-Deschner, Jasmin; Ozgodan, Huri; Caorsi, Roberta; Federici, Silvia; Finetti, Martina; Trachana, Maria; Brunner, Jurgen; Bezrodnik, Liliana; Pinedo Gago, Mari Carmen; Maggio, Maria Cristina; Tsitsami, Elena; Al Suwairi, Wafaa; Espada, Graciela; Shcherbina, Anna; Aksu, Guzide; Ruperto, Nicolino; Martini, Alberto; Ceccherini, Isabella; Gattorno, Marco

    2017-10-18

    Hereditary recurrent fevers (HRF) are a group of rare monogenic diseases leading to recurrent inflammatory flares. A large number of variants has been described for the four genes associated with the best known HRF, namely MEFV, NLRP3, MVK, TNFRSF1A. The Infevers database ( http://fmf.igh.cnrs.fr/ISSAID/infevers ) is a large international registry collecting variants reported in these genes. However, no genotype-phenotype associations are provided, but only the clinical phenotype of the first patient(s) described for each mutation. The aim of this study is to develop a registry of genotype-phenotype associations observed in patients with HRF, enrolled and validated in the Eurofever registry. Genotype-phenotype associations observed in all the patients with HRF enrolled in the Eurofever registry were retrospectively analyzed. For autosomal dominant diseases (CAPS and TRAPS), all mutations were individually analyzed. For autosomal recessive diseases (FMF and MKD), homozygous and heterozygous combinations were described. Mean age of onset, disease course (recurrent or chronic), mean duration of fever episodes, clinical manifestations associated with fever episodes, atypical manifestations, complications and response to treatment were also studied. Data observed in 751 patients (346 FMF, 133 CAPS, 114 MKD, 158 TRAPS) included in the Eurofever registry and validated by experts were summarized in Tables. A total of 149 variants were described: 46 TNFRSF1A and 27 NLRP3 variants, as well as various combinations of 48 MVK and 28 MEFV variants were available. We provide a potentially useful tool for physicians dealing with HRF, namely a registry of genotype-phenotype associations for patients enrolled in the Eurofever registry. This tool is complementary to the Infevers database and will be available at the Eurofever and Infevers websites.

  17. Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?

    Science.gov (United States)

    Procopio, V; Manti, S; Bianco, G; Conti, G; Romeo, A; Maimone, F; Arrigo, T; Cutrupi, M C; Salpietro, C; Cuppari, C

    2018-01-30

    Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype-phenotype correlation of FMF disease. To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model. A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3. 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met680Ile/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680Ile/wt genotype reported the most severe clinical phenotype. p.Ala744Ser/wt, p.Glu148Gln/Met680Ile, p.Met680Ile/Met680Ile, p.Met680Ile/Met694Val, p.Pro369Ser/wt, p.Met694Ile/wt, p.Glu148Gln/Glu148Gln, p.Lys695Arg/wt resulted in 100% pathogenicity. The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. THE EVOLUTION OF OPSINS AND COLOR VISION: CONNECTING GENOTYPE TO A COMPLEX PHENOTYPE

    OpenAIRE

    BLOCH, Natasha I

    2016-01-01

    Dissecting the genetic basis of adaptive traits is key to our understanding of evolutionary processes. A major and essential step in the study of evolutionary genetics is drawing link between genotype and phenotype, which depends on the difficult process of defining the phenotype at different levels, from functional to organismal. Visual pigments are a key component of the visual system and their evolution could also provide important clues on the evolution of visual sensory system in respons...

  19. Cluster analysis in severe emphysema subjects using phenotype and genotype data: an exploratory investigation

    Directory of Open Access Journals (Sweden)

    Martinez Fernando J

    2010-03-01

    Full Text Available Abstract Background Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity. Methods We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster. Results We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1 post-bronchodilator FEV1 percent predicted, 2 percent bronchodilator responsiveness, and quantitative CT measurements of 3 apical emphysema and 4 airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1 emphysema predominant, 2 bronchodilator responsive, with higher FEV1; 3 discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4 airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant was associated with TGFB1 SNP rs1800470. Conclusions Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies.

  20. HFE genotype affects exosome phenotype in cancer.

    Science.gov (United States)

    Mrowczynski, Oliver D; Madhankumar, A B; Slagle-Webb, Becky; Lee, Sang Y; Zacharia, Brad E; Connor, James R

    2017-08-01

    Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. Tumor progression and recurrence is common with little understanding of mechanisms. A major recent focus in cancer biology is the impact of exosomes on metastatic behavior and the tumor microenvironment. Exosomes have been demonstrated to contribute to the oncogenic effect on the surrounding tumor environment and also mediate resistance to therapy. The effect of genotype on exosomal phenotype has not yet been explored. We interrogated exosomes from human neuroblastoma cells that express wild-type or mutant forms of the HFE gene. HFE, one of the most common autosomal recessive polymorphisms in the Caucasian population, originally associated with hemochromatosis, has also been associated with increased tumor burden, therapeutic resistance boost, and negative impact on patient survival. Herein, we demonstrate that changes in genotype cause major differences in the molecular and functional properties of exosomes; specifically, HFE mutant derived exosomes have increased expression of proteins relating to invasion, angiogenesis, and cancer therapeutic resistance. HFE mutant derived exosomes were also shown to transfer this cargo to recipient cells and cause an increased oncogenic functionality in those recipient cells. Copyright © 2017. Published by Elsevier B.V.

  1. Dental management of amelogenesis imperfecta patients: a primer on genotype-phenotype correlations.

    Science.gov (United States)

    Ng, F K; Messer, L B

    2009-01-01

    Amelogenesis imperfecta (AI) represents a group of hereditary conditions which affects enamel formation in the primary and permanent dentitions. Mutations in genes critical for amelogenesis result in diverse phenotypes characterized by variably thin and/or defective enamel. To date, mutations in 5 genes are known to cause AI in humans. Understanding the molecular etiologies and associated inheritance patterns can assist in the early diagnosis of this condition. Recognition of genotype-phenotype correlations will allow clinicians to guide genetic testing and select appropriate management strategies for patients who express different phenotypes. The purpose of this paper was to provide a narrative review of the current literature on amelogenesis imperfecta, particularly regarding recent advances in the identification of candidate genes and the patterns of inheritance.

  2. Application of Unmanned Aircraft Systems (UAS) for phenotypic mapping of white spruce genotypes along environmental gradients

    Science.gov (United States)

    D'Odorico, P.; Wong, C. Y.; Besik, A.; Earon, E.; Isabel, N.; Ensminger, I.

    2017-12-01

    Rapid climate change is expected to cause a mismatch between locally adapted tree populations and the optimal climatic conditions to which they have adapted. Plant breeding and reforestation programs will increasingly need to rely on high-throughput precision phenotyping tools for the selection of genotypes with increased drought and stress tolerance. In this work, we present the possibilities offered by Unmanned Aircraft Systems (UAS) carrying optical sensors to monitor and assess differences in performance among white spruce genotypes. While high-throughput precision phenotyping using UAS has gained traction in agronomic crop research during the last few years, to our knowledge it is still at its infancy in forestry applications. UAS surveys were performed at different times during the growing season over large white spruce common garden experiments established by the Canadian Forest Service at four different sites, each characterized by 2000 clonally replicated genotypes. Sites are distributed over a latitudinal gradient, in Ontario and Quebec, Canada. The UAS payload consisted of a custom-bands multispectral sensor acquiring radiation at wavelength at which the reflectance spectrum of vegetation is known to capture physiological change under disturbance and stress. Ground based tree-top spectral reflectances and leaf level functional traits were also acquired for validation purposes parallel to UAS surveys. We will discuss the potential and the challenges of using optical sensors on UAS to infer genotypic variation in tree response to stress events and show how spectral data can function as the link between large-scale phenotype and genotype data.

  3. Exploring causal networks underlying fat deposition and muscularity in pigs through the integration of phenotypic, genotypic and transcriptomic data.

    Science.gov (United States)

    Peñagaricano, Francisco; Valente, Bruno D; Steibel, Juan P; Bates, Ronald O; Ernst, Catherine W; Khatib, Hasan; Rosa, Guilherme J M

    2015-09-16

    Joint modeling and analysis of phenotypic, genotypic and transcriptomic data have the potential to uncover the genetic control of gene activity and phenotypic variation, as well as shed light on the manner and extent of connectedness among these variables. Current studies mainly report associations, i.e. undirected connections among variables without causal interpretation. Knowledge regarding causal relationships among genes and phenotypes can be used to predict the behavior of complex systems, as well as to optimize management practices and selection strategies. Here, we performed a multistep procedure for inferring causal networks underlying carcass fat deposition and muscularity in pigs using multi-omics data obtained from an F2 Duroc x Pietrain resource pig population. We initially explored marginal associations between genotypes and phenotypic and expression traits through whole-genome scans, and then, in genomic regions with multiple significant hits, we assessed gene-phenotype network reconstruction using causal structural learning algorithms. One genomic region on SSC6 showed significant associations with three relevant phenotypes, off-midline10th-rib backfat thickness, loin muscle weight, and average intramuscular fat percentage, and also with the expression of seven genes, including ZNF24, SSX2IP, and AKR7A2. The inferred network indicated that the genotype affects the three phenotypes mainly through the expression of several genes. Among the phenotypes, fat deposition traits negatively affected loin muscle weight. Our findings shed light on the antagonist relationship between carcass fat deposition and lean meat content in pigs. In addition, the procedure described in this study has the potential to unravel gene-phenotype networks underlying complex phenotypes.

  4. PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature

    Science.gov (United States)

    Reijnders, Margot R F; Janowski, Robert; Alvi, Mohsan; Self, Jay E; van Essen, Ton J; Vreeburg, Maaike; Rouhl, Rob P W; Stevens, Servi J C; Stegmann, Alexander P A; Schieving, Jolanda; Pfundt, Rolph; van Dijk, Katinke; Smeets, Eric; Stumpel, Connie T R M; Bok, Levinus A; Cobben, Jan Maarten; Engelen, Marc; Mansour, Sahar; Whiteford, Margo; Chandler, Kate E; Douzgou, Sofia; Cooper, Nicola S; Tan, Ene-Choo; Foo, Roger; Lai, Angeline H M; Rankin, Julia; Green, Andrew; Lönnqvist, Tuula; Isohanni, Pirjo; Williams, Shelley; Ruhoy, Ilene; Carvalho, Karen S; Dowling, James J; Lev, Dorit L; Sterbova, Katalin; Lassuthova, Petra; Neupauerová, Jana; Waugh, Jeff L; Keros, Sotirios; Clayton-Smith, Jill; Smithson, Sarah F; Brunner, Han G; van Hoeckel, Ceciel; Anderson, Mel; Clowes, Virginia E; Siu, Victoria Mok; DDD study, The; Selber, Paulo; Leventer, Richard J; Nellaker, Christoffer; Niessing, Dierk; Hunt, David; Baralle, Diana

    2018-01-01

    Background De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. Objectives To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. Methods Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotype-phenotype correlations by analysis of both recurrent mutations as well as mutation classes. Results We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. Conclusion We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and

  5. The role of HFE genotype in macrophage phenotype.

    Science.gov (United States)

    Nixon, Anne M; Neely, Elizabeth; Simpson, Ian A; Connor, James R

    2018-02-01

    Iron regulation is essential for cellular energy production. Loss of cellular iron homeostasis has critical implications for both normal function and disease progression. The H63D variant of the HFE gene is the most common gene variant in Caucasians. The resulting mutant protein alters cellular iron homeostasis and is associated with a number of neurological diseases and cancer. In the brain, microglial and infiltrating macrophages are critical to maintaining iron homeostasis and modulating inflammation associated with the pathogenic process in multiple diseases. This study addresses whether HFE genotype affects macrophage function and the implications of these findings for disease processes. Bone marrow macrophages were isolated from wildtype and H67D HFE knock-in mice. The H67D gene variant in mice is the human equivalent of the H63D variant. Upon differentiation, the macrophages were used to analyze iron regulatory proteins, cellular iron release, migration, phagocytosis, and cytokine expression. The results of this study demonstrate that the H67D HFE genotype significantly impacts a number of critical macrophage functions. Specifically, fundamental activities such as proliferation in response to iron exposure, L-ferritin expression in response to iron loading, secretion of BMP6 and cytokines, and migration and phagocytic activity were all found to be impacted by genotype. Furthermore, we demonstrated that exposure to apo-Tf (iron-poor transferrin) can increase the release of iron from macrophages. In normal conditions, 70% of circulating transferrin is unsaturated. Therefore, the ability of apo-Tf to induce iron release could be a major regulatory mechanism for iron release from macrophages. These studies demonstrate that the HFE genotype impacts fundamental components of macrophage phenotype that could alter their role in degenerative and reparative processes in neurodegenerative disorders.

  6. The effects of stabilizing and directional selection on phenotypic and genotypic variation in a population of RNA enzymes.

    Science.gov (United States)

    Hayden, Eric J; Bratulic, Sinisa; Koenig, Iwo; Ferrada, Evandro; Wagner, Andreas

    2014-02-01

    The distribution of variation in a quantitative trait and its underlying distribution of genotypic diversity can both be shaped by stabilizing and directional selection. Understanding either distribution is important, because it determines a population's response to natural selection. Unfortunately, existing theory makes conflicting predictions about how selection shapes these distributions, and very little pertinent experimental evidence exists. Here we study a simple genetic system, an evolving RNA enzyme (ribozyme) in which a combination of high throughput genotyping and measurement of a biochemical phenotype allow us to address this question. We show that directional selection, compared to stabilizing selection, increases the genotypic diversity of an evolving ribozyme population. In contrast, it leaves the variance in the phenotypic trait unchanged.

  7. Querying phenotype-genotype relationships on patient datasets using semantic web technology: the example of Cerebrotendinous xanthomatosis.

    Science.gov (United States)

    Taboada, María; Martínez, Diego; Pilo, Belén; Jiménez-Escrig, Adriano; Robinson, Peter N; Sobrido, María J

    2012-07-31

    Semantic Web technology can considerably catalyze translational genetics and genomics research in medicine, where the interchange of information between basic research and clinical levels becomes crucial. This exchange involves mapping abstract phenotype descriptions from research resources, such as knowledge databases and catalogs, to unstructured datasets produced through experimental methods and clinical practice. This is especially true for the construction of mutation databases. This paper presents a way of harmonizing abstract phenotype descriptions with patient data from clinical practice, and querying this dataset about relationships between phenotypes and genetic variants, at different levels of abstraction. Due to the current availability of ontological and terminological resources that have already reached some consensus in biomedicine, a reuse-based ontology engineering approach was followed. The proposed approach uses the Ontology Web Language (OWL) to represent the phenotype ontology and the patient model, the Semantic Web Rule Language (SWRL) to bridge the gap between phenotype descriptions and clinical data, and the Semantic Query Web Rule Language (SQWRL) to query relevant phenotype-genotype bidirectional relationships. The work tests the use of semantic web technology in the biomedical research domain named cerebrotendinous xanthomatosis (CTX), using a real dataset and ontologies. A framework to query relevant phenotype-genotype bidirectional relationships is provided. Phenotype descriptions and patient data were harmonized by defining 28 Horn-like rules in terms of the OWL concepts. In total, 24 patterns of SWQRL queries were designed following the initial list of competency questions. As the approach is based on OWL, the semantic of the framework adapts the standard logical model of an open world assumption. This work demonstrates how semantic web technologies can be used to support flexible representation and computational inference mechanisms

  8. Genotype-phenotype correlation in boys with X-linked hypohidrotic ectodermal dysplasia.

    Science.gov (United States)

    Burger, Kristin; Schneider, Anne-Theres; Wohlfart, Sigrun; Kiesewetter, Franklin; Huttner, Kenneth; Johnson, Ramsey; Schneider, Holm

    2014-10-01

    X-linked hypohidrotic ectodermal dysplasia (XLHED), the most frequent form of ectodermal dysplasia, is a genetic disorder of ectoderm development characterized by malformation of multiple ectodermal structures such as skin, hair, sweat and sebaceous glands, and teeth. The disease is caused by a broad spectrum of mutations in the gene EDA. Although XLHED symptoms show inter-familial and intra-familial variability, genotype-phenotype correlation has been demonstrated with respect to sweat gland function. In this study, we investigated to which extent the EDA genotype correlates with the severity of XLHED-related skin and hair signs. Nineteen male children with XLHED (age range 3-14 years) and seven controls (aged 6-14 years) were examined by confocal microscopy of the skin, quantification of pilocarpine-induced sweating, semi-quantitative evaluation of full facial photographs with respect to XLHED-related skin issues, and phototrichogram analysis. All eight boys with known hypomorphic EDA mutations were able to produce at least some sweat and showed less severe cutaneous signs of XLHED than the anhidrotic XLHED patients (e.g., perioral and periorbital eczema or hyperpigmentation, regional hyperkeratosis, characteristic wrinkles under the eyes). As expected, individuals with XLHED had significantly less and thinner hair than healthy controls. However, there were also significant differences in hair number, diameter, and other hair characteristics between the group with hypomorphic EDA mutations and the anhidrotic patients. In summary, this study indicated a remarkable genotype-phenotype correlation of skin and hair findings in prepubescent males with XLHED. © 2014 Wiley Periodicals, Inc.

  9. Cardio-facio-cutaneous syndrome: does genotype predict phenotype?

    Science.gov (United States)

    Allanson, Judith E; Annerén, Göran; Aoki, Yoki; Armour, Christine M; Bondeson, Marie-Louise; Cave, Helene; Gripp, Karen W; Kerr, Bronwyn; Nystrom, Anna-Maja; Sol-Church, Katia; Verloes, Alain; Zenker, Martin

    2011-05-15

    Cardio-facio-cutaneous (CFC) syndrome is a sporadic multiple congenital anomalies/mental retardation condition principally caused by mutations in BRAF, MEK1, and MEK2. Mutations in KRAS and SHOC2 lead to a phenotype with overlapping features. In approximately 10–30% of individuals with a clinical diagnosis of CFC, a mutation in one of these causative genes is not found. Cardinal features of CFC include congenital heart defects, a characteristic facial appearance, and ectodermal abnormalities. Additional features include failure to thrive with severe feeding problems, moderate to severe intellectual disability and short stature with relative macrocephaly. First described in 1986, more than 100 affected individuals are reported. Following the discovery of the causative genes, more information has emerged on the breadth of clinical features. Little, however, has been published on genotype–phenotype correlations. This clinical study of 186 children and young adults with mutation-proven CFC syndrome is the largest reported to date. BRAF mutations are documented in 140 individuals (approximately 75%), while 46 (approximately 25%) have a mutation in MEK 1 or MEK 2. The age range is 6 months to 32 years, the oldest individual being a female from the original report [Reynolds et al. (1986); Am J Med Genet 25:413–427]. While some clinical data on 136 are in the literature, 50 are not previously published. We provide new details of the breadth of phenotype and discuss the frequency of particular features in each genotypic group. Pulmonary stenosis is the only anomaly that demonstrates a statistically significant genotype–phenotype correlation, being more common in individuals with a BRAF mutation.

  10. Genotypes in relation to phenotypic appearance and exposure to environmental factors in Graves' hyperthyroidism

    NARCIS (Netherlands)

    Vos, Xander G.; Endert, Erik; Tijssen, Jan G. P.; Wiersinga, Wilmar M.

    2012-01-01

    Background: Genetic polymorphisms and environmental factors are both involved in the pathogenesis of Graves' disease, but their interaction and effect on Graves' phenotypes have scarcely been investigated. Objective: To test the hypothesis that subjects with susceptibility genotypes develop more

  11. Relation between genotype, phenotype and therapeutic drug concentrations of nortriptyline or venlafaxine users in old age psychiatry

    NARCIS (Netherlands)

    Berm, E.J.J.; Kok, R.M.; Hak, E.; Wilffert, B.

    2015-01-01

    Background The relationship between phenotype and genotype of the polymorphic cytochrome P450 2D6 enzyme (CYP2D6) has been intensively studied, however few studies are conducted among older persons. In a study among 900 relatively young venlafaxine users (mean age 45 years), 83% were genotyped as an

  12. IDH Mutations: Genotype-Phenotype Correlation and Prognostic Impact

    Directory of Open Access Journals (Sweden)

    Xiao-Wei Wang

    2014-01-01

    Full Text Available IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1R132H, IDH1nonR132H, and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1nonR132H in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated—which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation prognostic impact and genotype-phenotype associations.

  13. VanA and VanB Positive Vancomycin-resistant Staphylococcus aureus Among Clinical Isolates in Shiraz, South of Iran

    Directory of Open Access Journals (Sweden)

    Sareh Saadat

    2014-09-01

    Full Text Available Objective: The purpose of this study was to determine the prevalence of vancomycin-resistant Staphylococcus aureus isolated from clinical samples in Shiraz hospitals. Methods: From March to December 2012, 100 S. aureus isolates (mainly from wound and blood were collected from three hospitals in Shiraz, south of Iran. After identification of Staphylococcus aureus by biochemical, microbiological and molecular methods, antibiotic susceptibility testing was performed by Kirby-Bauer disc diffusion test for 13 different antibiotics. Vancomycin-resistant Staphylococcus aureus isolates were determined by vancomycin agar screening test and PCR for vancomycin resistant genes (vanA and vanB. Results: The lowest and highest resistance was seen for quinupristin-dalfopristin (n=1 and ampicillin (n=95, respectively. Vancomycin agar screening test showed that 37 isolates can grow on these media. Further study by PCR also detected vanA and/or vanB genes in all of these strains. Also, 19 isolates showed either vanA or vanB but were susceptible according to vancomycin agar screening test. In total, vanA and vanB resistant genes were detected in 34% and 37% of clinical isolates, respectively. Conclusion: The results showed that the frequency of vancomycin resistance genes (vanA, vanB is very high in Staphylococcus aureus strains isolated from patients in south of Iran. Thus, urgent interventions are needed to keep the emergence and transmission of these isolates to a minimum.

  14. Mapping phenotypic plasticity and genotype-environment interactions affecting life-history traits in Caenorhabditis elegans

    NARCIS (Netherlands)

    Gutteling, E.W.; Riksen, J.A.G.; Bakker, J.; Kammenga, J.E.

    2007-01-01

    Phenotypic plasticity and genotype-environment interactions (GEI) play an important role in the evolution of life histories. Knowledge of the molecular genetic basis of plasticity and GEI provides insight into the underlying mechanisms of life-history changes in different environments. We used a

  15. Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge.

    Science.gov (United States)

    Lynch, Henry T; Lanspa, Stephen; Shaw, Trudy; Casey, Murray Joseph; Rendell, Marc; Stacey, Mark; Townley, Theresa; Snyder, Carrie; Hitchins, Megan; Bailey-Wilson, Joan

    2018-07-01

    Lynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer. It is caused by germline mutations in the mismatch repair genes. Both its phenotype and genotype show marked heterogeneity. This review gives a historical overview of the syndrome, its heterogeneity, its genomic landscape, and its implications for complex diagnosis, genetic counseling and putative implications for immunotherapy.

  16. The Chado Natural Diversity module: a new generic database schema for large-scale phenotyping and genotyping data.

    Science.gov (United States)

    Jung, Sook; Menda, Naama; Redmond, Seth; Buels, Robert M; Friesen, Maren; Bendana, Yuri; Sanderson, Lacey-Anne; Lapp, Hilmar; Lee, Taein; MacCallum, Bob; Bett, Kirstin E; Cain, Scott; Clements, Dave; Mueller, Lukas A; Main, Dorrie

    2011-01-01

    Linking phenotypic with genotypic diversity has become a major requirement for basic and applied genome-centric biological research. To meet this need, a comprehensive database backend for efficiently storing, querying and analyzing large experimental data sets is necessary. Chado, a generic, modular, community-based database schema is widely used in the biological community to store information associated with genome sequence data. To meet the need to also accommodate large-scale phenotyping and genotyping projects, a new Chado module called Natural Diversity has been developed. The module strictly adheres to the Chado remit of being generic and ontology driven. The flexibility of the new module is demonstrated in its capacity to store any type of experiment that either uses or generates specimens or stock organisms. Experiments may be grouped or structured hierarchically, whereas any kind of biological entity can be stored as the observed unit, from a specimen to be used in genotyping or phenotyping experiments, to a group of species collected in the field that will undergo further lab analysis. We describe details of the Natural Diversity module, including the design approach, the relational schema and use cases implemented in several databases.

  17. Pilistvere vana rehe all päästetakse Venemaad / Krista Valdvee

    Index Scriptorium Estoniae

    Valdvee, Krista, 1978-

    2008-01-01

    7. aug. Pilistvere vanas rehehoones esietendunud Ain Saviaugu kirjutatud ja lavastatud suvetükist "Rasputin". Suvelavastuse tõi välja Põltsamaa Teater Ellunäod koos professionaalsete näitlejatega. Nimiosas mängib näitlejast riigikogulane Indrek Saar

  18. New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients

    Institute of Scientific and Technical Information of China (English)

    Feng Lin; Zhi-Qiang Wang; Min-Ting Lin; Shen-Xing Murong; Ning Wang

    2015-01-01

    Background:Facioscapulohumeral muscular dystrophy (FSHD),a common autosomal dominant muscular disorder,is caused by contraction of the D4Z4 repeats on 4q35.The complicated genotype-phenotype correlation among different ethnic population remains a controversial subject.We aimed to refine this correlation in order to provide new information for genetic counseling.Methods:Here,a cohort of 136 Chinese families including 178 affected individuals and 137 unaffected members were investigated.Genetic analyses were performed using the pl3E-11,4qA and 4qB probes after pulsed field gel electrophoresis separation and southern blotting.A 10-grade FSHD clinical severity scale was adopted for clinical assessment.The genotype-phenotype correlation was established by linear regression analyses.Results:We observed a roughly inversed correlation between the short EcoRI fragment size and age-corrected clinical severity score in 154 symptomatic patients (P < 0.05).Compared to male patients,a significant higher proportion of females in both asymptomatic carriers and severe patients showed larger variation in the size of short EcoRI fragment.A high incidence (19/42,45.2%) of asymptomatic (or minimally affected) carriers was found in familial members.Conclusions:Although the number of D4Z4 repeats is known as one of the critical influences on genotype-phenotype correlation,a majority of phenotypic spectrum was still incompatible with their heterozygous contraction of the D4Z4 repeat,especial in female cases.Our results suggest that there are multi-factors synergistically modulating the phenotypic expression.

  19. Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.

    Science.gov (United States)

    Santen, Gijs W E; Aten, Emmelien; Vulto-van Silfhout, Anneke T; Pottinger, Caroline; van Bon, Bregje W M; van Minderhout, Ivonne J H M; Snowdowne, Ronelle; van der Lans, Christian A C; Boogaard, Merel; Linssen, Margot M L; Vijfhuizen, Linda; van der Wielen, Michiel J R; Vollebregt, M J Ellen; Breuning, Martijn H; Kriek, Marjolein; van Haeringen, Arie; den Dunnen, Johan T; Hoischen, Alexander; Clayton-Smith, Jill; de Vries, Bert B A; Hennekam, Raoul C M; van Belzen, Martine J

    2013-11-01

    De novo germline variants in several components of the SWI/SNF-like BAF complex can cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. We screened 63 patients with a clinical diagnosis of CSS for these genes (ARID1A, ARID1B, SMARCA2, SMARCA4, SMARCB1, and SMARCE1) and identified pathogenic variants in 45 (71%) patients. We found a high proportion of variants in ARID1B (68%). All four pathogenic variants in ARID1A appeared to be mosaic. By using all variants from the Exome Variant Server as test data, we were able to classify variants in ARID1A, ARID1B, and SMARCB1 reliably as being pathogenic or nonpathogenic. For SMARCA2, SMARCA4, and SMARCE1 several variants in the EVS remained unclassified, underlining the importance of parental testing. We have entered all variant and clinical information in LOVD-powered databases to facilitate further genotype-phenotype correlations, as these will become increasingly important because of the uptake of targeted and untargeted next generation sequencing in diagnostics. The emerging phenotype-genotype correlation is that SMARCB1 patients have the most marked physical phenotype and severe cognitive and growth delay. The variability in phenotype seems most marked in ARID1A and ARID1B patients. Distal limbs anomalies are most marked in ARID1A patients and least in SMARCB1 patients. Numbers are small however, and larger series are needed to confirm this correlation. © 2013 WILEY PERIODICALS, INC.

  20. CYP2C9 Genotype vs. Metabolic Phenotype for Individual Drug Dosing—A Correlation Analysis Using Flurbiprofen as Probe Drug

    Science.gov (United States)

    Vogl, Silvia; Lutz, Roman W.; Schönfelder, Gilbert; Lutz, Werner K.

    2015-01-01

    Currently, genotyping of patients for polymorphic enzymes responsible for metabolic elimination is considered a possibility to adjust drug dose levels. For a patient to profit from this procedure, the interindividual differences in drug metabolism within one genotype should be smaller than those between different genotypes. We studied a large cohort of healthy young adults (283 subjects), correlating their CYP2C9 genotype to a simple phenotyping metric, using flurbiprofen as probe drug. Genotyping was conducted for CYP2C9*1, *2, *3. The urinary metabolic ratio MR (concentration of CYP2C9-dependent metabolite divided by concentration of flurbiprofen) determined two hours after flurbiprofen (8.75 mg) administration served as phenotyping metric. Linear statistical models correlating genotype and phenotype provided highly significant allele-specific MR estimates of 0.596 for the wild type allele CYP2C9*1, 0.405 for CYP2C9*2 (68 % of wild type), and 0.113 for CYP2C9*3 (19 % of wild type). If these estimates were used for flurbiprofen dose adjustment, taking 100 % for genotype *1/*1, an average reduction to 84 %, 60 %, 68 %, 43 %, and 19 % would result for genotype *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Due to the large individual variation within genotypes with coefficients of variation ≥ 20 % and supposing the normal distribution, one in three individuals would be out of the average optimum dose by more than 20 %, one in 20 would be 40 % off. Whether this problem also applies to other CYPs and other drugs has to be investigated case by case. Our data for the given example, however, puts the benefit of individual drug dosing to question, if it is exclusively based on genotype. PMID:25775139

  1. CYP2C9 genotype vs. metabolic phenotype for individual drug dosing--a correlation analysis using flurbiprofen as probe drug.

    Science.gov (United States)

    Vogl, Silvia; Lutz, Roman W; Schönfelder, Gilbert; Lutz, Werner K

    2015-01-01

    Currently, genotyping of patients for polymorphic enzymes responsible for metabolic elimination is considered a possibility to adjust drug dose levels. For a patient to profit from this procedure, the interindividual differences in drug metabolism within one genotype should be smaller than those between different genotypes. We studied a large cohort of healthy young adults (283 subjects), correlating their CYP2C9 genotype to a simple phenotyping metric, using flurbiprofen as probe drug. Genotyping was conducted for CYP2C9*1, *2, *3. The urinary metabolic ratio MR (concentration of CYP2C9-dependent metabolite divided by concentration of flurbiprofen) determined two hours after flurbiprofen (8.75 mg) administration served as phenotyping metric. Linear statistical models correlating genotype and phenotype provided highly significant allele-specific MR estimates of 0.596 for the wild type allele CYP2C9*1, 0.405 for CYP2C9*2 (68 % of wild type), and 0.113 for CYP2C9*3 (19 % of wild type). If these estimates were used for flurbiprofen dose adjustment, taking 100 % for genotype *1/*1, an average reduction to 84 %, 60 %, 68 %, 43 %, and 19 % would result for genotype *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Due to the large individual variation within genotypes with coefficients of variation ≥ 20 % and supposing the normal distribution, one in three individuals would be out of the average optimum dose by more than 20 %, one in 20 would be 40 % off. Whether this problem also applies to other CYPs and other drugs has to be investigated case by case. Our data for the given example, however, puts the benefit of individual drug dosing to question, if it is exclusively based on genotype.

  2. CYP2C9 genotype vs. metabolic phenotype for individual drug dosing--a correlation analysis using flurbiprofen as probe drug.

    Directory of Open Access Journals (Sweden)

    Silvia Vogl

    Full Text Available Currently, genotyping of patients for polymorphic enzymes responsible for metabolic elimination is considered a possibility to adjust drug dose levels. For a patient to profit from this procedure, the interindividual differences in drug metabolism within one genotype should be smaller than those between different genotypes. We studied a large cohort of healthy young adults (283 subjects, correlating their CYP2C9 genotype to a simple phenotyping metric, using flurbiprofen as probe drug. Genotyping was conducted for CYP2C9*1, *2, *3. The urinary metabolic ratio MR (concentration of CYP2C9-dependent metabolite divided by concentration of flurbiprofen determined two hours after flurbiprofen (8.75 mg administration served as phenotyping metric. Linear statistical models correlating genotype and phenotype provided highly significant allele-specific MR estimates of 0.596 for the wild type allele CYP2C9*1, 0.405 for CYP2C9*2 (68 % of wild type, and 0.113 for CYP2C9*3 (19 % of wild type. If these estimates were used for flurbiprofen dose adjustment, taking 100 % for genotype *1/*1, an average reduction to 84 %, 60 %, 68 %, 43 %, and 19 % would result for genotype *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Due to the large individual variation within genotypes with coefficients of variation ≥ 20 % and supposing the normal distribution, one in three individuals would be out of the average optimum dose by more than 20 %, one in 20 would be 40 % off. Whether this problem also applies to other CYPs and other drugs has to be investigated case by case. Our data for the given example, however, puts the benefit of individual drug dosing to question, if it is exclusively based on genotype.

  3. Correlation between genotype and the tetrahydrobiopterin-responsive phenotype in Chinese patients with phenylketonuria.

    Science.gov (United States)

    Tao, Jing; Li, Nana; Jia, Haitao; Liu, Zhen; Li, Xiaohong; Song, Jiaping; Deng, Ying; Jin, Xi; Zhu, Jun

    2015-12-01

    A growing body of research has suggested that tetrahydrobiopterin (BH4) responsive phenotype can be predicted by the phenylalanine hydroxylase (PAH) genotype in patients with phenylketonuria (PKU), but data concerning the association between genotype and BH4 responsiveness are scarce in China. A total of 165 PKU patients from China who had undergone a 24-h loading test with BH4 administration were recruited. Genotyping was performed by the next-generation sequencing (NGS) technique. Using the predicted residual PAH activity, we analyzed the association between genotype and BH4-responsiveness. Among the 165 patients, 40 patients (24.24%) responded to BH4. A total of 74 distinct mutations were observed, including 13 novel mutations. The mutation p.R241C was most frequently associated with response. Two known mutations (p.A322T and p.Q419R) and two novel mutations (p.L98V and IVS3-2A>T) were first reported as responsive to BH4. Residual PAH activity of at least 12.5% was needed for responsive genotypes. Genotype-based predictions of BH4-responsiveness are only for selecting potential responders. Accordingly, it is necessary to test potential responders with a long-term BH4 challenge.

  4. (Epi)genotype-Phenotype Analysis in 69 Japanese Patients With Pseudohypoparathyroidism Type I

    Science.gov (United States)

    Sano, Shinichiro; Nakamura, Akie; Matsubara, Keiko; Nagasaki, Keisuke; Fukami, Maki; Kagami, Masayo

    2018-01-01

    Context: Pseudohypoparathyroidism type I (PHP-I) is divided into PHP-Ia with Albright hereditary osteodystrophy and PHP-Ib, which usually shows no Albright hereditary osteodystrophy features. Although PHP-Ia and PHP-Ib are typically caused by genetic defects involving α subunit of the stimulatory G protein (Gsα)–coding GNAS exons and methylation defects of the GNAS differentially methylated regions (DMRs) on the maternal allele, respectively, detailed phenotypic characteristics still remains to be examined. Objective: To clarify phenotypic characteristics according to underlying (epi)genetic causes. Patients and Methods: We performed (epi)genotype-phenotype analysis in 69 Japanese patients with PHP-I; that is, 28 patients with genetic defects involving Gsα-coding GNAS exons (group 1) consisting of 12 patients with missense variants (subgroup A) and 16 patients with null variants (subgroup B), as well as 41 patients with methylation defects (group 2) consisting of 21 patients with broad methylation defects of the GNAS-DMRs (subgroup C) and 20 patients with an isolated A/B-DMR methylation defect accompanied by the common STX16 microdeletion (subgroup D). Results: Although (epi)genotype-phenotype findings were grossly similar to those reported previously, several important findings were identified, including younger age at hypocalcemic symptoms and higher frequencies of hyperphosphatemia in subgroup C than in subgroup D, development of brachydactyly in four patients of subgroup C, predominant manifestation of subcutaneous ossification in subgroup B, higher frequency of thyrotropin resistance in group 1 than in group 2, and relatively low thyrotropin values in four patients with low T4 values and relatively low luteinizing hormone/follicle-stimulating hormone values in five adult females with ovarian dysfunction. Conclusion: The results imply the presence of clinical findings characteristic of each underlying cause and provide useful information on the imprinting

  5. The Face of Noonan Syndrome: Does Phenotype Predict Genotype

    Science.gov (United States)

    Allanson, Judith E.; Bohring, Axel; Dorr, Helmuth-Guenther; Dufke, Andreas; Gillessen-Kaesbach, Gabrielle; Horn, Denise; König, Rainer; Kratz, Christian P.; Kutsche, Kerstin; Pauli, Silke; Raskin, Salmo; Rauch, Anita; Turner, Anne; Wieczorek, Dagmar; Zenker, Martin

    2011-01-01

    The facial photographs of 81 individuals with Noonan syndrome, from infancy to adulthood, have been evaluated by two dysmorphologists (JA and MZ), each of whom has considerable experience with disorders of the Ras/MAPK pathway. Thirty-two of this cohort have PTPN11 mutations, 21 SOS1 mutations, 11 RAF1 mutations, and 17 KRAS mutations. The facial appearance of each person was judged to be typical of Noonan syndrome or atypical. In each gene category both typical and unusual faces were found. We determined that some individuals with mutations in the most commonly affected gene, PTPN11, which is correlated with the cardinal physical features, may have a quite atypical face. Conversely, some individuals with KRAS mutations, which may be associated with a less characteristic intellectual phenotype and a resemblance to Costello and cardio-facio-cutaneous syndromes, can have a very typical face. Thus, the facial phenotype, alone, is insufficient to predict the genotype, but certain facial features may facilitate an educated guess in some cases. PMID:20602484

  6. Generation of New Genotypic and Phenotypic Features in Artificial and Natural Yeast Hybrids

    Directory of Open Access Journals (Sweden)

    Walter P. Pfliegler

    2014-01-01

    Full Text Available Evolution and genome stabilization have mostly been studied on the Saccharomyces hybrids isolated from natural and alcoholic fermentation environments. Genetic and phenotypic properties have usually been compared to the laboratory and reference strains, as the true ancestors of the natural hybrid yeasts are unknown. In this way the exact impact of different parental fractions on the genome organization or metabolic activity of the hybrid yeasts is difficult to resolve completely. In the present work the evolution of geno- and phenotypic properties is studied in the interspecies hybrids created by the cross-breeding of S. cerevisiae with S. uvarum or S. kudriavzevii auxotrophic mutants. We hypothesized that the extent of genomic alterations in S. cerevisiae × S. uvarum and S. cerevisiae × S. kudriavzevii should affect the physiology of their F1 offspring in different ways. Our results, obtained by amplified fragment length polymorphism (AFLP genotyping and karyotyping analyses, showed that both subgenomes of the S. cerevisiae x S. uvarum and of S. cerevisiae × S. kudriavzevii hybrids experienced various modifications. However, the S. cerevisiae × S. kudriavzevii F1 hybrids underwent more severe genomic alterations than the S. cerevisiae × S. uvarum ones. Generation of the new genotypes also influenced the physiological performances of the hybrids and the occurrence of novel phenotypes. Significant differences in carbohydrate utilization and distinct growth dynamics at increasing concentrations of sodium chloride, urea and miconazole were observed within and between the S. cerevisiae × S. uvarum and S. cerevisiae × S. kudriavzevii hybrids. Parental strains also demonstrated different contributions to the final metabolic outcomes of the hybrid yeasts. A comparison of the genotypic properties of the artificial hybrids with several hybrid isolates from the wine-related environments and wastewater demonstrated a greater genetic variability of

  7. Genotypic and phenotypic diversity of Ralstonia pickettii and Ralstonia insidiosa isolates from clinical and environmental sources including High-purity Water.

    LENUS (Irish Health Repository)

    Ryan, Michael P

    2011-08-30

    Abstract Background Ralstonia pickettii is a nosocomial infectious agent and a significant industrial contaminant. It has been found in many different environments including clinical situations, soil and industrial High Purity Water. This study compares the phenotypic and genotypic diversity of a selection of strains of Ralstonia collected from a variety of sources. Results Ralstonia isolates (fifty-nine) from clinical, industrial and environmental origins were compared genotypically using i) Species-specific-PCR, ii) PCR and sequencing of the 16S-23S rRNA Interspatial region (ISR) iii) the fliC gene genes, iv) RAPD and BOX-PCR and v) phenotypically using biochemical testing. The species specific-PCR identified fifteen out of fifty-nine designated R. pickettii isolates as actually being the closely related species R. insidiosa. PCR-ribotyping of the 16S-23S rRNA ISR indicated few major differences between the isolates. Analysis of all isolates demonstrated different banding patterns for both the RAPD and BOX primers however these were found not to vary significantly. Conclusions R. pickettii species isolated from wide geographic and environmental sources appear to be reasonably homogenous based on genotypic and phenotypic characteristics. R. insidiosa can at present only be distinguished from R. pickettii using species specific PCR. R. pickettii and R. insidiosa isolates do not differ significantly phenotypically or genotypically based on environmental or geographical origin.

  8. Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype.

    LENUS (Irish Health Repository)

    FitzGerald, Oliver

    2015-05-07

    This review focuses on the genetic features of psoriatic arthritis (PsA) and their relationship to phenotypic heterogeneity in the disease, and addresses three questions: what do the recent studies on human leukocyte antigen (HLA) tell us about the genetic relationship between cutaneous psoriasis (PsO) and PsA - that is, is PsO a unitary phenotype; is PsA a genetically heterogeneous or homogeneous entity; and do the genetic factors implicated in determining susceptibility to PsA predict clinical phenotype? We first discuss the results from comparing the HLA typing of two PsO cohorts: one cohort providing the dermatologic perspective, consisting of patients with PsO without evidence of arthritic disease; and the second cohort providing the rheumatologic perspective, consisting of patients with PsA. We show that these two cohorts differ considerably in their predominant HLA alleles, indicating the heterogeneity of the overall PsO phenotype. Moreover, the genotype of patients in the PsA cohort was shown to be heterogeneous with significant elevations in the frequency of haplotypes containing HLA-B*08, HLA-C*06:02, HLA-B*27, HLA-B*38 and HLA-B*39. Because different genetic susceptibility genes imply different disease mechanisms, and possibly different clinical courses and therapeutic responses, we then review the evidence for a phenotypic difference among patients with PsA who have inherited different HLA alleles. We provide evidence that different alleles and, more importantly, different haplotypes implicated in determining PsA susceptibility are associated with different phenotypic characteristics that appear to be subphenotypes. The implication of these findings for the overall pathophysiologic mechanisms involved in PsA is discussed with specific reference to their bearing on the discussion of whether PsA is conceptualised as an autoimmune process or one that is based on entheseal responses.

  9. Correlation of Lactobacillus rhamnosus Genotypes and Carbohydrate Utilization Signatures Determined by Phenotype Profiling.

    Science.gov (United States)

    Ceapa, Corina; Lambert, Jolanda; van Limpt, Kees; Wels, Michiel; Smokvina, Tamara; Knol, Jan; Kleerebezem, Michiel

    2015-08-15

    Lactobacillus rhamnosus is a bacterial species commonly colonizing the gastrointestinal (GI) tract of humans and also frequently used in food products. While some strains have been studied extensively, physiological variability among isolates of the species found in healthy humans or their diet is largely unexplored. The aim of this study was to characterize the diversity of carbohydrate utilization capabilities of human isolates and food-derived strains of L. rhamnosus in relation to their niche of isolation and genotype. We investigated the genotypic and phenotypic diversity of 25 out of 65 L. rhamnosus strains from various niches, mainly human feces and fermented dairy products. Genetic fingerprinting of the strains by amplified fragment length polymorphism (AFLP) identified 11 distinct subgroups at 70% similarity and suggested niche enrichment within particular genetic clades. High-resolution carbohydrate utilization profiling (OmniLog) identified 14 carbon sources that could be used by all of the strains tested for growth, while the utilization of 58 carbon sources differed significantly between strains, enabling the stratification of L. rhamnosus strains into three metabolic clusters that partially correlate with the genotypic clades but appear uncorrelated with the strain's origin of isolation. Draft genome sequences of 8 strains were generated and employed in a gene-trait matching (GTM) analysis together with the publicly available genomes of L. rhamnosus GG (ATCC 53103) and HN001 for several carbohydrates that were distinct for the different metabolic clusters: l-rhamnose, cellobiose, l-sorbose, and α-methyl-d-glucoside. From the analysis, candidate genes were identified that correlate with l-sorbose and α-methyl-d-glucoside utilization, and the proposed function of these genes could be confirmed by heterologous expression in a strain lacking the genes. This study expands our insight into the phenotypic and genotypic diversity of the species L. rhamnosus

  10. Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness.

    Science.gov (United States)

    Jeannesson-Thivisol, Elise; Feillet, François; Chéry, Céline; Perrin, Pascal; Battaglia-Hsu, Shyue-Fang; Herbeth, Bernard; Cano, Aline; Barth, Magalie; Fouilhoux, Alain; Mention, Karine; Labarthe, François; Arnoux, Jean-Baptiste; Maillot, François; Lenaerts, Catherine; Dumesnil, Cécile; Wagner, Kathy; Terral, Daniel; Broué, Pierre; de Parscau, Loïc; Gay, Claire; Kuster, Alice; Bédu, Antoine; Besson, Gérard; Lamireau, Delphine; Odent, Sylvie; Masurel, Alice; Guéant, Jean-Louis; Namour, Fares

    2015-12-15

    Mutations in Phenylalanine Hydroxylase (PAH) gene cause phenylketonuria. Sapropterin (BH4), the enzyme cofactor, is an important therapeutical strategy in phenylketonuria. However, PAH is a highly polymorphic gene and it is difficult to identify BH4-responsive genotypes. We seek here to improve prediction of BH4-responsiveness through comparison of genotypes, BH4-loading test, predictions of responsiveness according to the literature and types and locations of mutations. A total of 364 French patients among which, 9 % had mild hyperphenylalaninemia, 17.7 % mild phenylketonuria and 73.1 % classical phenylketonuria, benefited from a 24-hour BH4-loading test and had the PAH gene sequenced and analyzed by Multiplex Ligation Probe Amplification. Overall, 31.6 % of patients were BH4-responsive. The number of different mutations found was 127, including 26 new mutations. The mutations c.434A > T, c.500A > T, c.529G > C, c.1045 T > G and c.1196 T > C were newly classified as being BH4-responsive. We identified 261 genotypes, among which 46 were newly recognized as being BH4-responsive. Even though patients carry 2 responsive alleles, BH4-responsiveness cannot be predicted with certainty unless they present mild hyperphenylalaninemia. BH4-responsiveness cannot be predicted in patients carrying one responsive mutation only. In general, the milder the phenotype is, the stronger the BH4-response is. Almost exclusively missense mutations, particularly in exons 12, 11 and 8, are associated with BH4-responsiveness and any other type of mutation predicts a negative response. This study is the first of its kind, in a French population, to identify the phenotype associated with several combinations of PAH mutations. As others, it highlights the necessity of performing simultaneously BH4 loading test and molecular analysis in monitoring phenylketonuria patients.

  11. Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson's disease: genetic and clinical homogeneity.

    Directory of Open Access Journals (Sweden)

    Relu Cocoş

    Full Text Available Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1 ∶ 1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18 ± 1 years showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.

  12. Gravimetric phenotyping of whole plant transpiration responses to atmospheric vapour pressure deficit identifies genotypic variation in water use efficiency.

    Science.gov (United States)

    Ryan, Annette C; Dodd, Ian C; Rothwell, Shane A; Jones, Ros; Tardieu, Francois; Draye, Xavier; Davies, William J

    2016-10-01

    There is increasing interest in rapidly identifying genotypes with improved water use efficiency, exemplified by the development of whole plant phenotyping platforms that automatically measure plant growth and water use. Transpirational responses to atmospheric vapour pressure deficit (VPD) and whole plant water use efficiency (WUE, defined as the accumulation of above ground biomass per unit of water used) were measured in 100 maize (Zea mays L.) genotypes. Using a glasshouse based phenotyping platform with naturally varying VPD (1.5-3.8kPa), a 2-fold variation in WUE was identified in well-watered plants. Regression analysis of transpiration versus VPD under these conditions, and subsequent whole plant gas exchange at imposed VPDs (0.8-3.4kPa) showed identical responses in specific genotypes. Genotype response of transpiration versus VPD fell into two categories: 1) a linear increase in transpiration rate with VPD with low (high WUE) or high (low WUE) transpiration rate at all VPDs, 2) a non-linear response with a pronounced change point at low VPD (high WUE) or high VPD (low WUE). In the latter group, high WUE genotypes required a significantly lower VPD before transpiration was restricted, and had a significantly lower rate of transpiration in response to VPD after this point, when compared to low WUE genotypes. Change point values were significantly positively correlated with stomatal sensitivity to VPD. A change point in stomatal response to VPD may explain why some genotypes show contradictory WUE rankings according to whether they are measured under glasshouse or field conditions. Furthermore, this novel use of a high throughput phenotyping platform successfully reproduced the gas exchange responses of individuals measured in whole plant chambers, accelerating the identification of plants with high WUE. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. The role of the Staphylococcal VraTSR regulatory system on vancomycin resistance and vanA operon expression in vancomycin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Qureshi, Nadia K; Yin, Shaohui; Boyle-Vavra, Susan

    2014-01-01

    Vancomycin is often the preferred treatment for invasive methicillin-resistant Staphylococcus aureus (MRSA) infection. With the increase in incidence of MRSA infections, the use of vancomycin has increased and, as feared, isolates of vancomycin-resistant Staphylococcus aureus (VRSA) have emerged. VRSA isolates have acquired the entercoccal vanA operon contained on transposon (Tn) 1546 residing on a conjugal plasmid. VraTSR is a vancomycin and β-lactam-inducible three-component regulatory system encoded on the S. aureus chromosome that modulates the cell-wall stress response to cell-wall acting antibiotics. Mutation in vraTSR has shown to increase susceptibility to β-lactams and vancomycin in clinical VISA strains and in recombinant strain COLVA-200 which expresses a plasmid borne vanA operon. To date, the role of VraTSR in vanA operon expression in VRSA has not been demonstrated. In this study, the vraTSR operon was deleted from the first clinical VRSA strain (VRS1) by transduction with phage harvested from a USA300 vraTSR operon deletion strain. The absence of the vraTSR operon and presence of the vanA operon were confirmed in the transductant (VRS1Δvra) by PCR. Broth MIC determinations, demonstrated that the vancomycin MIC of VRS1Δvra (64 µg/ml) decreased by 16-fold compared with VRS1 (1024 µg/ml). The effect of the vraTSR operon deletion on expression of the van gene cluster (vanA, vanX and vanR) was examined by quantitative RT-PCR using relative quantification. A 2-5-fold decreased expression of the vanA operon genes occured in strain VRS1Δvra at stationary growth phase compared with the parent strain, VRS1. Both vancomycin resistance and vancomycin-induced expression of vanA and vanR were restored by complementation with a plasmid harboring the vraTSR operon. These findings demonstrate that expression in S. aureus of the horizontally acquired enterococcal vanA gene cluster is enhanced by the staphylococcal three-component cell wall stress regulatory

  14. Recurrent mutations in the CDKL5 gene: genotype-phenotype relationships.

    Science.gov (United States)

    Bahi-Buisson, Nadia; Villeneuve, Nathalie; Caietta, Emilie; Jacquette, Aurélia; Maurey, Helene; Matthijs, Gert; Van Esch, Hilde; Delahaye, Andrée; Moncla, Anne; Milh, Mathieu; Zufferey, Flore; Diebold, Bertrand; Bienvenu, Thierry

    2012-07-01

    Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been described in epileptic encephalopathies in females with infantile spasms with features that overlap with Rett syndrome. With more than 80 reported patients, the phenotype of CDKL5-related encephalopathy is well-defined. The main features consist of seizures starting before 6 months of age, severe intellectual disability with absent speech and hand stereotypies and deceleration of head growth, which resembles Rett syndrome. However, some clinical discrepancies suggested the influence of genetics and/or environmental factors. No genotype-phenotype correlation has been defined and thus there is a need to examine individual mutations. In this study, we analyzed eight recurrent CDKL5 mutations to test whether the clinical phenotype of patients with the same mutation is similar and whether patients with specific CDKL5 mutations have a milder phenotype than those with other CDKL5 mutations. Patients bearing missense mutations in the ATP binding site such as the p.Ala40Val mutation typically walked unaided, had normocephaly, better hand use ability, and less frequent refractory epilepsy when compared to girls with other CDKL5 mutations. In contrast, patients with mutations in the kinase domain (such as p.Arg59X, p.Arg134X, p.Arg178Trp/Pro/Gln, or c.145 + 2T > C) and frameshift mutations in the C-terminal region (such as c.2635_2636delCT) had a more severe phenotype with infantile spasms, refractory epileptic encephalopathy, absolute microcephaly, and inability to walk. It is important for clinicians to have this information when such patients are diagnosed. Copyright © 2012 Wiley Periodicals, Inc.

  15. Clinical spectrum and genotype-phenotype associations of KCNA2-related encephalopathies.

    Science.gov (United States)

    Masnada, Silvia; Hedrich, Ulrike B S; Gardella, Elena; Schubert, Julian; Kaiwar, Charu; Klee, Eric W; Lanpher, Brendan C; Gavrilova, Ralitza H; Synofzik, Matthis; Bast, Thomas; Gorman, Kathleen; King, Mary D; Allen, Nicholas M; Conroy, Judith; Ben Zeev, Bruria; Tzadok, Michal; Korff, Christian; Dubois, Fanny; Ramsey, Keri; Narayanan, Vinodh; Serratosa, Jose M; Giraldez, Beatriz G; Helbig, Ingo; Marsh, Eric; O'Brien, Margaret; Bergqvist, Christina A; Binelli, Adrian; Porter, Brenda; Zaeyen, Eduardo; Horovitz, Dafne D; Wolff, Markus; Marjanovic, Dragan; Caglayan, Hande S; Arslan, Mutluay; Pena, Sergio D J; Sisodiya, Sanjay M; Balestrini, Simona; Syrbe, Steffen; Veggiotti, Pierangelo; Lemke, Johannes R; Møller, Rikke S; Lerche, Holger; Rubboli, Guido

    2017-09-01

    Recently, de novo mutations in the gene KCNA2, causing either a dominant-negative loss-of-function or a gain-of-function of the voltage-gated K+ channel Kv1.2, were described to cause a new molecular entity within the epileptic encephalopathies. Here, we report a cohort of 23 patients (eight previously described) with epileptic encephalopathy carrying either novel or known KCNA2 mutations, with the aim to detail the clinical phenotype associated with each of them, to characterize the functional effects of the newly identified mutations, and to assess genotype-phenotype associations. We identified five novel and confirmed six known mutations, three of which recurred in three, five and seven patients, respectively. Ten mutations were missense and one was a truncation mutation; de novo occurrence could be shown in 20 patients. Functional studies using a Xenopus oocyte two-microelectrode voltage clamp system revealed mutations with only loss-of-function effects (mostly dominant-negative current amplitude reduction) in eight patients or only gain-of-function effects (hyperpolarizing shift of voltage-dependent activation, increased amplitude) in nine patients. In six patients, the gain-of-function was diminished by an additional loss-of-function (gain-and loss-of-function) due to a hyperpolarizing shift of voltage-dependent activation combined with either decreased amplitudes or an additional hyperpolarizing shift of the inactivation curve. These electrophysiological findings correlated with distinct phenotypic features. The main differences were (i) predominant focal (loss-of-function) versus generalized (gain-of-function) seizures and corresponding epileptic discharges with prominent sleep activation in most cases with loss-of-function mutations; (ii) more severe epilepsy, developmental problems and ataxia, and atrophy of the cerebellum or even the whole brain in about half of the patients with gain-of-function mutations; and (iii) most severe early-onset phenotypes

  16. Phenotypic, Genotypic, and Antibiotic Sensitivity Patterns of Strains Isolated from the Cholera Epidemic in Zimbabwe

    NARCIS (Netherlands)

    Islam, Mohammad S.; Mahmud, Zahid H.; Ansaruzzaman, Mohammad; Faruque, Shah M.; Talukder, Kaisar A.; Qadri, Firdausi; Alam, Munirul; Islam, Shafiqul; Bardhan, Pradip K.; Mazumder, Ramendra N.; Khan, Azharul I.; Ahmed, Sirajuddin; Iqbal, Anwarul; Chitsatso, Owen; Mudzori, James; Patel, Sheetal; Midzi, Stanley M.; Charimari, Lincoln; Endtz, Hubert P.; Cravioto, Alejandro

    This paper details the phenotypic, genotypic, and antibiotic sensitivity patterns of 88 Vibrio cholerae strains from Zimbabwe. Of the 88 strains, 83 were classified as "altered El Tor" and 5 as "hybrid El Tor" strains. All of the strains were susceptible to tetracycline, doxycycline, ciprofloxacin,

  17. A prospective study to assess the association between genotype, phenotype and Prakriti in individuals on phenytoin monotherapy

    Directory of Open Access Journals (Sweden)

    Saket J. Thaker

    2017-01-01

    Conclusions: We did not find any association between Prakriti and either phenotype or genotypes suggesting that Prakriti assessment would be of limited utility in individualizing phenytoin therapy in epilepsy patients.

  18. Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype.

    Science.gov (United States)

    de Heredia, Miguel López; Clèries, Ramón; Nunes, Virginia

    2013-07-01

    Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. (i) 15% of published patients do not fulfill the current -inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient's genotypic class; and (vi) disease progression rate might depend on genotypic class. New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome.

  19. Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

    NARCIS (Netherlands)

    Koczkowska, M. (Magdalena); Chen, Y. (Yunjia); Callens, T. (Tom); Gomes, A. (Alicia); Sharp, A. (Angela); Johnson, S. (Sherrell); Hsiao, M.-C. (Meng-Chang); Chen, Z. (Zhenbin); Balasubramanian, M. (Meena); Barnett, C.P. (Christopher P.); Becker, T.A. (Troy A.); Ben-Shachar, S. (Shay); D.R. Bertola (Débora Romeo); J.O. Blakeley (Jaishri O.); Burkitt-Wright, E.M.M. (Emma M.M.); Callaway, A. (Alison); Crenshaw, M. (Melissa); Cunha, K.S. (Karin S.); Cunningham, M. (Mitch); M.D. D'Agostino (Maria Daniela); K. Dahan (Karin); De Luca, A. (Alessandro); A. Destrée (Anne); Dhamija, R. (Radhika); Eoli, M. (Marica); Evans, D.G.R. (D. Gareth R.); Galvin-Parton, P. (Patricia); George-Abraham, J.K. (Jaya K.); K.W. Gripp (Karen); Guevara-Campos, J. (Jose); Hanchard, N.A. (Neil A.); Hernández-Chico, C. (Concepcion); Immken, L. (LaDonna); S. Janssens (Sandra); K.J. Jones (Kristi); Keena, B.A. (Beth A.); Kochhar, A. (Aaina); Liebelt, J. (Jan); Martir-Negron, A. (Arelis); Mahoney, M.J. (Maurice J.); I. Maystadt (Isabelle); McDougall, C. (Carey); M. McEntagart (Meriel); N.J. Mendelsohn; Miller, D.T. (David T.); G. Mortier (Geert); J. Morton (Jenny); Pappas, J. (John); S.R. Plotkin (Scott R.); Pond, D. (Dinel); Rosenbaum, K. (Kenneth); Rubin, K. (Karol); Russell, L. (Laura); Rutledge, L.S. (Lane S.); Saletti, V. (Veronica); Schonberg, R. (Rhonda); Schreiber, A. (Allison); Seidel, M. (Meredith); Siqveland, E. (Elizabeth); D.W. Stockton (David); Trevisson, E. (Eva); N.J. Ullrich (Nicole J.); M. Upadhyaya (Meena); A.S. Thornton (Andrew); H. Verhelst (H.); M.R. Wallace (Margaret); Yap, Y.-S. (Yoon-Sim); Zackai, E. (Elaine); Zonana, J. (Jonathan); Zurcher, V. (Vickie); K. Claes (Kathleen); Martin, Y. (Yolanda); B. Korf (Bruce); E. Legius (Eric); L.M. Messiaen (Ludwine)

    2018-01-01

    textabstractNeurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations

  20. Signal Incongruence and its Consequences

    DEFF Research Database (Denmark)

    Vergne, Jean-Philippe; Wernicke, Maria Stokholm; Brenner, Steffen

    2018-01-01

    theory on signal incongruence, we find that firms engaged in philanthropy receive more media disapproval when they overcompensate their CEO, but they are also more likely to decrease CEO overcompensation as a response. Our study contributes to the signaling literature by theorizing about signal......We draw on the signaling and infomediary literatures to examine how media evaluations of CEO overcompensation (a negative cue associated with selfishness and greed) are affected by the presence of corporate philanthropy (a positive cue associated with altruism and generosity). In line with our...... incongruence, and to infomediary and corporate governance research by showing that media disapproval can lead to lower executive compensation. We also reconcile two conflicting views on firm prosocial behavior by showing that, in the presence of incongruent cues, philanthropy can simultaneously enhance...

  1. The genotype-phenotype landscape of familial amyotrophic lateral sclerosis in Australia.

    Science.gov (United States)

    McCann, E P; Williams, K L; Fifita, J A; Tarr, I S; O'Connor, J; Rowe, D B; Nicholson, G A; Blair, I P

    2017-09-01

    Amyotrophic lateral sclerosis (ALS) is a clinically and genetically heterogeneous fatal neurodegenerative disease. Around 10% of ALS cases are hereditary. ALS gene discoveries have provided most of our understanding of disease pathogenesis. We aimed to describe the genetic landscape of ALS in Australia by assessing 1013 Australian ALS patients for known ALS mutations by direct sequencing, whole exome sequencing or repeat primed polymerase chain reaction. Age of disease onset and disease duration were used for genotype-phenotype correlations. We report 60.8% of Australian ALS families in this cohort harbour a known ALS mutation. Hexanucleotide repeat expansions in C9orf72 accounted for 40.6% of families and 2.9% of sporadic patients. We also report ALS families with mutations in SOD1 (13.7%), FUS (2.4%), TARDBP (1.9%), UBQLN2 (.9%), OPTN (.5%), TBK1 (.5%) and CCNF (.5%). We present genotype-phenotype correlations between these genes as well as between gene mutations. Notably, C9orf72 hexanucleotide repeat expansion positive patients experienced significantly later disease onset than ALS mutation patients. Among SOD1 families, p.I114T positive patients had significantly later onset and longer survival. Our report highlights a unique spectrum of ALS gene frequencies among patients from the Australian population, and further, provides correlations between specific ALS mutations with disease onset and/or duration. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Genotypic and phenotypic diversity of Bacillus spp. isolated from steel plant waste

    Directory of Open Access Journals (Sweden)

    Chartone-Souza Edmar

    2008-10-01

    Full Text Available Abstract Background Molecular studies of Bacillus diversity in various environments have been reported. However, there have been few investigations concerning Bacillus in steel plant environments. In this study, genotypic and phenotypic diversity and phylogenetic relationships among 40 bacterial isolates recovered from steel plant waste were investigated using classical and molecular methods. Results 16S rDNA partial sequencing assigned all the isolates to the Bacillus genus, with close genetic relatedness to the Bacillus subtilis and Bacillus cereus groups, and to the species Bacillus sphaericus. tDNA-intergenic spacer length polymorphisms and the 16S–23S intergenic transcribed spacer region failed to identify the isolates at the species level. Genomic diversity was investigated by molecular typing with rep (repetitive sequence based PCR using the primer sets ERIC2 (enterobacterial repetitive intergenic consensus, (GTG5, and BOXAIR. Genotypic fingerprinting of the isolates reflected high intraspecies and interspecies diversity. Clustering of the isolates using ERIC-PCR fingerprinting was similar to that obtained from the 16S rRNA gene phylogenetic tree, indicating the potential of the former technique as a simple and useful tool for examining relationships among unknown Bacillus spp. Physiological, biochemical and heavy metal susceptibility profiles also indicated considerable phenotypic diversity. Among the heavy metal compounds tested Zn, Pb and Cu were least toxic to the bacterial isolates, whereas Ag inhibited all isolates at 0.001 mM. Conclusion Isolates with identical 16S rRNA gene sequences had different genomic fingerprints and differed considerably in their physiological capabilities, so the high levels of phenotypic diversity found in this study are likely to have ecological relevance.

  3. Phenotypic and Genotypic Characteristics of Listeria monocytogenes Isolated From Dairy and Meat Products

    OpenAIRE

    Bahador; Sadeghi Kalani; Valian; Irajian; Lotfollahi

    2015-01-01

    Background Listeria monocytogenes is a foodborne pathogen and a serious threat to the public health in the world. Consumption of traditional foods such as dairy and meat products can be a major reason for relative abundance and isolation of these bacteria. Objectives The purpose of this study was to determine the phenotypic and genotypic characteristics of L. monocytogenes strains isolated from dairy and meat products. ...

  4. Sisaliku jäljed piiblitõlkes : lõunaeestikeelse Vana Testamendi saatusest / Kristiina Ross

    Index Scriptorium Estoniae

    Ross, Kristiina, 1955-

    2011-01-01

    Uuritakse Kambja õpetaja Heinrich Anreas Erxlebeni lõunaeestikeelse Vana Testamendi tõlget (1796) ning leitakse, et sõnastuslikult langeb see suures osas kokku sada aastat varasema Andreas ja Adrian Virginiuse põhjaeestikeelse käsikirjaga

  5. Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations.

    Science.gov (United States)

    Fergelot, Patricia; Van Belzen, Martine; Van Gils, Julien; Afenjar, Alexandra; Armour, Christine M; Arveiler, Benoit; Beets, Lex; Burglen, Lydie; Busa, Tiffany; Collet, Marie; Deforges, Julie; de Vries, Bert B A; Dominguez Garrido, Elena; Dorison, Nathalie; Dupont, Juliette; Francannet, Christine; Garciá-Minaúr, Sixto; Gabau Vila, Elisabeth; Gebre-Medhin, Samuel; Gener Querol, Blanca; Geneviève, David; Gérard, Marion; Gervasini, Cristina Giovanna; Goldenberg, Alice; Josifova, Dragana; Lachlan, Katherine; Maas, Saskia; Maranda, Bruno; Moilanen, Jukka S; Nordgren, Ann; Parent, Philippe; Rankin, Julia; Reardon, Willie; Rio, Marlène; Roume, Joëlle; Shaw, Adam; Smigiel, Robert; Sojo, Amaia; Solomon, Benjamin; Stembalska, Agnieszka; Stumpel, Constance; Suarez, Francisco; Terhal, Paulien; Thomas, Simon; Touraine, Renaud; Verloes, Alain; Vincent-Delorme, Catherine; Wincent, Josephine; Peters, Dorien J M; Bartsch, Oliver; Larizza, Lidia; Lacombe, Didier; Hennekam, Raoul C

    2016-12-01

    Rubinstein-Taybi syndrome (RSTS) is a developmental disorder characterized by a typical face and distal limbs abnormalities, intellectual disability, and a vast number of other features. Two genes are known to cause RSTS, CREBBP in 60% and EP300 in 8-10% of clinically diagnosed cases. Both paralogs act in chromatin remodeling and encode for transcriptional co-activators interacting with >400 proteins. Up to now 26 individuals with an EP300 mutation have been published. Here, we describe the phenotype and genotype of 42 unpublished RSTS patients carrying EP300 mutations and intragenic deletions and offer an update on another 10 patients. We compare the data to 308 individuals with CREBBP mutations. We demonstrate that EP300 mutations cause a phenotype that typically resembles the classical RSTS phenotype due to CREBBP mutations to a great extent, although most facial signs are less marked with the exception of a low-hanging columella. The limb anomalies are more similar to those in CREBBP mutated individuals except for angulation of thumbs and halluces which is very uncommon in EP300 mutated individuals. The intellectual disability is variable but typically less marked whereas the microcephaly is more common. All types of mutations occur but truncating mutations and small rearrangements are most common (86%). Missense mutations in the HAT domain are associated with a classical RSTS phenotype but otherwise no genotype-phenotype correlation is detected. Pre-eclampsia occurs in 12/52 mothers of EP300 mutated individuals versus in 2/59 mothers of CREBBP mutated individuals, making pregnancy with an EP300 mutated fetus the strongest known predictor for pre-eclampsia. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Examining genotypic variation in autism spectrum disorder and its relationship to parental age and phenotype

    Directory of Open Access Journals (Sweden)

    Geier DA

    2016-07-01

    Full Text Available David A Geier,1,2 Janet K Kern,1,3 Lisa K Sykes,2 Mark R Geier1,2 1Research Department, The Institute of Chronic Illnesses, Inc, 2Research Department, CoMeD, Inc, Silver Spring, MD, 3Research Department, CONEM US Autism Research Group, Allen, TX, USA Background: Previous studies on genetic testing of chromosomal abnormalities in individuals diagnosed with autism spectrum disorder (ASD found that ~80% have negative genetic test results (NGTRs and ~20% have positive genetic test results (PGTRs, of which ~7% were probable de novo mutations (PDNMs. Research suggests that parental age is a risk factor for an ASD diagnosis. This study examined genotypic variation in ASD and its relationship to parental age and phenotype.Methods: Phenotype was derived from detailed clinical information, and genotype was derived from high-resolution blood chromosome and blood whole-genome copy number variant genetic testing on a consecutive cohort (born: 1983–2009 of subjects diagnosed with ASD (N=218.Results: Among the subjects examined, 80.3% had NGTRs and 19.7% had PGTRs, of which 6.9% had PDNMs. NGTR subjects were born more recently (the risk of PDNMs decreasing by 12% per more recent birth year and tended to have an increased male–female ratio compared to PDNM subjects. PDNM subjects had significantly increased mean parental age and paternal age at subject’s birth (the risk of a PDNM increasing by 7%–8% per year of parental or paternal age compared to NGTR subjects. PGTR and NGTR subjects showed significant improvements in speech/language/communication with increasing age. PGTR subjects showed significant improvements in sociability, a core feature of an ASD diagnosis, with increasing age, whereas NGTR subjects showed significant worsening in sociability with increasing age.Conclusion: This study helps to elucidate different phenotypic ASD subtypes and may even indicate the need for differential diagnostic classifications. Keywords: genotype, phenotype

  7. Genotypic Diversity Is Associated with Clinical Outcome and Phenotype in Cryptococcal Meningitis across Southern Africa.

    Directory of Open Access Journals (Sweden)

    Mathew A Beale

    Full Text Available Cryptococcal meningitis is a major cause of mortality throughout the developing world, yet little is known about the genetic markers underlying Cryptococcal virulence and patient outcome. We studied a cohort of 230 Cryptococcus neoformans (Cn isolates from HIV-positive South African clinical trial patients with detailed clinical follow-up using multi-locus sequence typing and in vitro phenotypic virulence assays, correlating these data with clinical and fungal markers of disease in the patient. South African Cn displayed high levels of genetic diversity and locus variability compared to globally distributed types, and we identified 50 sequence types grouped within the main molecular types VNI, VNII and VNB, with 72% of isolates typed into one of seven 'high frequency' sequence types. Spatial analysis of patients' cryptococcal genotype was not shown to be clustered geographically, which might argue against recent local acquisition and in favour of reactivation of latent infection. Through comparison of MLST genotyping data with clinical parameters, we found a relationship between genetic lineage and clinical outcome, with patients infected with the VNB lineage having significantly worse survival (n=8, HR 3.35, CI 1.51-7.20, p=0.003, and this was maintained even after adjustment for known prognostic indicators and treatment regimen. Comparison of fungal genotype with in vitro phenotype (phagocytosis, laccase activity and CSF survival performed on a subset of 89 isolates revealed evidence of lineage-associated virulence phenotype, with the VNII lineage displaying increased laccase activity (p=0.001 and ex vivo CSF survival (p=0.0001. These findings show that Cryptococcus neoformans is a phenotypically heterogeneous pathogen, and that lineage plays an important role in cryptococcal virulence during human infection. Furthermore, a detailed understanding of the genetic diversity in Southern Africa will support further investigation into how genetic

  8. Järgsilpide "o" ja "u" varieerumine ning traditsioonid vanas kirjakeeles / Külli Prillop

    Index Scriptorium Estoniae

    Prillop, Külli

    2009-01-01

    Kirjeldatakse, mida võib vanade tekstide põhjal oletada "o" ja "u" vaheldumisest ja selle põhjustest, kasutades eelkõige Georg Mülleri jutluste tekste. Selgitatakse ka probleeme vana kirjakeele tekstide põhjal keelemuutuste kohta järelduste tegemisel

  9. Severe Enterovirus Infections in Hospitalized Children in the South of England: Clinical Phenotypes and Causative Genotypes.

    Science.gov (United States)

    de Graaf, Hans; Pelosi, Emanuela; Cooper, Andrea; Pappachan, John; Sykes, Kim; MacIntosh, Iain; Gbesemete, Diane; Clark, Tristan W; Patel, Sanjay V; Faust, Saul N; Tebruegge, Marc

    2016-07-01

    Most enterovirus surveillance studies lack detailed clinical data, which limits their clinical usefulness. This study aimed to describe the clinical spectrum and outcome of severe enterovirus infections in children, and to determine whether there are associations between causative enterovirus genotypes and clinical phenotypes. Retrospective analysis of microbiological and clinical data from a tertiary children's hospital in the South of England over a 17-month period (2012-2013). In total, 30 patients were identified, comprising sepsis (n = 9), myocarditis (n = 8), meningitis (n = 8) and encephalitis (n = 5). Cases with sepsis or myocarditis were significantly younger than those with central nervous system disease (median age 21 and 15 days vs. 79 days; P = 0.0244 and P = 0.0310, respectively). There was considerable diversity in the causative genotypes in each of the clinical phenotypes, with some predominance of echoviruses in the meningitis group, and coxsackie B viruses in the myocarditis group. Thirteen cases required mechanical ventilation, 11 cases inotropic support, 3 cases dialysis and 3 cases extracorporal membrane oxygenation. The overall mortality was 10% (sepsis group, n = 1; myocarditis group, n = 2). Of the survivors, 5 (19%) had long-term sequelae (myocardial dysfunction, n = 2; neurological sequelae, n = 3). Patients with encephalitis had the longest hospital stay (median: 16 days), compared with 9, 6 and 3 days in patients with myocarditis, sepsis and meningitis, respectively (P = 0.005). Enterovirus infections, particularly enteroviral myocarditis and encephalitis, can cause significant morbidity and mortality. The results show that there are currently no strong associations between clinical phenotypes and particular causative enterovirus genotypes in the South of England.

  10. Genotypic and phenotypic evaluation of off-type grasses in hybrid Bermudagrass [Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy] putting greens using genotyping-by-sequencing and morphological characterization.

    Science.gov (United States)

    Reasor, Eric H; Brosnan, James T; Staton, Margaret E; Lane, Thomas; Trigiano, Robert N; Wadl, Phillip A; Conner, Joann A; Schwartz, Brian M

    2018-01-01

    Interspecific hybrid bermudagrass [ Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy] is one of the most widely used grasses on golf courses, with cultivars derived from 'Tifgreen' or 'Tifdwarf' particularly used for putting greens. Many bermudagrass cultivars established for putting greens can be genetically unstable and lead to the occurrence of undesirable off-type grasses that vary in phenotype. The objective of this research was to genetically and phenotypically differentiate off-type grasses and hybrid cultivars. Beginning in 2013, off-type and desirable hybrid bermudagrass samples were collected from golf course putting greens in the southeastern United States and genetically and phenotypically characterized using genotyping-by-sequencing and morphology. Genotyping-by-sequencing determined that 11% (5) of off-type and desirable samples from putting greens were genetically divergent from standard cultivars such as Champion, MiniVerde, Tifdwarf, TifEagle, and Tifgreen. In addition, genotyping-by-sequencing was unable to genetically distinguish all standard cultivars from one another due to their similar origin and clonal propagation; however, over 90,000 potentially informative nucleotide variants were identified among the triploid hybrid cultivars. Although few genetic differences were found in this research, samples harvested from golf course putting greens had variable morphology and were clustered into three distinct phenotypic groups. The majority of off-type grasses in hybrid bermudagrass putting greens were genetically similar with variable morphological traits. Off-type grasses within golf course putting greens have the potential to compromise putting surface functionality and aesthetics.

  11. Short communication prevalence of susceptibility to etravirine by genotype and phenotype in samples received for routine HIV type 1 resistance testing in the United States.

    Science.gov (United States)

    Picchio, Gaston; Vingerhoets, Johan; Tambuyzer, Lotke; Coakley, Eoin; Haddad, Mojgan; Witek, James

    2011-12-01

    Abstract The prevalence of susceptibility to etravirine was investigated among clinical samples submitted for routine clinical testing in the United States using two separate weighted genotypic scoring systems. The presence of etravirine mutations and susceptibility to etravirine by phenotype of clinical samples from HIV-1-infected patients, submitted to Monogram Biosciences for routine resistance testing between June 2008 and June 2009, were analyzed. Susceptibility by genotype was determined using the Monogram and Tibotec etravirine-weighted genotypic scoring systems, with scores of ≤3 and ≤2, respectively, indicating full susceptibility. Susceptibility by phenotype was determined using the PhenoSense HIV assay, with lower and higher clinical cut-offs of 2.9 and 10, respectively. The frequency of individual etravirine mutations and the impact of the K103N mutation on susceptibility to etravirine by genotype were also determined. Among the 5482 samples with ≥1 defined nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations associated with resistance, 67% were classed as susceptible to etravirine by genotype by both scoring systems. Susceptibility to etravirine by phenotype was higher (76%). The proportion of first-generation NNRTI-resistant samples with (n=3598) and without (n=1884) K103N with susceptibility to etravirine by genotype was 77% and 49%, respectively. Among samples susceptible to first-generation NNRTIs (n=9458), >99% of samples were susceptible to etravirine by phenotype (FC <2.9); the remaining samples had FC ≥2.9-10. In summary, among samples submitted for routine clinical testing in the United States, a high proportion of samples with first-generation NNRTI resistance was susceptible to etravirine by genotype and phenotype. A higher proportion of NNRTI-resistant samples with K103N than without was susceptible to etravirine.

  12. Genotype-phenotype correlation of xeroderma pigmentosum in a Chinese Han population.

    Science.gov (United States)

    Sun, Z; Zhang, J; Guo, Y; Ni, C; Liang, J; Cheng, R; Li, M; Yao, Z

    2015-04-01

    Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme sensitivity to sunlight, freckle-like pigmentation and a greatly increased incidence of skin cancers. Genetic mutation detection and genotype-phenotype analysis of XP are rarely reported in the Chinese Han population. To investigate the mutational spectrum of XP in a Chinese Han population, to discover any genotype-phenotype correlation and, consequently, to propose a simple and effective tool for the molecular diagnosis of XP. This study was carried out on 12 unrelated Chinese families that included 13 patients with clinically suspected XP. Genomic DNA was extracted from peripheral blood samples. Mutation screening was performed by direct sequencing of exons and flanking intron-exon boundaries for the entire coding region of eight XP genes. In 12 patients, direct sequencing of the whole coding region of eight XP genes revealed pathogenic mutations, including seven compound heterozygous mutations, three homozygous mutations and a Japanese founder mutation. Thirteen mutations have not been previously identified. This cohort was composed of four patients with XP-C (XPC), two with XP-G (ERCC5), three with XP-A (XPA) and three with XP-V (POLH). This study identified 13 novel mutations and extended the mutation spectrum of XP in the Chinese Han population. In this cohort, we found that patients with XP-G have no neurological symptoms, and patients with XP-A and XP-V have a high incidence of malignancy. Furthermore, lack of stringent protection against sunlight, late diagnosis and long duration of disease play an important role. © 2014 British Association of Dermatologists.

  13. Perceptual incongruence influences bistability and cortical activation

    NARCIS (Netherlands)

    Brouwer, G.J.; Tong, F.; Hagoort, P.; van Ee, R.

    2009-01-01

    We employed a parametric psychophysical design in combination with functional imaging to examine the influence of metric changes in perceptual incongruence on perceptual alternation rates and cortical responses. Subjects viewed a bistable stimulus defined by incongruent depth cues; bistability

  14. Grammatiseerumise ja leksikaliseerumise suhtest eesti vana kirjakeele modaalpartiklite näitel / Külli Habicht

    Index Scriptorium Estoniae

    Habicht, Külli, 1964-

    2006-01-01

    Uuritakse grammatiseerumist ja leksikaliseerumist ja püütakse jõuda jäeldusele, kas ainult nendega on võimalik hõlmata igasuguste keeleüksuste kujunemise protsessi. Näidetena kasutatakse vana kirjakeele modaalpartikleid

  15. Relentless spread and adaptation of non-typeable vanA vancomycin-resistant Enterococcus faecium: a genome-wide investigation.

    Science.gov (United States)

    van Hal, Sebastiaan J; Beukers, Alicia G; Timms, Verlaine J; Ellem, Justin A; Taylor, Peter; Maley, Michael W; Newton, Peter J; Ferguson, John K; Lee, Andie; Chen, Sharon C-A; Sintchenko, Vitali

    2018-03-16

    VRE are prevalent among patients in ICUs. Non-typeable vanA VRE, due to loss of one of the genes used for MLST (pstS), have increased in Australia, suggestive of a new, hospital-acquired lineage. To understand the significance of this lineage and its transmission using WGS of strains isolated from patients in ICUs across New South Wales, Australia. A total of 240 Enterococcus faecium isolates collected between February and May 2016, and identified by conventional PCR as vanA positive, were sequenced. Isolates originated from 12 ICUs in New South Wales, grouped according to six local health districts, and represented both rectal screening swab (n = 229) and clinical (n = 11) isolates. ST analysis revealed the absence of the pstS gene in 84.2% (202 of 240) of vanA isolates. Two different non-typeable STs were present based on different allelic backbone patterns. Loss of the pstS gene appeared to be the result of multiple recombination events across this region. Evidence for pstS-negative lineage spread across all six local health districts was observed suggestive of inter-hospital transmission. In addition, multiple outbreaks were detected, some of which were protracted and lasted for the duration of the study. These findings confirmed the evolution, emergence and dissemination of non-typeable vanA E. faecium. This study has highlighted the utility of WGS when attempting to describe accurately the hospital-based pathogen epidemiology, which in turn will continue to inform optimal infection control measures necessary to halt the spread of this important nosocomial organism.

  16. Phenotype-genotype correlation in Wilson disease in a large Lebanese family: association of c.2299insC with hepatic and of p. Ala1003Thr with neurologic phenotype.

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    Julnar Usta

    Full Text Available Genotype phenotype correlations in Wilson disease (WD are best established in homozygous patients or in compound heterozygous patients carrying the same set of mutations. We determined the clinical phenotype of patients with WD carrying the c.2298_2299insC in Exon 8 (c.2299insC or the p. Ala1003Thr missense substitution in Exon 13 mutations in the homozygous or compound heterozygous state. We investigated 76 members of a single large Lebanese family. Their genotypes were determined, and clinical assessments were carried out for affected subjects. We also performed a literature search retrieving the phenotypes of patients carrying the same mutations of our patients in the homozygous or compound heterozygous state. There were 7 consanguineous marriages in this family and the prevalence of WD was 8.9% and of carriers of ATP7B mutation 44.7%. WD was confirmed in 9 out of 76 subjects. All 9 had the c.2299insC mutation, 5 homozygous and 4-compound heterozygous with p. Ala1003Thr. Six of our patients had hepatic, 2 had neurologic and 1 had asymptomatic phenotype. Based on our data and a literature review, clear phenotypes were reported for 38 patients worldwide carrying the c.2299insC mutation. About 53% of those have hepatic and 29% have neurologic phenotype. Furthermore, there were 10 compound heterozygous patients carrying the p. Ala1003Thr mutation. Among those, 80% having c.2299insC as the second mutation had hepatic phenotype, and all others had neurologic phenotype. We hereby report an association between the c.2299insC mutation and hepatic phenotype and between the p. Ala1003Thr mutation and neurologic phenotype.

  17. Colonización por cepas de Enterococcus spp. VanA en pacientes del hospital universitario Manuel Núñez Tovar, Maturín, Venezuela | Colonization by strains of Enterococcus spp. VanA in patients of the university hospital Manuel Núñez Tovar, Maturín, Venezuela

    Directory of Open Access Journals (Sweden)

    Lorena Abadia-Patiño

    2017-10-01

    Full Text Available En el Hospital Universitario Manuel Núñez Tovar de Maturín (HUMNT, estado Monagas, se aislaron tres cepas de Enterococcus faecium VanA en la unidad de cuidados intensivos (UCI y una cepa de E. faecalis VanA en la unidad de hemodiálisis (HD. La prevalencia de colonización de Enterococcus vancomicino resistentes (EVR fenotipo VanA durante el período de estudio fue de 3% en los pacientes de HD y 9% en los de UCI. Los factores de riesgo para los pacientes fueron el uso indiscriminado de antibióticos como vancomicina y cefalosporinas de tercera generación y el tiempo de permanencia en UCI. Existe alto riesgo de infecciones endógenas por cepas EVR en el HUMNT.

  18. Evaluation of genotype-phenotype relationships in patients referred for endocrine assessment in suspected Pendred syndrome.

    Science.gov (United States)

    Soh, Lip Min; Druce, Maralyn; Grossman, Ashley B; Differ, Ann-Marie; Rajput, Liala; Bitner-Glindzicz, Maria; Korbonits, Márta

    2015-02-01

    Patients with Pendred syndrome have genotypic and phenotypic variability, leading to challenges in definitive diagnosis. Deaf children with enlarged vestibular aqueducts are often subjected to repeated investigations when tests for mutations in SLC26A4 are abnormal. This study provides genotype and phenotype information from patients with suspected Pendred syndrome referred to a single clinical endocrinology unit. A retrospective analysis of 50 patients with suspected Pendred syndrome to investigate the correlation between genetic, perchlorate discharge test (PDT) and endocrine status. Eight patients with monoallelic SLC26A4 mutations had normal PDT. Of the 33 patients with biallelic mutations, ten of 12 patients with >30% discharge developed hypothyroidism. In our cohort, c.626G>T and c.3-2A>G result in milder clinical presentations with lower median perchlorate discharge of 9.3% (interquartile range 4-15%) compared with 40% (interquartile range 21-60%) for the remaining mutations. Eight novel mutations were detected. All patients with PDT 30% have a high risk of developing goitre and hypothyroidism, and should have lifelong monitoring. © 2015 European Society of Endocrinology.

  19. Genotypic and phenotypic β-lactam resistance and presence of PVL gene in Staphylococci from dry bovine udder.

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    Vinodkumar Kulangara

    Full Text Available Dairy cows affected with subclinical mastitis can be sources of virulent, antimicrobial-resistant Staphylococci to humans because of the excretion of the bacteria through their milk. This study focussed on the phenotypic and genotypic antibiotic resistance patterns of Staphylococci isolated from dairy cows in early dry period. Among 96 isolates of Gram positive cocci from 157 cows, 76 were identified as Coagulase Negative Staphylococci and the remaining 20 were Staphylococcus aureus. Typical amplicons of coagulase gene were obtained for all 20 samples of S. aureus with three major coagulase types being identified as giving 627 bp (40%, 910 bp (35% and 710 bp (25% long PCR products. The groEL gene was amplified in PCR of all 76 isolates of Coagulase Negative Staphylococci, and incubation of PCR products with restriction enzyme PvuII yielded three distinct PCR-RFLP fragment patterns bearing resemblance to S. chromogenes and S. hyicus. Highest sensitivity of Coagulase Negative Staphylococci was noted for Azithromycin (92.5% and the least to Tetracyclines (76.3%, whereas for S. aureus, it was Cefoperazone (95% and Azithromycin (72.2% respectively. Phenotypic resistance to Oxacillin (25 isolates, and Cefoxitin (11 isolates was detected by dilution method with a commercial strip (Ezy MICTM. Genotypic resistance to β-Lactam antibiotics was found in 65 (34 with mecA gene and 31 with blaZ gene isolates. Eighteen isolates possessed both the genes, with the PVL gene for virulence being detected in five of them. Nine isolates which had mecA gene were phenotypically susceptible to oxacillin while phenotypic resistance to oxacillin was observed in seven isolates that did not have either mecA or blaZ gene. This is the first report of persistent Staphylococcal infections possessing PVL gene and high level of genotypic resistance to β-Lactam antibiotics in small- holder dairy cattle from India.

  20. Genotypic and phenotypic β-lactam resistance and presence of PVL gene in Staphylococci from dry bovine udder

    Science.gov (United States)

    Sivasailam, Asok; Sasidharan, Suchithra; Kollannur, Justin Davis; Syam, Radhika

    2017-01-01

    Dairy cows affected with subclinical mastitis can be sources of virulent, antimicrobial-resistant Staphylococci to humans because of the excretion of the bacteria through their milk. This study focussed on the phenotypic and genotypic antibiotic resistance patterns of Staphylococci isolated from dairy cows in early dry period. Among 96 isolates of Gram positive cocci from 157 cows, 76 were identified as Coagulase Negative Staphylococci and the remaining 20 were Staphylococcus aureus. Typical amplicons of coagulase gene were obtained for all 20 samples of S. aureus with three major coagulase types being identified as giving 627 bp (40%), 910 bp (35%) and 710 bp (25%) long PCR products. The groEL gene was amplified in PCR of all 76 isolates of Coagulase Negative Staphylococci, and incubation of PCR products with restriction enzyme PvuII yielded three distinct PCR-RFLP fragment patterns bearing resemblance to S. chromogenes and S. hyicus. Highest sensitivity of Coagulase Negative Staphylococci was noted for Azithromycin (92.5%) and the least to Tetracyclines (76.3%), whereas for S. aureus, it was Cefoperazone (95%) and Azithromycin (72.2%) respectively. Phenotypic resistance to Oxacillin (25 isolates), and Cefoxitin (11 isolates) was detected by dilution method with a commercial strip (Ezy MICTM). Genotypic resistance to β-Lactam antibiotics was found in 65 (34 with mecA gene and 31 with blaZ gene) isolates. Eighteen isolates possessed both the genes, with the PVL gene for virulence being detected in five of them. Nine isolates which had mecA gene were phenotypically susceptible to oxacillin while phenotypic resistance to oxacillin was observed in seven isolates that did not have either mecA or blaZ gene. This is the first report of persistent Staphylococcal infections possessing PVL gene and high level of genotypic resistance to β-Lactam antibiotics in small- holder dairy cattle from India. PMID:29091956

  1. Comparison phenotypic and genotypic identification of Staphylococcus species isolated from bovine mastitis

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    Felipe Freitas Guimarães

    Full Text Available ABSTRACT: In addition to Staphylococcus aureus nowadays other coagulase-positive staphylococci (CoPS and coagulase-negative staphylococci (CoNS, earlier considered of minor importance, are now accepted as relevant pathogens for humans and animals. The involvement of these microorganisms in bovine mastitis etiology and the possibility their transmission through milk to humans justify the requirement of developing reliable methods for identification of the most frequent species among them. The purpose of this study was to compare the phenotypic techniques with the genotypic method carried out by sequencing of the rpoB gene in identification of several species of the genus Staphylococcus isolated from bovine mastitis. A total of 300 staphylococci isolates of bovine mastitis cases from several Brazilian dairy herds were studied by phenotypic and genotypic techniques, respectively: 150 CoPS and 150 CoNS strains. A total of 18 CoNS different species and 4 CoPS species were identified. Among the CoNS the following species were recognized: 48 (32% Staphylococcus warneri, 22(15% S. epidermidis, 20(13% S. hyicus, 10(7% S. xylosus, 7(5% S. haemolyticus, 6(4% S. simulans, 6(4% S. schleiferi subsp schleiferi, 6(4% S. hominis, 5(3% S. pasteuri, 4(2.7% S. cohnii, 3(2% S. saprophyticus subsp. saprophyticus 3(2% S. chromogenes 3(2% S. sciuri, 2(1% S. saccharolyticus, 2(1% S. lugdunensi, 1(0,7% S. auricularis, 1(70% S. saprophyticus subsp. bovis, 1(0.7% S. capitis. And among the 150 CoPS were identified respectively: 105 (70% S. aureus, 21(14%, S. hyicus, 19(13% S. intermedius e 5(3% S. schleiferi subsp coagulans. Considering the 150 CoNS isolates, the identifications performed by phenotypic and genotypic tests presented 96.7% of concordance, kappa coefficient of agreement = 0.933, SE (standard error of kappa=0.021 (95% confidence interval: 0.893 to 0.974, Pearson’s correlation coefficient (r = 0.9977, (confidence interval 95%: 0.9938 a 0.9992 and in relation

  2. Can genotype determine the sports phenotype? A paradigm shift in sports medicine.

    Science.gov (United States)

    Ghosh, Amit; Mahajan, Preetam B

    2016-06-01

    In last two decades, there has been an evolution in sports medicine. Several researchers have worked on different domains of sports medicine, like strength, endurance, sports injury, and psychology. Besides this, several groups have explored the changes at cellular and molecular levels during exercise, which has led to the development of the new domain in sports science known as genetic medicine. Genetic medicine deals with the genotypic basis of sports phenotype. In this article, we try to provide an up-to-date review on genetic determinants of sports performance, which will be like a journey from the nostalgic past towards the traditional present and the romantic future of sports medicine. Endurance and power performance are two important domains of athletes. They vary in individuals, even among trained athletes. Researches indicate that the genetic makeup of sportsmen play a vital role in their performance. Several genetic factors are reported to be responsible for endurance, power, susceptibility to injury, and even psychology of the individual. Besides this, proper training, nutrition, and environment are also important in shaping their potential. The aim of this discussion is to understand the influence of the environment and the genetic makeup on the performance of the athletes. There is sufficient evidence to suggest that genotype determines the sports phenotype in an athlete. Choosing the right sports activity based on genetic endowment is the key for achieving excellence in sports.

  3. Novel mutations and their genotype-phenotype correlations in patients with Noonan syndrome, using next-generation sequencing.

    Science.gov (United States)

    Tafazoli, Alireza; Eshraghi, Peyman; Pantaleoni, Francesca; Vakili, Rahim; Moghaddassian, Morteza; Ghahraman, Martha; Muto, Valentina; Paolacci, Stefano; Golyan, Fatemeh Fardi; Abbaszadegan, Mohammad Reza

    2018-03-01

    Noonan Syndrome (NS) is an autosomal dominant disorder with many variable and heterogeneous conditions. The genetic basis for 20-30% of cases is still unknown. This study evaluates Iranian Noonan patients both clinically and genetically for the first time. Mutational analysis of PTPN11 gene was performed in 15 Iranian patients, using PCR and Sanger sequencing at phase one. Then, as phase two, Next Generation Sequencing (NGS) in the form of targeted resequencing was utilized for analysis of exons from other related genes. Homology modelling for the novel founded mutations was performed as well. The genotype, phenotype correlation was done according to the molecular findings and clinical features. Previously reported mutation (p.N308D) in some patients and a novel mutation (p.D155N) in one of the patients were identified in phase one. After applying NGS methods, known and new variants were found in four patients in other genes, including: CBL (p. V904I), KRAS (p. L53W), SOS1 (p. I1302V), and SOS1 (p. R552G). Structural studies of two deduced novel mutations in related genes revealed deficiencies in the mutated proteins. Following genotype, phenotype correlation, a new pattern of the presence of intellectual disability in two patients was registered. NS shows strong variable expressivity along the high genetic heterogeneity especially in distinct populations and ethnic groups. Also possibly unknown other causative genes may be exist. Obviously, more comprehensive and new technologies like NGS methods are the best choice for detection of molecular defects in patients for genotype, phenotype correlation and disease management. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

  4. Relation between CYP2D6 Genotype, Phenotype and Therapeutic Drug Concentrations among Nortriptyline and Venlafaxine Users in Old Age Psychiatry

    NARCIS (Netherlands)

    Berm, E; Kok, R.; Hak, E; Wilffert, B

    2016-01-01

    Objectives: To determine relations between drug concentrations and the cytochrome P450-CYP2D6 genotype or phenotype among elderly patients treated with nortriptyline or venlafaxine. Methods: A post-hoc analysis of a clinical trial was performed. Patients were grouped into phenotypes according to the

  5. Genotype, Phenotype and Outcomes of Nine Patients with T-B+NK+ SCID

    OpenAIRE

    Yu, Grace P; Nadeau, Kari C; Berk, David R; de Saint Basile, Geneviève; Lambert, Nathalie; Knapnougel, Perrine; Roberts, Joseph; Kavanau, Kristina; Dunn, Elizabeth; Stiehm, E. Richard; Lewis, David B; Umetsu, Dale T; Puck, Jennifer M; Cowan, Morton J

    2011-01-01

    There are few reports of clinical presentation, genotype, and hematopoietic cell transplant (HCT) outcomes for T-B+NK+ SCID patients. Between 1981 and 2007, 8 of 84 SCID patients who received and/or were followed after HCT at UCSF had the T-B+NK+ phenotype. One additional T-B+NK+ SCID patient was identified as the sibling of a patient treated at UCSF. Chart reviews were performed. Molecular analyses of IL7R, IL2RG, JAK3 and the genes encoding the CD3 T-cell receptor components δ (CD3D), ε (CD...

  6. Perceptual incongruence influences bistability and cortical activation.

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    Gijs Joost Brouwer

    Full Text Available We employed a parametric psychophysical design in combination with functional imaging to examine the influence of metric changes in perceptual incongruence on perceptual alternation rates and cortical responses. Subjects viewed a bistable stimulus defined by incongruent depth cues; bistability resulted from incongruence between binocular disparity and monocular perspective cues that specify different slants (slant rivalry. Psychophysical results revealed that perceptual alternation rates were positively correlated with the degree of perceived incongruence. Functional imaging revealed systematic increases in activity that paralleled the psychophysical results within anterior intraparietal sulcus, prior to the onset of perceptual alternations. We suggest that this cortical activity predicts the frequency of subsequent alternations, implying a putative causal role for these areas in initiating bistable perception. In contrast, areas implicated in form and depth processing (LOC and V3A were sensitive to the degree of slant, but failed to show increases in activity when these cues were in conflict.

  7. Evaluation of Lactococcus lactis Isolates from Nondairy Sources with Potential Dairy Applications Reveals Extensive Phenotype-Genotype Disparity and Implications for a Revised Species.

    Science.gov (United States)

    Cavanagh, Daniel; Casey, Aidan; Altermann, Eric; Cotter, Paul D; Fitzgerald, Gerald F; McAuliffe, Olivia

    2015-06-15

    Lactococcus lactis is predominantly associated with dairy fermentations, but evidence suggests that the domesticated organism originated from a plant niche. L. lactis possesses an unusual taxonomic structure whereby strain phenotypes and genotypes often do not correlate, which in turn has led to confusion in L. lactis classification. A bank of L. lactis strains was isolated from various nondairy niches (grass, vegetables, and bovine rumen) and was further characterized on the basis of key technological traits, including growth in milk and key enzyme activities. Phenotypic analysis revealed all strains from nondairy sources to possess an L. lactis subsp. lactis phenotype (lactis phenotype); however, seven of these strains possessed an L. lactis subsp. cremoris genotype (cremoris genotype), determined by two separate PCR assays. Multilocus sequence typing (MLST) showed that strains with lactis and cremoris genotypes clustered together regardless of habitat, but it highlighted the increased diversity that exists among "wild" strains. Calculation of average nucleotide identity (ANI) and tetranucleotide frequency correlation coefficients (TETRA), using the JSpecies software tool, revealed that L. lactis subsp. cremoris and L. lactis subsp. lactis differ in ANI values by ∼14%, below the threshold set for species circumscription. Further analysis of strain TIFN3 and strains from nonindustrial backgrounds revealed TETRA values of lactis taxonomy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Expansion of phenotype and genotypic data in CRB2-related syndrome.

    Science.gov (United States)

    Lamont, Ryan E; Tan, Wen-Hann; Innes, A Micheil; Parboosingh, Jillian S; Schneidman-Duhovny, Dina; Rajkovic, Aleksandar; Pappas, John; Altschwager, Pablo; DeWard, Stephanie; Fulton, Anne; Gray, Kathryn J; Krall, Max; Mehta, Lakshmi; Rodan, Lance H; Saller, Devereux N; Steele, Deanna; Stein, Deborah; Yatsenko, Svetlana A; Bernier, François P; Slavotinek, Anne M

    2016-10-01

    Sequence variants in CRB2 cause a syndrome with greatly elevated maternal serum alpha-fetoprotein and amniotic fluid alpha-fetoprotein levels, cerebral ventriculomegaly and renal findings similar to Finnish congenital nephrosis. All reported patients have been homozygotes or compound heterozygotes for sequence variants in the Crumbs, Drosophila, Homolog of, 2 (CRB2) genes. Variants affecting CRB2 function have also been identified in four families with steroid resistant nephrotic syndrome, but without any other known systemic findings. We ascertained five, previously unreported individuals with biallelic variants in CRB2 that were predicted to affect function. We compiled the clinical features of reported cases and reviewed available literature for cases with features suggestive of CRB2-related syndrome in order to better understand the phenotypic and genotypic manifestations. Phenotypic analyses showed that ventriculomegaly was a common clinical manifestation (9/11 confirmed cases), in contrast to the original reports, in which patients were ascertained due to renal disease. Two children had minor eye findings and one was diagnosed with a B-cell lymphoma. Further genetic analysis identified one family with two affected siblings who were both heterozygous for a variant in NPHS2 predicted to affect function and separate families with sequence variants in NPHS4 and BBS7 in addition to the CRB2 variants. Our report expands the clinical phenotype of CRB2-related syndrome and establishes ventriculomegaly and hydrocephalus as frequent manifestations. We found additional sequence variants in genes involved in kidney development and ciliopathies in patients with CRB2-related syndrome, suggesting that these variants may modify the phenotype.

  9. Diabetes and neurodegeneration in Wolfram syndrome: a multicenter study of phenotype and genotype.

    Science.gov (United States)

    Rohayem, Julia; Ehlers, Christian; Wiedemann, Bärbel; Holl, Reinhard; Oexle, Konrad; Kordonouri, Olga; Salzano, Giuseppina; Meissner, Thomas; Burger, Walter; Schober, Edith; Huebner, Angela; Lee-Kirsch, Min Ae

    2011-07-01

    To describe the diabetes phenotype in Wolfram syndrome compared with type 1 diabetes, to investigate the effect of glycemic control on the neurodegenerative process, and to assess the genotype-phenotype correlation. The clinical data of 50 patients with Wolfram syndrome-related diabetes (WSD) were reviewed and compared with the data of 24,164 patients with type 1 diabetes. Patients with a mean HbA1c during childhood and adolescence of ≤7.5 and >7.5% were compared with respect to the occurrence of additional Wolfram syndrome symptoms. The wolframin (WFS1) gene was screened for mutations in 39 patients. WFS1 genotypes were examined for correlation with age at onset of diabetes. WSD was diagnosed earlier than type 1 diabetes (5.4±3.8 vs. 7.9±4.2 years; P7.5% (P=0.031). Thirteen novel WSF1 mutations were identified. Predicted functional consequence of WFS1 mutations correlated with age at WSD onset (P=0.028). Endoplasmic reticulum stress-mediated decline of β-cells in WSD occurs earlier in life than autoimmune-mediated β-cell destruction in type 1 diabetes. This study establishes a role for WFS1 in determining the age at onset of diabetes in Wolfram syndrome and identifies glucose toxicity as an accelerating feature in the progression of disease.

  10. The Genotype and Phenotype (GaP) registry: a living biobank for the analysis of quantitative traits.

    Science.gov (United States)

    Gregersen, Peter K; Klein, Gila; Keogh, Mary; Kern, Marlena; DeFranco, Margaret; Simpfendorfer, Kim R; Kim, Sun Jung; Diamond, Betty

    2015-12-01

    We describe the development of the Genotype and Phenotype (GaP) Registry, a living biobank of normal volunteers who are genotyped for genetic markers related to human disease. Participants in the GaP can be recalled for hypothesis driven study of disease associated genetic variants. The GaP has facilitated functional studies of several autoimmune disease associated loci including Csk, Blk, PDRM1 (Blimp-1) and PTPN22. It is likely that expansion of such living biobank registries will play an important role in studying and understanding the function of disease associated alleles in complex disease.

  11. Host range of enterococcal vanA plasmids among Gram-positive intestinal bacteria

    DEFF Research Database (Denmark)

    Werner, Guido; Freitas, Ana R.; Coque, Teresa M.

    2010-01-01

    recipients. Transfer rates were calculated per donor and recipient. Transconjugants were confirmed by determining their phenotypic and genotypic properties. Stability of plasmids in the new host was assessed in long-term growth experiments. RESULTS: In total, 282 enterococcal matings and 73 inter...

  12. Genotypic and Phenotypic Diversity of Cryptococcus gattii VGII Clinical Isolates and Its Impact on Virulence

    Directory of Open Access Journals (Sweden)

    Vanessa A. Barcellos

    2018-02-01

    Full Text Available The Cryptococcus gattii species complex harbors the main etiological agents of cryptococcosis in immunocompetent patients. C. gattii molecular type VGII predominates in the north and northeastern regions of Brazil, leading to high morbidity and mortality rates. C. gattii VGII isolates have a strong clinical relevance and phenotypic variations. These phenotypic variations among C. gattii species complex isolates suggest that some strains are more virulent than others, but little information is available related to the pathogenic properties of those strains. In this study, we analyzed some virulence determinants of C. gattii VGII strains (CG01, CG02, and CG03 isolated from patients in the state of Piauí, Brazil. The C. gattii R265 VGIIa strain, which was isolated from the Vancouver outbreak, differed from C. gattii CG01, CG02 and CG03 isolates (also classified as VGII when analyzed the capsular dimensions, melanin production, urease activity, as well as the glucuronoxylomannan (GXM secretion. Those differences directly reflected in their virulence potential. In addition, CG02 displayed higher virulence compared to R265 (VGIIa strain in a cryptococcal murine model of infection. Lastly, we examined the genotypic diversity of these strains through Multilocus Sequence Type (MLST and one new subtype was described for the CG02 isolate. This study confirms the presence and the phenotypic and genotypic diversity of highly virulent strains in the Northeast region of Brazil.

  13. Phenotypic and Genotypic Analysis of Newly Obtained Interspecific Hybrids in the Campanula Genus.

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    Anna-Catharina Röper

    Full Text Available Interspecific hybridisation creates new phenotypes within several ornamental plant species including the Campanula genus. We have employed phenotypic and genotypic methods to analyse and evaluate interspecific hybridisation among cultivars of four Campanula species, i.e. C. cochleariifolia, C. isophylla, C. medium and C. formanekiana. Hybrids were analysed using amplified fragment length polymorphism (AFLP, flow cytometry and biometrical measurements. Results of correlation matrices demonstrated heterogeneous phenotypes for the parental species, which confirmed our basic premise for new phenotypes of interspecific hybrids. AFLP assays confirmed the hybridity and identified self-pollinated plants. Limitation of flow cytometry analysis detection was observed while detecting the hybridity status of two closely related parents, e.g. C. cochleariiafolia × C. isophylla. Phenotypic characteristics such as shoot habitus and flower colour were strongly influenced by one of the parental species in most crosses. Rooting analysis revealed that inferior rooting quality occurred more often in interspecific hybrids than in the parental species. Only interspecific hybrid lines of C. formanekiana 'White' × C. medium 'Pink' showed a high rooting level. Phenotype analyses demonstrated a separation from the interspecific hybrid lines of C. formanekiana 'White' × C. medium 'Pink' to the other clustered hybrids of C. formanekiana and C. medium. In our study we demonstrated that the use of correlation matrices is a suitable tool for identifying suitable cross material. This study presents a comprehensive overview for analysing newly obtained interspecific hybrids. The chosen methods can be used as guidance for analyses for further interspecific hybrids in Campanula, as well as in other ornamental species.

  14. PHENOTYPIC AND GENOTYPIC ANALYSIS OF AN ARCANOBACTERIUM PLURANIMALIUM ISOLATED FROM A MUSKOX (OVIBOS MOSCHATUS

    Directory of Open Access Journals (Sweden)

    Siti Gusti Ningrum

    2017-03-01

    Full Text Available The present study was designed to characterize an Arcanobacterium pluranimalium strain isolated from a muskox (Ovibos moschatus phenotypically, by MALDI-TOF MS analysis and genotypically using various molecular targets. The phenotypic properties, the MALDI-TOF MS analysis and sequencing the 16S rRNA gene, the β subunit of bacterial RNA polymerase encoding gene rpoB, the glyceraldehyde 3-phosphate dehydrogenase encoding gene gap, the elongation factor tu encoding gene tuf and the pluranimaliumlysin encoding gene pla allowed a successful identification of the isolated strain as A. pluranimalium. Gene pla could also be detected by a previously described loop-mediated isothermal amplification (LAMP assay. This is first report on the isolation and characterization of A. pluranimalium originated from a Muskox.

  15. Phylogenetic incongruence in E. coli O104: understanding the evolutionary relationships of emerging pathogens in the face of homologous recombination.

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    Weilong Hao

    Full Text Available Escherichia coli O104:H4 was identified as an emerging pathogen during the spring and summer of 2011 and was responsible for a widespread outbreak that resulted in the deaths of 50 people and sickened over 4075. Traditional phenotypic and genotypic assays, such as serotyping, pulsed field gel electrophoresis (PFGE, and multilocus sequence typing (MLST, permit identification and classification of bacterial pathogens, but cannot accurately resolve relationships among genotypically similar but pathotypically different isolates. To understand the evolutionary origins of E. coli O104:H4, we sequenced two strains isolated in Ontario, Canada. One was epidemiologically linked to the 2011 outbreak, and the second, unrelated isolate, was obtained in 2010. MLST analysis indicated that both isolates are of the same sequence type (ST678, but whole-genome sequencing revealed differences in chromosomal and plasmid content. Through comprehensive phylogenetic analysis of five O104:H4 ST678 genomes, we identified 167 genes in three gene clusters that have undergone homologous recombination with distantly related E. coli strains. These recombination events have resulted in unexpectedly high sequence diversity within the same sequence type. Failure to recognize or adjust for homologous recombination can result in phylogenetic incongruence. Understanding the extent of homologous recombination among different strains of the same sequence type may explain the pathotypic differences between the ON2010 and ON2011 strains and help shed new light on the emergence of this new pathogen.

  16. Neuroelectric Correlates of Pragmatic Emotional Incongruence Processing: Empathy Matters.

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    Dorian Dozolme

    Full Text Available The emotions people feel can be simulated internally based on emotional situational contexts. In the present study, we assessed the behavioral and neuroelectric effects of seeing an unexpected emotional facial expression. We investigated the correct answer rate, response times and Event-Related Potential (ERP effects during an incongruence paradigm between emotional faces and sentential contexts allowing emotional inferences. Most of the 36 healthy participants were recruited from a larger population (1 463 subjects, based on their scores on the Empathy Questionnaire (EQ. Regression analyses were conducted on these ratings using EQ factors as predictors (cognitive empathy, emotional reactivity and social skills. Recognition of pragmatic emotional incongruence was less accurate (P < .05 and slower (P < .05 than recognition of congruence. The incongruence effect on response times was inversely predicted by social skills. A significant N400 incongruence effect was found at the centro-parietal (P < .001 and centro-posterior midline (P < .01 electrodes. Cognitive empathy predicted the incongruence effect in the left occipital region, in the N400 time window. Finally, incongruence effects were also found on the LPP wave, in frontal midline and dorso-frontal regions, (P < .05, with no modulation by empathy. Processing pragmatic emotional incongruence is more cognitively demanding than congruence (as reflected by both behavioral and ERP data. This processing shows modulation by personality factors at the behavioral (through self-reported social skills and neuroelectric levels (through self-reported cognitive empathy.

  17. Skin reaction and regeneration after single sodium lauryl sulfate exposure stratified by filaggrin genotype and atopic dermatitis phenotype.

    Science.gov (United States)

    Bandier, J; Carlsen, B C; Rasmussen, M A; Petersen, L J; Johansen, J D

    2015-06-01

    Filaggrin is key for the integrity of the stratum corneum. Mutations in the filaggrin gene (FLGnull) play a prominent role in atopic dermatitis (AD) pathogenesis. People with AD have increased susceptibility to irritants. However, little is known about the effect of filaggrin genotype and AD phenotype on irritant response and skin regeneration. To investigate the role of FLGnull and AD groups for skin reaction and recovery after sodium lauryl sulfate (SLS) irritation. This is a case-control study comprising 67 subjects, including healthy controls and patients with and without FLGnull and AD. Reactivity to different doses of SLS at 24, 48, 72 and 145 h after SLS application was measured by transepidermal water loss (TEWL) and laser Doppler flowmetry (LDF). Reactivity was assessed univariately and by pattern analysis. All patient groups showed a higher degree of skin-barrier disruption and inflammation than did controls in response to SLS. Assessing reactivity by the delta value of the area under the curve for both TEWL and LDF showed significant differences between healthy controls and those with the AD phenotype, irrespective of filaggrin mutation. The poorest regeneration was among those with the AD phenotype. The two AD phenotype groups were separated by multivariate technique, due to earlier inflammatory reactivity among subjects with FLGnullplus AD compared with the AD phenotype alone. Both skin reaction and regeneration were significantly different between the patient population and the healthy controls. Additionally, response severity and regeneration depended more on AD phenotype than on filaggrin genotype, whereas the response was more rapid among the FLGnullplus AD individuals. © 2015 British Association of Dermatologists.

  18. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Andresen, B S; Olpin, S; Poorthuis, B J

    1999-01-01

    Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyop......Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence...... of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting......-phenotype relationship is in sharp contrast to what has been observed in medium-chain acyl-CoA dehydrogenase deficiency, in which no correlation between genotype and phenotype can be established....

  19. Phenotype-Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy.

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    Dandan Tan

    Full Text Available This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA-related muscular dystrophy (MD. The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293 cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD. Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.

  20. Cluster-distinguishing genotypic and phenotypic diversity of carbapenem-resistant Gram-negative bacteria in solid-organ transplantation patients: a comparative study.

    Science.gov (United States)

    Karampatakis, Theodoros; Geladari, Anastasia; Politi, Lida; Antachopoulos, Charalampos; Iosifidis, Elias; Tsiatsiou, Olga; Karyoti, Aggeliki; Papanikolaou, Vasileios; Tsakris, Athanassios; Roilides, Emmanuel

    2017-07-31

    Solid-organ transplant recipients may display high rates of colonization and/or infection by multidrug-resistant bacteria. We analysed and compared the phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolated from patients in the Solid Organ Transplantation department of our hospital. Between March 2012 and August 2013, 56 CR strains from various biological fluids underwent antimicrobial susceptibility testing with VITEK 2, molecular analysis by PCR amplification and genotypic analysis with pulsed-field gel electrophoresis (PFGE). They were clustered according to antimicrobial drug susceptibility and genotypic profiles. Diversity analyses were performed by calculating Simpson's diversity index and applying computed rarefaction curves.Results/Key findings. Among K. pneumoniae, KP-producers predominated (57.1 %). VIM and OXA-23 carbapenemases prevailed among P. aeruginosa and A. baumannii (89.4 and 88.9 %, respectively). KPC-producing K. pneumoniae and OXA-23 A. baumannii were assigned in single PFGE pulsotypes. VIM-producing P. aeruginosa generated multiple pulsotypes. CR K. pneumoniae strains displayed phenotypic diversity in tigecycline, colistin (CS), amikacin (AMK), gentamicin (GEN) and co-trimoxazole (SXT) (16 clusters); P. aeruginosa displayed phenotypic diversity in cefepime (FEP), ceftazidime, aztreonam, piperacillin, piperacillin-tazobactam, AMK, GEN and CS (9 clusters); and A. baumannii displayed phenotypic diversity in AMK, GEN, SXT, FEP, tobramycin and rifampicin (8 clusters). The Simpson diversity indices for the interpretative phenotype and PFGE analysis were 0.89 and 0.6, respectively, for K. pneumoniae strains (P<0.001); 0.77 and 0.6 for P. aeruginosa (P=0.22); and 0.86 and 0.19 for A. baumannii (P=0.004). The presence of different antimicrobial susceptibility profiles does not preclude the possibility that two CR K. pneumoniae or A. baumannii

  1. Epidemiological markers in Neisseria meningitidis: an estimate of the performance of genotyping vs phenotyping

    DEFF Research Database (Denmark)

    Weis, N; Lind, I

    1998-01-01

    In order to estimate the performance of genotypic vs phenotypic characterization of Neisseria meningitidis, 2 methods, DNA fingerprinting and multilocus enzyme electrophoresis (MEE), were assessed as regards applicability, reproducibility and discriminating capacity. 50 serogroup B and 52 serogroup...... C Neisseria meningitidis strains from 96 patients with meningococcal disease and 22 serogroup C strains from healthy carriers were investigated. Both methods were 100% applicable to meningococcal strains and results of DNA fingerprinting as well as of MEE were reproducible. The number of types...... defined by DNA fingerprinting and MEE as compared to that defined by phenotypic characteristics (serogroup, serotype, serosubtype and sulphonamide resistance) was as follows: for serogroup B strains from patients, 11 and 12 vs 8; for serogroup C strains from patients, 10 and 15 vs 8; and for serogroup C...

  2. Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

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    Renzhi Wang

    2016-09-01

    Full Text Available Adrenocorticotrophin (ACTH-secreting pituitary adenoma, also known as Cushing disease (CD, is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT. We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1, collagen type I α 1 chain (COL1A1, 5′-nucleotidase ecto (NT5E, HtrA serine peptidase 1 (HTRA1 and angiopoietin 1 (ANGPT1 and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

  3. Phenotypic and Genotypic Antibiotic Resistance of Salmonella from Chicken Carcasses Marketed at Ibague, Colombia

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    D Cortes Vélez

    Full Text Available ABSTRACT Salmonella enterica is responsible for alimentary toxic infections associated with the consumption of contaminated poultry products and the antimicrobial resistant patterns of Salmonella circulating in the Tolima region are currently unknown. To address this issue, both the phenotype and genotype antibiotic resistance patterns of 47 Salmonella isolated from raw chicken carcasses sold at the Ibague city were analyzed by the disc diffusion, microdilution and PCR assays. All 47 Salmonella isolates showed resistance to five or more antimicrobial agents. Resistance to Ampicillin (AMP, Amikacin (AMK, Gentamicin (GEN, Tobramycin (TOB, Cefazoline (CFZ, Cefoxitin (FOX, Nitrofurantoin (NIT, Trimethoprim-Sulfamethoxazole (SXT, Tetracycline (TET, Ciprofloxacin (CIP and Enrofloxacin (ENR was observed in 42.35% of Salmonella isolates. All tested S. Paratyphi B var Java isolates showed resistance to at least 12 antibiotics. S. Hvittingfoss showed resistance to 5 antibiotics, whereas S. Muenster showed resistance to seven antibiotics. Amplification of a number of antibiotic resistance genes showed that blaTEM (100% correlated well with resistance to Ampicilin and Cephalosporin, whereas aadB (87% correlated well with resistance to Aminoglycosides. It is concluded that Salmonella isolated from raw chicken meat marketed at Ibague showed MDR by both phenotypic and genotypic methods and they may represent an important threat to human health. Additional studies are needed to establish the relationship between antibiotic resistance in Salmonella from poultry products and clinical isolates.

  4. Genotype-phenotype correlations of dyshormonogenetic goiter in children and adolescents from South India

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    Bangaraiah Gari Ramesh

    2016-01-01

    Full Text Available Background: Dyshormonogenetic goiter is one of the most common causes of hypothyroidism in children and adolescents in iodine nonendemic areas. The exact genotype-phenotypic correlations (GPCs and risk categorization of hypothyroid phenotypes of dyshormonogenetic mutations are largely speculative. The genetic studies in pediatric dyshormonogenesis are very sparse from Indian sub-continent. In this context, we analyzed the implications of TPO, NIS, and DUOX2 gene mutations in hypothyroid children with dyshormonogenetic hypothyroidism (DH from South India. Materials and Methods: This is interdisciplinary prospective study, we employed eight sets of primers and screened for 142 known single nucleotide polymorphisms in TPO, NIS, and DUOX2 genes. The subjects were children and adolescents with hypothyroidism due to dyshormonogenetic goiter. Congenital hypothyroidism, iodine deficiency, and Hashimoto's thyroiditis cases were excluded. Results: We detected nine mutations in 8/22 (36% children. All the mutations were observed in the intronic regions of NIS gene and none in TPO or DUOX2 genes. Except for bi-allelic, synonymous polymorphism of TPO gene in child number 14, all other mutations were heterozygous in nature. GPCs show that our mutations significantly expressed the phenotypic traits such as overt hypothyroidism, goiter, and existence of family history. Other phenotypic characters such as sex predilection, the age of onset and transitory nature of hypothyroidism were not significantly affected by these mutations. Conclusion: NIS gene mutations alone appears to be most prevalent mutations in DH among South Indian children and these mutations significantly influenced phenotypic expressions such as severity of hypothyroidism, goiter rates, and familial clustering.

  5. Clonal expansion of the Pseudogymnoascus destructans genotype in North America is accompanied by significant variation in phenotypic expression.

    Science.gov (United States)

    Khankhet, Jordan; Vanderwolf, Karen J; McAlpine, Donald F; McBurney, Scott; Overy, David P; Slavic, Durda; Xu, Jianping

    2014-01-01

    Pseudogymnoascus destructans is the causative agent of an emerging infectious disease that threatens populations of several North American bat species. The fungal disease was first observed in 2006 and has since caused the death of nearly six million bats. The disease, commonly known as white-nose syndrome, is characterized by a cutaneous infection with P. destructans causing erosions and ulcers in the skin of nose, ears and/or wings of bats. Previous studies based on sequences from eight loci have found that isolates of P. destructans from bats in the US all belong to one multilocus genotype. Using the same multilocus sequence typing method, we found that isolates from eastern and central Canada also had the same genotype as those from the US, consistent with the clonal expansion of P. destructans into Canada. However, our PCR fingerprinting revealed that among the 112 North American isolates we analyzed, three, all from Canada, showed minor genetic variation. Furthermore, we found significant variations among isolates in mycelial growth rate; the production of mycelial exudates; and pigment production and diffusion into agar media. These phenotypic differences were influenced by culture medium and incubation temperature, indicating significant variation in environmental condition--dependent phenotypic expression among isolates of the clonal P. destructans genotype in North America.

  6. Clonal expansion of the Pseudogymnoascus destructans genotype in North America is accompanied by significant variation in phenotypic expression.

    Directory of Open Access Journals (Sweden)

    Jordan Khankhet

    Full Text Available Pseudogymnoascus destructans is the causative agent of an emerging infectious disease that threatens populations of several North American bat species. The fungal disease was first observed in 2006 and has since caused the death of nearly six million bats. The disease, commonly known as white-nose syndrome, is characterized by a cutaneous infection with P. destructans causing erosions and ulcers in the skin of nose, ears and/or wings of bats. Previous studies based on sequences from eight loci have found that isolates of P. destructans from bats in the US all belong to one multilocus genotype. Using the same multilocus sequence typing method, we found that isolates from eastern and central Canada also had the same genotype as those from the US, consistent with the clonal expansion of P. destructans into Canada. However, our PCR fingerprinting revealed that among the 112 North American isolates we analyzed, three, all from Canada, showed minor genetic variation. Furthermore, we found significant variations among isolates in mycelial growth rate; the production of mycelial exudates; and pigment production and diffusion into agar media. These phenotypic differences were influenced by culture medium and incubation temperature, indicating significant variation in environmental condition--dependent phenotypic expression among isolates of the clonal P. destructans genotype in North America.

  7. Difficulty scaling through incongruity

    NARCIS (Netherlands)

    Lankveld, van G.; Spronck, P.; Rauterberg, G.W.M.; Mateas, M.; Darken, C.

    2008-01-01

    In this paper we discuss our work on using the incongruity measure from psychological literature to scale the difficulty level of a game online to the capabilities of the human player. Our approach has been implemented in a small game called Glove.

  8. Phenotypic and genotypic variation in Iranian Pistachios

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    Somayeh Tayefeh Aliakbarkhani

    2015-12-01

    Full Text Available As Iran is one of the richest pistachio germplasms a few studies have been conducted on different sexes of pistachio trees, in areas where this crop emerged. To this end, 40 male and female Iranian pistachio genotypes from Feizabad region, Khorasan, Iran; were evaluated using morphological characters and randomly amplified polymorphic DNA (RAPD markers. For morphological assessments, 54 variables were considered to investigate similarities between and among the studied genotypes. Morphological data indicated relative superiority in some female genotypes (such as Sefid 1, Sefid Sabuni 2, Garmesiah, and Ghermezdorosht Z regarding characters such as halfcrackedness, the percentages of protein and fat content. 115 polymorphic bands were recorded with 92.83% average polymorphism among all primers. The total resolving power (Rp of the primers was 74.54. The range of genetic similarity varied from about 0.31 to about 0.70. Genotypes were segregated into eight groups at the similarity limit of 0.41. Results of present investigation could be helpful for strategic decisions for maintaining Iranian pistachio genotypes.

  9. Using artificial neural networks to select upright cowpea (Vigna unguiculata) genotypes with high productivity and phenotypic stability.

    Science.gov (United States)

    Barroso, L M A; Teodoro, P E; Nascimento, M; Torres, F E; Nascimento, A C C; Azevedo, C F; Teixeira, F R F

    2016-11-03

    Cowpea (Vigna unguiculata) is grown in three Brazilian regions: the Midwest, North, and Northeast, and is consumed by people on low incomes. It is important to investigate the genotype x environment (GE) interaction to provide accurate recommendations for farmers. The aim of this study was to identify cowpea genotypes with high adaptability and phenotypic stability for growing in the Brazilian Cerrado, and to compare the use of artificial neural networks with the Eberhart and Russell (1966) method. Six trials with upright cowpea genotypes were conducted in 2005 and 2006 in the States of Mato Grosso do Sul and Mato Grosso. The data were subjected to adaptability and stability analysis by the Eberhart and Russell (1966) method and artificial neural networks. The genotypes MNC99-537F-4 and EVX91-2E-2 provided grain yields above the overall environment means, and exhibited high stability according to both methods. Genotype IT93K-93-10 was the most suitable for unfavorable environments. There was a high correlation between the results of both methods in terms of classifying the genotypes by their adaptability and stability. Therefore, this new approach would be effective in quantifying the GE interaction in upright cowpea breeding programs.

  10. Cross-species amplification of microsatellites reveals incongruence in the molecular variation and taxonomic limits of the Pilosocereus aurisetus group (Cactaceae).

    Science.gov (United States)

    Moraes, Evandro M; Perez, Manolo F; Téo, Mariana F; Zappi, Daniela C; Taylor, Nigel P; Machado, Marlon C

    2012-09-01

    The Pilosocereus aurisetus group contains eight cactus species restricted to xeric habitats in eastern and central Brazil that have an archipelago-like distribution. In this study, 5-11 microsatellite markers previously designed for Pilosocereus machrisii were evaluated for cross-amplification and polymorphisms in ten populations from six species of the P. aurisetus group. The genotypic information was subsequently used to investigate the genetic relationships between the individuals, populations, and species analyzed. Only the Pmac101 locus failed to amplify in all of the six analyzed species, resulting in an 88 % success rate. The number of alleles per polymorphic locus ranged from 2 to 12, and the most successfully amplified loci showed at least one population with a larger number of alleles than were reported in the source species. The population relationships revealed clear genetic clustering in a neighbor-joining tree that was partially incongruent with the taxonomic limits between the P. aurisetus and P. machrisii species, a fact which parallels the problematic taxonomy of the P. aurisetus group. A Bayesian clustering analysis of the individual genotypes confirmed the observed taxonomic incongruence. These microsatellite markers provide a valuable resource for facilitating large-scale genetic studies on population structures, systematics and evolutionary history in this group.

  11. Kant's consideration of space and the puzzle of incongruence

    Directory of Open Access Journals (Sweden)

    Stojnić Una

    2009-01-01

    Full Text Available In this paper we are dealing with Kant's view on the phenomenon of incongruous counterparts, in particular with the argument from his article 'On the First Ground of the Distinction of Regions in Space', where the phenomenon of incongruous counterparts is used as an argument for the existence of the absolute and objective space, and with the argument from Kant's Inaugural Dissertation in which he uses the phenomenon of incongruous counterparts again, but this time for a different purpose - as an argument in favor of the idea of space as a pure intuition. Our aim is to show that Kant's argument from 'On the First Ground of the Distinction of Regions in Space', although it shows the inadequacy of Leibniz's definition of congruence, does not in fact represent the reductio ad absurdum of the relationist view, for his argument in favor of the existence of the absolute space represents merely the inference to the best explanation. We also propound an alternative account of the phenomenon of incongruous counterparts, which is in line with the relationist theory. Furthermore, we call in question Kant's argument from the Inaugural Dissertation, according to which incongruence could not be explained discursively, and we put forward a conceptual determination of incongruence in terms of the notions of similarity, equality and congruence, taken as the possibility of objects to be included within the same spatial boundaries.

  12. Cortical oscillations modulated by congruent and incongruent audiovisual stimuli.

    Science.gov (United States)

    Herdman, A T; Fujioka, T; Chau, W; Ross, B; Pantev, C; Picton, T W

    2004-11-30

    Congruent or incongruent grapheme-phoneme stimuli are easily perceived as one or two linguistic objects. The main objective of this study was to investigate the changes in cortical oscillations that reflect the processing of congruent and incongruent audiovisual stimuli. Graphemes were Japanese Hiragana characters for four different vowels (/a/, /o/, /u/, and /i/). They were presented simultaneously with their corresponding phonemes (congruent) or non-corresponding phonemes (incongruent) to native-speaking Japanese participants. Participants' reaction times to the congruent audiovisual stimuli were significantly faster by 57 ms as compared to reaction times to incongruent stimuli. We recorded the brain responses for each condition using a whole-head magnetoencephalograph (MEG). A novel approach to analysing MEG data, called synthetic aperture magnetometry (SAM), was used to identify event-related changes in cortical oscillations involved in audiovisual processing. The SAM contrast between congruent and incongruent responses revealed greater event-related desynchonization (8-16 Hz) bilaterally in the occipital lobes and greater event-related synchronization (4-8 Hz) in the left transverse temporal gyrus. Results from this study further support the concept of interactions between the auditory and visual sensory cortices in multi-sensory processing of audiovisual objects.

  13. De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder.

    Science.gov (United States)

    Reijnders, Margot R F; Miller, Kerry A; Alvi, Mohsan; Goos, Jacqueline A C; Lees, Melissa M; de Burca, Anna; Henderson, Alex; Kraus, Alison; Mikat, Barbara; de Vries, Bert B A; Isidor, Bertrand; Kerr, Bronwyn; Marcelis, Carlo; Schluth-Bolard, Caroline; Deshpande, Charu; Ruivenkamp, Claudia A L; Wieczorek, Dagmar; Baralle, Diana; Blair, Edward M; Engels, Hartmut; Lüdecke, Hermann-Josef; Eason, Jacqueline; Santen, Gijs W E; Clayton-Smith, Jill; Chandler, Kate; Tatton-Brown, Katrina; Payne, Katelyn; Helbig, Katherine; Radtke, Kelly; Nugent, Kimberly M; Cremer, Kirsten; Strom, Tim M; Bird, Lynne M; Sinnema, Margje; Bitner-Glindzicz, Maria; van Dooren, Marieke F; Alders, Marielle; Koopmans, Marije; Brick, Lauren; Kozenko, Mariya; Harline, Megan L; Klaassens, Merel; Steinraths, Michelle; Cooper, Nicola S; Edery, Patrick; Yap, Patrick; Terhal, Paulien A; van der Spek, Peter J; Lakeman, Phillis; Taylor, Rachel L; Littlejohn, Rebecca O; Pfundt, Rolph; Mercimek-Andrews, Saadet; Stegmann, Alexander P A; Kant, Sarina G; McLean, Scott; Joss, Shelagh; Swagemakers, Sigrid M A; Douzgou, Sofia; Wall, Steven A; Küry, Sébastien; Calpena, Eduardo; Koelling, Nils; McGowan, Simon J; Twigg, Stephen R F; Mathijssen, Irene M J; Nellaker, Christoffer; Brunner, Han G; Wilkie, Andrew O M

    2018-06-07

    Next-generation sequencing is a powerful tool for the discovery of genes related to neurodevelopmental disorders (NDDs). Here, we report the identification of a distinct syndrome due to de novo or inherited heterozygous mutations in Tousled-like kinase 2 (TLK2) in 38 unrelated individuals and two affected mothers, using whole-exome and whole-genome sequencing technologies, matchmaker databases, and international collaborations. Affected individuals had a consistent phenotype, characterized by mild-borderline neurodevelopmental delay (86%), behavioral disorders (68%), severe gastro-intestinal problems (63%), and facial dysmorphism including blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%). Analysis of cell lines from three affected individuals showed that mutations act through a loss-of-function mechanism in at least two case subjects. Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of these and other individuals with loss-of-function variants significantly overlapped with phenotypes of individuals with other variant types (missense and C-terminal truncating). This suggests that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. This work illustrates the power of international data sharing, by the identification of 40 individuals from 26 different centers in 7 different countries, allowing the identification, clinical delineation, and genotype-phenotype evaluation of a distinct NDD caused by mutations in TLK2. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Sensorimotor incongruence and body perception: an experimental investigation

    Directory of Open Access Journals (Sweden)

    Jens eFoell

    2013-06-01

    Full Text Available Objectives: Several studies have shown that mirrored arm or leg movements are related to altered body sensations. This includes the alleviation of chronic pain using congruent mirror feedback and the induction of abnormal sensation in healthy participants using incongruent mirror feedback. Prior research has identified neuronal and conceptual mechanisms of these phenomena. With the rising application of behavior-based methods for pain relief, a structured investigation of these reported effects seems necessary.Methods: We investigated a mirror setup that included congruent and incongruent hand and arm movements in 113 healthy participants and assessed the occurrence and intensity of unusual physical experiences such as pain, the sensation of missing or additional limbs, or changes in weight or temperature. A wooden surface instead of a mirror condition served as control. Results: As reported earlier, mirrored movements led to a variety of subjective reactions in both the congruent an incongruent movement condition, with the sensation of possessing a third limb being significantly more intense and frequent in the incongruent mirror condition. Reports of illusory pain were not more frequent during mirrored than during non-mirrored movements.Conclusions: These results suggest that hand movements with and without a mirror induce abnormal body perceptions but that the experience of an extra limb is most pronounced in the incongruent mirror movement condition. The frequent sensation of having a third arm may be related to brain processes designed to integrate input from several senses in a meaningful manner.

  15. Genotypic and Phenotypic Markers of Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC9 in Humans.

    Science.gov (United States)

    Ye, Xiaohua; Wang, Xiaolin; Fan, Yanping; Peng, Yang; Li, Ling; Li, Shunming; Huang, Jingya; Yao, Zhenjiang; Chen, Sidong

    2016-07-01

    Use of antimicrobials in industrial food animal production is associated with the presence of multidrug-resistant Staphylococcus aureus among animals and humans. The livestock-associated (LA) methicillin-resistant S. aureus (MRSA) clonal complex 9 (CC9) is associated with animals and related workers in Asia. This study aimed to explore the genotypic and phenotypic markers of LA-MRSA CC9 in humans. We conducted a cross-sectional study of livestock workers and controls in Guangdong, China. The study participants responded to a questionnaire and provided a nasal swab for S. aureus analysis. The resulting isolates were assessed for antibiotic susceptibility, multilocus sequence type, and immune evasion cluster (IEC) genes. Livestock workers had significantly higher rates of S. aureus CC9 (odds ratio [OR] = 30.98; 95% confidence interval [CI], 4.06 to 236.39) and tetracycline-resistant S. aureus (OR = 3.26; 95% CI, 2.12 to 5.00) carriage than controls. All 19 S. aureus CC9 isolates from livestock workers were MRSA isolates and also exhibited the characteristics of resistance to several classes of antibiotics and absence of the IEC genes. Notably, the interaction analyses indicated phenotype-phenotype (OR = 525.7; 95% CI, 60.0 to 4,602.1) and gene-environment (OR = 232.3; 95% CI, 28.7 to 1,876.7) interactions associated with increased risk for livestock-associated S. aureus CC9 carriage. These findings suggest that livestock-associated S. aureus and MRSA (CC9, IEC negative, and tetracycline resistant) in humans are associated with occupational livestock contact, raising questions about the potential for occupational exposure to opportunistic S. aureus This study adds to existing knowledge by giving insight into the genotypic and phenotypic markers of LA-MRSA. Our findings suggest that livestock-associated S. aureus and MRSA (CC9, IEC negative, and tetracycline resistant) in humans are associated with occupational livestock contact. Future studies should direct more

  16. Paranormal experience and the COMT dopaminergic gene: a preliminary attempt to associate phenotype with genotype using an underlying brain theory.

    Science.gov (United States)

    Raz, Amir; Hines, Terence; Fossella, John; Castro, Daniella

    2008-01-01

    Paranormal belief and suggestibility seem related. Given our recent findings outlining a putative association between suggestibility and a specific dopaminergic genetic polymorphism, we hypothesized that similar exploratory genetic data may offer supplementary insights into a similar correlation with paranormal belief. With more affordable costs and better technology in the aftermath of the human genome project, genotyping is increasingly ubiquitous. Compelling brain theories guide specific research hypotheses as scientists begin to unravel tentative relationships between phenotype and genotype. In line with a dopaminergic brain theory, we tried to correlate a specific phenotype concerning paranormal belief with a dopaminergic gene (COMT) known for its involvement in prefrontal executive cognition and for a polymorphism that is positively correlated with suggestibility. Although our preliminary findings are inconclusive, the research approach we outline should pave the road to a more scientific account of elucidating paranormal belief.

  17. Genotypic and Phenotypic Markers of Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC9 in Humans

    OpenAIRE

    Ye, Xiaohua; Wang, Xiaolin; Fan, Yanping; Peng, Yang; Li, Ling; Li, Shunming; Huang, Jingya; Yao, Zhenjiang; Chen, Sidong

    2016-01-01

    Use of antimicrobials in industrial food animal production is associated with the presence of multidrug-resistant Staphylococcus aureus among animals and humans. The livestock-associated (LA) methicillin-resistant S. aureus (MRSA) clonal complex 9 (CC9) is associated with animals and related workers in Asia. This study aimed to explore the genotypic and phenotypic markers of LA-MRSA CC9 in humans. We conducted a cross-sectional study of livestock workers and controls in Guangdong, China. The ...

  18. Towards systems genetic analyses in barley: Integration of phenotypic, expression and genotype data into GeneNetwork

    Directory of Open Access Journals (Sweden)

    Druka Arnis

    2008-11-01

    Full Text Available Abstract Background A typical genetical genomics experiment results in four separate data sets; genotype, gene expression, higher-order phenotypic data and metadata that describe the protocols, processing and the array platform. Used in concert, these data sets provide the opportunity to perform genetic analysis at a systems level. Their predictive power is largely determined by the gene expression dataset where tens of millions of data points can be generated using currently available mRNA profiling technologies. Such large, multidimensional data sets often have value beyond that extracted during their initial analysis and interpretation, particularly if conducted on widely distributed reference genetic materials. Besides quality and scale, access to the data is of primary importance as accessibility potentially allows the extraction of considerable added value from the same primary dataset by the wider research community. Although the number of genetical genomics experiments in different plant species is rapidly increasing, none to date has been presented in a form that allows quick and efficient on-line testing for possible associations between genes, loci and traits of interest by an entire research community. Description Using a reference population of 150 recombinant doubled haploid barley lines we generated novel phenotypic, mRNA abundance and SNP-based genotyping data sets, added them to a considerable volume of legacy trait data and entered them into the GeneNetwork http://www.genenetwork.org. GeneNetwork is a unified on-line analytical environment that enables the user to test genetic hypotheses about how component traits, such as mRNA abundance, may interact to condition more complex biological phenotypes (higher-order traits. Here we describe these barley data sets and demonstrate some of the functionalities GeneNetwork provides as an easily accessible and integrated analytical environment for exploring them. Conclusion By

  19. Genotype-phenotype variations in five Spanish families with Norrie disease or X-linked FEVR.

    Science.gov (United States)

    Riveiro-Alvarez, Rosa; Trujillo-Tiebas, Maria José; Gimenez-Pardo, Ascension; Garcia-Hoyos, Maria; Cantalapiedra, Diego; Lorda-Sanchez, Isabel; Rodriguez de Alba, Marta; Ramos, Carmen; Ayuso, Carmen

    2005-09-02

    Norrie disease (OMIM 310600) is a rare X-linked disorder characterized by congenital blindness in males. Approximately 40 to 50% of the cases develop deafness and mental retardation. X-linked familial exudative vitreoretinopathy (XL-FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Both X-linked disorders are due to mutations in the NDP gene, which encodes a 133 amino acid protein called Norrin, but autosomal recessive (AR) and autosomal dominant (AD) forms of FEVR have also been described. In this study, we report the molecular findings and the related phenotype in five Spanish families affected with Norrie disease or XL-FEVR due to mutations of the NDP gene. The study was conducted in 45 subjects from five Spanish families. These families were clinically diagnosed with Norrie disease or similar conditions. The three exons of the NDP gene were analyzed by automatic DNA sequencing. Haplotype analyses were also performed. Two new nonsense mutations, apart from other mutations previously described in the NDP gene, were found in those patients affected with ND or X-linked FEVR. An important genotype-phenotype variation was found in relation to the different mutations of the NDP gene. In fact, the same mutation may be responsible for different phenotypes. We speculate that there might be other molecular factors that interact in the retina with Norrin, which contribute to the resultant phenotypes.

  20. Phenotype determination guides swift genotyping of a DFNA2/KCNQ4 family with a hot spot mutation (W276S).

    NARCIS (Netherlands)

    Topsakal, V.; Pennings, R.J.E.; Brinke, H. te; Hamel, B.C.J.; Huygen, P.L.M.; Kremer, J.M.J.; Cremers, C.W.R.J.

    2005-01-01

    OBJECTIVE: Genotype a family trait with autosomal dominant nonsyndromic sensorineural hearing impairment guided only by the phenotype. STUDY DESIGN: Family study. SETTING: Tertiary referral center. PATIENTS: Fifteen family members. METHODS: In the first phase, sequence analysis was performed on DNA

  1. Phenotypes of organ involvement in sarcoidosis

    NARCIS (Netherlands)

    Schupp, Jonas Christian; Freitag-Wolf, Sandra; Bargagli, Elena; Mihailović-Vučinić, Violeta; Rottoli, Paola; Grubanovic, Aleksandar; Müller, Annegret; Jochens, Arne; Tittmann, Lukas; Schnerch, Jasmin; Olivieri, Carmela; Fischer, Annegret; Jovanovic, Dragana; Filipovic, Snežana; Videnovic-Ivanovic, Jelica; Bresser, Paul; Jonkers, René; O'Reilly, Kate; Ho, Ling-Pei; Gaede, Karoline I.; Zabel, Peter; Dubaniewicz, Anna; Marshall, Ben; Kieszko, Robert; Milanowski, Janusz; Günther, Andreas; Weihrich, Anette; Petrek, Martin; Kolek, Vitezslav; Keane, Michael P.; O'Beirne, Sarah; Donnelly, Seamas; Haraldsdottir, Sigridur Olina; Jorundsdottir, Kristin B.; Costabel, Ulrich; Bonella, Francesco; Wallaert, Benoît; Grah, Christian; Peroš-Golubičić, Tatjana; Luisetti, Mauritio; Kadija, Zamir; Pabst, Stefan; Grohé, Christian; Strausz, János; Vašáková, Martina; Sterclova, Martina; Millar, Ann; Homolka, Jiří; Slováková, Alena; Kendrick, Yvonne; Crawshaw, Anjali; Wuyts, Wim; Spencer, Lisa; Pfeifer, Michael; Valeyre, Dominique; Poletti, Venerino; Wirtz, Hubertus; Prasse, Antje; Schreiber, Stefan; Krawczak, Michael; Müller-Quernheim, Joachim

    2018-01-01

    Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis. The baseline

  2. Rotermanni vana ja uus jahuladu = The Rotermann Old and New Flour Storage / Margit Mutso

    Index Scriptorium Estoniae

    Mutso, Margit, 1966-

    2010-01-01

    Tallinna Rotermanni 8 asuvast Rotermanni uuest ja vanast jahulaost, mis pälvis 2009. a. EK arhitektuuri sihtkapitali arhitektuuripreemia linnaruumi tunnetava, uut ja vana tervikuks siduva arhitektuuri eest. Arhitektid: Hanno Grossschmidt, Tomomi Hayashi, Yoko Azukawa (HG Arhitektuur). Büroode üldkujundus: Tarmo Piirmets, Raul Tiitus (OÜ Pink). Žürii liige Kalle Komissarov žürii hinnangust hoonele

  3. Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Confirmed by Multiplex Ligation-Dependent Probe Amplification: Genotype-Phenotype Correlation in a Large Cohort.

    Science.gov (United States)

    Vengalil, Seena; Preethish-Kumar, Veeramani; Polavarapu, Kiran; Mahadevappa, Manjunath; Sekar, Deepha; Purushottam, Meera; Thomas, Priya Treesa; Nashi, Saraswathi; Nalini, Atchayaram

    2017-01-01

    Studies of cases of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) confirmed by multiplex ligation-dependent probe amplification (MLPA) have determined the clinical characteristics, genotype, and relations between the reading frame and phenotype for different countries. This is the first such study from India. A retrospective genotype-phenotype analysis of 317 MLPA-confirmed patients with DMD or BMD who visited the neuromuscular clinic of a quaternary referral center in southern India. The 317 patients comprised 279 cases of DMD (88%), 32 of BMD (10.1%), and 6 of intermediate phenotype (1.9%). Deletions accounted for 91.8% of cases, with duplications causing the remaining 8.2%. There were 254 cases of DMD (91%) with deletions and 25 (9%) due to duplications, and 31 cases (96.8%) of BMD with deletions and 1 (3.2%) due to duplication. All six cases of intermediate type were due to deletions. The most-common mutation was a single-exon deletion. Deletions of six or fewer exons constituted 68.8% of cases. The deletion of exon 50 was the most common. The reading-frame rule held in 90% of DMD and 94% of BMD cases. A tendency toward a lower IQ and earlier wheelchair dependence was observed with distal exon deletions, though a significant correlation was not found. The reading-frame rule held in 90% to 94% of children, which is consistent with reports from other parts of the world. However, testing by MLPA is a limitation, and advanced sequencing methods including analysis of the structure of mutant dystrophin is needed for more-accurate assessments of the genotype-phenotype correlation.

  4. Novel SOX2 mutations and genotype-phenotype correlation in anophthalmia and microphthalmia.

    Science.gov (United States)

    Schneider, Adele; Bardakjian, Tanya; Reis, Linda M; Tyler, Rebecca C; Semina, Elena V

    2009-12-01

    SOX2 represents a High Mobility Group domain containing transcription factor that is essential for normal development in vertebrates. Mutations in SOX2 are known to result in a spectrum of severe ocular phenotypes in humans, also typically associated with other systemic defects. Ocular phenotypes include anophthalmia/microphthalmia (A/M), optic nerve hypoplasia, ocular coloboma and other eye anomalies. We screened 51 unrelated individuals with A/M and identified SOX2 mutations in the coding region of the gene in 10 individuals. Seven of the identified mutations are novel alterations, while the remaining three individuals carry the previously reported recurrent 20-nucleotide deletion in SOX2, c.70del20. Among the SOX2-positive cases, seven patients had bilateral A/M and mutations resulting in premature termination of the normal protein sequence (7/38; 18% of all bilateral cases), one patient had bilateral A/M associated with a single amino acid insertion (1/38; 3% of bilateral cases), and the final two patients demonstrated unilateral A/M associated with missense mutations (2/13; 15% of all unilateral cases). These findings and review of previously reported cases suggest a potential genotype/phenotype correlation for SOX2 mutations with missense changes generally leading to less severe ocular defects. In addition, we report a new familial case of affected siblings with maternal mosaicism for the identified SOX2 mutation, which further underscores the importance of parental testing to provide accurate genetic counseling to families.

  5. Familial Case of Pelizaeus-Merzbacher Disorder Detected by Oligoarray Comparative Genomic Hybridization: Genotype-to-Phenotype Diagnosis

    Directory of Open Access Journals (Sweden)

    Kimia Najafi

    2017-01-01

    Full Text Available Introduction. Pelizaeus-Merzbacher disease (PMD is an X-linked recessive hypomyelinating leukodystrophy characterized by nystagmus, spastic quadriplegia, ataxia, and developmental delay. It is caused by mutation in the PLP1 gene. Case Description. We report a 9-year-old boy referred for oligoarray comparative genomic hybridization (OA-CGH because of intellectual delay, seizures, microcephaly, nystagmus, and spastic paraplegia. Similar clinical findings were reported in his older brother and maternal uncle. Both parents had normal phenotypes. OA-CGH was performed and a 436 Kb duplication was detected and the diagnosis of PMD was made. The mother was carrier of this 436 Kb duplication. Conclusion. Clinical presentation has been accepted as being the mainstay of diagnosis for most conditions. However, recent developments in genetic diagnosis have shown that, in many congenital and sporadic disorders lacking specific phenotypic manifestations, a genotype-to-phenotype approach can be conclusive. In this case, a diagnosis was reached by universal genomic testing, namely, whole genomic array.

  6. Phenotypic and genotypic changes in a new clone complex of Neisseria meningitidis causing disease in The Netherlands, 1958-1990

    NARCIS (Netherlands)

    Scholten, R. J.; Poolman, J. T.; Valkenburg, H. A.; Bijlmer, H. A.; Dankert, J.; Caugant, D. A.

    1994-01-01

    To characterize the phenotypic and genotypic changes that occurred in a new clone lineage of Neisseria meningitidis (lineage III) in the Netherlands, the electrophoretic type (ET) was determined for 79 serogroup B isolates of serotype 4 or subtype P1.4 (or both) obtained between 1958 and 1990 from

  7. Exploring links between genotypes, phenotypes, and clinical predictors of response to early intensive behavioural intervention in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Valsamma eEapen

    2013-09-01

    Full Text Available Autism Spectrum Disorder (ASD is amongst the most familial of psychiatric disorders. Twin and family studies have demonstrated a monozygotic concordance rate of 70–90%, dizygotic concordance of around 10% and more than a 20-fold increase in risk for first-degree relatives. Despite major advances in the genetics of autism, the relationship between different aspects of the behavioural and cognitive phenotype and their underlying genetic liability is still unclear. This is complicated by the heterogeneity of autism, which exists at both genetic and phenotypic levels. Given this heterogeneity, one method to find homogeneous entities and link these with specific genotypes would be to pursue endophenotypes. Evidence from neuroimaging, eye tracking and electrophysiology studies supports the hypothesis that, building on genetic vulnerability, ASD emerges from a developmental cascade in which a deficit in attention to social stimuli leads to impaired interactions with primary caregivers. This results in abnormal development of the neurocircuitry responsible for social cognition, which in turn adversely affects later behavioural and functional domains dependent on these early processes, such as language development. Such a model begets a heterogeneous clinical phenotype, and is also supported by studies demonstrating better clinical outcomes with earlier treatment. Treatment response following intensive early behavioural intervention in ASD is also distinctly variable; however, relatively little is known about specific elements of the clinical phenotype that may predict response to current behavioural treatments. This paper overviews the literature regarding genotypes, phenotypes and predictors of response to behavioural intervention in ASD and presents suggestions for future research to explore linkages between these that would enable better identification of, and increased treatment efficacy for, ASD.

  8. Genotypic and phenotypic diversity does not affect productivity and drought response in competitive stands of Trifolium repens

    Directory of Open Access Journals (Sweden)

    Heidrun eHuber

    2016-03-01

    Full Text Available Clonal plants can form dense canopies in which plants of different genetic origin are competing for the uptake of essential resources. The competitive relationships among these clones are likely to be affected by extreme environmental conditions, such as prolonged drought spells, which are predicted to occur more frequently due to global climate change. This, in turn, may alter characteristics of the ecological system and its associated functioning.We hypothesized that the relative success of individual clones will depend on the size of the ramets as ramets with larger leaves and longer petioles (large ramets were predicted to have a competitive advantage in terms of increased light interception over smaller-sized ramets. Under drier conditions the relative performances of genotypes were expected to change leading to a change in genotype ranking. We also hypothesized that increased genotypic and phenotypic diversity will increase stand performance and resistance to drought. These hypotheses and the mechanisms responsible for shifts in competitive relationships were investigated by subjecting genotypes of the important pasture legume Trifolium repens to competition with either genetically identical clones, genetically different but similarly sized clones, or genetically as well as morphologically different clones under well-watered and dry conditions.Competitive relationships were affected by ramet size with large genotypes outperforming small genotypes in diverse stands in terms of biomass production. However, large genotypes also produced relatively fewer ramets than small genotypes and could not benefit in terms of clonal reproduction from competing with smaller genotypes, indicating that evolutionary shifts in genotype composition will depend on whether ramet size or ramet number is under selection. In contrast to our hypotheses, diversity did not increase stand performance under different selection regimes and genotype ranking was hardly

  9. Genotypic and Phenotypic Diversity Does Not Affect Productivity and Drought Response in Competitive Stands of Trifolium repens.

    Science.gov (United States)

    Huber, Heidrun; During, Heinjo J; Bruine de Bruin, Fabienne; Vermeulen, Peter J; Anten, Niels P R

    2016-01-01

    Clonal plants can form dense canopies in which plants of different genetic origin are competing for the uptake of essential resources. The competitive relationships among these clones are likely to be affected by extreme environmental conditions, such as prolonged drought spells, which are predicted to occur more frequently due to global climate change. This, in turn, may alter characteristics of the ecological system and its associated functioning. We hypothesized that the relative success of individual clones will depend on the size of the ramets as ramets with larger leaves and longer petioles (large ramets) were predicted to have a competitive advantage in terms of increased light interception over smaller-sized ramets. Under drier conditions the relative performances of genotypes were expected to change leading to a change in genotype ranking. We also hypothesized that increased genotypic and phenotypic diversity will increase stand performance and resistance to drought. These hypotheses and the mechanisms responsible for shifts in competitive relationships were investigated by subjecting genotypes of the important pasture legume Trifolium repens to competition with either genetically identical clones, genetically different but similarly sized clones, or genetically as well as morphologically different clones under well-watered and dry conditions. Competitive relationships were affected by ramet size with large genotypes outperforming small genotypes in diverse stands in terms of biomass production. However, large genotypes also produced relatively fewer ramets than small genotypes and could not benefit in terms of clonal reproduction from competing with smaller genotypes, indicating that evolutionary shifts in genotype composition will depend on whether ramet size or ramet number is under selection. In contrast to our hypotheses, diversity did not increase stand performance under different selection regimes and genotype ranking was hardly affected by soil

  10. Validation and discovery of genotype-phenotype associations in chronic diseases using linked data.

    Science.gov (United States)

    Pathak, Jyotishman; Kiefer, Richard; Freimuth, Robert; Chute, Christopher

    2012-01-01

    This study investigates federated SPARQL queries over Linked Open Data (LOD) in the Semantic Web to validate existing, and potentially discover new genotype-phenotype associations from public datasets. In particular, we report our preliminary findings for identifying such associations for commonly occurring chronic diseases using the Online Mendelian Inheritance in Man (OMIM) and Database for SNPs (dbSNP) within the LOD knowledgebase and compare them with Gene Wiki for coverage and completeness. Our results indicate that Semantic Web technologies can play an important role for in-silico identification of novel disease-gene-SNP associations, although additional verification is required before such information can be applied and used effectively.

  11. An optimized methodology for combined phenotyping and genotyping on CYP2D6 and CYP2C19

    NARCIS (Netherlands)

    Tamminga, C.A; Wemer, J; Oosterhuis, B; Brakenhoff, J.P G; Gerrits, M.G F; de Zeeuw, R.A; de Leij, Lou; Jonkman, J.H.G.

    A method for simultaneous phenotyping and genotyping for CYP2D6 and CYP2C19 was tested. Six healthy volunteers were selected (three extensive and three poor metabolisers for CYP2D6). CYP2D6 was probed with dextromethorphan and metoprolol and CYP2C19 was probed with omeprazole. Blood samples were

  12. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies

    Directory of Open Access Journals (Sweden)

    Specht Günther

    2010-03-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. Description eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle, security aspects (by using database technology and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs. It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. Conclusions The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  13. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies.

    Science.gov (United States)

    Weissensteiner, Hansi; Schönherr, Sebastian; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

    2010-03-09

    Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  14. A window into the transcriptomic basis of genotype-by-genotype interactions in the legume-rhizobia mutualism.

    Science.gov (United States)

    Wood, Corlett W; Stinchcombe, John R

    2017-11-01

    The maintenance of genetic variation in the benefits provided by mutualists is an evolutionary puzzle (Heath & Stinchcombe, ). Over time, natural selection should favour the benefit strategy that confers the highest fitness, eroding genetic variation in partner quality. Yet abundant genetic variation in partner quality exists in many systems (Heath & Stinchcombe, ). One possible resolution to this puzzle is that the genetic identity of both a host and its partner affects the benefits each mutualist provides to the other, a pattern known as a genotype-by-genotype interaction (Figure ). Mounting evidence suggests that genotype-by-genotype interactions between partners are pervasive at the phenotypic level (Barrett, Zee, Bever, Miller, & Thrall, ; Heath, ; Hoeksema & Thompson, ). Ultimately, however, to link these phenotypic patterns to the maintenance of genetic variation in mutualisms we need to answer two questions: How much variation in mutualism phenotypes is attributable to genotype-by-genotype interactions, and what mutualistic functions are influenced by each partner and by the interaction between their genomes? In this issue of Molecular Ecology, Burghardt et al. (2017) use transcriptomics to address both questions in the legume-rhizobia mutualism. © 2017 John Wiley & Sons Ltd.

  15. Wnt signaling pathway involvement in genotypic and phenotypic variations in Waardenburg syndrome type 2 with MITF mutations.

    Science.gov (United States)

    Wang, Xue-Ping; Liu, Ya-Lan; Mei, Ling-Yun; He, Chu-Feng; Niu, Zhi-Jie; Sun, Jie; Zhao, Yu-Lin; Feng, Yong; Zhang, Hua

    2018-05-01

    Mutation in the gene encoding microphthalmia-associated transcription factor (MITF) lead to Waardenburg syndrome 2 (WS2), an autosomal dominantly inherited syndrome with auditory-pigmentary abnormalities, which is clinically and genetically heterogeneous. Haploinsufficiency may be the underlying mechanism for WS2. However, the mechanisms explaining the genotypic and phenotypic variations in WS2 caused by MITF mutations are unclear. A previous study revealed that MITF interacts with LEF-1, an important factor in the Wnt signaling pathway, to regulate its own transcription through LEF-1-binding sites on the MITF promoter. In this study, four different WS2-associated MITF mutations (p.R217I, p.R217G, p.R255X, p.R217del) that are associated with highly variable clinical features were chosen. According to the results, LEF-1 can activate the expression of MITF on its own, but MITF proteins inhibited the activation. This inhibition weakens when the dosage of MITF is reduced. Except for p.R217I, p.R255X, p.R217G, and p.R217del lose the ability to activate TYR completely and do not inhibit the LEF-1-mediated activation of the MITF-M promoter, and the haploinsufficiency created by mutant MITF can be overcome; correspondingly, the mutants' associated phenotypes are less severe than that of p.R217I. The dominant negative of p.R217del made it have a second-most severe phenotype. This study's data imply that MITF has a negative feedback loop of regulation to stabilize MITF gene dosage that involves the Wnt signaling pathway and that the interaction of MITF mutants with this pathway drives the genotypic and phenotypic differences observed in Waardenburg syndrome type 2 associated with MITF mutations.

  16. Identity of the xerophilic species Aspergillus penicillioides: Integrated analysis of the genotypic and phenotypic characters.

    Science.gov (United States)

    Tamura, Miki; Kawasaki, Hiroko; Sugiyama, Junta

    1999-02-01

    We examined the identity of Aspergillus penicillioides, the typical xerophilic and strictly anamorphic species, using an integrated analysis of the genotypic and phenotypic characters. Our experimental methods on two genotypic characters, i.e., DNA base composition using the HPLC method and DNA relatedness using the nitrocellulose filter hybridization technique between A. flavus, A. oryzae, and their close relations revealed a good agreement with the values by buoyant density (for DNA base composition) and spectrophotometric determination (for DNA relatedness) reported by Kurtzman et al. in 1986. On the basis of these comparisons, we examined DNA base composition and DNA relatedness of six selected strains of A. penicillioides, including IFO 8155 (originally described as A. vitricola), one strain of A. restrictus, and the respective strains from Eurotium amstelodami, E. repens, and E. rubrum. As a result, five strains within A. penicillioides, including the neotype strain NRRL 4548, had G+C contents of 46 to 49 mol%, whereas IFO 8155 had 50 mol%. A. restrictus had 52 mol%, and three Eurotium species ranged from 46 to 49 mol%. The DNA relatedness between A. penicillioides (five strains), except for IFO 8155, exhibited values greater than 70%, but the DNA complementarity between four strains and IFO 8155 in A. penicillioides revealed values of less than 40%. DNA relatedness values between three species of Eurotium were 65 to 72%. We determined 18S, 5.8S, and ITS rDNA sequences as other genotypic characters from A. penicillioides (six strains), A. restrictus, and related teleomorphic species of Eurotium. In three phylogenetic trees inferred from these sequences, five strains of A. penicillioides, including the neotype strain, were closely related to each other, whereas IFO 8155 was distantly related and grouped with other xerophilic species. Our results have suggested that A. penicillioides typified by NRRL 4548 and A. penicillioides IFO 8155 (ex holotype of A

  17. Audiological and vestibular features in affected subjects with USH3: a genotype/phenotype correlation.

    Science.gov (United States)

    Sadeghi, Mehdi; Cohn, Edward S; Kimberling, William J; Tranebjaerg, Lisbeth; Möller, Claes

    2005-05-01

    The aims were to compare the genotype/phenotype relationship between USH3 mutations and the consequent hearing and vestibular phenotype; and to compare hearing loss (HL) progression between Usher syndrome types IB, IIA and USH3. Genetic, audiometric and vestibular examinations were performed in 28 subjects with USH3. Five different mutations in USH3 were identified. Severe HL was present from an early age (4 to 6 years) in 35% of subjects with USH3. Progression of HL begins in the first decade, and approximately 50% of subjects with USH3 become profoundly deaf by age 40. Various vestibular abnormalities were found in about half (10/22) of the tested subjects with USH3. Depending on the severity of HL, subjects with USH3 might be misdiagnosed as either Usher type IB or IIA. The results from this study can be used as discriminatory features in differential diagnosis of this syndrome.

  18. The Bone Dysplasia Ontology: integrating genotype and phenotype information in the skeletal dysplasia domain

    Directory of Open Access Journals (Sweden)

    Groza Tudor

    2012-03-01

    Full Text Available Abstract Background Skeletal dysplasias are a rare and heterogeneous group of genetic disorders affecting skeletal development. Patients with skeletal dysplasias suffer from many complex medical issues including degenerative joint disease and neurological complications. Because the data and expertise associated with this field is both sparse and disparate, significant benefits will potentially accrue from the availability of an ontology that provides a shared conceptualisation of the domain knowledge and enables data integration, cross-referencing and advanced reasoning across the relevant but distributed data sources. Results We introduce the design considerations and implementation details of the Bone Dysplasia Ontology. We also describe the different components of the ontology, including a comprehensive and formal representation of the skeletal dysplasia domain as well as the related genotypes and phenotypes. We then briefly describe SKELETOME, a community-driven knowledge curation platform that is underpinned by the Bone Dysplasia Ontology. SKELETOME enables domain experts to use, refine and extend and apply the ontology without any prior ontology engineering experience--to advance the body of knowledge in the skeletal dysplasia field. Conclusions The Bone Dysplasia Ontology represents the most comprehensive structured knowledge source for the skeletal dysplasias domain. It provides the means for integrating and annotating clinical and research data, not only at the generic domain knowledge level, but also at the level of individual patient case studies. It enables links between individual cases and publicly available genotype and phenotype resources based on a community-driven curation process that ensures a shared conceptualisation of the domain knowledge and its continuous incremental evolution.

  19. Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.

    Directory of Open Access Journals (Sweden)

    Fanny Lanternier

    Full Text Available Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28 with those of patients whose disease started at adult's age (Group 2, n = 114. Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73% in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001. 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001. Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001. In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.

  20. Phenotypic and genotypic studies of ALS cases in ALS-SMA families.

    Science.gov (United States)

    Corcia, Philippe; Vourc'h, Patrick; Blasco, Helene; Couratier, Philippe; Dangoumau, Audrey; Bellance, Remi; Desnuelle, Claude; Viader, Fausto; Pautot, Vivien; Millecamps, Stephanie; Bakkouche, Salah; Salachas, FranÇois; Andres, Christian R; Meininger, Vincent; Camu, William

    2018-03-01

    Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are the most frequent motor neuron disorders in adulthood and infancy, respectively. There is a growing literature supporting common pathophysiological patterns between those disorders. One important clinical issue for that is the co-occurrence of both diseases within a family. To collect families in which ALS and SMA patients co-exist and describe the phenotype and the genotype of ALS patients. Nine families with co-occurrence of SMA and ALS have been gathered over the last 15 years. Epidemiological, phenotype and genetic status were collected. Out of the nine families, six corresponded to the criteria of familial ALS (FALS). Clinical data were available for 11 patients out of the 15 ALS cases. Mean age of onset was 58.5 years, site of onset was lower limbs in nine cases (81.8%), median duration was 22 months. Four ALS patients carried a mutation: three mutations in SOD1 gene (G147N in two cases and one with E121G) and one repeat expansion in the C9ORF72 gene. Three patients had abnormal SMN1 copy numbers. While the high proportion of familial history of ALS cases in these ALS-SMA pedigrees could have suggested that these familial clusters of the two most frequent MND rely on a genetic background, we failed to exclude that this occurred by chance.

  1. Phenotypic and genotypic variation of Phragmites australis: Comparison of populations in two human-made lakes of different age and history

    Czech Academy of Sciences Publication Activity Database

    Čurn, V.; Kubátová, B.; Vávřová, P.; Křiváčková; Suchá, O.; Čížková, Hana

    2007-01-01

    Roč. 86, - (2007), s. 321-330 ISSN 0304-3770 R&D Projects: GA ČR(CZ) GA526/06/0276 Institutional research plan: CEZ:AV0Z60870520 Keywords : Phragmites * Phenotypic variation * Genotypic variation * Lake * Clone Subject RIV: EF - Botanics Impact factor: 1.497, year: 2007

  2. NOD2/CARD15 Gene Polymorphisms in Crohn's Disease: A Genotype-Phenotype Analysis in Danish and Portuguese Patients and Controls

    DEFF Research Database (Denmark)

    Vind, Ida; Vieira, A; Hougs, L

    2005-01-01

    to a healthy background population and to compare genotype-phenotype relations in the two countries. METHODS: 58 Danish patients and 29 Portuguese patients with CD were matched for age, sex and disease behaviour at time of diagnosis and compared with 200 healthy Danish and Portuguese controls. Phenotypes were...... recorded at year of diagnosis, 3 years after diagnosis and at end of follow-up. Patients were genotyped for Arg702Trp, Gly908Arg and Leu1007InsC. RESULTS: 22% of the Danish patients vs. 9% of Danish controls compared to 21% of the Portuguese patients vs. 16% had at least one mutation. Mutation rates...... in Danish patients were significantly different (p=0.02) compared with Danish controls, no difference (p=0.51) was found between Portuguese patients and controls. However, a possible relationship between CD and presence of genetic mutations was found when comparing the two countries (p=0.03) using...

  3. Genotyping of Staphylococcus aureus in bovine mastitis and correlation to phenotypic characteristics.

    Science.gov (United States)

    Artursson, Karin; Söderlund, Robert; Liu, Lihong; Monecke, Stefan; Schelin, Jenny

    2016-09-25

    Reducing the prevalence of mastitis caused by Staphylococcus aureus (S. aureus) is essential to improve animal health and reduce economic losses for farmers. The clinical outcome of acute mastitis and risk of progression to persistent mastitis can, at least to some extent, be related to genetic variants of the strain causing the infection. In the present study we have used microarrays to investigate the presence of virulence genes in S. aureus isolates from dairy cows with acute clinical mastitis (n=70) and correlated the findings to other genotypic and phenotypic characteristics. Among the most commonly found virulence factors were genes encoding several hemolysin types, leukocidins D and lukM/lukF-P83, clumping factors A and B, fibrinogen binding protein and fibronectin-binding protein A. Some virulence factors e.g. fibronectin-binding protein B and Staphylococcus aureus surface protein G were less common. Genes coding for several staphylococcal enterotoxins and toxic shock syndrome toxin-1 (TSST-1) were commonly found, especially in one major pulsotype. No beta-lactamase genes were found in any common pulsotype, while present in some rare pulsotypes, indicated to be of human origin. Production of TSST-1, enterotoxins, hemolysins and beta-lactamase could all be positively correlated to presence of the corresponding genes. This study reveals a number of genotypic differences and similarities among common and rare pulsotypes of S. aureus from cases of mastitis in Sweden. The results could help the design of diagnostic tools to guide on-farm interventions according to the expected impact on udder health from a specific S. aureus genotype. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Incongruous consultation behaviour: results from a UK-wide population survey

    Directory of Open Access Journals (Sweden)

    Elliott Alison M

    2012-03-01

    Full Text Available Abstract Background Symptom characteristics are strong drivers of care seeking. Despite this, incongruous consultation behaviour occurs and has implications for both individuals and health-care services. The aim of this study was to determine how frequently incongruous consultation behaviour occurs, to examine whether it is more common for certain types of symptoms and to identify the factors associated with being an incongruous consulter. Methods An age and sex stratified random sample of 8,000 adults was drawn from twenty UK general practices. A postal questionnaire was used to collect detailed information on the presence and characteristics of 25 physical and psychological symptoms, actions taken to manage the symptoms, general health, attitudes to symptom management and demographic/socio-economic details. Two types of incongruous consultation behaviour were examined: i consultation with a GP for symptoms self-rated as low impact and ii no consultation with a GP for symptoms self-rated as high impact. Results A fifth of all symptoms experienced resulted in consultation behaviour which was incongruous based on respondents' own rating of the symptoms' impact. Low impact consultations were not common, although symptoms indicative of a potentially serious condition resulted in a higher proportion of low impact consultations. High impact non-consultations were more common, although there was no clear pattern in the type of associated symptoms. Just under half of those experiencing symptoms in the previous two weeks were categorised as an incongruous consulter (low impact consulter: 8.3%, high impact non-consulter: 37.1%. Employment status, having a chronic condition, poor health, and feeling that reassurance or advice from a health professional is important were associated with being a low impact consulter. Younger age, employment status, being an ex-smoker, poor health and feeling that not wasting the GPs time is important were associated with

  5. Thiopurine methyltransferase genotype-phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Lennard, Lynne; Cartwright, Cher Suzanne; Wade, Rachel; Richards, Susan M; Vora, Ajay

    2013-07-01

    In children with acute lymphoblastic leukaemia (ALL) bone marrow activity can influence red blood cell (RBC) kinetics, the surrogate tissue for thiopurine methyltransferase (TPMT) measurements. The aim of this study was to investigate TPMT phenotype-genotype concordance in ALL, and the influence of TPMT on thiopurine metabolite formation. We measured TPMT (activity, as units ml(-1) packed RBCs and genotype) at diagnosis (n = 1150) and TPMT and thioguanine nucleotide (TGN) and methylmercaptopurine nucleotide (MeMPN) metabolites (pmol/8 × 10(8) RBCs) during chemotherapy (n = 1131) in children randomized to thioguanine or mercaptopurine on the United Kingdom trial ALL97. Median TPMT activity at diagnosis (8.5 units) was significantly lower than during chemotherapy (13.8 units, median difference 5.1 units, 95% confidence interval (CI) 4.8, 5.4, P mercaptopurine, median TGNs were higher in TPMT heterozygous genotype (754 pmol) than wild-type (360 pmol) patients (median difference 406 pmol, 95% CI 332, 478, P products of the TPMT reaction, were higher in wild-type (10 650 pmol) than heterozygous patients (3868 pmol) (P < 0.0001). In TPMT intermediate activity patients with a wild-type genotype, TGN (median 366 pmol) and MeMPN (median 8590 pmol) concentrations were similar to those in wild-type, high activity patients. In childhood ALL, TPMT activity should not be used to predict heterozygosity particularly in blood samples obtained at disease diagnosis. Genotype is a better predictor of TGN accumulation during chemotherapy. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  6. Responses of nitrogen metabolism and seed nutrition to drought stress in soybean genotypes differing in slow-wilting phenotype

    Directory of Open Access Journals (Sweden)

    Nacer eBellaloui

    2013-12-01

    Full Text Available Recent advances in soybean breeding have resulted in genotypes that express the slow-wilting phenotype (trait under drought stress conditions. The physiological mechanisms of this trait remain unknown due to the complexity of trait × environment interactions. The objective of this research was to investigate nitrogen metabolism and leaf and seed nutrients composition of the slow-wilting soybean genotypes under drought stress conditions. A repeated greenhouse experiment was conducted using check genotypes: NC-Roy (fast wilting, Boggs (intermediate in wilting; and NTCPR94-5157 and N04-9646 (slow-wilting, SLW genotypes. Plants were either well-watered or drought stressed. Results showed that under well-watered conditions, nitrogen fixation (NF, nitrogen assimilation (NA, and leaf and seed composition differed between genotypes. Under drought stress, NF and NA were higher in NTCPR94-5157 and N04-9646 than in NC-Roy and Boggs. Under severe water stress, however, NA was low in all genotypes. Leaf water potential was significantly lower in checks (-2.00 MPa than in the SLW genotypes (-1.68 MPa. Leaf and seed concentrations of K, P, Ca, Cu, Na, B were higher in SLW genotypes than in the checks under drought stress conditions. Seed protein, oleic acid, and sugars were higher in SLW genotypes, and oil, linoleic and linolenic acids were lower in SLW genotypes. This research demonstrated that K, P, Ca, Cu, Na, and B may be involved in SLW trait by maintaining homeostasis and osmotic regulation. Maintaining higher leaf water potential in NTCPR94-5157 and N04-9646 under drought stress could be a possible water conservation mechanism to maintain leaf turgor pressure. The increase in osmoregulators such as minerals, raffinose and stachyose, and oleic acid could be beneficial for soybean breeders in selecting for drought stress tolerance.

  7. Phenotypic and Genotypic Eligible Methods for Salmonella Typhimurium Source Tracking.

    Science.gov (United States)

    Ferrari, Rafaela G; Panzenhagen, Pedro H N; Conte-Junior, Carlos A

    2017-01-01

    Salmonellosis is one of the most common causes of foodborne infection and a leading cause of human gastroenteritis. Throughout the last decade, Salmonella enterica serotype Typhimurium (ST) has shown an increase report with the simultaneous emergence of multidrug-resistant isolates, as phage type DT104. Therefore, to successfully control this microorganism, it is important to attribute salmonellosis to the exact source. Studies of Salmonella source attribution have been performed to determine the main food/food-production animals involved, toward which, control efforts should be correctly directed. Hence, the election of a ST subtyping method depends on the particular problem that efforts must be directed, the resources and the data available. Generally, before choosing a molecular subtyping, phenotyping approaches such as serotyping, phage typing, and antimicrobial resistance profiling are implemented as a screening of an investigation, and the results are computed using frequency-matching models (i.e., Dutch, Hald and Asymmetric Island models). Actually, due to the advancement of molecular tools as PFGE, MLVA, MLST, CRISPR, and WGS more precise results have been obtained, but even with these technologies, there are still gaps to be elucidated. To address this issue, an important question needs to be answered: what are the currently suitable subtyping methods to source attribute ST. This review presents the most frequently applied subtyping methods used to characterize ST, analyses the major available microbial subtyping attribution models and ponders the use of conventional phenotyping methods, as well as, the most applied genotypic tools in the context of their potential applicability to investigates ST source tracking.

  8. Phenotypic and Genotypic Eligible Methods for Salmonella Typhimurium Source Tracking

    Directory of Open Access Journals (Sweden)

    Rafaela G. Ferrari

    2017-12-01

    Full Text Available Salmonellosis is one of the most common causes of foodborne infection and a leading cause of human gastroenteritis. Throughout the last decade, Salmonella enterica serotype Typhimurium (ST has shown an increase report with the simultaneous emergence of multidrug-resistant isolates, as phage type DT104. Therefore, to successfully control this microorganism, it is important to attribute salmonellosis to the exact source. Studies of Salmonella source attribution have been performed to determine the main food/food-production animals involved, toward which, control efforts should be correctly directed. Hence, the election of a ST subtyping method depends on the particular problem that efforts must be directed, the resources and the data available. Generally, before choosing a molecular subtyping, phenotyping approaches such as serotyping, phage typing, and antimicrobial resistance profiling are implemented as a screening of an investigation, and the results are computed using frequency-matching models (i.e., Dutch, Hald and Asymmetric Island models. Actually, due to the advancement of molecular tools as PFGE, MLVA, MLST, CRISPR, and WGS more precise results have been obtained, but even with these technologies, there are still gaps to be elucidated. To address this issue, an important question needs to be answered: what are the currently suitable subtyping methods to source attribute ST. This review presents the most frequently applied subtyping methods used to characterize ST, analyses the major available microbial subtyping attribution models and ponders the use of conventional phenotyping methods, as well as, the most applied genotypic tools in the context of their potential applicability to investigates ST source tracking.

  9. Genotypic versus phenotypic identification of staphylococcal species of canine origin with special reference to Staphylococcus schleiferi subsp. coagulans.

    Science.gov (United States)

    Jousson, Olivier; Di Bello, Domenica; Vanni, Michele; Cardini, Giovanni; Soldani, Giulio; Pretti, Carlo; Intorre, Luigi

    2007-07-20

    A comparative study was performed to examine the respective accuracy of 16S rDNA sequencing and of the commercial biochemical assay ID32 STAPH (bioMérieux, Marcy l'Etoile, France) in the identification of 232 staphylococcal samples representing 20 species and subspecies isolated from 367 dogs. Notable differences in species distribution were observed by comparing genotypic and phenotypic data. Partial sequencing of 16S rDNA resulted in an unambiguous identification of 226 (97.4%) of the isolates, whereas the phenotypic approach resulted in a correct diagnosis of 162 (69.8%) of the isolates. Statistical agreement between genotypic and phenotypic identification of staphylococci was substantial (Kappa coefficient of 0.6-0.8) for Staphylococcus aureus, S. hominis, S. warneri, S. cohnii subsp. urealyticus, and S. simulans, and "almost perfect" (Kappa coefficient of 0.8-1) for S. intermedius, S. epidermidis, S. equorum, S. haemolyticus, S. sciuri, and S. kloosi. No agreement above that expected by chance (Kappa coefficient=0) was observed for S. schleiferi subsp. coagulans, which was either confounded with S. intermedius and S. capitis, or categorized as unacceptable by the biochemical assay. Given the growing importance of this pathogen in veterinary medicine and its frequent misidentification with related staphylococci, a PCR-RFLP approach producing a S. schleiferi-specific restriction profile was developed. This fast and reliable assay represents a valuable tool in assisting in the monitoring of this pathogen.

  10. A Multidisciplinary Phenotyping and Genotyping Analysis of a Mapping Population Enables Quality to Be Combined with Yield in Rice

    Directory of Open Access Journals (Sweden)

    Mariafe Calingacion

    2017-05-01

    Full Text Available In this study a mapping population (F8 of ca 200 progeny from a cross between the commercial rice varieties Apo and IR64 has been both genotyped and phenotyped. A genotyping-by-sequencing approach was first used to identify 2,681 polymorphic SNP markers which gave dense coverage of the genome with a good distribution across all 12 chromosomes. The coefficient of parentage was also low, at 0.13, confirming that the parents are genetically distant from each other. The progeny, together with both parents, were grown under irrigated and water restricted conditions in a randomised block design. All grain was harvested to determine variation in yield across the population. The grains were then polished following standard procedures prior to performing the phenotyping analyses. A Gas Chromatography—Mass Spectrometry approach was used to determine the volatile biochemical profiles of each line and after data curation and processing, discriminatory metabolites were putatively identified based on in-house and commercial spectral libraries. These data were used to predict the potential role of these metabolites in determining differences in aroma between genotypes. A number of QTLs for yield and for individual metabolites have been identified. Following these combined multi-disciplinary analyses, it proved possible to identify a number of lines which appeared to combine the favourable aroma attributes of IR64 with the favourable (higher yield potential of Apo. As such, these lines are excellent candidates to assess further as potential genotypes to work up into a new variety of rice which has both good yield and good quality, thus meeting the needs of both farmer and consumer alike.

  11. Cafe Variome: general-purpose software for making genotype-phenotype data discoverable in restricted or open access contexts.

    Science.gov (United States)

    Lancaster, Owen; Beck, Tim; Atlan, David; Swertz, Morris; Thangavelu, Dhiwagaran; Veal, Colin; Dalgleish, Raymond; Brookes, Anthony J

    2015-10-01

    Biomedical data sharing is desirable, but problematic. Data "discovery" approaches-which establish the existence rather than the substance of data-precisely connect data owners with data seekers, and thereby promote data sharing. Cafe Variome (http://www.cafevariome.org) was therefore designed to provide a general-purpose, Web-based, data discovery tool that can be quickly installed by any genotype-phenotype data owner, or network of data owners, to make safe or sensitive content appropriately discoverable. Data fields or content of any type can be accommodated, from simple ID and label fields through to extensive genotype and phenotype details based on ontologies. The system provides a "shop window" in front of data, with main interfaces being a simple search box and a powerful "query-builder" that enable very elaborate queries to be formulated. After a successful search, counts of records are reported grouped by "openAccess" (data may be directly accessed), "linkedAccess" (a source link is provided), and "restrictedAccess" (facilitated data requests and subsequent provision of approved records). An administrator interface provides a wide range of options for system configuration, enabling highly customized single-site or federated networks to be established. Current uses include rare disease data discovery, patient matchmaking, and a Beacon Web service. © 2015 WILEY PERIODICALS, INC.

  12. Revisiting genotype-phenotype overlap in neurogenetics: triplet-repeat expansions mimicking spastic paraplegias.

    Science.gov (United States)

    Bettencourt, Conceição; Quintáns, Beatriz; Ros, Raquel; Ampuero, Israel; Yáñez, Zuleima; Pascual, Samuel Ignacio; de Yébenes, Justo García; Sobrido, María-Jesús

    2012-09-01

    Hereditary spastic paraplegias (HSPs) constitute a heterogeneous group of neurological disorders, characterized primarily by progressive spasticity and weakness of the lower limbs. HSPs are caused by mutations in multiple genes (at least 48 loci and 28 causative genes). The clinical spectrum of HSPs is wide and important differences have been reported between patients with distinct mutations in the same gene, or even between different family members bearing the same mutation. Many patients with HSP present clinical deficits related to the involvement of neuronal systems other than corticospinal tracts, namely, peripheral nerves, sensory, or cerebellar pathways. These cases may be difficult to differentiate from other neurological diseases (e.g., hereditary ataxias), also genetically and clinically heterogeneous. As an illustration of how overlapping this genotype-phenotype relationship is, and the difficulties that it brings upon the development of neurogenetic algorithms and databases, we review the main clinical and genetic features of HSPs, and summarize reports on cases of triplet-repeat spinocerebellar ataxias that can mimic HSP phenotypes. This complex scenario makes the necessity of high-quality, curated mutation databases even more urgent, in order to develop adequate diagnostic guidelines, correct interpretation of genetic testing, and appropriate genetic counseling. © 2012 Wiley Periodicals, Inc.

  13. Sõnaliik kui rakenduslik probleem : sõnaliikide märgendamine vana kirjakeele korpuses / Külli Habicht, Pille Penjam, Külli Prillop

    Index Scriptorium Estoniae

    Habicht, Külli, 1964-

    2011-01-01

    Käsitletakse sõnade liigitamisega seotud probleeme eesti vana kirjakeele korpuse märgendamise praktikas. Tutvustatakse ka kasutusel olevat märgendussüsteemi ning raskusi selle tegelikul rakendamisel

  14. Investigating genotype-phenotype relationships in Saccharomyces cerevisiae metabolic network through stoichiometric modeling

    DEFF Research Database (Denmark)

    Brochado, Ana Rita

    processes. Metabolism is an extensively studied and characterised subcellular system, for which several modeling approaches have been proposed over the last 20 years. Nowadays, stoichiometric modeling of metabolism is done at the genome scale and it has diverse applications, many of them for helping....... This chapter aims at providing the reader with relevant state-of-the-art information concerning Systems Biology, Genome-Scale Metabolic Modeling and Metabolic Engineering. Particular attention is given to the yeast Saccharomyces cerevisiae, the eukaryotic model organism used thought the thesis.......A holistic view of the cell is fundamental for gaining insights into genotype to phenotype relationships. Systems Biology is a discipline within Biology, which uses such holistic approach by focusing on the development and application of tools for studying the structure and dynamics of cellular...

  15. GGCX-Associated Phenotypes: An Overview in Search of Genotype-Phenotype Correlations

    Directory of Open Access Journals (Sweden)

    Eva Y. G. De Vilder

    2017-01-01

    Full Text Available Gamma-carboxylation, performed by gamma-glutamyl carboxylase (GGCX, is an enzymatic process essential for activating vitamin K-dependent proteins (VKDP with important functions in various biological processes. Mutations in the encoding GGCX gene are associated with multiple phenotypes, amongst which vitamin K-dependent coagulation factor deficiency (VKCFD1 is best known. Other patients have skin, eye, heart or bone manifestations. As genotype–phenotype correlations were never described, literature was systematically reviewed in search of patients with at least one GGCX mutation with a phenotypic description, resulting in a case series of 47 patients. Though this number was too low for statistically valid correlations—a frequent problem in orphan diseases—we demonstrate the crucial role of the horizontally transferred transmembrane domain in developing cardiac and bone manifestations. Moreover, natural history suggests ageing as the principal determinant to develop skin and eye symptoms. VKCFD1 symptoms seemed more severe in patients with both mutations in the same protein domain, though this could not be linked to a more perturbed coagulation factor function. Finally, distinct GGCX functional domains might be dedicated to carboxylation of very specific VKDP. In conclusion, this systematic review suggests that there indeed may be genotype–phenotype correlations for GGCX-related phenotypes, which can guide patient counseling and management.

  16. Identification of associations between genotypes and longitudinal phenotypes via temporally-constrained group sparse canonical correlation analysis.

    Science.gov (United States)

    Hao, Xiaoke; Li, Chanxiu; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L; Saykin, Andrew J; Shen, Li; Zhang, Daoqiang

    2017-07-15

    Neuroimaging genetics identifies the relationships between genetic variants (i.e., the single nucleotide polymorphisms) and brain imaging data to reveal the associations from genotypes to phenotypes. So far, most existing machine-learning approaches are widely used to detect the effective associations between genetic variants and brain imaging data at one time-point. However, those associations are based on static phenotypes and ignore the temporal dynamics of the phenotypical changes. The phenotypes across multiple time-points may exhibit temporal patterns that can be used to facilitate the understanding of the degenerative process. In this article, we propose a novel temporally constrained group sparse canonical correlation analysis (TGSCCA) framework to identify genetic associations with longitudinal phenotypic markers. The proposed TGSCCA method is able to capture the temporal changes in brain from longitudinal phenotypes by incorporating the fused penalty, which requires that the differences between two consecutive canonical weight vectors from adjacent time-points should be small. A new efficient optimization algorithm is designed to solve the objective function. Furthermore, we demonstrate the effectiveness of our algorithm on both synthetic and real data (i.e., the Alzheimer's Disease Neuroimaging Initiative cohort, including progressive mild cognitive impairment, stable MCI and Normal Control participants). In comparison with conventional SCCA, our proposed method can achieve strong associations and discover phenotypic biomarkers across multiple time-points to guide disease-progressive interpretation. The Matlab code is available at https://sourceforge.net/projects/ibrain-cn/files/ . dqzhang@nuaa.edu.cn or shenli@iu.edu. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  17. dbVOR: a database system for importing pedigree, phenotype and genotype data and exporting selected subsets.

    Science.gov (United States)

    Baron, Robert V; Conley, Yvette P; Gorin, Michael B; Weeks, Daniel E

    2015-03-18

    When studying the genetics of a human trait, we typically have to manage both genome-wide and targeted genotype data. There can be overlap of both people and markers from different genotyping experiments; the overlap can introduce several kinds of problems. Most times the overlapping genotypes are the same, but sometimes they are different. Occasionally, the lab will return genotypes using a different allele labeling scheme (for example 1/2 vs A/C). Sometimes, the genotype for a person/marker index is unreliable or missing. Further, over time some markers are merged and bad samples are re-run under a different sample name. We need a consistent picture of the subset of data we have chosen to work with even though there might possibly be conflicting measurements from multiple data sources. We have developed the dbVOR database, which is designed to hold data efficiently for both genome-wide and targeted experiments. The data are indexed for fast retrieval by person and marker. In addition, we store pedigree and phenotype data for our subjects. The dbVOR database allows us to select subsets of the data by several different criteria and to merge their results into a coherent and consistent whole. Data may be filtered by: family, person, trait value, markers, chromosomes, and chromosome ranges. The results can be presented in columnar, Mega2, or PLINK format. dbVOR serves our needs well. It is freely available from https://watson.hgen.pitt.edu/register . Documentation for dbVOR can be found at https://watson.hgen.pitt.edu/register/docs/dbvor.html .

  18. Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD.

    Science.gov (United States)

    Andrews, Katrina A; Ascher, David B; Pires, Douglas Eduardo Valente; Barnes, Daniel R; Vialard, Lindsey; Casey, Ruth T; Bradshaw, Nicola; Adlard, Julian; Aylwin, Simon; Brennan, Paul; Brewer, Carole; Cole, Trevor; Cook, Jackie A; Davidson, Rosemarie; Donaldson, Alan; Fryer, Alan; Greenhalgh, Lynn; Hodgson, Shirley V; Irving, Richard; Lalloo, Fiona; McConachie, Michelle; McConnell, Vivienne P M; Morrison, Patrick J; Murday, Victoria; Park, Soo-Mi; Simpson, Helen L; Snape, Katie; Stewart, Susan; Tomkins, Susan E; Wallis, Yvonne; Izatt, Louise; Goudie, David; Lindsay, Robert S; Perry, Colin G; Woodward, Emma R; Antoniou, Antonis C; Maher, Eamonn R

    2018-06-01

    Germline pathogenic variants in SDHB/SDHC / SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype-phenotype correlations in a large cohort of SDHB/SDHC / SDHD mutation carriers. A retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB/SDHC / SDHD (n=673/43/160). Tumour risks were correlated with in silico structural prediction analyses. Tumour risks analysis provided novel penetrance estimates and genotype-phenotype correlations. In addition to tumour type susceptibility differences for individual genes, we confirmed that the SDHD: p.Pro81Leu mutation has a distinct phenotype and identified increased age-related tumour risks with highly destabilising SDHB missense mutations. By Kaplan-Meier analysis, the penetrance (cumulative risk of clinically apparent tumours) in SDHB and (paternally inherited) SDHD mutation-positive non-probands (n=371/67 with detailed clinical information) by age 60 years was 21.8% (95% CI 15.2% to 27.9%) and 43.2% (95% CI 25.4% to 56.7%), respectively. Risk of malignant disease at age 60 years in non-proband SDHB mutation carriers was 4.2%(95% CI 1.1% to 7.2%). With retrospective cohort analysis to adjust for ascertainment, cumulative tumour risks for SDHB mutation carriers at ages 60 years and 80 years were 23.9% (95% CI 20.9% to 27.4%) and 30.6% (95% CI 26.8% to 34.7%). Overall risks of clinically apparent tumours for SDHB mutation carriers are substantially lower than initially estimated and will improve counselling of affected families. Specific genotype-tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase

  19. Genetic diversity in soybean genotypes using phenotypic characters and enzymatic markers.

    Science.gov (United States)

    Zambiazzi, E V; Bruzi, A T; Sales, A P; Borges, I M M; Guilherme, S R; Zuffo, A M; Lima, J G; Ribeiro, F O; Mendes, A E S; Godinho, S H M; Carvalho, M L M

    2017-09-21

    The objective of this study was to evaluate the genetic diversity of soybean cultivars by adopting phenotypic traits and enzymatic markers, the relative contribution of agronomic traits to diversity, as well as diversity between the level of technology used in soybean cultivars and genetic breeding programs in which cultivars were inserted. The experiments were conducted on the field at the Center for Scientific and Technological Development in crop-livestock production and the Electrophoresis Laboratory of Lavras Federal University. The agronomic traits adopted were grain yield, plant height, first legume insertion, plant lodging, the mass of one thousand seeds, and days for complete maturation, in which the Euclidean distance, grouped by Tocher and UPGMA criteria, was obtained. After electrophorese gels for enzymatic systems, dehydrogenase alcohol, esterase, superoxide dismutase, and peroxidase were performed. The genetic similarity estimative was also obtained between genotypes by the Jaccard coefficient with subsequent grouping by the UPGMA method. The formation of two groups was shown using phenotypic characters in the genetic diversity study and individually discriminating the cultivar 97R73 RR. The character with the greatest contribution to the genetic divergence was grain yield with contribution higher than 90.0%. To obtain six different groups, individually discriminating the cultivars CG 8166 RR, FPS Jupiter RR, and BRS MG 780 RR, enzymatic markers were used. Cultivars carrying the RR technology presented more divergence than conventional cultivars and IPRO cultivars.

  20. Microarray and FISH-based genotype-phenotype analysis of 22 Japanese patients with Wolf-Hirschhorn syndrome.

    Science.gov (United States)

    Shimizu, Kenji; Wakui, Keiko; Kosho, Tomoki; Okamoto, Nobuhiko; Mizuno, Seiji; Itomi, Kazuya; Hattori, Shigeto; Nishio, Kimio; Samura, Osamu; Kobayashi, Yoshiyuki; Kako, Yuko; Arai, Takashi; Tsutomu, Oh-ishi; Kawame, Hiroshi; Narumi, Yoko; Ohashi, Hirofumi; Fukushima, Yoshimitsu

    2014-03-01

    Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome of the distal 4p chromosome, characterized by craniofacial features, growth impairment, intellectual disability, and seizures. Although genotype-phenotype correlation studies have previously been published, several important issues remain to be elucidated including seizure severity. We present detailed clinical and molecular-cytogenetic findings from a microarray and fluorescence in situ hybridization (FISH)-based genotype-phenotype analysis of 22 Japanese WHS patients, the first large non-Western series. 4p deletions were terminal in 20 patients and interstitial in two, with deletion sizes ranging from 2.06 to 29.42 Mb. The new Wolf-Hirschhorn syndrome critical region (WHSCR2) was deleted in all cases, and duplication of other chromosomal regions occurred in four. Complex mosaicism was identified in two cases: two different 4p terminal deletions; a simple 4p terminal deletion and an unbalanced translocation with the same 4p breakpoint. Seizures began in infancy in 33% (2/6) of cases with small (6 Mb). Status epilepticus occurred in 17% (1/6) with small deletions and in 87% (13/15) with larger deletions. Renal hypoplasia or dysplasia and structural ocular anomalies were more prevalent in those with larger deletions. A new susceptible region for seizure occurrence is suggested between 0.76 and 1.3 Mb from 4 pter, encompassing CTBP1 and CPLX1, and distal to the previously-supposed candidate gene LETM1. The usefulness of bromide therapy for seizures and additional clinical features including hypercholesterolemia are also described. © 2013 Wiley Periodicals, Inc.

  1. Genotype to phenotype mapping and the fitness landscape of the E. coli lac promoter.

    Directory of Open Access Journals (Sweden)

    Jakub Otwinowski

    Full Text Available Genotype-to-phenotype maps and the related fitness landscapes that include epistatic interactions are difficult to measure because of their high dimensional structure. Here we construct such a map using the recently collected corpora of high-throughput sequence data from the 75 base pairs long mutagenized E. coli lac promoter region, where each sequence is associated with its phenotype, the induced transcriptional activity measured by a fluorescent reporter. We find that the additive (non-epistatic contributions of individual mutations account for about two-thirds of the explainable phenotype variance, while pairwise epistasis explains about 7% of the variance for the full mutagenized sequence and about 15% for the subsequence associated with protein binding sites. Surprisingly, there is no evidence for third order epistatic contributions, and our inferred fitness landscape is essentially single peaked, with a small amount of antagonistic epistasis. There is a significant selective pressure on the wild type, which we deduce to be multi-objective optimal for gene expression in environments with different nutrient sources. We identify transcription factor (CRP and RNA polymerase binding sites in the promotor region and their interactions without difficult optimization steps. In particular, we observe evidence for previously unexplored genetic regulatory mechanisms, possibly kinetic in nature. We conclude with a cautionary note that inferred properties of fitness landscapes may be severely influenced by biases in the sequence data.

  2. Characterization of G6PD genotypes and phenotypes on the northwestern Thailand-Myanmar border.

    Directory of Open Access Journals (Sweden)

    Germana Bancone

    Full Text Available Mutations in the glucose-6-phosphate dehydrogenase (G6PD gene result in red blood cells with increased susceptibility to oxidative damage. Significant haemolysis can be caused by primaquine and other 8-aminoquinoline antimalarials used for the radical treatment of Plasmodium vivax malaria. The distribution and phenotypes of mutations causing G6PD deficiency in the male population of migrants and refugees in a malaria endemic region on the Thailand-Myanmar border were characterized. Blood samples for G6PD fluorescent spot test (FST, G6PD genotyping, and malaria testing were taken from 504 unrelated males of Karen and Burman ethnicities presenting to the outpatient clinics. The overall frequency of G6PD deficiency by the FST was 13.7%. Among the deficient subjects, almost 90% had the Mahidol variant (487G>A genotype. The remaining subjects had Chinese-4 (392G>T, Viangchan (871G>A, Açores (595A>G, Seattle (844G>C and Mediterranean (563C>T variants. Quantification of G6PD activity was performed using a modification of the standard spectrophotometric assay on a subset of 24 samples with Mahidol, Viangchan, Seattle and Chinese-4 mutations; all samples showed a residual enzymatic activity below 10% of normal and were diagnosed correctly by the FST. Further studies are needed to characterise the haemolytic risk of using 8-aminoquinolines in patients with these genotypes.

  3. Genotypic and Phenotypic Correlations of Multidrug-Resistant Acinetobacter baumannii-A. calcoaceticus Complex Strains Isolated from Patients at the National Naval Medical Center

    Science.gov (United States)

    Acinetobacter baumannii-calcoaceticus complex (ABC) infections have complicated the care of U.S. combat casualties. In this study, 102 ABC isolates from wounded soldiers treated at National Naval Medical Center (NNMC) were characterized by phenotype and genotype to identify clones in this population...

  4. COMPUTER APPROACHES TO WHEAT HIGH-THROUGHPUT PHENOTYPING

    Directory of Open Access Journals (Sweden)

    Afonnikov D.

    2012-08-01

    Full Text Available The growing need for rapid and accurate approaches for large-scale assessment of phenotypic characters in plants becomes more and more obvious in the studies looking into relationships between genotype and phenotype. This need is due to the advent of high throughput methods for analysis of genomes. Nowadays, any genetic experiment involves data on thousands and dozens of thousands of plants. Traditional ways of assessing most phenotypic characteristics (those with reliance on the eye, the touch, the ruler are little effective on samples of such sizes. Modern approaches seek to take advantage of automated phenotyping, which warrants a much more rapid data acquisition, higher accuracy of the assessment of phenotypic features, measurement of new parameters of these features and exclusion of human subjectivity from the process. Additionally, automation allows measurement data to be rapidly loaded into computer databases, which reduces data processing time.In this work, we present the WheatPGE information system designed to solve the problem of integration of genotypic and phenotypic data and parameters of the environment, as well as to analyze the relationships between the genotype and phenotype in wheat. The system is used to consolidate miscellaneous data on a plant for storing and processing various morphological traits and genotypes of wheat plants as well as data on various environmental factors. The system is available at www.wheatdb.org. Its potential in genetic experiments has been demonstrated in high-throughput phenotyping of wheat leaf pubescence.

  5. Mis juhtus Puhja kiriklas? : ühe vana tõlke algust otsides / Annika Kilgi, Inge Käsi, Aivar Põldvee ... [jt.

    Index Scriptorium Estoniae

    2014-01-01

    Otsitakse vastust küsimusele, kumb keel oli isa-poja Andreas ja Adrian Virginiuse tõlgitud Vana Testamendi sihtkeel, kas lõunaeesti või põhjaeesti keel ning kas Puhjas toimus midagi tõlketalgute taolist. Artikkel fikseerib uurimise hetkeseisu

  6. Phenotype/genotype correlation in a case series of Stargardt's patients identifies novel mutations in the ABCA4 gene.

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2013-11-01

    To investigate phenotypic variability in terms of best-corrected visual acuity (BCVA) in patients with Stargardt disease (STGD) and confirmed ABCA4 mutations. Entire coding region analysis of the ABCA4 gene by direct sequencing of seven patients with clinical findings of STGD seen in the Retina Clinics of Southampton Eye Unit between 2002 and 2011.Phenotypic variables recorded were BCVA, fluorescein angiographic appearance, electrophysiology, and visual fields. All patients had heterozygous amino acid-changing variants (missense mutations) in the ABCA4 gene. A splice sequence change was found in a 30-year-old patient with severly affected vision. Two novel sequence changes were identified: a missense mutation in a mildly affected 44-year-old patient and a frameshift mutation in a severly affected 34-year-old patient. The identified ABCA4 mutations were compatible with the resulting phenotypes in terms of BCVA. Higher BCVAs were recorded in patients with missense mutations. Sequence changes, predicted to have more deleterious effect on protein function, resulted in a more severe phenotype. This case series of STGD patients demonstrates novel genotype/phenotype correlations, which may be useful to counselling of patients. This information may prove useful in selection of candidates for clinical trials in ABCA4 disease.

  7. Analysis of phenotype, genotype and serotype distribution in erythromycin-resistant group B streptococci isolated from vaginal flora in Southern Ireland.

    LENUS (Irish Health Repository)

    Kiely, R A

    2010-02-01

    The screening of 2000 women of childbearing age in Cork between 2004 and 2006 produced 37 erythromycin-resistant group B streptococcus (GBS) isolates. PCR analysis was performed to determine the basis for erythromycin resistance. The ermTR gene was most frequently expressed (n = 19), followed by the ermB gene (n = 8). Four isolates harboured the mefA gene. Six isolates yielded no PCR products. Some phenotype-genotype correlation was observed. All isolates expressing the mefA gene displayed the M phenotype whilst all those expressing ermB displayed the constitutive macrolide resistance (cMLS(B)) phenotype. Of 19 isolates that expressed the ermTR gene, 16 displayed the inducible macrolide resistance (iMLS(B)) phenotype. Serotype analysis revealed that serotypes III and V predominated in these isolates. The identification of two erythromycin-resistant serotype VIII isolates among this collection represents the first reported finding of erythromycin resistance in this serotype. A single isolate was non-typable using two latex agglutination serotyping kits.

  8. The Flip Side of Holland Type Congruence: Incongruence and Job Satisfaction

    Science.gov (United States)

    Dik, Bryan J.; Strife, Samantha Roberts; Hansen, Jo-Ida C.

    2010-01-01

    This study examined the relationship between Holland type (Realistic, Investigative, Artistic, Social, Enterprising, and Conventional; Holland, 1959, 1997) congruence and incongruence (i.e., lack of ft between an occupation's 3-letter Holland code and a person's lowest 3 Holland interest types) and tested whether incongruence predicts unique…

  9. Unintentional eating. What determines goal-incongruent chocolate consumption?

    Science.gov (United States)

    Allan, Julia L; Johnston, Marie; Campbell, Neil

    2010-04-01

    Overeating can be automatically triggered by the presence of palatable food. When presented with an opportunity to consume unlimited chocolate under the guise of a consumer study, chocolate consumption in individuals (n=62) with healthy dietary intentions could be predicted from a psychological measure of cognitive inhibition. Individuals who were less able to suppress goal-incongruent responses in an established inhibitory task: (a) ate more chocolate and (b) had a higher body mass index than others suggesting that these individuals were less able to exert dietary control in the presence of palatable but intention-incongruent foods. Copyright 2010 Elsevier Ltd. All rights reserved.

  10. The Triticeae Toolbox: Combining Phenotype and Genotype Data to Advance Small-Grains Breeding

    Directory of Open Access Journals (Sweden)

    Victoria C. Blake

    2016-07-01

    Full Text Available The Triticeae Toolbox (; T3 is the database schema enabling plant breeders and researchers to combine, visualize, and interrogate the wealth of phenotype and genotype data generated by the Triticeae Coordinated Agricultural Project (TCAP. T3 enables users to define specific data sets for download in formats compatible with the external tools TASSEL, Flapjack, and R; or to use by software residing on the T3 server for operations such as Genome Wide Association and Genomic Prediction. New T3 tools to assist plant breeders include a Selection Index Generator, analytical tools to compare phenotype trials using common or user-defined indices, and a histogram generator for nursery reports, with applications using the Android OS, and a Field Plot Layout Designer in development. Researchers using T3 will soon enjoy the ability to design training sets, define core germplasm sets, and perform multivariate analysis. An increased collaboration with GrainGenes and integration with the small grains reference sequence resources will place T3 in a pivotal role for on-the-fly data analysis, with instant access to the knowledge databases for wheat and barley. T3 software is available under the GNU General Public License and is freely downloadable.

  11. Arheozooloogilised leiud inimese elutegevuse uurimise allikana : Vana-Pärnu jäätmeauk 17. sajandist / Ingrid Õunapuu, Liina Maldre

    Index Scriptorium Estoniae

    Õunapuu, Ingrid

    2010-01-01

    Vana-Pärnu muinsuskaitsealal avastatud 17. sajandi jäätmeaugus sisaldunud arheozooloogilisest materjalist. Leitud luude määrangu ja analüüsi põhjal saab teha järeldusi selle ajastu inimtegevuse ja koduloomade kohta

  12. Genotypic and Phenotypic Characteristics Associated with Biofilm Formation by Human Clinical Escherichia coli Isolates of Different Pathotypes.

    Science.gov (United States)

    Schiebel, Juliane; Böhm, Alexander; Nitschke, Jörg; Burdukiewicz, Michał; Weinreich, Jörg; Ali, Aamir; Roggenbuck, Dirk; Rödiger, Stefan; Schierack, Peter

    2017-12-15

    Bacterial biofilm formation is a widespread phenomenon and a complex process requiring a set of genes facilitating the initial adhesion, maturation, and production of the extracellular polymeric matrix and subsequent dispersal of bacteria. Most studies on Escherichia coli biofilm formation have investigated nonpathogenic E. coli K-12 strains. Due to the extensive focus on laboratory strains in most studies, there is poor information regarding biofilm formation by pathogenic E. coli isolates. In this study, we genotypically and phenotypically characterized 187 human clinical E. coli isolates representing various pathotypes (e.g., uropathogenic, enteropathogenic, and enteroaggregative E. coli ). We investigated the presence of biofilm-associated genes ("genotype") and phenotypically analyzed the isolates for motility and curli and cellulose production ("phenotype"). We developed a new screening method to examine the in vitro biofilm formation ability. In summary, we found a high prevalence of biofilm-associated genes. However, we could not detect a biofilm-associated gene or specific phenotype correlating with the biofilm formation ability. In contrast, we did identify an association of increased biofilm formation with a specific E. coli pathotype. Enteroaggregative E. coli (EAEC) was found to exhibit the highest capacity for biofilm formation. Using our image-based technology for the screening of biofilm formation, we demonstrated the characteristic biofilm formation pattern of EAEC, consisting of thick bacterial aggregates. In summary, our results highlight the fact that biofilm-promoting factors shown to be critical for biofilm formation in nonpathogenic strains do not reflect their impact in clinical isolates and that the ability of biofilm formation is a defined characteristic of EAEC. IMPORTANCE Bacterial biofilms are ubiquitous and consist of sessile bacterial cells surrounded by a self-produced extracellular polymeric matrix. They cause chronic and device

  13. Molecular analysis of diverse elements mediating VanA glycopeptide resistance in enterococci

    DEFF Research Database (Denmark)

    Palepou, M.F.I.; Adebiyi, A.M.A.; Tremlett, C.H.

    1998-01-01

    Differences were examined among 24 distinct elements mediating VanA-type glycopeptide resistance in enterococci isolated from hospital patients and non-human sources in the UK. The methods used included long-PCR restriction fragment length polymorphism (L-PCR RFLP) analysis and DNA hybridization...... characterized by the presence of an IS1216V/IS3-like/orf1 complex and a point mutation in vanX, both of which were absent from the other 23 groups of VanA elements. This finding is consistent with the dissemination of a stable resistance element. We conclude that L-PCR RFLP analysis, combined with DNA...

  14. Cortical oscillations related to processing congruent and incongruent grapheme-phoneme pairs.

    Science.gov (United States)

    Herdman, Anthony T; Fujioka, Takako; Chau, Wilkin; Ross, Bernhard; Pantev, Christo; Picton, Terence W

    2006-05-15

    In this study, we investigated changes in cortical oscillations following congruent and incongruent grapheme-phoneme stimuli. Hiragana graphemes and phonemes were simultaneously presented as congruent or incongruent audiovisual stimuli to native Japanese-speaking participants. The discriminative reaction time was 57 ms shorter for congruent than incongruent stimuli. Analysis of MEG responses using synthetic aperture magnetometry (SAM) revealed that congruent stimuli evoked larger 2-10 Hz activity in the left auditory cortex within the first 250 ms after stimulus onset, and smaller 2-16 Hz activity in bilateral visual cortices between 250 and 500 ms. These results indicate that congruent visual input can modify cortical activity in the left auditory cortex.

  15. The rapid distraction of attentional resources toward the source of incongruent stimulus input during multisensory conflict.

    Science.gov (United States)

    Donohue, Sarah E; Todisco, Alexandra E; Woldorff, Marty G

    2013-04-01

    Neuroimaging work on multisensory conflict suggests that the relevant modality receives enhanced processing in the face of incongruency. However, the degree of stimulus processing in the irrelevant modality and the temporal cascade of the attentional modulations in either the relevant or irrelevant modalities are unknown. Here, we employed an audiovisual conflict paradigm with a sensory probe in the task-irrelevant modality (vision) to gauge the attentional allocation to that modality. ERPs were recorded as participants attended to and discriminated spoken auditory letters while ignoring simultaneous bilateral visual letter stimuli that were either fully congruent, fully incongruent, or partially incongruent (one side incongruent, one congruent) with the auditory stimulation. Half of the audiovisual letter stimuli were followed 500-700 msec later by a bilateral visual probe stimulus. As expected, ERPs to the audiovisual stimuli showed an incongruency ERP effect (fully incongruent versus fully congruent) of an enhanced, centrally distributed, negative-polarity wave starting ∼250 msec. More critically here, the sensory ERP components to the visual probes were larger when they followed fully incongruent versus fully congruent multisensory stimuli, with these enhancements greatest on fully incongruent trials with the slowest RTs. In addition, on the slowest-response partially incongruent trials, the P2 sensory component to the visual probes was larger contralateral to the preceding incongruent visual stimulus. These data suggest that, in response to conflicting multisensory stimulus input, the initial cognitive effect is a capture of attention by the incongruent irrelevant-modality input, pulling neural processing resources toward that modality, resulting in rapid enhancement, rather than rapid suppression, of that input.

  16. The psychophysics of comic: Effects of incongruity in causality and animacy.

    Science.gov (United States)

    Parovel, Giulia; Guidi, Stefano

    2015-07-01

    According to several theories of humour (see Berger, 2012; Martin, 2007), incongruity - i.e., the presence of two incompatible meanings in the same situation - is a crucial condition for an event being evaluated as comical. The aim of this research was to test with psychophysical methods the role of incongruity in visual perception by manipulating the causal paradigm (Michotte, 1946/1963) to get a comic effect. We ran three experiments. In Experiment 1, we tested the role of speed ratio between the first and the second movement, and the effect of animacy cues (i.e. frog-like and jumping-like trajectories) in the second movement; in Experiment 2, we manipulated the temporal delay between the movements to explore the relationship between perceptual causal contingencies and comic impressions; in Experiment 3, we compared the strength of the comic impressions arising from incongruent trajectories based on animacy cues with those arising from incongruent trajectories not based on animacy cues (bouncing and rotating) in the second part of the causal event. General findings showed that the paradoxical juxtaposition of a living behaviour in the perceptual causal paradigm is a powerful factor in eliciting comic appreciations, coherently with the Bergsonian perspective in particular (Bergson, 2003), and with incongruity theories in general. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study.

    Science.gov (United States)

    Recordon-Pinson, Patricia; Soulié, Cathia; Flandre, Philippe; Descamps, Diane; Lazrek, Mouna; Charpentier, Charlotte; Montes, Brigitte; Trabaud, Mary-Anne; Cottalorda, Jacqueline; Schneider, Véronique; Morand-Joubert, Laurence; Tamalet, Catherine; Desbois, Delphine; Macé, Muriel; Ferré, Virginie; Vabret, Astrid; Ruffault, Annick; Pallier, Coralie; Raymond, Stéphanie; Izopet, Jacques; Reynes, Jacques; Marcelin, Anne-Geneviève; Masquelier, Bernard

    2010-08-01

    Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.

  18. Heterosis Is a Systemic Property Emerging From Non-linear Genotype-Phenotype Relationships: Evidence From in Vitro Genetics and Computer Simulations

    Directory of Open Access Journals (Sweden)

    Julie B. Fiévet

    2018-05-01

    Full Text Available Heterosis, the superiority of hybrids over their parents for quantitative traits, represents a crucial issue in plant and animal breeding as well as evolutionary biology. Heterosis has given rise to countless genetic, genomic and molecular studies, but has rarely been investigated from the point of view of systems biology. We hypothesized that heterosis is an emergent property of living systems resulting from frequent concave relationships between genotypic variables and phenotypes, or between different phenotypic levels. We chose the enzyme-flux relationship as a model of the concave genotype-phenotype (GP relationship, and showed that heterosis can be easily created in the laboratory. First, we reconstituted in vitro the upper part of glycolysis. We simulated genetic variability of enzyme activity by varying enzyme concentrations in test tubes. Mixing the content of “parental” tubes resulted in “hybrids,” whose fluxes were compared to the parental fluxes. Frequent heterotic fluxes were observed, under conditions that were determined analytically and confirmed by computer simulation. Second, to test this model in a more realistic situation, we modeled the glycolysis/fermentation network in yeast by considering one input flux, glucose, and two output fluxes, glycerol and acetaldehyde. We simulated genetic variability by randomly drawing parental enzyme concentrations under various conditions, and computed the parental and hybrid fluxes using a system of differential equations. Again we found that a majority of hybrids exhibited positive heterosis for metabolic fluxes. Cases of negative heterosis were due to local convexity between certain enzyme concentrations and fluxes. In both approaches, heterosis was maximized when the parents were phenotypically close and when the distributions of parental enzyme concentrations were contrasted and constrained. These conclusions are not restricted to metabolic systems: they only depend on the

  19. Now you hear it: a predictive coding model for understanding rhythmic incongruity

    DEFF Research Database (Denmark)

    Vuust, Peter; Dietz, Martin; Witek, Maria

    2018-01-01

    Rhythmic incongruity in the form of syncopation is a prominent feature of many contemporary musical styles. Syncopations afford incongruity between rhythmic patterns and the meter, giving rise to mental models of differently accented isochronous beats. Syncopations occur either in isolation or as...

  20. Mining Genotype-Phenotype Associations from Public Knowledge Sources via Semantic Web Querying

    Science.gov (United States)

    Kiefer, Richard C.; Freimuth, Robert R.; Chute, Christopher G; Pathak, Jyotishman

    Gene Wiki Plus (GeneWiki+) and the Online Mendelian Inheritance in Man (OMIM) are publicly available resources for sharing information about disease-gene and gene-SNP associations in humans. While immensely useful to the scientific community, both resources are manually curated, thereby making the data entry and publication process time-consuming, and to some degree, error-prone. To this end, this study investigates Semantic Web technologies to validate existing and potentially discover new genotype-phenotype associations in GWP and OMIM. In particular, we demonstrate the applicability of SPARQL queries for identifying associations not explicitly stated for commonly occurring chronic diseases in GWP and OMIM, and report our preliminary findings for coverage, completeness, and validity of the associations. Our results highlight the benefits of Semantic Web querying technology to validate existing disease-gene associations as well as identify novel associations although further evaluation and analysis is required before such information can be applied and used effectively. PMID:24303249

  1. Mining Genotype-Phenotype Associations from Public Knowledge Sources via Semantic Web Querying.

    Science.gov (United States)

    Kiefer, Richard C; Freimuth, Robert R; Chute, Christopher G; Pathak, Jyotishman

    2013-01-01

    Gene Wiki Plus (GeneWiki+) and the Online Mendelian Inheritance in Man (OMIM) are publicly available resources for sharing information about disease-gene and gene-SNP associations in humans. While immensely useful to the scientific community, both resources are manually curated, thereby making the data entry and publication process time-consuming, and to some degree, error-prone. To this end, this study investigates Semantic Web technologies to validate existing and potentially discover new genotype-phenotype associations in GWP and OMIM. In particular, we demonstrate the applicability of SPARQL queries for identifying associations not explicitly stated for commonly occurring chronic diseases in GWP and OMIM, and report our preliminary findings for coverage, completeness, and validity of the associations. Our results highlight the benefits of Semantic Web querying technology to validate existing disease-gene associations as well as identify novel associations although further evaluation and analysis is required before such information can be applied and used effectively.

  2. Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition.

    Directory of Open Access Journals (Sweden)

    Ellen Li

    Full Text Available We tested the hypothesis that Crohn's disease (CD-related genetic polymorphisms involved in host innate immunity are associated with shifts in human ileum-associated microbial composition in a cross-sectional analysis of human ileal samples. Sanger sequencing of the bacterial 16S ribosomal RNA (rRNA gene and 454 sequencing of 16S rRNA gene hypervariable regions (V1-V3 and V3-V5, were conducted on macroscopically disease-unaffected ileal biopsies collected from 52 ileal CD, 58 ulcerative colitis and 60 control patients without inflammatory bowel diseases (IBD undergoing initial surgical resection. These subjects also were genotyped for the three major NOD2 risk alleles (Leu1007fs, R708W, G908R and the ATG16L1 risk allele (T300A. The samples were linked to clinical metadata, including body mass index, smoking status and Clostridia difficile infection. The sequences were classified into seven phyla/subphyla categories using the Naïve Bayesian Classifier of the Ribosome Database Project. Centered log ratio transformation of six predominant categories was included as the dependent variable in the permutation based MANCOVA for the overall composition with stepwise variable selection. Polymerase chain reaction (PCR assays were conducted to measure the relative frequencies of the Clostridium coccoides - Eubacterium rectales group and the Faecalibacterium prausnitzii spp. Empiric logit transformations of the relative frequencies of these two microbial groups were included in permutation-based ANCOVA. Regardless of sequencing method, IBD phenotype, Clostridia difficile and NOD2 genotype were selected as associated (FDR ≤ 0.05 with shifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associated with shifts in the relative frequency of the C. coccoides--E. rectales group. IBD phenotype, smoking and IBD medications were selected as associated with shifts in the relative frequency of F. prausnitzii spp. These

  3. Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition.

    Science.gov (United States)

    Li, Ellen; Hamm, Christina M; Gulati, Ajay S; Sartor, R Balfour; Chen, Hongyan; Wu, Xiao; Zhang, Tianyi; Rohlf, F James; Zhu, Wei; Gu, Chi; Robertson, Charles E; Pace, Norman R; Boedeker, Edgar C; Harpaz, Noam; Yuan, Jeffrey; Weinstock, George M; Sodergren, Erica; Frank, Daniel N

    2012-01-01

    We tested the hypothesis that Crohn's disease (CD)-related genetic polymorphisms involved in host innate immunity are associated with shifts in human ileum-associated microbial composition in a cross-sectional analysis of human ileal samples. Sanger sequencing of the bacterial 16S ribosomal RNA (rRNA) gene and 454 sequencing of 16S rRNA gene hypervariable regions (V1-V3 and V3-V5), were conducted on macroscopically disease-unaffected ileal biopsies collected from 52 ileal CD, 58 ulcerative colitis and 60 control patients without inflammatory bowel diseases (IBD) undergoing initial surgical resection. These subjects also were genotyped for the three major NOD2 risk alleles (Leu1007fs, R708W, G908R) and the ATG16L1 risk allele (T300A). The samples were linked to clinical metadata, including body mass index, smoking status and Clostridia difficile infection. The sequences were classified into seven phyla/subphyla categories using the Naïve Bayesian Classifier of the Ribosome Database Project. Centered log ratio transformation of six predominant categories was included as the dependent variable in the permutation based MANCOVA for the overall composition with stepwise variable selection. Polymerase chain reaction (PCR) assays were conducted to measure the relative frequencies of the Clostridium coccoides - Eubacterium rectales group and the Faecalibacterium prausnitzii spp. Empiric logit transformations of the relative frequencies of these two microbial groups were included in permutation-based ANCOVA. Regardless of sequencing method, IBD phenotype, Clostridia difficile and NOD2 genotype were selected as associated (FDR ≤ 0.05) with shifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associated with shifts in the relative frequency of the C. coccoides--E. rectales group. IBD phenotype, smoking and IBD medications were selected as associated with shifts in the relative frequency of F. prausnitzii spp. These results indicate

  4. Incongruence between Verbal and Non-Verbal Information Enhances the Late Positive Potential.

    Science.gov (United States)

    Morioka, Shu; Osumi, Michihiro; Shiotani, Mayu; Nobusako, Satoshi; Maeoka, Hiroshi; Okada, Yohei; Hiyamizu, Makoto; Matsuo, Atsushi

    2016-01-01

    Smooth social communication consists of both verbal and non-verbal information. However, when presented with incongruence between verbal information and nonverbal information, the relationship between an individual judging trustworthiness in those who present the verbal-nonverbal incongruence and the brain activities observed during judgment for trustworthiness are not clear. In the present study, we attempted to identify the impact of incongruencies between verbal information and facial expression on the value of trustworthiness and brain activity using event-related potentials (ERP). Combinations of verbal information [positive/negative] and facial expressions [smile/angry] expressions were presented randomly on a computer screen to 17 healthy volunteers. The value of trustworthiness of the presented facial expression was evaluated by the amount of donation offered by the observer to the person depicted on the computer screen. In addition, the time required to judge the value of trustworthiness was recorded for each trial. Using electroencephalography, ERP were obtained by averaging the wave patterns recorded while the participants judged the value of trustworthiness. The amount of donation offered was significantly lower when the verbal information and facial expression were incongruent, particularly for [negative × smile]. The amplitude of the early posterior negativity (EPN) at the temporal lobe showed no significant difference between all conditions. However, the amplitude of the late positive potential (LPP) at the parietal electrodes for the incongruent condition [negative × smile] was higher than that for the congruent condition [positive × smile]. These results suggest that the LPP amplitude observed from the parietal cortex is involved in the processing of incongruence between verbal information and facial expression.

  5. Genotype-phenotype analysis of recombinant chromosome 4 syndrome: an array-CGH study and literature review.

    Science.gov (United States)

    Hemmat, Morteza; Hemmat, Omid; Anguiano, Arturo; Boyar, Fatih Z; El Naggar, Mohammed; Wang, Jia-Chi; Wang, Borris T; Sahoo, Trilochan; Owen, Renius; Haddadin, Mary

    2013-05-02

    Recombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. To date, 10 cases of recombinant chromosome 4 have been reported. We describe the second case in which array-CGH was used to characterize recombinant chromosome 4 syndrome. The patient was a one-year old boy with consistent clinical features. Conventional cytogenetics and FISH documented a recombinant chromosome 4, derived from a paternal pericentric inversion, leading to partial trisomy 4p and partial monosomy of 4q. Array-CGH, performed to further characterize the rearranged chromosome 4 and delineate the breakpoints, documented a small (4.36 Mb) 4q35.1 terminal deletion and a large (23.81 Mb) 4p15.1 terminal duplication. Genotype-phenotype analysis of 10 previously reported cases and the present case indicated relatively consistent clinical features and breakpoints. This consistency was more evident in our case and another characterized by array-CGH, where both showed the common breakpoints of p15.1 and q35.1. A genotype-phenotype correlation study between rec(4), dup(4p), and del(4q) syndromes revealed that urogenital and cardiac defects are probably due to the deletion of 4q whereas the other clinical features are likely due to 4p duplication. Our findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion. Recombinant chromosome 4 syndrome thus appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions.

  6. Phenotypic and genotypic profile of clinical and animal multidrug-resistant Salmonella enterica isolates from Mexico.

    Science.gov (United States)

    Aguilar-Montes de Oca, S; Talavera-Rojas, M; Soriano-Vargas, E; Barba-León, J; Vázquez-Navarrete, J; Acosta-Dibarrat, J; Salgado-Miranda, C

    2018-01-01

    The objective of this study was to obtain a phenotypic and genotypic profile of Salmonella enterica including multidrug-resistant (MDR) isolates from food-producing animals and clinical isolates, as well as their genetic relatedness in two different States of Mexico (Jalisco and State of Mexico). A total of 243 isolates were evaluated in terms of antimicrobial resistance (AMR) and related genes through a disk diffusion method and PCR respectively; we found 16 MDR isolates, all of them harbouring the bla CMY gene but not qnr genes, these isolates represent less than 10% of the collection. The pulsed-field gel electrophoresis revealed a higher genotypic similitude within isolates of State of Mexico than Jalisco. A low percentage of Salmonella isolates were resistant to relevant antibiotics in human health, nevertheless, the AMR and involved genes were similar despite the different serovars and origin of the isolates. This investigation provided an insight of the current status of AMR of Salmonella isolates in two States of Mexico and pinpoint the genes involved in AMR and their epidemiological relationship, the information could help to determine an adequate therapy in human and veterinary medicine. © 2017 The Society for Applied Microbiology.

  7. Humorous Names in the Light of Incongruity Theory

    Directory of Open Access Journals (Sweden)

    Mariusz Rutkowski

    2016-07-01

    Full Text Available The article addresses the humorous function of proper names in the light of incongruity theory. It aims at proving that, although names are often defined as pragmatically “transparent,” they may possess some humorous value due to semantic and pragmatic shifts resulting from the disturbance of ordinary patterns of proper names identification and interpretation. After a brief introduction, the author discusses different variants of incongruity theory as resented in the works by Victor Raskin and Thomas C. Veatch as well as their possible application to the study of humorous names. The second part of the paper provides an analysis of the humorous effects of proper names which includes anthroponyms, toponyms, trade names, football team names and names in literature. The first section of this part concentrates on names in which humour is unintentional and seems to be induced by the context, while the second section focuses on names which are intentionally humourous, i.e. supposed to amuse from the moment of their creation. The author argues that the incongruity theory can provide a useful framework for the study of the different mechanisms responsible of the semantic shifts which determine the variation of pragmatic values of proper names.

  8. Poor phenotype-genotype association in a large series of patients with Type III Bartter syndrome.

    Science.gov (United States)

    García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Álvaro; Chocrón, Sara; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; García Nieto, Víctor; Barajas de Frutos, David; Loza, Reyner; Pintos, Guillem; Castaño, Luis; Ariceta, Gema

    2017-01-01

    Type III Bartter syndrome (BS) is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS. Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR) followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses. Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG) in one patient and a small deletion (c.1026delC) in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype. A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort.

  9. Poor phenotype-genotype association in a large series of patients with Type III Bartter syndrome.

    Directory of Open Access Journals (Sweden)

    Alejandro García Castaño

    Full Text Available Type III Bartter syndrome (BS is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS.Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses.Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG in one patient and a small deletion (c.1026delC in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype.A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort.

  10. Members of the genera Paenibacillus and Rhodococcus harbor genes homologous to enterococcal glycopeptide resistance genes vanA and vanB

    DEFF Research Database (Denmark)

    Guardabassi, L.; Christensen, H.; Hasman, Henrik

    2004-01-01

    Genes homologous to enterococcal glycopeptide resistance genes vanA and vanB were found in glycopeptide-resistant Paenibacillus and Rhodococcus strains from soil. The putative D-Ala:D-Lac ligase genes in Paenibacillus thiaminolyticus PT-2B1 and Paenibacillus apiarius PA-B2B were closely related...

  11. Whole exome sequencing of wild-derived inbred strains of mice improves power to link phenotype and genotype.

    Science.gov (United States)

    Chang, Peter L; Kopania, Emily; Keeble, Sara; Sarver, Brice A J; Larson, Erica; Orth, Annie; Belkhir, Khalid; Boursot, Pierre; Bonhomme, François; Good, Jeffrey M; Dean, Matthew D

    2017-10-01

    The house mouse is a powerful model to dissect the genetic basis of phenotypic variation, and serves as a model to study human diseases. Despite a wealth of discoveries, most classical laboratory strains have captured only a small fraction of genetic variation known to segregate in their wild progenitors, and existing strains are often related to each other in complex ways. Inbred strains of mice independently derived from natural populations have the potential to increase power in genetic studies with the addition of novel genetic variation. Here, we perform exome-enrichment and high-throughput sequencing (~8× coverage) of 26 wild-derived strains known in the mouse research community as the "Montpellier strains." We identified 1.46 million SNPs in our dataset, approximately 19% of which have not been detected from other inbred strains. This novel genetic variation is expected to contribute to phenotypic variation, as they include 18,496 nonsynonymous variants and 262 early stop codons. Simulations demonstrate that the higher density of genetic variation in the Montpellier strains provides increased power for quantitative genetic studies. Inasmuch as the power to connect genotype to phenotype depends on genetic variation, it is important to incorporate these additional genetic strains into future research programs.

  12. Molecular methods for bacterial genotyping and analyzed gene regions

    Directory of Open Access Journals (Sweden)

    İbrahim Halil Yıldırım1, Seval Cing Yıldırım2, Nadir Koçak3

    2011-06-01

    Full Text Available Bacterial strain typing is an important process for diagnosis, treatment and epidemiological investigations. Current bacterial strain typing methods may be classified into two main categories: phenotyping and genotyping. Phenotypic characters are the reflection of genetic contents. Genotyping, which refers discrimination of bacterial strains based on their genetic content, has recently become widely used for bacterial strain typing. The methods already used in genotypingof bacteria are quite different from each other. In this review we tried to summarize the basic principles of DNA-based methods used in genotyping of bacteria and describe some important DNA regions that are used in genotyping of bacteria. J Microbiol Infect Dis 2011;1(1:42-46.

  13. Determination of enthalpy–temperature–composition relations in incongruent-melting phase change materials

    International Nuclear Information System (INIS)

    Desgrosseilliers, Louis; Allred, Paul; Groulx, Dominic; White, Mary Anne

    2013-01-01

    This paper demonstrates that liquidus line (T-x) data can be obtained from calorimetric determinations of phase transition enthalpy profiles (H-T) for incongruent-melting phase change materials (PCMs) more efficiently than using traditional cooling curves. An accurate and reliable equilibrium mixture enthalpy model bridges the H-T and T-x gap to provide a full suite of high density H-T-x data to assist latent heat energy storage researchers to evaluate composition-dependent two-phase equilibrium processes. The proposed method is validated for T-history method H-T determinations of 1:1 diluted sodium acetate trihydrate in water, and can also be used with other laboratory calorimetric techniques used to determine the phase transition enthalpy profiles of incongruent-melting compounds. -- Highlights: • H-T data can also be used to obtain valuable liquidus region T-x data. • Applies to all incongruent-melting compounds with known thermodynamic properties. • Reduces the effort and cost of assessing full suite H-T-x data for PCMs. • Uses existing T-x or H-T data of incongruent-melting PCMs to determine the other

  14. Defining the Role of the Environment in the Emergence and Persistence of vanA Vancomycin-Resistant Enterococcus (VRE) in an Intensive Care Unit: A Molecular Epidemiological Study.

    Science.gov (United States)

    Lee, Andie S; White, Elizabeth; Monahan, Leigh G; Jensen, Slade O; Chan, Raymond; van Hal, Sebastiaan J

    2018-06-01

    OBJECTIVETo describe the transmission dynamics of the emergence and persistence of vanA vancomycin-resistant enterococcus (VRE) in an intensive care unit (ICU) using whole-genome sequencing of patient and environmental isolates.DESIGNRetrospective cohort study.SETTINGICU in a tertiary referral center.PARTICIPANTSPatients admitted to the ICU over an 11-month period.METHODS VanA VRE isolated from patients (n=31) were sequenced using the Illumina MiSeq platform. Environmental samples from bed spaces, equipment, and waste rooms were collected. All vanA VRE-positive environmental samples (n=14) were also sequenced. Data were collected regarding patient ward and bed movements.RESULTSThe 31 patient vanA VRE isolates were from screening (n=19), urine (n=4), bloodstream (n=3), skin/wound (n=3), and intra-abdominal (n=2) sources. The phylogeny from sequencing data confirmed several VRE clusters, with 1 group accounting for 38 of 45 isolates (84%). Within this cluster, cross-transmission was extensive and complex across the ICU. Directionality indicated that colonized patients contaminated environmental sites. Similarly, environmental sources not only led to patient colonization but also to infection. Notably, shared equipment acted as a conduit for transmission between different ICU areas. Infected patients, however, were not linked to further VRE transmission.CONCLUSIONSGenomic sequencing confirmed a predominantly clonal outbreak of VRE with complex transmission dynamics. The environmental reservoir, particularly from shared equipment, played a key role in ongoing VRE spread. This study provides evidence to support the use of multifaceted strategies, with an emphasis on measures to reduce bacterial burden in the environment, for successful VRE control.Infect Control Hosp Epidemiol 2018;39:668-675.

  15. Bartter Syndrome Type 3: Phenotype-Genotype Correlation and Favorable Response to Ibuprofen

    Directory of Open Access Journals (Sweden)

    Xuejun Yang

    2018-05-01

    Full Text Available Objective: To investigate the phenotype-genotype correlation in different genetic kinds of Bartter syndrome type 3 in children.Methods: Clinical and genetic data of 2 patients with different mutations in Bartter syndrome type 3 was analyzed while the prognosis was compared after a 6-year follow-up or 2-year follow-up, respectively.Results: Bartter syndrome is a kind of autosomal recessive inherited renal disorder. The manifestation and prognosis of Bartter syndrome change with mutation types, and severe mutation were often accompanied with unfavorable prognosis. Comprehensive therapy with ibuprofen, antisterone, captopril, and potassium have remarkable effect, while ibuprofen may improve growth retardation partly.Conclusion: Bartter syndrome should be considered when children have unreasonable continuous electrolyte disturbance, metabolic alkalosis and growth retardation.As a genetic disease, its clinical features depend on the mutation type. It can be ameliorated by electrolyte supplementation, prostaglandin synthetase inhibitors, angiotensin-converting enzyme inhibitors and potassium-sparing diuretic. Considering the following electrolyte disturbances, infections, growth retardation, kidney failure and even death, Bartter syndrome need lifelong treatment, early diagnosis and treatment is the most important.

  16. Associations of MC1R Genotype and Patient Phenotypes with BRAF and NRAS Mutations in Melanoma.

    Science.gov (United States)

    Thomas, Nancy E; Edmiston, Sharon N; Kanetsky, Peter A; Busam, Klaus J; Kricker, Anne; Armstrong, Bruce K; Cust, Anne E; Anton-Culver, Hoda; Gruber, Stephen B; Luo, Li; Orlow, Irene; Reiner, Anne S; Gallagher, Richard P; Zanetti, Roberto; Rosso, Stefano; Sacchetto, Lidia; Dwyer, Terence; Parrish, Eloise A; Hao, Honglin; Gibbs, David C; Frank, Jill S; Ollila, David W; Begg, Colin B; Berwick, Marianne; Conway, Kathleen

    2017-12-01

    Associations of MC1R with BRAF mutations in melanoma have been inconsistent between studies. We sought to determine for 1,227 participants in the international population-based Genes, Environment, and Melanoma (GEM) study whether MC1R and phenotypes were associated with melanoma BRAF/NRAS subtypes. We used logistic regression adjusted by age, sex, and study design features and examined effect modifications. BRAF + were associated with younger age, blond/light brown hair, increased nevi, and less freckling, and NRAS + with older age relative to the wild type (BRAF - /NRAS - ) melanomas (all P < 0.05). Comparing specific BRAF subtypes to the wild type, BRAF V600E was associated with younger age, blond/light brown hair, and increased nevi and V600K with increased nevi and less freckling (all P < 0.05). MC1R was positively associated with BRAF V600E cases but only among individuals with darker phototypes or darker hair (P interaction < 0.05) but inversely associated with BRAF V600K (P trend  = 0.006) with no significant effect modification by phenotypes. These results support distinct etiologies for BRAF V600E, BRAF V600K, NRAS + , and wild-type melanomas. MC1R's associations with BRAF V600E cases limited to individuals with darker phenotypes indicate that MC1R genotypes specifically provide information about BRAF V600E melanoma risk in those not considered high risk based on phenotype. Our results also suggest that melanin pathways deserve further study in BRAF V600E melanomagenesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation.

    Science.gov (United States)

    Schüle, Birgitt; Oviedo, Angelica; Johnston, Kathreen; Pai, Shashidhar; Francke, Uta

    2005-12-01

    The rare, autosomal recessive Roberts syndrome (RBS) is characterized by tetraphocomelia, profound growth deficiency of prenatal onset, craniofacial anomalies, microcephaly, and mental deficiency. SC phocomelia (SC) has a milder phenotype, with a lesser degree of limb reduction and with survival to adulthood. Since heterochromatin repulsion (HR) is characteristic for both disorders and is not complemented in somatic-cell hybrids, it has been hypothesized that the disorders are allelic. Recently, mutations in ESCO2 (establishment of cohesion 1 homolog 2) on 8p21.1 have been reported in RBS. To determine whether ESCO2 mutations are also responsible for SC, we studied three families with SC and two families in which variable degrees of limb and craniofacial abnormalities, detected by fetal ultrasound, led to pregnancy terminations. All cases were positive for HR. We identified seven novel mutations in exons 3-8 of ESCO2. In two families, affected individuals were homozygous--for a 5-nucleotide deletion in one family and a splice-site mutation in the other. In three nonconsanguineous families, probands were compound heterozygous for a single-nucleotide insertion or deletion, a nonsense mutation, or a splice-site mutation. Abnormal splice products were characterized at the RNA level. Since only protein-truncating mutations were identified, regardless of clinical severity, we conclude that genotype does not predict phenotype. Having established that RBS and SC are caused by mutations in the same gene, we delineated the clinical phenotype of the tetraphocomelia spectrum that is associated with HR and ESCO2 mutations and differentiated it from other types of phocomelia that are negative for HR.

  18. MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

    Science.gov (United States)

    Makrythanasis, P; van Bon, B W; Steehouwer, M; Rodríguez-Santiago, B; Simpson, M; Dias, P; Anderlid, B M; Arts, P; Bhat, M; Augello, B; Biamino, E; Bongers, E M H F; Del Campo, M; Cordeiro, I; Cueto-González, A M; Cuscó, I; Deshpande, C; Frysira, E; Izatt, L; Flores, R; Galán, E; Gener, B; Gilissen, C; Granneman, S M; Hoyer, J; Yntema, H G; Kets, C M; Koolen, D A; Marcelis, C l; Medeira, A; Micale, L; Mohammed, S; de Munnik, S A; Nordgren, A; Psoni, S; Reardon, W; Revencu, N; Roscioli, T; Ruiterkamp-Versteeg, M; Santos, H G; Schoumans, J; Schuurs-Hoeijmakers, J H M; Silengo, M C; Toledo, L; Vendrell, T; van der Burgt, I; van Lier, B; Zweier, C; Reymond, A; Trembath, R C; Perez-Jurado, L; Dupont, J; de Vries, B B A; Brunner, H G; Veltman, J A; Merla, G; Antonarakis, S E; Hoischen, A

    2013-12-01

    Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Phenotypic and Genotypic Characterization of Indigenous Lactobacillus Community from Traditional Istrian Ewe's Cheese

    Directory of Open Access Journals (Sweden)

    Mirna Mrkonjić Fuka

    2012-01-01

    Full Text Available The objective of this study is to describe the diversity of indigenous cultivable community of the lactobacilli associated with the production of traditional Istrian cheese and to get a collection of well characterized strains. Raw milk and cheese samples were collected from three different farms in Istria during ripening. A total of 212 mesophilic and thermophilic Lactobacillus isolates as well as bulk colonies (consortia were investigated using culture-dependent approach combining phenotyping and genotyping. Biochemical fingerprinting with PhenePlate-LB system preliminary grouped 212 isolates in 16 distinct PhP types. Only one representative isolate from each PhP cluster was further analyzed by genotyping for a reliable identification at the genus and species level by employing PCR techniques and sequencing of 16S rRNA genes. Sequence analysis of 16S rRNA revealed the presence of Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus casei, Lactobacillus paracasei and Lactobacillus rhamnosus. Lactobacilli were screened for possible resistance against seven selected antibiotics: ampicillin, tetracycline, penicillin, rifampin, clindamycin, erythromycin and vancomycin. Although there was no clear pattern of antimicrobial susceptibility to most tested antibiotics, all representative isolates were resistant to vancomycin. The analysis of bulk colonies by denaturing gradient gel electrophoresis (DGGE identified Lactobacillus plantarum and Lactobacillus brevis as predominant members of Lactobacillus population. Pediococcus pentosaceus, Pediococcus acidilactici, Streptococcus sp. and Leuconostoc mesenteroides were also detected as part of the analysed consortia. The prevalence of identified species and community members of lactobacilli agrees with other studies of raw milk cheese and represents a useful base for further selection.

  20. Does incongruence of lexicosemantic and prosodic information cause discernible cognitive conflict?

    Science.gov (United States)

    Mitchell, Rachel L C

    2006-12-01

    We are often required to interpret discordant emotional signals. Whereas equivalent cognitive paradigms cause noticeable conflict via their behavioral and psychophysiological effects, the same may not necessarily be true for discordant emotions. Skin conductance responses (SCRs) and heart rates (HRs) were measured during a classic Stroop task and one in which the emotions conveyed by lexicosemantic content and prosody were congruent or incongruent. The participants' task was to identify the emotion conveyed by lexicosemantic content or prosody. No relationship was observed between HR and congruence. SCR was higher during incongruent than during congruent conditions of the experimental task (as well as in the classic Stroop task), but no difference in SCR was observed in a comparison between congruence effects during lexicosemantic emotion identification and those during prosodic emotion identification. It is concluded that incongruence between lexicosemantic and prosodic emotion does cause notable cognitive conflict. Functional neuroanatomic implications are discussed.

  1. Genotype, phenotype and in silico pathogenicity analysis of HEXB mutations: Panel based sequencing for differential diagnosis of gangliosidosis.

    Science.gov (United States)

    Mahdieh, Nejat; Mikaeeli, Sahar; Tavasoli, Ali Reza; Rezaei, Zahra; Maleki, Majid; Rabbani, Bahareh

    2018-04-01

    Gangliosidosis is an inherited metabolic disorder causing neurodegeneration and motor regression. Preventive diagnosis is the first choice for the affected families due to lack of straightforward therapy. Genetic studies could confirm the diagnosis and help families for carrier screening and prenatal diagnosis. An update of HEXB gene variants concerning genotype, phenotype and in silico analysis are presented. Panel based next generation sequencing and direct sequencing of four cases were performed to confirm the clinical diagnosis and for reproductive planning. Bioinformatic analyses of the HEXB mutation database were also performed. Direct sequencing of HEXA and HEXB genes showed recurrent homozygous variants at c.509G>A (p.Arg170Gln) and c.850C>T (p.Arg284Ter), respectively. A novel variant at c.416T>A (p.Leu139Gln) was identified in the GLB1 gene. Panel based next generation sequencing was performed for an undiagnosed patient which showed a novel mutation at c.1602C>A (p.Cys534Ter) of HEXB gene. Bioinformatic analysis of the HEXB mutation database showed 97% consistency of in silico genotype analysis with the phenotype. Bioinformatic analysis of the novel variants predicted to be disease causing. In silico structural and functional analysis of the novel variants showed structural effect of HEXB and functional effect of GLB1 variants which would provide fast analysis of novel variants. Panel based studies could be performed for overlapping symptomatic patients. Consequently, genetic testing would help affected families for patients' management, carrier detection, and family planning's. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Genotype-phenotype analysis of a rare type of osteogenesis imperfecta in four Chinese families with WNT1 mutations.

    Science.gov (United States)

    Liu, Yi; Song, Lijie; Ma, Doudou; Lv, Fang; Xu, Xiaojie; Wang, Jianyi; Xia, Weibo; Jiang, Yan; Wang, Ou; Song, Yuwen; Xing, Xiaoping; Asan; Li, Mei

    2016-10-01

    Osteogenesis imperfecta (OI) is a rare inherited disease characterized by increased bone fragility and vulnerability to fractures. Recently, WNT1 is identified as a new candidate gene for OI, here we detect pathogenic mutations in WNT1 and analyze the genotype-phenotype association in four Chinese families with OI. We designed a targeted next generation sequencing panel with known fourteen OI-related genes. We applied the approach to detect pathogenic mutations in OI patients and confirmed the mutations with Sanger sequencing and cosegregation analysis. Clinical fractures, bone mineral density (BMD) and the other clinical manifestations were evaluated. We also observed the effects of bisphosphonates in OI patients with WNT1 mutations. Four compound heterozygous mutations (c.110T>C; c.505 G>T; c. 385G>A; c.506 G>A) in WNT1 were detected in three unrelated families. These four mutations had not been reported yet. A recurrent homozygous mutation (c.506dupG) was identified in the other two families. These patients had moderate to severe OI, white to blue sclera, absence of dentinogenesis imperfecta and no brain malformation. We did not observe clear genotype-phenotype correlation in WNT1 mutated OI patients. Though bisphosphonates increased BMD in WNT1 related OI patients, height did not increase and fracture continued. We reported four novel heterozygous variants and confirmed a previous reported WNT1 mutation in four Chinese families with a clinical diagnosis of OI. Our study expanded OI spectrum and confirmed moderate to severe bone fragility induced by WNT1 defects. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Phenotypic characterization of papaya genotypes to determine powdery mildew resistance

    Directory of Open Access Journals (Sweden)

    Marcelo Vivas

    2017-06-01

    Full Text Available In support of breeding of papaya (Carica papaya, the disease incidence and severity of powdery mildew (Ovulariopsis caricicola were evaluated in papaya genotypes. Two experiments in complete randomized blocks were carried out, one in the field and the other in a greenhouse. In field experiments, the lowest mean disease incidence was observed on the genotypes ‘Costa Rica’ and ‘Baixinho Super’, and the lowest mean disease severity on ‘Caliman M5’, ‘GTF’, ‘SH 11-08’, and ‘JS 11’. In the greenhouse experiment, the genotypes ‘Caliman M5’, ‘Golden’, ‘Kapoho Solo’, ‘Waimanalo’, ‘Mamão Bené’, ‘SH 12-07’, ‘JS 12’, and ‘GTF’ had the lowest mean incidence in at least one evaluation. On the other hand, for severity, the genotypes ‘Diva’, ‘Sunrise Solo 72/12’, ‘Kapoho Solo PA’, ‘Waimanalo’, ‘Maradol’, ‘Maradol GL’, ‘SH 15-04’, ‘FMV, ‘JS 12-4’, ‘SH 12-07’ and ‘Sekati FLM’ had the lowest means. These results indicate these genotypes for a possible use in breeding for reduction of powdery mildew intensity

  4. Glucokinase gene mutations: structural and genotype-phenotype analyses in MODY children from South Italy.

    Directory of Open Access Journals (Sweden)

    Nadia Tinto

    Full Text Available BACKGROUND: Maturity onset diabetes of the young type 2 (or GCK MODY is a genetic form of diabetes mellitus provoked by mutations in the glucokinase gene (GCK. METHODOLOGY/PRINCIPAL FINDINGS: We screened the GCK gene by direct sequencing in 30 patients from South Italy with suspected MODY. The mutation-induced structural alterations in the protein were analyzed by molecular modeling. The patients' biochemical, clinical and anamnestic data were obtained. Mutations were detected in 16/30 patients (53%; 9 of the 12 mutations identified were novel (p.Glu70Asp, p.Phe123Leu, p.Asp132Asn, p.His137Asp, p.Gly162Asp, p.Thr168Ala, p.Arg392Ser, p.Glu290X, p.Gln106_Met107delinsLeu and are in regions involved in structural rearrangements required for catalysis. The prevalence of mutation sites was higher in the small domain (7/12: approximately 59% than in the large (4/12: 33% domain or in the connection (1/12: 8% region of the protein. Mild diabetic phenotypes were detected in almost all patients [mean (SD OGTT = 7.8 mMol/L (1.8] and mean triglyceride levels were lower in mutated than in unmutated GCK patients (p = 0.04. CONCLUSIONS: The prevalence of GCK MODY is high in southern Italy, and the GCK small domain is a hot spot for MODY mutations. Both the severity of the GCK mutation and the genetic background seem to play a relevant role in the GCK MODY phenotype. Indeed, a partial genotype-phenotype correlation was identified in related patients (3 pairs of siblings but not in two unrelated children bearing the same mutation. Thus, the molecular approach allows the physician to confirm the diagnosis and to predict severity of the mutation.

  5. Visual half-field presentations of incongruent color words: effects of gender and handedness.

    Science.gov (United States)

    Franzon, M; Hugdahl, K

    1986-09-01

    Right-handed (dextral) and left-handed (sinistral) males and females (N = 15) were compared for language lateralization in a visual half-field (VHF) incongruent color-words paradigm. The paradigm consists of repeated brief (less than 200 msec) presentations of color-words written in an incongruent color. Presentations are either to the right or to the left of center fixation. The task of the subject is to report the color the word is written in on each trial, ignoring the color-word. Color-bars and congruent color-words were used as control stimuli. Vocal reaction time (VRT) and error frequency were used as dependent measures. The logic behind the paradigm is that incongruent color-words should lead to a greater cognitive conflict when presented in the half-field contralateral to the dominant hemisphere. The results showed significantly longer VRTs in the right half-field for the dextral subjects. Furthermore, significantly more errors were observed in the male dextral group when the incongruent stimuli were presented in the right half-field. There was a similar trend in the data for the sinistral males. No differences between half-fields were observed for the female groups. It is concluded that the present results strengthen previous findings from our laboratory (Hugdahl and Franzon, 1985) that the incongruent color-words paradigm is a useful non-invasive technique for the study of lateralization in the intact brain.

  6. Complete genomes of Hairstreak butterflies, their speciation, and nucleo-mitochondrial incongruence.

    Science.gov (United States)

    Cong, Qian; Shen, Jinhui; Borek, Dominika; Robbins, Robert K; Otwinowski, Zbyszek; Grishin, Nick V

    2016-04-28

    Comparison of complete genomes of closely related species enables research on speciation and how phenotype is determined by genotype. Lepidoptera, an insect order of 150,000 species with diverse phenotypes, is well-suited for such comparative genomics studies if new genomes, which cover additional Lepidoptera families are acquired. We report a 729 Mbp genome assembly of the Calycopis cecrops, the first genome from the family Lycaenidae and the largest available Lepidoptera genome. As detritivore, Calycopis shows expansion in detoxification and digestion enzymes. We further obtained complete genomes of 8 Calycopis specimens: 3 C. cecrops and 5 C. isobeon, including a dry specimen stored in the museum for 30 years. The two species differ subtly in phenotype and cannot be differentiated by mitochondrial DNA. However, nuclear genomes revealed a deep split between them. Genes that can clearly separate the two species (speciation hotspots) mostly pertain to circadian clock, mating behavior, transcription regulation, development and cytoskeleton. The speciation hotspots and their function significantly overlap with those we previously found in Pterourus, suggesting common speciation mechanisms in these butterflies.

  7. Mutation frequency and genotype/phenotype correlation among phenylketonuria patients from Georgia

    Energy Technology Data Exchange (ETDEWEB)

    Woo, S.L.C.; Martinez, D.; Kuozmine, A. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). To determine the molecular basis of PKU in the state of Georgia, thirty-five Georgian PKU patients representing sixty independent alleles were examined by a combination of DGGE and direct sequence analysis. At present, this approach has led to the identification of 55/60 or about 92% of all mutant alleles. The relatively high frequencies of mutations common to the British Isles (R408W, I65T and L348V) are compatible with 1990 census data showing that 34% of the general Georgian population claim Irish, English or Scottish ancestors. Three new mutations, E76A (1/60), R241L (2/60), and R400R (2/60), were also detected in this study. Although the nucleotide substitution in codon 400 (AGG{r_arrow}CGG) did not change the amino acid sequence, it was the only base change detected in a scan of all 13 exons of two independent alleles. Since codon 400 is split between exons 11 and 12, this change may exert some effect on splicing, as has previously been seen in the PAH gene for the silent mutation Q304Q and the nonsense mutation Y356X, each of which effect codons immediately adjacent to splicing signals. This hypothesis remains to be tested by expression analysis or studies of ectopic transcripts. The remaining 19 characterized alleles contained one of 15 previously identified mutations. Twenty-five of the thirty non-related patients examined in this study were completely genotyped, and there was a strong correlation between mutant PAH genotype, PAH activity predicted from in vitro expression studies where known, and PKU or HPA phenotype. For mutations not yet studied by expression analysis, this correlation suggests that L213P, R241L, Y277D may drastically reduce residual PAH activity while F39L and E76A may retain significant amounts of PAH activity.

  8. Genotyping of Kell, Duffy, Kidd and RHD in patients with b Thalassemia

    Directory of Open Access Journals (Sweden)

    Castilho Lilian

    2000-01-01

    Full Text Available Determination of Rh, Kell, Duffy and Kidd phenotypes in addition to ABO is used to prevent the alloimmunization to red blood cells (RBCs antigens and as part of the antibody identification process in patients with beta Thalassemia. However, phenotyping in these patients can be time consuming and difficult to interpret. In these situations, it would be valuable to have an alternative to hemagglutination tests to determine the patient's antigen profile. We used PCR-RFLP to genotype such patients. DNA was prepared from 50 patients with beta Thalassemia who had been phenotyped by routine hemagglutination, and tested for Kell, Kidd, Duffy/GATA mutation by PCR-RFLP. RHD/non-D was analysed by PCR product size associated to RHD gene sequence in intron 4 and exon 10/3'UTR. The genotyping assays were performed without knowledge of phenotype results. For RHD/non-D, 47 were RhD+ and RHD+/RHCE+, and 3 were RhD- and RHD-/RHCE+. For Kell, 48 kk were K2K2 and 2 Kk were K1K2. For Duffy, of 44 samples that had normal GATA box, 8 Fy(a+b- were FYA/FYA, 15 Fy(a+b+ were FYB/FYB, and 19 Fy(a+b+ were FYA/FYB; of the other 4 samples 3 were FYA/FYB and heterozygous GATA mutation, and 1 Fy(a-b- was FYB/FYB, homozygous GATA mutation. Two samples phenotyped as Fy(a+b- that had normal GATA , presented the 265T/298A mutations and two samples phenotyped as Fy(a-b+ were genotyped was FYA/FYB.. For Kidd , 15 Jk(a+b were JKA/JKA, 12 Jk(a-b+ were JKB/JKB, and 20 Jk(a+b+ were JKA/JKB. Three samples phenotyped as JK(a+b+ were genotyped as JKB/JKB. Genotype is more accurate than phenotype for determination of blood groups in polytransfused patients with betaThalassemia. Genotyping in these patients can be helpful to select antigen-negative RBCs for transfusion.

  9. Phenotype, genotype, and antibiotic susceptibility of Swedish and Thai oral isolates of Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Susanne Blomqvist

    2015-04-01

    Full Text Available Objective: The present study investigated phenotypes, virulence genotypes, and antibiotic susceptibility of oral Staphylococcus aureus strains in order to get more information on whether oral infections with this bacterium are associated with certain subtypes or related to an over-growth of the S. aureus variants normally found in the oral cavity of healthy carriers. Materials and methods: A total number of 157 S. aureus strains were investigated. Sixty-two strains were isolated from Swedish adults with oral infections, 25 strains were from saliva of healthy Swedish dental students, and 45 strains were from tongue scrapings of HIV-positive subjects in Thailand, and 25 Thai strains from non-HIV controls. The isolates were tested for coagulase, nitrate, arginine, and hemolysin, and for the presence of the virulence genes: hlg, clfA, can, sdrC, sdrD, sdrE, map/eap (adhesins and sea, seb, sec, tst, eta, etb, pvl (toxins. MIC90 and MIC50 were determined by E-test against penicillin V, oxacillin, amoxicillin, clindamycin, vancomycin, fusidic acid, and cefoxitin. Results: While the hemolytic phenotype was significantly (p<0.001 more common among the Thai strains compared to Swedish strains, the virulence genes were found in a similar frequency in the S. aureus strains isolated from all four subject groups. The Panton-Valentine leukocidin (PVL genotype was found in 73–100% of the strains. More than 10% of the strains from Swedish oral infections and from Thai HIV-positives showed low antibiotic susceptibility, most commonly for clindamycin. Only three methicillin-resistant S. aureus (MRSA strains were identified, two from oral infections and one from a Thai HIV patient. Conclusions: S. aureus is occasionally occurring in the oral cavity in both health and disease in Sweden and Thailand. It is therefore most likely that S. aureus in opportunistic oral infections originate from the oral microbiota. S. aureus should be considered in case of oral

  10. Phenotypic plasticity, costs of phenotypes, and costs of plasticity

    DEFF Research Database (Denmark)

    Callahan, Hilary S; Maughan, Heather; Steiner, Uli

    2008-01-01

    Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

  11. Genetic variability in cowpea (Vigna unguiculata (L.) Walp.) genotypes

    African Journals Online (AJOL)

    sive protein in human diets with grains containing about. 23–25% protein ... Keywords: heritability, phenotype, principal component analysis, variance. Introduction .... be due to genotype, environment, and the interaction of genotype and ...

  12. Comparative Phenotypic and Molecular Genetic Profiling of Wild Lactococcus lactis subsp. lactis Strains of the L. lactis subsp. lactis and L. lactis subsp. cremoris Genotypes, Isolated from Starter-Free Cheeses Made of Raw Milk▿

    Science.gov (United States)

    Fernández, Elena; Alegría, Ángel; Delgado, Susana; Martín, M. Cruz; Mayo, Baltasar

    2011-01-01

    Twenty Lactococcus lactis strains with an L. lactis subsp. lactis phenotype isolated from five traditional cheeses made of raw milk with no added starters belonging to the L. lactis subsp. lactis and L. lactis subsp. cremoris genotypes (lactis and cremoris genotypes, respectively; 10 strains each) were subjected to a series of phenotypic and genetic typing methods, with the aims of determining their phylogenetic relationships and suitability as starters. Pulsed-field gel electrophoresis (PFGE) analysis of intact genomes digested with SalI and SmaI proved that all strains were different except for three isolates of the cremoris genotype, which showed identical PFGE profiles. Multilocus sequence typing (MLST) analysis using internal sequences of seven loci (namely, atpA, rpoA, pheS, pepN, bcaT, pepX, and 16S rRNA gene) revealed considerable intergenotype nucleotide polymorphism, although deduced amino acid changes were scarce. Analysis of the MLST data for the present strains and others from other dairy and nondairy sources showed that all of them clustered into the cremoris or lactis genotype group, by using both independent and combined gene sequences. These two groups of strains also showed distinctive carbohydrate fermentation and enzyme activity profiles, with the strains in the cremoris group showing broader profiles. However, the profiles of resistance/susceptibility to 16 antibiotics were very similar, showing no atypical resistance, except for tetracycline resistance in three identical cremoris genotype isolates. The numbers and concentrations of volatile compounds produced in milk by the strains belonging to these two groups were clearly different, with the cremoris genotype strains producing higher concentrations of more branched-chain, derived compounds. Together, the present results support the idea that the lactis and cremoris genotypes of phenotypic Lactococcus lactis subsp. lactis actually represent true subspecies. Some strains of the two subspecies

  13. Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?

    Science.gov (United States)

    Dzialanski, Zbigniew; Barany, Michael; Engfeldt, Peter; Magnuson, Anders; Olsson, Lovisa A; Nilsson, Torbjörn K

    2016-02-01

    According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist. To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test. A retrospective study using an oral lactose load test (n=487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n=274). Mean hydrogen levels in exhaled air at 120min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups. Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  14. Introduction to a special issue on genotype by environment interaction

    Science.gov (United States)

    Expression of a phenotype is a function of the genotype, the environment, and the differential sensitivity of certain genotypes to different environments, also known as genotype by environment (G × E) interaction. This special issue of Crop Science includes a collection of manuscripts that reviews t...

  15. The GP problem: quantifying gene-to-phenotype relationships.

    Science.gov (United States)

    Cooper, Mark; Chapman, Scott C; Podlich, Dean W; Hammer, Graeme L

    2002-01-01

    In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes.

  16. Tasting the Smell: scent Experts' and Laymen's Evaluation of Product (In)congruity

    OpenAIRE

    Adams, Carmen; Doucé, Lieve; Janssens, Wim; Vanrie, Jan; Petermans, Ann

    2013-01-01

    This research studies the effect of scent expertise on product and taste evaluations in the presence of an ambient scent (in)congruent with the products. In order to gain insight into this effect, we also examine the relationship of scent expertise with odour identification and odour awareness. An experiment with 93 participants revealed that (novice) scent experts evaluated the product incongruent with the ambient scent more negatively than laymen, supporting our assumption that (novice) sce...

  17. Norming the odd: creation, norming, and validation of a stimulus set for the study of incongruities across music and language.

    Science.gov (United States)

    Featherstone, Cara R; Waterman, Mitch G; Morrison, Catriona M

    2012-03-01

    Research into similarities between music and language processing is currently experiencing a strong renewed interest. Recent methodological advances have led to neuroimaging studies presenting striking similarities between neural patterns associated with the processing of music and language--notably, in the study of participants' responses to elements that are incongruous with their musical or linguistic context. Responding to a call for greater systematicity by leading researchers in the field of music and language psychology, this article describes the creation, selection, and validation of a set of auditory stimuli in which both congruence and resolution were manipulated in equivalent ways across harmony, rhythm, semantics, and syntax. Three conditions were created by changing the contexts preceding and following musical and linguistic incongruities originally used for effect by authors and composers: Stimuli in the incongruous-resolved condition reproduced the original incongruity and resolution into the same context; stimuli in the incongruous-unresolved condition reproduced the incongruity but continued postincongruity with a new context dictated by the incongruity; and stimuli in the congruous condition presented the same element of interest, but the entire context was adapted to match it so that it was no longer incongruous. The manipulations described in this article rendered unrecognizable the original incongruities from which the stimuli were adapted, while maintaining ecological validity. The norming procedure and validation study resulted in a significant increase in perceived oddity from congruous to incongruous-resolved and from incongruous-resolved to incongruous-unresolved in all four components of music and language, making this set of stimuli a theoretically grounded and empirically validated resource for this growing area of research.

  18. The Impact of Five VDR Polymorphisms on Multiple Sclerosis Risk and Progression: a Case-Control and Genotype-Phenotype Study.

    Science.gov (United States)

    Křenek, Pavel; Benešová, Yvonne; Bienertová-Vašků, Julie; Vašků, Anna

    2018-04-01

    Vitamin D receptor polymorphisms have been the target of many studies focusing on multiple sclerosis. However, previously reported results have been inconclusive. The objective of this study was to investigate the association between five vitamin D receptor polymorphisms (EcoRV, FokI, ApaI, TaqI, and BsmI) and multiple sclerosis susceptibility and its course. The study was carried out as a case-control and genotype-phenotype study, consisted of 296 Czech multiple sclerosis patients and 135 healthy controls. Genotyping was carried out using polymerase chain reaction and restriction analysis. In multiple sclerosis men, allele and/or genotype distributions differed in EcoRV, TaqI, BsmI, and ApaI polymorphisms as compared to controls (EcoRV, p a = 0.02; Taq, p g = 0.02, p a = 0.02; BsmI, p g = 0.02, p a = 0.04; ApaI, p g = 0.008, p a = 0.005). In multiple sclerosis women, differences in the frequency of alleles and genotypes were found to be significant in ApaI (controls vs multiple sclerosis women: p g = 0.01, p a = 0.05). Conclusive results were observed between multiple sclerosis women in the case of EcoRV [differences in Expanded Disability Status Scale (p = 0.05); CT genotype was found to increase the risk of primary progressive multiple sclerosis 5.5 times (CT vs CC+TT p corr = 0.01, sensitivity 0.833, specificity 0.525, power test 0.823)] and FokI [borderline difference in Multiple Sclerosis Severity Score (p = 0.05)]. Our results indicate that the distribution of investigated vitamin D receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and progression in the Czech population. The association between disease risk and polymorphisms was found to be stronger in men. The association of disease progression with polymorphisms was observed only in women.

  19. Sammenhaenge mellem patientens genotype og sygdommens forløb ved arvelige kraeftsygdomme

    DEFF Research Database (Denmark)

    Bisgaard, Marie Luise

    2006-01-01

    largest hereditary cancer groups, namely hereditary colorectal cancer and hereditary breast (and ovarian) cancer. It is concluded that knowledge about genotype-phenotype correlations is essential in the cancer genetic clinic; otherwise, the patient tends to base decisions on personal experience......The majority of hereditary cancers demonstrate extended variation of phenotype, not only between families, but also within a particular family, who supposedly have inherited the same pathogenic mutation. The present paper reviews genotype-phenotype correlations with examples mainly from the two...

  20. From genotype to phenotype; clinical variability in Lesch-Nyhan disease. The role of epigenetics.

    Science.gov (United States)

    Trigueros Genao, M; Torres, R J

    2014-11-01

    Lesch-Nyhan disease is a rare genetic disease characterized by a deficiency in the function of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Patients affected by this disease experience hyperuricemia, motor disorders, mental retardation and, in the most severe cases, self-mutilation. Its clinical manifestations depend on the enzymatic activity of HGPRT, which is classically linked to the type of alteration in the HGPRT gene. More than 400 mutations of this gene have been found. At present, one of the controversial aspects of the disease is the relationship between the genotype and phenotype; cases have been described lacking a mutation, such as the patient presented in this article, as well as families who despite sharing the same genetic defect show disorders with differing severity. Epigenetic processes, which modify the genetic expression without changing the sequence of the deoxyribonucleic acid (DNA), could explain the clinical variability observed in this disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  1. Similar predictions of etravirine sensitivity regardless of genotypic testing method used: comparison of available scoring systems.

    Science.gov (United States)

    Vingerhoets, Johan; Nijs, Steven; Tambuyzer, Lotke; Hoogstoel, Annemie; Anderson, David; Picchio, Gaston

    2012-01-01

    The aims of this study were to compare various genotypic scoring systems commonly used to predict virological outcome to etravirine, and examine their concordance with etravirine phenotypic susceptibility. Six etravirine genotypic scoring systems were assessed: Tibotec 2010 (based on 20 mutations; TBT 20), Monogram, Stanford HIVdb, ANRS, Rega (based on 37, 30, 27 and 49 mutations, respectively) and virco(®)TYPE HIV-1 (predicted fold change based on genotype). Samples from treatment-experienced patients who participated in the DUET trials and with both genotypic and phenotypic data (n=403) were assessed using each scoring system. Results were retrospectively correlated with virological response in DUET. κ coefficients were calculated to estimate the degree of correlation between the different scoring systems. Correlation between the five scoring systems and the TBT 20 system was approximately 90%. Virological response by etravirine susceptibility was comparable regardless of which scoring system was utilized, with 70-74% of DUET patients determined as susceptible to etravirine by the different scoring systems achieving plasma viral load <50 HIV-1 RNA copies/ml. In samples classed as phenotypically susceptible to etravirine (fold change in 50% effective concentration ≤3), correlations with genotypic score were consistently high across scoring systems (≥70%). In general, the etravirine genotypic scoring systems produced similar results, and genotype-phenotype concordance was high. As such, phenotypic interpretations, and in their absence all genotypic scoring systems investigated, may be used to reliably predict the activity of etravirine.

  2. Evaluation of lansoprazole as a probe for assessing cytochrome P450 2C19 activity and genotype-phenotype correlation in childhood.

    Science.gov (United States)

    Gumus, Ersin; Karaca, Ozgur; Babaoglu, Melih O; Baysoy, Gökhan; Balamtekin, Necati; Demir, Hulya; Uslu, Nuray; Bozkurt, Atilla; Yuce, Aysel; Yasar, Umit

    2012-05-01

    Lansoprazole, a cytochrome P450 2C19 (CYP2C19) substrate, has been widely used in children to manage acid-related diseases. CYP2C19 exhibits marked genetic polymorphisms, and distribution of these polymorphisms varies among different ethnic groups. There is limited data regarding the use of probe drugs for determining CYP2C19 activity in children. The aim of this study was to evaluate lansoprazole as an in vivo phenotyping probe for assessing CYP2C19 activity in children. The CYP2C19*2, *3, and *17 variants were determined in 244 children. Three hours after a single oral dose of lansoprazole (n = 94) or omeprazole (n = 19), plasma lansoprazole and 5-hydroxy lansoprazole or omeprazole and 5-hydroxy omeprazole concentrations were analyzed by high-performance liquid chromatography. The CYP2C19*17 was the most frequent variant allele (24.4%). The group of patients with CYP2C19*17*17 genotype had a 70% lower (p lansoprazole plasma concentration compared with the CYP2C19*1*1 genotype group, whereas the CYP2C19*2*2 group had 6.9-fold higher (p lansoprazole plasma concentration. Lansoprazole metabolic ratios (lansoprazole/5-hydroxy-lansoprazole) were found to be significantly lower in the *17*17 [mean ± standard deviation (SD); 2.8 ± 2.1] group and higher in the *2*2 group (63.5 ± 12.2) compared with that of the *1*1 genotype group (6.1 ± 4.5). According to our results from a Turkish pediatric population, lansoprazole is a suitable probe drug for phenotyping CYP2C19. The CYP2C19*2 and *17 variants should be taken into consideration in predicting the clinical outcome of therapy with lansoprazole in the pediatric population.

  3. Genotype-Phenotype Aspects of Type 2 Long QT Syndrome

    NARCIS (Netherlands)

    Shimizu, Wataru; Moss, Arthur J.; Wilde, Arthur A. M.; Towbin, Jeffrey A.; Ackerman, Michael J.; January, Craig T.; Tester, David J.; Zareba, Wojciech; Robinson, Jennifer L.; Qi, Ming; Vincent, G. Michael; Kaufman, Elizabeth S.; Hofman, Nynke; Noda, Takashi; Kamakura, Shiro; Miyamoto, Yoshihiro; Shah, Samit; Amin, Vinit; Goldenberg, Ilan; Andrews, Mark L.; McNitt, Scott

    2009-01-01

    Objectives The purpose of this study was to investigate the effect of location, coding type, and topology of KCNH2(hERG) mutations on clinical phenotype in type 2 long QT syndrome (LQTS). Background Previous studies were limited by population size in their ability to examine phenotypic effect of

  4. Congruent and Incongruent Cues in Highly Familiar Audiovisual Action Sequences: An ERP Study

    Directory of Open Access Journals (Sweden)

    SM Wuerger

    2012-07-01

    Full Text Available In a previous fMRI study we found significant differences in BOLD responses for congruent and incongruent semantic audio-visual action sequences (whole-body actions and speech actions in bilateral pSTS, left SMA, left IFG, and IPL (Meyer, Greenlee, & Wuerger, JOCN, 2011. Here, we present results from a 128-channel ERP study that examined the time-course of these interactions using a one-back task. ERPs in response to congruent and incongruent audio-visual actions were compared to identify regions and latencies of differences. Responses to congruent and incongruent stimuli differed between 240–280 ms, 340–420 ms, and 460–660 ms after stimulus onset. A dipole analysis revealed that the difference around 250 ms can be partly explained by a modulation of sources in the vicinity of the superior temporal area, while the responses after 400 ms are consistent with sources in inferior frontal areas. Our results are in line with a model that postulates early recognition of congruent audiovisual actions in the pSTS, perhaps as a sensory memory buffer, and a later role of the IFG, perhaps in a generative capacity, in reconciling incongruent signals.

  5. The role of the amygdala in incongruity resolution: the case of humor comprehension.

    Science.gov (United States)

    Nakamura, Tagiru; Matsui, Tomoko; Utsumi, Akira; Yamazaki, Mika; Makita, Kai; Harada, Tokiko; Tanabe, Hiroki C; Sadato, Norihiro

    2017-08-21

    A dominant theory of humor comprehension suggests that people understand humor by first perceiving some incongruity in an expression and then resolving it. This is called "the incongruity-resolution theory." Experimental studies have investigated the neural basis of humor comprehension, and multiple neural substrates have been proposed; however, the specific substrate for incongruity resolution is still unknown. The reason may be that the resolution phase, despite its importance in humor comprehension, has not been successfully distinguished from the perception phase because both phases occur almost simultaneously. To reveal the substrate, we conducted a functional magnetic resonance study using 51 healthy participants. We used a humor-producing frame of "Given A, I'd say B, because C" so as to focus on the resolution phase independently by suspending humor processing just after the perception phase. This frame allowed us to separate the two phases. Based on our results, incongruity resolution evoked positive emotion and activated the left amygdala, which is known to be related to positive emotion. On the basis of these findings, we argue that the amygdala plays an important role in humor comprehension, considering its functional role in emotional evaluation, particularly the relevance detection for incoming stimuli.

  6. Phenotypic and genotypic characterization of Thai isolates of Plasmodium falciparum after an artemisinin resistance containment project.

    Science.gov (United States)

    Thita, Thunyapit; Jadsri, Pimrat; Thamkhantho, Jarupatr; Ruang-Areerate, Toon; Suwandittakul, Nantana; Sitthichot, Naruemon; Mahotorn, Kittiya; Tan-Ariya, Peerapan; Mungthin, Mathirut

    2018-05-15

    In Thailand, artemisinin-based combination therapy (ACT) has been used to treat uncomplicated falciparum malaria since 1995. Unfortunately, artemisinin resistance has been reported from Thailand and other Southeast Asian countries since 2003. Malarone ® , a combination of atovaquone-proguanil (ATQ-PG), has been used to cease artemisinin pressure in some areas along Thai-Cambodia border, as part of an artemisinin resistance containment project since 2009. This study aimed to determine genotypes and phenotypes of Plasmodium falciparum isolates collected from the Thai-Cambodia border after the artemisinin resistance containment project compared with those collected before. One hundred and nine of P. falciparum isolates collected from Thai-Cambodia border from Chanthaburi and Trat provinces during 1988-2016 were used in this study. Of these, 58 isolates were collected after the containment. These parasite isolates were characterized for in vitro antimalarial sensitivities including chloroquine (CQ), quinine (QN), mefloquine (MQ), piperaquine (PPQ), artesunate (AS), dihydroartemisinin (DHA), ATQ and PG and genetic markers for drug resistance including the Kelch13 (k13), Plasmodium falciparum chloroquine resistance transporter (pfcrt), P. falciparum multidrug resistance 1 (pfmdr1) and cytochrome b (cytb) genes. Mean CQ, QN, MQ, PPQ and AS IC 50 s of the parasite isolates collected from 2009 to 2016 exhibited significantly higher than those of parasites collected before 2009. Approximately 57% exhibited in vitro MQ resistance. Approximately 94% of the isolates collected from 2009 to 2016 contained the pfmdr1 184F allele. Mutations of the k13 gene were detected in approximately 90% of the parasites collected from 2009 to 2016 which were significantly higher than the parasite isolates collected before. No ATQ-resistant genotype and phenotype of P. falciparum were found among the isolates collected after the containment project. Although the containment project had been

  7. NF1 Neuronal Genotype Phenotype Relationships

    Science.gov (United States)

    2017-06-01

    interesting results from the Drosophila functional assays, at present we have decided to focus our attention on selected NF1 patient missense mutations...complexity of NF1 disease phenotypes in different tissues, age and sex dependency of symptoms, impact of environmental factors and genetic heterogeneity...suggesting the role of modifier genes [12]. This work aims to shed light on this issue by studying the functional consequences of selected NF1

  8. Genotype and Phenotype of Echinococcus granulosus Derived from Wild Sheep (Ovis orientalis) in Iran.

    Science.gov (United States)

    Eslami, Ali; Meshgi, Behnam; Jalousian, Fatemeh; Rahmani, Shima; Salari, Mohammad Ali

    2016-02-01

    The aim of the present study is to determine the characteristics of genotype and phenotype of Echinococcus granulosus derived from wild sheep and to compare them with the strains of E. granulosus sensu stricto (sheep-dog) and E. granulosus camel strain (camel-dog) in Iran. In Khojir National Park, near Tehran, Iran, a fertile hydatid cyst was recently found in the liver of a dead wild sheep (Ovis orientalis). The number of protoscolices (n=6,000) proved enough for an experimental infection in a dog. The characteristics of large and small hooks of metacestode were statistically determined as the sensu stricto strain but not the camel strain (P=0.5). To determine E. granulosus genotype, 20 adult worms of this type were collected from the infected dog. The second internal transcribed spacer (ITS2) of the nuclear ribosomal DNA (rDNA) and cytochrome c oxidase 1 subunit (COX1) of the mitochondrial DNA were amplified from individual adult worm by PCR. Subsequently, the PCR product was sequenced by Sanger method. The lengths of ITS2 and COX1 sequences were 378 and 857 bp, respectively, for all the sequenced samples. The amplified DNA sequences from both ribosomal and mitochondrial genes were highly similar (99% and 98%, respectively) to that of the ovine strain in the GenBank database. The results of the present study indicate that the morpho-molecular features and characteristics of E. granulosus in the Iranian wild sheep are the same as those of the sheep-dog E. granulosus sensu stricto strain.

  9. Cow genotyping strategies for genomic selection in a small dairy cattle population.

    Science.gov (United States)

    Jenko, J; Wiggans, G R; Cooper, T A; Eaglen, S A E; Luff, W G de L; Bichard, M; Pong-Wong, R; Woolliams, J A

    2017-01-01

    This study compares how different cow genotyping strategies increase the accuracy of genomic estimated breeding values (EBV) in dairy cattle breeds with low numbers. In these breeds, few sires have progeny records, and genotyping cows can improve the accuracy of genomic EBV. The Guernsey breed is a small dairy cattle breed with approximately 14,000 recorded individuals worldwide. Predictions of phenotypes of milk yield, fat yield, protein yield, and calving interval were made for Guernsey cows from England and Guernsey Island using genomic EBV, with training sets including 197 de-regressed proofs of genotyped bulls, with cows selected from among 1,440 genotyped cows using different genotyping strategies. Accuracies of predictions were tested using 10-fold cross-validation among the cows. Genomic EBV were predicted using 4 different methods: (1) pedigree BLUP, (2) genomic BLUP using only bulls, (3) univariate genomic BLUP using bulls and cows, and (4) bivariate genomic BLUP. Genotyping cows with phenotypes and using their data for the prediction of single nucleotide polymorphism effects increased the correlation between genomic EBV and phenotypes compared with using only bulls by 0.163±0.022 for milk yield, 0.111±0.021 for fat yield, and 0.113±0.018 for protein yield; a decrease of 0.014±0.010 for calving interval from a low base was the only exception. Genetic correlation between phenotypes from bulls and cows were approximately 0.6 for all yield traits and significantly different from 1. Only a very small change occurred in correlation between genomic EBV and phenotypes when using the bivariate model. It was always better to genotype all the cows, but when only half of the cows were genotyped, a divergent selection strategy was better compared with the random or directional selection approach. Divergent selection of 30% of the cows remained superior for the yield traits in 8 of 10 folds. Copyright © 2017 American Dairy Science Association. Published by

  10. How long-lasting is the post-conflict slowing after incongruent trials? Evidence from the Stroop, Simon, and flanker tasks.

    Science.gov (United States)

    Rey-Mermet, Alodie; Meier, Beat

    2017-10-01

    The purpose of the present study was to determine how long-lasting the post-conflict slowing following incongruent stimuli is. In previous research, incongruent stimuli have been used to induce a conflict because they have relevant features for two different response alternatives. So far, the post-conflict slowing following incongruent stimuli has mainly been assessed up to one trial. In the first two experiments, we assessed the persistence of the post-conflict slowing across several trials. To this end, we presented a few incongruent stimuli among non-conflict stimuli. The results showed a consistent slowing for the first few trials immediately following the incongruent trials. In addition, a sporadic slowing was still found on later trials. In two subsequent experiments, we investigated to what extent the infrequency of incongruent trials - rather than their conflict - induced this slowing. To determine this, we used the same design as in the first two experiments, but we presented non-conflict stimuli as infrequent stimuli. The results showed a slowing on one subsequent trial, ruling out the possibility that the post-conflict slowing following incongruent trials was only caused by infrequency. Together, the findings of the present study indicate that the conflict induced by incongruent trials can have a longer lasting impact on subsequent trials than previously thought.

  11. Electroretinographic genotype-phenotype correlations for mouse and man at the dmd/DMD locus

    Energy Technology Data Exchange (ETDEWEB)

    Millers, D.M.; Weleber, R.G.; Woodward, W.R. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1994-09-01

    Reduced or absent b-waves in the dark-adapted electroretinogram (ERG) of Duchenne and Becker muscular dystrophy (DMD/BMD) patients led to the identification of dystrophin in human retina and the proposal that it plays a role in retinal electrophysiology. Study of a large group of Duchenne and Becker muscular dystrophy males to determine their ocular characteristics indicated that there were position-specific effects of deletions, with 3{prime} defects associated with severe electroretinographic changes, whereas some 5{prime} patients demonstrated less severe, or even normal, ERGs. We studied the mdx mouse, a model with X-linked muscular dystrophy and defective full-length dystrophin, which failed to show any ERG abnormalities. Given the presence of alternate isoforms of dystrophin in retina, and the 5{prime} deletion DMD/BMD patients with normal ERGs, we studied mouse models with differing dystrophin mutations (mdx{sup Cv3}, mdx{sup Cv5}) to determine the usefulness of alternate strains as models for the visual effects of dystropin. Abnormal ERGs similar to those seen in DMD/BMS patients exist in the mdx{sup Cv3} strain of muscular dystrophy mice. Normal ERGs were found the mdx{sup Cv5} strain. The mutations in the mdx and mdx{sup Cv5} mice have been mapped to the 5{prime} end of the dmd gene, while the mutation in the mdx{sup Cv3} mouse is in the 3{prime} end. Thus, there are position effects of the gene defect on the ERG phenotype that are conserved in the mouse. Such genotype-phenotype correlations may reflect differential expression of shorter isoforms of dystrophin.

  12. Utilizing intraspecific variation in phenotypic plasticity to bolster agricultural and forest productivity under climate change.

    Science.gov (United States)

    Aspinwall, Michael J; Loik, Michael E; Resco de Dios, Victor; Tjoelker, Mark G; Payton, Paxton R; Tissue, David T

    2015-09-01

    Climate change threatens the ability of agriculture and forestry to meet growing global demands for food, fibre and wood products. Information gathered from genotype-by-environment interactions (G × E), which demonstrate intraspecific variation in phenotypic plasticity (the ability of a genotype to alter its phenotype in response to environmental change), may prove important for bolstering agricultural and forest productivity under climate change. Nonetheless, very few studies have explicitly quantified genotype plasticity-productivity relationships in agriculture or forestry. Here, we conceptualize the importance of intraspecific variation in agricultural and forest species plasticity, and discuss the physiological and genetic factors contributing to intraspecific variation in phenotypic plasticity. Our discussion highlights the need for an integrated understanding of the mechanisms of G × E, more extensive assessments of genotypic responses to climate change under field conditions, and explicit testing of genotype plasticity-productivity relationships. Ultimately, further investigation of intraspecific variation in phenotypic plasticity in agriculture and forestry may prove important for identifying genotypes capable of increasing or sustaining productivity under more extreme climatic conditions. © 2014 John Wiley & Sons Ltd.

  13. Novel information theory-based measures for quantifying incongruence among phylogenetic trees.

    Science.gov (United States)

    Salichos, Leonidas; Stamatakis, Alexandros; Rokas, Antonis

    2014-05-01

    Phylogenies inferred from different data matrices often conflict with each other necessitating the development of measures that quantify this incongruence. Here, we introduce novel measures that use information theory to quantify the degree of conflict or incongruence among all nontrivial bipartitions present in a set of trees. The first measure, internode certainty (IC), calculates the degree of certainty for a given internode by considering the frequency of the bipartition defined by the internode (internal branch) in a given set of trees jointly with that of the most prevalent conflicting bipartition in the same tree set. The second measure, IC All (ICA), calculates the degree of certainty for a given internode by considering the frequency of the bipartition defined by the internode in a given set of trees in conjunction with that of all conflicting bipartitions in the same underlying tree set. Finally, the tree certainty (TC) and TC All (TCA) measures are the sum of IC and ICA values across all internodes of a phylogeny, respectively. IC, ICA, TC, and TCA can be calculated from different types of data that contain nontrivial bipartitions, including from bootstrap replicate trees to gene trees or individual characters. Given a set of phylogenetic trees, the IC and ICA values of a given internode reflect its specific degree of incongruence, and the TC and TCA values describe the global degree of incongruence between trees in the set. All four measures are implemented and freely available in version 8.0.0 and subsequent versions of the widely used program RAxML.

  14. Characterization of a Wild, Novel Nisin A-Producing Lactococcus Strain with an L. lactis subsp. cremoris Genotype and an L. lactis subsp. lactis Phenotype, Isolated from Greek Raw Milk

    Science.gov (United States)

    Parapouli, Maria; Delbès-Paus, Céline; Kakouri, Athanasia; Koukkou, Anna-Irini; Montel, Marie-Christine

    2013-01-01

    Several molecular taxonomic studies have revealed that many natural (wild) Lactococcus lactis strains of dairy origin which are phenotypically representative of the L. lactis subspecies lactis cluster genotypically within subspecies cremoris and vice versa. Recently, we isolated two wild nisin-producing (Nis+) L. lactis strains, M78 and M104, of the lactis phenotype from Greek raw milk (J. Samelis, A. Lianou, A. Kakouri, C. Delbès, I. Rogelj, B. B. Matijašic, and M. C. Montel, J. Food Prot. 72:783–790, 2009); strain M78 possess a novel nisin A sequence (GenBank accession number HM219853). In this study, the actual subspecies identity of M78 and M104 isolates was elucidated, using 16S rRNA and acmA (encoding lactococcal N-acetylmuramidase) gene and histidine biosynthesis operon polymorphisms and 16S rRNA and ldh (encoding lactate dehydrogenase) gene phylogenies. Except the acmA gene analysis, molecular tools revealed that isolates M78 and M104 clustered with strains of the cremoris genotype, including the LMG 6897T strain, while they were distant from strains of the lactis genotype, including the LMG 6890T strain. The two wild isolates had identical repetitive sequence-based PCR (rep-PCR), randomly amplified polymorphic DNA (RAPD), plasmid, and whole-cell protein profiles and shared high 16S rRNA (99.9%) and ldh (100%) gene sequence homologies. In contrast, they exhibited identical sugar fermentation and enzymatic patterns which were similar to those of the subspecies lactis LMG 6890T strain. To our knowledge, this is the first complete identification report on a wild L. lactis subsp. cremoris genotype of the lactis phenotype which is capable of nisin A production and, thus, has strong potential for use as a novel dairy starter and/or protective culture. PMID:23542625

  15. Population structure and genotype-phenotype associations in a collection of oat landraces and historic cultivars

    Directory of Open Access Journals (Sweden)

    Louisa Rosemarie Winkler

    2016-07-01

    Full Text Available Population structure and genetic architecture of phenotypic traits in oat (Avena sativa L. remain relatively under-researched compared to other small grain species. This study explores the historic context of current elite germplasm, including phenotypic and genetic characterization, with a particular focus on identifying under-utilized areas. A diverse panel of cultivated oat accessions was assembled from the USDA National Small Grains Collection to represent a gene pool relatively unaffected by twentieth century breeding activity and unlikely to have been included in recent molecular studies. The panel was genotyped using an oat iSelect 6K beadchip SNP array. The final dataset included 759 unique individuals and 2,715 polymorphic markers. Some population structure was apparent; with the first three principal components accounting for 38.8% of variation and 73% of individuals belonging to one of three clusters. One cluster with high genetic distinctness appears to have been largely overlooked in twentieth century breeding. Classification and phenotype data provided by the Germplasm Resources Information Network were evaluated for their relationship to population structure. Of the structuring variables evaluated, improvement status (cultivar or landrace was relatively unimportant, indicating that landraces and cultivars included in the panel were all sampled from a similar underlying population. Instead, lemma color and region of origin showed the strongest explanatory power. An exploratory association mapping study of the panel using a subset of 2,588 mapped markers generated novel indications of genomic regions associated with awn frequency, kernels per spikelet, lemma color and panicle type. Further results supported previous findings of loci associated with barley yellow dwarf virus tolerance, crown rust (caused by Puccinia coronata f. sp. avenae resistance, days to anthesis and growth habit (winter/spring. In addition, two novel loci were

  16. Phenotypic and genotypic evaluation of 18 Nocardia isolates from human clinical samples in Mexico.

    Science.gov (United States)

    Sánchez-Herrera, K; Sandoval, H; Couble, A; Mouniee, D; Ramírez-Durán, N; Uzcategui de Morillo, M; Serrano, J A; Bergeron, E; Boiron, P; Rodríguez-Nava, V

    2012-03-01

    Mexico has the largest number of clinical cases of actinomycetoma in North and South America. Species originally identified by less specific methods have been recently reclassified as other known species or as new species. To assess, by 16S rRNA gene sequencing and phenotypic methods, the species distribution of 18 human clinical isolates originally identified as N. brasiliensis, some of them isolated between 1947 and 1959 in Mexico City. Clinical isolates came from the Hospital General, "Dr. Manuel Gea Gonzalez", and Instituto Nacional de Diagnóstico y Referencia Epidemiológica (INDRE) in Mexico, D.F. The strains used in this study included 15 clinical strains isolated between 1947 and 1959 that were originally identified as N. brasiliensis and three more strains obtained in 2007 identified as Nocardia spp. The isolates were identified genotypically by sequencing the 16S rRNA gene, and their phenotypic profiles were obtained with the API Coryne(®) system. Antibiotic susceptibility patterns were tested according to the protocol of the Comité de l'antibiogramme de la Société française de microbiologie[4]. According to 16S rRNA gene, sequencing were identified among 18 human clinical isolates as Nocardia farcinica (n=11) and Nocardia brasiliensis (n=7). A high number of the strains were susceptible to the majority of the antibiotics tested. The phenotypic profiles of the strains were quite uniform for N. farcinica and some variability was observed for N. brasiliensis strains. N. farcinica was the most prevalent species identified. Modern methodologies should be applied in clinical laboratories to accurately identify etiological agents. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  17. A preliminary candidate genotype-intermediate phenotype study of satiation and gastric motor function in obesity.

    Science.gov (United States)

    Papathanasopoulos, Athanasios; Camilleri, Michael; Carlson, Paula J; Vella, Adrian; Nord, Sara J Linker; Burton, Duane D; Odunsi, Suwebatu T; Zinsmeister, Alan R

    2010-06-01

    Stomach motility contributes significantly to fullness sensation while eating and cessation of food intake in humans. Genes controlling adrenergic and serotonergic mechanisms (ADRA2A, GNB3, and SLC6A4) affect gastric emptying (GE), volume (GV), and satiation. Fat mass and obesity-associated gene (FTO) is linked with satiety. Our aim was to examine the association of these candidate genes with stomach functions that signal postprandial fullness: GE, GV, and maximum tolerated volume (MTV). These biomarkers constitute a component of the intermediate phenotype of satiation. A total of 62 overweight or obese participants underwent genotyping of the candidate genes, and validated measurements of GE of solids and liquids by scintigraphy, fasting and postprandial change in GV by SPECT (single photon emission computed tomography), and MTV by nutrient drink test. These markers of satiation were compared for 38 genetic variants in ADRA2A, ADR2C, ADRB3, uncoupling protein (UCP)-2 and -3, GNB3, FTO, and SLC6A4 using a recessive model of inheritance. ADRA2A, ADR2C, UCP-3, GNB3, and FTO loci were significantly associated with the intermediate phenotype markers of satiation: ADR2C (Ins-Del322_325) with accelerated GE; GNB3 (rs1047776) with delayed GE; ADRA2A (rs491589 and rs553668) and GNB3 (rs2269355, rs10849527, and rs3759348) with decreased postprandial GV; ADRA2A (rs3750625) and GNB3 (rs4963517 and rs1129649) with increased postprandial GV; UCP-3 (rs1685356) with increased MTV, and FTO (rs9939609) decreased MTV. Genetic susceptibility to postprandial satiation can be identified through intermediate phenotype markers. With independent validation, these markers may guide patient selection of weight-loss therapies directed at gastric motor functions.

  18. Phenotypic and genotypic characterization of Streptococcus uberis isolated from bovine subclinical mastitis in Argentinean dairy farms

    Directory of Open Access Journals (Sweden)

    Mirta C Lasagno

    2011-09-01

    Full Text Available The aim of this study was to investigate the phenotypic and genotypic characteristics of Streptococcus uberis isolated from subclinical mastitis (SCM cases, and to examine the possible association between both characteristics. A total of 32 S. uberis were isolated from 772 quarter milk samples (SCM > 250,000 cells/ml collected from 195 cows selected randomly from 18 dairy farms located in Argentina. The S. uberis strains were characterized phenotypically by the presence of virulence factors as plasminogen activator factor (PAF, hyaluronidase (HYA, capsule (CAP and CAMP factor, and were further characterized genotypically by pulsed-field gel electrophoresis (PFGE. S. uberis strains expressed plasminogen activator factor, hyaluronidase or capsule (65.5 %, 56.3 %, 59.4 %, respectively, but only 25 % of isolates were CAMP factor positive. Thirteen different virulence profiles were identified on the basis of the combination of virulence factors. Eighteen PFGE patterns with 90% of similarity were identified among 32 S. uberis. A great diversity of virulence profiles and PFGE patterns were present among dairy farms. S. uberis strains with the same PFGE pattern showed different virulence profiles. Bovine S. uberis strains causing SCM included in the present study showed heterogeneity in regard to their phenotypic and genotypic characteristics, and the PFGE patterns are not associated with the virulence profiles.Caracterización fenotípica y genotípica de Streptococcus uberis aislados de mastitis bovina subclínica en tambos de Argentina. El objetivo de este estudio fue investigar las características fenotípicas y genotípicas de Streptococcus uberis aislados de casos de mastitis subclínica (MSC y examinar la posible asociación entre ambas características. Un total de 32 cepas de S. uberis fueron aisladas de 772 muestras de leche de cuartos mamarios (MSC > 25 0000 células/ml colectadas de 195 vacas seleccionadas al azar pertenecientes a 18 tambos

  19. Genotypes and clinical phenotypes in children with cytochrome-c oxidase deficiency.

    Science.gov (United States)

    Darin, N; Moslemi, A-R; Lebon, S; Rustin, P; Holme, E; Oldfors, A; Tulinius, M

    2003-12-01

    Cytochrome c oxidase (COX) deficiency has been associated with a wide spectrum of clinical features and may be caused by mutations in different genes of both the mitochondrial and the nuclear DNA. In an attempt to correlate the clinical phenotype with the genotype in 16 childhood cases, mtDNA was analysed for deletion, depletion, and mutations in the three genes encoding COX subunits and the 22 tRNA genes. Furthermore, nuclear DNA was analysed for mutations in the SURF1, SCO2, COX10, and COX17 genes and cases with mtDNA depletion were analysed for mutations in the TK2 gene. SURF1-mutations were identified in three out of four cases with Leigh syndrome while a mutation in the mitochondrial tRNA (trp) gene was identified in the fourth. One case with mtDNA depletion had mutations in the TK2 gene. In two cases with leukoencephalopathy, one case with encephalopathy, five cases with fatal infantile myopathy and cardiomyopathy, two cases with benign infantile myopathy, and one case with mtDNA depletion, no mutations were identified. We conclude that COX deficiency in childhood should be suspected in a wide range of clinical settings and although an increasing number of genetic defects have been identified, the underlying mutations remain unclear in the majority of the cases.

  20. Network-based analysis of genotype-phenotype correlations between different inheritance modes.

    Science.gov (United States)

    Hao, Dapeng; Li, Chuanxing; Zhang, Shaojun; Lu, Jianping; Jiang, Yongshuai; Wang, Shiyuan; Zhou, Meng

    2014-11-15

    Recent studies on human disease have revealed that aberrant interaction between proteins probably underlies a substantial number of human genetic diseases. This suggests a need to investigate disease inheritance mode using interaction, and based on which to refresh our conceptual understanding of a series of properties regarding inheritance mode of human disease. We observed a strong correlation between the number of protein interactions and the likelihood of a gene causing any dominant diseases or multiple dominant diseases, whereas no correlation was observed between protein interaction and the likelihood of a gene causing recessive diseases. We found that dominant diseases are more likely to be associated with disruption of important interactions. These suggest inheritance mode should be understood using protein interaction. We therefore reviewed the previous studies and refined an interaction model of inheritance mode, and then confirmed that this model is largely reasonable using new evidences. With these findings, we found that the inheritance mode of human genetic diseases can be predicted using protein interaction. By integrating the systems biology perspectives with the classical disease genetics paradigm, our study provides some new insights into genotype-phenotype correlations. haodapeng@ems.hrbmu.edu.cn or biofomeng@hotmail.com Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Root phenotyping: from component trait in the lab to breeding.

    Science.gov (United States)

    Kuijken, René C P; van Eeuwijk, Fred A; Marcelis, Leo F M; Bouwmeester, Harro J

    2015-09-01

    In the last decade cheaper and faster sequencing methods have resulted in an enormous increase in genomic data. High throughput genotyping, genotyping by sequencing and genomic breeding are becoming a standard in plant breeding. As a result, the collection of phenotypic data is increasingly becoming a limiting factor in plant breeding. Genetic studies on root traits are being hampered by the complexity of these traits and the inaccessibility of the rhizosphere. With an increasing interest in phenotyping, breeders and scientists try to overcome these limitations, resulting in impressive developments in automated phenotyping platforms. Recently, many such platforms have been thoroughly described, yet their efficiency to increase genetic gain often remains undiscussed. This efficiency depends on the heritability of the phenotyped traits as well as the correlation of these traits with agronomically relevant breeding targets. This review provides an overview of the latest developments in root phenotyping and describes the environmental and genetic factors influencing root phenotype and heritability. It also intends to give direction to future phenotyping and breeding strategies for optimizing root system functioning. A quantitative framework to determine the efficiency of phenotyping platforms for genetic gain is described. By increasing heritability, managing effects caused by interactions between genotype and environment and by quantifying the genetic relation between traits phenotyped in platforms and ultimate breeding targets, phenotyping platforms can be utilized to their maximum potential. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Distinct genetic architectures for phenotype means and plasticities in Zea mays.

    Science.gov (United States)

    Kusmec, Aaron; Srinivasan, Srikant; Nettleton, Dan; Schnable, Patrick S

    2017-09-01

    Phenotypic plasticity describes the phenotypic variation of a trait when a genotype is exposed to different environments. Understanding the genetic control of phenotypic plasticity in crops such as maize is of paramount importance for maintaining and increasing yields in a world experiencing climate change. Here, we report the results of genome-wide association analyses of multiple phenotypes and two measures of phenotypic plasticity in a maize nested association mapping (US-NAM) population grown in multiple environments and genotyped with ~2.5 million single-nucleotide polymorphisms. We show that across all traits the candidate genes for mean phenotype values and plasticity measures form structurally and functionally distinct groups. Such independent genetic control suggests that breeders will be able to select semi-independently for mean phenotype values and plasticity, thereby generating varieties with both high mean phenotype values and levels of plasticity that are appropriate for the target performance environments.

  3. Comparative phenotypic and genotypic analyses of Salmonella Rissen that originated from food animals in Thailand and United States.

    Science.gov (United States)

    Pornsukarom, S; Patchanee, P; Erdman, M; Cray, P F; Wittum, T; Lee, J; Gebreyes, W A

    2015-03-01

    Salmonella enterica serovar Rissen has been recognized as one of the most common serovar among humans and pork production systems in different parts of the world, especially Asia. In the United States, this serovar caused outbreaks but its epidemiologic significance remains unknown. The objectives of this study were to compare the phenotypic (antimicrobial susceptibility) and genotypic attributes of Salmonella Rissen isolated in Thailand (Thai) and the United States (US). All the Thai isolates (n = 30) were recovered from swine faecal samples. The US isolates (n = 35) were recovered from swine faecal samples (n = 29), cattle (n = 2), chicken (n = 2), dog (n = 1) and a ready-to-eat product (n = 1). The antimicrobial susceptibility of isolates was determined using the Kirby-Bauer disk diffusion method with a panel of 12 antimicrobials. Pulse-field gel electrophoresis (PFGE) was used to determine the genotypic diversity of isolates. All Thai isolates showed multidrug resistance (MDR) with the most frequent antibiotic resistance shown against ampicillin (100%), sulfisoxazole (96.7%), tetracycline (93.3%), streptomycin (90%) and chloramphenicol (30%). About half of the isolates of USA origin were pan-susceptible and roughly 30% were resistant to only tetracycline (R-type: Te). Salmonella Rissen isolated from Thailand and the USA in this study were found to be clonally unrelated. Genotypic analyses indicated that isolates were clustered primarily based on the geographic origin implying the limited clonality among the strains. Clonal relatedness among different host species within the same geography (USA) was found. We found genotypic similarity in Thai and US isolates in few instances but with no epidemiological link. Further studies to assess propensity for increased inter-regional transmission and dissemination is warranted. © 2014 Blackwell Verlag GmbH.

  4. Phenotypic and genotypic characterization of two Toxoplasma gondii isolates in free-range chickens from Uberlândia, Brazil.

    Science.gov (United States)

    Lopes, C S; Franco, P S; Silva, N M; Silva, D A O; Ferro, E A V; Pena, H F J; Soares, R M; Gennari, S M; Mineo, J R

    2016-07-01

    The aim of this study was to determine the seroprevalence of Toxoplasma gondii infection in free-range chickens from Uberlândia, Minas Gerais state, Brazil, and characterize the genotypic and phenotypic features of two isolates of this parasite, considering the importance of these hosts in the epidemiology of toxoplasmosis. Serum samples from 108 free-range chickens were obtained from ten different districts, and submitted to the modified agglutination test (MAT) for the presence of anti-T. gondii antibodies, and brain and heart tissue samples from infected chickens were processed for mouse bioassay. An overall seroprevalence of 71·3% was found and antibody titres ranged from 16 to 4096. After confirmation of seropositivity by mouse bioassay, the determination of the T. gondii genotypes of two isolates was performed by PCR-RFLP, using primers for the following markers: SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, new SAG2, Apico and CS3. These T. gondii isolates, designated TgChBrUD1and TgChBrUD2, were obtained from heart samples of free-range chickens. The TgChBrUD1 isolate belonged to ToxoDB PCR-RFLP genotype 11 and the TgChBrUD2 isolate belonged to ToxoDB PCR-RFLP genotype 6. Both isolates demonstrated high virulence in a rodent model, with the TgChBrUD1 isolate able to induce brain cysts, in accord with its pattern of multiplication rates in human fibroblast culture. Taken together, these results reveal high prevalence of T. gondii infection in free-range chickens throughout Uberlândia, indicating an important degree of oocyst environmental contamination and the existence of considerable risk for T. gondii transmission to humans by consumption of free-range chicken as a food source.

  5. Mapping the functional landscape of frequent phenylalanine hydroxylase (PAH) genotypes promotes personalised medicine in phenylketonuria.

    Science.gov (United States)

    Danecka, Marta K; Woidy, Mathias; Zschocke, Johannes; Feillet, François; Muntau, Ania C; Gersting, Søren W

    2015-03-01

    In phenylketonuria, genetic heterogeneity, frequent compound heterozygosity, and the lack of functional data for phenylalanine hydroxylase genotypes hamper reliable phenotype prediction and individualised treatment. A literature search revealed 690 different phenylalanine hydroxylase genotypes in 3066 phenylketonuria patients from Europe and the Middle East. We determined phenylalanine hydroxylase function of 30 frequent homozygous and compound heterozygous genotypes covering 55% of the study population, generated activity landscapes, and assessed the phenylalanine hydroxylase working range in the metabolic (phenylalanine) and therapeutic (tetrahydrobiopterin) space. Shared patterns in genotype-specific functional landscapes were linked to biochemical and pharmacological phenotypes, where (1) residual activity below 3.5% was associated with classical phenylketonuria unresponsive to pharmacological treatment; (2) lack of defined peak activity induced loss of response to tetrahydrobiopterin; (3) a higher cofactor need was linked to inconsistent clinical phenotypes and low rates of tetrahydrobiopterin response; and (4) residual activity above 5%, a defined peak of activity, and a normal cofactor need were associated with pharmacologically treatable mild phenotypes. In addition, we provide a web application for retrieving country-specific information on genotypes and genotype-specific phenylalanine hydroxylase function that warrants continuous extension, updates, and research on demand. The combination of genotype-specific functional analyses with biochemical, clinical, and therapeutic data of individual patients may serve as a powerful tool to enable phenotype prediction and to establish personalised medicine strategies for dietary regimens and pharmacological treatment in phenylketonuria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Cerebral and non-cerebral coenurosis: on the genotypic and phenotypic diversity of Taenia multiceps.

    Science.gov (United States)

    Christodoulopoulos, Georgios; Dinkel, Anke; Romig, Thomas; Ebi, Dennis; Mackenstedt, Ute; Loos-Frank, Brigitte

    2016-12-01

    We characterised the causative agents of cerebral and non-cerebral coenurosis in livestock by determining the mitochondrial genotypes and morphological phenotypes of 52 Taenia multiceps isolates from a wide geographical range in Europe, Africa, and western Asia. Three studies were conducted: (1) a morphological comparison of the rostellar hooks of cerebral and non-cerebral cysts of sheep and goats, (2) a morphological comparison of adult worms experimentally produced in dogs, and (3) a molecular analysis of three partial mitochondrial genes (nad1, cox1, and 12S rRNA) of the same isolates. No significant morphological or genetic differences were associated with the species of the intermediate host. Adult parasites originating from cerebral and non-cerebral cysts differed morphologically, e.g. the shape of the small hooks and the distribution of the testes in the mature proglottids. The phylogenetic analysis of the mitochondrial haplotypes produced three distinct clusters: one cluster including both cerebral isolates from Greece and non-cerebral isolates from tropical and subtropical countries, and two clusters including cerebral isolates from Greece. The majority of the non-cerebral specimens clustered together but did not form a monophyletic group. No monophyletic groups were observed based on geography, although specimens from the same region tended to cluster. The clustering indicates high intraspecific diversity. The phylogenetic analysis suggests that all variants of T. multiceps can cause cerebral coenurosis in sheep (which may be the ancestral phenotype), and some variants, predominantly from one genetic cluster, acquired the additional capacity to produce non-cerebral forms in goats and more rarely in sheep.

  7. Novel mutations of RPGR in Chinese retinitis pigmentosa patients and the genotype-phenotype correlation.

    Science.gov (United States)

    Yang, Liping; Yin, Xiaobei; Feng, Lina; You, Debo; Wu, Lemeng; Chen, Ningning; Li, Aijun; Li, Genlin; Ma, Zhizhong

    2014-01-01

    X-linked Retinitis Pigmentosa (XLRP) accounts for 10-20% of all RP cases, and represents the most severe subtype of this disease. Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene are the most common causes of XLRP, accounting for over 70-75% of all XLRP cases. In this work, we analyzed all the exons of RPGR gene with Sanger sequencing in seven Chinese XLRP families, two of these with a provisional diagnosis of adRP but without male-to-male transmission. Three novel deletions (c.2233_34delAG; c.2236_37delGA and c.2403_04delAG) and two known nonsense mutations (c.851C→G and c.2260G→T) were identified in five families. Two novel deletions (c.2233_34delAG and c.2236_37delGA) resulted in the same frame shift (p.E746RfsX22), created similar phenotype in Family 3 and 4. The novel deletion (c.2403_04delAG; p.E802GfsX31) resulted in both XLRP and x-linked cone-rod dystrophy within the male patients of family 5, which suggested the presence of either genetic or environmental modifiers, or both, play a substantial role in disease expression. Genotype-phenotype correlation analysis suggested that (1) both patients and female carriers with mutation in Exon 8 (Family 1) manifest more severe disease than did those with ORF15 mutations (Family 2&3&4); (2) mutation close to downstream of ORF15 (Family 5) demonstrate the early preferential loss of cone function with moderate loss of rod function.

  8. Differences in the neural signature of remembering schema-congruent and schema-incongruent events.

    Science.gov (United States)

    Brod, Garvin; Lindenberger, Ulman; Werkle-Bergner, Markus; Shing, Yee Lee

    2015-08-15

    New experiences are remembered in relation to one's existing world knowledge or schema. Recent research suggests that the medial prefrontal cortex (mPFC) supports the retrieval of schema-congruent information. However, the neural mechanisms supporting memory for information violating a schema have remained elusive, presumably because incongruity is inherently ambiguous in tasks that rely on world knowledge. We present a novel paradigm that experimentally induces hierarchically structured knowledge to directly contrast neural correlates that contribute to the successful retrieval of schema-congruent versus schema-incongruent information. We hypothesize that remembering incongruent events engages source memory networks including the lateral PFC. In a sample of young adults, we observed enhanced activity in the dorsolateral PFC (DLPFC), in the posterior parietal cortex, and in the striatum when successfully retrieving incongruent events, along with enhanced connectivity between DLPFC and striatum. In addition, we found enhanced mPFC activity for successfully retrieved events that are congruent with the induced schema, presumably reflecting a role of the mPFC in biasing retrieval towards schema-congruent episodes. We conclude that medial and lateral PFC contributions to memory retrieval differ by schema congruency, and highlight the utility of the new experimental paradigm for addressing developmental research questions. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review.

    Science.gov (United States)

    Zollino, Marcella; Murdolo, Marina; Marangi, Giuseppe; Pecile, Vanna; Galasso, Cinzia; Mazzanti, Laura; Neri, Giovanni

    2008-11-15

    Based on genotype-phenotype correlation analysis of 80 Wolf-Hirschhorn syndrome (WHS) patients, as well as on review of relevant literature, we add further insights to the following aspects of WHS: (1) clinical delineation and phenotypic categories; (2) characterization of the basic genomic defect, mechanisms of origin and familiarity; (3) identification of prognostic factors for mental retardation; (4) chromosome mapping of the distinctive clinical signs, in an effort to identify pathogenic genes. Clinically, we consider that minimal diagnostic criteria for WHS, defining a "core" phenotype, are typical facial appearance, mental retardation, growth delay and seizures (or EEG anomalies). Three different categories of the WHS phenotype were defined, generally correlating with the extent of the 4p deletion. The first one comprises a small deletion not exceeding 3.5 Mb, that is usually associated with a mild phenotype, lacking major malformations. This category is likely under-diagnosed. The second and by far the more frequent category is identified by large deletions, averaging between 5 and 18 Mb, and causes the widely recognizable WHS phenotype. The third clinical category results from a very large deletion exceeding 22-25 Mb causing a severe phenotype, that can hardly be defined as typical WHS. Genetically, de novo chromosome abnormalities in WHS include pure deletions but also complex rearrangements, mainly unbalanced translocations. With the exception of t(4p;8p), WHS-associated chromosome abnormalities are neither mediated by segmental duplications, nor associated with a parental inversion polymorphism on 4p16.3. Factors involved in prediction of prognosis include the extent of the deletion, the occurrence of complex chromosome anomalies, and the severity of seizures. We found that the core phenotype maps within the terminal 1.9 Mb region of chromosome 4p. Therefore, WHSCR-2 should be considered the critical region for this condition. We also confirmed that the

  10. Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog.

    Science.gov (United States)

    Solomon, Benjamin D; Bear, Kelly A; Wyllie, Adrian; Keaton, Amelia A; Dubourg, Christele; David, Veronique; Mercier, Sandra; Odent, Sylvie; Hehr, Ute; Paulussen, Aimee; Clegg, Nancy J; Delgado, Mauricio R; Bale, Sherri J; Lacbawan, Felicitas; Ardinger, Holly H; Aylsworth, Arthur S; Bhengu, Ntombenhle Louisa; Braddock, Stephen; Brookhyser, Karen; Burton, Barbara; Gaspar, Harald; Grix, Art; Horovitz, Dafne; Kanetzke, Erin; Kayserili, Hulya; Lev, Dorit; Nikkel, Sarah M; Norton, Mary; Roberts, Richard; Saal, Howard; Schaefer, G B; Schneider, Adele; Smith, Erika K; Sowry, Ellen; Spence, M Anne; Shalev, Stavit A; Steiner, Carlos E; Thompson, Elizabeth M; Winder, Thomas L; Balog, Joan Z; Hadley, Donald W; Zhou, Nan; Pineda-Alvarez, Daniel E; Roessler, Erich; Muenke, Maximilian

    2012-07-01

    Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of non-chromosomal HPE. The severity spectrum is wide, ranging from incompatibility with extrauterine life to isolated midline facial differences. To characterise genetic and clinical findings in individuals with SHH mutations. Through the National Institutes of Health and collaborating centres, DNA from approximately 2000 individuals with HPE spectrum disorders were analysed for SHH variations. Clinical details were examined and combined with published cases. This study describes 396 individuals, representing 157 unrelated kindreds, with SHH mutations; 141 (36%) have not been previously reported. SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (pC-terminus (including accounting for the relative size of the coding regions, p=0.00010), no specific genotype-phenotype correlations could be established regarding mutation location. SHH mutations overall result in milder disease than mutations in other common HPE related genes. HPE is more frequent in individuals with truncating mutations, but clinical predictions at the individual level remain elusive.

  11. Genotype and ancestry modulate brain's DAT availability in healthy humans

    International Nuclear Information System (INIS)

    Shumay, E.; Chen, J.; Fowler, J.S.; Volkow, N.D.

    2011-01-01

    The dopamine transporter (DAT) is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3) is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET) with [ 11 C] cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms - 3-UTR- and intron 8- VNTRs. The main findings are the following: (1) both polymorphisms analyzed as single genetic markers and in combination (haplotype) modulate DAT density in midbrain; (2) ethnic background and age influence the strength of these associations; and (3) age-related changes in DAT availability differ in the 3-UTR and intron8 - genotype groups.

  12. Improving the phenotypic expression of rice genotypes: Rethinking “intensification” for production systems and selection practices for rice breeding

    Directory of Open Access Journals (Sweden)

    Norman Uphoff

    2015-06-01

    expression of rice plants' genetic potential, thereby creating more productive and robust phenotypes from given rice genotypes. Data indicate that increased plant density does not necessarily enhance crop yield potential, as classical breeding methods suggest. Developing cultivars that can achieve their higher productivity under a wide range of plant densities—breeding for density-neutral cultivars using alternative selection strategies—will enable more effective exploitation of available crop growth resources. Density-neutral cultivars that achieve high productivity under ample environmental growth resources can also achieve optimal productivity under limited resources, where lower densities can avert crop failure due to overcrowding. This will become more important to the extent that climatic and other factors become more adverse to crop production. Focusing more on which management practices can evoke the most productive and robust phenotypes from given genotypes is important for rice breeding and improvement programs since it is phenotypes that feed our human populations.

  13. Modelling the incongruent dissolution of hydrated cement minerals

    International Nuclear Information System (INIS)

    Berner, U.R.

    1988-01-01

    Hydrated calciumsilicates are the main constituents of hydrated portland cements. Their chemistry will strongly influence the longterm behaviour of a concrete system envisioned in use in radioactive waste repositories. Experimental data show that hydrated calciumsilicates dissolve incongruently, depending on the calcium/silicon ratio of the solid. A model that simulates the incongruent dissolution behaviour of these hydrated calciumsilicates is presented. In the model the hydrated calciumcilicates are represented as a mixture of two congruently soluble components. The dissolution of the particular components is described using the concept of variable activities in the solid state. Each component's activity in the solid state is obtained from a large body of solubility data by applying the Gibbs-Duhem equation for nonideal mixtures. Using this approach a simplified set of equations, which describe the solubility of the components as a function of the calcium/silicon ratio of the solid, is derived. As an application, the degradation of a standard portland cement in pure water and in a carbonate-rich groundwater is modelled. (orig.)

  14. Personalized medicine: from genotypes, molecular phenotypes and the quantified self, towards improved medicine.

    Science.gov (United States)

    Dudley, Joel T; Listgarten, Jennifer; Stegle, Oliver; Brenner, Steven E; Parts, Leopold

    2015-01-01

    Advances in molecular profiling and sensor technologies are expanding the scope of personalized medicine beyond genotypes, providing new opportunities for developing richer and more dynamic multi-scale models of individual health. Recent studies demonstrate the value of scoring high-dimensional microbiome, immune, and metabolic traits from individuals to inform personalized medicine. Efforts to integrate multiple dimensions of clinical and molecular data towards predictive multi-scale models of individual health and wellness are already underway. Improved methods for mining and discovery of clinical phenotypes from electronic medical records and technological developments in wearable sensor technologies present new opportunities for mapping and exploring the critical yet poorly characterized "phenome" and "envirome" dimensions of personalized medicine. There are ambitious new projects underway to collect multi-scale molecular, sensor, clinical, behavioral, and environmental data streams from large population cohorts longitudinally to enable more comprehensive and dynamic models of individual biology and personalized health. Personalized medicine stands to benefit from inclusion of rich new sources and dimensions of data. However, realizing these improvements in care relies upon novel informatics methodologies, tools, and systems to make full use of these data to advance both the science and translational applications of personalized medicine.

  15. Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.

    Science.gov (United States)

    Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

    2017-03-28

    Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

  16. Unsettling Melodies: A Cognitive Approach to Incongruent Film Music

    NARCIS (Netherlands)

    Willemsen, Steven; Kiss, Miklós

    2013-01-01

    Incongruent film music is a soundtrack, either diegetic or non- diegetic, which expresses qualities that stand in contrast to the emotions evoked by the events seen. The present article aims at covering two interconnected areas; the first is comprised of a critical recapitulation of available

  17. One gene, many phenotypes | Shawky | Egyptian Journal of Medical ...

    African Journals Online (AJOL)

    ... mechanisms underlying genotype-phenotype discrepancies is important, as it will move clinical genetics towards predictive medicine, allowing better selection of therapeutic strategies and individualized counseling of persons affected with genetic disorders. Keywords: Gene, phenotype, mosaicism, epigenetics, pleiotropy ...

  18. Phenotypic and Genotypic Characterization of Atypical Listeria monocytogenes and Listeria innocua Isolated from Swine Slaughterhouses and Meat Markets

    Directory of Open Access Journals (Sweden)

    Luisa Zanolli Moreno

    2014-01-01

    Full Text Available In the last decade, atypical Listeria monocytogenes and L. innocua strains have been detected in food and the environment. Because of mutations in the major virulence genes, these strains have different virulence intensities in eukaryotic cells. In this study, we performed phenotypic and genotypic characterization of atypical L. monocytogenes and L. innocua isolates obtained from swine slaughterhouses and meat markets. Forty strains were studied, including isolates of L. monocytogenes and L. innocua with low-hemolytic activity. The isolates were characterized using conventional phenotypic Listeria identification tests and by the detection and analysis of L. monocytogenes-specific genes. Analysis of 16S rRNA was used for the molecular identification of the Listeria species. The L. monocytogenes isolates were positive for all of the virulence genes studied. The atypical L. innocua strains were positive for hly, plcA, and inlC. Mutations in the InlC, InlB, InlA, PI-PLC, PC-PLC, and PrfA proteins were detected in the atypical isolates. Further in vitro and transcriptomic studies are being developed to confirm the role of these mutations in Listeria virulence.

  19. In-host microevolution of Aspergillus fumigatus: A phenotypic and genotypic analysis.

    Science.gov (United States)

    Ballard, Eloise; Melchers, Willem J G; Zoll, Jan; Brown, Alistair J P; Verweij, Paul E; Warris, Adilia

    2018-04-01

    In order to survive, Aspergillus fumigatus must adapt to specific niche environments. Adaptation to the human host includes modifications facilitating persistent colonisation and the development of azole resistance. The aim of this study is to advance understanding of the genetic and physiological adaptation of A. fumigatus in patients during infection and treatment. Thirteen A. fumigatus strains were isolated from a single chronic granulomatous disease patient suffering from persistent and recurrent invasive aspergillosis over a period of 2 years. All strains had identical microsatellite genotypes and were considered isogenic. Whole genome comparisons identified 248 non-synonymous single nucleotide polymorphisms. These non-synonymous mutations have potential to play a role in in-host adaptation. The first 2 strains isolated were azole susceptible, whereas later isolates were itraconazole, voriconazole and/or posaconazole resistant. Growth assays in the presence and absence of various antifungal stressors highlighted minor changes in growth rate and stress resistance, with exception of one isolate showing a significant growth defect. Poor conidiation was observed in later isolates. In certain drug resistant isolates conidiation was restored in the presence of itraconazole. Differences in virulence were observed as demonstrated in a Galleria mellonella infection model. We conclude that the microevolution of A. fumigatus in this patient has driven the emergence of both Cyp51A-independent and Cyp51A-dependent, azole resistance mechanisms, and additional phenotypes that are likely to have promoted fungal persistence. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Genotype-phenotype associations in filaggrin loss-of-function mutation carriers

    NARCIS (Netherlands)

    Landeck, Lilla; Visser, Maaike; Kezic, Sanja; John, Swen M.

    2013-01-01

    Loss-of-function mutations in the filaggrin gene (FLG) have been reported to be associated with specific phenotypic characteristics such as hyperlinearity and keratosis pilaris. To study phenotypic features in patients with occupational irritant contact eczema of the hands in relation to FLG

  1. Gene-environment and protein degradation signatures characterize genomic and phenotypic diversity in wild Caenorhabditis elegans populations

    NARCIS (Netherlands)

    Volkers, J.M.; Snoek, L.B.; Hellenberg Hubar, van C.J.; Coopman, R.; Chen, W.; Yang, Wentao; Sterken, M.G.; Schulenburg, H.; Braeckman, B.; Kammenga, J.E.

    2013-01-01

    Background: Analyzing and understanding the relationship between genotypes and phenotypes is at the heart of genetics. Research on the nematode Caenorhabditis elegans has been instrumental for unraveling genotype-phenotype relations, and has important implications for understanding the biology of

  2. (In)Congruence of implicit and explicit communal motives predicts the quality and stability of couple relationships.

    Science.gov (United States)

    Hagemeyer, Birk; Neberich, Wiebke; Asendorpf, Jens B; Neyer, Franz J

    2013-08-01

    Previous research has shown that motive congruence, as observed in convergingly high or low scores on implicit and explicit motive measures, promotes well-being and health. Extending this individual perspective to the realm of couple relationships, the present investigation examined intra- and interpersonal effects of communal motive (in)congruence on relationship satisfaction and stability. The implicit partner-related need for communion, the explicit desire for closeness, and relationship satisfaction were assessed in a sample of 547 heterosexual couples aged 18 to 73 years. In a one-year follow-up study, information on relationship stability was obtained, and relationship satisfaction was reassessed. The researchers tested cross-sectional and longitudinal effects of motive (in)congruence by dyadic moderation analyses. Individuals scoring congruently high on both motives reported the highest relationship satisfaction in concurrence with motive assessment and 1 year later. In addition, motive incongruence predicted an increased risk of relationship breakup over 1 year. The results highlight the significance of both implicit and explicit motives for couple relationships. Motive incongruence was confirmed as a dispositional risk factor that so far has not been considered in couple research. Future research directions addressing potential mediators of the observed effects and potential moderators of motive (in)congruence are discussed. © 2012 Wiley Periodicals, Inc.

  3. [Tuberous sclerosis: clinical characteristics and their relationship to genotype/phenotype].

    Science.gov (United States)

    Monteiro, T; Garrido, C; Pina, S; Chorão, R; Carrilho, I; Figueiroa, S; Santos, M; Temudo, T

    2014-11-01

    Tuberous sclerosis (TS) is an inherited disorder with multisystemic involvement and a high phenotypic variability. There are two genes that cause this condition: TSC1 and TSC2. Our goal was to clinically characterize patients with TS followed up in the Pediatric Neurology Clinic of a tertiary hospital during the last 10 years, and correlate the genotype with the severity of neurological manifestations and imaging studies. Retrospective analysis of patients with TS, including review of medical records and available MRI imaging. We studied 35 cases with a median age at diagnosis of ten months. Seizures were the first manifestation in 91.4% of cases, with a predominance of epileptic spasms. Over 50% had cognitive impairment and 49% behavioral disorders. A genetic study was performed on 24 children, and TSC2 mutations identified in 58.3% of them. Of the 11 cases of refractory epilepsy, six had the TSC2 gene mutation. In the group of eight patients with moderate/severe cognitive deficits, five had TSC2 mutations. We reviewed 26 MRI scans, in which it was observed that 76.9% had diffuse involvement of cerebral lobes, which reflects a greater burden of injury. Of the patients who had an MRI scan performed and had TSC2 mutations, all had a high tuber load, and5 of them had refractory epilepsy. In our sample we observe a high percentage of mutations in the TSC2 gene. This mutation carries a worse neurological prognosis, with drug-resistant epilepsy and a more severe cognitive impairment. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  4. Fire coral clones demonstrate phenotypic plasticity among reef habitats.

    Science.gov (United States)

    Dubé, Caroline E; Boissin, Emilie; Maynard, Jeffrey A; Planes, Serge

    2017-08-01

    Clonal populations are often characterized by reduced levels of genotypic diversity, which can translate into lower numbers of functional phenotypes, both of which impede adaptation. Study of partially clonal animals enables examination of the environmental settings under which clonal reproduction is favoured. Here, we gathered genotypic and phenotypic information from 3,651 georeferenced colonies of the fire coral Millepora platyphylla in five habitats with different hydrodynamic regimes in Moorea, French Polynesia. In the upper slope where waves break, most colonies grew as vertical sheets ("sheet tree") making them more vulnerable to fragmentation. Nearly all fire corals in the other habitats are encrusting or massive. The M. platyphylla population is highly clonal (80% of the colonies are clones), while characterized by the highest genotype diversity ever documented for terrestrial or marine populations (1,064 genotypes). The proportion of clones varies greatly among habitats (≥58%-97%) and clones (328 clonal lineages) are distributed perpendicularly from the reef crest, perfectly aligned with wave energy. There are six clonal lineages with clones dispersed in at least two adjacent habitats that strongly demonstrate phenotypic plasticity. Eighty per cent of the colonies in these lineages are "sheet tree" on the upper slope, while 80%-100% are encrusting or massive on the mid slope and back reef. This is a unique example of phenotypic plasticity among reef-building coral clones as corals typically have wave-tolerant growth forms in high-energy reef areas. © 2017 John Wiley & Sons Ltd.

  5. Novel mutations of RPGR in Chinese retinitis pigmentosa patients and the genotype-phenotype correlation.

    Directory of Open Access Journals (Sweden)

    Liping Yang

    Full Text Available X-linked Retinitis Pigmentosa (XLRP accounts for 10-20% of all RP cases, and represents the most severe subtype of this disease. Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR gene are the most common causes of XLRP, accounting for over 70-75% of all XLRP cases. In this work, we analyzed all the exons of RPGR gene with Sanger sequencing in seven Chinese XLRP families, two of these with a provisional diagnosis of adRP but without male-to-male transmission. Three novel deletions (c.2233_34delAG; c.2236_37delGA and c.2403_04delAG and two known nonsense mutations (c.851C→G and c.2260G→T were identified in five families. Two novel deletions (c.2233_34delAG and c.2236_37delGA resulted in the same frame shift (p.E746RfsX22, created similar phenotype in Family 3 and 4. The novel deletion (c.2403_04delAG; p.E802GfsX31 resulted in both XLRP and x-linked cone-rod dystrophy within the male patients of family 5, which suggested the presence of either genetic or environmental modifiers, or both, play a substantial role in disease expression. Genotype-phenotype correlation analysis suggested that (1 both patients and female carriers with mutation in Exon 8 (Family 1 manifest more severe disease than did those with ORF15 mutations (Family 2&3&4; (2 mutation close to downstream of ORF15 (Family 5 demonstrate the early preferential loss of cone function with moderate loss of rod function.

  6. Phenotypic Approaches to Drought in Cassava: Review

    Directory of Open Access Journals (Sweden)

    Emmanuel eOkogbenin

    2013-05-01

    Full Text Available Cassava is an important crop in Africa, Asia, Latin America and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12 - 18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance

  7. Coagulase-negative staphylococci (CoNS) isolated from ready-to-eat food of animal origin--phenotypic and genotypic antibiotic resistance.

    Science.gov (United States)

    Chajęcka-Wierzchowska, Wioleta; Zadernowska, Anna; Nalepa, Beata; Sierpińska, Magda; Łaniewska-Trokenheim, Łucja

    2015-04-01

    The aim of this work was to study the pheno- and genotypical antimicrobial resistance profile of coagulase negative staphylococci (CoNS) isolated from 146 ready-to-eat food of animal origin (cheeses, cured meats, sausages, smoked fishes). 58 strains were isolated, they were classified as Staphylococcus xylosus (n = 29), Staphylococcus epidermidis (n = 16); Staphylococcus lentus (n = 7); Staphylococcus saprophyticus (n = 4); Staphylococcus hyicus (n = 1) and Staphylococcus simulans (n = 1) by phenotypic and genotypic methods. Isolates were tested for resistance to erythromycin, clindamycin, gentamicin, cefoxitin, norfloxacin, ciprofloxacin, tetracycline, tigecycline, rifampicin, nitrofurantoin, linezolid, trimetoprim, sulphamethoxazole/trimethoprim, chloramphenicol, quinupristin/dalfopristin by the disk diffusion method. PCR was used for the detection of antibiotic resistance genes encoding: methicillin resistance--mecA; macrolide resistance--erm(A), erm(B), erm(C), mrs(A/B); efflux proteins tet(K) and tet(L) and ribosomal protection proteins tet(M). For all the tet(M)-positive isolates the presence of conjugative transposons of the Tn916-Tn1545 family was determined. Most of the isolates were resistant to cefoxitin (41.3%) followed by clindamycin (36.2%), tigecycline (24.1%), rifampicin (17.2%) and erythromycin (13.8%). 32.2% staphylococcal isolates were multidrug resistant (MDR). All methicillin resistant staphylococci harboured mecA gene. Isolates, phenotypic resistant to tetracycline, harboured at least one tetracycline resistance determinant on which tet(M) was most frequent. All of the isolates positive for tet(M) genes were positive for the Tn916-Tn1545 -like integrase family gene. In the erythromycin-resistant isolates, the macrolide resistance genes erm(C) or msr(A/B) were present. Although coagulase-negative staphylococci are not classical food poisoning bacteria, its presence in food could be of public health significance due to the possible spread of

  8. Genotypic and phenotypic properties of cattle-associated Campylobacter and their implications to public health in the USA.

    Directory of Open Access Journals (Sweden)

    Yasser M Sanad

    Full Text Available Since cattle are a major source of food and the cattle industry engages people from farms to processing plants and meat markets, it is conceivable that beef-products contaminated with Campylobacter spp. would pose a significant public health concern. To better understand the epidemiology of cattle-associated Campylobacter spp. in the USA, we characterized the prevalence, genotypic and phenotypic properties of these pathogens. Campylobacter were detected in 181 (19.2% out of 944 fecal samples. Specifically, 71 C. jejuni, 132 C. coli, and 10 other Campylobacter spp. were identified. The prevalence of Campylobacter varied regionally and was significantly (P<0.05 higher in fecal samples collected from the South (32.8% as compared to those from the North (14.8%, Midwest (15.83%, and East (12%. Pulsed Field Gel Electrophoresis (PFGE analysis showed that C. jejuni and C. coli isolates were genotypically diverse and certain genotypes were shared across two or more of the geographic locations. In addition, 13 new C. jejuni and two C. coli sequence types (STs were detected by Multi Locus Sequence Typing (MLST. C. jejuni associated with clinically human health important sequence type, ST-61 which was not previously reported in the USA, was identified in the present study. Most frequently observed clonal complexes (CC were CC ST-21, CC ST-42, and CC ST-61, which are also common in humans. Further, the cattle associated C. jejuni strains showed varying invasion and intracellular survival capacity; however, C. coli strains showed a lower invasion and intracellular survival potential compared to C. jejuni strains. Furthermore, many cattle associated Campylobacter isolates showed resistance to several antimicrobials including ciprofloxacin, erythromycin, and gentamicin. Taken together, our results highlight the importance of cattle as a potential reservoir for clinically important Campylobacter.

  9. Genotypic and Phenotypic Properties of Cattle-Associated Campylobacter and Their Implications to Public Health in the USA

    Science.gov (United States)

    Sanad, Yasser M.; Kassem, Issmat I.; Abley, Melanie; Gebreyes, Wondwossen; LeJeune, Jeffrey T.; Rajashekara, Gireesh

    2011-01-01

    Since cattle are a major source of food and the cattle industry engages people from farms to processing plants and meat markets, it is conceivable that beef-products contaminated with Campylobacter spp. would pose a significant public health concern. To better understand the epidemiology of cattle-associated Campylobacter spp. in the USA, we characterized the prevalence, genotypic and phenotypic properties of these pathogens. Campylobacter were detected in 181 (19.2%) out of 944 fecal samples. Specifically, 71 C. jejuni, 132 C. coli, and 10 other Campylobacter spp. were identified. The prevalence of Campylobacter varied regionally and was significantly (P<0.05) higher in fecal samples collected from the South (32.8%) as compared to those from the North (14.8%), Midwest (15.83%), and East (12%). Pulsed Field Gel Electrophoresis (PFGE) analysis showed that C. jejuni and C. coli isolates were genotypically diverse and certain genotypes were shared across two or more of the geographic locations. In addition, 13 new C. jejuni and two C. coli sequence types (STs) were detected by Multi Locus Sequence Typing (MLST). C. jejuni associated with clinically human health important sequence type, ST-61 which was not previously reported in the USA, was identified in the present study. Most frequently observed clonal complexes (CC) were CC ST-21, CC ST-42, and CC ST-61, which are also common in humans. Further, the cattle associated C. jejuni strains showed varying invasion and intracellular survival capacity; however, C. coli strains showed a lower invasion and intracellular survival potential compared to C. jejuni strains. Furthermore, many cattle associated Campylobacter isolates showed resistance to several antimicrobials including ciprofloxacin, erythromycin, and gentamicin. Taken together, our results highlight the importance of cattle as a potential reservoir for clinically important Campylobacter. PMID:22046247

  10. Maneuvering in the Complex Path from Genotype to Phenotype

    Science.gov (United States)

    Strohman, Richard

    2002-04-01

    Human disease phenotypes are controlled not only by genes but by lawful self-organizing networks that display system-wide dynamics. These networks range from metabolic pathways to signaling pathways that regulate hormone action. When perturbed, networks alter their output of matter and energy which, depending on the environmental context, can produce either a pathological or a normal phenotype. Study of the dynamics of these networks by approaches such as metabolic control analysis may provide new insights into the pathogenesis and treatment of complex diseases.

  11. Identification of a novel frameshift mutation in the ILDR1 gene in a UAE family, mutations review and phenotype genotype correlation.

    Directory of Open Access Journals (Sweden)

    Abdelaziz Tlili

    Full Text Available Autosomal recessive non-syndromic hearing loss is one of the most common monogenic diseases. It is characterized by high allelic and locus heterogeneities that make a precise diagnosis difficult. In this study, whole-exome sequencing was performed for an affected patient allowing us to identify a new frameshift mutation (c.804delG in the Immunoglobulin-Like Domain containing Receptor-1 (ILDR1 gene. Direct Sanger sequencing and segregation analysis were performed for the family pedigree. The mutation was homozygous in all affected siblings but heterozygous in the normal consanguineous parents. The present study reports a first ILDR1 gene mutation in the UAE population and confirms that the whole-exome sequencing approach is a robust tool for the diagnosis of monogenic diseases with high levels of allelic and locus heterogeneity. In addition, by reviewing all reported ILDR1 mutations, we attempt to establish a genotype phenotype correlation to explain the phenotypic variability observed at low frequencies.

  12. Phenotypes and genotypes in individuals with SMC1A variants

    DEFF Research Database (Denmark)

    Huisman, Sylvia; Mulder, Paul A; Redeker, Egbert

    2017-01-01

    , stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group...

  13. Plant phenomics and the need for physiological phenotyping across scales to narrow the genotype-to-phenotype knowledge gap

    Czech Academy of Sciences Publication Activity Database

    Grosskinsky, D. K.; Svensgaard, J.; Christensen, S.; Roitsch, Thomas

    2015-01-01

    Roč. 66, č. 18 (2015), s. 5429-5440 ISSN 0022-0957 Institutional support: RVO:67179843 Keywords : External phenotype * genome–environment–management interaction * genome–phenome map * internal phenotype * phenomics * physiological traits * physiology * plant phenotyping * predictors Subject RIV: EH - Ecology, Behaviour Impact factor: 5.677, year: 2015

  14. Presence of Glycopeptide-Encoding Plasmids in Enterococcal Isolates from Food and Humans in Denmark

    DEFF Research Database (Denmark)

    Migura, Lourdes Garcia; Valenzuela, Antonio Jesus Sanchez; Jensen, Lars Bogø

    2011-01-01

    developed techniques for classification of plasmids. Replicons associated with sex pheromone-inducible plasmids were detected in all GR E. faecalis, whereas GR Enterococcus faecium contained plasmids known to be widely distributed among enterococci. vanA resistance is common in E. faecium isolates from meat...... and animals in Europe and is rarely found in E. faecalis. This article describes the first characterization of MGE from vanA mediated E. faecalis, thus linking this resistance genotype to pheromone responding plasmids....

  15. Clinical and molecular epidemiology of hospital Enterococcus faecium isolates in eastern France. Members of Réseau Franc-Comtois de Lutte contr les Infections Nosocomiales.

    Science.gov (United States)

    Bertrand, X; Thouverez, M; Bailly, P; Cornette, C; Talon, D

    2000-06-01

    We carried out a surveillance study of Enterococcus faecium isolates in the Franche-Comtéregion of France over three years. Clinical and epidemiological strains were characterized by antibiotype and genotype (pulsed field gel electrophoresis, PFGE). Three case-control studies were performed to identify risk factors for colonization/infection with three defined resistant phenotypes (amoxycillin, high-level gentamicin and high-level kanamycin). The crude incidence of colonization/infection was 0.156%, and 68.8% of cases were classified as hospital-acquired. Incidence did not differ according to the type of hospitalization (middle term or acute care). The urinary tract was the major site of infection. Resistance rates were: 45.8% (amoxycillin), 18.7% (high-level gentamicin), 61.4% (high-level kanamycin) and 3.1% (vancomycin). No isolate produced b-lactamase and one isolate carried the vanA gene. PFGE revealed two major epidemic patterns each including resistant strains isolated in different hospitals and during different periods in the study. Previous antimicrobial treatment was not identified as a risk factor for colonization/infection with any resistant phenotype. Despite the low frequency of vancomycin-resistant isolates in this study, resistant strains were widely disseminated and had characteristics enabling them to persist and spread. If these strains acquired the vanA gene, the risk of an outbreak would be large. So, the prevalence of vancomycin-resistant E. faecium in hospitals should be carefully monitored in the future. Copyright 2000 The Hospital Infection Society.

  16. Low Motivational Incongruence Predicts Successful EEG Resting-state Neurofeedback Performance in Healthy Adults.

    Science.gov (United States)

    Diaz Hernandez, Laura; Rieger, Kathryn; Koenig, Thomas

    2018-05-15

    Neurofeedback is becoming increasingly sophisticated and widespread, although predictors of successful performance still remain scarce. Here, we explored the possible predictive value of psychological factors and report the results obtained from a neurofeedback training study designed to enhance the self-regulation of spontaneous EEG microstates of a particular type (microstate class D). Specifically, we were interested in life satisfaction (including motivational incongruence), body awareness, personality and trait anxiety. These variables were quantified with questionnaires before neurofeedback. Individual neurofeedback success was established by means of linear mixed models that accounted for the amount of observed target state (microstate class D contribution) as a function of time and training condition: baseline, training and transfer (results shown in Diaz Hernandez et al.). We found a series of significant negative correlations between motivational incongruence and mean percentage increase of microstate D during the condition transfer, across-sessions (36% of common variance) and mean percentage increase of microstate D during the condition training, within-session (42% of common variance). There were no significant correlations related to other questionnaires, besides a trend in a sub-scale of the Life Satisfaction questionnaire. We conclude that motivational incongruence may be a potential predictor for neurofeedback success, at least in the current protocol. The finding may be explained by the interfering effect on neurofeedback performance produced by incompatible simultaneously active psychological processes, which are indirectly measured by the Motivational Incongruence questionnaire. Copyright © 2016. Published by Elsevier Ltd.

  17. Allelic variance among ABO blood group genotypes in a population from the western region of Saudi Arabia.

    Science.gov (United States)

    Mohamed, Abdularahman B O; Hindawi, Salwa Ibrahim; Al-Harthi, Sameer; Alam, Qamre; Alam, Mohammad Zubair; Haque, Absarul; Ahmad, Waseem; Damanhouri, Ghazi A

    2016-12-01

    Characterization of the ABO blood group at the phenotype and genotype levels is clinically essential for transfusion, forensics, and population studies. This study elucidated ABO phenotypes and genotypes, and performed an evaluation of their distribution in individuals from the western region of Saudi Arabia. One-hundred and seven samples underwent standard serological techniques for ABO blood group phenotype analysis. ABO alleles and genotypes were identified using multiplex polymerase chain reaction, and electrophoretic analysis was performed to evaluate the highly polymorphic ABO locus. A phenotype distribution of 37.4%, 30.8%, 24.3%, and 7.5% was found for blood groups O, A, B, and AB respectively in our study cohort. Genotype analysis identified 10 genotype combinations with the O01/O02 and A102/O02 genotypes being the most frequent with frequencies of 33.6% and 14.95%, respectively. Common genotypes such as A101/A101 , A101/A102 , A101/B101 , B101/B101 , and O01/O01 were not detected. Similarly, the rare genotypes, cis-AB01/O02 , cis-AB01/O01 , and cis-AB01/A102 were not found in our cohort. The most frequently observed allele was O02 (35.98%) followed by the A102 allele (17.76%). Furthermore, our findings are discussed in reference to ABO allele and genotype frequencies found in other ethnic groups. The study has a significant implication on the management of blood bank and transfusion services in Saudi Arabian patients.

  18. Emotional Incongruence of Facial Expression and Voice Tone Investigated with Event-Related Brain Potentials of Infants

    Directory of Open Access Journals (Sweden)

    Kota Arai

    2011-10-01

    Full Text Available Human emotions are perceived from multi-modal information including facial expression and voice tone. We aimed to investigate development of neural mechanism for cross-modal perception of emotions. We presented congruent and incongruent combinations of facial expression (happy and voice tone (happy or angry, and measured EEG to analyze event-related brain potentials for 8-10 month-old infants and adults. Ten repetitions of 10 trials were presented in random order for each participant. Half of them performed 20% congruent (happy face with happy voice and 80% incongruent (happy face with angry voice trials, and the others performed 80% congruent and 20% incongruent trials. We employed the oddball paradigm, but did not instruct participants to count a target. The odd-ball (infrequent stimulus increased the amplitude of P2 and delayed its latency for infants in comparison with the frequent stimulus. When the odd-ball stimulus was also emotionally incongruent, P2 amplitude was more increased and its latency was more delayed than for the odd-ball and emotionally congruent stimulus. However, we did not find difference of P2 amplitude or latency for adults between conditions. These results suggested that the 8–10 month-old infants already have a neural basis for detecting emotional incongruence of facial expression and voice tone.

  19. Classification of Cryptococcus neoformans and yeast-like fungus isolates from pigeon droppings by colony phenotyping and ITS genotyping and their seasonal variations in Korea.

    Science.gov (United States)

    Chae, H S; Jang, G E; Kim, N H; Son, H R; Lee, J H; Kim, S H; Park, G N; Jo, H J; Kim, J T; Chang, K S

    2012-03-01

    Cryptococcus neoformans (C neoformans) is a frequent cause of invasive fungal disease in immunocompromised human hosts. Ninety-eight samples of pigeon droppings were collected from the pigeon shelters in Seoul, and cultured on birdseed agar (BSA) and Sabouraud dextrose agar (SDA). One hundred yeast-like colonies were selected and identified via phenotype characteristics, such as colony morphology and biochemical characteristics. This was then followed with genotyping via sequencing of the internal transcribed spacer (ITS) region. The colonies were classified into four kinds of colony color types: brown type (BrT), beige type (BeT), pink type (PT), and white type (WT). Numbers of isolated BrT, BeT, PT, and WT colonies were 22 (22%), 30 (30%), 19 (19%), and 39 (39%), respectively. All BrT colonies were identified as C neoformans. BeT were identified as 19 isolates of Cryptococcus laurentii, 10 isolates of Malassezia furfur, and 1 isolate of Cryptococcus uniguttulatus. PT was divided into two colony color types: light-PT (l-PT) and deep-PT (d-PT). Eighteen of l-PT and one of d-PT were identified as Rhodotorula glutinis and Rhodotorula mucilaginosa, respectively. WT were identified as 34 isolates of Cryptococcus guilliermondii, 3 isolates of Cryptococcus zeylanoides, 1 isolate of Cryptococcus sake, and 1 isolate of Stephanoascus ciferrii. Most strains were classified identically with the use of either phenotype or genotyping techniques, but C uniguttulatus and C sake classified by phenotyping were Pseudozyma aphidis and Cryptococcus famata by genotyping. This rapid screening technique of pathogenic yeast-like fungi by only colony characteristics is also expected to be very useful for primary yeast screening. Additionally, we investigated the seasonal variations of C neoformans and other yeast-like fungi from 379 pigeon-dropping samples that were collected from February 2011 to March 2011. We isolated 685 yeast-like fungi from the samples. Almost all C neoformans and

  20. Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency

    DEFF Research Database (Denmark)

    Olsen, Rikke K J; Andresen, Brage S; Christensen, Ernst

    2003-01-01

    activity, we have investigated the molecular genetic basis for disease development in nine patients representing the phenotypic spectrum of MADD. We report the genomic structures of the ETFA, ETFB, and ETFDH genes and the identification and characterization of seven novel and three previously reported...... disease-causing mutations. Our molecular genetic investigations of these nine patients are consistent with three clinical forms of MADD showing a clear relationship between the nature of the mutations and the severity of disease. Interestingly, our data suggest that homozygosity for two null mutations...... mutation identified in a patient with type III disease showed that the residual activity of the mutant enzyme could be rescued up to 59% of that of wild-type activity when ETFB-D128N-transformed E. coli cells were grown at low temperature. This indicates that the effect of the ETF/ETFDH genotype...

  1. BDNF rs6265 methylation and genotype interact on risk for schizophrenia.

    Science.gov (United States)

    Ursini, Gianluca; Cavalleri, Tommaso; Fazio, Leonardo; Angrisano, Tiziana; Iacovelli, Luisa; Porcelli, Annamaria; Maddalena, Giancarlo; Punzi, Giovanna; Mancini, Marina; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Calabrese, Francesca; Rampino, Antonio; Taurisano, Paolo; Di Giorgio, Annabella; Keller, Simona; Tarantini, Letizia; Sinibaldi, Lorenzo; Quarto, Tiziana; Popolizio, Teresa; Caforio, Grazia; Blasi, Giuseppe; Riva, Marco A; De Blasi, Antonio; Chiariotti, Lorenzo; Bollati, Valentina; Bertolino, Alessandro

    2016-01-01

    Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val(66)Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes.

  2. Molecular etiology and genotype-phenotype correlation of Chinese Han deaf patients with type I and type II Waardenburg Syndrome.

    Science.gov (United States)

    Sun, Lianhua; Li, Xiaohua; Shi, Jun; Pang, Xiuhong; Hu, Yechen; Wang, Xiaowen; Wu, Hao; Yang, Tao

    2016-10-19

    Waardenburg syndrome (WS) characterized by sensorineural hearing loss and pigmentary abnormalities is genetically heterogeneous and phenotypically variable. This study investigated the molecular etiology and genotype-phenotype correlation of WS in 36 Chinese Han deaf probands and 16 additional family members that were clinically diagnosed with WS type I (WS1, n = 8) and type II (WS2, n = 42). Mutation screening of six WS-associated genes detected PAX3 mutations in 6 (86%) of the 7 WS1 probands. Among the 29 WS2 probands, 13 (45%) and 10 (34%) were identified with SOX10 and MITF mutations, respectively. Nineteen of the 26 detected mutations were novel. In WS2 probands whose parental DNA samples were available, de novo mutations were frequently seen for SOX10 mutations (7/8) but not for MITF mutations (0/5, P = 0.005). Excessive freckle, a common feature of WS2 in Chinese Hans, was frequent in WS2 probands with MITF mutations (7/10) but not in those with SOX10 mutations (0/13, P = 4.9 × 10 -4 ). Our results showed that mutations in SOX10 and MITF are two major causes for deafness associated with WS2. These two subtypes of WS2 can be distinguished by the high de novo rate of the SOX10 mutations and the excessive freckle phenotype exclusively associated with the MITF mutations.

  3. Factor VII deficiency: a novel missense variant and genotype-phenotype correlation in patients from Southern Italy.

    Science.gov (United States)

    Tiscia, Giovanni; Favuzzi, Giovanni; Chinni, Elena; Colaizzo, Donatella; Fischetti, Lucia; Intrieri, Mariano; Margaglione, Maurizio; Grandone, Elvira

    2017-01-01

    This study aimed at attempting to correlate genotype and phenotype in factor VII deficiency. Here, we present molecular and clinical findings of 10 patients with factor VII deficiency. From 2013 to 2016, 10 subjects were referred to our center because of a prolonged prothrombin time identified during routine or presurgery examinations or after a laboratory assessment of a bleeding episode. Mutation characterization was performed using the bioinformatics applications PROMO, SIFT, and Polyphen-2. Structural changes in the factor VII protein were analyzed using the SPDB viewer tool. Of the 10 variants we identified, 1 was responsible for a novel missense change (c.1199G>C, p.Cys400Ser); in 2 cases we identified the c.-54G>A and c.509G>A (p.Arg170His) polymorphic variants in the 5'-upstream region of the factor VII gene and exon 6, respectively. To our knowledge, neither of these polymorphic variants has been described previously in factor VII-deficient patients. In silico predictions showed differences in binding sites for transcription factors caused by the c.-54G>A variant and a probable damaging effect of the p.Cys400Ser missense change on factor VII active conformation, leading to breaking of the Cys400-Cys428 disulfide bridge. Our findings further suggest that, independently of factor VII levels and of variants potentially affecting factor VII levels, environmental factors, e.g., trauma, could heavily influence the clinical phenotype of factor VII-deficient patients.

  4. Genonets server-a web server for the construction, analysis and visualization of genotype networks.

    Science.gov (United States)

    Khalid, Fahad; Aguilar-Rodríguez, José; Wagner, Andreas; Payne, Joshua L

    2016-07-08

    A genotype network is a graph in which vertices represent genotypes that have the same phenotype. Edges connect vertices if their corresponding genotypes differ in a single small mutation. Genotype networks are used to study the organization of genotype spaces. They have shed light on the relationship between robustness and evolvability in biological systems as different as RNA macromolecules and transcriptional regulatory circuits. Despite the importance of genotype networks, no tool exists for their automatic construction, analysis and visualization. Here we fill this gap by presenting the Genonets Server, a tool that provides the following features: (i) the construction of genotype networks for categorical and univariate phenotypes from DNA, RNA, amino acid or binary sequences; (ii) analyses of genotype network topology and how it relates to robustness and evolvability, as well as analyses of genotype network topography and how it relates to the navigability of a genotype network via mutation and natural selection; (iii) multiple interactive visualizations that facilitate exploratory research and education. The Genonets Server is freely available at http://ieu-genonets.uzh.ch. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Audiovisual Perception of Congruent and Incongruent Dutch Front Vowels

    Science.gov (United States)

    Valkenier, Bea; Duyne, Jurriaan Y.; Andringa, Tjeerd C.; Baskent, Deniz

    2012-01-01

    Purpose: Auditory perception of vowels in background noise is enhanced when combined with visually perceived speech features. The objective of this study was to investigate whether the influence of visual cues on vowel perception extends to incongruent vowels, in a manner similar to the McGurk effect observed with consonants. Method:…

  6. Phenotype-genotype correlation in β-thalassemia

    Directory of Open Access Journals (Sweden)

    R. Galanello

    2011-12-01

    Full Text Available The clinical manifestations of β-thalassemia are extremely heterogeneous, ranging from severe transfusion-dependent anemia, to the mild non transfusion dependent thalassemia intermedia and to the asymptomatic carrier state. The remarkable phenotypic variability is primary due to variations in the different globin genes (primary gene modifiers. The main pathophysiological determinant of the severity of β-thalassemia syndromes is the extent of a/non-a globin chain imbalance. Therefore, any factor capable of reducing the globin chain imbalance may have an ameliorating effect on the clinical picture. The most common mechanisms responsible of the amelioration of the phenotype are mild or silent β thalassemia alleles, coinheritance of a thalassemia, or of genetic determinants associated with increased g globin chain production. Rarely, other complex mechanisms including dominantly inherited β thalassemia, somatic deletion of β globin gene and coinheritance of extra a globin genes with heterozygous β thalassemia have been reported. In addition to the variability of the phenotype resulting from primary gene modifiers, other genetic factors (secondary gene modifiers, mapping outside the β and a globin cluster, may influence the disease complications. Among these factors the ones best so far defined are those affecting bilirubin, iron and bone metabolism. However, the new methods of DNA analysis (i.e. GWAS and related methods are expect expand the number of genes or gene variants involved in the phenotypic variability and in the response to treatment of β thalassemia. 从严重的输液依赖型贫血症到轻度非输液依赖性中间型地中海贫血,再到无症状携带状态,β地中海贫血的临床表现极度异源性。 由于不同珠蛋白基因(初级基因修饰因子)发生各种变异,主要表现为显著的表型变异。

  7. Phenotypic effects of salt and heat stress over three generations in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Léonie Suter

    Full Text Available Current and predicted environmental change will force many organisms to adapt to novel conditions, especially sessile organisms such as plants. It is therefore important to better understand how plants react to environmental stress and to what extent genotypes differ in such responses. It has been proposed that adaptation to novel conditions could be facilitated by heritable epigenetic changes induced by environmental stress, independent of genetic variation. Here we assessed phenotypic effects of heat and salt stress within and across three generations using four highly inbred Arabidopsis thaliana genotypes (Col, Cvi, Ler and Sha. Salt stress generally decreased fitness, but genotypes were differently affected, suggesting that susceptibility of A. thaliana to salt stress varies among genotypes. Heat stress at an early rosette stage had less detrimental effects but accelerated flowering in three out of four accessions. Additionally, we found three different modes of transgenerational effects on phenotypes, all harboring the potential of being adaptive: heat stress in previous generations induced faster rosette growth in Sha, both under heat and control conditions, resembling a tracking response, while in Cvi, the phenotypic variance of several traits increased, resembling diversified bet-hedging. Salt stress experienced in earlier generations altered plant architecture of Sha under salt but not control conditions, similar to transgenerational phenotypic plasticity. However, transgenerational phenotypic effects depended on the type of stress as well as on genotype, suggesting that such effects may not be a general response leading to adaptation to novel environmental conditions in A. thaliana.

  8. Analysis of the world epidemiological situation among vancomycin-resistant Enterococcus faecium infections and the current situation in Poland

    Science.gov (United States)

    Talaga-Ćwiertnia, Katarzyna; Bulanda, Małgorzata

    2018-01-01

    Vancomycin-resistant Enterococcus faecium (VREfm) strains have become an important hospital pathogen due to their rapid spread, high mortality rate associated with infections and limited therapeutic options. Vancomycin resistance is predominantly mediated by VanA or VanB phenotypes, which differ as regards maintaining sensitivity to teicoplanin in the VanB phenotype. The majority of VREfm cases in the United States, Europe, Korea, South America and Africa are currently caused by the VanA phenotype. However, the epidemics in Australia and Singapore are chiefly brought about by the VanB phenotype. The rate of VREfm isolate spread varies greatly. The greatest percentage of VREfm is now recorded in the USA, Ireland and Australia. Supervision of VRE is implemented to varying degrees. Therefore, the epidemiological situation in some countries is difficult to assess due to limited data or lack thereof.

  9. Pharmacologically Counteracting a Phenotypic Difference in Cerebellar GABAA Receptor Response to Alcohol Prevents Excessive Alcohol Consumption in a High Alcohol-Consuming Rodent Genotype.

    Science.gov (United States)

    Kaplan, Josh Steven; Nipper, Michelle A; Richardson, Ben D; Jensen, Jeremiah; Helms, Melinda; Finn, Deborah Ann; Rossi, David James

    2016-08-31

    Cerebellar granule cell GABAA receptor responses to alcohol vary as a function of alcohol consumption phenotype, representing a potential neural mechanism for genetic predilection for alcohol abuse (Kaplan et al., 2013; Mohr et al., 2013). However, there are numerous molecular targets of alcohol in the cerebellum, and it is not known how they interact to affect cerebellar processing during consumption of socially relevant amounts of alcohol. Importantly, direct evidence for a causative role of the cerebellum in alcohol consumption phenotype is lacking. Here we determined that concentrations of alcohol that would be achieved in the blood after consumption of 1-2 standard units (9 mm) suppresses transmission through the cerebellar cortex in low, but not high, alcohol consuming rodent genotypes (DBA/2J and C57BL/6J mice, respectively). This genotype-selective suppression is mediated exclusively by enhancement of granule cell GABAA receptor currents, which only occurs in DBA/2J mice. Simulating the DBA/2J cellular phenotype in C57BL/6J mice by infusing the GABAA receptor agonist, 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol hydrochloride, into cerebellar lobules IV-VI, in vivo, significantly reduced their alcohol consumption and blood alcohol concentrations achieved. 4,5,6,7-Tetrahydroisoxazolo-[5,4-c]pyridine-3-ol hydrochloride infusions also significantly decreased sucrose consumption, but they did not affect consumption of water or general locomotion. Thus, genetic differences in cerebellar response to alcohol contributes to alcohol consumption phenotype, and targeting the cerebellar GABAA receptor system may be a clinically viable therapeutic strategy for reducing excessive alcohol consumption. Alcohol abuse is a leading cause of preventable death and illness; and although alcohol use disorders are 50%-60% genetically determined, the cellular and molecular mechanisms of such genetic influences are largely unknown. Here we demonstrate that genetic differences in

  10. Genotype and ancestry modulate brain's DAT availability in healthy humans

    Energy Technology Data Exchange (ETDEWEB)

    Shumay, E.; Shumay, E.; Chen, J.; Fowler, J.S.; Volkow, N.D.

    2011-08-01

    The dopamine transporter (DAT) is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3) is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET) with [{sup 11}C] cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms - 3-UTR- and intron 8- VNTRs. The main findings are the following: (1) both polymorphisms analyzed as single genetic markers and in combination (haplotype) modulate DAT density in midbrain; (2) ethnic background and age influence the strength of these associations; and (3) age-related changes in DAT availability differ in the 3-UTR and intron8 - genotype groups.

  11. Trisomy 12p and monosomy 4p: phenotype-genotype correlation.

    Science.gov (United States)

    Benussi, Daniela Gambel; Costa, Paola; Zollino, Marcella; Murdolo, Marina; Petix, Vincenzo; Carrozzi, Marco; Pecile, Vanna

    2009-04-01

    4p Monosomy and 12p trisomy have been discussed and redefined along with recently reviewed chromosomal syndromes. 12p Trisomy syndrome is characterized by normal or increased birth weight, developmental delay with early hypotonia, psychomotor delay, and typical facial appearance. Most likely, the observed phenotypic variability depends on the type and extent of the associated partial monosomy. Partial deletions of the short arm of one chromosome 4 cause the Wolf-Hirschhorn syndrome (WHS). Affected patients present Greek helmet face, growth and mental retardation, hypotonia, and seizures. The combination of these characteristics constitutes the phenotypic core of WHS. We present a clinical and molecular cytogenetic characterization of a 4-year old mentally retarded girl with macrosomy, facial dysmorphisms, and epilepsy, in whom an unbalanced t(4;12)(p16.3;p13.3) translocation was detected, giving rise to partial 4p monosomy and partial 12p trisomy. Because the patient shows most of the phenotypic characteristics of 12p trisomy, this case could contribute to a better definition of the duplicate critical region that determines the phenotype of the 12p trisomy syndrome.

  12. Cognitive and Affective Consequences of Two Types of Incongruent Advertising

    NARCIS (Netherlands)

    J. Loef (Joost); P.W.J. Verlegh (Peter)

    2002-01-01

    textabstractIn this study, Heckler & Childers' (1992) two-dimensional conceptualization of incongruity is employed and related to the different schemas that consumers use in ad processing. Consumers can relate advertising to expectations about ads for the product concerned from the ad schema or to

  13. Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency.

    Science.gov (United States)

    Olsen, Rikke K J; Andresen, Brage S; Christensen, Ernst; Bross, Peter; Skovby, Flemming; Gregersen, Niels

    2003-07-01

    Mutations in electron transfer flavoprotein (ETF) and its dehydrogenase (ETFDH) are the molecular basis of multiple acyl-CoA dehydrogenation deficiency (MADD), an autosomal recessively inherited and clinically heterogeneous disease that has been divided into three clinical forms: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). To examine whether these different clinical forms could be explained by different ETF/ETFDH mutations that result in different levels of residual ETF/ETFDH enzyme activity, we have investigated the molecular genetic basis for disease development in nine patients representing the phenotypic spectrum of MADD. We report the genomic structures of the ETFA, ETFB, and ETFDH genes and the identification and characterization of seven novel and three previously reported disease-causing mutations. Our molecular genetic investigations of these nine patients are consistent with three clinical forms of MADD showing a clear relationship between the nature of the mutations and the severity of disease. Interestingly, our data suggest that homozygosity for two null mutations causes fetal development of congenital anomalies resulting in a type I disease phenotype. Even minute amounts of residual ETF/ETFDH activity seem to be sufficient to prevent embryonic development of congenital anomalies giving rise to type II disease. Overexpression studies of an ETFB-D128N missense mutation identified in a patient with type III disease showed that the residual activity of the mutant enzyme could be rescued up to 59% of that of wild-type activity when ETFB-D128N-transformed E. coli cells were grown at low temperature. This indicates that the effect of the ETF/ETFDH genotype in patients with milder forms of MADD, in whom residual enzyme activity allows modulation of the enzymatic phenotype, may be influenced by environmental factors like cellular temperature. Copyright

  14. Genotypic Variation of Early Maturing Soybean Genotypes for Phosphorus Utilization Efficiency under Field Grown Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Abaidoo, R. C. [Kwame Nkrumah University of Technology, Kumasi (Ghana); International Institute of Tropical Agriculture, Ibadan (Nigeria); Opoku, A.; Boahen, S. [Kwame Nkrumah University of Technology, Kumasi (Ghana); Dare, M. O. [Federal University of Agriculture, Abeokuta (Nigeria)

    2013-11-15

    Variability in the utilization of phosphorus (P) by 64 early-maturing soybean (Glycine max L. Merr.) genotypes under low-P soil conditions were evaluated in 2009 and 2010 at Shika, Nigeria. Fifteen phenotypic variables; number of nodules, nodule dry weight, grain yield, plant biomass, total biomass, biomass N and P content, Phosphorus Utilization Index (PUI), shoot P Utilization efficiency (PUIS), grain P Utilization efficiency (PUIG), Harvest Index (HI), Biological N fixed (BNF), total N fixed and N and P uptake were measured. The four clusters revealed by cluster analysis were basically divided along (1) plant biomass and uptake, (2) nutrient acquisition and utilization and (3) nodulation components. Three early maturing genotypes, TGx1842-14E, TGx1912-11F and TGx1913-5F, were identified as having high P utilization index and low P uptake. These genotypes could be a potential source for breeding for P use efficiency in early maturing soybean genotypes. (author)

  15. Pheno-phenotypes: a holistic approach to the psychopathology of schizophrenia.

    Science.gov (United States)

    Stanghellini, Giovanni; Rossi, Rodolfo

    2014-05-01

    Mental disorders are mainly characterized via symptom assessment. Symptoms are state-like macroscopic anomalies of behaviour, experience, and expression that are deemed relevant for diagnostic purposes. An alternative approach is based on the concept of endophenotypes, which are physiological or behavioural measures occupying the terrain between symptoms and risk genotypes. We will critically discuss these two approaches, and later focus on the concept of pheno-phenotype as it is revealed by recent phenomenological research on schizophrenia. Several studies have been recently published on the schizophrenic pheno-phenotype mainly addressing self-disorders, as well as disorders of time and bodily experience. The mainstream approach to psychopathological phenotypes is focussed on easy-to-assess operationalizable symptoms. Thinness of phenotypes and simplification of clinical constructs are the consequences of this. Also, this approach has not been successful in investigating the biological causes of mental disorders. An integrative approach is based on the concept of 'endophenotype'. Endophenotypes were conceptualized as a supportive tool for the genetic dissection of psychiatric disorders. The underlying rationale states that disease-specific phenotypes should be the upstream phenotypic manifestation of a smaller genotype than the whole disease-related genotype. Psychopathological phenotypes can also be characterized in terms of pheno-phenotypes. This approach aims at delineating the manifold phenomena experienced by patients in all of their concrete and distinctive features, so that the features of a pathological condition emerge, while preserving their peculiar feel, meaning, and value for the patient. Systematic explorations of anomalies in the patients' experience, for example, of time, space, body, self, and otherness, may provide a useful integration to the symptom-based and endophenotype-based approaches. These abnormal phenomena can be used as pointers to the

  16. Phenotypic diversity of basic characteristics of genotypes from the Serbia onion collection

    Directory of Open Access Journals (Sweden)

    Gvozdanović-Varga Jelica

    2013-01-01

    Full Text Available The onion is a widely distributed vegetable crop, which takes an important place in the vegetable production in Serbia. The traditional planting method is the one from sets. Old cultivars and populations and, in recent years, foreign cultivars are grown. The large variety of genotypes, including both domestic populations and cultivars, comprises the significant gene pool of this region. The onion collection of the Institute of Field and Vegetable Crops in Novi Sad is based on the populations and cultivars from the territory of the former Yugoslavia. This paper reviews 30 onion genotypes on the basic IPGRI descriptors (ANNEX I. Variability of the reviewed characteristics was determined by PC analysis. High variability values have been established for bulb skin color, bulb flesh color, bulb hearting and bulb skin thickness. The genotypes varied in bulb skin color as well as in bulb flesh color from white to dark violet. These two characteristics had the largest impact on clustering, with a single genotype being heterogeneous exactly for these two characteristics. [Projekat Ministarstva nauke Republike Srbije, br. TR 31030

  17. Genotypic and phenotypic diversity among Bacillus species isolated ...

    African Journals Online (AJOL)

    DIRECTOR

    2013-03-20

    Mar 20, 2013 ... 1Department of Food Engineering and Quality Control, University Institute of Technology,. P. O. Box 454 Ngaoundere, Cameroon. 2Department of ... potentially help in maintaining consumer health. (Mohamadou et ... used to this effect. Phenotypic ..... However, the detection of B. cereus, a food poisoning,.

  18. Archeology and Humanism: An Incongruent Foucault

    Directory of Open Access Journals (Sweden)

    Chris Calvert-Minor

    2010-06-01

    Full Text Available Atension exists in Foucault’s writings concerning his alleged antihumanism. While his early archaeological period is taken to sediment his post-structuralist, anti-humanist methodology, Foucault still lets humanism creep into his writing, particularly in his later work. In the spirit of charity, I consider two ways of reading Foucault to overcome this tension: either (1 emphasize his post-structuralism over his humanist leanings or (2 take his humanism seriously and minimize his post-structuralism. After analysis, neither reading is adequate. I conclude that Foucault’s oeuvre is best understood simply as incongruent, contrary to his own remarks to unify his writings and methodologies.

  19. ACE I/D genotype, adiposity, and blood pressure in children

    Directory of Open Access Journals (Sweden)

    Rothschild Max

    2009-03-01

    Full Text Available Abstract Background Angiotensin converting enzyme (ACE is a possible candidate gene that may influence both body fatness and blood pressure. Although several genetic studies have been conducted in adults, relatively few studies have examined the contribution of potential candidate genes, and specifically ACE I/D, on adiposity and BP phenotypes in childhood. Such studies may prove insightful for the development of the obesity-hypertension phenotype early in life. The purpose of this study was to examine differences in body fatness and resting blood pressure (BP by ACE I/D genotype, and determine if the association between adiposity and BP varies by ACE I/D genotype in children. Methods 152 children (75 girls, 77 boys were assessed for body composition (% body fat using dual energy x-ray absorbtiometry and resting BP according to American Heart Association recommendations. Buccal cell samples were genotyped using newly developed PCR-RFLP tests for two SNPs (rs4341 and rs4343 in complete linkage disequilibrium with the ACE I/D polymorphism. Partial correlations were computed to assess the ociations between % body fat and BP in the total sample and by genotype. ANCOVA was used to examine differences in resting BP by ACE I/D genotype and fatness groups. Results Approximately 39% of youth were overfat based on % body fat (>30% fat in girls, 25% fat in boys. Body mass, body mass index, and fat-free mass were significantly higher in the ACE D-carriers compared to the II group (p Conclusion ACE D-carriers are heavier than ACE II children; however, BP did not differ by ACE I/D genotype but was adversely influenced in the overfat D-carriers. Further studies are warranted to investigate the genetics of fatness and BP phenotypes in children.

  20. Identification of Candida albicans and Candida dubliniensis Species Isolated from Bronchoalveolar Lavage Samples Using Genotypic and Phenotypic Methods

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    Sahar Kianipour

    2018-01-01

    Full Text Available Background: Candida dubliniensis is a newly diagnosed species very similar to Candida albicans phenotypically and first discovered in the mouth of people with AIDS in 1995. Among the different phenotypic and genotypic methods, a cost-effective method should be selected which makes it possible to differentiate these similar species. Materials and Methods: Polymerase chain reaction (PCR-restriction fragment length polymorphism with MspI enzyme and the Duplex-PCR method were done by DNA extraction using boiling. The sequencing of the amplified ribosomal region was used to confirm the C. dubliniensis species. Direct examination and colony count of the yeasts were applied for bronchoalveolar lavage (BAL samples and the growth rate of the yeasts were studied at 45°C. To understand the ability formation of chlamydoconidia in yeast isolates, they were separately cultured on the sunflower seed agar, wheat flour agar, and corn meal agar media. Results: Fifty-nine (49.2% yeast colonies were identified from the total of 120 BAL specimens. Twenty-nine isolated yeasts; including 17 (58.6% of C. albicans/dubliniensis complex and 12 (41.4% of nonalbicans isolates produced pseudohypha or blastoconidia in direct smear with a mean colony count of 42000 CFU/mL. C. albicans with the frequency of 15 (42.9% were the most common isolated yeasts, whereas C. dubliniensis was identified in two nonHIV patients. Conclusion: Sequencing of the replicated gene fragment is the best method for identifying the yeasts, but the determination of the species by phenotypic methods such as the creation of chlamydoconidia in sunflower seeds agar and wheat flour agar media can be cost-effective, have sensitivity and acceptable quality.

  1. Identification of Candida albicans and Candida dubliniensis Species Isolated from Bronchoalveolar Lavage Samples Using Genotypic and Phenotypic Methods.

    Science.gov (United States)

    Kianipour, Sahar; Ardestani, Mohammad Emami; Dehghan, Parvin

    2018-01-01

    Candida dubliniensis is a newly diagnosed species very similar to Candida albicans phenotypically and first discovered in the mouth of people with AIDS in 1995. Among the different phenotypic and genotypic methods, a cost-effective method should be selected which makes it possible to differentiate these similar species. Polymerase chain reaction (PCR)-restriction fragment length polymorphism with MspI enzyme and the Duplex-PCR method were done by DNA extraction using boiling. The sequencing of the amplified ribosomal region was used to confirm the C. dubliniensis species. Direct examination and colony count of the yeasts were applied for bronchoalveolar lavage (BAL) samples and the growth rate of the yeasts were studied at 45°C. To understand the ability formation of chlamydoconidia in yeast isolates, they were separately cultured on the sunflower seed agar, wheat flour agar, and corn meal agar media. Fifty-nine (49.2%) yeast colonies were identified from the total of 120 BAL specimens. Twenty-nine isolated yeasts; including 17 (58.6%) of C. albicans / dubliniensis complex and 12 (41.4%) of nonalbicans isolates produced pseudohypha or blastoconidia in direct smear with a mean colony count of 42000 CFU/mL. C. albicans with the frequency of 15 (42.9%) were the most common isolated yeasts, whereas C. dubliniensis was identified in two nonHIV patients. Sequencing of the replicated gene fragment is the best method for identifying the yeasts, but the determination of the species by phenotypic methods such as the creation of chlamydoconidia in sunflower seeds agar and wheat flour agar media can be cost-effective, have sensitivity and acceptable quality.

  2. Spotted phenotypes in horses lost attractiveness in the Middle Ages

    DEFF Research Database (Denmark)

    Wutke, Saskia; Benecke, Norbert; Sandoval-Castellanos, Edson

    2016-01-01

    were influenced by humans. Our results from genotype analyses show a significant increase in spotted coats in early domestic horses (Copper Age to Iron Age). In contrast, medieval horses carried significantly fewer alleles for these phenotypes, whereas solid phenotypes (i.e., chestnut) became dominant...

  3. Molecular characterization of vancomycin-resistant Enterococcus faecium isolates from Bermuda.

    Directory of Open Access Journals (Sweden)

    Patrick Eberechi Akpaka

    Full Text Available Molecular characteristics of vancomycin resistant enterococci isolates from Bermuda Island is currently unknown. This study was conducted to investigate phenotypic and genotypic characteristics of VRE isolates from Bermuda Island using the chromogenic agar, E-tests, polymerase chain reaction (PCR, pulsed-field gel electrophoresis (PFGE and multilocus sequence typing (MLST. Eighteen E. faecium isolates were completely analyzed and were all resistant to vancomycin, susceptible to linezolid and quinupristin/dalfopristin, positive for vanA and esp genes. The MLST analysis confirmed most isolates were of the sequence types linked to clonal complex 17 (CC17 that is widely associated with outbreaks in hospitals. Infection control measures, antibiotic stewardship, and surveillance activities will continue to be a priority in hospital on the Island.

  4. Frequency of alpha- and beta-haemolysin in Staphylococcus aureus of bovine and human origin - A comparison between pheno- and genotype and variation in phenotypic expression

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Larsen, H.D.; Eriksen, N.H.R.

    1999-01-01

    The phenotypic expression of haemolysins and the presence of genes encoding alpha and beta-haemolysin were determined in 105 Sraphylococcus aureus isolates from bovine mastitis, 100 isolates from the nostrils of healthy humans, and 60 isolates from septicaemia in humans. Furthermore, the possible...... change in expression of haemolysins after subcultivation in human and bovine blood and milk was studied in selected isolates. alpha-haemolysin was expressed phenotypically in 39 (37%) of the bovine isolates, in 59 (59%) of the human carrier isolates, and in 40 (67%) of the isolates from septicaemia. beta......-haemolysin was expressed in 76 (72%) bovine, 11 (11%) carrier, and 8 (13%) septicaemia isolates. Significantly more bovine than human isolates expressed beta-haemolysin and significantly fewer expressed alpha-haemolysin. Genotypically, the gene encoding alpha-haemolysin was detected in all isolates. A significant...

  5. Early phenotypical diagnoses in Trembler-J mice model.

    Science.gov (United States)

    Rosso, Gonzalo; Cal, Karina; Canclini, Lucía; Damián, Juan Pablo; Ruiz, Paul; Rodríguez, Héctor; Sotelo, José Roberto; Vazquez, Cristina; Kun, Alejandra

    2010-06-30

    Pmp-22 mutant mice (Trembler-J: B6.D2-Pmp22/J), are used as a model to study Charcot-Marie-Tooth type 1A (CMT1A). The identification of individual genotypes is a routine in the management of the Tr(J) colony. The earliest phenotypic manifestation of the pmp-22 mutation is just about 20th postnatal days, when pups begin to tremble. In this study, a rapid and simple diagnostic method was developed by modifying the Tail Suspension Test (MTST) to determine the difference between the Tr(J) and the wild-type mice phenotype. The animal behavioral phenotypes generated during the test were consistent with the specific genotype of each animal. The MTST allowed us to infer the heterozygous genotype in early postnatal stages, at 11 days after birth. The motor impairment of Tr(J) mice was also analyzed by a Fixed Bar Test (FBT), which revealed the disease evolution according to age. The main advantages of MTST are its objectivity, simplicity, and from the viewpoint of animal welfare, it is a non-invasive technique that combined with his rapidity show its very well applicability for use from an early age in these mice. Copyright 2010 Elsevier B.V. All rights reserved.

  6. Adaptation to an extraordinary environment by evolution of phenotypic plasticity and genetic assimilation.

    Science.gov (United States)

    Lande, Russell

    2009-07-01

    Adaptation to a sudden extreme change in environment, beyond the usual range of background environmental fluctuations, is analysed using a quantitative genetic model of phenotypic plasticity. Generations are discrete, with time lag tau between a critical period for environmental influence on individual development and natural selection on adult phenotypes. The optimum phenotype, and genotypic norms of reaction, are linear functions of the environment. Reaction norm elevation and slope (plasticity) vary among genotypes. Initially, in the average background environment, the character is canalized with minimum genetic and phenotypic variance, and no correlation between reaction norm elevation and slope. The optimal plasticity is proportional to the predictability of environmental fluctuations over time lag tau. During the first generation in the new environment the mean fitness suddenly drops and the mean phenotype jumps towards the new optimum phenotype by plasticity. Subsequent adaptation occurs in two phases. Rapid evolution of increased plasticity allows the mean phenotype to closely approach the new optimum. The new phenotype then undergoes slow genetic assimilation, with reduction in plasticity compensated by genetic evolution of reaction norm elevation in the original environment.

  7. Chlorophyll a fluorescence to phenotype wheat genotypes for heat tolerance

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari; Andersen, Sven Bode; Ottosen, Carl-Otto

    In prospects of global climate change, heat stress is a rising constraint for the productivity of wheat (Triticum aestivum L.). It is a heat-susceptible crop beyond 17-23oC temperature throughout its phenological stages, flowering phase being the most sensitive stage. Chlorophyll a fluorescence...... parameter, maximum quantum yield efficiency of PSII (Fv/Fm) is used as a physiological marker for early stress detection in PSII in plants. We established a reproducible protocol to measure response of wheat genotypes to high temperature based on Fv/Fm. The heat treatment of 40°C in 300 µmol m-2s-1 PAR...... enabled the identification of contrasting wheat genotypes that can be used to study the genetic and physiological nature of heat stress tolerance to dissect quantitative traits into simpler and more heritable traits....

  8. Identification of a mutation that is associated with the saddle tan and black-and-tan phenotypes in Basset Hounds and Pembroke Welsh Corgis.

    Science.gov (United States)

    Dreger, Dayna L; Parker, Heidi G; Ostrander, Elaine A; Schmutz, Sheila M

    2013-01-01

    The causative mutation for the black-and-tan (a (t) ) phenotype in dogs was previously shown to be a SINE insertion in the 5' region of Agouti Signaling Protein (ASIP). Dogs with the black-and-tan phenotype, as well as dogs with the saddle tan phenotype, genotype as a (t) /_ at this locus. We have identified a 16-bp duplication (g.1875_1890dupCCCCAGGTCAGAGTTT) in an intron of hnRNP associated with lethal yellow (RALY), which segregates with the black-and-tan phenotype in a group of 99 saddle tan and black-and-tan Basset Hounds and Pembroke Welsh Corgis. In these breeds, all dogs with the saddle tan phenotype had RALY genotypes of +/+ or +/dup, whereas dogs with the black-and-tan phenotype were homozygous for the duplication. The presence of an a (y) /_ fawn or e/e red genotype is epistatic to the +/_ saddle tan genotype. Genotypes from 10 wolves and 1 coyote indicated that the saddle tan (+) allele is the ancestral allele, suggesting that black-and-tan is a modification of saddle tan. An additional 95 dogs from breeds that never have the saddle tan phenotype have all three of the possible RALY genotypes. We suggest that a multi-gene interaction involving ASIP, RALY, MC1R, DEFB103, and a yet-unidentified modifier gene is required for expression of saddle tan.

  9. Progress toward a genotype/phenotype correlation in galactosemia

    Energy Technology Data Exchange (ETDEWEB)

    Reichardt, J.K.V.; Lin, Hsien-Chin; Ng, Won G. [Univ. of Southern California School of Medicine, Los Angeles, CA (United States)

    1994-09-01

    Galactosemia is secondary to deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT). If untreated this condition results in severe neonatal symptoms and can be fatal. Most symptoms disappear upon the institution of a galactose-restricted diet. Therefore, most states in the US and many developed countries have implemented newborn screening programs for galactosemia. We have characterized thus far twelve disease-causing point mutations, four protein polymorphisms, one silent nucleotide substitution and a RFLP (restriction fragment length polymorphism) in over 200 patients. The most common galactosemia mutation, Q188R, is present on about 64% of Caucasian galactosemia alleles in the US. This mutation is present on 67% of {open_quotes}classic{close_quotes} Caucasian alleles with severe neonatal symptoms and undetectable crythrocytic GALT activity. Thus, Q188R almost defines the {open_quotes}classic{close_quotes} phenotype in Caucasian galactosemia patients. This mutation, however, is present on only 16% of the milder {open_quotes}variant{close_quotes} alleles and never in the homozygous state. Variant patients have up to 10% residual GALT activity in their red cells. Therefore, one or more as of yet uncharacterized mutations other than Q188R must be present in {open_quotes}variant{close_quotes} patients. The Q188R mutations is very rare in other ethnic and racial groups. Thus, Galactosemia is panethnic but the mutational basis of this disease differs among human populations. The frequency of Q188R is intermediate in Hispanic-American patients, probably reflecting the Spanish contribution to the gene pool in this population. We conclude that the Q188R mutation encodes the severe {open_quotes}classic{close_quotes}galactosemia phenotype in Caucasians and that other mutations produce the {open_quotes}variant{close_quotes} galactosemia phenotype.

  10. A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation.

    Science.gov (United States)

    Kamada, Fumiaki; Kure, Shigeo; Kudo, Takayuki; Suzuki, Yoichi; Oshima, Takeshi; Ichinohe, Akiko; Kojima, Kanako; Niihori, Tetsuya; Kanno, Junko; Narumi, Yoko; Narisawa, Ayumi; Kato, Kumi; Aoki, Yoko; Ikeda, Katsuhisa; Kobayashi, Toshimitsu; Matsubara, Yoichi

    2006-01-01

    Autosomal-dominant, nonsyndromic hearing impairment is clinically and genetically heterogeneous. We encountered a large Japanese pedigree in which nonsyndromic hearing loss was inherited in an autosomal-dominant fashion. A genome-wide linkage study indicated linkage to the DFNA2 locus on chromosome 1p34. Mutational analysis of KCNQ4 encoding a potassium channel revealed a novel one-base deletion in exon 1, c.211delC, which generated a profoundly truncated protein without transmembrane domains (p.Q71fsX138). Previously, six missense mutations and one 13-base deletion, c.211_223del, had been reported in KCNQ4. Patients with the KCNQ4 missense mutations had younger-onset and more profound hearing loss than patients with the 211_223del mutation. In our current study, 12 individuals with the c.211delC mutation manifested late-onset and pure high-frequency hearing loss. Our results support the genotype-phenotype correlation that the KCNQ4 deletions are associated with later-onset and milder hearing impairment than the missense mutations. The phenotypic difference may be caused by the difference in pathogenic mechanisms: haploinsufficiency in deletions and dominant-negative effect in missense mutations.

  11. Genotype-phenotype associations in obesity dependent on definition of the obesity phenotype

    DEFF Research Database (Denmark)

    Kring, Sofia Inez Iqbal; Larsen, Lesli Hingstrup; Holst, Claus

    2008-01-01

    In previous studies of associations of variants in the genes UCP2, UCP3, PPARG2, CART, GRL, MC4R, MKKS, SHP, GHRL, and MCHR1 with obesity, we have used a case-control approach with cases defined by a threshold for BMI. In the present study, we assess the association of seven abdominal, peripheral......, and overall obesity phenotypes, which were analyzed quantitatively, and thirteen candidate gene polymorphisms in these ten genes in the same cohort....

  12. Morphophysiology, Phenotypic and Molecular Diversity of Auxin-induced Passiflora mucronata Lam. (Passifloraceae).

    Science.gov (United States)

    França, Juliany M; Venial, Lucimara R; Costa, Eloá B; Schmildt, Edilson R; Schmildt, Omar; Bernardes, Paula M; Tatagiba, Sandro D; Lopes, José C; Ferreira, Marcia F S; Alexandre, Rodrigo S

    2018-01-01

    Genetic diversity allows identification of potential intraspecific genotypes in the genus Passiflora. The objective of this study was to examine the morphological and genetic diversity of auxin-induced Passiflora mucronata. The experiments were arranged in a complete randomized block design, with a 9 x 2 factorial arrangement (nine genotypes x presence and absence of auxin, indole-3-butyric acid (IBA)), with four replicates of 16 cuttings. The rooting and vegetative growth responses were variable. Genotype 5 was more responsive in the absence of IBA and genotypes 3, 8 and 9 were more responsive in the presence of IBA. Auxin increased rooting rate and percentage, reducing the average time of root protrusion in eight days. IBA also contributed to increase photosynthesis and dry root and shoot mass in 55.55 and 44.44% of the genotypes, respectively. The highest relative contribution to phenotypic diversity in the absence of auxin was rate (38.75%) and percentage (20.27%) of rooting, whereas in the presence of auxin was stomatal conductance (23.19%) and root dry mass (20.91%). Similarity was found for phenotypic and molecular divergence in the presence of IBA, in which genotypes 1 and 6; genotypes 5, 8 and 9; and genotype 3 were clustered in distinct groups.

  13. Cultural differences in sensitivity to social context: detecting affective incongruity using the N400.

    Science.gov (United States)

    Goto, Sharon G; Yee, Alicia; Lowenberg, Kelly; Lewis, Richard S

    2013-01-01

    East Asians and Asian-Americans tend to allocate relatively greater attention to background context compared to European Americans across a variety of cognitive and neural measures. We sought to extend these findings of cultural differences to affective stimuli using the N400, which has been shown to be sensitive to deep processing of affective information. The degree to which Asian-Americans and European Americans responded to semantic incongruity between emotionally expressive faces (i.e., smiling or frowning) and background affective scenes was measured. As predicted, Asian-Americans showed a greater N400 to incongruent trials than to congruent trials. In contrast, European Americans showed no difference in amplitude across the two conditions. Furthermore, greater affective N400 incongruity was associated with higher interdependent self-construals. These data suggest that Asian-Americans and those with interdependent self-construals process the relationship between perceived facial emotion and affective background context to a greater degree than European Americans and those with independent self-construals. Implications for neural and cognitive differences in everyday social interactions, and cultural differences in analytic and holistic thinking are discussed.

  14. Phenotypic and genetic characterization of Botrytis cinerea isolates from tomato

    Directory of Open Access Journals (Sweden)

    Kuzmanovska Biljana

    2012-01-01

    Full Text Available One hundred and twenty-three isolates of Botrytis cinerea were collected from 7 different areas in the Republic of Macedonia, where tomato is mostly grown in greenhouses and high tunnels. Based on the mycelial formation, intensity of sporulation and sclerotial production, 9 different phenotypes were detected: 4 mycelial and 5 sclerotial. One sclerotial morphological type has not been previously reported. The presence or absence of two transposable elements, boty and flipper, was detected by PCR. Out of 123 isolates, 20 had two transposable elements, boty and flipper (transposa genotype, 48 had neither of these elements (vacuma genotype and 55 had only the flipper element (flipper genotype. Isolates that contain only boty element were not detected. No relationship between the phenotypes, origin of isolates and the presence/absence of transposable elements, boty and flipper, was found.

  15. Genotypic and phenotypic characterization of Escherichia coli isolates from feces, hands, and soils in rural Bangladesh via the Colilert Quanti-Tray System.

    Science.gov (United States)

    Julian, Timothy R; Islam, M Aminul; Pickering, Amy J; Roy, Subarna; Fuhrmeister, Erica R; Ercumen, Ayse; Harris, Angela; Bishai, Jason; Schwab, Kellogg J

    2015-03-01

    The increased awareness of the role of environmental matrices in enteric disease transmission has resulted in the need for rapid, field-based methods for fecal indicator bacteria and pathogen detection. Evidence of the specificity of β-glucuronidase-based assays for detection of Escherichia coli from environmental matrices relevant to enteric pathogen transmission in developing countries, such as hands, soils, and surfaces, is limited. In this study, we quantify the false-positive rate of a β-glucuronidase-based E. coli detection assay (Colilert) for two environmental reservoirs in Bangladeshi households (hands and soils) and three fecal composite sources (cattle, chicken, and humans). We investigate whether or not the isolation source of E. coli influences phenotypic and genotypic characteristics. Phenotypic characteristics include results of biochemical assays provided by the API-20E test; genotypic characteristics include the Clermont phylogroup and the presence of enteric and/or environmental indicator genes sfmH, rfaI, and fucK. Our findings demonstrate no statistically significant difference in the false-positive rate of Colilert for environmental compared to enteric samples. E. coli isolates from all source types are genetically diverse, representing six of the seven phylogroups, and there is no difference in relative frequency of phylogroups between enteric and environmental samples. We conclude that Colilert, and likely other β-glucuronidase-based assays, is appropriate for detection of E. coli on hands and in soils with low false-positive rates. Furthermore, E. coli isolated from hands and soils in Bangladeshi households are diverse and indistinguishable from cattle, chicken, and human fecal isolates, using traditional biochemical assays and phylogrouping. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Phenotype and genotype of  lactic acid bacteria (LAB isolated from the tiger grouper Epinephelus fuscoguttatus alimentary tract [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Nursyirwani Nursyirwani

    2017-11-01

    Full Text Available Lactic acid bacteria (LAB have been isolated successfully from the tiger grouper Epinephelus fuscoguttatus intestine. However, their genus or species have not been identified. Therefore, the objective of the present study was to characterize the three isolated LAB (KSBU-12C, KSBU-5Da, and KSBU-9 based on their phenotype and genotype. The LAB phenotype was examined by observing morphological features including cell morphology, spore production and motility. The physiological tests were performed in 6.5% NaCl at the  temperatures of 10oC and 45oC, and the biochemical tests were evaluated based on the production of enzymes catalase, oxidase and arginine dehydrolase, following  the Standard Analytical Profile Index, API 50 CH kit.  The genotype was examined based on 16S rDNA gene sequence analysis , and the products were analyzed using the BLAST (Basic Local Alignment Search Tool NCBI database. The three isolates (KSBU-5Da, KSBU-12C, and KSBU-9 were categorized into the genus Enterococcus. 16S rDNA sequence analysis indicated that the isolates had 99% similarity to E. hirae ATCC 9790, registered in GenBank with accession number NR_075022.1. It was concluded that the three LAB isolates taken from the tiger grouper Epinephelus fuscoguttatus are E. hirae.

  17. Semiparametric Allelic Tests for Mapping Multiple Phenotypes: Binomial Regression and Mahalanobis Distance.

    Science.gov (United States)

    Majumdar, Arunabha; Witte, John S; Ghosh, Saurabh

    2015-12-01

    Binary phenotypes commonly arise due to multiple underlying quantitative precursors and genetic variants may impact multiple traits in a pleiotropic manner. Hence, simultaneously analyzing such correlated traits may be more powerful than analyzing individual traits. Various genotype-level methods, e.g., MultiPhen (O'Reilly et al. []), have been developed to identify genetic factors underlying a multivariate phenotype. For univariate phenotypes, the usefulness and applicability of allele-level tests have been investigated. The test of allele frequency difference among cases and controls is commonly used for mapping case-control association. However, allelic methods for multivariate association mapping have not been studied much. In this article, we explore two allelic tests of multivariate association: one using a Binomial regression model based on inverted regression of genotype on phenotype (Binomial regression-based Association of Multivariate Phenotypes [BAMP]), and the other employing the Mahalanobis distance between two sample means of the multivariate phenotype vector for two alleles at a single-nucleotide polymorphism (Distance-based Association of Multivariate Phenotypes [DAMP]). These methods can incorporate both discrete and continuous phenotypes. Some theoretical properties for BAMP are studied. Using simulations, the power of the methods for detecting multivariate association is compared with the genotype-level test MultiPhen's. The allelic tests yield marginally higher power than MultiPhen for multivariate phenotypes. For one/two binary traits under recessive mode of inheritance, allelic tests are found to be substantially more powerful. All three tests are applied to two different real data and the results offer some support for the simulation study. We propose a hybrid approach for testing multivariate association that implements MultiPhen when Hardy-Weinberg Equilibrium (HWE) is violated and BAMP otherwise, because the allelic approaches assume HWE

  18. Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders

    NARCIS (Netherlands)

    Andrews, T.; Meader, S.; Vulto-van Silfhout, A.T.; Taylor, A.; Steinberg, J.; Hehir-Kwa, J.; Pfundt, R.P.; Leeuw, N. de; Vries, B. de; Webber, C.

    2015-01-01

    Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far

  19. Parallel or convergent evolution in human population genomic data revealed by genotype networks

    OpenAIRE

    Vahdati, Ali R; Wagner, Andreas

    2016-01-01

    Background Genotype networks are representations of genetic variation data that are complementary to phylogenetic trees. A genotype network is a graph whose nodes are genotypes (DNA sequences) with the same broadly defined phenotype. Two nodes are connected if they differ in some minimal way, e.g., in a single nucleotide. Results We analyze human genome variation data from the 1,000 genomes project, and construct haploid genotype (haplotype) networks for 12,235 protein coding genes. The struc...

  20. The phenotype, psychotype and genotype of bruxism

    Science.gov (United States)

    Cruz-Fierro, Norma; Martínez-Fierro, Margarita; Cerda-Flores, Ricardo M.; Gómez-Govea, Mayra A.; Delgado-Enciso, Iván; Martínez-De-Villarreal, Laura E.; González-Ramírez, Mónica T.; Rodríguez-Sánchez, Irám Pablo

    2018-01-01

    Bruxism is a jaw muscle activity that involves physio-pathological, psycho-social, hereditary and genetic factors. The purpose of this study was to determine the associations between self-reported bruxism, anxiety, and neuroticism personality trait with the rs6313 polymorphism in the gene HTR2A. A sample of 171 subjects of both sexes (14–53 years of age) was included. The control group (group 1, n=60) exhibited no signs or symptoms of bruxism. The case group had signs and symptoms of bruxism (n=112) and was subdivided into group 2, bruxism during sleep (n=22); group 3, awake bruxism (n=44); and group 4 combined bruxism (n=46). As diagnostic tools, the Self-Reported Bruxism Questionnaire (SBQ), the Beck Anxiety Inventory (BAI) and the Eysenck Personality Questionnaire Revised-Abbreviated (EPQR-A) were used. HTR2A (rs6313) SNPs were determined by qPCR for all the participants. The packages SPSS, maxLik and EPI-INFO were used for data analysis. The combined bruxism group reported higher scores in bruxism symptoms, mean = 32.21; anxiety symptoms, mean = 14.80; and neuroticism, mean = 3.26. Combined bruxism was associated with a higher degree of neuroticism (OR=15.0; CI 1.52–148.32) and anxiety in grade 3-moderate (OR=3.56; CI 1.27–10.03), and grade 4-severe (OR=8.40; CI 1.45–48.61), as determined using EPISODE computer software. Genotypic homogeneity analysis revealed no significant differences in allele frequency (P=0.612) among the four groups. The population was in Hardy-Weinberg equilibrium (maxLik package). In conclusion, the three instruments confirm traits of bruxism, anxiety and neuroticism in individuals with bruxism. These data were ratified when the sample was divided by genotypic homogeneity. On the other hand, there was no significant difference between the groups in the SNPs rs6313 from the HTR2A gene. PMID:29599979

  1. To Resolve or Not To Resolve, that Is the Question: The Dual-Path Model of Incongruity Resolution and Absurd Verbal Humor by fMRI.

    Science.gov (United States)

    Dai, Ru H; Chen, Hsueh-Chih; Chan, Yu C; Wu, Ching-Lin; Li, Ping; Cho, Shu L; Hu, Jon-Fan

    2017-01-01

    It is well accepted that the humor comprehension processing involves incongruity detection and resolution and then induces a feeling of amusement. However, this three-stage model of humor processing does not apply to absurd humor (so-called nonsense humor). Absurd humor contains an unresolvable incongruity but can still induce a feeling of mirth. In this study, we used functional magnetic resonance imaging (fMRI) to identify the neural mechanisms of absurd humor. Specifically, we aimed to investigate the neural substrates associated with the complete resolution of incongruity resolution humor and partial resolution of absurd humor. Based on the fMRI data, we propose a dual-path model of incongruity resolution and absurd verbal humor. According to this model, the detection and resolution for the incongruity of incongruity resolution humor activate brain regions involved in the temporo-parietal lobe (TPJ) implicated in the integration of multiple information and precuneus, likely to be involved in the ability of perspective taking. The appreciation of incongruity resolution humor activates regions the posterior cingulate cortex (PCC), implicated in autobiographic or event memory retrieval, and parahippocampal gyrus (PHG), implying the funny feeling. By contrast, the partial resolution of absurd humor elicits greater activation in the fusiform gyrus which have been implicated in word processing, inferior frontal gyrus (IFG) for the process of incongruity resolution and superior temporal gyrus (STG) for the pragmatic awareness.

  2. Lessons from Cuba for Global Precision Medicine: CYP2D6 Genotype Is Not a Robust Predictor of CYP2D6 Ultrarapid Metabolism.

    Science.gov (United States)

    Dorado, Pedro; González, Idilio; Naranjo, María Eugenia G; de Andrés, Fernando; Peñas-Lledó, Eva María; Calzadilla, Luis Ramón; LLerena, Adrián

    2017-01-01

    A long-standing question and dilemma in precision medicine is whether and to what extent genotyping or phenotyping drug metabolizing enzymes such as CYP2D6 can be used in real-life global clinical and societal settings. Although in an ideal world using both genotype and phenotype biomarkers are desirable, this is not always feasible for economic and practical reasons. Moreover, an additional barrier for clinical implementation of precision medicine is the lack of correlation between genotype and phenotype, considering that most of the current methods include only genotyping. Thus, the present study evaluated, using dextromethorphan as a phenotyping probe, the relationship between CYP2D6 phenotype and CYP2D6 genotype, especially for the ultrarapid metabolizer (UM) phenotype. We report in this study, to the best of our knowledge, the first comparative clinical pharmacogenomics study in a Cuban population sample (N = 174 healthy volunteers) and show that the CYP2D6 genotype is not a robust predictor of the CYP2D6 ultrarapid metabolizer (mUM) status in Cubans. Importantly, the ultrarapid CYP2D6 phenotype can result in a host of health outcomes, such as drug resistance associated with subtherapeutic drug concentrations, overexposure to active drug metabolites, and altered sensitivity to certain human diseases by virtue of altered metabolism of endogenous substrates of CYP2D6. Hence, phenotyping tests for CYP2D6 UMs appear to be a particular necessity for precision medicine in the Cuban population. Finally, in consideration of ethical and inclusive representation in global science, we recommend further precision medicine biomarker research and funding in support of neglected or understudied populations worldwide.

  3. Nordic research infrastructures for plant phenotyping

    Directory of Open Access Journals (Sweden)

    Kristiina Himanen

    2018-03-01

    Full Text Available Plant phenomics refers to the systematic study of plant phenotypes. Together with closely monitored, controlled climates, it provides an essential component for the integrated analysis of genotype-phenotype-environment interactions. Currently, several plant growth and phenotyping facilities are under establishment globally, and numerous facilities are already in use. Alongside the development of the research infrastructures, several national and international networks have been established to support shared use of the new methodology. In this review, an overview is given of the Nordic plant phenotyping and climate control facilities. Since many areas of phenomics such as sensor-based phenotyping, image analysis and data standards are still developing, promotion of educational and networking activities is especially important. These facilities and networks will be instrumental in tackling plant breeding and plant protection challenges. They will also provide possibilities to study wild species and their ecological interactions under changing Nordic climate conditions.

  4. Uus pianistide põlvkond : seitsmes Eesti pianistide konkurss / Arbo Valdma, Lauri Väinmaa, Toomas Vana, Age Juurikas...[jt.] ; küsitlenud Nele-Eva Steinfeld

    Index Scriptorium Estoniae

    2008-01-01

    Intervjuu noorte pianistide konkursi žürii liikmete Arbo Valdma, Lauri Väinmaa, Toomas Vana, Age Juurikase ja Leelo Kõlariga Eesti Muusika- ja Teatriakadeemia ning Eesti Klaveriõpetajate Ühingu korraldatud VII Eesti pianistide konkursist. Konkursi võitjaks tuli Eesti Muusika- ja Teatriakadeemia üliõpilane Maksim Štšura. Auhinnalistele kohtadele tulid veel Ruslan Strogij, Margus Riimaa, Andre Hinn, Jaan Ots, Johan Randvere ja Aleksandra Kamenskaja

  5. The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome.

    Science.gov (United States)

    Becerra-Muñoz, Víctor Manuel; Gómez-Doblas, Juan José; Porras-Martín, Carlos; Such-Martínez, Miguel; Crespo-Leiro, María Generosa; Barriales-Villa, Roberto; de Teresa-Galván, Eduardo; Jiménez-Navarro, Manuel; Cabrera-Bueno, Fernando

    2018-01-22

    Marfan syndrome (MFS) is a disorder of autosomal dominant inheritance, in which aortic root dilation is the main cause of morbidity and mortality. Fibrillin-1 (FBN-1) gene mutations are found in more than 90% of MFS cases. The aim of our study was to summarise variants in FBN-1 and establish the genotype-phenotype correlation, with particular interest in the onset of aortic events, in a broad population of patients with an initial clinical suspicion of MFS. This single centre prospective cohort study included all patients presenting variants in the FBN-1 gene who visited a Hereditary Aortopathy clinic between September 2010 and October 2016. The study included 90 patients with FBN-1 variants corresponding to 58 non-interrelated families. Of the 57 FBN-1 variants found, 25 (43.9%) had previously been described, 23 of which had been identified as associated with MFS, while the the remainder are described for the first time. For 84 patients (93.3%), it was possible to give a definite diagnosis of Marfan syndrome in accordance with Ghent criteria. 44 of them had missense mutations, 6 of whom had suffered an aortic event (with either prophylactic surgery for aneurysm or dissection), whereas 20 of the 35 patients with truncating mutations had suffered an event (13.6% vs. 57.1%, p importance not only in the diagnosis, but also in risk stratification and clinical management of patients with suspected MFS.

  6. Phenotypic- and Genotypic-Resistance Detection for Adaptive Resistance Management in Tetranychus urticae Koch.

    Directory of Open Access Journals (Sweden)

    Deok Ho Kwon

    Full Text Available Rapid resistance detection is necessary for the adaptive management of acaricide-resistant populations of Tetranychus urticae. Detection of phenotypic and genotypic resistance was conducted by employing residual contact vial bioassay (RCV and quantitative sequencing (QS methods, respectively. RCV was useful for detecting the acaricide resistance levels of T. urticae, particularly for on-site resistance detection; however, it was only applicable for rapid-acting acaricides (12 out of 19 tested acaricides. QS was effective for determining the frequencies of resistance alleles on a population basis, which corresponded to 12 nonsynonymous point mutations associated with target-site resistance to five types of acaricides [organophosphates (monocrotophos, pirimiphos-methyl, dimethoate and chlorpyrifos, pyrethroids (fenpropathrin and bifenthrin, abamectin, bifenazate and etoxazole]. Most field-collected mites exhibited high levels of multiple resistance, as determined by RCV and QS data, suggesting the seriousness of their current acaricide resistance status in rose cultivation areas in Korea. The correlation analyses revealed moderate to high levels of positive relationships between the resistance allele frequencies and the actual resistance levels in only five of the acaricides evaluated, which limits the general application of allele frequency as a direct indicator for estimating actual resistance levels. Nevertheless, the resistance allele frequency data alone allowed for the evaluation of the genetic resistance potential and background of test mite populations. The combined use of RCV and QS provides basic information on resistance levels, which is essential for choosing appropriate acaricides for the management of resistant T. urticae.

  7. Phenotypic and Genotypic Characteristics of Listeria monocytogenes Isolated From Dairy and Meat Products

    Directory of Open Access Journals (Sweden)

    Bahador

    2015-08-01

    Full Text Available Background Listeria monocytogenes is a foodborne pathogen and a serious threat to the public health in the world. Consumption of traditional foods such as dairy and meat products can be a major reason for relative abundance and isolation of these bacteria. Objectives The purpose of this study was to determine the phenotypic and genotypic characteristics of L. monocytogenes strains isolated from dairy and meat products. Materials and Methods A total of 317 dairy products and meat-processed samples were collected. Antibiotic susceptibility test was performed on each sample by the disk diffusion method (Kirby Bauer. Five reference loci were used for typing of L. monocytogenes strains by MLVA (Multiple Locus VNTR Analysis Technique. Results A total of 24 L. monocytogenes isolates were collected from the dairy and meat products. Resistance of isolated L. monocytogenes strains to penicillin G were 54.54% (from dairy products and 46.15% (from processed meat. Genetic relatedness of isolates were assessed by MLVA. Out of 13 different types, type 2 with 6 strains and type 3 with 4 strains, were the most common types. Conclusions MLVA analysis showed that samples obtained from different sources could have similar genetic profile. As a result, administration of penicillin in patients with listeriosis (especially pregnant women and antibiotic susceptibility test are recommended. The fast and accurate methods such as MLVA for tracking of pollution sources of L. monocytogenes are recommended during outbreaks.

  8. Developmental plasticity: re-conceiving the genotype.

    Science.gov (United States)

    Sultan, Sonia E

    2017-10-06

    In recent decades, the phenotype of an organism (i.e. its traits and behaviour) has been studied as the outcome of a developmental 'programme' coded in its genotype. This deterministic view is implicit in the Modern Synthesis approach to adaptive evolution as a sorting process among genetic variants. Studies of developmental pathways have revealed that genotypes are in fact differently expressed depending on environmental conditions. Accordingly, the genotype can be understood as a repertoire of potential developmental outcomes or norm of reaction. Reconceiving the genotype as an environmental response repertoire rather than a fixed developmental programme leads to three critical evolutionary insights. First, plastic responses to specific conditions often comprise functionally appropriate trait adjustments, resulting in an individual-level, developmental mode of adaptive variation. Second, because genotypes are differently expressed depending on the environment, the genetic diversity available to natural selection is itself environmentally contingent. Finally, environmental influences on development can extend across multiple generations via cytoplasmic and epigenetic factors transmitted to progeny individuals, altering their responses to their own, immediate environmental conditions and, in some cases, leading to inherited but non-genetic adaptations. Together, these insights suggest a more nuanced understanding of the genotype and its evolutionary role, as well as a shift in research focus to investigating the complex developmental interactions among genotypes, environments and previous environments.

  9. Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

    DEFF Research Database (Denmark)

    Bruun, Camilla S.; Jørgensen, Claus B.; Bay, Lene

    2008-01-01

    Background: A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin...... of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 and ITGAV orthologs map to SSC15. In an experimentall family (n=113), showing segregation of the trait, the candidate region was confirmed by linkage...... splicing of the ITGB6 pre-mRNA was detected. For both ITGB6 and ITGAV quantitative PCR revealed no significant difference in the expression levels in normal and affected animals. In a western blot, ITGB6 was detected in lung protein samples of all three genotypes. This result was supported by flow...

  10. Spatial Hearing with Incongruent Visual or Auditory Room Cues

    Science.gov (United States)

    Gil-Carvajal, Juan C.; Cubick, Jens; Santurette, Sébastien; Dau, Torsten

    2016-11-01

    In day-to-day life, humans usually perceive the location of sound sources as outside their heads. This externalized auditory spatial perception can be reproduced through headphones by recreating the sound pressure generated by the source at the listener’s eardrums. This requires the acoustical features of the recording environment and listener’s anatomy to be recorded at the listener’s ear canals. Although the resulting auditory images can be indistinguishable from real-world sources, their externalization may be less robust when the playback and recording environments differ. Here we tested whether a mismatch between playback and recording room reduces perceived distance, azimuthal direction, and compactness of the auditory image, and whether this is mostly due to incongruent auditory cues or to expectations generated from the visual impression of the room. Perceived distance ratings decreased significantly when collected in a more reverberant environment than the recording room, whereas azimuthal direction and compactness remained room independent. Moreover, modifying visual room-related cues had no effect on these three attributes, while incongruent auditory room-related cues between the recording and playback room did affect distance perception. Consequently, the external perception of virtual sounds depends on the degree of congruency between the acoustical features of the environment and the stimuli.

  11. Genotypic and Phenotypic Characterization of Stenotrophomonas maltophilia Strains from a Pediatric Tertiary Care Hospital in Serbia.

    Directory of Open Access Journals (Sweden)

    Haowa Madi

    Full Text Available Stenotrophomonas maltophilia is an environmental bacterium and an opportunistic pathogen usually associated with healthcare-associated infections, which has recently been recognized as a globally multi-drug resistant organism. The aim of this study was genotyping and physiological characterization of Stenotrophomonas maltophilia isolated in a large, tertiary care pediatric hospital in Belgrade, Serbia, hosting the national reference cystic fibrosis (CF center for pediatric and adult patients.We characterized 42 strains of cystic fibrosis (CF and 46 strains of non-cystic fibrosis (non-CF origin isolated from 2013 to 2015 in order to investigate their genetic relatedness and phenotypic traits. Genotyping was performed using sequencing of 16S rRNA gene, Pulse Field Gel Electrophoresis (PFGE and Multi locus sequencing typing (MLST analysis. Sensitivity to five relevant antimicrobial agents was determined, namely trimethoprim/sulfamethoxazole (TMP/SMX, chloramphenicol, ciprofloxacin, levofloxacin and tetracycline. Surface characteristics, motility, biofilm formation and adhesion to mucin were tested in all strains. Statistical approach was used to determine correlations between obtained results.Most of the isolates were not genetically related. Six new sequence types were determined. Strains were uniformly sensitive to all tested antimicrobial agents. The majority of isolates (89.8% were able to form biofilm with almost equal representation in both CF and non-CF strains. Swimming motility was observed in all strains, while none of them exhibited swarming motility. Among strains able to adhere to mucin, no differences between CF and non-CF isolates were observed.High genetic diversity among isolates implies the absence of clonal spread within the hospital. Positive correlation between motility, biofilm formation and adhesion to mucin was demonstrated. Biofilm formation and motility were more pronounced among non-CF than CF isolates.

  12. Red blood cell phenotype prevalence in blood donors who self-identify as Hispanic

    DEFF Research Database (Denmark)

    Sheppard, Chelsea A; Bolen, Nicole L; Eades, Beth

    2017-01-01

    CONCLUSIONS: Molecular genotyping platforms provide a quick, high-throughput method for identifying red blood cell units for patients on extended phenotype-matching protocols, such as those with sickle cell disease or thalassemia. Most of the antigen prevalence data reported are for non-Hispanic ......CONCLUSIONS: Molecular genotyping platforms provide a quick, high-throughput method for identifying red blood cell units for patients on extended phenotype-matching protocols, such as those with sickle cell disease or thalassemia. Most of the antigen prevalence data reported are for non...

  13. Case Management of the Gender Incongruity Syndrome in Childhood and Adolescence

    Science.gov (United States)

    Higham, Eileen

    1976-01-01

    Evidence from both normal and incongruous gender differentiation shows that a rehabilitative rather than a curative approach may be an effect form of treatment for some gender transpositions. The approach to gender disturbances is consonant with the American Psychiatric Association's discontinuance of defining all homosexuality as a disease.…

  14. Genome-wide association mapping including phenotypes from relatives without genotypes in a single-step (ssGWAS for 6-week body weight in broiler chickens

    Directory of Open Access Journals (Sweden)

    Huiyu eWang

    2014-05-01

    Full Text Available The purpose of this study was to compare results obtained from various methodologies for genome-wide association studies, when applied to real data, in terms of number and commonality of regions identified and their genetic variance explained, computational speed, and possible pitfalls in interpretations of results. Methodologies include: two iteratively reweighted single-step genomic BLUP procedures (ssGWAS1 and ssGWAS2, a single-marker model (CGWAS, and BayesB. The ssGWAS methods utilize genomic breeding values (GEBVs based on combined pedigree, genomic and phenotypic information, while CGWAS and BayesB only utilize phenotypes from genotyped animals or pseudo-phenotypes. In this study, ssGWAS was performed by converting GEBVs to SNP marker effects. Unequal variances for markers were incorporated for calculating weights into a new genomic relationship matrix. SNP weights were refined iteratively. The data was body weight at 6 weeks on 274,776 broiler chickens, of which 4553 were genotyped using a 60k SNP chip. Comparison of genomic regions was based on genetic variances explained by local SNP regions (20 SNPs. After 3 iterations, the noise was greatly reduced of ssGWAS1 and results are similar to that of CGWAS, with 4 out of the top 10 regions in common. In contrast, for BayesB, the plot was dominated by a single region explaining 23.1% of the genetic variance. This same region was found by ssGWAS1 with the same rank, but the amount of genetic variation attributed to the region was only 3%. These finding emphasize the need for caution when comparing and interpreting results from various methods, and highlight that detected associations, and strength of association, strongly depends on methodologies and details of implementations. BayesB appears to overly shrink regions to zero, while overestimating the amount of genetic variation attributed to the remaining SNP effects. The real world is most likely a compromise between methods and remains to

  15. Genetic variants influencing phenotypic variance heterogeneity.

    Science.gov (United States)

    Ek, Weronica E; Rask-Andersen, Mathias; Karlsson, Torgny; Enroth, Stefan; Gyllensten, Ulf; Johansson, Åsa

    2018-03-01

    Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene × gene or gene × environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.

  16. Higher Language Ability is Related to Angular Gyrus Activation Increase During Semantic Processing, Independent of Sentence Incongruency

    Science.gov (United States)

    Van Ettinger-Veenstra, Helene; McAllister, Anita; Lundberg, Peter; Karlsson, Thomas; Engström, Maria

    2016-01-01

    This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task—which tapped language comprehension and inference, and modulated sentence congruency—employing functional magnetic resonance imaging (fMRI). We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, there was a significant increase of activation in the inferior frontal gyrus (IFG) bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing, is opposed to what the neural efficiency hypothesis would predict. We can conclude that no evidence is found for an interaction between semantic congruency related brain activation and high-level language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation. PMID

  17. Higher language ability is related to angular gyrus activation increase during semantic processing, independent of sentence incongruency

    Directory of Open Access Journals (Sweden)

    Helene eVan Ettinger-Veenstra

    2016-03-01

    Full Text Available This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task - which tapped language comprehension and inference, and modulated sentence congruency - employing functional magnetic resonance imaging. We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, a significant increase of activation in the inferior frontal gyrus bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing is opposed to what the neural efficiency hypothesis would predict. We can conclude that there is no evidence found for an interaction between semantic congruency related brain activation and high-level language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation.

  18. A European network for the investigation of gender incongruence: The ENIGI initiative

    NARCIS (Netherlands)

    Kreukels, B.P.C.; Haraldsen, I.R.; De Cuypere, G.; Richter-Appelt, H.; Gijs, L.; Cohen-Kettenis, P.T.

    2012-01-01

    Studies on diagnostic subtypes of gender identity disorder (GID) or gender incongruence (GI), comorbidity and treatment outcome show considerable variability in results. Clinic/country specific factors may account for the contradictory results, but these factors have never been studied. This article

  19. Effect of Genetics, Environment, and Phenotype on the Metabolome of Maize Hybrids Using GC/MS and LC/MS.

    Science.gov (United States)

    Tang, Weijuan; Hazebroek, Jan; Zhong, Cathy; Harp, Teresa; Vlahakis, Chris; Baumhover, Brian; Asiago, Vincent

    2017-06-28

    We evaluated the variability of metabolites in various maize hybrids due to the effect of environment, genotype, phenotype as well as the interaction of the first two factors. We analyzed 480 forage and the same number of grain samples from 21 genetically diverse non-GM Pioneer brand maize hybrids, including some with drought tolerance and viral resistance phenotypes, grown at eight North American locations. As complementary platforms, both GC/MS and LC/MS were utilized to detect a wide diversity of metabolites. GC/MS revealed 166 and 137 metabolites in forage and grain samples, respectively, while LC/MS captured 1341 and 635 metabolites in forage and grain samples, respectively. Univariate and multivariate analyses were utilized to investigate the response of the maize metabolome to the environment, genotype, phenotype, and their interaction. Based on combined percentages from GC/MS and LC/MS datasets, the environment affected 36% to 84% of forage metabolites, while less than 7% were affected by genotype. The environment affected 12% to 90% of grain metabolites, whereas less than 27% were affected by genotype. Less than 10% and 11% of the metabolites were affected by phenotype in forage and grain, respectively. Unsupervised PCA and HCA analyses revealed similar trends, i.e., environmental effect was much stronger than genotype or phenotype effects. On the basis of comparisons of disease tolerant and disease susceptible hybrids, neither forage nor grain samples originating from different locations showed obvious phenotype effects. Our findings demonstrate that the combination of GC/MS and LC/MS based metabolite profiling followed by broad statistical analysis is an effective approach to identify the relative impact of environmental, genetic and phenotypic effects on the forage and grain composition of maize hybrids.

  20. Work-Based Social Interactions, Perceived Stress, and Workload Incongruence as Antecedents of Athletic Trainer Burnout.

    Science.gov (United States)

    DeFreese, J D; Mihalik, Jason P

    2016-01-01

    Burnout is an important psychological health concern for working professionals. Understanding how psychological stress and markers of workload contribute to athletic trainers' (ATs') perceptions of burnout is highly valuable. Both positive (social support) and negative social interactions should be considered when examining relationships among markers of ATs' health and wellbeing. To examine the potential effects of social interactions on the relationships between (1) burnout and perceived stress and (2) burnout and workload incongruence in ATs. Cross-sectional study. Participating ATs completed a computer-based survey during the fall sports season. Responding participants were ATs randomly sampled from the National Athletic Trainers' Association membership (N = 154; men = 78, women = 76; age = 36.8 ± 9.5 years). Participants completed self-report assessments (Perceived Stress Scale, Social Support Questionnaire, Positive and Negative Social Exchanges, Maslach Burnout Inventory-Human Services Survey) via a secure e-mail link. Workload incongruence was calculated by subtracting anticipated work hours from actual current work hours (6.0 ± 9.6 hours). We used hierarchical multiple regression analyses to examine hypothesized relationships among study variables. Social interactions did not affect the relationships between burnout and perceived stress or workload incongruence at the global or dimensional level. However, perceived stress (β = .47, P stress perceptions and social support drive the dimensional AT burnout experience, whereas workload incongruence (emotional exhaustion) and negative social interactions (depersonalization) were linked to specific burnout dimensions. Social interactions and markers of stress and workload should be considered when seeking to understand ATs' experiences with burnout and to design workplace interventions.

  1. Genetic Regulation of Phenotypic Plasticity and Canalisation in Yeast Growth.

    Directory of Open Access Journals (Sweden)

    Anupama Yadav

    Full Text Available The ability of a genotype to show diverse phenotypes in different environments is called phenotypic plasticity. Phenotypic plasticity helps populations to evade extinctions in novel environments, facilitates adaptation and fuels evolution. However, most studies focus on understanding the genetic basis of phenotypic regulation in specific environments. As a result, while it's evolutionary relevance is well established, genetic mechanisms regulating phenotypic plasticity and their overlap with the environment specific regulators is not well understood. Saccharomyces cerevisiae is highly sensitive to the environment, which acts as not just external stimulus but also as signalling cue for this unicellular, sessile organism. We used a previously published dataset of a biparental yeast population grown in 34 diverse environments and mapped genetic loci regulating variation in phenotypic plasticity, plasticity QTL, and compared them with environment-specific QTL. Plasticity QTL is one whose one allele exhibits high plasticity whereas the other shows a relatively canalised behaviour. We mapped phenotypic plasticity using two parameters-environmental variance, an environmental order-independent parameter and reaction norm (slope, an environmental order-dependent parameter. Our results show a partial overlap between pleiotropic QTL and plasticity QTL such that while some plasticity QTL are also pleiotropic, others have a significant effect on phenotypic plasticity without being significant in any environment independently. Furthermore, while some plasticity QTL are revealed only in specific environmental orders, we identify large effect plasticity QTL, which are order-independent such that whatever the order of the environments, one allele is always plastic and the other is canalised. Finally, we show that the environments can be divided into two categories based on the phenotypic diversity of the population within them and the two categories have

  2. Genotype phenotype correlations of cardiac beta-myosin heavy chain mutations in Indian patients with hypertrophic and dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Rai, Taranjit Singh; Ahmad, Shamim; Bahl, Ajay

    2009-01-01

    The aim of the current study was to determine the frequency of mutations in the beta-myosin heavy chain gene (MYH7) in a cohort of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and their families, and to investigate correlations between genotype and phenotype. About 130...... consecutive patients diagnosed with HCM or DCM (69 with HCM and 61 with DCM) attending the cardiology clinic of Post Graduate Institute of Medical Education and Research were screened for mutations in the MYH7 gene. The control group for genetic studies consisted of 100 healthy subjects. We report 14...... mutations in 6 probands (5 probands in HCM and 1 proband in DCM) and their family members. Out of these 6 mutations, 3 are new and are being reported for the first time. One known mutation (p.Gly716Arg) was found to be "de novo" which resulted in severe asymmetric septal hypertrophy (31 mm) and resulted...

  3. The holist tradition in twentieth century genetics. Wilhelm Johannsen's genotype concept.

    Science.gov (United States)

    Roll-Hansen, Nils

    2014-06-01

    The terms 'genotype', 'phenotype' and 'gene' originally had a different meaning from that in the Modern Synthesis. These terms were coined in the first decade of the twentieth century by the Danish plant physiologist Wilhelm Johannsen. His bean selection experiment and his theoretical analysis of the difference between genotype and phenotype were important inputs to the formation of genetics as a well-defined special discipline. This paper shows how Johannsen's holistic genotype theory provided a platform for criticism of narrowly genocentric versions of the chromosome theory of heredity that came to dominate genetics in the middle decades of the twentieth century. Johannsen came to recognize the epoch-making importance of the work done by the Drosophila group, but he continued to insist on the incompleteness of the chromosome theory. Genes of the kind that they mapped on the chromosomes could only give a partial explanation of biological heredity and evolution. © 2014 The Author. The Journal of Physiology © 2014 The Physiological Society.

  4. Validation of two conceptualizations of fragile self-esteem: Contingent high self-esteem and incongruent high self-esteem

    OpenAIRE

    Bodroža Bojana

    2014-01-01

    The aim of this research was to validate two aspects of fragile high self-esteem: a combination of contingent and high (explicit) self-esteem and a combination of high explicit and low implicit self-esteem (i.e. incongruent high self-esteem), as well as to examine the relationship between these aspects of fragile self-esteem and narcissism. No convergence was found between contingent high and incongruent high self-esteem. The result was consistent regardles...

  5. Genetic evaluation with major genes and polygenic inheritance when some animals are not genotyped using gene content multiple-trait BLUP.

    Science.gov (United States)

    Legarra, Andrés; Vitezica, Zulma G

    2015-11-17

    In pedigreed populations with a major gene segregating for a quantitative trait, it is not clear how to use pedigree, genotype and phenotype information when some individuals are not genotyped. We propose to consider gene content at the major gene as a second trait correlated to the quantitative trait, in a gene content multiple-trait best linear unbiased prediction (GCMTBLUP) method. The genetic covariance between the trait and gene content at the major gene is a function of the substitution effect of the gene. This genetic covariance can be written in a multiple-trait form that accommodates any pattern of missing values for either genotype or phenotype data. Effects of major gene alleles and the genetic covariance between genotype at the major gene and the phenotype can be estimated using standard EM-REML or Gibbs sampling. Prediction of breeding values with genotypes at the major gene can use multiple-trait BLUP software. Major genes with more than two alleles can be considered by including negative covariances between gene contents at each different allele. We simulated two scenarios: a selected and an unselected trait with heritabilities of 0.05 and 0.5, respectively. In both cases, the major gene explained half the genetic variation. Competing methods used imputed gene contents derived by the method of Gengler et al. or by iterative peeling. Imputed gene contents, in contrast to GCMTBLUP, do not consider information on the quantitative trait for genotype prediction. GCMTBLUP gave unbiased estimates of the gene effect, in contrast to the other methods, with less bias and better or equal accuracy of prediction. GCMTBLUP improved estimation of genotypes in non-genotyped individuals, in particular if these individuals had own phenotype records and the trait had a high heritability. Ignoring the major gene in genetic evaluation led to serious biases and decreased prediction accuracy. CGMTBLUP is the best linear predictor of additive genetic merit including

  6. The vigour of glasshouse roses : scion - rootstock relationships : effects of phenotypic and genotypic variation

    NARCIS (Netherlands)

    Vries, de D.P.

    1993-01-01

    Glasshouse roses commonly are combination plants, consisting of a scion variety and a rootstock of different genotypes. In this study, various environmental and genotypic factors have been investigated that influence the vigour of rootstocks and scion varieties, separately and in graft

  7. [Phenotypic diversity of toxigenic Vibrio cholerae O1 El Tor strains identified in China].

    Science.gov (United States)

    Zhao, Xuan; Zhang, Li; Li, Jie; Kan, Biao; Liang, Weili

    2014-05-01

    To understand the phenotypic diversity of toxigenic Vibrio cholerae O1 El Tor strains isolated from different provinces in China during the last 50 years. Traditional biotyping testings including susceptibility to polymyxin B, sensitivity to group IV phage, Voges-Proskauer test and haemolysis of sheep erythrocytes were conducted. Data from Biotype-specific phenotype analysis revealed that only 133 isolates carried the typical El Tor phenotypes while the other 251 isolates displayed atypical El Tor phenotypes. Combined with ctxB, rstR genotypes and phenotypic characteristics, 64 isolates were identified as typical El Tor biotype, 21 were El Tor variants that showing the typical El Tor biotype-specific phenotype but with ctxB(class). 280 isolates were defined as the hybrid groups with traits of both classical and El Tor biotypes that could be further classified into 45 groups, based on the combination of genotypes of ctxB, rstR and phenotypic characteristics. Toxigenic Vibrio cholerae O1 El Tor strains that isolated from different provinces in China displayed high phenotypic diversity. The traditional biotype traits could not be used to correctly distinguish the two different biotypes.

  8. Testing local host adaptation and phenotypic plasticity in a herbivore when alternative related host plants occur sympatrically.

    Directory of Open Access Journals (Sweden)

    Lorena Ruiz-Montoya

    Full Text Available Host race formation in phytophagous insects can be an early stage of adaptive speciation. However, the evolution of phenotypic plasticity in host use is another possible outcome. Using a reciprocal transplant experiment we tested the hypothesis of local adaptation in the aphid Brevicoryne brassicae. Aphid genotypes derived from two sympatric host plants, Brassica oleracea and B. campestris, were assessed in order to measure the extent of phenotypic plasticity in morphological and life history traits in relation to the host plants. We obtained an index of phenotypic plasticity for each genotype. Morphological variation of aphids was summarized by principal components analysis. Significant effects of recipient host on morphological variation and life history traits (establishment, age at first reproduction, number of nymphs, and intrinsic growth rate were detected. We did not detected genotype × host plant interaction; in general the genotypes developed better on B. campestris, independent of the host plant species from which they were collected. Therefore, there was no evidence to suggest local adaptation. Regarding plasticity, significant differences among genotypes in the index of plasticity were detected. Furthermore, significant selection on PC1 (general aphid body size on B. campestris, and on PC1 and PC2 (body length relative to body size on B. oleracea was detected. The elevation of the reaction norm of PC1 and the slope of the reaction norm for PC2 (i.e., plasticity were under directional selection. Thus, host plant species constitute distinct selective environments for B. brassicae. Aphid genotypes expressed different phenotypes in response to the host plant with low or nil fitness costs. Phenotypic plasticity and gene flow limits natural selection for host specialization promoting the maintenance of genetic variation in host exploitation.

  9. Incongruity Humor in Language and Beyond: From Bergson to Digitally Enhanced Worlds

    NARCIS (Netherlands)

    Nijholt, Antinus

    2015-01-01

    Humour research is often about verbal humour. Language allows us to play with words and with its syntactic, semantic and pragmatic aspects. It provides us with building blocks that can be composed in unusual ways, introducing ambiguities, confusion, inappropriate language use, and incongruities.

  10. Infra-red thermography for high throughput field phenotyping in Solanum tuberosum.

    Directory of Open Access Journals (Sweden)

    Ankush Prashar

    Full Text Available The rapid development of genomic technology has made high throughput genotyping widely accessible but the associated high throughput phenotyping is now the major limiting factor in genetic analysis of traits. This paper evaluates the use of thermal imaging for the high throughput field phenotyping of Solanum tuberosum for differences in stomatal behaviour. A large multi-replicated trial of a potato mapping population was used to investigate the consistency in genotypic rankings across different trials and across measurements made at different times of day and on different days. The results confirmed a high degree of consistency between the genotypic rankings based on relative canopy temperature on different occasions. Genotype discrimination was enhanced both through normalising data by expressing genotype temperatures as differences from image means and through the enhanced replication obtained by using overlapping images. A Monte Carlo simulation approach was used to confirm the magnitude of genotypic differences that it is possible to discriminate. The results showed a clear negative association between canopy temperature and final tuber yield for this population, when grown under ample moisture supply. We have therefore established infrared thermography as an easy, rapid and non-destructive screening method for evaluating large population trials for genetic analysis. We also envisage this approach as having great potential for evaluating plant response to stress under field conditions.

  11. Empirical Statistical Power for Testing Multilocus Genotypic Effects under Unbalanced Designs Using a Gibbs Sampler

    Directory of Open Access Journals (Sweden)

    Chaeyoung Lee

    2012-11-01

    Full Text Available Epistasis that may explain a large portion of the phenotypic variation for complex economic traits of animals has been ignored in many genetic association studies. A Baysian method was introduced to draw inferences about multilocus genotypic effects based on their marginal posterior distributions by a Gibbs sampler. A simulation study was conducted to provide statistical powers under various unbalanced designs by using this method. Data were simulated by combined designs of number of loci, within genotype variance, and sample size in unbalanced designs with or without null combined genotype cells. Mean empirical statistical power was estimated for testing posterior mean estimate of combined genotype effect. A practical example for obtaining empirical statistical power estimates with a given sample size was provided under unbalanced designs. The empirical statistical powers would be useful for determining an optimal design when interactive associations of multiple loci with complex phenotypes were examined.

  12. Estabilidade fenotípica de genótipos de algodoeiro no Estado do Mato Grosso Phenotypic stability in cotton genotypes in Mato Grosso State, Brazil

    Directory of Open Access Journals (Sweden)

    Eulália Soler Sobreira Hoogerheide

    2007-05-01

    Full Text Available Foram avaliados oito genótipos de algodoeiro herbáceo, sendo três linhagens e cinco cultivares, com o objetivo de estimar a adaptabilidade e estabilidade fenotípica para o caráter produtividade de algodão em caroço, pelo método Eberhart e Russell. Foram conduzidos 12 experimentos em 11 locais no Estado do Mato Grosso, sob um delineamento de blocos ao acaso com oito repetições, no ano agrícola 2000/2001. Praticamente todos os genótipos apresentaram coeficiente de determinação acima de 85%, exceto Delta Opal. As estimativas de adaptabilidade indicam que todos os genótipos apresentaram adaptação ampla (b i = 1. Quanto à estabilidade, os genótipos CNPA ITA 90, BRS Antares, CNPA 96-124, CNPA 96-283 e BRS Aroeira revelaram-se estáveis (S²d i= 0. Os melhores genótipos, caracterizados pela maior produtividade, estabilidade e adaptabilidade ampla foram CNPA ITA 90, BRS Aroeira e CNPA 96-124.Eight cotton genotypes, three lines and five cultivars, were evaluated for estimation of phenotypic adaptability and stability parameters relative to cotton yield using the method proposed by Eberhart and Russell. Twelve yield trials, in randomized complete blocks, comprising eight replications, were carried out in 11 locations of the Mato Grosso State, during the 2000/2001 crop season. All the genotypes showed determination coefficient above of 85%, except Delta Opal. For the estimates of adaptability, all the genotypes presented broad adaptation (b i = 1. The genotypes CNPA ITA 90, BRS Antares, CNPA 96-124, CNPA 96-283 and BRS Aroeira showing hight stability (S²d i= 0. The best genotypes, characterized by higher yield, stability and broad adaptability, were CNPA ITA 90, BRS Aroeira and CNPA 96-124.

  13. Unisexual and heterosexual meiotic reproduction generate aneuploidy and phenotypic diversity de novo in the yeast Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Min Ni

    2013-09-01

    Full Text Available Aneuploidy is known to be deleterious and underlies several common human diseases, including cancer and genetic disorders such as trisomy 21 in Down's syndrome. In contrast, aneuploidy can also be advantageous and in fungi confers antifungal drug resistance and enables rapid adaptive evolution. We report here that sexual reproduction generates phenotypic and genotypic diversity in the human pathogenic yeast Cryptococcus neoformans, which is globally distributed and commonly infects individuals with compromised immunity, such as HIV/AIDS patients, causing life-threatening meningoencephalitis. C. neoformans has a defined a-α opposite sexual cycle; however, >99% of isolates are of the α mating type. Interestingly, α cells can undergo α-α unisexual reproduction, even involving genotypically identical cells. A central question is: Why would cells mate with themselves given that sex is costly and typically serves to admix preexisting genetic diversity from genetically divergent parents? In this study, we demonstrate that α-α unisexual reproduction frequently generates phenotypic diversity, and the majority of these variant progeny are aneuploid. Aneuploidy is responsible for the observed phenotypic changes, as chromosome loss restoring euploidy results in a wild-type phenotype. Other genetic changes, including diploidization, chromosome length polymorphisms, SNPs, and indels, were also generated. Phenotypic/genotypic changes were not observed following asexual mitotic reproduction. Aneuploidy was also detected in progeny from a-α opposite-sex congenic mating; thus, both homothallic and heterothallic sexual reproduction can generate phenotypic diversity de novo. Our study suggests that the ability to undergo unisexual reproduction may be an evolutionary strategy for eukaryotic microbial pathogens, enabling de novo genotypic and phenotypic plasticity and facilitating rapid adaptation to novel environments.

  14. Revisiting Robustness and Evolvability: Evolution in Weighted Genotype Spaces

    Science.gov (United States)

    Partha, Raghavendran; Raman, Karthik

    2014-01-01

    Robustness and evolvability are highly intertwined properties of biological systems. The relationship between these properties determines how biological systems are able to withstand mutations and show variation in response to them. Computational studies have explored the relationship between these two properties using neutral networks of RNA sequences (genotype) and their secondary structures (phenotype) as a model system. However, these studies have assumed every mutation to a sequence to be equally likely; the differences in the likelihood of the occurrence of various mutations, and the consequence of probabilistic nature of the mutations in such a system have previously been ignored. Associating probabilities to mutations essentially results in the weighting of genotype space. We here perform a comparative analysis of weighted and unweighted neutral networks of RNA sequences, and subsequently explore the relationship between robustness and evolvability. We show that assuming an equal likelihood for all mutations (as in an unweighted network), underestimates robustness and overestimates evolvability of a system. In spite of discarding this assumption, we observe that a negative correlation between sequence (genotype) robustness and sequence evolvability persists, and also that structure (phenotype) robustness promotes structure evolvability, as observed in earlier studies using unweighted networks. We also study the effects of base composition bias on robustness and evolvability. Particularly, we explore the association between robustness and evolvability in a sequence space that is AU-rich – sequences with an AU content of 80% or higher, compared to a normal (unbiased) sequence space. We find that evolvability of both sequences and structures in an AU-rich space is lesser compared to the normal space, and robustness higher. We also observe that AU-rich populations evolving on neutral networks of phenotypes, can access less phenotypic variation compared to

  15. The phenotypic variance gradient - a novel concept.

    Science.gov (United States)

    Pertoldi, Cino; Bundgaard, Jørgen; Loeschcke, Volker; Barker, James Stuart Flinton

    2014-11-01

    Evolutionary ecologists commonly use reaction norms, which show the range of phenotypes produced by a set of genotypes exposed to different environments, to quantify the degree of phenotypic variance and the magnitude of plasticity of morphometric and life-history traits. Significant differences among the values of the slopes of the reaction norms are interpreted as significant differences in phenotypic plasticity, whereas significant differences among phenotypic variances (variance or coefficient of variation) are interpreted as differences in the degree of developmental instability or canalization. We highlight some potential problems with this approach to quantifying phenotypic variance and suggest a novel and more informative way to plot reaction norms: namely "a plot of log (variance) on the y-axis versus log (mean) on the x-axis, with a reference line added". This approach gives an immediate impression of how the degree of phenotypic variance varies across an environmental gradient, taking into account the consequences of the scaling effect of the variance with the mean. The evolutionary implications of the variation in the degree of phenotypic variance, which we call a "phenotypic variance gradient", are discussed together with its potential interactions with variation in the degree of phenotypic plasticity and canalization.

  16. [Software for performing a global phenotypic and genotypic nutritional assessment].

    Science.gov (United States)

    García de Diego, L; Cuervo, M; Martínez, J A

    2013-01-01

    The nutritional assessment of a patient needs the simultaneous managing a extensive information and a great number of databases, as both aspects of the process of nutrition and the clinical situation of the patient are analyzed. The introduction of computers in the nutritional area constitutes an extraordinary advance in the administration of nutrition information, providing a complete assessment of nutritional aspects in a quick and easy way. To develop a computer program that can be used as a tool for assessing the nutritional status of the patient, the education of clinical staff, for epidemiological studies and for educational purposes. Based on a computer program which assists the health specialist to perform a full nutritional evaluation of the patient, through the registration and assessment of the phenotypic and genotypic features. The application provides nutritional prognosis based on anthropometric and biochemical parameters, images of states of malnutrition, questionnaires to characterize diseases, diagnostic criteria, identification of alleles associated with the development of specific metabolic illnesses and questionnaires of quality of life, for a custom actuation. The program includes, as part of the nutritional assessment of the patient, food intake analysis, design of diets and promotion of physical activity, introducing food frequency questionnaires, dietary recalls, healthy eating indexes, model diets, fitness tests, and recommendations, recalls and questionnaires of physical activity. A computer program performed under Java Swing, using SQLite database and some external libraries such as JfreeChart for plotting graphs. This brand new designed software is composed of five blocks categorized into ten modules named: Patients, Anthropometry, Clinical History, Biochemistry, Dietary History, Diagnostic (with genetic make up), Quality of life, Physical activity, Energy expenditure and Diets. Each module has a specific function which evaluates a

  17. Highly prevalent LIPH founder mutations causing autosomal recessive woolly hair/hypotrichosis in Japan and the genotype/phenotype correlations.

    Directory of Open Access Journals (Sweden)

    Kana Tanahashi

    Full Text Available Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH, and the 2 missense mutations c.736T>A (p.Cys246Ser and c.742C>A (p.His248Asn are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016, and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024. In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH.

  18. Phenotypic and Genotypic Comparison of Epidemic and Non-Epidemic Strains of Pseudomonas aeruginosa from Individuals with Cystic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Jessica Duong

    Full Text Available Epidemic strains of Pseudomonas aeruginosa have been found worldwide among the cystic fibrosis (CF patient population. Using pulse-field gel electrophoresis, the Prairie Epidemic Strain (PES has recently been found in one-third of patients attending the Calgary Adult CF Clinic in Canada. Using multi-locus sequence typing, PES isolates from unrelated patients were found to consistently have ST192. Though most patients acquired PES prior to enrolling in the clinic, some patients were observed to experience strain replacement upon transitioning to the clinic whereby local non-epidemic P. aeruginosa isolates were displaced by PES. Here we genotypically and phenotypically compared PES to other P. aeruginosa epidemic strains (OES found around the world as well as local non-epidemic CF P. aeruginosa isolates in order to characterize PES. Since some epidemic strains are associated with worse clinical outcomes, we assessed the pathogenic potential of PES to determine if these isolates are virulent, shared properties with OES, and if its phenotypic properties may offer a competitive advantage in displacing local non-epidemic isolates during strain replacement. As such, we conducted a comparative analysis using fourteen phenotypic traits, including virulence factor production, biofilm formation, planktonic growth, mucoidy, and antibiotic susceptibility to characterize PES, OES, and local non-epidemic isolates. We observed that PES and OES could be differentiated from local non-epidemic isolates based on biofilm growth with PES isolates being more mucoid. Pairwise comparisons indicated that PES produced significantly higher levels of proteases and formed better biofilms than OES but were more susceptible to antibiotic treatment. Amongst five patients experiencing strain replacement, we found that super-infecting PES produced lower levels of proteases and elastases but were more resistant to antibiotics compared to the displaced non-epidemic isolates. This

  19. Blood genotyping for improved outcomes in chronic transfusion patients: current and future perspectives

    Directory of Open Access Journals (Sweden)

    Kutner JM

    2014-09-01

    Full Text Available Jose Mauro Kutner,1 Mariza Mota,1 Fabiana Conti,1 Lilian Castilho1,2 1Hemotherapy and Cell Therapy Department, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; 2Hemocentro Unicamp, Campinas, SP, Brazil Abstract: Blood transfusions are life sustaining in chronically transfused patients. However, certain complications, such as alloimmunization to red blood cells, can create challenges in the management of those patients. Routine phenotyping of blood recipients and the use of phenotype-matched blood units for transfusion have been useful to lower the occurrence of red cell alloantibodies in chronically transfused individuals. Nevertheless, extensive phenotyping is expensive, laborious, and cannot be performed in certain situations. The molecular understanding of blood groups has enabled the design of assays that may be used to better guide matched red blood cell transfusions. This review summarizes key findings related to red cell alloimmunization, the already identified and potential future benefits of blood group genotyping, and how molecular typing is being incorporated in the blood bank's routine to improve clinical and long-term outcomes in chronically transfused patients. Keywords: blood group genotyping, chronically transfused patients, platelet genotyping, RBC alloimmunization

  20. Phenotypic and genetic diversification of Pseudanabaena spp. (cyanobacteria)

    NARCIS (Netherlands)

    Acinas, S.G.; Haverkamp, T.H.A.; Huisman, J.; Stal, L.J.

    2009-01-01

    Pseudanabaena species are poorly known filamentous bloom-forming cyanobacteria closely related to Limnothrix. We isolated 28 Pseudanabaena strains from the Baltic Sea (BS) and the Albufera de Valencia (AV; Spain). By combining phenotypic and genotypic approaches, the phylogeny, diversity and

  1. A genotype-first approach identifies an intellectual disability-overweight syndrome caused by PHIP haploinsufficiency

    DEFF Research Database (Denmark)

    Jansen, Sandra; Hoischen, Alexander; Coe, Bradley P

    2018-01-01

    Genotype-first combined with reverse phenotyping has shown to be a powerful tool in human genetics, especially in the era of next generation sequencing. This combines the identification of individuals with mutations in the same gene and linking these to consistent (endo)phenotypes to establish di...

  2. Phenotypic and molecular characterizations of Yersinia pestis isolates from Kazakhstan and adjacent regions.

    Science.gov (United States)

    Lowell, Jennifer L; Zhansarina, Aigul; Yockey, Brook; Meka-Mechenko, Tatyana; Stybayeva, Gulnaz; Atshabar, Bakyt; Nekrassova, Larissa; Tashmetov, Rinat; Kenghebaeva, Kuralai; Chu, May C; Kosoy, Michael; Antolin, Michael F; Gage, Kenneth L

    2007-01-01

    Recent interest in characterizing infectious agents associated with bioterrorism has resulted in the development of effective pathogen genotyping systems, but this information is rarely combined with phenotypic data. Yersinia pestis, the aetiological agent of plague, has been well defined genotypically on local and worldwide scales using multi-locus variable number tandem repeat analysis (MLVA), with emphasis on evolutionary patterns using old isolate collections from countries where Y. pestis has existed the longest. Worldwide MLVA studies are largely based on isolates that have been in long-term laboratory culture and storage, or on field material from parts of the world where Y. pestis has potentially circulated in nature for thousands of years. Diversity in these isolates suggests that they may no longer represent the wild-type organism phenotypically, including the possibility of altered pathogenicity. This study focused on the phenotypic and genotypic properties of 48 Y. pestis isolates collected from 10 plague foci in and bordering Kazakhstan. Phenotypic characterization was based on diagnostic tests typically performed in reference laboratories working with Y. pestis. MLVA was used to define the genotypic relationships between the central-Asian isolates and a group of North American isolates, and to examine Kazakh Y. pestis diversity according to predefined plague foci and on an intermediate geographical scale. Phenotypic properties revealed that a large portion of this collection lacks one or more plasmids necessary to complete the blocked flea/mammal transmission cycle, has lost Congo red binding capabilities (Pgm-), or both. MLVA analysis classified isolates into previously identified biovars, and in some cases groups of isolates collected within the same plague focus formed a clade. Overall, MLVA did not distinguish unique phylogeographical groups of Y. pestis isolates as defined by plague foci and indicated higher genetic diversity among older biovars.

  3. Impact of Information Incongruity and Authors Group Membership on Assimilation and Accommodation

    Science.gov (United States)

    Moskaliuk, J.; Matschke, C.

    2018-01-01

    Learning is a complex process that can be differentiated into assimilation and accommodation. The Internet enables both types of learning through collaboration. There is, however, little research investigating the specific impact of social and information incongruity on assimilation and accommodation. The current research investigates how the…

  4. Environmental influences on the Indo-Pacific octocoral Isis hippuris Linnaeus 1758 (Alcyonacea: Isididae): genetic fixation or phenotypic plasticity?

    Science.gov (United States)

    Rowley, Sonia J; Pochon, Xavier; Watling, Les

    2015-01-01

    As conspicuous modular components of benthic marine habitats, gorgonian (sea fan) octocorals have perplexed taxonomists for centuries through their shear diversity, particularly throughout the Indo-Pacific. Phenotypic incongruence within and between seemingly unitary lineages across contrasting environments can provide the raw material to investigate processes of disruptive selection. Two distinct phenotypes of the Isidid Isis hippurisLinnaeus, 1758 partition between differing reef environments: long-branched bushy colonies on degraded reefs, and short-branched multi/planar colonies on healthy reefs within the Wakatobi Marine National Park (WMNP), Indonesia. Multivariate analyses reveal phenotypic traits between morphotypes were likely integrated primarily at the colony level with increased polyp density and consistently smaller sclerite dimensions at the degraded site. Sediment load and turbidity, hence light availability, primarily influenced phenotypic differences between the two sites. This distinct morphological dissimilarity between the two sites is a reliable indicator of reef health; selection primarily acting on colony morphology, porosity through branching structure, as well as sclerite diversity and size. ITS2 sequence and predicted RNA secondary structure further revealed intraspecific variation between I. hippuris morphotypes relative to such environments (ΦST = 0.7683, P < 0.001). This evidence suggests-but does not confirm-that I. hippuris morphotypes within the WMNP are two separate species; however, to what extent and taxonomic assignment requires further investigation across its full geographic distribution. Incongruence between colonies present in the WMNP with tenuously described Isis alternatives (Isis reticulataNutting, 1910, Isis minorbrachyblastaZou, Huang & Wang, 1991), questions the validity of such assignments. Furthermore, phylogenetic analyses confirm early taxonomic suggestion that the characteristic jointed axis of the Isididae is in

  5. Environmental influences on the Indo–Pacific octocoral Isis hippuris Linnaeus 1758 (Alcyonacea: Isididae): genetic fixation or phenotypic plasticity?

    Science.gov (United States)

    Pochon, Xavier; Watling, Les

    2015-01-01

    As conspicuous modular components of benthic marine habitats, gorgonian (sea fan) octocorals have perplexed taxonomists for centuries through their shear diversity, particularly throughout the Indo–Pacific. Phenotypic incongruence within and between seemingly unitary lineages across contrasting environments can provide the raw material to investigate processes of disruptive selection. Two distinct phenotypes of the Isidid Isis hippuris Linnaeus, 1758 partition between differing reef environments: long-branched bushy colonies on degraded reefs, and short-branched multi/planar colonies on healthy reefs within the Wakatobi Marine National Park (WMNP), Indonesia. Multivariate analyses reveal phenotypic traits between morphotypes were likely integrated primarily at the colony level with increased polyp density and consistently smaller sclerite dimensions at the degraded site. Sediment load and turbidity, hence light availability, primarily influenced phenotypic differences between the two sites. This distinct morphological dissimilarity between the two sites is a reliable indicator of reef health; selection primarily acting on colony morphology, porosity through branching structure, as well as sclerite diversity and size. ITS2 sequence and predicted RNA secondary structure further revealed intraspecific variation between I. hippuris morphotypes relative to such environments (ΦST = 0.7683, P < 0.001). This evidence suggests—but does not confirm—that I. hippuris morphotypes within the WMNP are two separate species; however, to what extent and taxonomic assignment requires further investigation across its full geographic distribution. Incongruence between colonies present in the WMNP with tenuously described Isis alternatives (Isis reticulata Nutting, 1910, Isis minorbrachyblasta Zou, Huang & Wang, 1991), questions the validity of such assignments. Furthermore, phylogenetic analyses confirm early taxonomic suggestion that the characteristic jointed axis of the

  6. Environmental influences on the Indo–Pacific octocoral Isis hippuris Linnaeus 1758 (Alcyonacea: Isididae: genetic fixation or phenotypic plasticity?

    Directory of Open Access Journals (Sweden)

    Sonia J. Rowley

    2015-08-01

    Full Text Available As conspicuous modular components of benthic marine habitats, gorgonian (sea fan octocorals have perplexed taxonomists for centuries through their shear diversity, particularly throughout the Indo–Pacific. Phenotypic incongruence within and between seemingly unitary lineages across contrasting environments can provide the raw material to investigate processes of disruptive selection. Two distinct phenotypes of the Isidid Isis hippuris Linnaeus, 1758 partition between differing reef environments: long-branched bushy colonies on degraded reefs, and short-branched multi/planar colonies on healthy reefs within the Wakatobi Marine National Park (WMNP, Indonesia. Multivariate analyses reveal phenotypic traits between morphotypes were likely integrated primarily at the colony level with increased polyp density and consistently smaller sclerite dimensions at the degraded site. Sediment load and turbidity, hence light availability, primarily influenced phenotypic differences between the two sites. This distinct morphological dissimilarity between the two sites is a reliable indicator of reef health; selection primarily acting on colony morphology, porosity through branching structure, as well as sclerite diversity and size. ITS2 sequence and predicted RNA secondary structure further revealed intraspecific variation between I. hippuris morphotypes relative to such environments (ΦST = 0.7683, P < 0.001. This evidence suggests—but does not confirm—that I. hippuris morphotypes within the WMNP are two separate species; however, to what extent and taxonomic assignment requires further investigation across its full geographic distribution. Incongruence between colonies present in the WMNP with tenuously described Isis alternatives (Isis reticulata Nutting, 1910, Isis minorbrachyblasta Zou, Huang & Wang, 1991, questions the validity of such assignments. Furthermore, phylogenetic analyses confirm early taxonomic suggestion that the characteristic jointed

  7. Improving accuracy of genomic prediction in Brangus cattle by adding animals with imputed low-density SNP genotypes.

    Science.gov (United States)

    Lopes, F B; Wu, X-L; Li, H; Xu, J; Perkins, T; Genho, J; Ferretti, R; Tait, R G; Bauck, S; Rosa, G J M

    2018-02-01

    Reliable genomic prediction of breeding values for quantitative traits requires the availability of sufficient number of animals with genotypes and phenotypes in the training set. As of 31 October 2016, there were 3,797 Brangus animals with genotypes and phenotypes. These Brangus animals were genotyped using different commercial SNP chips. Of them, the largest group consisted of 1,535 animals genotyped by the GGP-LDV4 SNP chip. The remaining 2,262 genotypes were imputed to the SNP content of the GGP-LDV4 chip, so that the number of animals available for training the genomic prediction models was more than doubled. The present study showed that the pooling of animals with both original or imputed 40K SNP genotypes substantially increased genomic prediction accuracies on the ten traits. By supplementing imputed genotypes, the relative gains in genomic prediction accuracies on estimated breeding values (EBV) were from 12.60% to 31.27%, and the relative gain in genomic prediction accuracies on de-regressed EBV was slightly small (i.e. 0.87%-18.75%). The present study also compared the performance of five genomic prediction models and two cross-validation methods. The five genomic models predicted EBV and de-regressed EBV of the ten traits similarly well. Of the two cross-validation methods, leave-one-out cross-validation maximized the number of animals at the stage of training for genomic prediction. Genomic prediction accuracy (GPA) on the ten quantitative traits was validated in 1,106 newly genotyped Brangus animals based on the SNP effects estimated in the previous set of 3,797 Brangus animals, and they were slightly lower than GPA in the original data. The present study was the first to leverage currently available genotype and phenotype resources in order to harness genomic prediction in Brangus beef cattle. © 2018 Blackwell Verlag GmbH.

  8. A priori assumptions about characters as a cause of incongruence between molecular and morphological hypotheses of primate interrelationships.

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    Tornow, Matthew A; Skelton, Randall R

    2012-01-01

    When molecules and morphology produce incongruent hypotheses of primate interrelationships, the data are typically viewed as incompatible, and molecular hypotheses are often considered to be better indicators of phylogenetic history. However, it has been demonstrated that the choice of which taxa to include in cladistic analysis as well as assumptions about character weighting, character state transformation order, and outgroup choice all influence hypotheses of relationships and may positively influence tree topology, so that relationships between extant taxa are consistent with those found using molecular data. Thus, the source of incongruence between morphological and molecular trees may lie not in the morphological data themselves but in assumptions surrounding the ways characters evolve and their impact on cladistic analysis. In this study, we investigate the role that assumptions about character polarity and transformation order play in creating incongruence between primate phylogenies based on morphological data and those supported by multiple lines of molecular data. By releasing constraints imposed on published morphological analyses of primates from disparate clades and subjecting those data to parsimony analysis, we test the hypothesis that incongruence between morphology and molecules results from inherent flaws in morphological data. To quantify the difference between incongruent trees, we introduce a new method called branch slide distance (BSD). BSD mitigates many of the limitations attributed to other tree comparison methods, thus allowing for a more accurate measure of topological similarity. We find that releasing a priori constraints on character behavior often produces trees that are consistent with molecular trees. Case studies are presented that illustrate how congruence between molecules and unconstrained morphological data may provide insight into issues of polarity, transformation order, homology, and homoplasy.

  9. Strategy and model building in the fourth dimension: a null model for genotype x age interaction as a Gaussian stationary stochastic process.

    Science.gov (United States)

    Diego, Vincent P; Almasy, Laura; Dyer, Thomas D; Soler, Júlia M P; Blangero, John

    2003-12-31

    Using univariate and multivariate variance components linkage analysis methods, we studied possible genotype x age interaction in cardiovascular phenotypes related to the aging process from the Framingham Heart Study. We found evidence for genotype x age interaction for fasting glucose and systolic blood pressure. There is polygenic genotype x age interaction for fasting glucose and systolic blood pressure and quantitative trait locus x age interaction for a linkage signal for systolic blood pressure phenotypes located on chromosome 17 at 67 cM.

  10. Elevated temperature is more effective than elevated [CO2 ] in exposing genotypic variation in Telopea speciosissima growth plasticity: implications for woody plant populations under climate change.

    Science.gov (United States)

    Huang, Guomin; Rymer, Paul D; Duan, Honglang; Smith, Renee A; Tissue, David T

    2015-10-01

    Intraspecific variation in phenotypic plasticity is a critical determinant of plant species capacity to cope with climate change. A long-standing hypothesis states that greater levels of environmental variability will select for genotypes with greater phenotypic plasticity. However, few studies have examined how genotypes of woody species originating from contrasting environments respond to multiple climate change factors. Here, we investigated the main and interactive effects of elevated [CO2 ] (CE ) and elevated temperature (TE ) on growth and physiology of Coastal (warmer, less variable temperature environment) and Upland (cooler, more variable temperature environment) genotypes of an Australian woody species Telopea speciosissima. Both genotypes were positively responsive to CE (35% and 29% increase in whole-plant dry mass and leaf area, respectively), but only the Coastal genotype exhibited positive growth responses to TE . We found that the Coastal genotype exhibited greater growth response to TE (47% and 85% increase in whole-plant dry mass and leaf area, respectively) when compared with the Upland genotype (no change in dry mass or leaf area). No intraspecific variation in physiological plasticity was detected under CE or TE , and the interactive effects of CE and TE on intraspecific variation in phenotypic plasticity were also largely absent. Overall, TE was a more effective climate factor than CE in exposing genotypic variation in our woody species. Our results contradict the paradigm that genotypes from more variable climates will exhibit greater phenotypic plasticity in future climate regimes. © 2015 John Wiley & Sons Ltd.

  11. Genotypic and phenotypic characterization of multidrug resistant Salmonella Typhimurium and Salmonella Kentucky strains recovered from chicken carcasses.

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    Rizwana Tasmin

    Full Text Available Salmonella Typhimurium is the leading cause of human non-typhoidal gastroenteritis in the US. S. Kentucky is one the most commonly recovered serovars from commercially processed poultry carcasses. This study compared the genotypic and phenotypic properties of two Salmonella enterica strains Typhimurium (ST221_31B and Kentucky (SK222_32B recovered from commercially processed chicken carcasses using whole genome sequencing, phenotype characterizations and an intracellular killing assay. Illumina MiSeq platform was used for sequencing of two Salmonella genomes. Phylogenetic analysis employing homologous alignment of a 1,185 non-duplicated protein-coding gene in the Salmonella core genome demonstrated fully resolved bifurcating patterns with varying levels of diversity that separated ST221_31B and SK222_32B genomes into distinct monophyletic serovar clades. Single nucleotide polymorphism (SNP analysis identified 2,432 (ST19 SNPs within 13 Typhimurium genomes including ST221_31B representing Sequence Type ST19 and 650 (ST152 SNPs were detected within 13 Kentucky genomes including SK222_32B representing Sequence Type ST152. In addition to serovar-specific conserved coding sequences, the genomes of ST221_31B and SK222_32B harbor several genomic regions with significant genetic differences. These included phage and phage-like elements, carbon utilization or transport operons, fimbriae operons, putative membrane associated protein-encoding genes, antibiotic resistance genes, siderophore operons, and numerous hypothetical protein-encoding genes. Phenotype microarray results demonstrated that ST221_31B is capable of utilizing certain carbon compounds more efficiently as compared to SK222_3B; namely, 1,2-propanediol, M-inositol, L-threonine, α-D-lactose, D-tagatose, adonitol, formic acid, acetoacetic acid, and L-tartaric acid. ST221_31B survived for 48 h in macrophages, while SK222_32B was mostly eliminated. Further, a 3-fold growth of ST221_31B was

  12. A Causal Inference Model Explains Perception of the McGurk Effect and Other Incongruent Audiovisual Speech.

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    John F Magnotti

    2017-02-01

    Full Text Available Audiovisual speech integration combines information from auditory speech (talker's voice and visual speech (talker's mouth movements to improve perceptual accuracy. However, if the auditory and visual speech emanate from different talkers, integration decreases accuracy. Therefore, a key step in audiovisual speech perception is deciding whether auditory and visual speech have the same source, a process known as causal inference. A well-known illusion, the McGurk Effect, consists of incongruent audiovisual syllables, such as auditory "ba" + visual "ga" (AbaVga, that are integrated to produce a fused percept ("da". This illusion raises two fundamental questions: first, given the incongruence between the auditory and visual syllables in the McGurk stimulus, why are they integrated; and second, why does the McGurk effect not occur for other, very similar syllables (e.g., AgaVba. We describe a simplified model of causal inference in multisensory speech perception (CIMS that predicts the perception of arbitrary combinations of auditory and visual speech. We