WorldWideScience

Sample records for monogenic heritable asc

  1. Development of an autism severity score for mice using Nlgn4 null mutants as a construct-valid model of heritable monogenic autism.

    Science.gov (United States)

    El-Kordi, Ahmed; Winkler, Daniela; Hammerschmidt, Kurt; Kästner, Anne; Krueger, Dilja; Ronnenberg, Anja; Ritter, Caroline; Jatho, Jasmin; Radyushkin, Konstantin; Bourgeron, Thomas; Fischer, Julia; Brose, Nils; Ehrenreich, Hannelore

    2013-08-15

    Autism is the short name of a complex and heterogeneous group of disorders (autism spectrum disorders, ASD) with several lead symptoms required for classification, including compromised social interaction, reduced verbal communication and stereotyped repetitive behaviors/restricted interests. The etiology of ASD is still unknown in most cases but monogenic heritable forms exist that have provided insights into ASD pathogenesis and have led to the notion of autism as a 'synapse disorder'. Among the most frequent monogenic causes of autism are loss-of-function mutations of the NLGN4X gene which encodes the synaptic cell adhesion protein neuroligin-4X (NLGN4X). We previously described autism-like behaviors in male Nlgn4 null mutant mice, including reduced social interaction and ultrasonic communication. Here, we extend the phenotypical characterization of Nlgn4 null mutant mice to both genders and add a series of additional autism-relevant behavioral readouts. We now report similar social interaction and ultrasonic communication deficits in females as in males. Furthermore, aggression, nest-building parameters, as well as self-grooming and circling as indicators of repetitive behaviors/stereotypies were explored in both genders. The construction of a gender-specific autism severity composite score for Nlgn4 mutant mice markedly diminishes population/sample heterogeneity typically obtained for single tests, resulting in p values of 83% for female mice. Taken together, these data underscore the similarity of phenotypical consequences of Nlgn4/NLGN4X loss-of-function in mouse and man, and emphasize the high relevance of Nlgn4 null mutant mice as an ASD model with both construct and face validity.

  2. Monogenic Diabetes

    Science.gov (United States)

    ... form of monogenic diabetes? • What type of monogenic diabetes does my child (or do I) have? • What are the treatment options? • What are the advantages and disadvantages of each treatment option? • Should I see a diabetes educator? • Should I see an endocrinologist? Resources • Find- ...

  3. ASC-1

    DEFF Research Database (Denmark)

    Jakimoski, Goce; Khajuria, Samant

    2011-01-01

    The goal of the modes of operation for authenticated encryption is to achieve faster encryption and message authentication by performing both the encryption and the message authentication in a single pass as opposed to the traditional encrypt-then-mac approach, which requires two passes....... Unfortunately, the use of a block cipher as a building block limits the performance of the authenticated encryption schemes to at most one message block per block cipher evaluation. In this paper, we propose the authenticated encryption scheme ASC-1 (Authenticating Stream Cipher One). Similarly to LEX, ASC-1...... uses leak extraction from diÆerent AES rounds to compute the key material that is XOR-ed with the message to compute the ciphertext. Unlike LEX, the ASC-1 operates in a CFB fashion to compute an authentication tag over the encrypted message. We argue that ASC-1 is secure by reducingits (IND-CCA , INT...

  4. Monogenic diabetes and pregnancy

    OpenAIRE

    Murphy, Rinki

    2015-01-01

    Monogenic diabetes is frequently mistakenly diagnosed as either type 1 or type 2 diabetes, yet accounts for approximately 1–2% of diabetes. Identifying monogenic forms of diabetes has practical implications for specific therapy, screening of family members and genetic counselling. The most common forms of monogenic diabetes are due to glucokinase (GCK), hepatocyte nuclear factor (HNF)-1A and HNF-4A, HNF-1B, m.3243A>G gene defects. Practical aspects of their recognition, diagnosis and manageme...

  5. ASC-1

    DEFF Research Database (Denmark)

    Jakimoski, Goce; Khajuria, Samant

    2011-01-01

    The goal of the modes of operation for authenticated encryption is to achieve faster encryption and message authentication by performing both the encryption and the message authentication in a single pass as opposed to the traditional encrypt-then-mac approach, which requires two passes. Unfortun......The goal of the modes of operation for authenticated encryption is to achieve faster encryption and message authentication by performing both the encryption and the message authentication in a single pass as opposed to the traditional encrypt-then-mac approach, which requires two passes...... uses leak extraction from diÆerent AES rounds to compute the key material that is XOR-ed with the message to compute the ciphertext. Unlike LEX, the ASC-1 operates in a CFB fashion to compute an authentication tag over the encrypted message. We argue that ASC-1 is secure by reducingits (IND-CCA , INT...

  6. Monogenic human obesity syndromes

    National Research Council Canada - National Science Library

    Farooqi, I S; O'Rahilly, S

    2004-01-01

    .... This chapter will consider the human monogenic obesity syndromes that have been characterized to date and discuss how far such observations support the physiological role of these molecules in the regulation of human body weight and neuroendocrine function.

  7. Monogenic human obesity.

    Science.gov (United States)

    Farooqi, I Sadaf

    2008-01-01

    We and others have identified several single gene defects that disrupt the molecules in the leptinmelanocortin pathway causing severe obesity in humans. In this review, we consider these human monogenic obesity syndromes and discuss how far the characterisation of these patients has informed our understanding of the physiological role of leptin and the melanocortins in the regulation of human body weight and neuroendocrine function.

  8. ASC Champ Orbit Model

    DEFF Research Database (Denmark)

    Riis, Troels; Jørgensen, John Leif

    1999-01-01

    This documents describes a test of the implementation of the ASC orbit model for the Champ satellite.......This documents describes a test of the implementation of the ASC orbit model for the Champ satellite....

  9. Monogenic human obesity syndromes.

    Science.gov (United States)

    Farooqi, I S

    2006-01-01

    Over the past decade we have witnessed a major increase in the scale of scientific activity devoted to the study of energy balance and obesity. This explosion of interest has, to a large extent, been driven by the identification of genes responsible for murine obesity syndromes, and the novel physiological pathways revealed by those genetic discoveries. Others and we have also recently identified several single gene defects causing severe human obesity. Many of these defects have been in molecules identical or similar to those identified as a cause of obesity in rodents. I will review the human monogenic obesity syndromes that have been characterised to date and discuss how far such observations support the physiological role of these molecules in the regulation of human body weight and neuroendocrine function.

  10. Animal models of monogenic migraine.

    Science.gov (United States)

    Chen, Shih-Pin; Tolner, Else A; Eikermann-Haerter, Katharina

    2016-06-01

    Migraine is a highly prevalent and disabling neurological disorder with a strong genetic component. Rare monogenic forms of migraine, or syndromes in which migraine frequently occurs, help scientists to unravel pathogenetic mechanisms of migraine and its comorbidities. Transgenic mouse models for rare monogenic mutations causing familial hemiplegic migraine (FHM), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and familial advanced sleep-phase syndrome (FASPS), have been created. Here, we review the current state of research using these mutant mice. We also discuss how currently available experimental approaches, including epigenetic studies, biomolecular analysis and optogenetic technologies, can be used for characterization of migraine genes to further unravel the functional and molecular pathways involved in migraine. © International Headache Society 2016.

  11. Monogenic Functions in Conformal Geometry

    Directory of Open Access Journals (Sweden)

    Michael Eastwood

    2007-08-01

    Full Text Available Monogenic functions are basic to Clifford analysis. On Euclidean space they are defined as smooth functions with values in the corresponding Clifford algebra satisfying a certain system of first order differential equations, usually referred to as the Dirac equation. There are two equally natural extensions of these equations to a Riemannian spin manifold only one of which is conformally invariant. We present a straightforward exposition.

  12. Monogenic diabetes mellitus in Norway

    Directory of Open Access Journals (Sweden)

    Oddmund Søvika

    2013-06-01

    Full Text Available Here, we review data on monogenic diabetes mellitus in Norway based on the Norwegian MODY Registry at Haukeland University Hospital, Bergen. This registry comprises established or suspected cases of maturity-onset diabetes of the young (MODY referred to our laboratory for genetic testing. We also present data on neonatal diabetes, another group of monogenic diabetes. To date, we have genetically diagnosed nearly 500 MODY cases in Norway. Mutations in the HNF1A gene (MODY3 were detected in about 50% of families with clinical MODY. GCK-MODY (MODY2 was the second most prevalent type, but may be underreported. We have also found mutations in the monogenic genes ABCC8, CEL, HNF1B, HNF4A, INS, KCNJ11 and NEUROD1. Based on genetic screening in the Norwegian MODY Registry and HUNT2, we estimate the number of MODY cases in Norway to be at least 2500-5000. Founder effects may determine the geographical distribution of MODY mutations in Norway. The molecular genetic testing of MODY and neonatal diabetes is mandatory for correct diagnosis and prognosis as well as choice of therapy

  13. Early onset (childhood) monogenic neuropathies.

    Science.gov (United States)

    Landrieu, Pierre; Baets, Jonathan

    2013-01-01

    Hereditary neuropathies (HN) with onset in childhood are categorized according to clinical presentation, pathogenic mechanism based on electrophysiology, genetic transmission and, in selected cases, pathological findings. Especially relevant to pediatrics are the items "secondary" versus "primary" neuropathy, "syndromic versus nonsyndromic," and "period of life." Different combinations of these parameters frequently point toward specific monogenic disorders. Ruling out a neuropathy secondary to a generalized metabolic disorder remains the first concern in pediatrics. As a rule, metabolic diseases include additional, orienting symptoms or signs, and their biochemical diagnosis is based on logical algorithms. Primary, motor sensory are the most frequent HN and are dominated by demyelinating autosomal dominant (AD) forms (CMT1). Other forms include demyelinating autosomal recessive (AR) forms, axonal AD/AR forms, and forms with "intermediate" electrophysiological phenotype. Peripheral motor neuron disorders are dominated by AR SMN-linked spinal muscular atrophies. (Distal) hereditary motor neuropathies represent 40 genes with various biological functions have been found to be responsible for primary HN. Many are responsible for various phenotypes, including some without the polyneuropathic trait, and some for various types of transmission.

  14. 77 FR 25168 - Appraisal Subcommittee (ASC); ASC Rules of Operation; Amended

    Science.gov (United States)

    2012-04-27

    ... Federal Housing Finance Agency. The ASC Rules of Operation serve as corporate bylaws outlining the ASC's... amended numerous provisions in Title XI. The ASC Rules of Operation serve as corporate bylaws outlining...

  15. Advanced Stirling Convertor (ASC) Technology Maturation

    Science.gov (United States)

    Wong, Wayne A.; Wilson, Scott; Collins, Josh; Wilson, Kyle

    2016-01-01

    The Advanced Stirling Convertor (ASC) development effort was initiated by NASA Glenn Research Center with contractor Sunpower, Inc., to develop high-efficiency thermal-to-electric power conversion technology for NASA Radioisotope Power Systems (RPSs). Early successful performance demonstrations led to the expansion of the project as well as adoption of the technology by the Department of Energy (DOE) and system integration contractor Lockheed Martin Space Systems Company as part of the Advanced Stirling Radioisotope Generator (ASRG) flight project. The ASRG integrates a pair of ASCs to convert the heat from a pair of General Purpose Heat Source (GPHS) modules into electrical power. The expanded NASA ASC effort included development of several generations of ASC prototypes or engineering units to help prepare the ASC technology and Sunpower for flight implementation. Sunpower later had two parallel contracts allowing the last of the NASA engineering units called ASC-E3 to serve as pathfinders for the ASC-F flight convertors being built for DOE. The ASC-E3 convertors utilized the ASC-F flight specifications and were built using the ASC-F design and process documentation. Shortly after the first ASC-F pair achieved initial operation, due to budget constraints, the DOE ASRG flight development contract was terminated. NASA continues to invest in the development of Stirling RPS technology including continued production of the ASC-E3 convertors, seven of which have been delivered with one additional unit in production. Starting in fiscal year 2015, Stirling Convertor Technology Maturation has been reorganized as an element of the RPS Stirling Cycle Technology Development (SCTD) Project and long-term plans for continued Stirling technology advancement are in reformulation. This paper provides a status on the ASC project, an overview of advancements made in the design and production of the ASC at Sunpower, and a summary of acceptance tests, reliability tests, and tactical

  16. Monogenic Diabetes: A Diagnostic Algorithm for Clinicians

    Directory of Open Access Journals (Sweden)

    Richard W. Carroll

    2013-09-01

    Full Text Available Monogenic forms of beta cell diabetes account for approximately 1%–2% of all cases of diabetes, yet remain underdiagnosed. Overlapping clinical features with common forms of diabetes, make diagnosis challenging. A genetic diagnosis of monogenic diabetes in many cases alters therapy, affects prognosis, enables genetic counseling, and has implications for cascade screening of extended family members. We describe those types of monogenic beta cell diabetes which are recognisable by distinct clinical features and have implications for altered management; the cost effectiveness of making a genetic diagnosis in this setting; the use of complementary diagnostic tests to increase the yield among the vast majority of patients who will have commoner types of diabetes which are summarised in a clinical algorithm; and the vital role of cascade genetic testing to enhance case finding.

  17. Ambulatory Surgical Center (ASC) Payment System

    Data.gov (United States)

    U.S. Department of Health & Human Services — This file contains a summary of service utilization by ASC supplier and is derived from 2011 ASC line item level data, updated through June 2012, that is, line...

  18. Ambulatory Surgical Center (ASC) Payment System

    Data.gov (United States)

    U.S. Department of Health & Human Services — This file contains a summary of service utilization by ASC supplier and is derived from 2011 ASC line item level data, updated through June 2012, that is, line items...

  19. Molekylaer patogenese ved monogen og polygen fedme

    DEFF Research Database (Denmark)

    Larsen, Philip J; Echwald, Søren Morgenthaler; Sørensen, Thorkild I A

    2006-01-01

    During the last few years, studies of the molecular pathogenesis of obesity both in mouse models and in the rare cases of monogenic obesity in humans have added significantly to our understanding of the key role of the hypothalamus in mediating hunger and satiety. These insights have brought us...

  20. Lattice isomorphisms of bisimple monogenic orthodox semigroups

    CERN Document Server

    Goberstein, Simon M

    2011-01-01

    Using the classification and description of the structure of bisimple monogenic orthodox semigroups obtained in \\cite{key10}, we prove that every bisimple orthodox semigroup generated by a pair of mutually inverse elements of infinite order is strongly determined by the lattice of its subsemigroups in the class of all semigroups. This theorem substantially extends an earlier result of \\cite{key25} stating that the bicyclic semigroup is strongly lattice determined.

  1. Precision diabetes: learning from monogenic diabetes.

    Science.gov (United States)

    Hattersley, Andrew T; Patel, Kashyap A

    2017-05-01

    The precision medicine approach of tailoring treatment to the individual characteristics of each patient or subgroup has been a great success in monogenic diabetes subtypes, MODY and neonatal diabetes. This review examines what has led to the success of a precision medicine approach in monogenic diabetes (precision diabetes) and outlines possible implications for type 2 diabetes. For monogenic diabetes, the molecular genetics can define discrete aetiological subtypes that have profound implications on diabetes treatment and can predict future development of associated clinical features, allowing early preventative or supportive treatment. In contrast, type 2 diabetes has overlapping polygenic susceptibility and underlying aetiologies, making it difficult to define discrete clinical subtypes with a dramatic implication for treatment. The implementation of precision medicine in neonatal diabetes was simple and rapid as it was based on single clinical criteria (diagnosed precision diabetes approach in type 2 diabetes will require simple, quick, easily accessible stratification that is based on a combination of routine clinical data, rather than relying on newer technologies. Analysing existing clinical data from routine clinical practice and trials may provide early success for precision medicine in type 2 diabetes.

  2. Pathfinding the Flight Advanced Stirling Convertor Design with the ASC-E3

    Science.gov (United States)

    Wong, Wayne A.; Wilson, Kyle; Smith, Eddie; Collins, Josh

    2012-01-01

    The Advanced Stirling Convertor (ASC) was initially developed by Sunpower, Inc. under contract to NASA Glenn Research Center (GRC) as a technology development project. The ASC technology fulfills NASA's need for high efficiency power convertors for future Radioisotope Power Systems (RPS). Early successful technology demonstrations between 2003 to 2005 eventually led to the expansion of the project including the decision in 2006 to use the ASC technology on the Advanced Stirling Radioisotope Generator (ASRG). Sunpower has delivered 22 ASC convertors of progressively mature designs to date to GRC. Currently, Sunpower with support from GRC, Lockheed Martin Space System Company (LMSSC), and the Department of Energy (DOE) is developing the flight ASC-F in parallel with the ASC-E3 pathfinders. Sunpower will deliver four pairs of ASC-E3 convertors to GRC which will be used for extended operation reliability assessment, independent validation and verification testing, system interaction tests, and to support LMSSC controller verification. The ASC-E3 and -F convertors are being built to the same design and processing documentation and the same product specification. The initial two pairs of ASC-E3 are built before the flight units and will validate design and processing changes prior to implementation on the ASC-F flight convertors. This paper provides a summary on development of the ASC technology and the status of the ASC-E3 build and how they serve the vital pathfinder role ahead of the flight build for ASRG. The ASRG is part of two of the three candidate missions being considered for selection for the Discovery 12 mission.

  3. A Splice Variant of ASC Regulates IL-1β Release and Aggregates Differently from Intact ASC

    Directory of Open Access Journals (Sweden)

    Kazuhiko Matsushita

    2009-01-01

    Full Text Available The apoptosis-associated speck-like protein containing a caspase recruit domain (ASC is involved in apoptosis and innate immunity and is a major adaptor molecule responsible for procaspase-1 activation. ASC mRNA is encoded by three exons: exons 1 and 3 encode a pyrin domain (PYD and caspase recruit domain (CARD, respectively, and exon 2 encodes a proline and glycine-rich (PGR domain. Here, we identified a variant ASC protein (vASC lacking the PGR domain that was smaller than full length ASC (fASC derived from fully transcribed mRNA and searched for differences in biochemical and biological nature. Both fASC and vASC were found to activate procaspase-1 to a similar degree, but the efficiency of IL-1β excretion was significantly higher for vASC. There was also a marked structural difference observed in the fibrous aggregates formed by fASC and vASC. These results suggest that although the PGR domain is dispensable for procaspase-1 activation, it plays an important role in the regulation of the molecular structure and activity of ASC.

  4. Harmonic and Monogenic Potentials in Euclidean Halfspace

    Science.gov (United States)

    Brackx, F.; De Bie, H.; De Schepper, H.

    2011-09-01

    In the framework of Clifford analysis a chain of harmonic and monogenic potentials is constructed in the upper half of Euclidean space Rm+1. Their distributional limits at the boundary are computed, obtaining in this way well-known distributions in Rm such as the Dirac distribution, the Hilbert kernel, the square root of the negative Laplace operator, and the like. It is shown how each of those potentials may be recovered from an adjacent kernel in the chain by an appropriate convolution with such a distributional limit.

  5. ASC-PROBA Interface Control Document

    DEFF Research Database (Denmark)

    Betto, Maurizio; Jørgensen, John Leif; Jørgensen, Finn E;

    1999-01-01

    This document describes the Advanced Stellar Compass (ASC) and defines the interfaces between the instrument and the PROBA satellite. The ASC is a highly advanced and autonomous Stellar Reference Unit designed, developed and produced by the Space Instrumentation Group of the Department of Automat...

  6. Phenotypic heterogeneity of monogenic frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Alberto eBenussi

    2015-09-01

    Full Text Available Frontotemporal dementia (FTD is a genetically and pathologically heterogeneous disorder characterized by personality changes, language impairment and deficits of executive functions associated with frontal and temporal lobe degeneration. Different phenotypes have been defined on the basis of presenting clinical symptoms, i.e. the behavioral variant of FTD (bvFTD, the agrammatic variant of Primary Progressive Aphasia (avPPA and the semantic variant of PPA (svPPA. Some patients have an associated movement disorder, either parkinsonism, as in Progressive Supranuclear Palsy (PSP and Corticobasal Syndrome (CBS, or motor neuron disease (FTD-MND. A family history of dementia is found in 40% of cases of FTD and about 10% have a clear autosomal dominant inheritance. Genetic studies have identified several genes associated to monogenic FTD: microtubule-associated protein tau (MAPT, progranulin (GRN, TAR DNA-binding protein 43 (TARBDP, valosin-containing protein (VCP, charged multivesicular body protein 2B (CHMP2B, fused in sarcoma (FUS and the hexanucleotide repeat expansion in intron 1 of the chromosome 9 open reading frame 72 (C9orf72. Patients often present with an extensive phenotypic variability, even among different members of the same kindred carrying an identical disease mutation. The objective of the present work is to review and evaluate available literature data in order to highlight recent advances in clinical, biological and neuroimaging features of monogenic frontotemporal lobar degeneration and try to identify different mechanisms underlying the extreme phenotypic heterogeneity that characterizes this disease.

  7. Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-Onset Diabetes of the Young

    Science.gov (United States)

    ... Diabetes Monogenic Forms of Diabetes Monogenic Forms of Diabetes The most common forms of diabetes, type 1 ... is inherited from each parent. Monogenic Forms of Diabetes Some rare forms of diabetes result from mutations ...

  8. 75 FR 80813 - Appraisal Subcommittee (ASC); ASC Rules of Operation; Amended

    Science.gov (United States)

    2010-12-23

    ... and Urban Development. (See section 1.02 (4)). Section 3.02. General Powers. The affairs, business and... ASC's powers shall include those set forth in section 1106 of Title XI (12 U.S.C. 3335). The..., ] disapprove or veto. The matter shall be approved or disapproved by a majority vote of the ASC members...

  9. The RH boundary value problem of the k-monogenic functions

    Science.gov (United States)

    Bu, Yude; Du, Jinyuan

    2008-11-01

    In this paper we study the Riemann and Hilbert problems of k-monogenic functions. By using Euler operator, we transform the boundary value problem of k-monogenic functions into the boundary value problems of monogenic functions. Then by the Almansi-type theorem of k-monogenic functions, we get the solutions of these problems.

  10. A Boundary Value Problem for Hermitian Monogenic Functions

    Directory of Open Access Journals (Sweden)

    Reyes JuanBory

    2008-01-01

    Full Text Available Abstract We study the problem of finding a Hermitian monogenic function with a given jump on a given hypersurface in . Necessary and sufficient conditions for the solvability of this problem are obtained.

  11. Monogenic Autoinflammatory Diseases: Concept And Clinical Manifestations

    Science.gov (United States)

    De Jesus, Adriana Almeida; Goldbach-Mansky, Raphaela

    2013-01-01

    The objectives of this review are to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary “periodic fever syndromes”, familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and; 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) 6. very rare conditions presenting with autoinflammation and immunodeficiency. PMID:23711932

  12. Monogenic autoinflammatory diseases: concept and clinical manifestations.

    Science.gov (United States)

    Almeida de Jesus, Adriana; Goldbach-Mansky, Raphaela

    2013-06-01

    The objective of this review is to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary "periodic fever syndromes", familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and; 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) and 6. very rare conditions presenting with autoinflammation and immunodeficiency.

  13. Heritability of antisocial behaviour

    NARCIS (Netherlands)

    Kretschmer, Tina; DeLisi, Matt

    2016-01-01

    This chapter reviews important strands of research on the heritability of antisocial behavior and crime, including both quantitative genetic studies using twin or adoption designs as well as molecular genetic approaches. Study designs are introduced and findings discussed. Contemporary avenues inclu

  14. Heritable Disorders of Connective Tissue

    Science.gov (United States)

    ... Connective Tissue Find a Clinical Trial Journal Articles Connective Tissue August 2016 Questions and Answers about Heritable Disorders of Connective Tissue This publication contains general information about heritable (genetic) ...

  15. Heritability and biological explanation.

    Science.gov (United States)

    Turkheimer, E

    1998-10-01

    Modern neuroscientific and genetic technologies have provoked intense disagreement between scientists who envision a future in which biogenetic theories will enrich or even replace psychological theories, and others who consider biogenetic theories exaggerated, dehumanizing, and dangerous. Both sides of the debate about the role of genes and brains in the genesis of human behavior have missed an important point: All human behavior that varies among individuals is partially heritable and correlated with measurable aspects of brains, but the very ubiquity of these findings makes them a poor basis for reformulating scientists' conceptions of human behavior. Materialism requires psychological processes to be physically instantiated, but more crucial for psychology is the occasional empirical discovery of behavioral phenomena that are specific manifestations of low-level biological variables. Heritability and psychobiological association cannot be the basis for establishing whether behavior is genetic or biological, because to do so leads only to the banal tautology that all behavior is ultimately based in the genotype and brain.

  16. Heritability in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Gordon, Hannah; Trier Moller, Frederik; Andersen, Vibeke

    2015-01-01

    Since Tysk et al's pioneering analysis of the Swedish twin registry, twin and family studies continue to support a strong genetic basis of the inflammatory bowel diseases. The coefficient of heritability for siblings of inflammatory bowel disease probands is 25 to 42 for Crohn's disease and 4 to 15...... for ulcerative colitis. Heritability estimates for Crohn's disease and ulcerative colitis from pooled twin studies are 0.75 and 0.67, respectively. However, this is at odds with the much lower heritability estimates from Genome-Wide Association Studies (GWAS). This "missing heritability" is likely due...... to shortfalls in both family studies and GWAS. The coefficient of heritability fails to account for familial shared environment. Heritability calculations from twin data are based on Falconer's method, with premises that are increasingly understood to be flawed. GWAS based heritability estimates may...

  17. Chimpanzee intelligence is heritable.

    Science.gov (United States)

    Hopkins, William D; Russell, Jamie L; Schaeffer, Jennifer

    2014-07-21

    The role that genes play in human intelligence or IQ has remained a point of significant scientific debate dating back to the time of Galton [1]. It has now become increasingly clear that IQ is heritable in humans, but these effects can be modified by nongenetic mechanisms [2-4]. In contrast to human IQ, until recently, views of learning and cognition in animals have largely been dominated by the behaviorist school of thought, originally championed by Watson [5] and Skinner [6]. A large body of accumulated research now demonstrates a variety of cognitive abilities in nonhuman animals and challenges traditional behaviorist interpretations of performance [7, 8]. This, in turn, has led to a renewed interest in the role that social and biological factors might play in explaining individual and phylogenetic differences in cognition [9]. Specifically, aside from early attempts to selectively breed for learning skills in rodents [10-12], studies examining the role that genetic factors might play in individual variation in cognitive abilities in nonhuman animals, particularly nonhuman primates, are scarce. Here, we utilized a modified Primate Cognitive Test Battery [13] in conjunction with quantitative genetic analyses to examine whether cognitive performance is heritable in chimpanzees. We found that some but not all cognitive traits were significantly heritable in chimpanzees. We further found significant genetic correlations between different dimensions of cognitive functioning, suggesting that the genes that explain the variability of one cognitive trait might also explain that of other cognitive traits.

  18. The AscSimulationMode command

    DEFF Research Database (Denmark)

    Jørgensen, John Leif

    1998-01-01

    Complex instruments like the ASC may be quite difficult to test in closed loops. This problem is augmented by the fact, that no direct stimulation of the CHU is possible that will render the full performance, noise-spectrum and real-timeliness with high fidelity. In order to circumvent this impasse...

  19. A Multi-Model Stereo Similarity Function Based on Monogenic Signal Analysis in Poisson Scale Space

    Directory of Open Access Journals (Sweden)

    Jinjun Li

    2011-01-01

    Full Text Available A stereo similarity function based on local multi-model monogenic image feature descriptors (LMFD is proposed to match interest points and estimate disparity map for stereo images. Local multi-model monogenic image features include local orientation and instantaneous phase of the gray monogenic signal, local color phase of the color monogenic signal, and local mean colors in the multiscale color monogenic signal framework. The gray monogenic signal, which is the extension of analytic signal to gray level image using Dirac operator and Laplace equation, consists of local amplitude, local orientation, and instantaneous phase of 2D image signal. The color monogenic signal is the extension of monogenic signal to color image based on Clifford algebras. The local color phase can be estimated by computing geometric product between the color monogenic signal and a unit reference vector in RGB color space. Experiment results on the synthetic and natural stereo images show the performance of the proposed approach.

  20. Advanced Stirling Convertor (ASC) Development for NASA RPS

    Science.gov (United States)

    Wong, Wayne A.; Wilson, Scott; Collins, Josh

    2014-01-01

    Sunpower's Advanced Stirling Convertor (ASC) initiated development under contract to the NASA Glenn Research Center (GRC) and after a series of successful demonstrations, the ASC began transitioning from a technology development project to flight development project. The ASC has very high power conversion efficiency making it attractive for future Radioisotope Power Systems (RPS) in order to make best use of the low plutonium-238 fuel inventory in the U.S. In recent years, the ASC became part of the NASA-Department of Energy Advanced Stirling Radioisotope Generator (ASRG) Integrated Project. Sunpower held two parallel contracts to produce ASC convertors, one with the Department of Energy/Lockheed Martin to produce the ASC-F flight convertors, and one with NASA GRC for the production of ASC-E3 engineering units, the initial units of which served as production pathfinders. The integrated ASC technical team successfully overcame various technical challenges that led to the completion and delivery of the first two pairs of flight-like ASC-E3 by 2013. However, in late Fall 2013, the DOE initiated termination of the Lockheed Martin ASRG flight development contract driven primarily by budget constraints. NASA continues to recognize the importance of high efficiency ASC power conversion for RPS and continues investment in the technology including the continuation of ASC-E3 production at Sunpower and the assembly of the ASRG Engineering Unit #2. This paper provides a summary of ASC technical accomplishments, overview of tests at GRC, plans for continued ASC production at Sunpower, and status of Stirling technology development.

  1. A Boundary Value Problem for Hermitian Monogenic Functions

    Directory of Open Access Journals (Sweden)

    Ricardo Abreu Blaya

    2008-02-01

    Full Text Available We study the problem of finding a Hermitian monogenic function with a given jump on a given hypersurface in ℝm, m=2n. Necessary and sufficient conditions for the solvability of this problem are obtained.

  2. Heritability of caffeine metabolism

    DEFF Research Database (Denmark)

    Matthaei, Johannes; Tzvetkov, Mladen V; Strube, Jakob

    2016-01-01

    Heritability of caffeine pharmacokinetics and CYP1A2 activity is controversial. Here we analyzed the pharmacokinetics of caffeine, an in vivo probe drug for CYP1A2 and arylamine N-acetyltransferase 2 (NAT2) activity, in monozygotic and dizygotic twins. In the entire group, common and unique...... environmental effects explained most variation in caffeine AUC. Apparently, smoking and hormonal contraceptives masked the genetic effects on CYP1A2 activity. However, when excluding smokers and users of hormonal contraceptives, 89% of caffeine AUC variation was due to genetic effects and even in the entire...... group, 8% of caffeine AUC variation could be explained by a CYP1A1/1A2 promotor polymorphism (rs2470893). In contrast, nearly all of the variation (99%) of NAT2 activity was explained by genetic effects. This study illustrates two very different situations in pharmacogenetics, from an almost exclusively...

  3. Heritability of clubfoot

    DEFF Research Database (Denmark)

    Engell, Vilhelm; Nielsen, Jan; Damborg, Frank

    2014-01-01

    born in Denmark over the last 140 years. All 46,418 twin individuals born from 1931 through 1982, who had earlier consented to contact, received a 17-page Omnibus questionnaire in the spring of 2002. Data were analysed with structural equation models to identify the best fitting aetiological model...... representing 12 monozygotic, 22 same-sex dizygotic, 18 opposite-sex dizygotic, and 3 with unclassified zygosity. The model with only environmental factors (CE) was best fitting based on AIC, and the model with an additive genetic factor (ACE) came in second. Due to the small statistical power, we hypothesise...... based on a balance of goodness-of-fit and parsimony and to estimate heritability. RESULTS: We found an overall self-reported prevalence of congenital clubfoot of 0.0027 (95 % confidence interval 0.0022-0.0034). Fifty-five complete (both twins answered the question) twin pairs were identified...

  4. ASC Trilab L2 Codesign Milestone 2015

    Energy Technology Data Exchange (ETDEWEB)

    Trott, Christian Robert [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hammond, Simon David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Dinge, Dennis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lin, Paul T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Vaughan, Courtenay T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Cook, Jeanine [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Edwards, Harold C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rajan, Mahesh [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hoekstra, Robert J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-09-01

    For the FY15 ASC L2 Trilab Codesign milestone Sandia National Laboratories performed two main studies. The first study investigated three topics (performance, cross-platform portability and programmer productivity) when using OpenMP directives and the RAJA and Kokkos programming models available from LLNL and SNL respectively. The focus of this first study was the LULESH mini-application developed and maintained by LLNL. In the coming sections of the report the reader will find performance comparisons (and a demonstration of portability) for a variety of mini-application implementations produced during this study with varying levels of optimization. Of note is that the implementations utilized including optimizations across a number of programming models to help ensure claims that Kokkos can provide native-class application performance are valid. The second study performed during FY15 is a performance assessment of the MiniAero mini-application developed by Sandia. This mini-application was developed by the SIERRA Thermal-Fluid team at Sandia for the purposes of learning the Kokkos programming model and so is available in only a single implementation. For this report we studied its performance and scaling on a number of machines with the intent of providing insight into potential performance issues that may be experienced when similar algorithms are deployed on the forthcoming Trinity ASC ATS platform.

  5. Orthogonal basis for spherical monogenics by step two branching

    CERN Document Server

    Lavicka, R; Van Lancker, P

    2010-01-01

    Spherical monogenics can be regarded as a basic tool for the study of harmonic analysis of the Dirac operator in Euclidean space R^m. They play a similar role as spherical harmonics do in case of harmonic analysis of the Laplace operator on R^m. Fix the direct sum R^m = R^p x R^q. In this paper we will study the decomposition of the space M_n(R^m;C_m) of spherical monogenics of order n under the action of Spin(p) x Spin(q). As a result we obtain a Spin(p) x Spin(q)-invariant orthonormal basis for M_n(R^m;C_m). In particular, using the construction with p = 2 inductively, this yields a new orthonormal basis for the space M_n(R^m;C_m).

  6. Genomic Heritability: What Is It?

    DEFF Research Database (Denmark)

    de los Campos, Gustavo; Sorensen, Daniel; Gianola, Daniel

    2015-01-01

    of phenotypic variance that can be explained by regression on molecular markers. This is so even though some of the assumptions commonly adopted for data analysis are at odds with important quantitative genetic concepts. In this article we develop theory that leads to a precise definition of parameters arising...... in high dimensional genomic regressions; we focus on the so-called genomic heritability: the proportion of variance of a trait that can be explained (in the population) by a linear regression on a set of markers. We propose a definition of this parameter that is framed within the classical quantitative...... genetics theory and show that the genomic heritability and the trait heritability parameters are equal only when all causal variants are typed. Further, we discuss how the genomic variance and genomic heritability, defined as quantitative genetic parameters, relate to parameters of statistical models...

  7. Scalp fibroblasts have a shared expression profile in monogenic craniosynostosis

    OpenAIRE

    2009-01-01

    Background Craniosynostosis can be caused by both genetic and environmental factors, the relative contributions of which vary between patients. Genetic testing identifies a pathogenic mutation or chromosomal abnormality in ∼21% of cases, but it is likely that further causative mutations remain to be discovered. Objective To identify a shared signature of genetically determined craniosynostosis by comparing the expression patterns in three monogenic syndromes with a control group of patients w...

  8. Polar Body Diagnosis for Monogenic Disorders in Regensburg

    Directory of Open Access Journals (Sweden)

    Hehr A

    2009-01-01

    Full Text Available Polar body diagnosis (PBD is currently the only legal option to perform a preimplantation genetic diagnosis (PGD in Germany. The results of PBD for monogenic disorders performed at our center in Regensburg since 2001 are reported. Our data show that PBD can be safely performed on first and second polar bodies within the tight timeframe provided by the German Embryo Protection Act. It requires extensive interdisciplinary counseling of the couple, good and close cooperation between the IVF center and the genetics laboratory as well as meticulous development, validation, and performance of the individual genetic assay. Provided that these prerequisites are met, PBD can today be an acceptable option for German couples at high risk for a particular monogenic disorder in their offspring. Main arguments pro PBD usually include a decline of both conventional prenatal diagnosis and subsequently induced abortion of an affected offspring as well as the birth of an affected child. Major disadvantages of PBD in this situation include the requirement of assisted reproduction for couples in the absence of any obvious fertility problems with their immanent obstacles like pregnancy rate, remaining recurrence risk for the particular monogenic disorder, costs etc. Furthermore, PBD can only be offered for mutations, which are passed on by the female partner with her nuclear DNA (autosomal dominant, X-chromosomal as well as autosomal recessive traits. For heterozygous female mutation carriers of autosomal recessive or X-chromosomal inherited disorders PBD requires discarding all oocytes carrying the mutation, although they may result in healthy offspring if the sperm does not carry the mutation or the Y chromosome, respectively. Finally, both PBD as well as PGD can substantially reduce the recurrence risk for a particular monogenic disorder but not diminish it entirely. Therefore, conventional prenatal diagnosis (PND should still be offered and in fact has been

  9. Behaviour of the disease resistance gene Asc in protoplasts of Lycopersicon esculentum mill

    NARCIS (Netherlands)

    Moussatos, V.; Witsenboer, H.; Hille, J.; Gilchrist, D.

    1993-01-01

    Action of Asc, a single dominant Mendelian gene controlling disease response at the whole plant level, was detected at the level of individual cells. Protoplasts, freshly isolated from resistant (Asc/Asc) and susceptible (asc/asc) tomato isolines, were differentially sensitive to AAL toxin as observ

  10. Current Progress in Therapeutic Gene Editing for Monogenic Diseases.

    Science.gov (United States)

    Prakash, Versha; Moore, Marc; Yáñez-Muñoz, Rafael J

    2016-03-01

    Programmable nucleases allow defined alterations in the genome with ease-of-use, efficiency, and specificity. Their availability has led to accurate and widespread genome engineering, with multiple applications in basic research, biotechnology, and therapy. With regard to human gene therapy, nuclease-based gene editing has facilitated development of a broad range of therapeutic strategies based on both nonhomologous end joining and homology-dependent repair. This review discusses current progress in nuclease-based therapeutic applications for a subset of inherited monogenic diseases including cystic fibrosis, Duchenne muscular dystrophy, diseases of the bone marrow, and hemophilia and highlights associated challenges and future prospects.

  11. Advanced Stirling Converter (ASC) Phase III Progress Update

    Science.gov (United States)

    Wood, J. Gary; Wilson, Kyle; Buffalino, Andrew; Frye, Patrick; Matejczyk, Dan; Penswick, L. B.

    2007-01-01

    Progress in the development of the Advanced Stirling Convertor (ASC) is presented here. The ASC is being developed under contact with the NASA Glenn Research Center and is supported by the Science Mission Directorate for potential use in future radioisotope power systems having significantly increased efficiency and higher specific power compared to the current thermoelectric systems. Phase II of the effort successfully demonstrated very high conversion efficiency and also demonstrated the low mass capability of the ASC design. The non-hermetic ASC-1 converters demonstrated during Phase II employ superalloy heater heads designed for greater than 14 years life at 850 °C operation. Phase III, which is reported on here, includes the fabrication of multiple next generation hermetic ASC-2 units. Phase III also includes the development of multiple lower-temperature (650 °C hot end) convertors based on the basic ASC design and designated as ASC-0 units. Multiple converters are being built for extended life testing at NASA GRC.

  12. Heritability of adult body height

    DEFF Research Database (Denmark)

    Silventoinen, Karri; Sammalisto, Sampo; Perola, Markus

    2003-01-01

    /unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well...

  13. Genomic heritability: what is it?

    Directory of Open Access Journals (Sweden)

    Gustavo de Los Campos

    2015-05-01

    Full Text Available Whole-genome regression methods are being increasingly used for the analysis and prediction of complex traits and diseases. In human genetics, these methods are commonly used for inferences about genetic parameters, such as the amount of genetic variance among individuals or the proportion of phenotypic variance that can be explained by regression on molecular markers. This is so even though some of the assumptions commonly adopted for data analysis are at odds with important quantitative genetic concepts. In this article we develop theory that leads to a precise definition of parameters arising in high dimensional genomic regressions; we focus on the so-called genomic heritability: the proportion of variance of a trait that can be explained (in the population by a linear regression on a set of markers. We propose a definition of this parameter that is framed within the classical quantitative genetics theory and show that the genomic heritability and the trait heritability parameters are equal only when all causal variants are typed. Further, we discuss how the genomic variance and genomic heritability, defined as quantitative genetic parameters, relate to parameters of statistical models commonly used for inferences, and indicate potential inferential problems that are assessed further using simulations. When a large proportion of the markers used in the analysis are in LE with QTL the likelihood function can be misspecified. This can induce a sizable finite-sample bias and, possibly, lack of consistency of likelihood (or Bayesian estimates. This situation can be encountered if the individuals in the sample are distantly related and linkage disequilibrium spans over short regions. This bias does not negate the use of whole-genome regression models as predictive machines; however, our results indicate that caution is needed when using marker-based regressions for inferences about population parameters such as the genomic heritability.

  14. USDA-ASCS 1936-1939 Air Photos

    Data.gov (United States)

    Minnesota Department of Natural Resources — This data set is a digital version of aerial photographs taken during the 1936-1939 time frame for the USDA-ASCS. These photos were originally recorded at a scale of...

  15. Artificial Loading of ASC Specks with Cytosolic Antigens.

    Directory of Open Access Journals (Sweden)

    Ali Can Sahillioğlu

    Full Text Available Inflammasome complexes form upon interaction of Nod Like Receptor (NLR proteins with pathogen associated molecular patterns (PAPMS inside the cytosol. Stimulation of a subset of inflammasome receptors including NLRP3, NLRC4 and AIM2 triggers formation of the micrometer-sized spherical supramolecular complex called the ASC speck. The ASC speck is thought to be the platform of inflammasome activity, but the reason why a supramolecular complex is preferred against oligomeric platforms remains elusive. We observed that a set of cytosolic proteins, including the model antigen ovalbumin, tend to co-aggregate on the ASC speck. We suggest that co-aggregation of antigenic proteins on the ASC speck during intracellular infection might be instrumental in antigen presentation.

  16. Aquaculture Stewardship Council (ASC) ontwikkeltraject meerval : een inventarisatie

    NARCIS (Netherlands)

    Poelman, M.; Rothuis, A.J.; Bosma, R.H.

    2012-01-01

    Om een Aquaculture Stewardship Council (ASC) gecertificeerd product te krijgen is een standaard nodig, waaraan getoetst kan worden. Deze standaard geeft certificeerders een referentiekader. Pas als een standaard aanwezig is, kunnen producten gecertificeerd worden.

  17. Cost-effectiveness of DNA-diagnosis for four monogenic diseases

    NARCIS (Netherlands)

    A.A.P.M. van der Riet; B.A. van Hout (Ben); F.F.H. Rutten (Frans)

    1994-01-01

    textabstractIn this paper the costs and benefits associated with DNA-diagnosis of individuals who are at risk of a child with a monogenic disease and who seek genetic counselling because of their reproductive plans are predicted under various assumptions using a mathematical model. Four monogenic

  18. Cost-effectiveness of DNA-diagnosis for four monogenic diseases

    NARCIS (Netherlands)

    A.A.P.M. van der Riet; B.A. van Hout (Ben); F.F.H. Rutten (Frans)

    1994-01-01

    textabstractIn this paper the costs and benefits associated with DNA-diagnosis of individuals who are at risk of a child with a monogenic disease and who seek genetic counselling because of their reproductive plans are predicted under various assumptions using a mathematical model. Four monogenic

  19. Clinical, Biological, and Imaging Features of Monogenic Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Andrea Pilotto

    2013-01-01

    Full Text Available The discovery of monogenic forms of Alzheimer’s Disease (AD associated with mutations within PSEN1, PSEN2, and APP genes is giving a big contribution in the understanding of the underpinning mechanisms of this complex disorder. Compared with sporadic form, the phenotype associated with monogenic cases is somewhat broader including behavioural disturbances, epilepsy, myoclonus, and focal presentations. Structural and functional imaging show typical early changes also in presymptomatic monogenic carriers. Amyloid imaging and CSF tau/Aβ ratio may be useful in the differential diagnosis with other neurodegenerative dementias, especially, in early onset cases. However, to date any specific biomarkers of different monogenic cases have been identified. Thus, in clinical practice, the early identification is often difficult, but the copresence of different elements could help in recognition. This review will focus on the clinical and instrumental markers useful for the very early identification of AD monogenic cases, pivotal in the development, and evaluation of disease-modifying therapy.

  20. A dichotomy for upper domination in monogenic classes

    KAUST Repository

    AbouEisha, Hassan M.

    2014-01-01

    An upper dominating set in a graph is a minimal (with respect to set inclusion) dominating set of maximum cardinality. The problem of finding an upper dominating set is NP-hard for general graphs and in many restricted graph families. In the present paper, we study the computational complexity of this problem in monogenic classes of graphs (i.e. classes defined by a single forbidden induced subgraph) and show that the problem admits a dichotomy in this family. In particular, we prove that if the only forbidden induced subgraph is a P4 or a 2K2 (or any induced subgraph of these graphs), then the problem can be solved in polynomial time. Otherwise, it is NP-hard.

  1. Management of suspected monogenic lung fibrosis in a specialised centre

    Directory of Open Access Journals (Sweden)

    Raphael Borie

    2017-04-01

    Full Text Available At least 10% of patients with interstitial lung disease present monogenic lung fibrosis suspected on familial aggregation of pulmonary fibrosis, specific syndromes or early age of diagnosis. Approximately 25% of families have an identified mutation in genes mostly involved in telomere homeostasis, and more rarely in surfactant homeostasis. Beyond pathophysiological knowledge, detection of these mutations has practical consequence for patients. For instance, mutations involved in telomere homeostasis are associated with haematological complications after lung transplantation and may require adapted immunosuppression. Moreover, relatives may benefit from a clinical and genetic evaluation that should be specifically managed. The field of genetics of pulmonary fibrosis has made great progress in the last 10 years, raising specific problems that should be addressed by a specialised team.

  2. Sandia National Laboratories Advanced Simulation and Computing (ASC) software quality plan : ASC software quality engineering practices Version 3.0.

    Energy Technology Data Exchange (ETDEWEB)

    Turgeon, Jennifer L.; Minana, Molly A.; Hackney, Patricia; Pilch, Martin M.

    2009-01-01

    The purpose of the Sandia National Laboratories (SNL) Advanced Simulation and Computing (ASC) Software Quality Plan is to clearly identify the practices that are the basis for continually improving the quality of ASC software products. Quality is defined in the US Department of Energy/National Nuclear Security Agency (DOE/NNSA) Quality Criteria, Revision 10 (QC-1) as 'conformance to customer requirements and expectations'. This quality plan defines the SNL ASC Program software quality engineering (SQE) practices and provides a mapping of these practices to the SNL Corporate Process Requirement (CPR) 001.3.6; 'Corporate Software Engineering Excellence'. This plan also identifies ASC management's and the software project teams responsibilities in implementing the software quality practices and in assessing progress towards achieving their software quality goals. This SNL ASC Software Quality Plan establishes the signatories commitments to improving software products by applying cost-effective SQE practices. This plan enumerates the SQE practices that comprise the development of SNL ASC's software products and explains the project teams opportunities for tailoring and implementing the practices.

  3. Heritability of the limbic networks

    Science.gov (United States)

    Kawadler, Jamie M.; Dell'Acqua, Flavio; Rijsdijk, Frühling V.; Kane, Fergus; Picchioni, Marco; McGuire, Philip; Toulopoulou, Timothea; Georgiades, Anna; Kalidindi, Sridevi; Kravariti, Eugenia; Murray, Robin M.; Murphy, Declan G.; Craig, Michael C.; Catani, Marco

    2016-01-01

    Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins. We explored the connections that contribute to the activity of three distinct functional limbic networks, namely the dorsal cingulum (‘medial default-mode network’), the ventral cingulum and the fornix (‘hippocampal-diencephalic-retrosplenial network’) and the uncinate fasciculus (‘temporo-amygdala-orbitofrontal network’). Genetic and environmental variances were mapped for multiple tract-specific measures that reflect different aspects of the underlying anatomy. We report the highest heritability for the uncinate fasciculus, a tract that underpins emotion processing, semantic cognition, and social behaviour. High to moderate genetic and shared environmental effects were found for pathways important for social behaviour and memory, for example, fornix, dorsal and ventral cingulum. These findings indicate that within the limbic system inheritance of specific traits may rely on the anatomy of distinct networks and is higher for fronto-temporal pathways dedicated to complex social behaviour and emotional processing. PMID:26714573

  4. Monogenic forms of systemic lupus erythematosus: new insights into SLE pathogenesis

    Directory of Open Access Journals (Sweden)

    Belot Alexandre

    2012-08-01

    Full Text Available Abstract The pathogenesis of Systemic Lupus Erythematosus (SLE is complex and remains poorly understood. Infectious triggers, genetic background, immunological abnormalities and environmental factors are all supposed to interact for the disease development. Familial SLE as well as early-onset juvenile SLE studies make it possible to identify monogenic causes of SLE. Identification of these rare inherited conditions is of great interest to understand both SLE pathogenesis and molecular human tolerance mechanisms. Complement deficiencies, genetic overproduction of interferon-α and apoptosis defects are the main situations that can lead to monogenic SLE. Here, we review the different genes involved in monogenic SLE and highlight their importance in SLE pathogenesis.

  5. The heritability of blood donation

    DEFF Research Database (Denmark)

    Pedersen, Ole Birger; Axel, Skytthe; Rostgaard, Klaus

    2015-01-01

    BACKGROUND: Voluntary blood donation is believed to be mostly motivated by altruism. Because studies have suggested that altruistic personality is determined by both genetic and environmental factors, we speculated that willingness to donate blood could also be governed by constitutional factors...... active Danish blood donors from 2002 to 2012, to establish blood donor status for Danish twins, who at age 17 years became eligible for donation in 2002 or later. Casewise concordance in monozygotic (MZ) and dizygotic (DZ) twins were presented and heritability was estimated in Mx by variance component...... to donate blood, respectively. CONCLUSION: Becoming a volunteer blood donor is determined by both genetic and environmental factors shared within families....

  6. Heritability of Attractiveness to Mosquitoes

    Science.gov (United States)

    Fernández-Grandon, G. Mandela; Gezan, Salvador A.; Armour, John A. L.; Pickett, John A.; Logan, James G.

    2015-01-01

    Female mosquitoes display preferences for certain individuals over others, which is determined by differences in volatile chemicals produced by the human body and detected by mosquitoes. Body odour can be controlled genetically but the existence of a genetic basis for differential attraction to insects has never been formally demonstrated. This study investigated heritability of attractiveness to mosquitoes by evaluating the response of Aedes aegypti (=Stegomyia aegypti) mosquitoes to odours from the hands of identical and non-identical twins in a dual-choice assay. Volatiles from individuals in an identical twin pair showed a high correlation in attractiveness to mosquitoes, while non-identical twin pairs showed a significantly lower correlation. Overall, there was a strong narrow-sense heritability of 0.62 (SE 0.124) for relative attraction and 0.67 (0.354) for flight activity based on the average of ten measurements. The results demonstrate an underlying genetic component detectable by mosquitoes through olfaction. Understanding the genetic basis for attractiveness could create a more informed approach to repellent development. PMID:25901606

  7. Overview of ASC Capability Computing System Governance Model

    Energy Technology Data Exchange (ETDEWEB)

    Doebling, Scott W. [Los Alamos National Laboratory

    2012-07-11

    This document contains a description of the Advanced Simulation and Computing Program's Capability Computing System Governance Model. Objectives of the Governance Model are to ensure that the capability system resources are allocated on a priority-driven basis according to the Program requirements; and to utilize ASC Capability Systems for the large capability jobs for which they were designed and procured.

  8. Evaluating the Performance of Albanian Savings and Credit (ASC Union

    Directory of Open Access Journals (Sweden)

    Jonida Bou Dib (Lekocaj

    2013-04-01

    Full Text Available This research paper aimed to evaluate the role of ASC Union through three main poles:its performance in relation to outreach, its financial sustainability, and its welfare impact.It was based mainly on a descriptive study and focused on an accurate event, trying toanswer questions such as: what, where, how, who and when, through the use of differentinformation and already existing theories. Moreover, a triangulated methodologycombining interviews, questionnaires and observations was applied in order to analyze themicrocredit impacts.From the outreach angle, it was found that ASC Union's outreach has shown anincrement over the period of study with different rates of growth from 2003 to 2010 onaverage by 14.7%. On the other hand, the operational sustainability measured by returnon assets and return on equity showed instability over the period of the study, making theASC Union financial sustainability doubtful. In summary, the members confirmed thatASC Union helped them to improve their activities and income, where 87 out of 100farmers confirmed that their income increased in the last 3 years, while 31 farmers out of100, respectively 8, 9 and 10 year-old-members, proclaimed that using the micro-loanhelped them to expand their activities, while 56 farmers confirmed that microcredithelped them not only in improving their income and activity, but also their productionincrement and activity expansion.

  9. 42 CFR 416.164 - Scope of ASC services.

    Science.gov (United States)

    2010-10-01

    ... surgical procedure under § 416.166 include, but are not limited to— (1) Nursing, technician, and related... Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM AMBULATORY SURGICAL SERVICES Coverage, Scope of ASC Services, and...

  10. 76 FR 27668 - ASC Machine Tools, Inc., Spokane Valley, WA; Notice of Negative Determination on Reconsideration

    Science.gov (United States)

    2011-05-12

    ... Employment and Training Administration ASC Machine Tools, Inc., Spokane Valley, WA; Notice of Negative... Regarding Application for Reconsideration for the workers and former workers of ASC Machine Tools, Inc... adjustment assistance for workers and former workers of ASC Machine Tools, Inc., Spokane Valley,...

  11. Solidification of Spent Ion Exchange Resin Using ASC Cement

    Institute of Scientific and Technical Information of China (English)

    周耀中; 云桂春; 叶裕才

    2002-01-01

    Ion exchange resins (IERs) have been widely used in nuclear facilities. However, the spent radioactive IERs result in major quantities of low and intermediate level radioactive wastes. This article describes a laboratory experimental study on solidification processing of IERs using a new type of cement named ASC cement. The strength of the cementation matrix is in the range of 18-20 MPa (28 d); the loading of the spent IER in the cement-resin matrix is over 45% and leaching rates of 137Cs, 90Sr and 60Co are 7.92×10-5, 5.7×10-6, and 1.19×10-8 cm/d. The results show that ASC cement can be a preferable cementation material for immobilization of radioactive spent IER.

  12. Sandia National Laboratories Advanced Simulation and Computing (ASC) Software Quality Plan. Part 2, Mappings for the ASC software quality engineering practices. Version 1.0.

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, Molly A.; Heaphy, Robert; Sturtevant, Judith E.; Hodges, Ann Louise; Boucheron, Edward A.; Drake, Richard Roy; Forsythe, Christi A.; Schofield, Joseph Richard, Jr.; Pavlakos, Constantine James; Williamson, Charles Michael; Edwards, Harold Carter

    2005-01-01

    The purpose of the Sandia National Laboratories Advanced Simulation and Computing (ASC) Software Quality Plan is to clearly identify the practices that are the basis for continually improving the quality of ASC software products. The plan defines the ASC program software quality practices and provides mappings of these practices to Sandia Corporate Requirements CPR 1.3.2 and 1.3.6 and to a Department of Energy document, 'ASCI Software Quality Engineering: Goals, Principles, and Guidelines'. This document also identifies ASC management and software project teams responsibilities in implementing the software quality practices and in assessing progress towards achieving their software quality goals.

  13. Sandia National Laboratories Advanced Simulation and Computing (ASC) software quality plan. Part 1: ASC software quality engineering practices, Version 2.0.

    Energy Technology Data Exchange (ETDEWEB)

    Sturtevant, Judith E.; Heaphy, Robert; Hodges, Ann Louise; Boucheron, Edward A.; Drake, Richard Roy; Minana, Molly A.; Hackney, Patricia; Forsythe, Christi A.; Schofield, Joseph Richard, Jr. (,; .); Pavlakos, Constantine James; Williamson, Charles Michael; Edwards, Harold Carter

    2006-09-01

    The purpose of the Sandia National Laboratories Advanced Simulation and Computing (ASC) Software Quality Plan is to clearly identify the practices that are the basis for continually improving the quality of ASC software products. The plan defines the ASC program software quality practices and provides mappings of these practices to Sandia Corporate Requirements CPR 1.3.2 and 1.3.6 and to a Department of Energy document, ASCI Software Quality Engineering: Goals, Principles, and Guidelines. This document also identifies ASC management and software project teams responsibilities in implementing the software quality practices and in assessing progress towards achieving their software quality goals.

  14. Sandia National Laboratories Advanced Simulation and Computing (ASC) Software Quality Plan. Part 2, Mappings for the ASC software quality engineering practices. Version 1.0.

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, Molly A.; Heaphy, Robert; Sturtevant, Judith E.; Hodges, Ann Louise; Boucheron, Edward A.; Drake, Richard Roy; Forsythe, Christi A.; Schofield, Joseph Richard, Jr.; Pavlakos, Constantine James; Williamson, Charles Michael; Edwards, Harold Carter

    2005-01-01

    The purpose of the Sandia National Laboratories Advanced Simulation and Computing (ASC) Software Quality Plan is to clearly identify the practices that are the basis for continually improving the quality of ASC software products. The plan defines the ASC program software quality practices and provides mappings of these practices to Sandia Corporate Requirements CPR 1.3.2 and 1.3.6 and to a Department of Energy document, 'ASCI Software Quality Engineering: Goals, Principles, and Guidelines'. This document also identifies ASC management and software project teams responsibilities in implementing the software quality practices and in assessing progress towards achieving their software quality goals.

  15. ASC-ATDM Performance Portability Requirements for 2015-2019

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, Harold C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Computing Research Center; Trott, Christian Robert [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Computing Research Center

    2015-03-01

    This report outlines the research, development, and support requirements for the Advanced Simulation and Computing (ASC ) Advanced Technology, Development, and Mitigation (ATDM) Performance Portability (a.k.a., Kokkos) project for 2015 - 2019 . The research and development (R&D) goal for Kokkos (v2) has been to create and demonstrate a thread - parallel programming model a nd standard C++ library - based implementation that enables performance portability across diverse manycore architectures such as multicore CPU, Intel Xeon Phi, and NVIDIA Kepler GPU. This R&D goal has been achieved for algorithms that use data parallel pat terns including parallel - for, parallel - reduce, and parallel - scan. Current R&D is focusing on hierarchical parallel patterns such as a directed acyclic graph (DAG) of asynchronous tasks where each task contain s nested data parallel algorithms. This five y ear plan includes R&D required to f ully and performance portably exploit thread parallelism across current and anticipated next generation platforms (NGP). The Kokkos library is being evaluated by many projects exploring algorithm s and code design for NGP. Some production libraries and applications such as Trilinos and LAMMPS have already committed to Kokkos as their foundation for manycore parallelism an d performance portability. These five year requirements includes support required for current and antic ipated ASC projects to be effective and productive in their use of Kokkos on NGP. The greatest risk to the success of Kokkos and ASC projects relying upon Kokkos is a lack of staffing resources to support Kokkos to the degree needed by these ASC projects. This support includes up - to - date tutorials, documentation, multi - platform (hardware and software stack) testing, minor feature enhancements, thread - scalable algorithm consulting, and managing collaborative R&D.

  16. Advanced Stirling Convertor (ASC)--From Technology Development to Future Flight Product

    Science.gov (United States)

    Wong, Wayne A.; Wood, J. Gary; Wilson, Kyle

    2008-01-01

    The Advanced Stirling Convertor (ASC) is being developed by Sunpower Inc. under contract to NASA s Glenn Research Center (GRC) with critical technology support tasks led by GRC. The ASC development, funded by NASA s Science Mission Directorate, started in 2003 as one of 10 competitively awarded contracts that were intended to address the power conversion needs of future Radioisotope Power Systems (RPS). The ASC technology has since evolved through progressive convertor builds and successful testing to demonstrate high conversion efficiency (38 percent), low mass (1.3 kg), hermetic sealing, launch vibration simulation, EMI characterization, and is undergoing extended operation. The GRC and Sunpower team recently delivered two ASC-E convertors to the Department of Energy (DOE) and Lockheed Martin Space Systems Company for integration onto the Advanced Stirling Radioisotope Generator Engineering Unit (ASRG EU) plus one spare. The design of the next build, called the ASC-E2, has recently been initiated and is based on the heritage ASC-E with design refinements to increase reliability margin and offer higher temperature operation and improve performance. The ASC enables RPS system specific power of about 7 to 8 W/kg. This paper provides a chronology of ASC development to date and summarizes technical achievements including advancements toward flight implementation of the technology on ASRG by as early as 2013.

  17. Heritability of bipolar affective disorder: Family study

    OpenAIRE

    Obradović Tanja; Veličković Ružica; Timotijević Ivana; Anđelković Marko

    2011-01-01

    Background/Aim. Bipolar affective disorder is mental disorder with polygenic type of heredity. Heritability - relation between genetic and environmental variance is used to estimate the level of influence of genetic variance to phenotype variance. Study results show decreasing trend in the value of heritability of bipolar affective disorder, thus indicating that this disorder is a complex behavioral threshold characteristic. Therefore, the aim of this study was to estimate the contribut...

  18. Heritability of bipolar affective disorder: Family study

    Directory of Open Access Journals (Sweden)

    Obradović Tanja

    2011-01-01

    Full Text Available Background/Aim. Bipolar affective disorder is mental disorder with polygenic type of heredity. Heritability - relation between genetic and environmental variance is used to estimate the level of influence of genetic variance to phenotype variance. Study results show decreasing trend in the value of heritability of bipolar affective disorder, thus indicating that this disorder is a complex behavioral threshold characteristic. Therefore, the aim of this study was to estimate the contribution of genetic variance to phenotype variance of bipolar affective disorder, i.e. to estimate heritability of this disorder. Methods. By the use of a questionnaire, 80 patients with over crossed threshold for bipolar affective disorder were asked for functional information about the members of their families belonging to the first degree of relation (fathers, mothers and full- sibs. By using ”Applet for calculating heritability for threshold traits (disease“, and regression analysis, heritability of bipolar affective disorder as well as its statistical significance, were estimated (χ2 test. Results. Heritability and relationship of genetic and environmental variance of bipolar affective disorder is 0.2 with statistically significant difference from zero (p < 0.001. Conclusion. The estimated contribution of genetic variance to phenotype variance of bipolar affective disorder is low being 20%, while the contribution of environmental variance is 80%. This result contributes to the understanding of bipolar affective disorder as a complex behavioral threshold trait.

  19. Multi-vector Spherical Monogenics, Spherical Means and Distributions in Clifford Analysis

    Institute of Scientific and Technical Information of China (English)

    Fred BRACKX; Bram De KNOCK Hennie; De SCHEPPER

    2005-01-01

    New higher-dimensional distributions have been introduced in the framework of Clifford analysis in previous papers by Brackx, Delanghe and Sommen. Those distributions were defined using spherical co-ordinates, the "finite part" distribution Fp xμ+ on the real line and the generalized spherical means involving vector-valued spherical monogenics. In this paper, we make a second generalization,leading to new families of distributions, based on the generalized spherical means involving a multivector-valued spherical monogenic. At the same time, as a result of our attempt at keeping the paper self-contained, it offers an overview of the results found so far.

  20. Evaluation of a target region capture sequencing platform using monogenic diabetes as a study-model

    DEFF Research Database (Denmark)

    Gao, R.; Liu, Y. X.; Gjesing, A. P.;

    2014-01-01

    Background: Monogenic diabetes is a genetic disease often caused by mutations in genes involved in beta-cell function. Correct sub-categorization of the disease is a prerequisite for appropriate treatment and genetic counseling. Target-region capture sequencing is a combination of genomic region...... diabetes as a study-model. Results: The performance of the assay was evaluated in 70 patients carrying known disease causing mutations previously identified in HNF4A, GCK, HNF1A, HNF1B, INS, or KCNJ11. Target regions with a less than 20-fold sequencing depth were either introns or UTRs. When only...... of monogenic diabetes....

  1. Biological Treatments: New Weapons in the Management of Monogenic Autoinflammatory Disorders

    Directory of Open Access Journals (Sweden)

    Antonio Vitale

    2013-01-01

    Full Text Available Treatment of monogenic autoinflammatory disorders, an expanding group of hereditary diseases characterized by apparently unprovoked recurrent episodes of inflammation, without high-titre autoantibodies or antigen-specific T cells, has been revolutionized by the discovery that several of these conditions are caused by mutations in proteins involved in the mechanisms of innate immune response, including components of the inflammasome, cytokine receptors, receptor antagonists, and oversecretion of a network of proinflammatory molecules. Aim of this review is to synthesize the current experience and the most recent evidences about the therapeutic approach with biologic drugs in pediatric and adult patients with monogenic autoinflammatory disorders.

  2. Quantifying missing heritability at known GWAS loci.

    Directory of Open Access Journals (Sweden)

    Alexander Gusev

    Full Text Available Recent work has shown that much of the missing heritability of complex traits can be resolved by estimates of heritability explained by all genotyped SNPs. However, it is currently unknown how much heritability is missing due to poor tagging or additional causal variants at known GWAS loci. Here, we use variance components to quantify the heritability explained by all SNPs at known GWAS loci in nine diseases from WTCCC1 and WTCCC2. After accounting for expectation, we observed all SNPs at known GWAS loci to explain 1.29 x more heritability than GWAS-associated SNPs on average (P=3.3 x 10⁻⁵. For some diseases, this increase was individually significant: 2.07 x for Multiple Sclerosis (MS (P=6.5 x 10⁻⁹ and 1.48 x for Crohn's Disease (CD (P = 1.3 x 10⁻³; all analyses of autoimmune diseases excluded the well-studied MHC region. Additionally, we found that GWAS loci from other related traits also explained significant heritability. The union of all autoimmune disease loci explained 7.15 x more MS heritability than known MS SNPs (P 20,000 Rheumatoid Arthritis (RA samples typed on ImmunoChip, with 2.37 x more heritability from all SNPs at GWAS loci (P = 2.3 x 10⁻⁶ and 5.33 x more heritability from all autoimmune disease loci (P < 1 x 10⁻¹⁶ compared to known RA SNPs (including those identified in this cohort. Our methods adjust for LD between SNPs, which can bias standard estimates of heritability from SNPs even if all causal variants are typed. By comparing adjusted estimates, we hypothesize that the genome-wide distribution of causal variants is enriched for low-frequency alleles, but that causal variants at known GWAS loci are skewed towards common alleles. These findings have important ramifications for fine-mapping study design and our understanding of complex disease architecture.

  3. Sandia National Laboratories Advanced Simulation and Computing (ASC) : appraisal method for the implementation of the ASC software quality engineering practices: Version 1.0.

    Energy Technology Data Exchange (ETDEWEB)

    Turgeon, Jennifer; Minana, Molly A.

    2008-02-01

    This document provides a guide to the process of conducting software appraisals under the Sandia National Laboratories (SNL) ASC Program. The goal of this document is to describe a common methodology for planning, conducting, and reporting results of software appraisals thereby enabling: development of an objective baseline on implementation of the software quality engineering (SQE) practices identified in the ASC Software Quality Plan across the ASC Program; feedback from project teams on SQE opportunities for improvement; identification of strengths and opportunities for improvement for individual project teams; guidance to the ASC Program on the focus of future SQE activities Document contents include process descriptions, templates to promote consistent conduct of appraisals, and an explanation of the relationship of this procedure to the SNL ASC software program.

  4. Advanced Stirling Convertor (ASC) - From Technology Development to Future Flight Product

    Science.gov (United States)

    Wong, Wayne A.; Wood, J. Gary; Wilson, Kyle

    2008-01-01

    The Advanced Stirling Convertor (ASC) is being developed by Sunpower, Inc. under contract to NASA s Glenn Research Center (GRC) with critical technology support tasks lead by GRC. The ASC development, funded by NASA s Science Mission Directorate, started in 2003 as one of 10 competitively awarded contracts that were to address future Radioisotope Power System (RPS) advanced power conversion needs. The ASC technology has since evolved through progressive convertor builds and successful testing to demonstrate high conversion efficiency (38 %), low mass (1.3 kg), hermetic sealing, launch vibration simulation, EMI characterization, and is undergoing extended operation. The GRC and Sunpower team recently delivered three ASC-E machines to the Department of Energy (DOE) and Lockheed Martin Space Systems Company, two units for integration onto the Advanced Stirling Radioisotope Generator Engineering Unit (ASRG EU) plus one spare. The design has recently been initiated for the ASC-E2, an evolution from the ASC-E that substitutes higher temperature materials enabling improved performance and higher reliability margins. This paper summarizes the history and status of the ASC project and discusses plans for this technology which enables RPS specific power of 8 W/kg for future NASA missions.

  5. Heritable and non-heritable genetic effects on retained placenta in Meuse-Rhine-Yssel cattle

    NARCIS (Netherlands)

    Benedictus, L.; Koets, A.P.; Kuijpers, F.H.J.; Joosten, I.; Eldik, van P.; Heuven, H.C.M.

    2013-01-01

    Failure of the timely expulsion of the fetal membranes, called retained placenta, leads to reduced fertility, increased veterinary costs and reduced milk yields. The objectives of this study were to concurrently look at the heritable and non-heritable genetic effects on retained placenta and test th

  6. Depression and quality of life in monogenic compared to idiopathic, early-onset Parkinson's disease

    DEFF Research Database (Denmark)

    Kasten, Meike; Kertelge, Lena; Tadic, Vera

    2012-01-01

    , monogenic and IPD cases were comparable in QoL and depression characteristics. The QoL and, possibly, overall prognosis of all PD patients can be improved by appropriate attention and treatment for depression, sleep impairments, and anxiety, even if the treatment of the motor problems cannot be further...... optimized....

  7. Transcriptional, microscopic and macroscopic investigations into monogenic and polygenic interactions of tomato and powdery mildew

    NARCIS (Netherlands)

    Li Chengwei,

    2005-01-01

    Powdery mildew ( Oidium neolycopersici) is a worldwide obligate fungal disease of tomato ( Solanum lycopersicum ). Six monogenic Ol genes and three major QTLs were identified and mapped on tomato genome. In this thesis, the mechanisms of both compatible and incompatible interactions of tomato and O.

  8. Impaired sense of smell and color discrimination in monogenic and idiopathic Parkinson's disease

    DEFF Research Database (Denmark)

    Kertelge, Lena; Brüggemann, Norbert; Schmidt, Alexander

    2010-01-01

    Olfaction is typically impaired in idiopathic Parkinson's disease (IPD), but its role is uncertain in monogenic PD. Diminished color discrimination has been suggested as another early sign of dopaminergic dysfunction but not been systematically studied. Furthermore, it is unknown whether both def...

  9. Clinical genetics in 2014: New monogenic diseases span the immunological disease continuum.

    Science.gov (United States)

    Savic, Sinisa; McDermott, Michael F

    2015-02-01

    Three monogenic diseases, with features of both autoinflammation and autoimmunity, were described for the first time in 2014. As well as providing insights into the molecular basis of several rare immunological disorders, the discoveries have implications for their diagnosis and treatment.

  10. Characterization of rice blast resistance genes in rice germplasm with monogenic lines and pathogenicity assays

    Science.gov (United States)

    Resistance (R) genes have been effectively deployed in preventing rice crop losses due to the fungus Magnaporthe oryzae. In the present study, we studied the interaction between 24 monogenic lines carrying at least one major R gene, Pia, Pib, Pii, Pik, Pik-h, Pik-m, Pik-p, Pik-s, Pish, Pit, Pita, Pi...

  11. Evaluation of a target region capture sequencing platform using monogenic diabetes as a study-model

    DEFF Research Database (Denmark)

    Gao, Rui; Liu, Yanxia; Gjesing, Anette Marianne Prior;

    2014-01-01

    Monogenic diabetes is a genetic disease often caused by mutations in genes involved in beta-cell function. Correct sub-categorization of the disease is a prerequisite for appropriate treatment and genetic counseling. Target-region capture sequencing is a combination of genomic region enrichment...

  12. Depression and quality of life in monogenic compared to idiopathic, early-onset Parkinson's disease.

    NARCIS (Netherlands)

    Kasten, M.; Kertelge, L.; Tadic, V.; Bruggemann, N.; Schmidt, A.; Vegt, J.P.M. van der; Siebner, H.; Buhmann, C.; Lencer, R.; Kumar, K.R.; Lohmann, K.; Hagenah, J.; Klein, C.

    2012-01-01

    Quality of life (QoL) is decreased in PD and is linked with depression and anxiety. However, little is known about QoL in monogenic PD. Subjects with mutations in PD genes were recruited from ongoing family and genetic studies (manifesting carriers, n = 23; nonmanifesting carriers, n = 19). For comp

  13. Comparison of Effects of Mechanical Stretching on Osteogenic Potential of ASCs and BMSCs

    Institute of Scientific and Technical Information of China (English)

    Brian E. Grottkau; Xingmei Yang; Liang Zhang; Ling Ye; Yunfeng Lin

    2013-01-01

    Mechanical forces play critical roles in the development and remodeling processes of bone. As an alternative cell source for bone engineering, adipose-derived stem cells (ASCs) should be fully investigated for their responses to mechanical stress. Similarly, the osteogenic potential, stimulated by mechanical stress, should be compared with bone marrow stromal cells (BMSCs), which have been clinically used for bone tissue engineering. In this study, ASCs and BMSCs were osteogenic-induced for 48 hours, and then subjected to uniaxial mechanical stretching for 2 or 6 hours. Cell orientation, osteogenic regulatory genes, osteogenic genes and ALP activities were measured and compared between ASCs and BMSCs. ASCs could align in a perpendicular way to the direction of stretching stress, while BMSCs did not present a specific alignment. Both 2 and 6 hours mechanical stretching could enhance the mRNA expression of Osx and Runx2 in BMSCs and ASCs, while OCN mRNA only increased in ASCs after 6 hours mechanical loading. Mechanical stretching enhanced the BMP-2 mRNA expression in ASCs, while only after 6 hours of mechanical loading significantly increased the BMP-2 gene expression in BMSCs. Significant differences only exist between ASCs and BMSCs loaded at 2 hours of mechanical stretching. It is concluded that ASCs are more rapid responders to mechanical stress, and have greater potential than BMSCs in osteogenesis when stimulated by mechanical stretching, indicating their usefulness for bone study in a rat model.

  14. Environmental Loss Characterization of an Advanced Stirling Convertor (ASC-E2) Insulation Package Using a Mock Heater Head

    Science.gov (United States)

    Schifer, Nicholas A.; Briggs, Maxwell H.

    2012-01-01

    The U.S. Department of Energy (DOE) and Lockheed Martin Space Systems Company (LMSSC) have been developing the Advanced Stirling Radioisotope Generator (ASRG) for use as a power system for space science missions. This generator would use two highefficiency Advanced Stirling Convertors (ASCs), developed by Sunpower Inc. and NASA Glenn Research Center (GRC). As part of ground testing of these ASCs, different operating conditions are used to simulate expected mission conditions. These conditions require achieving a specified electrical power output for a given net heat input. While electrical power output can be precisely quantified, thermal power input to the Stirling cycle cannot be directly measured. In an effort to improve net heat input predictions, the Mock Heater Head was developed with the same relative thermal paths as a convertor using a conducting rod to represent the Stirling cycle and tested to provide a direct comparison to numerical and empirical models used to predict convertor net heat input. The Mock Heater Head also served as the pathfinder for a higher fidelity version of validation test hardware, known as the Thermal Standard. This paper describes how the Mock Heater Head was tested and utilized to validate a process for the Thermal Standard.

  15. Assessing the heritability of attentional networks

    Directory of Open Access Journals (Sweden)

    Fossella John A

    2001-09-01

    Full Text Available Abstract Background Current efforts to study the genetics of higher functions have been lacking appropriate phenotypes to describe cognition. One of the problems is that many cognitive concepts for which there is a single word (e.g. attention have been shown to be related to several anatomical networks. Recently we have developed an Attention Network Test (ANT that provides a separate measure for each of three anatomically defined attention networks. In this small scale study, we ran 26 pairs of MZ and DZ twins in an effort to determine if any of these networks show sufficient evidence of heritability to warrant further exploration of their genetic basis. Results The efficiency of the executive attention network, that mediates stimulus and response conflict, shows sufficient heritability to warrant further study. Alerting and overall reaction time show some evidence for heritability and in our study the orienting network shows no evidence of heritability. Conclusions These results suggest that genetic variation contributes to normal individual differences in higher order executive attention involving dopamine rich frontal areas including the anterior cingulate. At least the executive portion of the ANT may serve as a valid endophenotype for larger twin studies and subsequent molecular genetic analysis in normal subject populations.

  16. Sex differences in heritability of neck Pain

    DEFF Research Database (Denmark)

    Fejer, René; Hartvigsen, Jan; Kyvik, Kirsten Ohm

    2006-01-01

    Experimental studies have suggested biological factors as a possible explanation for gender disparities in perception of pain. Recently, heritability of liability to neck pain (NP) has been found to be statistically significantly larger in women compared to men. However, no studies have been cond...

  17. Characterization of ASC-2 as an antiatherogenic transcriptional coactivator of liver X receptors in macrophages.

    Science.gov (United States)

    Kim, Geun Hyang; Park, Keunhee; Yeom, Seon-Yong; Lee, Kyung Jin; Kim, Gukhan; Ko, Jesang; Rhee, Dong-Kwon; Kim, Young Hoon; Lee, Hye Kyung; Kim, Hae Won; Oh, Goo Taeg; Lee, Ki-Up; Lee, Jae W; Kim, Seung-Whan

    2009-07-01

    Activating signal cointegrator-2 (ASC-2) functions as a transcriptional coactivator of many nuclear receptors and also plays important roles in the physiology of the liver and pancreas by interacting with liver X receptors (LXRs), which antagonize the development of atherosclerosis. This study was undertaken to establish the specific function of ASC-2 in macrophages and atherogenesis. Intriguingly, ASC-2 was more highly expressed in macrophages than in the liver and pancreas. To inhibit LXR-specific activity of ASC-2, we used DN2, which contains the C-terminal LXXLL motif of ASC-2 and thereby acts as an LXR-specific, dominant-negative mutant of ASC-2. In DN2-overexpressing transgenic macrophages, cellular cholesterol content was higher and cholesterol efflux lower than in control macrophages. DN2 reduced LXR ligand-dependent increases in the levels of ABCA1, ABCG1, and apolipoprotein E (apoE) transcripts as well as the activity of luciferase reporters driven by the LXR response elements (LXREs) of ABCA1, ABCG1, and apoE genes. These inhibitory effects of DN2 were reversed by overexpression of ASC-2. Chromatin immunoprecipitation analysis demonstrated that ASC-2 was recruited to the LXREs of the ABCA1, ABCG1, and apoE genes in a ligand-dependent manner and that DN2 interfered with the recruitment of ASC-2 to these LXREs. Furthermore, low-density lipoprotein receptor (LDLR)-null mice receiving bone marrow transplantation from DN2-transgenic mice showed accelerated atherogenesis when administered a high-fat diet. Taken together, these results indicate that suppression of the LXR-specific activity of ASC-2 results in both defective cholesterol metabolism in macrophages and accelerated atherogenesis, suggesting that ASC-2 is an antiatherogenic coactivator of LXRs in macrophages.

  18. Sox9 Modulates Proliferation and Expression of Osteogenic Markers of Adipose-Derived Stem Cells (ASC

    Directory of Open Access Journals (Sweden)

    Sabine Stöckl

    2013-05-01

    Full Text Available Background: Mesenchymal stem cells (MSC are promising tools for tissue-engineering and musculoskeletal regeneration. They reside within various tissues, like adipose tissue, periosteum, synovia, muscle, dermis, blood and bone marrow, latter being the most common tissue used for MSC isolation. A promising alternative source for MSC is adipose tissue due to better availability and higher yield of MSC in comparison to bone marrow. A drawback is the yet fragmentary knowledge of adipose-derived stem cell (ASC physiology in order to make them a safe tool for in vivo application. Methods/Results: Here, we identified Sox9 as a highly expressed and crucial transcription factor in undifferentiated rat ASC (rASC. In comparison to rat bone marrow-derived stem cells (rBMSC, mRNA and protein levels of Sox9 were significantly higher in rASC. To study the role of Sox9 in detail, we silenced Sox9 with shRNA in rASC and examined proliferation, apoptosis and the expression of osteogenic differentiation markers. Our results clearly point to a difference in the expression profile of osteogenic marker genes between undifferentiated rASC and rBMSC in early passages. Sox9 silencing induced the expression of osteocalcin, Vegfα and Mmp13, and decreased rASC proliferation accompanied with an induction of p21 and cyclin D1 expression and delayed S-phase entry. Conclusions: We suggest a pro-proliferative role for Sox9 in undifferentiated rASC which may explain the higher proliferation rate of rASC compared to rBMSC. Moreover, we propose an osteogenic differentiation delaying role of Sox9 in rASC which suggests that Sox9 expression is needed to maintain rASC in an undifferentiated, proliferative state.

  19. Sandia National Laboratories Advanced Simulation and Computing (ASC) software quality plan part 2 mappings for the ASC software quality engineering practices, version 2.0.

    Energy Technology Data Exchange (ETDEWEB)

    Heaphy, Robert; Sturtevant, Judith E.; Hodges, Ann Louise; Boucheron, Edward A.; Drake, Richard Roy; Minana, Molly A.; Hackney, Patricia; Forsythe, Christi A.; Schofield, Joseph Richard, Jr. (,; .); Pavlakos, Constantine James; Williamson, Charles Michael; Edwards, Harold Carter

    2006-09-01

    The purpose of the Sandia National Laboratories Advanced Simulation and Computing (ASC) Software Quality Plan is to clearly identify the practices that are the basis for continually improving the quality of ASC software products. The plan defines the ASC program software quality practices and provides mappings of these practices to Sandia Corporate Requirements CPR001.3.2 and CPR001.3.6 and to a Department of Energy document, ''ASCI Software Quality Engineering: Goals, Principles, and Guidelines''. This document also identifies ASC management and software project teams' responsibilities in implementing the software quality practices and in assessing progress towards achieving their software quality goals.

  20. Sandia National Laboratories Advanced Simulation and Computing (ASC) software quality plan part 2 mappings for the ASC software quality engineering practices, version 2.0.

    Energy Technology Data Exchange (ETDEWEB)

    Heaphy, Robert; Sturtevant, Judith E.; Hodges, Ann Louise; Boucheron, Edward A.; Drake, Richard Roy; Minana, Molly A.; Hackney, Patricia; Forsythe, Christi A.; Schofield, Joseph Richard, Jr. (,; .); Pavlakos, Constantine James; Williamson, Charles Michael; Edwards, Harold Carter

    2006-09-01

    The purpose of the Sandia National Laboratories Advanced Simulation and Computing (ASC) Software Quality Plan is to clearly identify the practices that are the basis for continually improving the quality of ASC software products. The plan defines the ASC program software quality practices and provides mappings of these practices to Sandia Corporate Requirements CPR001.3.2 and CPR001.3.6 and to a Department of Energy document, ''ASCI Software Quality Engineering: Goals, Principles, and Guidelines''. This document also identifies ASC management and software project teams' responsibilities in implementing the software quality practices and in assessing progress towards achieving their software quality goals.

  1. SNP based heritability estimation using a Bayesian approach

    DEFF Research Database (Denmark)

    Krag, Kristian; Janss, Luc; Mahdi Shariati, Mohammad;

    2013-01-01

    Heritability is a central element in quantitative genetics. New molecular markers to assess genetic variance and heritability are continually under development. The availability of molecular single nucleotide polymorphism (SNP) markers can be applied for estimation of variance components and heri......Heritability is a central element in quantitative genetics. New molecular markers to assess genetic variance and heritability are continually under development. The availability of molecular single nucleotide polymorphism (SNP) markers can be applied for estimation of variance components...

  2. Sandia National Laboratories Advanced Simulation and Computing (ASC) software quality plan. Part 1 : ASC software quality engineering practices version 1.0.

    Energy Technology Data Exchange (ETDEWEB)

    Minana, Molly A.; Sturtevant, Judith E.; Heaphy, Robert; Hodges, Ann Louise; Boucheron, Edward A.; Drake, Richard Roy; Forsythe, Christi A.; Schofield, Joseph Richard, Jr.; Pavlakos, Constantine James; Williamson, Charles Michael; Edwards, Harold Carter

    2005-01-01

    The purpose of the Sandia National Laboratories (SNL) Advanced Simulation and Computing (ASC) Software Quality Plan is to clearly identify the practices that are the basis for continually improving the quality of ASC software products. Quality is defined in DOE/AL Quality Criteria (QC-1) as conformance to customer requirements and expectations. This quality plan defines the ASC program software quality practices and provides mappings of these practices to the SNL Corporate Process Requirements (CPR 1.3.2 and CPR 1.3.6) and the Department of Energy (DOE) document, ASCI Software Quality Engineering: Goals, Principles, and Guidelines (GP&G). This quality plan identifies ASC management and software project teams' responsibilities for cost-effective software engineering quality practices. The SNL ASC Software Quality Plan establishes the signatories commitment to improving software products by applying cost-effective software engineering quality practices. This document explains the project teams opportunities for tailoring and implementing the practices; enumerates the practices that compose the development of SNL ASC's software products; and includes a sample assessment checklist that was developed based upon the practices in this document.

  3. Specification of the ASC to be used on the PRC satellite (HITSAT)

    DEFF Research Database (Denmark)

    Jørgensen, Finn E; Thuesen, Gøsta; Kilsgaard, Søren;

    1999-01-01

    The document describes the technical specifications of the ASC Star Tracker and the requirements for the equipment onboard the satellite HITSAT .......The document describes the technical specifications of the ASC Star Tracker and the requirements for the equipment onboard the satellite HITSAT ....

  4. 75 FR 65516 - ASC Machine Tools, Inc., Spokane Valley, WA; Notice of Affirmative Determination Regarding...

    Science.gov (United States)

    2010-10-25

    ... Employment and Training Administration ASC Machine Tools, Inc., Spokane Valley, WA; Notice of Affirmative... apply for Trade Adjustment Assistance (TAA) applicable to workers and former workers of ASC Machine Tools, Inc., Spokane Valley, Washington (the subject firm). The Notice of negative determination...

  5. Determinants of Power in Gene-Based Burden Testing for Monogenic Disorders.

    Science.gov (United States)

    Guo, Michael H; Dauber, Andrew; Lippincott, Margaret F; Chan, Yee-Ming; Salem, Rany M; Hirschhorn, Joel N

    2016-09-01

    Whole-exome sequencing has enabled new approaches for discovering genes associated with monogenic disorders. One such approach is gene-based burden testing, in which the aggregate frequency of "qualifying variants" is compared between case and control subjects for each gene. Despite substantial successes of this approach, the genetic causes for many monogenic disorders remain unknown or only partially known. It is possible that particular genetic architectures lower rates of discovery, but the influence of these factors on power has not been rigorously evaluated. Here, we leverage large-scale exome-sequencing data to create an empirically based simulation framework to evaluate the impact of key parameters (background variation rates, locus heterogeneity, mode of inheritance, penetrance) on power in gene-based burden tests in the context of monogenic disorders. Our results demonstrate that across genes, there is a wide range in sample sizes needed to achieve power due to differences in the background rate of rare variants in each gene. Increasing locus heterogeneity results in rapid increases in sample sizes needed to achieve adequate power, particularly when individual genes contribute to less than 5% of cases under a dominant model. Interestingly, incomplete penetrance as low as 10% had little effect on power due to the low prevalence of monogenic disorders. Our results suggest that moderate incomplete penetrance is not an obstacle in this gene-based burden testing approach but that dominant disorders with high locus heterogeneity will require large sample sizes. Our simulations also provide guidance on sample size needs and inform study design under various genetic architectures.

  6. An online monogenic diabetes discussion group: supporting families and fueling new research.

    Science.gov (United States)

    Perrone, Marie E; Carmody, David; Philipson, Louis H; Greeley, Siri Atma W

    2015-11-01

    Many online support groups are available for patients with rare disorders, but scant evidence is available on how effectively such groups provide useful information or valuable psychosocial support to their participants. It is also unclear to what extent physicians and researchers may learn more about these disorders by participating in such groups. To formally assess the utility of the Kovler Monogenic Diabetes Registry online discussion group for patients and families affected by KATP channel-related monogenic neonatal diabetes in providing psychosocial and informational support and in identifying concerns unique to patients with this rare form of diabetes. We qualitatively analyzed all 1,410 messages from the online group that consisted of 64 participants affected by KATP channel monogenic diabetes and 11 researchers. We utilized the Social Behavior Support Code to assign each message to a support category and deductive thematic analysis to identify discussion topics addressed by each message. 44% of messages provided/requested informational support, whereas 31.4% of the messages contained psychosocial/emotional support. The most popular topics of postings to the forums were diabetes treatment (503 messages) and neurodevelopmental concerns (472 messages). Participation in the discussion led researchers to modify survey instruments and design new studies focusing on specific topics of concern, such as sleep. We demonstrate that an online support group for a monogenic form of diabetes is an effective informational tool that also provides psychosocial support. Participation by researchers and care providers can inform future research directions and highlight issues of patient concern. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias.

    Science.gov (United States)

    Johansen, Christopher T; Dubé, Joseph B; Loyzer, Melissa N; MacDonald, Austin; Carter, David E; McIntyre, Adam D; Cao, Henian; Wang, Jian; Robinson, John F; Hegele, Robert A

    2014-04-01

    We report the design of a targeted resequencing panel for monogenic dyslipidemias, LipidSeq, for the purpose of replacing Sanger sequencing in the clinical detection of dyslipidemia-causing variants. We also evaluate the performance of the LipidSeq approach versus Sanger sequencing in 84 patients with a range of phenotypes including extreme blood lipid concentrations as well as additional dyslipidemias and related metabolic disorders. The panel performs well, with high concordance (95.2%) in samples with known mutations based on Sanger sequencing and a high detection rate (57.9%) of mutations likely to be causative for disease in samples not previously sequenced. Clinical implementation of LipidSeq has the potential to aid in the molecular diagnosis of patients with monogenic dyslipidemias with a high degree of speed and accuracy and at lower cost than either Sanger sequencing or whole exome sequencing. Furthermore, LipidSeq will help to provide a more focused picture of monogenic and polygenic contributors that underlie dyslipidemia while excluding the discovery of incidental pathogenic clinically actionable variants in nonmetabolism-related genes, such as oncogenes, that would otherwise be identified by a whole exome approach, thus minimizing potential ethical issues.

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

    Science.gov (United States)

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

    2014-01-01

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

  9. Clinical Pregenetic Screening for Stroke Monogenic Diseases: Results From Lombardia GENS Registry.

    Science.gov (United States)

    Bersano, Anna; Markus, Hugh Stephen; Quaglini, Silvana; Arbustini, Eloisa; Lanfranconi, Silvia; Micieli, Giuseppe; Boncoraglio, Giorgio B; Taroni, Franco; Gellera, Cinzia; Baratta, Silvia; Penco, Silvana; Mosca, Lorena; Grasso, Maurizia; Carrera, Paola; Ferrari, Maurizio; Cereda, Cristina; Grieco, Gaetano; Corti, Stefania; Ronchi, Dario; Bassi, Maria Teresa; Obici, Laura; Parati, Eugenio A; Pezzini, Alessando; De Lodovici, Maria Luisa; Verrengia, Elena P; Bono, Giorgio; Mazucchelli, Francesca; Zarcone, Davide; Calloni, Maria Vittoria; Perrone, Patrizia; Bordo, Bianca Maria; Colombo, Antonio; Padovani, Alessandro; Cavallini, Anna; Beretta, Simone; Ferrarese, Carlo; Motto, Cristina; Agostoni, Elio; Molini, Graziella; Sasanelli, Francesco; Corato, Manuel; Marcheselli, Simona; Sessa, Maria; Comi, Giancarlo; Checcarelli, Nicoletta; Guidotti, Mario; Uccellini, Davide; Capitani, Erminio; Tancredi, Lucia; Arnaboldi, Marco; Incorvaia, Barbara; Tadeo, Carlo Sebastiano; Fusi, Laura; Grampa, Giampiero; Merlini, Giampaolo; Trobia, Nadia; Comi, Giacomo Pietro; Braga, Massimiliano; Vitali, Paolo; Baron, Pierluigi; Grond-Ginsbach, Caspar; Candelise, Livia

    2016-07-01

    Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of genetic analysis. In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease. In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series. © 2016 American Heart Association, Inc.

  10. Heritability in the genomics era--concepts and misconceptions.

    Science.gov (United States)

    Visscher, Peter M; Hill, William G; Wray, Naomi R

    2008-04-01

    Heritability allows a comparison of the relative importance of genes and environment to the variation of traits within and across populations. The concept of heritability and its definition as an estimable, dimensionless population parameter was introduced by Sewall Wright and Ronald Fisher nearly a century ago. Despite continuous misunderstandings and controversies over its use and application, heritability remains key to the response to selection in evolutionary biology and agriculture, and to the prediction of disease risk in medicine. Recent reports of substantial heritability for gene expression and new estimation methods using marker data highlight the relevance of heritability in the genomics era.

  11. Genetics, realized heritability and possible mechanism of chlorfenapyr resistance in Oxycarenus hyalinipennis (Lygaeidae: Hemiptera).

    Science.gov (United States)

    Ullah, Saif; Shah, Rizwan Mustafa; Shad, Sarfraz Ali

    2016-10-01

    Dusky cotton bug (DCB), Oxycarenus hyalinipennis (Lygaeidae: Hemiptera) is a serious pest of cotton and other malvaceous plants. Chlorfenapyr, a broad spectrum, N-substituted, halogenated pyrrole insecticide is used extensively to control many insect pests in cotton, including DCB. In this study, we investigated a field strain of DCB to assess its potential to develop resistance to chlorfenapyr. After six generations of continuous selection pressure with chlorfenapyr, DCB had a 7.24-fold and 149.06-fold resistance ratio (RR) at G1 and G6, respectively. The genetic basis of inheritance of chlorfenapyr resistance was also studied by crossing the chlorfenapyr selected (Chlorfenapyr-SEL) and laboratory population (Lab-PK). Results revealed an autosomal and incompletely dominant mode of inheritance for chlorfenapyr resistance in the Chlorfenapyr-SEL population of DCB. The results of the monogenic model test showed chlorfenapyr resistance was controlled by multiple genes. Estimated realized heritability for chlorfenapyr resistance in the tested DCB strain was 0.123. Synergism bioassays with piperonyl butoxide and S, S, S-butyl phosphorotrithioate revealed chlorfenapyr resistance might be due to esterase activity. These results would be useful for devising an effective resistance management strategy against DCB. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Potential Pitfalls in Estimating Viral Load Heritability.

    Science.gov (United States)

    Leventhal, Gabriel E; Bonhoeffer, Sebastian

    2016-09-01

    In HIV patients, the set-point viral load (SPVL) is the most widely used predictor of disease severity. Yet SPVL varies over several orders of magnitude between patients. The heritability of SPVL quantifies how much of the variation in SPVL is due to transmissible viral genetics. There is currently no clear consensus on the value of SPVL heritability, as multiple studies have reported apparently discrepant estimates. Here we illustrate that the discrepancies in estimates are most likely due to differences in the estimation methods, rather than the study populations. Importantly, phylogenetic estimates run the risk of being strongly confounded by unrealistic model assumptions. Care must be taken when interpreting and comparing the different estimates to each other.

  13. Novel molecular therapies for heritable skin disorders.

    Science.gov (United States)

    Uitto, Jouni; Christiano, Angela M; McLean, W H Irwin; McGrath, John A

    2012-03-01

    Tremendous progress has been made in the past two decades in molecular genetics of heritable skin diseases, and pathogenic mutations have been identified in as many as 500 distinct human genes. This progress has resulted in improved diagnosis with prognostic implications, has refined genetic counseling, and has formed the basis for prenatal and presymptomatic testing and preimplantation genetic diagnosis. However, there has been relatively little progress in developing effective and specific treatments for these often devastating diseases. However, very recently, a number of novel molecular strategies, including gene therapy, cell-based approaches, and protein replacement therapy, have been explored for the treatment of these conditions. This overview will focus on the prototypic heritable blistering disorders, epidermolysis bullosa, and related keratinopathies, in which significant progress has been made recently toward treatment, and it will illustrate how some of the translational research therapies have already entered the clinical arena.

  14. The heritability of leucocyte telomere length dynamics

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob B; Dalgård, Christine; Möller, Sören

    2015-01-01

    BACKGROUND: Leucocyte telomere length (LTL) is a complex trait associated with ageing and longevity. LTL dynamics are defined by LTL and its age-dependent attrition. Strong, but indirect evidence suggests that LTL at birth and its attrition during childhood largely explains interindividual LTL...... unique environmental factors, estimated at 72% (95% CI 56% to 84%) affected LTL attrition rate with no indication of shared environmental effects. CONCLUSIONS: This is the first study that estimated heritability of LTL and also its age-dependent attrition. As LTL attrition is much slower in adults than...... in children and given that having a long or a short LTL is largely determined before adulthood, our findings suggest that heritability and early life environment are the main determinants of LTL throughout the human life course. Thus, insights into factors that influence LTL at birth and its dynamics during...

  15. Food neophobia shows heritable variation in humans.

    Science.gov (United States)

    Knaapila, Antti; Tuorila, Hely; Silventoinen, Karri; Keskitalo, Kaisu; Kallela, Mikko; Wessman, Maija; Peltonen, Leena; Cherkas, Lynn F; Spector, Tim D; Perola, Markus

    2007-08-15

    Food neophobia refers to reluctance to eat unfamiliar foods. We determined the heritability of food neophobia in a family and a twin sample. The family sample consisted of 28 Finnish families (105 females, 50 males, aged 18-78 years, mean age 49 years) and the twin sample of 468 British female twin pairs (211 monozygous and 257 dizygous pairs, aged 17-82 years, mean age 55 years). Food neophobia was measured using the ten-item Food Neophobia Scale (FNS) questionnaire, and its internationally validated six-item modification. The heritability estimate for food neophobia was 69 and 66% in Finnish families (h(2)) and 67 and 66% in British female twins (a(2)+d(2)) using the ten- and six-item versions of the FNS, respectively. The results from both populations suggest that about two thirds of variation in food neophobia is genetically determined.

  16. Differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC regulates inflammasomes

    Directory of Open Access Journals (Sweden)

    Rojanasakul Yon

    2010-05-01

    Full Text Available Abstract Background The apoptotic speck-like protein containing a caspase recruitment domain (ASC is the essential adaptor protein for caspase 1 mediated interleukin (IL-1β and IL-18 processing in inflammasomes. It bridges activated Nod like receptors (NLRs, which are a family of cytosolic pattern recognition receptors of the innate immune system, with caspase 1, resulting in caspase 1 activation and subsequent processing of caspase 1 substrates. Hence, macrophages from ASC deficient mice are impaired in their ability to produce bioactive IL-1β. Furthermore, we recently showed that ASC translocates from the nucleus to the cytosol in response to inflammatory stimulation in order to promote an inflammasome response, which triggers IL-1β processing and secretion. However, the precise regulation of inflammasomes at the level of ASC is still not completely understood. In this study we identified and characterized three novel ASC isoforms for their ability to function as an inflammasome adaptor. Methods To establish the ability of ASC and ASC isoforms as functional inflammasome adaptors, IL-1β processing and secretion was investigated by ELISA in inflammasome reconstitution assays, stable expression in THP-1 and J774A1 cells, and by restoring the lack of endogenous ASC in mouse RAW264.7 macrophages. In addition, the localization of ASC and ASC isoforms was determined by immunofluorescence staining. Results The three novel ASC isoforms, ASC-b, ASC-c and ASC-d display unique and distinct capabilities to each other and to full length ASC in respect to their function as an inflammasome adaptor, with one of the isoforms even showing an inhibitory effect. Consistently, only the activating isoforms of ASC, ASC and ASC-b, co-localized with NLRP3 and caspase 1, while the inhibitory isoform ASC-c, co-localized only with caspase 1, but not with NLRP3. ASC-d did not co-localize with NLRP3 or with caspase 1 and consistently lacked the ability to function as an

  17. Heritable change caused by transient transcription errors.

    Directory of Open Access Journals (Sweden)

    Alasdair J E Gordon

    2013-06-01

    Full Text Available Transmission of cellular identity relies on the faithful transfer of information from the mother to the daughter cell. This process includes accurate replication of the DNA, but also the correct propagation of regulatory programs responsible for cellular identity. Errors in DNA replication (mutations and protein conformation (prions can trigger stable phenotypic changes and cause human disease, yet the ability of transient transcriptional errors to produce heritable phenotypic change ('epimutations' remains an open question. Here, we demonstrate that transcriptional errors made specifically in the mRNA encoding a transcription factor can promote heritable phenotypic change by reprogramming a transcriptional network, without altering DNA. We have harnessed the classical bistable switch in the lac operon, a memory-module, to capture the consequences of transient transcription errors in living Escherichia coli cells. We engineered an error-prone transcription sequence (A9 run in the gene encoding the lac repressor and show that this 'slippery' sequence directly increases epigenetic switching, not mutation in the cell population. Therefore, one altered transcript within a multi-generational series of many error-free transcripts can cause long-term phenotypic consequences. Thus, like DNA mutations, transcriptional epimutations can instigate heritable changes that increase phenotypic diversity, which drives both evolution and disease.

  18. Composition-dependent structural changes and antitumor activity of ASC-DP/DSPE-PEG nanoparticles.

    Science.gov (United States)

    Higashi, Kenjirou; Mibu, Fusako; Saito, Kengo; Limwikrant, Waree; Yamamoto, Keiji; Moribe, Kunikazu

    2017-03-01

    Ascorbyl 2,6-dipalmitate (ASC-DP) and distearoyl phosphatidylethanolamine polyethylene glycol 2000 (DSPE-PEG) formed stable nanoparticles at a molar ratio of less than or equal to 2:1 after dispersing the solvent-evaporated film in water. The mean particle sizes measured by dynamic light scattering were within the range of ca. 100-160nm. Composition-dependent changes of the ASC-DP and DSPE-PEG molecular states within the film were analyzed by wide-angle X-ray diffraction and infrared (IR) and solid-state nuclear magnetic resonance (NMR) spectroscopy. Transmission electron microscopy (TEM) of nanoparticles revealed that ASC-DP/DSPE-PEG changed from a micelle to a disk and tubular structure as the molar ratio increased. Quantitative solution-state (1)H NMR measurements elucidated the structure of nanoparticle in water; the core could be composed of ASC-DP and hydrophobic acyl chains of DSPE, whereas the hydrophilic PEG chains of DSPE-PEG on the surface form the hydration shell to stabilize the nanoparticle dispersion in water. Cytotoxicity of ASC-DP against cancer cell lines was observed by using ASC-DP/DSPE-PEG nanoparticles, and no cytotoxicity against normal cells was found. Thus, the ASC-DP/DSPE-PEG formulation, with tumor cell specific cytotoxicity, can be applicable for cancer monotherapy or in combination with other anticancer drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. ASC Predictive Science Academic Alliance Program Verification and Validation Whitepaper

    Energy Technology Data Exchange (ETDEWEB)

    Klein, R; Graziani, F; Trucano, T

    2006-03-31

    The purpose of this whitepaper is to provide a framework for understanding the role that verification and validation (V&V) are expected to play in successful ASC Predictive Science Academic Alliance (PSAA) Centers and projects. V&V have been emphasized in the recent specification of the PSAA (NNSA, 2006): (1) The resulting simulation models lend themselves to practical verification and validation methodologies and strategies that should include the integrated use of experimental and/or observational data as a key part of model and sub-model validation, as well as demonstrations of numerical convergence and accuracy for code verification. (2) Verification, validation and prediction methodologies and results must be much more strongly emphasized as research topics and demonstrated via the proposed simulations. (3) It is mandatory that proposals address the following two topics: (a) Predictability in science & engineering; and (b) Verification & validation strategies for large-scale simulations, including quantification of uncertainty and numerical convergence. We especially call attention to the explicit coupling of computational predictability and V&V in the third bullet above. In this whitepaper we emphasize this coupling, and provide concentrated guidance for addressing item 2. The whitepaper has two main components. First, we provide a brief and high-level tutorial on V&V that emphasizes critical elements of the program. Second, we state a set of V&V-related requirements that successful PSAA proposals must address.

  20. Revealing the complexity of a monogenic disease: rett syndrome exome sequencing.

    Directory of Open Access Journals (Sweden)

    Elisa Grillo

    Full Text Available Rett syndrome (OMIM#312750 is a monogenic disorder that may manifest as a large variety of phenotypes ranging from very severe to mild disease. Since there is a weak correlation between the mutation type in the Xq28 disease-gene MECP2/X-inactivation status and phenotypic variability, we used this disease as a model to unveil the complex nature of a monogenic disorder. Whole exome sequencing was used to analyze the functional portion of the genome of two pairs of sisters with Rett syndrome. Although each pair of sisters had the same MECP2 (OMIM*300005 mutation and balanced X-inactivation, one individual from each pair could not speak or walk, and had a profound intellectual deficit (classical Rett syndrome, while the other individual could speak and walk, and had a moderate intellectual disability (Zappella variant. In addition to the MECP2 mutation, each patient has a group of variants predicted to impair protein function. The classical Rett girls, but not their milder affected sisters, have an enrichment of variants in genes related to oxidative stress, muscle impairment and intellectual disability and/or autism. On the other hand, a subgroup of variants related to modulation of immune system, exclusive to the Zappella Rett patients are driving toward a milder phenotype. We demonstrate that genome analysis has the potential to identify genetic modifiers of Rett syndrome, providing insight into disease pathophysiology. Combinations of mutations that affect speaking, walking and intellectual capabilities may represent targets for new therapeutic approaches. Most importantly, we demonstrated that monogenic diseases may be more complex than previously thought.

  1. Revealing the complexity of a monogenic disease: rett syndrome exome sequencing.

    Science.gov (United States)

    Grillo, Elisa; Lo Rizzo, Caterina; Bianciardi, Laura; Bizzarri, Veronica; Baldassarri, Margherita; Spiga, Ottavia; Furini, Simone; De Felice, Claudio; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Ciccoli, Lucia; Mencarelli, Maria Antonietta; Hayek, Joussef; Meloni, Ilaria; Ariani, Francesca; Mari, Francesca; Renieri, Alessandra

    2013-01-01

    Rett syndrome (OMIM#312750) is a monogenic disorder that may manifest as a large variety of phenotypes ranging from very severe to mild disease. Since there is a weak correlation between the mutation type in the Xq28 disease-gene MECP2/X-inactivation status and phenotypic variability, we used this disease as a model to unveil the complex nature of a monogenic disorder. Whole exome sequencing was used to analyze the functional portion of the genome of two pairs of sisters with Rett syndrome. Although each pair of sisters had the same MECP2 (OMIM*300005) mutation and balanced X-inactivation, one individual from each pair could not speak or walk, and had a profound intellectual deficit (classical Rett syndrome), while the other individual could speak and walk, and had a moderate intellectual disability (Zappella variant). In addition to the MECP2 mutation, each patient has a group of variants predicted to impair protein function. The classical Rett girls, but not their milder affected sisters, have an enrichment of variants in genes related to oxidative stress, muscle impairment and intellectual disability and/or autism. On the other hand, a subgroup of variants related to modulation of immune system, exclusive to the Zappella Rett patients are driving toward a milder phenotype. We demonstrate that genome analysis has the potential to identify genetic modifiers of Rett syndrome, providing insight into disease pathophysiology. Combinations of mutations that affect speaking, walking and intellectual capabilities may represent targets for new therapeutic approaches. Most importantly, we demonstrated that monogenic diseases may be more complex than previously thought.

  2. Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes.

    Science.gov (United States)

    Yang, Yisheng; Chan, Lawrence

    2016-06-01

    To date, more than 30 genes have been linked to monogenic diabetes. Candidate gene and genome-wide association studies have identified > 50 susceptibility loci for common type 1 diabetes (T1D) and approximately 100 susceptibility loci for type 2 diabetes (T2D). About 1-5% of all cases of diabetes result from single-gene mutations and are called monogenic diabetes. Here, we review the pathophysiological basis of the role of monogenic diabetes genes that have also been found to be associated with common T1D and/or T2D. Variants of approximately one-third of monogenic diabetes genes are associated with T2D, but not T1D. Two of the T2D-associated monogenic diabetes genes-potassium inward-rectifying channel, subfamily J, member 11 (KCNJ11), which controls glucose-stimulated insulin secretion in the β-cell; and peroxisome proliferator-activated receptor γ (PPARG), which impacts multiple tissue targets in relation to inflammation and insulin sensitivity-have been developed as major antidiabetic drug targets. Another monogenic diabetes gene, the preproinsulin gene (INS), is unique in that INS mutations can cause hyperinsulinemia, hyperproinsulinemia, neonatal diabetes mellitus, one type of maturity-onset diabetes of the young (MODY10), and autoantibody-negative T1D. Dominant heterozygous INS mutations are the second most common cause of permanent neonatal diabetes. Moreover, INS gene variants are strongly associated with common T1D (type 1a), but inconsistently with T2D. Variants of the monogenic diabetes gene Gli-similar 3 (GLIS3) are associated with both T1D and T2D. GLIS3 is a key transcription factor in insulin production and β-cell differentiation during embryonic development, which perturbation forms the basis of monogenic diabetes as well as its association with T1D. GLIS3 is also required for compensatory β-cell proliferation in adults; impairment of this function predisposes to T2D. Thus, monogenic forms of diabetes are invaluable "human models" that have

  3. Engineering a bilayered hydrogel to control ASC differentiation.

    Science.gov (United States)

    Natesan, Shanmugasundaram; Zamora, David O; Suggs, Laura J; Christy, Robert J

    2012-05-25

    Natural polymers over the years have gained more importance because of their host biocompatibility and ability to interact with cells in vitro and in vivo. An area of research that holds promise in regenerative medicine is the combinatorial use of novel biomaterials and stem cells. A fundamental strategy in the field of tissue engineering is the use of three-dimensional scaffold (e.g., decellularized extracellular matrix, hydrogels, micro/nano particles) for directing cell function. This technology has evolved from the discovery that cells need a substrate upon which they can adhere, proliferate, and express their differentiated cellular phenotype and function. More recently, it has also been determined that cells not only use these substrates for adherence, but also interact and take cues from the matrix substrate (e.g., extracellular matrix, ECM). Therefore, the cells and scaffolds have a reciprocal connection that serves to control tissue development, organization, and ultimate function. Adipose-derived stem cells (ASCs) are mesenchymal, non-hematopoetic stem cells present in adipose tissue that can exhibit multi-lineage differentiation and serve as a readily available source of cells (i.e. pre-vascular endothelia and pericytes). Our hypothesis is that adipose-derived stem cells can be directed toward differing phenotypes simultaneously by simply co-culturing them in bilayered matrices. Our laboratory is focused on dermal wound healing. To this end, we created a single composite matrix from the natural biomaterials, fibrin, collagen, and chitosan that can mimic the characteristics and functions of a dermal-specific wound healing ECM environment.

  4. Representation of distributions by harmonic and monogenic potentials in Euclidean space

    OpenAIRE

    Brackx, Fred; De Bie, Hendrik; De Schepper, Hennie

    2015-01-01

    In the framework of Clifford analysis, a chain of harmonic and monogenic potentials in the upper half of Euclidean space $R^{m+1}_+$ was recently constructed, including a higher dimensional analogue of the logarithmic function in the complex plane, and their distributional boundary values were computed. In this paper we determine these potentials in lower half-space $R^{m+1}_-$ and investigate whether they can be extended through the boundary $R^m$. This is a stepping stone to the representat...

  5. Low heritability in pharmacokinetics of talinolol

    DEFF Research Database (Denmark)

    Matthaei, Johannes; Tzvetkov, Mladen V; Gal, Valerie;

    2016-01-01

    BACKGROUND: Efflux transporters like MDR1 and MRP2 may modulate the pharmacokinetics of about 50 % of all drugs. It is currently unknown how much of the variation in the activities of important drug membrane transporters like MDR1 or MRP2 is determined by genetic or by environmental factors....... In this study we assessed the heritability of the pharmacokinetics of talinolol as a putative probe drug for MDR1 and possibly other membrane transporters. METHODS: Talinolol pharmacokinetics were investigated in a repeated dose study in 42 monozygotic and 13 same-sex dizygotic twin pairs. The oral clearance...

  6. Immunomagnetic Separation of Fat Depot-Specific Sca1high Adipose-Derived Stem Cells (Ascs)

    Science.gov (United States)

    Barnes, Richard H; Chun, Tae-Hwa

    2016-01-01

    The isolation of adipose-derived stem cells (ASCs) is an important method in the field of adipose tissue biology, adipogenesis, and extracellular matrix (ECM) remodeling. In vivo, ECM-rich environment consisting of fibrillar collagens provides a structural support to adipose tissues during the progression and regression of obesity. Physiological ECM remodeling mediated by matrix metalloproteinases (MMPs) plays a major role in regulating adipose tissue size and function1, 2. The loss of physiological collagenolytic ECM remodeling may lead to excessive collagen accumulation (tissue fibrosis), macrophage infiltration, and ultimately, a loss of metabolic homeostasis including insulin resistance3, 4. When a phenotypic change of the adipose tissue is observed in gene-targeted mouse models, isolating primary ASCs from fat depots for in vitro studies is an effective approach to define the role of the specific gene in regulating the function of ASCs. In the following, we define an immunomagnetic separation of Sca1high ASCs. PMID:27583550

  7. Evaluation of replacement protocols and modifications to TCP to enhance ASC Wide Area Network performance.

    Energy Technology Data Exchange (ETDEWEB)

    Romero, Randy L. Jr.

    2004-09-01

    Historically, TCP/IP has been the protocol suite used to transfer data throughout the Advanced Simulation and Computing (ASC) community. However, TCP was developed many years ago for an environment very different from the ASC Wide Area Network (WAN) of today. There have been numerous publications that hint of better performance if modifications were made to the TCP algorithms or a different protocol was used to transfer data across a high bandwidth, high delay WAN. Since Sandia National Laboratories wants to maximize the ASC WAN performance to support the Thor's Hammer supercomputer, there is strong interest in evaluating modifications to the TCP protocol and in evaluating alternatives to TCP, such as SCTP, to determine if they provide improved performance. Therefore, the goal of this project is to test, evaluate, compare, and report protocol technologies that enhance the performance of the ASC WAN.

  8. Heritability of cognitive functions in families with bipolar disorder.

    Science.gov (United States)

    Antila, Mervi; Tuulio-Henriksson, Annamari; Kieseppä, Tuula; Soronen, Pia; Palo, Outi M; Paunio, Tiina; Haukka, Jari; Partonen, Timo; Lönnqvist, Jouko

    2007-09-01

    Bipolar disorder is highly heritable. Cognitive dysfunctions often observed in bipolar patients and their unaffected relatives implicate that these impairments may be associated with genetic predisposition to bipolar disorder and thus fulfill the criteria of a valid endophenotype for the disorder. However, the most fundamental criterion, their heritability, has not been directly studied in any bipolar population. This population-based study estimated the heritability of cognitive functions in bipolar disorder. A comprehensive neuropsychological test battery and the Structured Clinical Interview for DSM-IV were administered to a population-based sample of 110 individuals from 52 families with bipolar disorder. Heritability of cognitive functions as assessed with neuropsychological test scores were estimated using the Solar package. Significant additive heritabilities were found in verbal ability, executive functioning, and psychomotor processing speed. Genetic contribution was low to verbal learning functions. High heritability, in executive functioning and psychomotor processing speed suggest that these may be valid endophenotypic traits for genetic studies of bipolar disorder.

  9. Methylation mediated silencing of TMS1/ASC gene in prostate cancer

    Directory of Open Access Journals (Sweden)

    Gopisetty Gopal

    2006-07-01

    Full Text Available Abstract Background Transcriptional silencing associated with aberrant promoter methylation has been established as an alternate pathway for the development of cancer by inactivating tumor suppressor genes. TMS1 (Target of Methylation induced Silencing, also known as ASC (Apoptosis Speck like protein containing a CARD is a tumor suppressor gene which encodes for a CARD (caspase recruitment domain containing regulatory protein and has been shown to promote apoptosis directly and by activation of downstream caspases. This study describes the methylation induced silencing of TMS1/ASC gene in prostate cancer cell lines. We also examined the prevalence of TMS1/ASC gene methylation in prostate cancer tissue samples in an effort to correlate race and clinico-pathological features with TMS1/ASC gene methylation. Results Loss of TMS1/ASC gene expression associated with complete methylation of the promoter region was observed in LNCaP cells. Gene expression was restored by a demethylating agent, 5-aza-2'deoxycytidine, but not by a histone deacetylase inhibitor, Trichostatin A. Chromatin Immunoprecipitation (ChIP assay showed enrichment of MBD3 (methyl binding domain protein 3 to a higher degree than commonly associated MBDs and MeCP2. We evaluated the methylation pattern in 66 prostate cancer and 34 benign prostatic hyperplasia tissue samples. TMS1/ASC gene methylation was more prevalent in prostate cancer cases than controls in White patients (OR 7.6, p 0.002 while no difference between the cases and controls was seen in Black patients (OR 1.1, p 0.91. Conclusion Our study demonstrates that methylation-mediated silencing of TMS1/ASC is a frequent event in prostate cancer, thus identifying a new potential diagnostic and prognostic marker for the treatment of the disease. Racial differences in TMS1/ASC methylation patterns implicate the probable role of molecular markers in determining in susceptibility to prostate cancer in different ethnic groups.

  10. Overall accuracy of cervical cytology and clinicopathological significance of LSIL cells in ASC-H cytology.

    Science.gov (United States)

    Kim, S H; Lee, J M; Yun, H G; Park, U S; Hwang, S U; Pyo, J-S; Sohn, J H

    2017-02-01

    The aims of this study were (i) to investigate the diagnostic accuracy of Papanicolaou (Pap) smears and (ii) to evaluate the clinicopathological significance of the presence of low-grade squamous intraepithelial lesion (LSIL) cells in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) cytology. We retrospectively reviewed paired cytological and histological findings from 3141 patients. ASC-H cytology was classified as either ASC-H or LSIL with some features suggestive of the presence of a concurrent HSIL (LSIL-H). Clinicopathological characteristics were evaluated through a retrospective study and meta-analysis. The accuracy of the cytological diagnosis was 93.7% (2942 of 3141 cases). The positive predictive value (PPV) of ASC-H for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+ ) was 51.4%. In cases of LSIL-H, CIN 2+ histology was more prevalent in the pre-menopausal period (19-44 years) than in peri- and postmenopausal periods (older than 45 years) (P = 0.024). There was no difference in the ability of LSIL-H and ASC-H to predict CIN 2+. The Pap smear is a good cervical cancer screening method. Although there was no difference in the predictive value for CIN 2+ between LSIL-H and ASC-H, the presence of definite LSIL cells was more predictive of CIN 2+ in younger patients than in older patients. © 2016 John Wiley & Sons Ltd.

  11. Beyond missing heritability: prediction of complex traits.

    Directory of Open Access Journals (Sweden)

    Robert Makowsky

    2011-04-01

    Full Text Available Despite rapid advances in genomic technology, our ability to account for phenotypic variation using genetic information remains limited for many traits. This has unfortunately resulted in limited application of genetic data towards preventive and personalized medicine, one of the primary impetuses of genome-wide association studies. Recently, a large proportion of the "missing heritability" for human height was statistically explained by modeling thousands of single nucleotide polymorphisms concurrently. However, it is currently unclear how gains in explained genetic variance will translate to the prediction of yet-to-be observed phenotypes. Using data from the Framingham Heart Study, we explore the genomic prediction of human height in training and validation samples while varying the statistical approach used, the number of SNPs included in the model, the validation scheme, and the number of subjects used to train the model. In our training datasets, we are able to explain a large proportion of the variation in height (h(2 up to 0.83, R(2 up to 0.96. However, the proportion of variance accounted for in validation samples is much smaller (ranging from 0.15 to 0.36 depending on the degree of familial information used in the training dataset. While such R(2 values vastly exceed what has been previously reported using a reduced number of pre-selected markers (<0.10, given the heritability of the trait (∼ 0.80, substantial room for improvement remains.

  12. Insights from Mendelian Interferonopathies: Comparison of CANDLE, SAVI with AGS, Monogenic Lupus.

    Science.gov (United States)

    Kim, Hanna; Sanchez, Gina A Montealegre; Goldbach-Mansky, Raphaela

    2016-10-01

    Autoinflammatory disorders are sterile inflammatory conditions characterized by episodes of early-onset fever and disease-specific patterns of organ inflammation. Recently, the discoveries of monogenic disorders with strong type I interferon (IFN) signatures caused by mutations in proteasome degradation and cytoplasmic RNA and DNA sensing pathways suggest a pathogenic role of IFNs in causing autoinflammatory phenotypes. The IFN response gene signature (IGS) has been associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. In this review, we compare the clinical presentations and pathogenesis of two IFN-mediated autoinflammatory diseases, CANDLE and SAVI, with Aicardi Goutières syndrome (AGS) and monogenic forms of SLE (monoSLE) caused by loss-of-function mutations in complement 1 (C1q) or the DNA nucleases, DNASE1 and DNASE1L3. We outline differences in intracellular signaling pathways that fuel a pathologic type I IFN amplification cycle. While IFN amplification is caused by predominantly innate immune cell dysfunction in SAVI, CANDLE, and AGS, autoantibodies to modified RNA and DNA antigens interact with tissues and immune cells including neutrophils and contribute to IFN upregulation in some SLE patients including monoSLE, thus justifying a grouping of "autoinflammatory" and "autoimmune" interferonopathies. Understanding of the differences in the cellular sources and signaling pathways will guide new drug development and the use of emerging targeted therapies.

  13. Monogenic Auto-inflammatory Syndromes: A Review of the Literature.

    Science.gov (United States)

    Azizi, Gholamreza; Khadem Azarian, Shahin; Nazeri, Sepideh; Mosayebian, Ali; Ghiasy, Saleh; Sadri, Ghazal; Mohebi, Ali; Khan Nazer, Nikoo Hossein; Afraei, Sanaz; Mirshafiey, Abbas

    2016-12-01

    Auto-inflammatory syndromes are a new group of distinct hereditable disorders characterized by episodes of seemingly unprovoked inflammation (most commonly in skin, joints, gut, and eye), the absence of a high titer of auto-antibodies or auto-reactive T cells, and an inborn error of innate immunity. A narrative literature review was carried out of studies related to auto-inflammatory syndromes to discuss the pathogenesis and clinical manifestation of these syndromes. This review showed that the main monogenic auto-inflammatory syndromes are familial Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS), and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA). The data suggest that correct diagnosis and treatment of monogenic auto-inflammatory diseases relies on the physicians' awareness. Therefore, understanding of the underlying pathogenic mechanisms of auto-inflammatory syndromes, and especially the fact that these disorders are mediated by IL-1 secretion stimulated by monocytes and macrophages, facilitated significant progress in patient management.

  14. Intrusion detection on oil pipeline right of way using monogenic signal representation

    Science.gov (United States)

    Nair, Binu M.; Santhaseelan, Varun; Cui, Chen; Asari, Vijayan K.

    2013-05-01

    We present an object detection algorithm to automatically detect and identify possible intrusions such as construction vehicles and equipment on the regions designated as the pipeline right-of-way (ROW) from high resolution aerial imagery. The pipeline industry has buried millions of miles of oil pipelines throughout the country and these regions are under constant threat of unauthorized construction activities. We propose a multi-stage framework which uses a pyramidal template matching scheme in the local phase domain by taking a single high resolution training image to classify a construction vehicle. The proposed detection algorithm makes use of the monogenic signal representation to extract the local phase information. Computing the monogenic signal from a two dimensional object region enables us to separate out the local phase information (structural details) from the local energy (contrast) thereby achieving illumination invariance. The first stage involves the local phase based template matching using only a single high resolution training image in a local region at multiple scales. Then, using the local phase histogram matching, the orientation of the detected region is determined and a voting scheme gives a certain weightage to the resulting clusters. The final stage involves the selection of clusters based on the number of votes attained and using the histogram of oriented phase feature descriptor, the object is located at the correct orientation and scale. The algorithm is successfully tested on four different datasets containing imagery with varying image resolution and object orientation.

  15. Human induced pluripotent stem cells for monogenic disease modelling and therapy

    Institute of Scientific and Technical Information of China (English)

    Paola; Spitalieri; Valentina; Rosa; Talarico; Michela; Murdocca; Giuseppe; Novelli; Federica; Sangiuolo

    2016-01-01

    Recent and advanced protocols are now available toderive human induced pluripotent stem cells(hi PSCs)from patients affected by genetic diseases.No curative treatments are available for many of these diseases;thus,hiP SCs represent a major impact on patient’health.hiP SCs represent a valid model for the in vitro study of monogenic diseases,together with a better comprehension of the pathogenic mechanisms of the pathology,for both cell and gene therapy protocol applications.Moreover,these pluripotent cells represent a good opportunity to test innovative pharmacological treatments focused on evaluating the efficacy and toxicity of novel drugs.Today,innovative gene therapy protocols,especially gene editingbased,are being developed,allowing the use of these cells not only as in vitro disease models but also as an unlimited source of cells useful for tissue regeneration and regenerative medicine,eluding ethical and immune rejection problems.In this review,we will provide an upto-date of modelling monogenic disease by using hiP SCs and the ultimate applications of these in vitro models for cell therapy.We consider and summarize some peculiar aspects such as the type of parental cells used for reprogramming,the methods currently used to induce the transcription of the reprogramming factors,and the type of iP SC-derived differentiated cells,relating them to the genetic basis of diseases and to their inheritance model.

  16. Load Calculation of the American Criterion ASCE74%浅析美国规范ASCE74中的荷载计算

    Institute of Scientific and Technical Information of China (English)

    薛英

    2012-01-01

      在国际工程标书中,美国输电线路结构荷载导则《Guidelines for Electrical Transmission Line Structural Loading》(ASCE74-2009)经常是被业主青睐和采用的标准。本文结合工程实际介绍了ASCE74中,线路在大风工况、覆冰工况、安装维护以及断线等工况下的荷载计算,可供国际工程投标及设计使用。%  The requirements of(ASCE 74-2009) have been adopted in many international transmission line projects. The article introduced the basic requirements for extreme wind, ice and wind loading, construction&maintenance and for longitudinal load in ASCE74, which may be taken as the reference for the tender documents and design.

  17. Immunocytoexpression profile of ProExC in smears interpreted as ASC-US, ASC-H, and cervical intraepithelial lesion

    Directory of Open Access Journals (Sweden)

    Zeynep Tosuner

    2017-01-01

    Full Text Available Aims: We aimed to investigate the immunocytoexpression profiles of a novel assay ProEx C for topoisomerase II alpha (TOP2A and minichromosome maintenance protein 2 (MCM2 in abnormal interpreted smears. Settings and Design: Screening programs with Papanicolaou smear and high risk group human papilloma virus testing have yielded a dramatic reduction of cervical cancer incidence. However, both of these tests have limited specificity for the detection of clinically significant cervical high grade lesions. ProEx C for topoisomerase II alpha (TOP2A and minichromosome maintenance protein 2 (MCM2 has been considered to have tight association with high grade intraepithelial lesions. Materials and Methods: A total number of 54 SurePath cervical cytology specimens of patients previously interpreted as atypical squamous cells-undetermined significance (ASC-US, atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H, low grade squamous intraepithelial lesion (LSIL, and high grade squamous intraepithelial lesion (HSIL were included in our study. Results and Conclusions: ProEx C was positive in 14 of HSILs (100%, 3 of 19 LSILs (16%, 2 of 4 ASC-Hs, and none of ASC-USs (0%. The ProEx C test showed very intense nuclear staining in all cytologically abnormal cells. Further studies are indicated to evaluate the diagnostic role of ProEx C.

  18. Heritability of body weight: moving beyond genetics.

    Science.gov (United States)

    Russo, P; Lauria, F; Siani, A

    2010-12-01

    Obesity is a complex disease, arising from the interaction between several genetic and environmental factors. Until recently, the genetic basis of complex diseases in general, and of obesity in particular, were poorly characterized. While the relatively rare monogenic and syndromic forms of obesity clearly recognize a genetic origin, the actual worldwide epidemics of obesity represent a challenge for the identification of the genetic factors involved, being likely the effect of several loci each having a subtle influence on the phenotypic expression. Progress in DNA analysis techniques and in computational tools, and the increasing level of characterization of the variability of the human genome has recently allowed to study comprehensively the association between genetic variants and obesity. To date, well-conducted and powered genome-wide association studies allowed to consistently identify genomic regions - lying on different chromosomes and affecting different metabolic pathways - influencing the predisposition to the accumulation of body fat, ultimately leading to overweight and obesity. However, the population attributable risk for obesity linked to the most statistically significant loci, like FTO and MC4R, remains discouragingly low, explaining only small fractions of the overall variance of body weight. In the last few years, the role of the complex interaction between genetic determinants and environmental factors in the rapid global increase of obesity has been further challenged by the entry of new players, that is the transcriptional and post-transcriptional regulation, summarized under the emerging discipline of epigenetics. The key challenge now is to move from the identification of causal genes and variants to the integration of different "omics" disciplines, finally allowing the molecular understanding of obesity and related conditions. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Group differences in the heritability of items and test scores

    NARCIS (Netherlands)

    Wicherts, J.M.; Johnson, W.

    2009-01-01

    It is important to understand potential sources of group differences in the heritability of intelligence test scores. On the basis of a basic item response model we argue that heritabilities which are based on dichotomous item scores normally do not generalize from one sample to the next. If groups

  20. Heritable retinoblastoma and accelerated aortic valve disease

    Science.gov (United States)

    Abeyratne, L R; Kingston, J E; Onadim, Z; Dubrey, S W

    2013-01-01

    Heritable retinoblastoma is associated with a germline mutation in the tumour suppressor gene RBI. The Rb protein (pRb) arises from the RB1 gene, which was the first demonstrated cancer susceptibility gene in humans. 1 Second primary malignancies are recognised complications of retinoblastoma. Furthermore, pRb is implicated in valve remodelling in calcific aortic valve disease. 2 3 We report a family with hereditary retinoblastoma and associated secondary primary malignancies. There are two interesting aspects to this family. The first is the concept of ‘cancer susceptibility genes’; the RBI gene being the first reported in humans. A further feature of note is that two family members also have bicuspid aortic valves. We discuss a potential association between the gene defect responsible for retinoblastoma (with its associated propensity for further malignancies) and accelerated deterioration of the bicuspid aortic valve in the proband carrying this gene defect. PMID:23595191

  1. Heritable factors influence sexual orientation in women.

    Science.gov (United States)

    Bailey, J M; Pillard, R C; Neale, M C; Agyei, Y

    1993-03-01

    Homosexual female probands with monozygotic cotwins, dizygotic cotwins, or adoptive sisters were recruited using homophile publications. Sexual orientation of relatives was assessed either by asking relatives directly, or, when this was impossible, by asking the probands. Of the relatives whose sexual orientation could be confidently rated, 34 (48%) of 71 monozygotic cotwins, six (16%) of 37 dizygotic cotwins, and two (6%) of 35 adoptive sisters were homosexual. Probands also reported 10 (14%) nontwin biologic sisters to be homosexual, although those sisters were not contacted to confirm their orientations. Heritabilities were significant using a wide range of assumptions about both the base rate of homosexuality in the population and ascertainment bias. The likelihood that a monozygotic cotwin would also be homosexual was unrelated to measured characteristics of the proband such as self-reported history of childhood gender nonconformity. Concordant monozygotic twins reported similar levels of childhood gender nonconformity.

  2. Human somatic, germinal and heritable mutagenicity

    Energy Technology Data Exchange (ETDEWEB)

    Mendelsohn, M.L.

    1987-05-01

    This report deals with the general process of variant formation rather than with the consequences of a specific variant being present. It focusses on mutational mechanisms, mutagens, and the method for detecting de novo mutants and estimating mutation rate. It is to human genetics much like disease causation and prevention medicine are to medicine as a whole. The word ''mutagenicity'' is used in the title and throughout the text to connote the causation of all classes of genetic damage. Mutagenicity and the corresponding words mutation, mutagen and mutagenesis can have multiple meaning, sometimes relating to gene mutation, sometimes to heritable mutation, and somtimes to all types of genetic damage. 38 refs., 1 tab.

  3. Heritability of metoprolol and torsemide pharmacokinetics

    DEFF Research Database (Denmark)

    Matthaei, Johannes; Brockmöller, Jürgen; Tzvetkov, Mladen;

    2015-01-01

    Genetic variation in the pharmacokinetics of metoprolol and torsemide due to polymorphisms in CYP2D6, CYP2C9 and OATP1B1 has been extensively studied. However, it is still unknown how much of variation in pharmacokinetics of these two clinically important drugs in total is due to genetic factors....... Metoprolol and torsemide were intravenously administered to 44 monozygotic and 14 dizygotic twin pairs. Metoprolol AUC varied 4.7-fold and torsemide AUC 3.5-fold. A very high fraction of AUC variations, 91% of metoprolol and 86% of torsemide, were found to be due to additive genetic effects. However, known...... of the heritable variability in the pharmacokinetics of metoprolol and torsemide remains to be elucidated. This article is protected by copyright. All rights reserved....

  4. Familial aggregation and heritability of pyloric stenosis

    DEFF Research Database (Denmark)

    Krogh, Camilla; Fischer, Thea K; Skotte, Line;

    2010-01-01

    .1 for twins. The rate ratios of pyloric stenosis were 182 (95% confidence interval [CI], 70.7-467) for monozygotic twins, 29.4 (95% CI, 9.45-91.5) for dizygotic twins, 18.5 (95% CI, 13.7-25.1) for siblings, 4.99 (95% CI, 2.59-9.65) for half-siblings, 3.06 (95% CI, 2.10-4.44) for cousins, and 1.60 (95% CI, 0.......51-4.99) for half-cousins. We found no difference in rate ratios for maternal and paternal relatives of children with pyloric stenosis and no difference according to sex of cohort member or sex of relative. The heritability of pyloric stenosis was 87%. CONCLUSION: Pyloric stenosis in Danish children shows strong...

  5. Metabolic differences in ripening of Solanum lycopersicum 'Ailsa Craig' and three monogenic mutants.

    Science.gov (United States)

    Beisken, Stephan; Earll, Mark; Baxter, Charles; Portwood, David; Ament, Zsuzsanna; Kende, Aniko; Hodgman, Charlie; Seymour, Graham; Smith, Rebecca; Fraser, Paul; Seymour, Mark; Salek, Reza M; Steinbeck, Christoph

    2014-01-01

    Application of mass spectrometry enables the detection of metabolic differences between groups of related organisms. Differences in the metabolic fingerprints of wild-type Solanum lycopersicum and three monogenic mutants, ripening inhibitor (rin), non-ripening (nor) and Colourless non-ripening (Cnr), of tomato are captured with regard to ripening behaviour. A high-resolution tandem mass spectrometry system coupled to liquid chromatography produced a time series of the ripening behaviour at discrete intervals with a focus on changes post-anthesis. Internal standards and quality controls were used to ensure system stability. The raw data of the samples and reference compounds including study protocols have been deposited in the open metabolomics database MetaboLights via the metadata annotation tool Isatab to enable efficient re-use of the datasets, such as in metabolomics cross-study comparisons or data fusion exercises.

  6. Monogenic Autoinflammatory Syndromes: State of the Art on Genetic, Clinical, and Therapeutic Issues

    Science.gov (United States)

    Costa, Luisa; Atteno, Mariangela; Compagnone, Adele; Caso, Paolo; Frediani, Bruno; Galeazzi, Mauro; Punzi, Leonardo

    2013-01-01

    Monogenic autoinflammatory syndromes (MAISs) are caused by innate immune system dysregulation leading to aberrant inflammasome activation and episodes of fever and involvement of skin, serous membranes, eyes, joints, gastrointestinal tract, and nervous system, predominantly with a childhood onset. To date, there are twelve known MAISs: familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, familial cold urticaria syndrome, Muckle-Wells syndrome, CINCA syndrome, mevalonate kinase deficiency, NLRP12-associated autoinflammatory disorder, Blau syndrome, early-onset sarcoidosis, PAPA syndrome, Majeed syndrome, and deficiency of the interleukin-1 receptor antagonist. Each of these conditions may manifest itself with more or less severe inflammatory symptoms of variable duration and frequency, associated with findings of increased inflammatory parameters in laboratory investigation. The purpose of this paper is to describe the main genetic, clinical, and therapeutic aspects of MAISs and their most recent classification with the ultimate goal of increasing awareness of autoinflammation among various internal medicine specialists. PMID:24282415

  7. Monogenic Autoinflammatory Syndromes: State of the Art on Genetic, Clinical, and Therapeutic Issues

    Directory of Open Access Journals (Sweden)

    Francesco Caso

    2013-01-01

    Full Text Available Monogenic autoinflammatory syndromes (MAISs are caused by innate immune system dysregulation leading to aberrant inflammasome activation and episodes of fever and involvement of skin, serous membranes, eyes, joints, gastrointestinal tract, and nervous system, predominantly with a childhood onset. To date, there are twelve known MAISs: familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, familial cold urticaria syndrome, Muckle-Wells syndrome, CINCA syndrome, mevalonate kinase deficiency, NLRP12-associated autoinflammatory disorder, Blau syndrome, early-onset sarcoidosis, PAPA syndrome, Majeed syndrome, and deficiency of the interleukin-1 receptor antagonist. Each of these conditions may manifest itself with more or less severe inflammatory symptoms of variable duration and frequency, associated with findings of increased inflammatory parameters in laboratory investigation. The purpose of this paper is to describe the main genetic, clinical, and therapeutic aspects of MAISs and their most recent classification with the ultimate goal of increasing awareness of autoinflammation among various internal medicine specialists.

  8. Metabolic dysregulation in monogenic disorders and cancer - finding method in madness.

    Science.gov (United States)

    Erez, Ayelet; DeBerardinis, Ralph J

    2015-07-01

    Cancer is a prime example of a disease process in which carcinogenic and metabolic changes are intertwined to promote cell survival and growth. One approach to unravel this complex relationship is by studying rare, monogenic disorders caused by mutations in genes encoding metabolic enzymes or regulators. There are hundreds of these diseases, most of which manifest in childhood and are collectively termed 'inborn errors of metabolism' (IEMs). Several IEMs demonstrate the consequences of chronic, systemic loss of a particular metabolic activity that can result in malignancy. In this Opinion article, we present a conceptual categorization of IEMs associated with cancer and discuss how assessment of these rare diseases might inform us about the biological foundations of common types of cancer and opportunities for cancer diagnosis and therapy.

  9. Estimating heritability from nuclear family and pedigree data.

    Science.gov (United States)

    Bochud, Murielle

    2012-01-01

    Heritability is a measure of familial resemblance. Estimating the heritability of a trait represents one of the first steps in the gene mapping process. This chapter describes how to estimate heritability for quantitative traits from nuclear and pedigree data using the ASSOC program in the Statistical Analysis for Genetic Epidemiology (S.A.G.E.) software package. Estimating heritability rests on the assumption that the total phenotypic variance of a quantitative trait can be partitioned into independent genetic and environmental components. In turn, the genetic variance can be divided into an additive (polygenic) genetic variance, a dominance variance (nonlinear interaction effects between alleles at the same locus), and an epistatic variance (interaction effects between alleles at different loci). The last two are often assumed to be zero. The additive genetic variance represents the average effects of individual alleles on the phenotype and reflects transmissible resemblance between relatives. Heritability in the narrow sense (h (2)) refers to the ratio of the additive genetic variance to the total phenotypic variance. Heritability is a dimensionless population-specific parameter. ASSOC estimates association parameters (regression coefficients) and variance components from family data. ASSOC uses a linear regression model in which the total residual variance is partitioned, after regressing on covariates, into the sum of a random additive polygenic component, a random sibship component, random nuclear family components, a random marital component, and an individual-specific random component. Assortative mating, nonrandom ascertainment of families and failure to account for key confounding factors may bias heritability estimates.

  10. Comparison of Simulated Microgravity and Hydrostatic Pressure for Chondrogenesis of hASC.

    Science.gov (United States)

    Mellor, Liliana F; Steward, Andrew J; Nordberg, Rachel C; Taylor, Michael A; Loboa, Elizabeth G

    2017-04-01

    Cartilage tissue engineering is a growing field due to the lack of regenerative capacity of native tissue. The use of bioreactors for cartilage tissue engineering is common, but the results are controversial. Some studies suggest that microgravity bioreactors are ideal for chondrogenesis, while others show that mimicking hydrostatic pressure is crucial for cartilage formation. A parallel study comparing the effects of loading and unloading on chondrogenesis has not been performed. The goal of this study was to evaluate chondrogenesis of human adipose-derived stem cells (hASC) under two different mechanical stimuli relative to static culture: microgravity and cyclic hydrostatic pressure (CHP). Pellets of hASC were cultured for 14 d under simulated microgravity using a rotating wall vessel bioreactor or under CHP (7.5 MPa, 1 Hz, 4 h · d-1) using a hydrostatic pressure vessel. We found that CHP increased mRNA expression of Aggrecan, Sox9, and Collagen II, caused a threefold increase in sulfated glycosaminoglycan production, and resulted in stronger vimentin staining intensity and organization relative to microgravity. In addition, Wnt-signaling patterns were altered in a manner that suggests that simulated microgravity decreases chondrogenic differentiation when compared to CHP. Our goal was to compare chondrogenic differentiation of hASC using a microgravity bioreactor and a hydrostatic pressure vessel, two commonly used bioreactors in cartilage tissue engineering. Our results indicate that CHP promotes hASC chondrogenesis and that microgravity may inhibit hASC chondrogenesis. Our findings further suggest that cartilage formation and regeneration might be compromised in space due to the lack of mechanical loading.Mellor LF, Steward AJ, Nordberg RC, Taylor MA, Loboa EG. Comparison of simulated microgravity and hydrostatic pressure for chondrogenesis of hASC. Aerosp Med Hum Perform. 2017; 88(4):377-384.

  11. Genetics and realized heritability of resistance to imidacloprid in a poultry population of house fly, Musca domestica L. (Diptera: Muscidae) from Pakistan.

    Science.gov (United States)

    Khan, Hussnain; Abbas, Naeem; Shad, Sarfraz Ali; Afzal, Muhammad Babar Shahzad

    2014-09-01

    Imidacloprid, a post-synaptic, nicotinic insecticide, has been commonly used for the management of different pests including Musca domestica worldwide. Many pests have developed resistance to this insecticide. A 16-fold imidacloprid-resistant population of M. domestica infesting poultry was selected using imidacloprid for 13 continuous generations to study the inheritance and realized heritability of resistance. Toxicological bioassay at G14 showed that the imidacloprid-selected population developed 106-fold resistance when compared to the susceptible population. Reciprocal crosses of susceptible and resistant populations showed an autosomal trait of resistance to imidacloprid in M. domestica. There was incompletely recessive resistance in F1 (Imida-SEL ♂ × Susceptible ♀) and F1(†) (Imida-SEL ♀ × Susceptible ♂) having dominance value 0.53 and 0.31, respectively. Monogenic model of inheritance showed that imidacloprid resistance was controlled by multiple factors. The realized heritability value was 0.09 in the imidacloprid-selected population of M. domestica. It was concluded that imidacloprid resistance in M. domestica was autosomally inherited, incompletely recessive and polygenic. These findings should be helpful for better and more successful management of M. domestica.

  12. ASC-H in Pap test- definitive categorization of cytomorphological spectrum

    Directory of Open Access Journals (Sweden)

    Chivukula Mamatha

    2006-05-01

    Full Text Available Abstract Objective The American Society for Colposcopy and Cervical Pathology (ASCCP guidelines for management of ASC-H is colposcopic examination followed by biopsy. HPV testing (HPVT is recommended after a negative biopsy result. More definitive interpretation of ASC-H could prevent discomfort and minimize the cost. The purpose of this study was to evaluate association of various cytomorphological patterns of ASC-H with various clinical scenarios. Methods We reviewed SurePath™ (TriPath Imaging, Inc. Burlington, NC, USA cervical smears interpreted as ASC-H in 161 women (mean age, 37 {15 to 78} years, over 24 months (2002 to 2003. HPVT (Digene, Hybrid Capture® II HPV test, Digene Corporation, Gaithersburg, MD, USA was performed in 20% of cases (33/161 and biopsy results were available in 54 cases (19 with and 35 without HPVT. Results HPVT was positive in 64% (21/33 cases, and negative in 36% (12/33 cases. In the follow-up biopsies of 71% (15/21 of cases with positive HPVT, 27% showed HPV changes or CIN1, 27% showed CIN2-3, and 46% were negative for epithelial abnormality. Follow-up biopsies from cases with negative HPVT (33%, 4/12 cases, 8% showed CIN1 and 25% were negative for any epithelial abnormality. Six cytomorphological patterns of ASC-H correlated with different clinical categories in relation to HPVT and biopsy results. 35% (19 out of 54 ASC-H cases in which biopsy results were available could be interpreted definitively as HSIL by cytopathology, 11% (6/54 cases as LSIL with cyanophilic atypical parakeratotic pattern, and 31% (17/54 cases as reactive, with HPV status. The interpretation had to be continued as ASC-H in 22% (12/54 cases. Conclusion ASC-H demonstrated a spectrum of cytomorphological patterns. Some of these patterns in liquid-based cervical smears may be more specifically interpreted as LSIL, HSIL, or benign if HPV status is known.

  13. Fundamentals of civil engineering an introduction to the ASCE body of knowledge

    CERN Document Server

    McCuen, Richard H; Wong, Melanie K

    2011-01-01

    While the ASCE Body of Knowledge (BOK2) is the codified source for all technical and non-technical information necessary for those seeking to attain licensure in civil engineering, recent graduates have notoriously been lacking in the non-technical aspects even as they excel in the technical. Fundamentals of Civil Engineering: An Introduction to the ASCE Body of Knowledge addresses this shortfall and helps budding engineers develop the knowledge, skills, and attitudes suggested and implied by the BOK2. Written as a resource for all of the non-technical outcomes not specifically covered in the

  14. MicroASC instrument onboard Juno spacecraft utilizing inertially controlled imaging

    DEFF Research Database (Denmark)

    Pedersen, David Arge Klevang; Jørgensen, Andreas Härstedt; Benn, Mathias

    2016-01-01

    This contribution describes the post-processing of the raw image data acquired by the microASC instrument during the Earth-fly-by of the Juno spacecraft. The images show a unique view of the Earth and Moon system as seen from afar. The procedure utilizes attitude measurements and inter......-calibration of the Camera Head Units of the microASC system to trigger the image capturing. The triggering is synchronized with the inertial attitude and rotational phase of the sensor acquiring the images. This is essentially works as inertially controlled imaging facilitating image acquisition from unexplored...

  15. Alzheimer's disease: analyzing the missing heritability.

    Directory of Open Access Journals (Sweden)

    Perry G Ridge

    Full Text Available Alzheimer's disease (AD is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer's Disease Genetics Consortium to assess the phenotypic variance explained first by known late-onset AD loci, and then by all SNPs in the Alzheimer's Disease Genetics Consortium dataset. In all, 33% of total phenotypic variance is explained by all common SNPs. APOE alone explained 6% and other known markers 2%, meaning more than 25% of phenotypic variance remains unexplained by known markers, but is tagged by common SNPs included on genotyping arrays or imputed with HapMap genotypes. Novel AD markers that explain large amounts of phenotypic variance are likely to be rare and unidentifiable using genome-wide association studies. Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer's disease.

  16. Heritability of metoprolol and torsemide pharmacokinetics.

    Science.gov (United States)

    Matthaei, J; Brockmöller, J; Tzvetkov, M V; Sehrt, D; Sachse-Seeboth, C; Hjelmborg, J B; Möller, S; Halekoh, U; Hofmann, U; Schwab, M; Kerb, R

    2015-12-01

    Genetic variation in the pharmacokinetics of metoprolol and torsemide due to polymorphisms in CYP2D6, CYP2C9, and OATP1B1 has been extensively studied. However, it is still unknown how much of the variation in pharmacokinetics of these two clinically important drugs in total is due to genetic factors. Metoprolol and torsemide were intravenously administered to 44 monozygotic and 14 dizygotic twin pairs. Metoprolol area under the curve (AUC) varied 4.7-fold and torsemide AUC 3.5-fold. A very high fraction of AUC variations, 91% of metoprolol and 86% of torsemide, were found to be due to additive genetic effects. However, known genetic variants of CYP2D6, -2C9, and OATP1B1 explained only 39%, 2%, and 39% of that variation, respectively. Comparable results for genetically explained variation in pharmacokinetics and pharmacodynamics have been found for other substrates of these enzymes earlier. These findings indicate that a substantial fraction of the heritable variability in the pharmacokinetics of metoprolol and torsemide remains to be elucidated.

  17. Inheritance, realized heritability and biochemical mechanism of acetamiprid resistance in the cotton mealybug, Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae).

    Science.gov (United States)

    Afzal, Muhammad Babar Shahzad; Abbas, Naeem; Shad, Sarfraz Ali

    2015-07-01

    The cotton mealybug, Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae) is a serious pest in many countries of the world because of its polyphagous nature and has caused huge losses to the cotton crop. The aim of present study was to explore the mode of inheritance and mechanism of acetamiprid resistance in P. solenopsis. After five rounds of selection with acetamiprid, P. solenopsis developed a 315-fold resistance compared with the laboratory susceptible population. The LC50 values of progenies of both reciprocal crosses (F1 and F1') showed no significant difference and degree of dominance values were 0.56 and 0.93 for F1 and F1', respectively. Monogenic model of inheritance and Lande's method revealed that more than one factors were involved in acetamiprid resistance. Realized heritability (h(2)) value was 0.58 for acetamiprid resistance. A synergism study of piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioate (DEF) with acetamiprid also showed the significant presence of P-450 mono-oxygenase and esterase in the acetamiprid resistance. Hence, acetamiprid resistance in the P. solenopsis was autosomal, incompletely dominant and polygenic. These results are a source of basic information to design and plan fruitful management programmes to control P. solenopsis.

  18. Tic symptom dimensions and their heritabilities in Tourette's syndrome

    NARCIS (Netherlands)

    de Haan, Marcel J; Delucchi, Kevin L; Mathews, Carol M; Cath, Danielle C

    2015-01-01

    INTRODUCTION: Gilles de la Tourette's syndrome (TS) is both genotypically and phenotypically heterogeneous. Gene-finding strategies have had limited success, possibly because of symptom heterogeneity. OBJECTIVE: This study aimed at specifically investigating heritabilities of tic symptom factors in

  19. Tic symptom dimensions and their heritabilities in Tourette's syndrome

    NARCIS (Netherlands)

    de Haan, Marcel J; Delucchi, Kevin L; Mathews, Carol M; Cath, Danielle C

    2015-01-01

    INTRODUCTION: Gilles de la Tourette's syndrome (TS) is both genotypically and phenotypically heterogeneous. Gene-finding strategies have had limited success, possibly because of symptom heterogeneity. OBJECTIVE: This study aimed at specifically investigating heritabilities of tic symptom factors in

  20. Tic symptom dimensions and their heritabilities in Tourette's syndrome

    NARCIS (Netherlands)

    de Haan, Marcel J; Delucchi, Kevin L; Mathews, Carol M; Cath, Danielle C

    INTRODUCTION: Gilles de la Tourette's syndrome (TS) is both genotypically and phenotypically heterogeneous. Gene-finding strategies have had limited success, possibly because of symptom heterogeneity. OBJECTIVE: This study aimed at specifically investigating heritabilities of tic symptom factors in

  1. ANOPHTHALMIA: A NON-HERITABLE EYE DEFORMITY IN Oreochromis mossambicus

    Directory of Open Access Journals (Sweden)

    D. Tave

    1998-12-01

    Full Text Available Seven male Oreochromis mossambicus with anophthalmia were found in a hatchery population. The deformity was not observed in either the Fl or F2 generations; consequently, it was a non-heritable congenital deformity.

  2. An Effective Method to Identify Heritable Components from Multivariate Phenotypes.

    Directory of Open Access Journals (Sweden)

    Jiangwen Sun

    Full Text Available Multivariate phenotypes may be characterized collectively by a variety of low level traits, such as in the diagnosis of a disease that relies on multiple disease indicators. Such multivariate phenotypes are often used in genetic association studies. If highly heritable components of a multivariate phenotype can be identified, it can maximize the likelihood of finding genetic associations. Existing methods for phenotype refinement perform unsupervised cluster analysis on low-level traits and hence do not assess heritability. Existing heritable component analytics either cannot utilize general pedigrees or have to estimate the entire covariance matrix of low-level traits from limited samples, which leads to inaccurate estimates and is often computationally prohibitive. It is also difficult for these methods to exclude fixed effects from other covariates such as age, sex and race, in order to identify truly heritable components. We propose to search for a combination of low-level traits and directly maximize the heritability of this combined trait. A quadratic optimization problem is thus derived where the objective function is formulated by decomposing the traditional maximum likelihood method for estimating the heritability of a quantitative trait. The proposed approach can generate linearly-combined traits of high heritability that has been corrected for the fixed effects of covariates. The effectiveness of the proposed approach is demonstrated in simulations and by a case study of cocaine dependence. Our approach was computationally efficient and derived traits of higher heritability than those by other methods. Additional association analysis with the derived cocaine-use trait identified genetic markers that were replicated in an independent sample, further confirming the utility and advantage of the proposed approach.

  3. Dual role of apoptosis-associated speck-like protein containing a CARD (ASC) in tumorigenesis of human melanoma

    NARCIS (Netherlands)

    Liu, W.; Luo, Y.; Dunn, J.H.; Norris, D.A.; Dinarello, C.A.; Fujita, M.

    2013-01-01

    Apoptosis-associated Speck-like protein containing a CARD (caspase recruitment domain) (ASC) was originally named because it triggered apoptosis in certain tumors. More recently, however, ASC was found to be a central adaptor protein of inflammasome, which mediates the secretion of protumorigenic

  4. Quercetin Inhibits Inflammasome Activation by Interfering with ASC Oligomerization and Prevents Interleukin-1 Mediated Mouse Vasculitis

    Science.gov (United States)

    Domiciano, Talita P.; Wakita, Daiko; Jones, Heather D.; Crother, Timothy R.; Verri, Waldiceu A.; Arditi, Moshe; Shimada, Kenichi

    2017-01-01

    Interleukin-1β (IL-1β) is a highly inflammatory cytokine that significantly contributes to both acute and chronic inflammatory diseases. The secretion of IL-1β requires a unique protease, caspase-1, which is activated by various protein platforms called inflammasomes. Data suggests a key role for mitochondrial reactive oxygen species for inflammasome activation. Flavonoids constitute a group of naturally occurring polyphenolic molecules with many biological activities, including antioxidant effects. In this study, we investigated the effect of three flavonoids, quercetin (QUC), naringenin, and silymarim on inflammasome activation. We found that QUC inhibits IL-1β secretion by both the NLRP3 and AIM2 inflammasome in a dose dependent manner, but not the NLRC4 inflammasome. QUC inhibition of the inflammasome was still observed in Atg16l1 knockout macrophages, indicating that QUC’s effect was autophagy independent. Since QUC inhibited both NLRP3 and AIM2 inflammasomes but not NLRC4, we assessed ASC speck formation. QUC reduced ASC speck formation and ASC oligomerization compared with controls. Additionally, QUC inhibited IL-1β in Cryopyrin-Associated Periodic Syndromes (CAPS) macrophages, where NLRP3 inflammasome is constitutively activated. In conclusion, QUC inhibits both the NLRP3 and AIM2 inflammasome by preventing ASC oligomerization and may be a potential therapeutic candidate for Kawasaki disease vasculitis and other IL-1 mediated inflammatory diseases. PMID:28148962

  5. Quercetin Inhibits Inflammasome Activation by Interfering with ASC Oligomerization and Prevents Interleukin-1 Mediated Mouse Vasculitis.

    Science.gov (United States)

    Domiciano, Talita P; Wakita, Daiko; Jones, Heather D; Crother, Timothy R; Verri, Waldiceu A; Arditi, Moshe; Shimada, Kenichi

    2017-02-02

    Interleukin-1β (IL-1β) is a highly inflammatory cytokine that significantly contributes to both acute and chronic inflammatory diseases. The secretion of IL-1β requires a unique protease, caspase-1, which is activated by various protein platforms called inflammasomes. Data suggests a key role for mitochondrial reactive oxygen species for inflammasome activation. Flavonoids constitute a group of naturally occurring polyphenolic molecules with many biological activities, including antioxidant effects. In this study, we investigated the effect of three flavonoids, quercetin (QUC), naringenin, and silymarim on inflammasome activation. We found that QUC inhibits IL-1β secretion by both the NLRP3 and AIM2 inflammasome in a dose dependent manner, but not the NLRC4 inflammasome. QUC inhibition of the inflammasome was still observed in Atg16l1 knockout macrophages, indicating that QUC's effect was autophagy independent. Since QUC inhibited both NLRP3 and AIM2 inflammasomes but not NLRC4, we assessed ASC speck formation. QUC reduced ASC speck formation and ASC oligomerization compared with controls. Additionally, QUC inhibited IL-1β in Cryopyrin-Associated Periodic Syndromes (CAPS) macrophages, where NLRP3 inflammasome is constitutively activated. In conclusion, QUC inhibits both the NLRP3 and AIM2 inflammasome by preventing ASC oligomerization and may be a potential therapeutic candidate for Kawasaki disease vasculitis and other IL-1 mediated inflammatory diseases.

  6. The standardized psychometric assessment of altered states of consciousness (ASCs) in humans.

    Science.gov (United States)

    Dittrich, A

    1998-07-01

    The APZ questionnaire was developed in order to explore hypotheses on ASCs. First -- in a series of 11 experiments using different induction methods on N = 393 healthy subjects -- the hypothesis was tested that ASCs have major dimensions in common irrespective of the mode of their induction. In the International Study on Altered States of Consciousness (ISASC) the external validity of the experimental results was assessed. The ISASC was carried out on a total of N = 1133 subjects in six countries. The main results of the experimental studies were corroborated in the field studies. The results can be summarized as follows: the common denominator of ASCs is described by three oblique dimensions, designated as "Oceanic Boundlessness (OSE)", "Dread of Ego Dissolution (AIA)" and "Visionary Restructuralization (VUS)". The reliability and validity of the scales are satisfactory. Tested versions of the APZ scales are available in English (UK, USA), German, Italian and Portuguese. Psychometrically as yet untested versions exist in Dutch, Finnish, French, Greek, Spanish and Russian. The APZ questionnaire has become the international standard for the assessment of ASCs, thus helping to integrate research. A psychometrically improved version exists in German (OAV questionnaire). The BETA questionnaire, which measures the dimensions "Vigilance Reduction (VIR)" and "Auditive Alteration (AVE)" is also available in German. These dimensions are most likely etiology-dependent.

  7. 18 CFR Appendix 1 to Part 301 - ASC Utility Filing Template

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false ASC Utility Filing Template 1 Appendix 1 to Part 301 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS FOR FEDERAL POWER MARKETING ADMINISTRATIONS AVERAGE SYSTEM...

  8. ASC Computational Environment (ACE) requirements version 8.0 final report.

    Energy Technology Data Exchange (ETDEWEB)

    Larzelere, Alex R. (Exagrid Engineering, Alexandria, VA); Sturtevant, Judith E.

    2006-11-01

    A decision was made early in the Tri-Lab Usage Model process, that the collection of the user requirements be separated from the document describing capabilities of the user environment. The purpose in developing the requirements as a separate document was to allow the requirements to take on a higher-level view of user requirements for ASC platforms in general. In other words, a separate ASC user requirement document could capture requirements in a way that was not focused on ''how'' the requirements would be fulfilled. The intent of doing this was to create a set of user requirements that were not linked to any particular computational platform. The idea was that user requirements would endure from one ASC platform user environment to another. The hope was that capturing the requirements in this way would assist in creating stable user environments even though the particular platforms would be evolving and changing. In order to clearly make the separation, the Tri-lab S&CS program decided to create a new title for the requirements. The user requirements became known as the ASC Computational Environment (ACE) Requirements.

  9. Heritabilities of somatotype components in a population from rural Mozambique.

    Science.gov (United States)

    Saranga, Sílvio Pedro José; Prista, António; Nhantumbo, Leonardo; Beunen, Gaston; Rocha, Jorge; Williams-Blangero, Sarah; Maia, José A

    2008-01-01

    There have been few genetic studies of normal variation in body size and composition conducted in Africa. In particular, the genetic determinants of somatotype remain to be established for an African population. (1) To estimate the heritabilities of aspects of somatotype and (2) to compare the quantitative genetic effects in an African population to those that have been assessed in European and American populations. The sample composed of 329 subjects (173 males and 156 females) aged 7-17 years, belonging to 132 families. The sibships in the sample ranged in size from two to seven individuals. All sampled individuals were residents of the Calanga region, an area located to the north of Maputo in Mozambique. Somatotype was assessed using the Heath-Carter technique. Herit abilities were estimated using SAGE software. Moderate heritabilities were determined for each trait. Between 30 and 40% of the variation in each somatotype measure was attributable to genetic factors. The heritability of ectomorphy was 31%. Mesomorphy was similarly moderately heritable, with approximately 30% of the variationattributable to genetic factors. The heritability of endomorph was higher in the Calanga population (h(2) = 0.40). Quantitative genetic analyses of somatotype variation among siblings indicate that genetic factors significantly influence endomorphy, mesomorhpy, and ectomorphy. However, environmental factors also have significant effects on the variation in physique present in the population of Calanga. Lack of proper nutrition, housing, medical assistance, and primary health care, together with very demanding and sex-specific daily chores may contribute to the environmental effects on these traits.

  10. Genomic Heritability of Bovine Growth Using a Mixed Model

    Directory of Open Access Journals (Sweden)

    Jihye Ryu

    2014-11-01

    Full Text Available This study investigated heritability for bovine growth estimated with genomewide single nucleotide polymorphism (SNP information obtained from a DNA microarray chip. Three hundred sixty seven Korean cattle were genotyped with the Illumina BovineSNP50 BeadChip, and 39,112 SNPs of 364 animals filtered by quality assurance were analyzed to estimate heritability of body weights at 6, 9, 12, 15, 18, 21, and 24 months of age. Restricted maximum likelihood estimate of heritability was obtained using covariance structure of genomic relationships among animals in a mixed model framework. Heritability estimates ranged from 0.58 to 0.76 for body weights at different ages. The heritability estimates using genomic information in this study were larger than those which had been estimated previously using pedigree information. The results revealed a trend that the heritability for body weight increased at a younger age (6 months. This suggests an early genetic evaluation for bovine growth using genomic information to increase genetic merits of animals.

  11. Evidence for a heritable unidimensional symptom factor underlying obsessionality.

    Science.gov (United States)

    Mathews, Carol A; Greenwood, Tiffany; Wessel, Jennifer; Azzam, Amin; Garrido, Helena; Chavira, Denise A; Chandavarkar, Uma; Bagnarello, Monica; Stein, Murray; Schork, Nicholas J

    2008-09-05

    The division of obsessive-compulsive symptoms (OCS) into specific factors is now widely accepted. However, the utility of these categories for genetic studies remains unclear, as studies examining their heritability have been inconsistent. Less attention has been paid to the possibility that clinically significant obsessionality is primarily determined by a "core" group of OCS that crosses the boundaries between symptom subgroups. The aim of this study is to determine whether such a core group exists, and to compare its heritability to that of the more traditionally derived symptom factors. We examined the properties and heritability of obsessive-compulsive symptoms in college students, medical students, and obsessive-compulsive disorder (OCD) families using the Leyton Obsessional Inventory. In each of the three samples, we identified a core group of symptoms that comprised a single unique construct and accounted for over 90% of the variation of the four more traditional symptom factors. This core construct was highly correlated with OCD in our families and had a heritability estimate of 0.19 when OCD was not included as a covariate and 0.49 when OCD was included as a covariate. In contrast, the four symptom factors were not heritable. There appears to be an underlying unidimensional component to obsessionality, both in non-clinical and clinical samples. This component, which is heritable, accounts for the majority of the variation of the more traditionally derived symptom factors in our sample, and is composed of OCS that are not specific to any of the symptom subgroups.

  12. Heritability of compulsive Internet use in adolescents.

    Science.gov (United States)

    Vink, Jacqueline M; van Beijsterveldt, Toos C E M; Huppertz, Charlotte; Bartels, Meike; Boomsma, Dorret I

    2016-03-01

    Over the past decades, Internet use has grown substantially, and it now serves people as a supportive tool that is used regularly and-in large parts of the world-inevitably. Some people develop problematic Internet use, which may lead to addictive behavior and it is becoming important to explore the risk factors for compulsive Internet use. Data were analyzed on compulsive Internet use [with the Compulsive Internet Use Scale (CIUS)] from 5247 monozygotic (MZ) and dizygotic (DZ) adolescent twins registered with the Netherlands Twin Register. The participants form a sample that is informative for genetic analyses, allowing the investigation of the causes of individual differences in compulsive Internet use. The internal consistency of the instrument was high and the 1.6-year test-retest correlation in a subsample (n = 902) was 0.55. CIUS scores increased slightly with age. Remarkably, gender did not explain variation in CIUS scores, as mean scores on the CIUS were the same in boys and girls. However, the time spent on specific Internet activities differed: boys spent more time on gaming, whereas girls spent more time on social network sites and chatting. The heritability estimates were the same for boys and girls: 48 percent of the individual differences in CIUS score were influenced by genetic factors. The remaining variance (52 percent) was due to environmental influences that were not shared between family members. Because a life without Internet is almost impossible nowadays, it is important to further explore the determinants of compulsive Internet use, including genetic risk factors.

  13. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

    NARCIS (Netherlands)

    Sampson, Joshua N; Wheeler, William A; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I; Lan, Qing; Abnet, Christian C; Amundadottir, Laufey T; Figueroa, Jonine D; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A; Taylor, Philip R; Vivo, Immaculata De; McGlynn, Katherine A; Purdue, Mark P; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L; Angelucci, Emanuele; Ansell, Stephen M; Arici, Cecilia; Armstrong, Bruce K; Arslan, Alan A; Austin, Melissa A; Baris, Dalsu; Barkauskas, Donald A; Bassig, Bryan A; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A; Birmann, Brenda M; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M; Brinton, Louise; Brooks-Wilson, Angela R; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K C; Chang, Ellen T; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S; Comperat, Eva; Conde, Lucia; Connors, Joseph M; Conti, David; Cortessis, Victoria K; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G; Ding, Ti; Diver, W Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J; Ennas, Maria Grazia; Erickson, Ralph L; Feychting, Maria; Flanagan, Adrienne M; Foretova, Lenka; Fraumeni, Joseph F; Freedman, Neal D; Beane Freeman, Laura E; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D; Gastier-Foster, Julie; Gaudet, Mia M; Gaziano, J Michael; Giffen, Carol; Giles, Graham G; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M; Haiman, Christopher A; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R; Holly, Elizabeth A; Hong, Yun-Chul; Hoover, Robert N; Horn-Ross, Pamela L; Hosain, G M Monawar; Hosgood, H Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D; Jackson, Rebecca D; Jacobs, Eric J; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R; Kelly, Rachel S; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M; Klein, Alison P; Klein, Robert J; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S; Link, Brian K; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Lollo, Simonetta Di; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Marchand, Loic Le; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S; Michaud, Dominique S; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E; Novak, Anne J; Oberg, Ann L; Offit, Kenneth; Oh, In-Jae; Olson, Sara H; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H M; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M; Picci, Piero; Pike, Malcolm C; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M; Sanjose, Silvia de; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K; Shanafelt, Tait D; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F; Smith, Alex; Smith, Martyn T; Southey, Melissa C; Spinelli, John J; Staines, Anthony; Stampfer, Meir; Stern, Marianna C; Stevens, Victoria L; Stolzenberg-Solomon, Rachael S; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A; Tinker, Lesley F; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M; Vermeulen, Roel C H; Villano, Danylo J; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E; Wolpin, Brian M; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M; Cerhan, James R; Ferri, Giovanni M; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M; Smedby, Karin E; Teras, Lauren R; Vijai, Joseph; Wang, Sophia S; Brennan, Paul; Caporaso, Neil E; Hunter, David J; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T; Slager, Susan L; Chanock, Stephen J; Chatterjee, Nilanjan

    2015-01-01

    BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.

  14. Composite PLGA/AgNpPGA/AscH nanospheres with combined osteoinductive, antioxidative, and antimicrobial activities.

    Science.gov (United States)

    Stevanović, Magdalena; Uskoković, Vuk; Filipović, Miloš; Škapin, Srečo D; Uskoković, Dragan

    2013-09-25

    The global rise in the resistance of pathogens to conventional antibiotics has created an intensive search for alternative materials with antimicrobial properties. This study is performed with an intention to investigate the combined effects of poly(l-glutamic acid)-capped silver nanoparticles (AgNpPGA) and ascorbic acid (AscH) encapsulated within freeze-dried poly(lactide-co-glycolide) (PLGA) nanospheres to obtain a nanomaterial with simultaneous osteoinductive, antioxidative, and prolonged antimicrobial properties. The influence of PLGA/AgNpPGA/AscH particles on (i) viability and superoxide production of human umbilical vein endothelial cells in vitro, (ii) morphology and expression of osteogenic markers in osteoblastic MC3T3-E1 cells in vitro, and (iii) antimicrobial activity against a Gram-positive bacterium, methicillin-resistant Staphylococcus aureus, and a Gram-negative bacterium, Escherichia coli, was investigated. PLGA/AgNpPGA/AscH nanoparticles showed a superior and extended antibacterial activity against both types of bacteria. The nanoparticles appeared to be capable of delivering ascorbate to the cells, which was evidenced by the significant decrease in the level of superoxides in human umbilical vein endothelial cells and which could have a therapeutic potential in preventing oxidative stress. PLGA/AgNpPGA/AscH nanoparticles had a positive effect on MC3T3-E1 osteoblastic cells in vitro, promoting: (i) an intimate contact with the cells and preservation of their healthy morphologies; (ii) unreduced cell viability; and (iii) multiple-fold upregulation of two osteogenic markers: osteocalcin and type I procollagen. It is concluded that PLGA/AgNpPGA/AscH nanospheres present a promising new material for the treatment of infections and use in wound dressings and other prophylactic applications.

  15. Disease-modifying genes and monogenic disorders: experience in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Gallati S

    2014-07-01

    Full Text Available Sabina Gallati Division of Human Genetics, Department of Pediatrics, and Department of Clinical Research, Inselspital, University of Berne, Berne, Switzerland Abstract: The mechanisms responsible for the determination of phenotypes are still not well understood; however, it has become apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of Mendelian disorders. Significant advances in genetic technologies and molecular medicine allow huge amounts of information to be generated from individual samples within a reasonable time frame. This review focuses on the role of modifier genes using the example of cystic fibrosis, the most common lethal autosomal recessive disorder in the white population, and discusses the advantages and limitations of candidate gene approaches versus genome-wide association studies. Moreover, the implications of modifier gene research for other monogenic disorders, as well as its significance for diagnostic, prognostic, and therapeutic approaches are summarized. Increasing insight into modifying mechanisms opens up new perspectives, dispelling the idea of genetic disorders being caused by one single gene. Keywords: modifier genes, cystic fibrosis, genome wide association studies, candidate gene approach, genotype, phenotype

  16. Study of ASC in Cervical Exfoliated Cytology%宫颈脱落细胞学中 ASC 的研究与分析

    Institute of Scientific and Technical Information of China (English)

    张志兴

    2015-01-01

    Objective To investigate the significance of thinprep cytoligic test (TCT) in the diagnosis of atypical squamous cells.Methods A retrospective analysis was conducted among TCT samples from which those with atypical squamous cells were diag-nosed from July 2012 till July 2014.Results Of all 349 cases, 152 were HPV-positive, and 44.7% were diagnosed with cervical intraepithelial neoplasia or cervical cancer; among 197 cases of HPV-negative patients, 8 cases of patients were with cervical intraepi-thelial neoplasia or cervical cancer.since atypical squamous cells were correlated with age, women older than 40 years old composed the main part of ASC.Conclusion TCT was meaningful for an early detection of cervical lesions and cervical cancer.Increasing awareness of ASC and attention to patients may avoid delay in diagnosis and treatment of cervical lesions.%目的:探讨薄层液基细胞学检测(Thinprep cytoligic test, TCT)在诊断非典型鳞状细胞的意义。方法回顾性分析某医院2012年7月至2014年7月期间 TCT 标本中诊断为非典型鳞状细胞患者的结局。结果349例宫颈非典型鳞状细胞中,152例患者 HPV 阳性,44.7%存在宫颈上皮内瘤变或宫颈癌;197例 HPV 阴性患者中,8例患者存在宫颈上皮内瘤变或宫颈癌。同时非典型鳞状细胞的诊断与年龄存在相关性,年龄在40岁以上的妇女被诊断为 ASC 的人数较多。结论宫颈 TCT 及 HPV 筛查对于宫颈癌前病变及宫颈癌的早期发现有重要价值。应提高对 ASC 认识及对患者重视,以免耽误宫颈病变的诊断和治疗。

  17. Heritability of substance dependence in a native American population.

    Science.gov (United States)

    Wilhelmsen, Kirk C; Ehlers, Cindy

    2005-06-01

    To estimate the heritability of substance dependence and associated symptoms in a sample of Southwest California (Mission) Indians. Families from eight contiguous Indian reservations were recruited in order to ascertain information on substance dependence symptoms and diagnoses using a semi-structured diagnostic interview. Dependence diagnoses for alcohol, marijuana, stimulants and a measure of regular tobacco usage, any drug dependence or tobacco usage were obtained. Composite measures of alcohol dependence symptoms for withdrawal, drinking severity, antisocial problems and interpersonal problems were constructed from the nine groups of symptoms summarized in the diagnostic interview. Heritability estimates were calculated using variance component methods, as implemented in SOLAR. In this population, marijuana dependence (0.38) and regular tobacco use (0.43), alcohol dependence (DSM-III-R 0.19; ICD-10, 0.29) and stimulant dependence (0.25) showed evidence for moderate genetic influences as determined by heritability estimates. Four phenotypes constructed using the composite symptoms of alcohol dependence revealed that withdrawal had the highest heritability estimate (0.71), followed by antisocial problems (0.36) and drinking severity (0.34). Symptom clusters reflecting interpersonal problems did not appear to be highly heritable (0.19). Marijuana dependence, regular tobacco usage and composite phenotypes constructed from alcohol dependence symptoms for antisocial problems, drinking severity and withdrawal generally have patterns of familial aggregation, suggesting that they can be successfully used for linkage analysis in this Southwest California Indian sample.

  18. Ascídias (Tnicata, Ascidiacea) do Espírito Santo, Brasil

    OpenAIRE

    Gamba, Gustavo Antunes

    2013-01-01

    Resumo: De acordo com o banco de dados The World Register of Marine Species existem em torno de 2900 espécies de ascídias descritas. No Brasil, o conhecimento sobre a fauna desses animais é ainda insuficiente, com muitas espécies de ascídias ainda não conhecidas. Acredita-se que existam aproximadamente 130 espécies válidas no país, mas aproximadamente 100 estão atualmente registradas. O Espírito Santo é um dos vários estados brasileiros para o qual pouco se conhece a fauna desse táxon, pois o...

  19. Checklist das ascídias (Tunicata, Ascidiacea) do Estado de São Paulo, Brasil

    OpenAIRE

    Rocha,Rosana Moreira da; Dias,Gustavo Muniz; Lotufo,Tito Monteiro da Cruz

    2011-01-01

    Ascídias são organismos marinhos que, em sua maioria, vivem fixados a substratos consolidados desde as regiões costeiras até às grandes profundidades. Apesar de serem cordados, apresentam um plano corporal adulto muito modificado em função de seu hábito de vida. O Estado de São Paulo é o que apresenta o melhor conhecimento da fauna de ascídias, tanto em termos de sua biodiversidade como em aspectos ecológicos. No estado, a região do município de São Sebastião foi a mais estudada em função da ...

  20. ASC Tri-lab Co-design Level 2 Milestone Report 2015

    Energy Technology Data Exchange (ETDEWEB)

    Hornung, Rich [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Jones, Holger [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Keasler, Jeff [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Neely, Rob [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Pearce, Olga [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hammond, Si [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Trott, Christian [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lin, Paul [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Vaughan, Courtenay [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Cook, Jeanine [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hoekstra, Rob [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bergen, Ben [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Payne, Josh [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Womeldorff, Geoff [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-09-23

    In 2015, the three Department of Energy (DOE) National Laboratories that make up the Advanced Sci- enti c Computing (ASC) Program (Sandia, Lawrence Livermore, and Los Alamos) collaboratively explored performance portability programming environments in the context of several ASC co-design proxy applica- tions as part of a tri-lab L2 milestone executed by the co-design teams at each laboratory. The programming environments that were studied included Kokkos (developed at Sandia), RAJA (LLNL), and Legion (Stan- ford University). The proxy apps studied included: miniAero, LULESH, CoMD, Kripke, and SNAP. These programming models and proxy-apps are described herein. Each lab focused on a particular combination of abstractions and proxy apps, with the goal of assessing performance portability using those. Performance portability was determined by: a) the ability to run a single application source code on multiple advanced architectures, b) comparing runtime performance between \

  1. The Astrobiology in Secondary Classrooms (ASC) curriculum: focusing upon diverse students and teachers.

    Science.gov (United States)

    Arino de la Rubia, Leigh S

    2012-09-01

    The Minority Institution Astrobiology Collaborative (MIAC) began working with the NASA Goddard Center for Astrobiology in 2003 to develop curriculum materials for high school chemistry and Earth science classes based on astrobiology concepts. The Astrobiology in Secondary Classrooms (ASC) modules emphasize interdisciplinary connections in astronomy, biology, chemistry, geoscience, physics, mathematics, and ethics through hands-on activities that address national educational standards. Field-testing of the Astrobiology in Secondary Classrooms materials occurred over three years in eight U.S. locations, each with populations that are underrepresented in the career fields of science, technology, engineering, and mathematics. Analysis of the educational research upon the high school students participating in the ASC project showed statistically significant increases in students' perceived knowledge and science reasoning. The curriculum is in its final stages, preparing for review to become a NASA educational product.

  2. Bacillus thuringiensis monogenic strains: screening and interactions with insecticides used against rice pests

    Directory of Open Access Journals (Sweden)

    Laura M.N. Pinto

    2012-06-01

    Full Text Available The screening of Bacillus thuringiensis (Bt Cry proteins with high potential to control insect pests has been the goal of numerous research groups. In this study, we evaluated six monogenic Bt strains (Bt dendrolimus HD-37, Bt kurstaki HD-1, Bt kurstaki HD-73, Bt thuringiensis 4412, Bt kurstaki NRD-12 and Bt entomocidus 60.5, which codify the cry1Aa, cry1Ab, cry1Ac, cry1Ba, cry1C, cry2A genes respectively as potential insecticides for the most important insect pests of irrigated rice: Spodoptera frugiperda, Diatraea saccharalis, Oryzophagus oryzae, Oebalus poecilus and Tibraca limbativentris. We also analyzed their compatibility with chemical insecticides (thiamethoxam, labdacyhalothrin, malathion and fipronil, which are extensively used in rice crops. The bioassay results showed that Bt thuringiensis 4412 and Bt entomocidus 60.5 were the most toxic for the lepidopterans, with a 93% and 82% mortality rate for S. frugiperda and D. saccharalis, respectively. For O. oryzae, the Bt kurstaki NRD-12 (64% and Bt dendrolimus HD-37 (62% strains were the most toxic. The Bt dendrolimus HD-37 strain also caused high mortality (82% to O. poecilus, however the strains assessed to T. limbativentris caused a maximum rate of 5%. The assays for the Bt strains interaction with insecticides revealed the compatibility of the six strains with the four insecticides tested. The results from this study showed the high potential of cry1Aa and cry1Ba genes for genetic engineering of rice plants or the strains to biopesticide formulations.

  3. Heritability of sex tendency in a harpacticoid copepod, Tigriopus californicus.

    Science.gov (United States)

    Voordouw, Maarten J; Anholt, Bradley R

    2002-09-01

    Systems with genetic variation for the primary sex ratio are important for testing sex-ratio theory and for understanding how this variation is maintained. Evidence is presented for heritable variation of the primary sex ratio in the harpacticoid copepod Tigriopus californicus. Variation in the primary sex ratio among families cannot be accounted for by Mendelian segregation of sex chromosomes. The covariance in sex phenotype between full-sibling clutches and between mothers and offspring suggests that this variation has a polygenic basis. Averaged over four replicates, the full-sibling heritability of sex tendency is 0.13 +/- 0.040; and the mother-offspring heritability of sex tendency is 0.31 +/- 0.216. Genetic correlations in the sex phenotype across two temperature treatments indicate large genotype-by-temperature interactions. Future experiments need to distinguish between zygotic, parental, or cytoplasmic mechanisms of sex determination in T. californicus.

  4. The Human Microbiome and the Missing Heritability Problem

    Directory of Open Access Journals (Sweden)

    Santiago Sandoval-Motta

    2017-06-01

    Full Text Available The “missing heritability” problem states that genetic variants in Genome-Wide Association Studies (GWAS cannot completely explain the heritability of complex traits. Traditionally, the heritability of a phenotype is measured through familial studies using twins, siblings and other close relatives, making assumptions on the genetic similarities between them. When this heritability is compared to the one obtained through GWAS for the same traits, a substantial gap between both measurements arise with genome wide studies reporting significantly smaller values. Several mechanisms for this “missing heritability” have been proposed, such as epigenetics, epistasis, and sequencing depth. However, none of them are able to fully account for this gap in heritability. In this paper we provide evidence that suggests that in order for the phenotypic heritability of human traits to be broadly understood and accounted for, the compositional and functional diversity of the human microbiome must be taken into account. This hypothesis is based on several observations: (A The composition of the human microbiome is associated with many important traits, including obesity, cancer, and neurological disorders. (B Our microbiome encodes a second genome with nearly a 100 times more genes than the human genome, and this second genome may act as a rich source of genetic variation and phenotypic plasticity. (C Human genotypes interact with the composition and structure of our microbiome, but cannot by themselves explain microbial variation. (D Microbial genetic composition can be strongly influenced by the host's behavior, its environment or by vertical and horizontal transmissions from other hosts. Therefore, genetic similarities assumed in familial studies may cause overestimations of heritability values. We also propose a method that allows the compositional and functional diversity of our microbiome to be incorporated to genome wide association studies.

  5. ASC-H诊断的临床指导意义

    Institute of Scientific and Technical Information of China (English)

    白合尼莎·阿不都热西提; 迪丽努尔·吐尔逊

    2007-01-01

    目的 分析不除外高度上皮内病变的不典型鳞状上皮细胞(ASC-H)在宫颈病变中的诊断意义.方法 ASC-H病例行阴道镜检查并取活检,结果作对照分析.结果 细胞学诊断的40例ASCH病例中,33例有病理对照,其中有20例病理结果显示慢性宫颈炎,3例LSIL(低度鳞状上皮内病变)、8例HSIL(高度鳞状上皮内病变)、1例鳞状细胞癌(SCC)、1例息肉(polyp).结论 ASC-H有预示CIN2和CIN3的阳性价值.

  6. Intracellular invasion of Orientia tsutsugamushi activates inflammasome in asc-dependent manner.

    Directory of Open Access Journals (Sweden)

    Jung-Eun Koo

    Full Text Available Orientia tsutsugamushi, a causative agent of scrub typhus, is an obligate intracellular bacterium, which escapes from the endo/phagosome and replicates in the host cytoplasm. O. tsutsugamushi infection induces production of pro-inflammatory mediators including interleukin-1β (IL-1β, which is secreted mainly from macrophages upon cytosolic stimuli by activating cysteine protease caspase-1 within a complex called the inflammasome, and is a key player in initiating and maintaining the inflammatory response. However, the mechanism for IL-1β maturation upon O. tsutsugamushi infection has not been identified. In this study, we show that IL-1 receptor signaling is required for efficient host protection from O. tsutsugamushi infection. Live Orientia, but not heat- or UV-inactivated Orientia, activates the inflammasome through active bacterial uptake and endo/phagosomal maturation. Furthermore, Orientia-stimulated secretion of IL-1β and activation of caspase-1 are ASC- and caspase-1- dependent since IL-1β production was impaired in Asc- and caspase-1-deficient macrophages but not in Nlrp3-, Nlrc4- and Aim2-deficient macrophages. Therefore, live O. tsutsugamushi triggers ASC inflammasome activation leading to IL-1β production, which is a critical innate immune response for effective host defense.

  7. A Comparison of ASCE and FAO56 Reference Evapotranspiration at Different Subdaily Timescales: a Numerical Study

    Directory of Open Access Journals (Sweden)

    Farzin Parchami-Araghi

    2017-01-01

    Full Text Available Introduction: Subdaily estimates of reference evapotranspiration (ETo are needed in many applications such as dynamic agro-hydrological modeling. The ASCE and FAO56 Penman–Monteith models (ASCE-PM and FAO56-PM, respectively has received favorable acceptance and application over much of the world, including the United States, for establishing a reference evapotranspiration (ETo index as a function of weather parameters. In the past several years various studies have evaluated ASCE-PM and FAO56-PM models for calculating the commonest hourly or 15-min ETo either by comparing them with lysimetric measurements or by comparison with one another (2, 3, 5, 9, 10, 11, 16, 17, 19. In this study, sub-daily ET o estimates made by the ASCE-PM and FAO56-PM models at different timescales (1-360 min were compared through conduction of a computational experiment, using a daily to sub-daily disaggregation framework developed by Parchami-Araghi et al. (14. Materials and Methods: Daily and sub-daily weather data at different timescales (1-360 min were generated via a daily-to-sub-daily weather data disaggregation framework developed by Parchami-Araghi et al. (14, using long-term (59 years daily weather data obtained from Abadan synoptic weather station. Daily/sub-daily net long wave radiation (Rnl was estimated through 6 different approaches, including using two different criteria for identifying the daytime/nighttime periods : 1 the standard criteria implemented in both ASCE-PM and FAO56-PM models and 2 criterion of actual time of sunset and sunrise in combination with 1 estimation of clear-sky radiation (Rso based on the standard approach implemented in both ASCE-PM and FAO56-PM models (1st and 2nd Rnl estimation approaches, respectively, 2 integral of the Rso estimates derived via a physically based solar radiation model developed by Yang et al. (25, YNG model, for one-second time-steps (3rd and 4th Rnl estimation approaches, respectively, and 3 integral of

  8. Heritability of aerobic power of individuals in northeast Brazil.

    Science.gov (United States)

    Alonso, L; Souza, Ec; Oliveira, Mv; do Nascimento, Lfe; Dantas, Pms

    2014-12-01

    The objective of this study was to evaluate the genetic and environmental contribution to variation in aerobic power in monozygotic (MZ) and dizygotic (DZ) twins. The sample consisted of 20 MZ individuals (12 females and 8 males) and 16 DZ individuals (12 females and 4 males), aged from 8 to 26 years, residents in Natal, Rio Grande do Norte. The twins were assessed by a multistage fitness test. The rate of heritability found for aerobic power was 77%. Based on the results, the estimated heritability was largely responsible for the differences in aerobic power. This implies that such measures are under strong genetic influence.

  9. The Astrobiology in Secondary Classroom (ASC) Curriculum Development Project: Focusing Upon Diverse Students and Teachers in the Pilot Testing Process

    Science.gov (United States)

    Butler, J.; Arino de La Rubia, L.; Gary, T.; Kuner, S.; Ceballos, R. M.; Pfiffner, S.; Brown, S.

    2010-04-01

    The ASC curriculum guide is designed to address the learning styles present in diverse classrooms by incorporating research-based teaching strategies that increase participation of underrepresented groups in STEM fields.

  10. New therapy with ASC-J9® to suppress the prostatitis via altering the cytokine CCL2 signals.

    Science.gov (United States)

    Lin, Shin-Jen; Chou, Fu-Ju; Lin, Chang-Yi; Chang, Hong-Chiang; Yeh, Shuyuan; Chang, Chawnshang

    2016-10-11

    Prostatitis is a common disease contributing to 8% of all urologist visits. Yet the etiology and effective treatment remain to be further elucidated. Using a non-obese diabetes mouse model that can be induced by autoimmune response for the spontaneous development of prostatitis, we found that injection of the ASC-J9® at 75 mg/Kg body weight/48 hours led to significantly suppressed prostatitis that was accompanied with reduction of lymphocyte infiltration with reduced CD4+ T cells in prostate. In vitro studies with a co-culture system also confirmed that ASC-J9® treatment could suppress the CD4+ T cell migration to prostate stromal cells. Mechanisms dissection indicated that ASC-J9® can suppress CD4+ T cell migration via decreasing the cytokine CCL2 in vitro and in vivo, and restoring CCL2 could interrupt the ASC-J9® suppressed CD4+ T cell migration. Together, results from in vivo and in vitro studies suggest that ASC-J9® can suppress prostatitis by altering the autoimmune response induced by CD4+ T cell recruitment, and using ASC-J9® may help us to develop a potential new therapy to battle the prostatitis with little side effects.

  11. Estimation of cardiac motion in cine-MRI sequences by correlation transform optical flow of monogenic features distance

    Science.gov (United States)

    Gao, Bin; Liu, Wanyu; Wang, Liang; Liu, Zhengjun; Croisille, Pierre; Delachartre, Philippe; Clarysse, Patrick

    2016-12-01

    Cine-MRI is widely used for the analysis of cardiac function in clinical routine, because of its high soft tissue contrast and relatively short acquisition time in comparison with other cardiac MRI techniques. The gray level distribution in cardiac cine-MRI is relatively homogenous within the myocardium, and can therefore make motion quantification difficult. To ensure that the motion estimation problem is well posed, more image features have to be considered. This work is inspired by a method previously developed for color image processing. The monogenic signal provides a framework to estimate the local phase, orientation, and amplitude, of an image, three features which locally characterize the 2D intensity profile. The independent monogenic features are combined into a 3D matrix for motion estimation. To improve motion estimation accuracy, we chose the zero-mean normalized cross-correlation as a matching measure, and implemented a bilateral filter for denoising and edge-preservation. The monogenic features distance is used in lieu of the color space distance in the bilateral filter. Results obtained from four realistic simulated sequences outperformed two other state of the art methods even in the presence of noise. The motion estimation errors (end point error) using our proposed method were reduced by about 20% in comparison with those obtained by the other tested methods. The new methodology was evaluated on four clinical sequences from patients presenting with cardiac motion dysfunctions and one healthy volunteer. The derived strain fields were analyzed favorably in their ability to identify myocardial regions with impaired motion.

  12. [Monogenic form of diabetes mellitus due to HNF4α mutation (MODY-1) - the first case in Hungary].

    Science.gov (United States)

    Jermendy, György; Balogh, István; Gaál, Zsolt

    2016-03-20

    The classification of diabetes mellitus in adolescents and young adults is often difficult. The diagnosis of the monogenic form of diabetes may have substantial influence on quality of life, prognosis and the choice of the appropriate treatment of affected patients. Among MODY (maturity-onset of diabetes in the young) MODY-1 is rarely detected, only 13 families were described in 2000, and 103 different mutations in 173 families were known in 2013 worldwide. The authors present the first Hungarian case of a monogenic form of diabetes due to HNF4α mutation (MODY-1). The diabetes of the index patient No. 1 (42-year-old woman with insulin treated diabetes) was diagnosed as gestational diabetes at age of 20 when she was treated with diet only. Later, insulin treatment has been initiated when marked hyperglycaemia was detected during an episode of acute pneumonia at age of 26. The diabetes of the index patient No. 2 (20-year-old daughter of the index patient No. 1, treated also with insulin) was diagnosed as type 2 diabetes at age of 13 and the patient was treated with diet only. Later the classification was modified to type 1 and insulin therapy was initiated at age of 14. The manifestation of diabetes, the familial occurrence and the low dose insulin requirement were suggestive for monogenic diabetes. Using molecular genetic method a mutation (c.869G>A, p.R290H) of HNF4α gene was found and MODY-1 was diagnosed in both cases. Insulin therapy was switched to treatment with low dose sulfanylurea and an excellent glycaemic control was achieved and sustained at follow-up of 1-year. No further positive cases were found during screening of other family members.

  13. Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study.

    Science.gov (United States)

    Dreesen, Jos; Destouni, Aspasia; Kourlaba, Georgia; Degn, Birte; Mette, Wulf Christensen; Carvalho, Filipa; Moutou, Celine; Sengupta, Sioban; Dhanjal, Seema; Renwick, Pamela; Davies, Steven; Kanavakis, Emmanouel; Harton, Gary; Traeger-Synodinos, Joanne

    2014-08-01

    Preimplantation genetic diagnosis (PGD) for monogenic disorders currently involves polymerase chain reaction (PCR)-based methods, which must be robust, sensitive and highly accurate, precluding misdiagnosis. Twelve adverse misdiagnoses reported to the ESHRE PGD-Consortium are likely an underestimate. This retrospective study, involving six PGD centres, assessed the validity of PCR-based PGD through reanalysis of untransferred embryos from monogenic-PGD cycles. Data were collected on the genotype concordance at PGD and follow-up from 940 untransferred embryos, including details on the parameters of PGD cycles: category of monogenic disease, embryo morphology, embryo biopsy and genotype assay strategy. To determine the validity of PCR-based PGD, the sensitivity (Se), specificity (Sp) and diagnostic accuracy were calculated. Stratified analyses were also conducted to assess the influence of the parameters above on the validity of PCR-based PGD. The analysis of overall data showed that 93.7% of embryos had been correctly classified at the time of PGD, with Se of 99.2% and Sp of 80.9%. The stratified analyses found that diagnostic accuracy is statistically significantly higher when PGD is performed on two cells versus one cell (P=0.001). Se was significantly higher when multiplex protocols versus singleplex protocols were applied (P=0.005), as well as for PGD applied on cells from good compared with poor morphology embryos (P=0.032). Morphology, however, did not affect diagnostic accuracy. Multiplex PCR-based methods on one cell, are as robust as those on two cells regarding false negative rate, which is the most important criteria for clinical PGD applications. Overall, this study demonstrates the validity, robustness and high diagnostic value of PCR-based PGD.

  14. Heritability of cold tolerance in Nile tilapia, Oreochromis niloticus, juveniles

    NARCIS (Netherlands)

    Charo-Karisa, H.; Rezk, M.A.; Bovenhuis, H.; Komen, J.

    2005-01-01

    The inability of tilapia to tolerate low temperatures is of major economic concern as it reduces their growing season and leads to over winter mortality. In this study, cold tolerance of juvenile Nile tilapia, Oreochromis niloticus, was investigated and heritability estimates obtained. A total of 80

  15. Race/class : Jamaica's discourse of heritable identity

    Directory of Open Access Journals (Sweden)

    Diane J. Austin-Broos

    1994-07-01

    Full Text Available Argues that Jamaican notions of 'race' and 'class' can be rendered as a discourse of heritable biological and environmental identity. There has been a movement in the meaning of colour categories from an emphasis on biology, to a greater emphasis on environment. This transition has been encouraged by the emergence of class as a 20th-c. idiom.

  16. Equality in Educational Policy and the Heritability of Educational Attainment.

    Science.gov (United States)

    Colodro-Conde, Lucía; Rijsdijk, Frühling; Tornero-Gómez, María J; Sánchez-Romera, Juan F; Ordoñana, Juan R

    2015-01-01

    Secular variation in the heritability of educational attainment are proposed to be due to the implementation of more egalitarian educational policies leading to increased equality in educational opportunities in the second part of the 20th century. The action of effect is hypothesized to be a decrease of shared environmental (e.g., family socioeconomic status or parents' education) influences on educational attainment, giving more room for genetic differences between individuals to impact on the variation of the trait. However, this hypothesis has not yet found consistent evidence. Support for this effect relies mainly on comparisons between countries adopting different educational systems or between different time periods within a country reflecting changes in general policy. Using a population-based sample of 1271 pairs of adult twins, we analyzed the effect of the introduction of a specific educational policy in Spain in 1970. The shared-environmental variance decreased, leading to an increase in heritability in the post-reform cohort (44 vs. 67%) for males. Unstandardized estimates of genetic variance were of a similar magnitude (.56 vs. .57) between cohorts, while shared environmental variance decreased from .56 to .04. Heritability remained in the same range for women (40 vs. 34%). Our results support the role of educational policy in affecting the relative weight of genetic and environmental factors on educational attainment, such that increasing equality in educational opportunities increases heritability estimates by reducing variation of non-genetic familial origin.

  17. Heritability of decisions and outcomes of public goods games.

    Science.gov (United States)

    Hiraishi, Kai; Shikishima, Chizuru; Yamagata, Shinji; Ando, Juko

    2015-01-01

    Prosociality is one of the most distinctive features of human beings but there are individual differences in cooperative behavior. Employing the twin method, we examined the heritability of cooperativeness and its outcomes on public goods games using a strategy method. In two experiments (Study 1 and Study 2), twin participants were asked to indicate (1) how much they would contribute to a group when they did not know how much the other group members were contributing, and (2) how much they would contribute if they knew the contributions of others. Overall, the heritability estimates were relatively small for each type of decision, but heritability was greater when participants knew that the others had made larger contributions. Using registered decisions in Study 2, we conducted seven Monte Carlo simulations to examine genetic and environmental influences on the expected game payoffs. For the simulated one-shot game, the heritability estimates were small, comparable to those of game decisions. For the simulated iterated games, we found that the genetic influences first decreased, then increased as the numbers of iterations grew. The implication for the evolution of individual differences in prosociality is discussed.

  18. Equality in Educational Policy and the Heritability of Educational Attainment.

    Directory of Open Access Journals (Sweden)

    Lucía Colodro-Conde

    Full Text Available Secular variation in the heritability of educational attainment are proposed to be due to the implementation of more egalitarian educational policies leading to increased equality in educational opportunities in the second part of the 20th century. The action of effect is hypothesized to be a decrease of shared environmental (e.g., family socioeconomic status or parents' education influences on educational attainment, giving more room for genetic differences between individuals to impact on the variation of the trait. However, this hypothesis has not yet found consistent evidence. Support for this effect relies mainly on comparisons between countries adopting different educational systems or between different time periods within a country reflecting changes in general policy. Using a population-based sample of 1271 pairs of adult twins, we analyzed the effect of the introduction of a specific educational policy in Spain in 1970. The shared-environmental variance decreased, leading to an increase in heritability in the post-reform cohort (44 vs. 67% for males. Unstandardized estimates of genetic variance were of a similar magnitude (.56 vs. .57 between cohorts, while shared environmental variance decreased from .56 to .04. Heritability remained in the same range for women (40 vs. 34%. Our results support the role of educational policy in affecting the relative weight of genetic and environmental factors on educational attainment, such that increasing equality in educational opportunities increases heritability estimates by reducing variation of non-genetic familial origin.

  19. Heritability of decisions and outcomes of public goods games

    Directory of Open Access Journals (Sweden)

    Kai eHiraishi

    2015-04-01

    Full Text Available Prosociality is one of the most distinctive features of human beings but there are individual differences in cooperative behavior. Employing the twin method, we examined the heritability of cooperativeness and its outcomes on public goods games using a strategy method. In two experiments (Study 1 and Study 2, twin participants were asked to indicate 1 how much they would contribute to a group when they did not know how much the other group members were contributing, and 2 how much they would contribute if they knew the contributions of others. Overall, the heritability estimates were relatively small for each type of decision, but heritability was greater when participants knew that the others had made larger contributions. Using registered decisions in Study 2, we conducted five Monte Carlo simulations to examine genetic and environmental influences on the expected game payoffs. For the simulated one-shot game, the heritability estimates were small, comparable to those of game decisions. For the simulated iterated games, we found that the genetic influences first decreased, then increased as the numbers of iterations grew. The implication for the evolution of individual differences in prosociality is discussed.

  20. Partitioning heritability by functional category using GWAS summary statistics

    DEFF Research Database (Denmark)

    Finucane, Hilary K.; Bulik-Sullivan, Brendan; Gusev, Alexander

    2015-01-01

    in genome-wide association studies (GWAS) of 17 complex diseases and traits with an average sample size of 73,599. To enable this analysis, we introduce a new method, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers. This new...

  1. The heritability of chimpanzee and human brain asymmetry.

    Science.gov (United States)

    Gómez-Robles, Aida; Hopkins, William D; Schapiro, Steven J; Sherwood, Chet C

    2016-12-28

    Human brains are markedly asymmetric in structure and lateralized in function, which suggests a relationship between these two properties. The brains of other closely related primates, such as chimpanzees, show similar patterns of asymmetry, but to a lesser degree, indicating an increase in anatomical and functional asymmetry during hominin evolution. We analysed the heritability of cerebral asymmetry in chimpanzees and humans using classic morphometrics, geometric morphometrics, and quantitative genetic techniques. In our analyses, we separated directional asymmetry and fluctuating asymmetry (FA), which is indicative of environmental influences during development. We show that directional patterns of asymmetry, those that are consistently present in most individuals in a population, do not have significant heritability when measured through simple linear metrics, but they have marginally significant heritability in humans when assessed through three-dimensional configurations of landmarks that reflect variation in the size, position, and orientation of different cortical regions with respect to each other. Furthermore, genetic correlations between left and right hemispheres are substantially lower in humans than in chimpanzees, which points to a relatively stronger environmental influence on left-right differences in humans. We also show that the level of FA has significant heritability in both species in some regions of the cerebral cortex. This suggests that brain responsiveness to environmental influences, which may reflect neural plasticity, has genetic bases in both species. These results have implications for the evolvability of brain asymmetry and plasticity among humans and our close relatives.

  2. Heritability of telomere length in the Zebra Finch

    NARCIS (Netherlands)

    Atema, Els; Mulder, Ellis; Dugdale, Hannah L.; Briga, Michael; van Noordwijk, Arie J.; Verhulst, Simon

    2015-01-01

    Telomere length predicts survival in birds, and many stressors that presumably reduce fitness have also been linked to telomere length. The response to selection of telomere length will be largely determined by the heritability of this trait; however, little is known about the genetic component of t

  3. 40 CFR 798.5460 - Rodent heritable translocation assays.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Rodent heritable translocation assays. 798.5460 Section 798.5460 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC...) Species. The mouse is the species generally used, and is recommended. (ii) Age. Healthy sexually...

  4. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

    NARCIS (Netherlands)

    Sampson, Joshua N; Wheeler, William A; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I; Lan, Qing; Abnet, Christian C; Amundadottir, Laufey T; Figueroa, Jonine D; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A; Taylor, Philip R; Vivo, Immaculata De; McGlynn, Katherine A; Purdue, Mark P; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L; Angelucci, Emanuele; Ansell, Stephen M; Arici, Cecilia; Armstrong, Bruce K; Arslan, Alan A; Austin, Melissa A; Baris, Dalsu; Barkauskas, Donald A; Bassig, Bryan A; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A; Birmann, Brenda M; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M; Brinton, Louise; Brooks-Wilson, Angela R; Bueno-de-Mesquita, H Bas|info:eu-repo/dai/nl/06929528X; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K C; Chang, Ellen T; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S; Comperat, Eva; Conde, Lucia; Connors, Joseph M; Conti, David; Cortessis, Victoria K; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G; Ding, Ti; Diver, W Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J; Ennas, Maria Grazia; Erickson, Ralph L; Feychting, Maria; Flanagan, Adrienne M; Foretova, Lenka; Fraumeni, Joseph F; Freedman, Neal D; Beane Freeman, Laura E; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D; Gastier-Foster, Julie; Gaudet, Mia M; Gaziano, J Michael; Giffen, Carol; Giles, Graham G; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M; Haiman, Christopher A; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R; Holly, Elizabeth A; Hong, Yun-Chul; Hoover, Robert N; Horn-Ross, Pamela L; Hosain, G M Monawar; Hosgood, H Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D; Jackson, Rebecca D; Jacobs, Eric J; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R; Kelly, Rachel S; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M; Klein, Alison P; Klein, Robert J; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S; Link, Brian K; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Lollo, Simonetta Di; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Marchand, Loic Le; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S; Michaud, Dominique S; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E; Novak, Anne J; Oberg, Ann L; Offit, Kenneth; Oh, In-Jae; Olson, Sara H; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H M|info:eu-repo/dai/nl/074099655; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M; Picci, Piero; Pike, Malcolm C; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M; Sanjose, Silvia de; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K; Shanafelt, Tait D; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F; Smith, Alex; Smith, Martyn T; Southey, Melissa C; Spinelli, John J; Staines, Anthony; Stampfer, Meir; Stern, Marianna C; Stevens, Victoria L; Stolzenberg-Solomon, Rachael S; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A; Tinker, Lesley F; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M; Vermeulen, Roel C H; Villano, Danylo J; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E; Wolpin, Brian M; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M; Cerhan, James R; Ferri, Giovanni M; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M; Smedby, Karin E; Teras, Lauren R; Vijai, Joseph; Wang, Sophia S; Brennan, Paul; Caporaso, Neil E; Hunter, David J; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T; Slager, Susan L; Chanock, Stephen J; Chatterjee, Nilanjan

    2015-01-01

    BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. METHO

  5. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

    NARCIS (Netherlands)

    Sampson, Joshua N; Wheeler, William A; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I; Lan, Qing; Abnet, Christian C; Amundadottir, Laufey T; Figueroa, Jonine D; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A; Taylor, Philip R; Vivo, Immaculata De; McGlynn, Katherine A; Purdue, Mark P; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L; Angelucci, Emanuele; Ansell, Stephen M; Arici, Cecilia; Armstrong, Bruce K; Arslan, Alan A; Austin, Melissa A; Baris, Dalsu; Barkauskas, Donald A; Bassig, Bryan A; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A; Birmann, Brenda M; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M; Brinton, Louise; Brooks-Wilson, Angela R; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K C; Chang, Ellen T; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S; Comperat, Eva; Conde, Lucia; Connors, Joseph M; Conti, David; Cortessis, Victoria K; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G; Ding, Ti; Diver, W Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J; Ennas, Maria Grazia; Erickson, Ralph L; Feychting, Maria; Flanagan, Adrienne M; Foretova, Lenka; Fraumeni, Joseph F; Freedman, Neal D; Beane Freeman, Laura E; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D; Gastier-Foster, Julie; Gaudet, Mia M; Gaziano, J Michael; Giffen, Carol; Giles, Graham G; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M; Haiman, Christopher A; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R; Holly, Elizabeth A; Hong, Yun-Chul; Hoover, Robert N; Horn-Ross, Pamela L; Hosain, G M Monawar; Hosgood, H Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D; Jackson, Rebecca D; Jacobs, Eric J; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R; Kelly, Rachel S; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M; Klein, Alison P; Klein, Robert J; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S; Link, Brian K; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Lollo, Simonetta Di; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Marchand, Loic Le; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S; Michaud, Dominique S; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E; Novak, Anne J; Oberg, Ann L; Offit, Kenneth; Oh, In-Jae; Olson, Sara H; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H M; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M; Picci, Piero; Pike, Malcolm C; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M; Sanjose, Silvia de; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K; Shanafelt, Tait D; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F; Smith, Alex; Smith, Martyn T; Southey, Melissa C; Spinelli, John J; Staines, Anthony; Stampfer, Meir; Stern, Marianna C; Stevens, Victoria L; Stolzenberg-Solomon, Rachael S; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A; Tinker, Lesley F; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M; Vermeulen, Roel C H; Villano, Danylo J; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E; Wolpin, Brian M; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M; Cerhan, James R; Ferri, Giovanni M; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M; Smedby, Karin E; Teras, Lauren R; Vijai, Joseph; Wang, Sophia S; Brennan, Paul; Caporaso, Neil E; Hunter, David J; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T; Slager, Susan L; Chanock, Stephen J; Chatterjee, Nilanjan

    2015-01-01

    BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. METHO

  6. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types

    Science.gov (United States)

    Wheeler, William A.; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I.; Lan, Qing; Abnet, Christian C.; Amundadottir, Laufey T.; Figueroa, Jonine D.; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A.; Taylor, Philip R.; Vivo, Immaculata De; McGlynn, Katherine A.; Purdue, Mark P.; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Angelucci, Emanuele; Ansell, Stephen M.; Arici, Cecilia; Armstrong, Bruce K.; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A.; Birmann, Brenda M.; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brinton, Louise; Brooks-Wilson, Angela R.; Bueno-de-Mesquita, H. Bas; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K. C.; Chang, Ellen T.; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C.; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S.; Comperat, Eva; Conde, Lucia; Connors, Joseph M.; Conti, David; Cortessis, Victoria K.; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G.; Ding, Ti; Diver, W. Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J.; Ennas, Maria Grazia; Erickson, Ralph L.; Feychting, Maria; Flanagan, Adrienne M.; Foretova, Lenka; Fraumeni, Joseph F.; Freedman, Neal D.; Beane Freeman, Laura E.; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D.; Gastier-Foster, Julie; Gaudet, Mia M.; Gaziano, J. Michael; Giffen, Carol; Giles, Graham G.; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M.; Haiman, Christopher A.; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R.; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Horn-Ross, Pamela L.; Hosain, G. M. Monawar; Hosgood, H. Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D.; Jackson, Rebecca D.; Jacobs, Eric J.; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R.; Kelly, Rachel S.; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert J.; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M.; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S.; Link, Brian K.; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Lollo, Simonetta Di; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Marchand, Loic Le; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S.; Michaud, Dominique S.; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E.; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E.; Novak, Anne J.; Oberg, Ann L.; Offit, Kenneth; Oh, In-Jae; Olson, Sara H.; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A.; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M.; de Sanjose, Silvia; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K.; Shanafelt, Tait D.; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F.; Smith, Alex; Smith, Martyn T.; Southey, Melissa C.; Spinelli, John J.; Staines, Anthony; Stampfer, Meir; Stern, Marianna C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael S.; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A.; Tinker, Lesley F.; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C.; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M.; Vermeulen, Roel C. H.; Villano, Danylo J.; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J.; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M.; Cerhan, James R.; Ferri, Giovanni M.; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M.; Smedby, Karin E.; Teras, Lauren R.; Vijai, Joseph; Wang, Sophia S.; Brennan, Paul; Caporaso, Neil E.; Hunter, David J.; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T.; Slager, Susan L.; Chanock, Stephen J.; Chatterjee, Nilanjan

    2015-01-01

    Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl 2, on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our

  7. Heritability of cortisol response to confinement stress in European sea bass dicentrarchus labrax

    NARCIS (Netherlands)

    Volckaert, F.A.M.; Hellemans, B.; Batargias, C.; Louro, B.; Massault, C.; Houdt, Van J.K.J.; Haley, C.; Koning, de D.J.; Canario, A.V.M.

    2012-01-01

    Background: In fish, the most studied production traits in terms of heritability are body weight or growth, stress or disease resistance, while heritability of cortisol levels, widely used as a measure of response to stress, is less studied. In this study, we have estimated heritabilities of two gro

  8. Antiproliferative effect of ASC-J9 delivered by PLGA nanoparticles against estrogen-dependent breast cancer cells.

    Science.gov (United States)

    Verderio, Paolo; Pandolfi, Laura; Mazzucchelli, Serena; Marinozzi, Maria Rosaria; Vanna, Renzo; Gramatica, Furio; Corsi, Fabio; Colombo, Miriam; Morasso, Carlo; Prosperi, Davide

    2014-08-04

    Among polymeric nanoparticles designed for cancer therapy, PLGA nanoparticles have become one of the most popular polymeric devices for chemotherapeutic-based nanoformulations against several kinds of malignant diseases. Promising properties, including long-circulation time, enhanced tumor localization, interference with "multidrug" resistance effects, and environmental biodegradability, often result in an improvement of the drug bioavailability and effectiveness. In the present work, we have synthesized 1,7-bis(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one (ASC-J9) and developed uniform ASC-J9-loaded PLGA nanoparticles of about 120 nm, which have been prepared by a single-emulsion process. Structural and morphological features of the nanoformulation were analyzed, followed by an accurate evaluation of the in vitro drug release kinetics, which exhibited Fickian law diffusion over 10 days. The intracellular degradation of ASC-J9-bearing nanoparticles within estrogen-dependent MCF-7 breast cancer cells was correlated to a time- and dose-dependent activity of the released drug. A cellular growth inhibition associated with a specific cell cycle G2/M blocking effect caused by ASC-J9 release inside the cytosol allowed us to put forward a hypothesis on the action mechanism of this nanosystem, which led to the final cell apoptosis. Our study was accomplished using Annexin V-based cell death analysis, MTT assessment of proliferation, radical scavenging activity, and intracellular ROS evaluation. Moreover, the intracellular localization of nanoformulated ASC-J9 was confirmed by a Raman optical imaging experiment designed ad hoc. PLGA nanoparticles and ASC-J9 proved also to be safe for a healthy embryo fibroblast cell line (3T3-L1), suggesting a possible clinical translation of this potential nanochemotherapeutic to expand the inherently poor bioavailability of hydrophobic ASC-J9 that could be proposed for the treatment of malignant breast cancer.

  9. Heritability of retinal vascular fractals: a twin study

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line

    Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50-degree, disc-centred fundus photographs from 59 monozygotic and 55 dizygotic, same-sex twin pairs aged 20-46 years....... The retinal vascular fractal dimension was measured using the box-counting method and compared within monozygotic and dizygotic twin pairs using Pearson correlation coefficents. Falconer´s formula and quantitative genetic models were used to determine the genetic component of variation. Results: The retinal...... for quantitative analysis of heritability. The intrapair correlation was markedly higher (0.505, p=0.0002) in monozygotic twins than in dizygotic twins (0.108, p=0.46), corresponding to a heritability h2 for the fractal dimension of 0.79. In quantitative genetic models, 54% of the variation was explained...

  10. Heritability and genetics of lipid metabolism

    DEFF Research Database (Denmark)

    Fenger, Mogens

    2007-01-01

    In this article, the concept of heritability and genetic effect will be reviewed and our current knowledge of the genetics of lipid metabolism summarized. The concepts of polygenic conditions and epistasis are discussed at length, and an effort is made to put the biological processes in context i...... in the search for genetic factors influencing the metabolic pathways. Particular physiological heterogeneity is addressed and procedures to handle this complex issue are suggested.......In this article, the concept of heritability and genetic effect will be reviewed and our current knowledge of the genetics of lipid metabolism summarized. The concepts of polygenic conditions and epistasis are discussed at length, and an effort is made to put the biological processes in context...

  11. Optimizing the ASC WAN: evaluating network performance tools for comparing transport protocols.

    Energy Technology Data Exchange (ETDEWEB)

    Lydick, Christopher L.

    2007-07-01

    The Advanced Simulation & Computing Wide Area Network (ASC WAN), which is a high delay-bandwidth network connection between US Department of Energy National Laboratories, is constantly being examined and evaluated for efficiency. One of the current transport-layer protocols which is used, TCP, was developed for traffic demands which are different from that on the ASC WAN. The Stream Control Transport Protocol (SCTP), on the other hand, has shown characteristics which make it more appealing to networks such as these. Most important, before considering a replacement for TCP on any network, a testing tool that performs well against certain criteria needs to be found. In order to try to find such a tool, two popular networking tools (Netperf v.2.4.3 & v.2.4.6 (OpenSS7 STREAMS), and Iperf v.2.0.6) were tested. These tools implement both TCP and SCTP and were evaluated using four metrics: (1) How effectively can the tool reach a throughput near the bandwidth? (2) How much of the CPU does the tool utilize during operation? (3) Is the tool freely and widely available? And, (4) Is the tool actively developed? Following the analysis of those tools, this paper goes further into explaining some recommendations and ideas for future work.

  12. University of Utah ASC site review. August 24-25, 2006

    Energy Technology Data Exchange (ETDEWEB)

    Hertel, Eugene S., Jr. (.,; .)

    2007-02-01

    This report is a review of progress made by the Center for the Simulation of Accidental Fires and Explosions (C-SAFE) at the University of Utah, during the ninth year (Fiscal 2006) of its existence as an activity funded by the Department of Energy's Advanced Simulation and Computing Program (ASC). The ten-member Review Team composed of the TST and AST spent two days (August 24-25, 2006) at the University, reviewing formal presentations and demonstrations by the C-SAFE researchers and conferring privately. The Review Team found that the C-SAFE project administrators and staff had prepared well for the review. C-SAFE management and staff openly shared extensive answers to unexpected questions and the advance materials were well prepared and very informative. We believe that the time devoted to the review was used effectively and hope that the recommendations included in this 2006 report will provide helpful guidance to C-SAFE personnel and ASC managers.

  13. Aeroacoustics research in Europe: The CEAS-ASC report on 2014 highlights

    Science.gov (United States)

    Detandt, Yves

    2015-11-01

    The Council of European Aerospace Societies (CEAS) Aeroacoustics Specialists Committee (ASC) supports and promotes the interests of the scientific and industrial aeroacoustics community on an European scale and European aeronautics activities internationally. Each year the committee highlights some of the research and development projects in Europe. This paper is the 2014 issue of this collection of Aeroacoustic Highlights, compiled from informations submitted to the CEAS-ASC. The contributions are classified in different topics; the first categories being related to specific aeroacoustic challenges (airframe noise, fan and jet noise, helicopter noise, aircraft interior noise) and two last sections are respectively devoted to recent improvements and emerging techniques and to general advances in aeroacoustics. For each section, the present paper focus on accomplished projects, providing the state of the art in each research category in 2014. A number of research programmes involving aeroacoustics were funded by the European Commission. Some of the highlights from these programmes are summarised in this paper, as well as highlights funded by national programmes or by industry.

  14. Comparison of lysimeter based and calculated ASCE reference evapotranspiration in a subhumid climate

    Science.gov (United States)

    Nolz, Reinhard; Cepuder, Peter; Eitzinger, Josef

    2016-04-01

    The standardized form of the well-known FAO Penman-Monteith equation, published by the Environmental and Water Resources Institute of the American Society of Civil Engineers (ASCE-EWRI), is recommended as a standard procedure for calculating reference evapotranspiration (ET ref) and subsequently plant water requirements. Applied and validated under different climatic conditions it generally achieved good results compared to other methods. However, several studies documented deviations between measured and calculated reference evapotranspiration depending on environmental and weather conditions. Therefore, it seems generally advisable to evaluate the model under local environmental conditions. In this study, reference evapotranspiration was determined at a subhumid site in northeastern Austria from 2005 to 2010 using a large weighing lysimeter (ET lys). The measured data were compared with ET ref calculations. Daily values differed slightly during a year, at which ET ref was generally overestimated at small values, whereas it was rather underestimated when ET was large, which is supported also by other studies. In our case, advection of sensible heat proved to have an impact, but it could not explain the differences exclusively. Obviously, there were also other influences, such as seasonal varying surface resistance or albedo. Generally, the ASCE-EWRI equation for daily time steps performed best at average weather conditions. The outcomes should help to correctly interpret ET ref data in the region and in similar environments and improve knowledge on the dynamics of influencing factors causing deviations.

  15. Heritability and genetics of lipid metabolism

    DEFF Research Database (Denmark)

    Fenger, Mogens

    2007-01-01

    In this article, the concept of heritability and genetic effect will be reviewed and our current knowledge of the genetics of lipid metabolism summarized. The concepts of polygenic conditions and epistasis are discussed at length, and an effort is made to put the biological processes in context...... in the search for genetic factors influencing the metabolic pathways. Particular physiological heterogeneity is addressed and procedures to handle this complex issue are suggested....

  16. Will Big Data Close the Missing Heritability Gap?

    Science.gov (United States)

    Kim, Hwasoon; Grueneberg, Alexander; Vazquez, Ana I; Hsu, Stephen; de Los Campos, Gustavo

    2017-09-11

    Despite the important discoveries reported by Genome-Wide Association studies, for most traits and diseases the prediction R-squared (R-sq.) achieved with genetic scores remains considerably lower than the trait heritability. Modern biobanks will soon deliver unprecedentedly large biomedical data sets: Will the advent of Big Data close the gap between the trait heritability and the proportion of variance that can be explained by a genomic predictor? We addressed this question using Bayesian methods and a data analysis approach that produces a surface response relating prediction R-sq. with sample size and model complexity (e.g., number of SNPs). We applied the methodology to data from the interim release of the UK Biobank. Focusing on human height as a model trait and using 80,000 records for model training, we achieved a prediction R-sq. in testing (n=22,221) of 0.24 (95% CI: 0.23-0.25). Our estimates show that prediction R-sq. increases with sample size reaching an estimated plateau at values that ranged from 0.1 to 0.37 for models using 500 and 50,000 (GWA-selected) SNPs, respectively. Soon much larger data sets will become available. Using the estimated surface response, we forecast that larger sample sizes will lead to further improvements in prediction R-sq. We conclude that Big Data will lead to a substantial reduction of the gap between trait heritability and the proportion of inter-individual differences that can be explained with a genomic predictor. However, even with the power of Big Data, for complex traits, we anticipate that the gap between prediction R-sq. and trait heritability will not be fully closed. Copyright © 2017, Genetics.

  17. Heritable retroviral transgenes are highly expressed in chickens.

    OpenAIRE

    Briskin, M J; Hsu, R Y; Boggs, T; Schultz, J. A.; Rishell, W; Bosselman, R A

    1991-01-01

    This report describes expression of heritable reticuloendotheliosis virus (REV) vector ME111 in 20 independent lines of transgenic chickens. The results are strikingly different from studies of Moloney virus in transgenic mice, where restricted expression of inherited proviruses has led to their use primarily as insertional mutagens rather than general agents for gene transfer. In contrast, the REV ME111 provirus is actively transcribed in a variety of tissues from transgenic chickens, is exp...

  18. Heritability of heart rate recovery and vagal rebound after exercise.

    Science.gov (United States)

    Nederend, Ineke; Schutte, Nienke M; Bartels, Meike; Ten Harkel, Arend D J; de Geus, Eco J C

    2016-12-01

    The prognostic power of heart rate recovery (HRR) after exercise has been well established but the exact origin of individual differences in HRR remains unclear. This study aims to estimate the heritability of HRR and vagal rebound after maximal exercise in adolescents. Furthermore, the role of voluntary regular exercise behavior (EB) in HRR and vagal rebound is tested. 491 healthy adolescent twins and their siblings were recruited for maximal exercise testing, followed by a standardized cooldown with measurement of the electrocardiogram and respiratory frequency. Immediate and long-term HRR (HRR60 and HRR180) and vagal rebound (heart rate variability in the respiratory frequency range) were assessed 1 and 3 min after exercise. Multivariate twin modeling was used to estimate heritability of all measured variables and to compute the genetic contribution to their covariance. Heritability of HRR60, HRR180 and immediate and long-term vagal rebound is 60 % (95 % CI: 48-67), 65 % (95 % CI: 54-73), 23 % (95 % CI: 11-35) and 3 % (95 % CI: 0-11), respectively. We find evidence for two separate genetic factors with one factor influencing overall cardiac vagal control, including resting heart rate and respiratory sinus arrhythmia, and a specific factor for cardiac vagal exercise recovery. EB was only modestly associated with resting heart rate (r = -0.27) and HRR (rHRR60 = 0.10; rHRR180 = 0.19) with very high genetic contribution to these associations (88-91 %). Individual differences in HRR and immediate vagal rebound can to a large extent be explained by genetic factors. These innate cardiac vagal exercise recovery factors partly reflect the effects of heritable differences in EB.

  19. Heritable temperament pathways to early callous-unemotional behaviour.

    Science.gov (United States)

    Waller, Rebecca; Trentacosta, Christopher J; Shaw, Daniel S; Neiderhiser, Jenae M; Ganiban, Jody M; Reiss, David; Leve, Leslie D; Hyde, Luke W

    2016-12-01

    Early callous-unemotional behaviours identify children at risk for antisocial behaviour. Recent work suggests that the high heritability of callous-unemotional behaviours is qualified by interactions with positive parenting. To examine whether heritable temperament dimensions of fearlessness and low affiliative behaviour are associated with early callous-unemotional behaviours and whether parenting moderates these associations. Using an adoption sample (n = 561), we examined pathways from biological mother self-reported fearlessness and affiliative behaviour to child callous-unemotional behaviours via observed child fearlessness and affiliative behaviour, and whether adoptive parent observed positive parenting moderated pathways. Biological mother fearlessness predicted child callous-unemotional behaviours via earlier child fearlessness. Biological mother low affiliative behaviour predicted child callous-unemotional behaviours, although not via child affiliative behaviours. Adoptive mother positive parenting moderated the fearlessness to callous-unemotional behaviour pathway. Heritable fearlessness and low interpersonal affiliation traits contribute to the development of callous-unemotional behaviours. Positive parenting can buffer these risky pathways. © The Royal College of Psychiatrists 2016.

  20. Mutagen sensitivity has high heritability: evidence from a twin study.

    Science.gov (United States)

    Wu, Xifeng; Spitz, Margaret R; Amos, Christopher I; Lin, Jie; Shao, Lina; Gu, Jian; de Andrade, Mariza; Benowitz, Neal L; Shields, Peter G; Swan, Gary E

    2006-06-15

    Despite numerous studies showing that mutagen sensitivity is a cancer predisposition factor, the heritability of mutagen sensitivity has not been clearly established. In this report, we used a classic twin study design to examine the role of genetic and environmental factors on the mutagen sensitivity phenotype. Mutagen sensitivity was measured in peripheral blood lymphocytes from 460 individuals [148 pairs of monozygotic (MZ) twins, 57 pairs of dizygotic (DZ) twins, and 50 siblings]. The intraclass correlation coefficients were all significantly higher in MZ twins than in dizygotes (DZ pairs and MZ-sibling pairs combined) for sensitivity to four different mutagen challenges. Applying biometric genetic modeling, we calculated a genetic heritability of 40.7%, 48.0%, 62.5%, and 58.8% for bleomycin, benzo[a]pyrene diol epoxide, gamma-radiation, and 4-nitroquinoline-1-oxide sensitivity, respectively. This study provides the strongest and most direct evidence that mutagen sensitivity is highly heritable, thereby validating the use of mutagen sensitivity as a cancer susceptibility factor.

  1. Leveraging population admixture to explain missing heritability of complex traits

    Science.gov (United States)

    Zaitlen, Noah; Pasaniuc, Bogdan; Sankararaman, Sriram; Bhatia, Gaurav; Zhang, Jianqi; Gusev, Alexander; Young, Taylor; Tandon, Arti; Pollack, Samuela; Vilhjálmsson, Bjarni J.; Assimes, Themistocles L.; Berndt, Sonja I.; Blot, William J.; Chanock, Stephen; Franceschini, Nora; Goodman, Phyllis G.; He, Jing; Hennis, Anselm JM; Hsing, Ann; Ingles, Sue A.; Isaacs, William; Kittles, Rick A.; Klein, Eric A.; Lange, Leslie A.; Nemesure, Barbara; Patterson, Nick; Reich, David; Rybicki, Benjamin A.; Stanford, Janet L.; Stevens, Victoria L; Strom, Sara S.; Whitsel, Eric A; Witte, John S.; Xu, Jianfeng; Haiman, Christopher; Wilson, James G.; Kooperberg, Charles; Stram, Daniel; Reiner, Alex P.; Tang, Hua; Price, Alkes L.

    2014-01-01

    Despite recent progress on estimating the heritability explained by genotyped SNPs (hg2), a large gap between hg2 and estimates of total narrow-sense heritability (h2) remains. Explanations for this gap include rare variants, or upward bias in family-based estimates of h2 due to shared environment or epistasis. We estimate h2 from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (hγ2). We show that hγ2 = 2FSTCθ(1−θ)h2, where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We examined 21,497 African Americans from three cohorts, analyzing 13 phenotypes. For height and BMI, we obtained h2 estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of hg2 in these and other data, but smaller than family-based estimates of h2. PMID:25383972

  2. Dominant-lethal mutations and heritable translocations in mice

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

  3. Heritable variation in garter snake color patterns in postglacial populations.

    Directory of Open Access Journals (Sweden)

    Michael F Westphal

    Full Text Available Global climate change is expected to trigger northward shifts in the ranges of natural populations of plants and animals, with subsequent effects on intraspecific genetic diversity. Investigating how genetic diversity is patterned among populations that arose following the last Ice Age is a promising method for understanding the potential future effects of climate change. Theoretical and empirical work has suggested that overall genetic diversity can decrease in colonial populations following rapid expansion into postglacial landscapes, with potential negative effects on the ability of populations to adapt to new environmental regimes. The crucial measure of this genetic variation and a population's overall adaptability is the heritable variation in phenotypic traits, as it is this variation that mediates the rate and direction of a population's multigenerational response to selection. Using two large full-sib quantitative genetic studies (N(Manitoba = 144; N(South Dakota = 653 and a smaller phenotypic analysis from Kansas (N(Kansas = 44, we compared mean levels of pigmentation, genetic variation and heritability in three pigmentation traits among populations of the common garter snake, Thamnophis sirtalis, along a north-south gradient, including a postglacial northern population and a putative southern refuge population. Counter to our expectations, we found that genetic variance and heritability for the three pigmentation traits were the same or higher in the postglacial population than in the southern population.

  4. The role of colposcopy and typization of human papillomavirus in further diagnostic proceedings in patients with ASC-US cytological finding of the uterine cervix

    Directory of Open Access Journals (Sweden)

    Živadinović Radomir

    2009-01-01

    Full Text Available Background/Aim. Bethesda system of classification of cytological findings was introduced in 2001 two subcategories in the category of atypical squamous cells (ASC findings: ASC of undetermined significance (ASC-US and ASC which cannot exclude high-grade intraepithelial lesions (ASC-H. The aim of our study was to assess a possible association of these two subcategories with pathologic biopsy finding and to find out the best further diagnostic proceedings. Methods. At the Clinic of Gynecology and Obstetrics, Niš 130 patients with ASC findings were analyzed. Colposcopy was performed in all study participants. Patients with pathological colposcopic findings underwent cervical biopsy. In 10 patients with pathologic histologic and 15 with benign findings human papilloma virus (HPV typization was done using the Hybrid Capture method. Results. Patients with ASC-H finding had significantly more pathologic biopsies compared with patients with ASC-US finding (57.84: 20.72. Conclusion. Colposcopy was exhibited somewhat higher sensitivity compared to HPV typization (94.7 : 90, but lower sensitivity (79.27 : 86.6. The usage of HPV typization in the triage of patients with ASC cytologic smear induces statistically significant reduction of unnecessary percentage of cervical biopsies.

  5. Atypical squamous cells, cannot exclude high grade squamous intraepithelial (ASC-H in HIV-positive women

    Directory of Open Access Journals (Sweden)

    Michelow Pam

    2010-01-01

    Full Text Available Objective: South Africa has very high rates of both HIV infection and cervical pathology. The management of ASC-H is colposcopy and directed biopsy, but with so many women diagnosed with HSIL and a dearth of colposcopy centres in South Africa, women with cytologic diagnosis of ASC-H may not be prioritized for colposcopy. The aim of this study was to determine if HIV-positive women with a cytologic diagnosis of ASC-H should undergo immediate colposcopy or whether colposcopy can be delayed, within the context of an underfunded health care setting with so many competing health needs. Materials and Methods: A computer database search was performed from the archives of an NGO-administered clinic that offers comprehensive HIV care. All women with a cytologic diagnosis of ASC-H on cervical smears from September 2005 until August 2009 were identified. Histologic follow up was sought in all patients. Results: A total of 2111 cervical smears were performed and 41 diagnosed as ASC-H (1.94%. No histologic follow up data was available in 15 cases. Follow up histologic results were as follows: three negative (11.5%, five koilocytosis and/ or CIN1 (19.2%, ten CIN2 (38.5% and eight CIN3 (30.8%. There were no cases of invasive carcinoma on follow up. Conclusion: The current appropriate management of HIV-positive women in low-resource settings with a diagnosis of ASC-H on cervical smear is colposcopy, despite the costs involved. In the future and if cost-effective in developing nations, use of novel markers may help select which HIV-positive women can be managed conservatively and which ones referred for more active treatment. More research in this regard is warranted.

  6. Visualization on supercomputing platform level II ASC milestone (3537-1B) results from Sandia.

    Energy Technology Data Exchange (ETDEWEB)

    Geveci, Berk (Kitware, Inc., Clifton Park, NY); Fabian, Nathan; Marion, Patrick (Kitware, Inc., Clifton Park, NY); Moreland, Kenneth D.

    2010-09-01

    This report provides documentation for the completion of the Sandia portion of the ASC Level II Visualization on the platform milestone. This ASC Level II milestone is a joint milestone between Sandia National Laboratories and Los Alamos National Laboratories. This milestone contains functionality required for performing visualization directly on a supercomputing platform, which is necessary for peta-scale visualization. Sandia's contribution concerns in-situ visualization, running a visualization in tandem with a solver. Visualization and analysis of petascale data is limited by several factors which must be addressed as ACES delivers the Cielo platform. Two primary difficulties are: (1) Performance of interactive rendering, which is most computationally intensive portion of the visualization process. For terascale platforms, commodity clusters with graphics processors(GPUs) have been used for interactive rendering. For petascale platforms, visualization and rendering may be able to run efficiently on the supercomputer platform itself. (2) I/O bandwidth, which limits how much information can be written to disk. If we simply analyze the sparse information that is saved to disk we miss the opportunity to analyze the rich information produced every timestep by the simulation. For the first issue, we are pursuing in-situ analysis, in which simulations are coupled directly with analysis libraries at runtime. This milestone will evaluate the visualization and rendering performance of current and next generation supercomputers in contrast to GPU-based visualization clusters, and evaluate the performance of common analysis libraries coupled with the simulation that analyze and write data to disk during a running simulation. This milestone will explore, evaluate and advance the maturity level of these technologies and their applicability to problems of interest to the ASC program. Scientific simulation on parallel supercomputers is traditionally performed in four

  7. Post-processing V&V level II ASC milestone (2360) results.

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Elmer; Karelitz, David B.; Brunner, Thomas A.; Trucano, Timothy Guy; Moreland, Kenneth D.; Weirs, V. Gregory; Shead, Timothy M.

    2007-09-01

    The 9/30/2007 ASC Level 2 Post-Processing V&V Milestone (Milestone 2360) contains functionality required by the user community for certain verification and validation tasks. These capabilities include loading of edge and face data on an Exodus mesh, run-time computation of an exact solution to a verification problem, delivery of results data from the server to the client, computation of an integral-based error metric, simultaneous loading of simulation and test data, and comparison of that data using visual and quantitative methods. The capabilities were tested extensively by performing a typical ALEGRA HEDP verification task. In addition, a number of stretch criteria were met including completion of a verification task on a 13 million element mesh.

  8. Sliding and Rocking of Unanchored Components and Structures: Chapter 7.6 ASCE 4 Revision 2

    Energy Technology Data Exchange (ETDEWEB)

    S. R. Jensen

    2011-04-01

    Chapter 7.6 of ASCE 4-Rev 2, Seismic Analysis of Safety-Related Nuclear Structures: Standard and Commentary, provides updated guidance for analysis of rocking and sliding of unanchored structures and components subjected to seismic load. This guidance includes provisions both for simplified approximate energy-based approaches, and for detailed probabilistic time history analysis using nonlinear methods. Factors to be applied to the analytical results are also provided with the intent of ensuring achievement of the 80% non-exceedence probability target of the standard. The present paper surveys the published literature supporting these provisions. The results of available testing and analysis are compared to results produced by both simplified and probabilistic approaches. In addition, adequacy of the standard's provisions for analysis methods and factors is assessed. A comparison is made between the achieved level of conservatism and the standard's non-exceedence probability target.

  9. Evaluation and Validation of Organic Materials for Advanced Stirling Convertors (ASCs): Overview

    Science.gov (United States)

    Shin, Euy-Sik Eugene

    2015-01-01

    Various organic materials are used as essential parts in Stirling Convertors for their unique properties and functionalities such as bonding, potting, sealing, thread locking, insulation, and lubrication. More efficient Advanced Stirling Convertors (ASC) are being developed for future space applications especially with a long mission cycle, sometimes up to 17 years, such as deep space exploration or lunar surface power or Mars rovers, and others. Thus, performance, durability, and reliability of those organics should be critically evaluated in every possible material-process-fabrication-service environment relations based on their mission specifications. In general, thermal stability, radiation hardness, outgassing, and material compatibility of the selected organics have been systematically evaluated while their process and fabrication conditions and procedures were being optimized. Service environment-simulated long term aging tests up to 4 years were performed as a function of temperature for durability assessment of the most critical organic material systems.

  10. Aorta measurements are heritable and influenced by bicuspid aortic valve

    Directory of Open Access Journals (Sweden)

    Lisa J Martin

    2011-09-01

    Full Text Available Abstract: Word Count 266, 1609 charactersObjectives: To determine whether the contributions of genetics and bicuspid aortic valve (BAV independently influence aortic (Ao dimensions.Background: Ao dilation is a risk factor for aneurysm, dissection, and sudden cardiac death. Frequent association of BAV with Ao dilation implicates a common underlying defect possibly due to genetic factors. Methods: Families enriched for BAV underwent standardized transthoracic echocardiography. In addition to BAV status, echocardiographic measures of Ao (annulus to descending Ao, pulmonary artery and mitral valve annulus diameters were obtained. Using variance components analysis, heritability was estimated with and without BAV status. Additionally, bivariate genetic analyses between Ao dimensions and BAV were performed.Results: Our cohort was obtained from 209 families enriched for BAV. After adjusting for age, body surface area and sex, individuals with BAV had a statistically significant increase in all echocardiographic measurements (p < 0.006 except descending Ao and mitral valve annulus. Individuals with BAV were at greater odds of having Ao dilation (OR = 4.44, 95% CI 2.93 – 6.72 than family members without BAV. All echocardiographic measurements exhibited moderate to strong heritability (0.25 to 0.53, and these estimates were not influenced by inclusion of BAV as a covariate. Bivariate genetic analyses supported that the genetic correlation between BAV and echo measures were not significantly different from zero.Conclusions: We show for the first time that echocardiographic measurements of Ao, pulmonary artery and mitral valve annulus diameters are quantitative traits that exhibit significant heritability. In addition, our results suggest the presence of BAV independently influences the proximal Ao and pulmonary artery measures but not those in the descending Ao or mitral valve annulus.

  11. Lessons on the pathogenesis of aneurysm from heritable conditions

    Science.gov (United States)

    Lindsay, Mark E.; Dietz, Harry C.

    2013-01-01

    Aortic aneurysm is common, accounting for 1–2% of all deaths in industrialized countries. Early theories of the causes of human aneurysm mostly focused on inherited or acquired defects in components of the extracellular matrix in the aorta. Although several mutations in the genes encoding extracellular matrix proteins have been recognized, more recent discoveries have shown important perturbations in cytokine signalling cascades and intracellular components of the smooth muscle contractile apparatus. The modelling of single-gene heritable aneurysm disorders in mice has shown unexpected involvement of the transforming growth factor-β cytokine pathway in aortic aneurysm, highlighting the potential for new therapeutic strategies. PMID:21593863

  12. Heritability of several traits in a early population of maize

    OpenAIRE

    1987-01-01

    [EN] The heritability in the narrow sense of days to pollen shedding, days to silking plant height, ear height, lodging, kernel moisture, number of ears per plant, number of ear rows, ear length, 1000-kernel weight and yield were estimated in an early population of maize (Zea mays L) using 40 families of half sibs grown in a blocks-in-replications desing for two years. The estimates ranged from 0.13 for kernel moisture to 1.00 for number of ear rows. The heritabiliy for yield was 0.38. [ES...

  13. Heritability of psoriasis in a large twin sample

    DEFF Research Database (Denmark)

    Lønnberg, Ann Sophie; Skov, L; Skytthe, A;

    2013-01-01

    AIM: To study the concordance of psoriasis in a population-based twin sample. METHODS: Data on psoriasis in 10,725 twin pairs, 20-71 years of age, from the Danish Twin Registry was collected via a questionnaire survey. The concordance and heritability of psoriasis were estimated. RESULTS: In total......, 4.1% of the men and 4.2% of the women had a lifetime history of psoriasis. The probandwise concordance for psoriasis was larger in monozygotic than in dizygotic twins, 0.33 vs. 0.17. Genetic factors explained 68% (60-75%) of the variation in the susceptibility to psoriasis, whereas the rest...

  14. Prospects for DNA methods to measure human heritable mutation rates

    Energy Technology Data Exchange (ETDEWEB)

    Mendelsohn, M.L.

    1985-06-14

    A workshop cosponsored by ICPEMC and the US Department of Energy was held in Alta, Utah, December 9-13, 1984 to examine the extent to which DNA-oriented methods might provide new approaches to the important but intractable problem of measuring mutation rates in control and exposed human populations. The workshop identified and analyzed six DNA methods for detection of human heritable mutation, including several created at the meeting, and concluded that none of the methods combine sufficient feasibility and efficiency to be recommended for general application. 8 refs.

  15. [Heritability of neurodynamics and psychodynamics in human populations].

    Science.gov (United States)

    Bulaeva, K B; Trubnikov, V I; Isaĭchev, S A; Pavlova, T A; Dubinin, N P

    1986-06-01

    A component analysis of human neurodynamic and psychodynamic characters in the norm was carried out in 8 human populations characterized by different degrees of isolation and ethnic origin. An increase in phenotypic variability and a decrease in heritability with increasing complexity of organization of the characters under study were demonstrated for all these populations. The additive effect plays the major role in genetic determination of neurodynamic and psychodynamic characters studied. For a number of neurodynamic parameters the effect of intralocus dominance indicative of the oligogenic determination system was observed. Data in favour of real contribution of the factors linked to X-chromosome were obtained for simple sensomotor reactions.

  16. Are range-size distributions consistent with species-level heritability?

    DEFF Research Database (Denmark)

    Borregaard, Michael Krabbe; Gotelli, Nicholas; Rahbek, Carsten

    2012-01-01

    been that it is not compatible with the observed shape of present-day species range-size distributions (SRDs), a claim that has never been tested. To assess this claim, we used forward simulation of range-size evolution in clades with varying degrees of range-size heritability, and compared the output...... of three different models to the range-size distribution of the South American avifauna. Although there were differences among the models, a moderate-to-high degree of range-size heritability consistently leads to SRDs that were similar to empirical data. These results suggest that range-size heritability......The concept of species-level heritability is widely contested. Because it is most likely to apply to emergent, species-level traits, one of the central discussions has focused on the potential heritability of geographic range size. However, a central argument against range-size heritability has...

  17. Targeting ASC in NLRP3 inflammasome by caffeic acid phenethyl ester: a novel strategy to treat acute gout

    Science.gov (United States)

    Lee, Hye Eun; Yang, Gabsik; Kim, Nam Doo; Jeong, Seongkeun; Jung, Yunjin; Choi, Jae Young; Park, Hyun Ho; Lee, Joo Young

    2016-01-01

    Gouty arthritis is caused by the deposition of uric acid crystals, which induce the activation of NOD-like receptor family, pyrin domain containing 3(NLRP3) inflammasome. The NLRP3 inflammasome, composed of NLRP3, the adaptor protein ASC, and caspase-1, is closely linked to the pathogenesis of various metabolic diseases including gouty arthritis. We investigated whether an orally administrable inhibitor of NLRP3 inflammasome was effective for alleviating the pathological symptoms of gouty arthritis and what was the underlying mechanism. In primary mouse macrophages, caffeic acid phenethyl ester(CAPE) blocked caspase-1 activation and IL-1β production induced by MSU crystals, showing that CAPE suppresses NLRP3 inflammasome activation. In mouse gouty arthritis models, oral administration of CAPE suppressed MSU crystals-induced caspase-1 activation and IL-1β production in the air pouch exudates and the foot tissues, correlating with attenuation of inflammatory symptoms. CAPE directly associated with ASC as shown by SPR analysis and co-precipitation, resulting in blockade of NLRP3-ASC interaction induced by MSU crystals. Our findings provide a novel regulatory mechanism by which small molecules harness the activation of NLRP3 inflammasome by presenting ASC as a new target. Furthermore, the results suggest the preventive or therapeutic strategy for NLRP3-related inflammatory diseases such as gouty arthritis using orally available small molecules. PMID:27934918

  18. To treat or not to treat; the clinical dilemma of atypical squamous cells of undetermined significance (ASC-US)

    NARCIS (Netherlands)

    Bie, R.P. de; Massuger, L.F.A.G.; Dongen, R.A. van; Snijders, M.P.; Bulten, J.; Melchers, W.J.G.; Bekkers, R.L.M.

    2011-01-01

    OBJECTIVE: Management of patients diagnosed on cervical smears with twice consecutively atypical squamous cells of undetermined significance (ASC-US) remains a clinical dilemma. We describe a follow-up of aggressive vs. less aggressive colposcopic treatment in order to determine which treatment is p

  19. The Asc locus for resistance to Alternaria stem canker in tomato does not encode the enzyme aspartate carbamoyltransferase

    NARCIS (Netherlands)

    Overduin, Bert; Hogenhout, Saskia A.; Biezen, Erik A. van der; Haring, Michel A.; Nijkamp, H. John J.; Hille, Jacques

    1993-01-01

    The fungal disease resistance locus Alternaria stem canker (Asc) in tomato has been suggested to encode the enzyme aspartate carbamoyltransferase (ACTase). To test this hypothesis a segment of the tomato ACTase gene was amplified by the polymerase chain reaction (PCR) using degenerate primers. The P

  20. Molecular genetic characterisation of the Asc locus of tomato conferring resistance to the fungal pathogen Alternaria alternata f. sp. lycopersici

    NARCIS (Netherlands)

    Biezen, E.A. van der; Overduin, B.; Kneppers, T.J.A.; Mesbah, L.A.; Nijkamp, H.J.J.; Hille, J.

    1994-01-01

    The Alternaria stem canker disease of tomato is caused by the fungal pathogen Alternaria alternata f. sp. lycopersici and its host-selective AAL-toxins. Resistance to the pathogen and insensitivity to the toxins are conferred by the Asc locus on chromosome 3L. Sensitivity to AAL-toxins is a relative

  1. Human adipose stromal cells (ASC for the regeneration of injured cartilage display genetic stability after in vitro culture expansion.

    Directory of Open Access Journals (Sweden)

    Simona Neri

    Full Text Available Mesenchymal stromal cells are emerging as an extremely promising therapeutic agent for tissue regeneration due to their multi-potency, immune-modulation and secretome activities, but safety remains one of the main concerns, particularly when in vitro manipulation, such as cell expansion, is performed before clinical application. Indeed, it is well documented that in vitro expansion reduces replicative potential and some multi-potency and promotes cell senescence. Furthermore, during in vitro aging there is a decrease in DNA synthesis and repair efficiency thus leading to DNA damage accumulation and possibly inducing genomic instability. The European Research Project ADIPOA aims at validating an innovative cell-based therapy where autologous adipose stromal cells (ASCs are injected in the diseased articulation to activate regeneration of the cartilage. The primary objective of this paper was to assess the safety of cultured ASCs. The maintenance of genetic integrity was evaluated during in vitro culture by karyotype and microsatellite instability analysis. In addition, RT-PCR array-based evaluation of the expression of genes related to DNA damage signaling pathways was performed. Finally, the senescence and replicative potential of cultured cells was evaluated by telomere length and telomerase activity assessment, whereas anchorage-independent clone development was tested in vitro by soft agar growth. We found that cultured ASCs do not show genetic alterations and replicative senescence during the period of observation, nor anchorage-independent growth, supporting an argument for the safety of ASCs for clinical use.

  2. Expressions of ASC and caspase-1 but not AIM2 are disrupted in chronic HBV infected patients

    Directory of Open Access Journals (Sweden)

    Gholamhossein Hassanshahi

    2014-08-01

    Full Text Available Objective: To determine the mRNA levels of absent in melanoma 2 (AIM2, apoptosis-associated speck like protein containing a caspase recruitment domain (ASC and caspase-1 in the peripheral blood mononuclear cells of chronic hepatitis B virus (CHB infected patients. Methods: This study was conducted on 60 CHB patients and 60 healthy controls and the mRNA levels of AIM2, ASC and caspase-1 were examined in parallel with beta-actin (as housekeeping gene using real-time polymerase chain reaction technique. Results: Our results indicated that expression of ASC and caspase-1 but not AIM2 were significantly decreased in peripheral blood mononuclear cells isolated from CHB patients compared to healthy controls. Conclusions: According to our results, it is likely that CHB patients are unable to firmly express ASC and caspase-1 genes and in turn properly activate IL1β and IL-18 subsequent to hepatitis B virus infection. Thus, these results propose a mechanism which almost partially may describe a reasonable fact that why the infection is sustained in the CHB patients.

  3. Targeting ASC in NLRP3 inflammasome by caffeic acid phenethyl ester: a novel strategy to treat acute gout.

    Science.gov (United States)

    Lee, Hye Eun; Yang, Gabsik; Kim, Nam Doo; Jeong, Seongkeun; Jung, Yunjin; Choi, Jae Young; Park, Hyun Ho; Lee, Joo Young

    2016-12-09

    Gouty arthritis is caused by the deposition of uric acid crystals, which induce the activation of NOD-like receptor family, pyrin domain containing 3(NLRP3) inflammasome. The NLRP3 inflammasome, composed of NLRP3, the adaptor protein ASC, and caspase-1, is closely linked to the pathogenesis of various metabolic diseases including gouty arthritis. We investigated whether an orally administrable inhibitor of NLRP3 inflammasome was effective for alleviating the pathological symptoms of gouty arthritis and what was the underlying mechanism. In primary mouse macrophages, caffeic acid phenethyl ester(CAPE) blocked caspase-1 activation and IL-1β production induced by MSU crystals, showing that CAPE suppresses NLRP3 inflammasome activation. In mouse gouty arthritis models, oral administration of CAPE suppressed MSU crystals-induced caspase-1 activation and IL-1β production in the air pouch exudates and the foot tissues, correlating with attenuation of inflammatory symptoms. CAPE directly associated with ASC as shown by SPR analysis and co-precipitation, resulting in blockade of NLRP3-ASC interaction induced by MSU crystals. Our findings provide a novel regulatory mechanism by which small molecules harness the activation of NLRP3 inflammasome by presenting ASC as a new target. Furthermore, the results suggest the preventive or therapeutic strategy for NLRP3-related inflammatory diseases such as gouty arthritis using orally available small molecules.

  4. Genetic and physical analysis of a YAC contig spanning the fungal disease resistance locus Asc of tomato (Lycopersicon esculentum)

    NARCIS (Netherlands)

    Mesbah, L.A.; Kneppers, T.J.A.; Takken, F.L.W.; Laurent, P.; Hille, J.; Nijkamp, H.J.J.

    1998-01-01

    The Alternaria stem canker disease of tomato is caused by the necrotrophic fungal pathogen Alternaria alternata f. sp. lycopersici (AAL). The fungus produces AAL toxins that kill the plant tissue. Resistance to the fungus segregates as a single locus, called Asc, and has been genetically mapped on c

  5. 42 CFR 413.118 - Payment for facility services related to covered ASC surgical procedures performed in hospitals...

    Science.gov (United States)

    2010-10-01

    ... ASC surgical procedures performed in hospitals on an outpatient basis. 413.118 Section 413.118 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM... PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Specific Categories of Costs §...

  6. To treat or not to treat; the clinical dilemma of atypical squamous cells of undetermined significance (ASC-US)

    NARCIS (Netherlands)

    Bie, R.P. de; Massuger, L.F.A.G.; Dongen, R.A. van; Snijders, M.P.; Bulten, J.; Melchers, W.J.G.; Bekkers, R.L.M.

    2011-01-01

    OBJECTIVE: Management of patients diagnosed on cervical smears with twice consecutively atypical squamous cells of undetermined significance (ASC-US) remains a clinical dilemma. We describe a follow-up of aggressive vs. less aggressive colposcopic treatment in order to determine which treatment is p

  7. Identification of a heritable polymorphism in bovine PRNP associated with genetic transmissible spongiform encephalopathy: evidence of heritable BSE.

    Directory of Open Access Journals (Sweden)

    Eric M Nicholson

    Full Text Available BACKGROUND: Bovine spongiform encephalopathy (BSE is a transmissible spongiform encephalopathy (TSE of cattle. Classical BSE is associated with ingestion of BSE-contaminated feedstuffs. H- and L-type BSE, collectively known as atypical BSE, differ from classical BSE by displaying a different disease phenotype and they have not been linked to the consumption of contaminated feed. Interestingly, the 2006 US H-type atypical BSE animal had a polymorphism at codon 211 of the bovine prion gene resulting in a glutamic acid to lysine substitution (E211K. This substitution is analogous a human polymorphism associated with the most prevalent form of heritable TSE in humans, and it is considered to have caused BSE in the 2006 US atypical BSE animal. In order to determine if this amino acid change is a heritable trait in cattle, we sequenced the prion alleles of the only known offspring of this animal, a 2-year-old heifer. PRINCIPAL FINDINGS: Sequence analysis revealed that both the 2006 US atypical BSE animal and its 2-year-old heifer were heterozygous at bovine prion gene nucleotides 631 through 633 for GAA (glutamic acid and AAA (lysine. Both animals carry the E211K polymorphism, indicating that the allele is heritable and may persist within the cattle population. CONCLUSIONS: This is the first evidence that the E211K polymorphism is a germline polymorphism, not a somatic mutation, suggesting BSE may be transmitted genetically in cattle. In the event that E211K proves to result in a genetic form of BSE, this would be the first indication that all 3 etiologic forms of TSEs (spontaneous, hereditary, and infectious are present in a non-human species. Atypical BSE arising as both genetic and spontaneous disease, in the context of reports that at least some forms of atypical BSE can convert to classical BSE in mice, suggests a cattle origin for classical BSE.

  8. ASC provides a potential link between depression and inflammatory disorders: A clinical study of depressed Iranian medical students.

    Science.gov (United States)

    Momeni, Mohammad; Ghorban, Khodayar; Dadmanesh, Maryam; Khodadadi, Hassan; Bidaki, Reza; Kazemi Arababadi, Mohammad; Kennedy, Derek

    2016-01-01

    Background and aims AIM2 is a component of inflammasomes which can activate caspase-1 via an adaptor protein (ASC) after pathogen-associated molecular pattern (PAMP) or danger-associated molecular pattern (DAMP) recognition. Activation of caspase-1 is a trigger for the induction of IL-1 and IL-18 which are important pro-inflammatory cytokines. Furthermore, IL-1β, which can regulate inflammatory responses, has also been associated with depression. Previous studies revealed that patients suffering from depression may also have altered immune responses, but the mechanisms underlying this correlation are unclear. Thus, the aim of this study was to determine the mRNA levels of AIM2 and ASC in the peripheral blood mononuclear cells (PBMCs) isolated from Iranian medical students suffering from depression. Materials and methods The participants used for the study included 38 Iranian medical students diagnosed with depression and 43 non-depressed students as a control group. The mRNA levels of AIM2 and ASC were evaluated by quantitative real-time polymerase chain reaction (PCR) using β-actin as a housekeeping gene for the normalization of expression. Results The results showed that mRNA levels of AIM2 were similar in both groups. However, ASC levels were significantly increased in PBMCs isolated from individuals with elevated depressive symptoms when compared to non-depressed participants. Conclusions Based on the current results, it appears that ASC transcript expression may be a surrogate marker for depression and may represent a link between depression and the altered immune responses observed in these categories of individuals with elevated depressive symptoms.

  9. Glycolic Acid Silences Inflammasome Complex Genes, NLRC4 and ASC, by Inducing DNA Methylation in HaCaT Cells.

    Science.gov (United States)

    Tang, Sheau-Chung; Yeh, Jih-I; Hung, Sung-Jen; Hsiao, Yu-Ping; Liu, Fu-Tong; Yang, Jen-Hung

    2016-03-01

    AHAs (α-hydroxy acids), including glycolic acid (GA), have been widely used in cosmetic products and superficial chemical peels. Inflammasome complex has been shown to play critical roles in inflammatory pathways in human keratinocytes. However, the anti-inflammatory mechanism of GA is still unknown. The aim of this study is to investigate the relationship between the expression of the inflammasome complex and epigenetic modification to elucidate the molecular mechanism of the anti-inflammatory effect of GA in HaCaT cells. We evaluated NLRP3, NLRC4, AIM2, and ASC inflammasome complex gene expression on real-time polymerase chain reaction (PCR). Methylation changes were detected in these genes following treatment with DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-Aza) with or without the addition of GA using methylation-specific PCR (MSP). GA inhibited the expressions of these inflammasome complex genes, and the decreases in the expressions of mRNA were reversed by 5-Aza treatment. Methylation was detected in NLRC4 and ASC on MSP, but not in NLRP3 or AIM2. GA decreased NLRC4 and ASC gene expression by increasing not only DNA methyltransferase 3B (DNMT-3B) protein level, but also total DNMT activity. Furthermore, silencing of DNMT-3B (shDNMT-3B) increased the expressions of NLRC4 and ASC. Our data demonstrated that GA treatment induces hypermethylation of promoters of NLRC4 and ASC genes, which may subsequently lead to the hindering of the assembly of the inflammasome complex in HaCaT cells. These results highlight the anti-inflammatory potential of GA-containing cosmetic agents in human skin cells and demonstrate for the first time the role of aberrant hypermethylation in this process.

  10. Repeatability and heritability of response to superovulation in Holstein cows.

    Science.gov (United States)

    Tonhati, H; Lôbo, R B; Oliveira, H N

    1999-04-15

    The objective of this study was to estimate the relative effects of genetic and phenotypic factors on the efficacy and efficiency of superovulation for Holstein-Friesian cows reared in Brazil. A database, established by the Associacao Brasileira de Criadores de Bovinos da Raca Holandesa, consisting of a total of 5387 superovulations of 2941 cows distributed over 473 herds and sired by 690 bulls was used for the analysis. The records were analyzed by MTDFREML (Multiple Trait Derivative-Free Restricted Maximum Likelihood), using a repeatability animal model. The fixed effects included in the model were contemporaneous group (veterinarian, herd, year and season of the superovulation); number of semen doses; cow age; and superovulation order. The estimated repeatability of the number of the transferable embryos was low (0.13), and the estimated heritability was 0.03. These results indicate that environmental factors play a critical role in the response of a cow to a superovulation treatment. There is little evidence that future responses to superovulation by individual females can be predicted by previous treatment(s) or that superovulation response is an heritable trait.

  11. Dark matter: are mice the solution to missing heritability?

    Directory of Open Access Journals (Sweden)

    Clarissa Carlin Parker

    2011-06-01

    Full Text Available Genome-wide association studies (GWAS in humans have identified hundreds of single nucleotide polymorphisms associated with complex traits, yet for most traits studied, the sum total of all these identified variants fail to explain a significant portion of the heritable variation. Reasons for this missing heritability are thought to include the existence of rare causative variants not captured by current genotyping arrays, structural variants that go undetected by existing technology, insufficient power to identify multi-gene interactions, small sample sizes, and the influence of environmental and epigenetic effects. As genotyping technologies have evolved it has become inexpensive and relatively straightforward to perform GWAS in mice. Mice offer a powerful tool for elucidating the genetic architecture of behavioral and physiological traits, and are complementary to human studies. Unlike F2 crosses of inbred strains, advanced intercross lines, heterogeneous stocks, outbred, and wild-caught mice have more rapid breakdown of linkage disequilibrium which allow for increasingly high resolution mapping. Because some of these populations are created using a small number of founder chromosomes they are not expected to harbor rare alleles. We discuss the differences between these mouse populations and examine their potential to overcome some of the pitfalls that have plagued human GWAS studies.

  12. Heritable site-specific mutagenesis using TALENs in maize.

    Science.gov (United States)

    Char, Si Nian; Unger-Wallace, Erica; Frame, Bronwyn; Briggs, Sarah A; Main, Marcy; Spalding, Martin H; Vollbrecht, Erik; Wang, Kan; Yang, Bing

    2015-09-01

    Transcription activator-like effector nuclease (TALEN) technology has been utilized widely for targeted gene mutagenesis, especially for gene inactivation, in many organisms, including agriculturally important plants such as rice, wheat, tomato and barley. This report describes application of this technology to generate heritable genome modifications in maize. TALENs were employed to generate stable, heritable mutations at the maize glossy2 (gl2) locus. Transgenic lines containing mono- or di-allelic mutations were obtained from the maize genotype Hi-II at a frequency of about 10% (nine mutated events in 91 transgenic events). In addition, three of the novel alleles were tested for function in progeny seedlings, where they were able to confer the glossy phenotype. In a majority of the events, the integrated TALEN T-DNA segregated independently from the new loss of function alleles, producing mutated null-segregant progeny in T1 generation. Our results demonstrate that TALENs are an effective tool for genome mutagenesis in maize, empowering the discovery of gene function and the development of trait improvement.

  13. Apoptosis-associated speck-like protein containing a CARD (ASC) expression profiles in familial Mediterranean fever (FMF) patients with different MEFV mutation patterns.

    Science.gov (United States)

    Nalbantoglu, S; Tanyolac, B; Berdeli, A

    2013-01-01

    The inflammasome complex and the inflammatory pathway have been implicated in the pathogenesis of the most common autoinflammatory disorder, familial Mediterranean fever (FMF). Pyrin, the protein product of the FMF gene MEFV, interacts with the inflammasome complex adaptor protein ASC/PYCARD (apoptosis-associated speck-like protein with a CARD). Pyrin and ASC can both function as either inducers or suppressors of the cellular inflammatory response. We aimed to characterize ASC-induced gene expression profiles in FMF patients with different MEFV mutation patterns. A total of 165 Caucasian patients with clinical and molecular FMF diagnoses were enrolled in the study. ASC gene expression was quantified by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). ASC mRNA expression was increased in the MEFV mutation-positive group compared to the mutation-negative group (p = 0.001). The fold changes of ASC expression in the M694V homozygous (p = 0.02), M694V heterozygous (p = 0.012), compound heterozygous (p = 0.002), and R202Q/P369S/R408Q (p = 0.00) groups relative to the MEFV mutation-negative group were +2.4, +2.7, +3, and +3.4, respectively. qRT-PCR did not reveal a significant difference in ASC mRNA expression levels among the MEFV mutation-positive groups (p > 0.05). ASC mRNA expression was up-regulated in patients carrying MEFV mutations independent of mutation type. There was no significant relationship between specific MEFV genotypes and the level of ASC expression in the patient group analysed. Thus, the findings of this work may suggest a crucial relationship between mutant MEFV/pyrin and remarkable ASC up-regulation in FMF inflammation.

  14. Heritability of Biomarkers of Oxidized Lipoproteins: Twin Pair Study.

    Science.gov (United States)

    Rao, Fangwen; Schork, Andrew J; Maihofer, Adam X; Nievergelt, Caroline M; Marcovina, Santica M; Miller, Elizabeth R; Witztum, Joseph L; O'Connor, Daniel T; Tsimikas, Sotirios

    2015-07-01

    To determine whether biomarkers of oxidized lipoproteins are genetically determined. Lipoprotein(a) (Lp[a]) is a heritable risk factor and carrier of oxidized phospholipids (OxPL). We measured oxidized phospholipids on apolipoprotein B-containing lipoproteins (OxPL-apoB), Lp(a), IgG, and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes in 386 monozygotic and dizygotic twins to estimate trait heritability (h(2)) and determine specific genetic effects among traits. A genome-wide linkage study followed by genetic association was performed. The h(2) (scale: 0-1) for Lp(a) was 0.91±0.01 and for OxPL-apoB 0.87±0.02, which were higher than physiological, inflammatory, or lipid traits. h(2) of IgM malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes were 0.69±0.04, 0.67±0.05, and 0.80±0.03, respectively, and for IgG malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes 0.62±0.05, 0.52±0.06, and 0.53±0.06, respectively. There was an inverse correlation between the major apo(a) isoform and OxPL-apoB (R=-0.49; Plipoprotein and copper oxidized low-density lipoprotein, and apoB-immune complexes. Sib-pair genetic linkage of the Lp(a) trait revealed that single nucleotide polymorphism rs10455872 was significantly associated with OxPL-apoB after adjusting for Lp(a). OxPL-apoB and other biomarkers of oxidized lipoproteins are highly heritable cardiovascular risk factors that suggest novel genetic origins of atherothrombosis. © 2015 American Heart Association, Inc.

  15. Syntheses, structure and intercalation properties of low-dimensional phenylarsonates, A(HO3AsC6H5)(H2O3AsC6H5) (A = Tl, Na, K and Rb)

    Indian Academy of Sciences (India)

    Bonthu Krishna Kishore Reddy; K Prabhakara Rao; K Vidyasagar

    2006-01-01

    Four new low-dimensional phenylarsonates, A(HO3AsC6H5)(H2O3AsC6H5) (A = Tl(1), Na(2), K(3) and Rb(4)), have been synthesized and characterized by X-ray diffraction, spectroscopic and thermal studies. They crystallize in triclinic unit cells and have approximately planar arrangement of A+ ions, coordinated to oxygen atoms of phenylarsonates, on both sides. Structure of thallium phenylarsonate as determined by single crystal X-ray diffraction, is one-dimensional, whereas those of alkalimetal analogues are two-dimensional. Successful intercalation reactions of compounds 1 and 2 with primary -alkyl amines have been demonstrated.

  16. Statistical guidance for experimental design and data analysis of mutation detection in rare monogenic mendelian diseases by exome sequencing.

    Directory of Open Access Journals (Sweden)

    Degui Zhi

    Full Text Available Recently, whole-genome sequencing, especially exome sequencing, has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. However, it is unclear whether this approach can be generalized and effectively applied to other Mendelian diseases with high locus heterogeneity. Moreover, the current exome sequencing approach has limitations such as false positive and false negative rates of mutation detection due to sequencing errors and other artifacts, but the impact of these limitations on experimental design has not been systematically analyzed. To address these questions, we present a statistical modeling framework to calculate the power, the probability of identifying truly disease-causing genes, under various inheritance models and experimental conditions, providing guidance for both proper experimental design and data analysis. Based on our model, we found that the exome sequencing approach is well-powered for mutation detection in recessive, but not dominant, Mendelian diseases with high locus heterogeneity. A disease gene responsible for as low as 5% of the disease population can be readily identified by sequencing just 200 unrelated patients. Based on these results, for identifying rare Mendelian disease genes, we propose that a viable approach is to combine, sequence, and analyze patients with the same disease together, leveraging the statistical framework presented in this work.

  17. The Role of Wellbeing and Wellness: A Positive Psychological Model in Supporting Young People With ASCs

    Directory of Open Access Journals (Sweden)

    Irina Roncaglia

    2017-04-01

    Full Text Available In the last 10 years sport psychology expanded its applicability in a variety of fields which have helped to address some of the challenges related to high level performance and sport competition. When we talk about performance in its wider sense, sport psychology is able to help develop a better understanding on how strategies can be adopted in improving general human performance levels. This includes increasing the knowledge of key concepts such as motivation, self-confidence and resilience. Furthermore performance in its wider sense helps in the understanding of the impact of stress and arousal and how these can affect both positively and negatively performance levels including appreciating individual differences as well as dynamics between groups of individuals. In this paper performance rather than solely be related to the field of competitive or professional sport has been discussed in people with ASCs and aims to explore how by adopting a positive psychological model in the formulation of individual assessments and subsequent interventions have led to improvement in individual skills, participation, engagement and ultimately quality of life. Positive psychological principles, such as the role of wellbeing and wellness, the PERMA Model has increased our understanding of human potentials, performance and wellbeing. The aim of this paper is to present and reflect on the applicability and benefits of adopting sport psychology models, the PERMA model and positive psychological principles in special education and care settings with the presentation and discussion of their theoretical and some practical implementation in two case studies.

  18. Heritability of eleven metabolic phenotypes in Danish and Chinese twins

    DEFF Research Database (Denmark)

    Li, Shuxia; Duan, Hongmei; Pang, Zengchang

    2013-01-01

    A twin-based comparative study on the genetic influences in metabolic endophenotypes in two populations of substantial ethnic, environmental, and cultural differences was performed. Design and Methods: Data on 11 metabolic phenotypes including anthropometric measures, blood glucose, and lipids...... levels as well as blood pressure were available from 756 pairs of Danish twins (309 monozygotic and 447 dizygotic twin pairs) with a mean age of 38 years (range: 18-67) and from 325 pairs of Chinese twins (183 monozygotic and 142 dizygotic twin pairs) with a mean age of 40.5 years (range: 18-69). Twin...... similar heritability patterns in the two samples with body weight showing only a slight difference. Higher genetic influences were estimated for fasting blood glucose level in Chinese twins, whereas the Danish twins showed more genetic regulation over most lipids phenotypes. Systolic blood pressure...

  19. Estimating heritability for cause specific mortality based on twin studies

    DEFF Research Database (Denmark)

    Scheike, Thomas; Holst, Klaus Kähler; von Bornemann Hjelmborg, Jacob

    2014-01-01

    There has been considerable interest in studying the magnitude and type of inheritance of specific diseases. This is typically derived from family or twin studies, where the basic idea is to compare the correlation for different pairs that share different amount of genes. We here consider data from...... the Danish twin registry and discuss how to define heritability for cancer occurrence. The key point is that this should be done taking censoring as well as competing risks due to e.g.  death into account. We describe the dependence between twins on the probability scale and show that various models can...... be used to achieve sensible estimates of the dependence within monozygotic and dizygotic twin pairs that may vary over time. These dependence measures can subsequently be decomposed into a genetic and environmental component using random effects models. We here present several novel models that in essence...

  20. Marfan Syndrome and Related Heritable Thoracic Aortic Aneurysms and Dissections.

    Science.gov (United States)

    De Backer, Julie; Renard, Marjolijn; Campens, Laurence; Mosquera, Laura Muino; De Paepe, Anne; Coucke, Paul; Callewaert, Bert; Kodolitsch, Yskert von

    2015-01-01

    In this overview we aim to address a number of recent insights and developments regarding clinical aspects, etiology, and treatment of Heritable Thoracic Aortic Disease (H-TAD). We will focus on monogenetic disorders related to aortic aneurysms. H-TADs are rare but they provide a unique basis for the study of underlying pathogenetic pathways in the complex disease process of aneurysm formation. The understanding of pathomechanisms may help us to identify medical treatment targets to improve prognosis. Among the monogenetic aneurysm disorders, Marfan syndrome is considered as a paradigm entity and many insights are derived from the study of clinical, genetic and animal models for Marfan syndrome. We will therefore first provide a detailed overview of the various aspects of Marfan syndrome after which we will give an overview of related H-TAD entities.

  1. Heritability of Blood Pressure in an Iranian Population

    Directory of Open Access Journals (Sweden)

    M Saadat

    2001-07-01

    Full Text Available The fact that life styles and personal interests, aggregate within families suggests that shared environment in addition to shared bioligical factors could play a role in determining the phenotypic similarity of idividuals living in the same household. It is a major concern of cardiovascular epidemiologists to know how much of the familial aggregation of blood pressure is attributable to shared genes and/or shared family environment. Genetic and environmental influences on blood pressure was examined in a sample representative of the adult population of Shiraz, Fars province, south of Iran. The studied population was the 107 pairs of mother and dauther. Analysis of the data suggest that the genetic heritabilities were estimated to be 0.58,0.30, 0.60 for systolic, diastolic, and mean blood pressure, respectively.

  2. Small RNAs and heritable epigenetic variation in plants.

    Science.gov (United States)

    Bond, Donna M; Baulcombe, David C

    2014-02-01

    Recent studies suggest that inheritance of phenotypes in plants is more likely to involve epigenetics than in mammals. There are two reasons for this difference. First, there is a RNA-based system in plants involving small (s)RNAs that influences de novo establishment and maintenance of DNA methylation at many sites in plant genomes. These regions of methylated DNA are epigenetic marks with the potential to affect gene expression that are transmitted between dividing cells of the same generation. Second, unlike mammals, DNA methyltransferases in plants are active during gametogenesis and embryogenesis so that patterns of DNA methylation can persist from parent to progeny and do not need to be reset. We discuss how the effects of stress and genome interactions in hybrid plants are two systems that illustrate how RNA-based mechanisms can influence heritable phenotypes in plants.

  3. Pectus excavatum and heritable disorders of the connective tissue.

    Science.gov (United States)

    Tocchioni, Francesca; Ghionzoli, Marco; Messineo, Antonio; Romagnoli, Paolo

    2013-09-24

    Pectus excavatum, the most frequent congenital chest wall deformity, may be rarely observed as a sole deformity or as a sign of an underlying connective tissue disorder. To date, only few studies have described correlations between this deformity and heritable connective tissue disorders such as Marfan, Ehlers-Danlos, Poland, MASS (Mitral valve prolapse, not progressive Aortic enlargement, Skeletal and Skin alterations) phenotype among others. When concurring with connective tissue disorder, cardiopulmonary and vascular involvement may be associated to the thoracic defect. Ruling out the concomitance of pectus excavatum and connective tissue disorders, therefore, may have a direct implication both on surgical outcome and long term prognosis. In this review we focused on biological bases of connective tissue disorders which may be relevant to the pathogenesis of pectus excavatum, portraying surgical and clinical implication of their concurrence.

  4. Pectus excavatum and heritable disorders of the connective tissue

    Directory of Open Access Journals (Sweden)

    Francesca Tocchioni

    2013-09-01

    Full Text Available Pectus excavatum, the most frequent congenital chest wall deformity, may be rarely observed as a sole deformity or as a sign of an underlying connective tissue disorder. To date, only few studies have described correlations between this deformity and heritable connective tissue disorders such as Marfan, Ehlers-Danlos, Poland, MASS (Mitral valve prolapse, not progressive Aortic enlargement, Skeletal and Skin alterations phenotype among others. When concurring with connective tissue disorder, cardiopulmonary and vascular involvement may be associated to the thoracic defect. Ruling out the concomitance of pectus excavatum and connective tissue disorders, therefore, may have a direct implication both on surgical outcome and long term prognosis. In this review we focused on biological bases of connective tissue disorders which may be relevant to the pathogenesis of pectus excavatum, portraying surgical and clinical implication of their concurrence.

  5. Diagnosis of human heritable diseases--laboratory approaches and outcomes.

    Science.gov (United States)

    Dowton, S B; Slaugh, R A

    1995-05-01

    Detection of mutant human genes is rapidly becoming an integral part of clinical practice. Human disease may arise by genetic deletion, insertion, fusion, point mutation, or amplification of unstable sequences. Such changes in structure may occur in germ cells or somatically. Rapid advances in understanding the complex nuclear and mitochondrial genomes necessitates deployment of a variety of methods to identify aberrant genes. These techniques include polymerase chain reaction, Southern transfer, and allele-specific hybridization studies, as well as methods to unmask mismatches between mutant and normal sequences. Development of protein truncation tests has added a vehicle for assessing larger DNA segments for mutations that cause premature translational termination. Linkage analysis remains an important tool where direct assay of disease-causing mutations is not possible. Considerations of confidentiality, informed consent, and insurability are important whenever genetic testing is used. These issues will assume increasing importance as presymptomatic testing for heritable predispositions emerges for common conditions.

  6. Inflammasome adaptor protein Apoptosis-associated speck-like protein containing CARD (ASC) is critical for the immune response and survival in west Nile virus encephalitis.

    Science.gov (United States)

    Kumar, Mukesh; Roe, Kelsey; Orillo, Beverly; Muruve, Daniel A; Nerurkar, Vivek R; Gale, Michael; Verma, Saguna

    2013-04-01

    West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans. The WNV-induced innate immune response, including production of antiviral cytokines, is critical for controlling virus infection. The adaptor protein ASC mediates a critical step in innate immune signaling by bridging the interaction between the pathogen recognition receptors and caspase 1 in inflammasome complexes, but its role in WNV immunopathogenesis is not defined. Here, we demonstrate that ASC is essential for interleukin-1β (IL-1β) production and development of effective host immunity against WNV. ASC-deficient mice exhibited increased susceptibility to WNV infection, and reduced survival was associated with enhanced virus replication in the peripheral tissues and central nervous system (CNS). Infection of cultured bone marrow-derived dendritic cells showed that ASC was essential for the activation of caspase 1, a key component of inflammasome assembly. ASC(-/-) mice exhibited attenuated levels of proinflammatory cytokines in the serum. Intriguingly, infected ASC(-/-) mice also displayed reduced levels of alpha interferon (IFN-α) and IgM in the serum, indicating the overall protective role of ASC in restricting WNV infection. However, brains from ASC(-/-) mice displayed unrestrained inflammation, including elevated levels of proinflammatory cytokines and chemokines, such as IFN-γ, CCL2, and CCL5, which correlated with more pronounced activation of the astrocytes, enhanced infiltration of peripheral immune cells in the CNS, and increased neuronal cell death. Collectively, our data provide new insights into the role of ASC as an essential modulator of inflammasome-dependent and -independent immune responses to effectively control WNV infection.

  7. Describing the genetic architecture of epilepsy through heritability analysis.

    Science.gov (United States)

    Speed, Doug; O'Brien, Terence J; Palotie, Aarno; Shkura, Kirill; Marson, Anthony G; Balding, David J; Johnson, Michael R

    2014-10-01

    Epilepsy is a disease with substantial missing heritability; despite its high genetic component, genetic association studies have had limited success detecting common variants which influence susceptibility. In this paper, we reassess the role of common variants on epilepsy using extensions of heritability analysis. Our data set consists of 1258 UK patients with epilepsy, of which 958 have focal epilepsy, and 5129 population control subjects, with genotypes recorded for over 4 million common single nucleotide polymorphisms. Firstly, we show that on the liability scale, common variants collectively explain at least 26% (standard deviation 5%) of phenotypic variation for all epilepsy and 27% (standard deviation 5%) for focal epilepsy. Secondly we provide a new method for estimating the number of causal variants for complex traits; when applied to epilepsy, our most optimistic estimate suggests that at least 400 variants influence disease susceptibility, with potentially many thousands. Thirdly, we use bivariate analysis to assess how similar the genetic architecture of focal epilepsy is to that of non-focal epilepsy; we demonstrate both significant differences (P = 0.004) and significant similarities (P = 0.01) between the two subtypes, indicating that although the clinical definition of focal epilepsy does identify a genetically distinct epilepsy subtype, there is also scope to improve the classification of epilepsy by incorporating genotypic information. Lastly, we investigate the potential value in using genetic data to diagnose epilepsy following a single epileptic seizure; we find that a prediction model explaining 10% of phenotypic variation could have clinical utility for deciding which single-seizure individuals are likely to benefit from immediate anti-epileptic drug therapy.

  8. Human-directed social behaviour in dogs shows significant heritability.

    Science.gov (United States)

    Persson, M E; Roth, L S V; Johnsson, M; Wright, D; Jensen, P

    2015-04-01

    Through domestication and co-evolution with humans, dogs have developed abilities to attract human attention, e.g. in a manner of seeking assistance when faced with a problem solving task. The aims of this study were to investigate within breed variation in human-directed contact seeking in dogs and to estimate its genetic basis. To do this, 498 research beagles, bred and kept under standardized conditions, were tested in an unsolvable problem task. Contact seeking behaviours recorded included both eye contact and physical interactions. Behavioural data was summarized through a principal component analysis, resulting in four components: test interactions, social interactions, eye contact and physical contact. Females scored significantly higher on social interactions and physical contact and age had an effect on eye contact scores. Narrow sense heritabilities (h(2) ) of the two largest components were estimated at 0.32 and 0.23 but were not significant for the last two components. These results show that within the studied dog population, behavioural variation in human-directed social behaviours was sex dependent and that the utilization of eye contact seeking increased with age and experience. Hence, heritability estimates indicate a significant genetic contribution to the variation found in human-directed social interactions, suggesting that social skills in dogs have a genetic basis, but can also be shaped and enhanced through individual experiences. This research gives the opportunity to further investigate the genetics behind dogs' social skills, which could also play a significant part into research on human social disorders such as autism.

  9. High heritability is compatible with the broad distribution of set point viral load in HIV carriers.

    Directory of Open Access Journals (Sweden)

    Sebastian Bonhoeffer

    2015-02-01

    Full Text Available Set point viral load in HIV patients ranges over several orders of magnitude and is a key determinant of disease progression in HIV. A number of recent studies have reported high heritability of set point viral load implying that viral genetic factors contribute substantially to the overall variation in viral load. The high heritability is surprising given the diversity of host factors associated with controlling viral infection. Here we develop an analytical model that describes the temporal changes of the distribution of set point viral load as a function of heritability. This model shows that high heritability is the most parsimonious explanation for the observed variance of set point viral load. Our results thus not only reinforce the credibility of previous estimates of heritability but also shed new light onto mechanisms of viral pathogenesis.

  10. More heritability probably captured by psoriasis genome-wide association study in Han Chinese.

    Science.gov (United States)

    Jiang, Long; Liu, Lu; Cheng, Yuyan; Lin, Yan; Shen, Changbing; Zhu, Caihong; Yang, Sen; Yin, Xianyong; Zhang, Xuejun

    2015-11-15

    Missing heritability is a common problem in genome-wide association studies in complex diseases/traits. To quantify the unbiased heritability estimate, we applied the phenotype correlation-genotype correlation regression in psoriasis genome-wide association data in Han Chinese which comprises 1139 cases and 1132 controls. We estimated that 45.7% heritability of psoriasis in Han Chinese were captured by common variants (s.e.=12.5%), which reinforced that the majority of psoriasis heritability can be covered by common variants in genome-wide association data (68.2%). The results provided evidence that the heritability covered by psoriasis genome-wide genotyping data was probably underestimated in previous restricted maximum likelihood method. Our study highlights the broad role of common variants in the etiology of psoriasis and sheds light on the possibility to identify more common variants of small effect by increasing the sample size in psoriasis genome-wide association studies.

  11. Using extended genealogy to estimate components of heritability for 23 quantitative and dichotomous traits.

    Science.gov (United States)

    Zaitlen, Noah; Kraft, Peter; Patterson, Nick; Pasaniuc, Bogdan; Bhatia, Gaurav; Pollack, Samuela; Price, Alkes L

    2013-05-01

    Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by genetic factors. Here, we make use of extensive phenotype data in Iceland, long-range phased genotypes, and a population-wide genealogical database to examine the heritability of 11 quantitative and 12 dichotomous phenotypes in a sample of 38,167 individuals. Most previous estimates of heritability are derived from family-based approaches such as twin studies, which may be biased upwards by epistatic interactions or shared environment. Our estimates of heritability, based on both closely and distantly related pairs of individuals, are significantly lower than those from previous studies. We examine phenotypic correlations across a range of relationships, from siblings to first cousins, and find that the excess phenotypic correlation in these related individuals is predominantly due to shared environment as opposed to dominance or epistasis. We also develop a new method to jointly estimate narrow-sense heritability and the heritability explained by genotyped SNPs. Unlike existing methods, this approach permits the use of information from both closely and distantly related pairs of individuals, thereby reducing the variance of estimates of heritability explained by genotyped SNPs while preventing upward bias. Our results show that common SNPs explain a larger proportion of the heritability than previously thought, with SNPs present on Illumina 300K genotyping arrays explaining more than half of the heritability for the 23 phenotypes examined in this study. Much of the remaining heritability is likely to be due to rare alleles that are not captured by standard genotyping arrays.

  12. Using extended genealogy to estimate components of heritability for 23 quantitative and dichotomous traits.

    Directory of Open Access Journals (Sweden)

    Noah Zaitlen

    2013-05-01

    Full Text Available Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by genetic factors. Here, we make use of extensive phenotype data in Iceland, long-range phased genotypes, and a population-wide genealogical database to examine the heritability of 11 quantitative and 12 dichotomous phenotypes in a sample of 38,167 individuals. Most previous estimates of heritability are derived from family-based approaches such as twin studies, which may be biased upwards by epistatic interactions or shared environment. Our estimates of heritability, based on both closely and distantly related pairs of individuals, are significantly lower than those from previous studies. We examine phenotypic correlations across a range of relationships, from siblings to first cousins, and find that the excess phenotypic correlation in these related individuals is predominantly due to shared environment as opposed to dominance or epistasis. We also develop a new method to jointly estimate narrow-sense heritability and the heritability explained by genotyped SNPs. Unlike existing methods, this approach permits the use of information from both closely and distantly related pairs of individuals, thereby reducing the variance of estimates of heritability explained by genotyped SNPs while preventing upward bias. Our results show that common SNPs explain a larger proportion of the heritability than previously thought, with SNPs present on Illumina 300K genotyping arrays explaining more than half of the heritability for the 23 phenotypes examined in this study. Much of the remaining heritability is likely to be due to rare alleles that are not captured by standard genotyping arrays.

  13. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.

    Directory of Open Access Journals (Sweden)

    Lea K Davis

    2013-10-01

    Full Text Available The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD and Tourette Syndrome (TS, using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12 for TS, and 0.37 (se = 0.07, p = 1.5e-07 for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum for which we had available expression quantitative trait loci (eQTLs. Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002. These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

  14. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

    Science.gov (United States)

    Davis, Lea K.; Yu, Dongmei; Keenan, Clare L.; Gamazon, Eric R.; Konkashbaev, Anuar I.; Derks, Eske M.; Neale, Benjamin M.; Yang, Jian; Lee, S. Hong; Evans, Patrick; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrio, Gabriel Bedoya; Bienvenu, Oscar J.; Bloch, Michael H.; Blom, Rianne M.; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond; Cappi, Carolina; Cardona Silgado, Julio C.; Cath, Danielle C.; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Conti, David V.; Cook, Edwin H.; Coric, Vladimir; Cullen, Bernadette A.; Deforce, Dieter; Delorme, Richard; Dion, Yves; Edlund, Christopher K.; Egberts, Karin; Falkai, Peter; Fernandez, Thomas V.; Gallagher, Patience J.; Garrido, Helena; Geller, Daniel; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Haddad, Stephen; Heiman, Gary A.; Hemmings, Sian M. J.; Hounie, Ana G.; Illmann, Cornelia; Jankovic, Joseph; Jenike, Michael A.; Kennedy, James L.; King, Robert A.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Macciardi, Fabio; McCracken, James T.; McGrath, Lauren M.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Ochoa, William Cornejo; Ophoff, Roel A.; Osiecki, Lisa; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias J.; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosàrio, Maria C.; Rosenberg, David; Rouleau, Guy A.; Ruhrmann, Stephan; Ruiz-Linares, Andres; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, E.; Tischfield, Jay A.; Valencia Duarte, Ana V.; Vallada, Homero; Van Nieuwerburgh, Filip; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R.; Westenberg, Herman G. M.; Shugart, Yin Yao; Miguel, Euripedes C.; McMahon, William; Wagner, Michael; Nicolini, Humberto; Posthuma, Danielle; Hanna, Gregory L.; Heutink, Peter; Denys, Damiaan; Arnold, Paul D.; Oostra, Ben A.; Nestadt, Gerald; Freimer, Nelson B.; Pauls, David L.; Wray, Naomi R.

    2013-01-01

    The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures. PMID:24204291

  15. Completion Report for Multi-Site Incentive MRT 2779 Implement ASC Tripod Initiative by 30SEP08

    Energy Technology Data Exchange (ETDEWEB)

    East, D; Cerutti, J; Noe, J; Cupps, K; Loncaric, J; Sturtevant, J

    2008-09-22

    This report provides documentation and evidence for the completion of the deployment of the Tripod common operating system (TripodOS, also known as and generally referred to below as TOSS). Background documents for TOSS are provided in Appendices A and B, including the initial TOSS proposal accepted by ASC HQ and Executives in July 2007 and a Governance Model defined by a Tri-Lab working group in September 2007. Appendix C contains a document that clarifies the intent and requirements for the completion criteria associated with MRT 2779. The deployment of TOSS is a Multi-Site Incentive from the ASC FY08-09 Implementation Plan due at the end of Quarter 4 in FY08.

  16. Multifunctional nanocrystalline calcium phosphates loaded with Tetracycline antibiotic combined with human adipose derived mesenchymal stromal stem cells (hASCs).

    Science.gov (United States)

    Marycz, K; Pazik, R; Zawisza, K; Wiglusz, K; Maredziak, M; Sobierajska, P; Wiglusz, R J

    2016-12-01

    Osteoconductive drug delivery system composed of nanocrystalline calcium phosphates (Ca10(PO4)6(OH)2/β-Ca3(PO4)2) co-doped with Yb(3+)/Er(3+) ions loaded with Tetracycline antibiotic (TC) was developed. Their effect on human adipose derived mesenchymal stromal stem cells (hASCs) as a potential reconstructive biomaterial for bone tissue regeneration was studied. The XRD and TEM measurements were used in order to determine the crystal structure and morphology of the final products. The characteristics of nanocomposites with the TC and hASCs as potential regenerative materials as well as the antimicrobial activity of the nanoparticles against: Staphylococcus aureus ATCC 25923 as a model of the Gram-positive bacteria, Escherichia coli ATCC 8739 of the Gram-negative bacteria, were shown. These combinations can be a promising material for theranostic due to its regenerative, antimicrobial and fluorescent properties.

  17. Asc-1, PAT2 and P2RX5 are novel cell surface markers for white, beige and brown adipocytes

    OpenAIRE

    Ussar, Siegfried; Lee, Kevin Y.; Dankel, Simon N.; Boucher, Jeremie; Haering, Max-Felix; Kleinridders, Andre; Thomou, Thomas; Xue, Ruidan; Macotela, Yazmin; Cypess, Aaron M.; Tseng, Yu-Hua; Mellgren, Gunnar; Kahn, C. Ronald

    2014-01-01

    White, beige and brown adipocytes are developmentally and functionally distinct but often occur mixed together within individual depots. To target white, beige and brown adipocytes for diagnostic or therapeutic purposes, a better understanding of the cell surface properties of these cell types is essential. Using a combination of in silico, in vitro and in vivo methods, we have identified three new cell surface markers of adipose cell types. The amino acid transporter Asc-1 is a white adipocy...

  18. Fluorescent immortalized human adipose derived stromal cells (hASCs-TS/GFP+) for studying cell drug delivery mediated by microvesicles.

    Science.gov (United States)

    Coccè, Valentina; Balducci, Luigi; Falchetti, Maria Laura; Pascucci, Luisa; Ciusani, Emilio; Brini, Anna Teresa; Sisto, Francesca; Piovani, Giovanna; Alessandri, Giulio; Parati, Eugenio; Cabeza, Laura; Pessina, Augusto

    2017-03-27

    A new tool for the drug delivery is based on the use of Mesenchymal Stromal Cells (MSCs) loaded in vitro with anti-cancer drugs. Unfortunately, the restricted lifespan of MSCs represents a significant limitation to produce them in high amounts and for long time studies. Immortalized MSCs from adipose tissue (hASC) have been generated as good source of cells with stable features. These cells could improve the development of standardized procedures for both in vitro and preclinical studies. Furthermore they facilitate procedures for preparing large amounts of secretome containing microvesicles (MVs). We used human adipose tissue derived MSCs immortalized with hTERT+SV40 (TS) genes and transfected with GFP (hASCs-TS/GFP+). This line was investigate for its ability to uptake and release anticancer drugs. Microvesicles associated to paclitaxel (MVs/PTX) were isolated, quantified, and tested on pancreatic cancer cells. The line hASCs-TS/GFP+ maintained the main mesenchymal characters and was able to uptake and release, in active form, both paclitaxel and gemcitabine. From paclitaxel loaded hASCs-TS/GFP+ cells were isolated microvesicles in sufficient amount to inhibit "in vitro" the proliferation of pancreatic tumor cells. Our study suggests that human immortalized MSCs could be used for a large scale production of cells for mediated drug delivery. Moreover, the secretion of drug-associated MVs could represent a new way for producing new drug formulation by "biogenesis". In the context of the "advanced cell therapy procedure", the MVs/PTX production would be less resource and time consuming and it could possibly contribute to simplification of GMP procedures. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Cross-resistance, genetics, and realized heritability of resistance to fipronil in the house fly, Musca domestica (Diptera: Muscidae): a potential vector for disease transmission.

    Science.gov (United States)

    Abbas, Naeem; Khan, Hafiz Azhar Ali; Shad, Sarfraz Ali

    2014-04-01

    Houseflies, Musca domestica (L.), are ubiquitous pests that have the potential to spread a variety of pathogens to humans, poultries, and dairies. Pesticides are commonly used for the management of this pest. Fipronil is a GABA-gated chloride channel-inhibiting insecticide that has been commonly used for the management of different pests including M. domestica throughout the world. Many pests have developed resistance to this insecticide. A field-collected strain of M. domestica was selected with fipronil for continuous 11 generations to assess the cross-resistance, genetics, and realized heritability for designing a resistance management strategy. Laboratory bioassays were performed using the feeding method of mixing insecticide concentrations with 20% sugar solutions and cotton soaks dipped in insecticide solutions were provided to tested adult flies. Bioassay results at G12 showed that the fipronil-selected strain developed a resistance ratio of 140-fold compared to the susceptible strain. Synergism bioassay with piperonyl butoxide (PBO) and S,S,S,-tributyl phosphorotrithioate (DEF) indicated that fipronil resistance was associated with microsomal oxidase and also esterase. Reciprocal crosses between resistant and susceptible strains showed an autosomal and incompletely dominant resistance to fipronil. The LC50 values of F1 and F'1 strains were not significantly different and dominance values were 0.74 and 0.64, respectively. The resistance to fipronil was completely recessive (D(ML) = 0.00) at the highest dose and incompletely dominant at the lowest dose (D(ML) = 0.87). The monogenic resistance based on chi-square goodness of fit test and calculation of the minimum number of segregating genes showed that resistance to fipronil is controlled by multiple genes. The fipronil resistance strain confirmed very low cross-resistance to emamectin benzoate and spinosad while no cross-resistance to chlorpyrifos and acetamiprid when compared to that of the field population

  20. ASCS online fault detection and isolation based on an improved MPCA

    Science.gov (United States)

    Peng, Jianxin; Liu, Haiou; Hu, Yuhui; Xi, Junqiang; Chen, Huiyan

    2014-09-01

    Multi-way principal component analysis (MPCA) has received considerable attention and been widely used in process monitoring. A traditional MPCA algorithm unfolds multiple batches of historical data into a two-dimensional matrix and cut the matrix along the time axis to form subspaces. However, low efficiency of subspaces and difficult fault isolation are the common disadvantages for the principal component model. This paper presents a new subspace construction method based on kernel density estimation function that can effectively reduce the storage amount of the subspace information. The MPCA model and the knowledge base are built based on the new subspace. Then, fault detection and isolation with the squared prediction error (SPE) statistic and the Hotelling ( T 2) statistic are also realized in process monitoring. When a fault occurs, fault isolation based on the SPE statistic is achieved by residual contribution analysis of different variables. For fault isolation of subspace based on the T 2 statistic, the relationship between the statistic indicator and state variables is constructed, and the constraint conditions are presented to check the validity of fault isolation. Then, to improve the robustness of fault isolation to unexpected disturbances, the statistic method is adopted to set the relation between single subspace and multiple subspaces to increase the corrective rate of fault isolation. Finally fault detection and isolation based on the improved MPCA is used to monitor the automatic shift control system (ASCS) to prove the correctness and effectiveness of the algorithm. The research proposes a new subspace construction method to reduce the required storage capacity and to prove the robustness of the principal component model, and sets the relationship between the state variables and fault detection indicators for fault isolation.

  1. ASCS Online Fault Detection and Isolation Based on an Improved MPCA

    Institute of Scientific and Technical Information of China (English)

    PENG Jianxin; LIU Haiou; HU Yuhui; XI Junqiang; CHEN Huiyan

    2014-01-01

    Multi-way principal component analysis (MPCA) has received considerable attention and been widely used in process monitoring. A traditional MPCA algorithm unfolds multiple batches of historical data into a two-dimensional matrix and cut the matrix along the time axis to form subspaces. However, low efficiency of subspaces and difficult fault isolation are the common disadvantages for the principal component model. This paper presents a new subspace construction method based on kernel density estimation function that can effectively reduce the storage amount of the subspace information. The MPCA model and the knowledge base are built based on the new subspace. Then, fault detection and isolation with the squared prediction error (SPE) statistic and the Hotelling (T2) statistic are also realized in process monitoring. When a fault occurs, fault isolation based on the SPE statistic is achieved by residual contribution analysis of different variables. For fault isolation of subspace based on the T2 statistic, the relationship between the statistic indicator and state variables is constructed, and the constraint conditions are presented to check the validity of fault isolation. Then, to improve the robustness of fault isolation to unexpected disturbances, the statistic method is adopted to set the relation between single subspace and multiple subspaces to increase the corrective rate of fault isolation. Finally fault detection and isolation based on the improved MPCA is used to monitor the automatic shift control system (ASCS) to prove the correctness and effectiveness of the algorithm. The research proposes a new subspace construction method to reduce the required storage capacity and to prove the robustness of the principal component model, and sets the relationship between the state variables and fault detection indicators for fault isolation.

  2. Land Cover Information for the Upper Colorado River Basin in Maurer et al. (2002) Climate Data resolution (nlcd_UCRB_Maurer_resolution.asc)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — nlcd_UCRB_Maurer_resolution.asc is an Esri ASCII grid representing land cover information for the Upper Colorado River Basin. The 2011 National Land Cover Database...

  3. Hydrologic Soil Group for the Upper Colorado River Basin in Maurer et al. (2002) Climate Data resolution (hsg_UCRB_Maurer_resolution.asc)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — hsg_UCRB_Maurer_resolution.asc is an Esri ASCII grid representing the hydrologic soil group (HSG) for the Upper Colorado River Basin. The HSG for an area is...

  4. Available Water Capacity for the Upper Colorado River Basin in Maurer et al. (2002) Climate Data resolution (awc_UCRB_Maurer_resolution.asc)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — awc_UCRB_Maurer_resolution.asc is an Esri ASCII grid representing the available water capacity (AWC) for the Upper Colorado River Basin. AWC is the amount of water...

  5. Overland Flow Direction Information for the Upper Colorado River Basin in Maurer et al. (2002) Climate Data resolution (overland_flow_direction_UCRB_Maurer_resolution.asc)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — overland_flow_direction_UCRB_Maurer_resolution.asc is an Esri ASCII grid representing overland flow direction in the Upper Colorado River Basin using the D8...

  6. Digital dermatoglyphic heritability differences as evidenced by a female twin study.

    Science.gov (United States)

    Machado, João Felipe; Fernandes, Paula Roquetti; Roquetti, Ricardo Wagner; Filho, José Fernandes

    2010-10-01

    The genetic and environmental contributions to determine digital dermatoglyphic traits were investigated by using female dizygotic and monozygotic twin pairs to estimate heritability indexes (h(2)). The evaluated sample was composed by 20 monozygotic twin pairs and 13 dizygotic twin pairs. A significant heritability (h(2) = 0.65 to 0.96) was observed for 12 dermatoglyphic characteristics (delta indexes and ridge counts for right hand, left hand and both hands, and ridge counts for most individual fingers). A negative correlation between the ridge counts and heritability indexes from individual fingers was found for the left hand, which appears to be associated to a higher arch pattern frequency in most left-hand fingers, since this frequency was negatively correlated with ridge counts and positively correlated with heritability indexes. Heritability indexes of right-hand fingers were positively correlated with loop pattern frequency and negatively correlated with whorl pattern frequency. The low heritability of ridge counts from left thumb, ring and little fingers (h(2) = 0.11 to 0.32) indicates a higher chance that the chorion type had an influence in the intra-pair variance of monozygotic twins. Results confirmed the predominant genetic influence on the total ridge count. The heritability indexes varied in up to 8 times between different fingers and its association to ridge counts and pattern frequency was very variable between hands, evidencing that the use of dermatoglyphic traits from individual fingers as indicators of genetic influences to other human traits should consider this variability.

  7. Heritability of ECG Biomarkers in the Netherlands Twin Registry Measured from Holter ECGs.

    Science.gov (United States)

    Hodkinson, Emily C; Neijts, Melanie; Sadrieh, Arash; Imtiaz, Mohammad S; Baumert, Mathias; Subbiah, Rajesh N; Hayward, Christopher S; Boomsma, Dorret; Willemsen, Gonneke; Vandenberg, Jamie I; Hill, Adam P; De Geus, Eco

    2016-01-01

    The resting ECG is the most commonly used tool to assess cardiac electrophysiology. Previous studies have estimated heritability of ECG parameters based on these snapshots of the cardiac electrical activity. In this study we set out to determine whether analysis of heart rate specific data from Holter ECGs allows more complete assessment of the heritability of ECG parameters. Holter ECGs were recorded from 221 twin pairs and analyzed using a multi-parameter beat binning approach. Heart rate dependent estimates of heritability for QRS duration, QT interval, Tpeak-Tend and Theight were calculated using structural equation modeling. QRS duration is largely determined by environmental factors whereas repolarization is primarily genetically determined. Heritability estimates of both QT interval and Theight were significantly higher when measured from Holter compared to resting ECGs and the heritability estimate of each was heart rate dependent. Analysis of the genetic contribution to correlation between repolarization parameters demonstrated that covariance of individual ECG parameters at different heart rates overlap but at each specific heart rate there was relatively little overlap in the genetic determinants of the different repolarization parameters. Here we present the first study of heritability of repolarization parameters measured from Holter ECGs. Our data demonstrate that higher heritability can be estimated from the Holter than the resting ECG and reveals rate dependence in the genetic-environmental determinants of the ECG that has not previously been tractable. Future applications include deeper dissection of the ECG of participants with inherited cardiac electrical disease.

  8. Heritability of ECG Biomarkers in the Netherlands Twin Registry Measured from Holter ECGs

    Science.gov (United States)

    Hodkinson, Emily C.; Neijts, Melanie; Sadrieh, Arash; Imtiaz, Mohammad S.; Baumert, Mathias; Subbiah, Rajesh N.; Hayward, Christopher S.; Boomsma, Dorret; Willemsen, Gonneke; Vandenberg, Jamie I.; Hill, Adam P.; De Geus, Eco

    2016-01-01

    Introduction: The resting ECG is the most commonly used tool to assess cardiac electrophysiology. Previous studies have estimated heritability of ECG parameters based on these snapshots of the cardiac electrical activity. In this study we set out to determine whether analysis of heart rate specific data from Holter ECGs allows more complete assessment of the heritability of ECG parameters. Methods and Results: Holter ECGs were recorded from 221 twin pairs and analyzed using a multi-parameter beat binning approach. Heart rate dependent estimates of heritability for QRS duration, QT interval, Tpeak–Tend and Theight were calculated using structural equation modeling. QRS duration is largely determined by environmental factors whereas repolarization is primarily genetically determined. Heritability estimates of both QT interval and Theight were significantly higher when measured from Holter compared to resting ECGs and the heritability estimate of each was heart rate dependent. Analysis of the genetic contribution to correlation between repolarization parameters demonstrated that covariance of individual ECG parameters at different heart rates overlap but at each specific heart rate there was relatively little overlap in the genetic determinants of the different repolarization parameters. Conclusions: Here we present the first study of heritability of repolarization parameters measured from Holter ECGs. Our data demonstrate that higher heritability can be estimated from the Holter than the resting ECG and reveals rate dependence in the genetic—environmental determinants of the ECG that has not previously been tractable. Future applications include deeper dissection of the ECG of participants with inherited cardiac electrical disease. PMID:27199769

  9. Monogenic mutations differentially impact the quantity and quality of T follicular helper cells in human primary immunodeficiencies

    Science.gov (United States)

    Ma, Cindy S; Wong, Natalie; Rao, Geetha; Avery, Danielle T; Torpy, James; Hambridge, Thomas; Bustamante, Jacinta; Okada, Satoshi; Stoddard, Jennifer L; Deenick, Elissa K; Pelham, Simon J; Payne, Katherine; Boisson-Dupuis, Stéphanie; Puel, Anne; Kobayashi, Masao; Arkwright, Peter D; Kilic, Sara Sebnem; Baghdadi, Jamila El; Nonoyama, Shigeaki; Minegishi, Yoshiyuki; Mahdaviani, Seyed Alireza; Mansouri, Davood; Bousfiha, Aziz; Blincoe, Annaliesse K; French, Martyn A; Hsu, Peter; Campbell, Dianne E.; Stormon, Michael O; Wong, Melanie; Adelstein, Stephen; Smart, Joanne M; Fulcher, David A; Cook, Matthew C; Phan, Tri G; Stepensky, Polina; Boztug, Kaan; Kansu, Aydan; Ikincioğullari, Aydan; Baumann, Ulrich; Beier, Rita; Roscioli, Tony; Ziegler, John B; Gray, Paul; Picard, Capucine; Grimbacher, Bodo; Warnatz, Klaus; Holland, Steven M; Casanova, Jean-Laurent; Uzel, Gulbu; Tangye, Stuart G

    2016-01-01

    Background T follicular helper (Tfh) cells underpin T-cell dependent humoral immunity and the success of most vaccines. Tfh cells also contribute to human immune disorders such as autoimmunity, immunodeficiency and malignancy. Understanding the molecular requirements for the generation and function of Tfh cells will provide strategies for targeting these cells to modulate their behavior in the setting of these immunological abnormalities. Objective To determine the signaling pathways and cellular interactions required for the development and function of Tfh cells in humans. Methods Human primary immunodeficiencies (PIDs) resulting from monogenic mutations provide a unique opportunity to assess the requirement for particular molecules in regulating human lymphocyte function. Circulating Tfh (cTfh) cell subsets, memory B cells and serum Ig levels were quantified and functionally assessed in healthy controls as well as patients with PIDs resulting from mutations in STAT3, STAT1, TYK2, IL21, IL21R, IL10R, IFNGR1/2, IL12RB1, CD40LG, NEMO, ICOS or BTK. Results Loss-of function (LOF) mutations in STAT3, IL10R, CD40LG, NEMO, ICOS or BTK reduced cTfh frequencies. STAT3, IL21/R LOF and STAT1 gain-of function mutations skewed cTfh differentiation towards a phenotype characterized by over-expression of IFNγ and programmed death -1 (PD-1). IFNγ inhibited cTfh function in vitro and in vivo, corroborated by hypergammaglobulinemia in patients with IFNGR1/2, STAT1 and IL12RB1 LOF mutations. Conclusion Specific mutations impact the quantity and quality of cTfh cells, highlighting the need to assess Tfh cells in patients by multiple criteria, including phenotype and function. Furthermore, IFNγ functions in vivo to restrain Tfh-induced B cell differentiation. These findings shed new light on Tfh biology and the integrated signaling pathways required for their generation, maintenance and effector function, and explain compromised humoral immunity in some PIDs. PMID:26162572

  10. Monogenic diabetes syndromes: Locus‐specific databases for Alström, Wolfram, and Thiamine‐responsive megaloblastic anemia

    Science.gov (United States)

    Astuti, Dewi; Sabir, Ataf; Fulton, Piers; Zatyka, Malgorzata; Williams, Denise; Hardy, Carol; Milan, Gabriella; Favaretto, Francesca; Yu‐Wai‐Man, Patrick; Rohayem, Julia; López de Heredia, Miguel; Hershey, Tamara; Tranebjaerg, Lisbeth; Chen, Jian‐Hua; Chaussenot, Annabel; Nunes, Virginia; Marshall, Bess; McAfferty, Susan; Tillmann, Vallo; Maffei, Pietro; Paquis‐Flucklinger, Veronique; Geberhiwot, Tarekign; Mlynarski, Wojciech; Parkinson, Kay; Picard, Virginie; Bueno, Gema Esteban; Dias, Renuka; Arnold, Amy; Richens, Caitlin; Paisey, Richard; Urano, Fumihiko; Semple, Robert; Sinnott, Richard

    2017-01-01

    Abstract We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease‐associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine‐responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype–phenotype relations for the WFS1 gene. The presence of biallelic loss‐of‐function variants predicted Wolfram syndrome defined by insulin‐dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI 75%–83%) and specificity of 92% (83%–97%). The presence of minor loss‐of‐function variants in WFS1 predicted isolated diabetes, isolated deafness, or isolated congenital cataracts without development of the full syndrome (sensitivity 100% [93%–100%]; specificity 78% [73%–82%]). The ability to provide a prognostic prediction based on genotype will lead to improvements in patient care and counseling. The development of the database as a repository for monogenic diabetes gene variants will allow prognostic predictions for other diabetes syndromes as next‐generation sequencing expands the repertoire of genotypes and phenotypes. The database is publicly available online at https://lovd.euro-wabb.org. PMID:28432734

  11. Monogenic diabetes syndromes: Locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia.

    Science.gov (United States)

    Astuti, Dewi; Sabir, Ataf; Fulton, Piers; Zatyka, Malgorzata; Williams, Denise; Hardy, Carol; Milan, Gabriella; Favaretto, Francesca; Yu-Wai-Man, Patrick; Rohayem, Julia; López de Heredia, Miguel; Hershey, Tamara; Tranebjaerg, Lisbeth; Chen, Jian-Hua; Chaussenot, Annabel; Nunes, Virginia; Marshall, Bess; McAfferty, Susan; Tillmann, Vallo; Maffei, Pietro; Paquis-Flucklinger, Veronique; Geberhiwot, Tarekign; Mlynarski, Wojciech; Parkinson, Kay; Picard, Virginie; Bueno, Gema Esteban; Dias, Renuka; Arnold, Amy; Richens, Caitlin; Paisey, Richard; Urano, Fumihiko; Semple, Robert; Sinnott, Richard; Barrett, Timothy G

    2017-07-01

    We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine-responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype-phenotype relations for the WFS1 gene. The presence of biallelic loss-of-function variants predicted Wolfram syndrome defined by insulin-dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI 75%-83%) and specificity of 92% (83%-97%). The presence of minor loss-of-function variants in WFS1 predicted isolated diabetes, isolated deafness, or isolated congenital cataracts without development of the full syndrome (sensitivity 100% [93%-100%]; specificity 78% [73%-82%]). The ability to provide a prognostic prediction based on genotype will lead to improvements in patient care and counseling. The development of the database as a repository for monogenic diabetes gene variants will allow prognostic predictions for other diabetes syndromes as next-generation sequencing expands the repertoire of genotypes and phenotypes. The database is publicly available online at https://lovd.euro-wabb.org. © 2017 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

  12. Heritability of the somatotype components in Biscay families.

    Science.gov (United States)

    Rebato, E; Jelenkovic, A; Salces, I

    2007-01-01

    The anthropometric somatotype is a quantitative description of body shape and composition. Familial studies indicate the existence of a familial resemblance for this phenotype and they suggest a substantial action by genetic factors on this aggregation. The aim of this study is to examine the degree of familial resemblance of the somatotype components and of a factor of shape, in a sample of Biscay nuclear families (Basque Country, Spain). One thousand three hundred and thirty nuclear families were analysed. The anthropometric somatotype components [Carter, J.E.L., Heath, B.H., 1990. Somatotyping. Development and applications. Cambridge University Press, Cambridge, p. 503] were computed. Each component was fitted for the other two through a stepwise multiple regression, and also fitted through the LMS method [Cole, T., 1988. Fitting smoothed centile curves to reference data. J. Roy. Stat. Soc. 151, 385-418] in order to eliminate the age, sex and generation effects. The three raw components were introduced in a PCA from which a shape factor (PC1) was extracted for each generation. The correlations analysis was performed with the SEGPATH package [Province, M.A., Rao, D.C., 1995. General purpose model and computer programme for combined segregation and path analysis (SEGPATH): automatically creating computer from symbolic language model specifications. Genet. Epidemiol. 12, 203-219]. A general model of transmission and nine reduced models were tested. Maximal heritability was estimated with the formula of [Rice, T., Warwick, D.E., Gagnon, J., Bouchard, C., Leon, A.S., Skinner, J.S., Wilmore, J.H., Rao, D.C., 1997. Familial resemblance for body composition measures: the HERITAGE family study. Obes. Res. 5, 557-562]. The correlations were higher between offspring than in parents and offspring and a significant resemblance between mating partners existed. Maximum heritabilities were 55%, 52% and 46% for endomorphy, mesomorphy and ectomorphy, respectively, and 52% for PC1

  13. Draft Genome Sequence of Heavy Metal-Resistant Cupriavidus alkaliphilus ASC-732T, Isolated from Agave Rhizosphere in the Northeast of Mexico

    Science.gov (United States)

    Rojas-Rojas, Fernando Uriel; Huntemann, Marcel; Clum, Alicia; Pillay, Manoj; Palaniappan, Krishnaveni; Varghese, Neha; Mikhailova, Natalia; Stamatis, Dimitrios; Reddy, T. B. K.; Markowitz, Victor; Ivanova, Natalia; Kyrpides, Nikos; Woyke, Tanja; Shapiro, Nicole

    2016-01-01

    Cupriavidus alkaliphilus ASC-732T was isolated from the rhizosphere of agave plant growing in alkaline soils in San Carlos, Tamaulipas, Mexico. The species is able to grow in the presence of arsenic, zinc, and copper. The genome sequence of strain ASC-732T is 6,125,055 bp with 5,586 genes and an average G+C content of 67.81%. PMID:27660789

  14. Draft Genome Sequence of Heavy Metal-Resistant Cupriavidus alkaliphilus ASC-732T, Isolated from Agave Rhizosphere in the Northeast of Mexico.

    Science.gov (United States)

    Rojas-Rojas, Fernando Uriel; Huntemann, Marcel; Clum, Alicia; Pillay, Manoj; Palaniappan, Krishnaveni; Varghese, Neha; Mikhailova, Natalia; Stamatis, Dimitrios; Reddy, T B K; Markowitz, Victor; Ivanova, Natalia; Kyrpides, Nikos; Woyke, Tanja; Shapiro, Nicole; Ibarra, J Antonio; Estrada-de Los Santos, Paulina

    2016-09-22

    Cupriavidus alkaliphilus ASC-732(T) was isolated from the rhizosphere of agave plant growing in alkaline soils in San Carlos, Tamaulipas, Mexico. The species is able to grow in the presence of arsenic, zinc, and copper. The genome sequence of strain ASC-732(T) is 6,125,055 bp with 5,586 genes and an average G+C content of 67.81%.

  15. Heritability of telomere length in a study of long-lived families

    DEFF Research Database (Denmark)

    Honig, Lawrence S; Kang, Min Suk; Cheng, Rong

    2015-01-01

    in a given age group, it has been hypothesized to be a marker of biological aging. However, the principal basis for the variation of human LTL has not been established, although various studies have reported heritability. Here, we use a family-based study of longevity to study heritability of LTL in 3037...... individuals. We show that LTL is shorter in older individuals, and in males, and has a high heritability (overall h(2) = 0.54). In the offspring generation, who are in middle-life, we find an ordinal relationship: persons more-closely-related to elderly probands have longer LTL than persons less...

  16. Evidence for a heritable predisposition to Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Bateman Lucinda

    2011-05-01

    Full Text Available Abstract Background Chronic Fatigue Syndrome (CFS came to attention in the 1980s, but initial investigations did not find organic causes. Now decades later, the etiology of CFS has yet to be understood, and the role of genetic predisposition in CFS remains controversial. Recent reports of CFS association with the retrovirus xenotropic murine leukemic virus-related virus (XMRV or other murine leukemia related retroviruses (MLV might also suggest underlying genetic implications within the host immune system. Methods We present analyses of familial clustering of CFS in a computerized genealogical resource linking multiple generations of genealogy data with medical diagnosis data of a large Utah health care system. We compare pair-wise relatedness among cases to expected relatedness in the Utah population, and we estimate risk for CFS for first, second, and third degree relatives of CFS cases. Results We observed significant excess relatedness of CFS cases compared to that expected in this population. Significant excess relatedness was observed for both close (p Conclusions These analyses provide strong support for a heritable contribution to predisposition to Chronic Fatigue Syndrome. A population of high-risk CFS pedigrees has been identified, the study of which may provide additional understanding.

  17. Ionizing radiation induces heritable disruption of epithelial cell interactions

    Science.gov (United States)

    Park, Catherine C.; Henshall-Powell, Rhonda L.; Erickson, Anna C.; Talhouk, Rabih; Parvin, Bahram; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; Chatterjee, A. (Principal Investigator)

    2003-01-01

    Ionizing radiation (IR) is a known human breast carcinogen. Although the mutagenic capacity of IR is widely acknowledged as the basis for its action as a carcinogen, we and others have shown that IR can also induce growth factors and extracellular matrix remodeling. As a consequence, we have proposed that an additional factor contributing to IR carcinogenesis is the potential disruption of critical constraints that are imposed by normal cell interactions. To test this hypothesis, we asked whether IR affected the ability of nonmalignant human mammary epithelial cells (HMEC) to undergo tissue-specific morphogenesis in culture by using confocal microscopy and imaging bioinformatics. We found that irradiated single HMEC gave rise to colonies exhibiting decreased localization of E-cadherin, beta-catenin, and connexin-43, proteins necessary for the establishment of polarity and communication. Severely compromised acinar organization was manifested by the majority of irradiated HMEC progeny as quantified by image analysis. Disrupted cell-cell communication, aberrant cell-extracellular matrix interactions, and loss of tissue-specific architecture observed in the daughters of irradiated HMEC are characteristic of neoplastic progression. These data point to a heritable, nonmutational mechanism whereby IR compromises cell polarity and multicellular organization.

  18. Repeatability and Heritability of Behavioural Types in a Social Cichlid

    Directory of Open Access Journals (Sweden)

    Noémie Chervet

    2011-01-01

    Full Text Available Aim. The quantitative genetics underlying correlated behavioural traits (‘‘animal personality’’ have hitherto been studied mainly in domesticated animals. Here we report the repeatability ( and heritability (ℎ2 of behavioural types in the highly social cichlid fish Neolamprologus pulcher. Methods. We tested 1779 individuals repeatedly and calculated the ℎ2 of behavioural types by variance components estimation (GLMM REML, using 1327 offspring from 162 broods from 74 pairs. Results. Repeatability of behavioural types was significant and considerable (0.546, but declined from 0.83 between tests conducted on the same day, to 0.19 on tests conducted up to 1201 days apart. All ℎ2 estimates were significant but low (e.g., pair identity ℎ2=0.15±0.03 SE. Additionally, we found significant variation between broods nested within the parent(s, but these were not related to several environmental factors tested. Conclusions. We conclude that despite a considerable , ℎ2 in this cichlid species is low, and variability in behavioural type appears to be strongly affected by other (nongenetic effects.

  19. An evolutionary perspective on epistasis and the missing heritability.

    Directory of Open Access Journals (Sweden)

    Gibran Hemani

    2013-02-01

    Full Text Available The relative importance between additive and non-additive genetic variance has been widely argued in quantitative genetics. By approaching this question from an evolutionary perspective we show that, while additive variance can be maintained under selection at a low level for some patterns of epistasis, the majority of the genetic variance that will persist is actually non-additive. We propose that one reason that the problem of the "missing heritability" arises is because the additive genetic variation that is estimated to be contributing to the variance of a trait will most likely be an artefact of the non-additive variance that can be maintained over evolutionary time. In addition, it can be shown that even a small reduction in linkage disequilibrium between causal variants and observed SNPs rapidly erodes estimates of epistatic variance, leading to an inflation in the perceived importance of additive effects. We demonstrate that the perception of independent additive effects comprising the majority of the genetic architecture of complex traits is biased upwards and that the search for causal variants in complex traits under selection is potentially underpowered by parameterising for additive effects alone. Given dense SNP panels the detection of causal variants through genome-wide association studies may be improved by searching for epistatic effects explicitly.

  20. Handedness, heritability, neurocognition and brain asymmetry in schizophrenia.

    Science.gov (United States)

    Deep-Soboslay, Amy; Hyde, Thomas M; Callicott, Joseph P; Lener, Marc S; Verchinski, Beth A; Apud, José A; Weinberger, Daniel R; Elvevåg, Brita

    2010-10-01

    Higher rates of non-right-handedness (i.e. left- and mixed-handedness) have been reported in schizophrenia and have been a centrepiece for theories of anomalous lateralization in this disorder. We investigated whether non-right-handedness is (i) more prevalent in patients as compared with unaffected siblings and healthy unrelated control participants; (ii) familial; (iii) associated with disproportionately poorer neurocognition; and (iv) associated with grey matter volume asymmetries. We examined 1445 participants (375 patients with schizophrenia, 502 unaffected siblings and 568 unrelated controls) using the Edinburgh Handedness Inventory, a battery of neuropsychological tasks and structural magnetic resonance imaging data. Patients displayed a leftward shift in Edinburgh Handedness Inventory laterality quotient scores as compared with both their unaffected siblings and unrelated controls, but this finding disappeared when sex was added to the model. Moreover, there was no evidence of increased familial risk for non-right-handedness. Non-right-handedness was not associated with disproportionate neurocognitive disadvantage or with grey matter volume asymmetries in the frontal pole, lateral occipital pole or temporal pole. Non-right-handedness was associated with a significant reduction in left asymmetry in the superior temporal gyrus in both patients and controls. Our data neither provide strong support for 'atypical' handedness as a schizophrenia risk-associated heritable phenotype nor that it is associated with poorer neurocognition or anomalous cerebral asymmetries.

  1. Clinical significance of detection of HPV feedback on patients with cervical cytology ASC-H%对宫颈细胞学ASC-H患者进行反馈性HPV检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    林文毅; 陈颖; 王世凤; 胡志敏; 赖娜; 王敏

    2015-01-01

    Objective: To discuss the clinical significance of HPV (human papilloma virus)-detection in women with cervical ASC-H (atypical squamous cell cannotexclude high-grade squamous intraepithelial lesion). Methods: Retrospective analysis of the HPV-feedback test and histopathological findings in 197 cases of patients with ASC-H from June 2012 to June 2014. Results: Collected 197 cases of ASC-H patients diagnosed through cervical cytology in our hospital from June 2012 to June 2014. 124 cases gave the feedback tests of HPV and cervical tissue examination results, who were female, aged 25-63 years, with an average age of about 46 years old;clinical manifestations include cervical erosion,the real bleeding,physical examinations and others. 92 cases with the HPV positive, including histopathological findings as inflammation and 22 normal cases,accounting for about 23.91%, 15 cases with the low level of cervical intraepithelial neoplasia (CINI) ,accounting for about 16.3% , 45 cases with advanced differentiation of cervical intraepithelial neoplasia (cervical intraepithelial neopsia. CINII/CINIII), 10 cases with carcinoma, accounted for 59.78%, 32 cases of HPV negative, including histopathological findings as inflammation and 23 cases of normal, accounting for about 71.88%,8 cases with the low level of cervical intraepithelial neoplasia (CINI),accounting for about 25%,1 case with advanced differentiation of cervical intraepithelial neoplasia (CINII), accounting for about 3.12%, CINIII and squamous cell carcinoma were detected negatively. Thus the HPV detection has higher predictive value for lesions in high grade cervical intraepithelial cancer , risk of high-grade cervical intraepithelial lesion in HPV positive ASC-H patients were higher than the negative group (P< 0.05). Conclusion HPV feedback inspection in all ASC-H patients is very useful. Treatments could be provided more reasonable and personalized, while excessive examinations and treatments could be avoided and the

  2. Estimate of Heritability for Maturity Characteristics of an Early x Late ...

    African Journals Online (AJOL)

    Narrow sense heritabilities of maturity characteristics of common beans were estimated using the ... additive gene effects play an important. role in the inheritance of DFF, hence early generation .... mean of the original F z population (Xo)'.

  3. Literacy and numeracy are more heritable than intelligence in primary school.

    Science.gov (United States)

    Kovas, Yulia; Voronin, Ivan; Kaydalov, Andrey; Malykh, Sergey B; Dale, Philip S; Plomin, Robert

    2013-10-01

    Because literacy and numeracy are the focus of teaching in schools, whereas general cognitive ability (g, intelligence) is not, it would be reasonable to expect that literacy and numeracy are less heritable than g. Here, we directly compare heritabilities of multiple measures of literacy, numeracy, and g in a United Kingdom sample of 7,500 pairs of twins assessed longitudinally at ages 7, 9, and 12. We show that differences between children are significantly and substantially more heritable for literacy and numeracy than for g at ages 7 and 9, but not 12. We suggest that the reason for this counterintuitive result is that universal education in the early school years reduces environmental disparities so that individual differences that remain are to a greater extent due to genetic differences. In contrast, the heritability of g increases during development as individuals select and create their own environments correlated with their genetic propensities.

  4. Body mass index modulates blood pressure heritability: the Family Blood Pressure Program.

    Science.gov (United States)

    Simino, Jeannette; Shi, Gang; Weder, Alan; Boerwinkle, Eric; Hunt, Steven C; Rao, Dabeeru C

    2014-04-01

    Candidate gene and twin studies suggest that interactions between body mass index (BMI) and genes contribute to the variability of blood pressure (BP). To determine whether there is evidence for gene-BMI interactions, we investigated the modulation of BP heritability by BMI using 4,153 blacks, 1,538 Asians, 4,013 whites, and 2,199 Hispanic Americans from the Family Blood Pressure Program. To capture the BP heritability dependence on BMI, we employed a generalized variance components model incorporating linear and Gaussian interactions between BMI and the genetic component. Within each race and network subgroup, we used the Akaike information criterion and likelihood ratio test to select the appropriate interaction function for each BP trait (systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)) and determine interaction significance, respectively. BP heritabilities were significantly modified by BMI in the GenNet and SAPPHIRe Networks, which contained the youngest and least-obese participants, respectively. GenNet Whites had unimodal SBP, MAP, and PP heritabilities that peaked between BMI values of 33 and 37kg/m(2). The SBP and MAP heritabilities in GenNet Hispanic Americans, as well as the PP heritability in GenNet blacks, were increasing functions of BMI. The DBP and SBP heritabilities in the SAPPHIRe Chinese and Japanese, respectively, were decreasing functions of BMI. BP heritability differed by BMI in the youngest and least-obese networks, although the shape of this dependence differed by race. Use of nonlinear gene-BMI interactions may enhance BP gene discovery efforts in individuals of European ancestry.

  5. Estimating the Broad-Sense Heritability of Early Growth of Cowpea

    OpenAIRE

    Xu, Nicole W.; Xu, Shizhong; Ehlers, Jeff

    2009-01-01

    Cowpea is an important tropical crop. It provides a large proportion of the food resource for the African human population and their livestock. The yield and quality of cowpea have been dramatically improved through traditional breeding strategies for the past few decades. However, reports of heritability estimates for early growth of cowpea are rare. We designed a simple experiment to estimate the broad-sense heritability of early growth. We randomly selected 15 cowpea varieties among a tota...

  6. Prevalence of cervical intraepithelial neoplasia grades II/III and cervical cancer in patients with cytological diagnosis of atypical squamous cells when high-grade intraepithelial lesions (ASC-H cannot be ruled out

    Directory of Open Access Journals (Sweden)

    Andréa Cytryn

    Full Text Available CONTEXT AND OBJECTIVE: The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS into ASC-US (undetermined significance and ASC-H (high-grade intraepithelial lesion cannot be ruled out. The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF with ASC-H cytology, and compare them with ASC-US cases. DESIGN AND SETTING: Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. METHODS: ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis was taken as the gold standard. RESULTS: The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55% and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764. Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83; P = 0.2786998. There were no uterine cervical cancer cases. CONCLUSION: The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.

  7. Monogenic mutations differentially affect the quantity and quality of T follicular helper cells in patients with human primary immunodeficiencies.

    Science.gov (United States)

    Ma, Cindy S; Wong, Natalie; Rao, Geetha; Avery, Danielle T; Torpy, James; Hambridge, Thomas; Bustamante, Jacinta; Okada, Satoshi; Stoddard, Jennifer L; Deenick, Elissa K; Pelham, Simon J; Payne, Kathryn; Boisson-Dupuis, Stéphanie; Puel, Anne; Kobayashi, Masao; Arkwright, Peter D; Kilic, Sara Sebnem; El Baghdadi, Jamila; Nonoyama, Shigeaki; Minegishi, Yoshiyuki; Mahdaviani, Seyed Alireza; Mansouri, Davood; Bousfiha, Aziz; Blincoe, Annaliesse K; French, Martyn A; Hsu, Peter; Campbell, Dianne E; Stormon, Michael O; Wong, Melanie; Adelstein, Stephen; Smart, Joanne M; Fulcher, David A; Cook, Matthew C; Phan, Tri Giang; Stepensky, Polina; Boztug, Kaan; Kansu, Aydan; İkincioğullari, Aydan; Baumann, Ulrich; Beier, Rita; Roscioli, Tony; Ziegler, John B; Gray, Paul; Picard, Capucine; Grimbacher, Bodo; Warnatz, Klaus; Holland, Steven M; Casanova, Jean-Laurent; Uzel, Gulbu; Tangye, Stuart G

    2015-10-01

    Follicular helper T (TFH) cells underpin T cell-dependent humoral immunity and the success of most vaccines. TFH cells also contribute to human immune disorders, such as autoimmunity, immunodeficiency, and malignancy. Understanding the molecular requirements for the generation and function of TFH cells will provide strategies for targeting these cells to modulate their behavior in the setting of these immunologic abnormalities. We sought to determine the signaling pathways and cellular interactions required for the development and function of TFH cells in human subjects. Human primary immunodeficiencies (PIDs) resulting from monogenic mutations provide a unique opportunity to assess the requirement for particular molecules in regulating human lymphocyte function. Circulating follicular helper T (cTFH) cell subsets, memory B cells, and serum immunoglobulin levels were quantified and functionally assessed in healthy control subjects, as well as in patients with PIDs resulting from mutations in STAT3, STAT1, TYK2, IL21, IL21R, IL10R, IFNGR1/2, IL12RB1, CD40LG, NEMO, ICOS, or BTK. Loss-of-function (LOF) mutations in STAT3, IL10R, CD40LG, NEMO, ICOS, or BTK reduced cTFH cell frequencies. STAT3 and IL21/R LOF and STAT1 gain-of-function mutations skewed cTFH cell differentiation toward a phenotype characterized by overexpression of IFN-γ and programmed death 1. IFN-γ inhibited cTFH cell function in vitro and in vivo, as corroborated by hypergammaglobulinemia in patients with IFNGR1/2, STAT1, and IL12RB1 LOF mutations. Specific mutations affect the quantity and quality of cTFH cells, highlighting the need to assess TFH cells in patients by using multiple criteria, including phenotype and function. Furthermore, IFN-γ functions in vivo to restrain TFH cell-induced B-cell differentiation. These findings shed new light on TFH cell biology and the integrated signaling pathways required for their generation, maintenance, and effector function and explain the compromised

  8. Monogenic diabetes syndromes

    DEFF Research Database (Denmark)

    Astuti, Dewi; Sabir, Ataf; Fulton, Piers

    2017-01-01

    We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1...... for the WFS1 gene. The presence of biallelic loss-of-function variants predicted Wolfram syndrome defined by insulin-dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI 75%-83%) and specificity of 92% (83%-97%). The presence of minor loss-of-function variants in WFS1 predicted isolated...... diabetes, isolated deafness, or isolated congenital cataracts without development of the full syndrome (sensitivity 100% [93%-100%]; specificity 78% [73%-82%]). The ability to provide a prognostic prediction based on genotype will lead to improvements in patient care and counseling. The development...

  9. Monogenic obesity in humans.

    Science.gov (United States)

    Farooqi, I Sadaf; O'Rahilly, Stephen

    2005-01-01

    Until relatively recently, the small number of identifiable inherited human diseases associated with marked obesity were complex, pleiotropic developmental disorders, the molecular basis for which were entirely obscure. The molecular basis for many of these complex syndromes, such as Bardet Beidl syndrome, has been revealed, providing novel insights into processes essential for human hypothalamic function and energy balance. In addition to these discoveries, which were the fruits of positional cloning, the molecular constituents of the signaling pathways responsible for the control of mammalian energy homeostasis have been identified, largely through the study of natural or artificial mutations in mice. We discuss the increasing number of human disorders that result from genetic disruption of the leptin-melanocortin pathways that have been identified. Practical implications of these findings for genetic counseling, prognostication, and even therapy have already emerged.

  10. Heritability of MMPI-2 scales in the UCSF Family Alcoholism Study

    Science.gov (United States)

    Gizer, Ian R.; Seaton-Smith, Kimberley L.; Ehlers, Cindy L.; Vietan, Cassandra; Wilhelmsen, Kirk C.

    2009-01-01

    The present study evaluated the heritability of personality traits and psychopathology symptoms assessed by the Minnesota Multiphasic Personality Interview 2nd edition (MMPI-2) in a family-based sample selected for alcohol dependence. Participants included 950 probands and 1204 first-degree relatives recruited for the UCSF Family Alcoholism Study. Heritability estimates (h2) for MMPI-2 scales ranged from .25–.49. When alcohol dependence was used as a covariate, heritability estimates remained significant but generally declined. However, when the MMPI-2 scales were used as covariates to estimate the heritability of alcohol dependence, scales measuring antisocial behavior (ASP), depressive symptoms (DEP), and addictive behavior (MAC-R) led to moderate increases in the heritability of alcohol dependence. This suggests that the ASP, DEP, and MAC-R scales may explain some of the non-genetic variance in the alcohol dependence diagnosis in this population when utilized as covariates, and thus may serve to produce a more homogeneous and heritable alcohol dependence phenotype. PMID:20390702

  11. The contribution of social effects to heritable variation in finishing traits of domestic pigs (Sus scrofa).

    Science.gov (United States)

    Bergsma, R; Kanis, E; Knol, E F; Bijma, P

    2008-03-01

    Social interactions among individuals are ubiquitous both in animals and in plants, and in natural as well as domestic populations. These interactions affect both the direction and the magnitude of responses to selection and are a key factor in evolutionary success of species and in the design of breeding schemes in agriculture. At present, however, very little is known of the contribution of social effects to heritable variance in trait values. Here we present estimates of the direct and social genetic variance in growth rate, feed intake, back fat thickness, and muscle depth in a population of 14,032 domestic pigs with known pedigree. Results show that social effects contribute the vast majority of heritable variance in growth rate and feed intake in this population. Total heritable variance expressed relative to phenotypic variance was 71% for growth rate and 70% for feed intake. These values clearly exceed the usual range of heritability for those traits. Back fat thickness and muscle depth showed no heritable variance due to social effects. Our results suggest that genetic improvement in agriculture can be substantially advanced by redirecting breeding schemes, so as to capture heritable variance due to social effects.

  12. Heritability of lumbar trabecular bone mechanical properties in baboons.

    Science.gov (United States)

    Havill, L M; Allen, M R; Bredbenner, T L; Burr, D B; Nicolella, D P; Turner, C H; Warren, D M; Mahaney, M C

    2010-03-01

    Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6-32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone cores were scanned with microCT then tested in monotonic compression to determine apparent ultimate stress, modulus, and toughness. Age and sex effects and heritability (h(2)) were assessed using maximum likelihood-based variance components methods. Additive effects of genes on residual trait variance were significant for ultimate stress (h(2)=0.58), toughness (h(2)=0.64), and BV/TV (h(2)=0.55). When BV/TV was accounted for, the residual variance in ultimate stress accounted for by the additive effects of genes was no longer significant. Toughness, however, showed evidence of a non-BV/TV-related genetic effect. Overall, maximum stress and modulus show strong genetic effects that are nearly entirely due to bone volume. Toughness shows strong genetic effects related to bone volume and shows additional genetic effects (accounting for 10% of the total trait variance) that are independent of bone volume. These results support continued use of bone volume as a focal trait to identify genes related to skeletal fragility, but also show that other focal traits related to toughness and variation in the organic component of bone matrix will enhance our ability to find additional genes that are particularly relevant to fatigue-related fractures.

  13. Some Opinion on the Term of ASC-US in Cervical Cytological Test%关于子宫颈细胞学检查ASC-US术语的几点认识

    Institute of Scientific and Technical Information of China (English)

    李晴; 黄美娥; 古晓红; 麦凤珍; 刘植华

    2007-01-01

    子宫颈脱落细胞学检查被认为是医学史上最成功的早期癌症筛查方法之一。1988年美国阴道镜和细胞病理协会(ASCCP)修改了宫颈/阴道细胞病理学诊断方式,废除“巴氏五级分类法”,推出描述性诊断报告方式(Thebe—thesda system,TBS),由此,报告中出现了一种“不能明确诊断意义的不典型鳞状上皮细胞(ASC-US)”的术语。目前对ASC—US的临床意义有多种释义,在临床工作中可能出现一些认识误区。现对我院2005年子宫颈脱落细胞学检查筛查出的ASC-US病例资料进行分析,

  14. Clay hydration and crystal growth in expansive anhydritic claystone. The Ascó Power Plant case

    Science.gov (United States)

    Alonso, Eduardo; Ramon, Anna

    2015-04-01

    A large power plant directly founded on a hard claystone experienced, soon after the construction of the foundation slabs, a continuous heave developing at decreasing rate, which has been active for the last 35 years. When undisturbed (i.e., at some depth, in the range of several meters) Ascó claystone exhibits high unconfined compressive strengths (30-40 MPa). In high quality cores the rock has a massive aspect and discontinuities are difficult to observe. The rock has a Tertiary origin and horizontal layers at spacing of 1-4 m could be identified. Whitish seams of gypsum, bassanite or anhydrite are also observed within the reddish rock matrix. Minerals identified in deep cores are quartz (10%), calcite and dolomite (50-70%), clay minerals (10-20%) and gypsum and anhydrite (2-20%). Among the clay minerals, illite dominates (10%). Smectite or smectite-interbedded minerals do not amount in general to more than 5%. The undisturbed rock has a low porosity (6-11%) and low water content (2-5%). Because of the presence of hydrated sulphates, water content and degree of saturation (Sr=0.8-0.9 was found) are somewhat uncertain. However, high suctions were found in recovered cores. This rock changes into a weathered material at shallow depths. Mineralogy is not much affected but porosity increases to 22-29% and water content increases to 10-19%. Strength drops to small values (soil like) and a lower "in situ" suction has been measured (0.4-7.1 MPa). The added pore volume of the weathered material, if compared with the deep rock, is filled with water. The heave of the station was attributed to the hydration of undisturbed rock under the building slabs of the power plant. In fact, large excavations preceded the layout of foundations. As a result, atmospheric water had an easy access to the intact rock. The installation of a compacted soil fill around the buildings allowed the presence of a permanent water table which could infiltrate into the rock. Piezometric data provided

  15. Low-frequency, low-magnitude vibrations (LFLM enhances chondrogenic differentiation potential of human adipose derived mesenchymal stromal stem cells (hASCs

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2016-02-01

    Full Text Available The aim of this study was to evaluate if low-frequency, low-magnitude vibrations (LFLM could enhance chondrogenic differentiation potential of human adipose derived mesenchymal stem cells (hASCs with simultaneous inhibition of their adipogenic properties for biomedical purposes. We developed a prototype device that induces low-magnitude (0.3 g low-frequency vibrations with the following frequencies: 25, 35 and 45 Hz. Afterwards, we used human adipose derived mesenchymal stem cell (hASCS, to investigate their cellular response to the mechanical signals. We have also evaluated hASCs morphological and proliferative activity changes in response to each frequency. Induction of chondrogenesis in hASCs, under the influence of a 35 Hz signal leads to most effective and stable cartilaginous tissue formation through highest secretion of Bone Morphogenetic Protein 2 (BMP-2, and Collagen type II, with low concentration of Collagen type I. These results correlated well with appropriate gene expression level. Simultaneously, we observed significant up-regulation of α3, α4, β1 and β3 integrins in chondroblast progenitor cells treated with 35 Hz vibrations, as well as Sox-9. Interestingly, we noticed that application of 35 Hz frequencies significantly inhibited adipogenesis of hASCs. The obtained results suggest that application of LFLM vibrations together with stem cell therapy might be a promising tool in cartilage regeneration.

  16. Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations.

    Science.gov (United States)

    Bevan, Steve; Traylor, Matthew; Adib-Samii, Poneh; Malik, Rainer; Paul, Nicola L M; Jackson, Caroline; Farrall, Martin; Rothwell, Peter M; Sudlow, Cathie; Dichgans, Martin; Markus, Hugh S

    2012-12-01

    The contribution of genetics to stroke risk, and whether this differs for different stroke subtypes, remainsuncertain. Genomewide complex trait analysis allows heritability to be assessed from genomewide association study (GWAS) data. Previous candidate gene studies have identified many associations with stoke but whether these are important requires replication in large independent data sets. GWAS data sets provide a powerful resource to perform replication studies. We applied genomewide complex trait analysis to a GWAS data set of 3752 ischemic strokes and 5972 controls and determined heritability for all ischemic stroke and the most common subtypes: large-vessel disease, small-vessel disease, and cardioembolic stroke. By systematic review we identified previous candidate gene and GWAS associations with stroke and previous GWAS associations with related cardiovascular phenotypes (myocardial infarction, atrial fibrillation, and carotid intima-media thickness). Fifty associations were identified. For all ischemic stroke, heritability was 37.9%. Heritability varied markedly by stroke subtype being 40.3% for large-vessel disease and 32.6% for cardioembolic but lower for small-vessel disease (16.1%). No previously reported candidate gene was significant after rigorous correction for multiple testing. In contrast, 3 loci from related cardiovascular GWAS studies were significant: PHACTR1 in large-vessel disease (P=2.63e(-6)), PITX2 in cardioembolic stroke (P=4.78e(-8)), and ZFHX3 in cardioembolic stroke (P=5.50e(-7)). There is substantial heritability for ischemic stroke, but this varies for different stroke subtypes. Previous candidate gene associations contribute little to this heritability, but GWAS studies in related cardiovascular phenotypes are identifying robust associations. The heritability data, and data from GWAS, suggest detecting additional associations will depend on careful stroke subtyping.

  17. Heritability of antibody isotype and subclass responses to Plasmodium falciparum antigens.

    Directory of Open Access Journals (Sweden)

    Nancy O Duah

    Full Text Available BACKGROUND: It is important to understand the extent to which genetic factors regulate acquired immunity to common infections. A classical twin study design is useful to estimate the heritable component of variation in measurable immune parameters. METHODOLOGY/PRINCIPAL FINDINGS: This study assessed the relative heritability of different plasma antibody isotypes and subclasses (IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE naturally acquired to P. falciparum blood stage antigens AMA1, MSP1-19, MSP2 (two allelic types and MSP3 (two allelic types. Separate analyses were performed on plasma from 213 pairs of Gambian adult twins, 199 child twin pairs sampled in a dry season when there was little malaria transmission, and another set of 107 child twin pairs sampled at the end of the annual wet season when malaria was common. There were significantly positive heritability (h(2 estimates for 48% (20/42 of the specific antibody assays (for the seven isotypes and subclasses to the six antigens tested among the adults, 48% (20/42 among the children in the dry season and 31% (13/42 among the children in the wet season. In children, there were significant heritability estimates for IgG4 reactivity against each of the antigens, and this subclass had higher heritability than the other subclasses and isotypes. In adults, 75% (15/20 of the significantly heritable antigen-specific isotype responses were attributable to non-HLA class II genetic variation, whereas none showed a significant HLA contribution. SIGNIFICANCE: Genome-wide approaches are now warranted to map the major genetic determinants of variable antibody isotype and subclass responses to malaria, alongside evaluation of their impact on infection and disease. Although plasma levels of IgG4 to malaria antigens are generally low, the exceptionally high heritability of levels of this subclass in children deserves particular investigation.

  18. Heritability of racing durability traits in the Australian and Hong Kong Thoroughbred racing populations.

    Science.gov (United States)

    Velie, B D; Hamilton, N A; Wade, C M

    2016-05-01

    Many attempts have been made to improve the well-being of racing Thoroughbreds through improvements in management and veterinary care. However, these attempts are often limited by the industry's ability to regulate a large number of environmental variables and as a result have arguably had limited success in providing long-lasting change for the breed. To identify heritable durability traits for Thoroughbred horses racing in Australia and Hong Kong. Heritability analysis of a longitudinal dataset. Performance data on the Thoroughbred populations racing in Australia and Hong Kong between 2000 and 2011 (n = 168,993) were used to estimate the heritabilities and probability values of fixed effects and covariates for a range of racing durability traits. Heritabilities for all durability traits were estimated using a single trait animal model. Each model included, as a minimum, the effects of sex and trainer. Racing longevity (0.12 ± 0.01), racing persistence (0.10 ± 0.01), racing frequency (0.03 ± 0.01), spells (a time period between consecutive races, official trials and/or jump-outs greater than 90 days in length) per year (0.05 ± 0.01), spells per 10 starts (0.03 ± 0.01) and variation of days between races (0.08 ± 0.03) were all significantly heritable for horses racing in Australia. Racing longevity (0.08 ± 0.02), racing persistence (0.04 ± 0.02), spells per year (0.06 ± 0.02) and spells per 10 starts (0.11 ± 0.04) were significantly heritable for horses racing in Hong Kong. The heritabilities estimated for durability traits in this study provide support for the successful and practical application of genetic selection methodologies to improving the well-being of racing Thoroughbreds. © 2015 EVJ Ltd.

  19. Estimates of repeatability and heritability of productive and reproductive traits in a herd of Jersey cattle

    Directory of Open Access Journals (Sweden)

    Roman R.M.

    2000-01-01

    Full Text Available Estimates of the repeatability and heritability of 19 measures of performance in Jersey cows were obtained using an animal model with a relationship matrix and a derivative-free restricted maximum likelihood algorithm. The data consisted of 935 records for 374 cows by 69 sires over the period 1969-1987. The estimates were similar to those obtained by ordinary least squares methods reported for the same data set and in other studies, but had smaller error variances. A likelihood ratio test showed agreement between these heritability estimates and those in the literature. The heritability estimates of milk, fat, protein, lactose-mineral, solids-not-fat, and total solids yields were about 0.25; for the corresponding percentages, and for the protein to fat and solids-not-fat to fat ratios, the estimates were 0.50. Heritability estimates were 0.10 or less for the time from parturition to first breeding and for three measures of somatic cell counts. These estimates of heritability in a dairy cattle population in a subtropical environment were not different from those of populations in temperate climates.

  20. Evidence for higher heritability of somatotype compared to body mass index in female twins.

    Science.gov (United States)

    Reis, Victor Machado; Machado, João V; Fortes, Marcos S; Fernandes, Paula Roquetti; Silva, António José; Dantas, Paulo Silva; Filho, José Fernandes

    2007-01-01

    The influence of genetics on human physique and obesity has been addressed by the literature. Evidence for heritability of anthropometric characteristics has been previously described, mainly for the body mass index (BMI). However, few studies have investigated the influence of genetics on the Heath-Carter somatotype. The aim of the present study was to assess the heritability of BMI and somatotype (endomorphy, mesomorphy, and ectomorphy) in a group of female monozygotic and dizygotic twins from childhood to early adulthood. A total of 28 females aged from 7 to 19 years old were studied. The group included 5 monozygotic and 9 dizygotic pairs of twins. The heritability was assessed by the twin method (h(2)). The anthropometric measures and somatotype were assessed using standard validated procedures. Significant differences between monozygotic and dizygotic pairs of twins were found for height, endomorphy, ectomorphy, and mesomorphy, and the heritability for these measures was high (h(2) between 0.88 and 0.97). No significant differences were found between monozygotic and dizygotic twins for weight, and the BMI and the heritability indexes were lower for these measures (respectively 0.42 and 0.52). The results of the present study have indicated that the somatotype may be more sensible to genetic influences than the BMI in females.

  1. On the Estimation of Heritability with Family-Based and Population-Based Samples

    Directory of Open Access Journals (Sweden)

    Youngdoe Kim

    2015-01-01

    Full Text Available For a family-based sample, the phenotypic variance-covariance matrix can be parameterized to include the variance of a polygenic effect that has then been estimated using a variance component analysis. However, with the advent of large-scale genomic data, the genetic relationship matrix (GRM can be estimated and can be utilized to parameterize the variance of a polygenic effect for population-based samples. Therefore narrow sense heritability, which is both population and trait specific, can be estimated with both population- and family-based samples. In this study we estimate heritability from both family-based and population-based samples, collected in Korea, and the heritability estimates from the pooled samples were, for height, 0.60; body mass index (BMI, 0.32; log-transformed triglycerides (log TG, 0.24; total cholesterol (TCHL, 0.30; high-density lipoprotein (HDL, 0.38; low-density lipoprotein (LDL, 0.29; systolic blood pressure (SBP, 0.23; and diastolic blood pressure (DBP, 0.24. Furthermore, we found differences in how heritability is estimated—in particular the amount of variance attributable to common environment in twins can be substantial—which indicates heritability estimates should be interpreted with caution.

  2. Heritability estimates of the Big Five personality traits based on common genetic variants.

    Science.gov (United States)

    Power, R A; Pluess, M

    2015-07-14

    According to twin studies, the Big Five personality traits have substantial heritable components explaining 40-60% of the variance, but identification of associated genetic variants has remained elusive. Consequently, knowledge regarding the molecular genetic architecture of personality and to what extent it is shared across the different personality traits is limited. Using genomic-relatedness-matrix residual maximum likelihood analysis (GREML), we here estimated the heritability of the Big Five personality factors (extraversion, agreeableness, conscientiousness, neuroticism and openness for experience) in a sample of 5011 European adults from 527,469 single-nucleotide polymorphisms across the genome. We tested for the heritability of each personality trait, as well as for the genetic overlap between the personality factors. We found significant and substantial heritability estimates for neuroticism (15%, s.e. = 0.08, P = 0.04) and openness (21%, s.e. = 0.08, P agreeableness and conscientiousness. The bivariate analyses showed that the variance explained by common variants entirely overlapped between neuroticism and openness (rG = 1.00, P personality traits using the GREML approach. Findings should be considered exploratory and suggest that detectable heritability estimates based on common variants is shared between neuroticism and openness to experiences.

  3. Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History.

    Science.gov (United States)

    Greenwood, Tiffany A; Light, Gregory A; Swerdlow, Neal R; Calkins, Monica E; Green, Michael F; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Sugar, Catherine A; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Freedman, Robert; Braff, David L

    2016-04-01

    The Consortium on the Genetics of Schizophrenia Family Study evaluated 12 primary and other supplementary neurocognitive and neurophysiological endophenotypes in schizophrenia probands and their families. Previous analyses of prepulse inhibition (PPI) and P50 gating measures in this sample revealed heritability estimates that were lower than expected based on earlier family studies. Here the authors investigated whether gating measures were more heritable in multiply affected families with a positive family history compared with families with only a single affected proband (singleton). A total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons. Both PPI and P50 gating displayed substantially increased heritability in the 97 multiply affected families (47% and 36%, respectively) compared with estimates derived from the entire sample of 296 families (29% and 20%, respectively). However, no evidence for heritability was observed for either measure in the 96 singleton families. Schizophrenia probands derived from the multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those from singleton families. PPI and P50 gating measures demonstrate substantially increased heritability in schizophrenia families with a higher genetic vulnerability for illness, providing further support for the commonality of genes underlying both schizophrenia and gating measures.

  4. 美国输电线路风荷载计算介绍%Introduction of Wind Load Computation of Transmission Line in ASCE74-2009

    Institute of Scientific and Technical Information of China (English)

    王振华

    2012-01-01

    了解《美国输电线路结构荷载指南》( ASCE74-2009)对从事涉外工程和提高工程师设计水平都有着重要意义.风荷载是输电线路设计的控制荷载,了解ASCE74-2009风荷载计算方法非常有必要.本文介绍了ASCE74-2009输电线路风荷载的计算方法,并对基本风速、风压高度变化系数、体型系数、风荷载调整系数、地形影响因子和斜向风荷载计算方法及其计算参数进行了说明.%It is very important to comprehend 《 Guidelines for electrical transmission line structural loading》 (ASCE74-2009) for overseas projects and improve the design level of engineer. Wind load is the control load for transmission line, so it is necessary to master wind load computation method of ASCE74-2009. Wind load computation formulas for transmission line of ASCE74-2009 are introduced in this paper. The computation parameters of basic wind speed, height variation factor of wind pressure, shape factor, wind load factor, topographic factor and yawed wind load computation method are illustrated in detail.

  5. Differential expression of specific FGF ligands and receptor isoforms during osteogenic differentiation of mouse Adipose-derived Stem Cells (mASCs) recapitulates the in vivo osteogenic pattern.

    Science.gov (United States)

    Quarto, Natalina; Longaker, Michael T

    2008-11-15

    The ability of Adipose-derived Stem Cells (ASCs) to differentiate into various tissues in vitro and in vivo, a function known as "stem cell plasticity", makes them an appealing cell source for tissue engineering. Our laboratory is particularly focused on the potential role of adipose tissue as a readily available postnatal source of osteoprogenitor. Fibroblast growth factors (FGF) and their receptors (FGFR) are important regulators of osteogenesis. The goal of this study was to elucidate how changes in temporal expression patterns of individual components of the fibroblast growth factor (FGF) signaling axis correlate with osteogenic differentiation of mASCs. Our results indicate that FGF ligand genes, such as Fgf-2, -4, -8, and -18, displayed a differential and dynamic profile during mouse ASC (mASC) osteogenesis. Fgf-2 transcript was down-regulated, while Fgf-18 transcript level was strongly up-regulated. Interestingly, a drift in the ratio of different FGF-2 protein forms, with translation favoring the HMWFGF-2 forms, occurred during osteogenic differentiation, whereas, the expression of LMWFGF-2 form was down-regulated. This finding shares similarity with a previous study suggesting that preferential expression of the HMWFGF-2 forms is associated with a more osteogenic differentiated state of calvarial osteoblast. Moreover, a differential expression of Fgf Receptor 1 and 2 resembling that previously found in in vivo osteogenic study was observed. Thus, mASCs undergoing osteogenesis recapitulate the in vivo osteogenic differentiation expression pattern of FGF ligands and receptors of calvarial mesenchymal cells during their own osteogenic differentiation. Indeed, this observation further validates ASCs as a suitable resource for skeletal tissue engineering.

  6. Gaia16asc, Gaia16ase, Gaia16asj and Gaia16ask candidate supernovae near galaxies confirmed by Mercator/Maia imaging

    Science.gov (United States)

    Blanco-Cuaresma, S.; Semaan, T.; Roelens, M.; Palaversa, L.; Mowlavi, N.; Eyer, L.

    2016-07-01

    We report confirmation of Gaia Science Alerts transients Gaia16asc, Gaia16ase, Gaia16asj and Gaia16ask. Images were obtained in G and R bands of the Maia instrument mounted to the Flemish 1.2m Mercator telescope at Roque de los Muchachos observatory, La Palma, Canary Islands, Spain, on 2016 July 02 - 04. These new sources are supernovae candidates near galaxies and they are not visible in archival 2MASS and DSS images: Gaia16asc, Gaia16ase, Gaia16asj and Gaia16ask.

  7. The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists

    Science.gov (United States)

    Boycott, Kym; Hartley, Taila; Adam, Shelin; Bernier, Francois; Chong, Karen; Fernandez, Bridget A; Friedman, Jan M; Geraghty, Michael T; Hume, Stacey; Knoppers, Bartha M; Laberge, Anne-Marie; Majewski, Jacek; Mendoza-Londono, Roberto; Meyn, M Stephen; Michaud, Jacques L; Nelson, Tanya N; Richer, Julie; Sadikovic, Bekim; Skidmore, David L; Stockley, Tracy; Taylor, Sherry; van Karnebeek, Clara; Zawati, Ma'n H; Lauzon, Julie; Armour, Christine M

    2015-01-01

    Purpose and scope The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Methods of statement development Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Results and conclusions Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes

  8. Heritability of Tpeak-Tend Interval and T-wave Amplitude: A Twin Study

    DEFF Research Database (Denmark)

    Haarmark, Christian; Kyvik, Kirsten O; Vedel-Larsen, Esben;

    2011-01-01

    BACKGROUND: -Tpeak-Tend interval (TpTe) and T-wave amplitude (Tamp) carry diagnostic and prognostic information regarding cardiac morbidity and mortality. Heart rate and QT interval are known to be heritable traits. The heritability of T-wave morphology parameters such as TpTe and Tamp is unknown....... TpTe and Tamp were evaluated in a large sample of twins. METHODS AND RESULTS: -Twins from the GEMINAKAR study (611 pairs, 246 monozygotic, 365 dizygotic, aged 38±11 years, 49 % men) who had an ECG performed during 1997-2000 were included. Tamp was measured in leads V1 and V5. Duration variables (RR...... are heritable ECG parameters....

  9. Heritability and complex segregation analysis of hypoadrenocorticism in the standard poodle.

    Science.gov (United States)

    Famula, T R; Belanger, J M; Oberbauer, A M

    2003-01-01

    The heritability of hypoadrenocorticism (Addison's disease) was evaluated in 778 standard poodles with known Addisonian phenotypes. Addisonian status was confirmed clinically by adrenocorticotropic hormone (ACTH) challenge and 8.6 per cent of the poodles enrolled in the study were classified as being Addisonian. Hypoadrenocorticism affected both sexes with equal probability (P > 0.1). The most common coat colours had a negligible effect on the incidence of hypoadrenocorticism (P > 0.09), although red coat colour had a significant impact on the disease, probably due to the relatively small numbers of dogs with that coat colour. The heritability of hypoadrenocorticism in the standard poodle was estimated to be 0.75. Complex segregation analyses suggested that hypoadrenocorticism in the breed is influenced by an autosomal recessive locus. Clarification of both the heritability and mode of inheritance of hypoadrenocorticism in the standard poodle allows for better-informed breeding decisions.

  10. The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob B; Scheike, Thomas; Holst, Klaus

    2014-01-01

    Background: Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age. Methods: To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18......,680 monozygotic and 30,054 dizygotic same sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer...... diagnoses was significantly shorter for MZ than DZ pairs (median 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability (heritability=58% (95% CI 52%-63%) of developing prostate cancer. The relative contribution of genetic factors...

  11. Familial Risk and Heritability of Cancer Among Twins in Nordic Countries

    DEFF Research Database (Denmark)

    Mucci, Lorelei A; Hjelmborg, Jacob B; Harris, Jennifer R

    2016-01-01

    (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. RESULTS: A total of 27,156 incident cancers were diagnosed in 23...... with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin......IMPORTANCE: Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. OBJECTIVE: To estimate familial risk and heritability of cancer types in a large twin cohort. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 80,309 monozygotic...

  12. Interpreting estimates of heritability--a note on the twin decomposition.

    Science.gov (United States)

    Stenberg, Anders

    2013-03-01

    While most outcomes may in part be genetically mediated, quantifying genetic heritability is a different matter. To explore data on twins and decompose the variation is a classical method to determine whether variation in outcomes, e.g. IQ or schooling, originate from genetic endowments or environmental factors. Despite some criticism, the model is still widely used. The critique is generally related to how estimates of heritability may encompass environmental mediation. This aspect is sometimes left implicit by authors even though its relevance for the interpretation is potentially profound. This short note is an appeal for clarity from authors when interpreting the magnitude of heritability estimates. It is demonstrated how disregarding existing theoretical contributions can easily lead to unnecessary misinterpretations and/or controversies. The key arguments are relevant also for estimates based on data of adopted children or from modern molecular genetics research. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Heritability maps of human face morphology through large-scale automated three-dimensional phenotyping

    Science.gov (United States)

    Tsagkrasoulis, Dimosthenis; Hysi, Pirro; Spector, Tim; Montana, Giovanni

    2017-04-01

    The human face is a complex trait under strong genetic control, as evidenced by the striking visual similarity between twins. Nevertheless, heritability estimates of facial traits have often been surprisingly low or difficult to replicate. Furthermore, the construction of facial phenotypes that correspond to naturally perceived facial features remains largely a mystery. We present here a large-scale heritability study of face geometry that aims to address these issues. High-resolution, three-dimensional facial models have been acquired on a cohort of 952 twins recruited from the TwinsUK registry, and processed through a novel landmarking workflow, GESSA (Geodesic Ensemble Surface Sampling Algorithm). The algorithm places thousands of landmarks throughout the facial surface and automatically establishes point-wise correspondence across faces. These landmarks enabled us to intuitively characterize facial geometry at a fine level of detail through curvature measurements, yielding accurate heritability maps of the human face (www.heritabilitymaps.info).

  14. Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

    DEFF Research Database (Denmark)

    Gusev, Alexander; Lee, S Hong; Trynka, Gosia

    2014-01-01

    Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common...... diseases to partition the heritability explained by genotyped SNPs (hg(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach...... partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg(2) from imputed SNPs (5.1× enrichment...

  15. Heritability and correlation between selected phenotypical characters of soybean under the climatic conditions of Poland

    Directory of Open Access Journals (Sweden)

    Edward Warzecha

    2013-12-01

    Full Text Available The variability of characters connected with yield structure in soybean is much more influenced by environmental conditions than the genotype as indicated by heritability coefficients (h2, calculated on the basis of trials performed during several years under the climatic conditions of Poland. The length of the vegetation period, however, is determined predominantly by the genotype since high reproducibility of h2 values in different years was found. The heritability coefficients obtained for the agronomic characters of soybean grown in Poland were relatively similar to analogous data from the USA. Phenotypical correlations calculated for the whole group together with correlations between the length of the vegetation period and other characters calculated for individual varieties, provided information on the interrelationship between characters in soybean grown in Poland. This, together with calculated heritability coefficients could be useful for soybean breeding in Poland.

  16. Heritability of hemivertebrae in the French bulldog using an animal threshold model.

    Science.gov (United States)

    Schlensker, Eva; Distl, Ottmar

    2016-01-01

    Ordinal regression and animal threshold analyses were used to estimate the influence of fixed effects and heritabilities on the number and grade of hemivertebrae, as well as the number of coccygeal vertebrae, in 105 French bulldogs. The fixed effects of sex, year and month of birth were not significant (P > 0.05). The prevalence of hemivertebrae was 0.85 with a slightly higher prevalence in females compared with males. Heritability estimates for the number and grade of hemivertebrae were 0.58 and 0.53, respectively. The number of coccygeal vertebrae showed a heritability estimate of 0.35. In addition, the number of coccygeal vertebrae was negatively correlated with the number and grade of hemivertebrae. The prevalence of hemivertebrae could increase if dogs with shorter tails are preferentially selected for breeding purposes.

  17. The high heritability of educational achievement reflects many genetically influenced traits, not just intelligence.

    Science.gov (United States)

    Krapohl, Eva; Rimfeld, Kaili; Shakeshaft, Nicholas G; Trzaskowski, Maciej; McMillan, Andrew; Pingault, Jean-Baptiste; Asbury, Kathryn; Harlaar, Nicole; Kovas, Yulia; Dale, Philip S; Plomin, Robert

    2014-10-21

    Because educational achievement at the end of compulsory schooling represents a major tipping point in life, understanding its causes and correlates is important for individual children, their families, and society. Here we identify the general ingredients of educational achievement using a multivariate design that goes beyond intelligence to consider a wide range of predictors, such as self-efficacy, personality, and behavior problems, to assess their independent and joint contributions to educational achievement. We use a genetically sensitive design to address the question of why educational achievement is so highly heritable. We focus on the results of a United Kingdom-wide examination, the General Certificate of Secondary Education (GCSE), which is administered at the end of compulsory education at age 16. GCSE scores were obtained for 13,306 twins at age 16, whom we also assessed contemporaneously on 83 scales that were condensed to nine broad psychological domains, including intelligence, self-efficacy, personality, well-being, and behavior problems. The mean of GCSE core subjects (English, mathematics, science) is more heritable (62%) than the nine predictor domains (35-58%). Each of the domains correlates significantly with GCSE results, and these correlations are largely mediated genetically. The main finding is that, although intelligence accounts for more of the heritability of GCSE than any other single domain, the other domains collectively account for about as much GCSE heritability as intelligence. Together with intelligence, these domains account for 75% of the heritability of GCSE. We conclude that the high heritability of educational achievement reflects many genetically influenced traits, not just intelligence.

  18. Heritability of face shape in twins: a preliminary study using 3D stereophotogrammetry and geometric morphometrics

    Directory of Open Access Journals (Sweden)

    Seth M. Weinberg

    2013-11-01

    Full Text Available Introduction: Previous research suggests that aspects of facial surface morphology are heritable.  Traditionally, heritability studies have used a limited set of linear distances to quantify facial morphology and often employ statistical methods poorly designed to deal with biological shape.  In this preliminary report, we use a combination of 3D photogrammetry and landmark-based morphometrics to explore which aspects of face shape show the strongest evidence of heritability in a sample of twins. Methods: 3D surface images were obtained from 21 twin pairs (10 monozygotic, 11 same-sex dizygotic.  Thirteen 3D landmarks were collected from each facial surface and their coordinates subjected to geometric morphometric analysis.  This involved superimposing the individual landmark configurations and then subjecting the resulting shape coordinates to a principal components analysis.  The resulting PC scores were then used to calculate rough narrow-sense heritability estimates. Results: Three principal components displayed evidence of moderate to high heritability and were associated with variation in the breadth of orbital and nasal structures, upper lip height and projection, and the vertical and forward projection of the root of the nose due to variation in the position of nasion. Conclusions: Aspects of facial shape, primarily related to variation in length and breadth of central midfacial structures, were shown to demonstrate evidence of strong heritability. An improved understanding of which facial features are under strong genetic control is an important step in the identification of specific genes that underlie normal facial variation.

  19. Degree of inheritance and heritability of yield in parental genotypes and F1 hybrids of tobacco

    Directory of Open Access Journals (Sweden)

    Aleksoski Jane A.

    2011-01-01

    Full Text Available The mode and level of inheritance of green and dry mass yield per stalk were investigated in four parental genotypes (Burley - B 2/93, Suchum - S1, Suchum - S2 and Prilep - P-84 and in their six diallel F1 hybrids. The trial was set up in 2007, 2008 and 2009 in the field of Tobacco Institute-Prilep in a randomized block design with four replications. The aim of the investigation was to estimate the heritability as an indicator of the inheritance of the yield as one of the most important quantitative characters of tobacco, in order to give suggestions for the selection of parental genotypes and directions for the creation of new varieties. The mode of inheritance was estimated according to the test - significance of the mean value of F1 progeny compared to the parental average. Narrow-sense heritability was estimated after Allard (1960, while broad-sense heritability and genetic components were estimated after Mather and Jinks (1974. The mode of inheritance in the hybrids was different. Positive heterosis for green and dry mass yields per stalk was recorded in S1 x S2. Negative heterosis for green mass yields per stalk was recorded in S1 x P-84 and S2 x P-84, while for dry mass yield it was recorded in S1 x P-84. Inheritance of the characters during the three years of investigation was identical. The higher heritability index of both types was recorded for dry mass yield. As regards inheritance of the yield, the values of broad-sense heritability were higher than those of narrow-sense heritability.

  20. Heritability of high reading ability and its interaction with parental education.

    Science.gov (United States)

    Friend, Angela; DeFries, John C; Olson, Richard K; Pennington, Bruce; Harlaar, Nicole; Byrne, Brian; Samuelsson, Stefan; Willcutt, Erik G; Wadsworth, Sally J; Corley, Robin; Keenan, Janice M

    2009-07-01

    Moderation of the level of genetic influence on children's high reading ability by environmental influences associated with parental education was explored in two independent samples of identical and fraternal twins from the United States and Great Britain. For both samples, the heritability of high reading performance increased significantly with lower levels of parental education. Thus, resilience (high reading ability despite lower environmental support) is more strongly influenced by genotype than is high reading ability with higher environmental support. This result provides a coherent account when considered alongside results of previous research showing that heritability for low reading ability decreased with lower levels of parental education.

  1. M(o)bius Transformation and Poisson Integral Representation for Monogenic Functions%M(o)bius变换和正则函数的Poisson积分表示

    Institute of Scientific and Technical Information of China (English)

    张忠祥

    2013-01-01

    In this paper,the hyper-complex forms of equations for the plane and the sphere in R3 are given.Then,the concept of symmetric points with respect to the plane and the sphere in R3 is introduced,equivalent equations for symmetric points respect to the plane and the sphere are given.Some special M(o)bius transformations in hyper-complex space Cl3 are considered.Some properties of the mentioned M(o)bius transformation are given.For example,the M(o)bius transformation maps the plane and the sphere in R3 one-to-one onto the plane or the sphere,the M(o)bius transformation preserves the symmetric points with respect to the plane and the sphere in Cl3,the cross ratio of four distinct points is also invariant under the M(o)bius transformation.A relation between the monogenic function and M(o)bius transformation is shown.Secondly,a generalized Cauchy theorem and generalized Cauchy integral formula over the sphere for monogenic functions are proved.By combining the Cauchy integral formula for monogenic functions with the integral representation at the symmetric point with respect to the sphere,the Poisson integral representation for monogenic function is obtained.Finally,based on the properties of M(o)bius transformations,integral formulas for change of variables under M(o)bius transformations are constructed.%首先,给出了R3中平面和球面方程的超复形式,接着提出了R3中关于平面和球面对称点的概念,并给出了关于平面和球面对称点所满足的等价方程.我们考虑了超复空间Cl3中的一些特殊的M(o)bius变换,并给出了其一些性质,比如:保持球面或平面不变性,保持关于平面和球面对称性不变性,保持交比不变性等.文中给出了正则函数和M(o)bius变换的关系.其次,证明了R3中球内正则函数的推广的Cauchy定理和Cauchy积分公式.借助于上述正则函数的Cauchy积分公式和其对称点的积分表示,给出了正则函数的Poisson积分表示.最后,在M(o)bius变换的

  2. Overexpression of the tomato asc-1 gene mediates high insensitivity to AAL toxins and fumonisin B-1 in tomato hairy roots and confers resistance to Alternaria alternata f. sp lycopersici in Nicotiana umbratica plants

    NARCIS (Netherlands)

    Brandwagt, BF; Kneppers, TJA; Nijkamp, HJJ; Hille, J

    2002-01-01

    The sphinganine-analog mycotoxins (SAMs) fumonisin B-1 and AAL toxins are inhibitors of eukaryotic sphinganine N-acyltransferase in vitro. Treatment of eukaryotes with SAMs generally results in an accumulation of sphingoid base precursors and a depletion of complex sphingolipids. The asc,asc genotyp

  3. Overexpression of the Tomato Asc-1 Gene Mediates High Insensitivity to AAL Toxins and Fumonisin B1 in Tomato Hairy Roots and Confers Resistance to Alternaria alternata f. sp. lycopersici in Nicotiana umbratica Plants

    NARCIS (Netherlands)

    Brandwagt, Bas F.; Kneppers, Tarcies J.A.; Nijkamp, H. John J.; Hille, Jacques

    2002-01-01

    The sphinganine-analog mycotoxins (SAMs) fumonisin B1 and AAL toxins are inhibitors of eukaryotic sphinganine N-acyltransferase in vitro. Treatment of eukaryotes with SAMs generally results in an accumulation of sphingoid base precursors and a depletion of complex sphingolipids. The asc,asc genotype

  4. The heritability of G2 chromosomal radiosensitivity and its association with cancer in Danish cancer survivors and their offspring

    DEFF Research Database (Denmark)

    Curwen, Gillian B; Cadwell, Kevin K; Winther, Jeanette Falck;

    2010-01-01

    To investigate the relationship between chromosomal radiosensitivity and early-onset cancer under the age of 35 years and to examine the heritability of chromosomal radiosensitivity.......To investigate the relationship between chromosomal radiosensitivity and early-onset cancer under the age of 35 years and to examine the heritability of chromosomal radiosensitivity....

  5. Face recognition algorithm based on pattern of monogenic magni-tudes with same phase%基于单演同相幅值模式的人脸识别方法

    Institute of Scientific and Technical Information of China (English)

    刘机福; 王炼红; 汤春龙

    2014-01-01

    针对单演信号表述仅利用幅值和方向而忽略相位信息的问题,提出了一种单演同相幅值模式方法。用多尺度的单演滤波器提取人脸的单演幅值和相位信息,将相位量化并根据相位量化的结果对幅值累加和二值编码,从而获得若干张单演同相幅值模式图。将每一张PMMSP图分块并提取直方图特征,用BFLD对特征进行降维。这样能有效提升特征的判别能力并降低算法的时间和空间复杂度。在CAS-PEAL人脸库和AR人脸库上的实验证明了该算法的有效性。%In order to take advantages of the monogenic magnitude and phase information for face recognition, a new method based on pattern of monogenic magnitudes with same phase is proposed. Multi-scale monogenic filters are used to extract the monogenic magnitude and phase information of the image. This paper obtains the phase quantization images, accumu-lates the magnitude according to the quantization results and codes the accumulative results by binary strategy. After that the patterns of monogenic magnitudes with same phase image are obtained. PMMSP maps are divided into blocks and the histo-gram is extracted from the blocks. BFLD is not only used to reduce the dimension of the features but also enhance its discrimi-native power. The experimental results on the CAS-PEAL and AR face databases show that the proposed algorithm is effective.

  6. The effect of magnetic stimulation on the osteogenic and chondrogenic differentiation of human stem cells derived from the adipose tissue (hASCs)

    Energy Technology Data Exchange (ETDEWEB)

    Lima, João; Gonçalves, Ana I.; Rodrigues, Márcia T.; Reis, Rui L. [3Bs Research Group–Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães (Portugal); ICVS/3Bs–PT Government Associate Laboratory, Braga/Guimarães (Portugal); Gomes, Manuela E., E-mail: megomes@dep.uminho.pt [3Bs Research Group–Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães (Portugal); ICVS/3Bs–PT Government Associate Laboratory, Braga/Guimarães (Portugal)

    2015-11-01

    The use of magnetic nanoparticles (MNPs) towards the musculoskeletal tissues has been the focus of many studies, regarding MNPs ability to promote and direct cellular stimulation and orient tissue responses. This is thought to be mainly achieved by mechano-responsive pathways, which can induce changes in cell behavior, including the processes of proliferation and differentiation, in response to external mechanical stimuli. Thus, the application of MNP-based strategies in tissue engineering may hold potential to propose novel solutions for cell therapy on bone and cartilage strategies to accomplish tissue regeneration. The present work aims at studying the influence of MNPs on the osteogenic and chondrogenic differentiation of human adipose derived stem cells (hASCs). MNPs were incorporated in hASCs and cultured in medium supplemented for osteogenic and chondrogenic differentiation. Cultures were maintained up to 28 days with/without an external magnetic stimulus provided by a magnetic bioreactor, to determine if the MNPs alone could affect the osteogenic or chondrogenic phenotype of the hASCs. Results indicate that the incorporation of MNPs does not negatively affect the viability nor the proliferation of hASCs. Furthermore, Alizarin Red staining evidences an enhancement in extracellular (ECM) mineralization under the influence of an external magnetic field. Although not as evident as for osteogenic differentiation, Toluidine blue and Safranin-O stainings also suggest the presence of a cartilage-like ECM with glycosaminoglycans and proteoglycans under the magnetic stimulus provided. Thus, MNPs incorporated in hASCs under the influence of an external magnetic field have the potential to induce differentiation towards the osteogenic and chondrogenic lineages. - Highlights: • Cellular viability was not negatively influenced by the nanoparticles. • Chondrogenic medium influences more the synthesis of cartilage-like ECM than MNPs. • Synergetic effect among

  7. The effect of magnetic stimulation on the osteogenic and chondrogenic differentiation of human stem cells derived from the adipose tissue (hASCs)

    Science.gov (United States)

    Lima, João; Gonçalves, Ana I.; Rodrigues, Márcia T.; Reis, Rui L.; Gomes, Manuela E.

    2015-11-01

    The use of magnetic nanoparticles (MNPs) towards the musculoskeletal tissues has been the focus of many studies, regarding MNPs ability to promote and direct cellular stimulation and orient tissue responses. This is thought to be mainly achieved by mechano-responsive pathways, which can induce changes in cell behavior, including the processes of proliferation and differentiation, in response to external mechanical stimuli. Thus, the application of MNP-based strategies in tissue engineering may hold potential to propose novel solutions for cell therapy on bone and cartilage strategies to accomplish tissue regeneration. The present work aims at studying the influence of MNPs on the osteogenic and chondrogenic differentiation of human adipose derived stem cells (hASCs). MNPs were incorporated in hASCs and cultured in medium supplemented for osteogenic and chondrogenic differentiation. Cultures were maintained up to 28 days with/without an external magnetic stimulus provided by a magnetic bioreactor, to determine if the MNPs alone could affect the osteogenic or chondrogenic phenotype of the hASCs. Results indicate that the incorporation of MNPs does not negatively affect the viability nor the proliferation of hASCs. Furthermore, Alizarin Red staining evidences an enhancement in extracellular (ECM) mineralization under the influence of an external magnetic field. Although not as evident as for osteogenic differentiation, Toluidine blue and Safranin-O stainings also suggest the presence of a cartilage-like ECM with glycosaminoglycans and proteoglycans under the magnetic stimulus provided. Thus, MNPs incorporated in hASCs under the influence of an external magnetic field have the potential to induce differentiation towards the osteogenic and chondrogenic lineages.

  8. Environmental impact of non-certified versus certified (ASC) intensive Pangasius aquaculture in Vietnam, a comparison based on a statistically supported LCA.

    Science.gov (United States)

    Nhu, Trang T; Schaubroeck, Thomas; Henriksson, Patrik J G; Bosma, Roel; Sorgeloos, Patrick; Dewulf, Jo

    2016-12-01

    Pangasius production in Vietnam is widely known as a success story in aquaculture, the fastest growing global food system because of its tremendous expansion by volume, value and the number of international markets to which Pangasius has been exported in recent years. While certification schemes are becoming significant features of international fish trade and marketing, an increasing number of Pangasius producers have followed at least one of the certification schemes recognised by international markets to incorporate environmental and social sustainability practices in aquaculture, typically the Pangasius Aquaculture Dialogue (PAD) scheme certified by the Aquaculture Stewardship Council (ASC). An assessment of the environmental benefit of applying certification schemes on Pangasius production, however, is still needed. This article compared the environmental impact of ASC-certified versus non-ASC certified intensive Pangasius aquaculture, using a statistically supported LCA. We focused on both resource-related (water, land and total resources) and emissions-related (global warming, acidification, freshwater and marine eutrophication) categories. The ASC certification scheme was shown to be a good approach for determining adequate environmental sustainability, especially concerning emissions-related categories, in Pangasius production. However, the non-ASC certified farms, due to the large spread, the impact (e.g., water resources and freshwater eutrophication) was possibly lower for a certain farm. However, this result was not generally prominent. Further improvements in intensive Pangasius production to inspire certification schemes are proposed, e.g., making the implementation of certification schemes more affordable, well-oriented and facilitated; reducing consumed feed amounts and of the incorporated share in fishmeal, especially domestic fishmeal, etc. However, their implementation should be vetted with key stakeholders to assess their feasibility. Copyright

  9. Natural epigenetic variation contributes to heritable flowering divergence in a widespread asexual dandelion lineage.

    Science.gov (United States)

    Wilschut, Rutger A; Oplaat, Carla; Snoek, L Basten; Kirschner, Jan; Verhoeven, Koen J F

    2016-04-01

    Epigenetic variation has been proposed to contribute to the success of asexual plants, either as a contributor to phenotypic plasticity or by enabling transient adaptation via selection on transgenerationally stable, but reversible, epialleles. While recent studies in experimental plant populations have shown the potential for epigenetic mechanisms to contribute to adaptive phenotypes, it remains unknown whether heritable variation in ecologically relevant traits is at least partially epigenetically determined in natural populations. Here, we tested the hypothesis that DNA methylation variation contributes to heritable differences in flowering time within a single widespread apomictic clonal lineage of the common dandelion (Taraxacum officinale s. lat.). Apomictic clone members of the same apomictic lineage collected from different field sites showed heritable differences in flowering time, which was correlated with inherited differences in methylation-sensitive AFLP marker profiles. Differences in flowering between apomictic clone members were significantly reduced after in vivo demethylation using the DNA methyltransferase inhibitor zebularine. This synchronization of flowering times suggests that flowering time divergence within an apomictic lineage was mediated by differences in DNA methylation. While the underlying basis of the methylation polymorphism at functional flowering time-affecting loci remains to be demonstrated, our study shows that epigenetic variation contributes to heritable phenotypic divergence in ecologically relevant traits in natural plant populations. This result also suggests that epigenetic mechanisms can facilitate adaptive divergence within genetically uniform asexual lineages. © 2015 John Wiley & Sons Ltd.

  10. A review and meta-analysis of the heritability of specific phobia subtypes and corresponding fears.

    Science.gov (United States)

    Van Houtem, C M H H; Laine, M L; Boomsma, D I; Ligthart, L; van Wijk, A J; De Jongh, A

    2013-05-01

    Evidence from twin studies suggests that genetic factors contribute to the risk of developing a fear or a phobia. The aim of the present study was to review the current literature regarding twin studies describing the genetic basis of specific phobias and their corresponding fears. The analysis included five twin studies on fears and ten twin studies on specific phobias. Heritability estimates of fear subtypes and specific phobia subtypes both varied widely, even within the subtypes. A meta-analysis performed on the twin study results indicated that fears and specific phobias are moderately heritable. The highest mean heritability (±SEM) among fear subtypes was found for animal fear (45%±0.004), and among specific phobias for the blood-injury-injection phobia (33%±0.06). For most phenotypes, variance could be explained solely by additive genetic and unique environmental effects. Given the dearth of independent data on the heritability of specific phobias and fears, additional research is needed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Sex differences and heritability of two indices of heart rate dynamics : A twin study

    NARCIS (Netherlands)

    Snieder, Harold; van Doornen, Lorenz J. P.; Boomsma, Dorret I.; Thayer, Julian F.

    2007-01-01

    We investigated whether women show larger heart rate variability (HRV) than men after controlling for a large number of health-related covariates, using two indices of HRV, namely respiratory sinus arrhythmia (RSA) and approximate entropy (ApEn). In a twin design, the heritability of both indices wa

  12. Prevalence, concordance, and heritability of Scheuermann kyphosis based on a study of twins

    DEFF Research Database (Denmark)

    Damborg, Frank; Engell, Vilhelm; Andersen, Mikkel;

    2006-01-01

    BACKGROUND: The purpose of this study was to establish a cohort of symptomatic twins with Scheuermann kyphosis to provide estimates of prevalence, concordance, odds ratio, and heritability. These estimates indicate to what extent genetic factors contribute to the etiology of this disease. METHODS...

  13. Revertant Mosaicism in Heritable Skin Diseases - Mechanisms of Natural Gene Therapy

    NARCIS (Netherlands)

    Pasmooij, Anna M. G.; Jonkman, Marcel F.; Uitto, Jouni

    Revertant mosaicism (RM) refers to the co-existence of cells carrying disease-causing mutations with cells in which the inherited mutation is genetically corrected by a spontaneous event. It has been discovered in an increasing number of heritable skin diseases: ichthyosis with confetti and

  14. Repeatability and heritability of exploratory behaviour in great tits from the wild

    NARCIS (Netherlands)

    Dingemanse, NJ; Both, C; Drent, PJ; Van Oers, K; Van Noordwijk, AJ; Drent, Piet J.; Noordwijk, Arie J. van

    2002-01-01

    We investigated whether individual great tits, Parus major, vary consistently in their exploratory behaviour in a novel environment and measured the repeatability and heritability of this trait. Wild birds were caught in their natural habitat, tested in the laboratory in an open field test on the fo

  15. 75 FR 2554 - Advisory Committee on Heritable Disorders in Newborns and Children

    Science.gov (United States)

    2010-01-15

    ... should have expertise in dealing with heritable disorders and genetic diseases that affect the racial and ethnic and geographical diversity of newborns served by the State newborn screening programs. The... be impaired. Appointments shall be made without discrimination on the basis of age, ethnicity,...

  16. Heritability of insulin sensitivity and lipid profile depend on BMI : evidence for gene-obesity interaction

    NARCIS (Netherlands)

    Wang, X.; Ding, X.; Su, S.; Spector, T. D.; Mangino, M.; Iliadou, A.; Snieder, H.

    2009-01-01

    Evidence from candidate gene studies suggests that obesity may modify genetic susceptibility to type 2 diabetes and dyslipidaemia. On an aggregate level, gene-obesity interactions are expected to result in different heritability estimates at different obesity levels. However, this hypothesis has nev

  17. Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

    Science.gov (United States)

    Gusev, Alexander; Lee, S. Hong; Trynka, Gosia; Finucane, Hilary; Vilhjálmsson, Bjarni J.; Xu, Han; Zang, Chongzhi; Ripke, Stephan; Bulik-Sullivan, Brendan; Stahl, Eli; Ripke, Stephan; Neale, Benjamin M.; Corvin, Aiden; Walters, James T.R.; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A.; Huang, Hailiang; Pers, Tune H.; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A.; Begemann, Martin; Belliveau, Richard A.; Bene, Judit; Bergen, Sarah E.; Bevilacqua, Elizabeth; Bigdeli, Tim B.; Black, Donald W.; Børglum, Anders D.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberly D.; Chan, Raymond C.K.; Chen, Ronald Y.L.; Chen, Eric Y.H.; Cheng, Wei; Cheung, Eric F.C.; Chong, Siow Ann; Cloninger, C. Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; Del Favero, Jurgen; DeLisi, Lynn E.; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H.; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Friedman, Joseph I.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Giusti-Rodrguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; Grove, Jakob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V.; Hougaard, David M.; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kahn, René S.; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kelly, Brian J.; Kennedy, James L.; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A.; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K.; Laurent, Claudine; Keong, Jimmy Lee Chee; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M.; Lubinski, Jan; Lnnqvist, Jouko; Macek, Milan; Magnusson, Patrik K.E.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Mller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O’Callaghan, Eadbhard; O’Dushlaine, Colm; O’Neill, F. Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; Van Os, Jim; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T.; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O.; Pietilinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Powell, John; Price, Alkes; Pulver, Ann E.; Purcell, Shaun M.; Quested, Digby; Rasmussen, Henrik B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Schall, Ulrich; Schubert, Christian R.; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M.; Sim, Kang; Slominsky, Petr; Smoller, Jordan W.; So, Hon-Cheong; Spencer, Chris C.A.; Stahl, Eli A.; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Sderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tooney, Paul A.; Tosato, Sarah; Veijola, Juha

    2014-01-01

    Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (hg2) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg2 from imputed SNPs (5.1× enrichment; p = 3.7 × 10−17) and 38% (SE = 4%) of hg2 from genotyped SNPs (1.6× enrichment, p = 1.0 × 10−4). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained <10% of hg2 despite having the highest enrichment. We replicated these findings but found no significant contribution from rare coding variants in independent schizophrenia cohorts genotyped on GWAS and exome chips. Our results highlight the value of analyzing components of heritability to unravel the functional architecture of common disease. PMID:25439723

  18. 78 FR 23770 - Establishment of the Discretionary Advisory Committee on Heritable Disorders in Newborns and...

    Science.gov (United States)

    2013-04-22

    ... authorizing directive and guidelines under the Federal Advisory Committee Act (FACA), a charter will be filed... state and local health agencies to provide for newborn and child screening, counseling and health care..., counseling, testing, or specialty services for newborns and children at risk for heritable disorders;...

  19. P300 event-related potential heritability in monozygotic and dizygotic twins.

    Science.gov (United States)

    Katsanis, J; Iacono, W G; McGue, M K; Carlson, S R

    1997-01-01

    The present study examined the heritability of the P3 waveform and the N1, P2, and N2 components by assessing the visual event-related potential (ERP) of 30 monozygotic (MZ) and 34 dizygotic (DZ) twin pairs. Electroencephalogram activity was recorded from Pz, P3, and P4 scalp sites while individuals performed a reaction time task involving two conditions differing in difficulty. Genetic modeling indicated substantial genetic influence on P3 amplitude, P3 latency, and manual reaction time for the difficult condition. No significant heritability was found for the latency of P3 or manual reaction time for the easy condition, but P3 amplitude was heritable for this condition. The amplitude of the early components (N1, P2, and N2) was heritable, but no significant genetic influences were found for the latency of these components. Compared with the DZ twins, the greater similarity of the MZ pairs on the event-related potential measures was not due to their greater similarity in either head dimensions or mental ability, despite the facts that IQ scores were weakly correlated with P3 and N2 amplitude and that amplitude and latency were related to some measures of head size. These findings suggest that P3 amplitude and the amplitude of earlier ERP components are under partial genetic control, supporting the notion that these ERP components could perhaps be used to identify genetic risk for psychopathology.

  20. Transcriptional infidelity promotes heritable phenotypic change in a bistable gene network.

    Directory of Open Access Journals (Sweden)

    Alasdair J E Gordon

    2009-02-01

    Full Text Available Bistable epigenetic switches are fundamental for cell fate determination in unicellular and multicellular organisms. Regulatory proteins associated with bistable switches are often present in low numbers and subject to molecular noise. It is becoming clear that noise in gene expression can influence cell fate. Although the origins and consequences of noise have been studied, the stochastic and transient nature of RNA errors during transcription has not been considered in the origin or modeling of noise nor has the capacity for such transient errors in information transfer to generate heritable phenotypic change been discussed. We used a classic bistable memory module to monitor and capture transient RNA errors: the lac operon of Escherichia coli comprises an autocatalytic positive feedback loop producing a heritable all-or-none epigenetic switch that is sensitive to molecular noise. Using single-cell analysis, we show that the frequency of epigenetic switching from one expression state to the other is increased when the fidelity of RNA transcription is decreased due to error-prone RNA polymerases or to the absence of auxiliary RNA fidelity factors GreA and GreB (functional analogues of eukaryotic TFIIS. Therefore, transcription infidelity contributes to molecular noise and can effect heritable phenotypic change in genetically identical cells in the same environment. Whereas DNA errors allow genetic space to be explored, RNA errors may allow epigenetic or expression space to be sampled. Thus, RNA infidelity should also be considered in the heritable origin of altered or aberrant cell behaviour.

  1. Diet, lifestyle, heritable factors and colorectal carcinogenesis: associations with histopathological and molecular endpoints

    NARCIS (Netherlands)

    Wark, P.A.

    2007-01-01

    Background: Diet, lifestyle and heritable factors have been related to colorectal cancer risk; to date, their relevance to the overall scope of colorectal carcinogenesis, has not been clearly established.Aim and Methods: To evaluate whether distinguishing colorectal tissue by its histopathological a

  2. Heritability of Antisocial Behaviour at 9: Do Callous-Unemotional Traits Matter?

    Science.gov (United States)

    Viding, Essi; Jones, Alice P.; Paul, J. Frick; Moffitt, Terrie E.; Plomin, Robert

    2008-01-01

    A previous finding from our group indicated that teacher-rated antisocial behaviour (AB) among 7-year-olds is particularly heritable in the presence of callous-unemotional (CU) traits. Using a sample of 1865 same-sex twin pairs, we employed DeFries-Fulker extremes analysis to investigate whether teacher-rated AB with/without CU traits also shows…

  3. DNA evidence for strong genetic stability and increasing heritability of intelligence from age 7 to 12.

    Science.gov (United States)

    Trzaskowski, M; Yang, J; Visscher, P M; Plomin, R

    2014-03-01

    Two genetic findings from twin research have far-reaching implications for understanding individual differences in the development of brain function as indexed by general cognitive ability (g, aka intelligence): (1) The same genes affect g throughout development, even though (2) heritability increases. It is now possible to test these hypotheses using DNA alone. From 1.7 million DNA markers and g scores at ages 7 and 12 on 2875 children, the DNA genetic correlation from age 7 to 12 was 0.73, highly similar to the genetic correlation of 0.75 estimated from 6702 pairs of twins from the same sample. DNA-estimated heritabilities increased from 0.26 at age 7 to 0.45 at age 12; twin-estimated heritabilities also increased from 0.35 to 0.48. These DNA results confirm the results of twin studies indicating strong genetic stability but increasing heritability for g, despite mean changes in brain structure and function from childhood to adolescence.

  4. Sudden unexplained death: Heritability and diagnostic yield of cardiological and genetic examination in surviving relatives

    NARCIS (Netherlands)

    Tan, Hanno L.; Hofman, Nynke; Van Langen, Irene M.; Van Der Wal, Allard C.; Wilde, Arthur A. M.

    2005-01-01

    Background-Sudden death mostly follows from cardiac disorders that elicit lethal ventricular arrhythmias. In young individuals, it often remains unexplained because history and/or postmortem analysis are absent or provide no clue. Because such sudden unexplained deaths (SUDs) may have heritable caus

  5. 78 FR 25447 - Establishment of the Discretionary Advisory Committee on Heritable Disorders in Newborns and...

    Science.gov (United States)

    2013-05-01

    ... for Healthcare Research and Quality; and the Commissioner of the Food and Drug Administration--or... ethics and heritable disorders who have worked and published material in the area of public health and..., email, telephone number, professional or business affiliation, type of expertise (i.e.,...

  6. Shared genetic variance between the features of the metabolic syndrome: Heritability studies

    NARCIS (Netherlands)

    Povel, C.M.; Boer, J.M.A.; Feskens, E.J.M.

    2011-01-01

    Heritability estimates of MetS range from approximately 10%–30%. The genetic variation that is shared among MetS features can be calculated by genetic correlation coefficients. The objective of this paper is to identify MetS feature as well as MetS related features which have much genetic variation

  7. Heritability of preferences for multiple cues of mate quality in humans.

    Science.gov (United States)

    Zietsch, Brendan P; Verweij, Karin J H; Burri, Andrea V

    2012-06-01

    Human mate preferences have received a great deal of attention in recent decades because of their centrality to sexual selection, which is thought to play a substantial role in human evolution. Most of this attention has been on universal aspects of mate preferences, but variation between individuals is less understood. In particular, the relative contribution of genetic and environmental influences to variation in mate preferences is key to sexual selection models but has barely been investigated in humans, and results have been mixed in other species. Here, we used data from over 4000 mostly female twins who ranked the importance of 13 key traits in a potential partner. We used the classical twin design to partition variation in these preferences into that due to genes, family environment, and residual factors. In women, there was significant variability in the broad-sense heritability of individual trait preferences, with physical attractiveness the most heritable (29%) and housekeeping ability the least (5%). Over all the trait preferences combined, broad-sense heritabilities were highly significant in women and marginally significant in men, accounting for 20% and 19% of the variation, respectively; family environmental influences were much smaller. Heritability was a little higher in reproductive aged than in nonreproductive aged women, but the difference was not significant. © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.

  8. Social disinhibition is a heritable subphenotype of tics in Tourette syndrome.

    Science.gov (United States)

    Hirschtritt, Matthew E; Darrow, Sabrina M; Illmann, Cornelia; Osiecki, Lisa; Grados, Marco; Sandor, Paul; Dion, Yves; King, Robert A; Pauls, David L; Budman, Cathy L; Cath, Danielle C; Greenberg, Erica; Lyon, Gholson J; Yu, Dongmei; McGrath, Lauren M; McMahon, William M; Lee, Paul C; Delucchi, Kevin L; Scharf, Jeremiah M; Mathews, Carol A

    2016-08-02

    To identify heritable symptom-based subtypes of Tourette syndrome (TS). Forty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined. A 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 × 10(-18)). Expanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies. © 2016 American Academy of Neurology.

  9. A multicenter study to map genes for Fuchs endothelial corneal dystrophy: baseline characteristics and heritability.

    Science.gov (United States)

    Louttit, Megan D; Kopplin, Laura J; Igo, Robert P; Fondran, Jeremy R; Tagliaferri, Angela; Bardenstein, David; Aldave, Anthony J; Croasdale, Christopher R; Price, Marianne O; Rosenwasser, George O; Lass, Jonathan H; Iyengar, Sudha K

    2012-01-01

    To describe the methods for family and case-control recruitment for a multicenter genetic and associated heritability analyses of Fuchs endothelial corneal dystrophy (FECD). Twenty-nine enrolling sites with 62 trained investigators and coordinators gathered individual and family information, graded the phenotype, and collected blood and/or saliva for genetic analysis on all individuals with and without FECD. The degree of FECD was assessed in a 0 to 6 semiquantitative scale using standardized clinical methods with pathological verification of FECD on at least 1 member of each family. Central corneal thickness was measured by ultrasonic pachymetry. Three hundred twenty-two families with 330 affected sibling pairs with FECD were enrolled and included a total of 650 sibling pairs of all disease grades. Using the entire 7-step FECD grading scale or a dichotomous definition of severe disease, heritability was assessed in families via sib-sib correlations. Both binary indicators of severe disease and semiquantitative measures of disease severity were significantly heritable, with heritability estimates of 30% for severe disease, 37% to 39% for FECD score, and 47% for central corneal thickness. Genetic risk factors have a strong role in the severity of the FECD phenotype and corneal thickness. Genotyping this cohort with high-density genetic markers followed by appropriate statistical analyses should lead to novel loci for disease susceptibility.

  10. Heritability of performance deficit accumulation during acute sleep deprivation in twins.

    Science.gov (United States)

    Kuna, Samuel T; Maislin, Greg; Pack, Frances M; Staley, Bethany; Hachadoorian, Robert; Coccaro, Emil F; Pack, Allan I

    2012-09-01

    To determine if the large and highly reproducible interindividual differences in rates of performance deficit accumulation during sleep deprivation, as determined by the number of lapses on a sustained reaction time test, the Psychomotor Vigilance Task (PVT), arise from a heritable trait. Prospective, observational cohort study. Academic medical center. There were 59 monozygotic (mean age 29.2 ± 6.8 [SD] yr; 15 male and 44 female pairs) and 41 dizygotic (mean age 26.6 ± 7.6 yr; 15 male and 26 female pairs) same-sex twin pairs with a normal polysomnogram. Thirty-eight hr of monitored, continuous sleep deprivation. Patients performed the 10-min PVT every 2 hr during the sleep deprivation protocol. The primary outcome was change from baseline in square root transformed total lapses (response time ≥ 500 ms) per trial. Patient-specific linear rates of performance deficit accumulation were separated from circadian effects using multiple linear regression. Using the classic approach to assess heritability, the intraclass correlation coefficients for accumulating deficits resulted in a broad sense heritability (h(2)) estimate of 0.834. The mean within-pair and among-pair heritability estimates determined by analysis of variance-based methods was 0.715. When variance components of mixed-effect multilevel models were estimated by maximum likelihood estimation and used to determine the proportions of phenotypic variance explained by genetic and nongenetic factors, 51.1% (standard error = 8.4%, P sleep deprivation.

  11. Effects of red grape skin and seed extract supplementation on atherosclerosis in Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Frederiksen, Hanne; Mortensen, Alicja; Schrøder, Malene;

    2007-01-01

    Epidemiological studies have suggested an association between consumption of red wine and other polyphenolic compounds and prevention of cardiovascular diseases. In the present study, Watanabe heritable hyperlipidemic (WHHL) rabbits were used to investigate the effects of polyphenols in a red gra...

  12. Heritability of head size in dutch and Australian twin families at ages 0-50 years.

    NARCIS (Netherlands)

    Smit, D.J.; Luciano, M.; Bartels, M.; Beijsterveldt, C.E. van; Wright, M.J.; Hansell, N.K.; Brunner, H.G.; Estourgie-van Burk, G.F.; Geus, E.J. de; Martin, N.G.; Boomsma, D.I.

    2010-01-01

    We assessed the heritability of head circumference, an approximation of brain size, in twin-sib families of different ages. Data from the youngest participants were collected a few weeks after birth and from the oldest participants around age 50 years. In nearly all age groups the largest part of th

  13. [Heritability analysis on serum lipids of adult twins in Qingdao City

    DEFF Research Database (Denmark)

    Lan, Jinfeng; Pang, Zengchang; Wang, Shaojie

    2010-01-01

    OBJECTIVE: To study the level and heritability of serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) in adult twins sampled from Qingdao City of China. METHODS: 316 pairs of healthy twin aged 18 to 60 years...

  14. Cytochrome P450 gene CYP337 and heritability of fitness traits in the Glanville fritillary butterfly.

    Science.gov (United States)

    de Jong, M A; Wong, S C; Lehtonen, R; Hanski, I

    2014-04-01

    Fitness-related life history traits often show substantial heritable genetic variation in natural populations, but knowledge of the genetic architecture of these traits is limited. In the Glanville fritillary butterfly, we measured the heritability of key life history traits in a large outdoor population cage during 2 years and generations and combined this experiment with an association study of a set of candidate genes. The genes were selected on the basis of previous genomic and transcriptomic studies and have been linked to the physiology and life history of this or other arthropod species. Heritability was high and significant for two traits, post-diapause larval development time (h(2) = 0.37) and lifetime egg (and larval) production (h(2) = 0.62); the latter is closely related to lifetime reproductive success and therefore fitness. We discovered a strong association between genetic polymorphism in the cytochrome P450 gene CYP337 and lifetime egg production, which accounted for 14% of the additive variance in egg production. This gene belongs to a group of cytochrome P450 genes that have a well-documented role in host plant adaptations in Lepidoptera and other insects and is likely to play an important role in the ecology and microevolution of the Glanville fritillary. This study provides a prime example of a gene associated with heritable fitness variation, measured under semi-natural ecological conditions. © 2014 John Wiley & Sons Ltd.

  15. Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder

    NARCIS (Netherlands)

    Rommelse, Nanda N. J.; Franke, Barbara; Geurts, Hilde M.; Hartman, Catharina A.; Buitelaar, Jan K.

    2010-01-01

    Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting

  16. Diet, lifestyle, heritable factors and colorectal carcinogenesis: associations with histopathological and molecular endpoints

    NARCIS (Netherlands)

    Wark, P.A.

    2007-01-01

    Background: Diet, lifestyle and heritable factors have been related to colorectal cancer risk; to date, their relevance to the overall scope of colorectal carcinogenesis, has not been clearly established.Aim and Methods: To evaluate whether distinguishing colorectal tissue by its histopathological

  17. Estimation of Epistatic Variance Components and Heritability in Founder Populations and Crosses

    Science.gov (United States)

    Young, Alexander I.; Durbin, Richard

    2014-01-01

    Genetic association studies have explained only a small proportion of the estimated heritability of complex traits, leaving the remaining heritability “missing.” Genetic interactions have been proposed as an explanation for this, because they lead to overestimates of the heritability and are hard to detect. Whether this explanation is true depends on the proportion of variance attributable to genetic interactions, which is difficult to measure in outbred populations. Founder populations exhibit a greater range of kinship than outbred populations, which helps in fitting the epistatic variance. We extend classic theory to founder populations, giving the covariance between individuals due to epistasis of any order. We recover the classic theory as a limit, and we derive a recently proposed estimator of the narrow sense heritability as a corollary. We extend the variance decomposition to include dominance. We show in simulations that it would be possible to estimate the variance from pairwise interactions with samples of a few thousand from strongly bottlenecked human founder populations, and we provide an analytical approximation of the standard error. Applying these methods to 46 traits measured in a yeast (Saccharomyces cerevisiae) cross, we estimate that pairwise interactions explain 10% of the phenotypic variance on average and that third- and higher-order interactions explain 14% of the phenotypic variance on average. We search for third-order interactions, discovering an interaction that is shared between two traits. Our methods will be relevant to future studies of epistatic variance in founder populations and crosses. PMID:25326236

  18. Heritability of insulin sensitivity and lipid profile depend on BMI : evidence for gene-obesity interaction

    NARCIS (Netherlands)

    Wang, X.; Ding, X.; Su, S.; Spector, T. D.; Mangino, M.; Iliadou, A.; Snieder, H.

    2009-01-01

    Evidence from candidate gene studies suggests that obesity may modify genetic susceptibility to type 2 diabetes and dyslipidaemia. On an aggregate level, gene-obesity interactions are expected to result in different heritability estimates at different obesity levels. However, this hypothesis has

  19. Heritability of phenotypes associated with glucose homeostasis and adiposity in a rural area of Brazil.

    Science.gov (United States)

    Pena, Geórgia G; Dutra, Míriam Santos; Gazzinelli, Andrea; Corrêa-Oliveira, Rodrigo; Velasquez-Melendez, Gustavo

    2014-01-01

    We aimed to estimate the heritability and genetic correlation between glucose homeostasis and adiposity traits in a population in a rural community in Brazil. The Jequitinhonha Community Family Study cohort consists of subjects aged ≥18 years residing in rural areas in Brazil. The data on the following traits were assembled for 280 individuals (51.7% women): body mass index (BMI), body fat percentage, waist and mid-upper arm circumferences, triceps skinfold, conicity index, insulin, glucose, high-density lipoprotein cholesterol (HDLc), triglycerides and C-reactive protein. Extended pedigrees were constructed up to the third generation of individuals using the data management software PEDSYS. The heritability and genetic correlations were estimated using a variance component method. The age- and sex-adjusted heritability values estimated for insulin (h(2) = 52%), glucose (h(2) = 51%), HDLc (h(2) = 58%), and waist circumference (WC; h(2) = 49%) were high. Significantly adjusted genetic correlations were observed between insulin paired with each of the following phenotypes; (BMI; ρg = 0.48), WC (ρg = 0.47) and HDLc (ρg = -0.47). The homeostasis model assessment of insulin resistance (HOMA-IR) was genetically correlated with BMI (ρg = 0.53) and HDLc (ρg = -0.58). The adjusted genetic correlations between traits were consistently higher compared with the environmental correlations. In conclusion, glucose metabolism and adiposity traits are highly heritable and share common genetic effects with body adiposity traits.

  20. Heritability, evolvability, phenotypic plasticity and temporal variation in sperm-competition success of Drosophila melanogaster.

    Science.gov (United States)

    Dobler, R; Reinhardt, K

    2016-05-01

    Sperm-competition success (SCS) is seen as centrally important for evolutionary change: superior fathers sire superior sons and thereby inherit the traits that make them superior. Additional hypotheses, that phenotypic plasticity in SCS and sperm ageing explain variation in paternity, are less considered. Even though various alleles have individually been shown to be correlated with variation in SCS, few studies have addressed the heritability, or evolvability, of overall SCS. Those studies that have addressed found low or no heritability and have not examined evolvability. They have further not excluded phenotypic plasticity, and temporal effects on SCS, despite their known dramatic effects on sperm function. In Drosophila melanogaster, we found that both standard components of sperm competition, sperm defence and sperm offence, showed nonsignificant heritability across several offspring cohorts. Instead, our analysis revealed, for the first time, the existence of phenotypic plasticity in SCS across an extreme environment (5% CO2 ), and an influence of sperm ageing. Evolvability of SCS was substantial for sperm defence but weak for sperm offence. Our results suggest that the paradigm of explaining evolution by sperm competition is more complex and will benefit from further experimental work on the heritability or evolvability of SCS, measuring phenotypic plasticity, and separating the effects of sperm competition and sperm ageing.

  1. [Heritability analysis on serum lipids of adult twins in Qingdao City

    DEFF Research Database (Denmark)

    Lan, Jinfeng; Pang, Zengchang; Wang, Shaojie

    2010-01-01

    were recruited from the database of Qingdao City twin registry. Fasting serum lipids were detected by automatic biochemical analyzer. The zygosity of twins was established by using polymorphic DNA-based microsatellite markers. The heritability was estimated by formulating univariate ACE twin mode in Mx...

  2. The executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable.

    Science.gov (United States)

    Mez, Jesse; Mukherjee, Shubhabrata; Thornton, Timothy; Fardo, David W; Trittschuh, Emily; Sutti, Sheila; Sherva, Richard; Kauwe, John S; Naj, Adam C; Beecham, Gary W; Gross, Alden; Saykin, Andrew J; Green, Robert C; Crane, Paul K

    2016-05-01

    Late-onset Alzheimer's disease (LOAD) can present heterogeneously, with several subtypes recognized, including dysexecutive AD. One way to identify people with dysexecutive AD is to consider the difference between memory and executive functioning, which we refer to as the executive prominent/memory prominent spectrum. We aimed to determine if this spectrum was heritable. We used neuropsychological and genetic data from people with mild LOAD (Clinical Dementia Rating 0.5 or 1.0) from the National Alzheimer's Coordinating Center and the Alzheimer's Disease Neuroimaging Initiative. We cocalibrated the neuropsychological data to obtain executive functioning and memory scores and used their difference as a continuous phenotype to calculate its heritability overall and by chromosome. Narrow-sense heritability of the difference between memory and executive functioning scores was 0.68 (standard error 0.12). Single nucleotide polymorphisms on chromosomes 1, 2, 4, 11, 12, and 18 explained the largest fraction of phenotypic variance, with signals from each chromosome accounting for 5%-7%. The chromosomal pattern of heritability differed substantially from that of LOAD itself.

  3. The Heritability of Breast Cancer among women in the Nordic Twin Study of Cancer

    DEFF Research Database (Denmark)

    Möller, Sören; Mucci, Lorelei A; Harris, Jennifer R;

    2016-01-01

    and heritability of breast cancer among 21,054 monozygotic and 30,939 dizygotic female twin pairs from the Nordic Twin Study of Cancer, the largest twin study of cancer in the world. We accounted for left-censoring, right-censoring, as well as the competing risk of death. Results From 1943 through 2010, 3...

  4. Heritability of feather pecking and open-field response of laying hens at two different ages

    NARCIS (Netherlands)

    Rodenburg, T.B.; Buitenhuis, A.J.; Ask, B.; Uitdehaag, K.A.; Koene, P.; Poel, van der J.J.; Bovenhuis, H.

    2003-01-01

    The objective of the current study was to estimate heritabilities. (h(2)) of feather pecking and open-field response of laying hens at two different ages. An F-2 cross, originating from a high and a low feather pecking line of laying hens, was used for the experiment. Each of the 630 birds of the F-

  5. Appetitive operant conditioning in mice: heritability and dissociability of training stages

    NARCIS (Netherlands)

    Malkki, H.A.I.; Donga, L.A.B.; de Groot, S.E.; Battaglia, F.P.; Brussaard, A.B.; Borst, J.G.G.; Elgersma, Y.; Galjart, N.; van der Horst, G.T.; Levelt, C.N.; Pennartz, C.M.A.; Smit, A.B.; Spruijt, B.M.; Verhage, M.; de Zeeuw, C.I.

    2010-01-01

    To study the heritability of different training stages of appetitive operant conditioning, we carried out behavioral screening of 5 standard inbred mouse strains, 28 recombinant-inbred (BxD) mouse lines and their progenitor strains C57BL/6J and DBA/2J. We also computed correlations between

  6. Variability in the heritability of body mass index: a systematic review and meta-regression

    Directory of Open Access Journals (Sweden)

    Cathy E Elks

    2012-02-01

    Full Text Available Evidence for a major role of genetic factors in the determination of body mass index (BMI comes from studies of related individuals. However, heritability estimates for BMI vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified eighty-eight independent estimates of BMI heritability from twin studies (total 140,525 twins and twenty-seven estimates from family studies (42,968 family members. BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87 and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68. Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P=0.001 higher in children than in adults; estimates increased with mean age among childhood studies (+0.012 per year, P=0.002, but decreased with mean age in adult studies (-0.002 per year, P=0.002. Heritability estimates derived from AE twin models (which assume no contribution of shared environment were 0.12 higher than those from ACE models (P<0.001, whilst lower estimates were associated with self-reported versus DNA-based determination of zygosity (-0.04, P=0.02, and with self-reported versus measured BMI (-0.05, P=0.03. Together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.

  7. Heritability of the Severity of the Metabolic Syndrome in Whites and Blacks in 3 Large Cohorts.

    Science.gov (United States)

    Musani, Solomon K; Martin, Lisa J; Woo, Jessica G; Olivier, Michael; Gurka, Matthew J; DeBoer, Mark D

    2017-04-01

    Although dichotomous criteria for the metabolic syndrome (MetS) appear heritable, it is not known whether MetS severity as assessed by a continuous MetS score is heritable and whether this varies by race. We used SOLAR (Sequential Oligogenic Linkage Analysis Routines) to evaluate heritability of Adult Treatment Panel-III MetS and a sex- and race-specific MetS severity Z score among 3 large familial cohorts: the JHS (Jackson Heart Study, 1404 black participants), TOPS (Take Off Pounds Sensibly, 1947 white participants), and PLRS (Princeton Lipid Research Study, 229 black and 527 white participants). Heritability estimates were larger for Adult Treatment Panel-III MetS among black compared with white cohort members (JHS 0.48; 95% confidence interval [CI], 0.28-0.68 and PLRS blacks 0.93 [95% CI, 0.73-1.13] versus TOPS 0.21 [95% CI, -0.18 to 0.60] and PLRS whites 0.27 [95% CI, -0.04 to 0.58]). The difference by race narrowed when assessing heritability of the MetS severity score (JHS 0.52 [95% CI, 0.38, 0.66] and PLRS blacks 0.64 [95% CI, 0.13-1.15] versus TOPS 0.23 [95% CI, 0.15-0.31] and PLRS whites 0.60 [95% CI, 0.33-0.87]). There was a high degree of genetic and phenotypic correlation between MetS severity and the individual components of MetS among all groups, although the genetic correlations failed to reach statistical significance among PLRS blacks. Meta-analyses revealed a combined heritability estimate for Adult Treatment Panel-III MetS of 0.24 (95% CI, 0.11-0.36) and for the MetS severity score of 0.50 (95% CI, -0.05 to 0.99). MetS severity seems highly heritable among whites and blacks. This continuous MetS severity Z score may provide a more useful means of characterizing phenotypic MetS in genetic studies by minimizing racial differences. © 2017 American Heart Association, Inc.

  8. The heritability of glaucoma-related traits corneal hysteresis, central corneal thickness, intraocular pressure, and choroidal blood flow pulsatility.

    Directory of Open Access Journals (Sweden)

    Ellen E Freeman

    Full Text Available PURPOSE: The purpose of this work was to investigate the heritability of potential glaucoma endophenotypes. We estimated for the first time the heritability of the pulsatility of choroidal blood flow. We also sought to confirm the heritability of corneal hysteresis, central corneal thickness, and 3 ways of measuring intraocular pressure. METHODS: Measurements were performed on 96 first-degree relatives recruited from Maisonneuve-Rosemont Hospital in Montreal. Corneal hysteresis was determined using the Reichert Ocular Response Analyser. Central corneal thickness was measured with an ultrasound pachymeter. Three measures of intraocular pressure were obtained: Goldmann-correlated and corneal compensated intraocular pressure using the Ocular Response Analyser, and Pascal intraocular pressure using the Pascal Dynamic Contour Tonometer. The pulsatility of choroidal blood velocity and flow were measured in the sub-foveolar choroid using single-point laser Doppler flowmetry (Oculix. We estimated heritability using maximum-likelihood variance components methods implemented in the SOLAR software. RESULTS: No significant heritability was detected for the pulsatility of choroidal blood flow or velocity. The Goldman-correlated, corneal compensated, and Pascal measures of intraocular pressure measures were all significantly heritable at 0.94, 0.79, and 0.53 after age and sex adjustment (p = 0.0003, p = 0.0023, p = 0.0239. Central corneal thickness was significantly heritable at 0.68 (p = 0.0078. Corneal hysteresis was highly heritable but the estimate was at the upper boundary of 1.00 preventing us from giving a precise estimate. CONCLUSION: Corneal hysteresis, central corneal thickness, and intraocular pressure are all heritable and may be suitable as glaucoma endophenotypes. The pulsatility of choroidal blood flow and blood velocity were not significantly heritable in this sample.

  9. Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis.

    Science.gov (United States)

    Alexander, Eileen S; Martin, Lisa J; Collins, Margaret H; Kottyan, Leah C; Sucharew, Heidi; He, Hua; Mukkada, Vincent A; Succop, Paul A; Abonia, J Pablo; Foote, Heather; Eby, Michael D; Grotjan, Tommie M; Greenler, Alexandria J; Dellon, Evan S; Demain, Jeffrey G; Furuta, Glenn T; Gurian, Larry E; Harley, John B; Hopp, Russell J; Kagalwalla, Amir; Kaul, Ajay; Nadeau, Kari C; Noel, Richard J; Putnam, Philip E; von Tiehl, Karl F; Rothenberg, Marc E

    2014-11-01

    Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown. To quantify the risk associated with genes and environment on familial clustering of EoE. Family history was obtained from a hospital-based cohort of 914 EoE probands (n = 2192 first-degree "Nuclear-Family" relatives) and an international registry of monozygotic and dizygotic twins/triplets (n = 63 EoE "Twins" probands). Frequencies, recurrence risk ratios (RRRs), heritability, and twin concordance were estimated. Environmental exposures were preliminarily examined. Analysis of the Nuclear-Family-based cohort revealed that the rate of EoE, in first-degree relatives of a proband, was 1.8% (unadjusted) and 2.3% (sex-adjusted). RRRs ranged from 10 to 64, depending on the family relationship, and were higher in brothers (64.0; P = .04), fathers (42.9; P = .004), and males (50.7; P Twins cohort, genetic heritability was 14.5% ± 4.0% (P twins was 57.9% ± 9.5% compared with 36.4% ± 9.3% in dizygotic co-twins (P = .11). Greater birth weight difference between twins (P = .01), breast-feeding (P = .15), and fall birth season (P = .02) were associated with twin discordance in disease status. EoE RRRs are increased 10- to 64-fold compared with the general population. EoE in relatives is 1.8% to 2.4%, depending on relationship and sex. Nuclear-Family heritability appeared to be high (72.0%). However, the Twins cohort analysis revealed a powerful role for common environment (81.0%) compared with additive genetic heritability (14.5%). Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  10. Sexual variation in heritability and genetic correlations of morphological traits in house sparrow (Passer domesticus).

    Science.gov (United States)

    Jensen, H; Saether, B E; Ringsby, T H; Tufto, J; Griffith, S C; Ellegren, H

    2003-11-01

    Estimates of genetic components are important for our understanding of how individual characteristics are transferred between generations. We show that the level of heritability varies between 0.12 and 0.68 in six morphological traits in house sparrows (Passer domesticus L.) in northern Norway. Positive and negative genetic correlations were present among traits, suggesting evolutionary constraints on the evolution of some of these characters. A sexual difference in the amount of heritable genetic variation was found in tarsus length, wing length, bill depth and body condition index, with generally higher heritability in females. In addition, the structure of the genetic variance-covariance matrix for the traits differed between the sexes. Genetic correlations between males and females for the morphological traits were however large and not significantly different from one, indicating that sex-specific responses to selection will be influenced by intersexual differences in selection differentials. Despite this, some traits had heritability above 0.1 in females, even after conditioning on the additive genetic covariance between sexes and the additive genetic variances in males. Moreover, a meta-analysis indicated that higher heritability in females than in males may be common in birds. Thus, this indicates sexual differences in the genetic architecture of birds. Consequently, as in house sparrows, the evolutionary responses to selection will often be larger in females than males. Hence, our results suggest that sex-specific additive genetic variances and covariances, although ignored in most studies, should be included when making predictions of evolutionary changes from standard quantitative genetic models.

  11. CLASSIFICATION OF GROUND BEETLES (COLEOPTERA, CARABIDAE IN SPECIES AND GENERA USING ASC-ANALYSIS OF THEIR IMAGES

    Directory of Open Access Journals (Sweden)

    Lutsenko Y. V.

    2016-09-01

    considered the further possibility of using the method of ASC- analysis to classify insects, not only in species but also in genera, orders, thereby increasing the reliability of determination of ground beetles, which will be done in this article. A numerical example is given. We also have gained a successful experience of solving such problems in other subject areas. This article can be considered as a continuation of the series of works dedicated to governmental use of the automated system-cognitive analysis (ASC-analysis and its software tools – the system of "Eidos"

  12. Impacto da estocagem sobre atividade antioxidante e teor de ácido ascórbico em sucos e refrescos de tangerina

    Directory of Open Access Journals (Sweden)

    Carolina Ferraz Figueiredo Moreira

    2012-12-01

    Full Text Available OBJETIVO: Objetivou-se avaliar a estabilidade do ácido ascórbico em suco in natura de tangerina cultivar Ponkan sob diferentes condições de armazenamento, e em 13 amostras de bebidas industrializadas de tangerina, bem como a estabilidade da atividade antioxidante no suco in natura. MÉTODOS: O suco in natura de tangerina foi armazenado em três temperaturas: ambiente, refrigeração e congelamento. Amostras de tangerinas foram armazenadas sob refrigeração. Treze marcas de bebidas industrializadas de tangerina foram adquiridas e mantidas sob refrigeração. Foram determinados o teor de ácido ascórbico pelo método titulométrico de Tillmans (Association of Official Analytical Chemists e a atividade antioxidante por meio da capacidade sequestradora do radical 2,2-difenil-1-picril-hidrazila. RESULTADOS: O suco in natura apresentou teor médio de ácido ascórbico de 32,40mg/100mL; a taxa de redução deste nutriente foi maior em temperatura de estocagem mais elevada. A atividade antioxidante média foi de 89,74% de inibição do radical 2,2-difenil-1-picril-hidrazila, apresentando variações de até 4,26% durante o armazenamento. Nas bebidas industrializadas, o teor médio de ácido ascórbico variou entre 1,01 e 10,72mg/100mL, com perdas de até 82,76%. Com base na legislação brasileira, seis marcas de bebidas industrializadas apresentaram não conformidades em relação à declaração do teor de ácido ascórbico nos rótulos. CONCLUSÃO: O suco de tangerina cultivar Ponkan apresenta elevada atividade antioxidante, inclusive durante o armazenamento. Observou-se superioridade nutricional do suco fresco em comparação às bebidas industrializadas, considerando o teor de ácido ascórbico e sua estabilidade. Adicionalmente, os dados obtidos apontam para a necessidade de maior fiscalização em relação à rotulagem nutricional.

  13. The deoxyhypusine synthase mutant dys1-1 reveals the association of eIF5A and Asc1 with cell wall integrity.

    Directory of Open Access Journals (Sweden)

    Fabio Carrilho Galvão

    Full Text Available The putative eukaryotic translation initiation factor 5A (eIF5A is a highly conserved protein among archaea and eukaryotes that has recently been implicated in the elongation step of translation. eIF5A undergoes an essential and conserved posttranslational modification at a specific lysine to generate the residue hypusine. The enzymes deoxyhypusine synthase (Dys1 and deoxyhypusine hydroxylase (Lia1 catalyze this two-step modification process. Although several Saccharomyces cerevisiae eIF5A mutants have importantly contributed to the study of eIF5A function, no conditional mutant of Dys1 has been described so far. In this study, we generated and characterized the dys1-1 mutant, which showed a strong depletion of mutated Dys1 protein, resulting in more than 2-fold decrease in hypusine levels relative to the wild type. The dys1-1 mutant demonstrated a defect in total protein synthesis, a defect in polysome profile indicative of a translation elongation defect and a reduced association of eIF5A with polysomes. The growth phenotype of dys1-1 mutant is severe, growing only in the presence of 1 M sorbitol, an osmotic stabilizer. Although this phenotype is characteristic of Pkc1 cell wall integrity mutants, the sorbitol requirement from dys1-1 is not associated with cell lysis. We observed that the dys1-1 genetically interacts with the sole yeast protein kinase C (Pkc1 and Asc1, a component of the 40S ribosomal subunit. The dys1-1 mutant was synthetically lethal in combination with asc1Δ and overexpression of TIF51A (eIF5A or DYS1 is toxic for an asc1Δ strain. Moreover, eIF5A is more associated with translating ribosomes in the absence of Asc1 in the cell. Finally, analysis of the sensitivity to cell wall-perturbing compounds revealed a more similar behavior of the dys1-1 and asc1Δ mutants in comparison with the pkc1Δ mutant. These data suggest a correlated role for eIF5A and Asc1 in coordinating the translational control of a subset of m

  14. The deoxyhypusine synthase mutant dys1-1 reveals the association of eIF5A and Asc1 with cell wall integrity.

    Science.gov (United States)

    Galvão, Fabio Carrilho; Rossi, Danuza; Silveira, Wagner da Silva; Valentini, Sandro Roberto; Zanelli, Cleslei Fernando

    2013-01-01

    The putative eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein among archaea and eukaryotes that has recently been implicated in the elongation step of translation. eIF5A undergoes an essential and conserved posttranslational modification at a specific lysine to generate the residue hypusine. The enzymes deoxyhypusine synthase (Dys1) and deoxyhypusine hydroxylase (Lia1) catalyze this two-step modification process. Although several Saccharomyces cerevisiae eIF5A mutants have importantly contributed to the study of eIF5A function, no conditional mutant of Dys1 has been described so far. In this study, we generated and characterized the dys1-1 mutant, which showed a strong depletion of mutated Dys1 protein, resulting in more than 2-fold decrease in hypusine levels relative to the wild type. The dys1-1 mutant demonstrated a defect in total protein synthesis, a defect in polysome profile indicative of a translation elongation defect and a reduced association of eIF5A with polysomes. The growth phenotype of dys1-1 mutant is severe, growing only in the presence of 1 M sorbitol, an osmotic stabilizer. Although this phenotype is characteristic of Pkc1 cell wall integrity mutants, the sorbitol requirement from dys1-1 is not associated with cell lysis. We observed that the dys1-1 genetically interacts with the sole yeast protein kinase C (Pkc1) and Asc1, a component of the 40S ribosomal subunit. The dys1-1 mutant was synthetically lethal in combination with asc1Δ and overexpression of TIF51A (eIF5A) or DYS1 is toxic for an asc1Δ strain. Moreover, eIF5A is more associated with translating ribosomes in the absence of Asc1 in the cell. Finally, analysis of the sensitivity to cell wall-perturbing compounds revealed a more similar behavior of the dys1-1 and asc1Δ mutants in comparison with the pkc1Δ mutant. These data suggest a correlated role for eIF5A and Asc1 in coordinating the translational control of a subset of mRNAs associated with cell

  15. ADAPTIVE SYNTHESIS OF INTELLIGENT MEASUREMENT SYSTEMS WITH THE USE OF ASC-ANALYSIS AND "EIDOS" SYSTEM. SYSTEM IDENTIFICATION IN ECONOMETRICS, BIOMETRICS, ECOLOGY, PEDAGOGY, PSYCHOLOGY AND MEDICINE

    Directory of Open Access Journals (Sweden)

    Lutsenko Y. V.

    2016-02-01

    Full Text Available The article proposes using the automated system-cognitive analysis (ASC-analysis and its software tool, which is the system called "Eidos" for synthesis and application of adaptive intelligent measuring systems to measure values of parameters of objects, and for system state identification of complex multivariable nonlinear dynamic systems. The article briefly describes the mathematical method of ASC-analysis, implemented in the software tool – universal cognitive analytical system named "Eidos-X++". The mathematical method of ASC-analysis is based on system theory of information (STI which was created in the conditions of implementation of program ideas of generalizations of all the concepts of mathematics, in particularly, the information theory based on the set theory, through a total replacement of the concept of “many” with the more general concept of system and detailed tracking of all the consequences of this replacement. Due to the mathematical method, which is the basis of ASC-analysis, this method is nonparametric and allows you to process comparably tens and hundreds of thousands of gradations of factors and future conditions of the control object (class in incomplete (fragmented, noisy data numeric and non-numeric nature which are measured in different units of measurement. We provide a detailed numerical example of the application of ASC-analysis and the system of "Eidos-X++" as a synthesis of systemic-cognitive model, providing a multiparameter typization of the states of complex systems, and system identification of their states, as well as for making decisions about managing the impact of changing the composition of the control object to get its quality (level of consistency maximally increased at minimum cost. For a numerical example of a complex system we have selected the team of the company, and its component – employees and applicants (staff. However, it must be noted that this example should be considered even wider

  16. Face recognition method fusing Monogenic magnitude and phase%融合Monogenic幅值和相位的人脸识别方法

    Institute of Scientific and Technical Information of China (English)

    李昆明; 王玲; 闫海停; 刘机福

    2013-01-01

    针对仅利用图像滤波幅值信息进行识别而忽视相位信息的问题,提出一种融合Monogenic局部相位和幅值的识别方法.该方法先对相位进行量化和异或,并结合方向和尺度信息得到相位编码(MLXP);其次,分别对相位编码和基于幅值的二值编码进行分块,计算直方图特征;然后,采用基于分块的线性判别进行降维,提高特征的判别能力;最后在评分层实行融合.在ORL和CAS-PEAL人脸数据库上,相位方法MLXP的平均识别率分别为0.97和0.94,融合Monogenic相位和幅值的方法平均识别率分别为0.99和0.979,超越实验中其他所有方法.实验结果表明,相位利用方法MLXP是有效的,融合Monogenic相位和幅值的方法不但能够避免传统线性判别中的小样本(3S)问题,而且能以较低的时间和空间复杂度,有效地提高身份的正确识别率.%In order to use the magnitude and phase information of filtered image for face recognition,a new method fusing Monogenic local phase and local magnitude was proposed.Firstly,the authors encoded the phase using the exclusive or (XOR) operator,and combined the orientation and scale information.Then the authors divided the phase pattern maps and binary pattern maps based on magnitude into blocks.After that,they extracted the histograms from blocks.Secondly,they used the block-based Fisher principle to reduce the feature dimension and improve the discrimination ability.At last,the authors fused the cosine similarity of magnitude and phase at score level.The phase method Monogenic Local XOR Pattern (MLXP) reached the recognition rate of 0.97 and 0.94,and the fusing method recognition rate was 0.99 and 0.979 on the ORL and CAS-PEAL face databases respectively and the fusing method outperformed all the other methods used in the experiment.The results verify that the MLXP method is effective.And the method fusing the Monogenic magnitude and phase not only avoids the Small Sample Size (3S

  17. The astrocytic transporter SLC7A10 (Asc-1) mediates glycinergic inhibition of spinal cord motor neurons

    Science.gov (United States)

    Ehmsen, Jeffrey T.; Liu, Yong; Wang, Yue; Paladugu, Nikhil; Johnson, Anna E.; Rothstein, Jeffrey D.; du Lac, Sascha; Mattson, Mark P.; Höke, Ahmet

    2016-01-01

    SLC7A10 (Asc-1) is a sodium-independent amino acid transporter known to facilitate transport of a number of amino acids including glycine, L-serine, L-alanine, and L-cysteine, as well as their D-enantiomers. It has been described as a neuronal transporter with a primary role related to modulation of excitatory glutamatergic neurotransmission. We find that SLC7A10 is substantially enriched in a subset of astrocytes of the caudal brain and spinal cord in a distribution corresponding with high densities of glycinergic inhibitory synapses. Accordingly, we find that spinal cord glycine levels are significantly reduced in Slc7a10-null mice and spontaneous glycinergic postsynaptic currents in motor neurons show substantially diminished amplitudes, demonstrating an essential role for SLC7A10 in glycinergic inhibitory function in the central nervous system. These observations establish the etiology of sustained myoclonus (sudden involuntary muscle movements) and early postnatal lethality characteristic of Slc7a10-null mice, and implicate SLC7A10 as a candidate gene and auto-antibody target in human hyperekplexia and stiff person syndrome, respectively. PMID:27759100

  18. Transcriptional signature of human adipose tissue-derived stem cells (hASCs) preconditioned for chondrogenesis in hypoxic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Pilgaard, L.; Lund, P.; Duroux, M. [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark); Lockstone, H.; Taylor, J. [Bioinformatics and Statistical Genetics, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN (United Kingdom); Emmersen, J.; Fink, T. [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark); Ragoussis, J. [Genomics, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN (United Kingdom); Zachar, V., E-mail: vlaz@hst.aau.dk [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark)

    2009-07-01

    Hypoxia is an important factor involved in the control of stem cells. To obtain a better insight into the phenotypical changes brought about by hypoxic preconditioning prior to chondrogenic differentiation; we have investigated growth, colony-forming and chondrogenic capacity, and global transcriptional responses of six adipose tissue-derived stem cell lines expanded at oxygen concentrations ranging from ambient to 1%. The assessment of cell proliferation and colony-forming potential revealed that the hypoxic conditions corresponding to 1% oxygen played a major role. The chondrogenic inducibility, examined by high-density pellet model, however, did not improve on hypoxic preconditioning. While the microarray analysis revealed a distinctive inter-donor variability, the exposure to 1% hypoxia superseded the biological variability and produced a specific expression profile with 2581 significantly regulated genes and substantial functional enrichment in the pathways of cell proliferation and apoptosis. Additionally, exposure to 1% oxygen resulted in upregulation of factors related to angiogenesis and cell growth. In particular, leptin (LEP), the key regulator of body weight and food intake was found to be highly upregulated. In conclusion, the results of this investigation demonstrate the significance of donor demographics and the importance of further studies into the use of regulated oxygen tension as a tool for preparation of ASCs in order to exploit their full potential.

  19. Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds.

    Science.gov (United States)

    Temple, Joshua P; Hutton, Daphne L; Hung, Ben P; Huri, Pinar Yilgor; Cook, Colin A; Kondragunta, Renu; Jia, Xiaofeng; Grayson, Warren L

    2014-12-01

    The treatment of large craniomaxillofacial bone defects is clinically challenging due to the limited availability of transplantable autologous bone grafts and the complex geometry of the bones. The ability to regenerate new bone tissues that faithfully replicate the anatomy would revolutionize treatment options. Advances in the field of bone tissue engineering over the past few decades offer promising new treatment alternatives using biocompatible scaffold materials and autologous cells. This approach combined with recent advances in three-dimensional (3D) printing technologies may soon allow the generation of large, bioartificial bone grafts with custom, patient-specific architecture. In this study, we use a custom-built 3D printer to develop anatomically shaped polycaprolactone (PCL) scaffolds with varying internal porosities. These scaffolds are assessed for their ability to support induction of human adipose-derived stem cells (hASCs) to form vasculature and bone, two essential components of functional bone tissue. The development of functional tissues is assessed in vitro and in vivo. Finally, we demonstrate the ability to print large mandibular and maxillary bone scaffolds that replicate fine details extracted from patient's computed tomography scans. The findings of this study illustrate the capabilities and potential of 3D printed scaffolds to be used for engineering autologous, anatomically shaped, vascularized bone grafts.

  20. Heritability estimate of yearling and post-yearling muscle index in Nellore cattle

    Directory of Open Access Journals (Sweden)

    Carolina Cesarino Coutinho

    2013-12-01

    Full Text Available The objective of this study was to estimate heritability of carcass muscle index (MI in yearling (MIy and post-yearling (MIp Nellore cattle. MI is the measure of longissimus muscle area (LMA expressed in relation to body weight (MI=100×LMA/BW, being an indicative of animal muscularity. The records of LMA, obtained by ultrasound, and body weight (BW were from the three Nellore herds reared at Centro APTA Bovinos de Corte, Instituto de Zootecnia, Sertãozinho-SP, born between 1999 to 2011, excepting 1998, 2000 and 2003. The measures were collected when the animals were on average 372 ± 26 days (yearling and 562 ± 33 days (post-yearling of age. The animals are progeny of 163 bulls and relationship matrix included 3436 animals. Variance components were estimated by REML in two single-trait analyses. The model included the fixed effects of contemporary group (herd-year-sex, i=1, …, 48, month of birth (j=1, …, 3 and dam age (linear and quadratic effects and animal age at measurement (linear effect, and random effects of animal and residual. The average of LMA and BW were: 48.4 ± 10.7 cm² and 287±59 kg; 50.5 ± 9.2 cm² and 339 ± 64 kg, respectively for yearling and post-yearling. Despite the differences between yearling and post-yearling LMA and BW (plus 2.2 cm ² and 52 kg at post-yearling than yearling, the same was not observed for MI. BW has increased from yearling to post-yearling, LMA has not increased proportionally, and MIps was smaller than MIy. The heritability estimates for IMy and IMp were medium to high magnitude indicating that part of the variation in these traits are attributable to genes of additive effects. In previous studies, the heritability of LMA at yearling was also higher than heritability of LMA at post-yearling, however, heritability of yearling weight was lower than heritability of post-yearling weight. More studies are required to estimate genetic correlations of MIy and MIp and weight and percentage of retail

  1. Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis

    Science.gov (United States)

    Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah; Sucharew, Heidi; He, Hua; Mukkada, Vincent A.; Succop, Paul A.; Abonia, J. Pablo; Foote, Heather; Eby, Michael D.; Grotjan, Tommie M.; Greenler, Alexandria J.; Dellon, Evan S.; Demain, Jeffrey G.; Furuta, Glenn T.; Gurian, Larry E.; Harley, John B.; Hopp, Russell J.; Kaul, Ajay; Nadeau, Kari C.; Noel, Richard J.; Putnam, Philip E.; von Tiehl, Karl F.; Rothenberg, Marc E.

    2014-01-01

    Background Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown. Objective To quantify risk associated with genes and environment on familial clustering of EoE. Methods Family history was obtained from a hospital-based cohort of 914 EoE probands, (n=2192 first-degree “Nuclear-Family” relatives) and the new international registry of monozygotic and dizygotic twins/triplets (n=63 EoE “Twins” probands). Frequencies, recurrence risk ratios (RRRs), heritability and twin concordance were estimated. Environmental exposures were preliminarily examined. Results Analysis of the Nuclear-Family–based cohort revealed that the rate of EoE, in first-degree relatives of a proband, was 1.8% (unadjusted) and 2.3% (sex-adjusted). RRRs ranged from 10–64, depending on the family relationship, and were higher in brothers (64.0; p=0.04), fathers (42.9; p=0.004) and males (50.7; p<0.001) compared to sisters, mothers and females, respectively. Risk of EoE for other siblings was 2.4%. In the Nuclear-Families, combined gene and common environment heritability (hgc2) was 72.0±2.7% (p<0.001). In the Twins cohort, genetic heritability was 14.5±4.0% (p<0.001), and common family environment contributed 81.0±4% (p<0.001) to phenotypic variance. Proband-wise concordance in MZ co-twins was 57.9±9.5% compared to 36.4±9.3% in DZ (p=0.11). Greater birth-weight difference between twins (p=0.01), breastfeeding (p=0.15) and Fall birth season (p=0.02) were associated with twin discordance in disease status. Conclusions EoE recurrence risk ratios are increased 10–64-fold compared with the general population. EoE in relatives is 1.8–2.4%, depending upon relationship and sex. Nuclear-Family heritability appeared to be high (72.0%). However, Twins cohort analysis revealed a powerful role for common environment (81

  2. Unpacking the heritability of diabetes: The problem of attempting to quantify the relative contributions of nature and nuture

    OpenAIRE

    Chaufan, Claudia MD, PhD

    2008-01-01

    In this paper I analyze the concept of heritability as used technically in medical research. I use diabetes as a paradigmatic “common disease” whose heritability is computed with a view to disentangling the relative contributions of “nature” and “nurture”. I show what heritability measures and what it does not, and theorize about the scope of application of this measurement for diabetes-relevant medical research, health care practices, and public health policies. I argue that this analysis ap...

  3. Network protocol changes can improve DisCom WAN performance : evaluating TCP modifications and SCTP in the ASC tri-lab environment.

    Energy Technology Data Exchange (ETDEWEB)

    Tolendino, Lawrence F.; Hu, Tan Chang

    2005-06-01

    The Advanced Simulation and Computing (ASC) Distance Computing (DisCom) Wide Area Network (WAN) is a high performance, long distance network environment that is based on the ubiquitous TCP/IP protocol set. However, the Transmission Control Protocol (TCP) and the algorithms that govern its operation were defined almost two decades ago for a network environment vastly different from the DisCom WAN. In this paper we explore and evaluate possible modifications to TCP that purport to improve TCP performance in environments like the DisCom WAN. We also examine a much newer protocol, SCTP (Stream Control Transmission Protocol) that claims to provide reliable network transport while also implementing multi-streaming, multi-homing capabilities that are appealing in the DisCom high performance network environment. We provide performance comparisons and recommendations for continued development that will lead to network communications protocol implementations capable of supporting the coming ASC Petaflop computing environments.

  4. Heritability and environmental effects for self-reported periods with stuttering: A twin study from Denmark

    DEFF Research Database (Denmark)

    Fagnani, Corrado; Fibiger, Steen; Skytthe, Axel;

    2011-01-01

    Genetic influence for stuttering was studied based on adult self-reporting. Using nation-wide questionnaire answers from 33,317 Danish twins, a univariate biometric analysis based on the liability threshold model was performed in order to estimate the heritability of stuttering. The self......-reported incidences for stuttering were from less than 4% for females to near 9% for males. Both probandwise concordance rate and tetrachoric correlation were substantially higher for monozygotic compared to dizygotic pairs, indicating substantial genetic influence on individual liability. Univariate biometric...... analyses showed that additive genetic and unique environmental factors best explained the observed concordance patterns. Heritability estimates for males/females were 0.84/0.81. Moderate unique environmental effects were also found. Genetic influence for stuttering was studied based on adult self...

  5. Heritability and genetic trends of number of kits born alive in a synthetic maternal rabbit line

    Directory of Open Access Journals (Sweden)

    Zsolt Szendrő

    2010-01-01

    Full Text Available Heritability and genetic trends for number of kits born alive in a synthetic maternal rabbit line were estimated in this study. The data were collected from 1999 to 2007 on 5640 kindlings of 1425 does. The total number of animals in the pedigree was 2576. The mean number of kits born alive was 8.42 with a standard deviation of 2.87. Genetic parameters and breeding values were estimated using the VCE-5 and PEST software based on the REML and BLUP methods using a repeatability animal model. For litter size, the first, second and third parities were treated as repeated trait, while the fourth and further parities were pooled and considered as same repetition. The estimated heritability and the repeatability for number of kits born alive were low (0.05 and 0.14. The observed selection response was about 0.04 rabbits/year.

  6. The Tapestry of Life: Lateral Transfers of Heritable Elements - Scientific Meeting

    Energy Technology Data Exchange (ETDEWEB)

    Claire M. Fraser, Ph.D.

    2005-12-31

    The Sackler Colloquium The Tapestry of Life: Lateral Transfers of Heritable Elements was held on December 12-13, 2005. What Darwin saw as a tree of life descending in a linear fashion, is now more accurately seen as a tapestry of life, an anastomosing network, with important lateral transfers of heritable elements among parallel lines of descent These transfers range in complexity from small insertion sequences, to whole genes, gene islands, and portions of whole genomes which may be combined in symbiogenesis. The colloquium brought together researchers, empirical and theoretical, working at all levels on genomics, comparative genomics, and metagenomics to identify common and differentiating features of lateral gene transfer and to examine their implications for science and for human concerns.

  7. Estrus Traits Derived from Activity Measurements are Heritable and Closely Related to Conventional

    DEFF Research Database (Denmark)

    Ismael, Ahmed Ismael Sayed; Kargo, Morten; Fogh, Anders

    This study was aimed at assessing the genetic parameters for fertility-related traits, comparing the interval from calving to first insemination (ICF) to physical activity traits, especially days from calving to first high activity, DFHA. Data from commercial Holstein herds included insemination...... dates of 11,363 cows for ICF. The activity traits were derived from electronic activity tags for 3533 Holstein cows. Estimates of heritability were 0.05 for ICF and 0.15 for DFHA. The genetic correlation between ICF and DFHA was strong (0.92). The high heritability estimate and the strong genetic...... correlation between ICF and DFHA suggest that genetic gain in ICF can be improved by including DFHA as a supplementary trait in the genetic evaluation of female fertility...

  8. Heritability and environmental effects for self-reported periods with stuttering: A twin study from Denmark

    DEFF Research Database (Denmark)

    Fagnani, Corrado; Fibiger, Steen; Skytthe, Axel

    2011-01-01

    Genetic influence for stuttering was studied based on adult self-reporting. Using nation-wide questionnaire answers from 33,317 Danish twins, a univariate biometric analysis based on the liability threshold model was performed in order to estimate the heritability of stuttering. The self......-reported incidences for stuttering were from less than 4% for females to near 9% for males. Both probandwise concordance rate and tetrachoric correlation were substantially higher for monozygotic compared to dizygotic pairs, indicating substantial genetic influence on individual liability. Univariate biometric...... analyses showed that additive genetic and unique environmental factors best explained the observed concordance patterns. Heritability estimates for males/females were 0.84/0.81. Moderate unique environmental effects were also found. Genetic influence for stuttering was studied based on adult self...

  9. The effect of intraspecific variation and heritability on community pattern and robustness.

    Science.gov (United States)

    Barabás, György; D'Andrea, Rafael

    2016-08-01

    Intraspecific trait variation is widespread in nature, yet its effects on community dynamics are not well understood. Here we explore the consequences of intraspecific trait variation for coexistence in two- and multispecies competitive communities. For two species, the likelihood of coexistence is in general reduced by intraspecific variation, except when the species have almost equal trait means but different trait variances, such that one is a generalist and the other a specialist consumer. In multispecies communities, the only strong effect of non-heritable intraspecific variation is to reduce expected species richness. However, when intraspecific variation is heritable, allowing for the possibility of trait evolution, communities are much more resilient against environmental disturbance and exhibit far more predictable trait patterns. Our results are robust to varying model parameters and relaxing model assumptions.

  10. Using genetic markers in unpedigreed populations to detect a heritable trait

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Before a breeder invests selection pressure on a trait of interest, it needs to be established whether that trait is actually heritable. Some traits may not have been measured widely in pedigreed populations, for example, a disease or deformity may become more prevalent than previously, but is still relatively rare. One approach to detect inheritance would be to screen a commercial population to obtain a sample of "affecteds" (the test group) and to also obtain a random control group. These individuals are then genotyped with a set of genetic markers and the relationships between individuals within each group estimated. If the relatedness is higher in the test group than in the control group, this provides initial evidence for the trait being heritable. A power simulation shows that this approach is feasible with moderate resources.

  11. Twin study of heritability of eating bread in Danish and Finnish men and women

    DEFF Research Database (Denmark)

    Hasselbalch, Ann Louise; Silventoinen, Karri; Keskitalo, Kaisu;

    2010-01-01

    Bread is an elementary part of the western diet, and especially rye bread is regarded as an important source of fibre. We investigated the heritability of eating bread in terms of choice of white and rye bread and use-frequency of bread in female and male twins in Denmark and Finland. The study...... cohorts included 575 Danish (age range 18-67 years) and 2009 Finnish (age range 22-27 years) adult twin pairs. Self-reported frequency of eating bread was obtained by food frequency questionnaires. Univariate models based on linear structural equations for twin data were used to estimate the relative...... magnitude of the additive genetic, shared environmental and individual environmental effects on bread eating frequency and choice of bread. The analysis of bread intake frequency demonstrated moderate heritability ranging from 37-40% in the Finnish cohort and 23-26% in the Danish cohort. The genetic...

  12. Heritability estimates for methane emission in Holstein cows using breath measurements

    DEFF Research Database (Denmark)

    Lassen, Jan; Madsen, Jørgen; Løvendahl, Peter

    2012-01-01

    Enteric methane emission from ruminants contributes substantially to the greenhouse effect. Few studies have focused on the genetic variation in enteric methane emission from dairy cattle. The objective of this study was to estimate the heritability for enteric methane emission from Danish Holstein...... of economic importance in the breeding goal as well as the possibility to use methane as an indicator of feed efficiency. It is concluded that FTIR breath analysis is effective for measuring GHG emissions and may find further applications with a wider panel of gases including acetone and its relation...... model included fixed effects of herd, month, days in milk, lactation number, and random effects of animal and residual. Variance components were estimated in an animal model design using a pedigree containing 9661 animals. The heritability of the methane to carbon dioxide ratio was moderate (0...

  13. Heritable and precise zebrafish genome editing using a CRISPR-Cas system.

    Directory of Open Access Journals (Sweden)

    Woong Y Hwang

    Full Text Available We have previously reported a simple and customizable CRISPR (clustered regularly interspaced short palindromic repeats RNA-guided Cas9 nuclease (RGN system that can be used to efficiently and robustly introduce somatic indel mutations in endogenous zebrafish genes. Here we demonstrate that RGN-induced mutations are heritable, with efficiencies of germline transmission reaching as high as 100%. In addition, we extend the power of the RGN system by showing that these nucleases can be used with single-stranded oligodeoxynucleotides (ssODNs to create precise intended sequence modifications, including single nucleotide substitutions. Finally, we describe and validate simple strategies that improve the targeting range of RGNs from 1 in every 128 basepairs (bps of random DNA sequence to 1 in every 8 bps. Together, these advances expand the utility of the CRISPR-Cas system in the zebrafish beyond somatic indel formation to heritable and precise genome modifications.

  14. A note on the heritability of reactivity assessed at field tests for Danish Warmblood horses

    DEFF Research Database (Denmark)

    Nielsen, Janne Rothmann; Christensen, Ole Fredslund; Søndergaard, Eva

    2014-01-01

    Temperament traits in horses, especially reactivity, are an important trait in relation to human–horse accidents and the welfare of the horses. However, so far, temperament is often not included in many horse breeding programs. Most of the behavioral genetic studies in horses have been based......, a high standard error was untainted. Nevertheless, results suggested a genetic variation of reactivity when assessed at field tests, but further research is needed before reactivity can be incorporated as a selection criteria into a breeding program....... on indirect indications of a sire effect and not on estimations of the heritability of temperament traits. Therefore, the aim of this study was to estimate the heritability of behavior reactions related to reactivity observed in a practical situation, that is, during the evaluation of the conformation...

  15. Heritability of pain catastrophizing and associations with experimental pain outcomes: a twin study.

    Science.gov (United States)

    Trost, Zina; Strachan, Eric; Sullivan, Michael; Vervoort, Tine; Avery, Ally R; Afari, Niloofar

    2015-03-01

    This study used a twin paradigm to examine genetic and environmental contributions to pain catastrophizing and the observed association between pain catastrophizing and cold-pressor task (CPT) outcomes. Male and female monozygotic (n = 206) and dizygotic twins (n = 194) from the University of Washington Twin Registry completed a measure of pain catastrophizing and performed a CPT challenge. As expected, pain catastrophizing emerged as a significant predictor of several CPT outcomes, including cold-pressor Immersion Tolerance, Pain Tolerance, and Delayed Pain Rating. The heritability estimate for pain catastrophizing was found to be 37% with the remaining 63% of variance attributable to unique environmental influence. Additionally, the observed associations between pain catastrophizing and CPT outcomes were not found attributable to shared genetics or environmental exposure, which suggests a direct relationship between catastrophizing and experimental pain outcomes. This study is the first to examine the heritability of pain catastrophizing and potential processes by which pain catastrophizing is related to experimental pain response.

  16. Efecto de la densidad de siembra y la adición de ácido ascórbico en el cultivo de Osteoglossum bicirrhosum

    Directory of Open Access Journals (Sweden)

    Carolina Cuaical T.

    2013-11-01

    Full Text Available Objetivo. Evaluar el efecto de la densidad de siembra y la adición de ácido ascórbico en la alimentación de alevinos de O. bicirrhosum, cultivados en jaulas. Materiales y métodos. Se incluyeron 396 alevinos y se distribuyeron en nueve tratamientos, resultado de la combinación de los niveles del factor densidad de siembra: 1pez/5 L; 1pez/10 L y 1pez/15 L y los niveles de ácido ascórbico: 0; 500 y 1000 mg/kg. Los datos obtenidos se evaluaron mediante el análisis de varianza del diseño factorial 32. Resultados. La densidad de siembra presentó diferencias estadísticas significativas en el incremento de peso. Las variables incremento de longitud y tasa de crecimiento específico no presentaron diferencias estadísticas. En cuanto a la conversión alimenticia aparente, se demostraron diferencias significativas en los dos factores: La densidad de 1pez/10 L indicó la mejor conversión con un valor de 1.50, asimismo, la inclusión de 1000 mg de ácido ascórbico por Kg de alimento mostró los mejores promedios con 1.55. En la sobrevivencia se precisaron diferencias estadísticas entre los tratamientos de la densidad de 1pez/5 L, siendo mejores aquellos que incluyeron ácido ascórbico en la dieta. Conclusiones. La densidad de 1pez/10 L registró el mayor incremento de peso con 31.83 g en 87 días. La sobrevivencia general fue del 96%, lo que demuestra la eficiencia del sistema de cultivo utilizado, al tiempo que actúa de manera positiva en el desarrollo de esta especie.

  17. ASC-J9 Suppresses Castration-Resistant Prostate Cancer Growth through Degradation of Full-length and Splice Variant Androgen Receptors

    Directory of Open Access Journals (Sweden)

    Shinichi Yamashita

    2012-01-01

    Full Text Available Early studies suggested androgen receptor (AR splice variants might contribute to the progression of prostate cancer (PCa into castration resistance. However, the therapeutic strategy to target these AR splice variants still remains unresolved. Through tissue survey of tumors from the same patients before and after castration resistance, we found that the expression of AR3, a major AR splice variant that lacks the AR ligand-binding domain, was substantially increased after castration resistance development. The currently used antiandrogen, Casodex, showed little growth suppression in CWR22Rv1 cells. Importantly, we found that AR degradation enhancer ASC-J9 could degrade both full-length (fAR and AR3 in CWR22Rv1 cells as well as in C4-2 and C81 cells with addition of AR3. The consequences of such degradation of both fAR and AR3 might then result in the inhibition of AR transcriptional activity and cell growth in vitro. More importantly, suppression of AR3 specifically by short-hairpin AR3 or degradation of AR3 by ASC-J9 resulted in suppression of AR transcriptional activity and cell growth in CWR22Rv1-fARKD (fAR knockdown cells in which DHT failed to induce, suggesting the importance of targeting AR3. Finally, we demonstrated the in vivo therapeutic effects of ASC-J9 by showing the inhibition of PCa growth using the xenografted model of CWR22Rv1 cells orthotopically implanted into castrated nude mice with undetectable serum testosterone. These results suggested that targeting both fAR- and AR3-mediated PCa growth by ASC-J9 may represent the novel therapeutic approach to suppress castration-resistant PCa. Successful clinical trials targeting both fAR and AR3 may help us to battle castration-resistant PCa in the future.

  18. DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Marchetti, Francesco; Wryobek, Andrew J

    2008-02-21

    The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7- 1 dbf). Analysis of chromosomalaberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.

  19. DNA Repair Decline During Mouse Spermiogenesis Results in the Accumulation of Heritable DNA Damage

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Marchetti, Francesco; Wyrobek, Andrew J.

    2007-12-01

    The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.

  20. A review and meta-analysis of the heritability of specific phobia subtypes and corresponding fears

    OpenAIRE

    van Houtem, C.M.H.H.; Laine, M.L.; Boomsma, D.I.; Ligthart, L.; van Wijk, A J; De Jongh, A.

    2013-01-01

    Evidence from twin studies suggests that genetic factors contribute to the risk of developing a fear or a phobia. The aim of the present study was to review the current literature regarding twin studies describing the genetic basis of specific phobias and their corresponding fears. The analysis included five twin studies on fears and ten twin studies on specific phobias. Heritability estimates of fear subtypes and specific phobia subtypes both varied widely, even within the subtypes. A meta-a...

  1. Source of variation and heritability of directly measured traits in performance testing of Simmental bulls

    Directory of Open Access Journals (Sweden)

    Bogdanović Vladan

    2012-01-01

    Full Text Available In order to study the variability and heritability of directly measured traits (growth and body development traits in performance test of Simmental bulls the data on 371 bulls born and tested over the period of 13 years were used in the analysis. The data were analyzed in order to estimate year and month of calving, herd of origin and group in test effect as well as error components. The components of variance were obtained using restricted maximum likelihood (REML methodology applied to sire model. The year and month of birth had different effect on the variability of the growth traits, while the herd of origin and the test group manifested a consistent, highly significant effect on those growth traits which they could have an effect on. On the other hand, all the body development traits were under a constant and highly significant effect manifested by the year of calving, while the month of calving manifested its effect, during test, at different levels of statistical significance. A decreased effect of herd of origin on almost all body dimensions from the start until the end of performance test was universally observed. Heritability estimates for pre-test ADG, in-test and lifetime ADG were 0.27, 0.39 and 0.29, respectively. Heritability estimates for body weights were 0.23, 0.25, and 0.30 for birth weight, test-on weight, and test-off weight, respectively. Heritability estimates for test-off height at withers, circumference of chest, depth of chest and body length were 0.43, 0.30, 0.33 and 0.29.

  2. Superparasitism Drives Heritable Symbiont Epidemiology and Host Sex Ratio in a Wasp.

    Directory of Open Access Journals (Sweden)

    Steven R Parratt

    2016-06-01

    Full Text Available Heritable microbial symbionts have profound impacts upon the biology of their arthropod hosts. Whilst our current understanding of the dynamics of these symbionts is typically cast within a framework of vertical transmission only, horizontal transmission has been observed in a number of cases. For instance, several symbionts can transmit horizontally when their parasitoid hosts share oviposition patches with uninfected conspecifics, a phenomenon called superparasitism. Despite this, horizontal transmission, and the host contact structures that facilitates it, have not been considered in heritable symbiont epidemiology. Here, we tested for the importance of host contact, and resulting horizontal transmission, for the epidemiology of a male-killing heritable symbiont (Arsenophonus nasoniae in parasitoid wasp hosts. We observed that host contact through superparasitism is necessary for this symbiont's spread in populations of its primary host Nasonia vitripennis, such that when superparasitism rates are high, A. nasoniae almost reaches fixation, causes highly female biased population sex ratios and consequently causes local host extinction. We further tested if natural interspecific variation in superparasitism behaviours predicted symbiont dynamics among parasitoid species. We found that A. nasoniae was maintained in laboratory populations of a closely related set of Nasonia species, but declined in other, more distantly related pteromalid hosts. The natural proclivity of a species to superparasitise was the primary factor determining symbiont persistence. Our results thus indicate that host contact behaviour is a key factor for heritable microbe dynamics when horizontal transmission is possible, and that 'reproductive parasite' phenotypes, such as male-killing, may be of secondary importance in the dynamics of such symbiont infections.

  3. Heritability and fitness correlates of personality in the Ache, a natural-fertility population in Paraguay.

    Directory of Open Access Journals (Sweden)

    Drew H Bailey

    Full Text Available The current study assessed the heritability of personality in a traditional natural-fertility population, the Ache of eastern Paraguay. Self-reports (n = 110 and other-reports (n = 66 on the commonly used Big Five Personality Inventory (i.e., extraversion, agreeableness, conscientiousness, neuroticism, openness were collected. Self-reports did not support the Five Factor Model developed with Western samples, and did not correlate with other-reports for three of the five measured personality factors. Heritability was assessed using factors that were consistent across self- and other-reports and factors assessed using other-reports that showed reliabilities similar to those found in Western samples. Analyses of these items in combination with a multi-generation pedigree (n = 2,132 revealed heritability estimates similar to those found in most Western samples, although we were not able to separately estimate the influence of the common environment on these traits. We also assessed relations between personality and reproductive success (RS, allowing for a test of several mechanisms that might be maintaining heritable variation in personality. Phenotypic analyses, based largely on other-reports, revealed that extraverted men had higher RS than other men, but no other dimensions of personality predicted RS in either sex. Mothers with more agreeable children had more children, and parents mated assortatively on personality. Of the evolutionary processes proposed to maintain variation in personality, assortative mating, selective neutrality, and temporal variation in selection pressures received the most support. However, the current study does not rule out other processes affecting the evolution and maintenance of individual differences in human personality.

  4. Lambing Ease is Heritable but not Correlated to Litter Size in Danish Meat Sheep Breeds

    DEFF Research Database (Denmark)

    Sørensen, Anders Christian; Valasek, P; Pedersen, Jørn;

    The aim of this study was to estimate genetic parameters of lambing ease (LE) and litter size (LS) in four common Danish meat sheep breeds. Data from 1990 to 2006 were analysed. A bivariate animal model was used for estimation of genetic parameters. Lambing ease showed a low heritability, both...... the LE and LS was found, which means that selection to improve one trait should not affect the other trait. Lambing ease should therefore be included in the selection criterion....

  5. Lessons from model organisms: phenotypic robustness and missing heritability in complex disease.

    Directory of Open Access Journals (Sweden)

    Christine Queitsch

    Full Text Available Genetically tractable model organisms from phages to mice have taught us invaluable lessons about fundamental biological processes and disease-causing mutations. Owing to technological and computational advances, human biology and the causes of human diseases have become accessible as never before. Progress in identifying genetic determinants for human diseases has been most remarkable for Mendelian traits. In contrast, identifying genetic determinants for complex diseases such as diabetes, cancer, and cardiovascular and neurological diseases has remained challenging, despite the fact that these diseases cluster in families. Hundreds of variants associated with complex diseases have been found in genome-wide association studies (GWAS, yet most of these variants explain only a modest amount of the observed heritability, a phenomenon known as "missing heritability." The missing heritability has been attributed to many factors, mainly inadequacies in genotyping and phenotyping. We argue that lessons learned about complex traits in model organisms offer an alternative explanation for missing heritability in humans. In diverse model organisms, phenotypic robustness differs among individuals, and those with decreased robustness show increased penetrance of mutations and express previously cryptic genetic variation. We propose that phenotypic robustness also differs among humans and that individuals with lower robustness will be more responsive to genetic and environmental perturbations and hence susceptible to disease. Phenotypic robustness is a quantitative trait that can be accurately measured in model organisms, but not as yet in humans. We propose feasible approaches to measure robustness in large human populations, proof-of-principle experiments for robustness markers in model organisms, and a new GWAS design that takes differences in robustness into account.

  6. Superparasitism Drives Heritable Symbiont Epidemiology and Host Sex Ratio in a Wasp.

    Directory of Open Access Journals (Sweden)

    Steven R Parratt

    2016-06-01

    Full Text Available Heritable microbial symbionts have profound impacts upon the biology of their arthropod hosts. Whilst our current understanding of the dynamics of these symbionts is typically cast within a framework of vertical transmission only, horizontal transmission has been observed in a number of cases. For instance, several symbionts can transmit horizontally when their parasitoid hosts share oviposition patches with uninfected conspecifics, a phenomenon called superparasitism. Despite this, horizontal transmission, and the host contact structures that facilitates it, have not been considered in heritable symbiont epidemiology. Here, we tested for the importance of host contact, and resulting horizontal transmission, for the epidemiology of a male-killing heritable symbiont (Arsenophonus nasoniae in parasitoid wasp hosts. We observed that host contact through superparasitism is necessary for this symbiont's spread in populations of its primary host Nasonia vitripennis, such that when superparasitism rates are high, A. nasoniae almost reaches fixation, causes highly female biased population sex ratios and consequently causes local host extinction. We further tested if natural interspecific variation in superparasitism behaviours predicted symbiont dynamics among parasitoid species. We found that A. nasoniae was maintained in laboratory populations of a closely related set of Nasonia species, but declined in other, more distantly related pteromalid hosts. The natural proclivity of a species to superparasitise was the primary factor determining symbiont persistence. Our results thus indicate that host contact behaviour is a key factor for heritable microbe dynamics when horizontal transmission is possible, and that 'reproductive parasite' phenotypes, such as male-killing, may be of secondary importance in the dynamics of such symbiont infections.

  7. The heritability of Cluster B personality disorders assessed both by personal interview and questionnaire.

    Science.gov (United States)

    Torgersen, Svenn; Myers, John; Reichborn-Kjennerud, Ted; Røysamb, Espen; Kubarych, Thomas S; Kendler, Kenneth S

    2012-12-01

    Whereas the heritability of common personality traits has been firmly established, the results of the few published studies on personality disorders (PDs) are highly divergent, with some studies finding high heredity and others very low. A problem with assessing personality disorders by means of interview is errors connected with interviewer bias. A way to overcome the problem is to use self-report questionnaires in addition to interviews. This study used both interview and questionnaire for assessing DSM-IV Cluster B personality disorders: antisocial personality disorder (APD), borderline (BPD), narcissistic (NPD), and histrionic (HPD). We assessed close to 2,800 twins from the Norwegian Institute of Public Health Twin Panel using a self-report questionnaire and, a few years later, the Structured Interview for DSM-IV Personality (SIDP-IV). Items from the self-report questionnaire that best predicted the PDs captured by the interview were then selected. Measurement models combining questionnaire and interview information were applied and were fitted using Mx. Whereas the heritability of Cluster B PDs assessed by interview was around .30, and around .40-.50 when assessed by self-report questionnaire, the heritability of the convergent latent factor, including information from both interview and self-report questionnaire was .69 for APD, .67 for BPD, .71 for NPD, and .63 for HPD. As is usually found for personality, the effect of shared-in families (familial) environment was zero. In conclusion, when both interview and self-report questionnaire are taken into account, the heritability of Cluster B PD appears to be in the upper range of previous findings for mental disorders.

  8. Heritability of physical activity traits in Brazilian families: the Baependi Heart Study.

    Science.gov (United States)

    Horimoto, Andréa R V R; Giolo, Suely R; Oliveira, Camila M; Alvim, Rafael O; Soler, Júlia P; de Andrade, Mariza; Krieger, José E; Pereira, Alexandre C

    2011-11-29

    It is commonly recognized that physical activity has familial aggregation; however, the genetic influences on physical activity phenotypes are not well characterized. This study aimed to (1) estimate the heritability of physical activity traits in Brazilian families; and (2) investigate whether genetic and environmental variance components contribute differently to the expression of these phenotypes in males and females. The sample that constitutes the Baependi Heart Study is comprised of 1,693 individuals in 95 Brazilian families. The phenotypes were self-reported in a questionnaire based on the WHO-MONICA instrument. Variance component approaches, implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package, were applied to estimate the heritability and to evaluate the heterogeneity of variance components by gender on the studied phenotypes. The heritability estimates were intermediate (35%) for weekly physical activity among non-sedentary subjects (weekly PA_NS), and low (9-14%) for sedentarism, weekly physical activity (weekly PA), and level of daily physical activity (daily PA). Significant evidence for heterogeneity in variance components by gender was observed for the sedentarism and weekly PA phenotypes. No significant gender differences in genetic or environmental variance components were observed for the weekly PA_NS trait. The daily PA phenotype was predominantly influenced by environmental factors, with larger effects in males than in females. Heritability estimates for physical activity phenotypes in this sample of the Brazilian population were significant in both males and females, and varied from low to intermediate magnitude. Significant evidence for heterogeneity in variance components by gender was observed. These data add to the knowledge of the physical activity traits in the Brazilian study population, and are concordant with the notion of significant biological determination in active behavior.

  9. Heritability of volumetric brain changes and height in children entering puberty.

    Science.gov (United States)

    van Soelen, Inge L C; Brouwer, Rachel M; van Baal, G Caroline M; Schnack, Hugo G; Peper, Jiska S; Chen, Lei; Kahn, René S; Boomsma, Dorret I; Hulshoff Pol, Hilleke E

    2013-03-01

    The human brain undergoes structural changes in children entering puberty, while simultaneously children increase in height. It is not known if brain changes are under genetic control, and whether they are related to genetic factors influencing the amount of overall increase in height. Twins underwent magnetic resonance imaging brain scans at age 9 (N = 190) and 12 (N = 125). High heritability estimates were found at both ages for height and brain volumes (49-96%), and high genetic correlation between ages were observed (r(g) > 0.89). With increasing age, whole brain (+1.1%), cerebellum (+4.2%), cerebral white matter (+5.1%), and lateral ventricle (+9.4%) volumes increased, and third ventricle (-4.0%) and cerebral gray matter (-1.6%) volumes decreased. Children increased on average 13.8 cm in height (9.9%). Genetic influences on individual difference in volumetric brain and height changes were estimated, both within and across traits. The same genetic factors influenced both cerebral (20% heritable) and cerebellar volumetric changes (45%). Thus, the extent to which changes in cerebral and cerebellar volumes are heritable in children entering puberty are due to the same genes that influence change in both structures. The increase in height was heritable (73%), and not associated with cerebral volumetric change, but positively associated with cerebellar volume change (r(p) = 0.24). This association was explained by a genetic correlation (r(g) = 0.48) between height and cerebellar change. Brain and body each expand at their own pace and through separate genetic pathways. There are distinct genetic processes acting on structural brain development, which cannot be explained by genetic increase in height.

  10. Heritability and confirmation of genetic association studies for childhood asthma in twins.

    Science.gov (United States)

    Ullemar, V; Magnusson, P K E; Lundholm, C; Zettergren, A; Melén, E; Lichtenstein, P; Almqvist, C

    2016-02-01

    Although the genetics of asthma has been extensively studied using both quantitative and molecular genetic analysis methods, both approaches lack studies specific to the childhood phenotype and including other allergic diseases. This study aimed to give specific estimates for the heritability of childhood asthma and other allergic diseases, to attempt to replicate findings from genomewide association studies (GWAS) for childhood asthma and to test the same variants against other allergic diseases. In a cohort of 25 306 Swedish twins aged 9 or 12 years, data on asthma were available from parental interviews and population-based registers. The interviews also inquired about wheeze, hay fever, eczema, and food allergy. Through structural equation modeling, the heritability of all phenotypes was calculated. A subset of 10 075 twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from previous GWAS; these were first tested for association with asthma and significant findings also against the other allergic diseases. The heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other allergic diseases, the range was approximately 0.60-0.80. Associations for six SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80, 95% CI 0.74-0.86, P = 1.5*10(-8) ; other significant associations all below P = 3.5*10(-4) ). Of these, only rs3771180 in IL1RL1 was associated with any other allergic disease (for hay fever, OR 0.64, 95% CI 0.53-0.77, P = 2.5*10(-6) ). Asthma and allergic diseases of childhood are highly heritable, and these high-risk genetic variants associated specifically with childhood asthma, except for one SNP shared with hay fever. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Heritable symbiosis: The advantages and perils of an evolutionary rabbit hole.

    Science.gov (United States)

    Bennett, Gordon M; Moran, Nancy A

    2015-08-18

    Many eukaryotes have obligate associations with microorganisms that are transmitted directly between generations. A model for heritable symbiosis is the association of aphids, a clade of sap-feeding insects, and Buchnera aphidicola, a gammaproteobacterium that colonized an aphid ancestor 150 million years ago and persists in almost all 5,000 aphid species. Symbiont acquisition enables evolutionary and ecological expansion; aphids are one of many insect groups that would not exist without heritable symbiosis. Receiving less attention are potential negative ramifications of symbiotic alliances. In the short run, symbionts impose metabolic costs. Over evolutionary time, hosts evolve dependence beyond the original benefits of the symbiosis. Symbiotic partners enter into an evolutionary spiral that leads to irreversible codependence and associated risks. Host adaptations to symbiosis (e.g., immune-system modification) may impose vulnerabilities. Symbiont genomes also continuously accumulate deleterious mutations, limiting their beneficial contributions and environmental tolerance. Finally, the fitness interests of obligate heritable symbionts are distinct from those of their hosts, leading to selfish tendencies. Thus, genes underlying the host-symbiont interface are predicted to follow a coevolutionary arms race, as observed for genes governing host-pathogen interactions. On the macroevolutionary scale, the rapid evolution of interacting symbiont and host genes is predicted to accelerate host speciation rates by generating genetic incompatibilities. However, degeneration of symbiont genomes may ultimately limit the ecological range of host species, potentially increasing extinction risk. Recent results for the aphid-Buchnera symbiosis and related systems illustrate that, whereas heritable symbiosis can expand ecological range and spur diversification, it also presents potential perils.

  12. Heritability of glutathione and related metabolites in stored red blood cells.

    Science.gov (United States)

    van 't Erve, Thomas J; Doskey, Claire M; Wagner, Brett A; Hess, John R; Darbro, Benjamin W; Ryckman, Kelli K; Murray, Jeffrey C; Raife, Thomas J; Buettner, Garry R

    2014-11-01

    Red blood cells (RBCs) collected for transfusion deteriorate during storage. This deterioration is termed the "RBC storage lesion." There is increasing concern over the safety, therapeutic efficacy, and toxicity of transfusing longer-stored units of blood. The severity of the RBC storage lesion is dependent on storage time and varies markedly between individuals. Oxidative damage is considered a significant factor in the development of the RBC storage lesion. In this study, the variability during storage and heritability of antioxidants and metabolites central to RBC integrity and function were investigated. In a classic twin study, we determined the heritability of glutathione (GSH), glutathione disulfide (GSSG), the status of the GSSG,2H(+)/2GSH couple (Ehc), and total glutathione (tGSH) in donated RBCs over 56 days of storage. Intracellular GSH and GSSG concentrations both decrease during storage (median net loss of 0.52 ± 0.63 mM (median ± SD) and 0.032 ± 0.107 mM, respectively, over 42 days). Taking into account the decline in pH, Ehc became more positive (oxidized) during storage (median net increase of 35 ± 16 mV). In our study population heritability estimates for GSH, GSSG, tGSH, and Ehc measured over 56 days of storage are 79, 60, 67, and, 75%, respectively. We conclude that susceptibility of stored RBCs to oxidative injury due to variations in the GSH redox buffer is highly variable among individual donors and strongly heritable. Identifying the genes that regulate the storage-related changes in this redox buffer could lead to the development of new methods to minimize the RBC storage lesion.

  13. Heritability of Sex Tendency in a Harpacticoid Copepod, Tigriopus californicus

    OpenAIRE

    Voordouw, Maarten J; Anholt, Bradley R.

    2011-01-01

    Systems with genetic variation for the primary sex ratio are important for testing sex-ratio theory and for understanding how this variation is maintained. Evidence is presented for heritable variation of the primary sex ratio in the harpacticoid copepod Tigriopus californicus. Variation in the primary sex ratio among families cannot be accounted for by Mendelian segregation of sex chromosomes. The covariance in sex phenotype between full-sibling clutches and between mothers and offspring sug...

  14. Heritability of physical activity traits in Brazilian families: the Baependi Heart Study

    Directory of Open Access Journals (Sweden)

    Horimoto Andréa RVR

    2011-11-01

    Full Text Available Abstract Background It is commonly recognized that physical activity has familial aggregation; however, the genetic influences on physical activity phenotypes are not well characterized. This study aimed to (1 estimate the heritability of physical activity traits in Brazilian families; and (2 investigate whether genetic and environmental variance components contribute differently to the expression of these phenotypes in males and females. Methods The sample that constitutes the Baependi Heart Study is comprised of 1,693 individuals in 95 Brazilian families. The phenotypes were self-reported in a questionnaire based on the WHO-MONICA instrument. Variance component approaches, implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines computer package, were applied to estimate the heritability and to evaluate the heterogeneity of variance components by gender on the studied phenotypes. Results The heritability estimates were intermediate (35% for weekly physical activity among non-sedentary subjects (weekly PA_NS, and low (9-14% for sedentarism, weekly physical activity (weekly PA, and level of daily physical activity (daily PA. Significant evidence for heterogeneity in variance components by gender was observed for the sedentarism and weekly PA phenotypes. No significant gender differences in genetic or environmental variance components were observed for the weekly PA_NS trait. The daily PA phenotype was predominantly influenced by environmental factors, with larger effects in males than in females. Conclusions Heritability estimates for physical activity phenotypes in this sample of the Brazilian population were significant in both males and females, and varied from low to intermediate magnitude. Significant evidence for heterogeneity in variance components by gender was observed. These data add to the knowledge of the physical activity traits in the Brazilian study population, and are concordant with the notion of significant

  15. Heritability and fitness correlates of personality in the Ache, a natural-fertility population in Paraguay.

    Science.gov (United States)

    Bailey, Drew H; Walker, Robert S; Blomquist, Gregory E; Hill, Kim R; Hurtado, A Magdalena; Geary, David C

    2013-01-01

    The current study assessed the heritability of personality in a traditional natural-fertility population, the Ache of eastern Paraguay. Self-reports (n = 110) and other-reports (n = 66) on the commonly used Big Five Personality Inventory (i.e., extraversion, agreeableness, conscientiousness, neuroticism, openness) were collected. Self-reports did not support the Five Factor Model developed with Western samples, and did not correlate with other-reports for three of the five measured personality factors. Heritability was assessed using factors that were consistent across self- and other-reports and factors assessed using other-reports that showed reliabilities similar to those found in Western samples. Analyses of these items in combination with a multi-generation pedigree (n = 2,132) revealed heritability estimates similar to those found in most Western samples, although we were not able to separately estimate the influence of the common environment on these traits. We also assessed relations between personality and reproductive success (RS), allowing for a test of several mechanisms that might be maintaining heritable variation in personality. Phenotypic analyses, based largely on other-reports, revealed that extraverted men had higher RS than other men, but no other dimensions of personality predicted RS in either sex. Mothers with more agreeable children had more children, and parents mated assortatively on personality. Of the evolutionary processes proposed to maintain variation in personality, assortative mating, selective neutrality, and temporal variation in selection pressures received the most support. However, the current study does not rule out other processes affecting the evolution and maintenance of individual differences in human personality.

  16. Heritability and prevalence of selected osteochondrosis lesions in yearling Thoroughbred horses.

    Science.gov (United States)

    Russell, J; Matika, O; Russell, T; Reardon, R J M

    2017-05-01

    Osteochondrosis is considered multifactorial in origin, with factors such as nutrition, conformation, body size, trauma and genetics thought to contribute to its pathogenesis. Few studies have investigated the effects of genetic variability of osteochondrosis in Thoroughbreds. To describe the prevalence and genetic variability of a subset of osteochondrosis lesions in a group of Thoroughbred yearlings. Retrospective cohort study. Radiographs of 1962 Thoroughbred yearlings were retrieved from clinical records obtained between 2005 and 2013. Pedigree information was obtained from the Australian Stud Book. Osteochondrosis lesions were documented in selected joints and estimates of heritability were obtained by fitting linear mixed models in ASREML software. The overall prevalence of osteochondrosis was 23%. Osteochondrosis was identified in 10% of stifle joints, 6% of hock joints and 8% of fetlock joints. The heritability estimates ranged from 0 to 0.21. The largest estimates were 0.10, 0.14, 0.16 and 0.21 for lesions of the distal intermediate ridge of the tibia, dorso-proximal proximal phalanx (P1), any stifle osteochondrosis, and lesions of the lateral trochlear ridge of the distal femur, respectively. Although calculated heritability estimates had high standard errors, meta-analyses combining the present results with published estimates were significant at 0.10, 0.17, 0.15 and 0.20 for stifle, tarsal, fetlock and these joints combined, respectively. In addition, there was a permanent environment attributable to the dam effect. Inclusion criteria were based on radiographic findings in specific joints at a specific age range in Thoroughbreds. The present results indicate that only a proportion of osteochondrosis in Thoroughbreds is heritable. The permanent environment effects of the dam were observed to have effects on some categories of osteochondrosis. © 2016 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.

  17. Roles of HNF1α and HNF4α in pancreatic β-cells: lessons from a monogenic form of diabetes (MODY).

    Science.gov (United States)

    Yamagata, Kazuya

    2014-01-01

    Mutations in the genes encoding hepatocyte nuclear factor (HNF)1α and HNF4α cause a monogenic form of diabetes mellitus known as maturity-onset diabetes of the young (MODY). The primary cause of MODY is an impairment of glucose-stimulated insulin secretion by pancreatic β-cells, indicating the important roles of HNF1α and HNF4α in β-cells. Large-scale genetic studies have clarified that the common variants of HNF1α and HNF4α genes are also associated with type 2 diabetes, suggesting that they are involved in the pathogenesis of both diseases. Recent experimental studies revealed that HNF1α controls both β-cell function and growth by regulating target genes such as glucose transporter 2, pyruvate kinase, collectrin, hepatocyte growth factor activator, and HNF4α. In contrast, HNF4α mainly regulates the function of β-cells. Although direct target genes of HNF4α in β-cells are largely unknown, we recently identified Anks4b as a novel target of HNF4α that regulates β-cell susceptibility to endoplasmic reticulum stress. Studies of MODY have led to a better understanding of the molecular mechanism of glucose-stimulated insulin secretion by pancreatic β-cells.

  18. Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children.

    Science.gov (United States)

    Ozen, Seza; Demirkaya, Erkan; Amaryan, Gayane; Koné-Paut, Isabelle; Polat, Adem; Woo, Pat; Uziel, Yosef; Modesto, Consuelo; Finetti, Martina; Quartier, Pierre; Papadopoulou-Alataki, Efimia; Al-Mayouf, Sulaiman M; Fabio, Giovanna; Gallizzi, Romina; Cantarini, Luca; Frenkel, Joost; Nielsen, Susan; Hofer, Michael; Insalaco, Antonella; Acikel, C; Ozdogan, Huri; Martini, Alberto; Ruperto, Nicolino; Gattorno, Marco

    2014-04-01

    Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations of the MEFV gene. We analyse the impact of ethnic, environmental and genetic factors on the severity of disease presentation in a large international registry. Demographic, genetic and clinical data from validated paediatric FMF patients enrolled in the Eurofever registry were analysed. Three subgroups were considered: (i) patients living in the eastern Mediterranean countries; (ii) patients with an eastern Mediterranean ancestry living in western Europe; (iii) Caucasian patients living in western European countries. A score for disease severity at presentation was elaborated. Since November 2009, 346 FMF paediatric patients were enrolled in the Eurofever registry. The genetic and demographic features (ethnicity, age of onset, age at diagnosis) were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. European patients had a lower frequency of the high penetrance M694V mutation and a significant delay of diagnosis (pMediterranean countries had a higher frequency of fever episodes/year and more frequent arthritis, pericarditis, chest pain, abdominal pain and vomiting compared to the other two groups. Multivariate analysis showed that the variables independently associated with severity of disease presentation were country of residence, presence of M694V mutation and positive family history. Eastern Mediterranean FMF patients have a milder disease phenotype once they migrate to Europe, reflecting the effect of environment on the expression of a monogenic disease.

  19. Long-lasting response to oral therapy in a young male with monogenic diabetes as part of HNF1B-related disease

    Directory of Open Access Journals (Sweden)

    Elena Carrillo

    2017-06-01

    Full Text Available Mutations in hepatocyte nuclear factor 1β gene (HNF1B are responsible for a multisystemic syndrome where monogenic diabetes (classically known as MODY 5 and renal anomalies, mostly cysts, are the most characteristic findings. Urogenital malformations, altered liver function tests, hypomagnesemia or hyperuricemia and gout are also part of the syndrome. Diabetes in these patients usually requires early insulinization. We present the case of a young non-obese male patient with a personal history of renal multicystic dysplasia and a debut of diabetes during adolescence with simple hyperglycemia, negative pancreatic autoimmunity and detectable C-peptide levels. He also presented epididymal and seminal vesicle cysts, hypertransaminasemia, hyperuricemia and low magnesium levels. In the light of these facts we considered the possibility of a HNF1B mutation. The sequencing study of this gene confirmed a heterozygous mutation leading to a truncated and less functional protein. Genetic studies of his relatives were negative; consequently, it was classified as a de novo mutation. In particular, our patient maintained good control of his diabetes on oral antidiabetic agents for a long period of time. He eventually needed insulinization although oral therapy was continued alongside, allowing reduction of prandial insulin requirements. The real prevalence of mutations in HNF1B is probably underestimated owing to a wide phenotypical variability. As endocrinologists, we should consider this possibility in young non-obese diabetic patients with a history of chronic non-diabetic nephropathy, especially in the presence of some of the other characteristic manifestations.

  20. Jet Formation Mechanism Contrast Between ASC and LSC%环型与线型聚能装药射流成型机理对比

    Institute of Scientific and Technical Information of China (English)

    傅磊; 王伟力; 吕进; 李永胜

    2014-01-01

    Asymmetry exists during the process of jet formation of Annular shaped charge (ASC) liner, and the existing theo-ry on the linear shaped charge (LSC) jet formation cannot be used directly. DNYA 3D software was used to simulate the jet formation process of ASC and LSC with the structure of same section. Through contrast, the slug and jet parameter charac-teristics of ASC were analyzed, and it might provide reference to the theoretical research and engineering application.%环型聚能装药药型罩2侧在挤压汇聚形成射流过程中存在不对称性,不能完全套用线型聚能装药射流成型的现有理论。利用DYNA3D软件对相同剖面结构的环型、线型聚能装药射流成型过程进行数值模拟,通过比较分析得出了环型聚能装药形成杵体及射流参数的分布特性,为进一步理论研究及工程应用提供参考。

  1. Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality.

    Science.gov (United States)

    Lewis, G J; Panizzon, M S; Eyler, L; Fennema-Notestine, C; Chen, C-H; Neale, M C; Jernigan, T L; Lyons, M J; Dale, A M; Kremen, W S; Franz, C E

    2014-12-01

    While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean=55 years) male twins (complete MZ pairs=120; complete DZ pairs=84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (r(p)) and genetic (r(g)) correlations were observed between left amygdala volume and positive emotionality (r(p)=.16, porbitofrontal cortex thickness and negative emotionality were also observed (r(g)=.34, p<.01; r(e)=-.19, p<.05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation.

  2. Child food neophobia is heritable, associated with less compliant eating, and moderates familial resemblance for BMI.

    Science.gov (United States)

    Faith, Myles S; Heo, Moonseong; Keller, Kathleen L; Pietrobelli, Angelo

    2013-08-01

    The heritability of food neophobia, the tendency to avoid new foods, was tested in 4-7-year-old twins. We also examined whether food neophobia is associated with parent-child feeding relations or child body fat. 66 same-sex twin pairs, including 37 monozygotic (MZ) and 29 dizygotic (DZ) pairs were studied. Food neophobia was assessed by parent questionnaire (Child Food Neophobia Scale, CFNS), as were child-feeding practices and "division of responsibility" feeding relations. Child anthropometry and percent body fat were directly measured. MZ and DZ twin pair correlations for food neophobia were r = 0.71 and r = -0.01, respectively: heritability= 72%. Greater food neophobia was associated with reduced child eating compliance of prompted foods (P foods (P food demands (P = 0.01). Interestingly, the correlation between maternal BMI and child BMI z-score was significant only for children high (P = 0.03), but not low (P = 0.55), in food neophobia. Child food neophobia, a highly heritable trait previously linked to emotionality, was associated with less compliant parent-child feeding relations. Strategies to combat food neophobia and foster more harmonious feeding relationships may have a role in obesity prevention. Copyright © 2013 The Obesity Society.

  3. Heritability of word recognition in middle-aged men varies as a function of parental education.

    Science.gov (United States)

    Kremen, William S; Jacobson, Kristen C; Xian, Hong; Eisen, Seth A; Waterman, Brian; Toomey, Rosemary; Neale, Michael C; Tsuang, Ming T; Lyons, Michael J

    2005-07-01

    Although it is of lifelong importance, reading ability is studied primarily in children and adolescents. We examined variation in word recognition in 347 middle-aged male twin pairs. Overall heritability (a2) was 0.45, and shared environmental influences (c2) were 0.28. However, parental education moderated heritability such that a2 was 0.21 at the lowest parental education level and 0.69 at the highest level; c2 was 0.52 and 0.00, respectively. This constitutes a parental education x environment interaction. The higher heritability was due to a decrease in the magnitude of shared environmental factors, rather than an increase in the magnitude of genetic factors. Other cognitive studies have reported gene x environment interactions, but patterns may differ as a function of age or specific cognitive abilities. Our results suggest that shared environmental factors in families with low parental education have long-lasting effects on word recognition ability, well beyond any critical period for developing reading proficiency.

  4. Personality Traits in Rhesus Macaques (Macaca mulatta) Are Heritable but Do Not Predict Reproductive Output.

    Science.gov (United States)

    Brent, Lauren J N; Semple, Stuart; Maclarnon, Ann; Ruiz-Lambides, Angelina; Gonzalez-Martinez, Janis; Platt, Michael L

    2014-02-01

    There is growing evidence that behavioral tendencies, or "personalities," in animals are an important aspect of their biology, yet their evolutionary basis is poorly understood. Specifically, how individual variation in personality arises and is subsequently maintained by selection remains unclear. To address this gap, studies of personality require explicit incorporation of genetic information. Here, we explored the genetic basis of personality in rhesus macaques by determining the heritability of personality components and by examining the fitness consequences of those components. We collected observational data for 108 adult females living in three social groups in a free-ranging population via focal animal sampling. We applied principal component analysis to nine spontaneously occurring behaviors and identified six putative personality components, which we named Meek, Bold, Aggressive, Passive, Loner, and Nervous. All components were repeatable and heritable, with heritability estimates ranging from 0.14 to 0.35. We found no evidence of an association with reproductive output, measured either by infant survival or by interbirth interval, for any of the personality components. This finding suggests either that personality does not have fitness-related consequences in this population or that selection has acted to reduce fitness-associated variation in personality.

  5. Heritability of the shape of subcortical brain structures in the general population

    Science.gov (United States)

    Roshchupkin, Gennady V.; Gutman, Boris A.; Vernooij, Meike W.; Jahanshad, Neda; Martin, Nicholas G.; Hofman, Albert; McMahon, Katie L.; van der Lee, Sven J.; van Duijn, Cornelia M.; de Zubicaray, Greig I.; Uitterlinden, André G.; Wright, Margaret J.; Niessen, Wiro J.; Thompson, Paul M.; Ikram, M. Arfan; Adams, Hieab H. H.

    2016-01-01

    The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures. PMID:27976715

  6. An experimental analysis of the heritability of variation in glucocorticoid concentrations in a wild avian population

    Science.gov (United States)

    Jenkins, Brittany R.; Vitousek, Maren N.; Hubbard, Joanna K.; Safran, Rebecca J.

    2014-01-01

    Glucocorticoid hormones (CORT) are predicted to promote adaptation to variable environments, yet little is known about the potential for CORT secretion patterns to respond to selection in free-living populations. We assessed the heritable variation underlying differences in hormonal phenotypes using a cross-foster experimental design with nestling North American barn swallows (Hirundo rustica erythrogaster). Using a bivariate animal model, we partitioned variance in baseline and stress-induced CORT concentrations into their additive genetic and rearing environment components and estimated their genetic correlation. Both baseline and stress-induced CORT were heritable with heritability of 0.152 and 0.343, respectively. We found that the variation in baseline CORT was best explained by rearing environment, whereas the variation in stress-induced CORT was contributed to by a combination of genetic and environmental factors. Further, we did not detect a genetic correlation between these two hormonal traits. Although rearing environment appears to play an important role in the secretion of both types of CORT, our results suggest that stress-induced CORT levels are underlain by greater additive genetic variance compared with baseline CORT levels. Accordingly, we infer that the glucocorticoid response to stress has a greater potential for evolutionary change in response to selection compared with baseline glucocorticoid secretion patterns. PMID:25056627

  7. An experimental analysis of the heritability of variation in glucocorticoid concentrations in a wild avian population.

    Science.gov (United States)

    Jenkins, Brittany R; Vitousek, Maren N; Hubbard, Joanna K; Safran, Rebecca J

    2014-09-01

    Glucocorticoid hormones (CORT) are predicted to promote adaptation to variable environments, yet little is known about the potential for CORT secretion patterns to respond to selection in free-living populations. We assessed the heritable variation underlying differences in hormonal phenotypes using a cross-foster experimental design with nestling North American barn swallows (Hirundo rustica erythrogaster). Using a bivariate animal model, we partitioned variance in baseline and stress-induced CORT concentrations into their additive genetic and rearing environment components and estimated their genetic correlation. Both baseline and stress-induced CORT were heritable with heritability of 0.152 and 0.343, respectively. We found that the variation in baseline CORT was best explained by rearing environment, whereas the variation in stress-induced CORT was contributed to by a combination of genetic and environmental factors. Further, we did not detect a genetic correlation between these two hormonal traits. Although rearing environment appears to play an important role in the secretion of both types of CORT, our results suggest that stress-induced CORT levels are underlain by greater additive genetic variance compared with baseline CORT levels. Accordingly, we infer that the glucocorticoid response to stress has a greater potential for evolutionary change in response to selection compared with baseline glucocorticoid secretion patterns.

  8. The heritable basis of gene-environment interactions in cardiometabolic traits.

    Science.gov (United States)

    Poveda, Alaitz; Chen, Yan; Brändström, Anders; Engberg, Elisabeth; Hallmans, Göran; Johansson, Ingegerd; Renström, Frida; Kurbasic, Azra; Franks, Paul W

    2017-03-01

    Little is known about the heritable basis of gene-environment interactions in humans. We therefore screened multiple cardiometabolic traits to assess the probability that they are influenced by genotype-environment interactions. Fourteen established environmental risk exposures and 11 cardiometabolic traits were analysed in the VIKING study, a cohort of 16,430 Swedish adults from 1682 extended pedigrees with available detailed genealogical, phenotypic and demographic information, using a maximum likelihood variance decomposition method in Sequential Oligogenic Linkage Analysis Routines software. All cardiometabolic traits had statistically significant heritability estimates, with narrow-sense heritabilities (h (2)) ranging from 24% to 47%. Genotype-environment interactions were detected for age and sex (for the majority of traits), physical activity (for triacylglycerols, 2 h glucose and diastolic BP), smoking (for weight), alcohol intake (for weight, BMI and 2 h glucose) and diet pattern (for weight, BMI, glycaemic traits and systolic BP). Genotype-age interactions for weight and systolic BP, genotype-sex interactions for BMI and triacylglycerols and genotype-alcohol intake interactions for weight remained significant after multiple test correction. Age, sex and alcohol intake are likely to be major modifiers of genetic effects for a range of cardiometabolic traits. This information may prove valuable for studies that seek to identify specific loci that modify the effects of lifestyle in cardiometabolic disease.

  9. Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD.

    Science.gov (United States)

    Guo, W; Samuels, J F; Wang, Y; Cao, H; Ritter, M; Nestadt, P S; Krasnow, J; Greenberg, B D; Fyer, A J; McCracken, J T; Geller, D A; Murphy, D L; Knowles, J A; Grados, M A; Riddle, M A; Rasmussen, S A; McLaughlin, N C; Nurmi, E L; Askland, K D; Cullen, B A; Piacentini, J; Pauls, D L; Bienvenu, O J; Stewart, S E; Goes, F S; Maher, B; Pulver, A E; Valle, D; Mattheisen, M; Qian, J; Nestadt, G; Shugart, Y Y

    2017-07-01

    Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10(-7) in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data. Published by Elsevier B.V.

  10. Heritability of Renal Function and Inflammatory Markers in Adult Male Twins

    Science.gov (United States)

    Raggi, Paolo; Su, Shaoyong; Karohl, Cristina; Veledar, Emir; Rojas-Campos, Enrique; Vaccarino, Viola

    2010-01-01

    Background Loss of renal function is accompanied by a progressive increase in markers of inflammation; it is unknown whether they share common genetic pathways. Study Design We evaluated the shared heritability of estimated glomerular filtration rate (eGFR) and markers of inflammation and endothelial activation in 524 twin males from the Vietnam Era Twin Registry; 9 twins were excluded due to incomplete or incorrect data. Models were adjusted for age, race, body mass index, smoking, hypertension, diabetes mellitus, prior coronary artery disease and intercurrent medications. Results The mean eGFR was 89 ± 13 ml/min/1.73 m2 (range 35–146); eGFR, intracellular adhesion molecule (ICAM) and TNF-α receptor (TNF-αR) were moderately heritable (all ∼50%), while IL-6 receptor (IL-6R) and P-selectin were highly heritable (68 and 76%, respectively). IL-6R and TNF-αR showed a significant inverse association with eGFR (p = 0.04 and p renal function and inflammation. Thus, increased inflammation represents a response to declining renal function rather than being a mechanism contributing to renal deterioration. PMID:20720405

  11. Variance components and heritabilities for sow productivity traits estimated from purebred versus crossbred sows.

    Science.gov (United States)

    Ehlers, M J; Mabry, J W; Bertrand, J K; Stalder, K J

    2005-10-01

    Genetic parameters were estimated for number of pigs born alive (NBA), adjusted litter weaning weight (ALWT), and the interval from weaning to first service (W2E) using 2002 purebred litter records and 14 583 crossbred litter records from a swine production unit with a defined great-grandparent, grandparent, and parent stock genetic system structure. Estimation of (co)variance components was carried out by REML methods. Heritability estimates from this study for NBA were 0.155, 0.146, 0.145 for the purebred, crossbred, and pooled data, respectively. Heritability estimates for ALWT were 0.162, 0.195, and 0.183 for the purebred, crossbred and pooled data, respectively. Heritability estimates for W2E were 0.205, 0.239 and 0.202 for the purebred, crossbred and pooled data, respectively. Genetic correlations between NBA and ALWT were weak and positive for the three groups. The genetic correlation between W2E and ALWT were -0.158 for the purebred Yorkshires, 0.031 for the crossbreds and 0.051 for the pooled data. The genetic correlation between W2E and NBA was -0.027 for the purebred Yorkshires, 0.310 for the crossbreds and 0.236 for the pooled data. These similarities suggest that pooling of purebred and crossbred data may be considered, which may potentially increase the accuracy of breeding value estimates, which would result in increased genetic progress.

  12. Heritable genome editing with CRISPR/Cas9 in the silkworm, Bombyx mori.

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    Wei Wei

    Full Text Available We report the establishment of an efficient and heritable gene mutagenesis method in the silkworm Bombyx mori using modified type II clustered regularly interspaced short palindromic repeats (CRISPR with an associated protein (Cas9 system. Using four loci Bm-ok, BmKMO, BmTH, and Bmtan as candidates, we proved that genome alterations at specific sites could be induced by direct microinjection of specific guide RNA and Cas9-mRNA into silkworm embryos. Mutation frequencies of 16.7-35.0% were observed in the injected generation, and DNA fragments deletions were also noted. Bm-ok mosaic mutants were used to test for mutant heritability due to the easily determined translucent epidermal phenotype of Bm-ok-disrupted cells. Two crossing strategies were used. In the first, injected Bm-ok moths were crossed with wild-type moths, and a 28.6% frequency of germline mutation transmission was observed. In the second strategy, two Bm-ok mosaic mutant moths were crossed with each other, and 93.6% of the offsprings appeared mutations in both alleles of Bm-ok gene (compound heterozygous. In summary, the CRISPR/Cas9 system can act as a highly specific and heritable gene-editing tool in Bombyx mori.

  13. Heritabilities and genetic trends for reproductive traits in a population of Romosinuano cattle in Colombia

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    Oscar Vergara G.

    2015-12-01

    Full Text Available Objective. The aim of this study was to estimate heritabilities and genetic trends for reproductive traits in a beef cattle population Romosinuano. Material and methods. Age at first calving (AFC, first calving interval (FCI, and second calving interval (SCI were evaluated from a database generated from 1951 to 2011 by Research Center Turipana. Unicaracter animal model was used, which included fixed of contemporary group (year-season, random direct genetic additives effects and residual. Estimates of variance components and genetic parameters were obtained through Restricted Maximum Likelihood procedure, using AIREMLF90 program. Genetic trends were calculated as a linear regression of weighted averages of breeding values over the years, using the REG procedure of Statistical Analysis System. Results. The indices of heritability for additive genetic effects were 0.04 ± 0.05 for AFC, 0.06 ± 0.06 for FCI, and 0.09 ± 0.06 for SCI. Conclusions. Low heritabilities indicating that should improve nutritional and management conditions in the herd, so that they can better express the traits evaluated. The estimated genetic trends were near zero, which shows that the objective of the CI Turipaná regarding this population has complied fully preserving the genetic variability of the breed Romosinuano.

  14. Heritability of body weight and resistance to ammonia in the Pacific white shrimp Litopenaeus vannamei juveniles

    Science.gov (United States)

    Li, Wenjia; Lu, Xia; Luan, Sheng; Luo, Kun; Sui, Juan; Kong, Jie

    2016-09-01

    Ammonia, toxic to aquaculture organisms, represents a potential problem in aquaculture systems, and the situation is exacerbated in closed and intensive shrimp farming operations, expecially for Litopenaeus vannamei. Assessing the potential for the genetic improvement of resistance to ammonia in L. vannamei requires knowledge of the genetic parameters of this trait. The heritability of resistance to ammonia was estimated using two descriptors in the present study: the survival time (ST) and the survival status at half lethal time (SS50) for each individual under high ammonia challenge. The heritability of ST and SS50 were low (0.154 4±0.044 6 and 0.147 5±0.040 0, respectively), but they were both significantly different from zero ( P0.05), suggesting that ST and SS50 could be used as suitable indicators for resistance to ammonia. There were also positive phenotypic and genetic correlation between resistance to ammonia and body weight, which means that resistance to ammonia can be enhanced by the improvement of husbandry practices that increase the body weight. The results from the present study suggest that the selection for higher body weight does not have any negative consequences for resistance to ammonia. In addition to quantitative genetics, tools from molecular genetics can be applied to selective breeding programs to improve the efficiency of selection for traits with low heritability.

  15. Estimating heritability of wool shedding in a cross-bred ewe population.

    Science.gov (United States)

    Vargas Jurado, N; Leymaster, K A; Kuehn, L A; Lewis, R M

    2016-10-01

    Low wool prices and high production costs in sheep systems have resulted in the introduction of genotypes that shed wool into flocks to reduce shearing costs. Wool shedding occurs naturally in a few breeds and can be incorporated by cross-breeding. The opportunity to enhance shedding through selection depends on the extent of genetic variability present. Genetic and environmental parameters for wool shedding for ewes from a three-breed composite population were estimated using Bayesian inference. Data on 2025 cross-bred ewes, including 3345 wool shedding scores (WS) and 1647 breeding weight (BW) records, were analysed using bivariate and, for WS, univariate animal repeatability models. Breeding weight was included to account for possible selection bias. Breeding weight was moderately heritable and highly repeatable with means of 0.317 and 0.724, respectively. Under both models, WS was found to be moderately heritable and repeatable with means of 0.256 and 0.399, respectively. Based on a cumulative link model and contingency table analysis, age and reproductive activity influenced the extent of WS (p < 0.05). Given that WS is moderately heritable, selective gain in WS can be achieved.

  16. Heritability of audiometric shape parameters and familial aggregation of presbycusis in an elderly Flemish population.

    Science.gov (United States)

    Demeester, Kelly; van Wieringen, Astrid; Hendrickx, Jan-jaap; Topsakal, Vedat; Huyghe, Jeroen; Fransen, Erik; Van Laer, Lut; Van Camp, Guy; Van de Heyning, Paul

    2010-06-14

    This study describes the heritability of audiometric shape parameters and the familial aggregation of different types of presbycusis in a healthy, otologically screened population between 50 and 75 years old. About 342 siblings of 64 families (average family-size: 5.3) were recruited through population registries. Audiometric shape was mathematically quantified by objective parameters developed to measure size, slope, concavity, percentage of frequency-dependent and frequency-independent hearing loss and Bulge Depth. The heritability of each parameter was calculated using a variance components model. Logistic regression models were used to estimate the odds ratios (ORs). Estimates of sibling recurrence risk ratios (lambda(s)) are also provided. Heritability estimates were generally higher compared to previous studies. ORs and lambda(s) for the parameters Total Hearing Loss (size), Uniform Hearing Loss (percentage of frequency-dependent hearing loss) and Bulge Depth suggest a higher heredity for severe types of presbycusis compared to moderate or mild types. Our results suggest that the separation of the parameter 'Total Hearing Loss' into the two parameters 'Uniform Hearing Loss' and 'Non-uniform Hearing Loss' could lead to the discovery of different genetic subtypes of presbycusis. The parameter 'Bulge Depth', instead of 'Concavity', seemed to be an important parameter for classifying subjects into 'susceptible' or 'resistant' to societal or intensive environmental exposure.

  17. Heritable alteration of DNA methylation induced by whole-chromosome aneuploidy in wheat.

    Science.gov (United States)

    Gao, Lihong; Diarso, Moussa; Zhang, Ai; Zhang, Huakun; Dong, Yuzhu; Liu, Lixia; Lv, Zhenling; Liu, Bao

    2016-01-01

    Aneuploidy causes changes in gene expression and phenotypes in all organisms studied. A previous study in the model plant Arabidopsis thaliana showed that aneuploidy-generated phenotypic changes can be inherited to euploid progenies and implicated an epigenetic underpinning of the heritable variations. Based on an analysis by amplified fragment length polymorphism and methylation-sensitive amplified fragment length polymorphism markers, we found that although genetic changes at the nucleotide sequence level were negligible, extensive changes in cytosine DNA methylation patterns occurred in all studied homeologous group 1 whole-chromosome aneuploid lines of common wheat (Triticum aestivum), with monosomic 1A showing the greatest amount of methylation changes. The changed methylation patterns were inherited by euploid progenies derived from the aneuploid parents. The aneuploidy-induced DNA methylation alterations and their heritability were verified at selected loci by bisulfite sequencing. Our data have provided empirical evidence supporting earlier suggestions that heritability of aneuploidy-generated, but aneuploidy-independent, phenotypic variations may have an epigenetic basis. That at least one type of aneuploidy - monosomic 1A - was able to cause significant epigenetic divergence of the aneuploid plants and their euploid progenies also lends support to recent suggestions that aneuploidy may have played an important and protracted role in polyploid genome evolution.

  18. Heritability of shoulder ulcers and genetic correlations with mean piglet weight and sow body condition.

    Science.gov (United States)

    Lundgren, H; Zumbach, B; Lundeheim, N; Grandinson, K; Vangen, O; Olsen, D; Rydhmer, L

    2012-01-01

    The objective of this paper was to estimate the heritability for shoulder ulcers and the genetic correlations between shoulder ulcers, mean piglet weight and sow body condition. The analyses were based on information on 5549 Norwegian Landrace sows and their 7614 purebred litters. The genetic analysis was performed using the Gibbs sampling method. Shoulder ulcers were analyzed as a threshold trait. Sow body condition and mean piglet weight were analyzed as linear traits. The heritability of shoulder ulcers was estimated at 0.25 (s.d. = 0.03). The heritability for sow body condition was estimated at 0.14 (s.d. = 0.02) and that for mean piglet weight at 0.23 (s.d. = 0.02). The genetic correlation between shoulder ulcers and sow body condition was negative (-0.59, s.d. = 0.09). The genetic correlation between shoulder ulcers and mean piglet weight was positive (0.23, s.d. = 0.10) and the genetic correlation between sow body condition and mean piglet weight was negative (-0.24, s.d. = 0.10).

  19. Heritability of problem drinking and the genetic overlap with personality in a general population sample

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    Marleen H.M. De Moor

    2011-11-01

    Full Text Available This study examined the heritability of problem drinking and investigated the phenotypic and genetic relationships between problem drinking and personality. It was conducted in a sample of 5,870 twins and siblings and 4,420 additional family members from the Netherlands Twin Register. Data on problem drinking (assessed with the AUDIT and CAGE; 12 items and personality (NEO-FFI; 60 items were collected in 2009/2010 through surveys. Factor analysis on the AUDIT and CAGE items showed that the items clustered on two separate but highly correlated (r=0.74 underlying factors. A higher order factor was extracted that reflected those aspects of problem drinking that are common to the AUDIT and CAGE , which showed a heritability of 40%. The correlations between problem drinking and the five dimensions of personality were small but significant, ranging from 0.06 for Extraversion to -0.12 for Conscientiousness. All personality dimensions (with broad-sense heritabilities between 32% and 55%, and some evidence for non-additive genetic influences were genetically correlated with problem drinking. The genetic correlations were small to modest (between |0.12-0.41|. Future studies with longitudinal data and DNA polymorphisms are needed to determine the biological mechanisms that underlie the genetic link between problem drinking and personality.

  20. Diversity and heritability of the maize rhizosphere microbiome under field conditions.

    Science.gov (United States)

    Peiffer, Jason A; Spor, Aymé; Koren, Omry; Jin, Zhao; Tringe, Susannah Green; Dangl, Jeffery L; Buckler, Edward S; Ley, Ruth E

    2013-04-16

    The rhizosphere is a critical interface supporting the exchange of resources between plants and their associated soil environment. Rhizosphere microbial diversity is influenced by the physical and chemical properties of the rhizosphere, some of which are determined by the genetics of the host plant. However, within a plant species, the impact of genetic variation on the composition of the microbiota is poorly understood. Here, we characterized the rhizosphere bacterial diversity of 27 modern maize inbreds possessing exceptional genetic diversity grown under field conditions. Randomized and replicated plots of the inbreds were planted in five field environments in three states, each with unique soils and management conditions. Using pyrosequencing of bacterial 16S rRNA genes, we observed substantial variation in bacterial richness, diversity, and relative abundances of taxa between bulk soil and the maize rhizosphere, as well as between fields. The rhizospheres from maize inbreds exhibited both a small but significant proportion of heritable variation in total bacterial diversity across fields, and substantially more heritable variation between replicates of the inbreds within each field. The results of this study should facilitate expanded studies to identify robust heritable plant-microbe interactions at the level of individual polymorphisms by genome wide association, so that plant-microbiome interactions can ultimately be incorporated into plant breeding.

  1. Heritability of Stroop and flanker performance in 12-year old children

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    Polderman Tinca JC

    2004-12-01

    Full Text Available Abstract Background There is great interest in appropriate phenotypes that serve as indicator of genetically transmitted frontal (dysfunction, such as ADHD. Here we investigate the ability to deal with response conflict, and we ask to what extent performance variation on response interference tasks is caused by genetic variation. We tested a large sample of 12-year old monozygotic and dizygotic twins on two well-known and closely related response interference tasks; the color Stroop task and the Eriksen flanker task. Using structural equation modelling we assessed the heritability of several performance indices derived from those tasks. Results In the Stroop task we found high heritabilities of overall reaction time and – more important – Stroop interference (h2 = nearly 50 %. In contrast, we found little evidence of heritability on flanker performance. For both tasks no effects of sex on performance variation were found. Conclusions These results suggest that normal variation in Stroop performance is influenced by underlying genetic variation. Given that Stroop performance is often hampered not only in people suffering from frontal dysfunction, but also in their unaffected relatives, we conclude that this variable may constitute a suitable endophenotype for future genetic studies. We discuss several reasons for the absence of genetic effects on the flanker task.

  2. Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality

    Science.gov (United States)

    Lewis, G.J.; Panizzon, M.S.; Eyler, L.; Fennema-Notestine, C.; Chen, C.-H.; Neale, M.C.; Jernigan, T.L.; Lyons, M.J.; Dale, A.M.; Kremen, W.S.; Franz, C.E.

    2015-01-01

    While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean = 55 years) male twins (complete MZ pairs = 120; complete DZ pairs = 84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (rp) and genetic (rg) correlations were observed between left amygdala volume and positive emotionality (rp = .16, p < .01; rg = .23, p < .05, respectively). In addition, after adjusting for mean cortical thickness, genetic and nonshared-environmental correlations (re) between left medial orbitofrontal cortex thickness and negative emotionality were also observed (rg = .34, p < .01; re = −.19, p < .05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation. PMID:25263286

  3. On the nature and nurture of intelligence and specific cognitive abilities: the more heritable, the more culture dependent.

    Science.gov (United States)

    Kan, Kees-Jan; Wicherts, Jelte M; Dolan, Conor V; van der Maas, Han L J

    2013-12-01

    To further knowledge concerning the nature and nurture of intelligence, we scrutinized how heritability coefficients vary across specific cognitive abilities both theoretically and empirically. Data from 23 twin studies (combined N = 7,852) showed that (a) in adult samples, culture-loaded subtests tend to demonstrate greater heritability coefficients than do culture-reduced subtests; and (b) in samples of both adults and children, a subtest's proportion of variance shared with general intelligence is a function of its cultural load. These findings require an explanation because they do not follow from mainstream theories of intelligence. The findings are consistent with our hypothesis that heritability coefficients differ across cognitive abilities as a result of differences in the contribution of genotype-environment covariance. The counterintuitive finding that the most heritable abilities are the most culture-dependent abilities sheds a new light on the long-standing nature-nurture debate of intelligence.

  4. Heritability of ambulatory and beat-to-beat office blood pressure in large multigenerational Arab pedigrees: the 'Oman Family study'.

    Science.gov (United States)

    Albarwani, Sulayma; Muñoz, M Loretto; Voruganti, V Saroja; Jaju, Deepali; Al-Yahyaee, V Saeed; Rizvi, Syed G; Lopez-Alvarenga, Juan C; Al-Anqoudi, Zahir M; Bayoumi, Riad A; Comuzzie, Anthony G; Snieder, Harold; Hassan, Mohammed O

    2012-12-01

    To estimate the heritability of ambulatory blood pressure (BP), heart rate (HR), and beat-to-beat office BP and HR in an isolated, environmentally and genetically homogeneous Omani Arab population. Ambulatory BP measurements were recorded in 1,124 subjects with a mean age of 33.8 ± 16.2 years, using the auscultatory mode of the validated Schiller ambulatory BP Monitor. Beat-to-beat BP and HR were recorded by the Task Force Monitor. Heritability was estimated using quantitative genetic analysis. This was achieved by applying the maximum-likelihood-based variance decomposition method implemented in SOLAR software. We detected statistically significant heritability estimates for office beat-to-beat, 24-hour, daytime, and sleep HR of 0.31, 0.21, 0.20, and 0.07, respectively. Heritability estimates in the above mentioned conditions for systolic BP (SBP)/diastolic BP (DBP)/mean BP (MBP)were all significant and estimated at 0.19/0.19/0.19, 0.30/0.44/0.41, 0.28/0.38/0.39, and 0.21/0.18/0.20,respectively. Heritability estimates for 24-hour and daytime ambulatory SBP, DBP, and MBP ranged from 0.28 to 0.44, and were higher than the heritability estimates for beat-to-beat recordings and sleep periods,which were estimated within a narrow range of 0.18-0.21. In this cohort, because shared environments are common to all, the environmental influence that occurs is primarily due to the variation in non-shared environment that is unique to the individual. We demonstrated significant heritability estimates for both beat-to-beat office and ambulatory BP and HR recordings, but 24-hour and daytime ambulatory heritabilities are higher than those from beat-to-beat resting levels and ambulatory night-time recordings.

  5. Heritability of cardiovascular and personality traits in 6,148 Sardinians.

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    Giuseppe Pilia

    2006-08-01

    Full Text Available In family studies, phenotypic similarities between relatives yield information on the overall contribution of genes to trait variation. Large samples are important for these family studies, especially when comparing heritability between subgroups such as young and old, or males and females. We recruited a cohort of 6,148 participants, aged 14-102 y, from four clustered towns in Sardinia. The cohort includes 34,469 relative pairs. To extract genetic information, we implemented software for variance components heritability analysis, designed to handle large pedigrees, analyze multiple traits simultaneously, and model heterogeneity. Here, we report heritability analyses for 98 quantitative traits, focusing on facets of personality and cardiovascular function. We also summarize results of bivariate analyses for all pairs of traits and of heterogeneity analyses for each trait. We found a significant genetic component for every trait. On average, genetic effects explained 40% of the variance for 38 blood tests, 51% for five anthropometric measures, 25% for 20 measures of cardiovascular function, and 19% for 35 personality traits. Four traits showed significant evidence for an X-linked component. Bivariate analyses suggested overlapping genetic determinants for many traits, including multiple personality facets and several traits related to the metabolic syndrome; but we found no evidence for shared genetic determinants that might underlie the reported association of some personality traits and cardiovascular risk factors. Models allowing for heterogeneity suggested that, in this cohort, the genetic variance was typically larger in females and in younger individuals, but interesting exceptions were observed. For example, narrow heritability of blood pressure was approximately 26% in individuals more than 42 y old, but only approximately 8% in younger individuals. Despite the heterogeneity in effect sizes, the same loci appear to contribute to variance

  6. Heritability of Cardiovascular and Personality Traits in 6,148 Sardinians

    Science.gov (United States)

    Scuteri, Angelo; Orrú, Marco; Albai, Giuseppe; Dei, Mariano; Lai, Sandra; Usala, Gianluca; Lai, Monica; Loi, Paola; Mameli, Cinzia; Vacca, Loredana; Deiana, Manila; Olla, Nazario; Masala, Marco; Cao, Antonio; Najjar, Samer S; Terracciano, Antonio; Nedorezov, Timur; Sharov, Alexei; Zonderman, Alan B; Abecasis, Gonçalo R; Costa, Paul; Lakatta, Edward; Schlessinger, David

    2006-01-01

    In family studies, phenotypic similarities between relatives yield information on the overall contribution of genes to trait variation. Large samples are important for these family studies, especially when comparing heritability between subgroups such as young and old, or males and females. We recruited a cohort of 6,148 participants, aged 14–102 y, from four clustered towns in Sardinia. The cohort includes 34,469 relative pairs. To extract genetic information, we implemented software for variance components heritability analysis, designed to handle large pedigrees, analyze multiple traits simultaneously, and model heterogeneity. Here, we report heritability analyses for 98 quantitative traits, focusing on facets of personality and cardiovascular function. We also summarize results of bivariate analyses for all pairs of traits and of heterogeneity analyses for each trait. We found a significant genetic component for every trait. On average, genetic effects explained 40% of the variance for 38 blood tests, 51% for five anthropometric measures, 25% for 20 measures of cardiovascular function, and 19% for 35 personality traits. Four traits showed significant evidence for an X-linked component. Bivariate analyses suggested overlapping genetic determinants for many traits, including multiple personality facets and several traits related to the metabolic syndrome; but we found no evidence for shared genetic determinants that might underlie the reported association of some personality traits and cardiovascular risk factors. Models allowing for heterogeneity suggested that, in this cohort, the genetic variance was typically larger in females and in younger individuals, but interesting exceptions were observed. For example, narrow heritability of blood pressure was approximately 26% in individuals more than 42 y old, but only approximately 8% in younger individuals. Despite the heterogeneity in effect sizes, the same loci appear to contribute to variance in young and old

  7. Comparison between multitrait and unitrait analysis in the heritability estimate of electrical conductivity of milk

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    Daniella Flavia Vilas Boas

    2012-12-01

    Full Text Available Electrical conductivity of milk is an indirect method for diagnosis of mastitis that can be used as criterion of selection in breeding programs, to obtain more resistant animals to infection. Data from 9,302 records of electrical conductivity from the morning milking (ECM, 13,070 milk yield records (MY and 11,560 records of milking time (MT, of 1,129 first lactation Holstein cows, calving from 2001 to 2011, were used in statistical analysis. Data of eight herds of Southeast region of Brazil were obtained by the WESTFALIA® electronic milking machines, with “Dairyplan” management system. Two analysis were performed: a multitrait, including MY, MT and ECM, and an unitrait, considering only test-day morning electrical conductivity. The model included additive genetic, permanent environmental and residual effects as random. Additionally, contemporary groups (CG, the age of cow at calving (AGC and days in milk (DIM (linear and quadratic regression were included as fixed effects. The CG was composed by herd, year and month of test. DIM classes were formed with weekly intervals, constituting a total of 42 classes. The variance components were estimated by Restricted Maximum Likelihood Method (REML, using the Wombat software. The average and standard deviation of ECM were 4.80 mS cm-1 and 0.54 mS cm-1, respectively. The heritability estimates by multitrait model and their standard errors were 0.33 (0.05, 0.15 (0.03 and 0.22 (0.03 for ECM, MY and MT, respectively. Genetic correlation was 0.74 for MY and MT, 0.37 for MY and ECM and -0.09 for MY and ECM. In the unitrait analysis, the heritability estimate for ECM was 0.35 with a standard error of 0.05. These results agree with the literature that reported heritability estimates for electrical conductivity ranging from 0.26 to 0.39. Although the estimates were close, the heritability estimated by unitrait analysis was slightly higher that estimated by multtrait probably because the pedigree file was the

  8. The Accuracy of p16/Ki-67 and HPV Test in the Detection of CIN2/3 in Women Diagnosed with ASC-US or LSIL.

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    Júlio C Possati-Resende

    Full Text Available The objective of this study was to compare the accuracies of double staining for p16/Ki-67 and the molecular test for high-risk HPV (hr-HPV to identify high-grade cervical intraepithelial neoplasia (CIN2/CIN3 in women with cervical cytology of atypical squamous cells of undetermined significance (ASC-US and low-grade squamous intraepithelial lesion (LSIL. Data were collected from 201 women who underwent cervical cytology screening in the Barretos Cancer Hospital and their results were categorized as ASC-US (n=96 or LSIL (n=105. All patients underwent colposcopy with or without cervical biopsy for diagnosis of CIN2/CIN3. The hr-HPV test (Cobas 4800 test and immunocytochemistry were performed to detect biomarkers p16/Ki-67 (CINtec PLUS test. Two samples (1 ASC-US/1 LSIL were excluded from the analysis due to inconclusive results of the histologic examination. There were 8 cases of CIN2/CIN3 among 95 women with ASC-US (8.4%, and 23 cases of CIN2/CIN3 among 104 women with LSIL (22.1%. In the group of women with ASC-US, the sensitivity and specificity in diagnosing CIN2/CIN3 were 87.5% and 79.5% for the HPV test and 62.5% and 93.1% for p16/Ki-67. Among women with LSIL, the sensitivity and specificity in the diagnosis of CIN2/CIN3 were 87% and 34.7% for the HPV test and 69.6% and 75.3% for immunocytochemistry. Superior performance was observed for p16/Ki-67 double staining, especially among women under 30 for whom the test had an area under the ROC curve of 0.762 (p30 years. In younger women (≤30 years with LSIL, p16/Ki-67 had greater accuracy in identifying precursor lesions. Among women >30 years diagnosed with LSIL, the two methods showed similar performance.

  9. Report of experiments and evidence for ASC L2 milestone 4467 : demonstration of a legacy application's path to exascale.

    Energy Technology Data Exchange (ETDEWEB)

    Curry, Matthew L.; Ferreira, Kurt Brian; Pedretti, Kevin Thomas Tauke; Leung, Vitus Joseph; Moreland, Kenneth D.; Lofstead, Gerald Fredrick, II; Gentile, Ann C. (Sandia National Laboratories, Livermore, CA); Klundt, Ruth Ann; Ward, H. Lee; Laros, James H., III; Hemmert, Karl Scott; Fabian, Nathan D.; Levenhagen, Michael J.; Barrett, Brian W.; Brightwell, Ronald Brian; Barrett, Richard; Wheeler, Kyle Bruce; Kelly, Suzanne Marie; Rodrigues, Arun F.; Brandt, James M. (Sandia National Laboratories, Livermore, CA); Thompson, David (Sandia National Laboratories, Livermore, CA); VanDyke, John P.; Oldfield, Ron A.; Tucker, Thomas (Open Grid Computing, Inc., Austin, TX); Vaughan, Courtenay Thomas

    2012-03-01

    This report documents thirteen of Sandia's contributions to the Computational Systems and Software Environment (CSSE) within the Advanced Simulation and Computing (ASC) program between fiscal years 2009 and 2012. It describes their impact on ASC applications. Most contributions are implemented in lower software levels allowing for application improvement without source code changes. Improvements are identified in such areas as reduced run time, characterizing power usage, and Input/Output (I/O). Other experiments are more forward looking, demonstrating potential bottlenecks using mini-application versions of the legacy codes and simulating their network activity on Exascale-class hardware. The purpose of this report is to prove that the team has completed milestone 4467-Demonstration of a Legacy Application's Path to Exascale. Cielo is expected to be the last capability system on which existing ASC codes can run without significant modifications. This assertion will be tested to determine where the breaking point is for an existing highly scalable application. The goal is to stretch the performance boundaries of the application by applying recent CSSE RD in areas such as resilience, power, I/O, visualization services, SMARTMAP, lightweight LWKs, virtualization, simulation, and feedback loops. Dedicated system time reservations and/or CCC allocations will be used to quantify the impact of system-level changes to extend the life and performance of the ASC code base. Finally, a simulation of anticipated exascale-class hardware will be performed using SST to supplement the calculations. Determine where the breaking point is for an existing highly scalable application: Chapter 15 presented the CSSE work that sought to identify the breaking point in two ASC legacy applications-Charon and CTH. Their mini-app versions were also employed to complete the task. There is no single breaking point as more than one issue was found with the two codes. The results were

  10. ASC Weekly News Notes

    Energy Technology Data Exchange (ETDEWEB)

    Womble, David E.

    2016-05-01

    Unified collision operator demonstrated for both radiation transport and PIC-DSMC. A side-by-side comparison between the DSMC method and the radiation transport method was conducted for photon attenuation in the atmosphere over 2 kilometers in physical distance with a reduction of photon density of six orders of magnitude. Both DSMC and traditional radiation transport agreed with theory to two digits. This indicates that PIC-DSMC operators can be unified with the radiation transport collision operators into a single code base and that physics kernels can remain unique to the actual collision pairs. This simulation example provides an initial validation of the unified collision theory approach that will later be implemented into EMPIRE.

  11. Efeitos do ácido ascórbico nos biomarcadores de estresse oxidativo em nadadores de elite

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    Monike Garlipp-Picchi

    2013-12-01

    Full Text Available OBJETIVO: O objetivo do estudo foi verificar os efeitos da oferta de vitamina C através de um suplemento alimentar e dieta rica em ácido ascórbico (AA no estresse oxidativo induzido pelo exercício. MÉTODOS: A amostra foi composta por 13 nadadores de elite (seis homens e sete mulheres com idades entre 18 e 26 anos. Os mesmos atletas foram submetidos a sessão de exercício agudo em três fases, com diferentes tratamentos: controle (C, dieta rica em AA (D e suplemento de AA (S, nas quais amostras de sangue foram colhidas antes, imediatamente após e 24 horas depois do exercício. Para comparação entre as fases e etapas foi utilizado o modelo de regressão linear com efeitos mistos. RESULTADOS: O consumo alimentar habitual de antioxidantes não foi diferente entre as fases, apenas a ingestão de AA foi maior na fase D e S em relação à fase C. O uso de dieta rica em AA favoreceu uma menor peroxidação lipídica, devido aos menores valores de hidroperóxidos lipídicos (FOX, diminuição da peroxidação após exercício, pela diminuição de substâncias reativas ao ácido tiobarbitúrico (TBARS e aumento dos níveis de vitamina C logo após o exercício. O uso de suplemento de AA também conteve a peroxidação lipídica após exercício e aumentou o poder antioxidante, devido aos maiores níveis de glutationa reduzida (GSH. Sem adição de AA os nadadores tiveram um maior dano hepático, pois apresentaram maiores níveis de transaminase-glutâmico-oxalacética (TGO, menores níveis de antioxidantes (vitamina C e GSH e aumento do ácido úrico. CONCLUSÃO: Assim, as mudanças observadas com a adição de AA à dieta de nadadores sugerem um importante papel deste micronutriente na defesa contra o estresse oxidativo induzido pelo exercício.

  12. A veritable menagerie of heritable bacteria from ants, butterflies, and beyond: broad molecular surveys and a systematic review.

    Directory of Open Access Journals (Sweden)

    Jacob A Russell

    Full Text Available Maternally transmitted bacteria have been important players in the evolution of insects and other arthropods, affecting their nutrition, defense, development, and reproduction. Wolbachia are the best studied among these and typically the most prevalent. While several other bacteria have independently evolved a heritable lifestyle, less is known about their host ranges. Moreover, most groups of insects have not had their heritable microflora systematically surveyed across a broad range of their taxonomic diversity. To help remedy these shortcomings we used diagnostic PCR to screen for five groups of heritable symbionts-Arsenophonus spp., Cardinium hertigii, Hamiltonella defensa, Spiroplasma spp., and Wolbachia spp.-across the ants and lepidopterans (focusing, in the latter case, on two butterfly families-the Lycaenidae and Nymphalidae. We did not detect Cardinium or Hamiltonella in any host. Wolbachia were the most widespread, while Spiroplasma (ants and lepidopterans and Arsenophonus (ants only were present at low levels. Co-infections with different Wolbachia strains appeared especially common in ants and less so in lepidopterans. While no additional facultative heritable symbionts were found among ants using universal bacterial primers, microbes related to heritable enteric bacteria were detected in several hosts. In summary, our findings show that Wolbachia are the dominant heritable symbionts of ants and at least some lepidopterans. However, a systematic review of symbiont frequencies across host taxa revealed that this is not always the case across other arthropods. Furthermore, comparisons of symbiont frequencies revealed that the prevalence of Wolbachia and other heritable symbionts varies substantially across lower-level arthropod taxa. We discuss the correlates, potential causes, and implications of these patterns, providing hypotheses on host attributes that may shape the distributions of these influential bacteria.

  13. A Veritable Menagerie of Heritable Bacteria from Ants, Butterflies, and Beyond: Broad Molecular Surveys and a Systematic Review

    Science.gov (United States)

    Russell, Jacob A.; Funaro, Colin F.; Giraldo, Ysabel M.; Goldman-Huertas, Benjamin; Suh, David; Kronauer, Daniel J. C.; Moreau, Corrie S.; Pierce, Naomi E.

    2012-01-01

    Maternally transmitted bacteria have been important players in the evolution of insects and other arthropods, affecting their nutrition, defense, development, and reproduction. Wolbachia are the best studied among these and typically the most prevalent. While several other bacteria have independently evolved a heritable lifestyle, less is known about their host ranges. Moreover, most groups of insects have not had their heritable microflora systematically surveyed across a broad range of their taxonomic diversity. To help remedy these shortcomings we used diagnostic PCR to screen for five groups of heritable symbionts—Arsenophonus spp., Cardinium hertigii, Hamiltonella defensa, Spiroplasma spp., and Wolbachia spp.—across the ants and lepidopterans (focusing, in the latter case, on two butterfly families—the Lycaenidae and Nymphalidae). We did not detect Cardinium or Hamiltonella in any host. Wolbachia were the most widespread, while Spiroplasma (ants and lepidopterans) and Arsenophonus (ants only) were present at low levels. Co-infections with different Wolbachia strains appeared especially common in ants and less so in lepidopterans. While no additional facultative heritable symbionts were found among ants using universal bacterial primers, microbes related to heritable enteric bacteria were detected in several hosts. In summary, our findings show that Wolbachia are the dominant heritable symbionts of ants and at least some lepidopterans. However, a systematic review of symbiont frequencies across host taxa revealed that this is not always the case across other arthropods. Furthermore, comparisons of symbiont frequencies revealed that the prevalence of Wolbachia and other heritable symbionts varies substantially across lower-level arthropod taxa. We discuss the correlates, potential causes, and implications of these patterns, providing hypotheses on host attributes that may shape the distributions of these influential bacteria. PMID:23284655

  14. Antocianinas, ácido ascórbico, polifenoles totales y actividad antioxidante, en la cáscara de camu-camu (Myrciaria dubia (H.B.K McVaugh Antocianinas, ácido ascórbico, polifenóis totais e atividade antioxidante na casca do camu-camu (Myrciaria dubia (H.B.K McVaugh

    Directory of Open Access Journals (Sweden)

    Juan Edson Villanueva-Tiburcio

    2010-05-01

    Full Text Available Este trabajo fue realizado en la UNAS, Tingo María, Perú. Los objetivos fueron evaluar el contenido de antocianinas, ácido ascórbico, y polifenoles totales, en la cáscara fresca y seca de camu-camu (Myrciaria dubia (H.B.K McVaugh en diferentes estados de madurez; evaluar la actividad antioxidante en la cáscara seca, usando diferentes tipos de radicales (DPPH, ABTS+ y Peroxilo y correlacionar el valor de ácido ascórbico y polifenoles totales con la actividad antioxidante. La extracción fue realizada en medio acuoso, y los resultados de las evaluaciones de cada experimento fueron analizados por un diseño completamente al azar (DCA, según la prueba de t-student (p A pesquisa foi realizada na UNAS em Tingo Maria, Peru, teve como objetivos: avaliar o teor de antocianinas, ácido ascórbico e polifenóis totais, na casca fresca e na casca seca do camu-camu (Myrciaria dubia (HBK McVaugh em diferentes tempos de maturação; avaliar a atividade antioxidante na casca seca utilizando diferentes tipos de radicais (DPPH, ABTS+ e Peroxilo e correlacionar o teor de ácido ascórbico e polifenóis totais com a atividade antioxidante. A extraç��o foi realizada em meio aquoso, os resultados das avaliações de cada experiência são analisados no delineamento inteiramente casualizado (DIC, pelo teste de t-student (p < 0,05. O extrato da casca da amostra madura fresca apresentou as concentrações mais elevadas de ácido ascórbico e de antocianinas em relação a meio madura e verde, com 21,95 mg.g-1 de casca e 46,42 mg.L-1 de cianidin-3-glucosídeo, respectivamente, enquanto que o extrato da casca seca meio madura apresentou o maior teor de ácido ascórbico em relação a madura e verde (53,49 mg.g-1 e de polifenóis totais: 7,70 mg Ác. Gálico/g. A maior atividade antioxidante foi encontrada no extrato da casca seca da amostra meio madura com IC50 = 46,20; 20,25 e 8,30 μg.mL-1, em comparação com DPPH radical, ABTS+ e Perox

  15. Heritability of peripheral refraction in Chinese children and adolescents: the Guangzhou Twin Eye study.

    Science.gov (United States)

    Ding, Xiaohu; Lin, Zhi; Huang, Qunxiao; Zheng, Yingfeng; Congdon, Nathan; He, Mingguang

    2012-01-10

    To estimate the heritability of peripheral refraction in Chinese children and adolescents. The authors examined 72 monozygotic (MZ) twins and 48 dizygotic (DZ) twins aged 8 to 20 years from a population-based twin registry. Temporal and nasal peripheral refraction, each 40° from the visual axis, and axial refraction were measured using an autorefractor. Relative peripheral refractive error (RPRE) was defined as the peripheral refraction minus the axial refraction. Heritability was assessed by structural equation modeling after adjustment for age and sex. The mean and SD of temporal refraction (T(40)), nasal refraction (N(40)), RPRE-T(40), RPRE-N(40), and T(40)-N(40) asymmetry were -0.27 ± 2.0 D, 0.36 ± 2.19 D, 1.18 ± 1.39 D, 1.80 ± 1.69 D, and -0.62 ± 1.58 D, respectively. The intraclass correlations for T(40) refraction, N(40) refraction, RPRE-T(40), RPRE-N(40), and T(40)-N(40) asymmetry were 0.87, 0.83, 0.65, 0.74, and 0.58 for MZ pairs and 0.49, 0.42, 0.30, 0.41, and 0.32 for DZ pairs, respectively. A model with additive genetic and unique environmental effects was the most parsimonious, with heritability values estimated as 0.84, 0.76, 0.63, 0.70, and 0.55, respectively, for the peripheral refractive parameters. Additive genetic effects appear to explain most of the variance in peripheral refraction and relative peripheral refraction when adjusting for the effects of axial refraction.

  16. Sex differences and heritability of two indices of heart rate dynamics: a twin study.

    Science.gov (United States)

    Snieder, Harold; van Doornen, Lorenz J P; Boomsma, Dorret I; Thayer, Julian F

    2007-04-01

    We investigated whether women show larger heart rate variability (HRV) than men after controlling for a large number of health-related covariates, using two indices of HRV, namely respiratory sinus arrhythmia (RSA) and approximate entropy (ApEn). In a twin design, the heritability of both indices was examined. The covariation between RSA and ApEn, a measure of heart rate dynamics derived from nonlinear dynamical systems theory, was decomposed into genetic and environmental components. Subjects were 196 male and 210 female middle-aged twins. Females showed larger HRV than men before (ApEn: p RSA: p = .052) and after adjustment for covariates (ApEn: p RSA: p = .015). This sex difference was confirmed by significant intrapair differences in the opposite-sex twin pairs for both ApEn (p RSA (p = .03). In addition to sex, only heart period and age (both p RSA was also influenced by respiration rate and smoking (both p RSA and ApEn, respectively. Oral contraceptive use and menopausal status had no effect on HRV. Genetic model fitting yielded moderate heritability estimates for RSA (30%) and ApEn (40%) for both males and females. The correlation between RSA and ApEn (r = .60) could be attributed to genetic factors (48%), environmental factors (36%) and age (16%). The present study found support for a gender difference in HRV with women having greater HRV than men even after controlling for a large number of potential confounders. Indices of heart rate dynamics derived from nonlinear dynamical systems theory are moderately heritable and may be more sensitive than traditional indices of HRV to reveal subtle sex differences with important implications for health and disease.

  17. Heritability and genetic correlation of hair cortisol in vervet monkeys in low and higher stress environments.

    Science.gov (United States)

    Fairbanks, Lynn A; Jorgensen, Matthew J; Bailey, Julia N; Breidenthal, Sherry E; Grzywa, Rachel; Laudenslager, Mark L

    2011-09-01

    Chronic activation of the hypothalamic-pituitary adrenal (HPA) system is a risk factor for a variety of physical and mental disorders, and yet the complexity of the system has made it difficult to define the role of genetic and environmental factors in producing long-term individual differences in HPA activity. Cortisol levels in hair have been suggested as a marker of total HPA activation over a period of several months. This study takes advantage of a pedigreed nonhuman primate colony to investigate genetic and environmental influences on hair cortisol levels before and after an environmental change. A sample of 226 adult female vervet monkeys (age 3-18) living in multigenerational, matrilineal social groups at the Vervet Research Colony were sampled in a stable low stress baseline environment and 6 months after the entire colony was moved to a new facility with more frequent handling and group disturbances (higher stress environment). Variance components analysis using the extended colony pedigree was applied to determine heritability of hair cortisol levels in the two environments. Bivariate genetic correlation assessed degree of overlap in genes influencing hair cortisol levels in the low and higher stress environments. The results showed that levels of cortisol in hair of female vervets increased significantly from the baseline to the post-move environment. Hair cortisol levels were heritable in both environments (h(2)=0.31), and there was a high genetic correlation across environments (rhoG=0.79), indicating substantial overlap in the genes affecting HPA activity in low and higher stress environments. This is the first study to demonstrate that the level of cortisol in hair is a heritable trait. It shows the utility of hair cortisol as a marker for HPA activation, and a useful tool for identifying genetic influences on long term individual differences in HPA activity. The results provide support for an additive model of the effects of genes and environment

  18. Heritability of in vitro phenotypes exhibited by murine adipose-derived stromal cells.

    Science.gov (United States)

    Jiang, Zixuan; Harrison, David E; Parsons, Makayla E; McClatchy, Susan; Jacobs, Lawrence; Pazdro, Robert

    2016-10-01

    Adipose-derived stromal cells (ADSCs) exhibit significant potential as therapeutic agents to promote tissue regeneration. Success of ADSC-based therapies is dependent upon efficient cell expansion in vitro as well as postinjection survival in the caustic milieu of damaged tissue. Genetic background regulates ADSC proliferative capacity and stress resistance, but the extent of the genetic effect size is not completely defined. The present study aimed to quantify phenotypic ranges and heritability of in vitro ADSC characteristics. ADSCs were isolated from mice representing 16 genetically diverse inbred mouse strains, including 12 classical inbred strains and four wild-derived strains. Cells were grown in vitro, and proliferative capacity and oxidative stress resistance were assessed. The fold change for ADSC growth ranged from 0.87 (BALB/cByJ) to 23.60 (POHN/DehJ), relative to original seeding density. The heritability of proliferative capacity was estimated to be 0.6462 (p = 9.967 × 10(-15)), and this phenotype was not associated with other ADSC traits. Cell viability following H2O2 treatment ranged from 39.81 % (CAST/EiJ) to 91.60 % (DBA/2 J), and the heritability of this phenotype was calculated as 0.6146 (p = 1.22 × 10(-12)). Relationships between cell viability and weight of the donor fat pad were also discovered. Donor genetic background is a major determinant of in vitro ADSC phenotypes. This study supports the development of forward genetics strategies to identify genes that underlie ADSC phenotypic diversity, which will inform efforts to improve cell-based therapies.

  19. Heritabilities and genetic and phenotypic correlations of litter uniformity and litter size in Large White sows

    Institute of Scientific and Technical Information of China (English)

    ZHANG Tian; ZHAO Ke-bin; WANG Li-xian; WANG Li-gang; SHI Hui-bi; YAN Hua; ZHANG Long-chao; LIU Xin; PU Lei; LIANG Jing; ZHANG Yue-bo

    2016-01-01

    Litter uniformity, which is usualy represented by within-litter weight coefifcient of variation at birth (CVB), could inlfuence litter performance of sows and the proiftability of pig enterprises. The objective of this study was to characterize CVB and its effect on other reproductive traits in Large White sows. Genetic parameters and genetic correlation of the reproductive traits, including CVB, within-litter weight coefifcient of variation at three weeks (CVT), total number born (TNB), number born alive (NBA), number born dead (NBD), gestation length (GL), piglet mortality at birth (M0), piglet mortality at three weeks (M3), total litter weight at birth (TLW0), and total litter weight at three weeks (TLW3) were estimated for 2032 Large White litters. The effects of parity and classiifed litter size on CVB, CVT, TNB, NBA, NBD, GL, M0, M3, TLW0, and TLW3 were also estimated. The heritabilities of these reproductive traits ranged from 0.06 to 0.17, with the lowest heritability for CVB and the highest heritability for TLW0. Phenotypic and genetic correlations between these reproductive traits were low to highly positive and negative (ranging from −0.03 to 0.93, and −0.53 to 0.93, respectively). The genetic correlations between TNB and CVB, and between M0 and CVB were 0.32 and 0.29, respectively. In addition, CVB was signiifcantly inlfuenced by parity and litter size class (P<0.05). Al the results suggest that piglet uniformity should be maintained in pig production practices and pig breeding programs.

  20. Variation and Heritability of Phenology in the Fungus Monilinia vaccinii-corymbosi on Blueberry.

    Science.gov (United States)

    Lehman, J S; Oudemans, P V

    2000-04-01

    ABSTRACT The germination of field-collected pseudosclerotia and the development of apothecia from eight New Jersey populations of the mummy berry fungus Monilinia vaccinii-corymbosi were evaluated under controlled conditions in the greenhouse. Development data for apothecia were used to describe the timing of apothecium formation and to estimate broad- and narrow-sense heritabilities of fungal phenology. Mean development times for the formation of apothecia ranged from 35.4 to 54.7 days. The mean development times for populations collected from early-season cv. Weymouth ranged from 35.4 to 39.6 days and were significantly shorter than the development times for three of the four populations collected from late-season cv. Jersey (46.9 to 54.7 days) or for the population collected from mixed stands of cultivated blueberries (42.7 days). The development of populations from late cultivars planted in very close proximity to early cv. Weymouth was early (36.5 to 39.0 days) and not significantly different from the development of populations collected from cv. Weymouth. Phenotypic and genetic variances of apothecium development for individual populations ranged from 18.9 to 44.8 and 7.2 to 30.9, respectively. Broad-sense heritabilities of apothecia development for each fungal population, calculated by partitioning phenotypic variation into genetic and environmental components, ranged from 0.31 to 0.78. Narrow-sense heritabilities of apothecia development, based on parent-offspring regression, ranged from 0.58 to 0.78. These results indicate that populations of M. vaccinii-corymbosi differ in phenology and that a significant portion of the phenological variation within populations is genetic. Thus, it is plausible to propose that the phenology of apothecium development is a component of fungal fitness and that host phenology can influence the timing of pathogen development.

  1. Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways.

    Science.gov (United States)

    Bossini-Castillo, Lara; López-Isac, Elena; Martín, Javier

    2015-11-01

    Systemic sclerosis (SSc) is a clinically heterogeneous connective tissue disorder of complex etiology. The development of large-scale genetic studies, such as genome-wide association studies (GWASs) or the Immunochip platform, has achieved remarkable progress in the knowledge of the genetic background of SSc. Herein, we provide an updated picture SSc genetic factors, offering an insight into their role in pathogenic mechanisms that characterize the disease. We review the most recent findings in the HLA region and the well-established non-HLA loci. Up to 18 non-HLA risk factors fulfilled the selected criteria and they were classified according to their role in the innate or adaptive immune response, in apoptosis, autophagy or fibrosis. Additionally, SSc heritability has remained as a controversial question since twin studies provided low SSc heritability estimates. However, we have recalculated the lower bond of narrow sense SSc heritability using GWAS data. Remarkably, our results suggest a greater influence of genetics on SSc than previously reported. Furthermore, we also offer a functional classification of SSc-associated SNPs and their proxies, based on annotated data, to provide clues for the identification of causal variants in these loci. Finally, we explore the genetic overlap between SSc and other autoimmune diseases (ADs). The vast majority of SSc risk loci are shared with at least one additional AD, being the overlap between SSc and systemic lupus erythematous the largest. Nevertheless, we found that an important portion of SSc risk factors are also common to rheumatoid arthritis or primary biliary cirrhosis. Considering all these evidences, we are confident that future research will be successful in understanding the relevant altered pathways in SSc and in identifying new biomarkers and therapeutic targets for the disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Survey of the Heritability and Sparse Architecture of Gene Expression Traits across Human Tissues

    Science.gov (United States)

    Wheeler, Heather E.; Shah, Kaanan P.; Brenner, Jonathon; Garcia, Tzintzuni; Aquino-Michaels, Keston; Cox, Nancy J.; Nicolae, Dan L.

    2016-01-01

    Understanding the genetic architecture of gene expression traits is key to elucidating the underlying mechanisms of complex traits. Here, for the first time, we perform a systematic survey of the heritability and the distribution of effect sizes across all representative tissues in the human body. We find that local h2 can be relatively well characterized with 59% of expressed genes showing significant h2 (FDR compute distal h2. Bayesian Sparse Linear Mixed Model (BSLMM) analysis provides strong evidence that the genetic contribution to local expression traits is dominated by a handful of genetic variants rather than by the collective contribution of a large number of variants each of modest size. In other words, the local architecture of gene expression traits is sparse rather than polygenic across all 40 tissues (from DGN and GTEx) examined. This result is confirmed by the sparsity of optimal performing gene expression predictors via elastic net modeling. To further explore the tissue context specificity, we decompose the expression traits into cross-tissue and tissue-specific components using a novel Orthogonal Tissue Decomposition (OTD) approach. Through a series of simulations we show that the cross-tissue and tissue-specific components are identifiable via OTD. Heritability and sparsity estimates of these derived expression phenotypes show similar characteristics to the original traits. Consistent properties relative to prior GTEx multi-tissue analysis results suggest that these traits reflect the expected biology. Finally, we apply this knowledge to develop prediction models of gene expression traits for all tissues. The prediction models, heritability, and prediction performance R2 for original and decomposed expression phenotypes are made publicly available (https://github.com/hakyimlab/PrediXcan). PMID:27835642

  3. Heritability in the efficiency of nonsense-mediated mRNA decay in humans

    KAUST Repository

    Seoighe, Cathal

    2010-07-21

    Background: In eukaryotes mRNA transcripts of protein-coding genes in which an intron has been retained in the coding region normally result in premature stop codons and are therefore degraded through the nonsense-mediated mRNA decay (NMD) pathway. There is evidence in the form of selective pressure for in-frame stop codons in introns and a depletion of length three introns that this is an important and conserved quality-control mechanism. Yet recent reports have revealed that the efficiency of NMD varies across tissues and between individuals, with important clinical consequences. Principal Findings: Using previously published Affymetrix exon microarray data from cell lines genotyped as part of the International HapMap project, we investigated whether there are heritable, inter-individual differences in the abundance of intron-containing transcripts, potentially reflecting differences in the efficiency of NMD. We identified intronic probesets using EST data and report evidence of heritability in the extent of intron expression in 56 HapMap trios. We also used a genome-wide association approach to identify genetic markers associated with intron expression. Among the top candidates was a SNP in the DCP1A gene, which forms part of the decapping complex, involved in NMD. Conclusions: While we caution that some of the apparent inter-individual difference in intron expression may be attributable to different handling or treatments of cell lines, we hypothesize that there is significant polymorphism in the process of NMD, resulting in heritable differences in the abundance of intronic mRNA. Part of this phenotype is likely to be due to a polymorphism in a decapping enzyme on human chromosome 3. © 2010 Seoighe, Gehring.

  4. Heritability in the efficiency of nonsense-mediated mRNA decay in humans.

    LENUS (Irish Health Repository)

    Seoighe, Cathal

    2010-01-01

    BACKGROUND: In eukaryotes mRNA transcripts of protein-coding genes in which an intron has been retained in the coding region normally result in premature stop codons and are therefore degraded through the nonsense-mediated mRNA decay (NMD) pathway. There is evidence in the form of selective pressure for in-frame stop codons in introns and a depletion of length three introns that this is an important and conserved quality-control mechanism. Yet recent reports have revealed that the efficiency of NMD varies across tissues and between individuals, with important clinical consequences. PRINCIPAL FINDINGS: Using previously published Affymetrix exon microarray data from cell lines genotyped as part of the International HapMap project, we investigated whether there are heritable, inter-individual differences in the abundance of intron-containing transcripts, potentially reflecting differences in the efficiency of NMD. We identified intronic probesets using EST data and report evidence of heritability in the extent of intron expression in 56 HapMap trios. We also used a genome-wide association approach to identify genetic markers associated with intron expression. Among the top candidates was a SNP in the DCP1A gene, which forms part of the decapping complex, involved in NMD. CONCLUSIONS: While we caution that some of the apparent inter-individual difference in intron expression may be attributable to different handling or treatments of cell lines, we hypothesize that there is significant polymorphism in the process of NMD, resulting in heritable differences in the abundance of intronic mRNA. Part of this phenotype is likely to be due to a polymorphism in a decapping enzyme on human chromosome 3.

  5. Heritability and factors associated with number of harness race starts in the Spanish Trotter horse population.

    Science.gov (United States)

    Solé, M; Valera, M; Gómez, M D; Sölkner, J; Molina, A; Mészáros, G

    2017-05-01

    Longevity/durability is a relevant trait in racehorses. Genetic analysis and knowledge of factors that influence number of harness race starts would be advantageous for both horse welfare and the equine industry. To perform a genetic analysis on harness racing using number of races as a measure of longevity/durability and to identify factors associated with career length in Spanish Trotter Horses (STH). Longitudinal study. Performance data (n = 331,970) on the STH population for harness racing at national level between 1990 and 2014 were used. A grouped data model was fitted to assess factors influencing the risk of ending harness racing career and to estimate the heritability and breeding values for total number of harness races starts as an indicator of horses' longevity and durability. The model included sex, age at first race and first start earnings as time-independent effects, and the calendar year, driver, trainer, racetrack category and season of competition as time-dependent effects. Across the whole dataset, the average number of harness races horses achieved in Spain was 54.7 races, and this was associated with the horses' sex, age at first race and first start earnings, calendar year, driver, racetrack category, and season. The heritability estimated (0.17 ± 0.01) for number of harness race starts indicates that a beneficial response to direct genetic selection can be expected. Data on horses' health status were not available. Horses' total number of harness race starts is a promising tool for genetic analysis and the evaluation of racing longevity and durability. The estimated heritability provides evidence to support the application of genetic selection of total career number of races to improve longevity/durability of STH. © 2016 EVJ Ltd.

  6. Sexual dimorphism in melanin pigmentation, feather coloration and its heritability in the barn swallow (Hirundo rustica).

    Science.gov (United States)

    Saino, Nicola; Romano, Maria; Rubolini, Diego; Teplitsky, Celine; Ambrosini, Roberto; Caprioli, Manuela; Canova, Luca; Wakamatsu, Kazumasa

    2013-01-01

    Melanin is the main pigment in animal coloration and considerable variation in the concentrations of the two melanin forms (pheo- and eumlanin) in pigmented tissues exists among populations and individuals. Melanin-based coloration is receiving increasing attention particularly in socio-sexual communication contexts because the melanocortin system has been hypothesized to provide a mechanistic basis for covariation between coloration and fitness traits. However, with few notable exceptions, little detailed information is available on inter-individual and inter-population variation in melanin pigmentation and on its environmental, genetic and ontogenetic components. Here, we investigate melanin-based coloration in an Italian population of a passerine bird, the barn swallow (Hirundo rustica rustica), its sex- and age-related variation, and heritability. The concentrations of eu- and pheomelanin in the throat (brown) and belly (white-to-brownish) feathers differed between sexes but not according to age. The relative concentration of either melanin (Pheo:Eu) differed between sexes in throat but not in belly feathers, and the concentrations in males compared to females were larger in belly than in throat feathers. There were weak correlations between the concentrations of melanins within as well as among plumage regions. Coloration of belly feathers was predicted by the concentration of both melanins whereas coloration of throat feathers was only predicted by pheomelanin in females. In addition, Pheo:Eu predicted coloration of throat feathers in females and that of belly feathers in males. Finally, we found high heritability of color of throat feathers. Melanization was found to differ from that recorded in Hirundo rustica rustica from Scotland or from H. r. erythrogaster from North America. Hence, present results show that pigmentation strategies vary in a complex manner according to sex and plumage region, and also among geographical populations, potentially

  7. Heritability of hsp70 expression in the beetle Tenebrio molitor: Ontogenetic and environmental effects.

    Science.gov (United States)

    Lardies, Marco A; Arias, María Belén; Poupin, María Josefina; Bacigalupe, Leonardo D

    2014-08-01

    Ectotherms constitute the vast majority of terrestrial biodiversity and are especially likely to be vulnerable to climate warming because their basic physiological functions such as locomotion, growth, and reproduction are strongly influenced by environmental temperature. An integrated view about the effects of global warming will be reached not just establishing how the increase in mean temperature impacts the natural populations but also establishing the effects of the increase in temperature variance. One of the molecular responses that are activated in a cell under a temperature stress is the heat shock protein response (HSP). Some studies that have detected consistent differences among thermal treatments and ontogenetic stages in HSP70 expression have assumed that these differences had a genetic basis and consequently expression would be heritable. We tested for changes in quantitative genetic parameters of HSP70 expression in a half-sib design where individuals of the beetle Tenebrio molitor were maintained in constant and varying thermal environments. We estimated heritability of HSP70 expression using a linear mixed modelling approach in different ontogenetic stages. Expression levels of HSP70 were consistently higher in the variable environment and heritability estimates were low to moderate. The results imply that within each ontogenetic stage additive genetic variance was higher in the variable environment and in adults compared with constant environment and larvae stage, respectively. We found that almost all the genetic correlations across ontogenetic stages and environment were positive. These suggest that directional selection for higher levels of expression in one environment will result in higher expression levels of HSP70 on the other environment for the same ontogenetic stage.

  8. Heritability in the efficiency of nonsense-mediated mRNA decay in humans.

    Directory of Open Access Journals (Sweden)

    Cathal Seoighe

    Full Text Available BACKGROUND: In eukaryotes mRNA transcripts of protein-coding genes in which an intron has been retained in the coding region normally result in premature stop codons and are therefore degraded through the nonsense-mediated mRNA decay (NMD pathway. There is evidence in the form of selective pressure for in-frame stop codons in introns and a depletion of length three introns that this is an important and conserved quality-control mechanism. Yet recent reports have revealed that the efficiency of NMD varies across tissues and between individuals, with important clinical consequences. PRINCIPAL FINDINGS: Using previously published Affymetrix exon microarray data from cell lines genotyped as part of the International HapMap project, we investigated whether there are heritable, inter-individual differences in the abundance of intron-containing transcripts, potentially reflecting differences in the efficiency of NMD. We identified intronic probesets using EST data and report evidence of heritability in the extent of intron expression in 56 HapMap trios. We also used a genome-wide association approach to identify genetic markers associated with intron expression. Among the top candidates was a SNP in the DCP1A gene, which forms part of the decapping complex, involved in NMD. CONCLUSIONS: While we caution that some of the apparent inter-individual difference in intron expression may be attributable to different handling or treatments of cell lines, we hypothesize that there is significant polymorphism in the process of NMD, resulting in heritable differences in the abundance of intronic mRNA. Part of this phenotype is likely to be due to a polymorphism in a decapping enzyme on human chromosome 3.

  9. Heritability estimates for methane emission in Holstein cows using breath measurements

    DEFF Research Database (Denmark)

    Lassen, Jan; Madsen, Jørgen; Løvendahl, Peter

    2012-01-01

    cows. On a total of 683 dairy cows a Fourier Transformed Infrared (FTIR) measuring unit was used to make large scale individual methane emission records. The cows were measured in 7 herds during their visits to automatic milking systems (AMS). The FTIR unit air inlet was mounted in the front part...... model included fixed effects of herd, month, days in milk, lactation number, and random effects of animal and residual. Variance components were estimated in an animal model design using a pedigree containing 9661 animals. The heritability of the methane to carbon dioxide ratio was moderate (0...

  10. Nest-mate recognition based on heritable odors in the termite Microcerotermes arboreus.

    Science.gov (United States)

    Adams, E S

    1991-03-01

    Workers of the Neotropical termite Microcerotermes arboreus distinguish nest mates from other conspecifics by odor. A controlled breeding experiment demonstrated a genetic component to variation in colony odors. Workers were less aggressive toward unfamiliar relatives than toward nonrelatives and distinguished degree of relatedness among unfamiliar workers. Unfamiliar relatives were attacked more often than nest mates, despite similar levels of genetic relatedness; thus, nest-mate recognition is not based solely upon heritable characteristics of individual workers. No difference was detected between the effects of cues inherited through the mother and cues inherited through the father.

  11. Association Between Mortality and Heritability of the Scale of Aging Vigor in Epidemiology

    DEFF Research Database (Denmark)

    Sanders, Jason L; Singh, Jatinder; Minster, Ryan L

    2016-01-01

    (LLFS) in the United States and Denmark. PARTICIPANTS: Long-lived individuals (N = 4,875, including 4,075 genetically related individuals) and their families (N = 551). MEASUREMENTS: The SAVE was administered to 3,599 participants and included weight change, weakness (grip strength), fatigue......OBJECTIVES: To investigate the association between mortality and heritability of a rescaled Fried frailty index, the Scale of Aging Vigor in Epidemiology (SAVE), to determine its value for genetic analyses. DESIGN: Longitudinal, community-based cohort study. SETTING: The Long Life Family Study......, suggesting a genetic component to age-related vigor and frailty and supporting its use for further genetic analyses....

  12. Heritable influence of DBH on adrenergic and renal function: twin and disease studies.

    Directory of Open Access Journals (Sweden)

    Dalal N Pasha

    Full Text Available BACKGROUND: Elevated sympathetic activity is associated with kidney dysfunction. Here we used twin pairs to probe heritability of GFR and its genetic covariance with other traits. METHODS: We evaluated renal and adrenergic phenotypes in twins. GFR was estimated by CKD-EPI algorithm. Heritability and genetic covariance of eGFR and associated risk traits were estimated by variance-components. Meta-analysis probed reproducibility of DBH genetic effects. Effect of DBH genetic variation on renal disease was tested in the NIDDK-AASK cohort. RESULTS: Norepinephrine secretion rose across eGFR tertiles while eGFR fell (p<0.0001. eGFR was heritable, at h(2 = 67.3±4.7% (p = 3.0E-18, as were secretion of norepinephrine (h(2 = 66.5±5.0%, p = 3.2E-16 and dopamine (h(2 = 56.5±5.6%, p = 1.8E-13, and eGFR displayed genetic co-determination (covariance with norepinephrine (ρG = -0.557±0.088, p = 1.11E-08 as well as dopamine (ρG = -0.223±0.101, p = 2.3E-02. Since dopamine β-hydroxylase (DBH catalyzes conversion of dopamine to norepinephrine, we studied functional variation at DBH; DBH promoter haplotypes predicted transcriptional activity (p<0.001, plasma DBH (p<0.0001 and norepinephrine (p = 0.0297 secretion; transcriptional activity was inversely (p<0.0001 associated with basal eGFR. Meta-analysis validated DBH haplotype effects on eGFR across 3 samples. In NIDDK-AASK, we established a role for DBH promoter variation in long-term renal decline rate (GFR slope, p = 0.003. CONCLUSIONS: The heritable GFR trait shares genetic determination with catecholamines, suggesting new pathophysiologic, diagnostic and therapeutic approaches towards disorders of GFR as well as CKD. Adrenergic activity may play a role in progressive renal decline, and genetic variation at DBH may assist in profiling subjects for rational preventive treatment.

  13. Heritability of strabismus: genetic influence is specific to eso-deviation and independent of refractive error.

    Science.gov (United States)

    Sanfilippo, Paul G; Hammond, Christopher J; Staffieri, Sandra E; Kearns, Lisa S; Melissa Liew, S H; Barbour, Julie M; Hewitt, Alex W; Ge, Dongliang; Snieder, Harold; Mackinnon, Jane R; Brown, Shayne A; Lorenz, Birgit; Spector, Tim D; Martin, Nicholas G; Wilmer, Jeremy B; Mackey, David A

    2012-10-01

    Strabismus represents a complex oculomotor disorder characterized by the deviation of one or both eyes and poor vision. A more sophisticated understanding of the genetic liability of strabismus is required to guide searches for associated molecular variants. In this classical twin study of 1,462 twin pairs, we examined the relative influence of genes and environment in comitant strabismus, and the degree to which these influences can be explained by factors in common with refractive error. Participants were examined for the presence of latent ('phoria') and manifest ('tropia') strabismus using cover-uncover and alternate cover tests. Two phenotypes were distinguished: eso-deviation (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural equation modeling was subsequently employed to partition the observed phenotypic variation in the twin data into specific variance components. The prevalence of eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso-deviation, the polychoric correlation was significantly greater in monozygotic (MZ) (r = 0.65) compared to dizygotic (DZ) twin pairs (r = 0.33), suggesting a genetic role (p = .003). There was no significant difference in polychoric correlation between MZ (r = 0.55) and DZ twin pairs (r = 0.53) for exo-deviation (p = .86), implying that genetic factors do not play a significant role in the etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI 0.50-0.75). The additive genetic correlation for eso-deviation and refractive error was 0.13 and the bivariate heritability (i.e., shared variance) was less than 1%, suggesting negligible shared genetic effect. This study documents a substantial heritability of 64% for eso-deviation, yet no corresponding heritability for exo-deviation, suggesting that the genetic contribution to strabismus may be specific to eso-deviation. Future studies are now needed to identify the genes associated with eso-deviation and

  14. Heritable oxidative phosphorylation differences in a pollutant resistant Fundulus heteroclitus population

    Energy Technology Data Exchange (ETDEWEB)

    Du, Xiao, E-mail: xdu@rsmas.miami.edu [Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Science, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33149 (United States); Crawford, Douglas L. [Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Science, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33149 (United States); Nacci, Diane E. [Population Ecology Branch, Atlantic Ecology Division, Office of Research and Development, U.S. Environmental Protection Agency, 27 Tarzwell Dr., Narragansett, RI 02882 (United States); Oleksiak, Marjorie F., E-mail: moleksiak@rsmas.miami.edu [Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Science, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33149 (United States)

    2016-08-15

    Highlights: • Laboratory reared fish from a highly polluted and clean reference population were compared. • Oxidative phosphorylation (e.g., State 3, enzymes, and proton LEAK) was quantified. • Laboratory reared F3 fish from polluted population displayed higher routine metabolism and complex II activity but lower complex I enzyme activity. • Enhanced OxPhos metabolism and toxicity resistance were retained in laboratory reared F3 fish from the polluted population. - Abstract: Populations can adapt to stress including recent anthropogenic pollution. Our published data suggests heritable differences in hepatocyte oxidative phosphorylation (OxPhos) metabolism in field-caught killifish (Fundulus heteroclitus) from the highly polluted Elizabeth River, VA, USA, relative to fish from a nearby, relatively unpolluted reference site in King’s Creek VA. Consistent with other studies showing that Elizabeth River killifish are resistant to some of the toxic effects of certain contaminants, OxPhos measurements in hepatocytes from field-caught King’s Creek but not field-caught Elizabeth River killifish were altered by acute benzo [a] pyrene exposures. To more definitively test whether the enhanced OxPhos metabolism and toxicity resistance are heritable, we measured OxPhos metabolism in a laboratory-reared F3 generation from the Elizabeth River population versus a laboratory-reared F1 generation from the King’s Creek population and compared these results to previous data from the field-caught fish. The F3 Elizabeth River fish compared to F1 King’s Creek fish had significantly higher State 3 respiration (routine metabolism) and complex II activity, and significantly lower complex I activity. The consistently higher routine metabolism in the F3 and field-caught Elizabeth River fish versus F1 and field-caught King’s Creek fish implies a heritable change in OxPhos function. The observation that LEAK, E-State, Complex I and Complex II were different in laboratory bred

  15. hESC expansion and stemness are independent of connexin forty-three-mediated intercellular communication between hESCs and hASC feeder cells.

    Directory of Open Access Journals (Sweden)

    Jin-Su Kim

    Full Text Available BACKGROUND: Human embryonic stem cells (hESCs are a promising and powerful source of cells for applications in regenerative medicine, tissue engineering, cell-based therapies, and drug discovery. Many researchers have employed conventional culture techniques using feeder cells to expand hESCs in significant numbers, although feeder-free culture techniques have recently been developed. In regard to stem cell expansion, gap junctional intercellular communication (GJIC is thought to play an important role in hESC survival and differentiation. Indeed, it has been reported that hESC-hESC communication through connexin 43 (Cx43, one of the major gap junctional proteins is crucial for the maintenance of hESC stemness during expansion. However, the role of GJIC between hESCs and feeder cells is unclear and has not yet been reported. METHODOLOGY/PRINCIPAL FINDINGS: This study therefore examined whether a direct Cx43-mediated interaction between hESCs and human adipose-derived stem cells (hASCs influences the maintenance of hESC stemness. Over 10 passages, hESCs cultured on a layer of Cx43-downregulated hASC feeder cells showed normal morphology, proliferation (colony growth, and stemness, as assessed by alkaline phosphatase (AP, OCT4 (POU5F1-Human gene Nomenclature Database, SOX2, and NANOG expression. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that Cx43-mediated GJIC between hESCs and hASC feeder cells is not an important factor for the conservation of hESC stemness and expansion.

  16. Critical role of <