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Sample records for molecular genetics approach

  1. A molecular-genetic approach to studying source-sink interactions in Arabidopsis thalian. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, S. I.

    2000-06-01

    This is a final report describing the results of the research funded by the DOE Energy Biosciences Program grant entitled ''A Molecular-Genetic Approach to Studying Source-Sink Interactions in Arabidiopsis thaliana''.

  2. [Molecular genetic bases of adaptation processes and approaches to their analysis].

    Science.gov (United States)

    Salmenkova, E A

    2013-01-01

    Great interest in studying the molecular genetic bases of the adaptation processes is explained by their importance in understanding evolutionary changes, in the development ofintraspecific and interspecific genetic diversity, and in the creation of approaches and programs for maintaining and restoring the population. The article examines the sources and conditions for generating adaptive genetic variability and contribution of neutral and adaptive genetic variability to the population structure of the species; methods for identifying the adaptive genetic variability on the genome level are also described. Considerable attention is paid to the potential of new technologies of genome analysis, including next-generation sequencing and some accompanying methods. In conclusion, the important role of the joint use of genomics and proteomics approaches in understanding the molecular genetic bases of adaptation is emphasized.

  3. Genetic approaches to the molecular/neuronal mechanisms underlying learning and memory in the mouse.

    Science.gov (United States)

    Nakajima, Akira; Tang, Ya-Ping

    2005-09-01

    Learning and memory is an essential component of human intelligence. To understand its underlying molecular and neuronal mechanisms is currently an extensive focus in the field of cognitive neuroscience. We have employed advanced mouse genetic approaches to analyze the molecular and neuronal bases for learning and memory, and our results showed that brain region-specific genetic manipulations (including transgenic and knockout), inducible/reversible knockout, genetic/chemical kinase inactivation, and neuronal-based genetic approach are very powerful tools for studying the involvements of various molecules or neuronal substrates in the processes of learning and memory. Studies using these techniques may eventually lead to the understanding of how new information is acquired and how learned information is memorized in the brain.

  4. Molecular Population Genetics

    Science.gov (United States)

    Casillas, Sònia; Barbadilla, Antonio

    2017-01-01

    Molecular population genetics aims to explain genetic variation and molecular evolution from population genetics principles. The field was born 50 years ago with the first measures of genetic variation in allozyme loci, continued with the nucleotide sequencing era, and is currently in the era of population genomics. During this period, molecular population genetics has been revolutionized by progress in data acquisition and theoretical developments. The conceptual elegance of the neutral theory of molecular evolution or the footprint carved by natural selection on the patterns of genetic variation are two examples of the vast number of inspiring findings of population genetics research. Since the inception of the field, Drosophila has been the prominent model species: molecular variation in populations was first described in Drosophila and most of the population genetics hypotheses were tested in Drosophila species. In this review, we describe the main concepts, methods, and landmarks of molecular population genetics, using the Drosophila model as a reference. We describe the different genetic data sets made available by advances in molecular technologies, and the theoretical developments fostered by these data. Finally, we review the results and new insights provided by the population genomics approach, and conclude by enumerating challenges and new lines of inquiry posed by increasingly large population scale sequence data. PMID:28270526

  5. Molecular Population Genetics.

    Science.gov (United States)

    Casillas, Sònia; Barbadilla, Antonio

    2017-03-01

    Molecular population genetics aims to explain genetic variation and molecular evolution from population genetics principles. The field was born 50 years ago with the first measures of genetic variation in allozyme loci, continued with the nucleotide sequencing era, and is currently in the era of population genomics. During this period, molecular population genetics has been revolutionized by progress in data acquisition and theoretical developments. The conceptual elegance of the neutral theory of molecular evolution or the footprint carved by natural selection on the patterns of genetic variation are two examples of the vast number of inspiring findings of population genetics research. Since the inception of the field, Drosophila has been the prominent model species: molecular variation in populations was first described in Drosophila and most of the population genetics hypotheses were tested in Drosophila species. In this review, we describe the main concepts, methods, and landmarks of molecular population genetics, using the Drosophila model as a reference. We describe the different genetic data sets made available by advances in molecular technologies, and the theoretical developments fostered by these data. Finally, we review the results and new insights provided by the population genomics approach, and conclude by enumerating challenges and new lines of inquiry posed by increasingly large population scale sequence data. Copyright © 2017 Casillas and Barbadilla.

  6. Molecular Genetic Approaches to Human Diseases Involving Mental Retardation.

    Science.gov (United States)

    Latt, Samuel A.; And Others

    1984-01-01

    Recombinant DNA techniques provide new approaches to the diagnosis and analysis of inherited human diseases associated with mental retardation, such as Lesch-Nyhan syndrome, phenylketonauria, the Fragile X syndrome, Down syndrome, and those associated with deletions or duplications of subchromosomal regions. (Author/CL)

  7. [Modern evolutional developmental biology: mechanical and molecular genetic or phenotypic approaches?].

    Science.gov (United States)

    Vorob'eva, É I

    2010-01-01

    Heightened interest in the evolutionary problems of developmental biology in the 1980s was due to the success of molecular genetics and disappointment in the synthetic theory of evolution, where the chapters of embryology and developmental biology seem to have been left out. Modern evo-devo, which turned out to be antipodean to the methodology of the synthetic theory of evolution, propagandized in the development of evolutionary problems only the mechanical and molecular genetic approach to the evolution of ontogenesis, based on cellular and intercellular interactions. The phonotypical approach to the evaluation of evolutionary occurrences in ontogenesis, which aids in the joining of the genetic and epigenetic levels of research, the theory of natural selection, the nomogenetic conception, and the problem of the wholeness of the organism in onto- and phylogenesis may be against this. The phenotypic approach to ontogenesis is methodologically the most perspective for evolutionary developmental biology.

  8. Understanding the complex etiologies of developmental disorders: behavioral and molecular genetic approaches.

    Science.gov (United States)

    Willcutt, Erik G; Pennington, Bruce F; Duncan, Laramie; Smith, Shelley D; Keenan, Janice M; Wadsworth, Sally; Defries, John C; Olson, Richard K

    2010-09-01

    This article has 2 primary goals. First, a brief tutorial on behavioral and molecular genetic methods is provided for readers without extensive training in these areas. To illustrate the application of these approaches to developmental disorders, etiologically informative studies of reading disability (RD), math disability (MD), and attention-deficit hyperactivity disorder (ADHD) are then reviewed. Implications of the results for these specific disorders and for developmental disabilities as a whole are discussed, and novel directions for future research are highlighted. Previous family and twin studies of RD, MD, and ADHD are reviewed systematically, and the extensive molecular genetic literatures on each disorder are summarized. To illustrate 4 novel extensions of these etiologically informative approaches, new data are presented from the Colorado Learning Disabilities Research Center, an ongoing twin study of the etiology of RD, ADHD, MD, and related disorders. RD, MD, and ADHD are familial and heritable, and co-occur more frequently than expected by chance. Molecular genetic studies suggest that all 3 disorders have complex etiologies, with multiple genetic and environmental risk factors each contributing to overall risk for each disorder. Neuropsychological analyses indicate that the 3 disorders are each associated with multiple neuropsychological weaknesses, and initial evidence suggests that comorbidity between the 3 disorders is due to common genetic risk factors that lead to slow processing speed.

  9. Genetic and Molecular Approaches to Study Neuronal Migration in the Developing Cerebral Cortex.

    Science.gov (United States)

    Dudok, Jacobus J; Leonards, Pim E G; Wijnholds, Jan

    2017-05-05

    The migration of neuronal cells in the developing cerebral cortex is essential for proper development of the brain and brain networks. Disturbances in this process, due to genetic abnormalities or exogenous factors, leads to aberrant brain formation, brain network formation, and brain function. In the last decade, there has been extensive research in the field of neuronal migration. In this review, we describe different methods and approaches to assess and study neuronal migration in the developing cerebral cortex. First, we discuss several genetic methods, techniques and genetic models that have been used to study neuronal migration in the developing cortex. Second, we describe several molecular approaches to study aberrant neuronal migration in the cortex which can be used to elucidate the underlying mechanisms of neuronal migration. Finally, we describe model systems to investigate and assess the potential toxicity effect of prenatal exposure to environmental chemicals on proper brain formation and neuronal migration.

  10. Endometriosis: A New Cellular and Molecular Genetic Approach for understanding the pathogenesis and evolutivity

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    Jean eBouquet De Joliniere

    2014-05-01

    Full Text Available ABSTRACT. Endometriosis is a benign disease with high prevalence in women of reproductive age estimated between 10 and 15% and is associated with considerable morbidity. Its etiology and pathogenesis are controversial but it is believed to involve multiple genetic, environmental, immunological, angiogenic and endocrine processes. Altered expressions of growth factors, cytokines, adhesion molecules, matrix metalloproteinases, and enzymes for estrogen synthesis and metabolism have been frequently observed in this condition. The possibility of genetic basis of endometriosis is demonstrated in studies of familial disease, in which the incidence of endometriosis is higher for first-degree relatives of probands as compared to controls. This review describes mainly the cellular, cytochemical, cytogenetic and molecular genetic features of endometriotic lesions and cultured endometriotic cells. In attempts to identify candidate gene (s involved in the pathogenesis of endometriosis, a tissue-based approaches including conventional cytogenetics (RHG-banding, loss of heterozygosity (LOH and Comparative Genomic Hybridization (CGH were employed. In addition to the karyotipic anomalies, consistent chromosome instability was confirmed by CGH and Fluorescence in Situ Hybridization (FISH. The nature and significance of the molecular genetic aberrations in relation to the locations and function of oncogenes and tumor supressor genes will be discussed. At last, a possible pathogenic role of embryonic duct remnants was observed in 7 female foetal reproductive tract in endometriosis and may induce a discussion about the begining of ovarian tumors and malignant proliferations

  11. Developmental psychopathology in an era of molecular genetics and neuroimaging: A developmental neurogenetics approach.

    Science.gov (United States)

    Hyde, Luke W

    2015-05-01

    The emerging field of neurogenetics seeks to model the complex pathways from gene to brain to behavior. This field has focused on imaging genetics techniques that examine how variability in common genetic polymorphisms predict differences in brain structure and function. These studies are informed by other complimentary techniques (e.g., animal models and multimodal imaging) and have recently begun to incorporate the environment through examination of Imaging Gene × Environment interactions. Though neurogenetics has the potential to inform our understanding of the development of psychopathology, there has been little integration between principles of neurogenetics and developmental psychopathology. The paper describes a neurogenetics and Imaging Gene × Environment approach and how these approaches have been usefully applied to the study of psychopathology. Six tenets of developmental psychopathology (the structure of phenotypes, the importance of exploring mechanisms, the conditional nature of risk, the complexity of multilevel pathways, the role of development, and the importance of who is studied) are identified, and how these principles can further neurogenetics applications to understanding the development of psychopathology is discussed. A major issue of this piece is how neurogenetics and current imaging and molecular genetics approaches can be incorporated into developmental psychopathology perspectives with a goal of providing models for better understanding pathways from among genes, environments, the brain, and behavior.

  12. Molecular approach to genetic and epigenetic pathogenesisof early-onset colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Colorectal cancer (CRC) is the third most frequent cancertype and the incidence of this disease is increasinggradually per year in individuals younger than 50 yearsold. The current knowledge is that early-onset CRC(EOCRC) cases are heterogeneous population thatincludes both hereditary and sporadic forms of theCRC. Although EOCRC cases have some distinguishingclinical and pathological features than elder age CRC,the molecular mechanism underlying the EOCRC ispoorly clarified. Given the significance of CRC in theworld of medicine, the present review will focus on therecent knowledge in the molecular basis of genetic andepigenetic mechanism of the hereditary forms of EOCRC,which includes Lynch syndrome, Familial CRC type X,Familial adenomatous polyposis, MutYH-associatedpolyposis, Juvenile polyposis syndrome, Peutz-JeghersSyndrome and sporadic forms of EOCRC. Recent findingsabout molecular genetics and epigenetic basis of EOCRCgave rise to new alternative therapy protocols. Althoughexact diagnosis of these cases still remains complicated,the present review paves way for better predictions andcontributes to more accurate diagnostic and therapeuticstrategies into clinical approach.

  13. Unambiguous molecular detections with multiple genetic approach for the complicated chromosome 22q11 deletion syndrome

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    Lin Lung-Huang

    2009-02-01

    Full Text Available Abstract Background Chromosome 22q11 deletion syndrome (22q11DS causes a developmental disorder during the embryonic stage, usually because of hemizygous deletions. The clinical pictures of patients with 22q11DS vary because of polymorphisms: on average, approximately 93% of affected individuals have a de novo deletion of 22q11, and the rest have inherited the same deletion from a parent. Methods using multiple genetic markers are thus important for the accurate detection of these microdeletions. Methods We studied 12 babies suspected to carry 22q11DS and 18 age-matched healthy controls from unrelated Taiwanese families. We determined genomic variance using microarray-based comparative genomic hybridization (array-CGH, quantitative real-time polymerase chain reaction (qPCR and multiplex ligation-dependent probe amplification (MLPA. Results Changes in genomic copy number were significantly associated with clinical manifestations for the classical criteria of 22q11DS using MPLA and qPCR (p Conclusion Both MLPA and qPCR could produce a clearly defined range of deleted genomic DNA, whereas there must be a deleted genome that is not distinguishable using MLPA. These data demonstrate that such multiple genetic approaches are necessary for the unambiguous molecular detection of these types of complicated genomic syndromes.

  14. Genetic approaches for studying myiasis-causing flies: molecular markers and mitochondrial genomics.

    Science.gov (United States)

    de Azeredo-Espin, Ana Maria Lima; Lessinger, Ana Cláudia

    2006-01-01

    "Myiasis-causing flies" is a generic term that includes species from numerous dipteran families, mainly Calliphoridae and Oestridae, of which blowflies, screwworm flies and botflies are among the most important. This group of flies is characterized by the ability of their larvae to develop in animal flesh. When the host is a live vertebrate, such parasitism by dipterous larvae is known as primary myiasis. Myiasis-causing flies can be classified as saprophagous (free-living species), facultative or obligate parasites. Many of these flies are of great medical and veterinary importance in Brazil because of their role as key livestock insect-pests and vectors of pathogens, in addition to being considered important legal evidence in forensic entomology. The characterization of myiasis-causing flies using molecular markers to study mtDNA (by RFLP) and nuclear DNA (by RAPD and microsatellite) has been used to identify the evolutionary mechanisms responsible for specific patterns of genetic variability. These approaches have been successfully used to analyze the population structures of the New World screwworm fly Cochliomyia hominivorax and the botfly Dermatobia hominis. In this review, various aspects of the organization, evolution and potential applications of the mitochondrial genome of myiasis-causing flies in Brazil, and the analysis of nuclear markers in genetic studies of populations, are discussed.

  15. Molecular and genetics approaches for investigation of phospholipase D role in plant cells

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    Volotovsky I. D.

    2010-04-01

    Full Text Available The review is devoted to the analysis of publications ñoncerning the role of phospholipase D (PLD in regulation of metabolism in plant cells. Analysis of molecular and genetic studies suggest that PLD is an important component of various hormonal and stress signaling pathways

  16. Genetic characterization, species differentiation and detection of Fasciola spp. by molecular approaches

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    Li Hai-Long

    2011-06-01

    Full Text Available Abstract Liver flukes belonging to the genus Fasciola are among the causes of foodborne diseases of parasitic etiology. These parasites cause significant public health problems and substantial economic losses to the livestock industry. Therefore, it is important to definitively characterize the Fasciola species. Current phenotypic techniques fail to reflect the full extent of the diversity of Fasciola spp. In this respect, the use of molecular techniques to identify and differentiate Fasciola spp. offer considerable advantages. The advent of a variety of molecular genetic techniques also provides a powerful method to elucidate many aspects of Fasciola biology, epidemiology, and genetics. However, the discriminatory power of these molecular methods varies, as does the speed and ease of performance and cost. There is a need for the development of new methods to identify the mechanisms underpinning the origin and maintenance of genetic variation within and among Fasciola populations. The increasing application of the current and new methods will yield a much improved understanding of Fasciola epidemiology and evolution as well as more effective means of parasite control. Herein, we provide an overview of the molecular techniques that are being used for the genetic characterization, detection and genotyping of Fasciola spp..

  17. Molecular genetic approach to human meningioma: loss of genes on chromosome 22

    Energy Technology Data Exchange (ETDEWEB)

    Seizinger, B.R.; De La Monte, S.; Atkins, L.; Gusella, J.F.; Martuza, R.L.

    1987-08-01

    A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, the authors propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system.

  18. Genetic and molecular bases of yield-associated traits: a translational biology approach between rice and wheat.

    Science.gov (United States)

    Valluru, Ravi; Reynolds, Matthew P; Salse, Jerome

    2014-07-01

    Transferring the knowledge bases between related species may assist in enlarging the yield potential of crop plants. Being cereals, rice and wheat share a high level of gene conservation; however, they differ at metabolic levels as a part of the environmental adaptation resulting in different yield capacities. This review focuses on the current understanding of genetic and molecular regulation of yield-associated traits in both crop species, highlights the similarities and differences and presents the putative knowledge gaps. We focus on the traits associated with phenology, photosynthesis, and assimilate partitioning and lodging resistance; the most important drivers of yield potential. Currently, there are large knowledge gaps in the genetic and molecular control of such major biological processes that can be filled in a translational biology approach in transferring genomics and genetics informations between rice and wheat.

  19. Identifying human disease genes: advances in molecular genetics and computational approaches.

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    Bakhtiar, S M; Ali, A; Baig, S M; Barh, D; Miyoshi, A; Azevedo, V

    2014-07-04

    The human genome project is one of the significant achievements that have provided detailed insight into our genetic legacy. During the last two decades, biomedical investigations have gathered a considerable body of evidence by detecting more than 2000 disease genes. Despite the imperative advances in the genetic understanding of various diseases, the pathogenesis of many others remains obscure. With recent advances, the laborious methodologies used to identify DNA variations are replaced by direct sequencing of genomic DNA to detect genetic changes. The ability to perform such studies depends equally on the development of high-throughput and economical genotyping methods. Currently, basically for every disease whose origen is still unknown, genetic approaches are available which could be pedigree-dependent or -independent with the capacity to elucidate fundamental disease mechanisms. Computer algorithms and programs for linkage analysis have formed the foundation for many disease gene detection projects, similarly databases of clinical findings have been widely used to support diagnostic decisions in dysmorphology and general human disease. For every disease type, genome sequence variations, particularly single nucleotide polymorphisms are mapped by comparing the genetic makeup of case and control groups. Methods that predict the effects of polymorphisms on protein stability are useful for the identification of possible disease associations, whereas structural effects can be assessed using methods to predict stability changes in proteins using sequence and/or structural information.

  20. Primer on molecular genetics

    Energy Technology Data Exchange (ETDEWEB)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  1. A molecular genetic approach for traceability of the source milk in cheese

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    E. Pieragostini

    2011-03-01

    Full Text Available The valorisation of typical cheeses meets the needs of preserving the local country culture and tradition as well of guaranteeing consumer health by the control of all the steps of production (herd, milk quality, cheese making technology. Among the variability factors significantly affecting cheese peculiarity, biodiversity plays an important role (Gandini et al., 1996; Pieragostini et al., 2002. The possibility of identifying or tracing the primary product, mainly the origin breed, by the use of biologic markers, is an important goal for the safeguard and valorisation of national goat cheese. In this field great interest is paid to milk protein genetic polymorphism. A first study was carried out in order to investigate the possibility of tracing the source milk in dairy products. In particular, the use of molecular techniques for the detection of casein polymorphisms.........

  2. Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease.

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    Hoban, Megan D; Orkin, Stuart H; Bauer, Daniel E

    2016-02-18

    Effective medical management for sickle cell disease (SCD) remains elusive. As a prevalent and severe monogenic disorder, SCD has been long considered a logical candidate for gene therapy. Significant progress has been made in moving toward this goal. These efforts have provided substantial insight into the natural regulation of the globin genes and illuminated challenges for genetic manipulation of the hematopoietic system. The initial γ-retroviral vectors, next-generation lentiviral vectors, and novel genome engineering and gene regulation approaches each share the goal of preventing erythrocyte sickling. After years of preclinical studies, several clinical trials for SCD gene therapies are now open. This review focuses on progress made toward achieving gene therapy, the current state of the field, consideration of factors that may determine clinical success, and prospects for future development.

  3. Mouse Aortic Ring Assay: A New Approach of the Molecular Genetics of Angiogenesis

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    Masson Véronique

    2002-01-01

    Full Text Available Angiogenesis, a key step in many physiological and pathological processes, involves proteolysis of the extracellular matrix. To study the role of two enzymatic families, serine-proteases and matrix metalloproteases in angiogenesis, we have adapted to the mouse, the aortic ring assay initially developed in the rat. The use of deficient mice allowed us to demonstrate that PAI-1 is essential for angiogenesis while the absence of an MMP, MMP-11, did not affect vessel sprouting. We report here that this model is attractive to elucidate the cellular and molecular mechanisms of angiogenesis, to identify, characterise or screen "pro- or anti-angiogenic agents that could be used for the treatment of angiogenesis-dependent diseases. Approaches include using recombinant proteins, synthetic molecules and adenovirus-mediated gene transfer.

  4. Evolving Molecular Genetics of Glioblastoma

    Institute of Scientific and Technical Information of China (English)

    Qiu-Ju Li; Jin-Quan Cai; Cheng-Yin Liu

    2016-01-01

    Objective: To summary the recent advances in molecular research of glioblastoma (GBM) and current trends in personalized therapy of this disease.Data Sources: Data cited in this review were obtained mainly from PubMed in English up to 2015, with keywords "molecular", "genetics", "GBM", "isocitrate dehydrogenase", "telomerase reverse transcriptase", "epidermal growth factor receptor", "PTPRZ1-MET", and "clinical treatment".Study Selection: Articles regarding the morphological pathology of GBM, the epidemiology of GBM, genetic alteration of GBM, and the development of treatment for GBM patients were identified, retrieved, and reviewed.Results: There is a large amount of data supporting the view that these recurrent genetic aberrations occur in a specific context of cellular origin, co-oncogenic hits and are present in distinct patient populations.Primary and secondary GBMs are distinct disease entities that affect different age groups of patients and develop through distinct genetic aberrations.These differences are important, especially because they may affect sensitivity to radio-and chemo-therapy and should thus be considered in the identification of targets for novel therapeutic approaches.Conclusion: This review highlights the molecular and genetic alterations of GBM, indicating that they are of potential value in the diagnosis and treatment for patients with GBM.

  5. Molecular genetics of ependymoma

    Institute of Scientific and Technical Information of China (English)

    Yuan Yao; Stephen C.Mack; Michael D.Taylor

    2011-01-01

    Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical burden.Its mechanism of pathogenesis,reliable prognostic indicators,and effective treatments other than surgical resection have all remained elusive.Until recently,cytogenetic techniques,and lack of cell lines and animal models.Ependymoma heterogeneity,which manifests as variations in tumor location,patient age,histological grade,and clinical behavior,together with the observation of a balanced genomic profile in up to 50% of cases,presents additional challenges in understanding the development and progression of this disease.Despite these difficulties,we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic (copy number) and transcriptome profiling platforms.Genetic characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of origin.This review summarizes our current knowledge in the molecular genetics of ependymoma and proposesfuture research directions necessary to further advance this field.

  6. State-of-the-art molecular approaches to elucidate the genetic inventory of spacecraft surfaces and associated environments

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    Venkateswaran, Kasthuri; La Duc, Myron; James; Osman, Shariff; Andersen, Gary; Huber, Julie; Sogin, Mitchell

    The scientific literature teems with reports of microbial diversity from seemingly every niche imaginable, from deep within Antarctic ice to ocean-floor hydrothermal systems. The fields of applied microbiology and molecular biology have made enormous technological advancements over the past two decades, from the development of PCR-amplification of DNA to the forensic detection of what many consider to be "miniscule" amounts of blood and other such biomatter. Despite advances in the specificity and sensitivity of molecular biological technologies, the abilities to efficiently sample and extract nucleic acids from low-biomass matrices, and accurately describe the true microbial diversity housed in such samples, remain significant challenges. To minimize the likelihood of forward contamination of Mars, Europa, or any other extraterrestrial environment, significant effort is invested to ensure that environments in which spacecraft are assembled are maintained appropriately and kept as free of microbial contamination as possible. To this end, routine analyses, largely based on spore-counts and cultivation-based approaches, are carried out to validate the cleanliness of such surfaces. However, only by applying the most efficient and accurate molecular means of analysis can conclusions be drawn on the actual bioburden and microbial diversity associated with these environments. For any measure of sample-derived bioburden, a large portion is inevitably lost in sampling. Furthermore, a 90 Since the surface area of a spacecraft is fixed, it is not possible to simply increase sample size to improve yield. It is therefore critical to assure that current methods of purification of biomolecules sampled from this limited resource are 1) optimal for achieving total yield of biota present and 2) conserving of the true microbial diversity of the sampled environment. This project focuses on the development of capabilities to effectively and efficiently generate a genetic inventory of

  7. [Molecular-genetic approaches to diagnosis and intraspecific typing of causative agents of glanders and melioidosis].

    Science.gov (United States)

    Antonov, V A; Iliukhin, V I

    2005-01-01

    Pathogenic Burkholderia--Burkholderia mallei and Burkholderia pseudomallei--are causative agents of glanders and melioidosis, severe infectious diseases of man and animals. They are regarded as potential agents of bioterrorism. The existing bacteriological and immunological methods of identification of B. mallei and B. pseudomallei are not efficient enough for the rapid diagnosis and typing of strains. Described in the paper are molecular methods of detection of the agents by PCR, hybridization and strain typing made on the basis of bacterial total cell protein profiles, RAPD, ribotyping as well as of plasmid and DNA microrestriction analyses.

  8. Rice allergenic protein and molecular-genetic approach for hypoallergenic rice.

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    Nakamura, R; Matsuda, T

    1996-08-01

    Allergenic proteins with a molecular mass of about 14 to 16 kDa were isolated from a rice salt-soluble fraction based on the reactivity with IgE antibodies from patients allergic to rice. cDNA clones encoding these allergenic proteins were isolated from a cDNA library of maturing rice seeds, and the deduced amino acid sequences showed considerable similarity to wheat and barley alpha-amylase/trypsin inhibitors, which have recently been identified as major allergens associated with baker's asthma. An antisense RNA strategy was applied to repress the allergen gene expression in maturing rice seeds. Immunoblotting and ELISA analyses of the seeds using a monoclonal antibody to a 16-kDa allergen showed that allergen content of seeds from several transgenic rice plants was markedly lower than that of the seeds from parental wild type rice.

  9. Classical and molecular genetic mapping

    Science.gov (United States)

    A brief history of classical genetic mapping in soybean [Glycine max (L.) Merr.] is described. Detailed descriptions are given of the development of molecular genetic linkage maps based upon various types of DNA markers Like many plant and animal species, the first molecular map of soybean was bas...

  10. Development of enhanced radioprotectors - Biochemical and molecular genetical approaches on the radioprotective mechanism of natural products

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Hee; Lee, Eun Ju; Hong, Jung A [Kyunghee University, Seoul (Korea)

    2000-04-01

    To identify radio-protective agent candidate among medicinal plants and to elucidate the mechanism of action of the candidate material by using modern biochemical and molecular biological methods, we screened radio-protective activity among 48 medicinal plants. Seven samples showed above 20% protective activities against oxidative cell damage: Euryale ferox, Glycyrrhiza uralensis, Salvia miltiorrhiza, Eucomia ulmoides, Paeonia suffruticosa, Spirodela polyrrhiza, and Nelumbo nucifera. We also screened for oxidative stress sensitizing activity among other 51 medicinal plants. Among those samples, 11 samples showed good sensitizing effect; Melia azedarach, Agastache rugosa, Catalpa ovata, Prunus persica, Sinomenium acutum, Pulsatilla koreana, Oldenlandia diffusa, Anthriscus sylvestris, Schizandra chinensis, Gleditsia sinensis, and Cridium officinale. We also reported the radio-protective effect of DTT. The treatment of DTT increased cell survival after gamma-irradiation, decreased in the frequencies of micronucleus, and reduction in DNA fragmentation and apoptotic cells. Induction of apoptosis after UV-C irradiation was revealed by the changes in the relative cell death, increase in the relative amount of apoptotic cells, and the induction of DNA fragmentation. 165 refs., 9 figs., 8 tabs. (Author)

  11. Genetic dissection of sexual orientation: behavioral, cellular, and molecular approaches in Drosophila melanogaster.

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    Yamamoto, D; Ito, H; Fujitani, K

    1996-10-01

    Insertional mutagenesis using P-element vectors yielded several independent mutations that cause male homosexuality in Drosophila melanogaster. Subsequent analyses revealed that all of these insertions were located at the same chromosomal division, 91B, where one of the inversion breakpoints responsible for the bisexual phenotype of the fruitless (fru) mutant has been mapped. In addition to the altered sexual orientation, the fru mutants displayed a range of defects in the formation of a male-specific muscle, the muscle of Lawrence. Since the male-specific formation of this muscle was dependent solely on the sex of the innervating nerve and not on the sex of the muscle itself, the primary site of action of the fru gene should be in the neural cells. satori, one of the P-insertion alleles of fru which we isolated, carried the lacZ gene of E. coli as a reporter, and beta-galactosidase expression was found in a subset of brain cells including those in the antennal lobe in the satori mutant. Targeted expression of a sex determination gene, transformer (tra), was used to produce chromosomally male flies with certain feminized glomeruli in the antennal lobe. Such sexually mosaic flies courted not only females but also males when the DM2, DA3 and DA4 glomeruli were feminized, indicating that these substructures in the antennal lobe may be involved in the determination of the sexual orientation of flies. Molecular cloning and analyses of the genomic and complementary DNAs indicated that transcription of the fru locus yields several different transcripts, one of which encodes a putative transcription regulator with a BTB domain and two zinc finger motifs. In the 5' non-coding region, three putative Transformer binding sites were identified. It appears plausible therefore that the fru gene is one of the elements in the sex determination cascade that controls sexual fates of certain neuronal cells. Improper sex determination in these neural cells may lead to altered sexual

  12. Molecular genetics made simple

    Directory of Open Access Journals (Sweden)

    Heba Sh. Kassem

    2012-07-01

    Full Text Available Genetics have undoubtedly become an integral part of biomedical science and clinical practice, with important implications in deciphering disease pathogenesis and progression, identifying diagnostic and prognostic markers, as well as designing better targeted treatments. The exponential growth of our understanding of different genetic concepts is paralleled by a growing list of genetic terminology that can easily intimidate the unfamiliar reader. Rendering genetics incomprehensible to the clinician however, defeats the very essence of genetic research: its utilization for combating disease and improving quality of life. Herein we attempt to correct this notion by presenting the basic genetic concepts along with their usefulness in the cardiology clinic. Bringing genetics closer to the clinician will enable its harmonious incorporation into clinical care, thus not only restoring our perception of its simple and elegant nature, but importantly ensuring the maximal benefit for our patients.

  13. Molecular Genetics in Glaucoma

    OpenAIRE

    Liu, Yutao; Allingham, R Rand

    2011-01-01

    Glaucoma is a family of diseases whose pathology is defined by the progressive loss of retinal ganglion cells. Clinically, glaucoma presents as a distinctive optic neuropathy with associated visual field loss. Primary open-angle glaucoma (POAG), chronic angle closure glaucoma (ACG), and exfoliation glaucoma (XFG) are the most prevalent forms of glaucoma globally and are the most common causes of glaucoma-related blindness worldwide. A host of genetic and environmental factors contribute to gl...

  14. Molecular genetics of cataract.

    Directory of Open Access Journals (Sweden)

    Kannabiran Chitra

    2000-01-01

    Full Text Available Studies on hereditary congenital cataracts have led to the identification of genes involved in formation of these cataracts. Knowledge of the structure and function of a particular gene and the effect of disease-associated mutations on its function are providing insights into the mechanisms of cataract. Identification of the disease gene requires both the relevant clinical data as well as genetic data on the entire pedigree in which the disease is found to occur. Genes for hereditary cataract have been mapped by genetic linkage analysis, in which one examines the inheritance pattern of DNA markers throughout the genome in all individuals of the pedigree, and compares those with the inheritance of the disease. Cosegregation of a set of markers with disease implies that the disease gene is present at the same chromosomal location as those markers. The genes so far identified for hereditary cataracts in both humans and animal models encode structural lens proteins, gap junction proteins, membrane proteins and regulatory proteins involved in lens development. Understanding of the mechanisms of hereditary cataract may also help us understand the manner in which environmental and nutritional factors act on the lens to promote opacification.

  15. Using a Molecular-Genetic Approach to Investigate Bacterial Physiology in a Continuous, Research-Based, Semester-Long Laboratory for Undergraduates

    Directory of Open Access Journals (Sweden)

    Jeremiah Foster Ault

    2011-09-01

    Full Text Available Designing investigative laboratory exercises that encourage critical thinking, problem solving, and independent thought for upper-division biology courses is a difficult but worthwhile task. In an effort to do so, we developed a semester-long, continuous, research-based investigative laboratory that integrates numerous genetic and molecular biology methods into the investigation of a bacterial physiological process. In this lab, students use random Tn5 transposon mutagenesis to create prodigiosin pigment mutants in the bacterium, Serratia marcescens. This is followed by phenotypic characterization, cloning, and sequencing the Tn insertion site to identify genes involved in pigment biosynthesis. During this lab, students gain ample experience performing basic lab techniques while learning about — and applying — methods for elucidating gene function. The approach to the laboratory and the outcomes are intimately integrated into the teaching of many fundamental physiological processes underlying prodigiosin production in bacteria. The result is a cohesive course that integrates the theory and application of molecular genetic techniques with the study of bacterial physiology. Assessments of student learning objectives demonstrated that students greatly improved their understanding of both physiological processes and the genetic techniques used to investigate them. In addition, students felt that this semester-long exercise provided the necessary laboratory experience they needed and desired in preparation for careers in molecular biology, microbiology, and biochemistry.

  16. Using a molecular-genetic approach to investigate bacterial physiology in a continuous, research-based, semester-long laboratory for undergraduates.

    Science.gov (United States)

    Ault, Jeremiah Foster; Renfro, Betsey Marie; White, Andrea Kirsten

    2011-01-01

    Designing investigative laboratory exercises that encourage critical thinking, problem solving, and independent thought for upper-division biology courses is a difficult but worthwhile task. In an effort to do so, we developed a semester-long, continuous, research-based investigative laboratory that integrates numerous genetic and molecular biology methods into the investigation of a bacterial physiological process. In this lab, students use random Tn5 transposon mutagenesis to create prodigiosin pigment mutants in the bacterium, Serratia marcescens. This is followed by phenotypic characterization, cloning, and sequencing the Tn insertion site to identify genes involved in pigment biosynthesis. During this lab, students gain ample experience performing basic lab techniques while learning about - and applying - methods for elucidating gene function. The approach to the laboratory and the outcomes are intimately integrated into the teaching of many fundamental physiological processes underlying prodigiosin production in bacteria. The result is a cohesive course that integrates the theory and application of molecular genetic techniques with the study of bacterial physiology. Assessments of student learning objectives demonstrated that students greatly improved their understanding of both physiological processes and the genetic techniques used to investigate them. In addition, students felt that this semester-long exercise provided the necessary laboratory experience they needed and desired in preparation for careers in molecular biology, microbiology, and biochemistry.

  17. Cell-Type-Specific Differentiation and Molecular Profiles in Skin Transplantation: Implication of Medical Approach for Genetic Skin Diseases

    Directory of Open Access Journals (Sweden)

    Noritaka Oyama

    2011-01-01

    Full Text Available Skin is highly accessible and valuable organ, which holds promise to accelerate the understanding of future medical innovation in association with skin transplantation, engineering, and wound healing. In skin transplantation biology, multistage and multifocal damages occur in both grafted donor and perilesional host skin and need to be repaired properly for the engraftment and maintenance of characteristic skin architecture. These local events are more unlikely to be regulated by the host immunity, because human skin transplantation has accomplished the donor skin engraftment onto the immunocompromised or immunosuppressive animals. Recent studies have emerged the importance of α-smooth muscle actin- (SMA- positive myofibroblasts, via stage- and cell-specific contribution of TGFβ, PDGF, ET-1, CCN-2 signalling pathways, and mastocyte-derived mediators (e.g., histamine and tryptase, for the functional reorganisation of the grafted skin. Moreover, particular cell lineages from bone marrow (BM cells have been shown to harbour the diferentiation capacity into multiple skin cell phenotypes, including epidermal keratinocytes and dermal endothelial cells and pericytes, undercontrolled by chemokines or cytokines. From a dermatological viewpoint, we review the recent update of cell-type- and molecular-specific action associated with reconstitution of the grafted skin and also focus on the novel application of BM transplantation medicine in genetic skin diseases.

  18. Integrating evolutionary and molecular genetics of aging.

    Science.gov (United States)

    Flatt, Thomas; Schmidt, Paul S

    2009-10-01

    Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940s and 1950s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980s and 1990s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging.

  19. Dictyostelium discoideum: Molecular approaches to cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Spudich, J.A.

    1987-01-01

    The central point of this book is to present Dictyostelium as a valuable eukaryotic organism for those interested in molecular studies that require a combined biochemical, structural, and genetic approach. The book is not meant to be a comprehensive compilation of all methods involving Dictyostelium, but instead is a selective set of chapters that demonstrates the utility of the organism for molecular approaches to interesting cell biological problems.

  20. Pragmatic approaches to genetic screening.

    NARCIS (Netherlands)

    Mallia, P.; Have, H.A.M.J. ten

    2005-01-01

    Pragmatic approaches to genetic testing are discussed and appraised. Whilst there are various schools of pragmatism, the Deweyan approach seems to be the most appreciated in bioethics as it allows a historical approach indebted to Hegel. This in turn allows the pragmatist to specify and balance prin

  1. Microbial biofilms: from ecology to molecular genetics.

    Science.gov (United States)

    Davey, M E; O'toole, G A

    2000-12-01

    Biofilms are complex communities of microorganisms attached to surfaces or associated with interfaces. Despite the focus of modern microbiology research on pure culture, planktonic (free-swimming) bacteria, it is now widely recognized that most bacteria found in natural, clinical, and industrial settings persist in association with surfaces. Furthermore, these microbial communities are often composed of multiple species that interact with each other and their environment. The determination of biofilm architecture, particularly the spatial arrangement of microcolonies (clusters of cells) relative to one another, has profound implications for the function of these complex communities. Numerous new experimental approaches and methodologies have been developed in order to explore metabolic interactions, phylogenetic groupings, and competition among members of the biofilm. To complement this broad view of biofilm ecology, individual organisms have been studied using molecular genetics in order to identify the genes required for biofilm development and to dissect the regulatory pathways that control the plankton-to-biofilm transition. These molecular genetic studies have led to the emergence of the concept of biofilm formation as a novel system for the study of bacterial development. The recent explosion in the field of biofilm research has led to exciting progress in the development of new technologies for studying these communities, advanced our understanding of the ecological significance of surface-attached bacteria, and provided new insights into the molecular genetic basis of biofilm development.

  2. Microbial Biofilms: from Ecology to Molecular Genetics

    Science.gov (United States)

    Davey, Mary Ellen; O'toole, George A.

    2000-01-01

    Biofilms are complex communities of microorganisms attached to surfaces or associated with interfaces. Despite the focus of modern microbiology research on pure culture, planktonic (free-swimming) bacteria, it is now widely recognized that most bacteria found in natural, clinical, and industrial settings persist in association with surfaces. Furthermore, these microbial communities are often composed of multiple species that interact with each other and their environment. The determination of biofilm architecture, particularly the spatial arrangement of microcolonies (clusters of cells) relative to one another, has profound implications for the function of these complex communities. Numerous new experimental approaches and methodologies have been developed in order to explore metabolic interactions, phylogenetic groupings, and competition among members of the biofilm. To complement this broad view of biofilm ecology, individual organisms have been studied using molecular genetics in order to identify the genes required for biofilm development and to dissect the regulatory pathways that control the plankton-to-biofilm transition. These molecular genetic studies have led to the emergence of the concept of biofilm formation as a novel system for the study of bacterial development. The recent explosion in the field of biofilm research has led to exciting progress in the development of new technologies for studying these communities, advanced our understanding of the ecological significance of surface-attached bacteria, and provided new insights into the molecular genetic basis of biofilm development. PMID:11104821

  3. genetics and molecular diagnosis of cardiomyopathy

    African Journals Online (AJOL)

    Enrique

    This article reviews the impact of new genetic information on the clinical manage- ment of ... defect and molecular pathogenesis of many monogenic disorders of the cardiovascular system ..... Human Genetics, Departments of. Medicine and ...

  4. Novel approach of molecular genetic understanding of iridology: relationship between iris constitution and angiotensin converting enzyme gene polymorphism.

    Science.gov (United States)

    Um, Jae-Young; An, Nyeon-Hyoung; Yang, Gui-Bi; Lee, Geon-Mok; Cho, Ju-Jang; Cho, Jae-Woon; Hwang, Woo-Jun; Chae, Han-Jung; Kim, Hyung-Ryong; Hong, Seung-Heon; Kim, Hyung-Min

    2005-01-01

    Iridology is the study of the iris of the eye to detect the conditions of the body and its organs, genetic strengths and weaknesses, etc. Although iridology is not widely used as a scientific tool for healthcare professionals to get to the source of people's health conditions, it has been used as a supplementary source to help the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris among some Korean Oriental medical doctors. Angiotensin converting enzyme (ACE) gene polymorphism is one of the most well studied genetic markers of vascular disease. We investigated the relationship between iridological constitution and ACE polymorphism in hypertensives. We classified 87 hypertensives and 79 controls according to iris constitution and determined the ACE genotype of each individual. DD genotype was more prevalent in patients with a neurogenic constitution than in controls. This finding supports the hypothesis that D allele is a candidate gene for hypertension and demonstrates the association among ACE genotype, Korean hypertensives and iris constitution.

  5. (-)-Menthol biosynthesis and molecular genetics

    Science.gov (United States)

    Croteau, Rodney B.; Davis, Edward M.; Ringer, Kerry L.; Wildung, Mark R.

    2005-12-01

    (-)-Menthol is the most familiar of the monoterpenes as both a pure natural product and as the principal and characteristic constituent of the essential oil of peppermint ( Mentha x piperita). In this paper, we review the biosynthesis and molecular genetics of (-)-menthol production in peppermint. In Mentha species, essential oil biosynthesis and storage is restricted to the peltate glandular trichomes (oil glands) on the aerial surfaces of the plant. A mechanical method for the isolation of metabolically functional oil glands, has provided a system for precursor feeding studies to elucidate pathway steps, as well as a highly enriched source of the relevant biosynthetic enzymes and of their corresponding transcripts with which cDNA libraries have been constructed to permit cloning and characterization of key structural genes. The biosynthesis of (-)-menthol from primary metabolism requires eight enzymatic steps, and involves the formation and subsequent cyclization of the universal monoterpene precursor geranyl diphosphate to the parent olefin (-)-(4 S)-limonene as the first committed reaction of the sequence. Following hydroxylation at C3, a series of four redox transformations and an isomerization occur in a general “allylic oxidation-conjugate reduction” scheme that installs three chiral centers on the substituted cyclohexanoid ring to yield (-)-(1 R, 3 R, 4 S)-menthol. The properties of each enzyme and gene of menthol biosynthesis are described, as are their probable evolutionary origins in primary metabolism. The organization of menthol biosynthesis is complex in involving four subcellular compartments, and regulation of the pathway appears to reside largely at the level of gene expression. Genetic engineering to up-regulate a flux-limiting step and down-regulate a side route reaction has led to improvement in the composition and yield of peppermint oil.

  6. A genetic engineering approach to genetic algorithms.

    Science.gov (United States)

    Gero, J S; Kazakov, V

    2001-01-01

    We present an extension to the standard genetic algorithm (GA), which is based on concepts of genetic engineering. The motivation is to discover useful and harmful genetic materials and then execute an evolutionary process in such a way that the population becomes increasingly composed of useful genetic material and increasingly free of the harmful genetic material. Compared to the standard GA, it provides some computational advantages as well as a tool for automatic generation of hierarchical genetic representations specifically tailored to suit certain classes of problems.

  7. New Approaches to Establish Genetic Causality

    Science.gov (United States)

    McNally, Elizabeth M.; George, Alfred L.

    2015-01-01

    Cardiovascular medicine has evolved rapidly in the era of genomics with many diseases having primary genetic origins becoming the subject of intense investigation. The resulting avalanche of information on the molecular causes of these disorders has prompted a revolution in our understanding of disease mechanisms and provided new avenues for diagnoses. At the heart of this revolution is the need to correctly classify genetic variants discovered during the course of research or reported from clinical genetic testing. This review will address current concepts related to establishing the cause and effect relationship between genomic variants and heart diseases. A survey of general approaches used for functional annotation of variants will also be presented. PMID:25864169

  8. Genetics and molecular biology of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.

    1992-12-31

    This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

  9. Workshop on molecular methods for genetic diagnosis. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Rinchik, E.M.

    1997-07-01

    The Sarah Lawrence College Human Genetics Program received Department of Energy funding to offer a continuing medical education workshop for genetic counselors in the New York metropolitan area. According to statistics from the National Society of Genetic Counselors, there are approximately 160 genetic counselors working in the tri-state area (New York, New Jersey, and Connecticut), and many of them had been working in the field for more than 10 years. Thus, there was a real need to offer these counselors an in-depth opportunity to learn the specifics of the major advances in molecular genetics, and, in particular, the new approaches to diagnostic testing for genetic disease. As a result of the DOE Award DE-FG02-95ER62048 ($20,583), in July 1995 we offered the {open_quotes}Workshop on Molecular Methods for Genetic Diagnosis{close_quotes} for 24 genetic counselors in the New York metropolitan area. The workshop included an initial review session on the basics of molecular biology, lectures and discussions on past and current topics in molecular genetics and diagnostic procedures, and, importantly, daily laboratory exercises. Each counselor gained not only background, but also firsthand experience, in the major techniques of biochemical and molecular methods for diagnosing genetic diseases as well as in mathematical and computational techniques involved in human genetics analyses. Our goal in offering this workshop was not to make genetic counselors experts in these laboratory diagnostic techniques, but to acquaint them, by hands-on experience, about some of the techniques currently in use. We also wanted to provide them a technical foundation upon which they can understand and appreciate new technical developments arising in the near future.

  10. Using a Molecular-Genetic Approach to Investigate Bacterial Physiology in a Continuous, Research-Based, Semester-Long Laboratory for Undergraduates †

    OpenAIRE

    Jeremiah Foster Ault; Betsey Marie Renfro; Andrea Kirsten White

    2011-01-01

    Designing investigative laboratory exercises that encourage critical thinking, problem solving, and independent thought for upper-division biology courses is a difficult but worthwhile task. In an effort to do so, we developed a semester-long, continuous, research-based investigative laboratory that integrates numerous genetic and molecular biology methods into the investigation of a bacterial physiological process. In this lab, students use random Tn5 transposon mutagenesis to create prodigi...

  11. Molecular approaches to contraceptive development

    Indian Academy of Sciences (India)

    Usha Natraj

    2001-11-01

    The next generation of contraceptives will be based on the identification of novel molecules essential for reproductive processes and will rely on the refinement of older as well as newer technologies. Functional analysis of naturally occurring reproductive genetic disorders and creation of mice null for specific genes would greatly assist in the choice of genetic targets for contraceptive development. Structure-based design of drugs as exemplified by the preparation of an orally active non-peptide gonadotropin releasing hormone (GnRH) would revolutionize drug formulation and delivery for a peptide analogue. This review examines some of the molecular targets that may change contraceptive choices in the future.

  12. Molecular Genetics of Mitochondrial Disorders

    Science.gov (United States)

    Wong, Lee-Jun C.

    2010-01-01

    Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically and clinically heterogeneous diseases because of the fact that protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure, and function of mitochondria, including DNA…

  13. Alport syndrome. Molecular genetic aspects

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    2009-01-01

    Alport syndrome (AS) is a progressive renal disease that is characterised by hematuria and progressive renal failure, and often accompanied by progressive high-tone sensorineural hearing loss and ocular changes in form of macular flecks and lenticonus. AS is a genetic heterogenous disease, and X...... practice for carrier detection and prenatal diagnosis, in order to be able to offer a better genetic counselling to the families. Knowledge of a possible correlation between genotype and phenotype can be of help in predicting the prognosis. Samples from 135 probands suspected of AS and 359...... of their relatives were collected, together with available clinical information. Southern blotting analysis and multiplex ligation-dependent probe amplification (MLPA) were used to screen for larger structural rearrangements (deletions and duplications). cDNA probes covering the entire coding region of the COL4A5...

  14. Reverse Genetic Approaches in Zebrafish

    Institute of Scientific and Technical Information of China (English)

    Peng Huang; Zuoyan Zhu; Shuo Lin; Bo Zhang

    2012-01-01

    Zebrafish (Danio rerio) is a well-established vertebrate animal model.A comprehensive collection of reverse genetics tools has been developed for studying gene function in this useful organism.Morpholino is the most widely used reagent to knock down target gene expression post-transcriptionally.For a long time,targeted genome modification has been heavily relied on large-scale traditional forward genetic screens,such as ENU (N-ethyl-N-nitrosourea) mutagenesis derived TILLING (Targeting Induced Local Lesions IN Genomes)strategy and pseudo-typed retrovirus mediated insertional mutagenesis.Recently,engineered endonucleases,including ZFNs (zinc finger nucleases) and TALENs (transcription activator-like effector nucleases),provide new and efficient strategies to directly generate sitespecific indel mutations by inducing double strand breaks in target genes.Here we summarize the major reverse genetic approaches for loss-of-function studies used and emerging in zebrafish,including strategies based on genome-wide mutagenesis and methods for sitespecific gene targeting.Future directions and expectations will also be discussed.

  15. Molecular Genetics of Lactase Deficiencies

    OpenAIRE

    Kuokkanen, Mikko

    2006-01-01

    Congenital lactase deficiency (CLD) (MIM 223000) is a rare autosomal recessive gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. The CLD locus was previously assigned by linkage and linkage disequilibrium analyses on 2q21 in 19 Finnish families. In this study, the molecular background of this disorder is reported. The CLD locus was refined in 32 CLD patients in 24 families by using microsatellite and single nucleot...

  16. Molecular genetics of human obesity: A comprehensive review.

    Science.gov (United States)

    Singh, Rajan Kumar; Kumar, Permendra; Mahalingam, Kulandaivelu

    2017-02-01

    Obesity and its related health complications is a major problem worldwide. Hypothalamus and their signalling molecules play a critical role in the intervening and coordination with energy balance and homeostasis. Genetic factors play a crucial role in determining an individual's predisposition to the weight gain and being obese. In the past few years, several genetic variants were identified as monogenic forms of human obesity having success over common polygenic forms. In the context of molecular genetics, genome-wide association studies (GWAS) approach and their findings signified a number of genetic variants predisposing to obesity. However, the last couple of years, it has also been noticed that alterations in the environmental and epigenetic factors are one of the key causes of obesity. Hence, this review might be helpful in the current scenario of molecular genetics of human obesity, obesity-related health complications (ORHC), and energy homeostasis. Future work based on the clinical discoveries may play a role in the molecular dissection of genetic approaches to find more obesity-susceptible gene loci. Copyright © 2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  17. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  18. Reverse Genetics Approaches to Control Arenavirus.

    Science.gov (United States)

    Martínez-Sobrido, Luis; Cheng, Benson Yee Hin; de la Torre, Juan Carlos

    2016-01-01

    Several arenavirus cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. To date, no licensed vaccines are available to combat human arenavirus infections, and anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetics approaches provides investigators with a novel and powerful approach for the investigation of the arenavirus molecular and cell biology. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription and the identification of novel anti-arenaviral drug targets without requiring the use of live forms of arenaviruses. Likewise, it is now feasible to rescue infectious arenaviruses entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify anti-arenaviral drugs and development of novel live-attenuated arenavirus vaccines. Recently, reverse genetics have also allowed the generation of tri-segmented arenaviruses expressing foreign genes, facilitating virus detection and opening the possibility of implementing live-attenuated arenavirus-based vaccine vector approaches. Likewise, the development of single-cycle infectious, reporter-expressing, arenaviruses has provided a new experimental method to study some aspects of the biology of highly pathogenic arenaviruses without the requirement of high-security biocontainment required to study HF-causing arenaviruses. In this chapter we summarize the current knowledge on arenavirus reverse genetics and the implementation of plasmid-based reverse genetics techniques for the development of arenavirus vaccines and vaccine vectors.

  19. Molecular genetics in affective illness

    Energy Technology Data Exchange (ETDEWEB)

    Mendlewicz, J.; Sevy, S.; Mendelbaum, K. (Erasme Univ. Hospital, Brussels (Belgium))

    1993-01-01

    Genetic transmission in manic depressive illness (MDI) has been explored in twins, adoption, association, and linkage studies. The X-linked transmission hypothesis has been tested by using several markers on chromosome X: Xg blood group, color blindness, glucose-6-phosphate dehydrogenase (G6PD), factor IX (hemophilia B), and DNA probes such as DXS15, DXS52, F8C, ST14. The hypothesis of autosomal transmission has been tested by association studies with the O blood group located on chromosome 9, as well as linkage studies on chromosome 6 with the Human Leucocyte Antigens (HLA) haplotypes and on Chromosome 11 with DNA markers for the following genes: D2 dopamine receptor, tyrosinase, C-Harvey-Ras-A (HRAS) oncogene, insuline (ins), and tyrosine hydroxylase (TH). Although linkage studies support the hypothesis of a major locus for the transmission of MDI in the Xq27-28 region, several factors are limiting the results, and are discussed in the present review. 105 refs., 1 fig., 2 tabs.

  20. Variational Approach to Molecular Kinetics.

    Science.gov (United States)

    Nüske, Feliks; Keller, Bettina G; Pérez-Hernández, Guillermo; Mey, Antonia S J S; Noé, Frank

    2014-04-08

    The eigenvalues and eigenvectors of the molecular dynamics propagator (or transfer operator) contain the essential information about the molecular thermodynamics and kinetics. This includes the stationary distribution, the metastable states, and state-to-state transition rates. Here, we present a variational approach for computing these dominant eigenvalues and eigenvectors. This approach is analogous to the variational approach used for computing stationary states in quantum mechanics. A corresponding method of linear variation is formulated. It is shown that the matrices needed for the linear variation method are correlation matrices that can be estimated from simple MD simulations for a given basis set. The method proposed here is thus to first define a basis set able to capture the relevant conformational transitions, then compute the respective correlation matrices, and then to compute their dominant eigenvalues and eigenvectors, thus obtaining the key ingredients of the slow kinetics.

  1. Molecular genetics of dyslexia: an overview.

    Science.gov (United States)

    Carrion-Castillo, Amaia; Franke, Barbara; Fisher, Simon E

    2013-11-01

    Dyslexia is a highly heritable learning disorder with a complex underlying genetic architecture. Over the past decade, researchers have pinpointed a number of candidate genes that may contribute to dyslexia susceptibility. Here, we provide an overview of the state of the art, describing how studies have moved from mapping potential risk loci, through identification of associated gene variants, to characterization of gene function in cellular and animal model systems. Work thus far has highlighted some intriguing mechanistic pathways, such as neuronal migration, axon guidance, and ciliary biology, but it is clear that we still have much to learn about the molecular networks that are involved. We end the review by highlighting the past, present, and future contributions of the Dutch Dyslexia Programme to studies of genetic factors. In particular, we emphasize the importance of relating genetic information to intermediate neurobiological measures, as well as the value of incorporating longitudinal and developmental data into molecular designs.

  2. Genetic neurological channelopathies: molecular genetics and clinical phenotypes.

    Science.gov (United States)

    Spillane, J; Kullmann, D M; Hanna, M G

    2016-01-01

    Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Genetics of asthma: a molecular biologist perspective

    Directory of Open Access Journals (Sweden)

    Ghosh Balaram

    2009-05-01

    Full Text Available Abstract Asthma belongs to the category of classical allergic diseases which generally arise due to IgE mediated hypersensitivity to environmental triggers. Since its prevalence is very high in developed or urbanized societies it is also referred to as "disease of civilizations". Due to its increased prevalence among related individuals, it was understood quite long back that it is a genetic disorder. Well designed epidemiological studies reinforced these views. The advent of modern biological technology saw further refinements in our understanding of genetics of asthma and led to the realization that asthma is not a disorder with simple Mendelian mode of inheritance but a multifactorial disorder of the airways brought about by complex interaction between genetic and environmental factors. Current asthma research has witnessed evidences that are compelling researchers to redefine asthma altogether. Although no consensus exists among workers regarding its definition, it seems obvious that several pathologies, all affecting the airways, have been clubbed into one common category called asthma. Needless to say, genetic studies have led from the front in bringing about these transformations. Genomics, molecular biology, immunology and other interrelated disciplines have unearthed data that has changed the way we think about asthma now. In this review, we center our discussions on genetic basis of asthma; the molecular mechanisms involved in its pathogenesis. Taking cue from the existing data we would briefly ponder over the future directions that should improve our understanding of asthma pathogenesis.

  4. Genetic and molecular changes in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Robert L Hollis; Charlie Gourley

    2016-01-01

    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

  5. Molecular approach to echinoderm regeneration.

    Science.gov (United States)

    Thorndyke, M C; Chen, W C; Beesley, P W; Patruno, M

    2001-12-15

    Until very recently echinoderm regeneration research and indeed echinoderm research in general has suffered because of the lack of critical mass. In terms of molecular studies of regeneration, echinoderms in particular have lagged behind other groups in this respect. This is in sharp contrast to the major advances achieved with molecular and genetic techniques in the study of embryonic development in echinoderms. The aim of our studies has been to identify genes involved in the process of regeneration and in particular neural regeneration in different echinoderm species. Our survey included the asteroid Asterias rubens and provided evidence for the expression of Hox gene homologues in regenerating radial nerve cords. Present evidence suggests: 1) ArHox1 expression is maintained in intact radial nerve cord and may be upregulated during regeneration. 2) ArHox1 expression may contribute to the dedifferentiation and/or cell proliferation process during epimorphic regeneration. From the crinoid Antedon bifida, we have been successful in cloning a fragment of a BMP2/4 homologue (AnBMP2/4) and analysing its expression during arm regeneration. Here, we discuss the importance of this family of growth factors in several regulatory spheres, including maintaining the identity of pluripotent blastemal cells or as a classic skeletal morphogenic regulator. There is clearly substantial scope for future echinoderm research in the area of molecular biology and certain aspects are discussed in this review.

  6. Molecular Genetics and Genetic Testing in Myotonic Dystrophy Type 1

    Directory of Open Access Journals (Sweden)

    Dušanka Savić Pavićević

    2013-01-01

    Full Text Available Myotonic dystrophy type 1 (DM1 is the most common adult onset muscular dystrophy, presenting as a multisystemic disorder with extremely variable clinical manifestation, from asymptomatic adults to severely affected neonates. A striking anticipation and parental-gender effect upon transmission are distinguishing genetic features in DM1 pedigrees. It is an autosomal dominant hereditary disease associated with an unstable expansion of CTG repeats in the 3′-UTR of the DMPK gene, with the number of repeats ranging from 50 to several thousand. The number of CTG repeats broadly correlates with both the age-at-onset and overall severity of the disease. Expanded DM1 alleles are characterized by a remarkable expansion-biased and gender-specific germline instability, and tissue-specific, expansion-biased, age-dependent, and individual-specific somatic instability. Mutational dynamics in male and female germline account for observed anticipation and parental-gender effect in DM1 pedigrees, while mutational dynamics in somatic tissues contribute toward the tissue-specificity and progressive nature of the disease. Genetic test is routinely used in diagnostic procedure for DM1 for symptomatic, asymptomatic, and prenatal testing, accompanied with appropriate genetic counseling and, as recommended, without predictive information about the disease course. We review molecular genetics of DM1 with focus on those issues important for genetic testing and counseling.

  7. Molecular genetic framework for protophloem formation

    OpenAIRE

    Rodriguez-Villalon, Antia; Gujas, Bojan; Kang, Yeon Hee; Alice S. Breda; Cattaneo, Pietro; Depuydt, Stephen; Hardtke, Christian S

    2014-01-01

    The emergence of vascular tissues played a central role in the plant conquest of land. Both xylem and phloem are essential for the development of flowering plants, yet little is known about the molecular genetic control of phloem specification and differentiation. Here we show that delicate quantitative interplay between two opposing signaling pathways determines cellular commitment to protophloem sieve element fate in root meristems of the model plant Arabidopsis thaliana. Our data suggest t...

  8. Advances in molecular genetic systems in malaria.

    Science.gov (United States)

    de Koning-Ward, Tania F; Gilson, Paul R; Crabb, Brendan S

    2015-06-01

    Robust tools for analysing gene function in Plasmodium parasites, which are the causative agents of malaria, are being developed at an accelerating rate. Two decades after genetic technologies for use in Plasmodium spp. were first described, a range of genetic tools are now available. These include conditional systems that can regulate gene expression at the genome, transcriptional or protein level, as well as more sophisticated tools for gene editing that use piggyBac transposases, integrases, zinc-finger nucleases or the CRISPR-Cas9 system. In this Review, we discuss the molecular genetic systems that are currently available for use in Plasmodium falciparum and Plasmodium berghei, and evaluate the advantages and limitations of these tools. We examine the insights that have been gained into the function of genes that are important during the blood stages of the parasites, which may help to guide the development and improvement of drug therapies and vaccines.

  9. A molecular genetic toolbox for Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Bredeweg, Erin L.; Pomraning, Kyle R.; Dai, Ziyu

    2017-01-01

    Background: Yarrowia lipolytica is an ascomycete yeast used in biotechnological research for its abilities to secrete high concentrations of proteins and accumulate lipids. Genetic tools have been made in a variety of backgrounds with varying similarity to a comprehensively sequenced strain....... Results: We have developed a set of genetic and molecular tools in order to expand capabilities of Y. lipolytica for both biological research and industrial bioengineering applications. In this work, we generated a set of isogenic auxotrophic strains with decreased non-homologous end joining for targeted...... DNA incorporation. Genome sequencing, assembly, and annotation of this genetic background uncovers previously unidentified genes in Y. lipolytica. To complement these strains, we constructed plasmids with Y. lipolytica-optimized superfolder GFP for targeted overexpression and fluorescent tagging. We...

  10. [Molecular genetic investigations in muscular diseases].

    Science.gov (United States)

    Burgunder, J M

    2003-08-01

    The last couple of years have witnessed a rapid development in discoveries of the genetic background in myopathies. It is therefore timely to review the impact they have on clinical work. The recognition of a myopathy remains a clinical activity, and biopsy retains a major role. Molecular genetic investigation can be contemplated early in cases with certain typical clinical presentation. In others, the correct indication to such an investigation can only be made based on findings at biopsy. The information of precise mutation can be used for genetic counselling of the family. Knowledge of genes, whose mutations are sufficient to cause certain myopathies, have provided a great amount of knowledge about pathophysiological mechanisms involved. Some are arguably rare diseases, however, this knowledge also helps understand more frequent myopathies, as it has been the case in neurodegenerative disorders.

  11. Huntington Disease: Molecular Diagnostics Approach.

    Science.gov (United States)

    Bastepe, Murat; Xin, Winnie

    2015-10-06

    Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in the first exon of the Huntingtin (HTT) gene. Molecular testing of Huntington disease for diagnostic confirmation and disease prediction requires detection of the CAG repeat expansion. There are three main types of HD genetic testing: (1) diagnostic testing to confirm or rule out disease, (2) presymptomatic testing to determine whether an at-risk individual inherited the expanded allele, and (3) prenatal testing to determine whether the fetus has inherited the expanded allele. This unit includes protocols that describe the complementary use of polymerase chain reactions (PCR) and Southern blot hybridization to accurately measure the CAG trinucleotide repeat size and interpret the test results. In addition, an indirect linkage analysis that does not reveal the unwanted parental HD status in a prenatal testing will also be discussed.

  12. Molecular Approaches to Studying Denitrification

    Science.gov (United States)

    Voytek, M. A.

    2001-05-01

    Denitrification is carried out by a diverse array of microbes, mainly as an alternative mode of respiration that allows the organisms to respire using oxidized N compounds instead of oxygen. A common approach in biogeochemistry to the study of the regulation of denitrification is to assess activity by mass balance of substrates and products or direct rate measurements and has intrinsically assumed resource regulation of denitrification. Reported rates can vary significantly even among ecosystems characterized by similar environmental conditions, thus indicating that direct control by abiotic factors often is not sufficient to predict denitrification rates accurately in natural environments. Alternatively, a microbiological approach would proceed with the identification of the organisms responsible and an evaluation of the effect of environmental factors on the biochemical pathways involved. Traditional studies have relied on culturing techniques, such as most probable number enrichments, and have failed to assess the role of the predominately uncultivable members of the microbial community. A combination of biogeochemical measurements and the assessment of the microbial community is necessary and becoming increasingly possible with the development and application of molecular techniques. In order to understand how the composition and physiological behavior of the microbial community affects denitrification rates, we use a suite of molecular techniques developed for phylogenetic and metabolic characterization of denitrifying communities. Molecular tools available for quantifying denitrifying bacteria and assessing their diversity and activity are summarized. Their application is illustrated with examples from marine and freshwater environments. Emerging techniques and their application to ground water studies will be discussed.

  13. Molecular mechanisms underlying noncoding risk variations in psychiatric genetic studies.

    Science.gov (United States)

    Xiao, X; Chang, H; Li, M

    2017-01-03

    Recent large-scale genetic approaches such as genome-wide association studies have allowed the identification of common genetic variations that contribute to risk architectures of psychiatric disorders. However, most of these susceptibility variants are located in noncoding genomic regions that usually span multiple genes. As a result, pinpointing the precise variant(s) and biological mechanisms accounting for the risk remains challenging. By reviewing recent progresses in genetics, functional genomics and neurobiology of psychiatric disorders, as well as gene expression analyses of brain tissues, here we propose a roadmap to characterize the roles of noncoding risk loci in the pathogenesis of psychiatric illnesses (that is, identifying the underlying molecular mechanisms explaining the genetic risk conferred by those genomic loci, and recognizing putative functional causative variants). This roadmap involves integration of transcriptomic data, epidemiological and bioinformatic methods, as well as in vitro and in vivo experimental approaches. These tools will promote the translation of genetic discoveries to physiological mechanisms, and ultimately guide the development of preventive, therapeutic and prognostic measures for psychiatric disorders.Molecular Psychiatry advance online publication, 3 January 2017; doi:10.1038/mp.2016.241.

  14. Molecular Genetic Study of Human Esophageal Carcinoma

    Science.gov (United States)

    1991-07-16

    carcinogenic processes ( Doerfler , 1983). Direct evidence has shown that the DNA alkylation product, o’-methyl deoxyguanosine was higher in the DNA...of north China and the genetic approach to its control. Genes and Disease, (Science Press, Beijing, China) 1985. Doerfler , W. DNA methylation and

  15. Molecular Approaches to Genetically Improve the Accumulation of Health-Promoting Secondary Metabolites in Staple Crops-A Case Study: The Lipoxygenase-B1 Genes and Regulation of the Carotenoid Content in Pasta Products.

    Science.gov (United States)

    Borrelli, Grazia M; Trono, Daniela

    2016-07-21

    Secondary metabolites, also known as phytochemicals, represent a large subset of plant molecules that include compounds with health-promoting effects. Indeed, a number of epidemiological studies have shown that, when taken regularly and in adequate amounts, these molecules can have long-term beneficial effects on human health, through reduction of the incidence of degenerative diseases, such as cardiovascular diseases, obesity, diabetes, and cancer. As the dietary intake of these phytochemicals is often inadequate, various strategies are in use to improve their content in staple crops, and the end-products thereof. One of the most effective strategies is crop improvement through genetic approaches, as this is the only way to generate new cultivars in which the high accumulation of a given phytochemical is stably fixed. Efforts to genetically improve quality traits are rapidly evolving, from classical breeding to molecular-assisted approaches; these require sound understanding of the molecular bases underlying the traits, to identify the genes/alleles that control them. This can be achieved through global analysis of the metabolic pathway responsible for phytochemical accumulation, to identify the link between phytochemical content and the activities of key enzymes that regulate the metabolic pathway, and between the key enzymes and their encoding genes/alleles. Once these have been identified, they can be used as markers for selection of new improved genotypes through biotechnological approaches. This review provides an overview of the major health-promoting properties shown to be associated with the dietary intake of phytochemicals, and describes how molecular approaches provide means for improving the health quality of edible crops. Finally, a case study is illustrated, of the identification in durum wheat of the Lipoxygenase-B1 genes that control the final carotenoid content in semolina-based foods, such as pasta products.

  16. Molecular Approaches to Genetically Improve the Accumulation of Health-Promoting Secondary Metabolites in Staple Crops—A Case Study: The Lipoxygenase-B1 Genes and Regulation of the Carotenoid Content in Pasta Products

    Directory of Open Access Journals (Sweden)

    Grazia M. Borrelli

    2016-07-01

    Full Text Available Secondary metabolites, also known as phytochemicals, represent a large subset of plant molecules that include compounds with health-promoting effects. Indeed, a number of epidemiological studies have shown that, when taken regularly and in adequate amounts, these molecules can have long-term beneficial effects on human health, through reduction of the incidence of degenerative diseases, such as cardiovascular diseases, obesity, diabetes, and cancer. As the dietary intake of these phytochemicals is often inadequate, various strategies are in use to improve their content in staple crops, and the end-products thereof. One of the most effective strategies is crop improvement through genetic approaches, as this is the only way to generate new cultivars in which the high accumulation of a given phytochemical is stably fixed. Efforts to genetically improve quality traits are rapidly evolving, from classical breeding to molecular-assisted approaches; these require sound understanding of the molecular bases underlying the traits, to identify the genes/alleles that control them. This can be achieved through global analysis of the metabolic pathway responsible for phytochemical accumulation, to identify the link between phytochemical content and the activities of key enzymes that regulate the metabolic pathway, and between the key enzymes and their encoding genes/alleles. Once these have been identified, they can be used as markers for selection of new improved genotypes through biotechnological approaches. This review provides an overview of the major health-promoting properties shown to be associated with the dietary intake of phytochemicals, and describes how molecular approaches provide means for improving the health quality of edible crops. Finally, a case study is illustrated, of the identification in durum wheat of the Lipoxygenase-B1 genes that control the final carotenoid content in semolina-based foods, such as pasta products.

  17. Medulloblastoma: Molecular Genetics and Animal Models

    Directory of Open Access Journals (Sweden)

    Corey Raffel

    2004-07-01

    Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

  18. A molecular-genetic approach to studying source-sink interactions in Arabidopsis thaliana. Final report, April 1, 1995--March 31, 1998

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, S.I.

    1998-11-01

    The ultimate goal of this research is to elucidate the molecular mechanisms by which the complex interactions between sources and sinks of fixed carbon are controlled in plants. As soluble sugar levels have been shown to play a vital role in a variety of source-sink interactions, a key aspect of the authors research is to determine the role of sugar-regulated gene expression in mediating source-sink interactions. In addition, as a critical aspect of source-sink interactions is the channeling of fixed carbon into different storage forms, they have pursued the findings that fumaric acid represents a significant form of storage carbon in Arabidopsis thaliana and other plant species. In the future, a better understanding of the mechanisms by which interactions between sources and sinks of fixed carbon are coordinated will be a pre-requisite to developing more rationale approaches to improving harvest indices in crop species.

  19. Molecular approaches in experimental neuroimaging

    Energy Technology Data Exchange (ETDEWEB)

    Tavitian, B. [CEA Saclay, 91 - Gif sur Yvette (France)

    2009-07-01

    We quantified and compared six parameters (resolution, depth, sensitivity, portability, quantification and cost) of four molecular imaging techniques (MRI, optics, ultrasound and TEP), with the three types of electromagnetic radiation used in vivo (Frequencies (10{sup 6} to 10{sup 22} Hz), Photonic Energy (10{sup -4} to 10{sup 9} eV) and Wavelengths (10{sup -2} to 10{sup -15} m)). This form of molecular imaging demands the most sensitive technique available (Pl. 26-2 to 26-4). Four examples of experimental in vivo approaches on small animals are shown: molecular passage through the blood-brain barrier (endothelial cells, astrocytes and occludin, pharmacokinetics, studied with PET) (Pl. 2-5 to 2-11); imaging of receptors and ligands, especially peripheral benzodiazepine receptors (PBR) by PET and MRI in the rat (Pl. 2-12 to Pl. 2-15); neuro-pathology of neuro-degenerative and inflammatory diseases and stroke by PET and MRI in the rat (Pl. 2-16 to 2-17); and the study of responses to stimulation explored with in vivo imaging of calcium signals and their variations by photonic analysis, as on the scale of mitochondrial calcium (Pl.2-18 to Pl.2-22). (author)

  20. Molecular genetics of hereditary sensory neuropathies.

    Science.gov (United States)

    Auer-Grumbach, Michaela; Mauko, Barbara; Auer-Grumbach, Piet; Pieber, Thomas R

    2006-01-01

    Hereditary sensory neuropathies (HSN), also known as hereditary sensory and autonomic neuropathies (HSAN), are a clinically and genetically heterogeneous group of disorders. They are caused by neuronal atrophy and degeneration, predominantly affecting peripheral sensory and autonomic neurons. Both congenital and juvenile to adulthood onset is possible. Currently, the classification of the HSN depends on the mode of inheritance, age at onset, and clinical presentation. Hallmark features are progressive sensory loss, chronic skin ulcers, and other skin abnormalities. Spontaneous fractures and neuropathic arthropathy are frequent complications and often necessitate amputations. Autonomic features vary between different subgroups. Distal muscle weakness and wasting may be present and is sometimes so prominent that it becomes difficult to distinguish HSN from Charcot-Marie-Tooth syndrome. Recent major advances in molecular genetics have led to the identification of seven gene loci and six-disease causing genes for autosomal-dominant and autosomal-recessive HSN. These genes have been shown to play roles in lipid metabolism and the regulation of intracellular vesicular transport, but also a presumptive transcriptional regulator, a nerve growth factor receptor, and a nerve growth factor have been described among the causative genes in HSN. Nevertheless, it remains unclear how mutations in the known genes lead to the phenotype of HSN. In this review, we summarize the recent progress of the molecular genetics of the HSN and the implicated genes.

  1. Molecular Genetic Markers in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sophia Yohe

    2015-03-01

    Full Text Available Genetics play an increasingly important role in the risk stratification and management of acute myeloid leukemia (AML patients. Traditionally, AML classification and risk stratification relied on cytogenetic studies; however, molecular detection of gene mutations is playing an increasingly important role in classification, risk stratification, and management of AML. Molecular testing does not take the place of cytogenetic testing results, but plays a complementary role to help refine prognosis, especially within specific AML subgroups. With the exception of acute promyelocytic leukemia, AML therapy is not targeted but the intensity of therapy is driven by the prognostic subgroup. Many prognostic scoring systems classify patients into favorable, poor, or intermediate prognostic subgroups based on clinical and genetic features. Current standard of care combines cytogenetic results with targeted testing for mutations in FLT3, NPM1, CEBPA, and KIT to determine the prognostic subgroup. Other gene mutations have also been demonstrated to predict prognosis and may play a role in future risk stratification, although some of these have not been confirmed in multiple studies or established as standard of care. This paper will review the contribution of cytogenetic results to prognosis in AML and then will focus on molecular mutations that have a prognostic or possible therapeutic impact.

  2. Cardiac channelopathies: genetic and molecular mechanisms.

    Science.gov (United States)

    Abriel, Hugues; Zaklyazminskaya, Elena V

    2013-03-15

    Channelopathies are diseases caused by dysfunctional ion channels, due to either genetic or acquired pathological factors. Inherited cardiac arrhythmic syndromes are among the most studied human disorders involving ion channels. Since seminal observations made in 1995, thousands of mutations have been found in many of the different genes that code for cardiac ion channel subunits and proteins that regulate the cardiac ion channels. The main phenotypes observed in patients carrying these mutations are congenital long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome (SQTS) and variable types of conduction defects (CD). The goal of this review is to present an update of the main genetic and molecular mechanisms, as well as the associated phenotypes of cardiac channelopathies as of 2012. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Molecular genetics of human lactase deficiencies.

    Science.gov (United States)

    Järvelä, Irma; Torniainen, Suvi; Kolho, Kaija-Leena

    2009-01-01

    Lactase non-persistence (adult-type hypolactasia) is present in more than half of the human population and is caused by the down-regulation of lactase enzyme activity during childhood. Congenital lactase deficiency (CLD) is a rare severe gastrointestinal disorder of new-borns enriched in the Finnish population. Both lactase deficiencies are autosomal recessive traits and characterized by diminished expression of lactase activity in the intestine. Genetic variants underlying both forms have been identified. Here we review the current understanding of the molecular defects of human lactase deficiencies and their phenotype-genotype correlation, the implications on clinical practice, and the understanding of their function and role in human evolution.

  4. Genetics and molecular biology of hypotension

    Science.gov (United States)

    Robertson, D.

    1994-01-01

    Major strides in the molecular biology of essential hypertension are currently underway. This has tended to obscure the fact that a number of inherited disorders associated with low blood pressure exist and that these diseases may have milder and underrecognized phenotypes that contribute importantly to blood pressure variation in the general population. This review highlights some of the gene products that, if abnormal, could cause hypotension in some individuals. Diseases due to abnormalities in the catecholamine enzymes are discussed in detail. It is likely that genetic abnormalities with hypotensive phenotypes will be as interesting and diverse as those that give rise to hypertensive disorders.

  5. Integration of molecular genetic technology with quantitative genetic technology for maximizing the speed of genetic improvement

    Institute of Scientific and Technical Information of China (English)

    Jack; C.M.; DEKKERS

    2005-01-01

    To date,most genetic progress for quantita-tive traits in livestock has been made by selec-tion on phenotype or on estimates of breedingvalues(BBV)derived from phenotype,withoutknowledge of the number of genes that affect thetrait or the effects of each gene.In this quantita-tive genetic approach to genetic improvement,the genetic architecture of traits of interest hasessentially been treated as a‘black box’.De-spite this,the substantial rates of genetic im-provement that have been and continue to be a-chie...

  6. Implementation of molecular karyotyping in clinical genetics

    Directory of Open Access Journals (Sweden)

    Luca Lovrecic

    2013-11-01

    Full Text Available Rapid development of technologies for the study of the human genome is an expected step after the discovery and sequencing of the entire human genome. Chromosomal microarrays, which allow us to perform tens of thousands of previously individual experiments simultaneously, are being utilized in all areas of human genetics and genomics. Initially, this was applicable only for research purposes, but in the last few years their clinical diagnostic purposes are becoming more and more relevant. Using molecular karyotyping (also chromosomal microarray, comparative genomic hybridization with microarray, aCGH, one can analyze microdeletions / microduplications in the whole human genome at once. It is a first-tier cytogenetic diagnostic test instead of G-banded karyotyping in patients with developmental delay and/or congenital anomalies. Molecular karyotyping is used as a diagnostic test in patients with unexplained developmental delay and/or idiopathic intellectual disability and/or dysmorphic features and/or multiple congenital anomalies (DD/ID/DF/MCA. In addition, the method is used in prenatal diagnostics and in some centres also in preimplantation genetic diagnosis.The aim of this paper is to inform the professional community in the field about this new diagnostic method and its implementation in Slovenia, and to define the clinical situations where the method is appropriate.

  7. Molecular diversity and genetic relationships in Secale

    Indian Academy of Sciences (India)

    E. SANTOS; M. MATOS; P. SILVA; A. M. FIGUEIRAS; C. BENITO; O. PINTO-CARNIDE

    2016-06-01

    The objective of this study was to quantify the molecular diversity and to determine the genetic relationships amongSecalespp. and among cultivars ofSecale cerealeusing RAPDs, ISSRs and sequence analysis of six exons ofScMATE1gene.Thirteen ryes (cultivated and wild) were genotyped using 21 RAPD and 16 ISSR primers. A total of 435 markers (242 RAPDsand 193 ISSRs) were obtained, with 293 being polymorphic (146 RAPDs and 147 ISSRs). Two RAPD and nine ISSR primersgenerated more than 80% of polymorphism. The ISSR markers were more polymorphic and informative than RAPDs. Further,69% of the ISSR primers selected achieved at least 70% of DNA polymorphism. The study of six exons of theScMATE1gene also demonstrated a high genetic variability that subsists inSecalegenus. One difference observed in exon 1 sequencesfromS. vaviloviiseems to be correlated with Al sensitivity in this species. The genetic relationships obtained using RAPDs,ISSRs and exons ofScMATE1gene were similar.S. ancestrale ,S. kuprijanoviiandS. cerealewere grouped in the same clusterandS. segetalewas in another cluster.S. vaviloviishowed evidences of not being clearly an isolate species and having greatintraspecific difference

  8. [Molecular-genetic aspects of congenital hypothyroidism].

    Science.gov (United States)

    Lacka, Katarzyna; Ogrodowicz, Agnieszka

    2004-01-01

    Congenital hypothyroidism manifests a complex of symptoms caused by a total lack or significant deficiency of thyroxine (T4) and triiodothyronine (T3) in foetal life and in the first years of child's life. The incidence of congenital hypothyroidism is 1 per 3000-4000 newborns in the world and l per 4800 in Poland. There are two main causes of congenital hypothyroidism: defects of thyroid development (about 90%), defects of thyroid hormones biosynthesis (~10%), and the more seldom occurring defects of the TBG proteins (thyroxine binding globulin) or resistance. syndrome to thyroid hormones. Defects of thyroid gland development include ectopia, hypoplasia or complete lack of the thyroid (athyreosis). These defects are caused by immunological, factors, drugs as well as genetic factors such as: TSH receptor gene or thyroid transcription factors: PAX 8. TTF l, TTF 2, Pit 1, Prop 1. Defects of thyroid hormones biosynthesis are inherited as autosomal recessive. There are 5 main defects of thyroid hormones biosynthesis: iodide transport (mutation of hNIS gene), iodine oxygenation (mutation of TPO, THOX, PDS genes), the iodination of the tyrosine of thyroglobulin and their conjunction (the mutation of TPO TG, PDS genes), the hydrolysis of the T3 and T4 as well as deiodination. Searching molecular-genetic basis of congenital hypothyroidism may improve its diagnostics, make possible to introduce genetic examination among patients with congenital hypothyroidism and their family members and may make gene therapy possible in the future.

  9. Teaching molecular genetics: Chapter 1--Background principles and methods of molecular biology.

    NARCIS (Netherlands)

    Knoers, N.V.A.M.; Monnens, L.A.H.

    2006-01-01

    In this first chapter of the series "Teaching molecular genetics," an introduction to molecular genetics is presented. We describe the structure of DNA and genes and explain in detail the central dogma of molecular biology, that is, the flow of genetic information from DNA via RNA to polypeptide (pr

  10. Molecular and genetic bases of pancreatic cancer.

    Science.gov (United States)

    Vaccaro, Vanja; Gelibter, Alain; Bria, Emilio; Iapicca, Pierluigi; Cappello, Paola; Di Modugno, Francesca; Pino, Maria Simona; Nuzzo, Carmen; Cognetti, Francesco; Novelli, Francesco; Nistico, Paola; Milella, Michele

    2012-06-01

    Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

  11. An Integrated Approach to Crop Genetic Improvement

    Institute of Scientific and Technical Information of China (English)

    Martin A. J. Parry; Malcolm J. Hawkesford

    2012-01-01

    The balance between the supply and demand of the major food crops is fragile,fueling concerns for long-term global food security.The rising population,increasing wealth and a proliferation of nonfood uses (e.g.bioenergy) has led to growing demands on agriculture,while increased production is limited by greater urbanization,and the degradation of land.Furthermore,global climate change with increasing temperatures and lower,more erratic rainfall is projected to decrease agricultural yields.There is a predicted need to increase food production by at least 70% by 2050 and therefore an urgent need to develop novel and integrated approaches,incorporating high-throughput phenotyping that will both increase production per unit area and simultaneously improve the resource use efficiency of crops.Yield potential,yield stability,nutrient and water use are all complex multigenic traits and while there is genetic variability,their complexity makes such traits difficult to breed for directly.Nevertheless molecular plant breeding has the potential to deliver substantial improvements,once the component traits and the genes underlying these traits have been identified.In addition,interactions between the individual traits must also be taken into account,a demand that is difficult to fulfill with traditional screening approaches.Identified traits will be incorporated into new cultivars using conventional or biotechnological tools.In order to better understand the relationship between genotype,component traits,and environment over time,a multidisciplinary approach must be adopted to both understand the underlying processes and identify candidate genes,QTLs and traits that can be used to develop improved crops.

  12. [Incest--forensic genetic approach].

    Science.gov (United States)

    Raczek, Ewa

    2012-01-01

    The paper presents intimate relationships between biologically and legally close relatives, complicated in the social, culture and religion perspective. (art. 201 of the Penal Code), but it chiefly addresses problems associated with giving opinion on the fatherhood towards the incestuous child. The report calls for a broader interest in this issue from expert witnesses in forensic genetics, as well as encourages them to publish examples taken from their own professional experience that may unquestionably be helpful to other practitioners in this field and above all will lead to extending educational methods related to widely understood DNA analysis in giving an opinion on arguable fatherhood.

  13. Molecular Genetic Tools and Techniques in Fission Yeast.

    Science.gov (United States)

    Murray, Johanne M; Watson, Adam T; Carr, Antony M

    2016-05-02

    The molecular genetic tools used in fission yeast have generally been adapted from methods and approaches developed for use in the budding yeast, Saccharomyces cerevisiae Initially, the molecular genetics of Schizosaccharomyces pombe was developed to aid gene identification, but it is now applied extensively to the analysis of gene function and the manipulation of noncoding sequences that affect chromosome dynamics. Much current research using fission yeast thus relies on the basic processes of introducing DNA into the organism and the extraction of DNA for subsequent analysis. Targeted integration into specific genomic loci is often used to create site-specific mutants or changes to noncoding regulatory elements for subsequent phenotypic analysis. It is also regularly used to introduce additional sequences that generate tagged proteins or to create strains in which the levels of wild-type protein can be manipulated through transcriptional regulation and/or protein degradation. Here, we draw together a collection of core molecular genetic techniques that underpin much of modern research using S. pombe We summarize the most useful methods that are routinely used and provide guidance, learned from experience, for the successful application of these methods.

  14. Molecular basis and genetic predisposition to intracranial aneurysm.

    Science.gov (United States)

    Tromp, Gerard; Weinsheimer, Shantel; Ronkainen, Antti; Kuivaniemi, Helena

    2014-12-01

    Intracranial aneurysms, also called cerebral aneurysms, are dilatations in the arteries that supply blood to the brain. Rupture of an intracranial aneurysm leads to a subarachnoid hemorrhage, which is fatal in about 50% of the cases. Intracranial aneurysms can be repaired surgically or endovascularly, or by combining these two treatment modalities. They are relatively common with an estimated prevalence of unruptured aneurysms of 2%-6% in the adult population, and are considered a complex disease with both genetic and environmental risk factors. Known risk factors include smoking, hypertension, increasing age, and positive family history for intracranial aneurysms. Identifying the molecular mechanisms underlying the pathogenesis of intracranial aneurysms is complex. Genome-wide approaches such as DNA linkage and genetic association studies, as well as microarray-based mRNA expression studies, provide unbiased approaches to identify genetic risk factors and dissecting the molecular pathobiology of intracranial aneurysms. The ultimate goal of these studies is to use the information in clinical practice to predict an individual's risk for developing an aneurysm or monitor its growth or rupture risk. Another important goal is to design new therapies based on the information on mechanisms of disease processes to prevent the development or halt the progression of intracranial aneurysms.

  15. Molecular genetics of distal hereditary motor neuropathies.

    Science.gov (United States)

    Irobi, Joy; De Jonghe, Peter; Timmerman, Vincent

    2004-10-01

    Inherited peripheral neuropathies comprise a wide variety of diseases primarily affecting the peripheral nervous system. The best-known peripheral neuropathy is Charcot-Marie-Tooth disease (CMT) described in 1886 by J.-M. Charcot, P. Marie and H.H. Tooth. In 1980, A.E. Harding and P.K. Thomas showed that in a large group of individuals with CMT, several only had motor abnormalities on clinical and electrophysiological examination, whereas sensory abnormalities were absent. This exclusively motor variant of CMT was designated as spinal CMT or hereditary distal spinal muscular atrophy, and included in the distal hereditary motor neuropathies (distal HMN). The distal HMN are clinically and genetically heterogeneous and are subdivided according to the mode of inheritance, age at onset and clinical evolution. Since the introduction of positional cloning, 12 chromosomal loci and seven disease-causing genes have been identified for autosomal dominant and recessive distal HMN. Most of the genes involved have housekeeping functions, as in RNA processing, translation synthesis, glycosylation, stress response, apoptosis, but also axonal trafficking and editing. Functional characterization of the mutations will help to unravel the cellular processes that underlie the specificity of motor neuropathies leading to neurogenic muscular atrophy of distal limb muscles. Here we review the recent progress of the molecular genetics of distal HMN and discuss the genes implicated.

  16. The calculus a genetic approach

    CERN Document Server

    Toeplitz, Otto

    2007-01-01

    When first published posthumously in 1963, this book presented a radically different approach to the teaching of calculus.  In sharp contrast to the methods of his time, Otto Toeplitz did not teach calculus as a static system of techniques and facts to be memorized. Instead, he drew on his knowledge of the history of mathematics and presented calculus as an organic evolution of ideas beginning with the discoveries of Greek scholars, such as Archimedes, Pythagoras, and Euclid, and developing through the centuries in the work of Kepler, Galileo, Fermat, Newton, and Leibniz. Through this unique a

  17. Teaching molecular genetics: Chapter 1--Background principles and methods of molecular biology.

    Science.gov (United States)

    Knoers, Nine V A M; Monnens, Leo A H

    2006-02-01

    In this first chapter of the series "Teaching molecular genetics," an introduction to molecular genetics is presented. We describe the structure of DNA and genes and explain in detail the central dogma of molecular biology, that is, the flow of genetic information from DNA via RNA to polypeptide (protein). In addition, several basic and frequently used general molecular tools, such as restriction enzymes, Southern blotting, DNA amplification and sequencing are discussed, in order to lay the foundations for the forthcoming chapters.

  18. Genetic and genomic approaches to understanding macrophage identity and function.

    Science.gov (United States)

    Glass, Christopher K

    2015-04-01

    A major goal of our laboratory is to understand the molecular mechanisms that underlie the development and functions of diverse macrophage phenotypes in health and disease. Recent studies using genetic and genomic approaches suggest a relatively simple model of collaborative and hierarchical interactions between lineage-determining and signal-dependent transcription factors that enable selection and activation of transcriptional enhancers that specify macrophage identity and function. In addition, we have found that it is possible to use natural genetic variation as a powerful tool for advancing our understanding of how the macrophage deciphers the information encoded by the genome to attain specific phenotypes in a context-dependent manner. Here, I will describe our recent efforts to extend genetic and genomic approaches to investigate the roles of distinct tissue environments in determining the phenotypes of different resident populations of macrophages.

  19. MOLECULAR GENETIC MARKERS AND METHODS OF THEIR IDENTIFICATION IN MODERN FISH-FARMING

    Directory of Open Access Journals (Sweden)

    I. Hrytsyniak

    2014-03-01

    Full Text Available Purpose. The application of molecular genetic markers has been widely used in modern experimental fish-farming in recent years. This methodology is currently presented by a differentiated approach with individual mechanisms and clearly defined possibilities. Numerous publications in the scientific literature that are dedicated to molecular genetic markers for the most part offer purely practical data. Thus, the synthesis and analysis of existing information on the general principles of action and the limits of the main methods of using molecular genetic markers is an actual problem. In particular, such a description will make it possible to plan more effectively the experiment and to obtain the desired results with high reliability. Findings. The main types of variable parts of DNA that can be used as molecular genetic markers in determining the level of stock hybridization, conducting genetic inventory of population and solving other problems in modern fish-farming are described in this paper. Also, the article provides an overview of principal modern methods that can be used to identify molecular genetic markers. Originality. This work is a generalization of modern ideas about the mechanisms of experiments with molecular genetic markers in fish-farming. Information is provided in the form of consistent presentation of the principles and purpose of each method, as well as significant advances during their practical application. Practical value. The proposed review of classic and modern literature data on molecular genetic markers can be used for planning, modernization and correction of research activity in modern fish-farming.

  20. Cystic fibrosis, molecular genetics for all life

    Directory of Open Access Journals (Sweden)

    Ausilia Elce

    2015-10-01

    Full Text Available Cystic fibrosis (CF is the most frequent lethal autosomal recessive disorder among Caucasians (incidence: 1:2,500 newborn. In the last two decades CF prognosis considerably improved and many patients well survive into their adulthood. Furthermore, milder CF with a late onset was described. CF is a challenge for laboratory of molecular genetics that greatly contributes to the natural history of the disease since fetal age. Carrier screening and prenatal diagnosis, also by non-invasive analysis of maternal blood fetal DNA, are now available, and many labs offer preimplantation diagnosis. The major criticism in prenatal medicine is the lack of an effective multidisciplinary counseling that helps the couples to plan their reasoned reproductive choice. Most countries offer newborn screening that significantly reduce CF morbidity but different protocols based on blood trypsin, molecular analysis and sweat chloride cause a variable efficiency of the screening programs. Again, laboratory is crucial for CF diagnosis in symptomatic patients: sweat chloride is the diagnostic golden standard, but different methodologies and the lack of quality control in most labs reduce its effectiveness. Molecular analysis contributes to confirm diagnosis in symptomatic subjects; furthermore, it helps to predict the disease outcome on the basis of the mutation (genotype-phenotype correlation and mutations in a myriad of genes, inherited independently by CF transmembrane conductance regulator (CFTR, which may modulate the clinical expression of the disease in each single patient (modifier genes. More recently, the search of the CFTR mutations gained a role in selecting CF patients that may benefit from biological therapy based on correctors and potentiators that are effective in patients bearing specific mutations (personalized therapy. All such applications of molecular diagnostics confirm the “uniqueness” of each CF patient, offering to laboratory medicine the

  1. Child Development and Molecular Genetics: 14 Years Later

    Science.gov (United States)

    Plomin, Robert

    2013-01-01

    Fourteen years ago, the first article on molecular genetics was published in this journal: "Child Development, Molecular Genetics, and What to Do With Genes Once They Are Found" (R. Plomin & M. Rutter, 1998). The goal of the article was to outline what developmentalists can do with genes once they are found. These new directions for developmental…

  2. Child Development and Molecular Genetics: 14 Years Later

    Science.gov (United States)

    Plomin, Robert

    2013-01-01

    Fourteen years ago, the first article on molecular genetics was published in this journal: "Child Development, Molecular Genetics, and What to Do With Genes Once They Are Found" (R. Plomin & M. Rutter, 1998). The goal of the article was to outline what developmentalists can do with genes once they are found. These new directions for developmental…

  3. Plant genetic and molecular responses to water deficit

    Directory of Open Access Journals (Sweden)

    Silvio Salvi

    2011-02-01

    Full Text Available Plant productivity is severely affected by unfavourable environmental conditions (biotic and abiotic stresses. Among others, water deficit is the plant stress condition which mostly limits the quality and the quantity of plant products. Tolerance to water deficit is a polygenic trait strictly dependent on the coordinated expression of a large set of genes coding for proteins directly involved in stress-induced protection/repair mechanisms (dehydrins, chaperonins, enzymes for the synthesis of osmoprotectants and detoxifying compounds, and others as well as genes involved in transducing the stress signal and regulating gene expression (transcription factors, kinases, phosphatases. Recently, research activities in the field evolved from the study of single genes directly involved in cellular stress tolerance (functional genes to the identification and characterization of key regulatory genes involved in stress perception and transduction and able to rapidly and efficiently activate the complex gene network involved in the response to stress. The complexity of the events occurring in response to stress have been recently approached by genomics tools; in fact the analysis of transcriptome, proteome and metabolome of a plant tissue/cell in response to stress already allowed to have a global view of the cellular and molecular events occurring in response to water deficit, by the identification of genes activated and co-regulated by the stress conditions and the characterization of new signalling pathways. Moreover the recent application of forward and reverse genetic approaches, trough mutant collection development, screening and characterization, is giving a tremendous impulse to the identification of gene functions with key role in stress tolerance. The integration of data obtained by high-throughput genomic approaches, by means of powerful informatic tools, is allowing nowadays to rapidly identify of major genes/QTLs involved in stress tolerance

  4. Defining the molecular genetic basis of idiopathic dilated cardiomyopathy.

    Science.gov (United States)

    Olson, T M; Keating, M T

    1997-02-01

    Dilated cardiomyopathy (DCM) is a significant health care problem. The etiology is idiopathic in approximately half of the patients. Recognition that 20%-25% of idiopathic DCM cases are familial has advanced the hypothesis that single gene defects are important in the disease's pathogenesis. General linkage analyses in rare, large DCM families have determined the chromosome location of five idiopathic DCM genes. Candidate-gene mutational analyses in more typical, small pedigrees represent an alternative strategy for DCM gene identification. Human molecular genetics will play a fundamental role in defining pathogenic mechanisms for DCM with the prospect of new, molecular-based diagnostic and therapeutic approaches. (Trends Cardiovasc Med 1997;7:60-63). © 1997, Elsevier Science Inc.

  5. MOLECULAR GENETIC MARKERS AND METHODS OF THEIR IDENTIFICATION IN MODERN FISH-FARMING

    OpenAIRE

    I. Hrytsyniak; O. Zaloilo; I. Zaloilo; N. Borysenko

    2014-01-01

    Purpose. The application of molecular genetic markers has been widely used in modern experimental fish-farming in recent years. This methodology is currently presented by a differentiated approach with individual mechanisms and clearly defined possibilities. Numerous publications in the scientific literature that are dedicated to molecular genetic markers for the most part offer purely practical data. Thus, the synthesis and analysis of existing information on the general principles of action...

  6. Molecular genetic studies in flax (Linum usitatissimum L.)

    NARCIS (Netherlands)

    Vromans, J.

    2006-01-01

    In this thesis five molecular genetic studies on flax ( Linum usitatissimum L.) are described, of which two chapters aim to characterize the genetic structure and the amount of genetic diversity in the primary and secondary gene pool of the crop species. Three chapters describe the development of

  7. Molecular genetics at the Fort Collins Science Center

    Science.gov (United States)

    Oyler-McCance, S.J.; Stevens, P.D.

    2011-01-01

    The Fort Collins Science Center operates a molecular genetic and systematics research facility (FORT Molecular Ecology Laboratory) that uses molecular genetic tools to provide genetic information needed to inform natural resource management decisions. For many wildlife species, the data generated have become increasingly important in the development of their long-term management strategies, leading to a better understanding of species diversity, population dynamics and ecology, and future conservation and management needs. The Molecular Ecology Lab serves Federal research and resource management agencies by developing scientifically rigorous research programs using nuclear, mitochondrial and chloroplast DNA to help address many of today's conservation biology and natural resource management issues.

  8. [Advance in molecular genetic research on primary congenital glaucoma].

    Science.gov (United States)

    Li, Xiulan; Liu, Haotian; Zhang, Dingding

    2016-04-01

    Primary congenital glaucoma (PCG) is one of the major diseases causing blindness in children, but its pathogenesis has remained unclear. Genetic factors play an important role in the pathogenesis of PCG. Molecular genetics of candidate genes such as CYP1B1, MYOC, LTBP2 and FOXC1 has so far been explored, but no disease-causing gene has been identified. Molecular genetic research on PCG including candidate gene screening and research strategies are reviewed here.

  9. Genetic Algorithm Approaches for Actuator Placement

    Science.gov (United States)

    Crossley, William A.

    2000-01-01

    This research investigated genetic algorithm approaches for smart actuator placement to provide aircraft maneuverability without requiring hinged flaps or other control surfaces. The effort supported goals of the Multidisciplinary Design Optimization focus efforts in NASA's Aircraft au program. This work helped to properly identify various aspects of the genetic algorithm operators and parameters that allow for placement of discrete control actuators/effectors. An improved problem definition, including better definition of the objective function and constraints, resulted from this research effort. The work conducted for this research used a geometrically simple wing model; however, an increasing number of potential actuator placement locations were incorporated to illustrate the ability of the GA to determine promising actuator placement arrangements. This effort's major result is a useful genetic algorithm-based approach to assist in the discrete actuator/effector placement problem.

  10. genomic and transcriptomic approaches towards the genetic ...

    African Journals Online (AJOL)

    USER

    to the complex nature of these stresses, and the genotype x environment interaction (GxE). .... collection (Azam-Ali et al., 2001); (vi) biological .... Integrative platform to study gene function and gene evolution in legumes ..... a powerful dissection of the genetic control of ... complemented by a new approach called genomic.

  11. Molecular genetic strategies for species identification

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    This paper probes into the molecular genetic mechanism of the formation of species, subspecies and variety in evolving progression, and brings forward 5 criteria of an ideal strategy in species identification: stating the specific characteristics at species, subspecies and variety level without any interference of too high polymorphism at individual or population level; keys should be distributed as 0 or 1, e. g. yes or no; satisfying re-peatability and simple operation; high veracity and reliability; adaptability to widely various specimen. Respec-tively, this paper reviews two strategies focusing on detecting the fragment length polymorphism and base re-placement and lays out some detail methods under above strategies. It demonstrates that it is not possible to solve all species problems by pursuing identification with only a single gene or DNA fragment. Only based on thorough consideration of all strategies, a method or combined several methods could bring satisfying reliability. For advanced focuses, it requires not only development and optimization of methods under above strategies, but also new originality of creative strategies.

  12. Cellular biosensing: chemical and genetic approaches.

    Science.gov (United States)

    Haruyama, Tetsuya

    2006-05-24

    Biosensors have been developed to determine the concentration of specific compounds in situ. They are already widely employed as a practical technology in the clinical and healthcare fields. Recently, another concept of biosensing has been receiving attention: biosensing for the evaluation of molecular potency. The development of this novel concept has been supported by the development of related technologies, as such as molecular design, molecular biology (genetic engineering) and cellular/tissular engineering. This review is addresses this new concept of biosensing and its application to the evaluation of the potency of chemicals in biological systems, in the field of cellular/tissular engineering. Cellular biosensing may provide information on both pharmaceutical and chemical safety, and on drug efficacy in vitro as a screening tool.

  13. Genetic and Molecular Network Analysis of Behavior

    OpenAIRE

    Williams, Robert W.; Mulligan, Megan K.

    2012-01-01

    This chapter provides an introduction into the genetic control and analysis of behavioral variation using powerful online resources. We introduce you to the new field of systems genetics using "case studies" drawn from the world of behavioral genetics that exploit populations of genetically diverse lines of mice. These lines differ very widely in patterns of gene and protein expression in the brain and in patterns of behavior. In this chapter we address the following set of related questions:...

  14. A multiobjective approach to the genetic code adaptability problem.

    Science.gov (United States)

    de Oliveira, Lariza Laura; de Oliveira, Paulo S L; Tinós, Renato

    2015-02-19

    The organization of the canonical code has intrigued researches since it was first described. If we consider all codes mapping the 64 codes into 20 amino acids and one stop codon, there are more than 1.51×10(84) possible genetic codes. The main question related to the organization of the genetic code is why exactly the canonical code was selected among this huge number of possible genetic codes. Many researchers argue that the organization of the canonical code is a product of natural selection and that the code's robustness against mutations would support this hypothesis. In order to investigate the natural selection hypothesis, some researches employ optimization algorithms to identify regions of the genetic code space where best codes, according to a given evaluation function, can be found (engineering approach). The optimization process uses only one objective to evaluate the codes, generally based on the robustness for an amino acid property. Only one objective is also employed in the statistical approach for the comparison of the canonical code with random codes. We propose a multiobjective approach where two or more objectives are considered simultaneously to evaluate the genetic codes. In order to test our hypothesis that the multiobjective approach is useful for the analysis of the genetic code adaptability, we implemented a multiobjective optimization algorithm where two objectives are simultaneously optimized. Using as objectives the robustness against mutation with the amino acids properties polar requirement (objective 1) and robustness with respect to hydropathy index or molecular volume (objective 2), we found solutions closer to the canonical genetic code in terms of robustness, when compared with the results using only one objective reported by other authors. Using more objectives, more optimal solutions are obtained and, as a consequence, more information can be used to investigate the adaptability of the genetic code. The multiobjective approach

  15. Molecular approaches to Taenia asiatica.

    Science.gov (United States)

    Jeon, Hyeong-Kyu; Eom, Keeseon S

    2013-02-01

    Taenia solium, T. saginata, and T. asiatica are taeniid tapeworms that cause taeniasis in humans and cysticercosis in intermediate host animals. Taeniases remain an important public health concerns in the world. Molecular diagnostic methods using PCR assays have been developed for rapid and accurate detection of human infecting taeniid tapeworms, including the use of sequence-specific DNA probes, PCR-RFLP, and multiplex PCR. More recently, DNA diagnosis using PCR based on histopathological specimens such as 10% formalin-fixed paraffin-embedded and stained sections mounted on slides has been applied to cestode infections. The mitochondrial gene sequence is believed to be a very useful molecular marker for not only studying evolutionary relationships among distantly related taxa, but also for investigating the phylo-biogeography of closely related species. The complete sequence of the human Taenia tapeworms mitochondrial genomes were determined, and its organization and structure were compared to other human-tropic Taenia tapeworms for which complete mitochondrial sequence data were available. The multiplex PCR assay with the Ta4978F, Ts5058F, Tso7421F, and Rev7915 primers will be useful for differential diagnosis, molecular characterization, and epidemiological surveys of human Taenia tapeworms.

  16. Apocalypse... Now? Molecular epidemiology, predictive genetic tests, and social communication of genetic contents

    Directory of Open Access Journals (Sweden)

    Luis David Castiel

    Full Text Available The author analyzes the underlying theoretical aspects in the construction of the molecular watershed of epidemiology and the concept of genetic risk, focusing on issues raised by contemporary reality: new technologies, globalization, proliferation of communications strategies, and the dilution of identity matrices. He discusses problems pertaining to the establishment of such new interdisciplinary fields as molecular epidemiology and molecular genetics. Finally, he analyzes the repercussions of the social communication of genetic content, especially as related to predictive genetic tests and cloning of animals, based on triumphal, deterministic metaphors sustaining beliefs relating to the existence and supremacy of concepts such as 'purity', 'essence', and 'unification' of rational, integrated 'I's/egos'.

  17. Molecular approaches to bivalve population studies: a review

    Directory of Open Access Journals (Sweden)

    Dragomir-Cosmin David

    2011-12-01

    Full Text Available This paper presents a literature review concerning the importance of molecular approaches in bivalve’s population study. The class Bivalvia counts more than 20,000 species with a wide distribution both in freshwater and marine environment. Given their importance especially in aquaculture as a source of food, they have also a strong economic impact upon human society. This review encompasses best practices in bivalve studies from field sampling to laboratory analyses, addressing questions about molecular methods and tools commonly used by specialized researchers. Molecular tools specifically deals with phylogeography, population genetics, biology, ecology and taxonomy. In all these fields, molecular markers play an important role by completing some unanswered questions such as the role of the bivalves in the ecosystems in relation to anthropogenic and global change issues. Numerous genetic markers were developed for specific problems, thereferore we identify as a major issue the absence of uniform and universally recognized methods. The various sections of the paper emphasize from peer reviewed literature literature which are considered the most useful markers, costs and benefits of different methodology, major gaps of knowledge.in bivalve population studies. By reviewing virtually all genetic markers employed during nearly half a century of bivalve molecular research, in our opinion two are the best option “tools: the mitochondrial COI (cytochrome oxidase subunit I and nuclear ITS2 (internal transcribed spacer 2.

  18. WONOEP appraisal: new genetic approaches to study epilepsy

    Science.gov (United States)

    Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.

    2014-01-01

    Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non

  19. Lack of consistence between morphological and molecular genetic ...

    African Journals Online (AJOL)

    tdtzeng

    2011-02-14

    Feb 14, 2011 ... 454-bp at 5' end of mitochondrial DNA control region were conducted. ..... Molecular Evolutionary Genetics Analysis and sequence alignment. ... substitutions in the control region of mitochondrial DNA in humans.

  20. Molecular genetics of hemophilia A: Clinical perspectives

    African Journals Online (AJOL)

    Azza A.G. Tantawy

    Phenotypic heterogeneity of hemophilia is multifactorial, mainly related to F8 mutation ... Inhibitor development is mainly related to F8 null mutations, but other genetic and non genetic factors could .... Individuals with a history of a lifelong bleeding tendency ... nic and geographical variation in the allele frequencies of these.

  1. Improving human forensics through advances in genetics, genomics and molecular biology.

    Science.gov (United States)

    Kayser, Manfred; de Knijff, Peter

    2011-03-01

    Forensic DNA profiling currently allows the identification of persons already known to investigating authorities. Recent advances have produced new types of genetic markers with the potential to overcome some important limitations of current DNA profiling methods. Moreover, other developments are enabling completely new kinds of forensically relevant information to be extracted from biological samples. These include new molecular approaches for finding individuals previously unknown to investigators, and new molecular methods to support links between forensic sample donors and criminal acts. Such advances in genetics, genomics and molecular biology are likely to improve human forensic case work in the near future.

  2. Molecular approach of auditory neuropathy.

    Science.gov (United States)

    Silva, Magali Aparecida Orate Menezes da; Piatto, Vânia Belintani; Maniglia, Jose Victor

    2015-01-01

    Mutations in the otoferlin gene are responsible for auditory neuropathy. To investigate the prevalence of mutations in the mutations in the otoferlin gene in patients with and without auditory neuropathy. This original cross-sectional case study evaluated 16 index cases with auditory neuropathy, 13 patients with sensorineural hearing loss, and 20 normal-hearing subjects. DNA was extracted from peripheral blood leukocytes, and the mutations in the otoferlin gene sites were amplified by polymerase chain reaction/restriction fragment length polymorphism. The 16 index cases included nine (56%) females and seven (44%) males. The 13 deaf patients comprised seven (54%) males and six (46%) females. Among the 20 normal-hearing subjects, 13 (65%) were males and seven were (35%) females. Thirteen (81%) index cases had wild-type genotype (AA) and three (19%) had the heterozygous AG genotype for IVS8-2A-G (intron 8) mutation. The 5473C-G (exon 44) mutation was found in a heterozygous state (CG) in seven (44%) index cases and nine (56%) had the wild-type allele (CC). Of these mutants, two (25%) were compound heterozygotes for the mutations found in intron 8 and exon 44. All patients with sensorineural hearing loss and normal-hearing individuals did not have mutations (100%). There are differences at the molecular level in patients with and without auditory neuropathy. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  3. Molecular approach of auditory neuropathy

    Directory of Open Access Journals (Sweden)

    Magali Aparecida Orate Menezes da Silva

    2015-06-01

    Full Text Available INTRODUCTION: Mutations in the otoferlin gene are responsible for auditory neuropathy. OBJECTIVE: To investigate the prevalence of mutations in the mutations in the otoferlin gene in patients with and without auditory neuropathy. METHODS: This original cross-sectional case study evaluated 16 index cases with auditory neuropathy, 13 patients with sensorineural hearing loss, and 20 normal-hearing subjects. DNA was extracted from peripheral blood leukocytes, and the mutations in the otoferlin gene sites were amplified by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The 16 index cases included nine (56% females and seven (44% males. The 13 deaf patients comprised seven (54% males and six (46% females. Among the 20 normal-hearing subjects, 13 (65% were males and seven were (35% females. Thirteen (81% index cases had wild-type genotype (AA and three (19% had the heterozygous AG genotype for IVS8-2A-G (intron 8 mutation. The 5473C-G (exon 44 mutation was found in a heterozygous state (CG in seven (44% index cases and nine (56% had the wild-type allele (CC. Of these mutants, two (25% were compound heterozygotes for the mutations found in intron 8 and exon 44. All patients with sensorineural hearing loss and normal-hearing individuals did not have mutations (100%. CONCLUSION: There are differences at the molecular level in patients with and without auditory neuropathy.

  4. Analysis of Molecular Genetics Content in Spanish Secondary School Textbooks

    Science.gov (United States)

    Martinez-Gracia, M. V.; Gil-Quilez, M. J.; Osada, J.

    2006-01-01

    The treatment of molecular biology in thirty-four Spanish high school biology textbooks has been analysed using a check-list made up of twenty-three items. The study showed a tendency to confuse the genetic code with genetic information. The treatment of DNA transcription, regulation of gene expression and translation were presented as masses of…

  5. [Molecular genetics methods in the study of hereditary essential hypertension].

    Science.gov (United States)

    Jindra, A; Horký, K

    1998-01-26

    The main task in hypertension research is to explain genetic causes of a raised blood pressure. It is anticipated that advances in this area will promote not only a better understanding of the pathophysiology of hypertension but will make a more aimed approach to early diagnosis, prevention and therapy of essential hypertension possible. The greatest problems in investigations of the heredity of hypertension are; a) in cardiovascular control mechanisms several genes participate; b) factors of the external environment which act on a long-term basis interfere with the relationship of the genotype and phenotype individually, within the family and regionally; c) the blood pressure is a continuous variable and the definition of the phenotype of hypertension is inaccurate; d) inadequate number of family members where hypertension segregates. New methods in molecular biology and statistical genetics made it possible to assess a number of highly polymorphous genetic signs in several candidate genes and the subsequent investigation of their possible role in the pathogenesis of hypertension. The majority of hitherto accomplished studies was concentrated on genes coding different components of the renin-angiotensin system: renin, ACE, angiotensinogen and angiotensin II receptors. So far the most promising, though not consistent, results were obtained for angiotensinogen and the insulin receptor. Work focused on the relationship of the polymorphism of genes for ANF, growth hormone and kallikrein to essential hypertension is negative. The genetic heterogeneity of the human population, physiological differences in the genesis of high blood pressure in different ethnical groups and inaccurate measurements of specific phenotypes can contribute to different results of different studies.

  6. Molecular genetics of human pigmentation diversity

    National Research Council Canada - National Science Library

    Sturm, Richard A

    2009-01-01

    The genetic basis underlying normal variation in the pigmentary traits of skin, hair and eye colour has been the subject of intense research directed at understanding the diversity seen both between...

  7. Genetic and molecular aspects of spinocerebellar ataxias

    OpenAIRE

    Honti, Viktor; Vécsei, László

    2005-01-01

    The group of spinocerebellar ataxias (SCAs) includes more than 20 subgroups based only on genetic research. The “ataxia genes” are autosomal; the “disease-alleles” are dominant, and many of them, but not all, encode a protein with an abnormally long polyglutamine domain. In DNA, this domain can be detected as an elongated CAG repeat region, which is the basis of genetic diagnostics. The polyglutamine tails often tend to aggregate and form inclusions. In some cases, protein–protein interaction...

  8. Network medicine approaches to the genetics of complex diseases.

    Science.gov (United States)

    Silverman, Edwin K; Loscalzo, Joseph

    2012-08-01

    Complex diseases are caused by perturbations of biological networks. Genetic analysis approaches focused on individual genetic determinants are unlikely to characterize the network architecture of complex diseases comprehensively. Network medicine, which applies systems biology and network science to complex molecular networks underlying human disease, focuses on identifying the interacting genes and proteins which lead to disease pathogenesis. The long biological path between a genetic risk variant and development of a complex disease involves a range of biochemical intermediates, including coding and non-coding RNA, proteins, and metabolites. Transcriptomics, proteomics, metabolomics, and other -omics technologies have the potential to provide insights into complex disease pathogenesis, especially if they are applied within a network biology framework. Most previous efforts to relate genetics to -omics data have focused on a single -omics platform; the next generation of complex disease genetics studies will require integration of multiple types of -omics data sets in a network context. Network medicine may also provide insight into complex disease heterogeneity, serve as the basis for new disease classifications that reflect underlying disease pathogenesis, and guide rational therapeutic and preventive strategies.

  9. Micropropagation, genetic engineering, and molecular biology of Populus

    Science.gov (United States)

    N. B. Klopfenstein; Y. W. Chun; M. -S. Kim; M. A. Ahuja; M. C. Dillon; R. C. Carman; L. G. Eskew

    1997-01-01

    Thirty-four Populus biotechnology chapters, written by 85 authors, are comprised in 5 sections: 1) in vitro culture (micropropagation, somatic embryogenesis, protoplasts, somaclonal variation, and germplasm preservation); 2) transformation and foreign gene expression; 3) molecular biology (molecular/genetic characterization); 4) biotic and abiotic resistance (disease,...

  10. Determination of genetic structure of germplasm collections: are traditional hierarchical clustering methods appropriate for molecular marker data?

    NARCIS (Netherlands)

    Odong, T.L.; Heerwaarden, van J.; Jansen, J.; Hintum, van T.J.L.; Eeuwijk, van F.A.

    2011-01-01

    Despite the availability of newer approaches, traditional hierarchical clustering remains very popular in genetic diversity studies in plants. However, little is known about its suitability for molecular marker data. We studied the performance of traditional hierarchical clustering techniques using

  11. Estimation of the proportion of genetic variance explained by molecular markers

    OpenAIRE

    Bearzoti,Eduardo; Vencovsky, Roland

    1998-01-01

    Estimation of the proportion of genetic variance explained by molecular markers (p) plays an important role in basic studies of quantitative traits, as well as in marker-assisted selection (MAS), if the selection index proposed by Lande and Thompson (Genetics 124: 743-756, 1990) is used. Frequently, the coefficient of determination (R2) is used to account for this proportion. In the present study, a simple estimator of p is presented, which is applicable when a multiple regression approach is...

  12. Advantages of using molecular coancestry in the removal of introgressed genetic material

    Science.gov (United States)

    2013-01-01

    Background When introgression of undesired exogenous genetic material occurs in a population intended to remain pure, actions are necessary to recover the original background. It has been shown that genome-wide information can replace pedigree information for different objectives and is a valuable tool in the fields of genetic conservation and breeding. In this simulation study, molecular information provided by 50 000 SNP was used to minimise the molecular coancestry between individuals of an admixed population and the foreign individuals that originally introgressed a native population in order to remove the exogenous DNA. Results This management method, which detects the ‘purest’ individuals to be used as parents for the next generation, allowed recovery of the native genetic background to a great extent in all simulated scenarios. However, it also caused an increase in inbreeding larger than expected because of the lower number of individuals selected as parents and the higher coancestry between them. In scenarios involving several introgression events the method was more efficient than in those involving a single introgression event because part of the genetic information was mixed with the native genetic material for a shorter period. Conclusions Genome-wide information can be used to identify the purest individuals via the minimisation of molecular coancestry between individuals of the admixed and exogenous populations. Removal of the undesired genetic material is more efficient with a molecular-based approach than with a pedigree-based approach. PMID:23634969

  13. Molecular genetics of dyslexia: an overview

    NARCIS (Netherlands)

    Carrion-Castillo, A.; Franke, B.; Fisher, S.E.

    2013-01-01

    Dyslexia is a highly heritable learning disorder with a complex underlying genetic architecture. Over the past decade, researchers have pinpointed a number of candidate genes that may contribute to dyslexia susceptibility. Here, we provide an overview of the state of the art, describing how studies

  14. Molecular genetics of congenital nuclear cataract.

    Science.gov (United States)

    Deng, Hao; Yuan, Lamei

    2014-02-01

    A cataract is defined as opacification of the normally transparent crystalline lens. Congenital cataract (CC) is a type of cataract that presents at birth or during early childhood. CC is one of the most common causes of visual impairment or blindness in children worldwide. Approximately 50% of all CC cases may have a genetic cause which is quite heterogeneous. CC occurs in a variety of morphologic configurations, including polar/subcapsular, nuclear, lamellar, sutural, cortical, membranous/capsular and complete. Nuclear cataract refers to the opacification limited to the embryonic and/or fetal nuclei of the lens. Although congenital nuclear cataract can be caused by multiple factors, genetic mutation remains to be the most common cause. It can be inherited in one of the three patterns: autosomal dominant, autosomal recessive, or X-linked transmission. Autosomal dominant inheritance is the most frequent mode with high penetrance. There may be no obvious correlation between the genotype and phenotype of congenital nuclear cataract. Animal models have been established to study the pathogenesis of congenital nuclear cataract and to identify candidate genes. In this review, we highlight identified genetic mutations that account for congenital nuclear cataract. Our review may be helpful for genetic counseling and prenatal diagnosis.

  15. [Current methods in genetic analysis : an approach for genetics-based preventive medicine].

    Science.gov (United States)

    Klein, Hans-Georg; Rost, Imma

    2015-02-01

    Modern genetic analysis methods such as DNA arrays (gene chips) or high-throughput DNA sequencing of the next generation (Next Generation Sequencing, NGS) have once again accelerated the pace of innovation that has been powered by genome research over the past 10 years of the "post-genomic era". The present paper introduces array and NGS methods as two important innovation driving methods and provides examples for their application in large-scale scientific projects. However, a broad application of these very powerful technologies for genetic screening for the purpose of disease prevention is currently not yet in sight. The complexity of the interaction of genes, gene products and the environment has so far exceeded all expectations, suggesting that reliable statements about the medical relevance of common genetic variants can presently only be made in a few areas such as pharmacogenetics and oncology. We also discuss ethical issues raised by genetic population screening. The aim of this paper is to provide a brief outline of the development of methods in molecular genetics to the now dominant modern technologies and present their applications in research, in the diagnosis of rare diseases, and in terms of screening approaches.

  16. Molecular markers: a potential resource for ginger genetic diversity studies.

    Science.gov (United States)

    Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

    2016-12-01

    Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

  17. Impact of Molecular Genetic Research on Peanut Cultivar Development

    Directory of Open Access Journals (Sweden)

    Baozhu Guo

    2011-12-01

    Full Text Available Peanut (Arachis hypogaea L. has lagged other crops on use of molecular genetic technology for cultivar development in part due to lack of investment, but also because of low levels of molecular polymorphism among cultivated varieties. Recent advances in molecular genetic technology have allowed researchers to more precisely measure genetic polymorphism and enabled the development of low density genetic maps for A. hypogaea and the identification of molecular marker or QTL’s for several economically significant traits. Genomic research has also been used to enhance the amount of genetic diversity available for use in conventional breeding through the development of transgenic peanut, and the creation of TILLING populations and synthetic allotetraploids. Marker assisted selection (MAS is becoming more common in peanut cultivar development programs, and several cultivar releases are anticipated in the near future. There are also plans to sequence the peanut genome in the near future which should result in the development of additional molecular tools that will greatly advance peanut cultivar development.

  18. Recommendations for reporting results of diagnostic genetic testing (biochemical, cytogenetic and molecular genetic).

    Science.gov (United States)

    Claustres, Mireille; Kožich, Viktor; Dequeker, Els; Fowler, Brain; Hehir-Kwa, Jayne Y; Miller, Konstantin; Oosterwijk, Cor; Peterlin, Borut; van Ravenswaaij-Arts, Conny; Zimmermann, Uwe; Zuffardi, Orsetta; Hastings, Ros J; Barton, David E

    2014-02-01

    Genetic test results can have considerable importance for patients, their parents and more remote family members. Clinical therapy and surveillance, reproductive decisions and genetic diagnostics in family members, including prenatal diagnosis, are based on these results. The genetic test report should therefore provide a clear, concise, accurate, fully interpretative and authoritative answer to the clinical question. The need for harmonizing reporting practice of genetic tests has been recognised by the External Quality Assessment (EQA), providers and laboratories. The ESHG Genetic Services Quality Committee has produced reporting guidelines for the genetic disciplines (biochemical, cytogenetic and molecular genetic). These guidelines give assistance on report content, including the interpretation of results. Selected examples of genetic test reports for all three disciplines are provided in an annexe.

  19. Rett syndrome molecular diagnosis and implications in genetic counseling

    Directory of Open Access Journals (Sweden)

    Noruzinia M

    2007-01-01

    Full Text Available Rett syndrome is a rare genetic X-linked dominant disorder. This syndrome is the most frequent cause of mental retardation in girls. In the classical form of the disease, the presenting signs and the course of development are characteristic. However clinical diagnosis can be very difficult when the expression is not in the classical form. Mutations in MeCP2 are responsible for 80% of cases. When MeCP2 mutation is found in an index case, genetic counseling is similar to that in other X-linked dominant genetic diseases. However, mutations in this gene can cause a spectrum of atypical forms. On the other hand, other genetic conditions like translocations, sex chromosome numerical anomalies, and mutations in other genes can complicate genetic counseling in this syndrome. We present the first case of molecular diagnosis of Rett syndrome in Iran and discuss the recent developments in its genetic counseling.

  20. Molecular genetics of autism spectrum disorders.

    Science.gov (United States)

    Shastry, Barkur S

    2003-01-01

    Autistic disorder belongs to a broad spectrum of pervasive developmental disorders. Autism is a clinically and genetically heterogeneous condition. It is characterized by impairment in a broad range of social interactions, communication, and repetitive patterns of behavior and interest. Although the exact etiology of the condition is not known, family and twin studies strongly support genetic factors in autism. Genome-wide scans suggest several susceptibility loci that may contain one or more predisposing genes. However, no such genes have been identified so far that predispose patients to autism. The condition is over 90% heritable, but the mode of inheritance is not clear. Moreover, it does not seem to be a single gene disorder. There is no cure for autism. Individualized structured education, family support services, and antipsychotic drugs are recommended. These may alleviate some behavioral problems. The identification of autism genes, an understanding of the neurobiology of the condition, and additional clinical studies may help to develop pharmacological interventions in the future.

  1. Studying Human Disease Genes in "Caenorhabditis Elegans": A Molecular Genetics Laboratory Project

    Science.gov (United States)

    Cox-Paulson, Elisabeth A.; Grana, Theresa M.; Harris, Michelle A.; Batzli, Janet M.

    2012-01-01

    Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether "Caenorhabditis elegans" can be a useful model system for studying genes…

  2. Studying Human Disease Genes in "Caenorhabditis Elegans": A Molecular Genetics Laboratory Project

    Science.gov (United States)

    Cox-Paulson, Elisabeth A.; Grana, Theresa M.; Harris, Michelle A.; Batzli, Janet M.

    2012-01-01

    Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether "Caenorhabditis elegans" can be a useful model system for studying genes…

  3. Molecular Population Genetics of Rice Domestication

    Institute of Scientific and Technical Information of China (English)

    Tian Tang; Suhua Shi

    2007-01-01

    Domestication is a selection process that genetically modifies species to meet human needs. A most intriguing feature of domestication is the extreme phenotypic diversification among breeds. What could be the ultimate source of such genetic variations? Another notable outcome of artificial selection is the reduction in the fitness of domesticated species when they live in the wild without human assistance. The complete sequences of the two subspecies of rice cultivars provide an opportunity to address these questions. Between the two subspecies, we found much higher rates of non-synonymous (N) than synonymous (S) substitutions and the N/S ratios are higher between cultivars than between wild species. Most interestingly, substitutions of highly dissimilar amino acids that are deleterious and uncommon between natural species are disproportionately common between the two subspecies of rice. We suggest strong selection in the absence of effective recombination may be the driving force, which we called the domestication-associated Hill-Robertson effect. These hitchhiking mutations may contribute to some fitness reduction in cultivars. Comparisons of the two genomes also reveal the existence of highly divergent regions in the genomes. Haplotypes in these regions often form highly polymorphic linkage blocks that are much older than speciation between wild species. Genes from such regions could contribute to the differences between indica and japonica and are likely to be involved in the diversifying selection under domestication. Their existence suggests that the amount of genetic variation within the single progenitor species Oryza ruflpogon may be insufficient to account for the variation among rice cultivars, which may come from a more inclusive gene pool comprising most of the A-genome wild species. Genes from the highly polymorphic regions also provide strong support for the independent domestication of the two subspecies. The genomic variation in rice has revealing

  4. Quantitative Genetics in the Era of Molecular Genetics: Learning Abilities and Disabilities as an Example

    Science.gov (United States)

    Haworth, Claire M. A.; Plomin, Robert

    2010-01-01

    Objective: To consider recent findings from quantitative genetic research in the context of molecular genetic research, especially genome-wide association studies. We focus on findings that go beyond merely estimating heritability. We use learning abilities and disabilities as examples. Method: Recent twin research in the area of learning…

  5. The etiology and molecular genetics of human pigmentation disorders.

    Science.gov (United States)

    Baxter, Laura L; Pavan, William J

    2013-01-01

    Pigmentation, defined as the placement of pigment in skin, hair, and eyes for coloration, is distinctive because the location, amount, and type of pigmentation provides a visual manifestation of genetic heterogeneity in pathways regulating the pigment-producing cells, melanocytes. The scope of this genetic heterogeneity in humans ranges from normal to pathological pigmentation phenotypes. Clinically, normal human pigmentation encompasses a variety of skin and hair color as well as punctate pigmentation such as melanocytic nevi (moles) or ephelides (freckles), while abnormal human pigmentation exhibits markedly reduced or increased pigment levels, known as hypopigmentation and hyperpigmentation, respectively. Elucidation of the molecular genetics underlying pigmentation has revealed genes important for melanocyte development and function. Furthermore, many pigmentation disorders show additional defects in cells other than melanocytes, and identification of the genetic insults in these disorders has revealed pleiotropic genes, where a single gene is required for various functions in different cell types. Thus, unravelling the genetics of easily visualized pigmentation disorders has identified molecular similarities between melanocytes and less visible cell types/tissues, arising from a common developmental origin and/or shared genetic regulatory pathways. Herein we discuss notable human pigmentation disorders and their associated genetic alterations, focusing on the fact that the developmental genetics of pigmentation abnormalities are instructive for understanding normal pathways governing development and function of melanocytes. Copyright © 2012 Wiley Periodicals, Inc.

  6. Biosynthesis and molecular genetics of polyketides in marine dinoflagellates.

    Science.gov (United States)

    Kellmann, Ralf; Stüken, Anke; Orr, Russell J S; Svendsen, Helene M; Jakobsen, Kjetill S

    2010-03-31

    Marine dinoflagellates are the single most important group of algae that produce toxins, which have a global impact on human activities. The toxins are chemically diverse, and include macrolides, cyclic polyethers, spirolides and purine alkaloids. Whereas there is a multitude of studies describing the pharmacology of these toxins, there is limited or no knowledge regarding the biochemistry and molecular genetics involved in their biosynthesis. Recently, however, exciting advances have been made. Expressed sequence tag sequencing studies have revealed important insights into the transcriptomes of dinoflagellates, whereas other studies have implicated polyketide synthase genes in the biosynthesis of cyclic polyether toxins, and the molecular genetic basis for the biosynthesis of paralytic shellfish toxins has been elucidated in cyanobacteria. This review summarises the recent progress that has been made regarding the unusual genomes of dinoflagellates, the biosynthesis and molecular genetics of dinoflagellate toxins. In addition, the evolution of these metabolic pathways will be discussed, and an outlook for future research and possible applications is provided.

  7. Genetic, functional and molecular features of glucocorticoid receptor binding.

    Directory of Open Access Journals (Sweden)

    Francesca Luca

    Full Text Available Glucocorticoids (GCs are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR, which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI and 4 Tuscans (TSI lymphoblastoid cell lines (LCLs, we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative depending on the presence of specific interacting transcription factors. Accordingly, when we performed ChIP-seq for GR and NF-κB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches.

  8. A theoretical molecular network for dyslexia: integrating available genetic findings

    NARCIS (Netherlands)

    Poelmans, G.J.V.; Buitelaar, J.K.; Pauls, D.L.; Franke, B.

    2011-01-01

    Developmental dyslexia is a common specific childhood learning disorder with a strong heritable component. Previous studies using different genetic approaches have identified several genetic loci and candidate genes for dyslexia. In this article, we have integrated the current knowledge on 14 dyslex

  9. Primer on Molecular Genetics; DOE Human Genome Program

    Science.gov (United States)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  10. Primer on molecular genetics. DOE Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  11. The Molecular Genetics of Restless Legs Syndrome.

    Science.gov (United States)

    Rye, David B

    2015-09-01

    Restless legs syndrome (RLS) is a common sensorimotor trait defined by symptoms that interfere with sleep onset and maintenance in a clinically meaningful way. Nonvolitional myoclonus while awake and asleep is a sign of the disorder and an informative endophenotype. The genetic contributions to RLS/periodic leg movements are substantial, are among the most robust defined to date for a common disease, and account for much of the variance in disease expressivity. The disorder is polygenic, as revealed by recent genome-wide association studies. Experimental studies are revealing mechanistic details of how these common variants might influence RLS expressivity.

  12. Oligocone trichromacy: clinical and molecular genetic investigations

    DEFF Research Database (Denmark)

    Andersen, Mette K G; Christoffersen, Nynne L B; Sander, Birgit

    2010-01-01

    of congenital nystagmus, and subjectively normal or near-normal color vision; five patients reported photophobia. Clinical examinations revealed largely normal fundi, normal Goldmann visual field results with the IV/4e target, and normal color discrimination or mild color vision deficiency. Electrophysiological...... of unknown significance in CNGB3 and PDE6C in two other patients. CONCLUSIONS: Oligocone trichromacy is a heterogeneous condition with respect to both phenotypic appearance and genetic background. The finding of mutations in genes known to be involved in complete and incomplete achromatopsia supports...

  13. Silver-Russell syndrome: genetic basis and molecular genetic testing

    Directory of Open Access Journals (Sweden)

    Binder Gerhard

    2010-06-01

    Full Text Available Abstract Imprinted genes with a parent-of-origin specific expression are involved in various aspects of growth that are rooted in the prenatal period. Therefore it is predictable that many of the so far known congenital imprinting disorders (IDs are clinically characterised by growth disturbances. A noteable imprinting disorder is Silver-Russell syndrome (SRS, a congenital disease characterised by intrauterine and postnatal growth retardation, relative macrocephaly, a typical triangular face, asymmetry and further less characteristic features. However, the clinical spectrum is broad and the clinical diagnosis often subjective. Genetic and epigenetic disturbances can meanwhile be detected in approximately 50% of patients with typical SRS features. Nearly one tenth of patients carry a maternal uniparental disomy of chromosome 7 (UPD(7mat, more than 38% show a hypomethylation in the imprinting control region 1 in 11p15. More than 1% of patients show (submicroscopic chromosomal aberrations. Interestingly, in ~7% of 11p15 hypomethylation carriers, demethylation of other imprinted loci can be detected. Clinically, these patients do not differ from those with isolated 11p15 hypomethylation whereas the UPD(7mat patients generally show a milder phenotype. However, an unambiguous (epigenotype-phenotype correlation can not be delineated. We therefore suggest a diagnostic algorithm focused on the 11p15 hypomethylation, UPD(7mat and cryptic chromosomal imbalances for patients with typical SRS phenotype, but also with milder clinical signs only reminiscent for the disease.

  14. A novel mating approach for genetic algorithms.

    Science.gov (United States)

    Galán, Severino F; Mengshoel, Ole J; Pinter, Rafael

    2013-01-01

    Genetic algorithms typically use crossover, which relies on mating a set of selected parents. As part of crossover, random mating is often carried out. A novel approach to parent mating is presented in this work. Our novel approach can be applied in combination with a traditional similarity-based criterion to measure distance between individuals or with a fitness-based criterion. We introduce a parameter called the mating index that allows different mating strategies to be developed within a uniform framework: an exploitative strategy called best-first, an explorative strategy called best-last, and an adaptive strategy called self-adaptive. Self-adaptive mating is defined in the context of the novel algorithm, and aims to achieve a balance between exploitation and exploration in a domain-independent manner. The present work formally defines the novel mating approach, analyzes its behavior, and conducts an extensive experimental study to quantitatively determine its benefits. In the domain of real function optimization, the experiments show that, as the degree of multimodality of the function at hand grows, increasing the mating index improves performance. In the case of the self-adaptive mating strategy, the experiments give strong results for several case studies.

  15. Genetic classification and molecular mechanisms of primary dystonia

    Institute of Scientific and Technical Information of China (English)

    Xueping Chen; Huifang Shang; Zuming Luo

    2008-01-01

    BACKGROUND: Primary dystonia is a heterogeneous disease, with a complex genetic basis. In previous studies, primary dystonia was classified according to age of onset, involved regions, and other clinical characteristics. With the development of molecular genetics, new virulence genes and sites have been discovered. Therefore, there is a gradual understanding of the various forms of dystonia, based on new viewpoints. There are 15 subtypes of dystonia, based on the molecular level, i.e., DYT1 to DYT15. OBJECTIVE: To analyze the genetic development of dystonia in detail, and to further investigate molecular mechanisms of dystonia. RETRIEVAL STRATEGY: A computer-based online search was conducted in PubMed for English language publications containing the keywords "dystonia and genetic" from January 1980 to March 2007. There were 105 articles in total. Inclusion criteria: ① the contents of the articles should closely address genetic classification and molecular mechanisms of primary dystonia; ② the articles published in recent years or in high-impact journals took preference. Exclusion criteria: duplicated articles. LITERATURE EVALUATION: The selected articles were on genetic classification and molecular genetics mechanism of primary dystonia. Of those, 27 were basic or clinical studies. DATA SYNTHESIS: ① Dystonia is a heterogeneous disease, with a complex genetic basis. According to the classification of the Human Genome Organization, there are 15 dystonia subtypes, based on genetics, i.e., DYT1-DYT15,including primary dystonia, dystonia plus syndrome, degeneration plus dystonia, and paroxysmal dyskinesia plus dystonia. ② To date, the chromosomes of 13 subtypes have been localized; however, DYT2 and DYT4 remain unclear. Six subtypes have been located within virulence genes. Specifically, torsinA gene expression results in the DYT1 genotype; autosomal dominant GTP cyclohydrolase I gene expression and recessive tyrosine hydroxylase expression result in the DYT5

  16. Advances in molecular genetic studies of primary dystonia

    Directory of Open Access Journals (Sweden)

    MA Ling-yan

    2013-07-01

    Full Text Available Dystonias are heterogeneous hyperkinetic movement disorders characterized by involuntary muscle contractions which result in twisting, repetitive movements and abnormal postures. In recent years, there was a great advance in molecular genetic studies of primary dystonia. This paper will review the clinical characteristics and molecular genetic studies of primary dystonia, including early-onset generalized torsion dystonia (DYT1, whispering dysphonia (DYT4, dopa-responsive dystonia (DYT5, mixed-type dystonia (DYT6, paroxysmal kinesigenic dyskinesia (DYT10, myoclonus-dystonia syndrome (DYT11, rapid-onset dystonia parkinsonism (DYT12, adult-onset cervical dystonia (DYT23, craniocervical dystonia (DYT24 and primary torsion dystonia (DYT25.

  17. Molecular and genetic basis of depression

    Indian Academy of Sciences (India)

    Madhumita Roy; Madhu G. Tapadia; Shobhna Joshi; Biplob Koch

    2014-12-01

    Joyousness or sadness is normal reaction to state of life. If any of these lead to certain semi-permanent changes in daily life, then it is termed as mental disorder. Depression is one of the mental disorders with a state of low mood and aversion to activities that exerts a negative effect on a person’s thoughts and behaviour. Adolescent group is probably the world’s largest active group of people, who are getting prone to this state of mind leading to their diminished mental and physical abilities. Depression is closely linked to stress and thus a chronic stressful life can increase the risk of depression. Depression is a complex disease having both genetic and environmental components as contributing factors. In this study an attempt has been made to put forward the understanding of the known genes and their functional relationships with depression and stress with special reference to BDNF and 5-HTTLPR. Analysis of common genetic variants associated with depression, especially in the members of a family who had a previous history, might help in identifying the individuals at risk prior to the onset of depression.

  18. Molecular genetics and epigenetics of CACTA elements

    KAUST Repository

    Fedoroff, Nina V.

    2013-08-21

    The CACTA transposons, so named for a highly conserved motif at element ends, comprise one of the most abundant superfamilies of Class 2 (cut-and-paste) plant transposons. CACTA transposons characteristically include subterminal sequences of several hundred nucleotides containing closely spaced direct and inverted repeats of a short, conserved sequence of 14-15 bp. The Supressor-mutator (Spm) transposon, identified and subjected to detailed genetic analysis by Barbara McClintock, remains the paradigmatic element of the CACTA family. The Spm transposon encodes two proteins required for transposition, the transposase (TnpD) and a regulatory protein (TnpA) that binds to the subterminal repeats. Spm expression is subject to both genetic and epigenetic regulation. The Spm-encoded TnpA serves as an activator of the epigenetically inactivated, methylated Spm, stimulating both transient and heritable activation of the transposon. TnpA also serves as a negative regulator of the demethylated active element promoter and is required, in addition to the TnpD, for transposition. © Springer Science+Business Media, New York 2013.

  19. Food control and a citizen science approach for improving teaching of Genetics in universities.

    Science.gov (United States)

    Borrell, Y J; Muñoz-Colmenero, A M; Dopico, E; Miralles, L; Garcia-Vazquez, E

    2016-09-10

    A Citizen Science approach was implemented in the laboratory practices of Genetics at the University of Oviedo, related with the engaging topic of Food Control. Real samples of food products consumed by students at home (students as samplers) were employed as teaching material in three different courses of Genetics during the academic year 2014-2015: Experimental Methods in Food Production (MBTA) (Master level), and Applied Molecular Biology (BMA) and Conservation Genetics and Breeding (COMGE) (Bachelor/Degree level). Molecular genetics based on PCR amplification of DNA markers was employed for species identification of 22 seafood products in COMGE and MBTA, and for detection of genetically modified (GM) maize from nine products in BMA. In total six seafood products incorrectly labeled (27%), and two undeclared GM maize (22%) were found. A post-Laboratory survey was applied for assessing the efficacy of the approach for improving motivation in the Laboratory Practices of Genetics. Results confirmed that students that worked on their own samples from local markets were significantly more motivated and better evaluated their Genetic laboratory practices than control students (χ(2)  = 12.11 p = 0.033). Our results suggest that citizen science approaches could not be only useful for improving teaching of Genetics in universities but also to incorporate students and citizens as active agents in food control. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(5):450-462, 2016.

  20. Genetic Breeding and Diversity of the Genus Passiflora: Progress and Perspectives in Molecular and Genetic Studies

    Directory of Open Access Journals (Sweden)

    Carlos Bernard M. Cerqueira-Silva

    2014-08-01

    Full Text Available Despite the ecological and economic importance of passion fruit (Passiflora spp., molecular markers have only recently been utilized in genetic studies of this genus. In addition, both basic genetic researches related to population studies and pre-breeding programs of passion fruit remain scarce for most Passiflora species. Considering the number of Passiflora species and the increasing use of these species as a resource for ornamental, medicinal, and food purposes, the aims of this review are the following: (i to present the current condition of the passion fruit crop; (ii to quantify the applications and effects of using molecular markers in studies of Passiflora; (iii to present the contributions of genetic engineering for passion fruit culture; and (iv to discuss the progress and perspectives of this research. Thus, the present review aims to summarize and discuss the relationship between historical and current progress on the culture, breeding, and molecular genetics of passion fruit.

  1. Molecular Darwinism: the contingency of spontaneous genetic variation.

    Science.gov (United States)

    Arber, Werner

    2011-01-01

    The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions.

  2. Genetic diversity and molecular epidemiology of Anaplasma.

    Science.gov (United States)

    Battilani, Mara; De Arcangeli, Stefano; Balboni, Andrea; Dondi, Francesco

    2017-04-01

    Anaplasma are obligate intracellular bacteria of cells of haematopoietic origin and are aetiological agents of tick-borne diseases of both veterinary and medical interest common in both tropical and temperate regions. The recent disclosure of their zoonotic potential has greatly increased interest in the study of these bacteria, leading to the recent reorganisation of Rickettsia taxonomy and to the possible discovery of new species belonging to the genus Anaplasma. This review is particularly focused on the common and unique characteristics of Anaplasma marginale and Anaplasma phagocytophilum, with an emphasis on genetic diversity and evolution, and the main distinguishing features of the diseases caused by the different Anaplasma spp. are described as well. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Investigating Genetic Diversity of Foeniculum Vulgare Mill using Molecular Markers

    Directory of Open Access Journals (Sweden)

    Omid Jadidi

    2016-06-01

    Full Text Available Medicinal plants are considered valuable genetic resources in Iran. One of these medicinal as well as spice plants is Foeniculum Vulgare Mill from Umbellifetae family used in different industries such as food, medicine, and cosmetics. It seems that due to different climate conditions in Iran this plant represents a high and valuable genetic diversity; therefore, management of genetic resources protection and obtaining information about genetic diversity will help awareness of evolution processes as well as genetic erosion of this valuable plant. Genetic diversity in local masses of Foeniculum Vulgare Mill can be investigated using molecule markers such as AFLP, RAPD, ISSR, SRAP, RFLP, and so on. In investigation of over 30 ecotype of local Foeniculum Vulgare Mill, different markers have shown that mean polymorphic content (PIC is about 36% and mean genetic diversity is estimated about 40% in different samples. Data obtained from molecule software analyses help to categorize Foeniculum Vulgare Mill genotype in different groups based on climate and geographical conditions. Principle components analysis (PCOA has also confirmed the results of cluster analysis. Dendrogram obtained by cluster analysis based on similarity coefficient of simple matching (SM and UPGMA algorithm can also categorize population of Foeniculum Vulgare Mill in different groups. Results of molecular variance analysis (AMOVA have shown that most genetic variance between geographical groups can be seen in populations. In general, according to investigations, there is a significant genetic diversity regarding agronomic and molecular traits of Foeniculum Vulgare Mill masses in Iran and knowing this genetic diversity will help in breeding programs, complementary studies, categorization, and so on.

  4. Molecular Diagnostics and Genetic Counseling in Primary Congenital Glaucoma.

    Science.gov (United States)

    Faiq, Muneeb; Mohanty, Kuldeep; Dada, Rima; Dada, Tanuj

    2013-01-01

    Primary congenital glaucoma (PCG) is a childhood irreversible blinding disorder with onset at birth or in the first year of life. It is characterized by the classical traid of symptoms viz. epiphora (excessive tearing), photophobia (hypersensitivity to light) and blepharospasm (inflammation of eyelids). The only anatomical defect seen in PCG is trabecular meshwork dysgenesis. PCG shows autosomal recessive mode of inheritance with considerable number of sporadic cases. The etiology of this disease has not been fully understood but some genes like CYP1B1, MYOC, FOXC1, LTBP2 have been implicated. Various chromosomal aberrations and mutations in mitochondrial genome have also been reported. Molecular biology has developed novel techniques in order to do genetic and biochemical characterization of many genetic disorders including PCG. Techniques like polymerase chain reaction, single strand conformational polymorphism and sequencing are already in use for diagnosis of PCG and other techniques like protein truncation testing and functional genomics are beginning to find their way into molecular workout of this disorder. In the light of its genetic etiology, it is important to develop methods for genetic counseling for the patients and their families so as to bring down its incidence. In this review, we ought to develop a genetic insight into PCG with possible use of molecular biology and functional genomics in understanding the disease etiology, pathogenesis, pathology and mechanism of inheritance. We will also discuss the possibilities and use of genetic counseling in this disease. How to cite this article: Faiq M, Mohanty K, Dada R, Dada T. Molecular Diagnostics and Genetic Counseling in Primary Congenital Glaucoma. J Current Glau Prac 2013;7(1):25-35.

  5. Reverse genetics approaches to combat pathogenic arenaviruses.

    Science.gov (United States)

    de la Torre, Juan C

    2008-12-01

    Several arenaviruses cause hemorrhagic fever (HF) in humans, and evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. Moreover, arenaviruses pose a biodefense threat. No licensed anti-arenavirus vaccines are available, and current anti-arenavirus therapy is limited to the use of ribavirin, which is only partially effective and is associated with anemia and other side effects. Therefore, it is important to develop effective vaccines and better antiviral drugs to combat the dual threats of naturally occurring and intentionally introduced arenavirus infections. The development of arenavirus reverse genetic systems is allowing investigators to conduct a detailed molecular characterization of the viral cis-acting signals and trans-acting factors that control each of the steps of the arenavirus life cycle, including RNA synthesis, packaging and budding. Knowledge derived from these studies is uncovering potential novel targets for therapeutic intervention, as well as facilitating the establishment of assays to identify and characterize candidate antiviral drugs capable of interfering with specific steps of the virus life cycle. Likewise, the ability to generate predetermined specific mutations within the arenavirus genome and analyze their phenotypic expression would significantly contribute to the elucidation of arenavirus-host interactions, including the basis of their ability to cause severe HF. This, in turn, could lead to the development of novel, potent and safe arenavirus vaccines.

  6. Molecular road ecology: exploring the potential of genetics for investigating transportation impacts on wildlife.

    Science.gov (United States)

    Balkenhol, Niko; Waits, Lisette P

    2009-10-01

    Transportation infrastructures such as roads, railroads and canals can have major environmental impacts. Ecological road effects include the destruction and fragmentation of habitat, the interruption of ecological processes and increased erosion and pollution. Growing concern about these ecological road effects has led to the emergence of a new scientific discipline called road ecology. The goal of road ecology is to provide planners with scientific advice on how to avoid, minimize or mitigate negative environmental impacts of transportation. In this review, we explore the potential of molecular genetics to contribute to road ecology. First, we summarize general findings from road ecology and review studies that investigate road effects using genetic data. These studies generally focus only on barrier effects of roads on local genetic diversity and structure and only use a fraction of available molecular approaches. Thus, we propose additional molecular applications that can be used to evaluate road effects across multiple scales and dimensions of the biodiversity hierarchy. Finally, we make recommendations for future research questions and study designs that would advance molecular road ecology. Our review demonstrates that molecular approaches can substantially contribute to road ecology research and that interdisciplinary, long-term collaborations will be particularly important for realizing the full potential of molecular road ecology.

  7. Molecular Models of Genetic and Organismic Structures

    CERN Document Server

    Baianu, I C

    2004-01-01

    In recent studies we showed that the earlier relational theories of organismic sets (Rashevsky,1967), Metabolic-Replication (M,R)-systems (Rosen,1958)and molecular sets (Bartholomay,1968) share a joint foundation that can be studied within a unified categorical framework of functional organismic structures (Baianu,1980. This is possible because all relational theories have a biomolecular basis, that is, complex structures such as genomes, cells,organs and biological organisms are mathematically represented in terms of biomolecular properties and entities,(that are often implicit in their representation axioms. The definition of organismic sets, for example, requires that certain essential quantities be determined from experiment: these are specified by special sets of values of general observables that are derived from physicochemical measurements(Baianu,1970; Baianu,1980; Baianu et al, 2004a.)Such observables are context-dependent and lead directly to natural transformations in categories and Topoi, that are...

  8. [Molecular genetic mechanism of the kidney cancer].

    Science.gov (United States)

    Nakaigawa, N; Yao, M; Kishida, T; Kubota, Y

    2001-01-01

    The oncogenic mechanisms of renal cell carcinoma(RCC) are becoming elucidated with recent advances in molecular biology. von Hipple-Lindau disease(VHL) tumor suppressor gene is mutated and inactivated frequently in clear cell type RCCs. The VHL protein forms a complex which shows a ubiquitin ligase activity. The lost of the ubiquitin ligase activity of VHL protein may be a key step for clear cell tumorigenesis. Papillary renal cell carcinomas are caused by activating mutation in the tyrosine kinase domain of the MET gene. This tumorigenic pathway is regulated by c-Src. Immunogene therapies have been started for the patients with advanced RCC. The information based on microarray and Serial Analysis of Gene Expression(SAGE) will provide novel diagnosis and therapy which focus on the tumorigenic mechanism of RCC in the near future.

  9. Genetics and molecular biology in laboratory medicine, 1963-2013.

    Science.gov (United States)

    Whitfield, John B

    2013-01-01

    The past 50 years have seen many changes in laboratory medicine, either as causes or consequences of increases in productivity and expansion of the range of information which can be provided. The drivers and facilitators of change in relation to clinical applications of molecular biology included the need for diagnostic tools for genetic diseases and technical advances such as PCR and sequencing. However, molecular biology techniques have proved to have far wider applications, from detection of infectious agents to molecular characterization of tumors. Journals such as Clinical Chemistry and Laboratory Medicine play an important role in communication of these advances to the laboratory medicine community and in publishing evaluations of their practical value.

  10. Molecular-Genetic Aspects of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Krasteva M.

    2014-12-01

    Full Text Available Breast cancer is the most frequent malignancy among women. Advances in breast cancer knowledge have deciphered the involvement of a number of tumor suppressor genes and proto-oncogenes in disease pathogenesis. These genes are part of the complex biochemical pathways, which enable cell cycle control and maintenance of genome integrity. Their function may be disrupted as a result of alterations in gene sequence or misregulation of gene expression including alterations in DNA methylation pattern. The present review summarizes the main findings on major breast cancer related genes BRCA1/2, p53, ATM, CHEK2, HER2, PIK3CA and their tumorigenic inactivation/activation. The potential clinical importance of these genes with respect to patients’ prognosis and therapy are also discussed. The possible implication of other putative breast cancer related genes is also outlined. The first elaborate data on the genetic and epigenetic status of the above mentioned genes concerning Bulgarian patients with the sporadic form of the disease are presented. The studies indicate for a characteristic mutational spectrum in some of the genes for the Bulgarian patients and specific correlation between the status of different genes and clinicopathological characteristics.

  11. [Molecular genetic investigation of sugar beet (Beta vulgaris L.)].

    Science.gov (United States)

    Butorina, A K; Kornienko, A V

    2011-10-01

    Molecular genetic studies of sugar beet (Beta vulgaris L.) are reviewed as a basis for the development of genomics of this species. The methods used to study structural and functional genomics are considered. The results and their application to increase the efficiency of sugar beet breeding are discussed.

  12. Morphological and molecular genetic diversity of Syrian indigenous ...

    African Journals Online (AJOL)

    Tuoyo Aghomotsegin

    2016-05-04

    May 4, 2016 ... This study aimed to assess the morphological variation, genetic diversity and population ... goat breed was well differentiated and grouped into a separate cluster that suggests its evolutionary ... research and development centers in representative ... Phenotypic and molecular characterizations have been.

  13. [Hereditary optic neuropathies: clinical and molecular genetic characteristics].

    Science.gov (United States)

    Khanakova, N A; Sheremet, N L; Loginova, A N; Chukhrova, A L; Poliakov, A V

    2013-01-01

    The article presents a review of literature on hereditary optic neuropathies: Leber mitochondrial hereditary optic neuropathy, autosomal dominant and autosomal recessive optic neuropathies, X-linked optic atrophy. Clinical and molecular genetic characteristics are covered. Isolated optic neuropathies, as well as hereditary optic disorders, being a part of a complex syndromic disease are described.

  14. Promoting Middle School Students' Understandings of Molecular Genetics

    Science.gov (United States)

    Duncan, Ravit Golan; Freidenreich, Hava Bresler; Chinn, Clark A.; Bausch, Andrew

    2011-03-01

    Genetics is the cornerstone of modern biology and understanding genetics is a critical aspect of scientific literacy. Research has shown, however, that many high school graduates lack fundamental understandings in genetics necessary to make informed decisions or to participate in public debates over emerging technologies in molecular genetics. Currently, much of genetics instruction occurs at the high school level. However, recent policy reports suggest that we may need to begin introducing aspects of core concepts in earlier grades and to successively develop students' understandings of these concepts in subsequent grades. Given the paucity of research about genetics learning at the middle school level, we know very little about what students in earlier grades are capable of reasoning about in this domain. In this paper, we discuss a research study aimed at fostering deeper understandings of molecular genetics at the middle school level. As part of the research we designed a two-week model-based inquiry unit implemented in two 7th grade classrooms ( N = 135). We describe our instructional design and report results based on analysis of pre/post assessments and written artifacts of the unit. Our findings suggest that middle school students can develop: (a) a view of genes as productive instructions for proteins, (b) an understanding of the role of proteins in mediating genetic effects, and (c) can use this knowledge to reason about a novel genetic phenomena. However, there were significant differences in the learning gains in both classrooms and we provide speculative explanations of what may have caused these differences.

  15. Fuzzy Inspired Hybrid Genetic Approach to Optimize Travelling Salesman Problem

    Directory of Open Access Journals (Sweden)

    Bindu

    2012-06-01

    Full Text Available One of the category of algorithm Problems are basically exponential problems. These problems are basically exponential problems and take time to find the solution. In the present work we are optimising one of the common NP complete problem called Travelling Salesman Problem. In our work we have defined a genetic approach by combining fuzzy approach along with genetics. In this work we have implemented the modified DPX crossover to improve genetic approach. The work is implemented in MATLAB environment and obtained results shows the define approach has optimized the existing genetic algorithm results

  16. Molecular toolbox for the identification of unknown genetically modified organisms.

    Science.gov (United States)

    Ruttink, Tom; Demeyer, Rolinde; Van Gulck, Elke; Van Droogenbroeck, Bart; Querci, Maddalena; Taverniers, Isabel; De Loose, Marc

    2010-03-01

    Competent laboratories monitor genetically modified organisms (GMOs) and products derived thereof in the food and feed chain in the framework of labeling and traceability legislation. In addition, screening is performed to detect the unauthorized presence of GMOs including asynchronously authorized GMOs or GMOs that are not officially registered for commercialization (unknown GMOs). Currently, unauthorized or unknown events are detected by screening blind samples for commonly used transgenic elements, such as p35S or t-nos. If (1) positive detection of such screening elements shows the presence of transgenic material and (2) all known GMOs are tested by event-specific methods but are not detected, then the presence of an unknown GMO is inferred. However, such evidence is indirect because it is based on negative observations and inconclusive because the procedure does not identify the causative event per se. In addition, detection of unknown events is hampered in products that also contain known authorized events. Here, we outline alternative approaches for analytical detection and GMO identification and develop new methods to complement the existing routine screening procedure. We developed a fluorescent anchor-polymerase chain reaction (PCR) method for the identification of the sequences flanking the p35S and t-nos screening elements. Thus, anchor-PCR fingerprinting allows the detection of unique discriminative signals per event. In addition, we established a collection of in silico calculated fingerprints of known events to support interpretation of experimentally generated anchor-PCR GM fingerprints of blind samples. Here, we first describe the molecular characterization of a novel GMO, which expresses recombinant human intrinsic factor in Arabidopsis thaliana. Next, we purposefully treated the novel GMO as a blind sample to simulate how the new methods lead to the molecular identification of a novel unknown event without prior knowledge of its transgene

  17. [Molecular, genetic and physiological analysis of photoinhibition and photosynthetic

    Energy Technology Data Exchange (ETDEWEB)

    1992-01-01

    A major goal of this project is to use a combined molecular genetic, biochemical and physiological approach to understand the relationship between photosynthetic performance and the structure of the multifunctional D1 reaction center protein of Photosystem II encoded by the chloroplast psbA gene. Relative to other chloroplast proteins, turover of D1 is rapid and highly light dependent and de novo synthesis of D1 is required for a plant's recovery from short term exposure to irradiances which induce photoinhibitory damage. These observations have led to models for a damage/repair cycle of PSII involving the targeted degradation and replacement of photodamaged D1. To investigate the effects of perturbing the D1 cycle on photosynthesis and autotrophic growth under high and low irradiance, we have examined the consequences of site-specific mutations of the psbA and 16S rRNA genes affecting synthesis, maturation and function/stability of the D1 protein introduced into the chloroplast genome of wildtype strain of the green alga Chlamydomonas reinhardtii using biolistic transformation.

  18. Intelligent DNA-based molecular diagnostics using linked genetic markers

    Energy Technology Data Exchange (ETDEWEB)

    Pathak, D.K.; Perlin, M.W.; Hoffman, E.P.

    1994-12-31

    This paper describes a knowledge-based system for molecular diagnostics, and its application to fully automated diagnosis of X-linked genetic disorders. Molecular diagnostic information is used in clinical practice for determining genetic risks, such as carrier determination and prenatal diagnosis. Initially, blood samples are obtained from related individuals, and PCR amplification is performed. Linkage-based molecular diagnosis then entails three data analysis steps. First, for every individual, the alleles (i.e., DNA composition) are determined at specified chromosomal locations. Second, the flow of genetic material among the individuals is established. Third, the probability that a given individual is either a carrier of the disease or affected by the disease is determined. The current practice is to perform each of these three steps manually, which is costly, time consuming, labor-intensive, and error-prone. As such, the knowledge-intensive data analysis and interpretation supersede the actual experimentation effort as the major bottleneck in molecular diagnostics. By examining the human problem solving for the task, we have designed and implemented a prototype knowledge-based system capable of fully automating linkage-based molecular diagnostics in X-linked genetic disorders, including Duchenne Muscular Dystrophy (DMD). Our system uses knowledge-based interpretation of gel electrophoresis images to determine individual DNA marker labels, a constraint satisfaction search for consistent genetic flow among individuals, and a blackboard-style problem solver for risk assessment. We describe the system`s successful diagnosis of DMD carrier and affected individuals from raw clinical data.

  19. The spinocerebellar ataxias: clinical aspects and molecular genetics.

    Science.gov (United States)

    Matilla-Dueñas, Antoni; Corral-Juan, Marc; Volpini, Victor; Sanchez, Ivelisse

    2012-01-01

    Spinocerebellar ataxias (SCAs) are a highly heterogeneous group of inherited neurological disorders, based on clinical characterization alone with variable degrees of cerebellar ataxia often accompanied by additional cerebellar and noncerebellar symptoms which in most cases defy differentiation. Molecular causative deficits in at least 31 genes underlie the clinical symptoms in the SCAs by triggering cerebellar and, very frequently, brain stem dysfunction. The identification of the causative molecular deficits enables the molecular diagnosis of the different SCA subtypes and facilitates genetic counselling. Recent scientific advances are shedding light into developing therapeutic strategies. The scope of this chapter is to provide updated details of the spinocerebellar ataxias with particular emphasis on those aspects aimed at facilitating the clinical and genetic diagnoses.

  20. Genetic Approaches to Develop Salt Tolerant Germplasm

    KAUST Repository

    Tester, Mark A.

    2015-08-19

    Forty percent of the world\\'s food is produced under irrigation, and this is directly threatened by over-exploitation and changes in the global environment. One way to address this threat is to develop systems for increasing our ability to use lower quality water, in particular saline water. Low cost partial desalination of brackish water, use of saline water for cooling and increases in the salinity tolerance of crops can all contribute to the development of this new agricultural system. In this talk, the focus will be on the use of forward genetic approaches for discovery of genes related to salinity tolerance in barley and tomatoes. Rather than studying salinity tolerance as a trait in itself, we dissect salinity tolerance into a series of components that are hypothesised to contribute to overall salinity tolerance (following the paradigm of Munns & Tester, 2008). For example, one significant component of tolerance of most crop plants to moderate soil salinity is due to the ability to maintain low concentrations of Na+ in the leaves, and much analysis of this aspect has been done (e.g. Roy et al., 2013, 2014). A major site for the control of shoot Na+ accumulation is at the plasma membrane of the mature stele of the root. Alleles of HKT, a major gene underlying this transport process have been characterized and, in work led by Dr Rana Munns (CSIRO), have now been introgressed into commercial durum wheat and led to significantly increased yields in saline field conditions (Munns et al., 2012). The genotyping of mapping populations is now highly efficient. However, the ability to quantitatively phenotype these populations is now commonly limiting forward progress in plant science. The increasing power of digital imaging and computational technologies offers the opportunity to relieve this phenotyping bottleneck. The Plant Accelerator is a 4500m2 growth facility that provides non-destructive phenotyping of large populations of plants (http

  1. Corn Storage Protein - A Molecular Genetic Model

    Energy Technology Data Exchange (ETDEWEB)

    Messing, Joachim [Rutgers, The State University of New Jersey

    2013-05-31

    Corn is the highest yielding crop on earth and probably the most valuable agricultural product of the United States. Because it converts sun energy through photosynthesis into starch and proteins, we addressed energy savings by focusing on protein quality. People and animals require essential amino acids derived from the digestion of proteins. If proteins are relatively low in certain essential amino acids, the crop becomes nutritionally defective and has to be supplemented. Such deficiency affects meat and fish production and countries where corn is a staple. Because corn seed proteins have relatively low levels of lysine and methionine, a diet has to be supplemented with soybeans for the missing lysine and with chemically synthesized methionine. We therefore have studied genes expressed during maize seed development and their chromosomal organization. A critical technical requirement for the understanding of the molecular structure of genes and their positional information was DNA sequencing. Because of the length of sequences, DNA sequencing methods themselves were insufficient for this type of analysis. We therefore developed the so-called “DNA shotgun sequencing” strategy, where overlapping DNA fragments were sequenced in parallel and used to reconstruct large DNA molecules via overlaps. Our publications became the most frequently cited ones during the decade of 1981-1990 and former Associate Director of Science for the Office of Basic Energy Sciences Patricia M. Dehmer presented our work as one of the great successes of this program. A major component of the sequencing strategy was the development of bacterial strains and vectors, which were also used to develop the first biotechnology crops. These crops possessed new traits thanks to the expression of foreign genes in plants. To enable such expression, chimeric genes had to be constructed using our materials and methods by the industry. Because we made our materials and methods freely available to

  2. Hamartomatous polyps - a clinical and molecular genetic study

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie

    2016-01-01

    the knowledge on clinical course and molecular genetics in patients with HPs and HPS, and to investigate research participants' attitude towards the results of extensive genetic testing. Paper I: In the first paper we investigated the occurrence, anatomic distribution, and other demographics of juvenile polyps......-Jeghers syndrome, and the PTEN hamartoma tumour syndrome. Currently, the HPS diagnoses are based on clinical criteria and are often assisted with genetic testing as candidate genes have been described for each syndrome. This thesis is based on six scientific papers. The overall aim of the studies was to expand......% fulfilled to diagnostic criteria of JPS. The majority of patients had a single juvenile polyp. Paper II: In this paper we conducted a review of the HPS based on the current literature. Paper III: We investigated the hypothesis that patients with one or few HPs may have a HPS based on genetic screening. We...

  3. Of mice and men: molecular genetics of congenital heart disease.

    Science.gov (United States)

    Andersen, Troels Askhøj; Troelsen, Karin de Linde Lind; Larsen, Lars Allan

    2014-04-01

    Congenital heart disease (CHD) affects nearly 1 % of the population. It is a complex disease, which may be caused by multiple genetic and environmental factors. Studies in human genetics have led to the identification of more than 50 human genes, involved in isolated CHD or genetic syndromes, where CHD is part of the phenotype. Furthermore, mapping of genomic copy number variants and exome sequencing of CHD patients have led to the identification of a large number of candidate disease genes. Experiments in animal models, particularly in mice, have been used to verify human disease genes and to gain further insight into the molecular pathology behind CHD. The picture emerging from these studies suggest that genetic lesions associated with CHD affect a broad range of cellular signaling components, from ligands and receptors, across down-stream effector molecules to transcription factors and co-factors, including chromatin modifiers.

  4. Genetic diversity analysis of common beans based on molecular markers.

    Science.gov (United States)

    Gill-Langarica, Homar R; Muruaga-Martínez, José S; Vargas-Vázquez, M L Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

    2011-10-01

    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  5. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    2011-01-01

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  6. Genetic diversity analysis of common beans based on molecular markers

    Science.gov (United States)

    Gill-Langarica, Homar R.; Muruaga-Martínez, José S.; Vargas-Vázquez, M.L. Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

    2011-01-01

    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation. PMID:22215964

  7. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  8. Cytogenetics and Molecular Genetics of Myxoid Soft-Tissue Sarcomas

    Directory of Open Access Journals (Sweden)

    Jun Nishio

    2011-01-01

    Full Text Available Myxoid soft-tissue sarcomas represent a heterogeneous group of mesenchymal tumors characterized by a predominantly myxoid matrix, including myxoid liposarcoma (MLS, low-grade fibromyxoid sarcoma (LGFMS, extraskeletal myxoid chondrosarcoma (EMC, myxofibrosarcoma, myxoinflammatory fibroblastic sarcoma (MIFS, and myxoid dermatofibrosarcoma protuberans (DFSP. Cytogenetic and molecular genetic analyses have shown that many of these sarcomas are characterized by recurrent chromosomal translocations resulting in highly specific fusion genes (e.g., FUS-DDIT3 in MLS, FUS-CREB3L2 in LGFMS, EWSR1-NR4A3 in EMC, and COL1A1-PDGFB in myxoid DFSP. Moreover, recent molecular analysis has demonstrated a translocation t(1; 10(p22; q24 resulting in transcriptional upregulation of FGF8 and NPM3 in MIFS. Most recently, the presence of TGFBR3 and MGEA5 rearrangements has been identified in a subset of MIFS. These genetic alterations can be utilized as an adjunct in diagnostically challenging cases. In contrast, most myxofibrosarcomas have complex karyotypes lacking specific genetic alterations. This paper focuses on the cytogenetic and molecular genetic findings of myxoid soft-tissue sarcomas as well as their clinicopathological characteristics.

  9. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update.

    Science.gov (United States)

    Sharma, Aarti; Sharma, Kiran Lata; Gupta, Annapurna; Yadav, Alka; Kumar, Ashok

    2017-06-14

    Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines (http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.

  10. Molecular approaches to diversity of populations of apicomplexan parasites.

    Science.gov (United States)

    Beck, Hans-Peter; Blake, Damer; Dardé, Marie-Laure; Felger, Ingrid; Pedraza-Díaz, Susana; Regidor-Cerrillo, Javier; Gómez-Bautista, Mercedes; Ortega-Mora, Luis Miguel; Putignani, Lorenza; Shiels, Brian; Tait, Andrew; Weir, Willie

    2009-01-01

    Apicomplexan parasites include many parasites of importance either for livestock or as causative agents of human diseases. The importance of these parasites has been recognised by the European Commission and resulted in support of the COST (Cooperation in Science and Technology) Action 857 'Apicomplexan Biology in the Post-Genomic Era'. In this review we discuss the current understanding in 'Biodiversity and Population Genetics' of the major apicomplexan parasites, namely the Eimeria spp., Cryptosporidium spp., Toxoplasma gondii, Neospora caninum, Theileria spp. and Plasmodium spp. During the past decade molecular tools for characterizing and monitoring parasite populations have been firmly established as an integral part of field studies and intervention trials. Analyses have been conducted for most apicomplexan pathogens to describe the extent of genetic diversity, infection dynamics or population structure. The underlying key question for all parasites is to understand how genetic diversity influences epidemiology and pathogenicity and its implication in therapeutic and vaccination strategies as well as disease control. Similarities in the basic biology and disease or transmission patterns among this order of parasites promote multifaceted discussions and comparison of epidemiological approaches and methodological tools. This fosters mutual learning and has the potential for cross-fertilisation of ideas and technical approaches.

  11. Molecular Genetic Tools and Techniques for Marchantia polymorpha Research.

    Science.gov (United States)

    Ishizaki, Kimitsune; Nishihama, Ryuichi; Yamato, Katsuyuki T; Kohchi, Takayuki

    2016-02-01

    Liverworts occupy a basal position in the evolution of land plants, and are a key group to address a wide variety of questions in plant biology. Marchantia polymorpha is a common, easily cultivated, dioecious liverwort species, and is emerging as an experimental model organism. The haploid gametophytic generation dominates the diploid sporophytic generation in its life cycle. Genetically homogeneous lines in the gametophyte generation can be established easily and propagated through asexual reproduction, which aids genetic and biochemical experiments. Owing to its dioecy, male and female sexual organs are formed in separate individuals, which enables crossing in a fully controlled manner. Reproductive growth can be induced at the desired times under laboratory conditions, which helps genetic analysis. The developmental process from a single-celled spore to a multicellular body can be observed directly in detail. As a model organism, molecular techniques for M. polymorpha are well developed; for example, simple and efficient protocols of Agrobacterium-mediated transformation have been established. Based on them, various strategies for molecular genetics, such as introduction of reporter constructs, overexpression, gene silencing and targeted gene modification, are available. Herein, we describe the technologies and resources for reverse and forward genetics in M. polymorpha, which offer an excellent experimental platform to study the evolution and diversity of regulatory systems in land plants.

  12. Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era

    Directory of Open Access Journals (Sweden)

    Costain G

    2012-02-01

    Full Text Available Gregory Costain1,2, Anne S Bassett1–41Clinical Genetics Research Program, Centre for Addiction and Mental Health, 2Institute of Medical Science, University of Toronto, 3Division of Cardiology, Department of Medicine and Department of Psychiatry, University Health Network, 4Department of Psychiatry, University of Toronto, Toronto, Ontario, CanadaAbstract: Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new genetic technologies and advances in molecular medicine, there has recently been concrete progress in understanding some of the specific genetic causes of this serious psychiatric illness. In particular, several large rare structural variants have been convincingly associated with schizophrenia, in targeted studies over two decades with respect to 22q11.2 microdeletions, and more recently in large-scale, genome-wide case-control studies. These advances promise to help many families afflicted with this disease. In this review, we critically appraise recent developments in the field of schizophrenia genetics through the lens of immediate clinical applicability. Much work remains in translating the recent surge of genetic research discoveries into the clinic. The epidemiology and basic genetic parameters (such as penetrance and expression of most genomic disorders associated with schizophrenia are not yet well characterized. To date, 22q11.2 deletion syndrome is the only established genetic subtype of schizophrenia of proven clinical relevance. We use this well-established association as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia.Keywords: schizophrenia, genetics, 22q11 deletion syndrome, copy number variation, genetic counseling, genetic predisposition to disease

  13. Molecular genetics of DNA viruses: recombinant virus technology.

    Science.gov (United States)

    Neuhierl, Bernhard; Delecluse, Henri-Jacques

    2005-01-01

    Recombinant viral genomes cloned onto BAC vectors can be subjected to extensive molecular genetic analysis in the context of E. coli. Thus, the recombinant virus technology exploits the power of prokaryotic genetics to introduce all kinds of mutations into the recombinant genome. All available techniques are based on homologous recombination between a targeting vector carrying the mutated version of the gene of interest and the recombinant virus. After modification, the mutant viral genome is stably introduced into eukaryotic cells permissive for viral lytic replication. In these cells, mutant viral genomes can be packaged into infectious particles to evaluate the effect of these mutations in the context of the complete genome.

  14. The importance of molecular analyses for understanding the genetic diversity of Histoplasma capsulatum: an overview.

    Science.gov (United States)

    Vite-Garín, Tania; Estrada-Bárcenas, Daniel Alfonso; Cifuentes, Joaquín; Taylor, Maria Lucia

    2014-01-01

    Advances in the classification of the human pathogen Histoplasma capsulatum (H. capsulatum) (ascomycete) are sustained by the results of several genetic analyses that support the high diversity of this dimorphic fungus. The present mini-review highlights the great genetic plasticity of H. capsulatum. Important records with different molecular tools, mainly single- or multi-locus sequence analyses developed with this fungus, are discussed. Recent phylogenetic data with a multi-locus sequence analysis using 5 polymorphic loci support a new clade and/or phylogenetic species of H. capsulatum for the Americas, which was associated with fungal isolates obtained from the migratory bat Tadarida brasiliensis. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  15. The characterization of goat genetic diversity : Towards a genomic approach

    NARCIS (Netherlands)

    Ajmone-Marsan, P.; Colli, L.; Han, J. L.; Achilli, A.; Lancioni, H.; Joost, S.; Crepaldi, P.; Pilla, F.; Stella, A.; Taberlet, P.; Boettcher, P.; Negrini, R.; Lenstra, J. A.

    2014-01-01

    The investigation of genetic diversity at molecular level has been proposed as a valuable complement and sometimes proxy to phenotypic diversity of local breeds and is presently considered as one of the FAO priorities for breed characterization. By recommending a set of selected molecular markers fo

  16. The characterization of goat genetic diversity : Towards a genomic approach

    NARCIS (Netherlands)

    Ajmone-Marsan, P.; Colli, L.; Han, J. L.; Achilli, A.; Lancioni, H.; Joost, S.; Crepaldi, P.; Pilla, F.; Stella, A.; Taberlet, P.; Boettcher, P.; Negrini, R.; Lenstra, J. A.|info:eu-repo/dai/nl/067852335

    2014-01-01

    The investigation of genetic diversity at molecular level has been proposed as a valuable complement and sometimes proxy to phenotypic diversity of local breeds and is presently considered as one of the FAO priorities for breed characterization. By recommending a set of selected molecular markers

  17. The Genetic and Molecular Basis of Plant Resistance to Pathogens

    Institute of Scientific and Technical Information of China (English)

    Yan Zhang; Thomas Lubberstedt; Mingliang Xu

    2013-01-01

    Plant pathogens have evolved numerous strategies to obtain nutritive materials from their host,and plants in turn have evolved the preformed physical and chemical barriers as well as sophisticated two-tiered immune system to combat pathogen attacks.Genetically,plant resistance to pathogens can be divided into qualitative and quantitative disease resistance,conditioned by major gene(s) and multiple genes with minor effects,respectively.Qualitative disease resistance has been mostly detected in plant defense against biotrophic pathogens,whereas quantitative disease resistance is involved in defense response to all plant pathogens,from biotrophs,hemibiotrophs to necrotrophs.Plant resistance is achieved through interception of pathogen-derived effectors and elicitation of defense response.In recent years,great progress has been made related to the molecular basis underlying host-pathogen interactions.In this review,we would like to provide an update on genetic and molecular aspects of plant resistance to pathogens.

  18. Recent advances in the molecular genetics of resin biosynthesis and genetic engineering strategies to improve defenses in conifers

    Institute of Scientific and Technical Information of China (English)

    TANGWei

    2003-01-01

    Since the first terpenoid synthase cDNA was obtained by the reverse genetic approach from grand fir, great pro-gress in the molecular genetics of terpenoid formation has been made with angiosperms and genes encoding a monoterpene synthase, a sesquiterpene synthase, and a diterpene synthase. Tree killing bark beetles and their vectored fungal pathogens are the most destructive agents of conifer forests worldwide. Conifers defend against attack by the constitutive and inducible production of oleoresin that accumulates at the wound site to kill invaders and both flush and seal the injury. Although toxic to the bark beetle and fungal pathogen, oleoresin also plays a central role in the chemical ecology of these boring insects. Re-cent advances in the molecular genetics of terpenoid biosynthesis provide evidence for the evolutionary origins of oleoresin and permit consideration of genetic engineering strategies to improve conifer defenses as a component of modern forest bio-technology. This review described enzymes of resin biosynthesis, structural feathers of genes genomic intron and exon or-ganization, pathway organization and evolution, resin production and accumulation, interactions between conifer and bark beetle, and engineering strategies to improve conifer defenses.

  19. Molecular biology approaches in bioadhesion research

    Directory of Open Access Journals (Sweden)

    Marcelo Rodrigues

    2014-07-01

    Full Text Available The use of molecular biology tools in the field of bioadhesion is still in its infancy. For new research groups who are considering taking a molecular approach, the techniques presented here are essential to unravelling the sequence of a gene, its expression and its biological function. Here we provide an outline for addressing adhesion-related genes in diverse organisms. We show how to gradually narrow down the number of candidate transcripts that are involved in adhesion by (1 generating a transcriptome and a differentially expressed cDNA list enriched for adhesion-related transcripts, (2 setting up a BLAST search facility, (3 perform an in situ hybridization screen, and (4 functional analyses of selected genes by using RNA interference knock-down. Furthermore, latest developments in genome-editing are presented as new tools to study gene function. By using this iterative multi-technologies approach, the identification, isolation, expression and function of adhesion-related genes can be studied in most organisms. These tools will improve our understanding of the diversity of molecules used for adhesion in different organisms and these findings will help to develop innovative bio-inspired adhesives.

  20. [Primary failure of eruption (PFE). Clinical and molecular genetics analysis].

    Science.gov (United States)

    Stellzig-Eisenhauer, Angelika; Decker, Eva; Meyer-Marcotty, Philipp; Rau, Christiane; Fiebig, Britta S; Kress, Wolfram; Saar, Kathrin; Rüschendorf, Franz; Hubner, Norbert; Grimm, Tiemo; Witt, Emil; Weber, Bernhard H F

    2013-09-01

    The term "primary failure of eruption" (PFE) refers to the complete or partial failure of a primary non-ankylosed tooth to erupt due to a disturbance of the eruption mechanism. Up to now, the molecular basis for this failure was unknown. Four families were studied in whom at least two members were affected by non-syndromic PFE as part of a clinical and molecular genetics study. Radiological diagnostics (OPTs) were carried out in all patients and their unaffected relatives (control group). The genetic analysis included a genomewide linkage analysis followed by direct DNA sequencing of positional candidate genes. Starting from the index patients, we were able to reconstruct pedigrees over two and/or three generations in the families that indicated an autosomal-dominant mode of inheritance of non-syndromic PFE. Fifteen patients were diagnosed with PFE. Gender distribution was nearly equal (7 female, 8 male). Molecular genetic analysis of the PTHR1 gene revealed three distinct heterozygous mutations (c.1050-3C>G; c.543 + 1G>A; c.463G>T). Unaffected persons exhibited no mutations. Knowledge of the genetic causes of non-syndromic PFE can now be used for the differential diagnosis of eruption failure. It permits affected family members to be identified early and may lead to new treatment possibilities in the long term. The genetically-verified diagnosis of "primary failure of eruption" can protect patients and orthodontists from years of futile treatment, because orthodontic treatment alone does not lead to success. Moreover, it has a negative influence on unaffected teeth and areas of the jaw. © EDP Sciences, SFODF, 2013.

  1. Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy PRINCIPAL INVESTIGATOR: John F...information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and...maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other

  2. Antigenic variation: Molecular and genetic mechanisms of relapsing disease

    Energy Technology Data Exchange (ETDEWEB)

    Cruse, J.M.; Lewis, R.E.

    1987-01-01

    This book contains 10 chapters. They are: Contemporary Concepts of Antigenic Variation; Antigenic Variation in the Influenza Viruses; Mechanisms of Escape of Visna Lentiviruses from Immunological Control; A Review of Antigenic Variation by the Equine Infectious Anemia Virus; Biologic and Molecular Variations in AIDS Retrovirus Isolates; Rabies Virus Infection: Genetic Mutations and the Impact on Viral Pathogenicity and Immunity; Immunobiology of Relapsing Fever; Antigenic Variation in African Trypanosomes; Antigenic Variation and Antigenic Diversity in Malaria; and Mechanisms of Immune Evasion in Schistosomiasis.

  3. Molecular basis of telomere dysfunction in human genetic diseases.

    Science.gov (United States)

    Sarek, Grzegorz; Marzec, Paulina; Margalef, Pol; Boulton, Simon J

    2015-11-01

    Mutations in genes encoding proteins required for telomere structure, replication, repair and length maintenance are associated with several debilitating human genetic disorders. These complex telomere biology disorders (TBDs) give rise to critically short telomeres that affect the homeostasis of multiple organs. Furthermore, genome instability is often a hallmark of telomere syndromes, which are associated with increased cancer risk. Here, we summarize the molecular causes and cellular consequences of disease-causing mutations associated with telomere dysfunction.

  4. Whole genome approaches to quantitative genetics.

    Science.gov (United States)

    Visscher, Peter M

    2009-06-01

    Apart from parent-offspring pairs and clones, relative pairs vary in the proportion of the genome that they share identical by descent. In the past, quantitative geneticists have used the expected value of sharing genes by descent to estimate genetic parameters and predict breeding values. With the possibility to genotype individuals for many markers across the genome it is now possible to empirically estimate the actual relationship between relatives. We review some of the theory underlying the variation in genetic identity, show applications to estimating genetic variance for height in humans and discuss other applications.

  5. The molecular population genetics of shoot development in Arabidopsis thaliana.

    Science.gov (United States)

    Shepard, Kristen A

    2007-01-01

    Studies in Arabidopsis thaliana have provided us with a wealth of information about the genetic pathways that regulate plant morphogenesis. This developmental genetic treasure trove represents a fantastic resource for researchers interested in the microevolution of development. Several laboratories have begun using molecular population genetic analyses to investigate the evolutionary forces that act upon loci that regulate shoot morphogenesis. Much of this work has focused on coding sequence variation in transcription factors; however, recent studies have explored sequence variation in other types of proteins and in promoter regions. Several genes that regulate shoot development contain signatures of selective sweeps associated with positive selection or harbor putative balanced polymorphisms in coding and noncoding sequences. Other regulatory genes appear to be evolving neutrally, but have accumulated potentially deleterious replacement polymorphisms.

  6. Optimization of a genetic algorithm for searching molecular conformer space

    Science.gov (United States)

    Brain, Zoe E.; Addicoat, Matthew A.

    2011-11-01

    We present two sets of tunings that are broadly applicable to conformer searches of isolated molecules using a genetic algorithm (GA). In order to find the most efficient tunings for the GA, a second GA - a meta-genetic algorithm - was used to tune the first genetic algorithm to reliably find the already known a priori correct answer with minimum computational resources. It is shown that these tunings are appropriate for a variety of molecules with different characteristics, and most importantly that the tunings are independent of the underlying model chemistry but that the tunings for rigid and relaxed surfaces differ slightly. It is shown that for the problem of molecular conformational search, the most efficient GA actually reduces to an evolutionary algorithm.

  7. Human fertility, molecular genetics, and natural selection in modern societies.

    Directory of Open Access Journals (Sweden)

    Felix C Tropf

    Full Text Available Research on genetic influences on human fertility outcomes such as number of children ever born (NEB or the age at first childbirth (AFB has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758, results show significant additive genetic effects on both traits explaining 10% (SE = 5 of the variance in the NEB and 15% (SE = 4 in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02. This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size.

  8. Human fertility, molecular genetics, and natural selection in modern societies.

    Science.gov (United States)

    Tropf, Felix C; Stulp, Gert; Barban, Nicola; Visscher, Peter M; Yang, Jian; Snieder, Harold; Mills, Melinda C

    2015-01-01

    Research on genetic influences on human fertility outcomes such as number of children ever born (NEB) or the age at first childbirth (AFB) has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML) methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758), results show significant additive genetic effects on both traits explaining 10% (SE = 5) of the variance in the NEB and 15% (SE = 4) in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02). This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size.

  9. Molecular Genetics of Beauveria bassiana Infection of Insects.

    Science.gov (United States)

    Ortiz-Urquiza, A; Keyhani, N O

    2016-01-01

    Research on the insect pathogenic filamentous fungus, Beauveria bassiana has witnessed significant growth in recent years from mainly physiological studies related to its insect biological control potential, to addressing fundamental questions regarding the underlying molecular mechanisms of fungal development and virulence. This has been in part due to a confluence of robust genetic tools and genomic resources for the fungus, and recognition of expanded ecological interactions with which the fungus engages. Beauveria bassiana is a broad host range insect pathogen that has the ability to form intimate symbiotic relationships with plants. Indeed, there is an increasing realization that the latter may be the predominant environmental interaction in which the fungus participates, and that insect parasitism may be an opportunist lifestyle evolved due to the carbon- and nitrogen-rich resources present in insect bodies. Here, we will review progress on the molecular genetics of B. bassiana, which has largely been directed toward identifying genetic pathways involved in stress response and virulence assumed to have practical applications in improving the insect control potential of the fungus. Important strides have also been made in understanding aspects of B. bassiana development. Finally, although increasingly apparent in a number of studies, there is a need for progressing beyond phenotypic mutant characterization to sufficiently investigate the molecular mechanisms underlying B. bassiana's unique and diverse lifestyles as saprophyte, insect pathogen, and plant mutualist.

  10. 76 FR 18227 - Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of...

    Science.gov (United States)

    2011-04-01

    ... HUMAN SERVICES Food and Drug Administration Molecular and Clinical Genetics Panel of the Medical Devices... Molecular and Clinical Genetics Panel (the panel) of the Medical Devices Advisory Committee that published... meeting of the Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee, and the...

  11. Recent insights into the molecular genetics of the homocysteine metabolism.

    Science.gov (United States)

    Födinger, M; Wagner, O F; Hörl, W H; Sunder-Plassmann, G

    2001-02-01

    The homocysteine plasma level is determined by non-genetic and genetic factors. In recent years evidence has accumulated that the total homocysteine plasma level of patients under different forms of renal replacement therapy is influenced by a common mutation at nucleotide position 677 of the gene coding for 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T). Furthermore, compound heterozygosity for the 677T allele and a novel A-->C polymorphism at nucleotide position 1298 of MTHFR is suggested to correlate with a decrease of folate plasma concentrations. Because polymorphisms of genes coding for proteins involved in the metabolism of homocysteine may contribute to elevated total homocysteine plasma concentrations, molecular genetic analyses of the homocysteine pathways experienced a drift towards screening for candidate genes with a putative relationship to total homocysteine plasma levels. One example is the cloning of the FOLR1 gene coding for the folate-binding protein (Folbp1), which has recently been inactivated in mice, thus representing an elegant model to investigate the consequence on the homocysteine metabolism. Furthermore, the recent characterization of the CUBN gene encoding the intrinsic factor-vitamin B12 receptor (cubilin) provides a basis to identify the causative mutations in patients suffering from a hereditary syndrome of hyperhomocysteinemia that presents with megaloblastic anemia and proteinuria. This review focuses on recent insights into the molecular genetics of MTHFR, FOLR1, and CUBN, and their relationships to the metabolism of the amino acid homocysteine.

  12. Molecular genetics and genomics progress in urothelial bladder cancer.

    Science.gov (United States)

    Netto, George J

    2013-11-01

    The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers.

  13. Cellular and molecular approaches to memory storage.

    Science.gov (United States)

    Laroche, S

    2000-01-01

    There has been nearly a century of interest in the idea that information is stored in the brain as changes in the efficacy of synaptic connections on neurons that are activated during learning. The discovery and detailed report of the phenomenon generally known as long-term potentiation opened a new chapter in the study of synaptic plasticity in the vertebrate brain, and this form of synaptic plasticity has now become the dominant model in the search for the cellular bases of learning and memory. To date, considerable progress has been made in understanding the cellular and molecular mechanisms underlying synaptic plasticity and in identifying the neural systems which express it. In parallel, the hypothesis that the mechanisms underlying synaptic plasticity are activated during learning and serve learning and memory has gained much empirical support. Accumulating evidence suggests that the rapid activation of the genetic machinery is a key mechanism underlying the enduring modification of neural networks required for the laying down of memory. These advances are reviewed below.

  14. Classical and Molecular Genetic Research on General Cognitive Ability.

    Science.gov (United States)

    McGue, Matt; Gottesman, Irving I

    2015-01-01

    Arguably, no psychological variable has received more attention from behavioral geneticists than what has been called "general cognitive ability" (as well as "general intelligence" or "g"), and for good reason. GCA has a rich correlational network, implying that it may play an important role in multiple domains of functioning. GCA is highly correlated with various indicators of educational attainment, yet its predictive utility is not limited to academic achievement. It is also correlated with work performance, navigating the complexities of everyday life, the absence of various social pathologies (such as criminal convictions), and even health and mortality. Although the causal basis for these associations is not always known, it is nonetheless the case that research on GCA has the potential to provide insights into the origins of a wide range of important social outcomes. In this essay, our discussion of why GCA is considered a fundamentally important dimension of behavior on which humans differ is followed by a look at behavioral genetics research on CGA. We summarize behavioral genetics research that has sought to identify and quantify the total contributions of genetic and environmental factors to individual differences in GCA as well as molecular genetic research that has sought to identify genetic variants that underlie inherited effects. © 2015 The Hastings Center.

  15. The molecular genetic architecture of self-employment.

    Directory of Open Access Journals (Sweden)

    Matthijs J H M van der Loos

    Full Text Available Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σ(g(2/σ(P(2 = 25%, h(2 = 55%. However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10(-5 were tested in a replication sample (n = 3,271, but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039. Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.

  16. The Molecular Genetic Architecture of Self-Employment

    Science.gov (United States)

    van der Loos, Matthijs J. H. M.; Rietveld, Cornelius A.; Eklund, Niina; Koellinger, Philipp D.; Rivadeneira, Fernando; Abecasis, Gonçalo R.; Ankra-Badu, Georgina A.; Baumeister, Sebastian E.; Benjamin, Daniel J.; Biffar, Reiner; Blankenberg, Stefan; Boomsma, Dorret I.; Cesarini, David; Cucca, Francesco; de Geus, Eco J. C.; Dedoussis, George; Deloukas, Panos; Dimitriou, Maria; Eiriksdottir, Guðny; Eriksson, Johan; Gieger, Christian; Gudnason, Vilmundur; Höhne, Birgit; Holle, Rolf; Hottenga, Jouke-Jan; Isaacs, Aaron; Järvelin, Marjo-Riitta; Johannesson, Magnus; Kaakinen, Marika; Kähönen, Mika; Kanoni, Stavroula; Laaksonen, Maarit A.; Lahti, Jari; Launer, Lenore J.; Lehtimäki, Terho; Loitfelder, Marisa; Magnusson, Patrik K. E.; Naitza, Silvia; Oostra, Ben A.; Perola, Markus; Petrovic, Katja; Quaye, Lydia; Raitakari, Olli; Ripatti, Samuli; Scheet, Paul; Schlessinger, David; Schmidt, Carsten O.; Schmidt, Helena; Schmidt, Reinhold; Senft, Andrea; Smith, Albert V.; Spector, Timothy D.; Surakka, Ida; Svento, Rauli; Terracciano, Antonio; Tikkanen, Emmi; van Duijn, Cornelia M.; Viikari, Jorma; Völzke, Henry; Wichmann, H. -Erich; Wild, Philipp S.; Willems, Sara M.; Willemsen, Gonneke; van Rooij, Frank J. A.; Groenen, Patrick J. F.; Uitterlinden, André G.; Hofman, Albert; Thurik, A. Roy

    2013-01-01

    Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable–entrepreneurship–that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg2/σP2 = 25%, h2 = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10−5 were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases. PMID:23593239

  17. Simulation Approach for Timing Analysis of Genetic Logic Circuits.

    Science.gov (United States)

    Baig, Hasan; Madsen, Jan

    2017-02-01

    Constructing genetic logic circuits is an application of synthetic biology in which parts of the DNA of a living cell are engineered to perform a dedicated Boolean function triggered by an appropriate concentration of certain proteins or by different genetic components. These logic circuits work in a manner similar to electronic logic circuits, but they are much more stochastic and hence much harder to characterize. In this article, we introduce an approach to analyze the threshold value and timing of genetic logic circuits. We show how this approach can be used to analyze the timing behavior of single and cascaded genetic logic circuits. We further analyze the timing sensitivity of circuits by varying the degradation rates and concentrations. Our approach can be used not only to characterize the timing behavior but also to analyze the timing constraints of cascaded genetic logic circuits, a capability that we believe will be important for design automation in synthetic biology.

  18. Cellular and genetic approaches to myocardial regeneration

    NARCIS (Netherlands)

    Tuyn, John van

    2008-01-01

    Injection of (stem) cells into the damaged heart has a positive effect on cardiac function. In this thesis two strategies for improving myocardial regeneration over classical cell therapy were investigated. The first is to induce cardiomyogenic differentiation by genetically engineering cells to ex

  19. Neuroimaging genetic approaches to Posttraumatic Stress Disorder.

    Science.gov (United States)

    Lebois, Lauren A M; Wolff, Jonathan D; Ressler, Kerry J

    2016-10-01

    Neuroimaging genetic studies that associate genetic and epigenetic variation with neural activity or structure provide an opportunity to link genes to psychiatric disorders, often before psychopathology is discernable in behavior. Here we review neuroimaging genetics studies with participants who have Posttraumatic Stress Disorder (PTSD). Results show that genes related to the physiological stress response (e.g., glucocorticoid receptor and activity, neuroendocrine release), learning and memory (e.g., plasticity), mood, and pain perception are tied to neural intermediate phenotypes associated with PTSD. These genes are associated with and sometimes predict neural structure and function in areas involved in attention, executive function, memory, decision-making, emotion regulation, salience of potential threats, and pain perception. Evidence suggests these risk polymorphisms and neural intermediate phenotypes are vulnerabilities toward developing PTSD in the aftermath of trauma, or vulnerabilities toward particular symptoms once PTSD has developed. Work distinguishing between the re-experiencing and dissociative sub-types of PTSD, and examining other PTSD symptom clusters in addition to the re-experiencing and hyperarousal symptoms, will further clarify neurobiological mechanisms and inconsistent findings. Furthermore, an exciting possibility is that genetic associations with PTSD may eventually be understood through differential intermediate phenotypes of neural circuit structure and function, possibly underlying the different symptom clusters seen within PTSD. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Molecular mechanisms in atopic eczema: insights gained from genetic studies.

    Science.gov (United States)

    Brown, Sara J

    2017-01-01

    Atopic eczema (synonymous with atopic dermatitis) is a common heterogeneous phenotype with a wide spectrum of severity, from mild transient disease to a severe chronic disorder with atopic and non-atopic comorbidities. Eczema is a complex trait, resulting from the interaction of multiple genetic and environmental factors. The skin, as an organ that can be biopsied easily, provides opportunities for detailed molecular genetic analysis. Strategies applied to the investigation of atopic eczema include candidate gene and genome-wide studies, extreme phenotypes, and comparative analysis of inflammatory skin diseases. Genetic studies have identified a central role for skin barrier impairment in eczema predisposition and perpetuation; this has brought about a paradigm shift in understanding atopic disease, but specific molecular targets to improve skin barrier function remain elusive. The role of Th2-mediated immune dysfunction is also central to atopic inflammation, and has proved to be a powerful target for biological therapy in atopic eczema. Advances in understanding eczema pathogenesis have provided opportunities for patient stratification, primary prevention, and therapy development, but there remain considerable challenges in the application of this knowledge to optimize benefit for patients with atopic eczema in the era of personalized medicine. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. 1 Hierarchical Approaches to the Analysis of Genetic Diversity in ...

    African Journals Online (AJOL)

    2015-04-14

    Apr 14, 2015 ... Keywords: Genetic diversity, Hierarchical approach, Plant, Clustering,. Descriptive ... utilization) or by clustering (based on a phonetic analysis of individual ...... Improvement of Food Crop Preservatives for the next Millennium.

  2. Genetic and molecular dissection of naturally occurring variations in rice

    Energy Technology Data Exchange (ETDEWEB)

    Yano, Masahiro [National Institute of Agrobiological Sciences, Tsukuba, Ibaraki (Japan)

    2002-02-01

    The progress for structural analysis of the rice genome has allowed us to embark on the sequencing of the whole rice genome. Resources - genetic markers, sequence data, and genomic clones - derived from many efforts will be used for the functional analysis of rice genes in the next decade. Although artificially induced variations, such as mutants, have been used mainly for genetic and physiological studies in rice and other plant species, the development of DNA markers has made possible access to naturally occurring allelic variations underlying complex traits. Such analysis is often referred to as quantitative traits locus (QTL) analysis. Many QTLs have been mapped for many complex traits in rice. During the analyses of several quantitative traits by the DNA marker-assisted strategy, two questions about QTL analysis have been raised: 1) Does a QTL represent a single Mendelian locus or a cluster of multiple loci? 2) Is it possible to precisely map a QTL and identify QTLs at the molecular level using map-based or other strategies? To answer these questions, a series of analyses on heading date, including the identification of putative QTLs, characterization and fine mapping of QTLs using nearly isogenic lines (NILs), and identification of genes at QTLs for heading date by the map-based strategy has been performed. In addition, several primary permanent mapping populations and secondary genetic resources, such as chromosomal segmental substitution lines, have been developed to facilitate the genetic analysis of naturally occurring allelic variation. (M. Suetake)

  3. Molecular genetic evidence for polyandry in Ascaris suum.

    Science.gov (United States)

    Zhou, Chunhua; Yuan, Keng; Tang, Xiaoli; Hu, Ningyan; Peng, Weidong

    2011-03-01

    The aim of this study was to determine whether single Ascaris suum female could mate with multiple males. Seven sex-linked microsatellite markers were employed and paternal genetic analyses were conducted. Totally, 62 offspring individuals from three single females were screened, and the numbers of fathers in each family were determined using allele counting methods and the program GERUD, version 2.0. The seven sex-linked microsatellite loci showed high polymorphism and revealed that one out of three families (allele counts) and two out of three families (GERUD) of the sampled families had at least two sires (2-6), indicating that females of A. suum can mate with multiple males. These findings provide the first molecular genetic evidence for polyandry of female A. suum and lay a foundation for further studies on the impacts of polyandry on population genetic parameters, the parasite population's genetic diversity, the potential for infection of different host species, and for the rate of spread of drug resistance.

  4. Molecular Diversity and Genetic Structure of Durum Wheat Landraces

    Directory of Open Access Journals (Sweden)

    GULNAR SHIKHSEYIDOVA

    2015-06-01

    Full Text Available To determine the genetic diversity of durum wheat, 41 accessions from Morocco, Ethiopia, Turkey, Lebanon, Kazakhstan, China, and Mongolia were analyzed through Inter-Simple Sequence Repeats (ISSR molecular markers. Out of the used twenty primers, 15 primers that included a considerable polymorphism were selected for the analyses. Among the genotypes under study, 163 fragments (73.7% were polymorph. Several indexes were used to determine the most appropriate primers. While UBC812, UBC864, UBC840, and UBC808 primers were among those markers which produced the highest number of bands and polymorphic bands, they also dedicated the highest rate of polymorphic index content (PIC. These primers also possessed the highest amounts of effective multiplex ratio (EMR and marker index (MI. Therefore, these primers can be recommended for genetic evaluation of the durum wheat. The results of cluster analysis and principle component analysis indicated that the observed genetic diversity in wheat materials under study is geographically structured. The results also indicated that the genetic diversity index based on ISSR markers was higher for Turkey, Lebanon, Morocco, and Ethiopia accessions than for other countries. The high level of polymorphism in this collections durum wheat would agree with the suggestion that Fertile Crescent and parts of Africa are first possible diversity center of this crop.

  5. The molecular genetics of intrahepatic cholestasis of pregnancy

    Science.gov (United States)

    Dixon, P H; Williamson, C

    2008-01-01

    Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, causes maternal pruritus and liver impairment, and may be complicated by spontaneous preterm labour, fetal asphyxial events and intrauterine death. Our understanding of the aetiology of this disease has expanded significantly in the last decade due to a better understanding of the role played by genetic factors. In particular, advances in our knowledge of bile homeostasis has led to the identification of genes that play a considerable role in susceptibility to ICP. In this review we consider these advances and discuss the disease in the context of bile synthesis and metabolism, focusing on the genetic discoveries that have shed light on the molecular aetiology and pathophysiology of the condition. PMID:27582788

  6. The genetic and molecular basis of congenital cataract

    Directory of Open Access Journals (Sweden)

    Alessandro Santana

    2011-04-01

    Full Text Available Congenital cataracts are one of the most treatable causes of visual impairment and blindness during infancy, with an estimated prevalence of 1 to 6 cases per 10,000 live births. Approximately fifty percent of all congenital cataract cases may have a genetic cause. All three types of Mendelian inheritance have been reported for cataract; however, autosomal dominant transmission seems to be the most frequent. The transparency and high refractive index of the lens are achieved by the precise architecture of the fiber cells and the homeostasis of the lens proteins in terms of their concentration, stability, and supramolecular organization. Research on hereditary congenital cataract led to the identification of several classes of candidate genes that encode proteins such crystallins, lens specific connexins, aquaporine, cytoskeletal structural proteins, and developmental regulators. The purpose of this study was to review the literature on the recent advances made in understanding the molecular genetic basis of congenital cataracts.

  7. Stego-audio Using Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    V. Santhi

    2014-06-01

    Full Text Available With the rapid development of digital multimedia applications, the secure data transmission becomes the main issue in data communication system. So the multimedia data hiding techniques have been developed to ensure the secured data transfer. Steganography is an art of hiding a secret message within an image/audio/video file in such a way that the secret message cannot be perceived by hacker/intruder. In this study, we use RSA encryption algorithm to encrypt the message and Genetic Algorithm (GA to encode the message in the audio file. This study presents a method to access the negative audio bytes and includes the negative audio bytes in the message encoding and position embedding process. This increases the capacity of encoding message in the audio file. The use of GA operators in Genetic Algorithm reduces the noise distortions.

  8. Genetic & epigenetic approach to human obesity

    Directory of Open Access Journals (Sweden)

    K Rajender Rao

    2014-01-01

    Full Text Available Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D, cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12 th u0 pdate of Human Obesity Gene Map there are 253 quantity trait loci (QTL for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

  9. Genetic & epigenetic approach to human obesity.

    Science.gov (United States)

    Rao, K Rajender; Lal, Nirupama; Giridharan, N V

    2014-11-01

    Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th Update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

  10. Genetic & epigenetic approach to human obesity

    Science.gov (United States)

    Rao, K. Rajender; Lal, Nirupama; Giridharan, N.V.

    2014-01-01

    Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th Update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed. PMID:25579139

  11. Synthetic biology and molecular genetics in non-conventional yeasts: Current tools and future advances.

    Science.gov (United States)

    Wagner, James M; Alper, Hal S

    2016-04-01

    Coupling the tools of synthetic biology with traditional molecular genetic techniques can enable the rapid prototyping and optimization of yeast strains. While the era of yeast synthetic biology began in the well-characterized model organism Saccharomyces cerevisiae, it is swiftly expanding to include non-conventional yeast production systems such as Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. These yeasts already have roles in the manufacture of vaccines, therapeutic proteins, food additives, and biorenewable chemicals, but recent synthetic biology advances have the potential to greatly expand and diversify their impact on biotechnology. In this review, we summarize the development of synthetic biological tools (including promoters and terminators) and enabling molecular genetics approaches that have been applied in these four promising alternative biomanufacturing platforms. An emphasis is placed on synthetic parts and genome editing tools. Finally, we discuss examples of synthetic tools developed in other organisms that can be adapted or optimized for these hosts in the near future.

  12. Genetic confirmation of mungbean (Vigna radiata and mashbean (Vigna mungo interspecific recombinants using molecular markers

    Directory of Open Access Journals (Sweden)

    Ghulam eAbbas

    2015-12-01

    Full Text Available The present study was conducted with the aim to investigate recombination between mungbean (female and mashbean (male interspecific crosses using molecular markers i.e., URP (Universal Rice Primers, RAPD (Random Amplified Polymorphic DNA and SSR (Simple Sequence Repeats. As a first step parental screening was performed and polymorphic markers differentiating parent genotypes were identified. Recombinations were then confirmed through polymorphic DNA markers in many of the hybrids. The NM 2006 × Mash 88 was found to be most successful interspecific cross as many of true recombinants, confirmed by molecular markers, belonged to this cross combination. The SSR markers were more efficient in detecting genetic variability and recombinations with reference to specific chromosomes and particular loci, while SSR (RIS and RAPD identified variability dispersed throughout the genome. The DNA based marker assisted approach provided evidence for genetic confirmation of mungbean and mashbean interspecific recombinants and escalated the authenticity of selection in mungbean improvement programme.

  13. Molecular Genetic and Gene Therapy Studies of the Musculoskeletal System

    Science.gov (United States)

    2005-10-01

    Molecular Genetics Division, Ohio State University. For reporting purpose, the ’Smad2’ sign indicates a disabled copy of ’Smad2’ gene while the ’+’ sign...skeletal mass in third- and fourth-grade children : Effects of age, gender, ethnicity and body composition. Bone 20:73-78. 18. Thomas, T. and Burguera, B...strand buffer mix (250 mM Tris HCI (pH 8.3 at RT), 375 mM KCI, 15 mM MgCI, I ul of 0.1 M DTT and 1 ul of RNAse Out, recombinant RNAse inhibitor

  14. Molecular karyotyping: array CGH quality criteria for constitutional genetic diagnosis.

    Science.gov (United States)

    Vermeesch, Joris R; Melotte, Cindy; Froyen, Guy; Van Vooren, Steven; Dutta, Binita; Maas, Nicole; Vermeulen, Stefan; Menten, Björn; Speleman, Frank; De Moor, Bart; Van Hummelen, Paul; Marynen, Peter; Fryns, Jean-Pierre; Devriendt, Koen

    2005-03-01

    Array CGH (comparative genomic hybridization) enables the identification of chromosomal copy number changes. The availability of clone sets covering the human genome opens the possibility for the widespread use of array CGH for both research and diagnostic purposes. In this manuscript we report on the parameters that were critical for successful implementation of the technology, assess quality criteria, and discuss the potential benefits and pitfalls of the technology for improved pre- and postnatal constitutional genetic diagnosis. We propose to name the genome-wide array CGH "molecular karyotyping," in analogy with conventional karyotyping that uses staining methods to visualize chromosomes.

  15. Engaging nurses in genetics: the strategic approach of the NHS National Genetics Education and Development Centre.

    Science.gov (United States)

    Kirk, Maggie; Tonkin, Emma; Burke, Sarah

    2008-04-01

    The UK government announced the establishment of an NHS National Genetics Education and Development Centre in its Genetics White Paper. The Centre aims to lead and coordinate developments to enhance genetics literacy of health professionals. The nursing program takes a strategic approach based on Ajzen's Theory of Planned Behavior, using the UK nursing genetics competences as the platform for development. The program team uses innovative approaches to raise awareness of the relevance of genetics, working collaboratively with policy stakeholders, as key agents of change in promoting competence. Providing practical help in preparing learning and teaching resources lends further encouragement. Evaluation of the program is dependent on gathering baseline data, and the program has been informed by an education needs analysis. The challenges faced are substantial and necessitate international collaboration where expertise and resources can be shared to produce a global system of influence to facilitate the engagement of non-genetic nurses.

  16. Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention.

    Science.gov (United States)

    Goldman, Alica M; Behr, Elijah R; Semsarian, Christopher; Bagnall, Richard D; Sisodiya, Sanjay; Cooper, Paul N

    2016-01-01

    Epidemiologic studies clearly document the public health burden of sudden unexpected death in epilepsy (SUDEP). Clinical and experimental studies have uncovered dynamic cardiorespiratory dysfunction, both interictally and at the time of sudden death due to epilepsy. Genetic analyses in humans and in model systems have facilitated our current molecular understanding of SUDEP. Many discoveries have been informed by progress in the field of sudden cardiac death and sudden infant death syndrome. It is becoming apparent that SUDEP genomic complexity parallels that of sudden cardiac death, and that there is a pauci1ty of analytically useful postmortem material. Because many challenges remain, future progress in SUDEP research, molecular diagnostics, and prevention rests in international, collaborative, and transdisciplinary dialogue in human and experimental translational research of sudden death.

  17. Testicular germ cell tumors: Molecular genetic and clinicomorphological aspects

    Directory of Open Access Journals (Sweden)

    M. V. Nemtsova

    2015-01-01

    Full Text Available Testicular tumors are the most common form of solid cancer in young men. According to the 2004 WHO classification, testicular germ cell tumors (TGCT may present with different histological types. Embryonic cells of varying grade may be a source of TGCT and the occurrence of this type of tumors is directly related to the formation of a pool of male sex cells and gametogenesis. The paper gives information on mo- lecular stages for the process of formation of male sex cells in health, as well as ways of their impairments leading to TGCT. An investigation of the profiles of gene expression and the spectrum of molecular damages revealed genes responsible for a predisposition to the sporadic and hereditary forms of TGCT. The paper presents the current molecular genetic and clinicomorphological characteristics of TGCT. 

  18. Testicular germ cell tumors: Molecular genetic and clinicomorphological aspects

    Directory of Open Access Journals (Sweden)

    M. V. Nemtsova

    2015-03-01

    Full Text Available Testicular tumors are the most common form of solid cancer in young men. According to the 2004 WHO classification, testicular germ cell tumors (TGCT may present with different histological types. Embryonic cells of varying grade may be a source of TGCT and the occurrence of this type of tumors is directly related to the formation of a pool of male sex cells and gametogenesis. The paper gives information on mo- lecular stages for the process of formation of male sex cells in health, as well as ways of their impairments leading to TGCT. An investigation of the profiles of gene expression and the spectrum of molecular damages revealed genes responsible for a predisposition to the sporadic and hereditary forms of TGCT. The paper presents the current molecular genetic and clinicomorphological characteristics of TGCT. 

  19. Molecular and genetic aspects of odontogenic tumors: a review

    Directory of Open Access Journals (Sweden)

    Kavita Garg

    2015-06-01

    Full Text Available Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/controllers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors.

  20. Introduction to Focus Issue: Quantitative Approaches to Genetic Networks

    Science.gov (United States)

    Albert, Réka; Collins, James J.; Glass, Leon

    2013-06-01

    All cells of living organisms contain similar genetic instructions encoded in the organism's DNA. In any particular cell, the control of the expression of each different gene is regulated, in part, by binding of molecular complexes to specific regions of the DNA. The molecular complexes are composed of protein molecules, called transcription factors, combined with various other molecules such as hormones and drugs. Since transcription factors are coded by genes, cellular function is partially determined by genetic networks. Recent research is making large strides to understand both the structure and the function of these networks. Further, the emerging discipline of synthetic biology is engineering novel gene circuits with specific dynamic properties to advance both basic science and potential practical applications. Although there is not yet a universally accepted mathematical framework for studying the properties of genetic networks, the strong analogies between the activation and inhibition of gene expression and electric circuits suggest frameworks based on logical switching circuits. This focus issue provides a selection of papers reflecting current research directions in the quantitative analysis of genetic networks. The work extends from molecular models for the binding of proteins, to realistic detailed models of cellular metabolism. Between these extremes are simplified models in which genetic dynamics are modeled using classical methods of systems engineering, Boolean switching networks, differential equations that are continuous analogues of Boolean switching networks, and differential equations in which control is based on power law functions. The mathematical techniques are applied to study: (i) naturally occurring gene networks in living organisms including: cyanobacteria, Mycoplasma genitalium, fruit flies, immune cells in mammals; (ii) synthetic gene circuits in Escherichia coli and yeast; and (iii) electronic circuits modeling genetic networks

  1. Cognitive Radio — Genetic Algorithm Approach

    Science.gov (United States)

    Reddy, Y. B.

    2005-03-01

    Cognitive Radio (CR) is relatively a new technology, which intelligently detects a particular segment of the radio spectrum currently in use and selects unused spectrum quickly without interfering the transmission of authorized users. Cognitive Radios can learn about current use of spectrum in their operating area, make intelligent decisions, and react to immediate changes in the use of spectrum by other authorized users. The goal of CR technology is to relieve radio spectrum overcrowding, which actually translates to a lack of access to full radio spectrum utilization. Due to this adaptive behavior, the CR can easily avoid the interference of signals in a crowded radio frequency spectrum. In this research, we discuss the possible application of genetic algorithms (GA) to create a CR that can respond intelligently in changing and unanticipated circumstances and in the presence of hostile jammers and interferers. Genetic algorithms are problem solving techniques based on evolution and natural selection. GA models adapt Charles Darwin's evolutionary theory for analysis of data and interchanging design elements in hundreds of thousands of different combinations. Only the best-performing combinations are permitted to survive, and those combinations "reproduce" further, progressively yielding better and better results.

  2. Determining molecular structures and conformations directly from electron diffraction using a genetic algorithm.

    Science.gov (United States)

    Habershon, Scott; Zewail, Ahmed H

    2006-02-13

    A global optimization strategy, based upon application of a genetic algorithm (GA), is demonstrated as an approach for determining the structures of molecules possessing significant conformational flexibility directly from gas-phase electron diffraction data. In contrast to the common approach to molecular structure determination, based on trial-and-error assessment of structures available from quantum chemical calculations, the GA approach described here does not require expensive quantum mechanical calculations or manual searching of the potential energy surface of the sample molecule, relying instead upon simple comparison between the experimental and calculated diffraction pattern derived from a proposed trial molecular structure. Structures as complex as all-trans retinal and p-coumaric acid, both important chromophores in photosensing processes, may be determined by this approach. In the examples presented here, we find that the GA approach can determine the correct conformation of a flexible molecule described by 11 independent torsion angles. We also demonstrate applications to samples comprising a mixture of two distinct molecular conformations. With these results we conclude that applications of this approach are very promising in elucidating the structures of large molecules directly from electron diffraction data.

  3. MOLECULAR GENETIC MARKERS AS PREDICTORS OF SUPERFICIAL BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    A. Yu. Babayan

    2009-01-01

    Full Text Available A system of clinical and morphological criteria is currently used to determine the pattern of superficial bladder cancer (SBC. However, this system does not completely reflect the clinical potential of SBC and needs additional markers. The purpose of this study was to search for and evaluate molecular genetic disorders as additional markers of the course of SBC. The diagnostic panel included the deletion of the loci 3р14, 9р21, 9q34, 17р13 (ТР53, mutations of exon 7 of the FGFR3 gene, and hypermethylation of the promoter regions of the RASSF1, RARB, p16, p14, CDH1 genes. The study was made on 108 matched samples (tumor/peripheral blood obtained from patients with SBC. The deletions of the loci 3р14, 9р21 and anomalous methylation of the RARb and p16 genes are markers of the worse course of SBC while FGFR3 gene mutation is a marker of better prognosis. In the context of estimation of the relapsing potential of a primary tumor, the 9p21 locus deletion is a marker associated with recurrence within the first year after malignancy resection. The group of molecular genetic markers determined by the authors for poor prognosis in combination with classical clinical and morphological criteria will specify the pattern of the course of the disease and its prognosis.

  4. Molecular identification and genetic diversity among Photorhabdus and Xenorhabdus isolates.

    Science.gov (United States)

    Moghaieb, Reda E A; Abdelhadi, Abdelhadi A; El-Sadawy, Hanan A; Allam, Nesreen A T; Baiome, Baiome Abdelmaguid; Soliman, Mohamed H

    2017-05-01

    Five bacterial strains were isolated from the hemocoel of the greater wax moth larvae (Galleria mellonella) infected with the entomopathogenic nematodes: Heterorhabditis bacteriophora HP88, Heterorhabditis indicus RM1 and Heterorhabditis sp (S1), Steinernema abbasi and Steinernema sp. (S II). Strains were identified as Photorhabdus luminescens HRM1, P. luminescens HS1, P. luminescens HP88, Xenorhabdus indica and X. nematophila ATTC19061 using 16S rDNA sequence analysis. To reveal the genetic diversity among these strains, three molecular markers (RAPD, ISSR and SRAP) were employed. RAPD analysis showed 73.8 and 54.5 polymorphism percentages for the Photorhabdus and Xenorhabdus strains, respectively. ISSR analysis resulted in 70.1 and 75.2 polymorphism percentages among the Photorhabdus and Xenorhabdus strains, respectively. The SRAP analysis indicated that 75.6 and 61.2% genetic polymorphism was detected among Photorhabdus and Xenorhabdus strains, respectively. The cluster analysis grouped the three Photorhabdus strains together in one cluster and the two Xenorhabdus strains together in another cluster indicating the phylogenetic relationships among them. The genotype-specific markers detected from the three molecular markers (RAPD, ISSR and SRAP) were sufficient to distinguish between the different bacterial strains tested and can be used in the future IBM program that could be built on the use of these strains.

  5. The Molecular Genetics and Cellular Mechanisms Underlying Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Rajiv D. Machado

    2012-01-01

    Full Text Available Pulmonary arterial hypertension (PAH is an incurable disorder clinically characterised by a sustained elevation of mean arterial pressure in the absence of systemic involvement. As the adult circulation is a low pressure, low resistance system, PAH represents a reversal to a foetal state. The small pulmonary arteries of patients exhibit luminal occlusion resultant from the uncontrolled growth of endothelial and smooth muscle cells. This vascular remodelling is comprised of hallmark defects, most notably the plexiform lesion. PAH may be familial in nature but the majority of patients present with spontaneous disease or PAH associated with other complications. In this paper, the molecular genetic basis of the disorder is discussed in detail ranging from the original identification of the major genetic contributant to PAH and moving on to current next-generation technologies that have led to the rapid identification of additional genetic risk factors. The impact of identified mutations on the cell is examined, particularly, the determination of pathways disrupted in disease and critical to pulmonary vascular maintenance. Finally, the application of research in this area to the design and development of novel treatment options for patients is addressed along with the future directions PAH research is progressing towards.

  6. [Diagnosis of the peripheral hereditary neuropathies and its molecular genetics].

    Science.gov (United States)

    Hernández-Zamora, Edgar; Arenas-Sordo, María de la Luz

    2008-01-01

    Peripheral neuropathies include a wide range of pathological disorders characterized by damage of peripheral nerves. Among them, peripheral hereditary neuropathies are a group of frequent illnesses and early evolution. They have been named hereditary motor and sensory neuropathy (HMSN) or peripheral hereditary neuropathies type Charcot-Marie-Tooth (CMT). The most frequent types are CMT1, CMT2 and CMTX. Approximately 70% of the cases correspond to subtype CMT1A, associated with tandem duplication of a 1.5 Mb DNA fragment on chromosome 17p11.2-p12 that codifies the peripheral myelin protein PMP22. So far, there five different types of CMT (1,2,3,4,X) with approximately 32 subtypes, associated with more than 30 genes. Have been reported genetic heterogeneity and expression variability of the illness makes it necessary to carry on diagnostic strategies that integrate clinical study for determining genetic clinical history, family history, complete physical exploration, muscular strength, physical deformities, reflexes and sensitivity, and molecular studies allow detection of different types of mutations and help establish a correct diagnosis and an adequate genetic counseling.

  7. AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征

    2000-01-01

    Objectives. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-based case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel art and Falconer methods were used to analyze the segregation ratio and heritability. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significartly, OR is 3.905 ( 95 % CI = 1.079 ~ 14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blood relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LOH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome aberrations were observed. Conclusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  8. AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征

    2000-01-01

    Obieaites. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-besed case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel-Gart and Falconer methods were used to analyze the segregation ratio and heritability. Polymemse chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significantly, OR is 3.905(95% CI = 1.079—14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blnod relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LDH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome abermtions were observed.Condusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  9. Maximizing lifetime of wireless sensor networks using genetic approach

    DEFF Research Database (Denmark)

    Wagh, Sanjeev; Prasad, Ramjee

    2014-01-01

    the cluster head intelligently using auction data of node i.e. its local battery power, topology strength and external battery support. The network lifetime is the centre focus of the research paper which explores intelligently selection of cluster head using auction based approach. The multi......-objective parameters are considered to solve the problem using genetic algorithm of evolutionary approach....

  10. Simulation Approach for Timing Analysis of Genetic Logic Circuits

    DEFF Research Database (Denmark)

    Baig, Hasan; Madsen, Jan

    2017-01-01

    in a manner similar to electronic logic circuits, but they are much more stochastic and hence much harder to characterize. In this article, we introduce an approach to analyze the threshold value and timing of genetic logic circuits. We show how this approach can be used to analyze the timing behavior...

  11. Genetic Algorithm Approaches to Prebiobiotic Chemistry Modeling

    Science.gov (United States)

    Lohn, Jason; Colombano, Silvano

    1997-01-01

    We model an artificial chemistry comprised of interacting polymers by specifying two initial conditions: a distribution of polymers and a fixed set of reversible catalytic reactions. A genetic algorithm is used to find a set of reactions that exhibit a desired dynamical behavior. Such a technique is useful because it allows an investigator to determine whether a specific pattern of dynamics can be produced, and if it can, the reaction network found can be then analyzed. We present our results in the context of studying simplified chemical dynamics in theorized protocells - hypothesized precursors of the first living organisms. Our results show that given a small sample of plausible protocell reaction dynamics, catalytic reaction sets can be found. We present cases where this is not possible and also analyze the evolved reaction sets.

  12. Monogenec Arrhythmic Syndromes: From Molecular and Genetic Aspects to Bedside.

    Science.gov (United States)

    E Z, Golukhova; O I, Gromova; R A, Shomahov; N I, Bulaeva; L A, Bockeria

    2016-01-01

    The abrupt cessation of effective cardiac function that is generally due to heart rhythm disorders can cause sudden and unexpected death at any age and is referred to as a syndrome called "sudden cardiac death" (SCD). Annually, about 400,000 cases of SCD occur in the United States alone. Less than 5% of the resuscitation techniques are effective. The prevalence of SCD in a population rises with age according to the prevalence of coronary artery disease, which is the most common cause of sudden cardiac arrest. However, there is a peak in SCD incidence for the age below 5 years, which is equal to 17 cases per 100,000 of the population. This peak is due to congenital monogenic arrhythmic canalopathies. Despite their relative rarity, these cases are obviously the most tragic. The immediate causes, or mechanisms, of SCD are comprehensive. Generally, it is arrhythmic death due to ventricular tachyarrythmias - sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Bradyarrhythmias and pulseless electrical activity account for no more than 40% of all registered cardiac arrests, and they are more often the outcome of the abovementioned arrhythmias. Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, the fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of the heart rhythm (for example, the long QT syndrome). This review presents an overview of the molecular and genetic basis of SCD in the long QT syndrome, Brugada syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and idiopathic ventricular fibrillation, and arrhythmogenic right ventricular dysplasia, and sudden cardiac death prevention strategies by modern techniques (including implantable cardioverter-defibrillator).

  13. Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum.

    Science.gov (United States)

    Dewey, Ralph E; Xie, Jiahua

    2013-10-01

    Alkaloids represent an extensive group of nitrogen-containing secondary metabolites that are widely distributed throughout the plant kingdom. The pyridine alkaloids of tobacco (Nicotiana tabacum L.) have been the subject of particularly intensive investigation, driven largely due to the widespread use of tobacco products by society and the role that nicotine (16) (see Fig. 1) plays as the primary compound responsible for making the consumption of these products both pleasurable and addictive. In a typical commercial tobacco plant, nicotine (16) comprises about 90% of the total alkaloid pool, with the alkaloids nornicotine (17) (a demethylated derivative of nicotine), anatabine (15) and anabasine (5) making up most of the remainder. Advances in molecular biology have led to the characterization of the majority of the genes encoding the enzymes directly responsible the biosynthesis of nicotine (16) and nornicotine (17), while notable gaps remain within the anatabine (15) and anabasine (5) biosynthetic pathways. Several of the genes involved in the transcriptional regulation and transport of nicotine (16) have also been elucidated. Investigations of the molecular genetics of tobacco alkaloids have not only provided plant biologists with insights into the mechanisms underlying the synthesis and accumulation of this important class of plant alkaloids, they have also yielded tools and strategies for modifying the tobacco alkaloid composition in a manner that can result in changing the levels of nicotine (16) within the leaf, or reducing the levels of a potent carcinogenic tobacco-specific nitrosamine (TSNA). This review summarizes recent advances in our understanding of the molecular genetics of alkaloid biosynthesis in tobacco, and discusses the potential for applying information accrued from these studies toward efforts designed to help mitigate some of the negative health consequences associated with the use of tobacco products.

  14. Indel Group in Genomes (IGG) Molecular Genetic Markers1[OPEN

    Science.gov (United States)

    Burkart-Waco, Diana; Kuppu, Sundaram; Britt, Anne; Chetelat, Roger

    2016-01-01

    Genetic markers are essential when developing or working with genetically variable populations. Indel Group in Genomes (IGG) markers are primer pairs that amplify single-locus sequences that differ in size for two or more alleles. They are attractive for their ease of use for rapid genotyping and their codominant nature. Here, we describe a heuristic algorithm that uses a k-mer-based approach to search two or more genome sequences to locate polymorphic regions suitable for designing candidate IGG marker primers. As input to the IGG pipeline software, the user provides genome sequences and the desired amplicon sizes and size differences. Primer sequences flanking polymorphic insertions/deletions are produced as output. IGG marker files for three sets of genomes, Solanum lycopersicum/Solanum pennellii, Arabidopsis (Arabidopsis thaliana) Columbia-0/Landsberg erecta-0 accessions, and S. lycopersicum/S. pennellii/Solanum tuberosum (three-way polymorphic) are included. PMID:27436831

  15. Genetic Programming Approach for Predicting Surface Subsidence Induced by Mining

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The surface subsidence induced by mining is a complex problem, which is related with many complex and uncertain factors.Genetic programming (GP) has a good ability to deal with complex and nonlinear problems, therefore genetic programming approach is proposed to predict mining induced surface subsidence in this article.First genetic programming technique is introduced, second, surface subsidence genetic programming model is set up by selecting its main affective factors and training relating to practical engineering data, and finally, predictions are made by the testing of data, whose results show that the relative error is approximately less than 10%, which can meet the engineering needs, and therefore, this proposed approach is valid and applicable in predicting mining induced surface subsidence.The model offers a novel method to predict surface subsidence in mining.

  16. [A novel approach to techniques in genetic testing for cancer].

    Science.gov (United States)

    Kato, Jun-ichi

    2014-04-01

    In molecular targeted drug therapy, genetic screening is carried out to identify the existence of target genes that are specifically expressed in cancer cells. Conventional methods for detecting the mutation of genes in cancer cells through the use of purified DNA is time consuming, especially in the case of the enzymatic treatment of pathological specimens, and it is difficult to finish all these protocols on the same day. Also, depending on the condition of the patients, it may be difficult to perform surgery or biopsy, and pathological specimens are not always obtainable. Thus, sometimes genetic screening using purified DNA and the enzymatic treatment of pathological specimens cannot be performed. We have successfully solved these problems using i-densy, a genetic analysis device, and two different methods of genetic testing for cancer. The first is a method which, without extracting DNA, uses simply pretreated pathological specimens for genetic screening. Using deparaffinized specimens that have only been heat-treated for a short period of time, we were able to obtain the exact same results as if we had extracted DNA. The second is the highly specific genetic screening technique, the MBP-QP method. Using this method, we were able to confirm the detection of genetic mutation from the DNA of blood plasma. It is now possible to screen for the mutation of genes in cancer cells using just a blood sample from patients without using tissue or cells, which also has little burden on the patient.

  17. Integrating Genetic Algorithm, Tabu Search Approach for Job Shop Scheduling

    CERN Document Server

    Thamilselvan, R

    2009-01-01

    This paper presents a new algorithm based on integrating Genetic Algorithms and Tabu Search methods to solve the Job Shop Scheduling problem. The idea of the proposed algorithm is derived from Genetic Algorithms. Most of the scheduling problems require either exponential time or space to generate an optimal answer. Job Shop scheduling (JSS) is the general scheduling problem and it is a NP-complete problem, but it is difficult to find the optimal solution. This paper applies Genetic Algorithms and Tabu Search for Job Shop Scheduling problem and compares the results obtained by each. With the implementation of our approach the JSS problems reaches optimal solution and minimize the makespan.

  18. Multiple comparisons in genetic association studies: a hierarchical modeling approach.

    Science.gov (United States)

    Yi, Nengjun; Xu, Shizhong; Lou, Xiang-Yang; Mallick, Himel

    2014-02-01

    Multiple comparisons or multiple testing has been viewed as a thorny issue in genetic association studies aiming to detect disease-associated genetic variants from a large number of genotyped variants. We alleviate the problem of multiple comparisons by proposing a hierarchical modeling approach that is fundamentally different from the existing methods. The proposed hierarchical models simultaneously fit as many variables as possible and shrink unimportant effects towards zero. Thus, the hierarchical models yield more efficient estimates of parameters than the traditional methods that analyze genetic variants separately, and also coherently address the multiple comparisons problem due to largely reducing the effective number of genetic effects and the number of statistically "significant" effects. We develop a method for computing the effective number of genetic effects in hierarchical generalized linear models, and propose a new adjustment for multiple comparisons, the hierarchical Bonferroni correction, based on the effective number of genetic effects. Our approach not only increases the power to detect disease-associated variants but also controls the Type I error. We illustrate and evaluate our method with real and simulated data sets from genetic association studies. The method has been implemented in our freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/).

  19. Functional genomics bridges the gap between quantitative genetics and molecular biology.

    Science.gov (United States)

    Lappalainen, Tuuli

    2015-10-01

    Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field.

  20. Molecular, biochemical and genetic characteristics of BSE in Canada.

    Science.gov (United States)

    Dudas, Sandor; Yang, Jianmin; Graham, Catherine; Czub, Markus; McAllister, Tim A; Coulthart, Michael B; Czub, Stefanie

    2010-05-14

    The epidemiology and possibly the etiology of bovine spongiform encephalopathy (BSE) have recently been recognized to be heterogeneous. In particular, three types [classical (C) and two atypical (H, L)] have been identified, largely on the basis of characteristics of the proteinase K (PK)-resistant core of the misfolded prion protein associated with the disease (PrP(res)). The present study was conducted to characterize the 17 Canadian BSE cases which occurred prior to November 2009 based on the molecular and biochemical properties of their PrP(res), including immunoreactivity, molecular weight, glycoform profile and relative PK sensitivity. Two cases exhibited molecular weight and glycoform profiles similar to those of previously reported atypical cases, one corresponding to H-type BSE (case 6) and the other to L-type BSE (case 11). All other cases were classified as C-type. PK digestion under mild and stringent conditions revealed a reduced protease resistance in both of these cases compared to the C-type cases. With Western immunoblotting, N-terminal-specific antibodies bound to PrP(res) from case 6 but not to that from case 11 or C-type cases. C-terminal-specific antibodies revealed a shift in the glycoform profile and detected a fourth protein fragment in case 6, indicative of two PrP(res) subpopulations in H-type BSE. No mutations suggesting a genetic etiology were found in any of the 17 animals by sequencing the full PrP-coding sequence in exon 3 of the PRNP gene. Thus, each of the three known BSE types have been confirmed in Canadian cattle and show molecular characteristics highly similar to those of classical and atypical BSE cases described from Europe, Japan and the USA. The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide.

  1. Molecular, biochemical and genetic characteristics of BSE in Canada.

    Directory of Open Access Journals (Sweden)

    Sandor Dudas

    Full Text Available The epidemiology and possibly the etiology of bovine spongiform encephalopathy (BSE have recently been recognized to be heterogeneous. In particular, three types [classical (C and two atypical (H, L] have been identified, largely on the basis of characteristics of the proteinase K (PK-resistant core of the misfolded prion protein associated with the disease (PrP(res. The present study was conducted to characterize the 17 Canadian BSE cases which occurred prior to November 2009 based on the molecular and biochemical properties of their PrP(res, including immunoreactivity, molecular weight, glycoform profile and relative PK sensitivity. Two cases exhibited molecular weight and glycoform profiles similar to those of previously reported atypical cases, one corresponding to H-type BSE (case 6 and the other to L-type BSE (case 11. All other cases were classified as C-type. PK digestion under mild and stringent conditions revealed a reduced protease resistance in both of these cases compared to the C-type cases. With Western immunoblotting, N-terminal-specific antibodies bound to PrP(res from case 6 but not to that from case 11 or C-type cases. C-terminal-specific antibodies revealed a shift in the glycoform profile and detected a fourth protein fragment in case 6, indicative of two PrP(res subpopulations in H-type BSE. No mutations suggesting a genetic etiology were found in any of the 17 animals by sequencing the full PrP-coding sequence in exon 3 of the PRNP gene. Thus, each of the three known BSE types have been confirmed in Canadian cattle and show molecular characteristics highly similar to those of classical and atypical BSE cases described from Europe, Japan and the USA. The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide.

  2. Population genetic structure of rare and endangered plants using molecular markers

    Science.gov (United States)

    Raji, Jennifer; Atkinson, Carter T.

    2013-01-01

    This study was initiated to assess the levels of genetic diversity and differentiation in the remaining populations of Phyllostegia stachyoides and Melicope zahlbruckneri in Hawai`i Volcanoes National Park and determine the extent of gene flow to identify genetically distinct individuals or groups for conservation purposes. Thirty-six Amplified Fragment Length Polymorphic (AFLP) primer combinations generated a total of 3,242 polymorphic deoxyribonucleic acid (DNA) fragments in the P. stachyoides population with a percentage of polymorphic bands (PPB) ranging from 39.3 to 65.7% and 2,780 for the M. zahlbruckneri population with a PPB of 18.8 to 64.6%. Population differentiation (Fst) of AFLP loci between subpopulations of P. stachyoides was low (0.043) across populations. Analysis of molecular variance of P. stachyoides showed that 4% of the observed genetic differentiation occurred between populations in different kīpuka and 96% when individuals were pooled from all kīpuka. Moderate genetic diversity was detected within the M. zahlbruckneri population. Bayesian and multivariate analyses both classified the P. stachyoides and M. zahlbruckneri populations into genetic groups with considerable sub-structuring detected in the P. stachyoides population. The proportion of genetic differentiation among populations explained by geographical distance was estimated by Mantel tests. No spatial correlation was found between genetic and geographic distances in both populations. Finally, a moderate but significant gene flow that could be attributed to insect or bird-mediated dispersal of pollen across the different kīpuka was observed. The results of this study highlight the utility of a multi-allelic DNA-based marker in screening a large number of polymorphic loci in small and closely related endangered populations and revealed the presence of genetically unique groups of individuals in both M. zahlbruckneri and P. stachyoides populations. Based on these findings

  3. Genomics, Physiology, and Molecular Breeding Approaches for Improving Salt Tolerance.

    Science.gov (United States)

    Ismail, Abdelbagi M; Horie, Tomoaki

    2017-02-22

    Salt stress reduces land and water productivity and contributes to poverty and food insecurity. Increased salinization caused by human practices and climate change is progressively reducing agriculture productivity despite escalating calls for more food. Plant responses to salt stress are fairly well understood, involving numerous critical processes that are each controlled by multiple genes. Knowledge of the critical mechanisms controlling salt uptake and exclusion from functioning tissues, signaling of salt stress, and the arsenal of protective metabolites is advancing. However, little progress has been made in developing salt-tolerant varieties of crop species using standard (but slow) breeding approaches. The genetic diversity available within cultivated crops and their wild relatives provides rich sources for trait and gene discovery that has yet to be sufficiently utilized. Transforming this knowledge into modern approaches using genomics and molecular tools for precision breeding will accelerate the development of tolerant cultivars and help sustain food production. Expected final online publication date for the Annual Review of Plant Biology Volume 68 is April 29, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  4. Genetic diversity assessment of summer squash landraces using molecular markers.

    Science.gov (United States)

    Mady, Emad A; Helaly, Alaa Al-Din; Abu El-Hamd, Abdel Naem; Abdou, Arafa; Shanan, Shamel A; Craker, Lyle E

    2013-07-01

    Plant identification, classification, and genotyping within a germplasm collection are essential elements for establishing a breeding program that enhances the probability of plants with desirable characteristics in the market place. In this study, random amplified polymorphic DNA (RAPD) was used as a molecular tool to assess the diversity and relationship among 20 summer squash (Curcubita pepo L.) landraces traditionally used to treat hypertension and prostate hyperplasia. A total of 10 RAPD primers produced 65 reproducible bands of which 46 (70.77 %) were polymorphic, indicating a large number of genotypes within the summer squash lines. Cluster analysis divided the summer squash germplasm into two groups, one including one landrace and a second containing 19 landraces that could be divided into five sub-groups. Results of this study indicate the potential of RAPD markers for the identification and assessment of genetic variations among squash landraces and provide a number of choices for developing a successful breeding program to improve summer squash.

  5. [Clinical and molecular genetic analysis of hereditary optic neuropathies].

    Science.gov (United States)

    Avetisov, S É; Sheremet, N L; Vorob'eva, O K; Eliseeva, É G; Chukhrova, A L; Loginova, A N; Khanakova, N A; Poliakov, A V

    2013-01-01

    DNA samples of 50 patients with optic neuropathy (ON) associated with congenital cataract were studied to find 3 major mt-DNA mutations (m.11778G>A, m.3460G>A, m.14484T>C), mutations in "hot" regions of OPA 1 gene (exons 8, 14, 15, 16, 18, 27, 28) and in the entire coding sequence of OPA3 gene for molecular genetic confirmation of diagnosis of hereditary Leber and autosomal dominant ON. Primary mutations of mtDNA responsible for hereditary Leber ON were found in 16 patients (32%). Pathogenic mutations of OPAl gene (c.869G>A and c. 2850delT) were identified in 2 patients (4%), these mutations were not found in the literature. OPA3 gene mutations were not revealed.

  6. Molecular and genetic basis of X-linked immunodeficiency disorders

    Energy Technology Data Exchange (ETDEWEB)

    Puck, J.M. (National Center for Human Genome Research, Bethesda, MD (United States))

    1994-03-01

    Within a short time interval the specific gene defects causing three X-linked human immunodeficiencies, agammaglobulinemia (XLA), hyper-IgM syndrome (HIGM), and severe combined immunodeficiency (XSCID), have been identified. These represent the first human disease phenotypes associated with each of three gene families already recognized to be important in lymphocyte development and signaling: XLA is caused by mutations of a B cell-specific intracellular tyrosine kinase; HIGM, by mutations in the TNF-related CD40 ligand, through which T cells deliver helper signals by direct contact with B cell CD40; and XSCID, by mutations in the [gamma] chain of the lymphocyte receptor for IL-2. Each patient mutation analyzed to date has been unique, representing both a challenge for genetic diagnosis and management and an important resource for dissecting molecular domains and understanding the physiologic function of the gene products.

  7. Wrinkled Peas and White-Eyed Fruit Flies: The Molecular Basis of Two Classical Genetic Traits.

    Science.gov (United States)

    Guilfoile, Patrick

    1997-01-01

    Focuses on bridging the gap between classical and molecular genetics for two traits: wrinkled seeds in garden peas and white eye color in fruit flies. Discusses the molecular details of the underlying basis of these traits. Contains 15 references. (JRH)

  8. The molecular genetics of the corneal dystrophies--current status.

    Science.gov (United States)

    Klintworth, Gordon K

    2003-05-01

    The pertinent literature on inherited corneal diseases is reviewed in terms of the chromosomal localization and identification of the responsible genes. Disorders affecting the cornea have been mapped to human chromosome 1 (central crystalline corneal dystrophy, familial subepithelial corneal amyloidosis, early onset Fuchs dystrophy, posterior polymorphous corneal dystrophy), chromosome 4 (Bietti marginal crystalline dystrophy), chromosome 5 (lattice dystrophy types 1 and IIIA, granular corneal dystrophy types 1, 2 and 3, Thiel-Behnke corneal dystrophy), chromosome 9 (lattice dystrophy type II), chromosome 10 (Thiel-Behnke corneal dystrophy), chromosome 12 (Meesmann dystrophy), chromosome 16 (macular corneal dystrophy, fish eye disease, LCAT disease, tyrosinemia type II), chromosome 17 (Meesmann dystrophy, Stocker-Holt dystrophy), chromosome 20 (congenital hereditary endothelial corneal dystrophy types I and II, posterior polymorphous corneal dystrophy), chromosome 21 (autosomal dominant keratoconus) and the X chromosome (cornea verticillata, cornea farinata, deep filiform corneal dystrophy, keratosis follicularis spinulosa decalvans, Lisch corneal dystrophy). Mutations in nine genes (ARSC1, CHST6, COL8A2, GLA, GSN, KRT3, KRT12, M1S1and TGFBI [BIGH3]) account for some of the corneal diseases and three of them are associated with amyloid deposition in the cornea (GSN, M1S1, TGFBI) including most of the lattice corneal dystrophies (LCDs) [LCD types I, IA, II, IIIA, IIIB, IV, V, VI and VII] recognized by their lattice pattern of linear opacities. Genetic studies on inherited diseases affecting the cornea have provided insight into some of these disorders at a basic molecular level and it has become recognized that distinct clinicopathologic phenotypes can result from specific mutations in a particular gene, as well as some different mutations in the same gene. A molecular genetic understanding of inherited corneal diseases is leading to a better appreciation of the

  9. Choosing the right molecular genetic markers for studying biodiversity: from molecular evolution to practical aspects.

    Science.gov (United States)

    Chenuil, Anne; Anne, Chenuil

    2006-05-01

    The use of molecular genetic markers (MGMs) has become widespread among evolutionary biologists, and the methods of analysis of genetic data improve rapidly, yet an organized framework in which scientists can work is lacking. Elements of molecular evolution are summarized to explain the origin of variation at the DNA level, its measures, and the relationships linking genetic variability to the biological parameters of the studied organisms. MGM are defined by two components: the DNA region(s) screened, and the technique used to reveal its variation. Criteria of choice belong to three categories: (1) the level of variability, (2) the nature of the information (e.g. dominance vs. codominance, ploidy, ... ) which must be determined according to the biological question and (3) some practical criteria which mainly depend on the equipment of the laboratory and experience of the scientist. A three-step procedure is proposed for drawing up MGMs suitable to answer given biological questions, and compiled data are organized to guide the choice at each step: (1) choice, determined by the biological question, of the level of variability and of the criteria of the nature of information, (2) choice of the DNA region and (3) choice of the technique.

  10. Mining the human genome after Association for Molecular Pathology v. Myriad Genetics.

    Science.gov (United States)

    Evans, Barbara J

    2014-07-01

    The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved--but still imperfect--framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics.

  11. Chemical Genetics — A Versatile Method to Combine Science and Higher Level Teaching in Molecular Genetics

    Directory of Open Access Journals (Sweden)

    Björn Sandrock

    2012-10-01

    Full Text Available Phosphorylation is a key event in many cellular processes like cell cycle, transformation of environmental signals to transcriptional activation or polar growth. The chemical genetics approach can be used to analyse the effect of highly specific inhibition in vivo and is a promising method to screen for kinase targets. We have used this approach to study the role of the germinal centre kinase Don3 during the cell division in the phytopathogenic fungus Ustilago maydis. Due to the easy determination of the don3 phenotype we have chosen this approach for a genetic course for M.Sc. students and for IMPRS (International Max-Planck research school students. According to the principle of “problem-based learning” the aim of this two-week course is to transfer knowledge about the broad spectrum of kinases to the students and that the students acquire the ability to design their own analog-sensitive kinase of interest. In addition to these training goals, we benefit from these annual courses the synthesis of basic constructs for genetic modification of several kinases in our model system U. maydis.

  12. Molecular assessment of genetic diversity in mung bean germplasm

    Indian Academy of Sciences (India)

    G. Roopa Lavanya; Jyoti Srivastava; Shirish A. Ranade

    2008-04-01

    RAPD profiles were used to identify the extent of diversity among 54 accessions of mung bean that included both improved and local land races. Out of the 40 primers screened, seven primers generated 174 amplification products with an average of 24.85 bands per primer. The RAPD profiles were analysed for Jaccard’s similarity coefficients that was found to be in the range from 0 to 0.48, indicating the presence of wide range of genetic diversity at molecular level. Cluster analysis was carried out based on distances (1-similarity coefficient) using neighbour-joining method in Free Tree package. The dendrogram resolved all the accessions into two major clusters, I (with 11 accessions) and II (with 43 accessions). However, the cluster was further divided into four subclusters (II A with six, II B with nine, II C with 15 and II D with 13 accessions). The distribution of the accessions in different clusters and subclusters appeares to be related to their performance in field conditions for 10 morphological traits that were scored. This study indicated that the RAPD profiles provide an easy and simple technique for preliminary genetic diversity assessment of mung bean accessions that may reflect morphological trait differences among them.

  13. Basic Concepts in Molecular Biology Related to Genetics and Epigenetics.

    Science.gov (United States)

    Corella, Dolores; Ordovas, Jose M

    2017-09-01

    The observation that "one size does not fit all" for the prevention and treatment of cardiovascular disease, among other diseases, has driven the concept of precision medicine. The goal of precision medicine is to provide the best-targeted interventions tailored to an individual's genome. The human genome is composed of billions of sequence arrangements containing a code that controls how genes are expressed. This code depends on other nonstatic regulators that surround the DNA and constitute the epigenome. Moreover, environmental factors also play an important role in this complex regulation. This review provides a general perspective on the basic concepts of molecular biology related to genetics and epigenetics and a glossary of key terms. Several examples are given of polymorphisms and genetic risk scores related to cardiovascular risk. Likewise, an overview is presented of the main epigenetic regulators, including DNA methylation, methylcytosine-phosphate-guanine-binding proteins, histone modifications, other histone regulations, micro-RNA effects, and additional emerging regulators. One of the greatest challenges is to understand how environmental factors (diet, physical activity, smoking, etc.) could alter the epigenome, resulting in healthy or unhealthy cardiovascular phenotypes. We discuss some gene-environment interactions and provide a methodological overview. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Impact of molecular genetics on congenital adrenal hyperplasia management.

    Science.gov (United States)

    Balsamo, A; Baldazzi, L; Menabò, S; Cicognani, A

    2010-09-01

    Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by mutations in genes encoding the enzymes involved in one of the 5 steps of adrenal steroid synthesis or the electron donor P450 oxidoreductase (POR) enzyme. Steroid 21-hydroxylase deficiency (21-OHD), the principal focus of this review, accounts for about 90-95% of all CAH cases, and its biochemical and clinical severity depends on the underlying CYP21A2 gene disruption. Molecular genetic advancements have been achieved in recent years, and the aim of this review is to attempt to highlight its contribution to the comprehension and management of the disease. When possible, we will try to achieve this goal also by providing some results from our personal experience regarding: some aspects of CYP21A2 gene analysis, with basic genotype/phenotype relationships; its crucial role in both genetic counselling and in prenatal diagnosis and treatment in families at risk for 21-OHD; its help in the comprehension of the severity of the disease in patients diagnosed by neonatal screening and possibly treated before an evident salt-loss crisis or before performing adequate blood sampling; its usefulness in the definition of post ACTH 17-hydroxyprogesterone values, discriminating between non-classic, heterozygote and normal subjects; and finally the contribution of genes other than CYP21A2 whose function or dysfunction could influence 21-hydroxylase activity and modify the presentation or management of the disease.

  15. Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy.

    Science.gov (United States)

    Bai, Huimin; Cao, Dongyan; Yang, Jiaxin; Li, Menghui; Zhang, Zhenyu; Shen, Keng

    2016-04-01

    Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and tumoural heterogeneity (TH) has been blamed for treatment failure. The genomic and epigenomic atlas of EOC varies significantly with tumour histotype, grade, stage, sensitivity to chemotherapy and prognosis. Rapidly accumulating knowledge about the genetic and epigenetic events that control TH in EOC has facilitated the development of molecular-targeted therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors, designed to target homologous recombination, are poised to change how breast cancer susceptibility gene (BRCA)-related ovarian cancer is treated. Epigenetic treatment regimens being tested in clinical or preclinical studies could provide promising novel treatment approaches and hope for improving patient survival.

  16. Genetic and Molecular Dissection of Arsenic Hyperaccumulation in the fern Pteris vittata.

    Energy Technology Data Exchange (ETDEWEB)

    Jo Ann Banks; David Salt

    2008-04-04

    Pteris vittata is a fern that is extraordinary in its ability to tolerate hyperaccumulate high levels of arsenic (As). The goals of the proposed research, to identify the genes that are necessary for As hyperaccumulation in P. vittata using molecular and genetic approaches and to understand the physiology of arsenic uptake and distribution in the living plant, were accomplished during the funding period. The genes that have been identified may ultimately enable the engineering or selection of other plants capable of As hyperaccumulation. This is important for the phytoremediation of arsenic-contaminated soils in areas where P. vittata cannot grow.

  17. Genetic tools for wildlife management: New TWS Working Group focuses on molecular ecology

    Science.gov (United States)

    Latch, Emily; Crowhurst, Rachel S.; Oyler-McCance, Sara J.; Robinson, Stacie

    2014-01-01

    Granted interim status in November, 2013, The Wildlife Society’s (TWS) Molecular Ecology Working Group aims to promote scientific advancement by applying molecular techniques to wildlife ecology, management, and conservation. The working group—composed of sci - entists from diverse backgrounds—met for the first time in Pittsburgh at the TWS Annual Conference held in October. Our overarching goal is to enhance awareness of molecular ecology and genetic applica - tions to wildlife biology and act as an informational and networking resource. During the group’s interim status, which runs for three years, we intend to focus on a broad scope of molecular ecology that is applicable to wildlife including genetic and ge - nomic methods, conservation genetics, non-invasive genetic population monitoring, landscape genetics, evolutionary genetics, and molecular forensics

  18. Molecular Genetics of Root Thigmoresponsiveness in Arabidopsis thaliana

    Science.gov (United States)

    Masson, Patrick H.

    2002-01-01

    The molecular mechanisms that allow plant roots to use gravity and touch as growth guides are investigated. We are using a molecular genetic strategy in Arabidopsis thaliana to study these processes. When Arabidopsis thaliana seedlings grow on tilted hard-agar surfaces, their roots develop a wavy pattern of growth which appears to derive from a succession of left-handed and right-handed circumnutation-like processes triggered by gravity and touch stimulation (Okada and Shimura, 1990; Rutherford et al., 1998; Rutherford and Masson, 1996). Interestingly, mutations that affect root waving on tilted hard-agar surfaces can be identified and characterized. Some of these mutations affect root gravitropism, while others appear to be responsible for the production of abnormal waves (no waves, compressed or square waves, coils) without affecting gravitropism. The specific objectives of this project were to functionally characterize two genes (WVD2 and WVD6) which are required for root waving on tilted agar surfaces, but not for root gravitropism. Specific objectives included a physiological and cytological analysis of the mutants, and molecular cloning and characterization of the corresponding genes. As summarized in this paper, we have reached these objectives. We have also identified and partially characterized other mutations that affect root skewing on hard-agar surfaces (sku5-1 and ago1), and have completed our work on the root-wave phenotype associated with mutations in genes of the tryptophan biosynthesis pathway (Lynn et al., 1999; Rutherford et al., 1998; Sedbrook et al., 2000, 2002). We briefly describe our progress on the cloning and characterization of WVD6, WVD2 and SKU5, and provide a list of papers (published, or in preparation) that derived from this grant. We also discuss the biological implications of our findings, with special emphasis on the analysis of WVD2.

  19. Inherited colour vision deficiencies: From Dalton to molecular genetics

    Directory of Open Access Journals (Sweden)

    Cvetković Dragana

    2005-01-01

    Full Text Available In recent years, great advances have been made in our understanding of the molecular basis of colour vision defects, as well as of the patterns of genetic variation in individuals with normal colour vision. Molecular genetic analyses have explained the diversity of types and degrees of severity in colour vision anomalies, their frequencies, pronounced individual variations in test results, etc. New techniques have even enabled the determination of John Dalton’s real colour vision defect, 150 years after his death. Inherited colour vision deficiencies most often result from the mutations of genes that encode cone opsins. Cone opsin genes are linked to chromosomes 7 (the S or “blue” gene and X (the L or “red” gene and the M or “green” gene. The L and M genes are located on the q arm of the X chromosome in a head-to-tail array, composed of 2 to 6 (typically 3 genes - a single L is followed by one or more M genes. Only the first two genes of the array are expressed and contribute to the colour vision phenotype. The high degree of homology (96% between the L and M genes predisposes them to unequal recombination, leading to gene deletion or the formation of hybrid genes (comprising portions of both the L and M genes, explaining the majority of the common red-green colour vision deficiencies. The severity of any deficiency is influenced by the difference in spectral sensitivity between the opsins encoded by the first two genes of the array. A rare defect, S monochromacy, is caused either by the deletion of the regulatory region of the array or by mutations that inactivate the L and M genes. Most recent research concerns the molecular basis of complete achromatopsia, a rare disorder that involves the complete loss of all cone function. This is not caused by mutations in opsin genes, but in other genes that encode cone-specific proteins, e.g. channel proteins and transducin.

  20. Emerging molecular approaches in stem cell biology.

    Science.gov (United States)

    Jaishankar, Amritha; Vrana, Kent

    2009-04-01

    Stem cells are characterized by their ability to self-renew and differentiate into multiple adult cell types. Although substantial progress has been made over the last decade in understanding stem cell biology, recent technological advances in molecular and systems biology may hold the key to unraveling the mystery behind stem cell self-renewal and plasticity. The most notable of these advances is the ability to generate induced pluripotent cells from somatic cells. In this review, we discuss our current understanding of molecular similarities and differences among various stem cell types. Moreover, we survey the current state of systems biology and forecast future needs and direction in the stem cell field.

  1. Giardia duodenalis: genetic recombination and its implications for taxonomy and molecular epidemiology.

    Science.gov (United States)

    Cacciò, Simone M; Sprong, Hein

    2010-01-01

    Traditionally, species within the Giardia genus have been considered as eukaryotic organisms that show an absence of sexual reproduction in their simple life cycles. This apparent lack of sex has been challenged by a number of studies that have demonstrated (i) the presence in the Giardia duodenalis genome of true homologs of genes specifically involved in meiosis in other eukaryotes, and their stage-specific expression; (ii) the exchange of genetic material in different chromosomal regions among human isolates of the parasite; (iii) the fusion between cyst nuclei (karyogamy) and the transfer of genetic material (episomal plasmids) between them. These results are pivotal for the existence of sexual recombination. However, many details of the process remain elusive, and experimental data are still scarce. This review summarizes the experimental approaches and the results obtained, and discusses the implications of recombination from the standpoint of the taxonomy and molecular epidemiology of this widespread pathogen.

  2. Population Genetic Diversity in the Australian 'Seascape': A Bioregion Approach.

    Directory of Open Access Journals (Sweden)

    Lisa C Pope

    Full Text Available Genetic diversity within species may promote resilience to environmental change, yet little is known about how such variation is distributed at broad geographic scales. Here we develop a novel Bayesian methodology to analyse multi-species genetic diversity data in order to identify regions of high or low genetic diversity. We apply this method to co-distributed taxa from Australian marine waters. We extracted published summary statistics of population genetic diversity from 118 studies of 101 species and > 1000 populations from the Australian marine economic zone. We analysed these data using two approaches: a linear mixed model for standardised data, and a mixed beta-regression for unstandardised data, within a Bayesian framework. Our beta-regression approach performed better than models using standardised data, based on posterior predictive tests. The best model included region (Integrated Marine and Coastal Regionalisation of Australia (IMCRA bioregions, latitude and latitude squared. Removing region as an explanatory variable greatly reduced model performance (delta DIC 23.4. Several bioregions were identified as possessing notably high genetic diversity. Genetic diversity increased towards the equator with a 'hump' in diversity across the range studied (-9.4 to -43.7°S. Our results suggest that factors correlated with both region and latitude play a role in shaping intra-specific genetic diversity, and that bioregion can be a useful management unit for intra-specific as well as species biodiversity. Our novel statistical model should prove useful for future analyses of within species genetic diversity at broad taxonomic and geographic scales.

  3. Continuous Molecular Fields Approach Applied to Structure-Activity Modeling

    CERN Document Server

    Baskin, Igor I

    2013-01-01

    The Method of Continuous Molecular Fields is a universal approach to predict various properties of chemical compounds, in which molecules are represented by means of continuous fields (such as electrostatic, steric, electron density functions, etc). The essence of the proposed approach consists in performing statistical analysis of functional molecular data by means of joint application of kernel machine learning methods and special kernels which compare molecules by computing overlap integrals of their molecular fields. This approach is an alternative to traditional methods of building 3D structure-activity and structure-property models based on the use of fixed sets of molecular descriptors. The methodology of the approach is described in this chapter, followed by its application to building regression 3D-QSAR models and conducting virtual screening based on one-class classification models. The main directions of the further development of this approach are outlined at the end of the chapter.

  4. Review: domestic animal forensic genetics - biological evidence, genetic markers, analytical approaches and challenges.

    Science.gov (United States)

    Kanthaswamy, S

    2015-10-01

    This review highlights the importance of domestic animal genetic evidence sources, genetic testing, markers and analytical approaches as well as the challenges this field is facing in view of the de facto 'gold standard' human DNA identification. Because of the genetic similarity between humans and domestic animals, genetic analysis of domestic animal hair, saliva, urine, blood and other biological material has generated vital investigative leads that have been admitted into a variety of court proceedings, including criminal and civil litigation. Information on validated short tandem repeat, single nucleotide polymorphism and mitochondrial DNA markers and public access to genetic databases for forensic DNA analysis is becoming readily available. Although the fundamental aspects of animal forensic genetic testing may be reliable and acceptable, animal forensic testing still lacks the standardized testing protocols that human genetic profiling requires, probably because of the absence of monetary support from government agencies and the difficulty in promoting cooperation among competing laboratories. Moreover, there is a lack in consensus about how to best present the results and expert opinion to comply with court standards and bear judicial scrutiny. This has been the single most persistent challenge ever since the earliest use of domestic animal forensic genetic testing in a criminal case in the mid-1990s. Crime laboratory accreditation ensures that genetic test results have the courts' confidence. Because accreditation requires significant commitments of effort, time and resources, the vast majority of animal forensic genetic laboratories are not accredited nor are their analysts certified forensic examiners. The relevance of domestic animal forensic genetics in the criminal justice system is undeniable. However, further improvements are needed in a wide range of supporting resources, including standardized quality assurance and control protocols for sample

  5. Understanding the Science-Learning Environment: A Genetically Sensitive Approach

    Science.gov (United States)

    Haworth, Claire M. A.; Davis, Oliver S. P.; Hanscombe, Ken B.; Kovas, Yulia; Dale, Philip S.; Plomin, Robert

    2013-01-01

    Previous studies have shown that environmental influences on school science performance increase in importance from primary to secondary school. Here we assess for the first time the relationship between the science-learning environment and science performance using a genetically sensitive approach to investigate the aetiology of this link. 3000…

  6. Molecular approaches to study probiotic bacteria

    NARCIS (Netherlands)

    Vaughan, E.E.; Heilig, G.H.J.; Zoetendal, E.G.; Satokari, R.; Collins, J.K.; Akkermans, A.D.L.; Vos, de W.M.

    2000-01-01

    Functional foods comprising probiotic bacteria are receiving increasing attention from the scientific community and science funding agencies [1]. An essential aspect relating to the functionality of probiotic-based foods is to develop molecular methods to determine the presence, activity and viabili

  7. Approaches for molecular characterization of modified biopolymers

    NARCIS (Netherlands)

    Haar, ter R.

    2011-01-01

    In this thesis, research on the molecular characterization of products obtained after structure modification of oligosaccharides, starch, model peptides, and bovine α-lactalbumin is described. The research goals comprised the development of analytical tools as well as the elucidation of molecu

  8. A Baseline Algorithm for Molecular Diagnosis of Genetic Eye Diseases: Ophthalmologist’s Perspective

    Directory of Open Access Journals (Sweden)

    Hande Taylan Şekeroğlu

    2016-12-01

    Full Text Available To the Editor: Genetic eye diseases constitute a large and heterogeneous group. Individual diseases may cause multiple structural/functional anomalies and developmental features. Family history may be suggestive; however, it may also be challenging, particularly in late-onset conditions or in cases of variable expression. In the current era of genetic advances, diagnosis of a genetic eye disease is facilitated by well-established collaboration between ophthalmologists and geneticists, as increasingly more patients will be asking for genetic counseling and prenatal diagnosis in addition to ophthalmologic management. Molecular investigation of a genetic eye disease requires customized analysis and advanced technology in addition to the requisite detailed family history and accurate ophthalmological diagnosis. A common indication for genetic testing is the validation of a preliminary diagnosis made in clinical practice. The need to determine the prognostic implications of the genotype, assessment of the recurrence risk and in particular, the possibility of specific gene therapy in the near future encourages clinicians to pursue genetic research. We present here a baseline algorithm covering common genetic mechanisms in order to outline a basic molecular approach for ophthalmologists. The first step of the flow chart, a prudent clinical examination with complete description of the phenotype, is indispensible for making a precise and accurate preliminary diagnosis (Figure 1. If the phenotype is pathognomonic, Sanger sequencing is preferred for confirmation.1 A previously established genotype-phenotype correlation may add to the value, either by providing accurate prognostic information or by indicating which particular mutation to look for. One such example may be electroretinographic supranormal rod response, indicating KCNV2 mutation type cone dystrophy, which can be precisely detected by Sanger sequencing or qPCR.2 Conventional karyotyping reveals

  9. Genética molecular: avanços e problemas Molecular genetics: advances and problems

    Directory of Open Access Journals (Sweden)

    Eloi S. Garcia

    1996-03-01

    Full Text Available Este artigo traz a discussão sobre genética molecular em saúde ao campo da saúde pública. Com a revolução produzida pela chegada da engenharia genética, é importante discutir alguns dos avanços e problemas desta tecnologia para a sociedade. Está na hora de se fazer uma avaliação clara e bem informada acerca do que já se conseguiu e do que ainda podemos conseguir através desta tecnologia. A sociedade precisa compreender as implicações éticas e práticas de uma tecnologia capaz de produzir drogas milagrosas, dagnósticos modernos e a cura de todas as doenças. Alguns pontos particularmente delicados pertinentes às questões sociais ligadas à biologia molecular e ao projeto genoma humano são discutidos.This article is an attempt to draw the discussion on molecular genetics in health into the public health domain. Now that the genetic engineering revolution has arrived, it is important to point out the advances and problems this technology poses for society. It is time for a clear, informed assessment of what we have already achieved and may soon achieve using this technology. Clearly, society needs to understand the ethical and practical implications of a technology which can produce miracle drugs and modern diagnoses and cure virtually every disease. Important points from sensitive social issues raised by molecular biology and the human genome project are discussed.

  10. Automated discovery of single nucleotide polymorphism and simple sequence repeat molecular genetic markers.

    Science.gov (United States)

    Batley, Jacqueline; Jewell, Erica; Edwards, David

    2007-01-01

    Molecular genetic markers represent one of the most powerful tools for the analysis of genomes. Molecular marker technology has developed rapidly over the last decade, and two forms of sequence-based markers, simple sequence repeats (SSRs), also known as microsatellites, and single nucleotide polymorphisms (SNPs), now predominate applications in modern genetic analysis. The availability of large sequence data sets permits mining for SSRs and SNPs, which may then be applied to genetic trait mapping and marker-assisted selection. Here, we describe Web-based automated methods for the discovery of these SSRs and SNPs from sequence data. SSRPrimer enables the real-time discovery of SSRs within submitted DNA sequences, with the concomitant design of PCR primers for SSR amplification. Alternatively, users may browse the SSR Taxonomy Tree to identify predetermined SSR amplification primers for any species represented within the GenBank database. SNPServer uses a redundancy-based approach to identify SNPs within DNA sequence data. Following submission of a sequence of interest, SNPServer uses BLAST to identify similar sequences, CAP3 to cluster and assemble these sequences, and then the SNP discovery software autoSNP to detect SNPs and insertion/deletion (indel) polymorphisms.

  11. Teaching Applied Genetics and Molecular Biology to Agriculture Engineers. Application of the European Credit Transfer System

    Science.gov (United States)

    Weiss, J.; Egea-Cortines, M.

    2008-01-01

    We have been teaching applied molecular genetics to engineers and adapted the teaching methodology to the European Credit Transfer System. We teach core principles of genetics that are universal and form the conceptual basis of most molecular technologies. The course then teaches widely used techniques and finally shows how different techniques…

  12. Detection of selection utilizing molecular phylogenetics: a possible approach.

    Science.gov (United States)

    Yang, Ming; Wyckoff, Gerald J

    2011-05-01

    The neutral theory of molecular evolution (Kimura 1985) is the basis for most current statistical tests for detecting selection, mainly using polymorphism data within species, divergence data between species, and/or genomic structures like linkage disequilibrium (Wang et al. 2006). In most cases informative tests can only be constructed with ample variations within these parameters and many common tests are difficult to formulate when identity-by-descent is not clear, for example in gene families or repetitive elements. With the current progress being made toward whole-genome sequencing and re-sequencing efforts, as well as protein sequencing via tandem mass spectrometry where genomic sequencing is lacking, we felt it was necessary to re-visit possible methods for rapid screening and detection of evolutionary outliers. These outliers might be of interest for other research, such as candidate gene association studies or genome annotations, drug- and disease-target searches, and functional studies. We focused on methods that would work on both protein and nucleotide data, could be used on large gene or protein domain families, and could be generated quickly in order for "first pass" annotation of large scale data. For these reasons, we chose properties of trees generated routinely in molecular phylogenetic studies; genetic distance, tree shape and balance, and internal node statistics (Heard 1992). Our current research looking at protein domain family data and phylogenetic trees from PFAM (Finn et al. 2008) suggests this approach towards detecting evolutionary outliers is feasible, but additional work will be necessary to determine the parameters that suggest either positive or negative selection is occurring in specific gene families. This is particularly true when other factors such as rapid duplication and deletion of genes containing these domains is taking place, and we suggest phylogenetic statistics may be useful in combination with existing methodologies for

  13. Comparative approaches in evolutionary psychology: molecular neuroscience meets the mind.

    Science.gov (United States)

    Panksepp, Jaak; Moskal, Joseph R; Panksepp, Jules B; Kroes, Roger A

    2002-12-01

    Evolutionary psychologists often overlook a wealth of information existing between the proximate genotypic level and the ultimate phenotypic level. This commonly ignored level of biological organization is the ongoing activity of neurobiological systems. In this paper, we extend our previous arguments concerning strategic weaknesses of evolutionary psychology by advocating a foundational view that focuses on similarities in brain, behavior, and various basic psychological features across mammalian species. Such an approach offers the potential to link the emerging discipline of evolutionary psychology to its parent scientific disciplines such as biochemistry, physiology, molecular genetics, developmental biology and the neuroscientific analysis of animal behavior. We detail an example of this through our impending work using gene microarray technology to characterize gene expression patterns in rats during aggressive and playful social interactions. Through a focus on functional homologies and the experimental analysis of conserved, subcortical emotional and motivational brain systems, neuroevolutionary psychobiology can reveal ancient features of the human mind that are still shared with other animals. Claims regarding evolved, uniquely human, psychological constructs should be constrained by the rigorous evidentiary standards that are routine in other sciences.

  14. Molecular Approaches to Understand Nutritional Potential of Coarse Cereals.

    Science.gov (United States)

    Singh, Amit Kumar; Singh, Rakesh; Subramani, Rajkumar; Kumar, Rajesh; Wankhede, Dhammaprakash P

    2016-06-01

    Coarse grains are important group of crops that constitutes staple food for large population residing primarily in the arid and semi-arid regions of the world. Coarse grains are designated as nutri-cereals as they are rich in essential amino acids, minerals and vitamins. In spite of having several nutritional virtues in coarse grain as mentioned above, there is still scope for improvement in quality parameters such as cooking qualities, modulation of nutritional constituents and reduction or elimination of anti-nutritional factors. Besides its use in traditional cooking, coarse grains have been used mainly in the weaning food preparation and other malted food production. Improvement in quality parameters will certainly increase consumer's preference for coarse grains and increase their demand. The overall genetic gain in quality traits of economic importance in the cultivated varieties will enhance their industrial value and simultaneously increase income of farmers growing these varieties. The urgent step for improvement of quality traits in coarse grains requires a detailed understanding of molecular mechanisms responsible for varied level of different nutritional contents in different genotypes of these crops. In this review we have discussed the progresses made in understanding of coarse grain biology with various omics tool coupled with modern breeding approaches and the current status with regard to our effort towards dissecting traits related to improvement of quality and nutritional constituents of grains.

  15. Molecular epidemiology: a multidisciplinary approach to understanding parasitic zoonoses.

    Science.gov (United States)

    Traub, R J; Monis, P T; Robertson, I D

    2005-10-01

    Sound application of molecular epidemiological principles requires working knowledge of both molecular biological and epidemiological methods. Molecular tools have become an increasingly important part of studying the epidemiology of infectious agents. Molecular tools have allowed the aetiological agent within a population to be diagnosed with a greater degree of efficiency and accuracy than conventional diagnostic tools. They have increased the understanding of the pathogenicity, virulence, and host-parasite relationships of the aetiological agent, provided information on the genetic structure and taxonomy of the parasite and allowed the zoonotic potential of previously unidentified agents to be determined. This review describes the concept of epidemiology and proper study design, describes the array of currently available molecular biological tools and provides examples of studies that have integrated both disciplines to successfully unravel zoonotic relationships that would otherwise be impossible utilising conventional diagnostic tools. The current limitations of applying these tools, including cautions that need to be addressed during their application are also discussed.

  16. Clinical, molecular, and genetic evaluation of galactosemia in Turkish children

    Science.gov (United States)

    Atik, Sezen Ugan; Gürsoy, Semra; Koçkar, Tuba; Önal, Hasan; Adal, Servet Erdal

    2016-01-01

    Aim Galactosemia is a carbohydrate metabolism disorder with autosomal recessive inheritance. The most frequent enzyme deficiency is galactose-1-phosphate-uridylytransferase, which causes classic galactosemia. When the enzyme is absent, an infant cannot metabolize galactose-1-phosphate and it cumulates in liver, kidney, brain, tongue, lens, and skin. This study aimed to evaluate the clinical and molecular characteristics of patients with galactosemia, which is observed more frequently in our country than anywhere else in the world. Material and Methods This is a retrospective study that includes the moleculer and genetic charcteristics of 14 patient who were diagnosed as having galactosemia between January 2009 and January 2011. Results Nine patients were male and 5 female. Consanguineous marriage was detected in the family history of 7 patients. One patient had a history of a deceased sibling with a confirmed diagnosis of galactosemia. The main reasons for admission to the hospital were jaundice in 9, hypoglycemia in 2, sepsis in 2, and elevated liver enzymes in 1 patient. The Beutler test was positive in all patients. The mean enzyme activity was 0.36±0.26 μmol/mL. Only 6 of our cases were diagnosed in the early period (first 15 days). Cataract was present in four patients. Q188R mutation was observed in 13 patients, and homozygote N314D and homozygote E340X mutations were observed in one patient. Three patients had impaired neurologic development according to the Denver Developmental Screening Test II. Conclusion The most common genetic abnormality was Q188R mutation. Only 43% of our patients’s disease could be diagnosed at an early stage. We suggest that galactosemia should be included in the national newborn screening program in order to make earlier diagnoses. PMID:28123333

  17. [Nozological Heterogeneity, Molecular Genetics and Immunology of Autoimmune Diabetes Mellitus].

    Science.gov (United States)

    Dedov, I I; Shestakova, M V; Kuraeva, T L; Titovich, E V; Nikonova, T V

    2015-01-01

    Article is devoted to the review of literature data, and also the analysis of results of own researches concerning genetics, molecular genetics and immunological violations at various forms of the autoimmune diabetes (DM) including classical T1DM, LADA type and an autoimmune polyglandular syndrome of 1 type (APS1). In case of T1DM more than 80% of patients are carriers of one or two strongest predisposing haplotypes: DRB1*04-DQA1*0301-DQB1*0302 and DRB1*03-DQA1*0501-DQB1*0201 designated as DQ2 and DQ8. HLA genes can model a clinical features of disease. In Russian population, the children with diabetes manifestation up to 5-year age has significantly often high risk genotypes (DQ2/ DQ8) and significantly less the low risk genotypes in comparison with children, who had manifestation of T1DMin 10 years and later. The long-term 16-yearsfamily studies showed the maximum frequency of TJDMin high risk group, constantly accruing in process of increase in term of supervision, and in groups of an average and low risk lower and invariable. The highest risk of T1DM manifestation, reaching 90% at 10 years of supervision is defined by existence of HLA high risk genotypes and many antibodies, revealedfrom early age. LADA - the hybridform of autoimmune DM having signs of T1DM and T2DM in the basis. The development of autoimmune process against β-cells can be caused by only gene mutation (APS1). The part of T1DM cases which doesn't have the contributing HLA genes and autoimmune markers in process of studying of the importance of various genes and their biological value can be attributed to new, yet unknown forms of DM.

  18. Improved Student Linkage of Mendelian and Molecular Genetic Concepts through a Yeast-Based Laboratory Module

    Science.gov (United States)

    Wolyniak, Michael J.

    2013-01-01

    A study of modern genetics requires students to successfully unite the principles of Mendelian genetics with the functions of DNA. Traditional means of teaching genetics are often successful in teaching Mendelian and molecular ideas but not in allowing students to see how the two subjects relate. The laboratory module presented here attempts to…

  19. SNPs ANALYSIS AS A TOOL IN MOLECULAR GENETICS DIAGNOSTICS

    Directory of Open Access Journals (Sweden)

    Dewi Rusnita

    2015-05-01

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

  20. Molecular approaches to improvement of Jatropha curcas Linn. as a sustainable energy crop.

    Science.gov (United States)

    Sudhakar Johnson, T; Eswaran, Nalini; Sujatha, M

    2011-09-01

    With the increase in crude oil prices, climate change concerns and limited reserves of fossil fuel, attention has been diverted to alternate renewable energy sources such as biofuel and biomass. Among the potential biofuel crops, Jatropha curcas L, a non-domesticated shrub, has been gaining importance as the most promising oilseed, as it does not compete with the edible oil supplies. Economic relevance of J. curcas for biodiesel production has promoted world-wide prospecting of its germplasm for crop improvement and breeding. However, lack of adequate genetic variation and non-availability of improved varieties limited its prospects of being a successful energy crop. In this review, we present the progress made in molecular breeding approaches with particular reference to tissue culture and genetic transformation, genetic diversity assessment using molecular markers, large-scale transcriptome and proteome studies, identification of candidate genes for trait improvement, whole genome sequencing and the current interest by various public and private sector companies in commercial-scale cultivation, which highlights the revival of Jatropha as a sustainable energy crop. The information generated from molecular markers, transcriptome profiling and whole genome sequencing could accelerate the genetic upgradation of J. curcas through molecular breeding.

  1. Molecular genetic transfection of the coccidian parasite Sarcocystis neurona.

    Science.gov (United States)

    Gaji, Rajshekhar Y; Zhang, Deqing; Breathnach, Cormac C; Vaishnava, Shipra; Striepen, Boris; Howe, Daniel K

    2006-11-01

    Sarcocystis neurona is an apicomplexan parasite that is the major cause of equine protozoal myeloencephalitis (EPM). The biology of this pathogen remains poorly understood in part due to unavailability of molecular genetic tools. Hence, with an objective to develop DNA transfection capabilities for S. neurona, the 5' flanking region of the SnSAG1 gene was isolated from a genomic library and used to construct expression plasmids. In transient assays, the reporter molecules beta-galactosidase (beta-gal) and yellow fluorescent protein (YFP) could be detected in electroporated S. neurona, thereby confirming the feasibility of transgene expression in this organism. Stable transformation of S. neurona was achieved using a mutant dihydrofolate reductase thymidylate synthase (DHFR-TS) gene of Toxoplasma gondii that confers resistance to pyrimethamine. This selection system was used to create transgenic S. neurona that stably express beta-gal and YFP. As shown in this study, these transgenic clones can be useful for analyzing growth rate of parasites in vitro and for assessing drug sensitivities. More importantly, the DNA transfection methods described herein should greatly facilitate studies examining intracellular parasitism by this important coccidian pathogen.

  2. A genetic algorithm for flexible molecular overlay and pharmacophore elucidation

    Science.gov (United States)

    Jones, Gareth; Willett, Peter; Glen, Robert C.

    1995-12-01

    A genetic algorithm (GA) has been developed for the superimposition of sets of flexible molecules. Molecules are represented by a chromosome that encodes angles of rotation about flexible bonds and mappings between hydrogen-bond donor proton, acceptor lone pair and ring centre features in pairs of molecules. The molecule with the smallest number of features in the data set is used as a template, onto which the remaining molecules are fitted with the objective of maximising structural equivalences. The fitness function of the GA is a weighted combination of: (i) the number and the similarity of the features that have been overlaid in this way; (ii) the volume integral of the overlay; and (iii) the van der Waals energy of the molecular conformations defined by the torsion angles encoded in the chromosomes. The algorithm has been applied to a number of pharmacophore elucidation problems, i.e., angiotensin II receptor antagonists, Leu-enkephalin and a hybrid morphine molecule, 5-HT1D agonists, benzodiazepine receptor ligands, 5-HT3 antagonists, dopamine D2 antagonists, dopamine reuptake blockers and FKBP12 ligands. The resulting pharmacophores are generated rapidly and are in good agreement with those derived from alternative means.

  3. Malformations of cortical development: genetic mechanisms and diagnostic approach

    Science.gov (United States)

    2017-01-01

    Malformations of cortical development are rare congenital anomalies of the cerebral cortex, wherein patients present with intractable epilepsy and various degrees of developmental delay. Cases show a spectrum of anomalous cortical formations with diverse anatomic and morphological abnormalities, a variety of genetic causes, and different clinical presentations. Brain magnetic resonance imaging has been of great help in determining the exact morphologies of cortical malformations. The hypothetical mechanisms of malformation include interruptions during the formation of cerebral cortex in the form of viral infection, genetic causes, and vascular events. Recent remarkable developments in genetic analysis methods have improved our understanding of these pathological mechanisms. The present review will discuss normal cortical development, the current proposed malformation classifications, and the diagnostic approach for malformations of cortical development. PMID:28203254

  4. Cytogenetic and molecular genetic alterations in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sze-hang LAU; Xin-yuan GUAN

    2005-01-01

    Specific chromosome aberrations are frequently detected during the development of hepatocellular carcinoma. Molecular cytogenetic approaches such as comparative genomic hybridization and loss of heterozygosity analyses have provided fruitful information on changes in HCC cases at the genomic level. Mapping of chromosome gains and losses have frequently resulted in the identification of oncogenes and tumor suppressors, respectively. In this review, we summarize some frequently detected chromosomal aberrations reported for hepatocellular carcinoma cases using comparative genomic hybridization and loss of heterozygosity studies. Focus will be on gains of 1q, 8q, and 20q, and losses of 4q,8p, 13q, 16q, and 17p. We then examine the candidate oncogenes and tumor suppressors located within these regions, and explore their possible functions in hepatocarcinogenesis. Finally, the impact of microarray-based screening platforms will be discussed.

  5. Molecular Genetics of Metal Detoxification: Prospects for Phytoremediation

    Energy Technology Data Exchange (ETDEWEB)

    Ow, David W. ow@pgec.ams.usda.gov

    2000-09-01

    Unlike compounds that can be broken down, the remediation of most heavy metals and radionuclides requires physical extraction from contaminated sources. Plants can extract inorganics, but effective phytoextraction requires plants that produce high biomass, grow rapidly and possess high capacity-uptake for the inorganic substance. Either hyperaccumulator plants must be bred for increased growth and biomass or hyperaccumulation traits must be engineered into fast growing, high biomass plants. This latter approach requires fundamental knowledge of the molecular mechanisms in the uptake and storage of inorganics. Much has been learned in recent years on how plants and certain fungi chelate and transport selected heavy metals. This progress has been facilitated by the use of Schizosaccharomyces pombe as a model system. The use of a model organism for study permits rapid characterization of the molecular process. As target genes are identified in a model organism, their sequences can be modified for expression in a heterologous host or aid in the search of homologous genes in more complex organisms. Moreover, as plant nutrient uptake is intrinsically linked to the association with rhizospheric fungi, elucidating metal sequestration in this fungus permits additional opportunities for engineering rhizospheric microbes to assist in phytoextraction.

  6. Genetic dissimilarity among sweet potato genotypes using morphological and molecular descriptors

    Directory of Open Access Journals (Sweden)

    Elisângela Knoblauch Viega de Andrade

    2017-08-01

    Full Text Available This study aimed to evaluate the genetic dissimilarity among sweet potato genotypes using morphological and molecular descriptors. The experiment was conducted in the Olericulture Sector at Federal University of Jequitinhonha and Mucuri Valleys (UFVJM and evaluated 60 sweet potato genotypes. For morphological characterization, 24 descriptors were used. For molecular characterization, 11 microsatellite primers specific for sweet potatoes were used, obtaining 210 polymorphic bands. Morphological and molecular diversity was obtained by dissimilarity matrices based on the coefficient of simple matching and the Jaccard index for morphological and molecular data, respectively. From these matrices, dendrograms were built. There is a large amount of genetic variability among sweet potato genotypes of the germplasm bank at UFVJM based on morphological and molecular characterizations. There was no duplicate suspicion or strong association between morphological and molecular analyses. Divergent accessions have been identified by molecular and morphological analyses, which can be used as parents in breeding programmes to produce progenies with high genetic variability.

  7. Adaptive Molecular Resolution Approach in Hamiltonian Form: An Asymptotic Analysis

    CERN Document Server

    Zhu, Jinglong; Site, Luigi Delle

    2016-01-01

    Adaptive Molecular Resolution approaches in Molecular Dynamics are becoming relevant tools for the analysis of molecular liquids characterized by the interplay of different physical scales. The essential difference among these methods is in the way the change of molecular resolution is made in a buffer/transition region. In particular a central question concerns the possibility of the existence of a global Hamiltonian which, by describing the change of resolution, is at the same time physically consistent, mathematically well defined and numerically accurate. In this paper we present an asymptotic analysis of the adaptive process complemented by numerical results and show that under certain mathematical conditions a Hamiltonian, which is physically consistent and numerically accurate, may exist. \\blue{Such conditions show that molecular simulations in the current computational implementation require systems of large size and thus a Hamiltonian approach as the one proposed, at this stage, would not be practica...

  8. Arbitrariness is not enough: towards a functional approach to the genetic code.

    Science.gov (United States)

    Lacková, Ľudmila; Matlach, Vladimír; Faltýnek, Dan

    2017-05-09

    Arbitrariness in the genetic code is one of the main reasons for a linguistic approach to molecular biology: the genetic code is usually understood as an arbitrary relation between amino acids and nucleobases. However, from a semiotic point of view, arbitrariness should not be the only condition for definition of a code, consequently it is not completely correct to talk about "code" in this case. Yet we suppose that there exist a code in the process of protein synthesis, but on a higher level than the nucleic bases chains. Semiotically, a code should be always associated with a function and we propose to define the genetic code not only relationally (in basis of relation between nucleobases and amino acids) but also in terms of function (function of a protein as meaning of the code). Even if the functional definition of meaning in the genetic code has been discussed in the field of biosemiotics, its further implications have not been considered. In fact, if the function of a protein represents the meaning of the genetic code (the sign's object), then it is crucial to reconsider the notion of its expression (the sign) as well. In our contribution, we will show that the actual model of the genetic code is not the only possible and we will propose a more appropriate model from a semiotic point of view.

  9. Reverse Genetics Approaches for the Development of Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Aitor Nogales

    2016-12-01

    Full Text Available Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines.

  10. Reverse Genetics Approaches for the Development of Influenza Vaccines

    Science.gov (United States)

    Nogales, Aitor; Martínez-Sobrido, Luis

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

  11. Chemical genetics approaches for selective intervention in epigenetics.

    Science.gov (United States)

    Runcie, Andrew C; Chan, Kwok-Ho; Zengerle, Michael; Ciulli, Alessio

    2016-08-01

    Chemical genetics is the use of biologically active small molecules (chemical probes) to investigate the functions of gene products, through the modulation of protein activity. Recent years have seen significant progress in the application of chemical genetics to study epigenetics, following the development of new chemical probes, a growing appreciation of the role of epigenetics in disease and a recognition of the need and utility of high-quality, cell-active chemical probes. In this review, we single out the bromodomain reader domains as a prime example of both the success, and challenges facing chemical genetics. The difficulty in generating single-target selectivity has long been a thorn in the side of chemical genetics, however, recent developments in advanced forms of chemical genetics promise to bypass this, and other, limitations. The 'bump-and-hole' approach has now been used to probe - for the first time - the BET bromodomain subfamily with single-target selectivity and may be applicable to other epigenetic domains. Meanwhile, PROTAC compounds have been shown to be significantly more efficacious than standard domain inhibitors, and have the potential to enhance target selectivity.

  12. OPTIMIZING LOCALIZATION ROUTE USING PARTICLE SWARM-A GENETIC APPROACH

    Directory of Open Access Journals (Sweden)

    L. Lakshmanan

    2014-01-01

    Full Text Available One of the most key problems in wireless sensor networks is finding optimal algorithms for sending packets from source node to destination node. Several algorithms exist in literature, since some are in vital role other may not. Since WSN focus on low power consumption during packet transmission and receiving, finally we adopt by merging swarm particle based algorithm with genetic approach. Initially we order the nodes based on their energy criterion and then focusing towards node path; this can be done using Proactive route algorithm for finding optimal path between Source-Destination (S-D nodes. Fast processing and pre traversal can be done using selective flooding approach and results are in genetic. We have improved our results with high accuracy and optimality in rendering routes.

  13. Progress in the Study of Molecular Genetic Improvements of Poplar in China

    Institute of Scientific and Technical Information of China (English)

    Shan-Zhi Lin; Zhi-Yi Zhang; Qian Zhang; Yuan-Zhen Lin

    2006-01-01

    The poplar is one of the most economically important and intensively studied tree species owing to its wide application in the timber industry and as a model material for the study of woody plants. The natural resource of poplars in China is replete. Over the past 10 years, the application of molecular biological techniques to genetic improvements in poplar species has been widely studied in China. Recent advances in molecular genetic improvements of poplar, including cDNA library construction, gene cloning and identification, genetic engineering, gene expression, genetic linkage map construction, mapping of quantitative trait loci (QTL) and molecular-assisted selection, are reviewed in the present paper. In addition, the application of modern biotechnology to molecular improvements in the genetic traits of the poplar and some unsolved problems are discussed.

  14. Molecular Genetic Variation in a Clonal Plant Population of Leymus chinensis (Trin.) Tzvel.

    Institute of Scientific and Technical Information of China (English)

    Yu-Sheng WANG; Li-Ming ZHAO; Hua WANG; Jie WANG; Da-Ming HUANG; Rui-Min HONG; Xiao-Hua TENG; Nakamura MIKI

    2005-01-01

    Randomly amplified polymorphic DNA (RAPD) analysis was used to investigate the genetic variation among populations, between populations, and within populations, relationships between genetic distance and geographic distance, and the molecular variation and population size. The effects of geographic and genetic distances, as well as of genetic differentiation and population size, on genetic variations of Leymus chinensis (Trin.) Tzvel. are discussed. The present study showed that there was significant RAPD variation between the Baicheng region population and the Daqing region population, with a molecular variance of 6.35% (P < 0.04), and for differentiation among area populations of the Daqing region, with a molecular variance of 8.78% (P < 0.002). A 21.06% RAPD variation among all 16 populations among two regions was found (P < 0.001), as well as 72.59% variation within populations (P < 0.001). Molecular variation within populations was significantly different among 16 populations.

  15. Recommendations for reporting results of diagnostic genetic testing (biochemical, cytogenetic and molecular genetic)

    NARCIS (Netherlands)

    Claustres, Mireille; Kozich, Viktor; Dequeker, Els; Fowler, Brain; Hehir-Kwa, Jayne Y.; Miller, Konstantin; Oosterwijk, Cor; Peterlin, Borut; van Ravenswaaij-Arts, Conny; Zimmermann, Uwe; Zuffardi, Orsetta; Hastings, Ros J.; Barton, David E.

    Genetic test results can have considerable importance for patients, their parents and more remote family members. Clinical therapy and surveillance, reproductive decisions and genetic diagnostics in family members, including prenatal diagnosis, are based on these results. The genetic test report

  16. A genetic algorithm approach to routine gamma spectra analysis

    Energy Technology Data Exchange (ETDEWEB)

    Carlevaro, C M [Instituto de FIsica de LIquidos y Sistemas Biologicos, Calle 59 No 789, B1900BTE La Plata (Argentina); Wilkinson, M V [Autoridad Regulatoria Nuclear, Avda. del Libertador 8250, C1429BNP Buenos Aires (Argentina); Barrios, L A [Autoridad Regulatoria Nuclear, Avda. del Libertador 8250, C1429BNP Buenos Aires (Argentina)

    2008-01-15

    In this work we present an alternative method for performing routine gamma spectra analysis based on genetic algorithm techniques. The main idea is to search for patterns of single nuclide spectra obtained by simulation in a sample spectrum targeted for analysis. We show how this approach is applied to the analysis of simulated and real target spectra, and also to the study of interference resolution.

  17. Determination of genetic structure of germplasm collections: are traditional hierarchical clustering methods appropriate for molecular marker data?

    Science.gov (United States)

    Odong, T L; van Heerwaarden, J; Jansen, J; van Hintum, T J L; van Eeuwijk, F A

    2011-07-01

    Despite the availability of newer approaches, traditional hierarchical clustering remains very popular in genetic diversity studies in plants. However, little is known about its suitability for molecular marker data. We studied the performance of traditional hierarchical clustering techniques using real and simulated molecular marker data. Our study also compared the performance of traditional hierarchical clustering with model-based clustering (STRUCTURE). We showed that the cophenetic correlation coefficient is directly related to subgroup differentiation and can thus be used as an indicator of the presence of genetically distinct subgroups in germplasm collections. Whereas UPGMA performed well in preserving distances between accessions, Ward excelled in recovering groups. Our results also showed a close similarity between clusters obtained by Ward and by STRUCTURE. Traditional cluster analysis can provide an easy and effective way of determining structure in germplasm collections using molecular marker data, and, the output can be used for sampling core collections or for association studies.

  18. Genetics and cardiovascular disease: the impact of molecular diagnosis.

    Science.gov (United States)

    Vengoechea, Jaime; McKelvey, Kent D

    2013-04-01

    Information technology is exponentially reducing the cost of genetic testing while multiple clinical applications emerge. Genetic diagnosis increasingly impacts prevention, diagnosis and treatment of disease. In cardiovascular medicine, the establishment of a specific genetic diagnosis may affect management of cardiomyopathy, arrhythmia, connective tissue and metabolic disease. Econometric studies have determined that genetic testing is cost-effective in hypertrophic cardiomyopathy and disease-specific interventions are now available for specific conditions. Identification of a specific genetic disorder now allows for more precise medicine in the affected individual and more accurate preventive care for asymptomatic family members.

  19. A molecular dynamics approach to barrodiffusion

    Science.gov (United States)

    Cooley, James; Marciante, Mathieu; Murillo, Michael

    2016-10-01

    Unexpected phenomena in the reaction rates for Inertial Confinement Fusion (ICF) capsules have led to a renewed interest in the thermo-dynamically driven diffusion process for the past 10 years, often described collectively as barodiffusion. In the current context, barodiffusion would manifest as a process that separates ions of differing mass and charge ratios due to pressure and temperature gradients set-up through shock structures in the capsule core. Barrodiffusion includes additional mass transfer terms that account for the irreversible transport of species due to gradients in the system, both thermodynamic and electric e.g, i = - ρD [ ∇c +kp ∇ln(pi) +kT(i) ∇ln(Ti) +kt(e) ∇ln(Te) +eke/Ti ∇ϕ ] . Several groups have attacked this phenomena using continuum scale models and supplemented with kinetic theory to derive coefficients for the different diffusion terms based on assumptions about the collisional processes. In contrast, we have applied a molecular dynamics (MD) simulation to this system to gain a first-principle understanding of the rate kinetics and to assess the accuracy of the differin

  20. DNA enrichment approaches to identify unauthorized genetically modified organisms (GMOs).

    Science.gov (United States)

    Arulandhu, Alfred J; van Dijk, Jeroen P; Dobnik, David; Holst-Jensen, Arne; Shi, Jianxin; Zel, Jana; Kok, Esther J

    2016-07-01

    With the increased global production of different genetically modified (GM) plant varieties, chances increase that unauthorized GM organisms (UGMOs) may enter the food chain. At the same time, the detection of UGMOs is a challenging task because of the limited sequence information that will generally be available. PCR-based methods are available to detect and quantify known UGMOs in specific cases. If this approach is not feasible, DNA enrichment of the unknown adjacent sequences of known GMO elements is one way to detect the presence of UGMOs in a food or feed product. These enrichment approaches are also known as chromosome walking or gene walking (GW). In recent years, enrichment approaches have been coupled with next generation sequencing (NGS) analysis and implemented in, amongst others, the medical and microbiological fields. The present review will provide an overview of these approaches and an evaluation of their applicability in the identification of UGMOs in complex food or feed samples.

  1. Neuroblastoma: morphological pattern, molecular genetic features, and prognostic factors

    Directory of Open Access Journals (Sweden)

    A. M. Stroganova

    2016-01-01

    Full Text Available Neuroblastoma, the most common extracranial tumor of childhood, arises from the developing neurons of the sympathetic nervous system (neural cress stem cells and has various biological and clinical characteristics. The mean age at disease onset is 18 months. Neuroblastoma has a number of unique characteristics: a capacity for spontaneous regression in babies younger than 12 months even in the presence of distant metastases, for differentiation (maturation into ganglioneuroma in infants after the first year of life, and for swift aggressive development and rapid metastasis. There are 2 clinical classifications of neuroblastoma: the International neuroblastoma staging system that is based on surgical results and the International Neuroblastoma Risk Group Staging System. One of the fundamentally important problems for the clinical picture of neuroblastoma is difficulties making its prognosis. Along with clinical parameters (a patient’s age, tumor extent and site, some histological, molecular biochemical (ploidy and genetic (chromosomal aberrations, MYCN gene status, deletion of the locus 1p36 and 11q, the longer arm of chromosome 17, etc. characteristics of tumor cells are of considerable promise. MYCN gene amplification is observed in 20–30 % of primary neuroblastomas and it is one of the major indicators of disease aggressiveness, early chemotherapy resistance, and a poor prognosis. There are 2 types of MYCN gene amplification: extrachromosomal (double acentric chromosomes and intrachromosomal (homogenically painted regions. Examination of double acentric chromosomes revealed an interesting fact that it may be eliminated (removed from the nucleus through the formation of micronuclei. MYCN oncogene amplification is accompanied frequently by 1p36 locus deletion and longer 17q arm and less frequently by 11q23 deletion; these are poor prognostic factors for the disease. The paper considers in detail the specific, unique characteristics of the

  2. Current landscape and new paradigms of proficiency testing and external quality assessment for molecular genetics.

    Science.gov (United States)

    Kalman, Lisa V; Lubin, Ira M; Barker, Shannon; du Sart, Desiree; Elles, Rob; Grody, Wayne W; Pazzagli, Mario; Richards, Sue; Schrijver, Iris; Zehnbauer, Barbara

    2013-07-01

    Participation in proficiency testing (PT) or external quality assessment (EQA) programs allows the assessment and comparison of test performance among different clinical laboratories and technologies. In addition to the approximately 2300 tests for individual genetic disorders, recent advances in technology have enabled the development of clinical tests that quickly and economically analyze the entire human genome. New PT/EQA approaches are needed to ensure the continued quality of these complex tests. To review the availability and scope of PT/EQA for molecular genetic testing for inherited conditions in Europe, Australasia, and the United States; to evaluate the successes and demonstrated value of available PT/EQA programs; and to examine the challenges to the provision of comprehensive PT/EQA posed by new laboratory practices and methodologies. The available literature on this topic was reviewed and supplemented with personal experiences of several PT/EQA providers. Proficiency testing/EQA schemes are available for common genetic disorders tested in many clinical laboratories but are not available for most genetic tests offered by only one or a few laboratories. Provision of broad, method-based PT schemes, such as DNA sequencing, would allow assessment of many tests for which formal PT is not currently available. Participation in PT/EQA improves the quality of testing by identifying inaccuracies that laboratories can trace to errors in their testing processes. Areas of research and development to ensure that PT/EQA programs can meet the needs of new and evolving genetic tests and technologies are identified and discussed.

  3. Pharmacologically regulated induction of silent mutations (PRISM): combined pharmacological and genetic approaches for learning and memory.

    Science.gov (United States)

    Frankland, Paul W; Ohno, Masuo; Takahashi, Eiki; Chen, Adele R; Costa, Rui M; Kushner, Steven A; Silva, Alcino J

    2003-04-01

    Mouse transgenic and knock-out approaches have made fundamental contributions to our understanding of the molecular and cellular bases of learning and memory. These approaches have successfully identified a large number of molecules with either a central or modulatory role in learning and memory. However, there are limitations associated with first-generation mutant mice, which include, for example, the lack of temporal control over the mutation. Recent technical developments have started to address some of these shortcomings. Here, the authors review a newly developed inducible approach that takes advantage of synergistic interactions between subthreshold genetic and pharmacological manipulations. This approach is easily set up and can be used to study the functional interactions between molecules in signaling pathways.

  4. Toward Molecular Level of the “Salmonella-Victim” Ecology, Genetics, and Evolution

    Directory of Open Access Journals (Sweden)

    S.N. Rumyantsev

    2004-01-01

    Full Text Available Bacteria of the Salmonella genus are polypathogenic agents that can affect both men and animals, causing devastating and fatal illness. Despite considerable immunological, epidemiological, and genetic efforts, and increased understanding of how the Salmonella infection develops, many key questions concerning Salmonella infection remain unanswered. Salmonella can be carried as harmless commensals in some sectors of the population. In some individuals, however, the same microbes cause illness while others display immunity to primary Salmonella infection. Nothing is known about the molecular base of the Salmonella pathogenicity. Even the ability of Salmonella to destroy the victim’s cells has been the subject of century-long discussions. In this article, some key findings concerning ecology, molecular ecology, and cell level of the Salmonella infection genetics are summarized and interpreted from the viewpoint of evolutionary theory with certitude that this approach can help to decipher the undiscovered secrets of Salmonella infection’s epidemiology and pathogenesis, as well as the clinical course and severity, and to select ways for fighting against Salmonella.

  5. Estimation of the proportion of genetic variance explained by molecular markers

    Directory of Open Access Journals (Sweden)

    Bearzoti Eduardo

    1998-01-01

    Full Text Available Estimation of the proportion of genetic variance explained by molecular markers (p plays an important role in basic studies of quantitative traits, as well as in marker-assisted selection (MAS, if the selection index proposed by Lande and Thompson (Genetics 124: 743-756, 1990 is used. Frequently, the coefficient of determination (R2 is used to account for this proportion. In the present study, a simple estimator of p is presented, which is applicable when a multiple regression approach is used, and progenies are evaluated in replicated trials. The associated sampling distribution was obtained and compared with that of R2. Simulations indicated that, when the number of evaluated progenies is small, the statistics are not satisfactory, in general, due to bias and/or low precision. Coefficient R2 was found adequate in situations where p is high. If a large number of progenies is evaluated (say, a few hundreds, then the proposed estimator appears to be better, with acceptable precision and considerably lower bias than R2. A normal approximation to the sampling distribution of is given, using Taylor's expansion of the expectation and variance of this statistic. Approximate confidence intervals for p, based on normal distribution, are reasonable, if the number of progenies is large. The use of in MAS is illustrated for estimation of the weight given to the molecular score, when a selection index is used.

  6. Role of molecular genetics in transforming diagnosis of diabetes mellitus.

    Science.gov (United States)

    Molven, Anders; Njølstad, Pål R

    2011-04-01

    Most common diseases also run in families as rare, monogenic forms. Diabetes is no exception. Mutations in approximately 20 different genes are now known to cause monogenic diabetes, a disease group that can be subclassified into maturity-onset diabetes of the young, neonatal diabetes and mitochondrial diabetes. In some families, additional features, such as urogenital malformations, exocrine pancreatic dysfunction and neurological abnormalities, are present and may aid the diagnostic classification. The finding of a mutation in monogenic diabetes may have implications for the prediction of prognosis and choice of treatment. Mutations in the GCK gene cause a mild form of diabetes, which seldom needs insulin and has a low risk for complications. By contrast, HNF1A mutations lead to a diabetes form that in severity, treatment and complication risk resembles Type 1 diabetes, although these patients may experience a good effect of sulfonylurea treatment. The majority of neonatal diabetes cases are caused by mutations in the K(ATP) channel genes ABCC8 and KCNJ11, and sulfonylurea therapy is then usually superior to insulin. Diseases with a considerable genetic component may now be explored by genome-wide approaches using next-generation DNA sequencing technology. We expect that within a few years important breakthroughs will be made in mapping cases of diabetes with a suspected, but still unsolved monogenic basis.

  7. Quantitative genetics approaches to study evolutionary processes in ecotoxicology; a perspective from research on the evolution of resistance.

    Science.gov (United States)

    Klerks, Paul L; Xie, Lingtian; Levinton, Jeffrey S

    2011-05-01

    Quantitative genetic approaches are often used to study evolutionary processes in ecotoxicology. This paper focuses on the evolution of resistance to environmental contaminants-an important evolutionary process in ecotoxicology. Three approaches are commonly employed to study the evolution of resistance: (1) Assessing whether a contaminant-exposed population has an increased resistance relative to a control population, using either spatial or temporal comparisons. (2) Estimating a population's heritability of resistance. (3) Investigating responses in a laboratory selection experiment. All three approaches provide valuable information on the potential for contaminants to affect a population's evolutionary trajectory via natural selection. However, all three approaches have inherent limitations, including difficulty in separating the various genetic and environmental variance components, responses being dependent on specific population and testing conditions, and inability to fully capture natural conditions in the laboratory. In order to maximize insights into the long-term consequences of adaptation, it is important to not just look at resistance itself, but also at the fitness consequences and at correlated responses in characteristics other than resistance. The rapid development of molecular genetics has yielded alternatives to the "black box" approach of quantitative genetics, but the presence of different limitations and strengths in the two fields means that they should be viewed as complementary rather than exchangeable. Quantitative genetics is benefiting from the incorporation of molecular tools and remains an important field for studying evolutionary toxicology.

  8. Computer-Assisted Drug Design: Genetic Algorithms and Structures of Molecular Clusters of Aromatic Hydrocarbons and Actinomycin D-Deoxyguanosine

    Science.gov (United States)

    Xiao, Yong Liang

    Molecular packing, clustering, and docking computations have been performed by empirical intermolecular energy minimization methods. The main focus of this study is finding a robust global search algorithm to solve intermolecular interaction problems, especially to apply an efficient algorithm to large-scale complex molecular systems such as drug-DNA binding or site selectivity which has increasing importance in drug design and drug discovery. Molecular packing in benzene, naphthalene, and anthracene crystals is analyzed in terms of molecular dimer interaction. Intermolecular energies of the gas dimer molecules are calculated for various intermolecular distances and orientations using empirical potential energy functions. The gas dimers are compared to pairs of molecules extracted from the observed crystal structures. Net atomic charges are obtained by the potential-derived method from 6-31G and 6-31G^{**} level ab initio wavefunctions. A new approach using a genetic algorithm is applied to predict structures of benzene, naphthalene, and anthracene molecular clusters. The computer program GAME (genetic algorithm for minimization of energy) has been developed to obtain the global energy minimum of clusters of dimer, trimer, and tetramer molecules. This test model has been further developed to applications of molecular docking. Docking calculations of deoxyguanosine molecules to actinomycin D were performed successfully to identify the binding sites of the drug molecule, which was revealed by actinomycin D-deoxyguanosine complex from the solved x-ray crystal structure. The comparison between the evolutionary computing method and conventional local optimization methods concluded that genetic algorithms are very competitive when it comes to complex, large-scale optimization. Full power of genetic algorithms can be unveiled in computer-assisted drug design only when the difficulties of including optimized molecular conformation in the algorithm are overcome. These

  9. [Monogenic obesity - current status of molecular genetic research and clinical importance].

    Science.gov (United States)

    Aldhoon-Hainerová, Irena; Včelák, Josef; Zamrazilová, Hana

    2014-01-01

    Obesity and its comorbidities represent one of the major health problems worldwide. A positive energy balance due to inappropriate life-style changes plays a key role in the current obesity epidemic. The influence of genetic factors is also significant - several studies concluded that genes contribute to the development of obesity by 40-70%. Genetic variability predisposes an individual to tendency or resistance to increase body weight in obesogenic environment. Polygenic type of inheritance is responsible in most of obese individuals. However, an intensive research of the past 20 years has led to an identification of several genes causing monogenic forms of obesity. To date, several monogenic genes (leptin, leptin receptor, prohormon convertase 1, proopiomelanocortin, melanocortin 4 receptor, single-minded homolog 1, brain-derived neurotrophic factor, neurotrophic tyrosine kinase receptor type 2) that are either involved in the neuronal differentiation of the paraventricular nucleus or in the leptin-melanocortin pathway are known to cause obesity. Mutation carriers apart from severe early onset obesity manifest with additional phenotypic characteristics as adrenal insufficiency, impaired immunity and impaired fertility. This review provides an overview of molecular-genetic and clinical research in the field of monogenic obesities including therapeutical approaches.

  10. Studying human disease genes in Caenorhabditis elegans: a molecular genetics laboratory project.

    Science.gov (United States)

    Cox-Paulson, Elisabeth A; Grana, Theresa M; Harris, Michelle A; Batzli, Janet M

    2012-01-01

    Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether Caenorhabditis elegans can be a useful model system for studying genes associated with human disease. In a large-enrollment, sophomore-level laboratory course, groups of three to four students were assigned a gene associated with either breast cancer (brc-1), Wilson disease (cua-1), ovarian dysgenesis (fshr-1), or colon cancer (mlh-1). Students compared observable phenotypes of wild-type C. elegans and C. elegans with a homozygous deletion in the assigned gene. They confirmed the genetic deletion with nested polymerase chain reaction and performed a bioinformatics analysis to predict how the deletion would affect the encoded mRNA and protein. Students also performed RNA interference (RNAi) against their assigned gene and evaluated whether RNAi caused a phenotype similar to that of the genetic deletion. As a capstone activity, students prepared scientific posters in which they presented their data, evaluated whether C. elegans was a useful model system for studying their assigned genes, and proposed future directions. Assessment showed gains in understanding genotype versus phenotype, RNAi, common bioinformatics tools, and the utility of model organisms.

  11. 59. Cold Spring Harbor symposium on quantitative biology: Molecular genetics of cancer

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    Investigation of the mechanistic aspects of cancer has its roots in the studies on tumor viruses and their effects on cell proliferation, function, and growth. This outstanding progress was well documented in previous Cold Spring Harbor Symposia on Quantitative Biology. In the early to mid 1980s, progress on the development of chromosome mapping strategies and the accumulation of DNA probes that identified polymorphisms, encouraged by the international Human Genome Project, enabled the identification of other genes that contributed to familial inheritance of high susceptibility to specific cancers. This approach was very successful and led to a degree of optimism that one aspect of cancer, the multistep genetic process from early neoplasia to metastatic tumors, was beginning to be understood. It therefore seemed appropriate that the 59th Symposium on Quantitative Biology focus attention on the Molecular Genetics of Cancer. The concept was to combine the exciting progress on the identification of new genetic alterations in human tumor cells with studies on the function of the cancer gene products and how they go awry in tumor cells.

  12. Guidelines for molecular karyotyping in constitutional genetic diagnosis.

    NARCIS (Netherlands)

    Vermeesch, J.R.; Fiegler, H.; Leeuw, N. de; Szuhai, K.; Schoumans, J.; Ciccone, R.; Speleman, F.; Rauch, A.; Clayton-Smith, J.; Ravenswaaij-Arts, C.M.A. van; Sanlaville, D.; Patsalis, P.C.; Firth, H.; Devriendt, K.; Zuffardi, O.

    2007-01-01

    Array-based whole genome investigation or molecular karyotyping enables the genome-wide detection of submicroscopic imbalances. Proof-of-principle experiments have demonstrated that molecular karyotyping outperforms conventional karyotyping with regard to detection of chromosomal imbalances. This ar

  13. Guidelines for molecular karyotyping in constitutional genetic diagnosis

    NARCIS (Netherlands)

    Vermeesch, Joris Robert; Fiegler, Heike; de Leeuw, Nicole; Szuhai, Karoly; Schoumans, Jacqueline; Ciccone, Roberto; Speleman, Frank; Rauch, Anita; Clayton-Smith, Jill; Van Ravenswaaij, Conny; Sanlaville, Damien; Patsalis, Philippos C.; Firth, Helen; Devriendt, Koen; Zuffardi, Orsetta

    2007-01-01

    Array-based whole genome investigation or molecular karyotyping enables the genome-wide detection of submicroscopic imbalances. Proof-of-principle experiments have demonstrated that molecular karyotyping outperforms conventional karyotyping with regard to detection of chromosomal imbalances. This ar

  14. Molecular genetic contributions to socioeconomic status and intelligence.

    Science.gov (United States)

    Marioni, Riccardo E; Davies, Gail; Hayward, Caroline; Liewald, Dave; Kerr, Shona M; Campbell, Archie; Luciano, Michelle; Smith, Blair H; Padmanabhan, Sandosh; Hocking, Lynne J; Hastie, Nicholas D; Wright, Alan F; Porteous, David J; Visscher, Peter M; Deary, Ian J

    2014-05-01

    Education, socioeconomic status, and intelligence are commonly used as predictors of health outcomes, social environment, and mortality. Education and socioeconomic status are typically viewed as environmental variables although both correlate with intelligence, which has a substantial genetic basis. Using data from 6815 unrelated subjects from the Generation Scotland study, we examined the genetic contributions to these variables and their genetic correlations. Subjects underwent genome-wide testing for common single nucleotide polymorphisms (SNPs). DNA-derived heritability estimates and genetic correlations were calculated using the 'Genome-wide Complex Trait Analyses' (GCTA) procedures. 21% of the variation in education, 18% of the variation in socioeconomic status, and 29% of the variation in general cognitive ability was explained by variation in common SNPs (SEs ~ 5%). The SNP-based genetic correlations of education and socioeconomic status with general intelligence were 0.95 (SE 0.13) and 0.26 (0.16), respectively. There are genetic contributions to intelligence and education with near-complete overlap between common additive SNP effects on these traits (genetic correlation ~ 1). Genetic influences on socioeconomic status are also associated with the genetic foundations of intelligence. The results are also compatible with substantial environmental contributions to socioeconomic status.

  15. Molecular approaches to malaria and Babesisosis diagnosis

    Directory of Open Access Journals (Sweden)

    G. L. McLaughlin

    1992-01-01

    Full Text Available The development of additional methods for detecting and identifuing Babesia and Plasmodium infections may be useful in disease monitoring, management and control efforts. To preliminarily evaluate sunthetic peptide-based serodiagnosis, a hydrophilic sequence (DDESEFDKEKwas selected from published BabR gene of B. bovis. Immunization of rabbits and cattle with the hemocyanin-conjugated peptide elicited antibody responses that specifically detected both P. falciparum and B. bovis antigens by immunofluorescence and Western blots. Using a dot-ELISA with this peptide, antisera from immunized and naturally-infected cattle, and immunized rodents, were specifically detected. Reactivity was weak and correlated with peptide immunization or infection. DNA-based detection using repetitive DNA was species-specific in dot-blot formats for B. bovis DNA, and in both dot-blot and in situ formats for P. falciparum; a streamlined enzymelinked synthetic DNA assay for P. falciparum detected 30 parasites/mm(cúbicos from patient blood using either colorimetric (2-15 h color development or chemiluminescent detection (0.5-6-min. exposures. Serodiagnostic and DNA hybridization methods may be complementary in the respective detection of both chronic and acute infections. However, recent improvements in the polymerase chain reaction (PCR make feasible a more sensitive and uniform approach to the diagnosis of these and other infectious disease complexes, with appropriate primers and processing methods. An analysis of ribosomal DNA genes of Plasmodium and Toxoplasma identified Apicomplexa-conserved sequence regions. Specific and distinctive PCR profiles were obtained for primers spanning the internal transcribed spacer locus for each of several Plasmodium and Babesia species.

  16. Impact of genomics approaches on plant genetics and physiology.

    Science.gov (United States)

    Tabata, Satoshi

    2002-08-01

    Comprehensive analysis of genetic information in higher plants is under way for several plants of biological and agronomical importance. Among them, Arabidopsis thaliana, a member of Brassica family, and Oryza sativa(rice) have been chosen as model plants most suitable for genome analysis. Sequencing of the genome of A. thaliana was completed in December 2000, and rice genome sequencing is in progress. The accumulated genome sequences, together with the hundreds of thousands of ESTs from several tens of plant species, have drastically changed the strategy of plant genetics. By utilizing the information on the genome and gene structures, comprehensive approaches for genome-wide functional analysis of the genes, including transcriptome analysis using microarray systems and a comprehensive analysis of a large number of insertion mutant lines, have been widely adopted. As a consequence, a large quantity of information on both the structure and function of genes in these model plants has been accumulated. However, other plant species may have their own characteristics and advantages to study individual phenomena. Application of knowledge from the model plants to other plant species and vice versa through the common language, namely the genome information, should facilitate understanding of the genetic systems underlying a variety of biological phenomena. Introduction of this common language may not be very simple, especially in the case of complex pathways such as a process of cell-covering formation. Nevertheless, it should be emphasized that genomics approaches are the most promising way to understand these processes.

  17. Cellular and Molecular Biological Approaches to Interpreting Ancient Biomarkers

    Science.gov (United States)

    Newman, Dianne K.; Neubauer, Cajetan; Ricci, Jessica N.; Wu, Chia-Hung; Pearson, Ann

    2016-06-01

    Our ability to read the molecular fossil record has advanced significantly in the past decade. Improvements in biomarker sampling and quantification methods, expansion of molecular sequence databases, and the application of genetic and cellular biological tools to problems in biomarker research have enabled much of this progress. By way of example, we review how attempts to understand the biological function of 2-methylhopanoids in modern bacteria have changed our interpretation of what their molecular fossils tell us about the early history of life. They were once thought to be biomarkers of cyanobacteria and hence the evolution of oxygenic photosynthesis, but we now believe that 2-methylhopanoid biosynthetic capacity originated in the Alphaproteobacteria, that 2-methylhopanoids are regulated in response to stress, and that hopanoid 2-methylation enhances membrane rigidity. We present a new interpretation of 2-methylhopanes that bridges the gap between studies of the functions of 2-methylhopanoids and their patterns of occurrence in the rock record.

  18. Deciphering genetic diversity and inheritance of tomato fruit weight and composition through a systems biology approach.

    Science.gov (United States)

    Pascual, Laura; Xu, Jiaxin; Biais, Benoît; Maucourt, Mickaël; Ballias, Patricia; Bernillon, Stéphane; Deborde, Catherine; Jacob, Daniel; Desgroux, Aurore; Faurobert, Mireille; Bouchet, Jean-Paul; Gibon, Yves; Moing, Annick; Causse, Mathilde

    2013-12-01

    Integrative systems biology proposes new approaches to decipher the variation of phenotypic traits. In an effort to link the genetic variation and the physiological and molecular bases of fruit composition, the proteome (424 protein spots), metabolome (26 compounds), enzymatic profile (26 enzymes), and phenotypes of eight tomato accessions, covering the genetic diversity of the species, and four of their F1 hybrids, were characterized at two fruit developmental stages (cell expansion and orange-red). The contents of metabolites varied among the genetic backgrounds, while enzyme profiles were less variable, particularly at the cell expansion stage. Frequent genotype by stage interactions suggested that the trends observed for one accession at a physiological level may change in another accession. In agreement with this, the inheritance modes varied between crosses and stages. Although additivity was predominant, 40% of the traits were non-additively inherited. Relationships among traits revealed associations between different levels of expression and provided information on several key proteins. Notably, the role of frucktokinase, invertase, and cysteine synthase in the variation of metabolites was highlighted. Several stress-related proteins also appeared related to fruit weight differences. These key proteins might be targets for improving metabolite contents of the fruit. This systems biology approach provides better understanding of networks controlling the genetic variation of tomato fruit composition. In addition, the wide data sets generated provide an ideal framework to develop innovative integrated hypothesis and will be highly valuable for the research community.

  19. An Airborne Conflict Resolution Approach Using a Genetic Algorithm

    Science.gov (United States)

    Mondoloni, Stephane; Conway, Sheila

    2001-01-01

    An airborne conflict resolution approach is presented that is capable of providing flight plans forecast to be conflict-free with both area and traffic hazards. This approach is capable of meeting constraints on the flight plan such as required times of arrival (RTA) at a fix. The conflict resolution algorithm is based upon a genetic algorithm, and can thus seek conflict-free flight plans meeting broader flight planning objectives such as minimum time, fuel or total cost. The method has been applied to conflicts occurring 6 to 25 minutes in the future in climb, cruise and descent phases of flight. The conflict resolution approach separates the detection, trajectory generation and flight rules function from the resolution algorithm. The method is capable of supporting pilot-constructed resolutions, cooperative and non-cooperative maneuvers, and also providing conflict resolution on trajectories forecast by an onboard FMC.

  20. Comparison of genetic diversity structure analyses of SSR molecular marker data within apple (Malus×domestica) genetic resources.

    Science.gov (United States)

    Patzak, Josef; Paprštein, František; Henychová, Alena; Sedlák, Jiří

    2012-09-01

    The aim of this study was to compare traditional hierarchical clustering techniques and principal coordinate analysis (PCoA) with the model-based Bayesian cluster analyses in relation to subpopulation differentiation based on breeding history and geographical origin of apple (Malus×domestica Borkh.) cultivars and landraces. We presented the use of a set of 10 microsatellite (SSR) loci for genetic diversity structure analyses of 273 apple accessions from national genetic resources. These SSR loci yielded a total of 113 polymorphic SSR alleles, with 5-18 alleles per locus. SSR molecular data were successfully used in binary and allelic input format for all genetic diversity analyses, but allelic molecular data did not reveal reliable results with the NTSYS-pc and BAPS softwares. A traditional cluster analysis still provided an easy and effective way for determining genetic diversity structure in the apple germplasm collection. A model-based Bayesian analysis also provided the clustering results in accordance to traditional cluster analysis, but the analyses were distorted by the presence of a dominant group of apple genetic resources owing to the narrow origin of the apple genome. PCoA confirmed that there were no noticeable differences in genetic diversity structure of apple genetic resources during the breeding history. The results of our analyses are useful in the context of enhancing apple collection management, sampling of core collections, and improving breeding processes.

  1. New Genetic Approaches to AD: Lessons from APOE-TOMM40 Phylogenetics.

    Science.gov (United States)

    Lutz, Michael W; Crenshaw, Donna; Welsh-Bohmer, Kathleen A; Burns, Daniel K; Roses, Allen D

    2016-05-01

    Clinical trials for Alzheimer's disease are now focusing on the earliest stages of the disease with the goal of delaying dementia onset. There is great utility in using genetic variants to identify individuals at high age-dependent risk when the goal is to begin treatment before the development of any cognitive symptoms. Genetic variants identified through large-scale genome-wide association studies have not substantially improved the accuracy provided by APOE genotype to identify people at high risk of late-onset Alzheimer's disease (LOAD). We describe novel approaches, focused on molecular phylogenetics, to finding genetic variants that predict age at LOAD onset with sufficient accuracy and precision to be useful. We highlight the discovery of a polymorphism in TOMM40 that, in addition to APOE, may improve risk prediction and review how TOMM40 genetic variants may impact the develop of LOAD independently from APOE. The analysis methods described in this review may be useful for other genetically complex human diseases.

  2. The centenary progress of molecular genetics. A 100th anniversary of T. H. Morgan's discoveries.

    Science.gov (United States)

    Keros, Tomislav; Borovecki, Fran; Jemersić, Lorena; Konjević, Dean; Roić, Besi; Balatinec, Jelena

    2010-09-01

    A century ago, Thomas Hunt Morgan, the American scientist, studied the cytogenetic changes of drosophila and came to cytogenetic explanation of Mendel's basic laws of genetic heredity. These studies resulted in today's Mendel-Morgan chromosomal theory of heredity. On the occasion of the hundredth anniversary of this important discovery the authors have decided to give a review of the most significant achievements in the field of molecular genetics until the completion of the Human Genome Project. The most important points concerning the technology of DNA recombination and genetic engineering are also presented. The final section discusses the significance of previous achievements of molecular genetics in biomedicine and other related fields. There is also a tabular presentation of the sequence of the most important findings in the field of molecular genetics through time.

  3. Genetic Evolutionary Approach for Cutting Forces Prediction in Hard Milling

    Science.gov (United States)

    Taylan, Fatih; Kayacan, Cengiz

    2011-11-01

    Hard milling is a very common used machining procedure in the last years. Therefore the prediction of cutting forces is important. The paper deals with this prediction using genetic evolutionary programming (GEP) approach to set mathematical expression for out cutting forces. In this study, face milling was performed using DIN1.2842 (90MnCrV8) cold work tool steel, with a hardness of 61 HRC. Experimental parameters were selected using stability measurements and simulations. In the hard milling experiments, cutting force data in a total of three axes were collected. Feed direction (Fx) and tangential direction (Fy) cutting forces generated using genetic evolutionary programming were modelled. Cutting speed and feed rate values were treated as inputs in the models, and average cutting force values as output. Mathematical expressions were created to predict average Fxand Fy forces that can be generated in hard material milling.

  4. Molecular and pro-inflammatory genetic profile in gastric carcinomas

    NARCIS (Netherlands)

    Sitarz, R.

    2009-01-01

    Gastric cancer is a result from the combination of environmental factors and an accumulation of specific genetic alterations, and affects mainly the older population. It is known that genetic factors play a more important role in early onset gastric cancers than in conventional gastric cancer patien

  5. Use of Computer Simulations in Microbial and Molecular Genetics.

    Science.gov (United States)

    Wood, Peter

    1984-01-01

    Describes five computer programs: four simulations of genetic and physical mapping experiments and one interactive learning program on the genetic coding mechanism. The programs were originally written in BASIC for the VAX-11/750 V.3. mainframe computer and have been translated into Applesoft BASIC for Apple IIe microcomputers. (JN)

  6. Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

    Science.gov (United States)

    Czapiewski, Piotr; Kunc, Michał; Haybaeck, Johannes

    2016-01-01

    Olfactory neuroblastoma (ONB, Esthesioneuroblastoma) is an infrequent neoplasm of the head and neck area derived from olfactory neuroepithelium. Despite relatively good prognosis a subset of patients shows recurrence, progression and/or metastatic disease, which requires additional treatment. However, neither prognostic nor predictive factors are well specified. Thus, we performed a literature search for the currently available data on disturbances in molecular pathways, cytogenetic changes and results gained by next generation sequencing (NGS) approaches in ONB in order to gain an overview of genetic alterations which might be useful for treating patients with ONB. We present briefly ONB molecular pathogenesis and propose potential therapeutic targets and prognostic factors. Possible therapeutic targets in ONB include: receptor tyrosine kinases (c-kit, PDGFR-b, TrkB; EGFR); somatostatin receptor; FGF-FGFR1 signaling; Sonic hedgehog pathway; apoptosis-related pathways (Bcl-2, TRAIL) and neoangiogenesis (VEGF; KDR). Furthermore, we compare high- and low-grade ONB, and describe its frequent mimicker: sinonasal neuroendocrine carcinoma. ONB is often a therapeutic challenge, so our goal should be the implementation of acquired knowledge into clinical practice, especially at pretreated, recurrent and metastatic stages. Moreover, the multicenter molecular studies are needed to increase the amount of available data. PMID:27256979

  7. Chemicals from biotechnology: molecular plant genetics will challenge the chemical and the fermentation industry.

    Science.gov (United States)

    Wilke, D

    1999-08-01

    Industrial biotechnology has evolved as a significant manufacturing tool for products like fuel-grade ethanol, organic acids and bulk amino acids, but most items are still speciality products for food and pharmaceutical applications. Current development projects within the chemical industry, including lactic acid and 1,3-propanediol based polymers and plastics, indicate that new biotechnological processes and products may soon approach the market place, clearly targeted at the leading petrochemical bulk outlets. This is flanked by a strategic shift by the major chemical companies in to "life sciences"-pharmaceuticals, agrochemicals and the seed business as well as biotech fine chemicals. The recent tremendous achievements in molecular plant genetics and transgenic crop breeding will boost agrobiotechnology, agriculture and renewable raw materials as compelling projects for chemistry and biotechnology. New plant-based production routes may challenge established chemical and biochemical domains, but at the same time open new horizons to valuable feedstocks, intermediates and end-products.

  8. [The development of molecular human genetics and its significance for perspectives of modern medicine].

    Science.gov (United States)

    Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D

    1989-01-01

    The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.

  9. Major Results and Research Challenges in Cotton Molecular Genetics at CIRAD(France)

    Institute of Scientific and Technical Information of China (English)

    LACAPE; Jean-marc; CLAVERIE; M; DESSAUW; D; GIBAND; M; VIOT; C

    2008-01-01

    CIRAD(Montpellier,France) develops research activities centered on tropical and sub-tropical agricultural systems.Among others crops,cotton is the focus of a series of research programs in different disciplines from economics to breeding.Major areas in genetics and breeding relate to(1) genetic diversity,(2) cultivar development through classical and molecular breeding,and(3) applied

  10. Clusters of Concepts in Molecular Genetics: A Study of Swedish Upper Secondary Science Students' Understanding

    Science.gov (United States)

    Gericke, Niklas; Wahlberg, Sara

    2013-01-01

    To understand genetics, students need to be able to explain and draw connections between a large number of concepts. The purpose of the study reported herein was to explore the way upper secondary science students reason about concepts in molecular genetics in order to understand protein synthesis. Data were collected by group interviews. Concept…

  11. Clusters of Concepts in Molecular Genetics: A Study of Swedish Upper Secondary Science Students' Understanding

    Science.gov (United States)

    Gericke, Niklas; Wahlberg, Sara

    2013-01-01

    To understand genetics, students need to be able to explain and draw connections between a large number of concepts. The purpose of the study reported herein was to explore the way upper secondary science students reason about concepts in molecular genetics in order to understand protein synthesis. Data were collected by group interviews. Concept…

  12. Major Results and Research Challenges in Cotton Molecular Genetics at CIRAD (France)

    Institute of Scientific and Technical Information of China (English)

    LACAPE Jean-marc; CLAVERIE M; DESSAUW D; GIBAND M; VIOT C

    2008-01-01

    @@ CIRAD (Montpellier,France) develops research activities centered on tropical and sub-tropical agricultural systems.Among others crops,cotton is the focus of a series of research programs in different disciplines from economics to breeding.Major areas in genetics and breeding relate to (1) genetic diversity,(2) eultivar development through classical and molecular breeding,and (3) applied genomics.An important but under-exploited reservoir of genetic diversity exists within the genus Gossypium.

  13. An analytical approach to the implementation of genetically modified crops

    DEFF Research Database (Denmark)

    Borch, K.; Rasmussen, B.

    2000-01-01

    Public scepticism towards genetically modified (GM) crops is increasing. To address this, the risks and benefits of GM crops must be examined across scientific disciplines, and be discussed with the authorities, the agricultural industry and the consumers. In a feasibility study we have...... systematically analysed the challenges of the development and marketing of GM crops in Europe. A life-cycle inventory was used together with established technology foresight techniques in an interdisciplinary and empirical framework. The approach taken in this study established a dialogue between stakeholders...... and provided a framework for discussions about the future direction of GM crops....

  14. A reverse genetics approach to study feline infectious peritonitis.

    Science.gov (United States)

    Tekes, Gergely; Spies, Danica; Bank-Wolf, Barbara; Thiel, Volker; Thiel, Heinz-Jürgen

    2012-06-01

    Feline infectious peritonitis (FIP) is a lethal immunopathological disease caused by feline coronaviruses (FCoVs). Here, we describe a reverse genetics approach to study FIP by assessing the pathogenicity of recombinant type I and type II and chimeric type I/type II FCoVs. All recombinant FCoVs established productive infection in cats, and recombinant type II FCoV (strain 79-1146) induced FIP. Virus sequence analyses from FIP-diseased cats revealed that the 3c gene stop codon of strain 79-1146 has changed to restore a full-length open reading frame (ORF).

  15. Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective.

    Science.gov (United States)

    Albuquerque, David; Stice, Eric; Rodríguez-López, Raquel; Manco, Licíno; Nóbrega, Clévio

    2015-08-01

    It is well-known that obesity is a complex multifactorial and heterogeneous condition with an important genetic component. Recently, major advances in obesity research emerged concerning the molecular mechanisms contributing to the obese condition. This review outlines several studies and data concerning the genetics and other important factors in the susceptibility risk to develop obesity. Based in the genetic etiology three main categories of obesity are considered: monogenic, syndromic, and common obesity. For the monogenic forms of obesity, the gene causing the phenotype is clearly identified, whereas for the common obesity the loci architecture underlying the phenotype is still being characterized. Given that, in this review we focus mainly in this obesity form, reviewing loci found until now by genome-wide association studies related with the susceptibility risk to develop obesity. Moreover, we also detail the obesity-related loci identified in children and in different ethnic groups, trying to highlight the complexity of the genetics underlying the common obese phenotype. Importantly, we also focus in the evolutionary hypotheses that have been proposed trying to explain how natural selection favored the spread of genes that increase the risk for an obese phenotype and how this predisposition to obesity evolved. Other factors are important in the obesity condition, and thus, we also discuss the epigenetic mechanisms involved in the susceptibility and development of obesity. Covering all these topics we expect to provide a complete and recent perspective about the underlying mechanisms involved in the development and origin of obesity. Only with a full understanding of the factors and mechanisms contributing to obesity, it will be possible to provide and allow the development of new therapeutic approaches to this condition.

  16. Adaptive molecular resolution approach in Hamiltonian form: An asymptotic analysis

    Science.gov (United States)

    Zhu, Jinglong; Klein, Rupert; Delle Site, Luigi

    2016-10-01

    Adaptive molecular resolution approaches in molecular dynamics are becoming relevant tools for the analysis of molecular liquids characterized by the interplay of different physical scales. The essential difference among these methods is in the way the change of molecular resolution is made in a buffer (transition) region. In particular a central question concerns the possibility of the existence of a global Hamiltonian which, by describing the change of resolution, is at the same time physically consistent, mathematically well defined, and numerically accurate. In this paper we present an asymptotic analysis of the adaptive process complemented by numerical results and show that under certain mathematical conditions a Hamiltonian, which is physically consistent and numerically accurate, may exist. Such conditions show that molecular simulations in the current computational implementation require systems of large size, and thus a Hamiltonian approach such as the one proposed, at this stage, would not be practical from the numerical point of view. However, the Hamiltonian proposed provides the basis for a simplification and generalization of the numerical implementation of adaptive resolution algorithms to other molecular dynamics codes.

  17. Recommendations for reporting results of diagnostic genetic testing (biochemical, cytogenetic and molecular genetic)

    NARCIS (Netherlands)

    Claustres, Mireille; Kozich, Viktor; Dequeker, Els; Fowler, Brain; Hehir-Kwa, Jayne Y.; Miller, Konstantin; Oosterwijk, Cor; Peterlin, Borut; van Ravenswaaij-Arts, Conny; Zimmermann, Uwe; Zuffardi, Orsetta; Hastings, Ros J.; Barton, David E.

    2014-01-01

    Genetic test results can have considerable importance for patients, their parents and more remote family members. Clinical therapy and surveillance, reproductive decisions and genetic diagnostics in family members, including prenatal diagnosis, are based on these results. The genetic test report sho

  18. A genetic approach to understanding asthma and lung function development

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil

    2014-01-01

    Asthma is a common heritable disease of the airways with recurrent episodes of symptoms and reversible airflow obstruction that has increased dramatically in prevalence. The disease is highly heterogeneous with varying age at onset and clinical presentation and most likely represents several...... different subtypes of disease associated with distinct clinical features, divergent underlying molecular mechanisms, and individual treatment responses. Information obtained from genetic studies may be an important way of understanding underlying disease subtypes. Genome wide association studies (GWAS) have......, related traits and objective measures in order to disentangle the underlying pathophysiological disease mechanisms for the subtypes of disease. Several genes and loci have been found to be associated with adult lung function in GWAS, but it is currently unknown at what time in life these genes exert...

  19. Discovering Fuzzy Censored Classification Rules (Fccrs: A Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    Renu Bala

    2012-08-01

    Full Text Available Classification Rules (CRs are often discovered in the form of ‘If-Then’ Production Rules (PRs. PRs, beinghigh level symbolic rules, are comprehensible and easy to implement. However, they are not capable ofdealing with cognitive uncertainties like vagueness and ambiguity imperative to real word decision makingsituations. Fuzzy Classification Rules (FCRs based on fuzzy logic provide a framework for a flexiblehuman like reasoning involving linguistic variables. Moreover, a classification system consisting of simple‘If-Then’ rules is not competent in handling exceptional circumstances. In this paper, we propose aGenetic Algorithm approach to discover Fuzzy Censored Classification Rules (FCCRs. A FCCR is aFuzzy Classification Rule (FCRs augmented with censors. Here, censors are exceptional conditions inwhich the behaviour of a rule gets modified. The proposed algorithm works in two phases. In the firstphase, the Genetic Algorithm discovers Fuzzy Classification Rules. Subsequently, these FuzzyClassification Rules are mutated to produce FCCRs in the second phase. The appropriate encodingscheme, fitness function and genetic operators are designed for the discovery of FCCRs. The proposedapproach for discovering FCCRs is then illustrated on a synthetic dataset.

  20. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.;

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three...

  1. Use of molecular genetics and historical records to reconstruct the ...

    African Journals Online (AJOL)

    GRACE

    2006-12-29

    Dec 29, 2006 ... historical relationship of separated human populations. Some of the genetic markers .... ancient trade routes in Africa, inter-community marriages, and the spread of .... Islam in Southern Africa, 1653-1998. In: Nehemia. Levtzon ...

  2. Molecular Genetics Techniques to Develop New Treatments for Brain Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Jacob; Fathallan-Shaykh, Hassan

    2006-09-22

    The objectives of this report are: (1) to devise novel molecular gene therapies for malignant brain tumors, (2) advance our understanding of the immune system in the central nervous system; and (3) apply genomics to find molecular probes to diagnose brain tumors, predict prognosis, biological behavior and their response to treatment.

  3. Controlling Risk Exposure in Periodic Environments: A Genetic Algorithm Approach

    CERN Document Server

    Navarro, Emeterio

    2007-01-01

    In this paper, we compare the performance of different agent's investment strategies in an investment scenario with periodic returns and different types and levels of noise. We consider an investment model, where an agent decides the percentage of budget to risk at each time step. Afterwards, agent's investment is evaluated in the market via a return on investment (RoI), which we assume is a stochastic process with unknown periodicities and different levels of noise. To control the risk exposure, we investigate approaches based on: technical analysis (Moving Least Squares, MLS), and evolutionary computation (Genetic Algorithms, GA). In our comparison, we also consider two reference strategies for zero-knowledge and complete-knowledge behaviors, respectively. In our approach, the performance of a strategy corresponds to the average budget that can be obtained with this strategy over a certain number of time steps. To this end, we perform some computer experiments, where for each strategy the budget obtained af...

  4. A genetic algorithm approach to recognition and data mining

    Energy Technology Data Exchange (ETDEWEB)

    Punch, W.F.; Goodman, E.D.; Min, Pei [Michigan State Univ., East Lansing, MI (United States)] [and others

    1996-12-31

    We review here our use of genetic algorithm (GA) and genetic programming (GP) techniques to perform {open_quotes}data mining,{close_quotes} the discovery of particular/important data within large datasets, by finding optimal data classifications using known examples. Our first experiments concentrated on the use of a K-nearest neighbor algorithm in combination with a GA. The GA selected weights for each feature so as to optimize knn classification based on a linear combination of features. This combined GA-knn approach was successfully applied to both generated and real-world data. We later extended this work by substituting a GP for the GA. The GP-knn could not only optimize data classification via linear combinations of features but also determine functional relationships among the features. This allowed for improved performance and new information on important relationships among features. We review the effectiveness of the overall approach on examples from biology and compare the effectiveness of the GA and GP.

  5. Molecular structure and elastic properties of thermotropic liquid crystals: Integrated molecular dynamics—Statistical mechanical theory vs molecular field approach

    Science.gov (United States)

    Capar, M. Ilk; Nar, A.; Ferrarini, A.; Frezza, E.; Greco, C.; Zakharov, A. V.; Vakulenko, A. A.

    2013-03-01

    The connection between the molecular structure of liquid crystals and their elastic properties, which control the director deformations relevant for electro-optic applications, remains a challenging objective for theories and computations. Here, we compare two methods that have been proposed to this purpose, both characterized by a detailed molecular level description. One is an integrated molecular dynamics-statistical mechanical approach, where the bulk elastic constants of nematics are calculated from the direct correlation function (DCFs) and the single molecule orientational distribution function [D. A. McQuarrie, Statistical Mechanics (Harper & Row, New York, 1973)]. The latter is obtained from atomistic molecular dynamics trajectories, together with the radial distribution function, from which the DCF is then determined by solving the Ornstein-Zernike equation. The other approach is based on a molecular field theory, where the potential of mean torque experienced by a mesogen in the liquid crystal phase is parameterized according to its molecular surface. In this case, the calculation of elastic constants is combined with the Monte Carlo sampling of single molecule conformations. Using these different approaches, but the same description, at the level of molecular geometry and torsional potentials, we have investigated the elastic properties of the nematic phase of two typical mesogens, 4'-n-pentyloxy-4-cyanobiphenyl and 4'-n-heptyloxy-4-cyanobiphenyl. Both methods yield K3(bend) >K1 (splay) >K2 (twist), although there are some discrepancies in the average elastic constants and in their anisotropy. These are interpreted in terms of the different approximations and the different ways of accounting for the structural properties of molecules in the two approaches. In general, the results point to the role of the molecular shape, which is modulated by the conformational freedom and cannot be fully accounted for by a single descriptor such as the aspect ratio.

  6. Effects of Maternal Obesity on Fetal Programming: Molecular Approaches.

    Science.gov (United States)

    Neri, Caterina; Edlow, Andrea G

    2015-09-03

    Maternal obesity has become a worldwide epidemic. Obesity and a high-fat diet have been shown to have deleterious effects on fetal programming, predisposing offspring to adverse cardiometabolic and neurodevelopmental outcomes. Although large epidemiological studies have shown an association between maternal obesity and adverse outcomes for offspring, the underlying mechanisms remain unclear. Molecular approaches have played a key role in elucidating the mechanistic underpinnings of fetal malprogramming in the setting of maternal obesity. These approaches include, among others, characterization of epigenetic modifications, microRNA expression, the gut microbiome, the transcriptome, and evaluation of specific mRNA expression via quantitative reverse transcription polmerase chain reaction (RT-qPCR) in fetuses and offspring of obese females. This work will review the data from animal models and human fluids/cells regarding the effects of maternal obesity on fetal and offspring neurodevelopment and cardiometabolic outcomes, with a particular focus on molecular approaches.

  7. A chemical genetics approach for specific differentiation of stem cells to somatic cells: a new promising therapeutical approach.

    Science.gov (United States)

    Sachinidis, Agapios; Sotiriadou, Isaia; Seelig, Bianca; Berkessel, Albrecht; Hescheler, Jürgen

    2008-01-01

    Cell replacement therapy of severe degenerative diseases such as diabetes, myocardial infarction and Parkinson's disease through transplantation of somatic cells generated from embryonic stem (ES) cells is currently receiving considerable attention for the therapeutic applications. ES cells harvested from the inner cell mass (ICM) of the early embryo, can proliferate indefinitely in vitro while retaining the ability to differentiate into all somatic cells thereby providing an unlimited renewable source of somatic cells. In this context, identifying soluble factors, in particular chemically synthesized small molecules, and signal cascades involved in specific differentiation processes toward a defined tissue specific cell type are crucial for optimizing the generation of somatic cells in vitro for therapeutic approaches. However, experimental models are required allowing rapid and "easy-to-handle" parallel screening of chemical libraries to achieve this goal. Recently, the forward chemical genetic screening strategy has been postulated to screen small molecules in cellular systems for a specific desired phenotypic effect. The current review is focused on the progress of ES cell research in the context of the chemical genetics to identify small molecules promoting specific differentiation of ES cells to desired cell phenotype. Chemical genetics in the context of the cell ES-based cell replacement therapy remains a challenge for the near future for several scientific fields including chemistry, molecular biology, medicinal physics and robotic technologies.

  8. Genetic influences on attention deficit hyperactivity disorder symptoms from age 2 to 3: A quantitative and molecular genetic investigation

    Directory of Open Access Journals (Sweden)

    Saudino Kimberly J

    2010-12-01

    Full Text Available Abstract Background A twin study design was used to assess the degree to which additive genetic variance influences ADHD symptom scores across two ages during infancy. A further objective in the study was to observe whether genetic association with a number of candidate markers reflects results from the quantitative genetic analysis. Method We have studied 312 twin pairs at two time-points, age 2 and age 3. A composite measure of ADHD symptoms from two parent-rating scales: The Child Behavior Checklist/1.5 - 5 years (CBCL hyperactivity scale and the Revised Rutter Parent Scale for Preschool Children (RRPSPC was used for both quantitative and molecular genetic analyses. Results At ages 2 and 3 ADHD symptoms are highly heritable (h2 = 0.79 and 0.78, respectively with a high level of genetic stability across these ages. However, we also observe a significant level of genetic change from age 2 to age 3. There are modest influences of non-shared environment at each age independently (e2 = 0.22 and 0.21, respectively, with these influences being largely age-specific. In addition, we find modest association signals in DAT1 and NET1 at both ages, along with suggestive specific effects of 5-HTT and DRD4 at age 3. Conclusions ADHD symptoms are heritable at ages 2 and 3. Additive genetic variance is largely shared across these ages, although there are significant new effects emerging at age 3. Results from our genetic association analysis reflect these levels of stability and change and, more generally, suggest a requirement for consideration of age-specific genotypic effects in future molecular studies.

  9. The system of molecular-genetic triggers as self--organizing computing system

    Directory of Open Access Journals (Sweden)

    A. Profir

    2001-05-01

    Full Text Available In this paper is shown, that the system of molecular-genetic triggers can solve the SAT problem. The molecular-genetic trigger represents the self-organizing structure and has attractors. The signal from one attractor is transmitted to other attractor, from the first level to the second level of the system. Molecular-genetic triggers work separately. The system of molecular-genetic triggers represents an example of parallel computing system. Suppose, that the system can receive two types of signals. In the first case, the system switches with the help of signals of a molecular nature (concentration of activators x1, x>sub>2, x3, x4. In the second case, the signals of wave nature of a resonant frequency can be utilized. It is possible to show, that the molecular--genetic system, can recognize images encoded by 2-dimensional vectors. Thus, the cells can be considered as parallel self-organizing system producing, receiving and transmitting the information.

  10. Integrating molecular QTL data into genome-wide genetic association analysis: Probabilistic assessment of enrichment and colocalization

    Science.gov (United States)

    2017-01-01

    We propose a novel statistical framework for integrating the result from molecular quantitative trait loci (QTL) mapping into genome-wide genetic association analysis of complex traits, with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genetic variants and the colocalizations of the two types of association signals. We introduce a natural Bayesian hierarchical model that treats the latent association status of molecular QTLs as SNP-level annotations for candidate SNPs of complex traits. We detail a computational procedure to seamlessly perform enrichment, fine-mapping and colocalization analyses, which is a distinct feature compared to the existing colocalization analysis procedures in the literature. The proposed approach is computationally efficient and requires only summary-level statistics. We evaluate and demonstrate the proposed computational approach through extensive simulation studies and analyses of blood lipid data and the whole blood eQTL data from the GTEx project. In addition, a useful utility from our proposed method enables the computation of expected colocalization signals using simple characteristics of the association data. Using this utility, we further illustrate the importance of enrichment analysis on the ability to discover colocalized signals and the potential limitations of currently available molecular QTL data. The software pipeline that implements the proposed computation procedures, enloc, is freely available at https://github.com/xqwen/integrative. PMID:28278150

  11. Theory of molecular conductance using a modular approach

    Science.gov (United States)

    Hsu, Liang-Yan; Rabitz, Herschel

    2016-12-01

    This study probes the correlation between the conductance of a molecular wire (the property of a whole system) and its constituent backbone units (modules). By using a tight-binding Hamiltonian combined with single-particle Green's functions, we develop an approach that enables an estimate of a conductance decay constant in terms of the Hamiltonians of molecular backbone units and the couplings between two nearest-neighbor units in the off-resonant tunneling regime. For demonstration, we examine several representative molecular systems in a framework of the Hückel model (the simplest atomistic-level model). The Hückel model can be reduced to a single-orbital-per-site formulation [A. Nitzan, Annu. Rev. Phys. Chem. 52, 681 (2001)], and each energy level in the single-orbital-per-site picture can be expressed in an explicit form including the synergistic effect of all molecular orbitals of a molecular backbone unit. Based on the proposed approach, we show the correspondence between the complete destructive quantum interference and an infinite injection gap and derive the preconditions of the modified Simmons equation and the rule of intramolecular series circuits.

  12. Molecular genetics of schizophrenia: past, present and future

    Indian Academy of Sciences (India)

    Suman Prasad; Prachi Semwal; Smita Deshpande; Triptish Bhatia; V L Nimgaonkar; B K Thelma

    2002-02-01

    Schizophrenia is a severe neuropsychiatric disorder with a polygenic mode of inheritance which is also governed by non-genetic factors. Candidate genes identified on the basis of biochemical and pharmacological evidence are being tested for linkage and association studies. Neurotransmitters, especially dopamine and serotonin have been widely implicated in its etiology. Genome scan of all human chromosomes with closely spaced polymorphic markers is being used for linkage studies. The completion and availability of the first draft of Human Genome Sequence has provided a treasure-trove that can be utilized to gain insight into the so far inaccessible regions of the human genome. Significant technological advances for identification of single nucleotide polymorphisms (SNPs) and use of microarrays have further strengthened research methodologies for genetic analysis of complex traits. In this review, we summarize the evolution of schizophrenia genetics from the past to the present, current trends and future direction of research.

  13. Molecular imaging: a new approach to nuclear cardiology

    Energy Technology Data Exchange (ETDEWEB)

    Dobrucki, L.W.; Sinusas, A.J. [Yale Univ. School of Medicine, New Haven (United States). Section of Cardiovascular Medicine, Department of Internal Medicine

    2005-03-01

    Nuclear cardiology has historically played an important role in detection of cardiovascular disease as well as risk statification. With the growth of molecular biology have come new therapeutic interventions and the requirement for new diagnostic imaging approaches. Noninvasive targeted radiotracer based as well as transporter gene imaging strategies are evolving to meet these new needs, but require the development of an interdisciplinary approach which focuses on molecular processes, as well as the pathogenesis and progression of disease. This progress has been made possible with the availability of transgenic animal models along with many technological advances. Future adaptations of the developing experimental procedures and instrumentations will allow for the smooth translation and application to clinical practice. This review is intended as a brief overview on the subject molecular imaging. Basic concepts and historical perspective of molecular imaging will be reviewed first, followed by description of current technology, and concluding with current applications in cardiology. The emphasis will be on the use of both single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiotracers, although other imaging modalities will be also briefly discussed. The specific approaches presented here will include receptor-based and reporter gene imaging of natural and therapeutical angiogenesis.

  14. A new holistic genome viewer for molecular genetics.

    NARCIS (Netherlands)

    H.J.F.M.M. Eussen (Bert); M.J. Moorhouse (Michael); M. Lesnussa (Michael); M. Muetgeert (Maarten); T.A. Knoch (Tobias)

    2006-01-01

    textabstractGenomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of information. Their system-biological complexity remains, however, still largely mysterious, despite immense sequencing achievements and huge advances in the understanding of the

  15. A new holistic genome viewer for molecular genetics

    NARCIS (Netherlands)

    T.A. Knoch (Tobias); L.V. de Zeeuw (Luc)

    2006-01-01

    textabstractGenomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of information. Their system-biological complexity remains, however, still largely mysterious, despite immense sequencing achievements and huge advances in the understanding of th

  16. Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants.

    Science.gov (United States)

    Kujur, Alice; Saxena, Maneesha S; Bajaj, Deepak; Laxmi; Parida, Swarup K

    2013-12-01

    The enormous population growth, climate change and global warming are now considered major threats to agriculture and world's food security. To improve the productivity and sustainability of agriculture, the development of highyielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern -omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties.

  17. Translocation Properties of Primitive Molecular Machines and Their Relevance to the Structure of the Genetic Code

    CERN Document Server

    Aldana, M; Larralde, H; Martínez-Mekler, G; Aldana, Maximino; Cocho, Germinal; Larralde, Hernan; Martinez-Mekler, Gustavo

    2002-01-01

    We address the question, related with the origin of the genetic code, of why are there three bases per codon in the translation to protein process. As a followup to our previous work, we approach this problem by considering the translocation properties of primitive molecular machines, which capture basic features of ribosomal/messenger RNA interactions, while operating under prebiotic conditions. Our model consists of a short one-dimensional chain of charged particles(rRNA antecedent) interacting with a polymer (mRNA antecedent) via electrostatic forces. The chain is subject to external forcing that causes it to move along the polymer which is fixed in a quasi one dimensional geometry. Our numerical and analytic studies of statistical properties of random chain/polymer potentials suggest that, under very general conditions, a dynamics is attained in which the chain moves along the polymer in steps of three monomers. By adjusting the model in order to consider present day genetic sequences, we show that the ab...

  18. Genetic and Molecular Analysis of Suppressors of Ras Mutations

    Science.gov (United States)

    1999-10-01

    fication of vulval cell fates have defined many of the genes necessary for normal vulval differentiation (Korn- feld 1997; Stemberg and Han 1998... Stemberg . 1993. C. e]- egans Un-45 raf gene participates in let-60 ros-stimulated vulval differentiation. Nature 363: 133-140. Horvitz, H.R. and P.W... Stemberg , P.W. and M. Han. 1998. Genetics of Ras signaling in C. elegazss. Tiettds Genet. 14:466-472. Stewart, S., M. Sundaram, Y. Zhang, J. Lee, Y

  19. Molecular genetics of pancreatic carcinogenesis and their clinical significance

    NARCIS (Netherlands)

    Ottenhof, N.A.

    2012-01-01

    Like all types of cancer, pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, is a disease of the genes and the genetic alterations that are involved in the development of PDAC have been under investigation for many years. The research described in this thesis focuses on

  20. Morphological and molecular genetic diversity of Syrian indigenous ...

    African Journals Online (AJOL)

    This study aimed to assess the morphological variation, genetic diversity and ... questionnaire was used in recording both qualitative (coat color, eye color, horn ... these goat breeds have not yet undergone an organized breeding program. ... The Syrian goat populations had observed and expected heterozygosity values ...

  1. Genetic cholestasis : Lessons from the molecular physiology of bile formation

    NARCIS (Netherlands)

    Jansen, PLM; Muller, M

    2000-01-01

    Progressive familial intrahepatic cholestasis (PFIC) is a group of severe genetic cholestatic liver diseases of early life. PFIC types 1 and 2 are characterized by cholestasis and a low to normal serum gamma-glutamyltransferase (GGT) activity, whereas in PFIC type 3, the serum GGT activity is elevat

  2. Molecular and genetic basis of freezing tolerance in crucifer species

    NARCIS (Netherlands)

    Heo, J.

    2014-01-01

      Understanding genetic variation for freezing tolerance is important for unraveling an adaptative strategy of species and for finding out an effective way to improve crop productivity to unfavorable winter environments. The aim of this thesis was to examine natural variation for components of

  3. Exploring human brain lateralization with molecular genetics and genomics.

    Science.gov (United States)

    Francks, Clyde

    2015-11-01

    Lateralizations of brain structure and motor behavior have been observed in humans as early as the first trimester of gestation, and are likely to arise from asymmetrical genetic-developmental programs, as in other animals. Studies of gene expression levels in postmortem tissue samples, comparing the left and right sides of the human cerebral cortex, have generally not revealed striking transcriptional differences between the hemispheres. This is likely due to lateralization of gene expression being subtle and quantitative. However, a recent re-analysis and meta-analysis of gene expression data from the adult superior temporal and auditory cortex found lateralization of transcription of genes involved in synaptic transmission and neuronal electrophysiology. Meanwhile, human subcortical mid- and hindbrain structures have not been well studied in relation to lateralization of gene activity, despite being potentially important developmental origins of asymmetry. Genetic polymorphisms with small effects on adult brain and behavioral asymmetries are beginning to be identified through studies of large datasets, but the core genetic mechanisms of lateralized human brain development remain unknown. Identifying subtly lateralized genetic networks in the brain will lead to a new understanding of how neuronal circuits on the left and right are differently fine-tuned to preferentially support particular cognitive and behavioral functions. © 2015 New York Academy of Sciences.

  4. Genetic cholestasis : Lessons from the molecular physiology of bile formation

    NARCIS (Netherlands)

    Jansen, PLM; Muller, M

    Progressive familial intrahepatic cholestasis (PFIC) is a group of severe genetic cholestatic liver diseases of early life. PFIC types 1 and 2 are characterized by cholestasis and a low to normal serum gamma-glutamyltransferase (GGT) activity, whereas in PFIC type 3, the serum GGT activity is

  5. Molecular based assessment of genetic diversity of xoconostle ...

    African Journals Online (AJOL)

    aghomotsegin

    2014-01-08

    Jan 8, 2014 ... origin, to culture conditions, or to the current species classification. ... demonstrates the high genetic variation among genotypes of xoconostles, ... technology has led to the development of different ..... phenotypic plasticity and polyploidy level should also be .... geographic origins, and reticulate evolution.

  6. Human Fertility, Molecular Genetics, and Natural Selection in Modern Societies

    NARCIS (Netherlands)

    Tropf, Felix C.; Stulp, Gert; Barban, Nicola; Visscher, Peter M.; Yang, Jian; Snieder, Harold; Mills, Melinda C.

    2015-01-01

    Research on genetic influences on human fertility outcomes such as number of children ever born (NEB) or the age at first childbirth (AFB) has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances

  7. Genetic and molecular markers of proteinuria and glomerulosclerosis

    NARCIS (Netherlands)

    IJpelaar, Daphne Hubertina Thea

    2009-01-01

    The clinical course of renal diseases depends on the type of renal disorder, genetic factors, environmental influences, and the severity of renal fibrosis. Proteinuria is the abnormal amount of proteins present in the urine. Proteinuria is an independent risk factor for development of renal insuffic

  8. Linguini Models of Molecular Genetic Mapping and Fingerprinting.

    Science.gov (United States)

    Thompson, James N., Jr.; Gray, Stanton B.; Hellack, Jenna J.

    1997-01-01

    Presents an exercise using linguini noodles to demonstrate an aspect of DNA fingerprinting. DNA maps that show genetic differences can be produced by digesting a certain piece of DNA with two or more restriction enzymes both individually and in combination. By rearranging and matching linguini fragments, students can recreate the original pattern…

  9. Potato leafroll virus : molecular analysis and genetically engineered resistance

    NARCIS (Netherlands)

    Wilk, van der F.

    1995-01-01

    The nucleotide sequence of the genomic RNA of potato leafroll virus (PLRV) was elucidated and its genetic organization deduced (Chapter 2). Six open reading frames (ORFs) were shown to be present on the genome. Both the PLRV coat protein gene and the RNA- dependent RNA polymerase gene were

  10. Novel approach to improve molecular imaging research: Correlation between macroscopic and molecular pathological findings in patients

    Energy Technology Data Exchange (ETDEWEB)

    Boehm, Ingrid, E-mail: i.boehm@uni-bonn.de [Department of Diagnostic Radiology, ZARF Project, Center for Molecular Imaging Research MBMB, Philipps University of Marburg, Baldingerstrasse, 35039 Marburg (Germany)

    2011-09-15

    Purpose: Currently, clinical research approaches are sparse in molecular imaging studies. Moreover, possible links between imaging features and pathological laboratory parameters are unknown, so far. Therefore, the goal was to find a possible relationship between imaging features and peripheral blood cell apoptosis, and thereby to present a novel way to complement molecular imaging research. Materials and methods: The investigation has been done in systemic lupus erythematosus (SLE), a prototype of an autoimmune disease characterized by multiorgan involvement, autoantibody production, and disturbed apoptosis. Retrospectively, radiological findings have been compared to both autoantibody findings and percentage apoptotic blood cells. Results: Two SLE groups could be identified: patients with normal (annexin V binding < 20%), and with increased apoptosis (annexin V binding > 20%) of peripheral blood cells. The frequency of radiological examinations in SLE patients significantly correlated with an increased percentage of apoptotic cells (p < 0.005). In patients with characteristic imaging findings (e.g. lymph node swelling, pleural effusion) an elevated percentage of apoptotic cells was present. In contrast SLE-patients with normal imaging findings or uncharacteristic results of minimal severity had normal percentages of apoptotic blood cells. Conclusion: This correlation between radiographic findings and percentage of apoptotic blood cells provides (1) further insight into pathological mechanisms of SLE, (2) will offer the possibility to introduce apoptotic biomarkers as molecular probes for clinical molecular imaging approaches in future to early diagnose organ complaints in patients with SLE, and (3) is a plea to complement molecular imaging research by this clinical approach.

  11. Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach

    Science.gov (United States)

    Versmissen, Jorie; Oosterveer, Daniëlla M; Yazdanpanah, Mojgan; Dehghan, Abbas; Hólm, Hilma; Erdman, Jeanette; Aulchenko, Yurii S; Thorleifsson, Gudmar; Schunkert, Heribert; Huijgen, Roeland; Vongpromek, Ranitha; Uitterlinden, André G; Defesche, Joep C; van Duijn, Cornelia M; Mulder, Monique; Dadd, Tony; Karlsson, Hróbjartur D; Ordovas, Jose; Kindt, Iris; Jarman, Amelia; Hofman, Albert; van Vark-van der Zee, Leonie; Blommesteijn-Touw, Adriana C; Kwekkeboom, Jaap; Liem, Anho H; van der Ouderaa, Frans J; Calandra, Sebastiano; Bertolini, Stefano; Averna, Maurizio; Langslet, Gisle; Ose, Leiv; Ros, Emilio; Almagro, Fátima; de Leeuw, Peter W; Civeira, Fernando; Masana, Luis; Pintó, Xavier; Simoons, Maarten L; Schinkel, Arend FL; Green, Martin R; Zwinderman, Aeilko H; Johnson, Keith J; Schaefer, Arne; Neil, Andrew; Witteman, Jacqueline CM; Humphries, Steve E; Kastelein, John JP; Sijbrands, Eric JG

    2015-01-01

    Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis, we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (P<1 × 10−4). We examined the association of these SNPs with CHD risk in the replication samples. After Bonferroni correction, none of the SNPs either replicated or reached genome-wide significance after combining the discovery and replication samples. Therefore, we conclude that the genetics of CHD risk in FH is complex and even applying an ‘extreme genetics' approach we did not identify new genetic risk variants. Most likely, this method is not as effective in leveraging effect size as anticipated, and may, therefore, not lead to significant gains in statistical power. PMID:24916650

  12. Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

    Science.gov (United States)

    Traglia, Michela; Tsang, Kathryn; Bearden, Carrie E.; Rauen, Katherine A.

    2017-01-01

    Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs) in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies), we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0.02). We then screened genome-wide for interactors with RASopathy gene SNPs and showed strong enrichment in ASD-affected individuals (P < 2.2 x 10−16), with a number of pairwise interactions meeting genome-wide criteria for significance. Finally, we utilized quantitative measures of ASD symptoms in RASopathy-affected individuals to perform modifier mapping via GWAS. One top region overlapped between these independent approaches, and we showed dysregulation of a gene in this region, GPR141, in a RASopathy neural cell line. We thus used orthogonal approaches to provide strong evidence for a contribution of epistasis to ASDs, confirm a role for the Ras/MAPK pathway in idiopathic ASDs, and to identify a convergent candidate gene that may interact with the Ras/MAPK pathway. PMID:28076348

  13. Genetic Approach for the Fast Discovery of Phenazine Producing Bacteria

    Directory of Open Access Journals (Sweden)

    Johannes F. Imhoff

    2011-05-01

    Full Text Available A fast and efficient approach was established to identify bacteria possessing the potential to biosynthesize phenazines, which are of special interest regarding their antimicrobial activities. Sequences of phzE genes, which are part of the phenazine biosynthetic pathway, were used to design one universal primer system and to analyze the ability of bacteria to produce phenazine. Diverse bacteria from different marine habitats and belonging to six major phylogenetic lines were investigated. Bacteria exhibiting phzE gene fragments affiliated to Firmicutes, Alpha- and Gammaproteobacteria, and Actinobacteria. Thus, these are the first primers for amplifying gene fragments from Firmicutes and Alphaproteobacteria. The genetic potential for phenazine production was shown for four type strains belonging to the genera Streptomyces and Pseudomonas as well as for 13 environmental isolates from marine habitats. For the first time, the genetic ability of phenazine biosynthesis was verified by analyzing the metabolite pattern of all PCR-positive strains via HPLC-UV/MS. Phenazine production was demonstrated for the type strains known to produce endophenazines, 2-hydroxy-phenazine, phenazine-1-carboxylic acid, phenazine-1,6-dicarboxylic acid, and chlororaphin as well as for members of marine Actinobacteria. Interestingly, a number of unidentified phenazines possibly represent new phenazine structures.

  14. Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach

    Science.gov (United States)

    Risso, Davide; Taglioli, Luca; De Iasio, Sergio; Gueresi, Paola; Alfani, Guido; Nelli, Sergio; Rossi, Paolo; Paoli, Giorgio; Tofanelli, Sergio

    2015-01-01

    This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447–2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8–30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics. PMID:26452043

  15. Graphical approach to evaluate genetic estimates of calf survival.

    Science.gov (United States)

    Schlesser, H N; Shanks, R D; Berger, P J; Healey, M H

    2009-05-01

    Genetic variation and resemblance among relatives are fundamentals of quantitative genetics. Our purpose was to identify bulls with a bimodal pattern of inheritance in the quest for new discoveries about the inheritance of calf survival. A bimodal pattern of inheritance for calf survival was identified in sons of Holstein bulls. A bimodal pattern of inheritance indicates 2 groups of sons resulting from an allele effect, a grandsire effect, or some other common factor. Different combinations (AA, Aa, aa) of 2 alleles at a locus cause varying phenotypes to be expressed. Bulls that are heterozygous for loci affecting reproductive performance may have a bimodal pattern of inheritance if the difference in effect of the 2 alleles is large. If the bimodal pattern is caused by an allele effect, then molecular markers can be identified for use in marker-assisted selection breeding programs. Data on predicted transmitting ability for perinatal survival for the first parity of 8,678 sons of 599 sires were collected from 1984 through 1997 from the National Association of Animal Breeders calving ease database, which included 7 Midwestern states. Sixteen bulls were identified with a potential bimodal pattern of inheritance because they had 2 distinct groups of sons. The 2 groups of sons were separated by calculating the coefficient of variation for each possible combination of sons; the combination that gave the smallest coefficient of variation difference between the 2 groups was considered the correct distribution of the sons into those groups. Bulls with a bimodal distribution were analyzed to determine the distribution of the grandsons among the maternal grandsires (MGS) of the 2 groups of the bimodal distribution. The bimodal distribution may be a result of heterozygous sires or MGS that are homozygous for low or high survival. If the bimodal distribution is caused by a MGS effect, then marker-assisted selection can still be used by evaluating the MGS instead of the sires.

  16. A Full Bayesian Approach for Boolean Genetic Network Inference

    Science.gov (United States)

    Han, Shengtong; Wong, Raymond K. W.; Lee, Thomas C. M.; Shen, Linghao; Li, Shuo-Yen R.; Fan, Xiaodan

    2014-01-01

    Boolean networks are a simple but efficient model for describing gene regulatory systems. A number of algorithms have been proposed to infer Boolean networks. However, these methods do not take full consideration of the effects of noise and model uncertainty. In this paper, we propose a full Bayesian approach to infer Boolean genetic networks. Markov chain Monte Carlo algorithms are used to obtain the posterior samples of both the network structure and the related parameters. In addition to regular link addition and removal moves, which can guarantee the irreducibility of the Markov chain for traversing the whole network space, carefully constructed mixture proposals are used to improve the Markov chain Monte Carlo convergence. Both simulations and a real application on cell-cycle data show that our method is more powerful than existing methods for the inference of both the topology and logic relations of the Boolean network from observed data. PMID:25551820

  17. A full bayesian approach for boolean genetic network inference.

    Directory of Open Access Journals (Sweden)

    Shengtong Han

    Full Text Available Boolean networks are a simple but efficient model for describing gene regulatory systems. A number of algorithms have been proposed to infer Boolean networks. However, these methods do not take full consideration of the effects of noise and model uncertainty. In this paper, we propose a full Bayesian approach to infer Boolean genetic networks. Markov chain Monte Carlo algorithms are used to obtain the posterior samples of both the network structure and the related parameters. In addition to regular link addition and removal moves, which can guarantee the irreducibility of the Markov chain for traversing the whole network space, carefully constructed mixture proposals are used to improve the Markov chain Monte Carlo convergence. Both simulations and a real application on cell-cycle data show that our method is more powerful than existing methods for the inference of both the topology and logic relations of the Boolean network from observed data.

  18. Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach

    Science.gov (United States)

    Chaturvedi, Swati; Singh, Ashok K.; Maity, Siddhartha; Sarkar, Srimanta

    2016-01-01

    One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED) and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM) or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches. PMID:27051561

  19. A genetic epidemiology approach to cyber-security.

    Science.gov (United States)

    Gil, Santiago; Kott, Alexander; Barabási, Albert-László

    2014-07-16

    While much attention has been paid to the vulnerability of computer networks to node and link failure, there is limited systematic understanding of the factors that determine the likelihood that a node (computer) is compromised. We therefore collect threat log data in a university network to study the patterns of threat activity for individual hosts. We relate this information to the properties of each host as observed through network-wide scans, establishing associations between the network services a host is running and the kinds of threats to which it is susceptible. We propose a methodology to associate services to threats inspired by the tools used in genetics to identify statistical associations between mutations and diseases. The proposed approach allows us to determine probabilities of infection directly from observation, offering an automated high-throughput strategy to develop comprehensive metrics for cyber-security.

  20. Genetic diversity in cultivated carioca common beans based on molecular marker analysis

    Directory of Open Access Journals (Sweden)

    Juliana Morini Küpper Cardoso Perseguini

    2011-01-01

    Full Text Available A wide array of molecular markers has been used to investigate the genetic diversity among common bean species. However, the best combination of markers for studying such diversity among common bean cultivars has yet to be determined. Few reports have examined the genetic diversity of the carioca bean, commercially one of the most important common beans in Brazil. In this study, we examined the usefulness of two molecular marker systems (simple sequence repeats - SSRs and amplified fragment length polymorphisms - AFLPs for assessing the genetic diversity of carioca beans. The amount of information provided by Roger's modified genetic distance was used to analyze SSR data and Jaccards similarity coefficient was used for AFLP data. Seventy SSRs were polymorphic and 20 AFLP primer combinations produced 635 polymorphic bands. Molecular analysis showed that carioca genotypes were quite diverse. AFLPs revealed greater genetic differentiation and variation within the carioca genotypes (Gst = 98% and Fst = 0.83, respectively than SSRs and provided better resolution for clustering the carioca genotypes. SSRs and AFLPs were both suitable for assessing the genetic diversity of Brazilian carioca genotypes since the number of markers used in each system provided a low coefficient of variation. However, fingerprint profiles were generated faster with AFLPs, making them a better choice for assessing genetic diversity in the carioca germplasm.

  1. Molecular approaches to epidemiology and clinical aspects of malaria.

    Science.gov (United States)

    Brown, G V; Beck, H P; Molyneux, M; Marsh, K

    2000-10-01

    Malaria is a problem of global importance, responsible for 1-2 million deaths per year, mainly in African children, as well as considerable morbidity manifested as severe anaemia and encephalopathy in young children. Fundamental to the development of new tools for malaria control in humans is an increased understanding of key features of malaria infection, such as the diversity of outcome in different individuals, the understanding of different manifestations of the disease and of the mechanisms of immunity that allow clinical protection in the face of ongoing low-grade infection (concomitant immunity or premunition). Here, Graham Brown and colleagues review some of the ways in which molecular approaches might be used to increase our understanding of the epidemiology and clinical manifestations of malaria, as discussed at the Molecular Approaches to Malaria conference (MAM2000), Lorne, Australia, 2-5 February 2000.

  2. A novel genetic programming approach for epileptic seizure detection.

    Science.gov (United States)

    Bhardwaj, Arpit; Tiwari, Aruna; Krishna, Ramesh; Varma, Vishaal

    2016-02-01

    The human brain is a delicate mix of neurons (brain cells), electrical impulses and chemicals, known as neurotransmitters. Any damage has the potential to disrupt the workings of the brain and cause seizures. These epileptic seizures are the manifestations of epilepsy. The electroencephalograph (EEG) signals register average neuronal activity from the cerebral cortex and label changes in activity over large areas. A detailed analysis of these electroencephalograph (EEG) signals provides valuable insights into the mechanisms instigating epileptic disorders. Moreover, the detection of interictal spikes and epileptic seizures in an EEG signal plays an important role in the diagnosis of epilepsy. Automatic seizure detection methods are required, as these epileptic seizures are volatile and unpredictable. This paper deals with an automated detection of epileptic seizures in EEG signals using empirical mode decomposition (EMD) for feature extraction and proposes a novel genetic programming (GP) approach for classifying the EEG signals. Improvements in the standard GP approach are made using a Constructive Genetic Programming (CGP) in which constructive crossover and constructive subtree mutation operators are introduced. A hill climbing search is integrated in crossover and mutation operators to remove the destructive nature of these operators. A new concept of selecting the Globally Prime offspring is also presented to select the best fitness offspring generated during crossover. To decrease the time complexity of GP, a new dynamic fitness value computation (DFVC) is employed to increase the computational speed. We conducted five different sets of experiments to evaluate the performance of the proposed model in the classification of different mixtures of normal, interictal and ictal signals, and the accuracies achieved are outstandingly high. The experimental results are compared with the existing methods on same datasets, and these results affirm the potential use of

  3. Molecular approaches to screen bioactive compounds from endophytic fungi

    Directory of Open Access Journals (Sweden)

    M Vasundhara

    2016-11-01

    Full Text Available Endophytic fungi are capable of producing plant associated metabolites and their analogs with therapeutic value. In order to identify the potential endophytic isolates producing bioactive compounds, one need to screen all isolated endophytes, which may run into hundreds. Isolation of endophytic fungi is relatively a simple process; but screening of the isolated fungi for required metabolite production is a cumbersome process. Endophytic fungi producing plant associated metabolites may contain genes involved in the entire biosynthetic pathway(s. Therefore, ascertaining the presence of key enzymes of a particular biosynthetic pathway could serve as a molecular marker for screening of these endophytes to produce that metabolite. In absence of entire biosynthetic pathways in endophytic fungi, plant genes associated with that metabolic pathway could serve as markers. This review focuses on the impact of molecular approaches to screen the endophytic fungi for the production of bioactive compounds. An attempt has been made on screening of anticancer compounds like taxol (paclitaxel, podophyllotoxin and camptothecin using molecular markers. The advantages of molecular approaches over conventional methods to screen endophytic fungi and also identification of endophytic fungi are also discussed.

  4. Molecular Approaches to Screen Bioactive Compounds from Endophytic Fungi.

    Science.gov (United States)

    Vasundhara, M; Kumar, Anil; Reddy, M Sudhakara

    2016-01-01

    Endophytic fungi are capable of producing plant associated metabolites and their analogs with therapeutic value. In order to identify the potential endophytic isolates producing bioactive compounds, one need to screen all isolated endophytes, which may run into hundreds. Isolation of endophytic fungi is relatively a simple process; but screening of the isolated fungi for required metabolite production is a cumbersome process. Endophytic fungi producing plant associated metabolites may contain genes involved in the entire biosynthetic pathway(s). Therefore, ascertaining the presence of key enzymes of a particular biosynthetic pathway could serve as a molecular marker for screening of these endophytes to produce that metabolite. In absence of entire biosynthetic pathways in endophytic fungi, plant genes associated with that metabolic pathway could serve as markers. This review focuses on the impact of molecular approaches to screen the endophytic fungi for the production of bioactive compounds. An attempt has been made on screening of anticancer compounds like taxol (paclitaxel), podophyllotoxin, and camptothecin using molecular markers. The advantages of molecular approaches over conventional methods to screen endophytic fungi and also identification of endophytic fungi are discussed.

  5. Hamartomatous polyps - a clinical and molecular genetic study

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie

    2016-01-01

    are typically removed concurrently with endoscopy when located in the colon, rectum, or stomach, whereas polyps in the small bowel are removed during push-enteroscopy, device-assisted enteroscopy, or by surgery. HPs can be classified as juvenile polyps or Peutz-Jeghers polyps based on their histopathological......% fulfilled to diagnostic criteria of JPS. The majority of patients had a single juvenile polyp. Paper II: In this paper we conducted a review of the HPS based on the current literature. Paper III: We investigated the hypothesis that patients with one or few HPs may have a HPS based on genetic screening. We...... reported previously none could be classified as definitely pathogenic or likely pathogenic according to our variant classification scheme and thus we concluded that genetic screening of patients with one or few JPs are not indicated. Paper IV: In Paper IV we investigated one of the ethical aspects of next...

  6. [Research progress on molecular genetics of male homosexuality].

    Science.gov (United States)

    Tu, Dan; Xu, Ruiwei; Zhao, Guanglu; Wang, Binbin; Feng, Tiejian

    2016-08-01

    Sexual orientation is influenced by both environmental factors and biological factors. Family and twin studies have shown that genetic factors play an important role in the formation of male homosexuality. Genome-wide scan also revealed candidate chromosomal regions which may be associated with male homosexuality, but so far no clearly related genes have been found. This article reviews the progress of relevant studies and candidate genes which are related to male homosexuality.

  7. Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

    OpenAIRE

    Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S; Zhang, Yan-Bing; Zi, Xiaolin

    2014-01-01

    There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reacti...

  8. Genetic characterization of Aberdeen Angus cattle using molecular markers

    Directory of Open Access Journals (Sweden)

    Vasconcellos Luciana Pimentel de Mello Klocker

    2003-01-01

    Full Text Available Aberdeen Angus beef cattle from the Brazilian herd were studied genetically using restriction fragment length polymorphism (RFLP of the kappa-casein - HinfI (CSN3 - HinfI, beta-lactoglobulin - HaeIII (LGB - HaeIII and growth hormone AluI (GH- AluI genes, as well as four microsatellites (TEXAN15, CSFM50, BM1224 and BM7160. The RFLP genotypes were determined using the polymerase chain reaction (PCR followed by digestion with restriction endonucleases and electrophoresis in agarose gels. With the exception of the microsatellite BM7160, which was analyzed in an automatic sequencer, the PCR products were genotyped by silver staining. The allele and genotype frequencies, heterozygosities and gene diversity were estimated. The values for these parameters of variability were comparable to other cattle breeds. The genetic relationship of the Aberdeen Angus to other breeds (Caracu, Canchim, Charolais, Guzerath, Gyr, Nelore, Santa Gertrudis and Simmental was investigated using Nei's genetic distance. Cluster analysis placed the Aberdeen Angus in an isolated group in the Bos taurus breeds branch. This fact is in agreement with the geographic origin of this breed.

  9. Molecular genetic diversity of the Gyeongju Donggyeong dog in Korea.

    Science.gov (United States)

    Lee, Eun-Woo; Choi, Seong-Kyoon; Cho, Gil-Jae

    2014-10-01

    The present study was conducted to analyze the genetic characteristics of the Donggyeong dog and establish parentage conservation systems for it by using 10 microsatellite markers recommended by the International Society for Animal Genetics (ISAG). A total of 369 dogs from 12 dog breeds including the Donggyeong dog were genotyped using 10 microsatellite loci. The number of alleles per locus varied from 5 to 10 with a mean value of 7.6 in the Donggyeong dog. The observed heterozygosity and expected heterozygosity ranged from 0.4706 to 0.9020 (mean 0.7657) and from 0.4303 to 0.8394 (mean 0.7266), respectively. The total exclusion probability of 10 microsatellite loci was 0.99955. Of the 10 microsatellite markers, the AHT121, AHTh260 and CXX279 markers had relatively high PIC values (≥0.7). This study found that there were specific alleles, 116 allele at AHT121 in the Donggyeong dog when compared with other dog breeds. Also, the results showed two (Korean native dogs and the foreign dog breeds) distinct clusters. The closest distance (0.1184) was observed between the Donggyeong dog and Jindo dog, and the longest distance (0.3435) was observed between the Donggyeong dog and Bulgae. The Korean native dog breeds have comparatively near genetic distances between each other.

  10. [Citogenetic and molecular genetic studies in infertility in eastern Hungary].

    Science.gov (United States)

    Mokánszki, Attila; Ujfalusi, Anikó; Balogh, Erzsébet; Molnár, Zsuzsanna; Sápy, Tamás; Jakab, Attila; Varga, Attila; Oláh, Eva

    2013-01-13

    In developed countries 10-15% of the couples are affected by infertility. In half of them genetic factors can be identified. We studied genetic alterations in infertility in Hungarian patients. Cyogenetic analyses were performed in 195 females and 305 males. In 17 females FMR1 mutations, in 150 males Y microdeletions, and aneuploidy were studied in the sperm of 28 males. In a carrier male sperm meiotic segregation was studied. The most common aberrations in females were X chromosome aneuploidia and inversion (3.6%), while the same in males Klinefelter-syndrome (3.3%) and autosomal translocations (2%). In two females FMR1 premutation was found. While Y microdeletions were identified only in azoospermic and severe oligozoospermic men, partial microdeletions could also be detected in normozoospermic males. A higher aberration rate was found in cases with abnormality in both the number and motility of sperm. In a male patient with 46,XY,t(3;6)(q21;q23) karyotype, 53.2% of spem carried unbalanced chromosome assortment. Knowledge of abnormalities may help in genetic counseling and choosing the most effective reproduction technique.

  11. Panel 4: Recent Advances in Otitis Media in Molecular Biology, Biochemistry, Genetics, and Animal Models

    Science.gov (United States)

    Li, Jian-Dong; Hermansson, Ann; Ryan, Allen F.; Bakaletz, Lauren O.; Brown, Steve D.; Cheeseman, Michael T.; Juhn, Steven K.; Jung, Timothy T. K.; Lim, David J.; Lim, Jae Hyang; Lin, Jizhen; Moon, Sung-Kyun; Post, J. Christopher

    2014-01-01

    Background Otitis media (OM) is the most common childhood bacterial infection and also the leading cause of conductive hearing loss in children. Currently, there is an urgent need for developing novel therapeutic agents for treating OM based on full understanding of molecular pathogenesis in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Objective To provide a state-of-the-art review concerning recent advances in OM in the areas of molecular biology, biochemistry, genetics, and animal model studies and to discuss the future directions of OM studies in these areas. Data Sources and Review Methods A structured search of the current literature (since June 2007). The authors searched PubMed for published literature in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Results Over the past 4 years, significant progress has been made in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. These studies brought new insights into our understanding of the molecular and biochemical mechanisms underlying the molecular pathogenesis of OM and helped identify novel therapeutic targets for OM. Conclusions and Implications for Practice Our understanding of the molecular pathogenesis of OM has been significantly advanced, particularly in the areas of inflammation, innate immunity, mucus overproduction, mucosal hyperplasia, middle ear and inner ear interaction, genetics, genome sequencing, and animal model studies. Although these studies are still in their experimental stages, they help identify new potential therapeutic targets. Future preclinical and clinical studies will help to translate these exciting experimental research findings into clinical applications. PMID:23536532

  12. Molecular genetics of the Spodoptera exigua multicapsid nucleopolyhedrovirus genome.

    NARCIS (Netherlands)

    Heldens, J.G.M.

    1998-01-01

    Spodoptera exigua multicapsid nucleopolyhedrovirus (SeMNPV) is an attractive biological control agent for the beet army worm S. exigua . This baculovirus has a narrow host range and is relatively, compared to other baculoviruses, virulent for beet army worm larvae. The molecular principles that spec

  13. Genetic Diversity and Molecular evolution of Hepatitis C Virus

    NARCIS (Netherlands)

    S. Noppornpanth (Suwanna)

    2008-01-01

    textabstractHepatitis C virus (HCV), an enveloped positive stranded RNA virus, is the causative agent of non-A, non-B (NANB) hepatitis (27). The virus was identified and characterized by molecular cloning techniques using serum from a NANB hepatitis virus infected chimpanzee (15) and based on the si

  14. [Present status of the molecular genetics in epidermolytic palmoplantar keratoderma].

    Science.gov (United States)

    Zhang, Xian-ning; Mao, Wei; He, Xin-hui; Lai, Zheng

    2004-08-01

    In this article we reviewed the current researches on the molecular basis of epidermolytic palmoplantar keratoderma (EPPK) and the structure and function of the keratins with mutations that can cause inherited keratin disorders. Also summarized are seventeen mutations of keratin 9 in EPPK in different ethnic populations.

  15. Molecular dissection of white pine genetic resistance to Cronartium ribicola

    Science.gov (United States)

    Jun-Jun Liu; Richard Sniezko

    2011-01-01

    Pinus monticola (Dougl. ex D. Don.) maintains a complex defence system that detects white pine blister rust pathogen (Cronartium ribicola J.C.Fisch.) and activates resistance responses. A thorough understanding of how it functions at the molecular level would provide us new strategies for creating forest trees with durable disease resistance. Our research focuses on...

  16. A Structural and Molecular Approach for the Study Biomarkers

    Science.gov (United States)

    Thomas-Keprta, Kathie; Vali, Hojatollah; Sears, S. Kelly; Roh, Yul

    2001-01-01

    Investigation of the nucleation and growth of crystals in both abiotic and biotic systems is critical to seemingly diverse disciplines of geology, biology, environmental science, and astrobiology. While there are abundant studies devoted to the determination of the structure and composition of inorganic crystals, as well as to the development of thermodynamic and kinetic models, it is only recently that research efforts have been directed towards understanding mineralization in biological systems (i.e., biomineralization). Biomineralization refers to the processes by which living organisms form inorganic solids. Studies of the processes of biomineralization under low temperature aqueous conditions have focused primarily on magnetite forming bacteria and shell forming marine organisms. Many of the biological building materials consist of inorganic minerals (calcium carbonate, calcium phosphate, silica or iron oxide) intricately combined with organic polymers (like proteins). More recently, efforts have been undertaken to explore the nature of biological activities in ancient rocks. In the absence of well-preserved microorganisms or genetic material required for the polmerase chain reaction (PCR) method in molecular phylogenetic studies, using biominerals as biomarkers offers an alternative approach for the recognition of biogenic activity in both terrestrial and extraterrestrial environments. The primary driving force in biomineralization is the interaction between organic and inorganic phases. Thus, the investigation of the ultrastructure and the nature of reactions at the molecular level occurring at the interface between inorganic and organic phases is essential to understanding the processes leading to the nucleation and growth of crystals. It is recognized that crystal surfaces can serve as the substrate for the organization of organic molecules that lead to the formation of polymers and other complex organic molecules, and in discussions of the origins of life

  17. Early childhood hearing loss: clinical and molecular genetics. An educational slide set of the American College of Medical Genetics.

    Science.gov (United States)

    Alford, Raye L; Friedman, Thomas B; Keats, Bronya J B; Kimberling, William J; Proud, Virginia K; Smith, Richard J H; Arnos, Kathleen S; Korf, Bruce R; Rehm, Heidi L; Toriello, Helga V

    2003-01-01

    An educational slide set entitled "Early Childhood Hearing Loss: Clinical and Molecular Genetics" is offered by the American College of Medical Genetics (ACMG). The slide set is produced in Microsoft PowerPoint 2002. It is extensively illustrated and supported with teaching tools, explanations of each slide and figure, links to Internet resources, and a bibliography. The slide set is expected to be used as a resource for self-directed learning and in support of medical genetics teaching activities. The slide set is available through the ACMG (http://www.acmg.net) for $20, plus applicable tax and shipping. It is the first in a series of educational slide sets to be developed by the ACMG.

  18. Origin of microbial life: Nano- and molecular events, thermodynamics/entropy, quantum mechanisms and genetic instructions.

    Science.gov (United States)

    Trevors, J T

    2011-03-01

    Currently, there are no agreed upon mechanisms and supporting evidence for the origin of the first microbial cells on the Earth. However, some hypotheses have been proposed with minimal supporting evidence and experimentation/observations. The approach taken in this article is that life originated at the nano- and molecular levels of biological organization, using quantum mechanic principles that became manifested as classical microbial cell(s), allowing the origin of microbial life on the Earth with a core or minimal, organic, genetic code containing the correct instructions for cell(s) for growth and division, in a micron dimension environment, with a local entropy range conducive to life (present about 4 billion years ago), and obeying the laws of thermodynamics. An integrated approach that explores all encompassing factors necessary for the origin of life, may bring forth plausible hypotheses (and mechanisms) with much needed supporting experimentation and observations for an origin of life theory. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Structural modification of polysaccharides: A biochemical-genetic approach

    Science.gov (United States)

    Kern, Roger G.; Petersen, Gene R.

    1991-01-01

    Polysaccharides have a wide range of industrial and biomedical applications. An industry trend is underway towards the increased use of bacteria to produce polysaccharides. Long term goals of this work are the adaptation and enhancement of saccharide properties for electronic and optic applications. In this report we illustrate the application of enzyme-bearing bacteriophage on strains of the enteric bacterium Klebsiella pneumoniae, which produces a polysaccharide with the relatively rare rheological property of drag-reduction. This has resulted in the production of new polysaccharides with enhanced rheological properties. Our laboratory is developing techniques for processing and structurally modifying bacterial polysaccharides and oligosaccharides which comprise their basic polymeric repeat units. Our research has focused on bacteriophage which produce specific polysaccharide degrading enzymes. This has lead to the development of enzymes generated by bacteriophage as tools for polysaccharide modification and purification. These enzymes were used to efficiently convert the native material to uniform-sized high molecular weight polymers, or alternatively into high-purity oligosaccharides. Enzyme-bearing bacteriophage also serve as genetic selection tools for bacteria that produce new families of polysaccharides with modified structures.

  20. Next-generation sequencing approaches in genetic rodent model systems to study functional effects of human genetic variation

    NARCIS (Netherlands)

    Guryev, Victor; Cuppen, Edwin

    2009-01-01

    Rapid advances in DNA sequencing improve existing techniques and enable new approaches in genetics and functional genomics, bringing about unprecedented coverage, resolution and sensitivity. Enhanced toolsets can facilitate the untangling of connections between genomic variation, environmental

  1. Next-generation sequencing approaches in genetic rodent model systems to study functional effects of human genetic variation.

    NARCIS (Netherlands)

    Guryev, V.; Cuppen, E.

    2009-01-01

    Rapid advances in DNA sequencing improve existing techniques and enable new approaches in genetics and functional genomics, bringing about unprecedented coverage, resolution and sensitivity. Enhanced toolsets can facilitate the untangling of connections between genomic variation, environmental facto

  2. Next-generation sequencing approaches in genetic rodent model systems to study functional effects of human genetic variation

    NARCIS (Netherlands)

    Guryev, Victor; Cuppen, Edwin

    2009-01-01

    Rapid advances in DNA sequencing improve existing techniques and enable new approaches in genetics and functional genomics, bringing about unprecedented coverage, resolution and sensitivity. Enhanced toolsets can facilitate the untangling of connections between genomic variation, environmental facto

  3. A perspective on molecular genetic studies of tardive dyskinesia: one clue for individualized antipsychotic drug therapy.

    Science.gov (United States)

    Ohmori, Osamu; Shinkai, Takahiro; Hori, Hiroko; Matsumoto, Chima; Nakamura, Jun

    2003-06-01

    Interindividual genetic profile differences related to antipsychotic drug therapy may be determined based on molecular genetic studies of the pathogenesis of schizophrenia and studies of antipsychotic drug responses (therapeutic as well as adverse responses). In the present article, we review molecular genetic studies of tardive dyskinesia (TD), which is a representative adverse response to antipsychotic drugs. Such studies have been performed to explore the gene-associated pharmacokinetic and pharmacodynamic processes of antipsychotic drugs. Positive associations between several genes and TD have been reported. The accumulation of results from such studies will hopefully lead to individualized antipsychotic drug therapies that involve the application of new genomic techniques, including DNA microarrays. Subsequently, antipsychotic drugs may in the future be prescribed for smaller subgroups of patients who have been classified as having a particular genetic profile.

  4. Molecular genetic diversity and genetic structure of Vietnamese indigenous pig populations

    DEFF Research Database (Denmark)

    Pham, L. D.; Do, Duy Ngoc; Nam, L. Q.

    2014-01-01

    The study characterized genetic diversity and genetic structure of five indigenous pig populations (Ha Lang, Muong Te, Mong Cai, Lung and Lung Pu), two wild pig populations (Vietnamese and Thai wild pigs) and an exotic pig breed (Yorkshire) using FAO/ISAG recommended 16 microsatellite markers...... eight populations into four groups including Yorkshire, two wild populations, Mong Cai population and a group of four other indigenous populations. The Bayesian clustering with the admixture model implemented in Structure 2.1 indicated seven possible homogenous clusters among eight populations. From 79......% (Ha Lang) to 98% (Mong Cai). individuals in indigenous pigs were assigned to their own populations. The results confirmed high level of genetic diversity and shed a new light on genetic structure of Vietnam indigenous pig populations....

  5. Molecular genetics of Psoriasis (Principles, technology, gene location, genetic polymorphism and gene expression).

    Science.gov (United States)

    Al Robaee, Ahmad A

    2010-11-01

    Psoriasis is a common inflammatory skin disease with an etiology bases on both environmental and genetic factors. As is the case of many autoimmune diseases its real cause remains poorly defined. However, it is known that genetic factors contribute to disease susceptibility. The linkage analysis has been used to identify multiple loci and alleles that confer risk of the disease. Some other studies have focused upon single nucleotide polymorphisms (SNPs) for mapping of probable causal variants. Other studies, using genome-wide analytical techniques, tried to link the disease to copy number variants (CNVs) that are segments of DNA ranging in size from kilobases to megabases that vary in copy number. CNVs represent an important element of genomic polymorphism in humans and harboring dosage-sensitive genes may cause or predispose to a variety of human genetic diseases. The mechanisms giving rise to SNPs and CNVs can be considered as fundamental processes underlying gene duplications, deletions, insertions, inversions and complex combinations of rearrangements. The duplicated genes being the results of 'successful' copies are fixed and maintained in the population. Conversely, many 'unsuccessful' duplicates remain in the genome as pseudogenes. There is another form of genetic variations termed copy-neutral loss of heterozygosity (LOH) with less information about their potential impact on complex diseases. Additional studies would include associated gene expression variations with either SNPs or CNVs. Now many genetic techniques such as PCR, real time PCR, microarray and restriction fragment length analysis are available for detecting genetic polymorphisms, gene mapping and estimation of gene expression. Recently, the scientists have used these tools to define genetic signatures of disease, to understand genetic causes of disease and to characterize the effects of certain drugs on gene expression. This review highlights the principles, technology and applications on

  6. The molecular genetics of Marfan syndrome and related disorders

    Science.gov (United States)

    Robinson, P N; Arteaga‐Solis, E; Baldock, C; Collod‐Béroud, G; Booms, P; De Paepe, A; Dietz, H C; Guo, G; Handford, P A; Judge, D P; Kielty, C M; Loeys, B; Milewicz, D M; Ney, A; Ramirez, F; Reinhardt, D P; Tiedemann, K; Whiteman, P; Godfrey, M

    2006-01-01

    Marfan syndrome (MFS), a relatively common autosomal dominant hereditary disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular systems, is caused by mutations in the gene for fibrillin‐1 (FBN1). The leading cause of premature death in untreated individuals with MFS is acute aortic dissection, which often follows a period of progressive dilatation of the ascending aorta. Recent research on the molecular physiology of fibrillin and the pathophysiology of MFS and related disorders has changed our understanding of this disorder by demonstrating changes in growth factor signalling and in matrix‐cell interactions. The purpose of this review is to provide a comprehensive overview of recent advances in the molecular biology of fibrillin and fibrillin‐rich microfibrils. Mutations in FBN1 and other genes found in MFS and related disorders will be discussed, and novel concepts concerning the complex and multiple mechanisms of the pathogenesis of MFS will be explained. PMID:16571647

  7. [Molecular genetic examination in sex-linked color blindness].

    Science.gov (United States)

    Ladekjaer-Mikkelsen, A S; Jensen, H; Rosenberg, T; Jørgensen, A L

    1995-08-28

    The molecular structure of the X-linked colour-vision locus was studied in a family where mild red-green colour-vision deficiency (deuteranomaly) segregated, and in a male with complete absence of red and green colour-vision (blue cone monochromasy). In individuals with normal colour-vision the red and green pigment genes had normal molecular structure whereas individuals with deuteranomaly, in addition to normal red and green genes, also had an abnormal hybrid gene consisting of parts of the green and red pigment genes. The individual with blue cone monocromasy had only a red-green hybrid gene inactivated by a critical mutation in codon 203. Thus, the phenotypes predicted from the individual genotypes were in complete accord with the observed phenotypes.

  8. Clinical, Molecular, and Genetic Characteristics of PAPA Syndrome: A Review.

    Science.gov (United States)

    Smith, Elisabeth J; Allantaz, Florence; Bennett, Lynda; Zhang, Dongping; Gao, Xiaochong; Wood, Geryl; Kastner, Daniel L; Punaro, Marilynn; Aksentijevich, Ivona; Pascual, Virginia; Wise, Carol A

    2010-11-01

    PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) is an autosomal dominant, hereditary auto-inflammatory disease arising from mutations in the PSTPIP1/CD2BP1 gene on chromosome 15q. These mutations produce a hyper-phosphorylated PSTPIP1 protein and alter its participation in activation of the "inflammasome" involved in interleukin-1 (IL-1β) production. Overproduction of IL-1β is a clear molecular feature of PAPA syndrome. Ongoing research is implicating other biochemical pathways that may be relevant to the distinct pyogenic inflammation of the skin and joints characteristic of this disease. This review summarizes the recent and rapidly accumulating knowledge on these molecular aspects of PAPA syndrome and related disorders.

  9. Molecular genetics and diagnosis of phenylketonuria: state of the art.

    Science.gov (United States)

    Blau, Nenad; Shen, Nan; Carducci, Carla

    2014-07-01

    Detection of individuals with phenylketonuria (PKU), an autosomal recessively inherited disorder in phenylalanine degradation, is straightforward and efficient due to newborn screening programs. A recent introduction of the pharmacological treatment option emerged rapid development of molecular testing. However, variants responsible for PKU do not all suppress enzyme activity to the same extent. A spectrum of over 850 variants, gives rise to a continuum of hyperphenylalaninemia from very mild, requiring no intervention, to severe classical PKU, requiring urgent intervention. Locus-specific and genotypes database are today an invaluable resource of information for more efficient classification and management of patients. The high-tech molecular methods allow patients' genotype to be obtained in a few days, especially if each laboratory develops a panel for the most frequent variants in the corresponding population.

  10. MILLIMETER-SCALE GENETIC GRADIENTS AND COMMUNITY-LEVEL MOLECULAR CONVERGENCE IN A HYPERSALINE MICROBIAL MAT

    Energy Technology Data Exchange (ETDEWEB)

    Fenner, Marsha W; Kunin, Victor; Raes, Jeroen; Harris, J. Kirk; Spear, John R.; Walker, Jeffrey J.; Ivanova, Natalia; Mering, Christian von; Bebout, Brad M.; Pace, Norman R.; Bork, Peer; Hugenholtz, Philip

    2008-04-30

    To investigate the extent of genetic stratification in structured microbial communities, we compared the metagenomes of 10 successive layers of a phylogenetically complex hypersaline mat from Guerrero Negro, Mexico. We found pronounced millimeter-scale genetic gradients that are consistent with the physicochemical profile of the mat. Despite these gradients, all layers displayed near identical and acid-shifted isoelectric point profiles due to a molecular convergence of amino acid usage indicating that hypersalinity enforces an overriding selective pressure on the mat community.

  11. The genetic and molecular regulation of sleep: from fruit flies to humans

    OpenAIRE

    Cirelli, Chiara

    2009-01-01

    It has been known for a long time that genetic factors affect sleep quantity and quality. Genetic screens identified several mutations that affect sleep across species, pointing to an evolutionary conserved regulation of sleep. Moreover, it has also been recognized that sleep affects the expression of genes. These findings have given valuable clues about the molecular underpinnings of sleep regulation and function that might lead the way to more efficient treatments for sleep disorders.

  12. Clinical, Molecular, and Genetic Characteristics of PAPA Syndrome: A Review

    OpenAIRE

    Smith, Elisabeth J; Allantaz, Florence; Bennett, Lynda; Zhang, Dongping; Gao, Xiaochong; Wood, Geryl; Kastner, Daniel L.; Punaro, Marilynn; Aksentijevich, Ivona; Pascual, Virginia; Wise, Carol A.

    2010-01-01

    PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) is an autosomal dominant, hereditary auto-inflammatory disease arising from mutations in the PSTPIP1/CD2BP1 gene on chromosome 15q. These mutations produce a hyper-phosphorylated PSTPIP1 protein and alter its participation in activation of the “inflammasome” involved in interleukin-1 (IL-1β) production. Overproduction of IL-1β is a clear molecular feature of PAPA syndrome. Ongoing research is implicating other biochemical path...

  13. Genetic Diversity of Some Sweet Cherry Cultivars Based on Molecular Markers

    Directory of Open Access Journals (Sweden)

    Ioana Virginia Berindean

    2016-11-01

    Full Text Available Sweet cherry (Prunus avium L., originated around the Caspian and Black Sea, is an important fruit tree species of economic interest, and hence, breeding and conservation are requested (. Genetic analysis at the molecular level can be used effectively to study molecular polymorphism existing between intraspecific and interspecific tree species and phylogenetic relationships between them and their hybrids. The purpose of this study was to characterize and determine genetic relationships among the sweet cherry native genotypes belonging to Fruit Research & Development Station Bistrita, Romania, using RAPD markers. To eliminate the existence of possible synonyms from national romanian collection, we collect four Van cultivars, from four different national collection. For molecular analysis of the 16 varieties of sweet cherry were considered 13 RAPD primers selected from the literature. They were later used to determine the genetic variability at the molecular level using PAST program, and the dendrogram was generated based on Jaccard’s genetic distance. The dendrogram constructed by PAST software. The quantity and quality of the DNA obtained was suitable to achieve PCR amplification step. Only seven out of the 13 RAPD primers have generate polymorphic bands. The rest of seven were monomorphics. The most polymorphic primer was OPB10 which generated 11 bands from which 100% were polymorphic.Seven RAPD primers generated a high level of polymorphism which allowed to divide these cherry varieties into two groups according to their genetic geographical origin and the pedigree.

  14. Contrasting results from molecular and pedigree-based population diversity measures in captive zebra highlight challenges facing genetic management of zoo populations.

    Science.gov (United States)

    Ito, Hideyuki; Ogden, Rob; Langenhorst, Tanya; Inoue-Murayama, Miho

    2017-01-01

    Zoo conservation breeding programs manage the retention of population genetic diversity through analysis of pedigree records. The range of demographic and genetic indices determined through pedigree analysis programs allows the conservation of diversity to be monitored relative to the particular founder population for a species. Such approaches are based on a number of well-documented founder assumptions, however without knowledge of actual molecular genetic diversity there is a risk that pedigree-based measures will be misinterpreted and population genetic diversity misunderstood. We examined the genetic diversity of the captive populations of Grevy's zebra, Hartmann's mountain zebra and plains zebra in Japan and the United Kingdom through analysis of mitochondrial DNA sequences. Very low nucleotide variability was observed in Grevy's zebra. The results were evaluated with respect to current and historic diversity in the wild, and indicate that low genetic diversity in the captive population is likely a result of low founder diversity, which in turn suggests relatively low wild genetic diversity prior to recent population declines. Comparison of molecular genetic diversity measures with analogous diversity indices generated from the studbook data for Grevy's zebra and Hartmann's mountain zebra show contrasting patterns, with Grevy's zebra displaying markedly less molecular diversity than mountain zebra, despite studbook analysis indicating that the Grevy's zebra population has substantially more founders, greater effective population size, lower mean kinship, and has suffered less loss of gene diversity. These findings emphasize the need to validate theoretical estimates of genetic diversity in captive breeding programs with empirical molecular genetic data. Zoo Biol. 36:87-94, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Translating clinical research of Molecular Biology into a personalized, multidisciplinary approach of colorectal cancer patients.

    Science.gov (United States)

    Strambu, V; Garofil, D; Pop, F; Radu, P; Bratucu, M; Popa, F

    2014-03-15

    Although multimodal treatment has brought important benefit, there is still great heterogeneity regarding the indication and response to chemotherapy in Stage II and III, and individual variations related to both overall survival and toxicity of new therapies in metastatic disease or tumor relapse. Recent research in molecular biology led to the development of a large scale of genetic biomarkers, but their clinical use is not concordant with the high expectations. The Aim of this review is to identify and discuss the molecular markers with proven clinical applicability as prognostic and/or predictive factors in CRC and also to establish a feasible algorithm of molecular testing, as routine practice, in the personalized, multidisciplinary approach of colorectal cancer patients in our country. Despite the revolution that occurred in the field of molecular marker research, only Serum CEA, Immunohistochemical analysis of mismatch repair proteins and PCR testing for KRAS and BRAF mutations have confirmed their clinical utility in the management of colorectal cancer. Their implementation in the current practice should partially resolve some of the controversies related to this heterogenic pathology, in matters of prognosis in different TNM stages, stage II patient risk stratification, diagnosis of hereditary CRC and likelihood of benefit from anti EGFR therapy in metastatic disease. The proposed algorithms of molecular testing are very useful but still imperfect and require further validation and constant optimization.

  16. Genetic Diversity and Molecular Evolution of Chinese Waxy Maize Germplasm

    Science.gov (United States)

    Zheng, Hongjian; Wang, Hui; Yang, Hua; Wu, Jinhong; Shi, Biao; Cai, Run; Xu, Yunbi; Wu, Aizhong; Luo, Lijun

    2013-01-01

    Waxy maize (Zea mays L. var. certaina Kulesh), with many excellent characters in terms of starch composition and economic value, has grown in China for a long history and its production has increased dramatically in recent decades. However, the evolution and origin of waxy maize still remains unclear. We studied the genetic diversity of Chinese waxy maize including typical landraces and inbred lines by SSR analysis and the results showed a wide genetic diversity in the Chinese waxy maize germplasm. We analyzed the origin and evolution of waxy maize by sequencing 108 samples, and downloading 52 sequences from GenBank for the waxy locus in a number of accessions from genus Zea. A sharp reduction of nucleotide diversity and significant neutrality tests (Tajima’s D and Fu and Li’s F*) were observed at the waxy locus in Chinese waxy maize but not in nonglutinous maize. Phylogenetic analysis indicated that Chinese waxy maize originated from the cultivated flint maize and most of the modern waxy maize inbred lines showed a distinct independent origin and evolution process compared with the germplasm from Southwest China. The results indicated that an agronomic trait can be quickly improved to meet production demand by selection. PMID:23818949

  17. Molecular, genetic, and cellular bases for treating eosinophilic esophagitis.

    Science.gov (United States)

    Rothenberg, Marc E

    2015-05-01

    Eosinophilic esophagitis (EoE) was historically distinguished from gastroesophageal reflux disease on the basis of histology and lack of responsiveness to acid suppressive therapy, but it is now appreciated that esophageal eosinophilia can respond to proton pump inhibitors. Genetic and environmental factors contribute to risk for EoE, particularly early-life events. Disease pathogenesis involves activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]), impaired barrier function (mediated by loss of desmoglein-1), increased production and/or activity of transforming growth factor-β, and induction of allergic inflammation by eosinophils and mast cells. Susceptibility has been associated with variants at 5q22 (TSLP) and 2p23 (CAPN14), indicating roles for allergic sensitization and esophageal specific protease pathways. We propose that EoE is a unique disease characterized by food hypersensitivity; strong hereditability influenced by early-life exposures and esophageal-specific genetic risk variants; and allergic inflammation and that the disease is remitted by disrupting inflammatory and T-helper type 2 cytokine-mediated responses and through dietary elimination therapy.

  18. Molecular genetics of cancer and tumorigenesis: Drosophila models

    Institute of Scientific and Technical Information of China (English)

    Wu-Min Deng

    2011-01-01

    Why do some cells not respond to normal control of cell division and become tumorous? Which signals trigger some tumor cells to migrate and colonize other tissues? What genetic factors are responsible for tumorigenesis and cancer development? What environmental factors play a role in cancer formation and progression? In how many ways can our bodies prevent and restrict the growth of cancerous cells?How can we identify and deliver effective drugs to fight cancer? In the fight against cancer,which kills more people than any other disease,these and other questions have long interested researchers from a diverse range of fields.To answer these questions and to fight cancer more effectively,we must increase our understanding of basic cancer biology.Model organisms,including the fruit fly Drosophila melanogaster,have played instrumental roles in our understanding of this devastating disease and the search for effective cures.Drosophila and its highly effective,easy-touse,and ever-expanding genetic tools have contributed toand enriched our knowledge of cancer and tumor formation tremendously.

  19. Inflammation in Alzheimer's Disease and Molecular Genetics: Recent Update.

    Science.gov (United States)

    Zhang, Zhi-Gang; Li, Yan; Ng, Cheung Toa; Song, You-Qiang

    2015-10-01

    Alzheimer's disease (AD) is a complex age-related neurodegenerative disorder of the central nervous system. Since the first description of AD in 1907, many hypotheses have been established to explain its causes. The inflammation theory is one of them. Pathological and biochemical studies of brains from AD individuals have provided solid evidence of the activation of inflammatory pathways. Furthermore, people with long-term medication of anti-inflammatory drugs have shown a reduced risk to develop the disease. After three decades of genetic study in AD, dozens of loci harboring genetic variants influencing inflammatory pathways in AD patients has been identified through genome-wide association studies (GWAS). The most well-known GWAS risk factor that is responsible for immune response and inflammation in AD development should be APOE ε4 allele. However, a growing number of other GWAS risk AD candidate genes in inflammation have recently been discovered. In the present study, we try to review the inflammation in AD and immunity-associated GWAS risk genes like HLA-DRB5/DRB1, INPP5D, MEF2C, CR1, CLU and TREM2.

  20. Molecular genetics of mosquito resistance to malaria parasites.

    Science.gov (United States)

    Vernick, K D; Oduol, F; Lazzaro, B P; Glazebrook, J; Xu, J; Riehle, M; Li, J

    2005-01-01

    Malaria parasites are transmitted by the bite of an infected mosquito, but even efficient vector species possess multiple mechanisms that together destroy most of the parasites present in an infection. Variation between individual mosquitoes has allowed genetic analysis and mapping of loci controlling several resistance traits, and the underlying mechanisms of mosquito response to infection are being described using genomic tools such as transcriptional and proteomic analysis. Malaria infection imposes fitness costs on the vector, but various forms of resistance inflict their own costs, likely leading to an evolutionary tradeoff between infection and resistance. Plasmodium development can be successfully completed onlyin compatible mosquito-parasite species combinations, and resistance also appears to have parasite specificity. Studies of Drosophila, where genetic variation in immunocompetence is pervasive in wild populations, offer a comparative context for understanding coevolution of the mosquito-malaria relationship. More broadly, plants also possess systems of pathogen resistance with features that are structurally conserved in animal innate immunity, including insects, and genomic datasets now permit useful comparisons of resistance models even between such diverse organisms.

  1. Genetic diversity and molecular evolution of Chinese waxy maize germplasm.

    Directory of Open Access Journals (Sweden)

    Hongjian Zheng

    Full Text Available Waxy maize (Zea mays L. var. certaina Kulesh, with many excellent characters in terms of starch composition and economic value, has grown in China for a long history and its production has increased dramatically in recent decades. However, the evolution and origin of waxy maize still remains unclear. We studied the genetic diversity of Chinese waxy maize including typical landraces and inbred lines by SSR analysis and the results showed a wide genetic diversity in the Chinese waxy maize germplasm. We analyzed the origin and evolution of waxy maize by sequencing 108 samples, and downloading 52 sequences from GenBank for the waxy locus in a number of accessions from genus Zea. A sharp reduction of nucleotide diversity and significant neutrality tests (Tajima's D and Fu and Li's F* were observed at the waxy locus in Chinese waxy maize but not in nonglutinous maize. Phylogenetic analysis indicated that Chinese waxy maize originated from the cultivated flint maize and most of the modern waxy maize inbred lines showed a distinct independent origin and evolution process compared with the germplasm from Southwest China. The results indicated that an agronomic trait can be quickly improved to meet production demand by selection.

  2. [Genetic and molecular background in autoimmune diabetes mellitus].

    Science.gov (United States)

    Kantárová, D; Prídavková, D; Ságová, I; Vrlík, M; Mikler, J; Buc, M

    2015-09-01

    Type 1 diabetes mellitus (T1 DM) is caused by autoimmune-mediated and idiopathic beta-cell destruction of the pancreatic islets of Langerhans resulting in absolute insulin deficiency. Susceptibility to T1 DM is influenced by both genetic and environmental factors. It is generally believed that in genetically susceptible individuals, the disease is triggered by environmental agents, such as viral infections, dietary factors in early infancy, or climatic influences. Many candidate genes for diabetes have been reported; those within the Major Histocompatibility Complex being among the most important. The most common autoantigens are insulin, glutamic acid decarboxylase 65, insuloma-associated antigen 2, and zinc transporter ZnT8. The destruction of beta-cells is mediated mainly by cellular mechanisms; antibodies only seem to reflect the ongoing autoimmune processes and are not directly involved in the tissue damage. They, however, appear prior to the onset of insulin deficiency which makes them suitable for use in the prevention of the disease.

  3. Genetic diversity and molecular genealogy of local silkworm varieties

    Directory of Open Access Journals (Sweden)

    Zhouhe Du

    2013-03-01

    Full Text Available In order to explore the genetic diversity and systematic differentiation pattern among silkworm varieties, aiming to guide hybridization breeding, we sequenced a total of 72 Bmamy2 gene fragments from local silkworm varieties. The analysis of nucleotide sequence diversity and systematic differentiation indicated that there was rich genovariation in the sequencing region of Bmamy2 gene, and the base mutation rate is 5.6–8.2%, the haplotype diversity is 0.8294, and the nucleotide diversity is 0.0236±0.00122, suggesting Bmamy2 being a better marking gene with rich nucleotide sequence diversity, based on which the genetic diversity among different local silkworm varieties can be identified. The same heredity population structure is proclaimed by several analysis methods that every clade consisting of varieties from different geosystems and ecological types, while the varieties from the same geosystem and ecotype belong to different clades in the phylogeny. There is no population structure pattern that different varieties claded together according to geosystem or ecotype. It can be speculated that the silkworm origins from mixture of kinds of several voltinism mulberry silkworm, Bombyx mandarina, while the domestication events took place in several regions, from which the domesticated mulberry silkworms are all devoting to the domesticated silkworm population of today.

  4. Patterns of molecular genetic variation among cat breeds.

    Science.gov (United States)

    Menotti-Raymond, Marilyn; David, Victor A; Pflueger, Solveig M; Lindblad-Toh, Kerstin; Wade, Claire M; O'Brien, Stephen J; Johnson, Warren E

    2008-01-01

    Genetic variation in cat breeds was assessed utilizing a panel of short tandem repeat (STR) loci genotyped in 38 cat breeds and 284 single-nucleotide polymorphisms (SNPs) genotyped in 24 breeds. Population structure in cat breeds generally reflects their recent ancestry and absence of strong breed barriers between some breeds. There is a wide range in the robustness of population definition, from breeds demonstrating high definition to breeds with as little as a third of their genetic variation partitioning into a single population. Utilizing the STRUCTURE algorithm, there was no clear demarcation of the number of population subdivisions; 16 breeds could not be resolved into independent populations, the consequence of outcrossing in established breeds to recently developed breeds with common ancestry. These 16 breeds were divided into 6 populations. Ninety-six percent of cats in a sample set of 1040 were correctly assigned to their classified breed or breed group/population. Average breed STR heterozygosities ranged from moderate (0.53; Havana, Korat) to high (0.85; Norwegian Forest Cat, Manx). Most of the variation in cat breeds was observed within a breed population (83.7%), versus 16.3% of the variation observed between populations. The hierarchical relationships of cat breeds is poorly defined as demonstrated by phylogenetic trees generated from both STR and SNP data, though phylogeographic grouping of breeds derived completely or in part from Southeast Asian ancestors was apparent.

  5. Genetics in psychosomatic medicine : research designs and statistical approaches

    NARCIS (Netherlands)

    McCaffery, Jeanne M.; Snieder, Harold; Dong, Yanbin; de Geus, Eco

    2007-01-01

    It has become increasingly clear that genetic factors influence many of the behaviors and disease endpoints of interest to psychosomatic medicine researchers. There has been increasing interest in incorporating genetic variation markers into psychosomatic research. In this Statistical Corner article

  6. Pseudomonas viridiflava, a multi host plant pathogen with significant genetic variation at the molecular level.

    Directory of Open Access Journals (Sweden)

    Panagiotis F Sarris

    Full Text Available The pectinolytic species Pseudomonas viridiflava has a wide host range among plants, causing foliar and stem necrotic lesions and basal stem and root rots. However, little is known about the molecular evolution of this species. In this study we investigated the intraspecies genetic variation of P. viridiflava amongst local (Cretan, as well as international isolates of the pathogen. The genetic and phenotypic variability were investigated by molecular fingerprinting (rep-PCR and partial sequencing of three housekeeping genes (gyrB, rpoD and rpoB, and by biochemical and pathogenicity profiling. The biochemical tests and pathogenicity profiling did not reveal any variability among the isolates studied. However, the molecular fingerprinting patterns and housekeeping gene sequences clearly differentiated them. In a broader phylogenetic comparison of housekeeping gene sequences deposited in GenBank, significant genetic variability at the molecular level was found between isolates of P. viridiflava originated from different host species as well as among isolates from the same host. Our results provide a basis for more comprehensive understanding of the biology, sources and shifts in genetic diversity and evolution of P. viridiflava populations and should support the development of molecular identification tools and epidemiological studies in diseases caused by this species.

  7. Strengthening molecular genetics and training in craniosynostosis: The need of the hour

    Science.gov (United States)

    Barik, Mayadhar; Bajpai, Minu; Panda, Shasanka Shekhar; Malhotra, Arun; Samantaray, Jyotish Chandra; Dwivedi, Sada Nanda

    2014-01-01

    Craniosynostosis (CS) is premature fusion of skull. It is divided into two groups: Syndromic craniosynostosis (SCS) and non-syndromic craniosynostosis (NSC). Its incidence in Indian population is 1:1000 live births where as in the USA it is 1:2500 live births. Its incidence varies from country to country. Molecular genetics having great interest and relevance in medical students, faculty, scientist, pediatric neurosurgeon and staff nurses, our objective was to educate the medical students, residents, researchers, clinicians, pediatric neurosurgeon, anesthetists, pediatricians, staff nurses and paramedics. We summarized here including with diagnosis, investigations, surgical therapy, induction therapy, and molecular therapy. Molecular genetics training is needed to know the information regarding development of skull, cranial connective tissue, craniofacial dysplasia, frame work, network of receptors and its etiopathogenesis. The important part is clinically with molecular therapy (MT) how to manage CS in rural sector and metropolitan cities need a special attention. PMID:25288859

  8. Strengthening molecular genetics and training in craniosynostosis: The need of the hour

    Directory of Open Access Journals (Sweden)

    Mayadhar Barik

    2014-01-01

    Full Text Available Craniosynostosis (CS is premature fusion of skull. It is divided into two groups: Syndromic craniosynostosis (SCS and non-syndromic craniosynostosis (NSC. Its incidence in Indian population is 1:1000 live births where as in the USA it is 1:2500 live births. Its incidence varies from country to country. Molecular genetics having great interest and relevance in medical students, faculty, scientist, pediatric neurosurgeon and staff nurses, our objective was to educate the medical students, residents, researchers, clinicians, pediatric neurosurgeon, anesthetists, pediatricians, staff nurses and paramedics. We summarized here including with diagnosis, investigations, surgical therapy, induction therapy, and molecular therapy. Molecular genetics training is needed to know the information regarding development of skull, cranial connective tissue, craniofacial dysplasia, frame work, network of receptors and its etiopathogenesis. The important part is clinically with molecular therapy (MT how to manage CS in rural sector and metropolitan cities need a special attention.

  9. Approach to the genetics of alcoholism: a review based on pathophysiology.

    Science.gov (United States)

    Köhnke, Michael D

    2008-01-01

    Alcohol dependence is a common disorder with a heterogenous etiology. The results of family, twin and adoption studies on alcoholism are reviewed. These studies have revealed a heritability of alcoholism of over 50%. After evaluating the results, it was epidemiologically stated that alcoholism is heterogenous complex disorder with a multiple genetic background. Modern molecular genetic techniques allow examining specific genes involved in the pathophysiology of complex diseases such as alcoholism. Strategies for gene identification are introduced to the reader, including family-based and association studies. The susceptibility genes that are in the focus of this article have been chosen because they are known to encode for underlying mechanisms that are linked to the pathophysiology of alcoholism or that are important for the pharmacotherapeutic approaches in the treatment of alcohol dependence. Postulated candidate genes of the metabolism of alcohol and of the involved neurotransmitter systems are introduced. Genetic studies on alcoholism examining the metabolism of alcohol and the dopaminergic, GABAergic, glutamatergic, opioid, cholinergic and serotonergic neurotransmitter systems as well as the neuropeptide Y are presented. The results are critically discussed followed by a discussion of possible consequences.

  10. Application of Molecular Genetics to the Investigation of Inherited Bleeding Disorders

    DEFF Research Database (Denmark)

    Lethagen, Stefan Rune; Dunø, Morten; Nielsen, Lars Bo

    2013-01-01

    22. In hemophilia B, more than 1100 unique F9 mutations have been described scattered all over the gene. Carrier analysis, genetic counseling, prenatal and pre-implantation genetic diagnosis are all based on correct identifying the disease-causing mutation. Linkage analysis can be considered when...... the causative mutation is unknown. More rare bleeding disorders are generally recessively inherited, and are often caused by mutations that are specific for individual families, and mutations are scattered throughout the genes. Laboratories performing molecular genetic analyses must have validated internal...

  11. Radiation mutagenesis from molecular and genetic points of view

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Park, M.S.; Okinaka, R.T.; Jaberaboansari, A.

    1993-01-01

    An important biological effect of ionizing radiation on living organisms is mutation induction. Mutation is also a primary event in the etiology of cancer. The chain events, from induction of DNA damage by ionizing radiation to processing of these damages by the cellular repair/replication machinery, that lead to mutation are not well understood. The development of quantitative methods for measuring mutation-induction, such as the HPRT system, in cultured mammalian cells has provided an estimate of the mutagenic effects of x- and [gamma]-rays as wen as of high LET radiation in both rodent and human cells. A major conclusion from these mutagenesis data is that high LET radiation induces mutations more efficiently than g-rays. Molecular analysis of mutations induced by sparsely ionizing radiation have detected major structural alterations at the gene level. Our molecular results based on analysis of human HPRT deficient mutants induced by [gamma]-rays, [alpha]-particles and high energy charged particles indicate that higher LET radiation induce more total and large deletion mutations than [gamma]-rays. Utilizing molecular techniques including polymerase chain reaction (PCR), Single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE) and Direct DNA sequencing, mutational spectra induced by ionizing radiation have been compared in different cell systems. Attempts have also been made to determine the mutagenic potential and the nature of mutation induced by low dose rate [gamma]-rays. Defective repair, in the form of either a diminished capability for repair or inaccurate repair, can lead to increased risk of heritable mutations from radiation exposure. Therefore, the effects of DNA repair deficiency on the mutation induction in mammalian cells is reviewed.

  12. Radiation mutagenesis from molecular and genetic points of view

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Park, M.S.; Okinaka, R.T.; Jaberaboansari, A.

    1993-02-01

    An important biological effect of ionizing radiation on living organisms is mutation induction. Mutation is also a primary event in the etiology of cancer. The chain events, from induction of DNA damage by ionizing radiation to processing of these damages by the cellular repair/replication machinery, that lead to mutation are not well understood. The development of quantitative methods for measuring mutation-induction, such as the HPRT system, in cultured mammalian cells has provided an estimate of the mutagenic effects of x- and {gamma}-rays as wen as of high LET radiation in both rodent and human cells. A major conclusion from these mutagenesis data is that high LET radiation induces mutations more efficiently than g-rays. Molecular analysis of mutations induced by sparsely ionizing radiation have detected major structural alterations at the gene level. Our molecular results based on analysis of human HPRT deficient mutants induced by {gamma}-rays, {alpha}-particles and high energy charged particles indicate that higher LET radiation induce more total and large deletion mutations than {gamma}-rays. Utilizing molecular techniques including polymerase chain reaction (PCR), Single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE) and Direct DNA sequencing, mutational spectra induced by ionizing radiation have been compared in different cell systems. Attempts have also been made to determine the mutagenic potential and the nature of mutation induced by low dose rate {gamma}-rays. Defective repair, in the form of either a diminished capability for repair or inaccurate repair, can lead to increased risk of heritable mutations from radiation exposure. Therefore, the effects of DNA repair deficiency on the mutation induction in mammalian cells is reviewed.

  13. Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation

    Energy Technology Data Exchange (ETDEWEB)

    Calin-Jageman, Robert J

    2009-09-12

    Work funded on this grant has explored the mechanisms of long-term habituation, a ubiquitous form of learning that plays a key role in basic cognitive functioning. Specifically, behavioral, physiological, and molecular mechanisms of habituation have been explored using a simple model system, the tail-elicited siphon-withdrawal reflex (T-SWR) in the marine mollusk Aplysia californica. Substantial progress has been made on the first and third aims, providing some fundamental insights into the mechanisms by which memories are stored. We have characterized the physiological correlates of short- and long-term habituation. We found that short-term habituation is accompanied by a robust sensory adaptation, whereas long-term habituation is accompanied by alterations in sensory and interneuron synaptic efficacy. Thus, our data indicates memories can be shifted between different sites in a neural network as they are consolidated from short to long term. At the molecular level, we have accomplished microarray analysis comparing gene expression in both habituated and control ganglia. We have identified a network of putatively regulated transcripts that seems particularly targeted towards synaptic changes (e.g. SNAP25, calmodulin) . We are now beginning additional work to confirm regulation of these transcripts and build a more detailed understanding of the cascade of molecular events leading to the permanent storage of long-term memories. On the third aim, we have fostered a nascent neuroscience program via a variety of successful initiatives. We have funded over 11 undergraduate neuroscience scholars, several of whom have been recognized at national and regional levels for their research. We have also conducted a pioneering summer research program for community college students which is helping enhance access of underrepresented groups to life science careers. Despite minimal progress on the second aim, this project has provided a) novel insight into the network mechanisms by

  14. Tailoring approach for obtaining molecular orbitals of large systems

    Indian Academy of Sciences (India)

    Anuja P Rahalkar; Shridhar R Gadre

    2012-01-01

    Molecular orbitals (MO’s) within Hartree-Fock (HF) theory are of vital importance as they provide preliminary information of bonding and features such as electron localization and chemical reactivity. The contemporary literature treats the Kohn-Sham orbitals within density functional theory (DFT) equivalently to the MO's obtained within HF framework. The high scaling order of ab initio methods is the main hurdle in obtaining the MO's for large molecular systems. With this view, an attempt is made in the present work to employ molecular tailoring approach (MTA) for obtaining the complete set of MO's including occupied and virtual orbitals, for large molecules at HF and B3LYP levels of theory. The energies of highest occupied and lowest unoccupied molecular orbitals, and hence the band gaps, are accurately estimated by MTA for most of the test cases benchmarked in this study, which include -conjugated molecules. Typically, the root mean square errors of valence MO's are in range of 0.001 to 0.010 a.u. for all the test cases examined. MTA shows a time advantage factor of 2 to 3 over the corresponding actual calculation, for many of the systems reported.

  15. Molecular genetics and the evolution of ultraviolet vision in vertebrates

    Science.gov (United States)

    Shi, Yongsheng; Radlwimmer, F. Bernhard; Yokoyama, Shozo

    2001-01-01

    Despite the biological importance of UV vision, its molecular bases are not well understood. Here, we present evidence that UV vision in vertebrates is determined by eight specific amino acids in the UV pigments. Amino acid sequence analyses show that contemporary UV pigments inherited their UV sensitivities from the vertebrate ancestor by retaining most of these eight amino acids. In the avian lineage, the ancestral pigment lost UV sensitivity, but some descendants regained it by one amino acid change. Our results also strongly support the hypothesis that UV pigments have an unprotonated Schiff base-linked chromophore. PMID:11573008

  16. Genetics of Tinnitus: An Emerging Area for Molecular Diagnosis and Drug Development

    Science.gov (United States)

    Lopez-Escamez, Jose A.; Bibas, Thanos; Cima, Rilana F. F.; Van de Heyning, Paul; Knipper, Marlies; Mazurek, Birgit; Szczepek, Agnieszka J.; Cederroth, Christopher R.

    2016-01-01

    Subjective tinnitus is the perception of sound in the absence of external or bodily-generated sounds. Chronic tinnitus is a highly prevalent condition affecting over 70 million people in Europe. A wide variety of comorbidities, including hearing loss, psychiatric disorders, neurodegenerative disorders, and temporomandibular joint (TMJ) dysfunction, have been suggested to contribute to the onset or progression of tinnitus; however, the precise molecular mechanisms of tinnitus are not well understood and the contribution of genetic and epigenetic factors remains unknown. Human genetic studies could enable the identification of novel molecular therapeutic targets, possibly leading to the development of novel pharmaceutical therapeutics. In this article, we briefly discuss the available evidence for a role of genetics in tinnitus and consider potential hurdles in designing genetic studies for tinnitus. Since multiple diseases have tinnitus as a symptom and the supporting genetic evidence is sparse, we propose various strategies to investigate the genetic underpinnings of tinnitus, first by showing evidence of heritability using concordance studies in twins, and second by improving patient selection according to phenotype and/or etiology in order to control potential biases and optimize genetic data output. The increased knowledge resulting from this endeavor could ultimately improve the drug development process and lead to the preventive or curative treatment of tinnitus. PMID:27594824

  17. Genetics of tinnitus: an emerging area for molecular diagnosis and drug development

    Directory of Open Access Journals (Sweden)

    Jose Antonio Lopez-Escamez

    2016-08-01

    Full Text Available Subjective tinnitus is the perception of sound in the absence of external or bodily-generated sounds. Chronic tinnitus is a highly prevalent condition affecting over 70 million people in Europe. A wide variety of comorbidities, including hearing loss, psychiatric disorders, neurodegenerative disorders and temporomandibular joint dysfunction, have been suggested to contribute to the onset or progression of tinnitus, however the precise molecular mechanisms of tinnitus are not well understood and the contribution of genetic and epigenetic factors remains unknown. Human genetic studies could enable the identification of novel molecular therapeutic targets, possibly leading to the development of novel pharmaceutical therapeutics. In this article, we briefly discuss the available evidence for a role of genetics in tinnitus and consider potential hurdles in designing genetic studies for tinnitus. Since multiple diseases have tinnitus as a symptom and the supporting genetic evidence is sparse, we propose various strategies to investigate the genetic underpinnings of tinnitus, first by showing evidence of heritability using concordance studies in twins, and second by improving patient selection according to phenotype and/or etiology in order to control potential biases and optimize genetic data output. The increased knowledge resulting from this endeavor could ultimately improve the drug development process and lead to the preventive or curative treatment of tinnitus.

  18. Molecular and Genetic Basis of Inherited Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Maddalena Gigante

    2011-01-01

    Full Text Available Nephrotic syndrome is an heterogeneous disease characterized by increased permeability of the glomerular filtration barrier for macromolecules. Podocytes, the visceral epithelial cells of glomerulus, play critical role in ultrafiltration of plasma and are involved in a wide number of inherited and acquired glomerular diseases. The identification of mutations in nephrin and other podocyte genes as causes of genetic forms of nephrotic syndrome has revealed new important aspects of the pathogenesis of proteinuric kidney diseases and expanded our knowledge of the glomerular biology. Moreover, a novel concept of a highly dynamic slit diaphragm proteins is emerging. The most significant discoveries in our understanding of the structure and function of the glomerular filtration barrier are reviewed in this paper.

  19. Electroactive bacteria--molecular mechanisms and genetic tools.

    Science.gov (United States)

    Sydow, Anne; Krieg, Thomas; Mayer, Florian; Schrader, Jens; Holtmann, Dirk

    2014-10-01

    In nature, different bacteria have evolved strategies to transfer electrons far beyond the cell surface. This electron transfer enables the use of these bacteria in bioelectrochemical systems (BES), such as microbial fuel cells (MFCs) and microbial electrosynthesis (MES). The main feature of electroactive bacteria (EAB) in these applications is the ability to transfer electrons from the microbial cell to an electrode or vice versa instead of the natural redox partner. In general, the application of electroactive organisms in BES offers the opportunity to develop efficient and sustainable processes for the production of energy as well as bulk and fine chemicals, respectively. This review describes and compares key microbiological features of different EAB. Furthermore, it focuses on achievements and future prospects of genetic manipulation for efficient strain development.

  20. Molecular source of biomarkers by genetic engineering techniques

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The mutant lacking ORF469 fragment in Synechocystis sp. PCC 6803 (cyanobacterium) was created by means of DNA recombination. In its genome, ORF469, the key DNA fragment controlling the light-independent pathway of chlorophyll biosynthesis was deleted and replaced by erythromycin resistance cassette. The operation resulted in the fact that the content of chlorophyll in mutant cells was fully controlled by illumination and two kinds of cells were harvested, one is high chlorophyll with concentration of 9.427 m g.mg-1 and the other is low chlorophyll with concentration of 0.695 m g.mg-1. They were subjected to thermal simulation respectively at 300℃ for 100 h. The alkanes biomarkers from pyrolysates were analyzed by GC-MS and main difference between high and low chlorophyll cells was found at their contents of isoprenoid hydrocarbons. Pr/nC17 and Ph/nC18 from pyrolysate of low chlorophyll cells were 0.192 and 0.216 respectively, which were about 1/3 and 1/7 of that from high chlorophyll cells. The results provide direct evidence that isoprenoid hydrocarbons such as phytane(Ph) and pristane (Pr) could be derived from chlorophyll. The lipids in algal cells would be the most important contributors to hydrocarbon production in their thermal degradation. The results also indicated that the combination of molecular biology and organic geochemistry would provide a new path to investigate the molecular sources of biomarkers.

  1. Molecular genetics and evolution of disease resistance in cereals.

    Science.gov (United States)

    Krattinger, Simon G; Keller, Beat

    2016-10-01

    Contents 320 I. 320 II. 321 III. 321 IV. 322 V. 324 VI. 328 VII. 329 330 References 330 SUMMARY: Cereal crops produce a large part of the globally consumed food and feed. Because of the constant presence of devastating pathogens, the molecular characterization of disease resistance is a major research area and highly relevant for breeding. There has been recent and accelerating progress in the understanding of three distinct resistance mechanisms in cereals: resistance conferred by plasma membrane-localized receptor proteins; race-specific resistance conferred by intracellular immune receptors; and quantitative disease resistance. Intracellular immune receptors provide a particularly rich source for evolutionary studies, and have, for example, resulted in the recent discovery of a novel detection mechanism based on integrated decoy domains. Evolutionary studies have also revealed the origins of active resistance genes in both wild progenitors of today's cereals as well as in cultivated forms. In addition, independent evolution of orthologous genes in related cereals has resulted in resistance to different pathogen species. Quantitative resistance genes have been best characterized in wheat. The quantitative resistance genes identified so far in wheat encode transporter proteins or unusual kinase proteins. The recent discoveries in these three different resistance mechanisms have contributed to the basic molecular understanding of cereal immunity against pathogens and have suggested novel applications for resistance breeding.

  2. Master Equation Approach to Molecular Motor's Directed Motion

    Institute of Scientific and Technical Information of China (English)

    FENG Juan; ZHUO Yi-Zhong

    2005-01-01

    @@ The master equation approach based on the periodic one-dimensional three-state hopping model is developed to study the molecular motor's directed motion. An explicit solution Px ( t ) is obtained for the probability distribution as a function of the time for any initial distribution Px(0) with all the transients included. We introduce dj to represent the sub-step lengths, which can reflect how the external load affects the individual rate via load distribution factors θ+j and θ-j. A wide variety of molecular motor behaviour under external load f can readily be obtained by the unequal-distance transition model with load-dependent transition rates. By comparison with the experiments, namely of the drift velocity v and the randomness parameter r versus adenosine triphosphate concentration and external load f, it is shown that the model presented here can rather satisfactorily explain the available data.

  3. Integrating Survey and Molecular Approaches to Better Understand Wildlife Disease Ecology

    Science.gov (United States)

    Cowled, Brendan D.; Ward, Michael P.; Laffan, Shawn W.; Galea, Francesca; Garner, M. Graeme; MacDonald, Anna J.; Marsh, Ian; Muellner, Petra; Negus, Katherine; Quasim, Sumaiya; Woolnough, Andrew P.; Sarre, Stephen D.

    2012-01-01

    Infectious wildlife diseases have enormous global impacts, leading to human pandemics, global biodiversity declines and socio-economic hardship. Understanding how infection persists and is transmitted in wildlife is critical for managing diseases, but our understanding is limited. Our study aim was to better understand how infectious disease persists in wildlife populations by integrating genetics, ecology and epidemiology approaches. Specifically, we aimed to determine whether environmental or host factors were stronger drivers of Salmonella persistence or transmission within a remote and isolated wild pig (Sus scrofa) population. We determined the Salmonella infection status of wild pigs. Salmonella isolates were genotyped and a range of data was collected on putative risk factors for Salmonella transmission. We a priori identified several plausible biological hypotheses for Salmonella prevalence (cross sectional study design) versus transmission (molecular case series study design) and fit the data to these models. There were 543 wild pig Salmonella observations, sampled at 93 unique locations. Salmonella prevalence was 41% (95% confidence interval [CI]: 37–45%). The median Salmonella DICE coefficient (or Salmonella genetic similarity) was 52% (interquartile range [IQR]: 42–62%). Using the traditional cross sectional prevalence study design, the only supported model was based on the hypothesis that abundance of available ecological resources determines Salmonella prevalence in wild pigs. In the molecular study design, spatial proximity and herd membership as well as some individual risk factors (sex, condition score and relative density) determined transmission between pigs. Traditional cross sectional surveys and molecular epidemiological approaches are complementary and together can enhance understanding of disease ecology: abundance of ecological resources critical for wildlife influences Salmonella prevalence, whereas Salmonella transmission is driven by

  4. Integrating survey and molecular approaches to better understand wildlife disease ecology.

    Directory of Open Access Journals (Sweden)

    Brendan D Cowled

    Full Text Available Infectious wildlife diseases have enormous global impacts, leading to human pandemics, global biodiversity declines and socio-economic hardship. Understanding how infection persists and is transmitted in wildlife is critical for managing diseases, but our understanding is limited. Our study aim was to better understand how infectious disease persists in wildlife populations by integrating genetics, ecology and epidemiology approaches. Specifically, we aimed to determine whether environmental or host factors were stronger drivers of Salmonella persistence or transmission within a remote and isolated wild pig (Sus scrofa population. We determined the Salmonella infection status of wild pigs. Salmonella isolates were genotyped and a range of data was collected on putative risk factors for Salmonella transmission. We a priori identified several plausible biological hypotheses for Salmonella prevalence (cross sectional study design versus transmission (molecular case series study design and fit the data to these models. There were 543 wild pig Salmonella observations, sampled at 93 unique locations. Salmonella prevalence was 41% (95% confidence interval [CI]: 37-45%. The median Salmonella DICE coefficient (or Salmonella genetic similarity was 52% (interquartile range [IQR]: 42-62%. Using the traditional cross sectional prevalence study design, the only supported model was based on the hypothesis that abundance of available ecological resources determines Salmonella prevalence in wild pigs. In the molecular study design, spatial proximity and herd membership as well as some individual risk factors (sex, condition score and relative density determined transmission between pigs. Traditional cross sectional surveys and molecular epidemiological approaches are complementary and together can enhance understanding of disease ecology: abundance of ecological resources critical for wildlife influences Salmonella prevalence, whereas Salmonella transmission is

  5. Aptamers generated from cell-SELEX for molecular medicine: a chemical biology approach.

    Science.gov (United States)

    Fang, Xiaohong; Tan, Weihong

    2010-01-19

    Molecular medicine is an emerging field focused on understanding the molecular basis of diseases and translating this information into strategies for diagnosis and therapy. This approach could lead to personalized medical treatments. Currently, our ability to understand human diseases at the molecular level is limited by the lack of molecular tools to identify and characterize the distinct molecular features of the disease state, especially for diseases such as cancer. Among the new tools being developed by researchers including chemists, engineers, and other scientists is a new class of nucleic acid probes called aptamers, which are ssDNA/RNA molecules selected to target a wide range of molecules and even cells. In this Account, we will focus on the use of aptamers, generated from cell-based selections, as a novel molecular tool for cancer research. Cancers originate from mutations of human genes. These genetic alterations result in molecular changes to diseased cells, which, in turn, lead to changes in cell morphology and physiology. For decades, clinicians have diagnosed cancers primarily based on the morphology of tumor cells or tissues. However, this method does not always give an accurate diagnosis and does not allow clinicians to effectively assess the complex molecular alterations that are predictive of cancer progression. As genomics and proteomics do not yet allow a full access to this molecular knowledge, aptamer probes represent one effective and practical avenue toward this goal. One special feature of aptamers is that we can isolate them by selection against cancer cells without prior knowledge of the number and arrangement of proteins on the cellular surface. These probes can identify molecular differences between normal and tumor cells and can discriminate among tumor cells of different classifications, at different disease stages, or from different patients. This Account summarizes our recent efforts to develop aptamers through cell-SELEX for the

  6. [Molecular genetic makers for Vibrio parahaemolyticus--a review].

    Science.gov (United States)

    Han, Haihong; Li, Ning; Guo, Yunchang

    2015-01-04

    Vibrio parahaemolyticus is an important foodborne pathogen, of which the 03:K6 serotype caused many outbreaks in different countries since 1996. Based on the 10 years data (1992-2001) from China, gastroenteritis caused by Vibrio parahaemolyticus accounted for 31.1% of foodborne disease outbreaks that were resulted from microorganisms. Most environmental strains of Vibrio parahaemolyticus are non-pathogenic strains. However, clinical strains can producethermostable direct hemolysin (TDH), TDH-related hemolysin, and other virulence factors. Here we reviewed three commonly used molecular markers for Vibrio parahaemolyticus, including species-specific genes, the virulence genes and pandemic group-specific genes, so that to provide references for the rapid detection of Vibrio parahaemolyticus and the identification of its pathogenic factor.

  7. Molecular genetics and animal models in autistic disorder.

    Science.gov (United States)

    Andres, Christian

    2002-01-01

    Autistic disorder is a behavioural syndrome beginning before the age of 3 years and lasting over the whole lifetime. It is characterised by impaired communication, impaired social interactions, and repetitive interests and behaviour. The prevalence is about 7/10,000 taking a restrictive definition and more than 1/500 with a broader definition, including all the pervasive developmental disorders. The importance of genetic factors has been highlighted by epidemiological studies showing that autistic disorder is one of the most genetic neuropsychiatric diseases. The relative risk of first relatives is about 100-fold higher than the risk in the normal population and the concordance in monozygotic twin is about 60%. Different strategies have been applied on the track of susceptibility genes. The systematic search of linked loci led to contradictory results, in part due to the heterogeneity of the clinical definitions, to the differences in the DNA markers, and to the different methods of analysis used. An oversimplification of the inferred model is probably also cause of our disappointment. More work is necessary to give a clearer picture. One region emerges more frequently: the long arm of chromosome 7. Several candidate genes have been studied and some gave indications of association: the Reelin gene and the Wnt2 gene. Cytogenetical abnormalities are frequent at 15q11-13, the region of the Angelman and Prader-Willi syndrome. Imprinting plays an important role in this region, no candidate gene has been identified in autism. Biochemical abnormalities have been found in the serotonin system. Association and linkage studies gave no consistent results with some serotonin receptors and in the transporter, although it seems interesting to go further in the biochemical characterisation of the serotonin transporter activity, particularly in platelets, easily accessible. Two monogenic diseases have been associated with autistic disorder: tuberous sclerosis and fragile X. A

  8. Advances in molecular techniques for the detection and quantification of genetically modified organisms.

    Science.gov (United States)

    Elenis, Dimitrios S; Kalogianni, Despina P; Glynou, Kyriaki; Ioannou, Penelope C; Christopoulos, Theodore K

    2008-10-01

    Progress in genetic engineering has led to the introduction of genetically modified organisms (GMOs) whose genomes have been altered by the integration of a novel sequence conferring a new trait. To allow consumers an informed choice, many countries require food products to be labeled if the GMO content exceeds a certain threshold. Consequently, the development of analytical methods for GMO screening and quantification is of great interest. Exponential amplification by the polymerase chain reaction (PCR) remains a central step in molecular methods of GMO detection and quantification. In order to meet the challenge posed by the continuously increasing number of GMOs, various multiplex assays have been developed for the simultaneous amplification and/or detection of several GMOs. Classical agarose gel electrophoresis is being replaced by capillary electrophoresis (CE) systems, including CE chips, for the rapid and automatable separation of amplified fragments. Microtiter well-based hybridization assays allow high-throughput analysis of many samples in a single plate. Microarrays have been introduced in GMO screening as a technique for the simultaneous multianalyte detection of amplified sequences. Various types of biosensors, including surface plasmon resonance sensors, quartz crystal microbalance piezoelectric sensors, thin-film optical sensors, dry-reagent dipstick-type sensors and electrochemical sensors were introduced in GMO screening because they offer simplicity and lower cost. GMO quantification is performed by real-time PCR (rt-QPCR) and competitive PCR. New endogenous reference genes have been validated. rt-QPCR is the most widely used approach. Multiplexing is another trend in this field. Strategies for high-throughput multiplex competitive quantitative PCR have been reported.

  9. Genetic braid optimization: A heuristic approach to compute quasiparticle braids

    Science.gov (United States)

    McDonald, Ross B.; Katzgraber, Helmut G.

    2013-02-01

    In topologically protected quantum computation, quantum gates can be carried out by adiabatically braiding two-dimensional quasiparticles, reminiscent of entangled world lines. Bonesteel [Phys. Rev. Lett.10.1103/PhysRevLett.95.140503 95, 140503 (2005)], as well as Leijnse and Flensberg [Phys. Rev. B10.1103/PhysRevB.86.104511 86, 104511 (2012)], recently provided schemes for computing quantum gates from quasiparticle braids. Mathematically, the problem of executing a gate becomes that of finding a product of the generators (matrices) in that set that approximates the gate best, up to an error. To date, efficient methods to compute these gates only strive to optimize for accuracy. We explore the possibility of using a generic approach applicable to a variety of braiding problems based on evolutionary (genetic) algorithms. The method efficiently finds optimal braids while allowing the user to optimize for the relative utilities of accuracy and/or length. Furthermore, when optimizing for error only, the method can quickly produce efficient braids.

  10. Genetic programming approach to evaluate complexity of texture images

    Science.gov (United States)

    Ciocca, Gianluigi; Corchs, Silvia; Gasparini, Francesca

    2016-11-01

    We adopt genetic programming (GP) to define a measure that can predict complexity perception of texture images. We perform psychophysical experiments on three different datasets to collect data on the perceived complexity. The subjective data are used for training, validation, and test of the proposed measure. These data are also used to evaluate several possible candidate measures of texture complexity related to both low level and high level image features. We select four of them (namely roughness, number of regions, chroma variance, and memorability) to be combined in a GP framework. This approach allows a nonlinear combination of the measures and could give hints on how the related image features interact in complexity perception. The proposed complexity measure M exhibits Pearson correlation coefficients of 0.890 on the training set, 0.728 on the validation set, and 0.724 on the test set. M outperforms each of all the single measures considered. From the statistical analysis of different GP candidate solutions, we found that the roughness measure evaluated on the gray level image is the most dominant one, followed by the memorability, the number of regions, and finally the chroma variance.

  11. An unbiased systems genetics approach to mapping genetic loci modulating susceptibility to severe streptococcal sepsis.

    Directory of Open Access Journals (Sweden)

    Nourtan F Abdeltawab

    2008-04-01

    Full Text Available Striking individual differences in severity of group A streptococcal (GAS sepsis have been noted, even among patients infected with the same bacterial strain. We had provided evidence that HLA class II allelic variation contributes significantly to differences in systemic disease severity by modulating host responses to streptococcal superantigens. Inasmuch as the bacteria produce additional virulence factors that participate in the pathogenesis of this complex disease, we sought to identify additional gene networks modulating GAS sepsis. Accordingly, we applied a systems genetics approach using a panel of advanced recombinant inbred mice. By analyzing disease phenotypes in the context of mice genotypes we identified a highly significant quantitative trait locus (QTL on Chromosome 2 between 22 and 34 Mb that strongly predicts disease severity, accounting for 25%-30% of variance. This QTL harbors several polymorphic genes known to regulate immune responses to bacterial infections. We evaluated candidate genes within this QTL using multiple parameters that included linkage, gene ontology, variation in gene expression, cocitation networks, and biological relevance, and identified interleukin1 alpha and prostaglandin E synthases pathways as key networks involved in modulating GAS sepsis severity. The association of GAS sepsis with multiple pathways underscores the complexity of traits modulating GAS sepsis and provides a powerful approach for analyzing interactive traits affecting outcomes of other infectious diseases.

  12. Molecular and genetic profiles of radiographically defined de novo meningiomas.

    Science.gov (United States)

    Kitamura, Yohei; Sasaki, Hikaru; Yoshida, Kazunari

    2012-05-01

    With the exception of radiation-induced tumors, benign meningiomas that are known to have developed within a defined time period are extremely rare. We have genetically characterized two cases of radiographically defined de novo, sporadic meningiomas--a 5-cm, left parasagittal tumor in a 61-year-old male and a 2.3-cm, right falx tumor in a 53-year-old female. Neither tumor was observed during MRIs performed for unrelated complaints 49 and 28 months before surgery, respectively. Both tumors were totally resected, and histopathological examination revealed WHO grade I meningiomas. In both cases, the MIB-1 staining indices were high for grade I meningioma (5.6% for case 1 and 9.1% for case 2), and abnormal accumulation of p53 were observed by immunohistochemistry. The two tumors shared losses of chromosome arms 1p and 7p by comparative genomic hybridization. The tumor suppressor merlin, product of the NF2 gene, was not detected in either tumor. These abnormalities found in common in both of the de novo meningiomas likely to play significant roles in the pathogenesis and/or rapid development of meningiomas. Moreover, taken together with previous studies, our findings indicate that the combined loss of 1p and 7p may play a critical role in the tumorigenesis of de novo, aggressive meningiomas.

  13. Genetic Cholestasis: Lessons from the Molecular Physiology of Bile Formation

    Directory of Open Access Journals (Sweden)

    Peter LM Jansen

    2000-01-01

    Full Text Available Progressive familial intrahepatic cholestasis (PFIC is a group of severe genetic cholestatic liver diseases of early life. PFIC types 1 and 2 are characterized by cholestasis and a low to normal serum gamma-glutamyltransferase (GGT activity, whereas in PFIC type 3, the serum GGT activity is elevated. PFIC types 1 and 2 occur due to mutations in loci at chromosome 18 and chromosome 2, respectively. The pathophysiology of PFIC type 1 is not well understood. PFIC types 2 and 3 are caused by transport defects in the liver affecting the hepatobiliary secretion of bile acids and phospholipids, respectively. Benign recurrent intrahepatic cholestasis (BRIC is linked to a mutation in the same familial intrahepatic cholestasis 1 locus at chromosome 18. Defects of bile acid synthesis may be difficult to differentiate from these transport defects.Intrahepatic cholestasis of pregnancy (ICP appears to be related to these cholestatic diseases. For example, heterozygosity in families with PFIC type 3 is associated with ICP, but ICP has also been reported in families with BRIC.In Dubin-Johnson syndrome there is no cholestasis; only the hepatobiliary transport of conjugated bilirubin is affected. This, therefore, is a mild disease, and patients have a normal lifespan.

  14. Molecular genetics of a Chinese family with spinocerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Dan-dan WU

    2015-10-01

    Full Text Available Objective To study the genotype of the members of a Chinese family with spinocerebellar ataxia (SCA. Methods The peripheral blood samples of 6 patients and 40 asymptomatic people belonged to the family were collected. Referring to the clinical manifestations of the proband and second-generation sequencing results, the CAG trinucleotide repeats of the pathogenic gene ATXN2 were amplified by polymerase chain reaction (PCR. The repeated times of the trinucleotide in normally and abnormally amplified alleles were defined by agarose gel electrophoresis and PCR products sequencing. Results Autosomal dominant heredity was the cause of the SCA in this family. Six out of 46 in the fourth-generation were SCA2 patients, 7 were the carriers of pathogenic allele. The repeated times of CAG trinucleotide were within the normal range in one of the two alleles of ATXN2, but they were in abnormal range in the another one. The repeated times of CAG trinucleotide were 40-46 in abnormal alleles of patients. Conclusion Autosomal dominant heredity SCA2 has been diagnosed in this family caused by the dynamic nutation of CAG trinucleotide repeats, and 7 pathogenic allele carriers in this family were confirmed by genetic diagnosis. DOI: 10.11855/j.issn.0577-7402.2015.08.07

  15. Molecular genetic diversity of Punica granatum L. (pomegranate) as revealed by microsatellite DNA markers

    Science.gov (United States)

    Pomegranate (Punica granatum L.) is one of the oldest known edible fruits and more and more it arouse interest of scientific community given its numerous biological activities. However, information about its genetic resources and characterization using reliable molecular markers are still scarce. In...

  16. Genetics and Faith: Religious Enchantment through Creative Engagement with Molecular Biology

    Science.gov (United States)

    Jenkins, Kathleen E.

    2007-01-01

    In this article I develop heuristic types for understanding how the U.S. evangelical Christian subculture engages the newer science of molecular biology as it works to legitimate and enchant religious worldview: 1.) "symbolic engagement," employing genes and DNA as sacred icon; 2.) "disputatious engagement," debating genetic essentialism and…

  17. Scarlet Fever Upsurge in England and Molecular-Genetic Analysis in North-West London, 2014

    Centers for Disease Control (CDC) Podcasts

    2016-08-16

    Sarah Gregory reads an abridged version of the article, Scarlet Fever Upsurge in England and Molecular-Genetic Analysis in North-West London, 2014.  Created: 8/16/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/16/2016.

  18. Pitfalls in the molecular genetic diagnosis of Leber hereditary optic neuropathy (LHON)

    Energy Technology Data Exchange (ETDEWEB)

    Johns, D.R. (Beth Israel Hospital, Boston, MA (United States)); Neufeld, M.J. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States))

    1993-10-01

    Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. The authors found a number of mtDNA polymorphisms that occur adjacent to known LHON-associated mutations and that confound their molecular genetic detection. These transition mutations occur at mtDNA nt 11779 (SfaNI site loss, 11778 mutation), nt 3459 (BsaHI site loss, 3460 mutation), nt 15258 (AccI site loss, 15257 mutation), nt 14485 (mismatch primer Sau3AI site loss, 14484 mutation), and nt 13707 (BstNI site loss, 13708 mutation). Molecular genetic detection of the most common pathogenetic mtDNA mutations in LHON, using a single restriction enzyme, may be confounded by adjacent polymorphisms that occur with a false-positive rate of 2%-7%. 19 refs.

  19. Classical against molecular-genetic methods for susceptibility testing of antituberculotics.

    Science.gov (United States)

    Porvaznik, I; Mokry, J; Solovic, I

    2015-01-01

    Tuberculosis currently belongs to rare respiratory diseases in Slovakia. However, the emergence and spread of multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are major challenges for global tuberculosis control, since the treatment of resistant forms creates both medical and financial problems. Cultivation methods of diagnosis are time-consuming, many times exceeding the time of the initial phase of tuberculosis treatment. Therefore, in the presented study we compared the standard procedures, based on the cultivation of mycobacteria and subsequent drug susceptibility testing to antituberculotics, with molecular-genetic methods using PCR diagnostic kits. The molecular-genetic testing enables to obtain direct and fast evidence of Mycobacterium tuberculosis, with genomic verification of resistance to the most important anti-tuberculosis drugs - isoniazid and rifampicin in MDR-TB, and ethambutol, aminoglycosides, and fluoroquinolones in XDR-TB. In 2012-2013, we confirmed 19 cases of drug-resistant tuberculosis in Slovakia. The resistance to rifampicin was confirmed in all strains with both methods. In two cases, the molecular-genetic testing did not show resistance to isoniazid, as confirmed by conventional cultivation. Furthermore, two strains demonstrating susceptibility in conventional microbiological testing to ethambutol and five strains to fluoroquinolones were verified as actually being resistant using a PCR method. Rapid diagnosis and identification of MDR-TB or XDR-TB strains using molecular-genetic testing is an essential tool for the timely and appropriate drug treatment and prevention of spread of drug resistant strains.

  20. Molecular genetics of the Wolbachia endosymbionts that infect the parasitoids of tephritid fruit flies.

    Science.gov (United States)

    Limited information exists on the molecular genetics of the Wolbachia endosymbionts that infect the parasitoids of tephritid fruit flies. A better understanding of the bacteria could allow sex ratio manipulations that would improve the mass-rearing of natural enemies. Scientists at the Center for Me...

  1. Assessment of the Genetic Diversity in Forest Tree Populations Using Molecular Markers

    Directory of Open Access Journals (Sweden)

    Ilga Porth

    2014-04-01

    Full Text Available Molecular markers have proven to be invaluable tools for assessing plants’ genetic resources by improving our understanding with regards to the distribution and the extent of genetic variation within and among species. Recently developed marker technologies allow the uncovering of the extent of the genetic variation in an unprecedented way through increased coverage of the genome. Markers have diverse applications in plant sciences, but certain marker types, due to their inherent characteristics, have also shown their limitations. A combination of diverse marker types is usually recommended to provide an accurate assessment of the extent of intra- and inter-population genetic diversity of naturally distributed plant species on which proper conservation directives for species that are at risk of decline can be issued. Here, specifically, natural populations of forest trees are reviewed by summarizing published reports in terms of the status of genetic variation in the pure species. In general, for outbred forest tree species, the genetic diversity within populations is larger than among populations of the same species, indicative of a negligible local spatial structure. Additionally, as is the case for plants in general, the diversity at the phenotypic level is also much larger than at the marker level, as selectively neutral markers are commonly used to capture the extent of genetic variation. However, more and more, nucleotide diversity within candidate genes underlying adaptive traits are studied for signatures of selection at single sites. This adaptive genetic diversity constitutes important potential for future forest management and conservation purposes.

  2. Genetic diversity in Treponema pallidum: implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws.

    Science.gov (United States)

    Smajs, David; Norris, Steven J; Weinstock, George M

    2012-03-01

    Pathogenic uncultivable treponemes, similar to syphilis-causing Treponema pallidum subspecies pallidum, include T. pallidum ssp. pertenue, T. pallidum ssp. endemicum and Treponema carateum, which cause yaws, bejel and pinta, respectively. Genetic analyses of these pathogens revealed striking similarity among these bacteria and also a high degree of similarity to the rabbit pathogen, Treponema paraluiscuniculi, a treponeme not infectious to humans. Genome comparisons between pallidum and non-pallidum treponemes revealed genes with potential involvement in human infectivity, whereas comparisons between pallidum and pertenue treponemes identified genes possibly involved in the high invasivity of syphilis treponemes. Genetic variability within syphilis strains is considered as the basis of syphilis molecular epidemiology with potential to detect more virulent strains, whereas genetic variability within a single strain is related to its ability to elude the immune system of the host. Genome analyses also shed light on treponemal evolution and on chromosomal targets for molecular diagnostics of treponemal infections.

  3. Applications of Multiple Nuclear Genes to the Molecular Phylogeny, Population Genetics and Hybrid Identification in the Mangrove Genus Rhizophora.

    Directory of Open Access Journals (Sweden)

    Yongmei Chen

    Full Text Available The genus Rhizophora is one of the most important components of mangrove forests. It is an ideal system for studying biogeography, molecular evolution, population genetics, hybridization and conservation genetics of mangroves. However, there are no sufficient molecular markers to address these topics. Here, we developed 77 pairs of nuclear gene primers, which showed successful PCR amplifications across all five Rhizophora species and sequencing in R. apiculata. Here, we present three tentative applications using a subset of the developed nuclear genes to (I reconstruct the phylogeny, (II examine the genetic structure and (III identify natural hybridization in Rhizophora. Phylogenetic analyses support the hypothesis that Rhizophora had disappeared in the Atlantic-East Pacific (AEP region and was re-colonized from the IWP region approximately 12.7 Mya. Population genetics analyses in four natural populations of R. apiculata in Hainan, China, revealed extremely low genetic diversity, strong population differentiation and extensive admixture, suggesting that the Pleistocene glaciations, particularly the last glacial maximum, greatly influenced the population dynamics of R. apiculata in Hainan. We also verified the hybrid status of a morphologically intermediate individual between R. apiculata and R. stylosa in Hainan. Based on the sequences of five nuclear genes and one chloroplast intergenic spacer, this individual is likely to be an F1 hybrid, with R. stylosa as its maternal parent. The nuclear gene markers developed in this study should be of great value for characterizing the hybridization and introgression patterns in other cases of this genus and testing the role of natural selection using population genomics approaches.

  4. Molecular basis of glyphosate resistance: Different approaches through protein engineering

    Science.gov (United States)

    Pollegioni, Loredano; Schonbrunn, Ernst; Siehl, Daniel

    2011-01-01

    Glyphosate (N-phosphonomethyl-glycine) is the most-used herbicide in the world: glyphosate-based formulations exhibit broad-spectrum herbicidal activity with minimal human and environmental toxicity. The extraordinary success of this simple small molecule is mainly due to the high specificity of glyphosate towards the plant enzyme enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway leading to biosynthesis of aromatic amino acids. Starting in 1996, transgenic glyphosate-resistant plants were introduced thus allowing the application of the herbicide to the crop (post-emergence) to remove emerged weeds without crop damage. This review focuses on the evolution of mechanisms of resistance to glyphosate as obtained through natural diversity, the gene shuffling approach to molecular evolution, and a rational, structure-based approach to protein engineering. In addition, we offer rationale for the means by which the modifications made have had their intended effect. PMID:21668647

  5. EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders

    DEFF Research Database (Denmark)

    Eggermann, Katja; Bliek, Jet; Brioude, Frédéric

    2016-01-01

    Molecular genetic testing for the 11p15-associated imprinting disorders Silver-Russell and Beckwith-Wiedemann syndrome (SRS, BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. With the growing knowledge on the molecular basis of these diso......Molecular genetic testing for the 11p15-associated imprinting disorders Silver-Russell and Beckwith-Wiedemann syndrome (SRS, BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. With the growing knowledge on the molecular basis...

  6. Forward Genetic Approaches for Elucidation of Novel Regulators of Lyme Arthritis Severity

    Directory of Open Access Journals (Sweden)

    Kenneth K.C. Bramwell

    2014-06-01

    Full Text Available Patients experiencing natural infection with Borrelia burgdorferi display a spectrum of associated symptoms and severity, strongly implicating the impact of genetically determined host factors in the pathogenesis of Lyme disease. Herein, we provide a summary of the host genetic factors that have been demonstrated to influence the severity and chronicity of Lyme arthritis symptoms, and a review of the resources available, current progress, and added value of a forward genetic approach for identification of novel genetic regulators.

  7. [Molecular, genetic and physiological analysis of photoinhibition and photosynthetic]. Progress report, June 1991--November 1992

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-01

    A major goal of this project is to use a combined molecular genetic, biochemical and physiological approach to understand the relationship between photosynthetic performance and the structure of the multifunctional D1 reaction center protein of Photosystem II encoded by the chloroplast psbA gene. Relative to other chloroplast proteins, turover of D1 is rapid and highly light dependent and de novo synthesis of D1 is required for a plant`s recovery from short term exposure to irradiances which induce photoinhibitory damage. These observations have led to models for a damage/repair cycle of PSII involving the targeted degradation and replacement of photodamaged D1. To investigate the effects of perturbing the D1 cycle on photosynthesis and autotrophic growth under high and low irradiance, we have examined the consequences of site-specific mutations of the psbA and 16S rRNA genes affecting synthesis, maturation and function/stability of the D1 protein introduced into the chloroplast genome of wildtype strain of the green alga Chlamydomonas reinhardtii using biolistic transformation.

  8. Phenotypic, genetic and molecular characterization of a maize low phytic acid mutant (lpa241).

    Science.gov (United States)

    Pilu, R; Panzeri, D; Gavazzi, G; Rasmussen, S K; Consonni, G; Nielsen, E

    2003-10-01

    Phytic acid, myo-inositol 1,2,3,4,5,6-hexakisphosphate, is the major storage compound of phosphorous (P) in plants, predominantly accumulating in seeds (up to 4-5% of dry weight) and pollen. In cereals, phytic acid is deposited in embryo and aleurone grain tissues as a mixed "phytate" salt of potassium and magnesium, although phytates contain other mineral cations such as iron and zinc. During germination, phytates are broken down by the action of phytases, releasing their P, minerals and myo-inositol which become available to the growing seedling. Phytic acid represents an anti-nutritional factor for animals, and isolation of maize low phytic acid ( lpa) mutants provides a novel approach to study its biochemical pathway and to tackle the nutritional problems associated with it. Following chemical mutagenesis of pollen, we have isolated a viable recessive mutant named lpa 241 showing about 90% reduction of phytic acid and about a tenfold increase in seed-free phosphate content. Although germination rate was decreased by about 30% compared to wild-type, developement of mutant plants was apparentely unaffected. The results of the genetic, biochemical and molecular characterization experiments carried out by SSR mapping, MDD-HPLC and RT-PCR are consistent with a mutation affecting the MIPS1S gene, coding for the first enzyme of the phytic acid biosynthetic pathway.

  9. Gastrointestinal stromal tumor in Brazil: clinicopathology, immunohistochemistry, and molecular genetics of 513 cases.

    Science.gov (United States)

    Lopes, Lisandro Ferreira; Ojopi, Elida B; Bacchi, Carlos E

    2008-06-01

    The aim of the present study was to evaluate the clinicopathological, immunohistochemical, and molecular genetic features of gastrointestinal stromal tumors in Brazil and compare them with cases from other countries. Five hundred and thirteen cases were retrospectively analyzed. HE-stained sections and clinical information were reviewed and the immunohistochemical expression of CD117, CD34, smooth-muscle actin, S-100 protein, desmin, CD44v3 adhesion molecule, p53 protein, epidermal growth factor receptor, and Ki-67 antigen was studied using tissue microarrays. Mutation analysis of KIT and platelet-derived growth factor receptor-alpha genes was also performed. There was a slight female predominance (50.3%) and the median age at diagnosis was 59 years. The tumors were mainly located in the stomach (38.4%). Immunohistochemistry showed that CD117 was expressed in 95.7% of cases. Epidermal growth factor receptor expression was observed in 84.4% of tumors. p53 protein expression was found only in 2.6% of cases but all belonged to the high-risk group for aggressive behavior according to the National Institutes of Health consensus approach. No CD44v3 adhesion molecule expression was detected. KIT exon 11 mutations were the most frequent (62.2%). The present data confirm that gastrointestinal stromal tumors in Brazilian patients do not differ from tumors occurring in other countries.

  10. Molecular genetic and chemotaxonomic characterization of the terrestrial cyanobacterium Nostoc commune and its neighboring species.

    Science.gov (United States)

    Arima, Hiromi; Horiguchi, Noriomi; Takaichi, Shinichi; Kofuji, Rumiko; Ishida, Ken-Ichiro; Wada, Keishiro; Sakamoto, Toshio

    2012-01-01

    The phylogeny of the terrestrial cyanobacterium Nostoc commune and its neighboring Nostoc species was studied using molecular genetic and chemotaxonomic approaches. At least eight genotypes of N. commune were characterized by the differences among 16S rRNA gene sequences and the petH gene encoding ferredoxin-NADP⁺ oxidoreductase and by random amplified polymorphic DNA analysis. The genotypes of N. commune were distributed in Japan without regional specificity. The nrtP gene encoding NrtP-type nitrate/nitrite permease was widely distributed in the genus Nostoc, suggesting that the occurrence of the nrtP gene can be one of the characteristic features that separate cyanobacteria into two groups. The wspA gene encoding a 36-kDa water stress protein was only found in N. commune and Nostoc verrucosum, suggesting that these Nostoc species that form massive colonies with extracellular polysaccharides can be exclusively characterized by the occurrence of the wspA gene. Fifteen species of Nostoc and Anabaena were investigated by comparing their carotenoid composition. Three groups with distinct patterns of carotenoids were related to the phylogenic tree constructed on the basis of 16S rRNA sequences. Nostoc commune and Nostoc punctiforme were clustered in one monophyletic group and characterized by the occurrence of nostoxanthin, canthaxanthin, and myxol glycosides.

  11. Genetic diversity in palmyrah genotypes using morphological and molecular markers

    Directory of Open Access Journals (Sweden)

    V.Ponnuswami

    2010-07-01

    Full Text Available Palms are woody monocotyledons in the family Arecaceae which is placed in the order Arecales. Slow and tall growing,hardy and non branching, dioecious and perennial in nature, palmyrah palm has no distinguishing features to identify sex,stature and high neera yielding types until flowering age of about 12 to 15 years. Under these circumstances molecularmarkers can be effectively utilized to diagnose and select a genotype. Twenty palmyrah accessions were analysed usingRAPD and ISSR markers. In RAPD analysis, a total of 57 bands were obtained, among them 43 were polymorphic and restof them were monomorphic. Amplification size ranged between 250 and 3200 bp. UPGMA based cluster diagram showedthat all 20 different genotypes were grouped into four different clusters based on the stature, sex and high neera yieldingtypes. The distance matrix between genotypes showed an average distance range from 0.54 to 0.91 with a mean of 0.70. Atotal of 130 ISSR markers were scored, of which 65 were polymorphic, equivalent to 47.94% polymorphism. These markerswere used to estimate the genetic similarity among accessions using Jaccard’s similarity coefficient, with similarity valuesranging from 71.6 to 95.7%. The average number of markers produced per primer was 6.11. For each of the 21 ISSRprimers PIC value ranged between 0 and 0.46. Cluster analysis based on ISSR data grouped the 20 palmyrah accessions intotwo major clusters. PCA based on ISSR data clearly distinguished genotypes similar to the results of cluster analysis.

  12. Esophageal combined carcinomas: Immunohoistochemical and molecular genetic studies

    Institute of Scientific and Technical Information of China (English)

    Tadashi Terada; Hirotoshi Maruo

    2012-01-01

    Primary esophageal combined carcinoma is very rare.The authors herein report 2 cases.Case 1 was a combined squamous cell carcinoma and small cell carcinoma,and case 2 was a combined squamous cell carcinoma,adenocarcinoma,and small cell carcinoma.Case 1 was a 67-year-old man with complaints of dysphagia.Endoscopic examination revealed an ulcerated tumor in the middle esophagus,and 6 biopsies were obtained.All 6 biopsies revealed a mixture of squamous cell carcinoma and small cell carcinoma.Both elements were positive for cytokeratin,epithelial membrane antigen,and p53 protein,and had high Ki-67 labeling.The small cell carcinoma element was positive for synaptophysin,CD56,KIT,and platelet-derived growth factor-α (PDG-FRA),while the squamous cell carcinoma element was not.Genetically,no mutations of KIT and PDGFRA were recognized.The patient died of systemic carcinomatosis 15 mo after presentation.Case 2 was a 74-year-old man presenting with dysplasia.Endoscopy revealed a polypoid tumor in the distal esophagus.Seven biopsies were taken,and 6 showed a mixture of squamous cell carcinoma,small cell carcinoma,and adenocarcinoma.The 3 elements were positive for cytokeratins,epithelial membrane antigen,and p53 protein,and had high Ki-67 labeling.The adenocarcinoma element was positive for mucins.The small cell carcinoma element was positive for CD56,synaptophysin,KIT,and PDGFRA,but the other elements were not.Mutations of KIT and PDGFRA were not recognized.The patient died of systemic carcinomatosis 7 mo after presentation.These combined carcinomas may arise from enterochromaffin cells or totipotential stem cell in the esophagus or transdifferentiation of one element to another.A review of the literature was performed.

  13. Molecular and structural analysis of genetic variations in congenital cataract

    Science.gov (United States)

    Kumar, Manoj; Agarwal, Tushar; Kaur, Punit; Kumar, Manoj; Khokhar,, Sudarshan

    2013-01-01

    Objective To determine the relative contributions of mutations in congenital cataract cases in an Indian population by systematic screening of genes associated with cataract. Methods We enrolled 100 congenital cataract cases presenting at the Dr. R. P. Centre for Ophthalmic Sciences, a tertiary research and referral hospital (AIIMS, New Delhi, India). Crystallin, alpha A (CRYAA), CRYAB, CRYGs, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, beaded filament structural protein 1 (BFSP1), gap function protein, alpha 3 (GJA3), GJA8, and heat shock transcription factor 4 gene genes were amplified. Protein structure differences analysis was performed using Discovery Studio (DS) 2.0. Results The mean age of the patients was 17.45±16.51 months, and the age of onset was 1.618±0.7181 months. Sequencing analysis of 14 genes identified 18 nucleotide variations. Fourteen variations were found in the crystallin genes, one in Cx-46 (GJA3), and three in BFSP1. Conclusions Congenital cataract shows marked clinical and genetic heterogeneity. Five nucleotide variations (CRYBA4:p.Y67N, CRYBB1:p.D85N, CRYBB1:p.E75K, CRYBB1:p.E155K, and GJA3:p.M1V) were predicted to be pathogenic. Variants in other genes might also be involved in maintaining lens development, growth, and transparency. The study confirms that the crystallin beta cluster on chromosome 22, Cx-46, and BFSP1 plays a major role in maintaining lens transparency. This study also expands the mutation spectrum of the genes associated with congenital cataract. PMID:24319337

  14. Molecular genetics (HLA) of Behçet's disease.

    Science.gov (United States)

    Mizuki, N; Inoko, H; Ohno, S

    1997-12-01

    Behçet's disease (BD) has been known to be strongly associated with the human leukocyte antigen (HLA) B51. This B51 association has been confirmed in many different ethnic groups between the Middle East and Japan, and it has been proposed that BD is prevalent in those ethnic groups along the old Silk Route. The hypothesis could be made that B51 molecules are primarily involved in BD development through specific antigen presentation. However, polymorphic analyses of the TNFB gene and Tau-a microsatellite between the HLA-B and TNF genes indicate that the pathogenic gene of BD is not the HLA-B51 gene itself but another gene located around the HLA-B gene. HLA-C genotyping by the PCR-SSP method also suggests that the BD pathogenic gene is not the HLA-C gene itself but other gene located near the HLA-B gene. Recently we sequenced a single contig of 236,822 bp from the MICA gene (58.2 kb centromeric of HLA-B) to 90.8 kb telomeric of HLA-C and identified 8 novel genes designated NOB1-8 (NOB: new organization associated with HLA-B). During the course of the genomic sequence analysis we clarified the genetic structure of the MICA (MHC class I chain-related gene A) gene and found a triplet repeat microsatellite polymorphism of (GCT/AGC)n in the transmebrane (TM) region. Furthermore, the microsatellite allele consisting of 6 repetitions of GCT/AGC (MICA A6 allele) was present at a significantly higher frequency in the BD patient group than in the control group and a significant fraction of B51-negative patients were positive for this MICA A6 allele. These results suggest the possibility of a primary association of BD with MICA rather than HLA-B.

  15. Comprehensive genetic discrimination of Leonurus cardiaca populations by AFLP, ISSR, RAPD and IRAP molecular markers.

    Science.gov (United States)

    Khadivi-Khub, Abdollah; Soorni, Aboozar

    2014-06-01

    Leonurus cardiaca is well known for its medicinal importance. In this investigation, genotypic characterization of this species from six eco-geographical regions of Iran was evaluated by four molecular techniques (AFLP, RAPD, ISSR and IRAP). A total of 899 polymorphic fragments were detected by used molecular markers (AFLP = 356, RAPD = 325, ISSR = 113 and IRAP = 105) with an overall average polymorphism of 81.24%. Genetic variation calculated using Shannon's Information index (I) and Nei's gene diversity index (H) showed high genetic diversity in studied germplasm. Also, analysis of molecular variance showed high genetic variation among (55%) and within populations (45%). UPGMA dendrogram constructed from combined data of molecular markers distinguished studied populations in accordance with the results obtained by each marker which all individuals were clearly differentiated into two major clusters. The correlation coefficients were statistically significant for all marker systems with the highest correlation between similarity matrixes of RAPD and ISSR markers (r = 0.82). The present results have an important implication for L. cardiaca germplasm characterization, improvement, and conservation. Furthermore, the characterized individuals exhibited a great deal of molecular variation and they seem to have a rich gene pool for breeding programs.

  16. Molecular and genetic characteristics of hereditary autoinflammatory diseases.

    Science.gov (United States)

    Tunca, Mehmet; Ozdogan, Huri

    2005-02-01

    Autoinflammatory diseases are defined as recurrent "unprovoked" inflammatory events which do not produce high-titer autoantibodies or antigen-specific T cells. There are currently eight hereditary forms of these diseases: Familial Mediterranean fever (FMF), hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), chronic infantile neurologic cutaneous articular (CINCA) syndrome or neonatal-onset multisystem inflammatory disease (NOMID), pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA) and Blau syndrome. Apart from FMF (which has a prevalence of about 0.1 percent among non-Ashkenazi Jews, Armenians, Turks and Arabs), they are very rare disorders. FMF and HIDS are autosomal recessive diseases, all the other members of the family are autosomal and dominantly transmitted. Their common clinical features are recurrent and usually short attacks of synovitis and various skin eruptions; abdominal pain and fever are also frequently observed. The genes of all of these diseases have been discovered and, with the exception of HIDS, it was found that the proteins they encode share certain domains taking part in innate immunity and apoptosis. Thus it was evident that hereditary autoinflammatory diseases may help us understand better a number of important and prevalent pathologic events. We have reviewed the recent and rapidly accumulating knowledge on the molecular aspects of these disorders.

  17. Genetics and molecular biology of methanogen genes. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Konisky, J.

    1997-10-07

    Adenylate kinase has been isolated from four related methanogenic members of the Archaea. For each the optimum temperature for enzyme activity was similar to the temperature for optimal microbial growth and was approximately 30 C for Methanococcus voltage, 70 C for Methanococcus thermolithotrophicus, 80 C for Methanococcus igneus and 80--90 C for Methanococcus jannaschii. The enzymes were sensitive to the adenylate kinase inhibitor, Ap{sub 5}A [P{sup 1}, P{sup 5}-di(adenosine-5{prime}) pentaphosphate], a property that was exploited to purify the enzymes by CIBACRON Blue affinity chromatography. The enzymes had an estimated molecular weight (approximately 23--25 kDa) in the range common for adenylate kinases. Each of the enzymes had a region of amino acid sequence close to its N-terminus that was similar to the canonical P-loop sequence reported for all adenylate kinases. However, the methanogen sequences lacked a lysine residue that has previously been found to be invariant in adenylate kinases including an enzyme isolated from the Archeon, Sulfolobus acidocaldarius. If verified as a nucleotide binding domain, the methanogen sequence would represent a novel nucleotide binding motif. There was no correlation between amino acid abundance and the optimal temperature for enzyme activity.

  18. 76 FR 6623 - Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-02-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Molecular and Clinical Genetics Panel of the Medical Devices... (FDA). The meeting will be open to the public. Name of Committee: Molecular and Clinical Genetics...

  19. Representing genetic variation as continuous surfaces: An approach for identifying spatial dependency in landscape genetic studies

    Science.gov (United States)

    Melanie A. Murphy; Jeffrey S. Evans; Samuel A. Cushman; Andrew Storfer

    2008-01-01

    Landscape genetics, an emerging field integrating landscape ecology and population genetics, has great potential to influence our understanding of habitat connectivity and distribution of organisms. Whereas typical population genetics studies summarize gene flow as pairwise measures between sampling localities, landscape characteristics that influence population...

  20. The Genetic Blues: Understanding Genetic Principles Using a Practical Approach and a Historical Perspective.

    Science.gov (United States)

    Mysliwiec, Tami H.

    2003-01-01

    Incorporates history and genetics to explain how genetic traits are passed on to the next generation by focusing on methemoglobinemia, a rare genetic disease, and discusses how oxygen is carried by hemoglobin. Includes individual pedigree analysis and class pedigree analysis. (YDS)