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Sample records for genetics approach implicates

  1. Reproductive outcome of male carriers of chromosomal abnormalities: multidisciplinary approach for genetic counseling and its implications.

    Science.gov (United States)

    Guo, K M; Wu, B; Wang, H B; Tian, R H

    2016-12-02

    Chromosomal abnormality is the most common genetic cause of infertility. Infertility, as a psychological problem, has received an increasing amount of attention. Psychological interventions have been shown to have beneficial effects on infertile patients with chromosomal abnormalities. The present study explored reproductive outcome of male carriers of chromosomal abnormalities, who accepted genetic counseling and psychological support. Cytogenetic analysis was performed using cultured peripheral blood lymphocytes and G-banding. The detection rate of chromosomal abnormalities was 10.3% in pre-pregnancy counseled males, with polymorphisms being most common, followed by 47,XXY and balanced translocation. Follow-up of 170 carriers with normozoospermia, after 3 years, showed that 94.7% of the cases resulted in live births. In the carriers of polymorphisms, balanced translocation, inv(9), Robertsonian translocation, inversion, and 47,XYY, live birth rates were 96.8, 85.7, 100, 83.3, 75, and 100%, respectively. Follow-up of 54 carriers with oligozoospermia or azoospermia, after 3 years, showed that 14.8% of the cases resulted in live births. In the carriers of 47,XXY with severe oligozoospermia or azoospermia, 80 or 5.9% of the cases resulted in live births, respectively. Therefore, timely psychological support would be beneficial and multidisciplinary approach should be preferentially considered for the management of individuals with chromosomal abnormalities.

  2. Responding to the implications of the genetics revolution for the education and training of doctors: a medical humanities approach.

    Science.gov (United States)

    Kirklin, Deborah

    2003-02-01

    Rapid advances in the field of genetics continue to present medical educators with significant challenges. Whilst there is undoubtedly a pressing need to educate doctors about genetic disorders, research and therapies, there is a parallel need to provide a context for all of these. An interdisciplinary, arts and humanities based approach, responding to this need, is described. This teaching has been successfully delivered both as optional and core undergraduate teaching, and as part of continuing professional development. THE HUMAN PERSPECTIVE: STORIES NOT HISTORIES: Understanding of the patient's perspective can be significantly improved by drawing on both written and oral stories of illness. THE HISTORICAL PERSPECTIVE: LEARNING FROM THE PATIENT: Experiential learning provides insights into the social history of developments in genetics, thereby placing the current concern and debate about the new genetics in context. THE ROLE OF THE MEDIA: THE POWER TO PERSUADE: Critical reading skills can be developed and the power of the popular press to influence the reader acknowledged by analysing and employing the skills of the journalist when reporting developments in biotechnology. LEARNER ASSESSMENT AND EVALUATION: Assessment, both formative and summative, demonstrates sophisticated insights and perspectives into the lived experience of genetic illness. Learner evaluation of the teaching is high. Medical humanities offers a powerful way to convey an understanding of how genetic disorders impact on the lives of patients and families, and to set this against the background of a history rich in the uses, and abuses, of knowledge of heredity.

  3. A Systems Approach Implicates a Brain Mitochondrial Oxidative Homeostasis Co-expression Network in Genetic Vulnerability to Alcohol Withdrawal

    Science.gov (United States)

    Walter, Nicole A. R.; Denmark, DeAunne L.; Kozell, Laura B.; Buck, Kari J.

    2017-01-01

    Genetic factors significantly affect vulnerability to alcohol dependence (alcoholism). We previously identified quantitative trait loci on distal mouse chromosome 1 with large effects on predisposition to alcohol physiological dependence and associated withdrawal following both chronic and acute alcohol exposure in mice (Alcdp1 and Alcw1, respectively). We fine-mapped these loci to a 1.1–1.7 Mb interval syntenic with human 1q23.2-23.3. Alcw1/Alcdp1 interval genes show remarkable genetic variation among mice derived from the C57BL/6J and DBA/2J strains, the two most widely studied genetic animal models for alcohol-related traits. Here, we report the creation of a novel recombinant Alcw1/Alcdp1 congenic model (R2) in which the Alcw1/Alcdp1 interval from a donor C57BL/6J strain is introgressed onto a uniform, inbred DBA/2J genetic background. As expected, R2 mice demonstrate significantly less severe alcohol withdrawal compared to wild-type littermates. Additionally, comparing R2 and background strain animals, as well as reciprocal congenic (R8) and appropriate background strain animals, we assessed Alcw1/Alcdp1 dependent brain gene expression using microarray and quantitative PCR analyses. To our knowledge this includes the first Weighted Gene Co-expression Network Analysis using reciprocal congenic models. Importantly, this allows detection of co-expression patterns limited to one or common to both genetic backgrounds with high or low predisposition to alcohol withdrawal severity. The gene expression patterns (modules) in common contain genes related to oxidative phosphorylation, building upon human and animal model studies that implicate involvement of oxidative phosphorylation in alcohol use disorders (AUDs). Finally, we demonstrate that administration of N-acetylcysteine, an FDA-approved antioxidant, significantly reduces symptoms of alcohol withdrawal (convulsions) in mice, thus validating a phenotypic role for this network. Taken together, these studies

  4. 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

  5. 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.

  6. Genetic Counseling: Ethical and Professional Role Implications.

    Science.gov (United States)

    Witmer, J. Melvin; And Others

    1986-01-01

    Genetic counseling assists people in identifying potential or manifest genetic problems, understanding their implications, making decisions about what course to follow, and working through psychological and social aspects as they affect individuals or couples. Four ethical principles and related ethical issues pertaining to autonomy, beneficence…

  7. Genetics of scleroderma: implications for personalized medicine?

    Directory of Open Access Journals (Sweden)

    Assassi Shervin

    2013-01-01

    Full Text Available Abstract Significant advances have been made in understanding the genetic basis of systemic sclerosis (scleroderma in recent years. Can these discoveries lead to individualized monitoring and treatment? Besides robustly replicated genetic susceptibility loci, several genes have been recently linked to various systemic sclerosis disease manifestations. Furthermore, inclusion of genetic studies in design and analysis of drug trials could lead to development of genetic biomarkers that predict treatment response. Future genetic studies in well-characterized systemic sclerosis cohorts paired with advanced analytic approaches can lead to development of genetic biomarkers for targeted diagnostic and therapeutic interventions in systemic sclerosis.

  8. Genetics and implications in perioperative analgesia.

    Science.gov (United States)

    Trescot, Andrea M

    2014-06-01

    The wide range of patient responses to surgical pain, opioids, and anesthetic agents has puzzled anesthesiologists for many years. Much of the variation has been attributed to differences in patient size, technique, or prior drug use. However, recent genetic testing has revealed exciting clues into the basis for these variances, allowing us to start to predict which patients may have difficulties and start to select medications more rationally. In this manuscript, we discuss genetics and pain perception, genetic predisposition to pain, drug metabolism interactions, ethnogenetics, opioid metabolism, opioid receptors, genetic-related peri-anesthetic toxicity, as well as a clinical approach and a discussion regarding the future of genetic testing and anesthesia.

  9. 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.

  10. 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.

  11. Arenavirus genetic diversity and its biological implications.

    Science.gov (United States)

    Emonet, Sebastien F; de la Torre, Juan C; Domingo, Esteban; Sevilla, Noemí

    2009-07-01

    The Arenaviridae family currently comprises 22 viral species, each of them associated with a rodent species. This viral family is important both as tractable experimental model systems to study acute and persistent infections and as clinically important human pathogens. Arenaviruses are enveloped viruses with a bi-segmented negative-strand RNA genome. The interaction with the cellular receptor and subsequent entry into the host cell differs between Old World and New World arenavirus that use alpha-dystoglycan or human transferring receptor 1, respectively, as main receptors. The recent development of reverse genetic systems for several arenaviruses has facilitated progress in understanding the molecular biology and cell biology of this viral family, as well as opening new approaches for the development of novel strategies to combat human pathogenic arenaviruses. On the other hand, increased availability of genetic data has allowed more detailed studies on the phylogeny and evolution of arenaviruses. As with other riboviruses, arenaviruses exist as viral quasispecies, which allow virus adaptation to rapidly changing environments. The large number of different arenavirus host reservoirs and great genetic diversity among virus species provide the bases for the emergence of new arenaviruses potentially pathogenic for humans.

  12. Genetic Testing and Its Implications: Human Genetics Researchers Grapple with Ethical Issues.

    Science.gov (United States)

    Rabino, Isaac

    2003-01-01

    Contributes systematic data on the attitudes of scientific experts who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. Finds that they are highly supportive of voluntary testing and the right to know one's genetic heritage. Calls for greater genetic literacy. (Contains 87 references.) (Author/NB)

  13. [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.

  14. Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Robin Lemmens

    2011-01-01

    Full Text Available Atrial fibrillation is the most common cardiac arrhythmia mainly caused by valvular, ischemic, hypertensive, and myopathic heart disease. Atrial fibrillation can occur in families suggesting a genetic background especially in younger subjects. Additionally recent studies have identified common genetic variants to be associated with atrial fibrillation in the general population. This cardiac arrhythmia has important public health implications because of its main complications: congestive heart failure and ischemic stroke. Since atrial fibrillation can result in ischemic stroke, one might assume that genetic determinants of this cardiac arrhythmia are also implicated in cerebrovascular disease. Ischemic stroke is a multifactorial, complex disease where multiple environmental and genetic factors interact. Whether genetic variants associated with a risk factor for ischemic stroke also increase the risk of a particular vascular endpoint still needs to be confirmed in many cases. Here we review the current knowledge on the genetic background of atrial fibrillation and the consequences for cerebrovascular disease.

  15. Forward Genetic Approaches for Elucidation of Novel Regulators of Lyme Arthritis Severity

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    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.

  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. 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.

  18. 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.

  19. Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke

    OpenAIRE

    Robin Lemmens; Sylvia Hermans; Dieter Nuyens; Vincent Thijs

    2011-01-01

    Atrial fibrillation is the most common cardiac arrhythmia mainly caused by valvular, ischemic, hypertensive, and myopathic heart disease. Atrial fibrillation can occur in families suggesting a genetic background especially in younger subjects. Additionally recent studies have identified common genetic variants to be associated with atrial fibrillation in the general population. This cardiac arrhythmia has important public health implications because of its main complications: congestive heart...

  20. Advances in imaging-genetic relationships for Alzheimer's disease: clinical implications.

    Science.gov (United States)

    Bagnoli, Silvia; Piaceri, Irene; Sorbi, Sandro; Nacmias, Benedetta

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia and represents a major public health problem. From a clinical perspective, AD is devastating to patients and their families. The genetic approach to the study of dementia undoubtedly continues to provide a significant contribution to understanding the pathogenesis, diagnosis and therapeutic perspectives, but also raises important ethical implications. With advances in new technology, including genetics and PET/MRI scanning, the role of genetic studies and neuroimaging is being redefined as an aid in the clinical diagnosis of AD, and also in presymptomatic evaluation. Here, we review some of the issues related to the neuroimaging-genetic relationship in AD with a possible clinical implication as a preclinical biomarker for dementia and also for tracking disease progression.

  1. 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

  2. Genetic predisposition and implications for radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Streffer, Christian [University Clinics, Essen, Essen (Germany)

    2000-05-01

    Treatments of cancer patients with ionizing radiation have shown in some cases severe acute radiation effects after radiation doses which are very well tolerated by most patients. Skin fibroblasts of these patients studied after in vitro irradiation also showed a high radiosensitivity frequently. It was found that these effects are based on genetic predisposition which was usually inherited from their parents. During recent years quite a number of these syndromes have been described in humans and often the responsible genes have been characterized: Ataxia telangiectasia, Bloom's syndrome, Fanconi anemia, Li Fraumeni syndrome, Nevoid basal cell carcinoma syndrome, Neurofibromatosis, Nijmegen breakage syndrome, Retinoblastoma. In most cases it was found that the regulation processes of DNA repair processes and of the cell cycle for cell proliferation are disturbed. Frequently these processes cannot be separated from each other. Quite a number of these syndromes also show genomic instability which can also be induced by radiation exposures. These Phenomena have mainly been studied by determining the rate of chromosomal aberrations many cell generations after the exposure took place. Genomic instability apparently plays an important role for the development of stochastic late effects for which multistep events are necessary. This is especially for carcinogenesis the case. In mice it has been shown that radiation-induced genomic instability can be transmitted to the next mouse generation. In mouse models and also with radiotherapy patients it has been shown that genetic predisposition not only increases radiosensitivity with respect to cell survival and chromosomal damage but also to carcinogenesis. This has been observed cf. with p53-knock out mice and with children after radiotherapy cf. treatment of retinoblastoma. In the children with a genetic predisposition for retinoblastoma secondary tumours occurred to a much higher rate than in those children with

  3. Genetics of Cystic Fibrosis: Clinical Implications.

    Science.gov (United States)

    Egan, Marie E

    2016-03-01

    Cystic fibrosis (CF) is a common life-shortening autosomal recessive genetic disorder caused by mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator protein (CFTR). Almost 2000 variants in the CFTR gene have been identified. The mutational classes are based on the functional consequences on CFTR. New therapies are being developed to target mutant CFTR and restore CFTR function. Understanding specific CF genotypes is essential for providing state-of-the art care to patients. In addition to the variation in CFTR genotype, there are several modifier genes that contribute to the respiratory phenotype.

  4. 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.

  5. Implications of population structure and ancestry on asthma genetic studies.

    Science.gov (United States)

    Ortega, Victor E; Meyers, Deborah A

    2014-10-01

    The frequency and severity of asthma differ between different racial and ethnic groups. An understanding of the genetic basis for these differences could constitute future genetic biomarker panels for predicting asthma risk and progression in individuals from different ethnic groups. The recent mixing of different ancestries during the European colonization of the Americas and the African slave trade has resulted in the complex population structures identified in different ethnic groups. These population structures represent varying degrees of genetic diversity which impacts the allele frequency of individual variants and, thus, how the gene variation is utilized in genetic association studies. In this review, we will discuss the basis for the complex population structures of modern human genomes and the impact of genetic diversity on genetic studies in different ethnic groups. We will also highlight the potential for admixture and rare variant-based genetic studies to identify novel genetic loci for asthma susceptibility and severity. The ability to account for the consequences of genetic diversity in different racial and ethnic groups will be critical in developing genetic profiles for personalized or precision medicine approaches tailored to asthmatic patients from different ethnic groups.

  6. Potential International Approaches to Ownership/Control of Human Genetic Resources.

    Science.gov (United States)

    Rhodes, Catherine

    2016-09-01

    In its governance activities for genetic resources, the international community has adopted various approaches to their ownership, including: free access; common heritage of mankind; intellectual property rights; and state sovereign rights. They have also created systems which combine elements of these approaches. While governance of plant and animal genetic resources is well-established internationally, there has not yet been a clear approach selected for human genetic resources. Based on assessment of the goals which international governance of human genetic resources ought to serve, and the implications for how they will be accessed and utilised, it is argued that common heritage of mankind will be the most appropriate approach to adopt to their ownership/control. It does this with the aim of stimulating discussion in this area and providing a starting point for deeper consideration of how a common heritage of mankind, or similar, regime for human genetic resources would function and be implemented.

  7. THERAPEUTIC IMPLICATIONS OF GENETIC RISK VARIANTS FOR CORONARY ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    Rajiv Kumar Srivastava

    2017-02-01

    Full Text Available BACKGROUND This review covers therapeutic implication of genetic risk variant responsible for coronary artery disease by utilising the highdensity single-nucleotide microarrays to screen the entire human genome. The sequence of the human genome provides the blueprint for life. Approximately, 99.5% of the human genome Deoxyribonucleic Acid (DNA sequence is identical among humans with 0.5% of the genome sequence (15 million bps accounting for all individual differences. MATERIALS AND METHODS The new technology of the computerised chip array of millions of Single-Nucleotide Polymorphisms (SNPs as Deoxyribonucleic Acid (DNA markers makes it possible to study and detect genetic predisposition to common polygenic disorders such as Coronary Artery Disease (CAD. The sample sizes required for these studies are massive and large; worldwide consortiums such as Coronary Artery Disease Genome-wide Replication and Meta-Analysis (CARDIoGRAM study have been formed to accommodate this requirement. After the identification of 9p21 progress to detect genetic predisposition has been remarkable. RESULTS There are currently a total of 50 genetic risk variants predisposing to CAD of genome-wide significance with confirmation in independent populations. Rare variants (Minor Allele Frequency, MAF <5% will require direct sequencing to detect genetic predisposition. CONCLUSION We can develop new biomarkers for detecting early CAD as well as unique targets for novel therapy. The challenge for the future will be to identify the molecular mechanisms mediating the risk of those genetic risk variants that act through nonconventional risk factors. The ultimate objective for the future is the sequencing and functional analysis of the causative polymorphisms for its therapeutic implications.

  8. A novel mating approach for genetic algorithms.

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    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.

  9. Profiling of genetic switches using boolean implications in expression data.

    Science.gov (United States)

    Çakır, Mehmet Volkan; Binder, Hans; Wirth, Henry

    2014-01-01

    Correlation analysis assuming coexpression of the genes is a widely used method for gene expression analysis in molecular biology. Yet growing extent, quality and dimensionality of the molecular biological data permits emerging, more sophisticated approaches like Boolean implications. We present an approach which is a combination of the SOM (self organizing maps) machine learning method and Boolean implication analysis to identify relations between genes, metagenes and similarly behaving metagene groups (spots). Our method provides a way to assign Boolean states to genes/metagenes/spots and offers a functional view over significantly variant elements of gene expression data on these three different levels. While being able to cover relations between weakly correlated entities Boolean implication method also decomposes these relations into six implication classes. Our method allows one to validate or identify potential relationships between genes and functional modules of interest and to assess their switching behaviour. Furthermore the output of the method renders it possible to construct and study the network of genes. By providing logical implications as updating rules for the network it can also serve to aid modelling approaches.

  10. Determinism and Underdetermination in Genetics: Implications for Students' Engagement in Argumentation and Epistemic Practices

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    Jiménez-Aleixandre, María Pilar

    2012-11-01

    In the last two decades science studies and science education research have shifted from an interest in products (of science or of learning), to an interest in processes and practices. The focus of this paper is on students' engagement in epistemic practices (Kelly in Teaching scientific inquiry: Recommendations for research and implementation. Sense Publishers, Rotterdam, pp 99-117, 2008), or on their practical epistemologies (Wickman in Sci Educ 88(3):325-344, 2004). In order to support these practices in genetics classrooms we need to take into account domain-specific features of the epistemology of genetics, in particular issues about determinism and underdetermination. I suggest that certain difficulties may be related to the specific nature of causality in genetics, and in particular to the correspondence between a given set of factors and a range of potential effects, rather than a single one. The paper seeks to bring together recent developments in the epistemology of biology and of genetics, on the one hand, with science education approaches about epistemic practices, on the other. The implications of these perspectives for current challenges in learning genetics are examined, focusing on students' engagement in epistemic practices, as argumentation, understood as using evidence to evaluate knowledge claims. Engaging in argumentation in genetics classrooms is intertwined with practices such as using genetics models to build explanations, or framing genetics issues in their social context. These challenges are illustrated with studies making part of our research program in the USC.

  11. Causal attributions of obese men and women in genetic testing: implications of genetic/biological attributions.

    Science.gov (United States)

    Hilbert, Anja; Dierk, Jan-Michael; Conradt, Matthias; Schlumberger, Pia; Hinney, Anke; Hebebrand, Johannes; Rief, Winfried

    2009-09-01

    The present study sought to investigate genetic/biological attributions of obesity, their associations with a predisposition to obesity and their crossectional and longitudinal implications for weight regulation in obese individuals presenting for genetic testing and counselling. A total of 421 obese men and women underwent psychological and anthropometric assessment and a mutation screen of the melanocortin-4 receptor gene. At study entry, women revealed more genetic/biological attributions than men on the Revised Illness Perception Questionnaire adapted to obesity (86.2% versus 59.7%). Genetic/biological attributions of obesity were associated in both sexes with a family history of obesity, assessed through Stunkard's Figure Rating Scale. In both sexes, genetic/biological attributions were unrelated to weight regulation beliefs and behaviour (i.e. self-efficacy, controllability beliefs, restrained eating and physical activity), assessed through standardised questionnaires or interview at baseline and at six-month follow-up. In addition, causal attributions and weight regulation beliefs and behaviour were not predictive of body mass index at six-month follow-up. Overall, the results indicate that causal attributions of obesity to genetic/biological factors in obese individuals presenting for genetic screening and counselling are crossectionally and longitudinally unrelated to weight regulation and longer-term weight outcome. Those who attribute their obesity to genetic/biological factors likely have a familial obesity risk.

  12. Integrating Genetic, Psychopharmacological and Neuroimaging Studies: A Converging Methods Approach to Understanding the Neurobiology of ADHD

    Science.gov (United States)

    Durston, Sarah; Konrad, Kerstin

    2007-01-01

    This paper aims to illustrate how combining multiple approaches can inform us about the neurobiology of ADHD. Converging evidence from genetic, psychopharmacological and functional neuroimaging studies has implicated dopaminergic fronto-striatal circuitry in ADHD. However, while the observation of converging evidence from multiple vantage points…

  13. 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.

  14. 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

  15. The genetic epidemiology of prostate cancer and its clinical implications.

    Science.gov (United States)

    Eeles, Rosalind; Goh, Chee; Castro, Elena; Bancroft, Elizabeth; Guy, Michelle; Al Olama, Ali Amin; Easton, Douglas; Kote-Jarai, Zsofia

    2014-01-01

    Worldwide, familial and epidemiological studies have generated considerable evidence of an inherited component to prostate cancer. Indeed, rare highly penetrant genetic mutations have been implicated. Genome-wide association studies (GWAS) have also identified 76 susceptibility loci associated with prostate cancer risk, which occur commonly but are of low penetrance. However, these mutations interact multiplicatively, which can result in substantially increased risk. Currently, approximately 30% of the familial risk is due to such variants. Evaluating the functional aspects of these variants would contribute to our understanding of prostate cancer aetiology and would enable population risk stratification for screening. Furthermore, understanding the genetic risks of prostate cancer might inform predictions of treatment responses and toxicities, with the goal of personalized therapy. However, risk modelling and clinical translational research are needed before we can translate risk profiles generated from these variants into use in the clinical setting for targeted screening and treatment.

  16. Recent genetic discoveries implicating ion channels in human cardiovascular diseases.

    Science.gov (United States)

    George, Alfred L

    2014-04-01

    The term 'channelopathy' refers to human genetic disorders caused by mutations in genes encoding ion channels or their interacting proteins. Recent advances in this field have been enabled by next-generation DNA sequencing strategies such as whole exome sequencing with several intriguing and unexpected discoveries. This review highlights important discoveries implicating ion channels or ion channel modulators in cardiovascular disorders including cardiac arrhythmia susceptibility, cardiac conduction phenotypes, pulmonary and systemic hypertension. These recent discoveries further emphasize the importance of ion channels in the pathophysiology of human disease and as important druggable targets.

  17. 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

  18. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    OpenAIRE

    Manning, Alisa K; Hivert, Marie-France; Scott, Robert A.; Grimsby, Jonna L; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik

    2012-01-01

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associat...

  19. Recent biologic and genetic advances in neuroblastoma: Implications for diagnostic, risk stratification, and treatment strategies.

    Science.gov (United States)

    Newman, Erika A; Nuchtern, Jed G

    2016-10-01

    Neuroblastoma is an embryonic cancer of neural crest cell lineage, accounting for up to 10% of all pediatric cancer. The clinical course is heterogeneous ranging from spontaneous regression in neonates to life-threatening metastatic disease in older children. Much of this clinical variance is thought to result from distinct pathologic characteristics that predict patient outcomes. Consequently, many research efforts have been focused on identifying the underlying biologic and genetic features of neuroblastoma tumors in order to more clearly define prognostic subgroups for treatment stratification. Recent technological advances have placed emphasis on the integration of genetic alterations and predictive biologic variables into targeted treatment approaches to improve patient survival outcomes. This review will focus on these recent advances and the implications they have on the diagnostic, staging, and treatment approaches in modern neuroblastoma clinical management. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Complex genetic origin of Indian populations and its implications

    Indian Academy of Sciences (India)

    Rakesh Tamang; Lalji Singh; Kumarasamy Thangaraj

    2012-11-01

    Indian populations are classified into various caste, tribe and religious groups, which altogether makes them very unique compared to rest of the world. The long-term firm socio-religious boundaries and the strict endogamy practices along with the evolutionary forces have further supplemented the existing high-level diversity. As a result, drawing definite conclusions on its overall origin, affinity, health and disease conditions become even more sophisticated than was thought earlier. In spite of these challenges, researchers have undertaken tireless and extensive investigations using various genetic markers to estimate genetic variation and its implication in health and diseases. We have demonstrated that the Indian populations are the descendents of the very first modern humans, who ventured the journey of out-of-Africa about 65,000 years ago. The recent gene flow from east and west Eurasia is also evident. Thus, this review attempts to summarize the unique genetic variation among Indian populations as evident from our extensive study among approximately 20,000 samples across India.

  1. 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.

  2. The genetic population structure of northern Sweden and its implications for mapping genetic diseases.

    Science.gov (United States)

    Einarsdottir, Elisabet; Egerbladh, Inez; Beckman, Lars; Holmberg, Dan; Escher, Stefan A

    2007-11-01

    The northern Swedish population has a history of admixture of three ethnic groups and a dramatic population growth from a relatively small founder population. This has resulted in founder effects that together with unique resources for genealogical analyses provide excellent conditions for genetic mapping of monogenic diseases. Several recent examples of successful mapping of genetic factors underlying susceptibility to complex diseases have suggested that the population of northern Sweden may also be an important tool for efficient mapping of more complex phenotypes. A potential factor contributing to these effects may be population sub-isolates within the large river valleys, constituting a central geographic characteristic of this region. We here provide evidence that marriage patterns as well as the distribution of gene frequencies in a set of marker loci are compatible with this notion. The possible implications of this population structure on linkage- and association based strategies for identifying genes contributing risk to complex diseases are discussed.

  3. Genetic regulation of heart valve development: Clinical implications

    Directory of Open Access Journals (Sweden)

    Marc-Phillip Hitz

    2011-12-01

    Full Text Available Cardiac malformations, most commonly valve defects, are some of the predominant causes of cardiovascular morbidity and mortality worldwide. Up to a third of all patients with complex congenital heart defects and numerous syndromic conditions, as well as a significant amount of the general population, exhibit valve defects. These observations have not only major implications in infancy; they also have a major impact on the adult population and the growing number of adults with congenital malformations. Over recent years, a large number of Mendelian inheritance patterns and syndromic causes have been identified, shedding light on the importance of genes encoding components of the extracelluar matrix in valve disease. Nevertheless, we still know little about the genetic origin of sporadic and more complex family traits. It is unclear to what extent genetic variations play a role in disease pathogenesis and influences phenotypes rooted in early development. Such knowledge would be greatly beneficial for counseling and treatment of patients. Therefore, this review summarizes the findings in human non-syndromic and syndromic valve disease with a special focus on extracellular matrix proteins, and discusses them in the context of vertebrate valve development.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. Constructivism contested: implications of a genetic perspective in psychology.

    Science.gov (United States)

    Baerveldt, Cor

    2013-03-01

    Constructivism is an approach to knowledge and learning that focuses on the active role of knowers. Sanchez and Loredo (Integrative Psychological & Behavioral Science 43:332-349, 2009) propose a classification of constructivist thinkers and address what they perceive to be internal problems of present-day constructivism. The remedy they propose is a return to the genetic constructivism of James Mark Baldwin, Jean Piaget and Lev Vygotsky. In this article we first raise the question of whether thinkers like Baldwin, Vygotsky, Maturana and Varela are adequately depicted as constructivists, and subsequently argue that constructivism is caught in an overly epistemic version of the subject/object dichotomy. We then introduce a genetic logic that is not based on the Hegelian dialectics of negation and mediation, but rather on the idea of the recursive consensual coordination of actions that give rise to stylized cultural practices. We argue that a genuinely genetic and generative psychology should be concerned with the multifarious and ever-changing nature of human 'life' and not merely with the construction of knowledge about life.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Genetics of the cardiometabolic syndrome: new insights and therapeutic implications.

    Science.gov (United States)

    Sookoian, Silvia; Pirola, Carlos J

    2007-10-01

    Although the definition of the phenotype is imprecise, cardiometabolic syndrome (CMS) includes a constellation of complex diseases such as type 2 diabetes, dislipidemias, central obesity and hypertension, proinflammatory and prothrombotic states, ovarian polycystosis and fatty liver. The genetics of each disease is complex in itself and varies in spectrum from monogenic and syndromic models of inheritance, usually rare, to the most common polygenic and multifactorial forms. In addition, human studies using the candidate-gene approach indicate that common genetic variants of several genes are associated with the development of CMS. Genome-wide scans have also provided several chromosomal regions associated with some of the components of CMS. In addition, through comparative genomics animal models can generate a map for candidate loci in humans and a promising approach is offered by bioinformatic tools for gene prioritization. Lastly, the involvement of genes whose products are already the targets for approved drugs, such as SLC6A4, PPARalpha and PPARgamma , in the development of CMS suggests new avenues for CMS pharmacological treatment.

  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. Discursive Study of Religion : Approaches, Definitions, Implications

    NARCIS (Netherlands)

    von Stuckrad, Kocku

    2013-01-01

    The article explores recent approaches to historical analysis of discourse that have been developed in disciplines such as the sociology of knowledge and historical epistemology. These approaches have only sporadically been taken seriously in the academic study of religion, although they have a

  17. Discursive Study of Religion : Approaches, Definitions, Implications

    NARCIS (Netherlands)

    von Stuckrad, Kocku

    2013-01-01

    The article explores recent approaches to historical analysis of discourse that have been developed in disciplines such as the sociology of knowledge and historical epistemology. These approaches have only sporadically been taken seriously in the academic study of religion, although they have a grea

  18. 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.

  19. 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....

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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/).

  7. Constraints on decision making: implications from genetics, personality, and addiction.

    Science.gov (United States)

    Baker, Travis E; Stockwell, Tim; Holroyd, Clay B

    2013-09-01

    An influential neurocomputational theory of the biological mechanisms of decision making, the "basal ganglia go/no-go model," holds that individual variability in decision making is determined by differences in the makeup of a striatal system for approach and avoidance learning. The model has been tested empirically with the probabilistic selection task (PST), which determines whether individuals learn better from positive or negative feedback. In accordance with the model, in the present study we examined whether an individual's ability to learn from positive and negative reinforcement can be predicted by genetic factors related to the midbrain dopamine system. We also asked whether psychiatric and personality factors related to substance dependence and dopamine affect PST performance. Although we found characteristics that predicted individual differences in approach versus avoidance learning, these observations were qualified by additional findings that appear inconsistent with the predictions of the go/no-go model. These results highlight a need for future research to validate the PST as a measure of basal ganglia reward learning.

  8. 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

  9. Genetic and cellular basis of cerebral cavernous malformations: implications for clinical management.

    Science.gov (United States)

    Bacigaluppi, S; Retta, S F; Pileggi, S; Fontanella, M; Goitre, L; Tassi, L; La Camera, A; Citterio, A; Patrosso, M C; Tredici, G; Penco, S

    2013-01-01

    Cerebral cavernous malformations (CCMs) are a diffuse cerebrovascular disease affecting approximately 0.5% of the population. A CCM is characterized by abnormally enlarged and leaky capillaries arranged in mulberry-like structures with no clear flow pattern. The lesion might predispose to seizures, focal neurological deficits or fatal intracerebral hemorrhage. However, a CCM can also remain neurologically silent. It might either occur sporadically or as an inherited disorder with incomplete penetrance and variable expressivity. Due to advances in imaging techniques, the incidence of CCM diagnoses are increasing, and the patient must be managed on a multidisciplinary basis: genetic counselling, treatment if needed, and follow-up. Advances have been made using radiological and pathological correlates of CCM lesions adding to the accumulated knowledge of this disease, although management of these patients is very variable among centers. This review is aimed at providing an update in genetic and molecular insights of this condition. Included are implications for genetic counselling, and possible approaches to prevention and treatment that derive from the understanding of pathogenetic mechanisms. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  10. 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.

  11. 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.

  12. 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

  13. 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…

  14. 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.

  15. 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.

  16. 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.

  17. Ethical and Social Implications of Genetic Testing for Communication Disorders

    Science.gov (United States)

    Arnos, Kathleen S.

    2008-01-01

    Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in…

  18. The importance and implication of genetic resources in agriculture

    Directory of Open Access Journals (Sweden)

    Milošević Mirjana

    2010-01-01

    Full Text Available The maintenance and preservation of biodiversity is going through the processes of conservation and restoration of disturbed ecosystems and habitats, as well as the preservation and recovery of species. Genetic diversity means the variety and total number of genes contained in plant and animal species and microorganisms. Genetic diversity is the basic unit of diversity, which is responsible for differences between individuals, populations and species. Genetic diversity is very important for the preservation of biodiversity and can be saved in several ways. Part of the germplasm is maintained through breeding programs as they evaluate germplasm stored and used as a source of needed diversity. The Convention on Biological Diversity is one of the most important international agreements to protect nature and conserve genetic resources. International treaties governing the use of genetic resources for food and agriculture are a way to ensure the conservation and sustainable use of plant resources for food and agriculture, and to regulate the rights of farmers.

  19. Clinical implications of shared genetics and pathogenesis in autoimmune diseases.

    Science.gov (United States)

    Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca

    2013-11-01

    Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the presence of autoreactive T cells. They are caused by a complex genetic predisposition that is attributable to multiple genetic variants, each with a moderate-to-low effect size. Most of the genetic variants associated with a particular autoimmune endocrine disease are shared between other systemic and organ-specific autoimmune and inflammatory diseases, such as rheumatoid arthritis, coeliac disease, systemic lupus erythematosus and psoriasis. Here, we review the shared and specific genetic background of autoimmune diseases, summarize their treatment options and discuss how identifying the genetic and environmental factors that predispose patients to an autoimmune disease can help in the diagnosis and monitoring of patients, as well as the design of new treatments.

  20. Clinical implications of genomics for cancer risk genetics.

    Science.gov (United States)

    Thomas, David M; James, Paul A; Ballinger, Mandy L

    2015-06-01

    The study of human genetics has provided substantial insight into cancer biology. With an increase in sequencing capacity and a reduction in sequencing costs, genomics will probably transform clinical cancer genetics. A heritable basis for many cancers is accepted, but so far less than half the genetic drivers have been identified. Genomics will increasingly be applied to populations irrespective of family history, which will change the framework of phenotype-directed genetic testing. Panel testing and whole genome sequencing will identify novel, polygenic, and de-novo determinants of cancer risk, often with lower penetrance, which will challenge present binary clinical classification systems and management algorithms. In the future, genotype-stratified public screening and prevention programmes could form part of tailored population risk management. The integration of research with clinical practice will result in so-called discovery cohorts that will help identify clinically significant genetic variation.

  1. Genetic dissection of acute ethanol responsive gene networks in prefrontal cortex: functional and mechanistic implications.

    Directory of Open Access Journals (Sweden)

    Aaron R Wolen

    Full Text Available Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain across a highly diverse family of 27 isogenic mouse strains (BXD panel before and after treatment with ethanol.Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol's effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b, Gria1, Sncb and Nell2.The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence over the ethanol

  2. Genetic Dissection of Acute Ethanol Responsive Gene Networks in Prefrontal Cortex: Functional and Mechanistic Implications

    Science.gov (United States)

    Wolen, Aaron R.; Phillips, Charles A.; Langston, Michael A.; Putman, Alex H.; Vorster, Paul J.; Bruce, Nathan A.; York, Timothy P.; Williams, Robert W.; Miles, Michael F.

    2012-01-01

    Background Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain) across a highly diverse family of 27 isogenic mouse strains (BXD panel) before and after treatment with ethanol. Results Acute ethanol altered the expression of ∼2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol's effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b, Gria1, Sncb and Nell2. Conclusions The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence

  3. 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

  4. 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

  5. AMD and the alternative complement pathway: genetics and functional implications.

    Science.gov (United States)

    Tan, Perciliz L; Bowes Rickman, Catherine; Katsanis, Nicholas

    2016-06-21

    Age-related macular degeneration (AMD) is an ocular neurodegenerative disorder and is the leading cause of legal blindness in Western societies, with a prevalence of up to 8 % over the age of 60, which continues to increase with age. AMD is characterized by the progressive breakdown of the macula (the central region of the retina), resulting in the loss of central vision including visual acuity. While its molecular etiology remains unclear, advances in genetics and genomics have illuminated the genetic architecture of the disease and have generated attractive pathomechanistic hypotheses. Here, we review the genetic architecture of AMD, considering the contribution of both common and rare alleles to susceptibility, and we explore the possible mechanistic links between photoreceptor degeneration and the alternative complement pathway, a cascade that has emerged as the most potent genetic driver of this disorder.

  6. Genetic Diversity and Structure of Brazilian Populations of Diatraea saccharalis (Lepidoptera: Crambidae): Implications for Pest Management.

    Science.gov (United States)

    Silva-Brandão, Karina L; Santos, Thiago V; Cônsoli, Fernando L; Omoto, Celso

    2015-02-01

    The sugarcane borer, Diatraea saccharalis (F.), is the main pest of sugarcane in Brazil. Genetic variability and gene flow among 13 Brazilian populations of the species were evaluated based on mitochondrial DNA sequences to estimate the exchange of genetic information within and among populations. We found high genetic structure among sampled localities (ΦST=0.50923), and pairwise genetic distances were significantly correlated to geographic distances. Demographic analysis and genealogical network of mitochondrial sequences indicate population growth and admixture of D. saccharalis populations, events likely related to the sequential expansion of the corn and sugarcane crops in Brazil. The implications of these findings for pest management are discussed.

  7. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management

    Directory of Open Access Journals (Sweden)

    Leoz ML

    2015-04-01

    Full Text Available Maria Liz Leoz, Sabela Carballal, Leticia Moreira, Teresa Ocaña, Francesc Balaguer Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS, Barcelona, Catalonia, Spain Abstract: Familial adenomatous polyposis (FAP is an inherited disorder that represents the most common gastrointestinal polyposis syndrome. Germline mutations in the APC gene were initially identified as responsible for FAP, and later, several studies have also implicated the MUTYH gene as responsible for this disease, usually referred to as MUTYH-associated polyposis (MAP. FAP and MAP are characterized by the early onset of multiple adenomatous colorectal polyps, a high lifetime risk of colorectal cancer (CRC, and in some patients the development of extracolonic manifestations. The goal of colorectal management in these patients is to prevent CRC mortality through endoscopic and surgical approaches. Individuals with FAP and their relatives should receive appropriate genetic counseling and join surveillance programs when indicated. This review is focused on the description of the main clinical and genetic aspects of FAP associated with germline APC mutations and MAP. Keywords: colorectal cancer, familial adenomatous polyposis, MAP, APC, MUTYH

  8. Genetics and Common Disorders: Implications for Primary Care and Public Health Providers

    Energy Technology Data Exchange (ETDEWEB)

    McInerney, Joseph D.; Greendale, Karen; Peay, Holly L.

    2005-06-01

    We developed this program for primary care providers (PCPs) and public health professionals (PHPs) who are interested in increasing their understanding of the genetics of common chronic diseases and of the implications of genetics and genomics for their fields. The program differs from virtually all previous educational efforts in genetics for health professionals in that it focuses on the genetics of common chronic disease and on the broad principles that emerge when one views disease from the perspectives of variation and individuality, which are at the heart of thinking genetically. The CD-ROM introduces users to content that will improve their understanding of topics such as: • A framework for genetics and common disease; • Basic information on genetics, genomics, genetic medicine, and public health genetics, all in the context of common chronic disease; • The status of research on genetic contributions to specific common diseases, including a review of research methods; • Genetic/environmental interaction as the new “central dogma” of public health genetics; • The importance of taking and analyzing a family history; • The likely impact of potential gene discovery and genetic testing on genetic counseling and risk assessment and on the practices of PCPs and PHPs; • Stratification of populations into low-, moderate-, and high-risk categories; • The potential role of PCPs and PHPs in identifying high-risk individuals and families, in providing limited genetics services, and in referring to clinical genetics specialists; the potential for standard referral algorithms; • Implications of genetic insights for diagnosis and treatment; • Ethical, legal, and social issues that arise from genetic testing for common chronic diseases; and • Specific prevention strategies based on understanding of genetics and genetic/ environmental interactions. The interactive content – developed by experts in genetics, primary care, and public health – is

  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. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Genetic evolution of enterovirus 71: epidemiological and pathological implications.

    Science.gov (United States)

    Bible, Jon M; Pantelidis, Panagiotis; Chan, Paul K S; Tong, C Y William

    2007-01-01

    Since its discovery in the 1970s, enterovirus 71 (EV71) has become one of the most pathogenic enterovirus serotypes causing recurrent outbreaks in different parts of the world. Three waves of outbreaks globally have been recorded over the last three decades and more recently active circulation of EV71 is evident amongst countries in South East Asia and beyond. There is evidence of a continuous evolution in its genetic make up which is likely to impact on its epidemiology and pathological potential. This review examines the molecular genetics and evolution of EV71 in relation to its epidemiological and pathological properties. A thorough understanding of the relationship between the genetic changes and the resulting host-virus interaction is essential for successful control.

  16. 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.

  17. Investigation of previously implicated genetic variants in chronic tic disorders

    DEFF Research Database (Denmark)

    Abdulkadir, Mohamed; Londono, Douglas; Gordon, Derek

    2017-01-01

    Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 fam...

  18. Genetic heterogeneity in Alzheimer disease and implications for treatment strategies.

    Science.gov (United States)

    Ringman, John M; Goate, Alison; Masters, Colin L; Cairns, Nigel J; Danek, Adrian; Graff-Radford, Neill; Ghetti, Bernardino; Morris, John C

    2014-11-01

    Since the original publication describing the illness in 1907, the genetic understanding of Alzheimer's disease (AD) has advanced such that it is now clear that it is a genetically heterogeneous condition, the subtypes of which may not uniformly respond to a given intervention. It is therefore critical to characterize the clinical and preclinical stages of AD subtypes, including the rare autosomal dominant forms caused by known mutations in the PSEN1, APP, and PSEN2 genes that are being studied in the Dominantly Inherited Alzheimer Network study and its associated secondary prevention trial. Similar efforts are occurring in an extended Colombian family with a PSEN1 mutation, in APOE ε4 homozygotes, and in Down syndrome. Despite commonalities in the mechanisms producing the AD phenotype, there are also differences that reflect specific genetic origins. Treatment modalities should be chosen and trials designed with these differences in mind. Ideally, the varying pathological cascades involved in the different subtypes of AD should be defined so that both areas of overlap and of distinct differences can be taken into account. At the very least, clinical trials should determine the influence of known genetic factors in post hoc analyses.

  19. Adding 'epi-' to behaviour genetics: implications for animal domestication.

    Science.gov (United States)

    Jensen, Per

    2015-01-01

    In this review, it is argued that greatly improved understanding of domestication may be gained from extending the field of behaviour genetics to also include epigenetics. Domestication offers an interesting framework of rapid evolutionary changes caused by well-defined selection pressures. Behaviour is an important phenotype in this context, as it represents the primary means of response to environmental challenges. An overview is provided of the evidence for genetic involvement in behavioural control and the presently used methods for finding so-called behaviour genes. This shows that evolutionary changes in behaviour are to a large extent correlated to changes in patterns of gene expression, which brings epigenetics into the focus. This area is concerned with the mechanisms controlling the timing and extent of gene expression, and a lot of focus has been placed on methylation of cytosine in promoter regions, usually associated with genetic downregulation. The review considers the available evidence that environmental input, for example stress, can modify methylation and other epigenetic marks and subsequently affect behaviour. Furthermore, several studies are reviewed, demonstrating that acquired epigenetic modifications can be inherited and cause trans-generational behaviour changes. In conclusion, epigenetics may signify a new paradigm in this respect, as it shows that genomic modifications can be caused by environmental signals, and random mutations in DNA sequence are therefore not the only sources of heritable genetic variation.

  20. [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.

  1. 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.

  2. Genetically modified plants and food hypersensitivity diseases: usage and implications of experimental models for risk assessment.

    Science.gov (United States)

    Prescott, Vanessa E; Hogan, Simon P

    2006-08-01

    The recent advances in biotechnology in the plant industry have led to increasing crop production and yield that in turn has increased the usage of genetically modified (GM) food in the human food chain. The usage of GM foods for human consumption has raised a number of fundamental questions including the ability of GM foods to elicit potentially harmful immunological responses, including allergic hypersensitivity. To assess the safety of foods derived from GM plants including allergenic potential, the US FDA, Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO), and the EU have developed approaches for evaluation assessment. One assessment approach that has been a very active area of research and debate is the development and usage of animal models to assess the potential allergenicity of GM foods. A number of specific animal models employing rodents, pigs, and dogs have been developed for allergenicity assessment. However, validation of these models is needed and consideration of the criteria for an appropriate animal model for the assessment of allergenicity in GM plants is required. We have recently employed a BALB/c mouse model to assess the potential allergenicity of GM plants. We have been able to demonstrate that this model is able to detect differences in antigenicity and identify aspects of protein post-translational modifications that can alter antigenicity. Furthermore, this model has also enabled us to examine the usage of GM plants as a therapeutic approach for the treatment of allergic diseases. This review discusses the current approaches to assess the allergenic potential of GM food and particularly focusing on the usage of animal models to determine the potential allergenicity of GM foods and gives an overview of our recent findings and implications of these studies.

  3. 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.

  4. BRCA mutation genetic testing implications in the United States.

    Science.gov (United States)

    Bayraktar, Soley; Arun, Banu

    2017-02-01

    BRCA mutation carriers have a very high risk of breast and ovarian cancer by age 70, in the ranges 47%-66% and 40%-57%, respectively. Additionally, women with BRCA mutation-associated breast cancer also have an elevated risk of other or secondary malignancies. Fortunately, the breast and ovarian cancer outcome for BRCA1/2 mutation carriers is at least as good as for non-carriers with chemoprevention, prophylactic surgeries and appropriate use of therapies. Therefore, identification of those who might have a mutation is important so that genetic counseling, testing, screening and prevention strategies can be applied in a timely manner. This article reviews the impact of genetic testing in general, timing of genetic testing after diagnosis and prior knowledge of mutation status in BRCA carriers with newly diagnosed breast cancer. Additionally, risk-reducing surgeries including the prophylactic contralateral mastectomy, and bilateral salpingo-oophorectomy and the sensitivity of BRCA-defective breast cancer cell lines to differential chemotherapeutic agents will be discussed.

  5. 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.

  6. Multiplicity of experimental approaches to therapy for genetic muscle diseases and necessity for population screening.

    Science.gov (United States)

    Laing, Nigel G

    2008-01-01

    Currently a multiplicity of experimental approaches to therapy for genetic muscle diseases is being investigated. These include replacement of the missing gene, manipulation of the gene message, repair of the mutation, upregulation of an alternative gene and pharmacological interventions targeting a number of systems. A number of these approaches are in current clinical trials. There is considerable anticipation that perhaps more than one of the approaches will finally prove of clinical benefit, but there are many voices of caution. No matter which approaches might ultimately prove effective, there is a consensus that for most benefit to the patients it will be necessary to start treatment as early as possible. A consensus is also developing that the only way to do this is to implement population-based newborn screening to identify affected children shortly after birth. Population-based newborn screening is currently practised in very few places in the world and it brings with it implications for prevention rather than cure of genetic muscle diseases.

  7. Hybrid zone and its genetic analysis: implication for conservation

    Institute of Scientific and Technical Information of China (English)

    ZHENGDong; LIUXue-dong; MAJian-zhang

    2003-01-01

    Hybrid zone is a very critical concept within the evolutionary biology, because it would offer us a better insight to understand the evolutionary role of gene flow and hybridization based on the cline model. This minireview presents an expatia-tion of history perspectives and research developments upon basic concepts including hybrid zones, hybridization, hybrid and its the genetic cline model. Moreover, by figuring out the existing problem around the hybrids within conservative theory and prac-tices, it suggests that the theory of hybrid zone be introduced into conservation biology and it would be provide a broader and more open theoretical background for conservative research and practices.

  8. The Genetic Basis of Pheochromocytoma and Paraganglioma: Implications for Management

    Science.gov (United States)

    Shuch, Brian; Ricketts, Christopher J.; Pacak, Karol; Linehan, W. Marston

    2015-01-01

    Chromaffin cells are catecholamine-producing cells derived from neural crest tissue. Chromaffin tumors (ChT) are rare tumors arising from these cells and are divided into pheochromocytoma (PCC) arising from adrenal tissue and paraganglioma (PGL) arising from extra-adrenal ganglia. Previously, ∼10% were believed to be hereditary, but advances in genome sequencing has shown roughly 35% of apparently sporadic tumors have a hereditary component. In this review we describe both classic and newly discovered hereditary ChT syndromes and provide recommendations for genetic testing. In many cases the genes associated with these conditions are linked to common kidney cancer pathways familiar to urologic oncologists. PMID:24642075

  9. 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....

  10. 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).

  11. Genetic susceptibility to type 2 diabetes and implications for therapy.

    Science.gov (United States)

    Florez, Jose C

    2009-07-01

    Since 2000, we have witnessed an explosion of known genetic determinants of type 2 diabetes risk. These findings have seeded the expectation that our ability to make personalized, predictive, therapeutic clinical decisions is imminent. However, the loci discovered to date explain only a small fraction of overall inheritable risk for this disease. In many cases, the reported associations merely signal regions of the genome that are overrepresented in disease versus health but do not identify the causal variants. Well-powered cohort studies have shown that the set of markers detected thus far does not significantly improve individual risk prediction or stratification over common clinical variables, with the possible exception of younger subjects. On the other hand, risk genotypes may help target subgroups for more intensive surveillance or prevention efforts, although whether such a strategy improves patient outcomes and/or is cost-effective should be examined. Similarly, whether genetic information will help guide therapeutic decisions must be tested in adequately designed and rigorously conducted clinical trials. Copyright 2009 Diabetes Technology Society.

  12. The genetics of Hodgkin lymphoma: an overview and clinical implications.

    Science.gov (United States)

    Borchmann, Sven; Engert, Andreas

    2017-09-01

    The goal of this review is to give an overview of the genetics of classical Hodgkin lymphoma. Copy number changes, somatic mutations, genome-wide association studies, changes in gene expression, familial classical Hodgkin lymphoma and epigenetic changes will be reviewed. In doing so, special focus is placed on the way recent discoveries have influenced clinical research, diagnostics, treatment and remission monitoring. Furthermore, emphasis is put on how these advances can help to advance the treatment of elderly patients who have a markedly worse prognosis than younger patients. Frequent amplifications of the 9p24.1 locus in classical Hodgkin lymphoma could be the basis for the success of immune checkpoint inhibitors targeting PD-1 or PD-L1 in this disease. The same amplification also affects the JAK/STAT pathway, which has also been targeted in recent clinical trials. Hodgkin lymphoma-specific copy number alterations and mutations have recently been found to be detectable in cell-free DNA. This could provide the basis for advances in the detection of residual disease during treatment and while monitoring patients in remission. The advent of new technologies such as massive parallel sequencing has improved our understanding of the genetics of classical Hodgkin lymphoma. Some of these discoveries are now being translated into clinical research in the form of new diagnostics and treatments.

  13. 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.

  14. 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...

  15. Genetic basis of type 2 diabetes mellitus: implications for therapy

    DEFF Research Database (Denmark)

    Wolford, Johanna K; de Courten, Barbora

    2004-01-01

    in the management of type 2 diabetes include lifestyle intervention through diet modification and exercise, and oral or injected hypoglycemic agents; however, not all individuals with type 2 diabetes respond in the same way to these treatments. Because of variability in the clinical course of the disease......Type 2 diabetes mellitus represents a multifactorial, heterogeneous group of disorders, which result from defects in insulin secretion, insulin action, or both. The prevalence of type 2 diabetes has increased dramatically worldwide over the past several decades, a trend that has been heavily...... influenced by the relatively recent changes in diet and physical activity levels. There is also strong evidence supporting a genetic component to type 2 diabetes susceptibility and several genes underlying monogenic forms of diabetes have already been identified. However, common type 2 diabetes is likely...

  16. STAT4: genetics, mechanisms, and implications for autoimmunity.

    Science.gov (United States)

    Korman, Benjamin D; Kastner, Daniel L; Gregersen, Peter K; Remmers, Elaine F

    2008-09-01

    Recent advances in genetics and technology have led to breakthroughs in understanding the genes that predispose individuals to autoimmune diseases. A common haplotype of the signal transducer and activator of transcription 4 (STAT4) gene has been shown to be associated with susceptibility to rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome. STAT4 is a transcription factor that transduces interleukin-12, interleukin-23, and type 1 interferon cytokine signals in T cells and monocytes, leading to T-helper type 1 and T-helper type 17 differentiation, monocyte activation, and interferon-gamma production. Although the evidence for this association is very strong and well replicated, the exact mechanism by which polymorphisms in this gene lead to disease remains unknown. In concert with the identification of other disease-associated loci, elucidating how the variant form of STAT4 modulates immune function should lead to an improved understanding of the pathophysiology of autoimmunity.

  17. Population genetics of Ceratitis capitata in South Africa: implications for dispersal and pest management.

    Science.gov (United States)

    Karsten, Minette; van Vuuren, Bettine Jansen; Barnaud, Adeline; Terblanche, John S

    2013-01-01

    The invasive Mediterranean fruit fly (medfly), Ceratitis capitata, is one of the major agricultural and economical pests globally. Understanding invasion risk and mitigation of medfly in agricultural landscapes requires knowledge of its population structure and dispersal patterns. Here, estimates of dispersal ability are provided in medfly from South Africa at three spatial scales using molecular approaches. Individuals were genotyped at 11 polymorphic microsatellite loci and a subset of individuals were also sequenced for the mitochondrial cytochrome oxidase subunit I gene. Our results show that South African medfly populations are generally characterized by high levels of genetic diversity and limited population differentiation at all spatial scales. This suggests high levels of gene flow among sampling locations. However, natural dispersal in C. capitata has been shown to rarely exceed 10 km. Therefore, documented levels of high gene flow in the present study, even between distant populations (>1600 km), are likely the result of human-mediated dispersal or at least some form of long-distance jump dispersal. These findings may have broad applicability to other global fruit production areas and have significant implications for ongoing pest management practices, such as the sterile insect technique.

  18. 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.

  19. Novel Findings into AIRE Genetics and Functioning: Clinical Implications.

    Science.gov (United States)

    De Martino, Lucia; Capalbo, Donatella; Improda, Nicola; Lorello, Paola; Ungaro, Carla; Di Mase, Raffaella; Cirillo, Emilia; Pignata, Claudio; Salerno, Mariacarolina

    2016-01-01

    Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), formerly known as autoimmune polyendocrine syndrome type 1, is a paradigm of a monogenic autoimmune disease caused by mutations of a gene, named autoimmune regulator (AIRE). AIRE acts as a transcription regulator that promotes immunological central tolerance by inducing the ectopic thymic expression of many tissue-specific antigens. Although the syndrome is a monogenic disease, it is characterized by a wide variability of the clinical expression with no significant correlation between genotype and phenotype. Indeed, many aspects regarding the exact role of AIRE and APECED pathogenesis still remain unraveled. In the last decades, several studies in APECED and in its mouse experimental counterpart have revealed new insights on how immune system learns self-tolerance. Moreover, novel interesting findings have extended our understanding of AIRE's function and regulation thus improving our knowledge on the pathogenesis of APECED. In this review, we will summarize recent novelties on molecular mechanisms underlying the development of APECED and their clinical implications.

  20. Myeloma genetics and genomics: practice implications and future directions.

    Science.gov (United States)

    Faiman, Beth

    2014-12-01

    Multiple myeloma (MM) is a heterogeneous, clonal disorder of the plasma cells originating from the B-cell line. The diagnosis and monitoring of MM requires routine measurement of biomarkers such as serum protein electrophoresis, urine protein electrophoresis, serum free light chains, among others. Prognostic models such as the Durie-Salmon staging system and International Staging System are available and account for the disease burden. Advanced biomarker and genetic testing includes cytogenetics, fluorescent in situ hybridization, and gene expression profiling to estimate the aggressiveness of the disease and personalize the patient's treatment. Future goals of therapy will be to achieve minimal residual disease (MRD), which incorporates biomarkers and genomic data. MRD testing might provide a better estimate of the depth of response to therapy and overall survival. A robust genomic program of research is still needed to provide additional information for the best MM care practices and to gain new strategies to treat the disease, in particular, in the relapsed and/or refractory setting.

  1. Convergent genetic and expression data implicate immunity in Alzheimer's disease

    Science.gov (United States)

    Jones, Lesley; Lambert, Jean-Charles; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Vedernikov, Alexey; Escott-Price, Valentina; Stone, Timothy; Richards, Alexander; Bellenguez, Céline; Ibrahim-Verbaas, Carla A; Naj, Adam C; Sims, Rebecca; Gerrish, Amy; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letteneur, Luc; Kornhuber, Johanes; Tárraga, Lluís; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Emilsson, Valur; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Kehoe, Pat; Rogaeva, Ekaterina; Gallacher, John; George-Hyslop, Peter St; Clarimon, Jordi; Lleὀ, Alberti; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petra; Collinge, John; Sorbi, Sandro; Garcia, Florentino Sanchez; Fox, Nick; Hardy, John; Naranjo, Maria Candida Deniz; Razquin, Cristina; Bosco, Paola; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Moebus, Susanne; Mecocci, Patrizia; del Zompo, Maria; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Jessen, Frank; Dichgans, Martin; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alavarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee FAG; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John SK; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Pastor, Pau; Schmidt, Reinhold; Rujescu, Dan; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Haines, Jonathan L; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broekhoven, Christine; Ramirez, Alfredo; Schellenberg, Gerard D; Seshadri, Sudha; Amouyel, Philippe; Holmans, Peter A

    2015-01-01

    Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics. PMID:25533204

  2. Genetics of tuberous sclerosis complex: implications for clinical practice

    Directory of Open Access Journals (Sweden)

    Caban C

    2016-12-01

    Full Text Available Carolina Caban,1,2 Nubaira Khan,1,2 Daphne M Hasbani,3 Peter B Crino1,2 1Department of Neurology, 2Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, 3Department of Neurology, St. Christopher’s Hospital for Children, Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Tuberous sclerosis complex (TSC is a multisystem disorder that results from heterozygous mutations in either TSC1 or TSC2. The primary organ systems that are affected include the brain, skin, lung, kidney, and heart, all with variable frequency, penetrance, and severity. Neurological features include epilepsy, autism, and intellectual disability. There are more than 1,500 known pathogenic variants for TSC1 and TSC2, including deletion, nonsense, and missense mutations, and all pathogenic mutations are inactivating, leading to loss of function effects on the encoded proteins TSC1 and TSC2. These proteins form a complex to constitutively inhibit mechanistic target of rapamycin (mTOR signaling cascade, and as a consequence, mTOR signaling is constitutively active within all TSC-associated lesions. The mTOR inhibitors rapamycin (sirolimus and everolimus have been shown to reduce the size of renal and brain lesions and improve pulmonary function in TSC, and these compounds may also decrease seizure frequency. The clinical application of mTOR inhibitors in TSC has provided one of the first examples of precision medicine in a neurodevelopmental disorder. Keywords: TSC, epilepsy, genetics, mTOR, rapamycin

  3. [Implications in primary health care of medical genetics and genomic in type 2 diabetes mellitus].

    Science.gov (United States)

    Ramirez-Garcia, Sergio Alberto; Cabrera-Pivaral, Carlos E; Huacuja-Ruiz, Luis; Flores-Alvarado, Luis Javier; Pérez-García, Guillermo; González-Rico, José Luis; López-Velázquez, Alma; Topete-González, Luz Rosalba; Rosales-Góme, Roberto Carlos; Candelario-Mejía, Gerardo; Villa-Ruano, Nemesio

    2013-01-01

    Type 2 diabetes mellitus is a complex disease and a global health problem. Therefore, the first level of health care should handle the approaches of medical genetics and genomics to reduce its incidence. The aim is to present perspectives analyzed by our group in two areas of genetics and its clinical application. Emphasis is placed on the coexistence of several genetic forms clinically detectable in patients with diabetes, missing heritability associated with low penetrance, and epigenomics mechanism. It is discussed the effect of genetic variation associated with resistance to insulin, beta-cell dysfunction, shaft incretin, and other points of interest, such as thrifty genotype hypothesis, conformational disease, genetically unknown foods, phenocopies as clinically silent hypercortisolism, molecular phytopharmacology in the clinical management. Finally, the result was displayed in the Mexican population from genetic studies and new findings of clinical importance, such as involvement of melatonin and effect of variations in the number of copies in a genomic region.

  4. Global genetic variation at nine short tandem repeat loci and implications on forensic genetics.

    Science.gov (United States)

    Sun, Guangyun; McGarvey, Stephen T; Bayoumi, Riad; Mulligan, Connie J; Barrantes, Ramiro; Raskin, Salmo; Zhong, Yixi; Akey, Joshua; Chakraborty, Ranajit; Deka, Ranjan

    2003-01-01

    We have studied genetic variation at nine autosomal short tandem repeat loci in 20 globally distributed human populations defined by geographic and ethnic origins, viz., African, Caucasian, Asian, Native American and Oceanic. The purpose of this study is to evaluate the utility and applicability of these nine loci in forensic analysis in worldwide populations. The levels of genetic variation measured by number of alleles, allele size variance and heterozygosity are high in all populations irrespective of their effective sizes. Single- as well as multi-locus genotype frequencies are in conformity with the assumptions of Hardy-Weinberg equilibrium. Further, alleles across the entire set of nine loci are mutually independent in all populations. Gene diversity analysis shows that pooling of population data by major geographic groupings does not introduce substructure effects beyond the levels recommended by the National Research Council, validating the establishment of population databases based on major geographic and ethnic groupings. A network tree based on genetic distances further supports this assertion, in which populations of common ancestry cluster together. With respect to the power of discrimination and exclusion probabilities, even the relatively reduced levels of genetic variation at these nine STR loci in smaller and isolated populations provide an exclusionary power over 99%. However, in paternity testing with unknown genotype of the mother, the power of exclusion could fall below 80% in some isolated populations, and in such cases use of additional loci supplementing the battery of the nine loci is recommended.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. Internet addiction neuroscientific approaches and therapeutical implications including smartphone addiction

    CERN Document Server

    Reuter, Martin

    2017-01-01

    The second edition of this successful book provides further and in-depth insight into theoretical models dealing with Internet addiction, as well as includes new therapeutical approaches. The editors also broach the emerging topic of smartphone addiction. This book combines a scholarly introduction with state-of-the-art research in the characterization of Internet addiction. It is intended for a broad audience including scientists, students and practitioners. The first part of the book contains an introduction to Internet addiction and their pathogenesis. The second part of the book is dedicated to an in-depth review of neuroscientific findings which cover studies using a variety of biological techniques including brain imaging and molecular genetics. The third part of the book focuses on therapeutic interventions for Internet addiction. The fourth part of the present book is an extension to the first edition and deals with a new emerging potential disorder related to Internet addiction – smartphone addicti...

  15. 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

  16. 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

  17. 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

  18. [Approach to depressogenic genes from genetic analyses of animal models].

    Science.gov (United States)

    Yoshikawa, Takeo

    2004-01-01

    Human depression or mood disorder is defined as a complex disease, making positional cloning of susceptibility genes a formidable task. We have undertaken genetic analyses of three different animal models for depression, comparing our results with advanced database resources. We first performed quantitative trait loci (QTL) analysis on two mouse models of "despair", namely, the forced swim test (FST) and tail suspension test (TST), and detected multiple chromosomal loci that control immobility time in these tests. Since one QTL detected on mouse chromosome 11 harbors the GABA A receptor subunit genes, we tested these genes for association in human mood disorder patients. We obtained significant associations of the alpha 1 and alpha 6 subunit genes with the disease, particularly in females. This result was striking, because we had previously detected an epistatic interaction between mouse chromosomes 11 and X that regulates immobility time in these animals. Next, we performed genome-wide expression analyses using a rat model of depression, learned helplessness (LH). We found that in the frontal cortex of LH rats, a disease implicated region, the LIM kinase 1 gene (Limk 1) showed greatest alteration, in this case down-regulation. By combining data from the QTL analysis of FST/TST and DNA microarray analysis of mouse frontal cortex, we identified adenylyl cyclase-associated CAP protein 1 (Cap 1) as another candidate gene for depression susceptibility. Both Limk 1 and Cap 1 are key players in the modulation of actin G-F conversion. In summary, our current study using animal models suggests disturbances of GABAergic neurotransmission and actin turnover as potential pathophysiologies for mood disorder.

  19. Cultural beliefs on disease causation in the Philippines: challenge and implications in genetic counseling.

    Science.gov (United States)

    Abad, Peter James B; Tan, Michael L; Baluyot, Melissa Mae P; Villa, Angela Q; Talapian, Gay Luz; Reyes, Ma Elouisa; Suarez, Riza Concordia; Sur, Aster Lynn D; Aldemita, Vanessa Dyan R; Padilla, Carmencita David; Laurino, Mercy Ygona

    2014-10-01

    The provision of culturally competent health care is an important professional issue recognized by the pioneer genetic counselors in the Philippines. Being an archipelago consisting of 7,107 islands, the Philippines has approximately 175 ethnolinguistic groups with their own unique cultural identity and health practices. The emphasis on culture in our genetic counseling training recognizes its crucial role in molding an individual's conceptualization of health, as well as other life aspects, especially since the Filipino culture is a mixture of indigenous as well as imported and borrowed elements. As part of this endeavor, we will describe in this paper seven common Filipino cultural beliefs: namamana, lihi, sumpa, gaba, pasma, namaligno, and kaloob ng Diyos. We will also share examples on how these common beliefs provide explanation as cause of illness and its implications in our genetic counseling profession.

  20. 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

  1. Living donor liver hilar variations:surgical approaches and implications

    Institute of Scientific and Technical Information of China (English)

    Onur Yaprak; Tolga Demirbas; Cihan Duran; Murat Dayangac; Murat Akyildiz; Yaman Tokat; Yildiray Yuzer

    2011-01-01

    BACKGROUND: Varied vascular and biliary anatomies are common in the liver. Living donor hepatectomy requires precise recognition of the hilar anatomy. This study was undertaken to study donor vascular and biliary tract variations, surgical approaches and implications in living liver transplant patients. METHODS: Two hundred living donor liver transplantations were performed at our institution between 2004 and 2009. All donors were evaluated by volumetric computerized tomography (CT), CT angiography and magnetic resonance cholangiography in the preoperative period. Intraoperative ultrasonography and cholangiography were carried out. Arterial, portal and biliary anatomies were classified according to the Michels, Cheng and Huang criteria. RESULTS: Classical hepatic arterial anatomy was observed in 129 (64.5%) of the 200 donors. Fifteen percent of the donors had variation in the portal vein. Normal biliary anatomy was found in 126 (63%) donors, and biliary tract variation in 70% of donors with portal vein variations. In recipients with single duct biliary anastomosis, 16 (14.4%) developed biliary leak, and 9 (8.1%) developed biliary stricture; however more than one biliary anastomosis increased recipient biliary complications. Donor vascular variations did not increase recipient vascular complications. Variant anatomy was not associated with an increase in donor morbidity. CONCLUSIONS: Living donor liver transplantation provides information about variant hilar anatomy. The success of the procedure depends on a careful approach to anatomical variations. When the deceased donor supply is inadequate, living donor transplantation is a life-saving alternative and is safe for the donor and recipient, even if the donor has variant hilar anatomy.

  2. 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.

  3. 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.

  4. 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.

  5. The intersexual genetic correlation for lifetime fitness in the wild and its implications for sexual selection.

    Directory of Open Access Journals (Sweden)

    Jon E Brommer

    Full Text Available BACKGROUND: The genetic benefits of mate choice are limited by the degree to which male and female fitness are genetically correlated. If the intersexual correlation for fitness is small or negative, choosing a highly fit mate does not necessarily result in high fitness offspring. METHODOLOGY/PRINCIPAL FINDING: Using an animal-model approach on data from a pedigreed population of over 7,000 collared flycatchers (Ficedula albicollis, we estimate the intersexual genetic correlation in Lifetime Reproductive Success (LRS in a natural population to be negative in sign (-0.85+/-0.6. Simulations show this estimate to be robust in sign to the effects of extra-pair parentage. The genetic benefits in this population are further limited by a low level of genetic variation for fitness in males. CONCLUSIONS/SIGNIFICANCE: The potential for indirect sexual selection is nullified by sexual antagonistic fitness effects in this natural population. Our findings and the scarce evidence from other studies suggest that the intersexual genetic correlation for lifetime fitness may be very low in nature. We argue that this form of conflict can, in general, both constrain and maintain sexual selection, depending on the sex-specific additive genetic variances in lifetime fitness.

  6. 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...

  7. 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)

  8. Human loci involved in drug biotransformation: worldwide genetic variation, population structure, and pharmacogenetic implications.

    Science.gov (United States)

    Maisano Delser, Pierpaolo; Fuselli, Silvia

    2013-05-01

    genes. The population structure defined by PGx loci supports the presence of six genetic clusters reflecting geographic location of samples. In particular, the results of the DAPC analyses show that 27 SNPs substantially contribute to the first three discriminant functions. Among these SNPs, some, such as the intronic rs1403527 of NR1I2 and the non-synonymous rs699 of AGT, are known to be associated with specific drug responses. Their substantial variation between different groups of populations may have important implications for PGx practical applications.

  9. Genetic testing in congenital heart disease:A clinical approach

    Institute of Scientific and Technical Information of China (English)

    Marie A Chaix; Gregor Andelfinger; Paul Khairy

    2016-01-01

    Congenital heart disease(CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient followup. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.

  10. CONTEMPORARY APPROACH TO DIAGNOSIS OF GENETIC CAUSES OF INTELLECTUAL DISABILITY

    Directory of Open Access Journals (Sweden)

    Ana PETERLIN

    2016-09-01

    Full Text Available Intellectual disability is a lifelong debilitating developmental disorder with important genetic contribution, which remains challenging to investigate due to high clinical and genetic variability. Finding the etiologic diagnosis of ID, however comes with great benefits for patients and their families, therefore establishing a genetic diagnostic pathway with right combination and succession of diagnostic tools is crucial for both prevention and appropriate treatment and/or rehabilitation of patients with ID. New diagnostic tools in genetics such as array comparative genomic hybridization (aCGH and next-generation sequencing (NGS have much higher detection rate for genetic aberrations responsible for ID and have enormous potential to shorten the path to diagnosis, as early diagnosis is a cornerstone for medical and non-medical management of persons suffering from ID.

  11. Genetic structure of a unique admixed population: implications for medical research.

    Science.gov (United States)

    Patterson, Nick; Petersen, Desiree C; van der Ross, Richard E; Sudoyo, Herawati; Glashoff, Richard H; Marzuki, Sangkot; Reich, David; Hayes, Vanessa M

    2010-02-01

    STATEMENT: In naming population groups, we think a chief aim is to use terms that the group members use themselves, or find familiar and comfortable. The terms used in this manuscript to describe populations are as historically correct as possible and are chosen so as not to offend any population group. Two of the authors (DCP and REvdR) belong to the Coloured population, with one of the authors (REvdR) having contributed extensively to current literature on the history of the Coloured people of South Africa and served as Vice-President of the South African Institute of Race Relations. According to the 2001 South African census (http://www.statssa.gov.za/census01/HTML/CInBrief/CIB2001.pdf), "Statistics South Africa continues to classify people by population group, in order to monitor progress in moving away from the apartheid-based discrimination of the past. However, membership of a population group is now based on self-perception and self-classification, not on a legal definition. Five options were provided on the questionnaire, Black African, Coloured, Indian or Asian, White and Other. Responses in the category 'Other' were very few and were therefore imputed". We have elected to use the term Bushmen rather than San to refer to the hunter-gatherer people of Southern Africa. Although they have no collective name for themselves, this decision was based on the term Bushmen (or Bossiesman) being the more familiar to the communities themselves, while the term San is the more accepted academic classification. Understanding human genetic structure has fundamental implications for understanding the evolution and impact of human diseases. In this study, we describe the complex genetic substructure of a unique and recently admixed population arising approximately 350 years ago as a direct result of European settlement in South Africa. Analysis was performed using over 900 000 genome-wide single nucleotide polymorphisms in 20 unrelated ancestry-informative marker selected

  12. Exploration of transitional life events in individuals with Friedreich ataxia: Implications for genetic counseling

    Directory of Open Access Journals (Sweden)

    Farmer Jennifer M

    2010-10-01

    Full Text Available Abstract Background Human development is a process of change, adaptation and growth. Throughout this process, transitional events mark important points in time when one's life course is significantly altered. This study captures transitional life events brought about or altered by Friedreich ataxia, a progressive chronic illness leading to disability, and the impact of these events on an affected individual's life course. Methods Forty-two adults with Friedreich ataxia (18-65y were interviewed regarding their perceptions of transitional life events. Data from the interviews were coded and analyzed thematically using an iterative process. Results Identified transitions were either a direct outcome of Friedreich ataxia, or a developmental event altered by having the condition. Specifically, an awareness of symptoms, fear of falling and changes in mobility status were the most salient themes from the experience of living with Friedreich ataxia. Developmental events primarily influenced by the condition were one's relationships and life's work. Conclusions Friedreich ataxia increased the complexity and magnitude of transitional events for study participants. Transitional events commonly represented significant loss and presented challenges to self-esteem and identity. Findings from this study help alert professionals of potentially challenging times in patients' lives, which are influenced by chronic illness or disability. Implications for developmental counseling approaches are suggested for genetic counseling. Background Human development can be described in terms of key transitional events, or significant times of change. Transitional events initiate shifts in the meaning or direction of life and require the individual to develop skills or utilize coping strategies to adapt to a novel situation 12. A successful transition has been defined as the development of a sense of mastery over the changed event 3. Transitions can be influenced by a variety

  13. The genetics of celiac disease: A comprehensive review of clinical implications.

    Science.gov (United States)

    Dieli-Crimi, Romina; Cénit, M Carmen; Núñez, Concepción

    2015-11-01

    Celiac disease (CD) is a complex immune-related disease with a very strong genetic component. Multiple genetic findings over the last decade have added to the already known MHC influence numerous genetic variants associated to CD susceptibility. Currently, it is well-established that 6 MHC and 39 non-MHC loci, including a higher number of independent genetic variants, are associated to disease risk. Moreover, additional regions have been recently implicated in the disease, which would increase the number of involved loci. Together, the firmly described genetic variants account for roughly 31% of CD heritability, being 25% explained by the MHC influence. These new variants represent markers of disease risk and turn the identification of the causal genes and the causal variants inside the associated loci, as well as their precise biological role on the disease, into a major challenge in CD research. Numerous studies have been developed with this aim showing the high impact of risk variants on gene expression. These studies also indicate a central role of CD4(+) T cells in CD pathogenesis and point to B cells as important players, which is in accordance with the key steps highlighted by the immunological models of pathogenesis. We comprehensively summarize the current knowledge about the genetic architecture of CD, characterized by multiple low-risk variants located within diverse loci which are most likely affecting genes with immune-related functions. These findings are leading to a better understanding of CD pathogenesis and helping in the design of new treatments. The repertoire of potential drug targets for CD has largely broadened last years, bringing us closer to get alternative or complementary treatments to the life-long gluten-free diet, the only effective treatment so far. Epigenetics and microbiota are emerging as potent factors modulating disease risk and putatively affecting disease manifestation, which are also being explored as therapeutic targets.

  14. Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications.

    Science.gov (United States)

    Carlsten, Mattias; Childs, Richard W

    2015-01-01

    Given their rapid and efficient capacity to recognize and kill tumor cells, natural killer (NK) cells represent a unique immune cell to genetically reprogram in an effort to improve the outcome of cell-based cancer immunotherapy. However, technical and biological challenges associated with gene delivery into NK cells have significantly tempered this approach. Recent advances in viral transduction and electroporation have now allowed detailed characterization of genetically modified NK cells and provided a better understanding for how these cells can be utilized in the clinic to optimize their capacity to induce tumor regression in vivo. Improving NK cell persistence in vivo via autocrine IL-2 and IL-15 stimulation, enhancing tumor targeting by silencing inhibitory NK cell receptors such as NKG2A, and redirecting tumor killing via chimeric antigen receptors, all represent approaches that hold promise in preclinical studies. This review focuses on available methods for genetic reprograming of NK cells and the advantages and challenges associated with each method. It also gives an overview of strategies for genetic reprograming of NK cells that have been evaluated to date and an outlook on how these strategies may be best utilized in clinical protocols. With the recent advances in our understanding of the complex biological networks that regulate the ability of NK cells to target and kill tumors in vivo, we foresee genetic engineering as an obligatory pathway required to exploit the full potential of NK-cell based immunotherapy in the clinic.

  15. [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.

  16. Genetic variability of pain perception and treatment--clinical pharmacological implications.

    Science.gov (United States)

    Lötsch, Jörn

    2011-06-01

    Evidence of a genetic control of pain has led to efforts to exploit genotyping information from pain patients for the development of analgesics and for the selection of pharmacological approaches to pain. Research on translating the genetic bases of familial insensitivity to pain has contributed to the discovery of crucial molecular pathways of pain and to the identification of new analgesic targets (e.g., the Na(v)1.7 sodium channel, neurotrophic tyrosine kinase receptors, nerve growth factor). Moreover, human genetic variants leading to enhanced or reduced function of specific molecular pathways are employed as substitutes for the lack of modulator molecules usable in humans, enabling nociceptive or anti-nociceptive pathways in humans to be studied before drug development. Translational approaches have also been used to verify the importance of experimentally discovered pain pathways in humans, such as GTP cyclohydrolase 1 and the potassium channel K(v)9.1. In addition to these uses of genetics as a research tool, an individualized pharmacological therapy based on the patient's genotype has been attempted. In terms of analgesics in clinical use, such an approach is at the present time only marginally available. For future analgesic targeting, for example, Na(v)1.7 or TRPA1, the genotype may be the target of a selective cure for syndromes caused by increased-function mutations in the coding genes. The consideration of human genetics in drug studies may accelerate analgesic drug development while reducing cost because the clinical success may be partly anticipated by including information of functional genetic variants that mimic the action of future analgesics. These developments show that genotyping information obtained from studies on pain patients plays a role in the clinical pharmacology of pain.

  17. Investigating an Ethical Approach to Genetically Modified Crops in ...

    African Journals Online (AJOL)

    4carolinebell@gmail.com

    Genetically modified (GM) crops gained attention in southern Africa in the ... cited in Webster, 1999:414) states that political institutions find themselves .... means that risks are socially invisible and must clearly be brought to consciousness, ...

  18. Mobile transporter path planning using a genetic algorithm approach

    Science.gov (United States)

    Baffes, Paul; Wang, Lui

    1988-01-01

    The use of an optimization technique known as a genetic algorithm for solving the mobile transporter path planning problem is investigated. The mobile transporter is a traveling robotic vehicle proposed for the Space Station which must be able to reach any point of the structure autonomously. Specific elements of the genetic algorithm are explored in both a theoretical and experimental sense. Recent developments in genetic algorithm theory are shown to be particularly effective in a path planning problem domain, though problem areas can be cited which require more research. However, trajectory planning problems are common in space systems and the genetic algorithm provides an attractive alternative to the classical techniques used to solve these problems.

  19. Congenital hydrocephalus in clinical practice : A genetic diagnostic approach

    NARCIS (Netherlands)

    Verhagen, J. M. A.; Schrander-Stumpel, C. T. R. M.; Krapels, P. C.; de Die-Smulders, C. E. M.; van Lint, F. H. M.; Willekes, C.; Weber, J. W.; Gavilanes, A. W. D.; Macville, M. V. E.; Stegmann, A. P. A.; Engelen, J. J. M.; Bakker, J.; Vos, Y. J.; Frints, S. G. M.

    2011-01-01

    Congenital hydrocephalus is a common and often disabling disorder. The etiology is very heterogeneous. Little is known about the genetic causes of congenital hydrocephalus. A retrospective survey was performed including patients with primary congenital hydrocephalus referred to the Department of

  20. Integrating demographic and genetic approaches in plant conservation

    NARCIS (Netherlands)

    Oostermeijer, J.G.B.; Luijten, S.H.; den Nijs, J.C.M.

    2003-01-01

    We summarize the problems that populations of formerly common plants may encounter when habitat fragmentation isolates them and reduces population size. Genetic erosion, inbreeding depression, Allee-effects on reproductive success, catastrophes and environmental stochasticity are illustrated with st

  1. 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

  2. Combining Single (Mixed) Metric Approach and Genetic Algorithm for QoS Routing Problem

    Institute of Scientific and Technical Information of China (English)

    胡世余; 谢剑英

    2004-01-01

    A hybrid algorithm for the delay constrained least cost path problem is proposed through combination of single (mixed) metric approach and genetic algorithm. Compared with the known genetic algorithm for the same problem, the new algorithm adopts integral coding scheme and new genetic operator, which reduces the search space and improves the efficiency of genetic operation. Meanwhile, the single (mixed) approach accelerates the convergence speed. Simulation results indicate that the proposed algorithm can find near-optimal even optimal solutions within moderate numbers of generations.

  3. Bioethical – Theological and Legal approach in genetic testing of adult persons

    Directory of Open Access Journals (Sweden)

    George Katsimigas

    2012-07-01

    Full Text Available Thorough genetic testing gives possibility's diagnosis of genetic diseases or identity individuals, who genetic predisposed for disease outbreak Aims: To present/identify the ethical and religious issues, which arise from the application of genetic testing in humans. Furthermore, the principles from the European and Greek legislation regarding genetic testing will be discussed. Materials & Methods: A literature review based on both review and research literature, conducted during the period of (1993-2010, derived from MEDLINE, SCOPUS and ΙΑΤΡΟΤΕΚ databases using as key words: Bioethics, genetic testing, bioethics, access, genetic information, orthodox ethics, Legislation. Results: Genetic testing for disease prevention is of primary importance. The main ethical concerns however, are related to the dissemination/ disclosure and use of this information from insurance companies, healthcare authorities, scientists, forensic departments/services and employers. Similarly, the orthodox religion accepts the use of genetic testing for the prevention and treatment of diseases as long as there is no break of confidentiality. Finally, considering the legal issues, it is apparent that genetic information is regarded as personal information and as such it is protected from the national (Greek and international law. Conclusions: It is necessary to ensure that the public authorities protect the rights of their citizens regarding genetic testing and all insurance companies, employers, schools etc. should not be allowed to have access to genetic information. Such an approach will ensure that social discrimination, obstructions or other inequalities between people on the basis of genetic information is avoided.

  4. A propensity score approach to correction for bias due to population stratification using genetic and non-genetic factors.

    Science.gov (United States)

    Zhao, Huaqing; Rebbeck, Timothy R; Mitra, Nandita

    2009-12-01

    Confounding due to population stratification (PS) arises when differences in both allele and disease frequencies exist in a population of mixed racial/ethnic subpopulations. Genomic control, structured association, principal components analysis (PCA), and multidimensional scaling (MDS) approaches have been proposed to address this bias using genetic markers. However, confounding due to PS can also be due to non-genetic factors. Propensity scores are widely used to address confounding in observational studies but have not been adapted to deal with PS in genetic association studies. We propose a genomic propensity score (GPS) approach to correct for bias due to PS that considers both genetic and non-genetic factors. We compare the GPS method with PCA and MDS using simulation studies. Our results show that GPS can adequately adjust and consistently correct for bias due to PS. Under no/mild, moderate, and severe PS, GPS yielded estimated with bias close to 0 (mean=-0.0044, standard error=0.0087). Under moderate or severe PS, the GPS method consistently outperforms the PCA method in terms of bias, coverage probability (CP), and type I error. Under moderate PS, the GPS method consistently outperforms the MDS method in terms of CP. PCA maintains relatively high power compared to both MDS and GPS methods under the simulated situations. GPS and MDS are comparable in terms of statistical properties such as bias, type I error, and power. The GPS method provides a novel and robust tool for obtaining less-biased estimates of genetic associations that can consider both genetic and non-genetic factors.

  5. A genetic algorithm approach in interface and surface structure optimization

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jian [Iowa State Univ., Ames, IA (United States)

    2010-01-01

    The thesis is divided into two parts. In the first part a global optimization method is developed for the interface and surface structures optimization. Two prototype systems are chosen to be studied. One is Si[001] symmetric tilted grain boundaries and the other is Ag/Au induced Si(111) surface. It is found that Genetic Algorithm is very efficient in finding lowest energy structures in both cases. Not only existing structures in the experiments can be reproduced, but also many new structures can be predicted using Genetic Algorithm. Thus it is shown that Genetic Algorithm is a extremely powerful tool for the material structures predictions. The second part of the thesis is devoted to the explanation of an experimental observation of thermal radiation from three-dimensional tungsten photonic crystal structures. The experimental results seems astounding and confusing, yet the theoretical models in the paper revealed the physics insight behind the phenomena and can well reproduced the experimental results.

  6. [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.

  7. Patients' knowledge of cystic fibrosis: genetic determinism and implications for treatment.

    Science.gov (United States)

    Chapman, Elizabeth; Bilton, Diana

    2004-10-01

    This paper uses the self-regulation model of illness perceptions (Leventhal et al. , 1984) to consider the implications of different ways of thinking about the causes of illness. The relationship between anxiety/depression and knowledge or denial of illness is also considered. These issues are explored using adherence to treatment in cystic fibrosis (CF) as an example. Twenty-six CF patients took part in semistructured interviews and completed a standardized anxiety and depression scale (HAD, Zigmond and Snaith, 1983). Interview data were analyzed using Interpretative Phenomenological Analysis (Chapman and Smith, 2002). HAD data were analyzed using SPSS. The respondents displayed widely differing levels of knowledge of their condition. Some deterministic comments were also reported. Findings are discussed in relation to the information that physicians might provide to patients and families in the light of increasing knowledge about genetics in society and the genotyping of individuals with genetic conditions specifically. Any important gaps in patient knowledge could usefully be discussed at transition from pediatric to adult care and issues relating to control and genetic determinism discussed with the patients individually.

  8. Horizontal symmetry in the algebraic approach of genetic code

    CERN Document Server

    Godina-Nava, J J

    2013-01-01

    Using concepts of physics of elementary particles concerning the breaking of symmetry and grannd unified theory we propose to study with the algebraic approximation the degeneracy finded in the genetic code with the incorporation of a horizontal symmetry used in gauge theories to fit the contents of the multiplets of the genetic code. It is used the algebraic approch of Hornos et. al. \\cite{main,PRL71,PRE,MPLB}. We propose an example for the incorporation of horizontal symmetry to study mixtures of elements of the multiplets.

  9. Horizontal symmetry in the algebraic approach of genetic code

    OpenAIRE

    Godina-Nava, J. J.

    2013-01-01

    Using concepts of physics of elementary particles concerning the breaking of symmetry and grannd unified theory we propose to study with the algebraic approximation the degeneracy finded in the genetic code with the incorporation of a horizontal symmetry used in gauge theories to fit the contents of the multiplets of the genetic code. It is used the algebraic approch of Hornos et. al. \\cite{main,PRL71,PRE,MPLB}. We propose an example for the incorporation of horizontal symmetry to study mixtu...

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

    NARCIS (Netherlands)

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

    2016-01-01

    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 gener

  11. Congenital hydrocephalus in clinical practice : A genetic diagnostic approach

    NARCIS (Netherlands)

    Verhagen, J. M. A.; Schrander-Stumpel, C. T. R. M.; Krapels, P. C.; de Die-Smulders, C. E. M.; van Lint, F. H. M.; Willekes, C.; Weber, J. W.; Gavilanes, A. W. D.; Macville, M. V. E.; Stegmann, A. P. A.; Engelen, J. J. M.; Bakker, J.; Vos, Y. J.; Frints, S. G. M.

    2011-01-01

    Congenital hydrocephalus is a common and often disabling disorder. The etiology is very heterogeneous. Little is known about the genetic causes of congenital hydrocephalus. A retrospective survey was performed including patients with primary congenital hydrocephalus referred to the Department of Cli

  12. 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

  13. 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

  14. A Fuzzy Genetic Algorithm Approach to an Adaptive Information Retrieval Agent.

    Science.gov (United States)

    Martin-Bautista, Maria J.; Vila, Maria-Amparo; Larsen, Henrik Legind

    1999-01-01

    Presents an approach to a Genetic Information Retrieval Agent Filter (GIRAF) that filters and ranks documents retrieved from the Internet according to users' preferences by using a Genetic Algorithm and fuzzy set theory to handle the imprecision of users' preferences and users' evaluation of the retrieved documents. (Author/LRW)

  15. 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.

    2016-01-01

    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…

  16. 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''.

  17. A systems genetics approach provides a bridge from discovered genetic variants to biological pathways in rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Hirofumi Nakaoka

    Full Text Available Genome-wide association studies (GWAS have yielded novel genetic loci underlying common diseases. We propose a systems genetics approach to utilize these discoveries for better understanding of the genetic architecture of rheumatoid arthritis (RA. Current evidence of genetic associations with RA was sought through PubMed and the NHGRI GWAS catalog. The associations of 15 single nucleotide polymorphisms and HLA-DRB1 alleles were confirmed in 1,287 cases and 1,500 controls of Japanese subjects. Among these, HLA-DRB1 alleles and eight SNPs showed significant associations and all but one of the variants had the same direction of effect as identified in the previous studies, indicating that the genetic risk factors underlying RA are shared across populations. By receiver operating characteristic curve analysis, the area under the curve (AUC for the genetic risk score based on the selected variants was 68.4%. For seropositive RA patients only, the AUC improved to 70.9%, indicating good but suboptimal predictive ability. A simulation study shows that more than 200 additional loci with similar effect size as recent GWAS findings or 20 rare variants with intermediate effects are needed to achieve AUC = 80.0%. We performed the random walk with restart (RWR algorithm to prioritize genes for future mapping studies. The performance of the algorithm was confirmed by leave-one-out cross-validation. The RWR algorithm pointed to ZAP70 in the first rank, in which mutation causes RA-like autoimmune arthritis in mice. By applying the hierarchical clustering method to a subnetwork comprising RA-associated genes and top-ranked genes by the RWR, we found three functional modules relevant to RA etiology: "leukocyte activation and differentiation", "pattern-recognition receptor signaling pathway", and "chemokines and their receptors".These results suggest that the systems genetics approach is useful to find directions of future mapping strategies to illuminate

  18. Disorders of Sex Development in Indonesia: Natural course and the implications of a stepwise multidisciplinary approach

    NARCIS (Netherlands)

    A.Z. Juniarto (Achmad)

    2014-01-01

    markdownabstract__Abstract__ This thesis elaborates the stepwise diagnostic procedure in DSD patients using a multidiscipline approach to obtain the diagnosis of these patients which includes clinical assessment, hormonal, genetic, and pathological investigations, so that it is beneficial as the

  19. Energy Efficient Routing in Wireless Sensor Networks: A Genetic Approach

    CERN Document Server

    Chakraborty, Ayon; Naskar, Mrinal Kanti

    2011-01-01

    The key parameters that need to be addressed while designing protocols for sensor networks are its energy awareness and computational feasibility in resource constrained sensor nodes. Variation in the distances of nodes from the Base Station and differences in inter-nodal distances are primary factors causing unequal energy dissipation among the nodes. Thus energy difference among the nodes increases with time resulting in degraded network performance. The LEACH and PEGASIS schemes which provided elegant solutions to the problem suffer due to randomization of cluster heads and greedy chain formation respectively. In this paper, we propose a Genetic algorithm inspired ROUting Protocol (GROUP) which shows enhanced performance in terms of energy efficiency and network lifetime over other schemes. GROUP increases the network performance by ensuring a sub-optimal energy dissipation of the individual nodes despite their random deployment. It employs modern heuristics like Genetic Algorithms along with Simulated Ann...

  20. Genetic Approach to Elucidation of Sasang Constitutional Medicine

    OpenAIRE

    Bu-Yeo Kim; Seongwon Cha; Hee-Jeong Jin; Sangkyun Jeong

    2009-01-01

    Sasang Constitutional Medicine (SCM) offers a medical principle that classifies humans into four constitution groups and guides their treatment with constitution-matched medical assistance. The principle of this traditional medicine, although requires significant scientific support, appears to suggest a genetic influence on constitution type. The relative frequency of constitution types in a population, for instance, has remained relatively constant since Jema Lee first described them from hi...

  1. Theory of mind and the social brain: implications for understanding the genetic basis of schizophrenia.

    Science.gov (United States)

    Martin, A K; Robinson, G; Dzafic, I; Reutens, D; Mowry, B

    2014-01-01

    Genome-wide association studies in schizophrenia have recently made significant progress in our understanding of the complex genetic architecture of this disorder. Many genetic loci have been identified and now require functional investigation. One approach involves studying their correlation with neuroimaging and neurocognitive endophenotypes. Theory of Mind (ToM) deficits are well established in schizophrenia and they appear to fulfill criteria for being considered an endophenotype. We aim to review the behavioral and neuroimaging-based studies of ToM in schizophrenia, assess its suitability as an endophenotype, discuss current findings, and propose future research directions. Suitable research articles were sourced from a comprehensive literature search and from references identified through other studies. ToM deficits are repeatable, stable, and heritable: First-episode patients, those in remission and unaffected relatives all show deficits. Activation and structural differences in brain regions believed important for ToM are also consistently reported in schizophrenia patients at all stages of illness, although no research to date has examined unaffected relatives. Studies using ToM as an endophenotype are providing interesting genetic associations with both single nucleotide polymorphisms (SNPs) and specific copy number variations (CNVs) such as the 22q11.2 deletion syndrome. We conclude that ToM is an important cognitive endophenotype for consideration in future studies addressing the complex genetic architecture of schizophrenia, and may help identify more homogeneous clinical sub-types for further study.

  2. Hierarchical Genetic Algorithm Approach to Determine Pulse Sequences in NMR

    CERN Document Server

    Ajoy, Ashok

    2009-01-01

    We develop a new class of genetic algorithm that computationally determines efficient pulse sequences to implement a quantum gate U in a three-qubit system. The method is shown to be quite general, and the same algorithm can be used to derive efficient sequences for a variety of target matrices. We demonstrate this by implementing the inversion-on-equality gate efficiently when the spin-spin coupling constants $J_{12}=J_{23}=J$ and $J_{13}=0$. We also propose new pulse sequences to implement the Parity gate and Fanout gate, which are about 50% more efficient than the previous best efforts. Moreover, these sequences are shown to require significantly less RF power for their implementation. The proposed algorithm introduces several new features in the conventional genetic algorithm framework. We use matrices instead of linear chains, and the columns of these matrices have a well defined hierarchy. The algorithm is a genetic algorithm coupled to a fast local optimizer, and is hence a hybrid GA. It shows fast con...

  3. Context-sensitive network-based disease genetics prediction and its implications in drug discovery.

    Science.gov (United States)

    Chen, Yang; Xu, Rong

    2017-04-01

    Disease phenotype networks play an important role in computational approaches to identifying new disease-gene associations. Current disease phenotype networks often model disease relationships based on pairwise similarities, therefore ignore the specific context on how two diseases are connected. In this study, we propose a new strategy to model disease associations using context-sensitive networks (CSNs). We developed a CSN-based phenome-driven approach for disease genetics prediction, and investigated the translational potential of the predicted genes in drug discovery. We constructed CSNs by directly connecting diseases with associated phenotypes. Here, we constructed two CSNs using different data sources; the two networks contain 26 790 and 13 822 nodes respectively. We integrated the CSNs with a genetic functional relationship network and predicted disease genes using a network-based ranking algorithm. For comparison, we built Similarity-Based disease Networks (SBN) using the same disease phenotype data. In a de novo cross validation for 3324 diseases, the CSN-based approach significantly increased the average rank from top 12.6 to top 8.8% for all tested genes comparing with the SBN-based approach ( pdisease using CSNs, and demonstrated that the top-ranked genes are highly relevant to PD pathologenesis. We pin-pointed a top-ranked drug target gene for PD, and found its association with neurodegeneration supported by literature. In summary, CSNs lead to significantly improve the disease genetics prediction comparing with SBNs and provide leads for potential drug targets. nlp.case.edu/public/data/. rxx@case.edu.

  4. 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.

  5. Bolzano's Approach to the Paradoxes of Infinity: Implications for Teaching

    Science.gov (United States)

    Waldegg, Guillermina

    2005-01-01

    In this paper we analyze excerpts of "Paradoxes of the Infinite", the posthumous work of Bernard Bolzano (1781-1848), in order to show that Georg Cantor's (1845-1918) approach to the problem of defining actual mathematical infinity is not the most natural. In fact, Bolzano's approach to the paradoxes of infinity is more intuitive, while remaining…

  6. Postmodern Implications for Theoretical Integration of Counseling Approaches.

    Science.gov (United States)

    Hansen, James T.

    2002-01-01

    Theoretical integration refers to the conceptual unification of diverse counseling approaches. Contends that the general failure of integrative attempts is a by-product of the modernistic epistemic context in which the systems were considered and proposes an examination of common narrative features of counseling approaches in a postmodern…

  7. The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Daniel J. Guerra

    2011-01-01

    Full Text Available Autism spectrum disorders (ASDs have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD.

  8. The molecular genetics of autism spectrum disorders: genomic mechanisms, neuroimmunopathology, and clinical implications.

    Science.gov (United States)

    Guerra, Daniel J

    2011-01-01

    Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD.

  9. Low genetic diversity and high genetic differentiation in the critically endangered Omphalogramma souliei (Primulaceae):implications for its conservation

    Institute of Scientific and Technical Information of China (English)

    Yuan HUANG; Chang-Qin ZHANG; De-Zhu LI

    2009-01-01

    Omphalogramma souliei Franch. Is an endangered perennial herb only distributed in alpine areas of SW China. ISSR markers were applied to determine the genetic variation and genetic structure of 60 individuals of three populations of O. Souliei in NW Yunnan, China. The genetic diversity at the species level is low with P= 42.5% (percentage of polymorphic bands) and Hsp=0.1762 (total genetic diversity). However, a high level of genetic differentiation among populations was detected based on different measures (Nei's genetic diversity analysis: Gst=0.6038; AMOVA analysis: Fst=0.6797). Low level of genetic diversity within populations and significant genetic differentiation among populations might be due to the mixed mating system in which xenog-amy predominated and autogamy played an assistant role in O. Souliei. The genetic drift due to small population size and limited current gene flow also resulted in significant genetic differentiation. The assessment of genetic variation and differentiation of the endangered species provides important information for conservation on a genetic basis. Conservation strategies for this rare endemic species are proposed.

  10. Tissue-specific genetic control of splicing: implications for the study of complex traits.

    Directory of Open Access Journals (Sweden)

    Erin L Heinzen

    2008-12-01

    Full Text Available Numerous genome-wide screens for polymorphisms that influence gene expression have provided key insights into the genetic control of transcription. Despite this work, the relevance of specific polymorphisms to in vivo expression and splicing remains unclear. We carried out the first genome-wide screen, to our knowledge, for SNPs that associate with alternative splicing and gene expression in human primary cells, evaluating 93 autopsy-collected cortical brain tissue samples with no defined neuropsychiatric condition and 80 peripheral blood mononucleated cell samples collected from living healthy donors. We identified 23 high confidence associations with total expression and 80 with alternative splicing as reflected by expression levels of specific exons. Fewer than 50% of the implicated SNPs however show effects in both tissue types, reflecting strong evidence for distinct genetic control of splicing and expression in the two tissue types. The data generated here also suggest the possibility that splicing effects may be responsible for up to 13 out of 84 reported genome-wide significant associations with human traits. These results emphasize the importance of establishing a database of polymorphisms affecting splicing and expression in primary tissue types and suggest that splicing effects may be of more phenotypic significance than overall gene expression changes.

  11. The practice of genetic counselling: a Ccmparative approach to understanding genetic counselling in China

    NARCIS (Netherlands)

    Suli, S.

    2009-01-01

    This article provides an empirical account of the application of genetic counselling in China based on interviews, clinical observation and literature research during a field study from September 2008 to February 2009, carried out mainly in China and partly in Hong Kong and the United Kingdom.

  12. The practice of genetic counselling: a Ccmparative approach to understanding genetic counselling in China

    NARCIS (Netherlands)

    Suli, S.

    2009-01-01

    This article provides an empirical account of the application of genetic counselling in China based on interviews, clinical observation and literature research during a field study from September 2008 to February 2009, carried out mainly in China and partly in Hong Kong and the United Kingdom. Makin

  13. Invasion success in Cogongrass (Imperata cylindrica): A population genetic approach exploring genetic diversity and historical introductions

    Science.gov (United States)

    Rima D. Lucardi; Lisa E. Wallace; Gary N. Ervin

    2014-01-01

    Propagule pressure significantly contributes to and limits the potential success of a biological invasion, especially during transport, introduction, and establishment. Events such as multiple introductions of foreign parent material and gene flow among them can increase genetic diversity in founding populations, often leading to greater invasion success. We applied...

  14. A case-based approach to the development of practice-based competencies for accreditation of and training in graduate programs in genetic counseling.

    Science.gov (United States)

    Fiddler, M B; Fine, B A; Baker, D L

    1996-09-01

    The American Board of Genetic Counseling (ABGC) sponsored a consensus development conference with participation from directors of graduate programs in genetic counseling, board members, and expert consultants. Using a collective, narrative, and case-based approach, 27 competencies were identified as embedded in the practice of genetic counseling. These competencies were organized into four domains of skills: Communication; Critical Thinking; Interpersonal, Counseling, and Psychosocial Assessment; and Professional Ethics and Values. The adoption of a competency framework for accreditation has a variety of implications for curriculum design and implementation. We report here the process by which a set of practice-based genetic counseling competencies have been derived; and in an accompanying article, the competencies themselves are provided. We also discuss the application of the competencies to graduate program accreditation as well as some of the implications competency-based standards may have for education and the genetic counseling profession. These guidelines may also serve as a basis for the continuing education of practicing genetic counselors and a performance evaluation tool in the workplace.

  15. Linkage intensity learning approach with genetic algorithm for causality diagram

    Institute of Scientific and Technical Information of China (English)

    WANG Cheng-liang; CHEN Juan-juan

    2007-01-01

    The causality diagram theory, which adopts graphical expression of knowledge and direct intensity of causality, overcomes some shortages in belief network and has evolved into a mixed causality diagram methodology for discrete and continuous variable. But to give linkage intensity of causality diagram is difficult, particularly in many working conditions in which sampling data are limited or noisy. The classic learning algorithm is hard to be adopted. We used genetic algorithm to learn linkage intensity from limited data. The simulation results demonstrate that this algorithm is more suitable than the classic algorithm in the condition of sample shortage such as space shuttle's fault diagnoisis.

  16. A Genetic-Algorithms-Based Approach for Programming Linear and Quadratic Optimization Problems with Uncertainty

    Directory of Open Access Journals (Sweden)

    Weihua Jin

    2013-01-01

    Full Text Available This paper proposes a genetic-algorithms-based approach as an all-purpose problem-solving method for operation programming problems under uncertainty. The proposed method was applied for management of a municipal solid waste treatment system. Compared to the traditional interactive binary analysis, this approach has fewer limitations and is able to reduce the complexity in solving the inexact linear programming problems and inexact quadratic programming problems. The implementation of this approach was performed using the Genetic Algorithm Solver of MATLAB (trademark of MathWorks. The paper explains the genetic-algorithms-based method and presents details on the computation procedures for each type of inexact operation programming problems. A comparison of the results generated by the proposed method based on genetic algorithms with those produced by the traditional interactive binary analysis method is also presented.

  17. Classical mechanics approach applied to analysis of genetic oscillators.

    Science.gov (United States)

    Vasylchenkova, Anastasiia; Mraz, Miha; Zimic, Nikolaj; Moskon, Miha

    2016-04-05

    Biological oscillators present a fundamental part of several regulatory mechanisms that control the response of various biological systems. Several analytical approaches for their analysis have been reported recently. They are, however, limited to only specific oscillator topologies and/or to giving only qualitative answers, i.e., is the dynamics of an oscillator given the parameter space oscillatory or not. Here we present a general analytical approach that can be applied to the analysis of biological oscillators. It relies on the projection of biological systems to classical mechanics systems. The approach is able to provide us with relatively accurate results in the meaning of type of behaviour system reflects (i.e. oscillatory or not) and periods of potential oscillations without the necessity to conduct expensive numerical simulations. We demonstrate and verify the proposed approach on three different implementations of amplified negative feedback oscillator.

  18. Admixture in Mexico City: implications for admixture mapping of type 2 diabetes genetic risk factors.

    Science.gov (United States)

    Martinez-Marignac, Veronica L; Valladares, Adan; Cameron, Emily; Chan, Andrea; Perera, Arjuna; Globus-Goldberg, Rachel; Wacher, Niels; Kumate, Jesús; McKeigue, Paul; O'Donnell, David; Shriver, Mark D; Cruz, Miguel; Parra, Esteban J

    2007-02-01

    Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases showing prevalence differences between major continental groups. Type 2 diabetes (T2D) is at least twice as prevalent in Native American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis of this complex disease. We have characterized the admixture proportions in a sample of 286 unrelated T2D patients and 275 controls from Mexico City and we discuss the implications of the results for admixture mapping studies. Admixture proportions were estimated using 69 autosomal ancestry-informative markers (AIMs). Maternal and paternal contributions were estimated from geographically informative mtDNA and Y-specific polymorphisms. The average proportions of Native American, European and, West African admixture were estimated as 65, 30, and 5%, respectively. The contributions of Native American ancestors to maternal and paternal lineages were estimated as 90 and 40%, respectively. In a logistic model with higher educational status as dependent variable, the odds ratio for higher educational status associated with an increase from 0 to 1 in European admixture proportions was 9.4 (95%, credible interval 3.8-22.6). This association of socioeconomic status with individual admixture proportion shows that genetic stratification in this population is paralleled, and possibly maintained, by socioeconomic stratification. The effective number of generations back to unadmixed ancestors was 6.7 (95% CI 5.7-8.0), from which we can estimate that genome-wide admixture mapping will require typing about 1,400 evenly distributed AIMs to localize genes underlying disease risk between populations of European and Native American ancestry. Sample sizes of about 2,000 cases will be required to detect any locus that contributes an ancestry risk ratio of at least 1.5.

  19. The Interactional Approach to The Teaching Of Writing and Its Implications for Second Language Acquisition

    Directory of Open Access Journals (Sweden)

    Lies Amin Lestari

    2006-01-01

    Full Text Available Writing is a language skill which is relatively difficult to acquire. A number of efforts have been made to develop the students’ writing skill, among others is by applying different approaches to the teaching of writing. This article discusses the interactional approach to the teaching of writing and its implications for second language acquisition.

  20. The Interactional Approach to the Teaching of Writing and Its Implications for Second Language Acquisition

    Directory of Open Access Journals (Sweden)

    Lies Amin Lestari

    2008-01-01

    Full Text Available Writing is a language skill which is relatively difficult to acquire. A number of efforts have been made to develop the students' writing skill, among others is by applying different approaches to the teaching of writing. This article discusses the interactional approach to the teaching of writing and its implications for second language acquisition.  

  1. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

    Science.gov (United States)

    Manning, Alisa K; Hivert, Marie-France; Scott, Robert A; Grimsby, Jonna L; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik; Jackson, Anne U; Johnson, Toby; Kanoni, Stavroula; Ladenvall, Claes; Lagou, Vasiliki; Lahti, Jari; Lecoeur, Cecile; Liu, Yongmei; Martinez-Larrad, Maria Teresa; Montasser, May E; Navarro, Pau; Perry, John R B; Rasmussen-Torvik, Laura J; Salo, Perttu; Sattar, Naveed; Shungin, Dmitry; Strawbridge, Rona J; Tanaka, Toshiko; van Duijn, Cornelia M; An, Ping; de Andrade, Mariza; Andrews, Jeanette S; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Bandinelli, Stefania; Beckmann, Jacques S; Beilby, John P; Bellis, Claire; Bergman, Richard N; Blangero, John; Boban, Mladen; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L; Boomsma, Dorret I; Borecki, Ingrid B; Böttcher, Yvonne; Bouchard, Claude; Brunner, Eric; Budimir, Danijela; Campbell, Harry; Carlson, Olga; Chines, Peter S; Clarke, Robert; Collins, Francis S; Corbatón-Anchuelo, Arturo; Couper, David; de Faire, Ulf; Dedoussis, George V; Deloukas, Panos; Dimitriou, Maria; Egan, Josephine M; Eiriksdottir, Gudny; Erdos, Michael R; Eriksson, Johan G; Eury, Elodie; Ferrucci, Luigi; Ford, Ian; Forouhi, Nita G; Fox, Caroline S; Franzosi, Maria Grazia; Franks, Paul W; Frayling, Timothy M; Froguel, Philippe; Galan, Pilar; de Geus, Eco; Gigante, Bruna; Glazer, Nicole L; Goel, Anuj; Groop, Leif; Gudnason, Vilmundur; Hallmans, Göran; Hamsten, Anders; Hansson, Ola; Harris, Tamara B; Hayward, Caroline; Heath, Simon; Hercberg, Serge; Hicks, Andrew A; Hingorani, Aroon; Hofman, Albert; Hui, Jennie; Hung, Joseph; Jarvelin, Marjo-Riitta; Jhun, Min A; Johnson, Paul C D; Jukema, J Wouter; Jula, Antti; Kao, W H; Kaprio, Jaakko; Kardia, Sharon L R; Keinanen-Kiukaanniemi, Sirkka; Kivimaki, Mika; Kolcic, Ivana; Kovacs, Peter; Kumari, Meena; Kuusisto, Johanna; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; Lannfelt, Lars; Lathrop, G Mark; Launer, Lenore J; Leander, Karin; Li, Guo; Lind, Lars; Lindstrom, Jaana; Lobbens, Stéphane; Loos, Ruth J F; Luan, Jian'an; Lyssenko, Valeriya; Mägi, Reedik; Magnusson, Patrik K E; Marmot, Michael; Meneton, Pierre; Mohlke, Karen L; Mooser, Vincent; Morken, Mario A; Miljkovic, Iva; Narisu, Narisu; O'Connell, Jeff; Ong, Ken K; Oostra, Ben A; Palmer, Lyle J; Palotie, Aarno; Pankow, James S; Peden, John F; Pedersen, Nancy L; Pehlic, Marina; Peltonen, Leena; Penninx, Brenda; Pericic, Marijana; Perola, Markus; Perusse, Louis; Peyser, Patricia A; Polasek, Ozren; Pramstaller, Peter P; Province, Michael A; Räikkönen, Katri; Rauramaa, Rainer; Rehnberg, Emil; Rice, Ken; Rotter, Jerome I; Rudan, Igor; Ruokonen, Aimo; Saaristo, Timo; Sabater-Lleal, Maria; Salomaa, Veikko; Savage, David B; Saxena, Richa; Schwarz, Peter; Seedorf, Udo; Sennblad, Bengt; Serrano-Rios, Manuel; Shuldiner, Alan R; Sijbrands, Eric J G; Siscovick, David S; Smit, Johannes H; Small, Kerrin S; Smith, Nicholas L; Smith, Albert Vernon; Stančáková, Alena; Stirrups, Kathleen; Stumvoll, Michael; Sun, Yan V; Swift, Amy J; Tönjes, Anke; Tuomilehto, Jaakko; Trompet, Stella; Uitterlinden, Andre G; Uusitupa, Matti; Vikström, Max; Vitart, Veronique; Vohl, Marie-Claude; Voight, Benjamin F; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Watkins, Hugh; Wheeler, Eleanor; Widen, Elisabeth; Wild, Sarah H; Willems, Sara M; Willemsen, Gonneke; Wilson, James F; Witteman, Jacqueline C M; Wright, Alan F; Yaghootkar, Hanieh; Zelenika, Diana; Zemunik, Tatijana; Zgaga, Lina; Wareham, Nicholas J; McCarthy, Mark I; Barroso, Ines; Watanabe, Richard M; Florez, Jose C; Dupuis, Josée; Meigs, James B; Langenberg, Claudia

    2012-05-13

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

  2. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    Science.gov (United States)

    Manning, Alisa K.; Hivert, Marie-France; Scott, Robert A.; Grimsby, Jonna L.; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F.; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik; Jackson, Anne U.; Johnson, Toby; Kanoni, Stavroula; Ladenvall, Claes; Lagou, Vasiliki; Lahti, Jari; Lecoeur, Cecile; Liu, Yongmei; Martinez-Larrad, Maria Teresa; Montasser, May E.; Navarro, Pau; Perry, John R. B.; Rasmussen-Torvik, Laura J.; Salo, Perttu; Sattar, Naveed; Shungin, Dmitry; Strawbridge, Rona J.; Tanaka, Toshiko; van Duijn, Cornelia M.; An, Ping; de Andrade, Mariza; Andrews, Jeanette S.; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Bandinelli, Stefania; Beckmann, Jacques S.; Beilby, John P.; Bellis, Claire; Bergman, Richard N.; Blangero, John; Boban, Mladen; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Borecki, Ingrid B.; Böttcher, Yvonne; Bouchard, Claude; Brunner, Eric; Budimir, Danijela; Campbell, Harry; Carlson, Olga; Chines, Peter S.; Clarke, Robert; Collins, Francis S.; Corbatón-Anchuelo, Arturo; Couper, David; de Faire, Ulf; Dedoussis, George V; Deloukas, Panos; Dimitriou, Maria; Egan, Josephine M; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Eury, Elodie; Ferrucci, Luigi; Ford, Ian; Forouhi, Nita G.; Fox, Caroline S; Franzosi, Maria Grazia; Franks, Paul W; Frayling, Timothy M; Froguel, Philippe; Galan, Pilar; de Geus, Eco; Gigante, Bruna; Glazer, Nicole L.; Goel, Anuj; Groop, Leif; Gudnason, Vilmundur; Hallmans, Göran; Hamsten, Anders; Hansson, Ola; Harris, Tamara B.; Hayward, Caroline; Heath, Simon; Hercberg, Serge; Hicks, Andrew A.; Hingorani, Aroon; Hofman, Albert; Hui, Jennie; Hung, Joseph; Jarvelin, Marjo Riitta; Jhun, Min A.; Johnson, Paul C.D.; Jukema, J Wouter; Jula, Antti; Kao, W.H.; Kaprio, Jaakko; Kardia, Sharon L. R.; Keinanen-Kiukaanniemi, Sirkka; Kivimaki, Mika; Kolcic, Ivana; Kovacs, Peter; Kumari, Meena; Kuusisto, Johanna; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; Lannfelt, Lars; Lathrop, G Mark; Launer, Lenore J.; Leander, Karin; Li, Guo; Lind, Lars; Lindstrom, Jaana; Lobbens, Stéphane; Loos, Ruth J. F.; Luan, Jian’an; Lyssenko, Valeriya; Mägi, Reedik; Magnusson, Patrik K. E.; Marmot, Michael; Meneton, Pierre; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Miljkovic, Iva; Narisu, Narisu; O’Connell, Jeff; Ong, Ken K.; Oostra, Ben A.; Palmer, Lyle J.; Palotie, Aarno; Pankow, James S.; Peden, John F.; Pedersen, Nancy L.; Pehlic, Marina; Peltonen, Leena; Penninx, Brenda; Pericic, Marijana; Perola, Markus; Perusse, Louis; Peyser, Patricia A; Polasek, Ozren; Pramstaller, Peter P.; Province, Michael A.; Räikkönen, Katri; Rauramaa, Rainer; Rehnberg, Emil; Rice, Ken; Rotter, Jerome I.; Rudan, Igor; Ruokonen, Aimo; Saaristo, Timo; Sabater-Lleal, Maria; Salomaa, Veikko; Savage, David B.; Saxena, Richa; Schwarz, Peter; Seedorf, Udo; Sennblad, Bengt; Serrano-Rios, Manuel; Shuldiner, Alan R.; Sijbrands, Eric J.G.; Siscovick, David S.; Smit, Johannes H.; Small, Kerrin S.; Smith, Nicholas L.; Smith, Albert Vernon; Stančáková, Alena; Stirrups, Kathleen; Stumvoll, Michael; Sun, Yan V.; Swift, Amy J.; Tönjes, Anke; Tuomilehto, Jaakko; Trompet, Stella; Uitterlinden, Andre G.; Uusitupa, Matti; Vikström, Max; Vitart, Veronique; Vohl, Marie-Claude; Voight, Benjamin F.; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Watkins, Hugh; Wheeler, Eleanor; Widen, Elisabeth; Wild, Sarah H.; Willems, Sara M.; Willemsen, Gonneke; Wilson, James F.; Witteman, Jacqueline C.M.; Wright, Alan F.; Yaghootkar, Hanieh; Zelenika, Diana; Zemunik, Tatijana; Zgaga, Lina; Wareham, Nicholas J.; McCarthy, Mark I.; Barroso, Ines; Watanabe, Richard M.; Florez, Jose C.; Dupuis, Josée; Meigs, James B.; Langenberg, Claudia

    2013-01-01

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction, but contributed little to our understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways may be uncovered by accounting for differences in body mass index (BMI) and potential interaction between BMI and genetic variants. We applied a novel joint meta-analytical approach to test associations with fasting insulin (FI) and glucose (FG) on a genome-wide scale. We present six previously unknown FI loci at Pdiscovery and follow-up analyses of 52 studies comprising up to 96,496non-diabetic individuals. Risk variants were associated with higher triglyceride and lower HDL cholesterol levels, suggestive of a role for these FI loci in insulin resistance pathways. The localization of these additional loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. PMID:22581228

  3. Introduction: integrating genetic and cultural evolutionary approaches to language.

    Science.gov (United States)

    Mesoudi, Alex; McElligott, Alan G; Adger, David

    2011-04-01

    The papers in this special issue of Human Biology address recent research in the field of language evolution, both the genetic evolution of the language faculty and the cultural evolution of specific languages. While both of these areas have received increasing interest in recent years, there is also a need to integrate these somewhat separate efforts and explore the relevant gene-culture coevolutionary interactions. Here we summarize the individual contributions, set them in the context of the wider literature, and identify outstanding future research questions. The first set of papers concerns the comparative study of nonhuman communication in primates and birds from both a behavioral and neurobiological perspective, revealing evidence for several common language-related traits in various nonhuman species and providing clues as to the evolutionary origin and function of the human language faculty. The second set of papers discusses the consequences of viewing language as a culturally evolving system in its own right, including claims that this removes the need for strong genetic biases for language acquisition, and that phylogenetic evolutionary methods can be used to reconstruct language histories. We conclude by highlighting outstanding areas for future research, including identifying the precise selection pressures that gave rise to the language faculty in ancestral hominin species, and determining the strength, domain specificity, and origin of the cultural transmission biases that shape languages as they pass along successive generations of language learners.

  4. A candidate gene approach identifies an IL33 genetic variant as a novel genetic risk factor for GCA.

    Directory of Open Access Journals (Sweden)

    Ana Márquez

    Full Text Available Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition.A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays.A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (P(MH = 0.041, OR = 0.88, CI 95% 0.78-0.99 and recessive (P(MH = 3.40E-03, OR = 0.53, CI 95% 0.35-0.80 models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis.Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA.

  5. 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.

  6. AGROBACTERIUM-MEDIATED GENETIC TRANSFORMATION OF SORGHUM USING TISSUE CULTURE-BASED AND POLLEN-MEDIATED APPROACHES

    OpenAIRE

    Elkonin L.A.; O.N. Nosova; J.V. Italianskaya

    2012-01-01

    Genetic transformation is a powerful tool for genetic improvement of arable crops. Genetic engineering approaches are especially important for modification of starch and protein contents, vitamin and micronutrient concentration, improvement of nutritive value of protein fractions, and increase tolerance to environmental stresses. Application of transgenic technologies for genetic improvement of sorghum, a highly productive heat tolerant and drought resistant crop, is extremely important since...

  7. The Sociopolitical Importance of Genetic, Phenomenological Approaches to Science Teaching and Learning

    Science.gov (United States)

    Bazzul, Jesse

    2015-01-01

    This article discusses Wolff-Michael Roth's theoretical framework for a phenomenological, genetic approach to science teaching and learning based on the work of Edmund Husserl. This approach advocates the inclusion of student lifeworlds in science education and underlines the importance of thinking about subjectivity in both science and science…

  8. A Genetic Algorithms-based Approach for Optimized Self-protection in a Pervasive Service Middleware

    DEFF Research Database (Denmark)

    Zhang, Weishan; Ingstrup, Mads; Hansen, Klaus Marius

    2009-01-01

    the constraints of heterogeneous devices and networks. In this paper, we present a Genetic Algorithms-based approach for obtaining optimized security configurations at run time, supported by a set of security OWL ontologies and an event-driven framework. This approach has been realized as a prototype for self...

  9. The Sociopolitical Importance of Genetic, Phenomenological Approaches to Science Teaching and Learning

    Science.gov (United States)

    Bazzul, Jesse

    2015-01-01

    This article discusses Wolff-Michael Roth's theoretical framework for a phenomenological, genetic approach to science teaching and learning based on the work of Edmund Husserl. This approach advocates the inclusion of student lifeworlds in science education and underlines the importance of thinking about subjectivity in both science and science…

  10. Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach

    Science.gov (United States)

    Kumar, Alok; Ghosh, Devlina; Singh, R. L.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients. PMID:26317018

  11. Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Alok Kumar

    2013-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients.

  12. An approach for in vitro genetic networks assembly

    Science.gov (United States)

    Noireaux, Vincent; Bar-Ziv, Roy; Libchaber, Albert

    2004-03-01

    A cell-free expression extract has been used to assemble genetic circuits in vitro. The extract, which does not contained endogenous DNA and RNA, is used as a battery to carry out transcription and translation of genes inserted into plasmids. We engineered transcriptional activation and repression cascades, in which the protein product of each stage is the input required to drive or block the following stage. Although we can find regions of linear response for single stages, cascading to subsequent stages requires working in non-linear regimes. Substantial time delays and dramatic decreases in output production are incurred with each additional stage, due to a bottleneck at the translation machinery. Faster turnover of RNA message can relieve competition between genes and stabilize output against variations in input and parameters.

  13. Data Mining Using Neural–Genetic Approach: A Review

    Directory of Open Access Journals (Sweden)

    Parvez Rahi

    2014-04-01

    Full Text Available In the advance age of technology, there is an increasing availability of digital documents in various languages in various fields. Data mining is gaining popularity in field of knowledge discovery. Data mining is the knowledge discovery process by which we can analyze the large amounts of data from various data repositories and summarizing it into information useful to us. Due to its importance of extracting information/ knowledge from the large data repositories, data mining has become an essential part of human life in various fields. Data mining has a very wide area of applications, and these applications have enriched the human life in various fields including scientific, medical, business, education etc. Here in this paper we will discuss the emphasis of Neural Network and Genetic Algorithm in the field of data mining.

  14. 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...

  15. [Mendelian randomisation - a genetic approach to an epidemiological method].

    Science.gov (United States)

    Stensrud, Mats Julius

    2016-06-01

    BACKGROUND Genetic information is becoming more easily available, and rapid progress is being made in developing methods of illuminating issues of interest. Mendelian randomisation makes it possible to study causes of disease using observational data. The name refers to the random distribution of gene variants in meiosis. The methodology makes use of genes that influence a risk factor for a disease, without influencing the disease itself. In this review article I explain the principles behind Mendelian randomisation and present the areas of application for this methodology.MATERIAL AND METHOD Methodology articles describing Mendelian randomisation were reviewed. The articles were found through a search in PubMed with the combination «mendelian randomization» OR «mendelian randomisation», and a search in McMaster Plus with the combination «mendelian randomization». A total of 15 methodology articles were read in full text. Methodology articles were supplemented by clinical studies found in the PubMed search.RESULTS In contrast to traditional observational studies, Mendelian randomisation studies are not affected by two important sources of error: conventional confounding variables and reverse causation. Mendelian randomisation is therefore a promising tool for studying causality. Mendelian randomisation studies have already provided valuable knowledge on the risk factors for a wide range of diseases. It is nevertheless important to be aware of the limitations of the methodology. As a result of the rapid developments in genetics research, Mendelian randomisation will probably be widely used in future years.INTERPRETATION If Mendelian randomisation studies are conducted correctly, they may help to reveal both modifiable and non-modifiable causes of disease.

  16. 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.

  17. Genetic Approaches to Appearance and Ancestry : Improving Forensic DNA Analysis

    NARCIS (Netherlands)

    L.C. Chaitanya (Lakshmi)

    2016-01-01

    textabstractTraditionally, routine forensic casework is based on comparative grounds. DNA profiles obtained from crime-scenes are compared with those of potential suspects or DNA profiles deposited in forensic DNA databases. The principal limitation of such comparative approach is that trace donors

  18. 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)

  19. Genetic and metabolomic approaches for coronary heart disease risk prediction

    NARCIS (Netherlands)

    Vaarhorst, Anika Antoinette Maria

    2014-01-01

    The prediction of coronary heart disease (CHD) risk is currently based on traditional risk factors (TRFs) like age, sex, lipid levels, blood pressure. Here we investigated, using the CAREMA cohort, whether this prediction can potentially be improved by applying a metabolomics approach and by includi

  20. The underlying mechanisms of genetic innovation and speciation in the family Corynebacteriaceae: A phylogenomics approach.

    Science.gov (United States)

    Zhi, Xiao-Yang; Jiang, Zhao; Yang, Ling-Ling; Huang, Ying

    2017-02-01

    The pangenome of a bacterial species population is formed by genetic reduction and genetic expansion over the long course of evolution. Gene loss is a pervasive source of genetic reduction, and (exogenous and endogenous) gene gain is the main driver of genetic expansion. To understand the genetic innovation and speciation of the family Corynebacteriaceae, which cause a wide range of serious infections in humans and animals, we analyzed the pangenome of this family, and reconstructed its phylogeny using a phylogenomics approach. Genetic variations have occurred throughout the whole evolutionary history of the Corynebacteriaceae. Gene loss has been the primary force causing genetic changes, not only in terms of the number of protein families affected, but also because of its continuity on the time series. The variation in metabolism caused by these genetic changes mainly occurred for membrane transporters, two-component systems, and metabolism related to amino acids and carbohydrates. Interestingly, horizontal gene transfer (HGT) not only caused changes related to pathogenicity, but also triggered the acquisition of antimicrobial resistance. The Darwinian theory of evolution did not adequately explain the effects of dispersive HGT and/or gene loss in the evolution of the Corynebacteriaceae. These findings provide new insight into the evolution and speciation of Corynebacteriaceae and advance our understanding of the genetic innovation in microbial populations.

  1. A large health system's approach to utilization of the genetic counselor CPT® 96040 code.

    Science.gov (United States)

    Gustafson, Shanna L; Pfeiffer, Gail; Eng, Charis

    2011-12-01

    : In 2007, CPT® code 96040 was approved for genetic counseling services provided by nonphysician providers. Because of professional recognition and licensure limitations, experiences in direct billing by genetic counselors for these services are limited. A minority of genetics clinics report using this code because of limitations, including perceived denial of the code and confusion regarding compliant use of this code. We present results of our approach to 96040 billing for genetic counseling services under a supervising physicians National Provider ID number in a strategy for integration of genetics services within nongenetics specialty departments of a large academic medical center. : The 96040 billing encounters were tracked for a 14-month period and analyzed for reimbursement by private payers. Association of denial by diagnosis code or specialty of genetics service was statistically analyzed. Descriptive data regarding appointment availability are also summarized. : Of 350 encounters January 2008 to February 2009, 289 (82%) were billed to private payers. Of these, 62.6% received some level of reimbursement. No association was seen for denial when analyzed by the diagnosis code or by genetics focus. Through this model, genetics appointment availability minimally doubled. : Using 96040 allowed for expanding access to genetics services, increased appointment availability, and was successful in obtaining reimbursement for more than half of encounters billed.

  2. Empirical valence bond models for reactive potential energy surfaces: a parallel multilevel genetic program approach.

    Science.gov (United States)

    Bellucci, Michael A; Coker, David F

    2011-07-28

    We describe a new method for constructing empirical valence bond potential energy surfaces using a parallel multilevel genetic program (PMLGP). Genetic programs can be used to perform an efficient search through function space and parameter space to find the best functions and sets of parameters that fit energies obtained by ab initio electronic structure calculations. Building on the traditional genetic program approach, the PMLGP utilizes a hierarchy of genetic programming on two different levels. The lower level genetic programs are used to optimize coevolving populations in parallel while the higher level genetic program (HLGP) is used to optimize the genetic operator probabilities of the lower level genetic programs. The HLGP allows the algorithm to dynamically learn the mutation or combination of mutations that most effectively increase the fitness of the populations, causing a significant increase in the algorithm's accuracy and efficiency. The algorithm's accuracy and efficiency is tested against a standard parallel genetic program with a variety of one-dimensional test cases. Subsequently, the PMLGP is utilized to obtain an accurate empirical valence bond model for proton transfer in 3-hydroxy-gamma-pyrone in gas phase and protic solvent.

  3. Managerial implications and suitability of a master surgical scheduling approach

    NARCIS (Netherlands)

    J.M. van Oostrum (Jeroen); E. Bredenhoff (Eelco); E.W. Hans (Erwin)

    2008-01-01

    textabstractMaster surgical scheduling can improve manageability and efficiency of operating room departments. This approach cyclically executes a master surgical schedule of surgery types. These surgery types need to be constructed with low variability to be efficient. Each surgery type is schedule

  4. Managerial implications and suitability of a master surgical scheduling approach

    NARCIS (Netherlands)

    J.M. van Oostrum (Jeroen); E. Bredenhoff (Eelco); E.W. Hans (Erwin)

    2008-01-01

    textabstractMaster surgical scheduling can improve manageability and efficiency of operating room departments. This approach cyclically executes a master surgical schedule of surgery types. These surgery types need to be constructed with low variability to be efficient. Each surgery type is

  5. A Domain-Independent Window Approach to Multiclass Object Detection Using Genetic Programming

    Directory of Open Access Journals (Sweden)

    Mengjie Zhang

    2003-07-01

    Full Text Available This paper describes a domain-independent approach to the use of genetic programming for object detection problems in which the locations of small objects of multiple classes in large images must be found. The evolved program is scanned over the large images to locate the objects of interest. The paper develops three terminal sets based on domain-independent pixel statistics and considers two different function sets. The fitness function is based on the detection rate and the false alarm rate. We have tested the method on three object detection problems of increasing difficulty. This work not only extends genetic programming to multiclass-object detection problems, but also shows how to use a single evolved genetic program for both object classification and localisation. The object classification map developed in this approach can be used as a general classification strategy in genetic programming for multiple-class classification problems.

  6. 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.

  7. Search for genetic virulence markers in viral haemorrhagic septicaemia virus (VHSV) using a reverse genetics approach

    DEFF Research Database (Denmark)

    Stegmann, Anders; Biacchesi, S.; Bremont, M.

    2011-01-01

    VHSV is a negative strand RNA virus causing serious disease in farmed rainbow trout. Although VHSV has been eradicated by stamping out procedures in several fresh water bodies, recently including all streams in Denmark, the wildlife marine reservoir still represents a threat against rainbow trout...... farming. Particularly in Scandinavia, outbreaks of VHS in sea reared rainbow trout have demonstrated that although marine variants of VHSV are considered to be avirulent to rainbow trout, the virus is potentially able to adapt to this host and cause disease. Limited knowledge about the genetic background...

  8. A Detailed look of Audio Steganography Techniques using LSB and Genetic Algorithm Approach

    OpenAIRE

    Gunjan Nehru; Puja Dhar

    2012-01-01

    This paper is the study of various techniques of audio steganography using different algorithmis like genetic algorithm approach and LSB approach. We have tried some approaches that helps in audio steganography. As we know it is the art and science of writing hidden messages in such a way that no one, apart from the sender and intended recipient, suspects the existence of the message, a form of security through obscurity. In steganography, the message used to hide secret message is called hos...

  9. A Genetic Algorithms Based Approach for Group Multicast Routing

    Directory of Open Access Journals (Sweden)

    Luca Sanna Randaccio

    2006-08-01

    Full Text Available Whereas multicast transmission in one-to-many communications allows the operator to drastically save network resources, it also makes the routing of the traffic flows more complex then in unicast transmissions. A huge amount of possible trees have to be considered and analyzed to find the appropriate routing paths. To address this problem, we propose the use of the genetic algorithms (GA, which considerably reduce the number of solutions to be evaluated. A heuristic procedure is first used to discern a set of possible trees for each multicast session in isolation. Then, the GA are applied to find the appropriate combination of the trees to comply with the bandwidth needs of the group of multicast sessions simultaneously. The goodness of each solution is assessed by means of an expression that weights both network bandwidth allocation and one-way delay. The resulting cost function is guided by few parameters that can be easily tuned during traffic engineering operations; an appropriate setting of these parameters allows the operator to configure the desired balance between network resource utilization and provided quality of service. Simulations have been performed to compare the proposed algorithm with alternative solutions in terms of bandwidth utilization and transmission delay.

  10. Hybrid genetic algorithm approach for selective harmonic control

    Energy Technology Data Exchange (ETDEWEB)

    Dahidah, Mohamed S.A. [Faculty of Engineering, Multimedia University, 63100, Jalan Multimedia-Cyberjaya, Selangor (Malaysia); Agelidis, Vassilios G. [School of Electrical and Information Engineering, The University of Sydney, NSW (Australia); Rao, Machavaram V. [Faculty of Engineering and Technology, Multimedia University, 75450, Jalan Ayer Keroh Lama-Melaka (Malaysia)

    2008-02-15

    The paper presents an optimal solution for a selective harmonic elimination pulse width modulated (SHE-PWM) technique suitable for a high power inverter used in constant frequency utility applications. The main challenge of solving the associated non-linear equations, which are transcendental in nature and, therefore, have multiple solutions, is the convergence, and therefore, an initial point selected considerably close to the exact solution is required. The paper discusses an efficient hybrid real coded genetic algorithm (HRCGA) that reduces significantly the computational burden, resulting in fast convergence. An objective function describing a measure of the effectiveness of eliminating selected orders of harmonics while controlling the fundamental, namely a weighted total harmonic distortion (WTHD) is derived, and a comparison of different operating points is reported. It is observed that the method was able to find the optimal solution for a modulation index that is higher than unity. The theoretical considerations reported in this paper are verified through simulation and experimentally on a low power laboratory prototype. (author)

  11. 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.

  12. Diagnostic/genetic sreening - approach for genetic diagnoses and prevention of cleft lip and/or palate.

    Science.gov (United States)

    Natsume, Nagato; Kato, Tomoki; Hayakawa, Toko; Imura, Hideto

    2013-01-01

    The treatment, research and volunteer work for cleft lip and/or palate (CL/P) has been led for over 30 years by our team. Within this period, more than 4,000 cases of CL/P were treated and at the same time, and approximately 400 papers were published as the first or partner researcher in Nature Genetics, New England Journal of Medicine and others. In addition, with $20 million that was donated from companies and laypeople, and the grant from the Japanese government, CL/P centres in many countries and in Japan, the oral and craniofacial congenital anomaly gene bank in our CL/P centre was established by our leadership. In the bank there are genes from approximately more than 8,000 cases. The genes were mapped with Professor Jeffery Murray of Iowa University in the United States, the findings about genetic syndromes such as Van der Woude Syndrome and basal cell nevus syndrome were applied in clinical settings. The genetic counselling section that specialises in the oral and maxillofacial field was established by our effort for the first time in Japan. In this review, our clinical experience and approach for genetic diagnoses and prevention of cleft lip and/or palate will be discussed.

  13. Understanding of Genetic Information in Higher Secondary Students in Northeast India and the Implications for Genetics Education

    Science.gov (United States)

    Chattopadhyay, Ansuman

    2005-01-01

    Since the work of Watson and Crick in the mid-1950s, the science of genetics has become increasingly molecular. The development of recombinant DNA technologies by the agricultural and pharmaceutical industries led to the introduction of genetically modified organisms (GMOs). By the end of the twentieth century, reports of animal cloning and recent…

  14. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    NARCIS (Netherlands)

    Manning, Alisa K.; Hivert, Marie-France; Scott, Robert A.; Grimsby, Jonna L.; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F.; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik; Jackson, Anne U.; Johnson, Toby; Kanoni, Stavroula; Ladenvall, Claes; Lagou, Vasiliki; Lahti, Jari; Lecoeur, Cecile; Liu, Yongmei; Martinez-Larrad, Maria Teresa; Montasser, May E.; Navarro, Pau; Perry, John R. B.; Rasmussen-Torvik, Laura J.; Salo, Perttu; Sattar, Naveed; Shungin, Dmitry; Strawbridge, Rona J.; Tanaka, Toshiko; van Duijn, Cornelia M.; An, Ping; de Andrade, Mariza; Andrews, Jeanette S.; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Bandinelli, Stefania; Beckmann, Jacques S.; Beilby, John P.; Bellis, Claire; Bergman, Richard N.; Blangero, John; Boban, Mladen; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Borecki, Ingrid B.; Boettcher, Yvonne; Bouchard, Claude; Brunner, Eric; Budimir, Danijela; Campbell, Harry; Carlson, Olga; Chines, Peter S.; Clarke, Robert; Collins, Francis S.; Corbaton-Anchuelo, Arturo; Couper, David; de Faire, Ulf; Dedoussis, George V.; Deloukas, Panos; Dimitriou, Maria; Egan, Josephine M.; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Eury, Elodie; Ferrucci, Luigi; Ford, Ian; Forouhi, Nita G.; Fox, Caroline S.; Franzosi, Maria Grazia; Franks, Paul W.; Frayling, Timothy M.; Froguel, Philippe; Galan, Pilar; de Geus, Eco; Gigante, Bruna; Glazer, Nicole L.; Goel, Anuj; Groop, Leif; Gudnason, Vilmundur; Hallmans, Goeran; Hamsten, Anders; Hansson, Ola; Harris, Tamara B.; Hayward, Caroline; Heath, Simon; Hercberg, Serge; Hicks, Andrew A.; Hingorani, Aroon; Hofman, Albert; Hui, Jennie; Hung, Joseph; Jarvelin, Marjo-Riitta; Jhun, Min A.; Johnson, Paul C. D.; Jukema, J. Wouter; Jula, Antti; Kao, W. H.; Kaprio, Jaakko; Kardia, Sharon L. R.; Keinanen-Kiukaanniemi, Sirkka; Kivimaki, Mika; Kolcic, Ivana; Kovacs, Peter; Kumari, Meena; Kuusisto, Johanna; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; Lannfelt, Lars; Lathrop, G. Mark; Launer, Lenore J.; Leander, Karin; Li, Guo; Lind, Lars; Lindstrom, Jaana; Lobbens, Stephane; Loos, Ruth J. F.; Luan, Jian'an; Lyssenko, Valeriya; Magi, Reedik; Magnusson, Patrik K. E.; Marmot, Michael; Meneton, Pierre; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Miljkovic, Iva; Narisu, Narisu; O'Connell, Jeff; Ong, Ken K.; Oostra, Ben A.; Palmer, Lyle J.; Palotie, Aarno; Pankow, James S.; Peden, John F.; Pedersen, Nancy L.; Pehlic, Marina; Peltonen, Leena; Penninx, Brenda; Pericic, Marijana; Perola, Markus; Perusse, Louis; Peyser, Patricia A.; Polasek, Ozren; Pramstaller, Peter P.; Province, Michael A.; Raikkonen, Katri; Rauramaa, Rainer; Rehnberg, Emil; Rice, Ken; Rotter, Jerome I.; Rudan, Igor; Ruokonen, Aimo; Saaristo, Timo; Sabater-Lleal, Maria; Salomaa, Veikko; Savage, David B.; Saxena, Richa; Schwarz, Peter; Seedorf, Udo; Sennblad, Bengt; Serrano-Rios, Manuel; Shuldiner, Alan R.; Sijbrands, Eric J. G.; Siscovick, David S.; Smit, Johannes H.; Small, Kerrin S.; Smith, Nicholas L.; Smith, Albert Vernon; Stancakova, Alena; Stirrups, Kathleen; Stumvoll, Michael; Sun, Yan V.; Swift, Amy J.; Toenjes, Anke; Tuomilehto, Jaakko; Trompet, Stella; Uitterlinden, Andre G.; Uusitupa, Matti; Vikstrom, Max; Vitart, Veronique; Vohl, Marie-Claude; Voight, Benjamin F.; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M.; Watkins, Hugh; Wheeler, Eleanor; Widen, Elisabeth; Wild, Sarah H.; Willems, Sara M.; Willemsen, Gonneke; Wilson, James F.; Witteman, Jacqueline C. M.; Wright, Alan F.; Yaghootkar, Hanieh; Zelenika, Diana; Zemunik, Tatijana; Zgaga, Lina; Wareham, Nicholas J.; McCarthy, Mark I.; Barroso, Ines; Watanabe, Richard M.; Florez, Jose C.; Dupuis, Josee; Meigs, James B.; Langenberg, Claudia

    2012-01-01

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathw

  15. Strategic Decision Making for Organizational Sustainability: The Implications of Servant Leadership and Sustainable Leadership Approaches

    Directory of Open Access Journals (Sweden)

    Judita Peterlin

    2015-12-01

    Full Text Available This conceptual paper explores the implications of servant leadership and sustainable leadership for strategic decision making by the top management of an organization. It is argued that a different type of leadership is required if effective strategic decisions are to be made in organizations striving to become more sustainable and that servant leadership and sustainable leadership approaches provide a sound basis to inform these decisions. The contributions of these two leadership approaches are explored, before considering the implications for leadership development. Particularly, the inclusion in leadership development programmes of values based leadership, and the development of integrative thinking, is discussed.

  16. A genetic programming approach to oral cancer prognosis

    Directory of Open Access Journals (Sweden)

    Mei Sze Tan

    2016-09-01

    Full Text Available Background The potential of genetic programming (GP on various fields has been attained in recent years. In bio-medical field, many researches in GP are focused on the recognition of cancerous cells and also on gene expression profiling data. In this research, the aim is to study the performance of GP on the survival prediction of a small sample size of oral cancer prognosis dataset, which is the first study in the field of oral cancer prognosis. Method GP is applied on an oral cancer dataset that contains 31 cases collected from the Malaysia Oral Cancer Database and Tissue Bank System (MOCDTBS. The feature subsets that is automatically selected through GP were noted and the influences of this subset on the results of GP were recorded. In addition, a comparison between the GP performance and that of the Support Vector Machine (SVM and logistic regression (LR are also done in order to verify the predictive capabilities of the GP. Result The result shows that GP performed the best (average accuracy of 83.87% and average AUROC of 0.8341 when the features selected are smoking, drinking, chewing, histological differentiation of SCC, and oncogene p63. In addition, based on the comparison results, we found that the GP outperformed the SVM and LR in oral cancer prognosis. Discussion Some of the features in the dataset are found to be statistically co-related. This is because the accuracy of the GP prediction drops when one of the feature in the best feature subset is excluded. Thus, GP provides an automatic feature selection function, which chooses features that are highly correlated to the prognosis of oral cancer. This makes GP an ideal prediction model for cancer clinical and genomic data that can be used to aid physicians in their decision making stage of diagnosis or prognosis.

  17. The quantitative genetic basis of adaptive divergence in the moor frog (Rana arvalis) and its implications for gene flow.

    Science.gov (United States)

    Hangartner, S; Laurila, A; Räsänen, K

    2012-08-01

    Knowledge on the relative contribution of direct genetic, maternal and environmental effects to adaptive divergence is important for understanding the drivers of biological diversification. The moor frog (Rana arvalis) shows adaptive divergence in embryonic and larval fitness traits along an acidification gradient in south-western Sweden. To understand the quantitative genetic basis of this divergence, we performed reciprocal crosses between three divergent population pairs and reared embryos and larvae at acid and neutral pH in the laboratory. Divergence in embryonic acid tolerance (survival) was mainly determined by maternal effects, whereas the relative contributions of maternal, additive and nonadditive genetic effects in larval life-history traits differed between traits, population pairs and rearing environments. These results emphasize the need to investigate the quantitative genetic basis of adaptive divergence in multiple populations and traits, as well as different environments. We discuss the implications of our findings for maintenance of local adaptation in the context of migrant and hybrid fitness.

  18. Genetics

    Science.gov (United States)

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  19. Genetic algorithm based image binarization approach and its quantitative evaluation via pooling

    Science.gov (United States)

    Hu, Huijun; Liu, Ya; Liu, Maofu

    2015-12-01

    The binarized image is very critical to image visual feature extraction, especially shape feature, and the image binarization approaches have been attracted more attentions in the past decades. In this paper, the genetic algorithm is applied to optimizing the binarization threshold of the strip steel defect image. In order to evaluate our genetic algorithm based image binarization approach in terms of quantity, we propose the novel pooling based evaluation metric, motivated by information retrieval community, to avoid the lack of ground-truth binary image. Experimental results show that our genetic algorithm based binarization approach is effective and efficiency in the strip steel defect images and our quantitative evaluation metric on image binarization via pooling is also feasible and practical.

  20. [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.

  1. Genetic Evidence of Hybridization between the Endangered Native Species Iguana delicatissima and the Invasive Iguana iguana (Reptilia, Iguanidae in the Lesser Antilles: Management Implications.

    Directory of Open Access Journals (Sweden)

    Barbara Vuillaume

    Full Text Available The worldwide increase of hybridization in different groups is thought to have become more important with the loss of isolating barriers and the introduction of invasive species. This phenomenon could result in the extinction of endemic species. This study aims at investigating the hybridization dynamics between the endemic and threatened Lesser Antillean iguana (Iguana delicatissima and the invasive common green iguana (Iguana iguana in the Lesser Antilles, as well as assessing the impact of interspecific hybridization on the decline of I. delicatissima. 59 I. delicatissima (5 localities, 47 I. iguana (12 localities and 27 hybrids (5 localities, who were all identified based on morphological characters, have been genotyped at 15 microsatellites markers. We also sequenced hybrids using ND4 mitochondrial loci to further investigate mitochondrial introgression. The genetic clustering of species and hybrid genetic assignment were performed using a comparative approach, through the implementation of a Discriminant Analysis of Principal Component (DAPC based on statistics, as well as genetic clustering approaches based on the genetic models of several populations (Structure, NewHybrids and HIest, in order to get full characterization of hybridization patterns and introgression dynamics across the islands. The iguanas identified as hybrids in the wild, thanks to morphological analysis, were all genetically F1, F2, or backcrosses. A high proportion of individuals were also the result of a longer-term admixture. The absence of reproductive barriers between species leads to hybridization when species are in contact. Yet morphological and behavioral differences between species could explain why males I. iguana may dominate I. delicatissima, thus resulting in short-term species displacement and extinction by hybridization and recurrent introgression from I. iguana toward I. delicatissima. As a consequence, I. delicatissima gets eliminated through

  2. Loss of Genetic Diversity of Jatropha curcas L. through Domestication: Implications for Its Genetic Improvement

    DEFF Research Database (Denmark)

    Sanou, Haby; Angel Angulo-Escalante, Miguel; Martinez-Herrera, Jorge

    2015-01-01

    populations. Results confirmed very low genetic diversity in African and Asian landraces. Mexican populations from the regions of Veracruz, Puebla, and Morelos were also found to have low levels of diversity (mostly monomorphic), while populations from Chiapas were polymorphic with an expected heterozygosity....... Mating system could not be estimated in the landraces from Mali and populations from Veracruz, Puebla, and Morelos (Mexico), as these were highly monomorphic. The observed low level of genetic diversity in some of the populations and landraces suggests that breeding programs should test for genetic...

  3. Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism.

    Science.gov (United States)

    Bayefsky, Michelle J

    2016-12-01

    Unlike many European nations, the USA has no regulations concerning the use of preimplantation genetic diagnosis (PGD), a technique employed during some fertility treatments to select embryos based on their genes. As such, PGD can and is used for a variety of controversial purposes, including sex selection, selection for children with disabilities such as deafness, and selection for 'saviour siblings' who can serve as tissue donors for sick relatives. The lack of regulation, which is due to particular features of the US political and economic landscape, has ethical and practical implications for patients seeking PGD around the world. This paper contrasts the absence of PGD oversight in the USA with existing PGD policies in Switzerland, Italy, France and the UK. The primary reasons why PGD is not regulated in the USA are addressed, with consideration of factors such as funding for assisted reproductive technology treatmemt and the proximity of PGD to the contentious abortion debate. The obstacles that would need to be overcome in the USA for PGD to be regulated in the future are outlined. Then, the significance of the current divergence in PGD policy for patients around the world are discussed. Regulatory differences create opportunities for reproductive tourism, which result in legal, health and moral challenges. The paper concludes with comments on the need for policymakers around the world to balance respect for the characters and constitutions of their individual countries with appreciation of the needs of infertile patients across the globe.

  4. Genetic features of Huntington disease in Cuban population: implications for phenotype, epidemiology and predictive testing.

    Science.gov (United States)

    Vázquez-Mojena, Yaimeé; Laguna-Salvia, Leonides; Laffita-Mesa, José M; González-Zaldívar, Yanetza; Almaguer-Mederos, Luis E; Rodríguez-Labrada, Roberto; Almaguer-Gotay, Dennis; Zayas-Feria, Pedro; Velázquez-Pérez, Luis

    2013-12-15

    Huntington disease is the most frequent polyglutamine disorder with variable worldwide prevalence. Although some Latin American populations have been studied, HD prevalence in Cuban population remains unknown. In order to characterize the disease in Cuba, the relative frequency of HD was determined by studying 130 patients with chorea and 63 unrelated healthy controls, emphasizing in the molecular epidemiology of the disease. Sixty-two patients with chorea belonging to 16 unrelated families carried a pathological CAG expansion in the HTT gene, ranging from 39 to 67 repeats. Eighty-three percent of them come from the eastern region of the country. A significant inverse correlation between age at onset and expanded CAG repeats was seen. Intermediate alleles in affected individuals and controls represented 4.8% and 3.97% respectively, which have been a putative source of de novo mutation. This study represents the largest molecular characterization of Huntington disease in the Cuban population. These results may have significant implications for an understanding of the disease, its diagnosis and prognosis in Cuban patients, giving health professionals the tools to implement confirmatory genetic testing, pre-symptomatic testing and clinical trials in this population.

  5. Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism

    Directory of Open Access Journals (Sweden)

    Michelle J Bayefsky

    2016-12-01

    Full Text Available Unlike many European nations, the USA has no regulations concerning the use of preimplantation genetic diagnosis (PGD, a technique employed during some fertility treatments to select embryos based on their genes. As such, PGD can and is used for a variety of controversial purposes, including sex selection, selection for children with disabilities such as deafness, and selection for ‘saviour siblings’ who can serve as tissue donors for sick relatives. The lack of regulation, which is due to particular features of the US political and economic landscape, has ethical and practical implications for patients seeking PGD around the world. This paper contrasts the absence of PGD oversight in the USA with existing PGD policies in Switzerland, Italy, France and the UK. The primary reasons why PGD is not regulated in the USA are addressed, with consideration of factors such as funding for assisted reproductive technology treatmemt and the proximity of PGD to the contentious abortion debate. The obstacles that would need to be overcome in the USA for PGD to be regulated in the future are outlined. Then, the significance of the current divergence in PGD policy for patients around the world are discussed. Regulatory differences create opportunities for reproductive tourism, which result in legal, health and moral challenges. The paper concludes with comments on the need for policymakers around the world to balance respect for the characters and constitutions of their individual countries with appreciation of the needs of infertile patients across the globe.

  6. A Candidate Gene Approach Identifies an IL33 Genetic Variant as a Novel Genetic Risk Factor for GCA

    Science.gov (United States)

    Márquez, Ana; Solans, Roser; Hernández-Rodríguez, José; Cid, Maria C.; Castañeda, Santos; Ramentol, Marc; Rodriguez-Rodriguez, Luis; Narváez, Javier; Blanco, Ricardo; Ortego-Centeno, Norberto; Palm, Øyvind; Diamantopoulos, Andreas P.; Braun, Niko; Moosig, Frank; Witte, Torsten; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A.; Vaglio, Augusto; Salvarani, Carlo; González-Gay, Miguel A.; Martín, Javier

    2014-01-01

    Introduction Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition. Methods A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway) were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays. Results A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (PMH = 0.041, OR = 0.88, CI 95% 0.78–0.99) and recessive (PMH = 3.40E-03, OR = 0.53, CI 95% 0.35–0.80) models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis. Conclusions Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA. PMID:25409453

  7. Interpreting a genetic case-control finding: What can be said, what cannot be said and implications in Indian populations

    Directory of Open Access Journals (Sweden)

    Ghosh Saurabh

    2007-01-01

    Full Text Available Identification of genetic variants responsible for complex disorders using association mapping is an active area of research. There are two broad classes of association methodologies: population-based case-control studies and family-based transmission analyses. While case-control analyses are more popular and in general, more powerful than family-based analyses, they suffer from some inherent limitations. Thus, it is of importance, to understand the implications of an association finding obtained from a case-control study design. This article discusses the relative advantages and disadvantages of the two classes of association analyses, particularly in the context of genetic diversity in Indian populations.

  8. Origins of albino and hooded rats: implications from molecular genetic analysis across modern laboratory rat strains.

    Directory of Open Access Journals (Sweden)

    Takashi Kuramoto

    Full Text Available Albino and hooded (or piebald rats are one of the most frequently used laboratory animals for the past 150 years. Despite this fact, the origin of the albino mutation as well as the genetic basis of the hooded phenotype remained unclear. Recently, the albino mutation has been identified as the Arg299His missense mutation in the Tyrosinase gene and the hooded (H locus has been mapped to the ∼460-kb region in which only the Kit gene exists. Here, we surveyed 172 laboratory rat strains for the albino mutation and the hooded (h mutation that we identified by positional cloning approach to investigate possible genetic roots and relationships of albino and hooded rats. All of 117 existing laboratory albino rats shared the same albino missense mutation, indicating they had only one single ancestor. Genetic fine mapping followed by de novo sequencing of BAC inserts covering the H locus revealed that an endogenous retrovirus (ERV element was inserted into the first intron of the Kit gene where the hooded allele maps. A solitary long terminal repeat (LTR was found at the same position to the ERV insertion in another allele of the H locus, which causes the so called Irish (h(i phenotype. The ERV and the solitary LTR insertions were completely associated with the hooded and Irish coat patterns, respectively, across all colored rat strains examined. Interestingly, all 117 albino rat strains shared the ERV insertion without any exception, which strongly suggests that the albino mutation had originally occurred in hooded rats.

  9. Genetic and Modeling Approaches Reveal Distinct Components of Impulsive Behavior.

    Science.gov (United States)

    Nautiyal, Katherine M; Wall, Melanie M; Wang, Shuai; Magalong, Valerie M; Ahmari, Susanne E; Balsam, Peter D; Blanco, Carlos; Hen, René

    2017-01-18

    Impulsivity is an endophenotype found in many psychiatric disorders including substance use disorders, pathological gambling, and attention deficit hyperactivity disorder. Two behavioral features often considered in impulsive behavior are behavioral inhibition (impulsive action) and delayed gratification (impulsive choice). However, the extent to which these behavioral constructs represent distinct facets of behavior with discrete biological bases is unclear. To test the hypothesis that impulsive action and impulsive choice represent statistically independent behavioral constructs in mice, we collected behavioral measures of impulsivity in a single cohort of mice using well-validated operant behavioral paradigms. Mice with manipulation of serotonin 1B receptor (5-HT1BR) expression were included as a model of disordered impulsivity. A factor analysis was used to characterize correlations between the measures of impulsivity and to identify covariates. Using two approaches, we dissociated impulsive action from impulsive choice. First, the absence of 5-HT1BRs caused increased impulsive action, but not impulsive choice. Second, based on an exploratory factor analysis, a two-factor model described the data well, with measures of impulsive action and choice separating into two independent factors. A multiple-indicator multiple-causes analysis showed that 5-HT1BR expression and sex were significant covariates of impulsivity. Males displayed increased impulsivity in both dimensions, whereas 5-HT1BR expression was a predictor of increased impulsive action only. These data support the conclusion that impulsive action and impulsive choice are distinct behavioral phenotypes with dissociable biological influences that can be modeled in mice. Our work may help inform better classification, diagnosis, and treatment of psychiatric disorders, which present with disordered impulsivity.Neuropsychopharmacology advance online publication, 18 January 2017; doi:10.1038/npp.2016.277.

  10. A Quantitative Corpus-Based Approach to English Spatial Particles: Conceptual Symmetry and Its Pedagogical Implications

    Science.gov (United States)

    Chen, Alvin Cheng-Hsien

    2014-01-01

    The present study aims to investigate how conceptual symmetry plays a role in the use of spatial particles in English and to further examine its pedagogical implications via a corpus-based evaluation of the course books in senior high schools in Taiwan. More specifically, we adopt a quantitative corpus-based approach to investigate whether bipolar…

  11. Improving the accuracy of density-functional theory calculation: the genetic algorithm and neural network approach.

    Science.gov (United States)

    Li, Hui; Shi, LiLi; Zhang, Min; Su, Zhongmin; Wang, XiuJun; Hu, LiHong; Chen, GuanHua

    2007-04-14

    The combination of genetic algorithm and neural network approach (GANN) has been developed to improve the calculation accuracy of density functional theory. As a demonstration, this combined quantum mechanical calculation and GANN correction approach has been applied to evaluate the optical absorption energies of 150 organic molecules. The neural network approach reduces the root-mean-square (rms) deviation of the calculated absorption energies of 150 organic molecules from 0.47 to 0.22 eV for the TDDFTB3LYP6-31G(d) calculation, and the newly developed GANN correction approach reduces the rms deviation to 0.16 eV.

  12. Non-Genetic Engineering Approaches for Isolating and Generating Novel Yeasts for Industrial Applications

    Science.gov (United States)

    Chambers, P. J.; Bellon, J. R.; Schmidt, S. A.; Varela, C.; Pretorius, I. S.

    Generating novel yeast strains for industrial applications should be quite straightforward; after all, research into the genetics, biochemistry and physiology of Baker's Yeast, Saccharomyces cerevisiae, has paved the way for many advances in the modern biological sciences. We probably know more about this humble eukaryote than any other, and it is the most tractable of organisms for manipulation using modern genetic engineering approaches. In many countries, however, there are restrictions on the use of genetically-modified organisms (GMOs), particularly in foods and beverages, and the level of consumer acceptance of GMOs is, at best, variable. Thus, many researchers working with industrial yeasts use genetic engineering techniques primarily as research tools, and strain development continues to rely on non-GM technologies. This chapter explores the non-GM tools and strategies available to such researchers.

  13. Solving an aggregate production planning problem by using multi-objective genetic algorithm (MOGA approach

    Directory of Open Access Journals (Sweden)

    Ripon Kumar Chakrabortty

    2013-01-01

    Full Text Available In hierarchical production planning system, Aggregate Production Planning (APP falls between the broad decisions of long-range planning and the highly specific and detailed short-range planning decisions. This study develops an interactive Multi-Objective Genetic Algorithm (MOGA approach for solving the multi-product, multi-period aggregate production planning (APP with forecasted demand, related operating costs, and capacity. The proposed approach attempts to minimize total costs with reference to inventory levels, labor levels, overtime, subcontracting and backordering levels, and labor, machine and warehouse capacity. Here several genetic algorithm parameters are considered for solving NP-hard problem (APP problem and their relative comparisons are focused to choose the most auspicious combination for solving multiple objective problems. An industrial case demonstrates the feasibility of applying the proposed approach to real APP decision problems. Consequently, the proposed MOGA approach yields an efficient APP compromise solution for large-scale problems.

  14. 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.

  15. On Generating Optimal Signal Probabilities for Random Tests: A Genetic Approach

    Directory of Open Access Journals (Sweden)

    M. Srinivas

    1996-01-01

    Full Text Available Genetic Algorithms are robust search and optimization techniques. A Genetic Algorithm based approach for determining the optimal input distributions for generating random test vectors is proposed in the paper. A cost function based on the COP testability measure for determining the efficacy of the input distributions is discussed. A brief overview of Genetic Algorithms (GAs and the specific details of our implementation are described. Experimental results based on ISCAS-85 benchmark circuits are presented. The performance of our GAbased approach is compared with previous results. While the GA generates more efficient input distributions than the previous methods which are based on gradient descent search, the overheads of the GA in computing the input distributions are larger.

  16. Approaches for the Identification of Genetic Modifiers of Nutrient Dependent Phenotypes: Examples from Folate

    OpenAIRE

    MacFarlane, Amanda J.; Ian eZinck

    2014-01-01

    By combining the sciences of nutrition, bioinformatics, genomics, population genetics, and epidemiology, nutrigenomics is improving our understanding of how diet and nutrient intake can interact with or modify gene expression and disease risk. In this review, we explore various approaches to examine gene–nutrient interactions and the modifying role of nutrient consumption, as they relate to nutrient status and disease risk in human populations. Two common approaches include the use of SNPs in...

  17. A Genetic Algorithm Approach for Group Formation in Collaborative Learning Considering Multiple Student Characteristics

    Science.gov (United States)

    Moreno, Julian; Ovalle, Demetrio A.; Vicari, Rosa M.

    2012-01-01

    Considering that group formation is one of the key processes in collaborative learning, the aim of this paper is to propose a method based on a genetic algorithm approach for achieving inter-homogeneous and intra-heterogeneous groups. The main feature of such a method is that it allows for the consideration of as many student characteristics as…

  18. A Genetic Algorithm Approach for Group Formation in Collaborative Learning Considering Multiple Student Characteristics

    Science.gov (United States)

    Moreno, Julian; Ovalle, Demetrio A.; Vicari, Rosa M.

    2012-01-01

    Considering that group formation is one of the key processes in collaborative learning, the aim of this paper is to propose a method based on a genetic algorithm approach for achieving inter-homogeneous and intra-heterogeneous groups. The main feature of such a method is that it allows for the consideration of as many student characteristics as…

  19. Application of a single-objective, hybrid genetic algorithm approach to pharmacokinetic model building.

    Science.gov (United States)

    Sherer, Eric A; Sale, Mark E; Pollock, Bruce G; Belani, Chandra P; Egorin, Merrill J; Ivy, Percy S; Lieberman, Jeffrey A; Manuck, Stephen B; Marder, Stephen R; Muldoon, Matthew F; Scher, Howard I; Solit, David B; Bies, Robert R

    2012-08-01

    A limitation in traditional stepwise population pharmacokinetic model building is the difficulty in handling interactions between model components. To address this issue, a method was previously introduced which couples NONMEM parameter estimation and model fitness evaluation to a single-objective, hybrid genetic algorithm for global optimization of the model structure. In this study, the generalizability of this approach for pharmacokinetic model building is evaluated by comparing (1) correct and spurious covariate relationships in a simulated dataset resulting from automated stepwise covariate modeling, Lasso methods, and single-objective hybrid genetic algorithm approaches to covariate identification and (2) information criteria values, model structures, convergence, and model parameter values resulting from manual stepwise versus single-objective, hybrid genetic algorithm approaches to model building for seven compounds. Both manual stepwise and single-objective, hybrid genetic algorithm approaches to model building were applied, blinded to the results of the other approach, for selection of the compartment structure as well as inclusion and model form of inter-individual and inter-occasion variability, residual error, and covariates from a common set of model options. For the simulated dataset, stepwise covariate modeling identified three of four true covariates and two spurious covariates; Lasso identified two of four true and 0 spurious covariates; and the single-objective, hybrid genetic algorithm identified three of four true covariates and one spurious covariate. For the clinical datasets, the Akaike information criterion was a median of 22.3 points lower (range of 470.5 point decrease to 0.1 point decrease) for the best single-objective hybrid genetic-algorithm candidate model versus the final manual stepwise model: the Akaike information criterion was lower by greater than 10 points for four compounds and differed by less than 10 points for three

  20. Adaptive genetic potential of coniferous forest tree species under climate change: implications for sustainable forest management

    Science.gov (United States)

    Mihai, Georgeta; Birsan, Marius-Victor; Teodosiu, Maria; Dumitrescu, Alexandru; Daia, Mihai; Mirancea, Ionel; Ivanov, Paula; Alin, Alexandru

    2017-04-01

    Mountain ecosystems are extremely vulnerable to climate change. The real potential for adaptation depends upon the existence of a wide genetic diversity in trees populations, upon the adaptive genetic variation, respectively. Genetic diversity offers the guarantee that forest species can survive, adapt and evolve under the influence of changing environmental conditions. The aim of this study is to evaluate the genetic diversity and adaptive genetic potential of two local species - Norway spruce and European silver fir - in the context of regional climate change. Based on data from a long-term provenance experiments network and climate variables spanning over more than 50 years, we have investigated the impact of climatic factors on growth performance and adaptation of tree species. Our results indicate that climatic and geographic factors significantly affect forest site productivity. Mean annual temperature and annual precipitation amount were found to be statistically significant explanatory variables. Combining the additive genetic model with the analysis of nuclear markers we obtained different images of the genetic structure of tree populations. As genetic indicators we used: gene frequencies, genetic diversity, genetic differentiation, genetic variance, plasticity. Spatial genetic analyses have allowed identifying the genetic centers holding high genetic diversity which will be valuable sources of gene able to buffer the negative effects of future climate change. Correlations between the marginal populations and in the optimal vegetation, between the level of genetic diversity and ecosystem stability, will allow the assessment of future risks arising from current genetic structure. Therefore, the strategies for sustainable forest management have to rely on the adaptive genetic variation and local adaptation of the valuable genetic resources. This work was realized within the framework of the project GENCLIM (Evaluating the adaptive potential of the main

  1. Epigenetic-genetic chromosome dosage approach for fetal trisomy 21 detection using an autosomal genetic reference marker.

    Directory of Open Access Journals (Sweden)

    Yu K Tong

    Full Text Available BACKGROUND: The putative promoter of the holocarboxylase synthetase (HLCS gene on chromosome 21 is hypermethylated in placental tissues and could be detected as a fetal-specific DNA marker in maternal plasma. Detection of fetal trisomy 21 (T21 has been demonstrated by an epigenetic-genetic chromosome dosage approach where the amount of hypermethylated HLCS in maternal plasma is normalized using a fetal genetic marker on the Y chromosome as a chromosome dosage reference marker. We explore if this method can be applied on both male and female fetuses with the use of a paternally-inherited fetal single nucleotide polymorphism (SNP allele on a reference chromosome for chromosome dosage normalization. METHODOLOGY: We quantified hypermethylated HLCS molecules using methylation-sensitive restriction endonuclease digestion followed by real-time or digital PCR analyses. For chromosome dosage analysis, we compared the amount of digestion-resistant HLCS to that of a SNP allele (rs6636, a C/G SNP that the fetus has inherited from the father but absent in the pregnant mother. PRINCIPAL FINDINGS: Using a fetal-specific SNP allele on a reference chromosome, we analyzed 20 euploid and nine T21 placental tissue samples. All samples with the fetal-specific C allele were correctly classified. One sample from each of the euploid and T21 groups were misclassified when the fetal-specific G allele was used as the reference marker. We then analyzed 33 euploid and 14 T21 maternal plasma samples. All but one sample from each of the euploid and T21 groups were correctly classified using the fetal-specific C allele, while correct classification was achieved for all samples using the fetal-specific G allele as the reference marker. CONCLUSIONS: As a proof-of-concept study, we have demonstrated that the epigenetic-genetic chromosome dosage approach can be applied to the prenatal diagnosis of trisomy 21 for both male and female fetuses.

  2. Disorders of Sex Development in Indonesia: Natural course and the implications of a stepwise multidisciplinary approach

    NARCIS (Netherlands)

    A.Z. Juniarto (Achmad)

    2014-01-01

    markdownabstract__Abstract__ This thesis elaborates the stepwise diagnostic procedure in DSD patients using a multidiscipline approach to obtain the diagnosis of these patients which includes clinical assessment, hormonal, genetic, and pathological investigations, so that it is beneficial as the ba

  3. Resources and strategies to integrate the study of ethical, legal, and social implications of genetics into the undergraduate curriculum.

    Science.gov (United States)

    Garrett, Jinnie M; Triman, Kathleen L

    2009-01-01

    Gene therapy, genetically modified organisms, and the privacy of an individual's genetic information are just a few of the developments emerging from recent advances in molecular genetics that are controversial. Oversight and regulation of emerging technologies are the responsibility of both experts and the general public who both need to understand the science and the societal impact of its use. The study of ethical, legal, and social implications (ELSI) of advances in genetics provides a very powerful pedagogical tool to accomplish two goals. These are, first of all, to interest nonscientists in genetics and engage them in learning the science behind the ELSI developments they are considering, and secondly, to broaden the perspective of science students to consider the history and social consequences of the science they are studying. The resources and strategies presented in this chapter for teaching ELSI issues that arise in modern genetics are designed to aid in accomplishing these goals throughout the undergraduate curriculum. This chapter provides (1) a set of nine ELSI topic modules that can be incorporated into courses for both majors (from introductory to graduate level) and nonmajors and (2) examples of course pedagogy for specific classes.

  4. Implications of Host Genetic Variation on the Risk and Prevalence of Infectious Diseases Transmitted Through the Environment

    Science.gov (United States)

    Doeschl-Wilson, Andrea B.; Davidson, R.; Conington, J.; Roughsedge, T.; Hutchings, M. R.; Villanueva, B.

    2011-01-01

    Previous studies have shown that host genetic heterogeneity in the response to infectious challenge can affect the emergence risk and the severity of diseases transmitted through direct contact between individuals. However, there is substantial uncertainty about the degree and direction of influence owing to different definitions of genetic variation, most of which are not in line with the current understanding of the genetic architecture of disease traits. Also, the relevance of previous results for diseases transmitted through environmental sources is unclear. In this article a compartmental genetic–epidemiological model was developed to quantify the impact of host genetic diversity on epidemiological characteristics of diseases transmitted through a contaminated environment. The model was parameterized for footrot in sheep. Genetic variation was defined through continuous distributions with varying shape and degree of dispersion for different disease traits. The model predicts a strong impact of genetic heterogeneity on the disease risk and its progression and severity, as well as on observable host phenotypes, when dispersion in key epidemiological parameters is high. The impact of host variation depends on the disease trait for which variation occurs and on environmental conditions affecting pathogen survival. In particular, compared to homogeneous populations with the same average susceptibility, disease risk and severity are substantially higher in populations containing a large proportion of highly susceptible individuals, and the differences are strongest when environmental contamination is low. The implications of our results for the recording and analysis of disease data and for predicting response to selection are discussed. PMID:21527777

  5. Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

    Science.gov (United States)

    2015-10-01

    Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING...SUBTITLE Developiing Novel Therapeutic Approaches in Small Cell Lung 5a. CONTRACT NUMBER Carcinoma Using Genetically Engineered Mouse Models and 5b...biomarkers. 15. SUBJECT TERMS Small cell lung cancer (SCLC), Genetically engineered mouse model (GEMM), BH3 mimetic, TORC inhibitor, Apoptosis

  6. Genetic mutations in early-onset Parkinson's disease Mexican patients: molecular testing implications.

    Science.gov (United States)

    Monroy-Jaramillo, Nancy; Guerrero-Camacho, Jorge Luis; Rodríguez-Violante, Mayela; Boll-Woehrlen, Marie-Catherine; Yescas-Gómez, Petra; Alonso-Vilatela, María Elisa; López-López, Marisol

    2014-04-01

    Mutations in PARK2, PINK1, and DJ-1 have been associated with autosomal recessive early-onset Parkinson's disease. Here, we report the prevalence of sequence and structural mutations in these three main recessive genes in Mexican Mestizo patients. The complete sequences of these three genes were analyzed by homo/heteroduplex DNA formation and direct sequencing; exon dosage was determined by multiplex ligation-dependent probe amplification and real-time PCR in 127 patients belonging to 122 families and 120 healthy Mexican Mestizo controls. All individuals had been previously screened for the three most common LRRK2 mutations. The presence of two mutations in compound heterozygous or homozygous genotypes was found in 16 unrelated patients, 10 had mutations in PARK2, six in PINK1, and none in DJ-1. Two PARK2-PINK1 and one PARK2-LRRK2 digenic cases were observed. Novel mutations were identified in PARK2 and PINK1 genes, including PINK1 duplication for the first time. Exon dosage deletions were the most frequent mutations in PARK2 (mainly in exons 9 and 12), followed by those in PINK1. The high prevalence of heterozygous mutations in PARK2 (12.3%) and the novel heterozygous and homozygous point mutations in PINK1 observed in familial and sporadic cases from various states of Mexico support the concept that single heterozygous mutations in recessive Parkinson's disease genes play a pathogenic role. These data have important implications for genetic counseling of Mexican Mestizo patients with early-onset Parkinson's disease. The presence of digenic inheritance underscores the importance of studying several genes in this disease. A step-ordered strategy for molecular diagnosis is proposed.

  7. Bolzano`s Approach to the Paradoxes of Infinity: Implications for Teaching

    Science.gov (United States)

    Waldegg, Guillermina

    2005-08-01

    In this paper we analyze excerpts of Paradoxes of the Infinite, the posthumous work of Bernard Bolzano (1781-1848), in order to show that Georg Cantor‘s (1845-1918) approach to the problem of defining actual mathematical infinity is not the most natural. In fact, Bolzano‘s approach to the paradoxes of infinity is more intuitive, while remaining internally coherent. Bolzano‘s approach, however, had limitations. We discuss implications for teaching, which include a better understanding of the responses of students to situations involving actual mathematical infinity, for it is possible to draw a kind of parallel between these responses and Bolzano‘s reasoning.

  8. Proliferation and survival molecules implicated in the inhibition of BRAF pathway in thyroid cancer cells harbouring different genetic mutations

    Directory of Open Access Journals (Sweden)

    Seca Hugo

    2009-10-01

    Full Text Available Abstract Background Thyroid carcinomas show a high prevalence of mutations in the oncogene BRAF which are inversely associated with RAS or RET/PTC oncogenic activation. The possibility of using inhibitors on the BRAF pathway as became an interesting therapeutic approach. In thyroid cancer cells the target molecules, implicated on the cellular effects, mediated by inhibition of BRAF are not well established. In order to fill this lack of knowledge we studied the proliferation and survival pathways and associated molecules induced by BRAF inhibition in thyroid carcinoma cell lines harbouring distinct genetic backgrounds. Methods Suppression of BRAF pathway in thyroid cancer cell lines (8505C, TPC1 and C643 was achieved using RNA interference (RNAi for BRAF and the kinase inhibitor, sorafenib. Proliferation analysis was performed by BrdU incorporation and apoptosis was accessed by TUNEL assay. Levels of protein expression were analysed by western-blot. Results Both BRAF RNAi and sorafenib inhibited proliferation in all the cell lines independently of the genetic background, mostly in cells with BRAFV600E mutation. In BRAFV600E mutated cells inhibition of BRAF pathway lead to a decrease in ERK1/2 phosphorylation and cyclin D1 levels and an increase in p27Kip1. Specific inhibition of BRAF by RNAi in cells with BRAFV600E mutation had no effect on apoptosis. In the case of sorafenib treatment, cells harbouring BRAFV600E mutation showed increase levels of apoptosis due to a balance of the anti-apoptotic proteins Mcl-1 and Bcl-2. Conclusion Our results in thyroid cancer cells, namely those harbouring BRAFV600Emutation showed that BRAF signalling pathway provides important proliferation signals. We have shown that in thyroid cancer cells sorafenib induces apoptosis by affecting Mcl-1 and Bcl-2 in BRAFV600E mutated cells which was independent of BRAF. These results suggest that sorafenib may prove useful in the treatment of thyroid carcinomas, particularly

  9. Genetic diversity and the genetic structure of natural populations of Chamaecyparis obtusa: implications for management and conservation.

    Science.gov (United States)

    Tsumura, Y; Matsumoto, A; Tani, N; Ujino-Ihara, T; Kado, T; Iwata, H; Uchida, K

    2007-08-01

    We investigated 25 natural populations of Chamaecyparis obtusa using 51 cleaved amplified polymorphic sequence (CAPS) markers, which were developed using information on sequence-tagged sites (STS) in Cryptomeria japonica. Most CAPS markers have codominant expression patterns, and are suitable for population studies because of their robustness and convenience. We estimated various genetic diversity parameters, including average heterozygosity (H(e)) and allelic richness and found that the more peripheral populations tended to have lower genetic diversity than central populations, in agreement with a previous theoretical study. The overall genetic differentiation between populations was low, but statistically significant (G(ST)=0.039), and similar to the level reported in a previous allozyme study. We attempted to detect non-neutral loci associated with local adaptation to clarify the relationship between the fixation index (F(ST)) and H(e) values for each locus and found seven candidates non-neutral loci. Phylogenetic tree analysis of the populations and Bayesian clustering analysis revealed a pattern of gradually increasing isolation of populations with increasing geographical distance. Three populations had a high degree of linkage disequilibrium, which we attribute to severe bottlenecks due to human disturbance or competition with other species during their migration from refugia after the most recent glaciation. We concluded that the small populations in western Japan and in Kanto district are more important, from a conservation perspective, than the populations in central Japan, due to their genetic divergence, relatively small sizes and restricted areas.

  10. Evidence of two genetic clusters of manatees with low genetic diversity in Mexico and implications for their conservation

    Science.gov (United States)

    Nourisson, Coralie; Morales-Vela, Benjamin; Padilla-Saldivar, Janneth; Tucker, Kimberly Pause; Clark, Ann Marie; Olivera-Gomez, Leon David; Bonde, Robert; McGuire, Peter

    2011-01-01

    The Antillean manatee (Trichechus manatus manatus) occupies the tropical coastal waters of the Greater Antilles and Caribbean, extending from Mexico along Central and South America to Brazil. Historically, manatees were abundant in Mexico, but hunting during the pre-Columbian period, the Spanish colonization and throughout the history of Mexico, has resulted in the significantly reduced population occupying Mexico today. The genetic structure, using microsatellites, shows the presence of two populations in Mexico: the Gulf of Mexico (GMx) and Chetumal Bay (ChB) on the Caribbean coast, with a zone of admixture in between. Both populations show low genetic diversity (GMx: NA = 2.69; HE = 0.41 and ChB: NA = 3.0; HE = 0.46). The lower genetic diversity found in the GMx, the largest manatee population in Mexico, is probably due to a combination of a founder effect, as this is the northern range of the sub-species of T. m. manatus, and a bottleneck event. The greater genetic diversity observed along the Caribbean coast, which also has the smallest estimated number of individuals, is possibly due to manatees that come from the GMx and Belize. There is evidence to support limited or unidirectional gene flow between these two important areas. The analyses presented here also suggest minimal evidence of a handful of individual migrants possibly between Florida and Mexico. To address management issues we suggest considering two distinct genetic populations in Mexico, one along the Caribbean coast and one in the riverine systems connected to the GMx.

  11. Evidence of two genetic clusters of manatees with low genetic diversity in Mexico and implications for their conservation.

    Science.gov (United States)

    Nourisson, Coralie; Morales-Vela, Benjamín; Padilla-Saldívar, Janneth; Tucker, Kimberly Pause; Clark, Annmarie; Olivera-Gómez, Leon David; Bonde, Robert; McGuire, Peter

    2011-07-01

    The Antillean manatee (Trichechus manatus manatus) occupies the tropical coastal waters of the Greater Antilles and Caribbean, extending from Mexico along Central and South America to Brazil. Historically, manatees were abundant in Mexico, but hunting during the pre-Columbian period, the Spanish colonization and throughout the history of Mexico, has resulted in the significantly reduced population occupying Mexico today. The genetic structure, using microsatellites, shows the presence of two populations in Mexico: the Gulf of Mexico (GMx) and Chetumal Bay (ChB) on the Caribbean coast, with a zone of admixture in between. Both populations show low genetic diversity (GMx: N(A) = 2.69; H(E) = 0.41 and ChB: N(A) = 3.0; H(E) = 0.46). The lower genetic diversity found in the GMx, the largest manatee population in Mexico, is probably due to a combination of a founder effect, as this is the northern range of the sub-species of T. m. manatus, and a bottleneck event. The greater genetic diversity observed along the Caribbean coast, which also has the smallest estimated number of individuals, is possibly due to manatees that come from the GMx and Belize. There is evidence to support limited or unidirectional gene flow between these two important areas. The analyses presented here also suggest minimal evidence of a handful of individual migrants possibly between Florida and Mexico. To address management issues we suggest considering two distinct genetic populations in Mexico, one along the Caribbean coast and one in the riverine systems connected to the GMx.

  12. A cellular genetics approach identifies gene-drug interactions and pinpoints drug toxicity pathway nodes

    Directory of Open Access Journals (Sweden)

    Oscar Takeo Suzuki

    2014-08-01

    Full Text Available New approaches to toxicity testing have incorporated high-throughput screening across a broad-range of in vitro assays to identify potential key events in response to chemical or drug treatment. To date, these approaches have primarily utilized repurposed drug discovery assays. In this study, we describe an approach that combines in vitro screening with genetic approaches for the experimental identification of genes and pathways involved in chemical or drug toxicity. Primary embryonic fibroblasts isolated from 32 genetically-characterized inbred mouse strains were treated in concentration-response format with 65 compounds, including pharmaceutical drugs, environmental chemicals, and compounds with known modes-of-action. Integrated cellular responses were measured at 24 and 72 hours using high-content imaging and included cell loss, membrane permeability, mitochondrial function, and apoptosis. Genetic association analysis of cross-strain differences in the cellular responses resulted in a collection of candidate loci potentially underlying the variable strain response to each chemical. As a demonstration of the approach, one candidate gene involved in rotenone sensitivity, Cybb, was experimentally validated in vitro and in vivo. Pathway analysis on the combined list of candidate loci across all chemicals identified a number of over-connected nodes that may serve as core regulatory points in toxicity pathways.

  13. A fuzzy genetic approach for network reconfiguration to enhance voltage stability in radial distribution systems

    Energy Technology Data Exchange (ETDEWEB)

    Sahoo, N.C. [Faculty of Engineering and Technology, Multimedia University, Jalan Ayer Keroh Lama, Bukit Beruang, 75450 Melaka (Malaysia); Prasad, K. [Faculty of Information Science and Technology, Multimedia University, Jalan Ayer Keroh Lama, Bukit Beruang, 75450 Melaka (Malaysia)

    2006-11-15

    This paper presents a fuzzy genetic approach for reconfiguration of radial distribution systems (RDS) so as to maximize the voltage stability of the network for a specific set of loads. The network reconfiguration involves a mechanism for selection of the best set of branches to be opened, one from each loop, such that the reconfigured RDS possesses desired performance characteristics. This discrete solution space is better handled by the proposed scheme, which maximizes a suitable optimizing function (computed using two different approaches). In the first approach, this function is chosen as the average of a voltage stability index of all the buses in the RDS, while in the second approach, the complete RDS is reduced to a two bus equivalent system and the optimizing function is the voltage stability index of this reduced two bus system. The fuzzy genetic algorithm uses a suitable coding and decoding scheme for maintaining the radial nature of the network at every stage of genetic evolution, and it also uses a fuzzy rule based mutation controller for efficient search of the solution space. This method, tested on 69 bus and 33 bus RDSs, shows promising results for the both approaches. It is also observed that the network losses are reduced when the voltage stability is enhanced by the network reconfiguration. (author)

  14. [Recent progress in gene mapping through high-throughput sequencing technology and forward genetic approaches].

    Science.gov (United States)

    Lu, Cairui; Zou, Changsong; Song, Guoli

    2015-08-01

    Traditional gene mapping using forward genetic approaches is conducted primarily through construction of a genetic linkage map, the process of which is tedious and time-consuming, and often results in low accuracy of mapping and large mapping intervals. With the rapid development of high-throughput sequencing technology and decreasing cost of sequencing, a variety of simple and quick methods of gene mapping through sequencing have been developed, including direct sequencing of the mutant genome, sequencing of selective mutant DNA pooling, genetic map construction through sequencing of individuals in population, as well as sequencing of transcriptome and partial genome. These methods can be used to identify mutations at the nucleotide level and has been applied in complex genetic background. Recent reports have shown that sequencing mapping could be even done without the reference of genome sequence, hybridization, and genetic linkage information, which made it possible to perform forward genetic study in many non-model species. In this review, we summarized these new technologies and their application in gene mapping.

  15. Genetics of schizophrenia and smoking: an approach to studying their comorbidity based on epidemiological findings

    Science.gov (United States)

    de Leon, Jose; Diaz, Francisco J.

    2012-01-01

    The association between schizophrenia and tobacco smoking has been described in more than 1,000 articles, many with inadequate methodology. The studies on this association can focus on: (1) current smoking, ever smoking or smoking cessation; (2) non-psychiatric controls or controls with severe mental illness (e.g., bipolar disorder); and (3) higher smoking frequency or greater usage in smokers. The association with the most potential for genetic studies is that between ever daily smoking and schizophrenia; it may reflect a shared genetic vulnerability. To reduce the number of false-positive genes, we propose a three-stage approach derived from epidemiological knowledge. In the first stage, only genetic variations associated with ever daily smoking that are simultaneously significant within the non-psychiatric controls, the bipolar disorder controls and the schizophrenia cases will be selected. Only those genetic variations that are simultaneously significant in the three hypothesis tests will be tested in the second stage, where the prevalence of the genes must be significantly higher in schizophrenia than in bipolar disorder, and significantly higher in bipolar disorder than in controls. The genes simultaneously significant in the second stage will be included in a third stage where the gene variations must be significantly more frequent in schizophrenia patients who did not start smoking daily until their 20s (late start) versus those who had an early start. Any genetic approach to psychiatric disorders may fail if attention is not given to comorbidity and epidemiological studies that suggest which comorbidities are likely to be explained by genetics and which are not. Our approach, which examines the results of epidemiological studies on comorbidities and then looks for genes that simultaneously satisfy epidemiologically suggested sets of hypotheses, may also apply to the study of other major illnesses. PMID:22190153

  16. New statistical approaches exploit the polygenic architecture of schizophrenia - implications for the underlying neurobiology

    Science.gov (United States)

    Schork, Andrew J.; Wang, Yunpeng; Thompson, Wesley K.; Dale, Anders M.; Andreassen, Ole A.

    2017-01-01

    Schizophrenia is a complex disorder with high heritability. Recent findings from several large genetic studies suggest a large number of risk variants are involved (i.e., schizophrenia is a polygenic disorder) and analytic approaches could be tailored for this scenario. Novel statistical approaches for analyzing GWAS data have recently been developed to be more sensitive to polygenic traits. These approaches have provided intriguing new insights into neurobiological pathways and support for the involvement of regulatory mechanisms, neurotransmission (glutamate, dopamine, GABA), and immune and neurodevelopmental pathways. Integrating the emerging statistical genetics evidence with sound neurobiological experiments will be a critical, and challenging, next step in deciphering the specific disease mechanisms of schizophrenia. PMID:26555806

  17. Gene Prioritization for Imaging Genetics Studies Using Gene Ontology and a Stratified False Discovery Rate Approach.

    Science.gov (United States)

    Patel, Sejal; Park, Min Tae M; Chakravarty, M Mallar; Knight, Jo

    2016-01-01

    Imaging genetics is an emerging field in which the association between genes and neuroimaging-based quantitative phenotypes are used to explore the functional role of genes in neuroanatomy and neurophysiology in the context of healthy function and neuropsychiatric disorders. The main obstacle for researchers in the field is the high dimensionality of the data in both the imaging phenotypes and the genetic variants commonly typed. In this article, we develop a novel method that utilizes Gene Ontology, an online database, to select and prioritize certain genes, employing a stratified false discovery rate (sFDR) approach to investigate their associations with imaging phenotypes. sFDR has the potential to increase power in genome wide association studies (GWAS), and is quickly gaining traction as a method for multiple testing correction. Our novel approach addresses both the pressing need in genetic research to move beyond candidate gene studies, while not being overburdened with a loss of power due to multiple testing. As an example of our methodology, we perform a GWAS of hippocampal volume using both the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA2) and the Alzheimer's Disease Neuroimaging Initiative datasets. The analysis of ENIGMA2 data yielded a set of SNPs with sFDR values between 10 and 20%. Our approach demonstrates a potential method to prioritize genes based on biological systems impaired in a disease.

  18. A Genetic Algorithm and Fuzzy Logic Approach for Video Shot Boundary Detection

    Directory of Open Access Journals (Sweden)

    Dalton Meitei Thounaojam

    2016-01-01

    Full Text Available This paper proposed a shot boundary detection approach using Genetic Algorithm and Fuzzy Logic. In this, the membership functions of the fuzzy system are calculated using Genetic Algorithm by taking preobserved actual values for shot boundaries. The classification of the types of shot transitions is done by the fuzzy system. Experimental results show that the accuracy of the shot boundary detection increases with the increase in iterations or generations of the GA optimization process. The proposed system is compared to latest techniques and yields better result in terms of F1score parameter.

  19. A Genetic Algorithm and Fuzzy Logic Approach for Video Shot Boundary Detection.

    Science.gov (United States)

    Thounaojam, Dalton Meitei; Khelchandra, Thongam; Manglem Singh, Kh; Roy, Sudipta

    2016-01-01

    This paper proposed a shot boundary detection approach using Genetic Algorithm and Fuzzy Logic. In this, the membership functions of the fuzzy system are calculated using Genetic Algorithm by taking preobserved actual values for shot boundaries. The classification of the types of shot transitions is done by the fuzzy system. Experimental results show that the accuracy of the shot boundary detection increases with the increase in iterations or generations of the GA optimization process. The proposed system is compared to latest techniques and yields better result in terms of F1score parameter.

  20. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Lesley Jones

    Full Text Available BACKGROUND: Late Onset Alzheimer's disease (LOAD is the leading cause of dementia. Recent large genome-wide association studies (GWAS identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. METHODOLOGY: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset. PRINCIPAL FINDINGS: We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD. SIGNIFICANCE: Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.

  1. The New World of Human Genetics: A dialogue between Practitioners & the General Public on Ethical, Legal & Social Implications of the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Schofield, Amy

    2014-12-08

    The history and reasons for launching the Human Genome project and the current uses of genetic human material; Identifying and discussing the major issues stemming directly from genetic research and therapy-including genetic discrimination, medical/ person privacy, allocation of government resources and individual finances, and the effect on the way in which we perceive the value of human life; Discussing the sometimes hidden ethical, social and legislative implications of genetic research and therapy such as informed consent, screening and preservation of genetic materials, efficacy of medical procedures, the role of the government, and equal access to medical coverage.

  2. A nearest neighbour approach by genetic distance to the assignment of individual trees to geographic origin.

    Science.gov (United States)

    Degen, Bernd; Blanc-Jolivet, Céline; Stierand, Katrin; Gillet, Elizabeth

    2017-03-01

    During the past decade, the use of DNA for forensic applications has been extensively implemented for plant and animal species, as well as in humans. Tracing back the geographical origin of an individual usually requires genetic assignment analysis. These approaches are based on reference samples that are grouped into populations or other aggregates and intend to identify the most likely group of origin. Often this grouping does not have a biological but rather a historical or political justification, such as "country of origin". In this paper, we present a new nearest neighbour approach to individual assignment or classification within a given but potentially imperfect grouping of reference samples. This method, which is based on the genetic distance between individuals, functions better in many cases than commonly used methods. We demonstrate the operation of our assignment method using two data sets. One set is simulated for a large number of trees distributed in a 120km by 120km landscape with individual genotypes at 150 SNPs, and the other set comprises experimental data of 1221 individuals of the African tropical tree species Entandrophragma cylindricum (Sapelli) genotyped at 61 SNPs. Judging by the level of correct self-assignment, our approach outperformed the commonly used frequency and Bayesian approaches by 15% for the simulated data set and by 5-7% for the Sapelli data set. Our new approach is less sensitive to overlapping sources of genetic differentiation, such as genetic differences among closely-related species, phylogeographic lineages and isolation by distance, and thus operates better even for suboptimal grouping of individuals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. 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

  4. Landscape genetic approaches to guide native plant restoration in the Mojave Desert.

    Science.gov (United States)

    Shryock, Daniel F; Havrilla, Caroline A; DeFalco, Lesley A; Esque, Todd C; Custer, Nathan A; Wood, Troy E

    2017-03-01

    Restoring dryland ecosystems is a global challenge due to synergistic drivers of disturbance coupled with unpredictable environmental conditions. Dryland plant species have evolved complex life-history strategies to cope with fluctuating resources and climatic extremes. Although rarely quantified, local adaptation is likely widespread among these species and potentially influences restoration outcomes. The common practice of reintroducing propagules to restore dryland ecosystems, often across large spatial scales, compels evaluation of adaptive divergence within these species. Such evaluations are critical to understanding the consequences of large-scale manipulation of gene flow and to predicting success of restoration efforts. However, genetic information for species of interest can be difficult and expensive to obtain through traditional common garden experiments. Recent advances in landscape genetics offer marker-based approaches for identifying environmental drivers of adaptive genetic variability in non-model species, but tools are still needed to link these approaches with practical aspects of ecological restoration. Here, we combine spatially explicit landscape genetics models with flexible visualization tools to demonstrate how cost-effective evaluations of adaptive genetic divergence can facilitate implementation of different seed sourcing strategies in ecological restoration. We apply these methods to Amplified Fragment Length Polymorphism (AFLP) markers genotyped in two Mojave Desert shrub species of high restoration importance: the long-lived, wind-pollinated gymnosperm Ephedra nevadensis, and the short-lived, insect-pollinated angiosperm Sphaeralcea ambigua. Mean annual temperature was identified as an important driver of adaptive genetic divergence for both species. Ephedra showed stronger adaptive divergence with respect to precipitation variability, while temperature variability and precipitation averages explained a larger fraction of adaptive

  5. Landscape genetic approaches to guide native plant restoration in the Mojave Desert

    Science.gov (United States)

    Shryock, Daniel F.; Havrilla, Caroline A.; DeFalco, Lesley; Esque, Todd; Custer, Nathan; Wood, Troy E.

    2016-01-01

    Restoring dryland ecosystems is a global challenge due to synergistic drivers of disturbance coupled with unpredictable environmental conditions. Dryland plant species have evolved complex life-history strategies to cope with fluctuating resources and climatic extremes. Although rarely quantified, local adaptation is likely widespread among these species and potentially influences restoration outcomes. The common practice of reintroducing propagules to restore dryland ecosystems, often across large spatial scales, compels evaluation of adaptive divergence within these species. Such evaluations are critical to understanding the consequences of large-scale manipulation of gene flow and to predicting success of restoration efforts. However, genetic information for species of interest can be difficult and expensive to obtain through traditional common garden experiments. Recent advances in landscape genetics offer marker-based approaches for identifying environmental drivers of adaptive genetic variability in non-model species, but tools are still needed to link these approaches with practical aspects of ecological restoration. Here, we combine spatially-explicit landscape genetics models with flexible visualization tools to demonstrate how cost-effective evaluations of adaptive genetic divergence can facilitate implementation of different seed sourcing strategies in ecological restoration. We apply these methods to Amplified Fragment Length Polymorphism (AFLP) markers genotyped in two Mojave Desert shrub species of high restoration importance: the long-lived, wind-pollinated gymnosperm Ephedra nevadensis, and the short-lived, insect-pollinated angiosperm Sphaeralcea ambigua. Mean annual temperature was identified as an important driver of adaptive genetic divergence for both species. Ephedra showed stronger adaptive divergence with respect to precipitation variability, while temperature variability and precipitation averages explained a larger fraction of adaptive

  6. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    DEFF Research Database (Denmark)

    Manning, Alisa K; Hivert, Marie-France; Scott, Robert A

    2012-01-01

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance...... in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology....

  7. On the Implications of Task-based Approach for English Teaching

    Institute of Scientific and Technical Information of China (English)

    武安娇

    2016-01-01

    With the further development of globalization, more professionals with a good command of English are needed. This situation proposes new challenge for the traditional way of teaching. Many educators are engaged in exploring more feasible approaches in second language teaching, among which the Task-based Language Teaching is very prominent. This paper is mainly about the implications that the author gained from Task-based Language Teaching (TBLT).

  8. The Structure of Trade in Genetic Resources: Implications for the International ABS Regime Negotiation

    Directory of Open Access Journals (Sweden)

    Mikyung Yun

    2010-06-01

    Full Text Available The intensive exploitation of genetic resources at the international level has led to a negotiation of an international regime on Access and Benefit-Sharing (ABS of genetic resources. Due to lack of systematic data, little is known about the structure of trade in genetic resources to inform the negotiators. This study attempts to shed a greater insight into genetic resources trade in the pharmaceutical sector in Korea, mainly relying on interviews of industry practitioners and scientists in related fields. The study finds that Korea is mainly a genetic resource importer, but that pharmaceutical firms rarely carry out bioprospecting directly, relying on semi-processed biochemicals imports trough agents. Therefore, the impact of the to-be negotiated international ABS negotiation will be larger if derivatives are included in its scope. However, the general impact on the economy as a whole would be small, given the small share of genetic resources trade compared to total trade volumes.

  9. Genetic testing and Alzheimer's disease: implications for psychiatric-mental health nursing.

    Science.gov (United States)

    Schutte, Debra L

    2013-11-01

    Alzheimer's disease (AD), the most common cause of irreversible dementia, continues to grow in prevalence as well as public health impact. Extensive research into the genetic etiology of AD has yielded knowledge of some genetic factors that are causative and other genetic factors that increase risk for disease. Consequently, the possibility of genetic testing in individuals with or at risk for AD is a question that nurses may be asked. Psychiatric-mental health (PMH) professionals are in key positions to influence the care of individuals who are considering the effect of genetic information on their health care decisions. Whether by working within interdisciplinary genetic counseling teams to provide direct specialty services or by developing skills to identify and refer individuals at risk for or concerned about their risk for AD, PMH nurses can play an important role in the health care of individuals and families experiencing AD.

  10. 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.

  11. A pooling-based approach to mapping genetic variants associated with DNA methylation.

    Science.gov (United States)

    Kaplow, Irene M; MacIsaac, Julia L; Mah, Sarah M; McEwen, Lisa M; Kobor, Michael S; Fraser, Hunter B

    2015-06-01

    DNA methylation is an epigenetic modification that plays a key role in gene regulation. Previous studies have investigated its genetic basis by mapping genetic variants that are associated with DNA methylation at specific sites, but these have been limited to microarrays that cover map of DNA methylation. Compared to methods that do not account for ASM, our approach increases statistical power to detect associations while sharply reducing cost, effort, and experimental variability. As a proof of concept, we generated deep sequencing data from a pool of 60 human cell lines; we evaluated almost twice as many CpGs as the largest microarray studies and identified more than 2000 genetic variants associated with DNA methylation. We found that these variants are highly enriched for associations with chromatin accessibility and CTCF binding but are less likely to be associated with traits indirectly linked to DNA, such as gene expression and disease phenotypes. In summary, our approach allows genome-wide mapping of genetic variants associated with DNA methylation in any tissue of any species, without the need for individual-level genotype or methylation data.

  12. Genetic Diversity and Population Structure of Mesoamerican Jaguars (Panthera onca): Implications for Conservation and Management

    Science.gov (United States)

    Wultsch, Claudia; Caragiulo, Anthony; Dias-Freedman, Isabela; Quigley, Howard; Rabinowitz, Salisa; Amato, George

    2016-01-01

    Mesoamerican jaguars (Panthera onca) have been extirpated from over 77% of their historic range, inhabiting fragmented landscapes at potentially reduced population sizes. Maintaining and restoring genetic diversity and connectivity across human-altered landscapes has become a major conservation priority; nonetheless large-scale genetic monitoring of natural populations is rare. This is the first regional conservation genetic study of jaguars to primarily use fecal samples collected in the wild across five Mesoamerican countries: Belize, Costa Rica, Guatemala, Honduras, and Mexico. We genotyped 445 jaguar fecal samples and examined patterns of genetic diversity and connectivity among 115 individual jaguars using data from 12 microsatellite loci. Overall, moderate levels of genetic variation were detected (NA = 4.50 ± 1.05, AR = 3.43 ± 0.22, HE = 0.59 ± 0.04), with Mexico having the lowest genetic diversity, followed by Honduras, Guatemala, Belize, and Costa Rica. Population-based gene flow measures (FST = 0.09 to 0.15, Dest = 0.09 to 0.21), principal component analysis, and Bayesian clustering applied in a hierarchical framework revealed significant genetic structure in Mesoamerican jaguars, roughly grouping individuals into four genetic clusters with varying levels of admixture. Gene flow was highest among Selva Maya jaguars (northern Guatemala and central Belize), whereas genetic differentiation among all other sampling sites was moderate. Genetic subdivision was most pronounced between Selva Maya and Honduran jaguars, suggesting limited jaguar movement between these close geographic regions and ultimately refuting the hypothesis of contemporary panmixia. To maintain a critical linkage for jaguars dispersing through the Mesoamerican landscape and ensure long-term viability of this near threatened species, we recommend continued management and maintenance of jaguar corridors. The baseline genetic data provided by this study underscores the importance of

  13. GPA-MDS: A Visualization Approach to Investigate Genetic Architecture among Phenotypes Using GWAS Results.

    Science.gov (United States)

    Wei, Wei; Ramos, Paula S; Hunt, Kelly J; Wolf, Bethany J; Hardiman, Gary; Chung, Dongjun

    2016-01-01

    Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. Recently, there has been accumulating evidence suggesting that different complex traits share a common risk basis, namely, pleiotropy. Previously, a statistical method, namely, GPA (Genetic analysis incorporating Pleiotropy and Annotation), was developed to improve identification of risk variants and to investigate pleiotropic structure through a joint analysis of multiple GWAS datasets. While GPA provides a statistically rigorous framework to evaluate pleiotropy between phenotypes, it is still not trivial to investigate genetic relationships among a large number of phenotypes using the GPA framework. In order to address this challenge, in this paper, we propose a novel approach, GPA-MDS, to visualize genetic relationships among phenotypes using the GPA algorithm and multidimensional scaling (MDS). This tool will help researchers to investigate common etiology among diseases, which can potentially lead to development of common treatments across diseases. We evaluate the proposed GPA-MDS framework using a simulation study and apply it to jointly analyze GWAS datasets examining 18 unique phenotypes, which helps reveal the shared genetic architecture of these phenotypes.

  14. 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.

  15. Genetic parameters for carcass traits and body weight using a Bayesian approach in the Canchim cattle.

    Science.gov (United States)

    Meirelles, S L C; Mokry, F B; Espasandín, A C; Dias, M A D; Baena, M M; de A Regitano, L C

    2016-06-10

    Correlation between genetic parameters and factors such as backfat thickness (BFT), rib eye area (REA), and body weight (BW) were estimated for Canchim beef cattle raised in natural pastures of Brazil. Data from 1648 animals were analyzed using multi-trait (BFT, REA, and BW) animal models by the Bayesian approach. This model included the effects of contemporary group, age, and individual heterozygosity as covariates. In addition, direct additive genetic and random residual effects were also analyzed. Heritability estimated for BFT (0.16), REA (0.50), and BW (0.44) indicated their potential for genetic improvements and response to selection processes. Furthermore, genetic correlations between BW and the remaining traits were high (P > 0.50), suggesting that selection for BW could improve REA and BFT. On the other hand, genetic correlation between BFT and REA was low (P = 0.39 ± 0.17), and included considerable variations, suggesting that these traits can be jointly included as selection criteria without influencing each other. We found that REA and BFT responded to the selection processes, as measured by ultrasound. Therefore, selection for yearling weight results in changes in REA and BFT.

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

    Science.gov (United States)

    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.

  17. Infant development in family context: Call for a genetically informed approach

    Directory of Open Access Journals (Sweden)

    Stephanie H. Parade

    2012-09-01

    Full Text Available We call for a genetically informed approach in the examination of infant social and emotional development in family context. We recommend that scholars conceptualize family functioning as occurring on three unique levels: the parent-child dyad, the inter-parental dyad, and whole family functioning. Although advances in the area of understanding genetic variation in infants as a potential moderator of the influence of parent-child dyadic functioning have been made over the past decade, it is time to widen this inquiry to consider genetic variation in infants as a potential moderator of the influence of inter-parental dyadic and whole family functioning as well. A critical review of the literature also calls for additional examination of genetic variation in infants as a moderator of positive contextual influences, the integration of unique temperament variables with studies of infant genotype, consideration of the role of the gene-environment correlation, and epigenetic effects. Furthermore, we call for the application of genetically-informed research methods to these questions. Expanding knowledge in this area has the potential to refine treatment and prevention efforts aimed at promoting infant social and emotional development.

  18. Implications of isolation and low genetic diversity in peripheral populations of an amphi-Atlantic coral.

    Science.gov (United States)

    Nunes, F; Norris, R D; Knowlton, N

    2009-10-01

    Limited dispersal and connectivity in marine organisms can have negative fitness effects in populations that are small and isolated, but reduced genetic exchange may also promote the potential for local adaptation. Here, we compare the levels of genetic diversity and connectivity in the coral Montastraea cavernosa among both central and peripheral populations throughout its range in the Atlantic. Genetic data from one mitochondrial and two nuclear loci in 191 individuals show that M. cavernosa is subdivided into three genetically distinct regions in the Atlantic: Caribbean-North Atlantic, Western South Atlantic (Brazil) and Eastern Tropical Atlantic (West Africa). Within each region, populations have similar allele frequencies and levels of genetic diversity; indeed, no significant differentiation was found between populations separated by as much as 3000 km, suggesting that this coral species has the ability to disperse over large distances. Gene flow within regions does not, however, translate into connectivity across the entire Atlantic. Instead, substantial differences in allele frequencies across regions suggest that genetic exchange is infrequent between the Caribbean, Brazil and West Africa. Furthermore, markedly lower levels of genetic diversity are observed in the Brazilian and West African populations. Genetic diversity and connectivity may contribute to the resilience of a coral population to disturbance. Isolated peripheral populations may be more vulnerable to human impacts, disease or climate change relative to those in the genetically diverse Caribbean-North Atlantic region.

  19. A Genetic Study of Attention Deficit Hyperactivity Disorder, Conduct Disorder, Oppositional Defiant Disorder and Reading Disability: Aetiological Overlaps and Implications

    Science.gov (United States)

    Martin, Neilson C.; Levy, Florence; Pieka, Jan; Hay, David A.

    2006-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) commonly co-occurs with Oppositional Defiant Disorder, Conduct Disorder and Reading Disability. Twin studies are an important approach to understanding and modelling potential causes of such comorbidity. Univariate and bivariate genetic models were fitted to maternal report data from 2040 families of…

  20. An integrative systems genetics approach reveals potential causal genes and pathways related to obesity

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Zhernakova, Daria V.; Westra, Harm-Jan

    2015-01-01

    BACKGROUND: Obesity is a multi-factorial health problem in which genetic factors play an important role. Limited results have been obtained in single-gene studies using either genomic or transcriptomic data. RNA sequencing technology has shown its potential in gaining accurate knowledge about...... the transcriptome, and may reveal novel genes affecting complex diseases. Integration of genomic and transcriptomic variation (expression quantitative trait loci [eQTL] mapping) has identified causal variants that affect complex diseases. We integrated transcriptomic data from adipose tissue and genomic data from...... a porcine model to investigate the mechanisms involved in obesity using a systems genetics approach. METHODS: Using a selective gene expression profiling approach, we selected 36 animals based on a previously created genomic Obesity Index for RNA sequencing of subcutaneous adipose tissue. Differential...

  1. The introduction history of invasive garden ants in Europe: integrating genetic, chemical and behavioural approaches

    DEFF Research Database (Denmark)

    Ugelvig, Line; Drijfhout, Falko; Kronauer, Daniel;

    2008-01-01

    BACKGROUND: The invasive garden ant, Lasius neglectus, is the most recently detected pest ant and the first known invasive ant able to become established and thrive in the temperate regions of Eurasia. In this study, we aim to reconstruct the invasion history of this ant in Europe analysing 14...... populations with three complementary approaches: genetic microsatellite analysis, chemical analysis of cuticular hydrocarbon profiles and behavioural observations of aggression behaviour. We evaluate the relative informative power of the three methodological approaches and estimate both the number...... of independent introduction events from a yet unknown native range somewhere in the Black Sea area, and the invasive potential of the existing introduced populations. RESULTS: Three clusters of genetically similar populations were detected, and all but one population had a similar chemical profile. Aggression...

  2. Discovering Pair-Wise Genetic Interactions: An Information Theory-Based Approach

    Science.gov (United States)

    Ignac, Tomasz M.; Skupin, Alexander; Sakhanenko, Nikita A.; Galas, David J.

    2014-01-01

    Phenotypic variation, including that which underlies health and disease in humans, results in part from multiple interactions among both genetic variation and environmental factors. While diseases or phenotypes caused by single gene variants can be identified by established association methods and family-based approaches, complex phenotypic traits resulting from multi-gene interactions remain very difficult to characterize. Here we describe a new method based on information theory, and demonstrate how it improves on previous approaches to identifying genetic interactions, including both synthetic and modifier kinds of interactions. We apply our measure, called interaction distance, to previously analyzed data sets of yeast sporulation efficiency, lipid related mouse data and several human disease models to characterize the method. We show how the interaction distance can reveal novel gene interaction candidates in experimental and simulated data sets, and outperforms other measures in several circumstances. The method also allows us to optimize case/control sample composition for clinical studies. PMID:24670935

  3. Genetic engineering of industrial Saccharomyces cerevisiae strains using a selection/counter-selection approach.

    Science.gov (United States)

    Kutyna, Dariusz R; Cordente, Antonio G; Varela, Cristian

    2014-01-01

    Gene modification of laboratory yeast strains is currently a very straightforward task thanks to the availability of the entire yeast genome sequence and the high frequency with which yeast can incorporate exogenous DNA into its genome. Unfortunately, laboratory strains do not perform well in industrial settings, indicating the need for strategies to modify industrial strains to enable strain development for industrial applications. Here we describe approaches we have used to genetically modify industrial strains used in winemaking.

  4. An integrated approach to structural design of buildings using genetic algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Rafiq, M.Y.; Mathews, J.D. [Univ. of Plymouth (United Kingdom)

    1996-12-31

    This paper presents an evolutionary approach to the integration of design activities, in the area of structural design of buildings, using Genetic Algorithms (GA). Integration process is viewed in two contexts: (i) Integration across the design activities within a particular discipline, and (ii) Integration across of the disciplines involved in the design. Particular advantages of the integration of design activities during the conceptual stage of the design process are highlighted.

  5. The introduction history of invasive garden ants in Europe: Integrating genetic, chemical and behavioural approaches

    OpenAIRE

    Boomsma Jacobus J; Kronauer Daniel JC; Drijfhout Falko P; Ugelvig Line V; Pedersen Jes S; Cremer Sylvia

    2008-01-01

    Abstract Background The invasive garden ant, Lasius neglectus, is the most recently detected pest ant and the first known invasive ant able to become established and thrive in the temperate regions of Eurasia. In this study, we aim to reconstruct the invasion history of this ant in Europe analysing 14 populations with three complementary approaches: genetic microsatellite analysis, chemical analysis of cuticular hydrocarbon profiles and behavioural observations of aggression behaviour. We eva...

  6. 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.

  7. Kernel Approach for Modeling Interaction Effects in Genetic Association Studies of Complex Quantitative Traits.

    Science.gov (United States)

    Broadaway, K Alaine; Duncan, Richard; Conneely, Karen N; Almli, Lynn M; Bradley, Bekh; Ressler, Kerry J; Epstein, Michael P

    2015-07-01

    The etiology of complex traits likely involves the effects of genetic and environmental factors, along with complicated interaction effects between them. Consequently, there has been interest in applying genetic association tests of complex traits that account for potential modification of the genetic effect in the presence of an environmental factor. One can perform such an analysis using a joint test of gene and gene-environment interaction. An optimal joint test would be one that remains powerful under a variety of models ranging from those of strong gene-environment interaction effect to those of little or no gene-environment interaction effect. To fill this demand, we have extended a kernel machine based approach for association mapping of multiple SNPs to consider joint tests of gene and gene-environment interaction. The kernel-based approach for joint testing is promising, because it incorporates linkage disequilibrium information from multiple SNPs simultaneously in analysis and permits flexible modeling of interaction effects. Using simulated data, we show that our kernel machine approach typically outperforms the traditional joint test under strong gene-environment interaction models and further outperforms the traditional main-effect association test under models of weak or no gene-environment interaction effects. We illustrate our test using genome-wide association data from the Grady Trauma Project, a cohort of highly traumatized, at-risk individuals, which has previously been investigated for interaction effects. © 2015 WILEY PERIODICALS, INC.

  8. The introduction history of invasive garden ants in Europe: Integrating genetic, chemical and behavioural approaches

    Directory of Open Access Journals (Sweden)

    Boomsma Jacobus J

    2008-02-01

    Full Text Available Abstract Background The invasive garden ant, Lasius neglectus, is the most recently detected pest ant and the first known invasive ant able to become established and thrive in the temperate regions of Eurasia. In this study, we aim to reconstruct the invasion history of this ant in Europe analysing 14 populations with three complementary approaches: genetic microsatellite analysis, chemical analysis of cuticular hydrocarbon profiles and behavioural observations of aggression behaviour. We evaluate the relative informative power of the three methodological approaches and estimate both the number of independent introduction events from a yet unknown native range somewhere in the Black Sea area, and the invasive potential of the existing introduced populations. Results Three clusters of genetically similar populations were detected, and all but one population had a similar chemical profile. Aggression between populations could be predicted from their genetic and chemical distance, and two major clusters of non-aggressive groups of populations were found. However, populations of L. neglectus did not separate into clear supercolonial associations, as is typical for other invasive ants. Conclusion The three methodological approaches gave consistent and complementary results. All joint evidence supports the inference that the 14 introduced populations of L. neglectus in Europe likely arose from only very few independent introductions from the native range, and that new infestations were typically started through introductions from other invasive populations. This indicates that existing introduced populations have a very high invasive potential when the ants are inadvertently spread by human transport.

  9. Approaches for the identification of genetic modifiers of nutrient dependent phenotypes: Examples from folate

    Directory of Open Access Journals (Sweden)

    Amanda J. Macfarlane

    2014-07-01

    Full Text Available By combining the sciences of nutrition, bioinformatics, genomics, population genetics and epidemiology, nutrigenomics is improving our understanding of how diet and nutrient intake can interact with or modify gene expression and disease risk. In this review, we explore various approaches to examine gene-nutrient interactions and the modifying role of nutrient consumption, as they relate to nutrient status and disease risk in human populations. Two common approaches include the use of SNPs in candidate genes to identify their association with nutritional status or disease outcomes, or genome wide association studies to identify genetic polymorphisms associated with a given phenotype. Here, we examine the results of various gene-nutrient interaction studies, the association of genetic polymorphisms with disease expression and the identification of nutritional factors that modify gene-dependent disease phenotypes. We have focussed on specific examples from investigations of the interactions of folate and B-vitamin consumption and polymorphisms in the genes of B vitamin dependent enzymes and their association with disease risk, followed by an examination of the strengths and limitations of the methods employed. We also present suggestions for future studies, including an approach from an on-going large scale study, to examine the interaction of nutrient intake and genotypic variation and their impact on nutritional status.

  10. 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.

  11. Genetic diversity and population structure of locally adapted South African chicken lines: Implications for conservation.

    NARCIS (Netherlands)

    Marle-Koster, van E.; Hefer, C.A.; Nel, L.H.; Groenen, M.A.M.

    2008-01-01

    In this study microsatellite markers were applied to investigate the genetic diversity and population structure of the six local chicken lines kept in the “Fowls for Africa” program, for better clarification of parameters for breed differentiation and genetic conservation of this valuable resource.

  12. Genetics and Deafness: Implications for Education and Life Care of Deaf Students

    Science.gov (United States)

    Schein, Jerome D.; Miller, Maurice H.

    2008-01-01

    The severity of deafness can obscure the presence of other disabilities that may accompany genetic anomalies, such as occur in Alport and Usher syndromes. Recent advances in genetics have heightened attention to various disabilities and dysfunctions that may coexist with deafness. Failure to recognize these additional disabilities when they occur…

  13. Eugenics, Genetics, and the Minority Group Model of Disabilities: Implications for Social Work Advocacy

    Science.gov (United States)

    O'Brien, Gerald V.

    2011-01-01

    In the United States, genetic research, as well as policy and practice innovations based on this research, has expanded greatly over the past few decades. This expansion is indicated, for example, by the mapping of the human genome, an expansion of genetic counseling, and other biogenetic research. Also, a disability rights movement that in many…

  14. Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

    Science.gov (United States)

    2011-01-01

    Background A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Results Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Conclusions Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness. PMID:21284886

  15. Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

    Directory of Open Access Journals (Sweden)

    Penedo M Cecilia T

    2011-02-01

    Full Text Available Abstract Background A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Results Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Conclusions Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness.

  16. 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.

  17. Molecular mechanisms of paraptosis induction: implications for a non-genetically modified tumor vaccine.

    Directory of Open Access Journals (Sweden)

    Neil Hoa

    Full Text Available Paraptosis is the programmed cell death pathway that leads to cellular necrosis. Previously, rodent and human monocytes/macrophages killed glioma cells bearing the membrane macrophage colony stimulating factor (mM-CSF through paraptosis, but the molecular mechanism of this killing process was never identified. We have demonstrated that paraptosis of rat T9 glioma cells can be initiated through a large potassium channel (BK-dependent process initiated by reactive oxygen species. Macrophage mediated cytotoxicity upon the mM-CSF expressing T9-C2 cells was not prevented by the addition of the caspase inhibitor, zVAD-fmk. By a combination of fluorescent confocal and electron microscopy, flow cytometry, electrophysiology, pharmacology, and genetic knock-down approaches, we demonstrated that these ion channels control cellular swelling and vacuolization of rat T9 glioma cells. Cell lysis is preceded by a depletion of intracellular ATP. Six-hour exposure to BK channel activation caused T9 cells to over express heat shock proteins (Hsp 60, 70, 90 and gp96. This same treatment forced HMGB1 translocation from the nuclear region to the periphery. These last molecules are "danger signals" that can stimulate immune responses. Similar inductions of mitochondrial swelling and increased Hsp70 and 90 expressions by BK channel activation were observed with the non-immunogenic F98 glioma cells. Rats injected with T9 cells which were killed by prolonged BK channel activation developed immunity against the T9 cells, while the injection of x-irradiated apoptotic T9 cells failed to produce the vaccinating effect. These results are the first to show that glioma cellular death induced by prolonged BK channel activation improves tumor immunogenicity; this treatment reproduces the vaccinating effects of mM-CSF transduced cells. Elucidation of strategies as described in this study may prove quite valuable in the development of clinical immunotherapy against cancer.

  18. Potential Implications of Research on Genetic or Heritable Contributions to Pedophilia for the Objectives of Criminal Law

    Science.gov (United States)

    Berryessa, Colleen M.

    2015-01-01

    In recent years, there has been increasing scientific research on possible genetic or heritable influences to the etiology of pedophilia, driven by national and public concerns about better understanding the disorder in order to reduce children’s vulnerabilities to pedophilic and child sex offenders. This research has corresponded to growing academic dialogue on how advances in genetic research, especially concerning the causes and development of particular mental disorders or behaviors, may affect traditional practices of criminal law and how the justice system views, manages, and adjudicates different types of criminal behavior and offenders. This paper strives to supplement this dialogue by exploring several of the many possible effects and implications of research surrounding genetic or heritable contributions to pedophilia for the five widely accepted objectives that enforce and regulate the punishment of criminal law. These include retribution, incapacitation, deterrence, rehabilitation, and restoration. Although still currently in early stages, genetic and heritability research on the etiology of pedophilia may have the potential moving forward to influence the current and established punitive methods and strategies of how the justice system perceives, adjudicates, regulates, and punishes pedophilic and sex offenders, as well as how to best prevent sexual offending against children by pedophilic offenders in the future. PMID:25557668

  19. Potential implications of research on genetic or heritable contributions to pedophilia for the objectives of criminal law.

    Science.gov (United States)

    Berryessa, Colleen M

    2014-01-01

    In recent years, there has been increasing scientific research on possible genetic or heritable influences to the etiology of pedophilia, driven by national and public concerns about better understanding the disorder in order to reduce children's vulnerabilities to pedophilic and child sex offenders. This research has corresponded to growing academic dialogue on how advances in genetic research, especially concerning the causes and development of particular mental disorders or behaviors, may affect traditional practices of criminal law and how the justice system views, manages, and adjudicates different types of criminal behavior and offenders. This paper strives to supplement this dialogue by exploring several of the many possible effects and implications of research surrounding genetic or heritable contributions to pedophilia for the five widely accepted objectives that enforce and regulate the punishment of criminal law. These include retribution, incapacitation, deterrence, rehabilitation, and restoration. Although still currently in early stages, genetic and heritability research on the etiology of pedophilia may have the potential moving forward to influence the current and established punitive methods and strategies of how the justice system perceives, adjudicates, regulates, and punishes pedophilic and sex offenders, as well as how to best prevent sexual offending against children by pedophilic offenders in the future.

  20. An ICA with reference approach in identification of genetic variation and associated brain networks

    Directory of Open Access Journals (Sweden)

    Jingyu eLiu

    2012-02-01

    Full Text Available To address the statistical challenges associated with genome-wide association studies, we present an independent component analysis (ICA with reference approach to target a specific genetic variation and associated brain networks. First, a small set of single nucleotide polymorphisms (SNPs are empirically chosen to reflect a feature of interest and these SNPs are used as a reference when applying ICA to a full genomic SNP array. After extracting the genetic component maximally representing the characteristics of the reference, we test its association with brain networks in functional magnetic resonance imaging (fMRI data. The method was evaluated on both real and simulated datasets. Simulation demonstrates that ICA with reference can extract a specific genetic factor, even when the variance accounted for by such a factor is so small that a regular ICA fails. Our real data application from 48 schizophrenia patients and 40 healthy controls include 300K SNPs and fMRI images in an auditory oddball task. Using SNPs with allelic frequency difference in two groups as a reference, we extracted a genetic component that maximally differentiates patients from controls (p<4×10-17, and discovered a brain functional network that was significantly associated with this genetic component (p<1×10-4. The regions in the functional network mainly locate in the thalamus, anterior and posterior cingulate gyri. The contributing SNPs in the genetic factor mainly fall into two clusters centered at chromosome 7q21 and chromosome 5q35. The findings from the schizophrenia application are in concordance with previous knowledge about brain regions and gene function. All together, the results suggest that the ICA with reference can be particularly useful to explore the whole genome to find a specific factor of interest and further study its effect on brain.

  1. Genetic conservation and management of the California endemic, Torrey pine (Pinus torreyana Parry): implications of genetic rescue in a genetically depauperate species

    Science.gov (United States)

    Jill A. Hamilton; Raphaël Royauté; Jessica W. Wright; Paul Hodgskiss; F. Thomas Ledig

    2017-01-01

    Rare species present a challenge under changing environmental conditions as the genetic consequences of rarity may limit species ability to adapt to environmental change. To evaluate the evolutionary potential of a rare species, we assessed variation in traits important to plant fitness using multigenerational common garden experiments. Torrey pine, ...

  2. Comparative genetic approaches to the evolution of human brain and behavior.

    Science.gov (United States)

    Vallender, Eric J

    2011-01-01

    With advances in genomic technologies, the amount of genetic data available to scientists today is vast. Genomes are now available or planned for 14 different primate species and complete resequencing of numerous human individuals from numerous populations is underway. Moreover, high-throughput deep sequencing is quickly making whole genome efforts within the reach of single laboratories allowing for unprecedented studies. Comparative genetic approaches to the identification of the underlying basis of human brain, behavior, and cognitive ability are moving to the forefront. Two approaches predominate: inter-species divergence comparisons and intra-species polymorphism studies. These methodological differences are useful for different time scales of evolution and necessarily focus on different evolutionary events in the history of primate and hominin evolution. Inter-species divergence is more useful in studying large scale primate, or hominoid, evolution whereas intra-species polymorphism can be more illuminating of recent hominin evolution. These differences in methodological utility also extend to studies of differing genetic substrates; current divergence studies focus primarily on protein evolution whereas polymorphism studies are substrate ambivalent. Some of the issues inherent in these studies can be ameliorated by current sequencing capabilities whereas others remain intractable. New avenues are also being opened that allow for the incorporation of novel substrates and approaches. In the post-genomic era, the study of human evolution, specifically as it relates to the brain, is becoming more complete focusing increasingly on the totality of the system and better conceptualizing the entirety of the genetic changes that have lead to the human phenotype today.

  3. Low genetic diversity and minimal population substructure in the endangered Florida manatee: implications for conservation

    Science.gov (United States)

    Tucker, Kimberly Pause; Hunter, Margaret E.; Bonde, Robert K.; Austin, James D.; Clark, Ann Marie; Beck, Cathy A.; McGuire, Peter M.; Oli, Madan K.

    2012-01-01

    Species of management concern that have been affected by human activities typically are characterized by low genetic diversity, which can adversely affect their ability to adapt to environmental changes. We used 18 microsatellite markers to genotype 362 Florida manatees (Trichechus manatus latirostris), and investigated genetic diversity, population structure, and estimated genetically effective population size (Ne). The observed and expected heterozygosity and average number of alleles were 0.455 ± 0.04, 0.479 ± 0.04, and 4.77 ± 0.51, respectively. All measures of Florida manatee genetic diversity were less than averages reported for placental mammals, including fragmented or nonideal populations. Overall estimates of differentiation were low, though significantly greater than zero, and analysis of molecular variance revealed that over 95% of the total variance was among individuals within predefined management units or among individuals along the coastal subpopulations, with only minor portions of variance explained by between group variance. Although genetic issues, as inferred by neutral genetic markers, appear not to be critical at present, the Florida manatee continues to face demographic challenges due to anthropogenic activities and stochastic factors such as red tides, oil spills, and disease outbreaks; these can further reduce genetic diversity of the manatee population.

  4. Condemned by Birth: The implications of Genetics for the Theories of Crime and Punishment

    Directory of Open Access Journals (Sweden)

    Meghna Rajadhyaksha

    2010-01-01

    Full Text Available This article traces debates around relevance of genetics in determining culpability. The chief trends in this regard are illustrated by decisions of the American Courts over the past century, which have moved from applications of blind heredity to sophisticated molecular analyses. Since genetics impacts the basic assumption of "free will" in criminal law, its use as a defence has been examined at length. Finally, this article examines the methodsand theories of punishment, and their effectiveness in preventing and penalizing the actions of "genetic offenders".

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

    Directory of Open Access Journals (Sweden)

    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

  6. Gene networks associated with conditional fear in mice identified using a systems genetics approach

    Directory of Open Access Journals (Sweden)

    Eskin Eleazar

    2011-03-01

    Full Text Available Abstract Background Our understanding of the genetic basis of learning and memory remains shrouded in mystery. To explore the genetic networks governing the biology of conditional fear, we used a systems genetics approach to analyze a hybrid mouse diversity panel (HMDP with high mapping resolution. Results A total of 27 behavioral quantitative trait loci were mapped with a false discovery rate of 5%. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and also genotype information, two gene co-expression networks correlated with context-dependent immobility were identified. We prioritized the key markers and genes in these pathways using intramodular connectivity measures and structural equation modeling. Highly connected genes in the context fear modules included Psmd6, Ube2a and Usp33, suggesting an important role for ubiquitination in learning and memory. In addition, we surveyed the architecture of brain transcript regulation and demonstrated preservation of gene co-expression modules in hippocampus and striatum, while also highlighting important differences. Rps15a, Kif3a, Stard7, 6330503K22RIK, and Plvap were among the individual genes whose transcript abundance were strongly associated with fear phenotypes. Conclusion Application of our multi-faceted mapping strategy permits an increasingly detailed characterization of the genetic networks underlying behavior.

  7. Genetic variation in strains of zebrafish (Danio rerio) and the implications for ecotoxicology studies.

    Science.gov (United States)

    Coe, T S; Hamilton, P B; Griffiths, A M; Hodgson, D J; Wahab, M A; Tyler, C R

    2009-01-01

    There is substantial evidence that genetic variation, at both the level of the individual and population, has a significant effect on behaviour, fitness and response to toxicants. Using DNA microsatellites, we examined the genetic variation in samples of several commonly used laboratory strains of zebrafish, Danio rerio, a model species in toxicological studies. We compared the genetic variation to that found in a sample of wild fish from Bangladesh. Our findings show that the wild fish were significantly more variable than the laboratory strains for several measures of genetic variability, including allelic richness and expected heterozygosity. This lack of variation should be given due consideration for any study which attempts to extrapolate the results of ecotoxicological laboratory tests to wild populations.

  8. Genetic diversity and conservation implications of four Cupressus species in China as revealed by microsatellite markers.

    Science.gov (United States)

    Lu, Xu; Xu, Haiyan; Li, Zhonghu; Shang, Huiying; Adams, Robert P; Mao, Kangshan

    2014-04-01

    Understanding the extent and distribution of genetic diversity is crucial for the conservation and management of endangered species. Cupressus chengiana, C. duclouxiana, C. gigantea, and C. funebris are four ecologically and economically important species in China. We investigated their genetic diversity, population structure, and extant effective population size (35 populations, 484 individuals) employing six pairs of nuclear microsatellite markers (selected from 53). Their genetic diversity is moderate among conifers, and genetic differentiation among populations is much lower in C. gigantea than in the other three species; the estimated effective population size was largest for C. chengiana, at 1.70, 2.91, and 3.91 times the estimates for C. duclouxiana, C. funebris, and C. gigantea, respectively. According to Bayesian clustering analysis, the most plausible population subdivision scheme within species is two groups in C. chengiana, three groups in C. duclouxiana, and a single group for both C. funebris and C. gigantea. We propose a conservation strategy for these cypress species.

  9. Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

    OpenAIRE

    Penedo M Cecilia T; Weisenberger Mara E; Boyce Walter M; Johnson Christine K

    2011-01-01

    Abstract Background A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in Ne...

  10. Molecular diagnosis of Huntington disease in Portugal : implications for genetic counselling and clinical practice

    OpenAIRE

    2003-01-01

    Huntington disease (HD) is a eurodegenerative, autosomal dominant disorder of late-onset, caused by the expansion of a CAG repeat in the coding region of the gene. Ours is the reference laboratory for genetic testing in HD, in Portugal, since 1998; 90.1% of all 158 families known were identified for the first time, including patients with unusual presentation or without family history. A total of 338 genetic tests were performed: 234 for diagnosis, 96 for presymptomatic and four for prenat...

  11. Genetic Causal Attribution of Epilepsy and its Implications for Felt Stigma

    Science.gov (United States)

    Sabatello, Maya; Phelan, Jo C.; Hesdorffer, Dale C.; Shostak, Sara; Goldsmith, Jeff; Sorge, Shawn T.; Winawer, Melodie R.; Chung, Wendy K.; Ottman, Ruth

    2015-01-01

    Summary Objective Research in other disorders suggests that genetic causal attribution of epilepsy might be associated with increased stigma. We investigated this hypothesis in a unique sample of families containing multiple individuals with epilepsy. Methods 181 people with epilepsy and 178 biological relatives without epilepsy completed a self-administered survey. In people with epilepsy, felt stigma was assessed through the Epilepsy Stigma Scale (ESS), scored 1 to 7 with higher scores indicating more stigma and >4 indicating some felt stigma. Felt stigma related to having epilepsy in the family was assessed through the Family Epilepsy Stigma Scale (FESS), created by replacing “epilepsy” with “epilepsy in my family” in each ESS item. Genetic attribution was assessed through participants’ perceptions of the (1) role of genetics in causing epilepsy in the family, (2) chance they had an epilepsy-related mutation, and (3) (in people with epilepsy) influence of genetics in causing their epilepsy. Results Among people with epilepsy, 22% met criteria for felt stigma (ESS score >4). Scores were increased among individuals who were aged ≥60 years, were unemployed, reported epilepsy-related discrimination, or had seizures within the last year or >100 seizures in their lifetime. Adjusting for other variables, ESS scores in people with epilepsy were significantly higher among those who perceived genetics played a “medium” or “big” role in causing epilepsy in the family than in others (3.4 vs. 2.7, p=0.025). Only 4% of relatives without epilepsy had felt stigma. Scores in relatives were unrelated to genetic attribution. Significance In these unusual families, predictors of felt stigma in individuals with epilepsy are similar to those in other studies, and stigma levels are low in relatives without epilepsy. Felt stigma may be increased in people with epilepsy who believe epilepsy in the family has a genetic cause, emphasizing the need for sensitive

  12. Implications of genetics on the diagnosis and care of patients with Parkinson disease.

    Science.gov (United States)

    Klein, Christine

    2006-03-01

    The identification of several monogenic forms has established Parkinson disease (PD) as a movement disorder with a considerable genetic origin in at least a subset of patients. Four of the known forms, Parkin-, PINK1 (PTEN-induced putative kinase 1)-, DJ1-, and LRRK2 (leucine-rich repeat kinase 2)-linked PD, may present clinically as "idiopathic PD" and account for at least 1% of all cases of PD. However, all known monogenic forms combined explain about only 20% of early-onset PD and less than 3% of late-onset PD at best. Although the individual clinical course cannot be predicted, overall, many cases of genetic PD will progress more slowly and respond better to treatment than patients without mutations. Genetic testing frequently yields inconclusive results, is expensive, and should be used for diagnostic purposes only after careful consideration in selected cases at specialty centers. While genetic findings have greatly advanced our understanding of the pathophysiology of PD, we are faced with many novel challenges. These include the definition of the phenotypic and genotypic spectrum of the monogenic forms, a revised terminology and classification of parkinsonian syndromes, identification of genetic susceptibility factors, and development of guidelines for genetic testing and of new treatment options for PD.

  13. A Detailed look of Audio Steganography Techniques using LSB and Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    Gunjan Nehru

    2012-01-01

    Full Text Available This paper is the study of various techniques of audio steganography using different algorithmis like genetic algorithm approach and LSB approach. We have tried some approaches that helps in audio steganography. As we know it is the art and science of writing hidden messages in such a way that no one, apart from the sender and intended recipient, suspects the existence of the message, a form of security through obscurity. In steganography, the message used to hide secret message is called host message or cover message. Once the contents of the host message or cover message are modified, the resultant message is known as stego message. In other words, stego message is combination of host message and secret message. Audio steganography requires a text or audio secret message to be embedded within a cover audio message. Due to availability of redundancy, the cover audio message before steganography, stego message after steganography remains same. for information hiding.

  14. Lack of genetic differentiation between contrasted overwintering strategies of a major pest predator Episyrphus balteatus (Diptera: Syrphidae: implications for biocontrol.

    Directory of Open Access Journals (Sweden)

    Lucie Raymond

    Full Text Available Winter ecology of natural enemies has a great influence on the level and efficiency of biological control at spring. The hoverfly Episyrphus balteatus (DeGeer (Diptera: Syrphidae is one of the most important natural predators of crop aphids in Europe. Three different overwintering strategies coexist in this species which makes it a good model in order to study ecologically-based speciation processes. The purpose of this study was to determine whether E. balteatus populations with alternative overwintering strategies are genetically differentiated. To that aim, we developed 12 specific microsatellite markers and evaluated the level of neutral genetic differentiation between E. balteatus field populations that overwinter in the three different ways described in this species (i.e. migration, local overwintering at a pre-imaginal stage, and local overwintering at adult stage. Results showed a lack of neutral genetic differentiation between individuals with different overwintering strategies although there are strong ecological differences between them. All pair-wise FST values are below 0.025 and non-significant, and Bayesian clustering showed K=1 was the most likely number of genetic clusters throughout our sample. The three overwintering strategies form one unique panmictic population. This suggests that all the individuals may have genetic material for the expression of different overwintering phenotypes, and that their commitment in one particular overwintering strategy may depend on environmental and individual factors. Consequently, the prevalence of the different overwintering strategies would be potentially modified by landscape engineering and habitat management which could have major implications for biological control.

  15. Environmental and genetic sources of diversification in the timing of seed germination: implications for the evolution of bet hedging.

    Science.gov (United States)

    Simons, Andrew M; Johnston, Mark O

    2006-11-01

    Environmental variation that is not predictably related to cues is expected to drive the evolution of bet-hedging strategies. The high variance observed in the timing of seed germination has led to it being the most cited diversification strategy in the theoretical bet-hedging literature. Despite this theoretical focus, virtually nothing is known about the mechanisms responsible for the generation of individual-level diversification. Here we report analyses of sources of variation in timing of germination within seasons, germination fraction over two generations and three sequential seasons, and the genetic correlation structure of these traits using almost 10,000 seeds from more than 100 genotypes of the monocarpic perennial Lobelia inflata. Microenvironmental analysis of time to germination suggests that extreme sensitivity to environmental gradients, or microplasticity, even within a homogeneous growth chamber, may act as an effective individual-level diversification mechanism and explains more than 30% of variance in time to germination. The heritability of within-season timing of germination was low (h(2) = 0.07) but significant under homogeneous conditions. Consistent with individual-level diversification, this low h(2) was attributable not to low additive genetic variance, but to an unusually high coefficient of residual variation in time to germination. Despite high power to detect additive genetic variance in within-season diversification, it was low and indistinguishable from zero. Restricted maximum likelihood detected significant genetic variation for germination fraction (h(2) = 0.18) under homogeneous conditions. Unexpectedly, this heritability was positive when measured within a generation by sibling analysis and negative when measured across generations by offspring-on-parent regression. The consistency of dormancy fraction over multiple delays, a major premise of Cohen's classic model, was supported by a strong genetic correlation (r = 0

  16. Evaluation of a non-targeted "Omic"' approach in the safety assessment of genetically modified plants

    DEFF Research Database (Denmark)

    Metzdorff, Stine Broeng; Kok, E. J.; Knuthsen, Pia;

    2006-01-01

    Genetically modified plants must be approved before release in the European Union, and the approval is generally based upon a comparison of various characteristics between the transgenic plant and a conventional counterpart. As a case study, focusing on safety assessment of genetically modified...... plants, we here report the development and characterisation of six independently transformed Arabidopsis thaliana lines modified in the flavonoid biosynthesis. Analyses of integration events and comparative analysis for characterisation of the intended effects were performed by PCR, quantitative Real......, no unintended effects were identified. However, we found that the majority of genes showing differential expression were identified as stress-related genes and that environmental conditions had a large impact on the expression of several genes, proteins, and metabolites. We suggest that the microarray approach...

  17. Branch-pipe-routing approach for ships using improved genetic algorithm

    Science.gov (United States)

    Sui, Haiteng; Niu, Wentie

    2016-09-01

    Branch-pipe routing plays fundamental and critical roles in ship-pipe design. The branch-pipe-routing problem is a complex combinatorial optimization problem and is thus difficult to solve when depending only on human experts. A modified genetic-algorithm-based approach is proposed in this paper to solve this problem. The simplified layout space is first divided into threedimensional (3D) grids to build its mathematical model. Branch pipes in layout space are regarded as a combination of several two-point pipes, and the pipe route between two connection points is generated using an improved maze algorithm. The coding of branch pipes is then defined, and the genetic operators are devised, especially the complete crossover strategy that greatly accelerates the convergence speed. Finally, simulation tests demonstrate the performance of proposed method.

  18. A genetic approach for the identification of exosporium assembly determinants of Bacillus anthracis

    Science.gov (United States)

    Spreng, Krista A.; Thompson, Brian M.; Stewart, George C.

    2013-01-01

    The exosporium is the outermost layer of spores of the zoonotic pathogen Bacillus anthracis. The composition of the exosporium and its functions are only partly understood. Because this outer spore layer is refractive to traditional biochemical analysis, a genetic approach is needed in order to define the proteins which comprise this important spore layer and its assembly pathway. We have created a novel genetic screening system for the identification and isolation of mutants with defects in exosporium assembly during B. anthracis spore maturation. The system is based on the targeting sequence of the BclA exosporium nap layer glycoprotein and a fluorescent reporter. By utilizing this screening system and gene inactivation with Tn916, several novel putative exosporium-associated determinants were identified. A sampling of the mutants obtained was further characterized, confirming their exosporium defect and validating the utility of this screen to identify novel spore determinants in the genome of this pathogen. PMID:23411372

  19. The Genetics of Obsessive-Compulsive Disorder and Tourette Syndrome: An Epidemiological and Pathway-Based Approach for Gene Discovery

    Science.gov (United States)

    Grados, Marco A.

    2010-01-01

    Objective: To provide a contemporary perspective on genetic discovery methods applied to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). Method: A review of research trends in genetics research in OCD and TS is conducted, with emphasis on novel approaches. Results: Genome-wide association studies (GWAS) are now in progress in OCD…

  20. At risk, or not at risk: Epidemiological approaches for assessing psychiatric (genetic) risk factors in the general population

    NARCIS (Netherlands)

    Breetvelt, E.J.

    2013-01-01

    This thesis “At risk, or not at risk” describes several approaches - cross-sectional, prospective, phenotype mining and forward genetics - for assessing psychiatric (genetic) risk factors in a general population study. The aims were 1) to investigate how routine and follow-up data from populationbas

  1. The Genetics of Obsessive-Compulsive Disorder and Tourette Syndrome: An Epidemiological and Pathway-Based Approach for Gene Discovery

    Science.gov (United States)

    Grados, Marco A.

    2010-01-01

    Objective: To provide a contemporary perspective on genetic discovery methods applied to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). Method: A review of research trends in genetics research in OCD and TS is conducted, with emphasis on novel approaches. Results: Genome-wide association studies (GWAS) are now in progress in OCD…

  2. Neurodevelopmental disorders: theoretical approaches and its implications for education and rehabilitation

    Directory of Open Access Journals (Sweden)

    Maria Luísa Bissoto

    2011-06-01

    Full Text Available The neurodevelopmental disorders, mainly those genetics ones, are argued with the aim to analyze the human development conceptions that underlie these, and its impact for understanding who is the individual that carries this disorder. Methodologically, epistemological presupposition from “classical” neuropsychology and from “neuroconstructivist” neuropsychology had been compared. As results of this parallel had been considered relevant: a. the role of the individual surrounding, b. the question concerning the plasticity and dynamical character of development and c. the formal developmental process, from prenatal to postnatal period. The concluding comments claims that the Neuroconstructivist approaches allow conceiving the developmental process within genetics neurodevelopmental disorders not as a “fault” but as a differentiated and particular one. That should be understood in the Educational and Rehabilitation settings not as a nosological category but as a specific way of an individual acting while looking for a mode of being-in-the-world.

  3. Genetic diversity of the endangered species Rosa rugosa Thunb. in China and implications for conservation strategies

    Institute of Scientific and Technical Information of China (English)

    Ji-Hong YANG; Shu-Ping ZHANG; Jian LIU; Wen ZHAI; Ren-Qing WANG

    2009-01-01

    Rosa rugosa Thunb. is one of the dominant and important shrub species in estuary dunes and shingle beaches of northern China. However, its area of distribution, the number of populations, and the size of each population have decreased rapidly in the past two decades because of habitat degradation and loss. Random amplified polymorphic DNA markers were used to determine the genetic diversity of four remaining large natural populations of R. rugosa and to discuss an effective conservation strategy for this endangered species in China. High genetic variations were detected in R. rugosa populations in China. The mean percentage of polymorphic loci (P%) within four local populations was 57.99%, with the P% of the total population being 75.30%. Mean Shannon's information index (H_0) was 0.2826, whereas total H_0 was 0.3513. The genetic differentiation among populations was 0.1878, which indicates that most genetic diversity occurs within populations. Population Tumenjiang (TMJ) showed the highest genetic diversity (P% = 66.27%; H_0 = 0.3117) and contained two exclusive bands. Population Changshandao (CSD) showed higher genetic diversity (P% = 59.04%; H_0 = 0.3065). Populations TMJ and CSD contained 95.33% and 99.33%, respectively, of loci with moderate to high frequency (P>0.05) of the total population. These results indicate that populations TMJ and CSD should be given priority for in situ conservation and regarded as seed or propagule sources for ex situ conservation. The results of the present study also suggest that R. rugosa in China has become endangered as a result of human actions rather than genetic depression of populations; thus, human interference should be absolutely forbidden in R. rugosa habitats.

  4. Impact of virtual learning environment (VLE): A technological approach to genetics teaching on high school students' content knowledge, self-efficacy and career goal aspirations

    Science.gov (United States)

    Kandi, Kamala M.

    This study examines the effect of a technology-based instructional tool 'Geniverse' on the content knowledge gains, Science Self-Efficacy, Technology Self-Efficacy, and Career Goal Aspirations among 283 high school learners. The study was conducted in four urban high schools, two of which have achieved Adequate Yearly Progress (AYP) and two have not. Students in both types of schools were taught genetics either through Geniverse, a virtual learning environment or Dragon genetics, a paper-pencil activity embedded in traditional instructional method. Results indicated that students in all schools increased their knowledge of genetics using either type of instructional approach. Students who were taught using Geniverse demonstrated an advantage for genetics knowledge although the effect was small. These increases were more pronounced in the schools that had been meeting the AYP goal. The other significant effect for Geniverse was that students in the technology-enhanced classrooms increased in science Self-Efficacy while students in the non-technology enhanced classrooms decreased. In addition, students from Non-AYP schools showed an improvement in Science and Technology Self-Efficacy; however the effects were small. The implications of these results for the future use of technology-enriched classrooms were discussed. Keywords: Technology-based instruction, Self-Efficacy, career goals and Adequate Yearly Progress (AYP).

  5. Connecting Palau's marine protected areas: a population genetic approach to conservation

    Science.gov (United States)

    Cros, Annick; Toonen, Robert J.; Donahue, Megan J.; Karl, Stephen A.

    2017-09-01

    Bleaching events are becoming more frequent and are projected to become annual in Micronesia by 2040. To prepare for this threat, the Government of Palau is reviewing its marine protected area network to increase the resilience of the reefs by integrating connectivity into the network design. To support their effort, we used high-throughput sequencing of microsatellites to create genotypes of colonies of the coral Acropora hyacinthus to characterize population genetic structure and dispersal patterns that led to the recovery of Palau's reefs from a 1998 bleaching event. We found no evidence of a founder effect or refugium where colonies may have survived to recolonize the reef. Instead, we found significant pairwise F' st values, indicating population structure and low connectivity among most of the 25 sites around Palau. We used kinship to measure genetic differences at the individual level among sites and found that differences were best explained by the degree of exposure to the ocean [ F 1,20 = 3.015, Pr(> F) = 0.01], but with little of the total variation explained. A permutation test of the pairwise kinship coefficients revealed that there was self-seeding within sites. Overall, the data point to the population of A. hyacinthus in Palau recovering from a handful of surviving colonies with population growth primarily from self-seeding and little exchange among sites. This finding has significant implications for the management strategies for the reefs of Palau, and we recommend increasing the number and distribution of management areas around Palau to capture the genetic architecture and increase the chances of protecting potential refuges in the future.

  6. Enhancement of lipid production using biochemical, genetic and transcription factor engineering approaches.

    Science.gov (United States)

    Courchesne, Noémie Manuelle Dorval; Parisien, Albert; Wang, Bei; Lan, Christopher Q

    2009-04-20

    This paper compares three possible strategies for enhanced lipid overproduction in microalgae: the biochemical engineering (BE) approaches, the genetic engineering (GE) approaches, and the transcription factor engineering (TFE) approaches. The BE strategy relies on creating a physiological stress such as nutrient-starvation or high salinity to channel metabolic fluxes to lipid accumulation. The GE strategy exploits our understanding to the lipid metabolic pathway, especially the rate-limiting enzymes, to create a channelling of metabolites to lipid biosynthesis by overexpressing one or more key enzymes in recombinant microalgal strains. The TFE strategy is an emerging technology aiming at enhancing the production of a particular metabolite by means of overexpressing TFs regulating the metabolic pathways involved in the accumulation of target metabolites. Currently, BE approaches are the most established in microalgal lipid production. The TFE is a very promising strategy because it may avoid the inhibitive effects of the BE approaches and the limitation of "secondary bottlenecks" as commonly observed in the GE approaches. However, it is still a novel concept to be investigated systematically.

  7. A genetic algorithms approach for altering the membership functions in fuzzy logic controllers

    Science.gov (United States)

    Shehadeh, Hana; Lea, Robert N.

    1992-01-01

    Through previous work, a fuzzy control system was developed to perform translational and rotational control of a space vehicle. This problem was then re-examined to determine the effectiveness of genetic algorithms on fine tuning the controller. This paper explains the problems associated with the design of this fuzzy controller and offers a technique for tuning fuzzy logic controllers. A fuzzy logic controller is a rule-based system that uses fuzzy linguistic variables to model human rule-of-thumb approaches to control actions within a given system. This 'fuzzy expert system' features rules that direct the decision process and membership functions that convert the linguistic variables into the precise numeric values used for system control. Defining the fuzzy membership functions is the most time consuming aspect of the controller design. One single change in the membership functions could significantly alter the performance of the controller. This membership function definition can be accomplished by using a trial and error technique to alter the membership functions creating a highly tuned controller. This approach can be time consuming and requires a great deal of knowledge from human experts. In order to shorten development time, an iterative procedure for altering the membership functions to create a tuned set that used a minimal amount of fuel for velocity vector approach and station-keep maneuvers was developed. Genetic algorithms, search techniques used for optimization, were utilized to solve this problem.

  8. Genetic variability and population structure of Salvia lachnostachys: implications for breeding and conservation programs.

    Science.gov (United States)

    Erbano, Marianna; Schühli, Guilherme Schnell E; Santos, Élide Pereira Dos

    2015-04-08

    The genetic diversity and population structure of Salvia lachnostachys Benth were assessed. Inter Simple Sequence Repeat (ISSR) molecular markers were used to investigate the restricted distribution of S. lachnostachys in Parana State, Brazil. Leaves of 73 individuals representing three populations were collected. DNA was extracted and submitted to PCR-ISSR amplification with nine tested primers. Genetic diversity parameters were evaluated. Our analysis indicated 95.6% polymorphic loci (stress value 0.02) with a 0.79 average Simpson's index. The Nei-Li distance dendrogram and principal component analysis largely recovered the geographical origin of each sample. Four major clusters were recognized representing each collected population. Nei's gene diversity and Shannon's information index were 0.25 and 0.40 respectively. As is typical for outcrossing herbs, the majority of genetic variation occurred at the population level (81.76%). A high gene flow (Nm = 2.48) was observed with a correspondingly low fixation index. These values were generally similar to previous studies on congeneric species. The results of principal coordinate analysis (PCA) and of arithmetic average (UPGMA) were consistent and all three populations appear distinct as in STRUCTURE analysis. In addition, this analysis indicated a majority intrapopulation genetic variation. Despite the human pressure on natural populations our study found high levels of genetic diversity for S. lachnostachys. This was the first molecular assessment for this endemic species with medicinal proprieties and the results can guide for subsequent bioprospection, breeding programs or conservation actions.

  9. Genetic structure of three Croatian horse breeds: implications for their conservation strategy

    Directory of Open Access Journals (Sweden)

    Miljenko Konjačić

    2010-01-01

    Full Text Available The genetic variability for a sample of 107 animals from three autochthonous Croatian horse breeds was estimated using 20 microsatellites. The average number of alleles per locus (6.3 and proportion of heterozygosity (0.732 indicated a moderate variability. The expected heterozygosity was similar among all breeds and ranged between 0.724 in the Posavina horse, and 0.737 in the Croatian Coldblood and Murinsulaner horse. The inbreeding coefficient FIS was low and non-significant over the three populations. The genetic differentiation among the three populations was low (FST=0.026, suggesting that only 2.6% of the total genetic variability was due to differences between the breeds, and 97% to individual differences. The results of pairwise genetic differentiation suggest that the Posavina horse and the Croatian Coldblood were the most closely related populations (FST=0.016. These results are confirmed by Nei’s genetic distances with the highest value observed between the Posavina horse and the Murinsulaner (0.082 and the lowest between the Posavina horse and the Croatian Coldblood (0.044. An assignment test correctly assigned 82% of individuals to the correct breed. Strategies for preserving the original native genes in the Croatian native horse breeds should be considered in order to prevent these breeds from becoming extinct and include them in the future breeding programmes.

  10. High regional genetic differentiation of an endangered relict plant Craigia yunnanensis and implications for its conservation

    Directory of Open Access Journals (Sweden)

    Jing Yang

    2016-10-01

    Full Text Available Of the genus Craigia, widespread in the Tertiary, only two relict species survived to modern times. One species is now possibly extinct and the other one, Craigia yunnanensis, is severely endangered. Extensive surveys have located six C. yunnanensis populations in Yunnan province, southwest China. Using fluorescent amplified fragment length polymorphism (AFLP, the genetic diversity and population structure of these populations were examined. It was found that genetic diversity of C. yunnanensis was moderate at the species level, but low at regional and population levels. Analysis of population structure showed significant genetic differentiation between Wenshan and Dehong regions, apparently representing two geographically isolated for long time refuges. There are also clear indications of isolation between populations, which, together with anthropogenically caused decline of population size, will lead to general loss of the species genetic variation with subsequent loss of adaptive potential. To conserve the genetic integrity of C. yunnanensis, we recommend that ex-situ conservation should include representative samples from every population of the two differentiated regions (e.g. Wenshan and Dehong. The crosses between individuals originated from different regions should be avoided because of a high risk of outbreeding depression. As all the extant populations of C. yunnanensis are in unprotected areas with strong anthropogenic impact, there is no alternative to reintroduction of C. yunnanensis into suitable protected locations.

  11. Implications of genetics and current protected areas for conservation of 5 endangered primates in China.

    Science.gov (United States)

    Liu, Zhijin; Liu, Guangjian; Roos, Christian; Wang, Ziming; Xiang, ZuoFu; Zhu, Pingfen; Wang, Boshi; Ren, Baoping; Shi, Fanglei; Pan, Huijuan; Li, Ming

    2015-12-01

    Most of China's 24-28 primate species are threatened with extinction. Habitat reduction and fragmentation are perhaps the greatest threats. We used published data from a conservation genetics study of 5 endangered primates in China (Rhinopithecus roxellana, R. bieti, R. brelichi, Trachypithecus francoisi, and T. leucocephalus); distribution data on these species; and the distribution, area, and location of protected areas to inform conservation strategies for these primates. All 5 species were separated into subpopulations with unique genetic components. Gene flow appeared to be strongly impeded by agricultural land, meadows used for grazing, highways, and humans dwellings. Most species declined severely or diverged concurrently as human population and crop land cover increased. Nature reserves were not evenly distributed across subpopulations with unique genetic backgrounds. Certain small subpopulations were severely fragmented and had higher extinction risk than others. Primate mobility is limited and their genetic structure is strong and susceptible to substantial loss of diversity due to local extinction. Thus, to maximize preservation of genetic diversity in all these primate species, our results suggest protection is required for all sub-populations. Key priorities for their conservation include maintaining R. roxellana in Shennongjia national reserve, subpopulations S4 and S5 of R. bieti and of R. brelichi in Fanjingshan national reserve, subpopulation CGX of T. francoisi in central Guangxi Province, and all 3 T. leucocephalus sub-populations in central Guangxi Province. © 2015 Society for Conservation Biology.

  12. GROWTH ECONOMIC MODELS AND THEIR IMPLICATIONS TO FINANCIAL POLICY DURING TRANSITION. ATHEORETICAL APPROACH

    Directory of Open Access Journals (Sweden)

    BOGDAN FIRTESCU

    2012-05-01

    Full Text Available During 1989, the moment of changes in Eastern Europe, in socialist countries political system were transformed, by renouncing communism, and adopting market based economy. The process had major implications on economic systems in countries such Romania, Bulgaria, Hungary, Poland, Czechoslovakia, that from that moment engaged in wide-ranging political, social, economic and institutional reforms. The year 1989 also marked the beginning of the transition from socialist economy to a market economy to centralized countries mentioned, a process with profound implications on the economic system and financial default. This important structural reforms necessary functioning new economic framework and assumed behavior modification specific old economy, focused on socialist property, presumably achieve in conditions of relative stability allowing rapidly and sustainable growth. This paper takes into discussion some models used by FMI and World Bank (WB that had implications on financial policy applied in transition country, referring to absorption theory, monetary approach to balance of payment and stabilization programs, as short terms models, respectively.

  13. 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.

  14. Danish retinoblastoma patients 1943-2013 - genetic testing and clinical implications

    DEFF Research Database (Denmark)

    Gregersen, Pernille A; Urbak, Steen F; Funding, Mikkel

    2015-01-01

    of patients diagnosed before DNA testing was offered. Knowledge of heredity increases the chance of early diagnosis in offspring, leading to improved prognosis. We present data from the Danish retinoblastoma patients that emphasize the need for genetic counseling and RB1 screening in all untested......, the rate has been stable around 1 per 14 000 live births with 95% of the patients surviving their retinoblastoma. Stratifying data on the time of diagnosis and status of genetic testing, the number of screened patients gradually increased from 5% in the beginning of the period to 96% in the last five......-year period. A cohort of 181 retinoblastoma survivors with sporadic disease (15% heritable) did not receive genetic testing. Since the introduction of routine testing, one of 14 sporadic unilateral patients tested (7%) has been identified with a germline mutation. Before routine testing, five additional...

  15. Eugenics, genetics, and the minority group model of disabilities: implications for social work advocacy.

    Science.gov (United States)

    O'Brien, Gerald V

    2011-10-01

    In the United States, genetic research, as well as policy and practice innovations based on this research, has expanded greatly over the past few decades. This expansion is indicated, for example, by the mapping of the human genome, an expansion of genetic counseling, and other biogenetic research. Also, a disability rights movement that in many ways parallels other "minority" rights campaigns has expanded. The coexistence of these developments poses intriguing challenges for social work that the profession has yet to address in a meaningful way. These issues are especially pertinent for social work professionals in the crucial role as advocates for marginalized populations. This article describes some ofthe concerns of disability rights activists relative to genetic innovations and goals as well as the instrumental role of the social work community in this important debate.

  16. Genetic and Chemical Profiling of Gymnema sylvestre Accessions from Central India: Its Implication for Quality Control and Therapeutic Potential of Plant

    Science.gov (United States)

    Verma, Ashutosh Kumar; Dhawan, Sunita Singh; Singh, Seema; Bharati, Kumar Avinash; Jyotsana

    2016-01-01

    Background: Gymnema sylvestre, a vulnerable plant species, is mentioned in Indian Pharmacopeia as an antidiabetic drug Objective: Study of genetic and chemical diversity and its implications in accessions of G. sylvestre Materials and Methods: Fourteen accessions of G. sylvestre collected from Central India and assessment of their genetic and chemical diversity were carried out using ISSR (inter simple sequence repeat) and HPLC (high performance liquid chromatography) fingerprinting methods Results: Among the screened 40 ISSR primers, 15 were found polymorphic and collectively produced nine unique accession-specific bands. The maximum and minimum numbers of amplicones were noted for ISSR-15 and ISSR-11, respectively. The ISSR -11 and ISSR-13 revealed 100% polymorphism. HPLC chromatograms showed that accessions possess the secondary metabolites of mid-polarity with considerable variability. Unknown peaks with retention time 2.63, 3.41, 23.83, 24.50, and 44.67 were found universal type. Comparative hierarchical clustering analysis based on foresaid fingerprints indicates that both techniques have equal potential to discriminate accessions according to percentage gymnemic acid in their leaf tissue. Second approach was noted more efficiently for separation of accessions according to their agro-climatic/collection site Conclusion: Highly polymorphic ISSRs could be utilized as molecular probes for further selection of high gymnemic acid yielding accessions. Observed accession specific bands may be used as a descriptor for plant accessions protection and converted into sequence tagged sites markers. Identified five universal type peaks could be helpful in identification of G. sylvestre-based various herbal preparations. SUMMARY Nine accession specific unique bandsFive marker peaks for G. sylvestre.Suitability of genetic and chemical fingerprinting Abbreviations used: HPLC: High Performance Liquid Chromatography, ISSR: Inter Simple Sequence Repeats, CTAB: Cetyl

  17. A Genetic Algorithm-based Antenna Selection Approach for Large-but-Finite MIMO Networks

    KAUST Repository

    Makki, Behrooz

    2016-12-29

    We study the performance of antenna selectionbased multiple-input-multiple-output (MIMO) networks with large but finite number of transmit antennas and receivers. Considering the continuous and bursty communication scenarios with different users’ data request probabilities, we develop an efficient antenna selection scheme using genetic algorithms (GA). As demonstrated, the proposed algorithm is generic in the sense that it can be used in the cases with different objective functions, precoding methods, levels of available channel state information and channel models. Our results show that the proposed GAbased algorithm reaches (almost) the same throughput as the exhaustive search-based optimal approach, with substantially less implementation complexity.

  18. An Approach to Assembly Sequence Plannning Based on Hierarchical Strategy and Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    Niu Xinwen; Ding Han; Xiong Youlun

    2001-01-01

    Using group and subassembly cluster methods, the hierarchical structure of a product is.generated automatically, which largely reduces the complexity of planning. Based on genetic algofithn the optimal of assembly sequence of each stracture level can be obtained by sequence-bysequence search. As a result, a better assembly sequence of the product can be generated by combining the assembly sequences of all hierarchical structures, which provides more parallelism and flexibility for assembly operations. An industrial example is solved by this new approach.

  19. Genetic algorithm-fuzzy based dynamic motion planning approach for a mobile robot

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Presents the mobile robots dynamic motion planning problem with a task to find an obstacle-free route that requires minimum travel time from the start point to the destination point in a changing environment, due to the obstacle's moving. An Genetic Algorithm fuzzy(GA-Fuzzy)based optimal approach proposed to find any obstacle-free path and the GA used to select the optimal one, points ont that using this learned knowledge off line, a mobile robot can navigate to its goal point when it faces new scenario on-line. Concludes with the opti mal rule base given and the simulation results showing its effectiveness.

  20. Genetic and epigenetic alterations of microRNAs and implications for human cancers and other diseases.

    Science.gov (United States)

    Tuna, Musaffe; Machado, Andreia S; Calin, George A

    2016-03-01

    MicroRNAs (miRNAs) are a well-studied group of noncoding RNAs that control gene expression by interacting mainly with messenger RNA. It is known that miRNAs and their biogenesis regulatory machineries have crucial roles in multiple cell processes; thus, alterations in these genes often lead to disease, such as cancer. Disruption of these genes can occur through epigenetic and genetic alterations, resulting in aberrant expression of miRNAs and subsequently of their target genes. This review focuses on the disruption of miRNAs and their key regulatory machineries by genetic alterations, with emphasis on mutations and epigenetic changes in cancer and other diseases.

  1. A human phenome-interactome network of protein complexes implicated in genetic disorders

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Karlberg, Erik, Olof, Linnart; Størling, Zenia, Marian

    2007-01-01

    the known disease-causing protein as the top candidate, and in 870 intervals with no identified disease-causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type...

  2. General patterns of managerial approaches to work motivation: Implications for rehabilitation professionals involved in occupational rehabilitation.

    Science.gov (United States)

    Murphy, G C; Foreman, P

    1993-03-01

    Calls for rehabilitation counselors to learn more about the world of work have been recently repeated. The validity of these calls is suggested by a group of studies which indicate that the rehabilitation counseling literature has an established emphasis on matters of counseling and adjustment rather than on matters related to behavior in organizations. A survey of rehabilitation counsellors' beliefs about key topics in organizational behavior indicates that their beliefs are often discrepant with those of practicing managers and supervisors. A summary of dominant models of work motivation adopted by managerial workers is presented and some implications for occupational rehabilitation practice identified. Finally, some contemporary literature relevant to managerial approaches to employee motivation are identified and it is suggested that familiarity with this literature could assist rehabilitation practitioners move from a more narrow occupational rehabilitation role to a broader involvement in organizational life via the expansion of the disability management approach in work organizations.

  3. Interconnection between 802.15.4 Devices and IPv6: Implications and Existing Approaches

    CERN Document Server

    Hossen, Md Sakhawat; Khan, Razib Hayat; Azfar, Abdullah

    2010-01-01

    The increasing role of home automation in routine life and the rising demand for sensor networks enhanced wireless personal area networks (WPANs) development, pervasiveness of wireless & wired network, and research. Soon arose the need of implementing the Internet Protocol in these devices in order to WPAN standards, raising the way for questions on how to provide seamless communication between wired and wireless technologies. After a quick overview of the Low-rate WPAN standard (IEEE 802.15.4) and the Zigbee stack, this paper focuses on understanding the implications when interconnecting low powered IEEE 802.15.4 devices and a wired IPv6 domain. Subsequently the focus will be on existing approaches to connect LoWPAN devices to the internet and on how these approaches try to solve these challenges, concluding with a critical analysis of interoperability problems.

  4. Interconnection between 802.15.4 Devices and IPv6: Implications and Existing Approaches

    Directory of Open Access Journals (Sweden)

    Razib Hayat Khan

    2010-01-01

    Full Text Available The increasing role of home automation in routine life and the rising demand for sensor networks enhanced wireless personal area networks development, pervasiveness of wireless and wired network, and research. Soon arose the need of implementing the Internet Protocol in these devices in order to WPAN standards, raising the way for questions on how to provide seamless communication between wired and wireless technologies. After a quick overview of the Low-rate WPAN standard (IEEE 802.15.4 and the Zigbee stack, this paper focuses on understanding the implications when interconnecting low powered IEEE 802.15.4 devices and a wired IPv6 domain. Subsequently the focus will be on existing approaches to connect LoWPAN devices to the internet and on how these approaches try to solve these challenges, concluding with a critical analysis of interoperability problems.

  5. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  6. 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.

  7. New Approaches for Crop Genetic Adaptation to the Abiotic Stresses Predicted with Climate Change

    Directory of Open Access Journals (Sweden)

    Robert Redden

    2013-05-01

    Full Text Available Extreme climatic variation is predicted with climate change this century. In many cropping regions, the crop environment will tend to be warmer with more irregular rainfall and spikes in stress levels will be more severe. The challenge is not only to raise agricultural production for an expanding population, but to achieve this under more adverse environmental conditions. It is now possible to systematically explore the genetic variation in historic local landraces by using GPS locators and world climate maps to describe the natural selection for local adaptation, and to identify candidate germplasm for tolerances to extreme stresses. The physiological and biochemical components of these expressions can be genomically investigated with candidate gene approaches and next generation sequencing. Wild relatives of crops have largely untapped genetic variation for abiotic and biotic stress tolerances, and could greatly expand the available domesticated gene pools to assist crops to survive in the predicted extremes of climate change, a survivalomics strategy. Genomic strategies can assist in the introgression of these valuable traits into the domesticated crop gene pools, where they can be better evaluated for crop improvement. The challenge is to increase agricultural productivity despite climate change. This calls for the integration of many disciplines from eco-geographical analyses of genetic resources to new advances in genomics, agronomy and farm management, underpinned by an understanding of how crop adaptation to climate is affected by genotype × environment interaction.

  8. Developing approaches for linear mixed modeling in landscape genetics through landscape-directed dispersal simulations

    Science.gov (United States)

    Row, Jeffrey R.; Knick, Steven T.; Oyler-McCance, Sara J.; Lougheed, Stephen C.; Fedy, Bradley C.

    2017-01-01

    Dispersal can impact population dynamics and geographic variation, and thus, genetic approaches that can establish which landscape factors influence population connectivity have ecological and evolutionary importance. Mixed models that account for the error structure of pairwise datasets are increasingly used to compare models relating genetic differentiation to pairwise measures of landscape resistance. A model selection framework based on information criteria metrics or explained variance may help disentangle the ecological and landscape factors influencing genetic structure, yet there are currently no consensus for the best protocols. Here, we develop landscape-directed simulations and test a series of replicates that emulate independent empirical datasets of two species with different life history characteristics (greater sage-grouse; eastern foxsnake). We determined that in our simulated scenarios, AIC and BIC were the best model selection indices and that marginal R2 values were biased toward more complex models. The model coefficients for landscape variables generally reflected the underlying dispersal model with confidence intervals that did not overlap with zero across the entire model set. When we controlled for geographic distance, variables not in the underlying dispersal models (i.e., nontrue) typically overlapped zero. Our study helps establish methods for using linear mixed models to identify the features underlying patterns of dispersal across a variety of landscapes.

  9. Developing approaches for linear mixed modeling in landscape genetics through landscape-directed dispersal simulations.

    Science.gov (United States)

    Row, Jeffrey R; Knick, Steven T; Oyler-McCance, Sara J; Lougheed, Stephen C; Fedy, Bradley C

    2017-06-01

    Dispersal can impact population dynamics and geographic variation, and thus, genetic approaches that can establish which landscape factors influence population connectivity have ecological and evolutionary importance. Mixed models that account for the error structure of pairwise datasets are increasingly used to compare models relating genetic differentiation to pairwise measures of landscape resistance. A model selection framework based on information criteria metrics or explained variance may help disentangle the ecological and landscape factors influencing genetic structure, yet there are currently no consensus for the best protocols. Here, we develop landscape-directed simulations and test a series of replicates that emulate independent empirical datasets of two species with different life history characteristics (greater sage-grouse; eastern foxsnake). We determined that in our simulated scenarios, AIC and BIC were the best model selection indices and that marginal R(2) values were biased toward more complex models. The model coefficients for landscape variables generally reflected the underlying dispersal model with confidence intervals that did not overlap with zero across the entire model set. When we controlled for geographic distance, variables not in the underlying dispersal models (i.e., nontrue) typically overlapped zero. Our study helps establish methods for using linear mixed models to identify the features underlying patterns of dispersal across a variety of landscapes.

  10. Thermal genetic adaptation in the water flea Daphnia and its impact: an evolving metacommunity approach.

    Science.gov (United States)

    De Meester, Luc; Van Doorslaer, Wendy; Geerts, Aurora; Orsini, Luisa; Stoks, Robby

    2011-11-01

    Genetic adaptation to temperature change can impact responses of populations and communities to global warming. Here we integrate previously published results on experimental evolution trials with follow-up experiments involving the water flea Daphnia as a model system. Our research shows (1) the capacity of natural populations of this species to genetically adapt to changes in temperature in a time span of months to years, (2) the context-dependence of these genetic changes, emphasizing the role of ecology and community composition on evolutionary responses to climatic change, and (3) the impact of micro-evolutionary changes on immigration success of preadapted genotypes. Our study involves (1) experimental evolution trials in the absence and presence of the community of competitors, predators, and parasites, (2) life-table and competition experiments to assess the fitness consequences of micro-evolution, and (3) competition experiments with putative immigrant genotypes. We use these observations as building blocks of an evolving metacommunity to understand biological responses to climatic change. This approach integrates both local and regional responses at both the population and community levels. Finally, we provide an outline of current gaps in knowledge and suggest fruitful avenues for future research. © The Author 2011. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.

  11. The theological and legal approach of prenatal and preimplantation genetic control

    Directory of Open Access Journals (Sweden)

    George Katsimigas

    2012-04-01

    Full Text Available Aim: The investigation of the theological and legal questions derived from the application of prenatal and preimplantation genetic control on human embryos. Moreover, the review of the European and Greek legislation with regard to the prenatal and preimplantation control. Material and Method: A literature review based on both review and research literature, conducted during the period of 1984-2009, derived from MEDLINE, SCOPUS and ΙΑΤΡΟΤΕΚ databases using as key words Prenatal diagnosis , Bioethics, Orthodox ethics, preimplantation genetic diagnosis, Legislation. Results: The orthodox theology adopts a negative view for the abortion of fetus, which it is considered murder in any stage of growth. The legal approach brought two basic questions a the securing of consent from the examined individual and b the constitutional protection of fetus' life. Conclusions: The orthodox theology, through their teaching places the moral criteria for facing the moral questions derived from the application of prenatal and preimplantation genetic control on human embryos. Also, the Greek citizens need to be informed for all the diagnostic examinations on embryos that should be provided by all public health organizations.

  12. Genetic engineering represents a safe approach for innovations improving nutritional contents of major food crops

    Directory of Open Access Journals (Sweden)

    Werner Arber

    2017-05-01

    Full Text Available About 70 years ago early microbial genetic research revealed that inherited phenotypic traits become determined by DNA filaments composed of 4 different nucleotides that are linearly arranged. In the meantime we know that genes, the determinants of specific life functions, are genomic segments of an average size of about 1000 nucleotides, i.e. a very small part of a genome. Fundamental insights into the structures and functions of selected genes can be reached by sorting out the relevant short DNA segment, splicing this fragment into a natural gene vector such as a viral genome or a fertility plasmid. This allows the researchers to transfer the genetic hybrid into an appropriate host cell in order to produce many copies that can then serve for functional and structural analysis. This research approach became efficient in the 1970s. On the request of involved researchers, safety guidelines became proposed 1975 at the Asilomar Conference on Recombinant DNA (Berg, Baltimore, Brenner, Roblin, & Singer, 1975, then generally introduced and still largely followed nowadays. Carefully carried out genetic engineering by horizontally transferring a selected and functionally well known DNA segment into the genome of another organism has in many published biosafety investigations never shown any unexpected harmful effect. We will present below selected examples of research contributions enabling innovations for the benefit of human life conditions.

  13. Genetic diversity of variants involved in drug response and metabolism in Sri Lankan populations: implications for clinical implementation of pharmacogenomics

    Science.gov (United States)

    Chan, Sze Ling; Samaranayake, Nilakshi; Ross, Colin J.D.; Toh, Meng Tiak; Carleton, Bruce; Hayden, Michael R.; Teo, Yik Ying; Dissanayake, Vajira H.W.

    2016-01-01

    Background Interpopulation differences in drug responses are well documented, and in some cases they correspond to differences in the frequency of associated genetic markers. Understanding the diversity of genetic markers associated with drug response across different global populations is essential to infer population rates of drug response or risk for adverse drug reactions, and to guide implementation of pharmacogenomic testing. Sri Lanka is a culturally and linguistically diverse nation, but little is known about the population genetics of the major Sri Lankan ethnic groups. The objective of this study was to investigate the diversity of pharmacogenomic variants in the major Sri Lankan ethnic groups. Methods We examined the allelic diversity of more than 7000 variants in genes involved in drug biotransformation and response in the three major ethnic populations of Sri Lanka (Sinhalese, Sri Lankan Tamils, and Moors), and compared them with other South Asian, South East Asian, and European populations using Wright’s Fixation Index, principal component analysis, and STRUCTURE analysis. Results We observed overall high levels of similarity within the Sri Lankan populations (median FST=0.0034), and between Sri Lankan and other South Asian populations (median FST=0.0064). Notably, we observed substantial differentiation between Sri Lankan and European populations for important pharmacogenomic variants related to warfarin (VKORC1 rs9923231) and clopidogrel (CYP2C19 rs4986893) response. Conclusion These data expand our understanding of the population structure of Sri Lanka, provide a resource for pharmacogenomic research, and have implications for the clinical use of genetic testing of pharmacogenomic variants in these populations. PMID:26444257

  14. Giftedness and Genetics: The Emergenic-Epigenetic Model and Its Implications

    Science.gov (United States)

    Simonton, Dean Keith

    2005-01-01

    The genetic endowment underlying giftedness may operate in a far more complex manner than often expressed in most theoretical accounts of the phenomenon. First, an endowment may be emergenic. That is, a gift may consist of multiple traits (multidimensional) that are inherited in a multiplicative (configurational), rather than an additive (simple)…

  15. General Intelligence (g): Overview of a Complex Construct and Its Implications for Genetics Research.

    Science.gov (United States)

    Plucker, Jonathan A; Shelton, Amy L

    2015-01-01

    Current technology has dramatically increased the prevalence of studies to establish the genetic correlates of a wide variety of human characteristics, including not only the physical attributes that determine what we look like and the risk of physiological disease but also the psychological and cognitive characteristics that often define who we are as individuals. Perhaps one of the most deeply personal and often controversial characteristics is the concept of general intelligence, known in the psychological literature as "g." As with the genetic study of any complex trait, the first step in studying the genetics of g is to carefully define the characteristic of interest. For g, this entails establishing what intelligence means and providing a clear operational definition for how it will be measured. In this paper, we provide a brief historical and theoretical overview of the construct of general intelligence, describe its relationship to the contemporary measurement of intelligence, and discuss these concepts in light of the challenges associated with defining g as a characteristic in the study of genetics.

  16. Range-wide genetic connectivity of the Hawaiian monk seal and implications for translocation.

    Science.gov (United States)

    Schultz, Jennifer K; Baker, Jason D; Toonen, Robert J; Harting, Albert L; Bowen, Brian W

    2011-02-01

    The Hawaiian monk seal (Monachus schauinslandi) is one of the most critically endangered marine mammals. Less than 1200 individuals remain, and the species is declining at a rate of approximately 4% per year as a result of juvenile starvation, shark predation, and entanglement in marine debris. Some of these problems may be alleviated by translocation; however, if island breeding aggregates are effectively isolated subpopulations, moving individuals may disrupt local adaptations. In these circumstances, managers must balance the pragmatic need of increasing survival with theoretical concerns about genetic viability. To assess range-wide population structure of the Hawaiian monk seal, we examined an unprecedented, near-complete genetic inventory of the species (n =1897 seals, sampled over 14 years) at 18 microsatellite loci. Genetic variation was not spatially partitioned ((w) =-0.03, p = 1.0), and a Bayesian clustering method provided evidence of one panmictic population (K =1). Pairwise F(ST) comparisons (among 7 island aggregates over 14 annual cohorts) did not reveal temporally stable, spatial reproductive isolation. Our results coupled with long-term tag-resight data confirm seal movement and gene flow throughout the Hawaiian Archipelago. Thus, human-mediated translocation of seals among locations is not likely to result in genetic incompatibilities.

  17. Constraints on Allele size at microsatellite loci : Implications for genetic differentiation

    NARCIS (Netherlands)

    Nauta, M.J.; Weissing, F.J.

    1996-01-01

    Microsatellites are promising genetic markers for studying the demographic structure and phylogenetic history of populations. We present theoretical arguments indicating that the usefulness of microsatellite data for these purposes may be limited to a short time perspective and to relatively small p

  18. Sex change and effective population size: implications for population genetic studies in marine fish.

    Science.gov (United States)

    Coscia, I; Chopelet, J; Waples, R S; Mann, B Q; Mariani, S

    2016-10-01

    Large variance in reproductive success is the primary factor that reduces effective population size (Ne) in natural populations. In sequentially hermaphroditic (sex-changing) fish, the sex ratio is typically skewed and biased towards the 'first' sex, while reproductive success increases considerably after sex change. Therefore, sex-changing fish populations are theoretically expected to have lower Ne than gonochorists (separate sexes), assuming all other parameters are essentially equal. In this study, we estimate Ne from genetic data collected from two ecologically similar species living along the eastern coast of South Africa: one gonochoristic, the 'santer' sea bream Cheimerius nufar, and one protogynous (female-first) sex changer, the 'slinger' sea bream Chrysoblephus puniceus. For both species, no evidence of genetic structuring, nor significant variation in genetic diversity, was found in the study area. Estimates of contemporary Ne were significantly lower in the protogynous species, but the same pattern was not apparent over historical timescales. Overall, our results show that sequential hermaphroditism may affect Ne differently over varying time frames, and that demographic signatures inferred from genetic markers with different inheritance modes also need to be interpreted cautiously, in relation to sex-changing life histories.

  19. Genetic control of chromosome behaviour: Implications in evolution, crop improvement, and human biology

    Science.gov (United States)

    Chromosomes and chromosome pairing are pivotal to all biological sciences. The study of chromosomes helps unravel several aspects of an organism. Although the foundation of genetics occurred with the formulation of the laws of heredity in 1865, long before the discovery of chromosomes, their subsequ...

  20. Population genetics implications for the conservation of the Philippine Crocodile Crocodylus mindorensis Schmidt, 1935 (Crocodylia: Crocodylidae

    Directory of Open Access Journals (Sweden)

    M.R.P. Hinlo

    2014-03-01

    Full Text Available Limited information is available on the Philippine Crocodile, Crocodylus mindorensis, concerning levels of genetic diversity either relative to other crocodilian species or among populations of the species itself. With only two known extant populations of C. mindorensis remaining, potentially low levels of genetic diversity are a conservation concern. Here, we evaluated 619 putative Philippine Crocodiles using a suite of 11 microsatellite markers, and compared them to four other crocodilian species sample sets. The two remaining populations from the island of Luzon and the island of Mindanao, representing the extremes of the former species’ distribution, appear to be differentiated as a result of genetic drift rather than selection. Both extant populations demonstrate lower genetic diversity and effective population sizes relative to other studied crocodilian species. The 57 C. mindorensis and C. porosus, Saltwater Crocodile, hybrids identified earlier from the Palawan Wildlife Rescue and Conservation Center were revalidated with a suite of 20 microsatellite loci; however, the timing of the event and the prevalence of hybridization in the species had yet to be fully determined. We defined the hybrids as one first cross from a C. porosus female and a C. mindorensis male and 56 C. mindorensis backcross individuals. This hybridization event appears to be confined to the PWRCC collection.

  1. A genetic algorithm-based approach to flexible flow-line scheduling with variable lot sizes.

    Science.gov (United States)

    Lee, I; Sikora, R; Shaw, M J

    1997-01-01

    Genetic algorithms (GAs) have been used widely for such combinatorial optimization problems as the traveling salesman problem (TSP), the quadratic assignment problem (QAP), and job shop scheduling. In all of these problems there is usually a well defined representation which GA's use to solve the problem. We present a novel approach for solving two related problems-lot sizing and sequencing-concurrently using GAs. The essence of our approach lies in the concept of using a unified representation for the information about both the lot sizes and the sequence and enabling GAs to evolve the chromosome by replacing primitive genes with good building blocks. In addition, a simulated annealing procedure is incorporated to further improve the performance. We evaluate the performance of applying the above approach to flexible flow line scheduling with variable lot sizes for an actual manufacturing facility, comparing it to such alternative approaches as pair wise exchange improvement, tabu search, and simulated annealing procedures. The results show the efficacy of this approach for flexible flow line scheduling.

  2. Tracing Technological Development Trajectories: A Genetic Knowledge Persistence-Based Main Path Approach.

    Science.gov (United States)

    Park, Hyunseok; Magee, Christopher L

    2017-01-01

    The aim of this paper is to propose a new method to identify main paths in a technological domain using patent citations. Previous approaches for using main path analysis have greatly improved our understanding of actual technological trajectories but nonetheless have some limitations. They have high potential to miss some dominant patents from the identified main paths; nonetheless, the high network complexity of their main paths makes qualitative tracing of trajectories problematic. The proposed method searches backward and forward paths from the high-persistence patents which are identified based on a standard genetic knowledge persistence algorithm. We tested the new method by applying it to the desalination and the solar photovoltaic domains and compared the results to output from the same domains using a prior method. The empirical results show that the proposed method can dramatically reduce network complexity without missing any dominantly important patents. The main paths identified by our approach for two test cases are almost 10x less complex than the main paths identified by the existing approach. The proposed approach identifies all dominantly important patents on the main paths, but the main paths identified by the existing approach miss about 20% of dominantly important patents.

  3. Genetic Variability and Population Structure of Salvia lachnostachys: Implications for Breeding and Conservation Programs

    Directory of Open Access Journals (Sweden)

    Marianna Erbano

    2015-04-01

    Full Text Available The genetic diversity and population structure of Salvia lachnostachys Benth were assessed. Inter Simple Sequence Repeat (ISSR molecular markers were used to investigate the restricted distribution of S. lachnostachys in Parana State, Brazil. Leaves of 73 individuals representing three populations were collected. DNA was extracted and submitted to PCR-ISSR amplification with nine tested primers. Genetic diversity parameters were evaluated. Our analysis indicated 95.6% polymorphic loci (stress value 0.02 with a 0.79 average Simpson’s index. The Nei-Li distance dendrogram and principal component analysis largely recovered the geographical origin of each sample. Four major clusters were recognized representing each collected population. Nei’s gene diversity and Shannon’s information index were 0.25 and 0.40 respectively. As is typical for outcrossing herbs, the majority of genetic variation occurred at the population level (81.76%. A high gene flow (Nm = 2.48 was observed with a correspondingly low fixation index. These values were generally similar to previous studies on congeneric species. The results of principal coordinate analysis (PCA and of arithmetic average (UPGMA were consistent and all three populations appear distinct as in STRUCTURE analysis. In addition, this analysis indicated a majority intrapopulation genetic variation. Despite the human pressure on natural populations our study found high levels of genetic diversity for S. lachnostachys. This was the first molecular assessment for this endemic species with medicinal proprieties and the results can guide for subsequent bioprospection, breeding programs or conservation actions.

  4. Synthetic biology approaches in cancer immunotherapy, genetic network engineering, and genome editing.

    Science.gov (United States)

    Chakravarti, Deboki; Cho, Jang Hwan; Weinberg, Benjamin H; Wong, Nicole M; Wong, Wilson W

    2016-04-18

    Investigations into cells and their contents have provided evolving insight into the emergence of complex biological behaviors. Capitalizing on this knowledge, synthetic biology seeks to manipulate the cellular machinery towards novel purposes, extending discoveries from basic science to new applications. While these developments have demonstrated the potential of building with biological parts, the complexity of cells can pose numerous challenges. In this review, we will highlight the broad and vital role that the synthetic biology approach has played in applying fundamental biological discoveries in receptors, genetic circuits, and genome-editing systems towards translation in the fields of immunotherapy, biosensors, disease models and gene therapy. These examples are evidence of the strength of synthetic approaches, while also illustrating considerations that must be addressed when developing systems around living cells.

  5. An Approach to Derive Parametric L-System Using Genetic Algorithm

    Science.gov (United States)

    Farooq, Humera; Zakaria, M. Nordin; Hassan, Mohd. Fadzil; Sulaiman, Suziah

    In computer graphics, L-System is widely used to model artificial plants structures and fractals. The Genetic Algorithm (GA) is the most popular form of Evolutionary Algorithms. This paper examines a method for automatic plant modeling which is based on an integration of GA and Parametric L-System using appropriate fitness function. The approach is specifically based on the implementation of two layered GA to derive the rewriting rules of Parametric L-System. The higher level of GA deals with the evolution of symbols and lower level deals with the evolution of numerical parameters. Initial results derived from the approach are very promising, which shows that complicated branching structures can be easily derived by the multilayered architecture of GA.

  6. Challenges and implications of global modeling approaches that are alternatives to using constant plant functional types

    Science.gov (United States)

    Bodegom, P. V.

    2015-12-01

    In recent years a number of approaches have been developed to provide alternatives to the use of plant functional types (PFTs) with constant vegetation characteristics for simulating vegetation responses to climate changes. In this presentation, an overview of those approaches and their challenges is given. Some new approaches aim at removing PFTs altogether by determining the combination of vegetation characteristics that would fit local conditions best. Others describe the variation in traits within PFTs as a function of environmental drivers, based on community assembly principles. In the first approach, after an equilibrium has been established, vegetation composition and its functional attributes can change by allowing the emergence of a new type that is more fit. In the latter case, changes in vegetation attributes in space and time as assumed to be the result intraspecific variation, genetic adaptation and species turnover, without quantifying their respective importance. Hence, it is assumed that -by whatever mechanism- the community as a whole responds without major time lags to changes in environmental drivers. Recently, we showed that intraspecific variation is highly species- and trait-specific and that none of the current hypotheses on drivers of this variation seems to hold. Also genetic adaptation varies considerably among species and it is uncertain whether it will be fast enough to cope with climate change. Species turnover within a community is especially fast in herbaceous communities, but much slower in forest communities. Hence, it seems that assumptions made may not hold for forested ecosystems, but solutions to deal with this do not yet exist. Even despite the fact that responsiveness of vegetation to environmental change may be overestimated, we showed that -upon implementation of trait-environment relationships- major changes in global vegetation distribution are projected, to similar extents as to those without such responsiveness.

  7. A Parallel Approach To Optimum Actuator Selection With a Genetic Algorithm

    Science.gov (United States)

    Rogers, James L.

    2000-01-01

    Recent discoveries in smart technologies have created a variety of aerodynamic actuators which have great potential to enable entirely new approaches to aerospace vehicle flight control. For a revolutionary concept such as a seamless aircraft with no moving control surfaces, there is a large set of candidate locations for placing actuators, resulting in a substantially larger number of combinations to examine in order to find an optimum placement satisfying the mission requirements. The placement of actuators on a wing determines the control effectiveness of the airplane. One approach to placement Maximizes the moments about the pitch, roll, and yaw axes, while minimizing the coupling. Genetic algorithms have been instrumental in achieving good solutions to discrete optimization problems, such as the actuator placement problem. As a proof of concept, a genetic has been developed to find the minimum number of actuators required to provide uncoupled pitch, roll, and yaw control for a simplified, untapered, unswept wing model. To find the optimum placement by searching all possible combinations would require 1,100 hours. Formulating the problem and as a multi-objective problem and modifying it to take advantage of the parallel processing capabilities of a multi-processor computer, reduces the optimization time to 22 hours.

  8. Intrusion detection: a novel approach that combines boosting genetic fuzzy classifier and data mining techniques

    Science.gov (United States)

    Ozyer, Tansel; Alhajj, Reda; Barker, Ken

    2005-03-01

    This paper proposes an intelligent intrusion detection system (IDS) which is an integrated approach that employs fuzziness and two of the well-known data mining techniques: namely classification and association rule mining. By using these two techniques, we adopted the idea of using an iterative rule learning that extracts out rules from the data set. Our final intention is to predict different behaviors in networked computers. To achieve this, we propose to use a fuzzy rule based genetic classifier. Our approach has two main stages. First, fuzzy association rule mining is applied and a large number of candidate rules are generated for each class. Then the rules pass through pre-screening mechanism in order to reduce the fuzzy rule search space. Candidate rules obtained after pre-screening are used in genetic fuzzy classifier to generate rules for the specified classes. Classes are defined as Normal, PRB-probe, DOS-denial of service, U2R-user to root and R2L- remote to local. Second, an iterative rule learning mechanism is employed for each class to find its fuzzy rules required to classify data each time a fuzzy rule is extracted and included in the system. A Boosting mechanism evaluates the weight of each data item in order to help the rule extraction mechanism focus more on data having relatively higher weight. Finally, extracted fuzzy rules having the corresponding weight values are aggregated on class basis to find the vote of each class label for each data item.

  9. Process planning optimization on turning machine tool using a hybrid genetic algorithm with local search approach

    Directory of Open Access Journals (Sweden)

    Yuliang Su

    2015-04-01

    Full Text Available A turning machine tool is a kind of new type of machine tool that is equipped with more than one spindle and turret. The distinctive simultaneous and parallel processing abilities of turning machine tool increase the complexity of process planning. The operations would not only be sequenced and satisfy precedence constraints, but also should be scheduled with multiple objectives such as minimizing machining cost, maximizing utilization of turning machine tool, and so on. To solve this problem, a hybrid genetic algorithm was proposed to generate optimal process plans based on a mixed 0-1 integer programming model. An operation precedence graph is used to represent precedence constraints and help generate a feasible initial population of hybrid genetic algorithm. Encoding strategy based on data structure was developed to represent process plans digitally in order to form the solution space. In addition, a local search approach for optimizing the assignments of available turrets would be added to incorporate scheduling with process planning. A real-world case is used to prove that the proposed approach could avoid infeasible solutions and effectively generate a global optimal process plan.

  10. A Novel Approach for Discovery Quantitative Fuzzy Multi-Level Association Rules Mining Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Saad M. Darwish

    2016-10-01

    Full Text Available Quantitative multilevel association rules mining is a central field to realize motivating associations among data components with multiple levels abstractions. The problem of expanding procedures to handle quantitative data has been attracting the attention of many researchers. The algorithms regularly discretize the attribute fields into sharp intervals, and then implement uncomplicated algorithms established for Boolean attributes. Fuzzy association rules mining approaches are intended to defeat such shortcomings based on the fuzzy set theory. Furthermore, most of the current algorithms in the direction of this topic are based on very tiring search methods to govern the ideal support and confidence thresholds that agonize from risky computational cost in searching association rules. To accelerate quantitative multilevel association rules searching and escape the extreme computation, in this paper, we propose a new genetic-based method with significant innovation to determine threshold values for frequent item sets. In this approach, a sophisticated coding method is settled, and the qualified confidence is employed as the fitness function. With the genetic algorithm, a comprehensive search can be achieved and system automation is applied, because our model does not need the user-specified threshold of minimum support. Experiment results indicate that the recommended algorithm can powerfully generate non-redundant fuzzy multilevel association rules.

  11. The Displacement of Base Station in Mobile Communication with Genetic Approach

    Directory of Open Access Journals (Sweden)

    Kim Nam

    2008-01-01

    Full Text Available Abstract This paper addresses the displacement of a base station with optimization approach. A genetic algorithm is used as optimization approach. A new representation that describes base station placement, transmitted power with real numbers, and new genetic operators is proposed and introduced. In addition, this new representation can describe the number of base stations. For the positioning of the base station, both coverage and economy efficiency factors were considered. Using the weighted objective function, it is possible to specify the location of the base station, the cell coverage, and its economy efficiency. The economy efficiency indicates a reduction in the number of base stations for cost effectiveness. To test the proposed algorithm, the proposed algorithm was applied to homogeneous traffic environment. Following this, the proposed algorithm was applied to an inhomogeneous traffic density environment in order to test it in actual conditions. The simulation results show that the algorithm enables the finding of a near optimal solution of base station placement, and it determines the efficient number of base stations. Moreover, it can offer a proper solution by adjusting the weighted objective function.

  12. The Displacement of Base Station in Mobile Communication with Genetic Approach

    Directory of Open Access Journals (Sweden)

    Nam Kim

    2008-05-01

    Full Text Available This paper addresses the displacement of a base station with optimization approach. A genetic algorithm is used as optimization approach. A new representation that describes base station placement, transmitted power with real numbers, and new genetic operators is proposed and introduced. In addition, this new representation can describe the number of base stations. For the positioning of the base station, both coverage and economy efficiency factors were considered. Using the weighted objective function, it is possible to specify the location of the base station, the cell coverage, and its economy efficiency. The economy efficiency indicates a reduction in the number of base stations for cost effectiveness. To test the proposed algorithm, the proposed algorithm was applied to homogeneous traffic environment. Following this, the proposed algorithm was applied to an inhomogeneous traffic density environment in order to test it in actual conditions. The simulation results show that the algorithm enables the finding of a near optimal solution of base station placement, and it determines the efficient number of base stations. Moreover, it can offer a proper solution by adjusting the weighted objective function.

  13. Adolescent age moderates genetic and environmental influences on parent-adolescent positivity and negativity: Implications for genotype-environment correlation.

    Science.gov (United States)

    Marceau, Kristine; Knopik, Valerie S; Neiderhiser, Jenae M; Lichtenstein, Paul; Spotts, Erica L; Ganiban, Jody M; Reiss, David

    2016-02-01

    We examined how genotype-environment correlation processes differ as a function of adolescent age. We tested whether adolescent age moderates genetic and environmental influences on positivity and negativity in mother-adolescent and father-adolescent relationships using parallel samples of twin parents from the Twin and Offspring Study in Sweden and twin/sibling adolescents from the Nonshared Environment in Adolescent Development Study. We inferred differences in the role of passive and nonpassive genotype-environment correlation based on biometric moderation findings. The findings indicated that nonpassive gene-environment correlation played a stronger role for positivity in mother- and father-adolescent relationships in families with older adolescents than in families with younger adolescents, and that passive gene-environment correlation played a stronger role for positivity in the mother-adolescent relationship in families with younger adolescents than in families with older adolescents. Implications of these findings for the timing and targeting of interventions on family relationships are discussed.

  14. Implications of conflicting definitions of probability to health risk communication: a case study of familial cancer and genetic counselling.

    Science.gov (United States)

    O'Doherty, Kieran C

    2007-02-01

    The question of what probability actually is has long been debated in philosophy and statistics. Although the concept of probability is fundamental to many applications in the health sciences, these debates are generally not well known to health professionals. This paper begins with an outline of some of the different interpretations of probability. Examples are provided of how each interpretation manifests in clinical practice. The discipline of genetic counselling (familial cancer) is used to ground the discussion. In the second part of the paper, some of the implications that different interpretations of probability may have in practice are examined. The main purpose of the paper is to draw attention to the fact that there is much contention as to the nature of the concept of probability. In practice, this creates the potential for ambiguity and confusion. This paper constitutes a call for deeper engagement with the ways in which probability and risk are understood in health research and practice.

  15. Approaches to a cortical vision prosthesis: implications of electrode size and placement

    Science.gov (United States)

    Christie, Breanne P.; Ashmont, Kari R.; House, Paul A.; Greger, Bradley

    2016-04-01

    Objective. In order to move forward with the development of a cortical vision prosthesis, the critical issues in the field must be identified. Approach. To begin this process, we performed a brief review of several different cortical and retinal stimulation techniques that can be used to restore vision. Main results. Intracortical microelectrodes and epicortical macroelectrodes have been evaluated as the basis of a vision prosthesis. We concluded that an important knowledge gap necessitates an experimental in vivo performance evaluation of microelectrodes placed on the surface of the visual cortex. A comparison of the level of vision restored by intracortical versus epicortical microstimulation is necessary. Because foveal representation in the primary visual cortex involves more cortical columns per degree of visual field than does peripheral vision, restoration of foveal vision may require a large number of closely spaced microelectrodes. Based on previous studies of epicortical macrostimulation, it is possible that stimulation via surface microelectrodes could produce a lower spatial resolution, making them better suited for restoring peripheral vision. Significance. The validation of epicortical microstimulation in addition to the comparison of epicortical and intracortical approaches for vision restoration will fill an important knowledge gap and may have important implications for surgical strategies and device longevity. It is possible that the best approach to vision restoration will utilize both epicortical and intracortical microstimulation approaches, applying them appropriately to different visual representations in the primary visual cortex.

  16. Double trouble: medical implications of genetic duplication and amplification in bacteria.

    Science.gov (United States)

    Craven, Sarah H; Neidle, Ellen L

    2007-06-01

    Gene amplification allows organisms to adapt to changing environmental conditions. This type of increased gene dosage confers selectable benefits, typically by augmenting protein production. Gene amplification is a reversible process that does not require permanent genetic change. Although transient, altered gene dosage has significant medical impact. Recent examples of amplification in bacteria, described here, affect human disease by modifying antibiotic resistance, the virulence of pathogens, vaccine efficacy and antibiotic biosynthesis. Amplification is usually a two-step process whereby genetic duplication (step one) promotes further increases in copy number (step two). Both steps have important evolutionary significance for the emergence of innovative gene functions. Recent genome sequence analyses illustrate how genome plasticity can affect the evolution and immunogenic properties of bacterial pathogens.

  17. Population genetic structure of savannah elephants in Kenya: conservation and management implications

    DEFF Research Database (Denmark)

    Okello, John B A; Masembe, Charles; Rasmussen, Henrik B

    2008-01-01

    We investigated population genetic structure and regional differentiation among African savannah elephants in Kenya using mitochondrial and microsatellite markers. We observed mitochondrial DNA (mtDNA) nucleotide diversity of 1.68% and microsatellite variation in terms of average number of alleles...... through male-mediated gene flow. Our results depicting 3 broad regional mtDNA groups and the observed population genetic differentiation as well as connectivity patterns should be incorporated in the planning of future management activities such as translocations......., expected and observed heterozygosities in the total study population of 10.20, 0.75, and 0.69, respectively. Hierarchical analysis of molecular variance of mtDNA variation revealed significant differentiation among the 3 geographical regions studied (F(CT) = 0.264; P

  18. Development of the carapacial ridge: implications for the evolution of genetic networks in turtle shell development.

    Science.gov (United States)

    Moustakas, Jacqueline E

    2008-01-01

    Paleontologists and neontologists have long looked to development to understand the homologies of the dermal bones that form the "armor" of turtles, crocodiles, armadillos, and other vertebrates. This study shows molecular evidence supporting a dermomyotomal identity for the mesenchyme of the turtle carapacial ridge. The mesenchyme of the carapace primordium expresses Pax3, Twist1, Dermo1, En1, Sim1, and Gremlin at early stages and before overt ossification expresses Pax1. A hypothesis is proposed that this mesenchyme forms dermal bone in the turtle carapace. A comparison of regulatory gene expression in the primordia of the turtle carapace, the vertebrate limb, and the vertebral column implies the exaptation of key genetic networks in the development of the turtle shell. This work establishes a new role for this mesodermal compartment and highlights the importance of changes in genetic regulation in the evolution of morphology.

  19. Hg and As Minerals in Fluid Inclusions from the Williams Mine, Hemlo, and Their Genetic Implications

    Institute of Scientific and Technical Information of China (English)

    LU HUANZHANG(卢焕章); JAYANTA. GUHA; DON. C. HARRIS

    2002-01-01

    The Hemlo mineralization is enigmatic compared to general Archean lode gold deposits based on the fact that it is characterized by an exotic mineralogy containing elements such as As, Hg, Sb, Ba, V and Mo. The genetic concepts range from syngenetic to epigenetic types of mineralization. This reconnaissance study was designed to examine the relationship of Hg-As minerals with respect to fluid inclusions in the Williams mine (formerly known as the Page Williams mine) covering the A and C ore zones.

  20. Genetic characterization of wild swamp deer populations: ex situ conservation and forensics implications.

    Science.gov (United States)

    Kumar, Ved Prakash; Shrivastwa, Anupam; Nigam, Parag; Kumar, Dhyanendra; Goyal, Surendra Prakash

    2016-10-26

    Swamp deer (Rucervus duvaucelii) is an endemic, Scheduled I species under the Wildlife (Protection) Act 1972, India. According to variations in antler size, it has been classified into three subspecies, namely Western (R. duvaucelii duvaucelii), Central (R. duvaucelii branderi), and Eastern (R. duvaucelii ranjitsinhii). For planning effective ex situ and in situ conservation of a wide-ranging species in different bioclimatic regions and in wildlife forensic, the use of genetic characterization in defining morpho/ecotypes has been suggested because of the geographic clines and reproductive isolation. In spite of these morphotypes, very little is known about the genetic characteristics of the three subspecies, hence no strict subspecies-based breeding plan for retaining the evolutionary characteristics in captive populations for subsequent re-introduction is available except for a few studies. We describe the genetic characteristics of these three subspecies using cytochrome b of the mtDNA genome (400 bp). The DNA sequence data indicated 11 variable sites within the three subspecies. Two paraphyletic clades, namely the Central India and Western-Eastern populations were found, whereas the Western and Eastern populations are monophyletic with a bootstrap value of 69% within the clade. We suggest the need of sorting these three subspecies using different molecular mtDNA markers in zoos for captive breeding purposes so as to retain the genetic diversity of the separate geographic clines and to use a subspecies-specific fixed-state nucleotide to assess the extent of poaching to avoid any population demography stochastically in India.

  1. The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

    OpenAIRE

    Guerra, Daniel J.

    2011-01-01

    Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting th...

  2. Genetics implicate common mechanisms in autism and schizophrenia: synaptic activity and immunity.

    Science.gov (United States)

    Liu, Xiaoming; Li, Zhengwei; Fan, Conghai; Zhang, Dongli; Chen, Jiao

    2017-08-01

    The diagnosis of debilitating psychiatric disorders like autism spectrum disorder (ASD) and schizophrenia (SCHZ) is on the rise. These are severe conditions that lead to social isolation and require lifelong professional care. Improved diagnosis of ASD and SCHZ provides early access to medication and therapy, but the reality is that the mechanisms and the cellular pathology underlying these conditions are mostly unknown at this time. Although both ASD and SCHZ have strong inherited components, genetic risk seems to be distributed in hundreds of variants, each conferring low risk. The poor understanding of the genetics of ASD and SCHZ is a significant hurdle to developing effective treatments for these costly conditions. The recent implementation of next-generation sequencing technologies and the creation of large consortia have started to reveal the genetic bases of ASD and SCHZ. Alterations in gene expression regulation, synaptic architecture and activity and immunity seem to be the main cellular mechanisms contributing to both ASD and SCHZ, a surprising overlap given the distinct phenotypes and onset of these conditions. These diverse pathways seem to converge in aberrant synaptic plasticity and remodelling, which leads to altered connectivity between relevant brain regions. Continuous efforts to understand the genetic basis of ASD and SCHZ will soon lead to significant progress in the mechanistic understanding of these prominent psychiatric disorders and enable the development of disease-modifying therapies for these devastating conditions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. CONSUMER RESPONSE TO GENETICALLY MODIFIED FOODS: MARKET SEGMENT ANALYSIS AND IMPLICATIONS FOR PRODUCERS AND POLICY MAKERS

    OpenAIRE

    Baker, Gregory A.; Burnham, Thomas A.

    2001-01-01

    Conjoint analysis is used to elicit consumer preferences for attributes of genetically modified foods. Market segments are identified based on a cluster analysis of respondents' preferences for brand, price, and GMO content. A logit analysis is used to analyze consumer characteristics associated with the acceptance of GMO foods. Those consumers who were most risk averse, most likely to believe that GMOs improved the quality or safety of food, and most knowledgeable about biotechnology were th...

  4. Monkey-based research on human disease: the implications of genetic differences.

    Science.gov (United States)

    Bailey, Jarrod

    2014-11-01

    Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists.

  5. Genetic structure of Mediterranean chukar ( Alectoris chukar, Galliformes) populations: conservation and management implications

    Science.gov (United States)

    Barbanera, Filippo; Marchi, Chiara; Guerrini, Monica; Panayides, Panicos; Sokos, Christos; Hadjigerou, Pantelis

    2009-10-01

    The chukar ( Alectoris chukar, Galliformes) is a species hunted throughout its native range from the East Mediterranean to Manchuria and in the USA, which hosts the world’s largest introduced population. This study aims to investigate the genetic structure of Mediterranean chukar populations to aid management decisions. We genotyped 143 specimens at two regions of the mitochondrial DNA (mtDNA: cytochrome b, control region) and eight loci of the microsatellite DNA. Samples were collected in northern (Limnos, Lesvos, Chios) and southern (Crete) Aegean islands (Greece) and Cyprus. We also carried out mtDNA-based comparison with chukars ( n = 124) from Asia (16 countries) and the USA (five states). We propose six management units for Mediterranean populations. Given their genetic integrity, Limnos and Cyprus, which host different subspecies, proved to be of primary conservation interest. We found exotic A. chukar mtDNA lineages in Lesvos, Chios and Crete and produced definitive genetic evidence for the Asian origin of the US chukars.

  6. Population genetics of cancer cell clones: possible implications of cancer stem cells

    Directory of Open Access Journals (Sweden)

    Naugler Christopher T

    2010-11-01

    Full Text Available Abstract Background The population dynamics of the various clones of cancer cells existing within a tumour is complex and still poorly understood. Cancer cell clones can be conceptualized as sympatric asexual species, and as such, the application of theoretical population genetics as it pertains to asexual species may provide additional insights. Results The number of generations of tumour cells within a cancer has been estimated at a minimum of 40, but high cancer cell mortality rates suggest that the number of cell generations may actually be in the hundreds. Such a large number of generations would easily allow natural selection to drive clonal evolution assuming that selective advantages of individual clones are within the range reported for free-living animal species. Tumour cell clonal evolution could also be driven by variation in the intrinsic rates of increase of different clones or by genetic drift. In every scenario examined, the presence of cancer stem cells would require lower selection pressure or less variation in intrinsic rates of increase. Conclusions The presence of cancer stem cells may result in more rapid clonal evolution. Specific predictions from theoretical population genetics may lead to a greater understanding of this process.

  7. Genetic HLA Study of Kurds in Iraq, Iran and Tbilisi (Caucasus, Georgia): Relatedness and Medical Implications

    Science.gov (United States)

    Muñiz, Ester; Campos, Cristina; Alonso-Rubio, Javier; Gomez-Casado, Eduardo; Salih, Shadallah Fareq; Martin-Villa, Manuel; Al-Qadi, Rawand

    2017-01-01

    Kurds from Iraq (Dohuk and Erbil Area, North Iraq) have been analyzed for HLA genes. Their HLA genetic profile has been compared with that of other Kurd groups from Iran and Tbilisi (Georgia, Caucasus) and also Worldwide populations. A total of 7,746 HLA chromosomes have been used. Genetic distances, NJ dendrograms and correspondence analyses have been carried out. Haplotype HLA-B*52—DRB1*15 is present in all three analyzed Kurd populations. HLA-A*02-B*51-DRB1*11 is present in Iraq and Georgia Kurds. Haplotypes common to Iran and Iraq Kurds are HLA DRB1*11—DQB1*03, HLA DRB1*03—DQB1*02 and others in a lower frequency. Our HLA study conclusions are that Kurds most probably belong to an ancient Mediterranean / Middle East / Caucasian genetic substratum and that present results and those previously obtained by us in Kurds may be useful for Medicine in future Kurd transplantation programs, HLA Epidemiology (HLA linked diseases) and Pharmacogenomics (HLA-associated drug side effects) and also for Anthropology. It is discussed that one of the most ancient Kurd ancestor groups is in Hurrians (2,000 years BC). PMID:28114347

  8. Fine-scale genetic structure of Eremosparton songoricum and implication for conservation

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Eremosparton songoricum (Litv.) Vass. is a clonal shrub that reproduces both asexually by under-ground rhizomes and sexually by seeds. It is now a rare species with a narrow distribution in fragmented habitat patches in the Gurbantunggut Desert of Xinjiang, China. The objective of this study was to determine the spatial pattern or structure of genetic variation within population. The within-populations genetic structure of E. songoricum in a plot (10 m×10 m) was analyzed using inter simple sequence repeats (ISSR) markers. Correlograms of Moran’s I showed significant positive value was about 7 m, but changed into a negative correlation with the increase of distance, indicating strong genetic structure. The natural character of clonal reproduction, restricted seed and pollen dispersal were the main factors of influencing the spatial pattern. The knowledge of clonal structures within populations was crucial for understanding evolutionary processes and ecological adaptation. This study provided basic data for the conservation and management of E. songoricum, especially for sampling strategies for ex situ conservation.

  9. Mitochondrial and pedigree analysis in Przewalski's horse populations: implications for genetic management and reintroductions.

    Science.gov (United States)

    Liu, Gang; Xu, Chao-Qun; Cao, Qing; Zimmermann, Waltraut; Songer, Mellisa; Zhao, Sha-Sha; Li, Kai; Hu, De-Fu

    2014-08-01

    Przewalski's horses have been imported from the western zoos to China since 1985. Yet the genetic diversity in China's populations has not been studied, thus lacking of such knowledge inevitably affects this population's management. The aim of this study was to assess genetic diversity in Chinese population of Przewalski's horses via mitochondrial DNA (mtDNA) control region and pedigree analysis. Two captive and one reintroduced populations were examined based on mitochondrial DNA control region variation via fecal sampling from 2010 to 2012, together with pedigree analysis. Amplification success rates of fecal mtDNA were as high as 96.2% (93.8%-100%), and were higher for sample in winter than in summer and autumn. Two haplotypes were identified and shared among three populations, but the proportion of individuals with each haplotype varied among the three populations (F(ST) = 0.10874, p = 0.00978). Haplotype diversity in the released population (0.153) was much lower than that in the two captive populations (0.4011 and 0.4966), in accordance with the direction of increase in probability of identity at the dam lines. Future concerns in Przewalski's horse population management should emphasize on strict reproduction control to minimize inbreeding in captivity, followed by long-term genetic diversity guidelines and non-invasive monitoring in the reintroduction programmes.

  10. A New Spectral Shape-Based Record Selection Approach Using Np and Genetic Algorithms

    Directory of Open Access Journals (Sweden)

    Edén Bojórquez

    2013-01-01

    Full Text Available With the aim to improve code-based real records selection criteria, an approach inspired in a parameter proxy of spectral shape, named Np, is analyzed. The procedure is based on several objectives aimed to minimize the record-to-record variability of the ground motions selected for seismic structural assessment. In order to select the best ground motion set of records to be used as an input for nonlinear dynamic analysis, an optimization approach is applied using genetic algorithms focuse on finding the set of records more compatible with a target spectrum and target Np values. The results of the new Np-based approach suggest that the real accelerograms obtained with this procedure, reduce the scatter of the response spectra as compared with the traditional approach; furthermore, the mean spectrum of the set of records is very similar to the target seismic design spectrum in the range of interest periods, and at the same time, similar Np values are obtained for the selected records and the target spectrum.

  11. Examining the family-centred approach to genetic testing and counselling among UK Pakistanis: a community perspective.

    Science.gov (United States)

    Darr, A; Small, N; Ahmad, W I U; Atkin, K; Corry, P; Benson, J; Morton, R; Modell, B

    2013-01-01

    WHO advice suggests a family-centred approach for managing the elevated risk of recessively inherited disorders in consanguineous communities, whilst emerging policy recommends community engagement as an integral component of genetic service development. This paper explores the feasibility of the family-centred approach in the UK Pakistani origin community. The study took place within a context of debate in the media, professional and lay circles about cousin marriage causing disability in children. Using qualitative methods, a total of six single-sex focus group discussions (n = 50) were conducted in three UK cities with a high settlement of people of Pakistani origin. Tape-recorded transcripts were analysed using framework analysis. Kinship networks within Pakistani origin communities are being sustained and marriage between close blood relatives continues to take place alongside other marriage options. Study participants were critical of what was perceived as a prevalent notion that cousin marriage causes disability in children. They were willing to discuss cousin marriage and disability, share genetic information and engage with genetic issues. A desire for accurate information and a public informed about genetic issues was articulated whilst ineffective communication of genetic risk information undermined professionals in their support role. This study suggests a community that is embracing change, one in which kinship networks are still active and genetic information exchange is taking place. At the community level, these are conditions supportive of the family-centred approach to genetic testing and counselling.

  12. Pre-emptive resource-constrained multimode project scheduling using genetic algorithm: A dynamic forward approach

    Directory of Open Access Journals (Sweden)

    Aidin Delgoshaei

    2016-09-01

    Full Text Available Purpose: The issue resource over-allocating is a big concern for project engineers in the process of scheduling project activities. Resource over-allocating drawback is frequently seen after scheduling of a project in practice which causes a schedule to be useless. Modifying an over-allocated schedule is very complicated and needs a lot of efforts and time. In this paper, a new and fast tracking method is proposed to schedule large scale projects which can help project engineers to schedule the project rapidly and with more confidence. Design/methodology/approach: In this article, a forward approach for maximizing net present value (NPV in multi-mode resource constrained project scheduling problem while assuming discounted positive cash flows (MRCPSP-DCF is proposed. The progress payment method is used and all resources are considered as pre-emptible. The proposed approach maximizes NPV using unscheduled resources through resource calendar in forward mode. For this purpose, a Genetic Algorithm is applied to solve. Findings: The findings show that the proposed method is an effective way to maximize NPV in MRCPSP-DCF problems while activity splitting is allowed. The proposed algorithm is very fast and can schedule experimental cases with 1000 variables and 100 resources in few seconds. The results are then compared with branch and bound method and simulated annealing algorithm and it is found the proposed genetic algorithm can provide results with better quality. Then algorithm is then applied for scheduling a hospital in practice. Originality/value: The method can be used alone or as a macro in Microsoft Office Project® Software to schedule MRCPSP-DCF problems or to modify resource over-allocated activities after scheduling a project. This can help project engineers to schedule project activities rapidly with more accuracy in practice.

  13. Wolves Recolonizing Islands: Genetic Consequences and Implications for Conservation and Management.

    Directory of Open Access Journals (Sweden)

    Liivi Plumer

    Full Text Available After a long and deliberate persecution, the grey wolf (Canis lupus is slowly recolonizing its former areas in Europe, and the genetic consequences of this process are of particular interest. Wolves, though present in mainland Estonia for a long time, have only recently started to recolonize the country's two largest islands, Saaremaa and Hiiumaa. The main objective of this study was to analyse wolf population structure and processes in Estonia, with particular attention to the recolonization of islands. Fifteen microsatellite loci were genotyped for 185 individuals across Estonia. As a methodological novelty, all putative wolf-dog hybrids were identified and removed (n = 17 from the dataset beforehand to avoid interference of dog alleles in wolf population analysis. After the preliminary filtering, our final dataset comprised of 168 "pure" wolves. We recommend using hybrid-removal step as a standard precautionary procedure not only for wolf population studies, but also for other taxa prone to hybridization. STRUCTURE indicated four genetic groups in Estonia. Spatially explicit DResD analysis identified two areas, one of them on Saaremaa island and the other in southwestern Estonia, where neighbouring individuals were genetically more similar than expected from an isolation-by-distance null model. Three blending areas and two contrasting transition zones were identified in central Estonia, where the sampled individuals exhibited strong local differentiation over relatively short distance. Wolves on the largest Estonian islands are part of human-wildlife conflict due to livestock depredation. Negative public attitude, especially on Saaremaa where sheep herding is widespread, poses a significant threat for island wolves. To maintain the long-term viability of the wolf population on Estonian islands, not only wolf hunting quota should be targeted with extreme care, but effective measures should be applied to avoid inbreeding and minimize conflicts

  14. Wolves Recolonizing Islands: Genetic Consequences and Implications for Conservation and Management.

    Science.gov (United States)

    Plumer, Liivi; Keis, Marju; Remm, Jaanus; Hindrikson, Maris; Jõgisalu, Inga; Männil, Peep; Kübarsepp, Marko; Saarma, Urmas

    2016-01-01

    After a long and deliberate persecution, the grey wolf (Canis lupus) is slowly recolonizing its former areas in Europe, and the genetic consequences of this process are of particular interest. Wolves, though present in mainland Estonia for a long time, have only recently started to recolonize the country's two largest islands, Saaremaa and Hiiumaa. The main objective of this study was to analyse wolf population structure and processes in Estonia, with particular attention to the recolonization of islands. Fifteen microsatellite loci were genotyped for 185 individuals across Estonia. As a methodological novelty, all putative wolf-dog hybrids were identified and removed (n = 17) from the dataset beforehand to avoid interference of dog alleles in wolf population analysis. After the preliminary filtering, our final dataset comprised of 168 "pure" wolves. We recommend using hybrid-removal step as a standard precautionary procedure not only for wolf population studies, but also for other taxa prone to hybridization. STRUCTURE indicated four genetic groups in Estonia. Spatially explicit DResD analysis identified two areas, one of them on Saaremaa island and the other in southwestern Estonia, where neighbouring individuals were genetically more similar than expected from an isolation-by-distance null model. Three blending areas and two contrasting transition zones were identified in central Estonia, where the sampled individuals exhibited strong local differentiation over relatively short distance. Wolves on the largest Estonian islands are part of human-wildlife conflict due to livestock depredation. Negative public attitude, especially on Saaremaa where sheep herding is widespread, poses a significant threat for island wolves. To maintain the long-term viability of the wolf population on Estonian islands, not only wolf hunting quota should be targeted with extreme care, but effective measures should be applied to avoid inbreeding and minimize conflicts with local

  15. Comorbidity of intellectual disability confounds ascertainment of autism: implications for genetic diagnosis.

    Science.gov (United States)

    Polyak, Andrew; Kubina, Richard M; Girirajan, Santhosh

    2015-10-01

    While recent studies suggest a converging role for genetic factors towards risk for nosologically distinct disorders including autism, intellectual disability (ID), and epilepsy, current estimates of autism prevalence fail to take into account the impact of comorbidity of these disorders on autism diagnosis. We aimed to assess the effect of comorbidity on the diagnosis and prevalence of autism by analyzing 11 years (2000-2010) of special education enrollment data on approximately 6.2 million children per year. We found a 331% increase in the prevalence of autism from 2000 to 2010 within special education, potentially due to a diagnostic recategorization from frequently comorbid features such as ID. The decrease in ID prevalence equaled an average of 64.2% of the increase of autism prevalence for children aged 3-18 years. The proportion of ID cases potentially undergoing recategorization to autism was higher (P = 0.007) among older children (75%) than younger children (48%). Some US states showed significant negative correlations between the prevalence of autism compared to that of ID while others did not, suggesting state-specific health policy to be a major factor in categorizing autism. Further, a high frequency of autistic features was observed when individuals with classically defined genetic syndromes were evaluated for autism using standardized instruments. Our results suggest that current ascertainment practices are based on a single facet of autism-specific clinical features and do not consider associated comorbidities that may confound diagnosis. Longitudinal studies with detailed phenotyping and deep molecular genetic analyses are necessary to completely understand the cause of this complex disorder.

  16. A genetic comparison of West Greenland and Baffin Island (Canada walruses: Management implications

    Directory of Open Access Journals (Sweden)

    Liselotte Wesley Andersen

    2014-12-01

    Full Text Available Until recently Atlantic walruses (Odobenus rosmarus rosmarus have been subject to relatively intense exploitation in West Greenland. Animals in this stock have also been hunted in Nunavut/Canada. However, the demographic identity of these animals and their connection with walruses in neighbouring areas is poorly resolved, hampering the determination of sustainable harvest levels. It has been suggested that walruses in West Greenland are genetically linked with walruses at SE Baffin Island (Canada where they are also hunted for subsistence purposes. To determine the relationship(s between walruses in these areas we conducted a genetic analysis including recent samples from West Greenland, Southeast Baffin Island in western Davis Strait, Hudson Strait in Canada and Northwest Greenland in northern Baffin Bay. Seventeen microsatellite markers were applied to all samples. Walruses in West Greenland and at Southeast Baffin Island did not differ from each other and therefore may be regarded as belonging to the same stock. However, walruses in these two areas differed genetically from both Northwest Greenland and Hudson Strait walruses. These findings support (1 that there are subunits within the range of walruses in the Hudson Strait-Davis Strait-Baffin Bay region and (2 that walruses along E Baffin Island and W Greenland constitute a common population that receive some influx from Hudson Strait. Thus, sustainable catch levels in Southeast Baffin Island (Nunavut and in West Greenland must be set in light of the finding that they belong to the same stock, which is exploited in these two areas. This requires Canadian-Greenlandic co-management of the W Greenland-SE Baffin Island walrus stock.

  17. Parallel tagged next-generation sequencing on pooled samples - a new approach for population genetics in ecology and conservation.

    Science.gov (United States)

    Zavodna, Monika; Grueber, Catherine E; Gemmell, Neil J

    2013-01-01

    Next-generation sequencing (NGS) on pooled samples has already been broadly applied in human medical diagnostics and plant and animal breeding. However, thus far it has been only sparingly employed in ecology and conservation, where it may serve as a useful diagnostic tool for rapid assessment of species genetic diversity and structure at the population level. Here we undertake a comprehensive evaluation of the accuracy, practicality and limitations of parallel tagged amplicon NGS on pooled population samples for estimating species population diversity and structure. We obtained 16S and Cyt b data from 20 populations of Leiopelma hochstetteri, a frog species of conservation concern in New Zealand, using two approaches - parallel tagged NGS on pooled population samples and individual Sanger sequenced samples. Data from each approach were then used to estimate two standard population genetic parameters, nucleotide diversity (π) and population differentiation (FST), that enable population genetic inference in a species conservation context. We found a positive correlation between our two approaches for population genetic estimates, showing that the pooled population NGS approach is a reliable, rapid and appropriate method for population genetic inference in an ecological and conservation context. Our experimental design also allowed us to identify both the strengths and weaknesses of the pooled population NGS approach and outline some guidelines and suggestions that might be considered when planning future projects.

  18. 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.

  19. A Transformation-Based Approach to Implication of GSTE Assertion Graphs

    Directory of Open Access Journals (Sweden)

    Guowu Yang

    2013-01-01

    its powerful capacity in formal verification of VLSI systems. GSTE is an extension of symbolic trajectory evaluation (STE to the model checking of ω-regular properties. It is an alternative to classical model checking algorithms where properties are specified as finite-state automata. In GSTE, properties are specified as assertion graphs, which are labeled directed graphs where each edge is labeled with two labeling functions: antecedent and consequent. In this paper, we show the complement relation between GSTE assertion graphs and finite-state automata with the expressiveness of regular languages and ω-regular languages. We present an algorithm that transforms a GSTE assertion graph to a finite-state automaton and vice versa. By applying this algorithm, we transform the problem of GSTE assertion graphs implication to the problem of automata language containment. We demonstrate our approach with its application to verification of an FIFO circuit.

  20. Yellow fever virus: genetic and phenotypic diversity and implications for detection, prevention and therapy.

    Science.gov (United States)

    Beasley, David W C; McAuley, Alexander J; Bente, Dennis A

    2015-03-01

    Yellow fever virus (YFV) is the prototypical hemorrhagic fever virus, yet our understanding of its phenotypic diversity and any molecular basis for observed differences in disease severity and epidemiology is lacking, when compared to other arthropod-borne and haemorrhagic fever viruses. This is, in part, due to the availability of safe and effective vaccines resulting in basic YFV research taking a back seat to those viruses for which no effective vaccine occurs. However, regular outbreaks occur in endemic areas, and the spread of the virus to new, previously unaffected, areas is possible. Analysis of isolates from endemic areas reveals a strong geographic association for major genotypes, and recent epidemics have demonstrated the emergence of novel sequence variants. This review aims to outline the current understanding of YFV genetic and phenotypic diversity and its sources, as well as the available animal models for characterizing these differences in vivo. The consequences of genetic diversity for detection and diagnosis of yellow fever and development of new vaccines and therapeutics are discussed.

  1. Genetics of Resistance and Pathogenicity in the Maize/Setosphaeria turcica Pathosystem and Implications for Breeding

    Directory of Open Access Journals (Sweden)

    Ana L. Galiano-Carneiro

    2017-08-01

    Full Text Available Northern corn leaf blight (NCLB, the most devastating leaf pathogen in maize (Zea mays L., is caused by the heterothallic ascomycete Setosphaeria turcica. The pathogen population shows an extremely high genetic diversity in tropical and subtropical regions. Varietal resistance is the most efficient technique to control NCLB. Host resistance can be qualitative based on race-specific Ht genes or quantitative controlled by many genes with small effects. Quantitative resistance is moderately to highly effective and should be more durable combatting all races of the pathogen. Quantitative resistance must, however, be analyzed in many environments (= location × year combinations to select stable resistances. In the tropical and subtropical environments, quantitative resistance is the preferred option to manage NCLB epidemics. Resistance level can be increased in practical breeding programs by several recurrent selection cycles based on disease severity rating and/or by genomic selection. This review aims to address two important aspects of the NCLB pathosystem: the genetics of the fungus S. turcica and the modes of inheritance of the host plant maize, including successful breeding strategies regarding NCLB resistance. Both drivers of this pathosystem, pathogen, and host, must be taken into account to result in more durable resistance.

  2. Distribution of trinucleotide microsatellites in different categories of mammalian genomic sequence: Implications for human genetic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Stallings, R.L. (Univ. of Pittsburgh, PA (United States))

    1994-05-01

    The distribution of all trinucleotide microsatellite sequences in the GenBank database was surveyed to provide insight into human genetic disease syndromes that result from expansion of microsatellites. The microsatellite motif (CAG)[sub n] is one of the most abundant microsatellite motifs in human GenBank DNA sequences and is the most abundant microsatellite found in exons. This fact may explain why (CAG)[sub n] repeats are thus far the predominant microsatellites expanded in human genetic diseases. Surprisingly, (CAG)[sub n] microsatellites are excluded from intronic regions in a strand-specific fashion, possibly because of similarity to the 3[prime] consensus splice site, CAGG. A comparison of the positions of microsatellites in human vs rodent homologous sequences indicates that some arrays are not extensively conserved for long periods of time, even when they form parts of protein coding sequences. The general lack of conservation of trinucleotide repeat loci in diverse mammals indicates that animal models for some human microsatellite expansion syndromes may be difficult to find. 20 refs., 5 tabs.

  3. Genetic divergence and its implication in breeding of desired plant type in coriander -Coriandrum sativum L.-

    Directory of Open Access Journals (Sweden)

    Singh S.P.

    2005-01-01

    Full Text Available Seventy germplasm lines of coriander (Coriandrum sativum L. of diverse eco-geographical origin were undertaken in present investigation to determine the genetic divergence following multivariate and canonical analysis for seed yield and its 9 component traits. The 70 genotypes were grouped into 9 clusters depending upon the genetic architecture of genotypes and characters uniformity and confirmed by canonical analysis. Seventy percent of total genotypes (49/70 were grouped in 4 clusters (V, VI, VIII and IX, while apparent diversity was noticed for 30 percent genotypes (21/70 that diverged into 5 clusters (I, II, III, FV, and VII. The maximum inter cluster distance was between I and IV (96.20 followed by III and IV (91.13 and I and VII (87.15. The cluster VI was very unique having genotypes of high mean values for most of the component traits. The cluster VII had highest seeds/umbel (35.3 ± 2.24, and leaves/plant (12.93 ± 0.55, earliest flowering (65.05 ± 1.30 and moderately high mean values for other characters. Considering high mean and inter cluster distance breeding plan has been discussed to select desirable plant types.

  4. Balanced reciprocal translocation at amniocentesis: cytogenetic detection and implications for genetic counseling.

    Science.gov (United States)

    Zhang, H G; Zhang, X Y; Zhang, H Y; Tian, T; Xu, S B; Liu, R Z

    2016-08-19

    Balanced translocation is a common structural chromosomal rearrangement in humans. Carriers can be phenotypically normal but have an increased risk of pregnancy loss, fetal death, and the transmission of chromosomal abnormalities to their offspring. Existing prenatal screening technologies and diagnostic procedures fail to detect balanced translocation, so genetic counseling for carriers remains a challenge. Here, we report the characteristics of chromosomal reciprocal translocation in 3807 amniocentesis cases. Of the 16 detected cases of fetal reciprocal translocation, 8 cases (50%) showed positive biochemical marker screening; 3 cases (18.75%) were the parental carriers of a chromosomal abnormality; 2 (12.5%) were of advanced maternal age, 2 (12.5%) had a previous history of children with genetic disorders, and 1 case (6.25%) was associated with positive soft markers in obstetric ultrasound. Chromosomes 5 and 19 were the most commonly involved chromosomes in balanced translocations. Of the 13 cases with fetal balanced translocations, 8 (61.5%) were inherited from a paternal chromosome, 3 (23.1%) from a maternal chromosome, and 2 (15.4%) cases were de novo. The incidence of balanced translocation at amniocentesis was 0.42%. Male carriers of reciprocal chromosome translocation appear to have a higher chance of becoming a parent of a child born by normal childbirth than female carriers.

  5. Gene editing and genetic engineering approaches for advanced probiotics: A Review.

    Science.gov (United States)

    Yadav, Ruby; Kumar, Vishal; Baweja, Mehak; Shukla, Pratyoosh

    2017-01-10

    The applications of probiotics are significant and thus resulted in need of genome analysis of probiotic strains. Various omics methods and systems biology approaches enables us to understand and optimize the metabolic processes. These techniques have increased the researcher's attention towards gut microbiome and provided a new source for the revelation of uncharacterized biosynthetic pathways which enables novel metabolic engineering approaches. In recent years, the broad and quantitative analysis of modified strains relies on systems biology tools such as in silico design which are commonly used methods for improving strain performance. The genetic manipulation of probiotic microorganisms is crucial for defining their role in intestinal microbiota and exploring their beneficial properties. This review describes an overview of gene editing and system biology approaches, highlighting the advent of omics methods which allows the study of new routes for studying probiotic bacteria. We have also summarized gene editing tools like TALEN, ZFNs and CRISPR-Cas that edits or cleave the specific target DNA. Furthermore, in this review an overview of proposed design of advanced customized probiotic is also hypothesized to improvise the probiotics.

  6. Pharmaceutical proteins in plants. A strategic genetic engineering approach for the production of tuberculosis antigens.

    Science.gov (United States)

    Frutos, Roger; Denise, Hubert; Vivares, Christian; Neuhaus, Jean-Marc; Vitale, Sandro; Pedrazzini, Emmanuela; Ma, Julian; Dix, Phil; Gray, John; Pezzotti, Mario; Conrad, Udo; Robinson, David

    2008-12-01

    Tuberculosis (TB) is a re-emerging disease that is considered a major human health priority as well as an important disease of livestock. TB is also a zoonosis, and Mycobacterium tuberculosis and M. bovis, the human and bovine causative agents, respectively, are very closely related. Protection against TB is essentially achieved through vaccination with the Bacille Calmetle-Guerin (BCG) strain of M. bovis. Protection is, however, incomplete, and novel improved vaccines are currently under investigation. Production of protective antigens in transgenic plants, or "pharming," is a promising emerging approach, and a zoonosis-like TB is a good model for investigating the potential of this approach. Pharma-Planta, a European Commission-funded project and consortium, was set up to address this topic, within which a component is aimed at assessing the production efficacy and stability of the TB antigens in different compartments of the plant cell. This article is meant to introduce this promising approach for veterinary medicine by describing the ongoing project and its specific genetic engineering strategy.

  7. A HYBRID GENETIC ALGORITHM-NEURAL NETWORK APPROACH FOR PRICING CORES AND REMANUFACTURED CORES

    Directory of Open Access Journals (Sweden)

    M. Seidi

    2012-01-01

    Full Text Available

    ENGLISH ABSTRACT:Sustainability has become a major issue in most economies, causing many leading companies to focus on product recovery and reverse logistics. Remanufacturing is an industrial process that makes used products reusable. One of the important aspects in both reverse logistics and remanufacturing is the pricing of returned and remanufactured products (called cores. In this paper, we focus on pricing the cores and remanufactured cores. First we present a mathematical model for this purpose. Since this model does not satisfy our requirements, we propose a simulation optimisation approach. This approach consists of a hybrid genetic algorithm based on a neural network employed as the fitness function. We use automata learning theory to obtain the learning rate required for training the neural network. Numerical results demonstrate that the optimal value of the acquisition price of cores and price of remanufactured cores is obtained by this approach.

    AFRIKAANSE OPSOMMING: Volhoubaarheid het ‘n belangrike saak geword in die meeste ekonomieë, wat verskeie maatskappye genoop het om produkherwinning en omgekeerde logistiek te onder oë te neem. Hervervaardiging is ‘n industriële proses wat gebruikte produkte weer bruikbaar maak. Een van die belangrike aspekte in beide omgekeerde logistiek en hervervaardiging is die prysbepaling van herwinne en hervervaardigde produkte. Hierdie artikel fokus op die prysbepalingsaspekte by wyse van ‘n wiskundige model.

  8. A Modified Genetic Algorithm for Product Family Optimization with Platform Specified by Information Theoretical Approach

    Institute of Scientific and Technical Information of China (English)

    CHEN Chun-bao; WANG Li-ya

    2008-01-01

    Many existing product family design methods assume a given platform, However, it is not an in-tuitive task to select the platform and unique variable within a product family. Meanwhile, most approachesare single-platform methods, in which design variables are either shared across all product variants or not atall. While in multiple-platform design, platform variables can have special value with regard to a subset ofproduct variants within the product family, and offer opportunities for superior overall design. An informationtheoretical approach incorporating fuzzy clustering and Shannon's entropy was proposed for platform variablesselection in multiple-platform product family. A 2-level chromosome genetic algorithm (2LCGA) was proposedand developed for optimizing the corresponding product family in a single stage, simultaneously determiningthe optimal settings for the product platform and unique variables. The single-stage approach can yield im-provements in the overall performance of the product family compared with two-stage approaches, in which thefirst stage involves determining the best settings for the platform and values of unique variables are found foreach product in the second stage. An example of design of a family of universal motors was used to verify theproposed method.

  9. Current Status of Pharmaceutical and Genetic Therapeutic Approaches to Treat DMD

    Science.gov (United States)

    Pichavant, Christophe; Aartsma-Rus, Annemieke; Clemens, Paula R; Davies, Kay E; Dickson, George; Takeda, Shin'ichi; Wilton, Steve D; Wolff, Jon A; Wooddell, Christine I; Xiao, Xiao; Tremblay, Jacques P

    2011-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disease affecting about one in every 3,500 boys. This X-linked pathology is due to the absence of dystrophin in muscle fibers. This lack of dystrophin leads to the progressive muscle degeneration that is often responsible for the death of the DMD patients during the third decade of their life. There are currently no curative treatments for this disease but different therapeutic approaches are being studied. Gene therapy consists of introducing a transgene coding for full-length or a truncated version of dystrophin complementary DNA (cDNA) in muscles, whereas pharmaceutical therapy includes the use of chemical/biochemical substances to restore dystrophin expression or alleviate the DMD phenotype. Over the past years, many potential drugs were explored. This led to several clinical trials for gentamicin and ataluren (PTC124) allowing stop codon read-through. An alternative approach is to induce the expression of an internally deleted, partially functional dystrophin protein through exon skipping. The vectors and the methods used in gene therapy have been continually improving in order to obtain greater encapsidation capacity and better transduction efficiency. The most promising experimental approaches using pharmaceutical and gene therapies are reviewed in this article. PMID:21468001

  10. An Interval-Valued Approach to Business Process Simulation Based on Genetic Algorithms and the BPMN

    Directory of Open Access Journals (Sweden)

    Mario G.C.A. Cimino

    2014-05-01

    Full Text Available Simulating organizational processes characterized by interacting human activities, resources, business rules and constraints, is a challenging task, because of the inherent uncertainty, inaccuracy, variability and dynamicity. With regard to this problem, currently available business process simulation (BPS methods and tools are unable to efficiently capture the process behavior along its lifecycle. In this paper, a novel approach of BPS is presented. To build and manage simulation models according to the proposed approach, a simulation system is designed, developed and tested on pilot scenarios, as well as on real-world processes. The proposed approach exploits interval-valued data to represent model parameters, in place of conventional single-valued or probability-valued parameters. Indeed, an interval-valued parameter is comprehensive; it is the easiest to understand and express and the simplest to process, among multi-valued representations. In order to compute the interval-valued output of the system, a genetic algorithm is used. The resulting process model allows forming mappings at different levels of detail and, therefore, at different model resolutions. The system has been developed as an extension of a publicly available simulation engine, based on the Business Process Model and Notation (BPMN standard.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. DYNAMIC RELOCATION OF PLANT/WAREHOUSE FACILITIES:A FAST COMPACT GENETIC ALGORITHM APPROACH

    Institute of Scientific and Technical Information of China (English)

    Li Shugang; Wu Zhiming; Pang Xiaohong

    2004-01-01

    The problem of dynamic relocation and phase-out of combined manufacturing plant and warehousing facilities in the supply chain are concerned.A multiple time/multiple objective model is proposed to maximize total profit during the time horizon, minimize total access time from the plant/warehouse facilities to its suppliers and customers and maximize aggregated local incentives during the time horizon.The relocation problem keeps the feature of NP-hard and with the traditional method the optimal result cannot be got easily.So a compact genetic algorithm (CGA) is introduced to solve the problem.In order to accelerate the convergence speed of the CGA, the least square approach is introduced and a fast compact genetic algorithm (fCGA) is proposed.Finally, simulation results with the fCGA are compared with the CGA and classical integer programming (IP).The results show that the fCGA proposed is of high efficiency for Pareto optimality problem.

  13. A bayesian approach to inferring the genetic population structure of sugarcane accessions from INTA (Argentina

    Directory of Open Access Journals (Sweden)

    Mariana Inés Pocovi

    2015-06-01

    Full Text Available Understanding the population structure and genetic diversity in sugarcane (Saccharum officinarum L. accessions from INTA germplasm bank (Argentina will be of great importance for germplasm collection and breeding improvement as it will identify diverse parental combinations to create segregating progenies with maximum genetic variability for further selection. A Bayesian approach, ordination methods (PCoA, Principal Coordinate Analysis and clustering analysis (UPGMA, Unweighted Pair Group Method with Arithmetic Mean were applied to this purpose. Sixty three INTA sugarcane hybrids were genotyped for 107 Simple Sequence Repeat (SSR and 136 Amplified Fragment Length Polymorphism (AFLP loci. Given the low probability values found with AFLP for individual assignment (4.7%, microsatellites seemed to perform better (54% for STRUCTURE analysis that revealed the germplasm to exist in five optimum groups with partly corresponding to their origin. However clusters shown high degree of admixture, F ST values confirmed the existence of differences among groups. Dissimilarity coefficients ranged from 0.079 to 0.651. PCoA separated sugarcane in groups that did not agree with those identified by STRUCTURE. The clustering including all genotypes neither showed resemblance to populations find by STRUCTURE, but clustering performed considering only individuals displaying a proportional membership > 0.6 in their primary population obtained with STRUCTURE showed close similarities. The Bayesian method indubitably brought more information on cultivar origins than classical PCoA and hierarchical clustering method.

  14. 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.

  15. 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.

  16. Pollen Sterility—A Promising Approach to Gene Confinement and Breeding for Genetically Modified Bioenergy Crops

    Directory of Open Access Journals (Sweden)

    Albert P. Kausch

    2012-10-01

    Full Text Available Advanced genetic and biotechnology tools will be required to realize the full potential of food and bioenergy crops. Given current regulatory concerns, many transgenic traits might never be deregulated for commercial release without a robust gene confinement strategy in place. The potential for transgene flow from genetically modified (GM crops is widely known. Pollen-mediated transfer is a major component of gene flow in flowering plants and therefore a potential avenue for the escape of transgenes from GM crops. One approach for preventing and/or mitigating transgene flow is the production of trait linked pollen sterility. To evaluate the feasibility of generating pollen sterility lines for gene confinement and breeding purposes we tested the utility of a promoter (Zm13Pro from a maize pollen-specific gene (Zm13 for driving expression of the reporter gene GUS and the cytotoxic gene barnase in transgenic rice (Oryza sativa ssp. Japonica cv. Nipponbare as a monocot proxy for bioenergy grasses. This study demonstrates that the Zm13 promoter can drive pollen-specific expression in stably transformed rice and may be useful for gametophytic transgene confinement and breeding strategies by pollen sterility in food and bioenergy crops.

  17. Pediatric Cancer Genetics Research and an Evolving Preventive Ethics Approach for Return of Results after Death of the Subject.

    Science.gov (United States)

    Scollon, Sarah; Bergstrom, Katie; McCullough, Laurence B; McGuire, Amy L; Gutierrez, Stephanie; Kerstein, Robin; Parsons, D Williams; Plon, Sharon E

    2015-01-01

    The return of genetic research results after death in the pediatric setting comes with unique complexities. Researchers must determine which results and through which processes results are returned. This paper discusses the experience over 15 years in pediatric cancer genetics research of returning research results after the death of a child and proposes a preventive ethics approach to protocol development in order to improve the quality of return of results in pediatric genomic settings.

  18. Optimization of Electrical System for Offshore Wind Farms via a Genetic Algorithm Approach

    DEFF Research Database (Denmark)

    Zhao, Menghua

    to very different costs, system reliability, power quality, and power losses etc. Therefore, the optimization of electrical system design for offshore wind farms becomes more and more necessary. There are two tasks in this project: 1) the first one is to construct an algorithm for finding the capacity...... of a grid-connected wind farm; 2) the second one is the optimization of electrical system for offshore wind farms (OES-OWF). The capacity of a grid connected wind farm is limited by the transfer capability of the grid system, where the thermal limit of the transmission lines, the voltage stability......, and the LTC limitation of transformers, the power generation limits and the voltage operation range are considered as the constraints. The optimization method combined with probabilistic analysis is used to obtain the capacity of a given wind farm site. The OES-OWF is approached by Genetic Algorithm (GA...

  19. Optimization of Electrical System for Offshore Wind Farms via a Genetic Algorithm Approach

    DEFF Research Database (Denmark)

    Zhao, Menghua

    , and the LTC limitation of transformers, the power generation limits and the voltage operation range are considered as the constraints. The optimization method combined with probabilistic analysis is used to obtain the capacity of a given wind farm site. The OES-OWF is approached by Genetic Algorithm (GA...... to very different costs, system reliability, power quality, and power losses etc. Therefore, the optimization of electrical system design for offshore wind farms becomes more and more necessary. There are two tasks in this project: 1) the first one is to construct an algorithm for finding the capacity......). This platform is based on a knowledge database, and composed of several functional modules such as cost calculation, reliability evaluation, losses calculation, AC-DC integrated load flow algorithm etc. All these modules are based on a spreadsheet database which provides an interface for users to input...

  20. Nonlinear Electrical Circuit Oscillator Control Based on Backstepping Method: A Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    Mahsa Khoeiniha

    2012-01-01

    Full Text Available This paper investigated study of dynamics of nonlinear electrical circuit by means of modern nonlinear techniques and the control of a class of chaotic system by using backstepping method based on Lyapunov function. The behavior of such nonlinear system when they are under the influence of external sinusoidal disturbances with unknown amplitudes has been considered. The objective is to analyze the performance of this system at different amplitudes of disturbances. We illustrate the proposed approach for controlling duffing oscillator problem to stabilize this system at the equilibrium point. Also Genetic Algorithm method (GA for computing the parameters of controller has been used. GA can be successfully applied to achieve a better controller. Simulation results have shown the effectiveness of the proposed method.

  1. An Evolutionary Approach to Drug-Design Using a Novel Neighbourhood Based Genetic Algorithm

    CERN Document Server

    Ghosh, Arnab; Chowdhury, Arkabandhu; Konar, Amit

    2012-01-01

    The present work provides a new approach to evolve ligand structures which represent possible drug to be docked to the active site of the target protein. The structure is represented as a tree where each non-empty node represents a functional group. It is assumed that the active site configuration of the target protein is known with position of the essential residues. In this paper the interaction energy of the ligands with the protein target is minimized. Moreover, the size of the tree is difficult to obtain and it will be different for different active sites. To overcome the difficulty, a variable tree size configuration is used for designing ligands. The optimization is done using a novel Neighbourhood Based Genetic Algorithm (NBGA) which uses dynamic neighbourhood topology. To get variable tree size, a variable-length version of the above algorithm is devised. To judge the merit of the algorithm, it is initially applied on the well known Travelling Salesman Problem (TSP).

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

    Science.gov (United States)

    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. NOVEL APPROACH FOR ROBOT PATH PLANNING BASED ON NUMERICAL ARTIFICIAL POTENTIAL FIELD AND GENETIC ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    WANG Weizhong; ZHAO Jie; GAO Yongsheng; CAI Hegao

    2006-01-01

    A novel approach for collision-free path planning of a multiple degree-of-freedom (DOF)articulated robot in a complex environment is proposed. Firstly, based on visual neighbor point (VNP), a numerical artificial potential field is constructed in Cartesian space, which provides the heuristic information, effective distance to the goal and the motion direction for the motion of the robot joints. Secondly, a genetic algorithm, combined with the heuristic rules, is used in joint space to determine a series of contiguous configurations piecewise fiom initial configuration until the goal configuration is attained. A simulation shows that the method can not only handle issues on path planning of the articulated robots in environment with complex obstacles, but also improve the efficiency and quality of path planning.

  4. A NAÏVE APPROACH TO SPEED UP PORTFOLIO OPTIMIZATION PROBLEM USING A MULTIOBJECTIVE GENETIC ALGORITHM

    Directory of Open Access Journals (Sweden)

    Baixauli-Soler, J. Samuel

    2012-05-01

    Full Text Available Genetic algorithms (GAs are appropriate when investors have the objective of obtaining mean‑variance (VaR efficient frontier as minimising VaR leads to non‑convex and non‑differential risk‑return optimisation problems. However GAs are a time‑consuming optimisation technique. In this paper, we propose to use a naïve approach consisting of using samples split by quartile of risk to obtain complete efficient frontiers in a reasonable computation time. Our results show that using reduced problems which only consider a quartile of the assets allow us to explore the efficient frontier for a large range of risk values. In particular, the third quartile allows us to obtain efficient frontiers from the 1.8% to 2.5% level of VaR quickly, while that of the first quartile of assets is from 1% to 1.3% level of VaR.

  5. [A general approach to the structural shape optimization using genetic algorithms and geometric design elements].

    Science.gov (United States)

    Annicchiarico, W

    2001-01-01

    Structural optimization is an engineering field which deal with the improvement of existing solutions or even more find new solutions that are better than the previous ones under some selected criterion. Shape optimization is a research area in this field and it is involved in developing new methodologies to find better structural design based on the shape as resistant element, as for example solutions with the less stress concentration zones and made with the minimum amount of material. The goal of this doctoral dissertation is to present and discuss a general structural shape optimization methodology able to optimize several structural systems or mechanical devices. The approach presented herein is based on global search optimization tools such as Genetic Algorithms and geometric design elements by means of beta-splines curves and surfaces representation. Finally the great versatility of the developed tool is presented and discussed with an application example.

  6. Translational and clinical implications of the genetic landscape of prostate cancer.

    Science.gov (United States)

    Spratt, Daniel E; Zumsteg, Zachary S; Feng, Felix Y; Tomlins, Scott A

    2016-10-01

    Over the past several years, analyses of data from high-throughput studies have elucidated many fundamental insights into prostate cancer biology. These insights include the identification of molecular alterations and subtypes that drive tumour progression, recurrent aberrations in signalling pathways, the existence of substantial intertumoural and intratumoural heterogeneity, Darwinian evolution in response to therapeutic pressures and the complicated multidirectional patterns of spread between primary tumours and metastatic sites. However, these concepts have not yet been fully translated into clinical tools to improve prognostication, prediction and personalization of treatment of patients with prostate cancer. The current and future clinical implications of 'omics' level knowledge is not only revolutionizing our understanding of prostate cancer biology, but is also shaping ongoing, and future clinical investigations and practice. In this Review, we summarize these advances, and the remaining challenges surrounding tumour heterogeneity and the ability to overcome treatment resistance are also described.

  7. An Adaptive Agent-Based Model of Homing Pigeons: A Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    Francis Oloo

    2017-01-01

    Full Text Available Conventionally, agent-based modelling approaches start from a conceptual model capturing the theoretical understanding of the systems of interest. Simulation outcomes are then used “at the end” to validate the conceptual understanding. In today’s data rich era, there are suggestions that models should be data-driven. Data-driven workflows are common in mathematical models. However, their application to agent-based models is still in its infancy. Integration of real-time sensor data into modelling workflows opens up the possibility of comparing simulations against real data during the model run. Calibration and validation procedures thus become automated processes that are iteratively executed during the simulation. We hypothesize that incorporation of real-time sensor data into agent-based models improves the predictive ability of such models. In particular, that such integration results in increasingly well calibrated model parameters and rule sets. In this contribution, we explore this question by implementing a flocking model that evolves in real-time. Specifically, we use genetic algorithms approach to simulate representative parameters to describe flight routes of homing pigeons. The navigation parameters of pigeons are simulated and dynamically evaluated against emulated GPS sensor data streams and optimised based on the fitness of candidate parameters. As a result, the model was able to accurately simulate the relative-turn angles and step-distance of homing pigeons. Further, the optimised parameters could replicate loops, which are common patterns in flight tracks of homing pigeons. Finally, the use of genetic algorithms in this study allowed for a simultaneous data-driven optimization and sensitivity analysis.

  8. A statistical approach to quantification of genetically modified organisms (GMO) using frequency distributions.

    Science.gov (United States)

    Gerdes, Lars; Busch, Ulrich; Pecoraro, Sven

    2014-12-14

    According to Regulation (EU) No 619/2011, trace amounts of non-authorised genetically modified organisms (GMO) in feed are tolerated within the EU if certain prerequisites are met. Tolerable traces must not exceed the so-called 'minimum required performance limit' (MRPL), which was defined according to the mentioned regulation to correspond to 0.1% mass fraction per ingredient. Therefore, not yet authorised GMO (and some GMO whose approvals have expired) have to be quantified at very low level following the qualitative detection in genomic DNA extracted from feed samples. As the results of quantitative analysis can imply severe legal and financial consequences for producers or distributors of feed, the quantification results need to be utterly reliable. We developed a statistical approach to investigate the experimental measurement variability within one 96-well PCR plate. This approach visualises the frequency distribution as zygosity-corrected relative content of genetically modified material resulting from different combinations of transgene and reference gene Cq values. One application of it is the simulation of the consequences of varying parameters on measurement results. Parameters could be for example replicate numbers or baseline and threshold settings, measurement results could be for example median (class) and relative standard deviation (RSD). All calculations can be done using the built-in functions of Excel without any need for programming. The developed Excel spreadsheets are available (see section 'Availability of supporting data' for details). In most cases, the combination of four PCR replicates for each of the two DNA isolations already resulted in a relative standard deviation of 15% or less. The aims of the study are scientifically based suggestions for minimisation of uncertainty of measurement especially in -but not limited to- the field of GMO quantification at low concentration levels. Four PCR replicates for each of the two DNA isolations

  9. Genetic diversity within and among four South European native horse breeds based on microsatellite DNA analysis: implications for conservation.

    Science.gov (United States)

    Solis, A; Jugo, B M; Mériaux, J C; Iriondo, M; Mazón, L I; Aguirre, A I; Vicario, A; Estomba, A

    2005-01-01

    In the present study, genetic analyses of diversity and differentiation were performed on four Basque-Navarrese semiferal native horse breeds. In total, 417 animals were genotyped for 12 microsatellite markers. Mean heterozygosity was higher than in other horse breeds, surely as a consequence of management. Although the population size of some of these breeds has declined appreciably in the past century, no genetic bottleneck was detected in any of the breeds, possibly because it was not narrow enough to be detectable. In the phylogenetic tree, the Jaca Navarra breed was very similar to the Pottoka, but appeared to stand in an intermediate position between this and the meat breeds. Assuming that Pottoka is the breed less affected by admixture, the others gradually distanced themselves from it through varying influences from outside breeds, among other factors. In a comparative study with other breeds, the French breeds Ardanais, Comtois, and Breton were the closest to the four native breeds. Three different approaches for evaluating the distribution of genetic diversity were applied. The high intrabreed variability of Euskal Herriko Mendiko Zaldia (EHMZ) was pointed out in these analyses. In our opinion, cultural, economic, and scientific factors should also be considered in the management of these horse breeds.

  10. Transcriptome outlier analysis implicates schizophrenia susceptibility genes and enriches putatively functional rare genetic variants.

    Science.gov (United States)

    Duan, Jubao; Sanders, Alan R; Moy, Winton; Drigalenko, Eugene I; Brown, Eric C; Freda, Jessica; Leites, Catherine; Göring, Harald H H; Gejman, Pablo V

    2015-08-15

    We searched a gene expression dataset comprised of 634 schizophrenia (SZ) cases and 713 controls for expression outliers (i.e., extreme tails of the distribution of transcript expression values) with SZ cases overrepresented compared with controls. These outlier genes were enriched for brain expression and for genes known to be associated with neurodevelopmental disorders. SZ cases showed higher outlier burden (i.e., total outlier events per subject) than controls for genes within copy number variants (CNVs) associated with SZ or neurodevelopmental disorders. Outlier genes were enriched for CNVs and for rare putative regulatory variants, but this only explained a small proportion of the outlier subjects, highlighting the underlying presence of additional genetic and potentially, epigenetic mechanisms.

  11. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

    DEFF Research Database (Denmark)

    Wolff, Markus; Johannesen, Katrine M; Hedrich, Ulrike B S

    2017-01-01

    for which well-documented medical information was available. We find that the use of sodium channel blockers was often associated with clinically relevant seizure reduction or seizure freedom in children with early infantile epilepsies (...). Other known phenotypes include Ohtahara syndrome, epilepsy of infancy with migrating focal seizures, and intellectual disability or autism without epilepsy. To assess the response to antiepileptic therapy, we retrospectively reviewed the treatment regimen and the course of the epilepsy in 66 patients....... In contrast, sodium channel blockers were rarely effective in epilepsies with later onset (≥3 months) and sometimes induced seizure worsening. Regarding the genetic findings, truncating mutations were exclusively seen in patients with late onset epilepsies and lack of response to sodium channel blockers...

  12. Velo-cardio-facial syndrome and psychotic disorders: Implications for psychiatric genetics

    Energy Technology Data Exchange (ETDEWEB)

    Chow, W.C.; Bassett, A.S.; Weksberg, R. [Univ. of Toronto, Ontario (Canada)

    1994-06-15

    Psychiatric disorders have been reported in over 10% of patients with velo-cardio-facial syndrome (VCFS) in long-term follow-up. To further explore the behavioral and psychiatric findings associated with VCFS in adulthood, detailed clinical histories of two patients - one with VCFS who developed a psychotic illness, and one with schizophrenia who was found to have dysmorphological features associated with VCFS - are described in the current report. The observed overlap of physical and psychiatric symptoms in these two patients suggests that VCFS and psychotic disorders may share a pathogenetic mechanism. This could be consistent with a contiguous gene model for VCFS and psychosis, suggesting chromosome 22q11 as a possible candidate region for genetic studies of schizophrenia. 26 refs., 2 tabs.

  13. The genetics of Leigh syndrome and its implications for clinical practice and risk management.

    Science.gov (United States)

    Ruhoy, Ilene S; Saneto, Russell P

    2014-01-01

    Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient's family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms.

  14. The genetic basis of Lynch syndrome and its implications for clinical practice and risk management

    Directory of Open Access Journals (Sweden)

    Cohen SA

    2014-07-01

    Full Text Available Stephanie A Cohen,1 Anna Leininger2 1Cancer Genetics Risk Assessment Program, St Vincent Health, Indianapolis, IN, USA; 2Minnesota Oncology, Woodbury, MN, USA Abstract: Lynch syndrome is the most common cause of hereditary colon cancer, and accounts for as much as 3% of all colon and endometrial cancers. The identification and management of individuals with Lynch syndrome have evolved over the past 20 years, yet the syndrome remains vastly underdiagnosed. It is important for clinicians to recognize individuals and families who are at risk in order to be able to manage them appropriately and reduce their morbidity and mortality from this condition. This review will touch on the history of Lynch syndrome, the current knowledge of genotype–phenotype correlations, the cancers associated with Lynch syndrome, and management of individuals who are gene carriers. Keywords: Lynch syndrome, hereditary cancer, hereditary nonpolyposis colorectal cancer, mismatch repair, mismatch repair genes, immunohistochemistry, microsatellite instability

  15. Genetic variation of low-density lipoprotein-cholesterol and its clinical implications

    Institute of Scientific and Technical Information of China (English)

    Tsung O. Cheng

    2005-01-01

    @@ Plasma lipids are controlled by genes and play an important role in the development of atherosclerosis. Dysplipidemia is an important risk factor for coronary artery disease (CAD). Coronary artery disease is the leading cause of mortality and morbidity in the developed world. More than 14 million Americans are afflicted with clinically significant CAD.1 To illustrate the impact of CAD in developed countries, the medical and societal costs of CAD in the United States alone are in excess of $90 billion annually.1 More than 600 000 Americans each year develop new cardiac events, more than 10% of which occur in Americans <50 years of age.1 Identifying genetic predisposition to early onset of CAD could help in understanding basic disease mechanism, guiding targeted preventive efforts, and planning appropriate therapeutic strategies.

  16. Recommendations from a meeting on health implications of genetically modified organism (GMO).

    Science.gov (United States)

    Amofah, George

    2014-06-01

    The Ghana Public Health Association organized a scientific seminar to examine the introduction of genetically modified organisms into public use and the health consequences. The seminar was driven by current public debate on the subject. The seminar identified some of the advantages of GMOs and also the health concerns. It is clear that there is the need to enhance local capacity to research the introduction and use of GMOs; to put in place appropriate regulatory mechanisms including particularly the labeling of GMO products and post-marketing surveillance for possible negative health consequences in the long term. Furthermore the appropriate state agency should put in place advocacy strategies to keep the public informed about GMOs.

  17. STAT4: Genetics, Mechanisms, and Implications for Autoimmunity Review for Current Allergy and Asthma Reports

    Science.gov (United States)

    Korman, Benjamin D.; Kastner, Daniel L.; Gregersen, Peter K.

    2008-01-01

    Recent advances in genetics and technology have led to breakthroughs in understanding the genes that predispose individuals to autoimmune diseases. A common haplotype of the signal transducer and activator of transcription 4 (STAT4) gene has been shown to be associated with susceptibility to rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren’s syndrome. STAT4 is a transcription factor that transduces interleukin-12, interleukin-23, and type I interferon cytokine signals in T cells and monocytes, leading to T-helper type 1 and T-helper type 17 differentiation, monocyte activation, and production of interferon-γ. Although the evidence for this association is very strong and well replicated, the exact mechanism by which polymorphisms in this gene lead to disease remains unknown. In concert with the identification of other disease-associated loci, elucidating how the variant form of STAT4 modulates immune function should lead to an improved understanding of the pathophysiology of autoimmunity. PMID:18682104

  18. On the Predictability of Risk Box Approach by Genetic Programming Method for Bankruptcy Prediction

    Directory of Open Access Journals (Sweden)

    Alireza Bahiraie

    2009-01-01

    Full Text Available Problem statement: Theoretical based data representation is an important tool for model selection and interpretations in bankruptcy analysis since the numerical representation are much less transparent. Some methodological problems concerning financial ratios such as non-proportionality, non-asymetricity, non-scalicity are solved in this study and we presented a complementary technique for empirical analysis of financial ratios and bankruptcy risk. Approach: This study presented new geometric technique for empirical analysis of bankruptcy risk using financial ratios. Within this framework, we proposed the use of a new ratio representation which named Risk Box measure (RB. We demonstrated the application of this geometric approach for variable representation, data visualization and financial ratios at different stages of corporate bankruptcy prediction models based on financial balance sheet ratios. These stages were the selection of variables (predictors, accuracy of each estimation model and the representation of each model for transformed and common ratios. Results: We provided evidence of extent to which changes in values of this index were associated with changes in each axis values and how this may alter our economic interpretation of changes in the patterns and direction of risk components. Results of Genetic Programming (GP models were compared as different classification models and results showed the classifiers outperform by modified ratios. Conclusion/Recommendations: In this study, a new dimension to risk measurement and data representation with the advent of the Share Risk method (SR was proposed. Genetic programming method is substantially superior to the traditional methods such as MDA or Logistic method. It was strongly suggested the use of SR methodology for ratio analysis, which provided a conceptual and complimentary methodological solution to many problems associated with the use of ratios. Respectively, GP will provide

  19. Planning additional drilling campaign using two-space genetic algorithm: A game theoretical approach

    Science.gov (United States)

    Kumral, Mustafa; Ozer, Umit

    2013-03-01

    Grade and tonnage are the most important technical uncertainties in mining ventures because of the use of estimations/simulations, which are mostly generated from drill data. Open pit mines are planned and designed on the basis of the blocks representing the entire orebody. Each block has different estimation/simulation variance reflecting uncertainty to some extent. The estimation/simulation realizations are submitted to mine production scheduling process. However, the use of a block model with varying estimation/simulation variances will lead to serious risk in the scheduling. In the medium of multiple simulations, the dispersion variances of blocks can be thought to regard technical uncertainties. However, the dispersion variance cannot handle uncertainty associated with varying estimation/simulation variances of blocks. This paper proposes an approach that generates the configuration of the best additional drilling campaign to generate more homogenous estimation/simulation variances of blocks. In other words, the objective is to find the best drilling configuration in such a way as to minimize grade uncertainty under budget constraint. Uncertainty measure of the optimization process in this paper is interpolation variance, which considers data locations and grades. The problem is expressed as a minmax problem, which focuses on finding the best worst-case performance i.e., minimizing interpolation variance of the block generating maximum interpolation variance. Since the optimization model requires computing the interpolation variances of blocks being simulated/estimated in each iteration, the problem cannot be solved by standard optimization tools. This motivates to use two-space genetic algorithm (GA) approach to solve the problem. The technique has two spaces: feasible drill hole configuration with minimization of interpolation variance and drill hole simulations with maximization of interpolation variance. Two-space interacts to find a minmax solution

  20. A genetic algorithm approach for assessing soil liquefaction potential based on reliability method

    Indian Academy of Sciences (India)

    M H Bagheripour; I Shooshpasha; M Afzalirad

    2012-02-01

    Deterministic approaches are unable to account for the variations in soil’s strength properties, earthquake loads, as well as source of errors in evaluations of liquefaction potential in sandy soils which make them questionable against other reliability concepts. Furthermore, deterministic approaches are incapable of precisely relating the probability of liquefaction and the factor of safety (FS). Therefore, the use of probabilistic approaches and especially, reliability analysis is considered since a complementary solution is needed to reach better engineering decisions. In this study, Advanced First-Order Second-Moment (AFOSM) technique associated with genetic algorithm (GA) and its corresponding sophisticated optimization techniques have been used to calculate the reliability index and the probability of liquefaction. The use of GA provides a reliable mechanism suitable for computer programming and fast convergence. A new relation is developed here, by which the liquefaction potential can be directly calculated based on the estimated probability of liquefaction (), cyclic stress ratio (CSR) and normalized standard penetration test (SPT) blow counts while containing a mean error of less than 10% from the observational data. The validity of the proposed concept is examined through comparison of the results obtained by the new relation and those predicted by other investigators. A further advantage of the proposed relation is that it relates and FS and hence it provides possibility of decision making based on the liquefaction risk and the use of deterministic approaches. This could be beneficial to geotechnical engineers who use the common methods of FS for evaluation of liquefaction. As an application, the city of Babolsar which is located on the southern coasts of Caspian Sea is investigated for liquefaction potential. The investigation is based primarily on in situ tests in which the results of SPT are analysed.

  1. Talent or Talents: Intellectual Exceptionality Approaches and their Implications in the Educational Process

    Directory of Open Access Journals (Sweden)

    René Javier Barraza-López

    2015-09-01

    Full Text Available This paper points out the importance that, in the practice, the educational system gives to the academic talent, leaving in a second place other forms of talent, for example, those comprised in the multiple intelligence or emotional intelligence theories. The purpose of this paper is to present different underlying approaches of talent coexisting in education at various levels, demonstrating some of their potential implications in the educational practice and in the academic achievement of students. In this regard, the emergence of recent theories –as the multiple intelligence Gardner (2001, and the emotional intelligence Mayer and Salovey (1997 theories– has put into question the traditional intelligence approaches, which have influenced the concept and practice of teachers concerning a successful formal education. All of this tends to increase the gap between “smart” and “normal”, perpetuating the segregation culture through academic means. Based on this, this paper exposes the need to take into consideration the students’ different skills and talents when planning and evaluating the teaching-learning process, and enhance teaching training through didactic and evaluation methodologies to achieve such integration. For this, the present study provides some evaluation and classroom methodologies. The study also highlights the need to develop, systematize, and validate a broader range of teaching-learning methodologies that can be transmitted to the faculty, in order to gradually move towards a more inclusive, higher quality education.

  2. Integrating molecular and morphological approaches for characterizing parasite cryptic species: implications for parasitology.

    Science.gov (United States)

    Nadler, Steven A; DE León, Gerardo Pérez-Ponce

    2011-11-01

    Herein we review theoretical and methodological considerations important for finding and delimiting cryptic species of parasites (species that are difficult to recognize using traditional systematic methods). Applications of molecular data in empirical investigations of cryptic species are discussed from an historical perspective, and we evaluate advantages and disadvantages of approaches that have been used to date. Developments concerning the theory and practice of species delimitation are emphasized because theory is critical to interpretation of data. The advantages and disadvantages of different molecular methodologies, including the number and kind of loci, are discussed relative to tree-based approaches for detecting and delimiting cryptic species. We conclude by discussing some implications that cryptic species have for research programmes in parasitology, emphasizing that careful attention to the theory and operational practices involved in finding, delimiting, and describing new species (including cryptic species) is essential, not only for fully characterizing parasite biodiversity and broader aspects of comparative biology such as systematics, evolution, ecology and biogeography, but to applied research efforts that strive to improve development and understanding of epidemiology, diagnostics, control and potential eradication of parasitic diseases.

  3. A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches

    Science.gov (United States)

    Bartolomé, Nerea; Segarra, Sergi; Artieda, Marta; Francino, Olga; Sánchez, Elisenda; Szczypiorska, Magdalena; Casellas, Joaquim; Tejedor, Diego; Cerdeira, Joaquín; Martínez, Antonio; Velasco, Alfonso; Sánchez, Armand

    2015-01-01

    Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B) and case (D/E). C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85) and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors’ opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds. PMID:25874693

  4. A genetic predictive model for canine hip dysplasia: integration of Genome Wide Association Study (GWAS and candidate gene approaches.

    Directory of Open Access Journals (Sweden)

    Nerea Bartolomé

    Full Text Available Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B and case (D/E. C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85 and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors' opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds.

  5. A genetic predictive model for canine hip dysplasia: integration of Genome Wide Association Study (GWAS) and candidate gene approaches.

    Science.gov (United States)

    Bartolomé, Nerea; Segarra, Sergi; Artieda, Marta; Francino, Olga; Sánchez, Elisenda; Szczypiorska, Magdalena; Casellas, Joaquim; Tejedor, Diego; Cerdeira, Joaquín; Martínez, Antonio; Velasco, Alfonso; Sánchez, Armand

    2015-01-01

    Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B) and case (D/E). C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85) and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors' opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds.

  6. Genetic structure and seed germination in Portuguese populations of Cheirolophus uliginosus (Asteraceae: Implications for conservation strategies

    Directory of Open Access Journals (Sweden)

    Vitales, D.

    2013-12-01

    Full Text Available Cheirolophus uliginosus is a threatened species, endemic to the Atlantic coast of the Iberian Peninsula, where it occupies a few restricted localities. In our study we analysed the patterns of cpDNA haplotypes variation and reproductive success—germinability—among seven Portuguese populations of varying size. The aim was to examine the reproductive performance of Ch. uliginosus related to genetic structure and population size. The results showed very low within-population variability of cpDNA markers. Our study indicates that the germination rate is significantly reduced in small populations ( 250 individuals do not show any constraint. In the search for plausible causes explaining the lower germination success in the smallest populations, ecological concerns and genetic isolation must be taken into account. Besides, in large-sized populations of Ch. uliginosus (> 250 plants a higher incidence of predispersal seed predation was observed, maybe affecting their sexual reproductive response. Finally, smaller populations—presenting a reduced reproductive success—contain also the most evolutionary distant haplotypes, so their conservation should be a priority.Cheirolophus uliginosus es una especie amenazada endémica de la costa atlántica de la península ibérica, donde ocupa unas pocas y reducidas localidades. En nuestro estudio, analizamos los patrones de variación de los haplotipos de ADN cloroplástico y el éxito reproductivo —capacidad germinativa— en siete poblaciones portuguesas de diferente tamaño. El éxito reproductivo de Ch. uliginosus se ha examinado en relación con la estructura genética y el tamaño de sus poblaciones. Los resultados indican una variabilidad intrapoblacional muy baja para los marcadores cloroplásticos utilizados. Nuestro estudio muestra una tasa de germinación significativamente reducida en las poblaciones pequeñas ( 250 individuos. Para explicar este fenómeno, se deben tomar en consideración las

  7. Conservation of intron and intein insertion sites: implications for life histories of parasitic genetic elements

    Directory of Open Access Journals (Sweden)

    Senejani Alireza G

    2009-12-01

    Full Text Available Abstract Background Inteins and introns are genetic elements that are removed from proteins and RNA after translation or transcription, respectively. Previous studies have suggested that these genetic elements are found in conserved parts of the host protein. To our knowledge this type of analysis has not been done for group II introns residing within a gene. Here we provide quantitative statistical support from an analyses of proteins that host inteins, group I introns, group II introns and spliceosomal introns across all three domains of life. Results To determine whether or not inteins, group I, group II, and spliceosomal introns are found preferentially in conserved regions of their respective host protein, conservation profiles were generated and intein and intron positions were mapped to the profiles. Fisher's combined probability test was used to determine the significance of the distribution of insertion sites across the conservation profile for each protein. For a subset of studied proteins, the conservation profile and insertion positions were mapped to protein structures to determine if the insertion sites correlate to regions of functional activity. All inteins and most group I introns were found to be preferentially located within conserved regions; in contrast, a bacterial intein-like protein, group II and spliceosomal introns did not show a preference for conserved sites. Conclusions These findings demonstrate that inteins and group I introns are found preferentially in conserved regions of their respective host proteins. Homing endonucleases are often located within inteins and group I introns and these may facilitate mobility to conserved regions. Insertion at these conserved positions decreases the chance of elimination, and slows deletion of the elements, since removal of the elements has to be precise as not to disrupt the function of the protein. Furthermore, functional constrains on the targeted site make it more difficult

  8. Genetic relationships among members of the Ichthyobodo necator complex: implications for the management of aquaculture stocks.

    Science.gov (United States)

    Callahan, H A; Litaker, R W; Noga, E J

    2005-02-01

    Abstract Ichthyobodo necator (costia) is a common and important flagellate parasite that infests the skin and gills of many freshwater and marine fish. Costia infestations are often fatal and cause significant aquaculture losses worldwide. Recently it has been demonstrated that Ichthyobodo is a multispecies complex with differing host preferences. Knowing if those species have broad or narrow host specificity has important implications for the management of costia. To address the question of host specificity, genomic DNA was isolated from Ichthyobodo trophonts collected from rainbow trout, Oncorhynchus mykiss, koi, Cyprinus carpio, mirror carp, C. carpio, goldfish, Carassius auratus, channel catfish, Ictalurus punctatus, swordtail, Xiphophorus helleri, and Japanese flounder, Paralichthys olivaceus. The small subunit ribosomal RNA (SSU rRNA) gene from each isolate was analysed with previously published Ichthyobodo sequences using Bayesian phylogenetic methods. The internal transcribed spacers (ITS) from six isolates were also PCR-amplified, cloned and sequenced. Both the SSU rRNA phylogenetic analysis and the ITS rRNA sequence data support grouping the 22 Ichthyobodo isolates examined into a complex of nine different species. Many of these species were frequently isolated from multiple hosts, indicating that exchange of infested fish from one region to another has a high potential for spreading the disease. In one instance, the same species was obtained from marine and freshwater fish, further suggesting that certain Ichthyobodo species may not be limited by salinity.

  9. A population genetics-phylogenetics approach to inferring natural selection in coding sequences.

    Directory of Open Access Journals (Sweden)

    Daniel J Wilson

    2011-12-01

    Full Text Available Through an analysis of polymorphism within and divergence between species, we can hope to learn about the distribution of selective effects of mutations in the genome, changes in the fitness landscape that occur over time, and the location of sites involved in key adaptations that distinguish modern-day species. We introduce a novel method for the analysis of variation in selection pressures within and between species, spatially along the genome and temporally between lineages. We model codon evolution explicitly using a joint population genetics-phylogenetics approach that we developed for the construction of multiallelic models with mutation, selection, and drift. Our approach has the advantage of performing direct inference on coding sequences, inferring ancestral states probabilistically, utilizing allele frequency information, and generalizing to multiple species. We use a Bayesian sliding window model for intragenic variation in selection coefficients that efficiently combines information across sites and captures spatial clustering within the genome. To demonstrate the utility of the method, we infer selective pressures acting in Drosophila melanogaster and D. simulans from polymorphism and divergence data for 100 X-linked coding regions.

  10. Image Retrieval Approach Based on Intuitive Fuzzy Set Combined with Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-yin; XU Wei-hua; HU Chang-zhen

    2009-01-01

    Aiming at shortcomings of traditional image retrieval systems,a new image retrieval approach based on color features of image combining intuitive fuzzy theory with genetic algorithm is proposed.Each image is segmented into a constant number of sub-images in vertical direction.Color features are extracted from every sub-image to get chromosome coding.It is considered that fuzzy membership and intuitive fuzzy hesitancy degree of every pixel's color in image are associated to all the color histogram bins.Certain feature,fuzzy feature and intuitive fuzzy feature of colors in an image,are used together to describe the content of image.Efficient combinations of sub-image are selected according to operation of selecting,crossing and variation.Retrieval resuits are obtained from image matching based on these color feature combinations of sub-images.Tests show that this approach can improve the accuracy of image retrieval in the case of not decreasing the speed of image retrieval.Its mean precision is above 80%.

  11. Evaluation of a LASSO regression approach on the unrelated samples of Genetic Analysis Workshop 17.

    Science.gov (United States)

    Guo, Wei; Elston, Robert C; Zhu, Xiaofeng

    2011-11-29

    The Genetic Analysis Workshop 17 data we used comprise 697 unrelated individuals genotyped at 24,487 single-nucleotide polymorphisms (SNPs) from a mini-exome scan, using real sequence data for 3,205 genes annotated by the 1000 Genomes Project and simulated phenotypes. We studied 200 sets of simulated phenotypes of trait Q2. An important feature of this data set is that most SNPs are rare, with 87% of the SNPs having a minor allele frequency less than 0.05. For rare SNP detection, in this study we performed a least absolute shrinkage and selection operator (LASSO) regression and F tests at the gene level and calculated the generalized degrees of freedom to avoid any selection bias. For comparison, we also carried out linear regression and the collapsing method, which sums the rare SNPs, modified for a quantitative trait and with two different allele frequency thresholds. The aim of this paper is to evaluate these four approaches in this mini-exome data and compare their performance in terms of power and false positive rates. In most situations the LASSO approach is more powerful than linear regression and collapsing methods. We also note the difficulty in determining the optimal threshold for the collapsing method and the significant role that linkage disequilibrium plays in detecting rare causal SNPs. If a rare causal SNP is in strong linkage disequilibrium with a common marker in the same gene, power will be much improved.

  12. Assuring the safety of genetically modified (GM) foods: the importance of an holistic, integrative approach.

    Science.gov (United States)

    Cockburn, Andrew

    2002-09-11

    Genes change continuously by natural mutation and recombination enabling man to select and breed crops having the most desirable traits such as yield or flavour. Genetic modification (GM) is a recent development which allows specific genes to be identified, isolated, copied and inserted into other plants with a high level of specificity. The food safety considerations for GM crops are basically the same as those arising from conventionally bred crops, very few of which have been subject to any testing yet are generally regarded as being safe to eat. In contrast a rigorous safety testing paradigm has been developed for GM crops, which utilises a systematic, stepwise and holistic approach. The resultant science based process, focuses on a classical evaluation of the toxic potential of the introduced novel trait and the wholesomeness of the transformed crop. In addition, detailed consideration is given to the history and safe use of the parent crop as well as that of the gene donor. The overall safety evaluation is conducted under the concept known as substantial equivalence which is enshrined in all international crop biotechnology guidelines. This provides the framework for a comparative approach to identify the similarities and differences between the GM product and its comparator which has a known history of safe use. By building a detailed profile on each step in the transformation process, from parent to new crop, and by thoroughly evaluating the significance from a safety perspective, of any differences that may be detected, a very comprehensive matrix of information is constructed which enables the conclusion as to whether the GM crop, derived food or feed is as safe as its traditional counterpart. Using this approach in the evaluation of more than 50 GM crops which have been approved worldwide, the conclusion has been that foods and feeds derived from genetically modified crops are as safe and nutritious as those derived from traditional crops. The lack of

  13. Differentially Expressed Genes Distributed Over Chromosomes and Implicated in Certain Biological Processes for Site Insertion Genetically Modified Rice Kemingdao

    Directory of Open Access Journals (Sweden)

    Zhi Liu, Yunhe Li, Jie Zhao, Xiuping Chen, Guiliang Jian, Yufa Peng, Fangjun Qi

    2012-01-01

    Full Text Available Release of genetically modified (GM plants has sparked off intensive debates worldwide partly because of concerns about potential adverse unintended effects of GM plants to the agro system and the safety of foods. In this study, with the aim of revealing the molecular basis for unintended effects of a single site insertion GM Kemingdao (KMD rice transformed with a synthetic cry1Ab gene, and bridging unintended effects of KMD rice through clues of differentially expressed genes, comparative transcriptome analyses were performed for GM KMD rice and its parent rice of Xiushui11 (XS11. The results showed that 680 differentially expressed transcripts were identified from 30-day old seedlings of GM KMD rice. The absolute majority of these changed expression transcripts dispersed and located over all rice chromosomes, and existed physical distance on chromosome from the insertion site, while only two transcripts were found to be differentially expressed within the 21 genes located within 100 kb up and down-stream of the insertion site. Pathway and biology function analyses further revealed that differentially expressed transcripts of KMD rice were involved in certain biological processes, and mainly implicated in two types of pathways. One type was pathways implicated in plant stress/defense responses, which were considerably in coordination with the reported unintended effects of KMD rice, which were more susceptible to rice diseases compared to its parent rice XS11; the other type was pathways associated with amino acids metabolism. With this clue, new unintended effects for changes in amino acids synthesis of KMD rice leaves were successfully revealed. Such that an actual case was firstly provided for identification of unintended effects in GM plants by comparative transciptome analysis.

  14. The genetics of Leigh syndrome and its implications for clinical practice and risk management

    Directory of Open Access Journals (Sweden)

    Ruhoy IS

    2014-11-01

    Full Text Available Ilene S Ruhoy, Russell P Saneto Division of Pediatric Neurology, Seattle Children's Hospital/University of Washington, Seattle, WA, USAAbstract: Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient's family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms.Keywords: mitochondrial disorder, neurodegeneration, multisystemic disease, oxidative phosphorylation, mitochondrial DNA, neuroimaging, seizures

  15. Hepatitis C virus genotype 6: virology, epidemiology, genetic variation and clinical implication.

    Science.gov (United States)

    Thong, Vo Duy; Akkarathamrongsin, Srunthron; Poovorawan, Kittiyod; Tangkijvanich, Pisit; Poovorawan, Yong

    2014-03-21

    Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation worldwide. HCV genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also occasionally found in migrant patients from endemic countries. HCV-6 has considerable genetic diversity with 23 subtypes (a to w). Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping, there are also now rapid genotyping tests available such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics, Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes. Based on current evidence, the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk, although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response. In addition, the development of direct-acting antiviral agents is ongoing, and they give high response rate when combined with standard therapy. Herein, we review the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6.

  16. Constitutive RB1 mutation in a child conceived by in vitro fertilization: implications for genetic counseling

    Directory of Open Access Journals (Sweden)

    Lucena Evandro

    2009-07-01

    Full Text Available Abstract Background The purpose of this study was to identify mutations associated with bilateral retinoblastoma in a quadruplet conceived by in vitro fertilization, and to trace the parental origin of mutations in the four quadruplets and their father. Methods Mutational screening was carried out by sequencing. Genotyping was carried out for determining quadruplet zygosity. Results The proband was a carrier of a novel RB1 constitutive mutation (g.2056C>G which was not detected in her father or her unaffected sisters, and of two other mutations (g.39606 C>T and g.174351T>A also present in two monozygotic sisters. The novel mutation probably occurred de novo while the others were of likely maternal origin. The novel mutation, affecting the Kozak consensus at the 5'UTR of RB1 and g.174351T>A were likely associated to retinoblastoma in the proband. Conclusion Molecular diagnosis of retinoblastoma requires genotypic data of the family for determining hereditary transmission. In the case of children generated by IVF with oocytes from an anonymous donor which had been stored in a cell repository, this might not be successfully accomplished, making precise diagnosis impracticable for genetic counseling.

  17. Obstetric prognosis in sisters of preeclamptic women – implications for genetic linkage studies

    Directory of Open Access Journals (Sweden)

    Heinonen Seppo

    2003-02-01

    Full Text Available Abstract Background To investigate obstetric prognosis in sisters of preeclamptic women. Methods We identified consecutive 635 sib pairs from the Birth Registry data of Kuopio University Hospital who had their first delivery between January 1989 and December 1999 in our institution. Of these, in 530 pairs both sisters had non-preeclamptic pregnancies (the reference group, in 63 pairs one of the sisters had preeclampsia and the unaffected sisters were studied (study group I. In 42 pairs both sister's first delivery was affected (study group II. Pregnancy outcome measures in these groups were compared. Results Unaffected sisters of the index patients had uncompromised fetal growth in their pregnancies, and overall, as good obstetric outcomes as in the reference group. The data on affected sisters of the index patients showed an increased prematurity rate, and increased incidences of low birth weight and small-for-gestational age infants, as expected. Conclusion Unaffected sisters of the index patients had no signs of utero-placental insufficiency and they were at low risk with regard to adverse obstetric outcome, whereas affected sisters were high-risk. Clinically, affected versus unaffected status appears to be clear-cut in first-degree relatives regardless of their genetic susceptibility and unaffected sisters do not need special antepartum surveillance.

  18. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

    Science.gov (United States)

    Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga; Saxena, Richa; Soranzo, Nicole; Jackson, Anne U; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Gloyn, Anna L; Lindgren, Cecilia M; Mägi, Reedik; Morris, Andrew P; Randall, Joshua; Johnson, Toby; Elliott, Paul; Rybin, Denis; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Henneman, Peter; Grallert, Harald; Dehghan, Abbas; Hottenga, Jouke Jan; Franklin, Christopher S; Navarro, Pau; Song, Kijoung; Goel, Anuj; Perry, John R B; Egan, Josephine M; Lajunen, Taina; Grarup, Niels; Sparsø, Thomas; Doney, Alex; Voight, Benjamin F; Stringham, Heather M; Li, Man; Kanoni, Stavroula; Shrader, Peter; Cavalcanti-Proença, Christine; Kumari, Meena; Qi, Lu; Timpson, Nicholas J; Gieger, Christian; Zabena, Carina; Rocheleau, Ghislain; Ingelsson, Erik; An, Ping; O’Connell, Jeffrey; Luan, Jian'an; Elliott, Amanda; McCarroll, Steven A; Payne, Felicity; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ardlie, Kristin; Ariyurek, Yavuz; Balkau, Beverley; Barter, Philip; Beilby, John P; Ben-Shlomo, Yoav; Benediktsson, Rafn; Bennett, Amanda J; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bonnefond, Amélie; Bonnycastle, Lori L; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J; Charpentier, Guillaume; Chen, Yii-Der Ida; Chines, Peter; Clarke, Robert; Coin, Lachlan J M; Cooper, Matthew N; Cornelis, Marilyn; Crawford, Gabe; Crisponi, Laura; Day, Ian N M; de Geus, Eco; Delplanque, Jerome; Dina, Christian; Erdos, Michael R; Fedson, Annette C; Fischer-Rosinsky, Antje; Forouhi, Nita G; Fox, Caroline S; Frants, Rune; Franzosi, Maria Grazia; Galan, Pilar; Goodarzi, Mark O; Graessler, Jürgen; Groves, Christopher J; Grundy, Scott; Gwilliam, Rhian; Gyllensten, Ulf; Hadjadj, Samy; Hallmans, Göran; Hammond, Naomi; Han, Xijing; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hayward, Caroline; Heath, Simon C; Hercberg, Serge; Herder, Christian; Hicks, Andrew A; Hillman, David R; Hingorani, Aroon D; Hofman, Albert; Hui, Jennie; Hung, Joe; Isomaa, Bo; Johnson, Paul R V; Jørgensen, Torben; Jula, Antti; Kaakinen, Marika; Kaprio, Jaakko; Kesaniemi, Y Antero; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G Mark; Lawlor, Debbie A; Le Bacquer, Olivier; Lecoeur, Cécile; Li, Yun; Lyssenko, Valeriya; Mahley, Robert; Mangino, Massimo; Manning, Alisa K; Martínez-Larrad, María Teresa; McAteer, Jarred B; McCulloch, Laura J; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D; Morken, Mario A; Mukherjee, Sutapa; Naitza, Silvia; Narisu, Narisu; Neville, Matthew J; Oostra, Ben A; Orrù, Marco; Pakyz, Ruth; Palmer, Colin N A; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F; Pedersen, Nancy L.; Perola, Markus; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C; Pouta, Anneli; Province, Michael A; Psaty, Bruce M; Rathmann, Wolfgang; Rayner, Nigel W; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Roden, Michael; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Scott, Laura J; Seedorf, Udo; Sharp, Stephen J; Shields, Beverley; Sigurðsson, Gunnar; Sijbrands, Erik J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L; Sovio, Ulla; Swift, Amy; Syddall, Holly; Syvänen, Ann-Christine; Tanaka, Toshiko; Thorand, Barbara; Tichet, Jean; Tönjes, Anke; Tuomi, Tiinamaija; Uitterlinden, André G; van Dijk, Ko Willems; van Hoek, Mandy; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J; Walley, Andrew; Walters, G Bragi; Ward, Kim L; Watkins, Hugh; Weedon, Michael N; Wild, Sarah H; Willemsen, Gonneke; Witteman, Jaqueline C M; Yarnell, John W G; Zeggini, Eleftheria; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M Carola; Borecki, Ingrid B; Loos, Ruth J F; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M; Williams, Gordon H; Hattersley, Andrew T; Silander, Kaisa; Salomaa, Veikko; Smith, George Davey; Bornstein, Stefan R; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R; Cooper, Cyrus; Dedoussis, George V; Serrano-Ríos, Manuel; Morris, Andrew D; Lind, Lars; Palmer, Lyle J; Hu, Frank B.; Franks, Paul W; Ebrahim, Shah; Marmot, Michael; Kao, W H Linda; Pankow, James S; Sampson, Michael J; Kuusisto, Johanna; Laakso, Markku; Hansen, Torben; Pedersen, Oluf; Pramstaller, Peter Paul; Wichmann, H Erich; Illig, Thomas; Rudan, Igor; Wright, Alan F

    2010-01-01

    Circulating glucose levels are tightly regulated. To identify novel glycemic loci, we performed meta-analyses of 21 genome-wide associations studies informative for fasting glucose (FG), fasting insulin (FI) and indices of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 non-diabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with FG/HOMA-B and two associated with FI/HOMA-IR. These include nine new FG loci (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and FAM148B) and one influencing FI/HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB/TMEM195 with type 2 diabetes (T2D). Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify T2D risk loci, as well as loci that elevate FG modestly, but do not cause overt diabetes. PMID:20081858

  19. Genetic Diversity in the Lesser Antilles and Its Implications for the Settlement of the Caribbean Basin.

    Directory of Open Access Journals (Sweden)

    Jada Benn Torres

    Full Text Available Historical discourses about the Caribbean often chronicle West African and European influence to the general neglect of indigenous people's contributions to the contemporary region. Consequently, demographic histories of Caribbean people prior to and after European contact are not well understood. Although archeological evidence suggests that the Lesser Antilles were populated in a series of northward and eastern migratory waves, many questions remain regarding the relationship of the Caribbean migrants to other indigenous people of South and Central America and changes to the demography of indigenous communities post-European contact. To explore these issues, we analyzed mitochondrial DNA and Y-chromosome diversity in 12 unrelated individuals from the First Peoples Community in Arima, Trinidad, and 43 unrelated Garifuna individuals residing in St. Vincent. In this community-sanctioned research, we detected maternal indigenous ancestry in 42% of the participants, with the remainder having haplotypes indicative of African and South Asian maternal ancestry. Analysis of Y-chromosome variation revealed paternal indigenous American ancestry indicated by the presence of haplogroup Q-M3 in 28% of the male participants from both communities, with the remainder possessing either African or European haplogroups. This finding is the first report of indigenous American paternal ancestry among indigenous populations in this region of the Caribbean. Overall, this study illustrates the role of the region's first peoples in shaping the genetic diversity seen in contemporary Caribbean populations.

  20. Genetic affinities within a large global collection of pathogenic Leptospira: implications for strain identification and molecular epidemiology.

    Directory of Open Access Journals (Sweden)

    Kishore Nalam

    Full Text Available Leptospirosis is an important zoonosis with widespread human health implications. The non-availability of accurate identification methods for the individualization of different Leptospira for outbreak investigations poses bountiful problems in the disease control arena. We harnessed fluorescent amplified fragment length polymorphism analysis (FAFLP for Leptospira and investigated its utility in establishing genetic relationships among 271 isolates in the context of species level assignments of our global collection of isolates and strains obtained from a diverse array of hosts. In addition, this method was compared to an in-house multilocus sequence typing (MLST method based on polymorphisms in three housekeeping genes, the rrs locus and two envelope proteins. Phylogenetic relationships were deduced based on bifurcating Neighbor-joining trees as well as median joining network analyses integrating both the FAFLP data and MLST based haplotypes. The phylogenetic relationships were also reproduced through Bayesian analysis of the multilocus sequence polymorphisms. We found FAFLP to be an important method for outbreak investigation and for clustering of isolates based on their geographical descent rather than by genome species types. The FAFLP method was, however, not able to convey much taxonomical utility sufficient to replace the highly tedious serotyping procedures in vogue. MLST, on the other hand, was found to be highly robust and efficient in identifying ancestral relationships and segregating the outbreak associated strains or otherwise according to their genome species status and, therefore, could unambiguously be applied for investigating phylogenetics of Leptospira in the context of taxonomy as well as gene flow. For instance, MLST was more efficient, as compared to FAFLP method, in clustering strains from the Andaman island of India, with their counterparts from mainland India and Sri Lanka, implying that such strains share genetic

  1. Neurofibromatosis without Neurofibromas: Confirmation of a Genotype-Phenotype Correlation and Implications for Genetic Testing

    Directory of Open Access Journals (Sweden)

    B. Quintáns

    2011-04-01

    Full Text Available Neurofibromatosis type 1 (NF1 is a multisystem disease with autosomal dominant inheritance and complete penetrance diagnosed by clinical findings. Cutaneous neurofibromas are present in almost all adult patients in the dermis, epidermis or along the peripheral nerves. Plexiform neurofibromas are subcutaneous or deep lesions involving nerve plexuses or roots. Neurofibromas can degenerate into malignant tumors, with important prognostic implications. NF1 shows a broad clinic variability even within a single family. Exceptions are cases reporting the in-frame microdeletion c.2970_2972delAAT, presenting with the typical pigmentary features of NF1, but no cutaneous or plexiform neurofibromas. We report a patient with a de novo c.2970_2972delAAT mutation who had few café-au-lait spots, only 2 of which measured >15 mm, axillary and submammary freckling, a flat angioma extending over the neck, arm and trunk, a high arched palate, micrognathia, macrocephaly, pes cavus and scoliosis. There was complete absence of observable cutaneous neurofibromas as well as external plexiform neurofibromas. She had had epileptic seizures since childhood; however, a diagnosis of NF1 had not been confirmed until she was 38, partly due to the paucity of characteristic cutaneous stigmata. We confirm the association of the c.2970_2972delAAT mutation in NF1 with a particular clinical phenotype, especially with lack of detectable neurofibromas. For an appropriate management of patients and family counseling, molecular study of the NF1 gene should be considered in patients not fulfilling NIH criteria when other features suggestive of NF1 are present. In the absence of neurofibromas, starting NF1 testing with the screening of exon 17 may be worthwhile.

  2. Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

    NARCIS (Netherlands)

    B. Giardine (Belinda); J. Borg (Joseph); D.R. Higgs (Douglas); K.R. Peterson (Kenneth R.); J.N.J. Philipsen (Sjaak); D. Maglott (Donna); B.K. Singleton (Belinda K.); D.J. Anstee (David J.); A.N. Basak (Nazli); B.H. Clark (Bruce); F.C. Costa (Flavia C.); P. Faustino (Paula); H. Fedosyuk (Halyna); A.E. Felice (Alex); A. Francina (Alain); R. Galanello (Renzo); M.V.E. Gallivan (Monica V. E.); M. Georgitsi (Marianthi); R.J. Gibbons (Richard J.); P.C. Giordano (Piero Carlo); C.L. Harteveld (Cornelis); J.D. Hoyer (James D.); M. Jarvis (Martin); P. Joly (Philippe); E. Kanavakis (Emmanuel); P. Kollia (Panagoula); S. Menzel (Stephan); W.G. Miller (William); K. Moradkhani (Kamran); J. Old (John); A. Papachatzpoulou (Adamantia); M.N. Papadakis (Manoussos); P. Papadopoulos (Petros); S. Pavlovic (Sonja); L. Perseu (Lucia); M. Radmilovic (Milena); C. Riemer (Cathy); S. Satta (Stefania); I.A. Schrijver (Ingrid); M. Stojiljkovic (Maja); S.L. Thein; J. Traeger-Synodinos (Joanne); R. Tully (Ray); T. Wada (Takahito); J.S. Waye (John); C. Wiemann (Claudia); B. Zukic (Branka); D.H.K. Chui (David H. K.); H. Wajcman (Henri); R. Hardison (Ross); G.P. Patrinos (George)

    2011-01-01

    textabstractWe developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public

  3. Enhancing the Capability of N-Dimension Self-Organizing Petrinet using Neuro-Genetic Approach

    Directory of Open Access Journals (Sweden)

    Manuj Darbari

    2011-05-01

    Full Text Available The paper highlight intelligent Urban Traffic control using Neuro-Genetic Petrinet. The combination of genetic algorithm provides dynamic change of weight for faster learning and converging of Neuro-Petrinet.

  4. Applying new genetic approaches to improve quality of population assessment of green and loggerhead turtles

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — As the NOAA-Fisheries? National Sea Turtle Genetics Lab, the SWFSC Marine Turtle Genetics Program has the lead responsibility for generating, analyzing and...

  5. Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach.

    Science.gov (United States)

    Mariani, Louise-Laure; Tesson, Christelle; Charles, Perrine; Cazeneuve, Cécile; Hahn, Valérie; Youssov, Katia; Freeman, Leorah; Grabli, David; Roze, Emmanuel; Noël, Sandrine; Peuvion, Jean-Noel; Bachoud-Levi, Anne-Catherine; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra

    2016-09-01

    iron accumulation. We identified mutations in genes associated with neurodegeneration, including CACNA1A (n = 2), VPS13A (n = 1), UBQLN2 (n = 1), and VCP (n = 1). Huntington disease phenocopies without CAG repeat expansions in HTT are not rare, occurring in 12.4% (28 of 226) herein, and should be considered in genetic counseling. We used next-generation sequencing combined with clinical data and disease evolution to explore multiple etiologies simultaneously. Our combined clinical and genetic exploration of 28 HD phenocopies identified the underlying cause in 35.7% (10 of 28). In conclusion, the etiologies of HD phenocopies are heterogeneous, and clinical evolution should be taken into account when searching for a genetic cause. The panel of candidate genes to be examined is larger than expected but can be guided by specific imaging and clinical features. Other neurodegenerative diseases with late onset in which variant segregation cannot be verified could be productively explored with the combined approach illustrated herein.

  6. An Enterprising Approach to Regional Growth: Implications for Policy and the Role of VET--Support Document

    Science.gov (United States)

    Garlick, Steve; Taylor, Michael; Plummer, Paul

    2007-01-01

    "An Enterprising Approach to Regional Growth: Implications for Policy and the Role of Vocational Education and Training" explores patterns of regional economic growth in Australia over the period 1984 to 2002 with the aim of identifying the drivers of variation in regional growth; the research also aimed to identify regional opportunities and the…

  7. Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

    Science.gov (United States)

    Baumert, Philipp; Lake, Mark J; Stewart, Claire E; Drust, Barry; Erskine, Robert M

    2016-09-01

    Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage.

  8. Clinical and counselling implications of preimplantation genetic diagnosis for Huntington's disease in the UK.

    Science.gov (United States)

    Lashwood, A; Flinter, F

    2001-01-01

    Huntington's disease is an autosomal dominant neurodegenerative disorder that usually occurs in adult life. Individuals at risk can have a gene test before the onset of symptoms, and prenatal diagnosis is available. Preimplantation genetic diagnosis (PGD) for Huntington's disease is now available for couples in whom one partner has the gene for Huntington's disease. A licence to practise PGD is required from the Human Fertilisation and Embryology Authority, and there are several complex issues relating to PGD for Huntington's disease that require consideration. The partner of the Huntington's disease gene carrier should have a presymptomatic test to ensure accuracy in a PGD cycle. There should be a delay between blood sampling and testing for Huntington's disease to allow time for reflection and withdrawal from testing. All PGD treatment has an associated risk of misdiagnosis. If confirmatory prenatal testing is not undertaken after a successful PGD cycle, no confirmation of diagnosis will be obtained at birth. Guidelines indicate that individuals who are at risk cannot be tested before 18 years. There is concern over the ability of a child or adolescent to make an informed choice about testing before this age. Confirmatory testing at birth after PGD would be in direct contravention of these guidelines. In the UK, the law requires consideration of the welfare of children born after assisted conception treatment. Presenting symptoms of Huntington's disease may affect the parenting abilities of an affected individual. There is a need for an assessment of a patient's current Huntington's disease status and their planned provision of care of children if Huntington's disease affects parenting. It has been necessary to create a detailed working protocol for the management of PGD for Huntington's disease to address these issues.

  9. Intramolecular interactions in aminoacyl nucleotides: Implications regarding the origin of genetic coding and protein synthesis

    Science.gov (United States)

    Lacey, J. C., Jr.; Mullins, D. W., Jr.; Watkins, C. L.; Hall, L. M.

    1986-01-01

    Cellular organisms store information as sequences of nucleotides in double stranded DNA. This information is useless unless it can be converted into the active molecular species, protein. This is done in contemporary creatures first by transcription of one strand to give a complementary strand of mRNA. The sequence of nucleotides is then translated into a specific sequence of amino acids in a protein. Translation is made possible by a genetic coding system in which a sequence of three nucleotides codes for a specific amino acid. The origin and evolution of any chemical system can be understood through elucidation of the properties of the chemical entities which make up the system. There is an underlying logic to the coding system revealed by a correlation of the hydrophobicities of amino acids and their anticodonic nucleotides (i.e., the complement of the codon). Its importance lies in the fact that every amino acid going into protein synthesis must first be activated. This is universally accomplished with ATP. Past studies have concentrated on the chemistry of the adenylates, but more recently we have found, through the use of NMR, that we can observe intramolecular interactions even at low concentrations, between amino acid side chains and nucleotide base rings in these adenylates. The use of this type of compound thus affords a novel way of elucidating the manner in which amino acids and nucleotides interact with each other. In aqueous solution, when a hydrophobic amino acid is attached to the most hydrophobic nucleotide, AMP, a hydrophobic interaction takes place between the amino acid side chain and the adenine ring. The studies to be reported concern these hydrophobic interactions.

  10. Construction of the first compendium of chemical-genetic profiles in the fission yeast Schizosaccharomyces pombe and comparative compendium approach.

    Science.gov (United States)

    Han, Sangjo; Lee, Minho; Chang, Hyeshik; Nam, Miyoung; Park, Han-Oh; Kwak, Youn-Sig; Ha, Hye-Jeong; Kim, Dongsup; Hwang, Sung-Ook; Hoe, Kwang-Lae; Kim, Dong-Uk

    2013-07-12

    Genome-wide chemical genetic profiles in Saccharomyces cerevisiae since the budding yeast deletion library construction have been successfully used to reveal unknown mode-of-actions of drugs. Here, we introduce comparative approach to infer drug target proteins more accurately using two compendiums of chemical-genetic profiles from the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe. For the first time, we established DNA-chip based growth defect measurement of genome-wide deletion strains of S. pombe, and then applied 47 drugs to the pooled heterozygous deletion strains to generate chemical-genetic profiles in S. pombe. In our approach, putative drug targets were inferred from strains hypersensitive to given drugs by analyzing S. pombe and S. cerevisiae compendiums. Notably, many evidences in the literature revealed that the inferred target genes of fungicide and bactericide identified by such comparative approach are in fact the direct targets. Furthermore, by filtering out the genes with no essentiality, the multi-drug sensitivity genes, and the genes with less eukaryotic conservation, we created a set of drug target gene candidates that are expected to be directly affected by a given drug in human cells. Our study demonstrated that it is highly beneficial to construct the multiple compendiums of chemical genetic profiles using many different species. The fission yeast chemical-genetic compendium is available at http://pombe.kaist.ac.kr/compendium. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Reductions in genetic diversity of Schistosoma mansoni populations under chemotherapeutic pressure: the effect of sampling approach and parasite population definition.

    Science.gov (United States)

    French, Michael D; Churcher, Thomas S; Basáñez, María-Gloria; Norton, Alice J; Lwambo, Nicholas J S; Webster, Joanne P

    2013-11-01

    Detecting potential changes in genetic diversity in schistosome populations following chemotherapy with praziquantel (PZQ) is crucial if we are to fully understand the impact of such chemotherapy with respect to the potential emergence of resistance and/or other evolutionary outcomes of interventions. Doing so by implementing effective, and cost-efficient sampling protocols will help to optimise time and financial resources, particularly relevant to a disease such as schistosomiasis currently reliant on a single available drug. Here we explore the effect on measures of parasite genetic diversity of applying various field sampling approaches, both in terms of the number of (human) hosts sampled and the number of transmission stages (miracidia) sampled per host for a Schistosoma mansoni population in Tanzania pre- and post-treatment with PZQ. In addition, we explore population structuring within and between hosts by comparing the estimates of genetic diversity obtained assuming a 'component population' approach with those using an 'infrapopulation' approach. We found that increasing the number of hosts sampled, rather than the number of miracidia per host, gives more robust estimates of genetic diversity. We also found statistically significant population structuring (using Wright's F-statistics) and significant differences in the measures of genetic diversity depending on the parasite population definition. The relative advantages, disadvantages and, hence, subsequent reliability of these metrics for parasites with complex life-cycles are discussed, both for the specific epidemiological and ecological scenario under study here and for their future application to other areas and schistosome species.

  12. A general approach for combining diverse rare variant association tests provides improved robustness across a wider range of genetic architectures.

    Science.gov (United States)

    Greco, Brian; Hainline, Allison; Arbet, Jaron; Grinde, Kelsey; Benitez, Alejandra; Tintle, Nathan

    2016-05-01

    The widespread availability of genome sequencing data made possible by way of next-generation technologies has yielded a flood of different gene-based rare variant association tests. Most of these tests have been published because they have superior power for particular genetic architectures. However, for applied researchers it is challenging to know which test to choose in practice when little is known a priori about genetic architecture. Recently, tests have been proposed which combine two particular individual tests (one burden and one variance components) to minimize power loss while improving robustness to a wider range of genetic architectures. In our analysis we propose an expansion of these approaches, yielding a general method that works for combining any number of individual tests. We demonstrate that running multiple different tests on the same data set and using a Bonferroni correction for multiple testing is never better than combining tests using our general method. We also find that using a test statistic that is highly robust to the inclusion of non-causal variants (joint-infinity) together with a previously published combined test (sequence kernel adaptive test-optimal) provides improved robustness to a wide range of genetic architectures and should be considered for use in practice. Software for this approach is supplied. We support the increased use of combined tests in practice - as well as further exploration of novel combined testing approaches using the general framework provided here - to maximize robustness of rare variant testing strategies against a wide range of genetic architectures.

  13. Bioinformatics' approaches to detect genetic variation in whole genome sequencing data

    NARCIS (Netherlands)

    Kerstens, H.H.D.

    2010-01-01

    Current genetic marker repositories are not sufficient or even are completely lacking for most farm animals. However, genetic markers are essential for the development of a research tool facilitating discovery of genetic factors that contribute to resistance to disease and the overall welfare and pe

  14. Construction of the first compendium of chemical-genetic profiles in the fission yeast Schizosaccharomyces pombe and comparative compendium approach

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sangjo [Bioinformatics Lab, Healthcare Group, SK Telecom, 9-1, Sunae-dong, Pundang-gu, Sungnam-si, Kyunggi-do 463-784 (Korea, Republic of); Lee, Minho [Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Chang, Hyeshik [Department of Biological Science, Seoul National University, 599 Gwanakro, Gwanak-gu, Seoul 151-747 (Korea, Republic of); Nam, Miyoung [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764 (Korea, Republic of); Park, Han-Oh [Bioneer Corp., 8-11 Munpyeongseo-ro, Daedeok-gu, Daejeon 306-220 (Korea, Republic of); Kwak, Youn-Sig [Department of Applied Biology, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam 660-701 (Korea, Republic of); Ha, Hye-jeong [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-Gu, Daejeon 305-806 (Korea, Republic of); Kim, Dongsup [Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Hwang, Sung-Ook [Department of Obstetrics and Gynecology, Inha University Hospital, 7-206 Sinheung-dong, Jung-gu, Incheon 400-711 (Korea, Republic of); Hoe, Kwang-Lae [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764 (Korea, Republic of); Kim, Dong-Uk [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-Gu, Daejeon 305-806 (Korea, Republic of)

    2013-07-12

    Highlights: •The first compendium of chemical-genetic profiles form fission yeast was generated. •The first HTS of drug mode-of-action in fission yeast was performed. •The first comparative chemical genetic analysis between two yeasts was conducted. -- Abstract: Genome-wide chemical genetic profiles in Saccharomyces cerevisiae since the budding yeast deletion library construction have been successfully used to reveal unknown mode-of-actions of drugs. Here, we introduce comparative approach to infer drug target proteins more accurately using two compendiums of chemical-genetic profiles from the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe. For the first time, we established DNA-chip based growth defect measurement of genome-wide deletion strains of S. pombe, and then applied 47 drugs to the pooled heterozygous deletion strains to generate chemical-genetic profiles in S. pombe. In our approach, putative drug targets were inferred from strains hypersensitive to given drugs by analyzing S. pombe and S. cerevisiae compendiums. Notably, many evidences in the literature revealed that the inferred target genes of fungicide and bactericide identified by such comparative approach are in fact the direct targets. Furthermore, by filtering out the genes with no essentiality, the multi-drug sensitivity genes, and the genes with less eukaryotic conservation, we created a set of drug target gene candidates that are expected to be directly affected by a given drug in human cells. Our study demonstrated that it is highly beneficial to construct the multiple compendiums of chemical genetic profiles using many different species. The fission yeast chemical-genetic compendium is available at (http://pombe.kaist.ac.kr/compendium)

  15. Next Gen Pop Gen: implementing a high-throughput approach to population genetics in boarfish (Capros aper).

    Science.gov (United States)

    Farrell, Edward D; Carlsson, Jeanette E L; Carlsson, Jens

    2016-12-01

    The recently developed approach for microsatellite genotyping by sequencing (GBS) using individual combinatorial barcoding was further improved and used to assess the genetic population structure of boarfish (Capros aper) across the species' range. Microsatellite loci were developed de novo and genotyped by next-generation sequencing. Genetic analyses of the samples indicated that boarfish can be subdivided into at least seven biological units (populations) across the species' range. Furthermore, the recent apparent increase in abundance in the northeast Atlantic is better explained by demographic changes within this area than by influx from southern or insular populations. This study clearly shows that the microsatellite GBS approach is a generic, cost-effective, rapid and powerful method suitable for full-scale population genetic studies-a crucial element for assessment, sustainable management and conservation of valuable biological resources.

  16. The genetic structure of hawthorn-infesting Rhagoletis pomonella populations in Mexico: implications for sympatric host race formation.

    Science.gov (United States)

    Michel, Andrew P; Rull, Juan; Aluja, Martin; Feder, Jeffrey L

    2007-07-01

    The genetic origins of species may not all trace to the same time and place as the proximate cause(s) for population divergence. Moreover, inherent gene-flow barriers separating populations may not all have evolved under the same geographical circumstances. These considerations have lead to a greater appreciation of the plurality of speciation: that one geographical mode for divergence may not always be sufficient to describe a speciation event. The apple maggot fly, Rhagoletis pomonella, a model system for sympatric speciation via host-plant shifting, has been a surprising contributor to the concept of speciation mode plurality. Previous studies have suggested that past introgression of inversion polymorphism from a hawthorn-fly population in the trans-Mexican volcanic belt (EVTM) introduced diapause life-history variation into a more northern fly population that subsequently contributed to sympatric host race formation and speciation in the United States (US). Here, we report results from a microsatellite survey implying (i) that volcanic activity in the eastern EVTM may have been responsible for the initial geographical isolation of the Mexican and northern hawthorn-fly populations c. 1.57 mya; and (ii) that flies in the Sierra Madre Oriental Mountains (SMO) likely served as a conduit for past gene flow from the EVTM into the US. Indeed, the microsatellite data suggest that the current US population may represent a range expansion from the northern SMO. We discuss the implications of these findings for sympatric race formation in Rhagoletis and speciation theory.

  17. Genetic gating of human fear learning and extinction: possible implications for gene-environment interaction in anxiety disorder.

    Science.gov (United States)

    Lonsdorf, Tina B; Weike, Almut I; Nikamo, Pernilla; Schalling, Martin; Hamm, Alfons O; Ohman, Arne

    2009-02-01

    Pavlovian fear conditioning is a widely used model of the acquisition and extinction of fear. Neural findings suggest that the amygdala is the core structure for fear acquisition, whereas prefrontal cortical areas are given pivotal roles in fear extinction. Forty-eight volunteers participated in a fear-conditioning experiment, which used fear potentiation of the startle reflex as the primary measure to investigate the effect of two genetic polymorphisms (5-HTTLPR and COMTval158met) on conditioning and extinction of fear. The 5-HTTLPR polymorphism, located in the serotonin transporter gene, is associated with amygdala reactivity and neuroticism, whereas the COMTval158met polymorphism, which is located in the gene coding for catechol-O-methyltransferase (COMT), a dopamine-degrading enzyme, affects prefrontal executive functions. Our results show that only carriers of the 5-HTTLPR s allele exhibited conditioned startle potentiation, whereas carriers of the COMT met/met genotype failed to extinguish conditioned fear. These results may have interesting implications for understanding gene-environment interactions in the development and treatment of anxiety disorders.

  18. A synthesis of genetic connectivity in deep-sea fauna and implications for marine reserve design.

    Science.gov (United States)

    Baco, Amy R; Etter, Ron J; Ribeiro, Pedro A; von der Heyden, Sophie; Beerli, Peter; Kinlan, Brian P

    2016-07-01

    With anthropogenic impacts rapidly advancing into deeper waters, there is growing interest in establishing deep-sea marine protected areas (MPAs) or reserves. Reserve design depends on estimates of connectivity and scales of dispersal for the taxa of interest. Deep-sea taxa are hypothesized to disperse greater distances than shallow-water taxa, which implies that reserves would need to be larger in size and networks could be more widely spaced; however, this paradigm has not been tested. We compiled population genetic studies of deep-sea fauna and estimated dispersal distances for 51 studies using a method based on isolation-by-distance slopes. Estimates of dispersal distance ranged from 0.24 km to 2028 km with a geometric mean of 33.2 km and differed in relation to taxonomic and life-history factors as well as several study parameters. Dispersal distances were generally greater for fishes than invertebrates with the Mollusca being the least dispersive sampled phylum. Species that are pelagic as adults were more dispersive than those with sessile or sedentary lifestyles. Benthic species from soft-substrate habitats were generally less dispersive than species from hard substrate, demersal or pelagic habitats. As expected, species with pelagic and/or feeding (planktotrophic) larvae were more dispersive than other larval types. Many of these comparisons were confounded by taxonomic or other life-history differences (e.g. fishes being more dispersive than invertebrates) making any simple interpretation difficult. Our results provide the first rough estimate of the range of dispersal distances in the deep sea and allow comparisons to shallow-water assemblages. Overall, dispersal distances were greater for deeper taxa, although the differences were not large (0.3-0.6 orders of magnitude between means), and imbalanced sampling of shallow and deep taxa complicates any simple interpretation. Our analyses suggest the scales of dispersal and connectivity for reserve design

  19. An integrative systems genetics approach reveals potential causal genes and pathways related to obesity.

    Science.gov (United States)

    Kogelman, Lisette J A; Zhernakova, Daria V; Westra, Harm-Jan; Cirera, Susanna; Fredholm, Merete; Franke, Lude; Kadarmideen, Haja N

    2015-10-20

    Obesity is a multi-factorial health problem in which genetic factors play an important role. Limited results have been obtained in single-gene studies using either genomic or transcriptomic data. RNA sequencing technology has shown its potential in gaining accurate knowledge about the transcriptome, and may reveal novel genes affecting complex diseases. Integration of genomic and transcriptomic variation (expression quantitative trait loci [eQTL] mapping) has identified causal variants that affect complex diseases. We integrated transcriptomic data from adipose tissue and genomic data from a porcine model to investigate the mechanisms involved in obesity using a systems genetics approach. Using a selective gene expression profiling approach, we selected 36 animals based on a previously created genomic Obesity Index for RNA sequencing of subcutaneous adipose tissue. Differential expression analysis was performed using the Obesity Index as a continuous variable in a linear model. eQTL mapping was then performed to integrate 60 K porcine SNP chip data with the RNA sequencing data. Results were restricted based on genome-wide significant single nucleotide polymorphisms, detected differentially expressed genes, and previously detected co-expressed gene modules. Further data integration was performed by detecting co-expression patterns among eQTLs and integration with protein data. Differential expression analysis of RNA sequencing data revealed 458 differentially expressed genes. The eQTL mapping resulted in 987 cis-eQTLs and 73 trans-eQTLs (false discovery rate genes and disease-associated single nucleotide polymorphisms to detect obesity-related genes and pathways. Building a co-expression network using eQTLs resulted in the detection of a module strongly associated with lipid pathways. Furthermore, we detected several obesity candidate genes, for example, ENPP1, CTSL, and ABHD12B. To our knowledge, this is the first study to perform an integrated genomics and

  20. Clinical characteristics of men with non-mosaic Klinefelter syndrome in northeastern China: implications for genetic counseling.

    Science.gov (United States)

    Zhang, M; Fan, H-T; Zheng, H-S; Zhang, Q-S; Feng, S-Q; Li, R-W

    2015-09-10

    Klinefelter syndrome (KS) is the most common genetic cause of male infertility. Widespread development in assisted reproductive technology has provided non-mosaic KS patients with the opportunity of having biological children. Testosterone replacement therapy and micro-dissection testicular sperm extraction are effective sperm retrieval techniques for KS patients. Despite the success of sperm retrieval and intracytoplasmic sperm injection (ICSI), some areas of early aggressive hormonal spermatogenesis and appropriate management of KS remain controversial. Androgenotherapy, a common treatment for KS, carries a risk of decreasing focal spermatogenesis by lowering the gonadotropin content. Inadequately treated hypogonadism increases psychosocial morbidity in KS patients. Preventive care must be provided from the time of diagnosis, preferentially through a multidisciplinary approach. This indicates the need for improved genetic counseling of KS patients. The aim of this study was to report the prevalence of non-mosaic KS in a Chinese infertile male population. The rate of early diagnosis was lower in KS patients; most of these were diagnosed after rising concerns of reproductive capacity. The mean age of patients with sperm or germ cells was significantly lower, while the semen volume of these patients was significantly higher. However, the semen volume was negatively correlated with the age and ratio of luteinizing hormone/testosterone content in KS patients. Therefore, genetic counseling of KS patients should focus on early diagnosis and timely treatment, in addition to improving the quality of life of all KS patients. The use of testosterone replacement therapy and/ or micro-dissection testicular sperm extraction should be preferentially considered for fertility preservation.