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Sample records for spongiform encephalopathy-related phenotypic

  1. Transmissions of variant Creutzfeldt-Jakob disease from brain and lymphoreticular tissue show uniform and conserved bovine spongiform encephalopathy-related phenotypic properties on primary and secondary passage in wild-type mice.

    Science.gov (United States)

    Ritchie, Diane L; Boyle, Aileen; McConnell, Irene; Head, Mark W; Ironside, James W; Bruce, Moira E

    2009-12-01

    Prion strains are defined by their biological properties after transmission to wild-type mice, specifically by their incubation periods and patterns of vacuolar pathology ('lesion profiles'). Preliminary results from transmissions of variant Creutzfeldt-Jakob disease (vCJD) to wild-type mice provided the first compelling evidence for the close similarity of the vCJD agent to the agent causing bovine spongiform encephalopathy (BSE). Complete results from this investigation, including the transmission characteristics of vCJD from brain and peripheral tissues of 10 cases (after primary transmission and subsequent mouse-to-mouse passage), have now been analysed. All 10 vCJD sources resulted in consistent incubation periods and lesion profiles, suggesting that all 10 patients were infected with the same strain of agent. Incubation periods suggested that infectious titres may be subject to regional variation within the brain. Comparison of incubation periods and lesion profiles from transmission of brain and peripheral tissues showed no evidence of tissue-specific modification in the biological properties of the agent. Analysis of the protease-resistant prion protein (PrP(res)) by Western blotting from primary and subsequent passages in mice showed a glycosylation pattern closely resembling that of vCJD in humans, the so-called BSE 'glycoform signature'. Minor variations in PrP(res) fragment size were evident between mouse strains carrying different alleles of the gene encoding PrP both in primary transmissions and on further passages of vCJD brain. Overall, the results closely resembled those of previously reported transmissions of BSE in the same mouse strains, consistent with BSE being the origin of all of these vCJD cases.

  2. Transmissible spongiform encephalopathies.

    Science.gov (United States)

    Liemann, S; Glockshuber, R

    1998-09-18

    Scrapie, bovine spongiform encephalopathy (BSE), and the Creutzfeldt-Jakob disease (CJD) belong to a group of lethal neurodegenerative disorders in mammals. Prion diseases or transmissible spongiform encephalopathies (TSEs) are characterized by the accumulation of an abnormal isoform (PrPSc) of the host-encoded cellular prion protein (PrPC) in the brain. The infectious agent, the 'prion,' is believed to be devoid of informational nucleic acid and to consist largely, if not entirely, of PrPSc. The PrP isoforms contain identical amino acid sequences yet differ in their overall secondary structure with the PrPSc isoform possessing a higher beta-sheet and lower alpha-helix content than PrPC. Elucidation of the three-dimensional structure of PrPC has provided important clues on the molecular basis of inherited human TSEs and on the species barrier phenomenon of TSEs. Nevertheless, the molecular mechanism of the conformational rearrangement of PrPC into PrPSc is still unknown, mainly due to the lack of detailed structural information on PrPSc. Within the framework of the 'protein only' hypothesis, two plausible models for the self-replication of prions have been suggested, the conformational model and the nucleation-dependent polymerization model.

  3. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.

    2002-01-01

    ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology......ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology...

  4. IMMUNOLOGICAL STUDY OF SPONGIFORM ENCEPHALOPATHIES

    OpenAIRE

    J. Meenupriya

    2013-01-01

    Spongiform encephalopathies, categorized as a subclass of neuro-degenerative diseases and commonly known as prion diseases, are a group of progressive conditions that affect the brain and nervous system of many animals, including humans. Prion diseases are common among cannibalistic communities; further research has revealed that the infected or malformed prion protein (named PrPsc) spreads its virulence to the normal, healthy prion protein (named PrPc) when people consume...

  5. Mad Cow Disease-Bovine Spongiform Encephalopathy

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 4. Mad Cow Disease - Bovine Spongiform Encephalopathy. Ashutosh ... HP Agricultural University, Palampur 176 662, India. DES (Vety. Sei.) KVK (P A U) Old Gurunanak College Building Hardochhani Road Gurdaspur Punjab 143 521 India.

  6. Pathogenesis of bovine spongiform encephalopathy in sheep

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Vromans, M.E.W.; Dolstra, C.H.; Bossers, A.; Zijderveld, van F.G.

    2008-01-01

    The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was

  7. Toxic spongiform leucoencephalopathy after inhaling heroin vapour

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.; Henkes, H.; Kuehne, D. [Klinik fuer Allgemeine Roentgendiagnostik und Neuroradiologie, Alfried-Krupp-Krankenhaus, Alfried Krupp Strasse 21, D-45117, Essen (Germany); Moeller, P.; Bade, K. [Neurologische Klinik, Knappschafts-Krankenhaus, D-45657 Recklinghausen (Germany)

    1998-06-02

    This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism. (orig.) With 2 figs., 2 tabs., 26 refs.

  8. Toxic spongiform leucoencephalopathy after inhaling heroin vapour

    International Nuclear Information System (INIS)

    Weber, W.; Henkes, H.; Kuehne, D.; Moeller, P.; Bade, K.

    1998-01-01

    This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism. (orig.)

  9. [Update on transmissible spongiform subacute encephalopathies (TSSE)].

    Science.gov (United States)

    Brugère-Picoux, Jeanne; Adjou, Karim; Brugère, Henri

    2005-02-01

    This update concerns human and ruminant transmissible spongiform subacute encephalopathies (TSSE). The latest data on variant Creutzfeldt-Jakob disease confirm that new cases are less frequent than feared some years ago, but subclinical carriers could be a source of iatrogenic infection. The macaque is a good model of human oral transmission of bovine spongiform encephalopathy (BSE). The latest data on BSE in Europe confirm the effectiveness of precautionary measures taken in 1996 and 2000. Concerns in other ruminants include a chronic wasting disease of Cervidae in North America, the discovery of a BSE-like agent associated with natural scrapie in a French goat, maternal transmission of natural scrapie in sheep, with an exceptionally short incubation period (6.5 months), and doubts over the efficacy of genetic selection for combating ovine scrapie (atypical cases in " resistant " sheep, especially with the scrapie strain Nor 98 in Europe). These data demonstrate the value of active European surveillance of scrapie in small ruminants.

  10. Human transmissible spongiform encephalopathy: Case report

    OpenAIRE

    Duque Velásquez, Camilo; Garzón Álzate, Ánderson; Villegas Lanau, Andrés; Escobar Velásquez, Laura Marcela; Zea Lopera, Julián; Lopera, Francisco; Rodas González, Juan David

    2014-01-01

    We report the case of a 64 year-old woman with motor and cognitive deterioration that progressed rapidly during eight months. She was unsuccessfully treated with quinacrine, and died in a terminal status, by septic shock secondary to bronchopneumonia by broncho-aspiration. The brain was donated for research and the histopathological analysis showed spongiform changes, astrogliosis and prion protein (PrPRes) deposits, confirmed by Western blot (WB). These features are considered characteristic...

  11. Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development.

    Science.gov (United States)

    Chen, Xiao-Qiao; Zhang, Wei-Na; Hu, Lin-Yan; Liu, Meng-Jia; Zou, Li-Ping

    2016-03-01

    Epileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups. Electrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Bovine Spongiform Encephalopathy (BSE, Mad Cow Disease

    Directory of Open Access Journals (Sweden)

    G. K. Bruckner

    1997-07-01

    Full Text Available Mad Cow Disease or BSE (Bovine Spongiform Encephalopathy became a household name internationally and also in South Africa. International hysteria resulted following reports of a possible link between a disease diagnosed in cattle in Britain and a variant of the disease diagnosed in humans after the presumed ingestion or contact with meat from infected cattle. The European Union instituted a ban on the importation of beef from the United Kingdom during March 1996 that had a severe effect on the beef industry in the UK and also resulted in a world wide consumer resistance against beef consumption.

  13. Human transmissible spongiform encephalopathy: Case report

    Directory of Open Access Journals (Sweden)

    Duque Velásquez, Camilo

    2014-07-01

    Full Text Available We report the case of a 64 year-old woman with motor and cognitive deterioration that progressed rapidly during eight months. She was unsuccessfully treated with quinacrine, and died in a terminal status, by septic shock secondary to bronchopneumonia by broncho-aspiration. The brain was donated for research and the histopathological analysis showed spongiform changes, astrogliosis and prion protein (PrPRes deposits, confirmed by Western blot (WB. These features are considered characteristic of prion diseases, which are uncommon in Colombia. We highlight that its diagnosis was made for the first time in this country by the simultaneous use of immunohistochemistry and Western blot.

  14. Prions and animal transmissible spongiform encephalopathies

    Directory of Open Access Journals (Sweden)

    Juntes Polona

    2017-01-01

    Full Text Available Background. Transmissible spongiform encephalopathies (TSEs or prion diseases are a unique group of neurodegenerative diseases of animals and humans, which always have a fatal outcome and are transmissible among animals of the same or different species. Scope and Approach. The aim of this work is to review some recent data about animal TSEs, with the emphasis on their causative agents and zoonotic potential, and to discuss why the surveillance and control measures over animal TSEs should remain in force. Key Findings and Conclusions. We still have incomplete knowledge of prions and prion diseases. Scrapie has been present for a very long time and controlled with varied success. Bovine spongiform encephalopathy (BSE emerged unnoticed, and spread within a few years to epidemic proportions, entailing enormous economic consequences and public concerns. Currently, the classical BSE epidemic is under control, but atypical cases do, and probably will, persist in bovine populations. The Chronic Wasting Disease (CWD of the cervids has been spreading in North America and has recently been detected in Europe. Preventive measures for the control of classical BSE remain in force, including the feed ban and removal of specified risk materials. However, active BSE surveillance has considerably decreased. In the absence of such preventive and control measures, atypical BSE cases in healthy slaughtered bovines might persist in the human food chain, and BSE prions might resurface. Moreover, other prion strains might emerge and spread undetected if the appropriate preventive and surveillance measures were to cease, leaving behind inestimable consequences.

  15. Quantitative Risk Assessment of Bovine Spongiform Encephalopathy

    Science.gov (United States)

    Tsutsui, Toshiyuki; Kasuga, Fumiko

    Bovine spongiform encephalopathy (BSE) is a progressive neurological disease of cattle affecting the central nervous system and was first diagnosed in the United Kingdom (UK) in 1986 (Wells et al., 1987). This disease is one of the transmissible spongiform encephalopathy (TSE) which includes Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep. The causative agent of TSE is considered to be an abnormal form of prion protein. However, the details of its pathogenic mechanism have not been fully identified. Scrapie, which causes neurological symptoms in sheep and goats, has existed in the UK for 200 years (Hoinville, 1996) and spread across the rest of the world in the 1900s (Detwiler & Baylis, 2003). There has been no report so far that scrapie can be transmitted to humans. Initially, BSE was also considered as a disease affecting only animals. However, a variant type of Creutzfeldt-Jakob disease (vCJD) was first reported in the UK, and exposure to a BSE agent was suspected (Collinge, Sidle, Meads, Ironside, & Hill, 1996). vCJD is clinically and pathologically different from the sporadic type of CJD, and age at clinical onset of vCJD is younger than sporadic type (Will et al., 1996). Since the UK government announced the possible association between BSE and vCJD in 1996, BSE has become a huge public health concern all over the world. Of particular concern about vCJD, the fatal disease in younger age, distorted consumer confidence in beef safety, and as a result reduced beef consumption has been seen in many BSE-affected countries.

  16. A quantitative risk assessment for bovine spongiform encephalopathy in Japan

    NARCIS (Netherlands)

    Kadohira, M.; Stevenson, M.A.; Hogasen, H.R.; Koeijer, de A.A.

    2012-01-01

    A predictive case-cohort model was applied to Japanese data to analyze the interaction between challenge and stability factors for bovine spongiform encephalopathy (BSE) for the period 1985–2020. BSE risk in cattle was estimated as the expected number of detectable cases per year. The model was

  17. Chronic wasting disease of captive mule deer: a spongiform encephalopathy.

    Science.gov (United States)

    Williams, E S; Young, S

    1980-01-01

    In the past 12 years (1967-79) a syndrome we identify as chronic wasting disease has been observed in 53 mule deer (Odocoileus hemionus hemionus) and one black-tailed deer (Odocoileus hemionus columbianus) held in captivity in several wildlife facilities in Colorado and more recently in Wyoming. Clinical signs were seen in adult deer and included behavioral alterations, progressive weight loss and death in 2 weeks to 8 months. Gross necropsy findings included emaciation and excess rumen fluid admixed with sand and gravel. Consistent histopathologic change was limited to the central nervous system and characterized by widespread spongiform transformation of the neuropil, single of multiple intracytoplasmic vacuoles in neuronal perikaryons and intense astrocytic hypertrophy and hyperplasia. Presented is a clinical characterization of chronic wasting disease and pathologic evidence supporting the conclusion that the disease is a specific spontaneously occurring form of spongiform encephalopathy.

  18. Laboratory Examinations of Transmissible Spongiform Encephalopathies in Denmark during 2014

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre

    , Chapter 2.4.6 and Chapter 2.7.13) regarding diagnostic examinations. The DTU-VET is the national reference laboratory of bovine spongiform encephalopathy (BSE) and TSE/Scrapie, and therefore the results of all neuropathological examinations on BSE and Scrapie in Denmark are given in the present report......The aim of this report is to give detailed information on the diagnostic examination on transmissible spongiform encephalopathies (TSE) performed in Denmark during 2014. The present annual report is the 19th on this topic published by the National Veterinary Institute, Technical University...... of Denmark (DTU-VET). The report is made to fulfil the demands given by the EU Commission (Regulation No 999/2001 of the European Parliament and the Council of 22. May 2001) and the Office Inter-national des Epizooties (OIE) (Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, 5th edition 2008...

  19. Laboratory Examinations of Transmissible Spongiform Encephalopathies in Denmark during 2012

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre

    , Chapter 2.4.6 and Chapter 2.7.13) regarding diagnostic examinations. The DTU-VET is the national reference laboratory of bovine spongiform encephalopathy (BSE) and TSE/Scrapie, and therefore the results of all neuropathological examinations on BSE and Scrapie in Denmark are given in the present report......The aim of this report is to give detailed information on the diagnostic examination on trans-missible spongiform encephalopathies (TSE) performed in Denmark during 2012. The present annual report is the 17th on this topic published by the National Veterinary Institute, Technical University...... of Denmark (DTU-VET). The report is made to fulfil the demands given by the EU Commission (Regulation No 999/2001 of the European Parliament and the Council of 22. May 2001) and the Office Inter-national des Epizooties (OIE) (Manual of Diagnostic Tests and Vaccines for Terrestrial Ani-mals, 5th edition 2008...

  20. Laboratory examinations of transmissible spongiform encephalopathies in Denmark during 2016

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre

    , Chapter 2.4.6 and Chapter 2.7.13) regarding diagnostic examinations.The DTU-VET is the national reference laboratory of bovine spongiform encephalopathy (BSE) and TSE/Scrapie, and therefore the results of all neuropathological examinations on BSE and Scrapie in Denmark are given in the present report......The aim of this report is to give detailed information on the diagnostic examination on trans-missible spongiform encephalopathies (TSE) performed in Denmark during 2016. The present annual report is the 21st on this topic published by the National Veterinary Institute, Technical University...... of Denmark (DTU-VET). The report is made to fulfil the demands given by the EU Commission (Regulation No 999/2001 of the European Parliament and the Council of 22. May 2001) and the Office Inter-national des Epizooties (OIE) (Manual of Diagnostic Tests and Vaccines for Terrestrial Ani-mals, 5th edition 2008...

  1. Laboratory Examinations of Transmissible Spongiform Encephalopathies in Denmark during 2013

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre

    , Chapter 2.4.6 and Chapter 2.7.13) regarding diagnostic examinations. The DTU-VET is the national reference laboratory of bovine spongiform encephalopathy (BSE) and TSE/Scrapie, and therefore the results of all neuropathological examinations on BSE and Scrapie in Denmark are given in the present report......The aim of this report is to give detailed information on the diagnostic examination on trans-missible spongiform encephalopathies (TSE) performed in Denmark during 2013. The present annual report is the 18th on this topic published by the National Veterinary Institute, Technical University...... of Denmark (DTU-VET). The report is made to fulfil the demands given by the EU Commission (Regulation No 999/2001 of the European Parliament and the Council of 22. May 2001) and the Office Inter-national des Epizooties (OIE) (Manual of Diagnostic Tests and Vaccines for Terrestrial Ani-mals, 5th edition 2008...

  2. Infectivity in skeletal muscle of cattle with atypical bovine spongiform encephalopathy.

    Science.gov (United States)

    Suardi, Silvia; Vimercati, Chiara; Casalone, Cristina; Gelmetti, Daniela; Corona, Cristiano; Iulini, Barbara; Mazza, Maria; Lombardi, Guerino; Moda, Fabio; Ruggerone, Margherita; Campagnani, Ilaria; Piccoli, Elena; Catania, Marcella; Groschup, Martin H; Balkema-Buschmann, Anne; Caramelli, Maria; Monaco, Salvatore; Zanusso, Gianluigi; Tagliavini, Fabrizio

    2012-01-01

    The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those of typical BSE, resulting in a clinically and pathologically distinct phenotype. Whether peripheral tissues of BASE-affected cattle contain infectivity is unknown. This is a critical issue since the BASE prion is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. We carried out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases (∼70% versus ∼10%, respectively). This difference was likely related to different prion titers, possibly due to different stages of disease in the two conditions, i.e. terminal stage in experimental BASE and pre-symptomatic stage in natural BASE. The neuropathological phenotype and PrP(res) type were consistent in all affected mice and matched those of Tgbov XV mice infected with brain homogenate from natural BASE. The immunohistochemical analysis of skeletal muscles from cattle with natural and experimental BASE showed the presence of abnormal prion protein deposits within muscle fibers. Conversely, Tgbov XV mice challenged with lymphoid tissue and kidney from natural and experimental BASE did not develop disease. The novel information on the neuromuscular tropism of the BASE strain, efficiently overcoming species barriers, underlines the relevance of maintaining an active surveillance.

  3. Current status of transmissible spongiform encephalopathies in ruminants

    Directory of Open Access Journals (Sweden)

    Penders J.

    2004-01-01

    Full Text Available Transmissible spongiform encephalopathies (TSE encompass subacute neurological degenerative diseases for which the prototypes are scrapie in sheep and some forms of Creutzfeldt-Jakob disease in man. The emergence of a new form of TSE in cattle in United Kingdom (UK since 1986, namely bovine spongiform encephalopathy (BSE, sharply increased the interest for these diseases, especially because of the epidemic nature of BSE in UK, its subsequent spread in continental Europe and the later discovery of its zoonotic character. The number of measures of veterinary public health taken to control the disease and to prevent its spread to animals and human beings increased in time and culminated by the total feed ban. Indeed, since the beginning of 2001, feed containing proteins of animal origin is prohibited for the feeding of production animals, including ruminants and monogastric species. The effect of this total ban of mammalian meat and bone meal needs to be evaluated. The incidence of BSE has a trend to decrease in UK and in most of the other European member states. However, as BSE is a rare event distributed in a large bovine population, it is difficult to state unambiguously whether this trend is significant. Furthermore, the evaluation of this measure will be only effective at least five years after its introduction, since this period is the mean incubation time of BSE. The main concern is currently the eradication of BSE in the infected countries. Additionally, the control of scrapie is also carried out due to the possible contamination of sheep with the BSE agent. These actions must take into account several new facts: the recent discovery of BSE cases in countries with a low geographical BSE risk level as Japan, Canada and the United States of America (USA; the growing incidence of chronic wasting disease, a spongiform encephalopathy observed in deer in USA; the characterization of a new pattern of bovine amyloidotic spongiform encephalopathy in

  4. Cattle traceability system in Japan for bovine spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Katsuaki Sugiura

    2008-09-01

    Full Text Available To promote consumer confidence in the safety of beef and to ensure the proper implementation of eradication measures against bovine spongiform encephalopathy (BSE, the Cattle Traceability Law was approved by the Diet in June 2003 and a cattle traceability system has been in operation in Japan since December 2003. The system enables tracing the cohort and offspring animals of a BSE case within 24 h of its detection. The traceability database system also provides distributors, restaurants and consumers with information on the cattle from which the beef that they sell, serve and consume originate.

  5. [Risk assessment for importing bovine spongiform encephalopathy (BSE)].

    Science.gov (United States)

    Hörnlimann, B; Guidon, D; Griot, C

    1994-07-01

    Since the occurrence of bovine spongiform encephalopathy (BSE) in Switzerland in 1990, extensive epidemiological investigations and risk factor analyses were carried out. In this study, statistical data on meat and bone meal traded from 1985 to 1989 were analysed addressing the following questions: i) what amount of meat and bone meal was exported from Great Britain (GB) and where to and ii) what amount of meat and bone meal was imported into Switzerland and where from? The findings led to the hypothesis that imported material potentially infected with scrapie-like agents was the cause for BSE in Switzerland.

  6. Bovine spongiform encephalopathy--some surprises for biochemists.

    Science.gov (United States)

    Campbell, Peter N

    2005-01-01

    Bovine Spongiform Encephalopathy (BSE) is typical of the dementias that affect both animals and man; Scrapie in sheep, Creutzfeldt-Jakob disease in man. Global efforts have been made to determine the nature of the active agents in these diseases. At present the 'protein only hypothesis' of Prusiner holds. It was a surprise that a protein could per se be the active agent but other surprises for our traditional teaching of biochemistry arose. These are explained in a brief summary of our present understanding of the biochemistry of the active agents that cause the diseases.

  7. Melanoma-associated spongiform scleropathy: biochemical changes and possible relation to tumour extension

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Ribel-Madsen, S.; Heegaard, S.

    2003-01-01

    ophthalmology, melanoma-associated spongiform acleropathy (MASS), malignant melanoma, glycosaminoglycans (GAGs), collagen amino acids, tumour invasiveness, tumour extension, collagen degradation......ophthalmology, melanoma-associated spongiform acleropathy (MASS), malignant melanoma, glycosaminoglycans (GAGs), collagen amino acids, tumour invasiveness, tumour extension, collagen degradation...

  8. Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies

    Science.gov (United States)

    Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrPSc). Different strains of BSE exist...

  9. Use of murine bioassay to resolve ovine transmissible spongiform encephalopathy cases showing a bovine spongiform encephalopathy molecular profile.

    Science.gov (United States)

    Beck, Katy E; Sallis, Rosemary E; Lockey, Richard; Vickery, Christopher M; Béringue, Vincent; Laude, Hubert; Holder, Thomas M; Thorne, Leigh; Terry, Linda A; Tout, Anna C; Jayasena, Dhanushka; Griffiths, Peter C; Cawthraw, Saira; Ellis, Richard; Balkema-Buschmann, Anne; Groschup, Martin H; Simmons, Marion M; Spiropoulos, John

    2012-05-01

    Two cases of unusual transmissible spongiform encephalopathy (TSE) were diagnosed on the same farm in ARQ/ARQ PrP sheep showing attributes of both bovine spongiform encephalopathy (BSE) and scrapie. These cases, UK-1 and UK-2, were investigated further by transmissions to wild-type and ovine transgenic mice. Lesion profiles (LP) on primary isolation and subpassage, incubation period (IP) of disease, PrP(Sc) immunohistochemical (IHC) deposition pattern and Western blot profiles were used to characterize the prions causing disease in these sheep. Results showed that both cases were compatible with scrapie. The presence of BSE was contraindicated by the following: LP on primary isolation in RIII and/or MR (modified RIII) mice; IP and LP after serial passage in wild-type mice; PrP(Sc) deposition pattern in wild-type mice; and IP and Western blot data in transgenic mice. Furthermore, immunohistochemistry (IHC) revealed that each case generated two distinct PrP(Sc) deposition patterns in both wild-type and transgenic mice, suggesting that two scrapie strains coexisted in the ovine hosts. Critically, these data confirmed the original differential IHC categorization that these UK-1 and UK-2 cases were not compatible with BSE. © 2011 The Authors. Brain Pathology © 2011 International Society of Neuropathology.

  10. Encefalopatías espongiformes transmisibles Transmissible spongiform encephalopathies

    Directory of Open Access Journals (Sweden)

    Jorge E Delgado-Hachmeister

    2002-01-01

    Full Text Available Las encefalopatías espongiformes transmisibles (EET han cobrado gran importancia en los últimos años. Principalmente por el surgimiento de la encefalopatía espongiforme del bovino (EEB y la nueva variante de la ermedad de Creutzfeldt-Jakob (nvECJ, esta última probablemente adquirida por la ingesta de carne de bovino contaminada. Hasta la fecha se ha informado de 109 casos de la nvECJ en el humano y la gran mayoría de los casos ha ocurrido en el Reino Unido. No se sabe la magnitud real que podrán tener las EET en el humano, sin embargo algunos piensan que nos encontramos en el principio de una pandemia de la nvECJ. En el presente artículo se discuten varios aspectos de las EET y métodos para la prevención de la transmisión de estas enfermedades, tanto en rumiantes como en el humano.Transmissible spongiform encephalopathies (TSE are a group of diseases which have received a lot of attention in recent years. The interest on these diseases has been stimulated by the appearance of bovine spongiform encephalopathy (BSE and the new variant of Creutzfeldt-Jakob disease (nvCJD; the latter is likely to be acquired by ingesting contaminated beef. Until now 109 cases of nvCJD have been reported, most of them occurring in the United Kingdom. Some experts think that this is the beginning of a nvCJD pandemic. Deep knowledge of the mechanisms of transmission of TSE is needed to prevent the emergence of a TSE pandemic in humans.We address various aspects of TSE and discuss prevention methods of TSE in ruminants and humans.

  11. Human transmissible spongiform encephalopathies in eleven countries: Diagnostic pattern across time, 1993-2002

    NARCIS (Netherlands)

    J. de Pedro-Cuesta (Jesús); M. Glatzel (Markus); J. Almazán (Javier); K. Stoeck (Katharina); V. Mellina (Vittorio); M. Puopolo (Maria); M. Pocchiari (Maurizio); I. Zerr (Inga); H.A. Kretszchmar (Hans); J-P. Brandel (Jean-Philippe); N. Delasnerie-Laupretre (Nicole); A. Alperovitch (Annick); C.M. van Duijn (Cornelia); P. Sanchez-Juan (Pascual); S.J. Collins (Steven); V. Lewis (Victoria); G.H. Jansen (Gerard); M.B. Coulthart (Michael); E. Gelpi (Ellen); H. Budka (Herbert); E. Mitrová (Eva)

    2006-01-01

    textabstractBackground: The objective of this study was to describe the diagnostic panorama of human transmissible spongiform encephalopathies across 11 countries. Methods: From data collected for surveillance purposes, we describe annual proportions of deaths due to different human transmissible

  12. Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy.

    Science.gov (United States)

    Okada, Hiroyuki; Masujin, Kentaro; Miyazawa, Kohtaro; Iwamaru, Yoshihumi; Imamura, Morikazu; Matsuura, Yuichi; Arai, Shozo; Fukuda, Shigeo; Murayama, Yuichi; Yokoyama, Takashi

    2017-11-01

    H-type bovine spongiform encephalopathy (H-BSE) is an atypical form of BSE in cattle. During passaging of H-BSE in transgenic bovinized (TgBoPrP) mice, a novel phenotype of BSE, termed BSE-SW emerged and was characterized by a short incubation time and host weight loss. To investigate the biological and biochemical properties of the BSE-SW prion, a transmission study was conducted in cattle, which were inoculated intracerebrally with brain homogenate from BSE-SW-infected TgBoPrP mice. The disease incubation period was approximately 15 months. The animals showed characteristic neurological signs of dullness, and severe spongiform changes and a widespread, uniform distribution of disease-associated prion protein (PrP Sc ) were observed throughout the brain of infected cattle. Immunohistochemical PrP Sc staining of the brain revealed the presence of intraglial accumulations and plaque-like deposits. No remarkable differences were identified in vacuolar lesion scores, topographical distribution patterns, and staining types of PrP Sc in the brains of BSE-SW- vs H-BSE-infected cattle. PrP Sc deposition was detected in the ganglia, vagus nerve, spinal nerve, cauda equina, adrenal medulla, and ocular muscle. Western blot analysis revealed that the specific biochemical properties of the BSE-SW prion, with an additional 10- to 12-kDa fragment, were well maintained after transmission. These findings indicated that the BSE-SW prion has biochemical properties distinct from those of H-BSE in cattle, although clinical and pathologic features of BSW-SW in cattle are indistinguishable from those of H-BSE. The results suggest that the 2 infectious agents, BSE-SW and H-BSE, are closely related strains.

  13. Bovine spongiform encephalopathy in South America: a regional preventive approach.

    Science.gov (United States)

    van Gelderen, C; Gimeno, E J; Schudel, A A

    2003-04-01

    Bovine spongiform encephalopathy (BSE) is a neurodegenerative disease of cattle caused by prions that was first described in the United Kingdom (UK) in 1986. The BSE epizootic that commenced in the UK in the 1980s has since spread into other countries in Europe and Asia through exports of contaminated meat-and-bone meal or infected cattle. Over the past few years, other emerging or reemerging diseases have spread into previously free countries or regions through international trade. This negative effect of globalisation means that to implement successful preventive and strategic programmes to safeguard animal health, such programmes must, as a priority, take a regional approach. Global thinking, regional planning and local performance constitute the key factors for the successful control of animal diseases. In South America, initial preventive actions against BSE were adopted in 1989. Further measures adopted since then and based on new scientific and technical findings, have led to the demonstration that the region is free of BSE. These early preventive actions have reliably protected the region from importing BSE-infected material. An integral part of the project to determine the BSE status of South America was the training of personnel, the incorporation of technology and the provision of updated information through close relationships with international organisations and prominent international researcher workers. Regional activities aimed at harmonising BSE prevention programmes, producing objective and transparent data on the equivalence of regional BSE status and facilitating regional and international trade have recently been launched. Maintaining the BSE-free status of the region must be given high priority by the beef agro-industrial sectors.

  14. Immunohistochemical distinction between preclinical bovine spongiform encephalopathy and scrapie infection in sheep

    NARCIS (Netherlands)

    Thuring, C.M.A.; Keulen, van L.J.M.; Langeveld, J.P.M.; Vromans, M.E.W.; Zijderveld, van F.G.; Sweeney, T.

    2005-01-01

    Sheep are susceptible experimentally to bovine spongiform encephalopathy (BSE), the clinical signs being indistinguishable from those of scrapie. Because of the possibility of natural ovine BSE infection, laboratory tests are needed to distinguish between scrapie and BSE infection. The objectives of

  15. Comparison of MRI, CT, TCD and SPECT in patients with spongiform leukoencephalopathy after inhaling heroin vapor

    International Nuclear Information System (INIS)

    Wang Qun; Lu Bingxun; Yuan Huijuan

    2002-01-01

    Objective: To compare the characteristics of MRI, CT, single photon emission computed tomography (SPECT) and transcranial Doppler sonography (TCD) in patients with spongiform leukoencephalopathy after inhaling heroin vapor. Methods: Seventeen patients were investigated. MRI or CT was scanned in 17 patients, SPECT in 9 patients' and TCD in 11 patients. Results: MRI or CT: Brain MRI and CT revealed extensive symmetric white matter involvement of bilateral cerebral and cerebellar hemispheres and the brainstem. The lesions, which showed no contrast enhancement, were hypodense on CT and hypointense on T 1 -weighted and hyperintense on T 2 -weighted MRI. SPECT: The regional cerebral blood flows (rCBF) of white matter involvement on bilateral cerebral and cerebellar hemispheres was reduced obviously. The rCBF of temporal lobes, parietal lobes, occipital lobes, cerebellar hemispheres, and basal ganglion was reduced in varying degrees. TCD: The systolic peak became sharpened, and end-diastolic flow velocity and mean flow velocity were reduced obviously and pulsatile index was increased markedly in patients with spongiform leukoencephalopathy after inhaling heroin vapor. Conclusion: The characteristic manifestations of MRI and CT imaging may be regarded as the main foundation of diagnosing spongiform leukoencephalopathy after inhaling heroin vapor; SPECT and TCD can help comprehend the changes of hemodynamics of cerebral vessels and the degree of cerebral ischemia in patients with spongiform leukoencephalopathy after inhaling heroin vapor

  16. the role of mathematical modelling in understanding the epidemiology and control of sheep transmissible spongiform encephalopathies: a review

    NARCIS (Netherlands)

    Gubbins, S.; Touzeau, S.; Hagenaars, T.H.J.

    2010-01-01

    To deal with the incompleteness of observations and disentangle the complexities of transmission much use has been made of mathematical modelling when investigating the epidemiology of sheep transmissible spongiform encephalopathies (TSE) and, in particular, scrapie. Importantly, these modelling

  17. Risk analysis of Transmissible Spongiform Encephalopathies in animals: state-of-the-art

    DEFF Research Database (Denmark)

    Paisley, Larry; de Koeijer, Aline; Hagenaars, Thomas J.

    2008-01-01

    The Bovine Spongiform Encephalopathy (BSE) crisis of the last two decades has shown that proper interaction of risk assessment, risk management and risk communication is essential. Mathematical models and risk assessments have been used as a basis for BSE risk management options and much of the l......The Bovine Spongiform Encephalopathy (BSE) crisis of the last two decades has shown that proper interaction of risk assessment, risk management and risk communication is essential. Mathematical models and risk assessments have been used as a basis for BSE risk management options and much......). Nevertheless, the decline in the BSE epidemic in the UK and most European countries demonstrates that management has been, for the most part, sucessful. Literature pertaining to the three inter-related facets of risk analysis: risk assessment, risk management and risk communication of TSE's of animal origin...... was reviewed and used to describe the state-of-the-art of risk analysis for TSEs....

  18. PrP-C1 fragment in cattle brains reveals features of the transmissible spongiform encephalopathy associated PrPsc.

    Science.gov (United States)

    Serra, Fabienne; Müller, Joachim; Gray, John; Lüthi, Ramona; Dudas, Sandor; Czub, Stefanie; Seuberlich, Torsten

    2017-03-15

    Three different types of bovine spongiform encephalopathy (BSE) are known and supposedly caused by distinct prion strains: the classical (C-) BSE type that was typically found during the BSE epidemic, and two relatively rare atypical BSE types, termed H-BSE and L-BSE. The three BSE types differ in the molecular phenotype of the disease associated prion protein, namely the N-terminally truncated proteinase K (PK) resistant prion protein fragment (PrP res ). In this study, we report and analyze yet another PrP res type (PrP res-2011 ), which was found in severely autolytic brain samples of two cows in the framework of disease surveillance in Switzerland in 2011. Analysis of brain tissues from these animals by PK titration and PK inhibitor assays ruled out the process of autolysis as the cause for the aberrant PrP res profile. Immunochemical characterization of the PrP fragments present in the 2011 cases by epitope mapping indicated that PrP res-2011 corresponds in its primary sequence to the physiologically occurring PrP-C1 fragment. However, high speed centrifugation, sucrose gradient assay and NaPTA precipitation revealed biochemical similarities between PrP res-2011 and the disease-associated prion protein found in BSE affected cattle in terms of detergent insolubility, PK resistance and PrP aggregation. Although it remains to be established whether PrP res-2011 is associated with a transmissible disease, our results point out the need of further research on the role the PrP-C1 aggregation and misfolding in health and disease. Copyright © 2017. Published by Elsevier B.V.

  19. Bovine Spongiform Encephalopathy (BSE – Infectious, Contagious, Zoonotic or Production Disease?

    Directory of Open Access Journals (Sweden)

    Doherr Marcus G

    2003-03-01

    Full Text Available In 1986, a new progressive neurological condition similar to scrapie of sheep and goats was recognised in cattle in the United Kingdom (UK, and was named bovine spongiform encephalopathy (BSE. There is an ongoing discussion whether BSE should be classified as infectious, contagious, or zoonotic, and if it fits the definition of a production disease. The objective of this work is to briefly describe the main characteristics of transmissible spongiform encephalopathies (TSE, to review the epidemiology of BSE, and to address the question of how to classify BSE. TSEs are characterised as chronic wasting diseases with spongiform vacuolation and the accumulation of infectious prion protein (PrPSc in the central nervous system. TSE infectivity is very difficult to inactivate. Cattle BSE most likely originated from sheep scrapie, although this will remain to be an issue for debate. The disease can be transmitted from cattle to a range of species, and has resulted in smaller TSE epidemics in domestic cats, zoo cats and zoo ruminants, and in humans. Transmission in the field occurred through feed containing ruminant-derived protein, and measures to prevent the recycling of infectivity have proven effective to reduce the number of new infections. Mandatory reporting of clinical suspects combined with targeted screening of risk populations is needed to assess the BSE status of a country. Infection studies and the transmissibility to other species classify BSE as infectious and zoonotic. Absence of excretion of the agent, and therefor of horizontal transmission, categorise BSE as non-contagious. However, BSE is a multifactorial infectious disease that is dependent on management factors (mainly feeding, and therefore fits into the broader definition of production diseases.

  20. [Bovine spongiform encephalopathy. Second update of data collected since the report of February 6, 1996].

    Science.gov (United States)

    Brugère-Picoux, J; Lasmézas, C; Deslys, J P; Adjou, K; Rérat, A; Dormont, D

    1996-01-01

    The observation in 1995 and 1996 of 12 cases of a new variant of Creutzfeldt-Jakob disease (V-CJD) in U.K. suggested a possible relation between this human cases and bovine spongiform encephalopathy (BSE). Recent papers about this topic are reviewed: BSE transmission to macaques, transmission of scrapie with embryo transfer, incidence of maternal transmission, PrP protein released by platelets, diagnostic test by detection of PrP protein in tissues of sheep, epidemiology of BSE, french regulations, identification of cattle in U.K.

  1. Monitoring and analysis of bovine spongiform encephalopathy (BSE) testing in Denmark using statistical models

    DEFF Research Database (Denmark)

    Paisley, Larry

    2002-01-01

    The evolution of monitoring and surveillance for bovine spongiform encephalopathy (BSE) from the phase of passive surveillance that began in the United Kingdom in 1988 until the present is described. Currently, surveillance for BSE in Europe consists of mass testing of cattle slaughtered for human...... consumption and cattle from certain groups considered to be at higher risk of having clinical or detectable BSE. The results of the ongoing BSE testing in Denmark have been analyzed using two statistical approaches: the "classical" fequuentist and the Bayesian that is widely used in quantitative risk analysis...

  2. Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control.

    Science.gov (United States)

    Seuberlich, Torsten; Heim, Dagmar; Zurbriggen, Andreas

    2010-11-01

    Since 1987, when bovine spongiform encephalopathy (BSE) emerged as a novel disease in cattle, enormous efforts were undertaken to monitor and control the disease in ruminants worldwide. The driving force was its high economic impact, which resulted from trade restrictions and the loss of consumer confidence in beef products, the latter because BSE turned out to be a fatal zoonosis, causing variant Creutzfeldt-Jakob disease in human beings. The ban on meat and bone meal in livestock feed and the removal of specified risk materials from the food chain were the main measures to successfully prevent infection in cattle and to protect human beings from BSE exposure. However, although BSE is now under control, previously unknown, so-called atypical transmissible spongiform encephalopathies (TSEs) in cattle and small ruminants have been identified by enhanced disease surveillance. This report briefly reviews and summarizes the current level of knowledge on the spectrum of TSEs in cattle and small ruminants and addresses the question of the extent to which such atypical TSEs have an effect on disease surveillance and control strategies.

  3. Control of bovine spongiform encephalopathy by genetic engineering: possible approaches and regulatory considerations

    International Nuclear Information System (INIS)

    Gavora, J.S.; Kochhar, H.P.S.; Gifford, G.A.

    2005-01-01

    Transmissible spongiform encephalopathies (TSE) include bovine spongiform encephalopathy (BSE), scrapie in sheep and Creutzfeldt-Jakob disease (CJD) in humans. A new CJD variant (nvCJD) is believed to be related to consumption of meat from BSE cattle. In TSE individuals, prion proteins (PrP) with approximately 250 amino acids convert to the pathogenic prion PrP Sc , leading to a dysfunction of the central neural system. Research elsewhere with mice has indicated a possible genetic engineering approach to the introduction of BSE resistance: individuals with amino acid substitutions at positions 167 or 218, inoculated with a pathogenic prion protein, did not support PrP Sc replication. This raises the possibility of producing prion-resistant cattle with a single PrP amino acid substitution. Since prion-resistant animals might still harbour acquired prion infectivity, regulatory assessment of the engineered animals would need to ascertain that such possible 'carriers' do not result in a threat to animal and human health. (author)

  4. Generation of a persistently infected MDBK cell line with natural bovine spongiform encephalopathy (BSE.

    Directory of Open Access Journals (Sweden)

    Dongseob Tark

    Full Text Available Bovine spongiform encephalopathy (BSE is a zoonotic transmissible spongiform encephalopathy (TSE thought to be caused by the same prion strain as variant Creutzfeldt-Jakob disease (vCJD. Unlike scrapie and chronic wasting disease there is no cell culture model allowing the replication of proteinase K resistant BSE (PrPBSE and the further in vitro study of this disease. We have generated a cell line based on the Madin-Darby Bovine Kidney (MDBK cell line over-expressing the bovine prion protein. After exposure to naturally BSE-infected bovine brain homogenate this cell line has shown to replicate and accumulate PrPBSE and maintain infection up to passage 83 after initial challenge. Collectively, we demonstrate, for the first time, that the BSE agent can infect cell lines over-expressing the bovine prion protein similar to other prion diseases. These BSE infected cells will provide a useful tool to facilitate the study of potential therapeutic agents and the diagnosis of BSE.

  5. Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Tortosa Raül

    2011-10-01

    Full Text Available Abstract Gene expression analysis has proven to be a very useful tool to gain knowledge of the factors involved in the pathogenesis of diseases, particularly in the initial or preclinical stages. With the aim of finding new data on the events occurring in the Central Nervous System in animals affected with Bovine Spongiform Encephalopathy, a comprehensive genome wide gene expression study was conducted at different time points of the disease on mice genetically modified to model the bovine species brain in terms of cellular prion protein. An accurate analysis of the information generated by microarray technique was the key point to assess the biological relevance of the data obtained in terms of Transmissible Spongiform Encephalopathy pathogenesis. Validation of the microarray technique was achieved by RT-PCR confirming the RNA change and immunohistochemistry techniques that verified that expression changes were translated into variable levels of protein for selected genes. Our study reveals changes in the expression of genes, some of them not previously associated with prion diseases, at early stages of the disease previous to the detection of the pathological prion protein, that might have a role in neuronal degeneration and several transcriptional changes showing an important imbalance in the Central Nervous System homeostasis in advanced stages of the disease. Genes whose expression is altered at early stages of the disease should be considered as possible therapeutic targets and potential disease markers in preclinical diagnostic tool development. Genes non-previously related to prion diseases should be taken into consideration for further investigations.

  6. Possible case of maternal transmission of feline spongiform encephalopathy in a captive cheetah.

    Directory of Open Access Journals (Sweden)

    Anna Bencsik

    Full Text Available Feline spongiform encephalopathy (FSE is considered to be related to bovine spongiform encephalopathy (BSE and has been reported in domestic cats as well as in captive wild cats including cheetahs, first in the United Kingdom (UK and then in other European countries. In France, several cases were described in cheetahs either imported from UK or born in France. Here we report details of two other FSE cases in captive cheetah including a 2(nd case of FSE in a cheetah born in France, most likely due to maternal transmission. Complete prion protein immunohistochemical study on both brains and peripheral organs showed the close likeness between the two cases. In addition, transmission studies to the TgOvPrP4 mouse line were also performed, for comparison with the transmission of cattle BSE. The TgOvPrP4 mouse brains infected with cattle BSE and cheetah FSE revealed similar vacuolar lesion profiles, PrP(d brain mapping with occurrence of typical florid plaques. Collectively, these data indicate that they harbor the same strain of agent as the cattle BSE agent. This new observation may have some impact on our knowledge of vertical transmission of BSE agent-linked TSEs such as in housecat FSE, or vCJD.

  7. Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice

    NARCIS (Netherlands)

    Espinosa, J.C.; Andreoletti, O.; Castilla, J.; Herva, M.E.; Morales, M.; Alamillo, E.; San-Segundo, F.D.; Lacroux, C.; Lugan, S.; Salguero, F.J.; Langeveld, J.P.M.; Torres, J.M.

    2007-01-01

    Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions

  8. Animal feed controls implemented in Japan for the eradication of bovine spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Katsuaki Sugiura

    2009-06-01

    Full Text Available After the detection of the first case of bovine spongiform encephalopathy (BSE in Japan in September 2001, the Japanese government introduced a series of animal feed control measures to reduce the risk of the spread of the disease from a feed source. To ensure the proper implementation of these measures, the Food and Agricultural Materials Inspection Centre conducted audit inspections of feed importers, producers, distributors and end-users. The audit inspections include on-site inspection of the feed plants, warehouses, farms and other related premises and the laboratory analysis of feed samples taken from these premises to check for the presence of animal protein. The results of inspections conducted in recent years indicate good compliance with the feed control measures.

  9. Reflexive modernization at the source: local media coverage of bovine spongiform encephalopathy in rural Alberta.

    Science.gov (United States)

    Davidson, Debra J; Bogdan, Eva

    2010-11-01

    The potential for reflexive modernization is defined by multiple factors, but the acknowledgment of risk is crucial, particularly among social groups that play a key role in risk minimization. This study offers an examination of the role of local media in response to the outbreak of bovine spongiform encephalopathy (BSE) in beef-producing communities in rural Alberta. BSE is one of several global risk issues that reflexive modernization theorists argue have the potential to trigger a transformation toward a critically reflexive society in which such risks are minimized. Content analysis of newspapers in beef-producing regions in Alberta, however, shows how local media framed BSE in a manner that maximized community cohesion and protection of local culture. This selective coverage of BSE in rural Alberta is quite likely to have contributed to, or at least reinforced, support for the current institutional structure of Canadian agriculture in beef-producing regions, through the constriction of discourse.

  10. Postinhibitory rebound neurons and networks are disrupted in retrovirus-induced spongiform neurodegeneration.

    Science.gov (United States)

    Li, Ying; Davey, Robert A; Sivaramakrishnan, Shobhana; Lynch, William P

    2014-08-01

    Certain retroviruses induce progressive spongiform motor neuron disease with features resembling prion diseases and amyotrophic lateral sclerosis. With the neurovirulent murine leukemia virus (MLV) FrCasE, Env protein expression within glia leads to postsynaptic vacuolation, cellular effacement, and neuronal loss in the absence of neuroinflammation. To understand the physiological changes associated with MLV-induced spongiosis, and its neuronal specificity, we employed patch-clamp recordings and voltage-sensitive dye imaging in brain slices of the mouse inferior colliculus (IC), a midbrain nucleus that undergoes extensive spongiosis. IC neurons characterized by postinhibitory rebound firing (PIR) were selectively affected in FrCasE-infected mice. Coincident with Env expression in microglia and in glia characterized by NG2 proteoglycan expression (NG2 cells), rebound neurons (RNs) lost PIR, became hyperexcitable, and were reduced in number. PIR loss and hyperexcitability were reversed by raising internal calcium buffer concentrations in RNs. PIR-initiated rhythmic circuits were disrupted, and spontaneous synchronized bursting and prolonged depolarizations were widespread. Other IC neuron cell types and circuits within the same degenerative environment were unaffected. Antagonists of NMDA and/or AMPA receptors reduced burst firing in the IC but did not affect prolonged depolarizations. Antagonists of L-type calcium channels abolished both bursts and slow depolarizations. IC infection by the nonneurovirulent isogenic virus Friend 57E (Fr57E), whose Env protein is structurally similar to FrCasE, showed no RN hyperactivity or cell loss; however, PIR latency increased. These findings suggest that spongiform neurodegeneration arises from the unique excitability of RNs, their local regulation by glia, and the disruption of this relationship by glial expression of abnormal protein. Copyright © 2014 the American Physiological Society.

  11. Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies

    Directory of Open Access Journals (Sweden)

    Rhind Susan M

    2006-01-01

    Full Text Available Abstract Background Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE and variant CJD (vCJD, and the development of lymphoid tissue in the gut. Methods Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, rs, between available measures of Peyer's patch (PP development and the estimated risk of infection for an individual of the corresponding age. Results There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, rs = 0.913 (n = 19, P s = 0.933 (n = 19, P s = 0.693 (n = 94, P s = 0.384 (n = 46, P = 0.008. In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: rs = 0.360 (n = 46, P = 0.014. Conclusion Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species.

  12. Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy.

    Science.gov (United States)

    Lasmézas, C I; Deslys, J P; Demaimay, R; Adjou, K T; Hauw, J J; Dormont, D

    1996-07-01

    The development of transmissible spongiform encephalopathies in experimental models depends on two major factors: the intracerebral accumulation of an abnormal, protease-resistant isoform of PrP (PrPres), which is a host protein mainly expressed in neurons; and the existence of different strains of agent. In order to make a distinction between pathogenic mechanisms depending upon the accumulation of host-derived PrPres and the strain-specific effects, we quantified and compared the sequence of molecular [PrPres and glial fibrillary acidic protein (GFAP) accumulation] and pathological events in the brains of syngeneic mice throughout the course of infection with two different strains of agent. The bovine spongiform encephalopathy (BSE) agent exhibits properties different from any known scrapie source and has been studied in comparison with a classical scrapie strain. Convergent kinetic data in both models confirmed the cause-effect relationship between PrPres and pathological changes and showed that PrPres accumulation is directly responsible for astrocyte activation in vivo. Moreover, we observed a threshold level of PrPres for this effect on astroglial cells. However, despite similar infectivity titres, the BSE model produced less PrPres than scrapie, and the relative importance of gliosis was higher. The comparison of the molecular and pathological features after intracerebral or intraperitoneal inoculation also revealed differences between the models. Therefore, the mechanisms leading to the targeting and the fine regulation of the molecular events seem to be independent of the host PrP and to depend upon the agent. The possible involvement of a regulatory molecule accounting for these specificities has to be considered.

  13. High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

    National Research Council Canada - National Science Library

    Caughey, Byron

    2004-01-01

    Transmissible spongiform encephalopathies (TSEs) are fatal untreatable neurodegenerative diseases associated with the accumulation of a disease-specific form of prion protein (prp(expSc)) in the brain...

  14. Detection and localisation of PrP(Sc in the liver of sheep infected with scrapie and bovine spongiform encephalopathy.

    Directory of Open Access Journals (Sweden)

    Sally J Everest

    Full Text Available Prions are largely contained within the nervous and lymphoid tissue of transmissible spongiform encephalopathy (TSE infected animals. However, following advances in diagnostic sensitivity, PrP(Sc, a marker for prion disease, can now be located in a wide range of viscera and body fluids including muscle, saliva, blood, urine and milk, raising concerns that exposure to these materials could contribute to the spread of disease in humans and animals. Previously we demonstrated low levels of infectivity in the liver of sheep experimentally challenged with bovine spongiform encephalopathy. In this study we show that PrP(Sc accumulated in the liver of 89% of sheep naturally infected with scrapie and 100% of sheep challenged with BSE, at both clinical and preclinical stages of the disease. PrP(Sc was demonstrated in the absence of obvious inflammatory foci and was restricted to isolated resident cells, most likely Kupffer cells.

  15. Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle ? an update

    OpenAIRE

    Konold, Timm; Arnold, Mark E; Austin, Anthony R; Cawthraw, Saira; Hawkins, Steve AC; Stack, Michael J; Simmons, Marion M; Sayers, A Robin; Dawson, Michael; Wilesmith, John W; Wells, Gerald AH

    2012-01-01

    Abstract Background To provide information on dose–response and aid in modelling the exposure dynamics of the BSE epidemic in the United Kingdom groups of cattle were exposed orally to a range of different doses of brainstem homogenate of known infectious titre from clinical cases of classical bovine spongiform encephalopathy (BSE). Interim data from this study was published in 2007. This communication documents additional BSE cases, which occurred subsequently, examines possible influence of...

  16. A case of spongiform polioencephalomyelopathy in a cat with a history of behavioural problems

    Directory of Open Access Journals (Sweden)

    Tomàs Camps

    2015-08-01

    Full Text Available A 7-month-old, entire female, domestic shorthair cat was referred to our behavioural service owing to soiling in the house and a play-related problem. The owners’ complaints were that the cat had never used the litter tray, and it did not know how to play. After reviewing the behavioural history, a problem of substrate preferences acquisition was suspected with regard to the elimination problem. During the consultation, the physical examination was unremarkable, but the neurological examination revealed a moderate and hypermetric ataxic gait, and a bilateral lack of menace response. Some degree of visual impairment was suspected. The problem was located in the central nervous system (CNS; specifically, an intracranial and multifocal problem was diagnosed. After a complete work-up (complete ophthalmological examination, complete blood count and a complete biochemistry panel, feline immunodeficiency virus/feline leukaemia virus test, thorax radiographs, abdominal ultrasound, brain magnetic resonance imaging [0.2 T], cerebrospinal fluid analysis and a urinary metabolic screen test, a degenerative CNS problem was suspected. No treatment was prescribed for the neurological problem. Regarding the problem of soiling in the house, reward-based training with a clicker was used, and the cat partially improved in a few weeks. Three months later, the cat was referred to the neurology service in status epilepticus. A symptomatic treatment was prescribed, with a mild response. After 2 years of treatment and a progressive worsening, the cat was euthanased. Necropsy revealed spongiform polioencephalomyelopathy. In order to rule out prion aetiology a PrPsc inmunohistochemistry assay was performed, and the results were negative. Congenital spongiform polioencephalomyelopathy (CSP was diagnosed. We strongly suggest that the cat’s behavioural clinical signs were caused by the CSP, causing learning impairment. To the best of our knowledge, this would be the

  17. Sporadic fatal insomnia with spongiform degeneration in the thalamus and widespread PrPSc deposits in the brain.

    Science.gov (United States)

    Piao, Yue-Shan; Kakita, Akiyoshi; Watanabe, Hiroyuki; Kitamoto, Tetsuyuki; Takahashi, Hitoshi

    2005-06-01

    We report a case of human prion disease of 29 months duration in a 74-year-old Japanese man. The disease started with progressive sleeplessness and dementia. MRI showed gradually progressive cerebral atrophy. Neuronal loss, spongiform change and gliosis were evident in the thalamus and cerebral cortex, as well as in the striatum and amygdaloid nucleus. In the cerebellar cortex, mild-to-moderate depletion of Pukinje cells and spongiform change were observed. Mild neuronal loss in the inferior olivary nucleus was also seen. Immunohistochemistry revealed widespread perivacuolar deposits of abnormal prion protein (PrPsc) in the cerebral cortex, thalamus, basal ganglia, and brainstem, and minimal plaque-like deposits of PrPSc in the cerebellar cortex. In the cerebellar plaque-like deposits, the presence of amyloid fibrils was confirmed ultrastructurally. The entire pathology appeared to lie halfway between those of CJD and fatal insomnia, and further demonstrated the relationship between spongiform degeneration and PrPSc deposits, especially in the diseased thalamus. By immunoblotting, the thalamus was shown to contain the lowest amount of PrPSc among the brain regions examined. The PrPSc of type 2, in which the ratio of the three glycoforms was compatible with that of sporadic fatal insomnia (MM2-thalamic variant) reported previously, was also demonstrated. Analysis of the prion protein gene (PRNP) showed no mutation, and homozygosity for methionine at codon 129. In conclusion, we considered that this patient had been suffering from sporadic, pathologically atypical fatal insomnia.

  18. MRI features of patients with heroin spongiform leukoencephalopathy of different clinical stages

    International Nuclear Information System (INIS)

    Shi Zhu; Pan Suyue; Zhou Liang; Dong Zhao; Lu Bingxun

    2007-01-01

    Objective: To investigate radiological features of patients with heroin spongiform leukoencephalopathy (HSLE) of different clinical stages and discuss the evolutional characteristics of the disease. Methods: Thirty two patients with HSLE underwent precontrast MRI and postcontrast MRI. The history of addiction, clinical presentations, and brain MRI were analyzed and summarized according to the patient's clinical staging. There are 6 cases in I stage, 21 cases in II stage, 5 cases in III stage. Results: All patients had history of heroin vapor inhalation. Most of the cases developed subacute cerebellar impairment in earlier period. Brain MRI revealed symmetrical lesion within bilateral cerebellum in all patients. Splenium of the corpus callosum, posterior limb of the internal capsule, deep white matter of the occipital and parietal lobes, were gradually involved with progressive deterioration of HSLE. The brain stem and deep white matter of the frontal and temporal lobes were involved in some cases. Conclusions: The history of heated heroin vapor inhalation was the prerequisite for the diagnosis of HSLE. Brain MRI presented the characteristic lesion and its evolution of HSLE. Brain MRI was very important for accurate diagnosis and helpful to judge the clinical stages according to the involved brain region. (authors)

  19. Transient cardiac arrest in patient with left ventricular noncompaction (spongiform cardiomyopathy).

    Science.gov (United States)

    Yamazaki, Shinya; Ito, Hiroshi; Kawaai, Hiroyoshi

    2011-01-01

    Left ventricular noncompaction (LVNC), also known as spongiform cardiomyopathy, is a severe disease that has not previously been discussed with respect to general anesthesia. We treated a child with LVNC who experienced cardiac arrest. Dental treatment under general anesthesia was scheduled because the patient had a risk of endocarditis due to dental caries along with a history of being uncooperative for dental care. During sevoflurane induction, severe hypotension and laryngospasm resulted in cardiac arrest. Basic life support (cardiopulmonary resuscitation) was initiated to resuscitate the child, and his cardiorespiratory condition improved. Thereafter, an opioid-based anesthetic was performed, and recovery was smooth. In LVNC, opioid-based anesthesia is suggested to avoid the significant cardiac suppression seen with a volatile anesthetic, once intravenous access is established. Additionally, all operating room staff should master Advanced Cardiac Life Support/Pediatric Advanced Life Support (including intraosseous access), and more than 1 anesthesiologist should be present to induce general anesthesia, if possible, for this high-risk patient.

  20. The evolution of risk perceptions related to bovine spongiform encephalopathy--Canadian consumer and producer behavior.

    Science.gov (United States)

    Yang, Jun; Goddard, Ellen

    2011-01-01

    In this study the dynamics of risk perceptions related to bovine spongiform encephalopathy (BSE) held by Canadian consumers and cow-calf producers were evaluated. Since the first domestic case of BSE in 2003, Canadian consumers and cow-calf producers have needed to make decisions on whether or not their purchasing/production behavior should change. Such changes in their behavior may relate to their levels of risk perceptions about BSE, risk perceptions that may be evolving over time and be affected by BSE media information available. An econometric analysis of the behavior of consumers and cow-calf producers might identify the impacts of evolving BSE risk perceptions. Risk perceptions related to BSE are evaluated through observed market behavior, an approach that differs from traditional stated preference approaches to eliciting risk perceptions at a particular point in time. BSE risk perceptions may be specified following a Social Amplification of Risk Framework (SARF) derived from sociology, psychology, and economics. Based on the SARF, various quality and quantity indices related to BSE media information are used as explanatory variables in risk perception equations. Risk perceptions are approximated using a predictive difference approach as defined by Liu et al. (1998). Results showed that Canadian consumer and cow-calf producer risk perceptions related to BSE have been amplified or attenuated by both quantity and quality of BSE media information. Government policies on risk communications need to address the different roles of BSE information in Canadian consumers' and cow-calf producers' behavior.

  1. Toward unfolding the prion misfolding mystery: protein free radical chemistry in transmissible spongiform encephalopathies

    International Nuclear Information System (INIS)

    Yang Chiming

    2003-01-01

    Owing to the high oxygen-respiration in the brain of mammals, oxidative damage to prion protein has been suggested to be an additional factor. A large body of intriguing features of scrapie and prion diseases have provided multiple lines of indirect chemistry evidence, suggesting that the infectious agents may be putative forms of sequence-specific prion radicals (SSPR) and/or their immediate precursors in the transmissible spongiform encephalopathies (TSE). Here a molecular mechanism corresponding to the self-replication of scrapie protein mediated by prion free-radical processes, consonant with 'protein-only' hypotheses is proposed. This new theory may not only aid our understanding of the occurrence of prions, but also provides new insight into the possible chemistry principles underlying the neutrodegenerative disorders. It is anticipated that future studies based on this suggestion and chemistry principles of genetic diseases may allow us to determine an effective approach to stop mad cow disease and its human version, new variant of Creutzfeldt-Jakob disease (v CJD)

  2. Brain and buffy coat transmission of bovine spongiform encephalopathy to the primate Microcebus murinus.

    Science.gov (United States)

    Bons, Nöelle; Lehmann, Sylvain; Mestre-Francès, Nadine; Dormont, Dominique; Brown, Paul

    2002-05-01

    More than 100 cases of variant CJD resulting from infections with bovine spongiform encephalopathy (BSE) have accumulated in the United Kingdom since 1995. Concern about the possibility of secondary transmissions via blood and blood components donated by infected individuals has prompted a variety of international donor deferral policies that will continue until laboratory and epidemiologic evidence provides a consensus about potential risk. BSE was passaged through macaque monkeys and then adapted to the prosimian microcebe (Microcebus murinus). Brain homogenate and buffy coat from an affected microcebe were separately inoculated intracerebrally into three healthy microcebes (two animals received brain and one received buffy coat). All three inoculated microcebes became ill after incubation periods of 16 to 18 months. Clinical, histopathologic, and immunocytologic features were similar in each of the recipients. Buffy coat from a symptomatic microcebe infected 17 months earlier with BSE contained the infectious agent. This observation represents the first documented transmission of BSE from the blood of an experimentally infected primate, which in view of rodent buffy coat infectivity precedents and the known host range of BSE is neither unexpected nor cause for alarm.

  3. Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.

    Science.gov (United States)

    Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent

    2016-12-01

    Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP C ) and the infecting pathological PrP assemblies (PrP Sc ) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrP C and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrP Sc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. Whole Blood Gene Expression Profiling in Preclinical and Clinical Cattle Infected with Atypical Bovine Spongiform Encephalopathy.

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    Elena Xerxa

    Full Text Available Prion diseases, such as bovine spongiform encephalopathies (BSE, are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD, a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE is now rapidly disappearing as a result of appropriate measures to control animal feeding. Besides cBSE, two atypical forms (named H- and L-type BSE have recently been described in Europe, Japan, and North America. Here we describe the first wide-spectrum microarray analysis in whole blood of atypical BSE-infected cattle. Transcriptome changes in infected animals were analyzed prior to and after the onset of clinical signs. The microarray analysis revealed gene expression changes in blood prior to the appearance of the clinical signs and during the progression of the disease. A set of 32 differentially expressed genes was found to be in common between clinical and preclinical stages and showed a very similar expression pattern in the two phases. A 22-gene signature showed an oscillating pattern of expression, being differentially expressed in the preclinical stage and then going back to control levels in the symptomatic phase. One gene, SEL1L3, was downregulated during the progression of the disease. Most of the studies performed up to date utilized various tissues, which are not suitable for a rapid analysis of infected animals and patients. Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the preclinical identification of prion infection. Further, this study highlighted several pathways, such as immune response and metabolism that may play an important role in peripheral prion pathogenesis. Finally, the gene expression changes identified in the present study may be further investigated as a fingerprint for monitoring the progression of disease and for developing targeted therapeutic

  5. Recombinant PrP and Its Contribution to Research on Transmissible Spongiform Encephalopathies

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    Jorge M. Charco

    2017-12-01

    Full Text Available The misfolding of the cellular prion protein (PrPC into the disease-associated isoform (PrPSc and its accumulation as amyloid fibrils in the central nervous system is one of the central events in transmissible spongiform encephalopathies (TSEs. Due to the proteinaceous nature of the causal agent the molecular mechanisms of misfolding, interspecies transmission, neurotoxicity and strain phenomenon remain mostly ill-defined or unknown. Significant advances were made using in vivo and in cellula models, but the limitations of these, primarily due to their inherent complexity and the small amounts of PrPSc that can be obtained, gave rise to the necessity of new model systems. The production of recombinant PrP using E. coli and subsequent induction of misfolding to the aberrant isoform using different techniques paved the way for the development of cell-free systems that complement the previous models. The generation of the first infectious recombinant prion proteins with identical properties of brain-derived PrPSc increased the value of cell-free systems for research on TSEs. The versatility and ease of implementation of these models have made them invaluable for the study of the molecular mechanisms of prion formation and propagation, and have enabled improvements in diagnosis, high-throughput screening of putative anti-prion compounds and the design of novel therapeutic strategies. Here, we provide an overview of the resultant advances in the prion field due to the development of recombinant PrP and its use in cell-free systems.

  6. Quantitative analysis of wet-heat inactivation in bovine spongiform encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Yuichi; Ishikawa, Yukiko; Bo, Xiao; Murayama, Yuichi; Yokoyama, Takashi [Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan); Somerville, Robert A. [The Roslin Institute and Royal (Dick) School of Veterinary Studies, Roslin, Midlothian, EH25 9PS (United Kingdom); Kitamoto, Tetsuyuki [Division of CJD Science and Technology, Department of Prion Research, Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai 980-8575 (Japan); Mohri, Shirou, E-mail: shirou@affrc.go.jp [Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan)

    2013-03-01

    Highlights: ► We quantitatively analyzed wet-heat inactivation of the BSE agent. ► Infectivity of the BSE macerate did not survive 155 °C wet-heat treatment. ► Once the sample was dehydrated, infectivity was observed even at 170 °C. ► A quantitative PMCA assay was used to evaluate the degree of BSE inactivation. - Abstract: The bovine spongiform encephalopathy (BSE) agent is resistant to conventional microbial inactivation procedures and thus threatens the safety of cattle products and by-products. To obtain information necessary to assess BSE inactivation, we performed quantitative analysis of wet-heat inactivation of infectivity in BSE-infected cattle spinal cords. Using a highly sensitive bioassay, we found that infectivity in BSE cattle macerates fell with increase in temperatures from 133 °C to 150 °C and was not detected in the samples subjected to temperatures above 155 °C. In dry cattle tissues, infectivity was detected even at 170 °C. Thus, BSE infectivity reduces with increase in wet-heat temperatures but is less affected when tissues are dehydrated prior to the wet-heat treatment. The results of the quantitative protein misfolding cyclic amplification assay also demonstrated that the level of the protease-resistant prion protein fell below the bioassay detection limit by wet-heat at 155 °C and higher and could help assess BSE inactivation. Our results show that BSE infectivity is strongly resistant to wet-heat inactivation and that it is necessary to pay attention to BSE decontamination in recycled cattle by-products.

  7. Transmissibility of H-Type Bovine Spongiform Encephalopathy to Hamster PrP Transgenic Mice.

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    Hiroyuki Okada

    Full Text Available Two distinct forms of atypical bovine spongiform encephalopathies (H-BSE and L-BSE can be distinguished from classical (C- BSE found in cattle based on biochemical signatures of disease-associated prion protein (PrPSc. H-BSE is transmissible to wild-type mice-with infected mice showing a long survival period that is close to their normal lifespan-but not to hamsters. Therefore, rodent-adapted H-BSE with a short survival period would be useful for analyzing H-BSE characteristics. In this study, we investigated the transmissibility of H-BSE to hamster prion protein transgenic (TgHaNSE mice with long survival periods. Although none of the TgHaNSE mice manifested the disease during their lifespan, PrPSc accumulation was observed in some areas of the brain after the first passage. With subsequent passages, TgHaNSE mice developed the disease with a mean survival period of 220 days. The molecular characteristics of proteinase K-resistant PrPSc (PrPres in the brain were identical to those observed in first-passage mice. The distribution of immunolabeled PrPSc in the brains of TgHaNSE mice differed between those infected with H-BSE as compared to C-BSE or L-BSE, and the molecular properties of PrPres in TgHaNSE mice infected with H-BSE differed from those of the original isolate. The strain-specific electromobility, glycoform profiles, and proteolytic cleavage sites of H-BSE in TgHaNSE mice were indistinguishable from those of C-BSE, in which the diglycosylated form was predominant. These findings indicate that strain-specific pathogenic characteristics and molecular features of PrPres in the brain are altered during cross-species transmission. Typical H-BSE features were restored after back passage from TgHaNSE to bovinized transgenic mice, indicating that the H-BSE strain was propagated in TgHaNSE mice. This could result from the overexpression of the hamster prion protein.

  8. In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies.

    Science.gov (United States)

    Morawski, Aaron R; Carlson, Christina M; Chang, Haeyoon; Johnson, Christopher J

    2013-08-09

    Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn sheep (Ovis canadensis; BHS) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of CWD in cervids. No TSEs have been documented in BHS, but the susceptibility of this species to TSEs remains unknown. We acquired a library of BHS tissues and found no evidence of preexisting TSEs in these animals. The prion protein gene (Prnp) in all BHS in our library was identical to scrapie-susceptible domestic sheep (A136R154Q171 genotype). Using an in vitro prion protein conversion assay, which has been previously used to assess TSE species barriers and, in our study appears to recollect known species barriers in mice, we assessed the potential transmissibility of TSEs to BHS. As expected based upon Prnp genotype, we observed BHS prion protein conversion by classical scrapie agent and evidence for a species barrier between transmissible mink encephalopathy (TME) and BHS. Interestingly, our data suggest that the species barrier of BHS to white-tailed deer or wapiti CWD agents is likely low. We also used protein misfolding cyclic amplification to confirm that CWD, but not TME, can template prion protein misfolding in A136R154Q171 genotype sheep. Our results indicate the in vitro conversion assay used in our study does mimic the species barrier of mice to the TSE agents that we tested. Based on Prnp genotype and results from conversion assays, BHS are likely to be susceptible to infection by classical scrapie. Despite mismatches in amino acids thought to modulate prion protein conversion, our data indicate that A136R154Q171 genotype sheep prion protein is misfolded by CWD agent, suggesting that these animals could be susceptible to CWD. Further investigation of TSE transmissibility to BHS, including animal studies, is warranted

  9. Changes in retinal function and morphology are early clinical signs of disease in cattle with bovine spongiform encephalopathy.

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    M Heather West Greenlee

    Full Text Available Bovine spongiform encephalopathy (BSE belongs to a group of fatal, transmissible protein misfolding diseases known as transmissible spongiform encephalopathies (TSEs. All TSEs are caused by accumulation of misfolded prion protein (PrPSc throughout the central nervous system (CNS, which results in neuronal loss and ultimately death. Like other protein misfolding diseases including Parkinson's disease and Alzheimer's disease, TSEs are generally not diagnosed until the onset of disease after the appearance of unequivocal clinical signs. As such, identification of the earliest clinical signs of disease may facilitate diagnosis. The retina is the most accessible part of the central nervous system, and retinal pathology in TSE affected animals has been previously reported. Here we describe antemortem changes in retinal function and morphology that are detectable in BSE inoculated animals several months (up to 11 months prior to the appearance of any other signs of clinical disease. We also demonstrate that differences in the severity of these clinical signs reflect the amount of PrPSc accumulation in the retina and the resulting inflammatory response of the tissue. These results are the earliest reported clinical signs associated with TSE infection and provide a basis for understanding the pathology and evaluating therapeutic interventions.

  10. Phenotype spaces.

    Science.gov (United States)

    Mynard, Frédéric; Seal, Gavin J

    2010-02-01

    The topological viewpoint on spaces of phenotypes presented in Stadler et al. (J Theor Biol 213:241-274, 2001) is revisited, and a quantified version is proposed. While necessary probabilistic information can be encoded in a topological- like fashion, it turns out that it is not reflected adequately by the concept of continuity. We propose alternative models, but the behavior of maps make these models non-topological in fundamental ways.

  11. Immunohistochemical studies of scrapie archival material from Irish ARQ/ARQ sheep for evidence of bovine spongiform encephalopathy-derived disease

    NARCIS (Netherlands)

    Sharpe, A.; McElroy, M.; Langeveld, J.P.M.; Bassett, H.; O'Donoghue, A.M.; Sweeney, T.

    2005-01-01

    Since scrapie and bovine spongiform encephalopathy (BSE) in sheep are clinicopathologically indistinguishable, BSE in sheep may have been misdiagnosed as scrapie. Disease-specific prion protein (PrPd) patterns in archival tissues of 38 Irish ARQ/ARQ sheep diagnosed as scrapie-affected were compared

  12. Trends in scientific activity addressing transmissible spongiform encephalopathies: a bibliometric study covering the period 1973–2002

    Directory of Open Access Journals (Sweden)

    Iribarren-Maestro Isabel

    2006-10-01

    Full Text Available Abstract Background The purpose of this study is to analyse the trends in scientific research on transmissible spongiform encephalopathies by applying bibliometric tools to the scientific literature published between 1973 and 2002. Methods The data for the study were obtained from Medline database, in order to determine the volume of scientific output in the above period, the countries involved, the type of document and the trends in the subject matters addressed. The period 1973–2002 was divided in three sub-periods. Results We observed a significant growth in scientific production. The percentage of increase is 871.7 from 1973 to 2002. This is more evident since 1991 and particularly in the 1996–2001 period. The countries found to have the highest output were the United States, the United Kingdom, Japan, France and Germany. The evolution in the subject matters was almost constant in the three sub-periods in which the study was divided. In the first and second sub-periods, the subject matters of greatest interest were more general, i.e Nervous system or Nervous system diseases, Creutzfeldt-Jakob disease, Scrapie, and Chemicals and Drugs, but in the last sub-period, some changes were observed because the Prion-related matters had the greatest presence. Collaboration among authors is small from 1973 to 1992, but increases notably in the third sub-period, and also the number of authors and clusters formed. Some of the authors, like Gajdusek or Prusiner, appear in the whole period. Conclusion The study reveals a very high increase in scientific production. It is related also with the beginnings of research on bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease, with the establishment of progressive collaboration relationships and a reflection of public health concerns about this problem.

  13. A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation

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    Jo Moore

    2016-09-01

    Full Text Available In 2006, a case of H-type bovine spongiform encephalopathy (BSE-H was diagnosed in a cow that was associated with a heritable polymorphism in the bovine prion protein gene (PRNP resulting in a lysine for glutamine amino acid substitution at codon 211 (called E211K of the prion protein. Although the prevalence of this polymorphism is low, cattle carrying the K211 allele may be predisposed to rapid onset of BSE-H when exposed or to the potential development of a genetic BSE. This study was conducted to better understand the relationship between the K211 polymorphism and its effect on BSE phenotype. BSE-H from the US 2006 case was inoculated intracranially (IC in one PRNP wild type (EE211 calf and one EK211 calf. In addition, one wild type calf and one EK211 calf were inoculated IC with brain homogenate from a US 2003 classical BSE case. All cattle developed clinical disease. The survival times of the E211K BSE-H inoculated EK211 calf (10 months was shorter than the wild type calf (18 months. This genotype effect was not observed in classical BSE inoculated cattle (both 26 months. Significant changes in retinal function were observed in H-type BSE challenged cattle only. Cattle challenged with the same inoculum showed similar severity and neuroanatomical distribution of vacuolation and disease-associated prion protein deposition in the brain, though differences in neuropathology were observed between E211K BSE-H and classical BSE inoculated animals. Western blot results for brain tissue from challenged animals were consistent with the inoculum strains. This study demonstrates that the phenotype of E211K BSE-H remains stable when transmitted to cattle without the K211 polymorphism, and exhibits a number of features that differ from classical BSE in both wild type and heterozygous EK211 animals.

  14. Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein.

    Science.gov (United States)

    Wilson, Rona; Plinston, Chris; Hunter, Nora; Casalone, Cristina; Corona, Cristiano; Tagliavini, Fabrizio; Suardi, Silvia; Ruggerone, Margherita; Moda, Fabio; Graziano, Silvia; Sbriccoli, Marco; Cardone, Franco; Pocchiari, Maurizio; Ingrosso, Loredana; Baron, Thierry; Richt, Juergen; Andreoletti, Olivier; Simmons, Marion; Lockey, Richard; Manson, Jean C; Barron, Rona M

    2012-07-01

    The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several novel TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans.

  15. Guinea Pig Prion Protein Supports Rapid Propagation of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease Prions.

    Science.gov (United States)

    Watts, Joel C; Giles, Kurt; Saltzberg, Daniel J; Dugger, Brittany N; Patel, Smita; Oehler, Abby; Bhardwaj, Sumita; Sali, Andrej; Prusiner, Stanley B

    2016-11-01

    The biochemical and neuropathological properties of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) prions are faithfully maintained upon transmission to guinea pigs. However, primary and secondary transmissions of BSE and vCJD in guinea pigs result in long incubation periods of ∼450 and ∼350 days, respectively. To determine if the incubation periods of BSE and vCJD prions could be shortened, we generated transgenic (Tg) mice expressing guinea pig prion protein (GPPrP). Inoculation of Tg(GPPrP) mice with BSE and vCJD prions resulted in mean incubation periods of 210 and 199 days, respectively, which shortened to 137 and 122 days upon serial transmission. In contrast, three different isolates of sporadic CJD prions failed to transmit disease to Tg(GPPrP) mice. Many of the strain-specified biochemical and neuropathological properties of BSE and vCJD prions, including the presence of type 2 protease-resistant PrP Sc , were preserved upon propagation in Tg(GPPrP) mice. Structural modeling revealed that two residues near the N-terminal region of α-helix 1 in GPPrP might mediate its susceptibility to BSE and vCJD prions. Our results demonstrate that expression of GPPrP in Tg mice supports the rapid propagation of BSE and vCJD prions and suggest that Tg(GPPrP) mice may serve as a useful paradigm for bioassaying these prion isolates. Variant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE) prions are two of the prion strains most relevant to human health. However, propagating these strains in mice expressing human or bovine prion protein has been difficult because of prolonged incubation periods or inefficient transmission. Here, we show that transgenic mice expressing guinea pig prion protein are fully susceptible to vCJD and BSE prions but not to sporadic CJD prions. Our results suggest that the guinea pig prion protein is a better, more rapid substrate than either bovine or human prion protein for

  16. Impact of potential changes to the current bovine spongiform encephalopathy surveillance programs for slaughter cattle and fallen stock in Japan.

    Science.gov (United States)

    Sugiura, Katsuaki; Murray, Noel; Shinoda, Naoki; Onodera, Takashi

    2009-07-01

    Cattle slaughtered in Japan for human consumption, regardless of their age, have been tested for bovine spongiform encephalopathy (BSE) since October 2001. Beginning in April 2004, all fallen stock from 24 months of age also have been tested. We evaluated the impact of potential changes to the current BSE surveillance programs for both slaughter cattle and fallen stock using a simple stochastic model. We calculated the probability that a BSE-infected dairy cow, Wagyu beef animal, Wagyu-Holstein cross steer or heifer, or Holstein steer slaughtered for human consumption or arising as fallen stock would be tested and detected. Four surveillance strategies were explored for cattle slaughtered for human consumption, with the minimum age at testing set at 0, 21, 31, or 41 months. Three surveillance strategies were explored for fallen stock, with the minimum age at testing set at 24, 31, or 41 months. Increasing the minimum age of testing from 0 to 21 months for both dairy cattle and Wagyu beef cattle had very little impact on the probability that a BSE-infected animal slaughtered for human consumption would be detected. Although increasing the minimum age at testing from 21 to 31 or 41 months would lead to fewer slaughtered animals being tested, the impact on the probability of detecting infected animals would be insignificant. The probability of infected Wagyu-Holstein crosses and Holstein steers being detected at slaughter or as fallen stock would be very low under all surveillance strategies.

  17. Protective Effect of Val129-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

    Science.gov (United States)

    Fernández-Borges, Natalia; Espinosa, Juan Carlos; Marín-Moreno, Alba; Aguilar-Calvo, Patricia; Asante, Emmanuel A; Kitamoto, Tetsuyuki; Mohri, Shirou; Andréoletti, Olivier; Torres, Juan María

    2017-09-01

    Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met 129 ) or valine (Val 129 ) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met 129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val 129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met 129 Hu-PrP. In addition, the transmission of vCJD to transgenic mice homozygous for Val 129 Hu-PrP resulted in a prion with distinct strain features. These observations may indicate increased risk for vCJD secondary transmission in Val 129 Hu-PrP-positive humans with the emergence of new strain features.

  18. Real-Time Quaking-Induced Conversion Detection of Bovine Spongiform Encephalopathy Prions in a Subclinical Steer

    Directory of Open Access Journals (Sweden)

    Soyoun Hwang

    2018-01-01

    Full Text Available Bovine spongiform encephalopathy (BSE belongs to a group of fatal prion diseases that result from the misfolding of the cellular prion protein (PrPC into a pathogenic form (PrPSc that accumulates in the brain. In vitro assays such as serial protein misfolding amplification and real-time quaking-induced conversion (RT-QuIC allow assessment of the conversion of PrPC to PrPSc. RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals. However, there is no such comparison of RT-QuIC data between BSE positive and presymptomatic cattle. Further, the current study assesses prion distribution in multiple brain regions of clinically ill or subclinical animals. Here, we compare RT-QuIC reactions seeded with brain samples collected from experimentally inoculated cattle that were clinically ill or subclinically affected with BSE. The results demonstrate RT-QuIC seeding in various brain regions of an animal with subclinical BSE despite being determined negative by immunohistochemistry. Bioassay of the subclinical animal and RT-QuIC of brainstem from inoculated knockout (PRNP−/− cattle were used to confirm infectivity in the subclinical animal and determine that RT-QuIC reactions were not the result of residual inoculum, respectively. These results confirm that RT-QuIC is a highly sensitive prion detection assay that can detect prions in a steer prior to the onset of clinical signs of BSE.

  19. Immunohistochemical study of PrPSc distribution in neural and extraneural tissues of two cats with feline spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Wunderlin Sabina S

    2009-03-01

    Full Text Available Abstract Background Two domestic shorthair cats presenting with progressive hind-limb ataxia and increased aggressiveness were necropsied and a post mortem diagnosis of Feline Spongiform Encephalopathy (FSE was made. A wide spectrum of tissue samples was collected and evaluated histologically and immunohistologically for the presence of PrPSc. Results Histopathological examination revealed a diffuse vacuolation of the grey matter neuropil with the following areas being most severely affected: corpus geniculatum medialis, thalamus, gyrus dentatus of the hippocampus, corpus striatum, and deep layers of the cerebral and cerebellar cortex as well as in the brain stem. In addition, a diffuse glial reaction involving astrocytes and microglia and intraneuronal vacuolation in a few neurons in the brain stem was present. Heavy PrPSc immunostaining was detected in brain, retina, optic nerve, pars nervosa of the pituitary gland, trigeminal ganglia and small amounts in the myenteric plexus of the small intestine (duodenum, jejunum and slightly in the medulla of the adrenal gland. Conclusion The PrPSc distribution within the brain was consistent with that described in other FSE-affected cats. The pattern of abnormal PrP in the retina corresponded to that found in a captive cheetah with FSE, in sheep with scrapie and was similar to nvCJD in humans.

  20. High titers of transmissible spongiform encephalopathy infectivity associated with extremely low levels of PrPSc in vivo.

    Science.gov (United States)

    Barron, Rona M; Campbell, Susan L; King, Declan; Bellon, Anne; Chapman, Karen E; Williamson, R Anthony; Manson, Jean C

    2007-12-07

    Diagnosis of transmissible spongiform encephalopathy (TSE) disease in humans and ruminants relies on the detection in post-mortem brain tissue of the protease-resistant form of the host glycoprotein PrP. The presence of this abnormal isoform (PrP(Sc)) in tissues is taken as indicative of the presence of TSE infectivity. Here we demonstrate conclusively that high titers of TSE infectivity can be present in brain tissue of animals that show clinical and vacuolar signs of TSE disease but contain low or undetectable levels of PrP(Sc). This work questions the correlation between PrP(Sc) level and the titer of infectivity and shows that tissues containing little or no proteinase K-resistant PrP can be infectious and harbor high titers of TSE infectivity. Reliance on protease-resistant PrP(Sc) as a sole measure of infectivity may therefore in some instances significantly underestimate biological properties of diagnostic samples, thereby undermining efforts to contain and eradicate TSEs.

  1. Bovine spongiform encephalopathy induces misfolding of alleged prion-resistant species cellular prion protein without altering its pathobiological features.

    Science.gov (United States)

    Vidal, Enric; Fernández-Borges, Natalia; Pintado, Belén; Ordóñez, Montserrat; Márquez, Mercedes; Fondevila, Dolors; Torres, Juan María; Pumarola, Martí; Castilla, Joaquín

    2013-05-01

    Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrP(c)) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrP(C). Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species.

  2. Ultra-sensitive detection of prion protein fibrils by flow cytometry in blood from cattle affected with bovine spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Maas Elke

    2005-10-01

    Full Text Available Abstract Background The definite diagnosis of prion diseases such as Creutzfeldt-Jakob disease (CJD in humans or bovine spongiform encephalopathy (BSE in cattle currently relies on the post mortem detection of the pathological form of the prion protein (PrPSc in brain tissue. Infectivity studies indicate that PrPSc may also be present in body fluids, even at presymptomatic stages of the disease, albeit at concentrations well below the detection limits of currently available analytical methods. Results We developed a highly sensitive method for detecting prion protein aggregates that takes advantage of kinetic differences between seeded and unseeded polymerization of prion protein monomers. Detection of the aggregates was carried out by flow cytometry. In the presence of prion seeds, the association of labelled recombinant PrP monomers in plasma and serum proceeds much more efficiently than in the absence of seeds. In a diagnostic model system, synthetic PrP aggregates were detected down to a concentration of approximately 10-8 nM [0.24 fg/ml]. A specific signal was detected in six out of six available serum samples from BSE-positive cattle. Conclusion We have developed a method based on seed-dependent PrP fibril formation that shows promising results in differentiating a small number of BSE-positive serum samples from healthy controls. This method may provide the basis for an ante mortem diagnostic test for prion diseases.

  3. In situ formation of protease-resistant prion protein in transmissible spongiform encephalopathy-infected brain slices.

    Science.gov (United States)

    Bessen, R A; Raymond, G J; Caughey, B

    1997-06-13

    The transmissible spongiform encephalopathies (TSEs) comprise a group of fatal neurodegenerative diseases that are characterized by the conversion of the normal host cellular prion protein (PrPC), to the abnormal protease-resistant prion protein isoform (PrP-res). It has been proposed, though not proven, that the infectious TSE agent consists solely of PrP-res and that PrP-res-induced conformational conversion of PrPC to additional PrP-res represents agent replication. In this study we demonstrate in situ conversion of protease-sensitive PrPC to PrP-res in TSE-infected brain slices. One step in this process is the binding of soluble PrPC to endogenous PrP-res deposits. The newly formed PrP-res associated with the slices in a pattern that correlated with the pre-existing brain distribution of PrP-res. Punctate in situ PrP conversion was observed in brain regions containing PrP-res amyloid plaques, and a more dispersed conversion product was detected in areas containing diffuse PrP-res deposits. These studies provide direct evidence that PrP-res formation involves the incorporation of soluble PrPC into both nonfibrillar and fibrillar PrP-res deposits in TSE-infected brain. Our findings suggest that the in situ PrP conversion reaction leads to additional polymerization of endogenous PrP-res aggregates and is analogous to the process of PrP-res fibril and subfibril growth in vivo.

  4. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie.

    Directory of Open Access Journals (Sweden)

    Fiona Houston

    Full Text Available Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE, which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock. The unusually long observation period (6-8 years for most, but up to 12 years for others allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of

  5. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie

    Science.gov (United States)

    Houston, Fiona; Goldmann, Wilfred; Foster, James; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

    2015-01-01

    Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6–8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved

  6. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie.

    Science.gov (United States)

    Houston, Fiona; Goldmann, Wilfred; Foster, James; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

    2015-01-01

    Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6-8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved

  7. Expenses connected with disposing of animals with bovine spongiform encephalopathy in selected rendering plant in the Czech Republic

    Directory of Open Access Journals (Sweden)

    Richard Pospíšil

    2009-01-01

    Full Text Available The first case of bovine spongiform encephalopathy (BSE in the Czech Republic appeared in 2001 and since that a total of 28 infected cows have been detected. Two outbreaks of BSE in 2007 and no di­sea­sed animal in 2008 confirms that, in the Czech Republic, the disease incidence has a decreasing trend, which is in an agreement with the situation in other EU countries. According to the Veterinary Act No. 166/1999, farmers with BSE disease are indemnified from the state budget. The state, therefore, significantly contributes to the prevention and mitigation of BSE and ensures epidemiologic health in our country. Between the outbreak in 2001 and 2008, a total of 1 311 473 cows were exa­mi­ned and, based on the finding of 28 BSE-positive animals, 4 022 cows were subsequently slaughtered. BSE examination, killing and decontamination costs amounted to 18.9 million CZK, compensation costs for killed animals reached almost 163.9 million CZK and compensation for unaccomplished production accounted for over 13.6 million CZK. Together with other additional costs, the total financial compensations paid out during the period of BSE presence were almost 198 million CZK. A se­pa­ra­te budget is proportioned to subsequent safe disposing of carcasses in rendering plants. The rendering plant “Asanace, spol. s r. o., Zichlinek“ was appointed by the State Veterinary Administration to perform the disposal of carcasses. Since the beginning of 2003 to 2008, 22 cases of BSE were reported and 3 572 cows were killed and destroyed there, what represents 2 221 tons of material . The cost of processing of 1 kg of waste material ranged from 3.50 CZK to 6.50 CZK, total costs reached 9.315 thousand CZK. The final product – meat and bone meal – was incinerated in a cement factories at a cost of 1 CZK per 1 kg between years 2003–2006, now it is free of charge. This study does not include costs of disposal of Specific Risk Material, because it is

  8. Progressive accumulation of the abnormal conformer of the prion protein and spongiform encephalopathy in the obex of nonsymptomatic and symptomatic Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease

    Science.gov (United States)

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy, has been reported in captive and free-ranging cervids. An abnormal isoform of a prion protein (PrP-CWD) has been associated with CWD in Rocky Mountain elk (Cervus elaphus nelsoni) and this prion protein can be detected with i...

  9. Genotype to phenotype

    National Research Council Canada - National Science Library

    Malcolm, Sue; Goodship, Timothy H. J

    2001-01-01

    ... Disorders Molecular Genetics of Hypertension Human Gene EvolutionAnalysis of Multifactorial Disease Transcription Factors Molecular Genetics of Cancer, Second edition Genotype to Phenotype, second e...

  10. Risk of transmission of bovine spongiform encephalopathy to humans in the United States: report of the Council on Scientific Affairs. American Medical Association.

    Science.gov (United States)

    Tan, L; Williams, M A; Khan, M K; Champion, H C; Nielsen, N H

    The risk of possible transmission of bovine spongiform encephalopathy (BSE) in the United States is a substantial public health concern. To systematically review the current scientific literature and discuss legislation and regulations that have been implemented to prevent the disease. Literature review using the MEDLINE, EMBASE, and Lexis/Nexis databases for 1975 through 1997 on the terms bovine spongiform encephalopathy, prion diseases, prions, and Creutzfeldt-Jakob syndrome. The Internet was used to identify regulatory actions and health surveillance. MEDLINE, EMBASE, and Lexis/Nexis databases were searched from 1975 through 1997 for English-language articles that provided information on assessment of transmission risk. Unique circumstances in the United Kingdom caused the emergence and propagation of BSE in cattle, including widespread use of meat and bonemeal cattle feed derived from scrapie-infected sheep and the adoption of a new type of processing that did not reduce the amount of infectious prions prior to feeding. Many of these circumstances do not exist in the United States. In the United Kingdom, new variant Creutzfeldt-Jakob disease probably resulted from the ingestion of BSE-contaminated processed beef. The United Kingdom and the European Union now have strong regulations in place to stop the spread of BSE. While BSE has not been observed in the United States, the US government has surveillance and response plans in effect. Current risk of transmission of BSE in the United States is minimal because (1) BSE has not been shown to exist in this country; (2) adequate regulations exist to prevent entry of foreign sources of BSE into the United States; (3) adequate regulations exist to prevent undetected cases of BSE from uncontrolled amplification within the US cattle population; and (4) adequate preventive guidelines exist to prevent high-risk bovine materials from contaminating products intended for human consumption.

  11. Population-Level Retrospective Study of Neurologically Expressed Disorders in Ruminants before the Onset of Bovine Spongiform Encephalopathy (BSE) in Belgium, a BSE Risk III Country

    Science.gov (United States)

    Saegerman, C.; Berkvens, D.; Claes, L.; Dewaele, A.; Coignoul, F.; Ducatelle, R.; Cassart, D.; Brochier, B.; Costy, F.; Roels, S.; Deluyker, H.; Vanopdenbosch, E.; Thiry, E.

    2005-01-01

    A retrospective epidemiological study (n = 7,875) of neurologically expressed disorders (NED) in ruminants before the onset of the bovine spongiform encephalopathy epidemic (years studied, 1980 to 1997) was carried out in Belgium. The archives of all veterinary laboratories and rabies and transmissible spongiform encephalopathy (TSE) epidemiosurveillance networks were consulted. For all species, a significantly higher number of NED with virological causes (rabies) was reported south of the Sambre-Meuse Valley. During the period 1992 to 1997, for which the data were complete, (i) the predicted annual incidence of NED varied significantly as a function of species and area (higher numbers in areas where rabies was present) but was always above 100 cases per million, and (ii) the mean incidence of suspected TSE cases and, among them, those investigated by histopathological examination varied significantly as a function of species and area. The positive predictive value of a presumptive clinical diagnosis of NED ranged from 0.13 (game) to 0.63 (sheep). Knowledge of the positive predictive value permits the definition of a reference point before certain actions (e.g., awareness and training campaigns) are undertaken. It also shows the usefulness of a systematic necropsy or complementary laboratory tests to establish an etiological diagnosis. TSE analysis of a small, targeted historical sampling (n = 48) permitted the confirmation of one case and uncovered another case of scrapie. The results of the present study help to develop and maintain the quality of the worldwide clinical epidemiological networks for TSE, especially in countries that in the past imported live animals, animal products, and feedstuffs from countries with TSE cases. PMID:15695693

  12. Detection of PrP(Sc) in formalin-fixed, paraffin-embedded tissue by Western blot differentiates classical scrapie, Nor98 scrapie, and bovine spongiform encephalopathy.

    Science.gov (United States)

    Loiacono, Christina M; Beckwith, Nadine; Kunkle, Robert A; Orcutt, Dennis; Hall, S Mark

    2010-09-01

    Transmissible, spongiform encephalopathies including bovine spongiform encephalopathy (BSE) and scrapie are fatal neurodegenerative disorders associated with the presence of an infectious abnormal isoform of normal mammalian proteins called prions. Identification of the prion protein associated with scrapie (PrP(Sc)) in the central nervous system is typically based upon immunoassays including immunohistochemistry (IHC) using formalin-fixed tissues or Western blot (WB) assays using fresh and/or frozen, non-formalin-fixed tissues. Each assay can discriminate between BSE, classical scrapie, and a previously reported strain of scrapie recently identified in the United States named Nor98 scrapie. Different tissue samples are required from the same animal to run these 2 different immunoassays. This may result in inconsistent test results for the same animal. Sampling problems such as collecting insufficient volumes of fresh tissue or less than optimal anatomic location of brainstem for IHC can affect the ability of the test procedures to offer definitive and discriminatory results. Recently, a WB method using formalin-fixed, paraffin-embedded (FFPE) tissue to identify PrP(Sc) was developed that successfully identified PrP(Sc) in sheep affected by classical scrapie. In the current study, the use of this technique to produce discriminatory results identifying classical BSE in bovine tissue and both classical and Nor98 scrapie in ovine tissue using paraffin-embedded brain samples is described. Protein-banding patterns from WB using FFPE tissue were similar to protein-banding patterns produced by WB assays utilizing fresh tissues from the same animals, and results correlated well with the IHC PrP(Sc)-positive staining present in the cerebellum and obex regions of brain samples from these animals.

  13. Clinical phenotypes of asthma

    NARCIS (Netherlands)

    Bel, Elisabeth H.

    2004-01-01

    PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic

  14. The interpretation of disease phenotypes to identify TSE strains following murine bioassay: characterisation of classical scrapie.

    Science.gov (United States)

    Beck, Katy E; Vickery, Christopher M; Lockey, Richard; Holder, Thomas; Thorne, Leigh; Terry, Linda A; Denyer, Margaret; Webb, Paul; Simmons, Marion M; Spiropoulos, John

    2012-11-01

    Mouse bioassay can be readily employed for strain typing of naturally occurring transmissible spongiform encephalopathy cases. Classical scrapie strains have been characterised historically based on the established methodology of assessing incubation period of disease and the distribution of disease-specific vacuolation across the brain following strain stabilisation in a given mouse line. More recent research has shown that additional methods could be used to characterise strains and thereby expand the definition of strain "phenotype". Here we present the phenotypic characteristics of classical scrapie strains isolated from 24 UK ovine field cases through the wild-type mouse bioassay. PrPSc immunohistochemistry (IHC), paraffin embedded tissue blots (PET-blot) and Western blotting approaches were used to determine the neuroanatomical distribution and molecular profile of PrPSc associated with each strain, in conjunction with traditional methodologies. Results revealed three strains isolated through each mouse line, including a previously unidentified strain. Moreover IHC and PET-blot methodologies were effective in characterising the strain-associated types and neuroanatomical locations of PrPSc. The use of Western blotting as a parameter to define classical scrapie strains was limited. These data provide a comprehensive description of classical scrapie strain phenotypes on isolation through the mouse bioassay that can provide a reference for further scrapie strain identification.

  15. Phenotypic switching in bacteria

    Science.gov (United States)

    Merrin, Jack

    Living matter is a non-equilibrium system in which many components work in parallel to perpetuate themselves through a fluctuating environment. Physiological states or functionalities revealed by a particular environment are called phenotypes. Transitions between phenotypes may occur either spontaneously or via interaction with the environment. Even in the same environment, genetically identical bacteria can exhibit different phenotypes of a continuous or discrete nature. In this thesis, we pursued three lines of investigation into discrete phenotypic heterogeneity in bacterial populations: the quantitative characterization of the so-called bacterial persistence, a theoretical model of phenotypic switching based on those measurements, and the design of artificial genetic networks which implement this model. Persistence is the phenotype of a subpopulation of bacteria with a reduced sensitivity to antibiotics. We developed a microfluidic apparatus, which allowed us to monitor the growth rates of individual cells while applying repeated cycles of antibiotic treatments. We were able to identify distinct phenotypes (normal and persistent) and characterize the stochastic transitions between them. We also found that phenotypic heterogeneity was present prior to any environmental cue such as antibiotic exposure. Motivated by the experiments with persisters, we formulated a theoretical model describing the dynamic behavior of several discrete phenotypes in a periodically varying environment. This theoretical framework allowed us to quantitatively predict the fitness of dynamic populations and to compare survival strategies according to environmental time-symmetries. These calculations suggested that persistence is a strategy used by bacterial populations to adapt to fluctuating environments. Knowledge of the phenotypic transition rates for persistence may provide statistical information about the typical environments of bacteria. We also describe a design of artificial

  16. One gene, many phenotypes

    Directory of Open Access Journals (Sweden)

    Prasun P

    2007-01-01

    Full Text Available "Phenotype" is the visible or quantifiable effect of the expression of a gene, whereas the specific genetic constitution responsible for a phenotype is called "genotype". It was hoped that phenotype could be accurately predicted if the genotype could be characterized. But, the relationship between the genotype and phenotype is not straightforward. Similar genetic lesions can have entirely different phenotypes. In recent years, there has been tremendous progress in the understanding of the genetic basis of diseases. The extent to which it will be possible to relate findings at the DNA level to the clinical phenotype is difficult to delineate on many occasions. The elucidation of mechanisms underlying genotype-phenotype discrepancies is important as it will influence the use of DNA-based tests in the diagnosis, therapy and counseling of individuals affected with genetic disorders. This issue is pertinent to almost every aspect of medical practice and research in this post-genome era. In this article, we have tried to summarize those factors which are responsible for varied manifestations of lesion(s in a single gene.

  17. Enhanced virulence of sheep-passaged bovine spongiform encephalopathy agent is revealed by decreased polymorphism barriers in prion protein conversion studies.

    Science.gov (United States)

    Priem, Jan; Langeveld, Jan P M; van Keulen, Lucien J M; van Zijderveld, Fred G; Andreoletti, Olivier; Bossers, Alex

    2014-03-01

    Bovine spongiform encephalopathy (BSE) can be efficiently transmitted to small ruminants (sheep and goats) with certain prion protein (PrP) genotypes. Polymorphisms in PrP of both the host and donor influence the transmission efficiency of transmissible spongiform encephalopathies (TSEs) in general. These polymorphisms in PrP also modulate the PrP conversion underlying TSE agent replication. Here we demonstrate that single-round protein misfolding cyclic amplification (PMCA) can be used to assess species and polymorphism barriers at the molecular level. We assessed those within and between the ovine and bovine species in vitro using a variety of natural scrapie and experimentally generated cross-species BSE agents. These BSE agents include ovBSE-ARQ isolates (BSE derived from sheep having the ARQ/ARQ PrP genotype), and two unique BSE-derived variants: BSE passaged in VRQ/VRQ sheep and a cow BSE agent isolate generated by back-transmission of ovBSE-ARQ into its original host. PMCA allowed us to quantitatively determine PrP conversion profiles that correlated with known in vivo transmissibility and susceptibility in the two ruminant species in which strain-specific molecular signatures, like its molecular weight after protease digestion, were maintained. Furthermore, both BSE agent isolates from ARQ and VRQ sheep demonstrated a surprising transmission profile in which efficient transmissions to both sheep and bovine variants was combined. Finally, all data support the notion that ARQ-derived sheep BSE points to a significant increase in virulence compared to all other tested scrapie- and BSE-derived variants reflected by the increased conversion efficiencies of previously inefficient convertible PrP variants (including the so-called "resistant" sheep ARR variant). Prion diseases such as scrapie in sheep and goats, BSE in cattle, and Creutzfeldt-Jakob disease (CJD) in humans are fatal neurodegenerative diseases caused by prions. BSE is known to be transmissible to a

  18. The DFNA10 phenotype.

    NARCIS (Netherlands)

    Leenheer, E. de; Huygen, P.L.M.; Wayne, S.; Smith, R.J.H.; Cremers, C.W.R.J.

    2001-01-01

    We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available

  19. Down Syndrome: Cognitive Phenotype

    Science.gov (United States)

    Silverman, Wayne

    2007-01-01

    Down syndrome is the most prevalent cause of intellectual impairment associated with a genetic anomaly, in this case, trisomy of chromosome 21. It affects both physical and cognitive development and produces a characteristic phenotype, although affected individuals vary considerably with respect to severity of specific impairments. Studies…

  20. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  1. Comparison of the clinical course of Japanese MM1-type sporadic Creutzfeldt-Jakob disease between subacute spongiform encephalopathy and panencephalopathic-type.

    Science.gov (United States)

    Iwasaki, Yasushi; Tatsumi, Shinsui; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari

    2014-06-01

    Approximately half of Japanese sporadic Creutzfeldt-Jakob disease (sCJD) cases show panencephalopathic-type (PE-type) pathology, which is a rare subtype in North Americans and Europeans. Until now, the differences in the clinical course between subacute spongiform encephalopathy (SSE) cases and PE-type cases have been unclear. To investigate the clinical course of both subtypes, clinical findings from 42 Japanese MM1-type sCJD cases (20 SSE cases and 22 PE-type cases) were retrospectively evaluated by statistical analysis. No significant differences could be found regarding age at disease onset, the period between disease onset and first observation of myoclonus, the period between disease onset and the first observation of periodic sharp-wave complexes on electroencephalogram, or the period between disease onset and progression to the akinetic mutism state - whereas total disease duration and the period between the akinetic mutism state and death were significantly longer in PE-type cases. The prolonged disease duration was induced by the extended survival period in the akinetic mutism state. There was a statistically significant difference between the two series regarding performance of tube-feeding, but no statistically significant difference regarding performance of tracheotomy or gastrostomy. None of the cases received mechanical ventilation. We speculate that the most crucial factor of the prolonged survival period of Japanese sCJD cases, particularly in the PE-type, is that the introduction of tube-feeding in the akinetic mutism state leads to the stabilization of the patient's general condition. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

    Directory of Open Access Journals (Sweden)

    Konold Timm

    2012-03-01

    Full Text Available Abstract Background The majority of atypical bovine spongiform encephalopathy (BSE cases so far identified worldwide have been detected by active surveillance. Consequently the volume and quality of material available for detailed characterisation is very limiting. Here we report on a small transmission study of both atypical forms, H- and L-type BSE, in cattle to provide tissue for test evaluation and research, and to generate clinical, molecular and pathological data in a standardised way to enable more robust comparison of the two variants with particular reference to those aspects most relevant to case ascertainment and confirmatory diagnosis within existing regulated surveillance programmes. Results Two groups of four cattle, intracerebrally inoculated with L-type or H-type BSE, all presented with a nervous disease form with some similarities to classical BSE, which progressed to a more dull form in one animal from each group. Difficulty rising was a consistent feature of both disease forms and not seen in two BSE-free, non-inoculated cattle that served as controls. The pathology and molecular characteristics were distinct from classical BSE, and broadly consistent with published data, but with some variation in the pathological characteristics. Both atypical BSE types were readily detectable as BSE by current confirmatory methods using the medulla brain region at the obex, but making a clear diagnostic distinction between the forms was not consistently straightforward in this brain region. Cerebellum proved a more reliable sample for discrimination when using immunohistochemistry. Conclusions The prominent feature of difficulty rising in atypical BSE cases may explain the detection of naturally occurring cases in emergency slaughter cattle and fallen stock. Current confirmatory diagnostic methods are effective for the detection of such atypical cases, but consistently and correctly identifying the variant forms may require modifications to

  3. Removal of transmissible spongiform encephalopathy prion from large volumes of cell culture media supplemented with fetal bovine serum by using hollow fiber anion-exchange membrane chromatography.

    Science.gov (United States)

    Chou, Ming Li; Bailey, Andy; Avory, Tiffany; Tanimoto, Junji; Burnouf, Thierry

    2015-01-01

    Cases of variant Creutzfeldt-Jakob disease in people who had consumed contaminated meat products from cattle with bovine spongiform encephalopathy emphasize the need for measures aimed at preventing the transmission of the pathogenic prion protein (PrPSc) from materials derived from cattle. Highly stringent scrutiny is required for fetal bovine serum (FBS), a growth-medium supplement used in the production of parenteral vaccines and therapeutic recombinant proteins and in the ex vivo expansion of stem cells for transplantation. One such approach is the implementation of manufacturing steps dedicated to removing PrPSc from materials containing FBS. We evaluated the use of the QyuSpeed D (QSD) adsorbent hollow-fiber anion-exchange chromatographic column (Asahi Kasei Medical, Tokyo, Japan) for the removal of PrPSc from cell culture media supplemented with FBS. We first established that QSD filtration had no adverse effect on the chemical composition of various types of culture media supplemented with 10% FBS or the growth and viability characteristics of human embryonic kidney (HEK293) cells, baby hamster kidney (BHK-21) cells, African green monkey kidney (Vero) cells, and Chinese hamster ovary (CHO-k1) cells propagated in the various culture-medium filtrates. We used a 0.6-mL QSD column for removing PrPSc from up to 1000 mL of Dulbecco's modified Eagle's medium containing 10% FBS previously spiked with the 263K strain of hamster-adapted scrapie. The Western blot analysis, validated alongside an infectivity assay, revealed that the level of PrPSc in the initial 200mL flow-through was reduced by 2.5 to > 3 log10, compared with that of the starting material. These results indicate that QSD filtration removes PrPSc from cell culture media containing 10% FBS, and demonstrate the ease with which QSD filtration can be implemented in at industrial-scale to improve the safety of vaccines, therapeutic recombinant proteins, and ex vivo expanded stem cells produced using growth

  4. Subcritical Water Hydrolysis Effectively Reduces the In Vitro Seeding Activity of PrPSc but Fails to Inactivate the Infectivity of Bovine Spongiform Encephalopathy Prions.

    Science.gov (United States)

    Murayama, Yuichi; Yoshioka, Miyako; Okada, Hiroyuki; Takata, Eri; Masujin, Kentaro; Iwamaru, Yoshifumi; Shimozaki, Noriko; Yamamura, Tomoaki; Yokoyama, Takashi; Mohri, Shirou; Tsutsumi, Yuji

    2015-01-01

    The global outbreak of bovine spongiform encephalopathy (BSE) has been attributed to the recycling of contaminated meat and bone meals (MBMs) as feed supplements. The use of MBMs has been prohibited in many countries; however, the development of a method for inactivating BSE prions could enable the efficient and safe use of these products as an organic resource. Subcritical water (SCW), which is water heated under pressure to maintain a liquid state at temperatures below the critical temperature (374°C), exhibits strong hydrolytic activity against organic compounds. In this study, we examined the residual in vitro seeding activity of protease-resistant prion protein (PrPSc) and the infectivity of BSE prions after SCW treatments. Spinal cord homogenates prepared from BSE-infected cows were treated with SCW at 230-280°C for 5-7.5 min and used to intracerebrally inoculate transgenic mice overexpressing bovine prion protein. Serial protein misfolding cyclic amplification (sPMCA) analysis detected no PrPSc in the SCW-treated homogenates, and the mice treated with these samples survived for more than 700 days without any signs of disease. However, sPMCA analyses detected PrPSc accumulation in the brains of all inoculated mice. Furthermore, secondary passage mice, which inoculated with brain homogenates derived from a western blotting (WB)-positive primary passage mouse, died after an average of 240 days, similar to mice inoculated with untreated BSE-infected spinal cord homogenates. The PrPSc accumulation and vacuolation typically observed in the brains of BSE-infected mice were confirmed in these secondary passage mice, suggesting that the BSE prions maintained their infectivity after SCW treatment. One late-onset case, as well as asymptomatic but sPMCA-positive cases, were also recognized in secondary passage mice inoculated with brain homogenates from WB-negative but sPMCA-positive primary passage mice. These results indicated that SCW-mediated hydrolysis was

  5. Removal of transmissible spongiform encephalopathy prion from large volumes of cell culture media supplemented with fetal bovine serum by using hollow fiber anion-exchange membrane chromatography.

    Directory of Open Access Journals (Sweden)

    Ming Li Chou

    Full Text Available Cases of variant Creutzfeldt-Jakob disease in people who had consumed contaminated meat products from cattle with bovine spongiform encephalopathy emphasize the need for measures aimed at preventing the transmission of the pathogenic prion protein (PrPSc from materials derived from cattle. Highly stringent scrutiny is required for fetal bovine serum (FBS, a growth-medium supplement used in the production of parenteral vaccines and therapeutic recombinant proteins and in the ex vivo expansion of stem cells for transplantation. One such approach is the implementation of manufacturing steps dedicated to removing PrPSc from materials containing FBS. We evaluated the use of the QyuSpeed D (QSD adsorbent hollow-fiber anion-exchange chromatographic column (Asahi Kasei Medical, Tokyo, Japan for the removal of PrPSc from cell culture media supplemented with FBS. We first established that QSD filtration had no adverse effect on the chemical composition of various types of culture media supplemented with 10% FBS or the growth and viability characteristics of human embryonic kidney (HEK293 cells, baby hamster kidney (BHK-21 cells, African green monkey kidney (Vero cells, and Chinese hamster ovary (CHO-k1 cells propagated in the various culture-medium filtrates. We used a 0.6-mL QSD column for removing PrPSc from up to 1000 mL of Dulbecco's modified Eagle's medium containing 10% FBS previously spiked with the 263K strain of hamster-adapted scrapie. The Western blot analysis, validated alongside an infectivity assay, revealed that the level of PrPSc in the initial 200mL flow-through was reduced by 2.5 to > 3 log10, compared with that of the starting material. These results indicate that QSD filtration removes PrPSc from cell culture media containing 10% FBS, and demonstrate the ease with which QSD filtration can be implemented in at industrial-scale to improve the safety of vaccines, therapeutic recombinant proteins, and ex vivo expanded stem cells produced

  6. Transmissible Spongiform Encephalopathies (Prion Diseases)

    Science.gov (United States)

    ... when brain tissue is viewed under a microscope. Creutzfeldt-Jakob disease (CJD) is the most well-known of the ... when brain tissue is viewed under a microscope. Creutzfeldt-Jakob disease (CJD) is the most well-known of the ...

  7. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  8. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  9. Emerging molecular phenotypes of asthma

    Science.gov (United States)

    Ray, Anuradha; Oriss, Timothy B.

    2014-01-01

    Although asthma has long been considered a heterogeneous disease, attempts to define subgroups of asthma have been limited. In recent years, both clinical and statistical approaches have been utilized to better merge clinical characteristics, biology, and genetics. These combined characteristics have been used to define phenotypes of asthma, the observable characteristics of a patient determined by the interaction of genes and environment. Identification of consistent clinical phenotypes has now been reported across studies. Now the addition of various 'omics and identification of specific molecular pathways have moved the concept of clinical phenotypes toward the concept of molecular phenotypes. The importance of these molecular phenotypes is being confirmed through the integration of molecularly targeted biological therapies. Thus the global term asthma is poised to become obsolete, being replaced by terms that more specifically identify the pathology associated with the disease. PMID:25326577

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  11. The digital revolution in phenotyping.

    Science.gov (United States)

    Oellrich, Anika; Collier, Nigel; Groza, Tudor; Rebholz-Schuhmann, Dietrich; Shah, Nigam; Bodenreider, Olivier; Boland, Mary Regina; Georgiev, Ivo; Liu, Hongfang; Livingston, Kevin; Luna, Augustin; Mallon, Ann-Marie; Manda, Prashanti; Robinson, Peter N; Rustici, Gabriella; Simon, Michelle; Wang, Liqin; Winnenburg, Rainer; Dumontier, Michel

    2016-09-01

    Phenotypes have gained increased notoriety in the clinical and biological domain owing to their application in numerous areas such as the discovery of disease genes and drug targets, phylogenetics and pharmacogenomics. Phenotypes, defined as observable characteristics of organisms, can be seen as one of the bridges that lead to a translation of experimental findings into clinical applications and thereby support 'bench to bedside' efforts. However, to build this translational bridge, a common and universal understanding of phenotypes is required that goes beyond domain-specific definitions. To achieve this ambitious goal, a digital revolution is ongoing that enables the encoding of data in computer-readable formats and the data storage in specialized repositories, ready for integration, enabling translational research. While phenome research is an ongoing endeavor, the true potential hidden in the currently available data still needs to be unlocked, offering exciting opportunities for the forthcoming years. Here, we provide insights into the state-of-the-art in digital phenotyping, by means of representing, acquiring and analyzing phenotype data. In addition, we provide visions of this field for future research work that could enable better applications of phenotype data. © The Author 2015. Published by Oxford University Press.

  12. The interpretation of disease phenotypes to identify TSE strains in mice: characterisation of BSE using PrPSc distribution patterns in the brain.

    Science.gov (United States)

    Corda, Erica; Beck, Katy E; Sallis, Rosemary E; Vickery, Christopher M; Denyer, Margaret; Webb, Paul R; Bellworthy, Susan J; Spencer, Yvonne I; Simmons, Marion M; Spiropoulos, John

    2012-12-17

    In individual animals affected by transmissible spongiform encephalopathies, different disease phenotypes can be identified which are attributed to different strains of the agent. In the absence of reliable technology to fully characterise the agent, classification of disease phenotype has been used as a strain typing tool which can be applied in any host. This approach uses standardised data on biological parameters, established for a single host, to allow comparison of different prion sources. Traditionally prion strain characterisation in wild type mice is based on incubation periods and lesion profiles after the stabilisation of the agent into the new host which requires serial passages. Such analysis can take many years, due to prolonged incubation periods. The current study demonstrates that the PrPSc patterns produced by one serial passage in wild type mice of bovine or ovine BSE were consistent, stable and showed minimal and predictable differences from mouse-stabilised reference strains. This biological property makes PrPSc deposition pattern mapping a powerful tool in the identification and definition of TSE strains on primary isolation, making the process of characterisation faster and cheaper than a serial passage protocol. It can be applied to individual mice and therefore it is better suited to identify strain diversity within single inocula in case of co-infections or identify strains in cases where insufficient mice succumb to disease for robust lesion profiles to be constructed. The detailed description presented in this study provides a reference document for identifying BSE in wild type mice.

  13. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape

  14. Forensic DNA phenotyping : Regulatory issues

    NARCIS (Netherlands)

    Koops, E.J.; Schellekens, M.H.M.

    2008-01-01

    Forensic DNA phenotyping is an interesting new investigation method: crime-scene DNA is analyzed to compose a description of the unknown suspect, including external and behavioral features, geographic origin and perhaps surname. This method is allowed in some countries but prohibited in a few

  15. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  16. Phenotypic deconstruction of gene circuitry

    Science.gov (United States)

    Lomnitz, Jason G.; Savageau, Michael A.

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  17. Automated phenotyping of permanent crops

    Science.gov (United States)

    McPeek, K. Thomas; Steddom, Karl; Zamudio, Joseph; Pant, Paras; Mullenbach, Tyler

    2017-05-01

    AGERpoint is defining a new technology space for the growers' industry by introducing novel applications for sensor technology and data analysis to growers of permanent crops. Serving data to a state-of-the-art analytics engine from a cutting edge sensor platform, a new paradigm in precision agriculture is being developed that allows growers to understand the unique needs of each tree, bush or vine in their operation. Autonomous aerial and terrestrial vehicles equipped with multiple varieties of remote sensing technologies give AGERpoint the ability to measure key morphological and spectral features of permanent crops. This work demonstrates how such phenotypic measurements combined with machine learning algorithms can be used to determine the variety of crops (e.g., almond and pecan trees). This phenotypic and varietal information represents the first step in enabling growers with the ability to tailor their management practices to individual plants and maximize their economic productivity.

  18. Wine Expertise Predicts Taste Phenotype

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2011-01-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance – with appropriate caveats about populations tested, outcomes measured and psychophysical methods used – an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli. PMID:22888174

  19. Animal models of RLS phenotypes.

    Science.gov (United States)

    Allen, Richard P; Donelson, Nathan C; Jones, Byron C; Li, Yuqing; Manconi, Mauro; Rye, David B; Sanyal, Subhabrata; Winkelmann, Juliane

    2017-03-01

    Restless legs syndrome (RLS) is a complex disorder that involves sensory and motor systems. The major pathophysiology of RLS is low iron concentration in the substantia nigra containing the cell bodies of dopamine neurons that project to the striatum, an area that is crucial for modulating movement. People who have RLS often present with normal iron values outside the brain; recent studies implicate several genes are involved in the syndrome. Like most complex diseases, animal models usually do not faithfully capture the full phenotypic spectrum of "disease," which is a uniquely human construct. Nonetheless, animal models have proven useful in helping to unravel the complex pathophysiology of diseases such as RLS and suggesting novel treatment paradigms. For example, hypothesis-independent genome-wide association studies (GWAS) have identified several genes as increasing the risk for RLS, including BTBD9. Independently, the murine homolog Btbd9 was identified as a candidate gene for iron regulation in the midbrain in mice. The relevance of the phenotype of another of the GWAS identified genes, MEIS1, has also been explored. The role of Btbd9 in iron regulation and RLS-like behaviors has been further evaluated in mice carrying a null mutation of the gene and in fruit flies when the BTBD9 protein is degraded. The BTBD9 and MEIS1 stories originate from human GWAS research, supported by work in a genetic reference population of mice (forward genetics) and further verified in mice, fish flies, and worms. Finally, the role of genetics is further supported by an inbred mouse strain that displays many of the phenotypic characteristics of RLS. The role of animal models of RLS phenotypes is also extended to include periodic limb movements. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Adaptive evolution of molecular phenotypes

    International Nuclear Information System (INIS)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-01-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak. (paper)

  1. Drivers of the Warburg phenotype.

    Science.gov (United States)

    Cairns, Rob A

    2015-01-01

    The Warburg effect was first described by Otto Warburg in the 1920s and describes the preferential conversion of glucose to lactate as opposed to its metabolism through the citric acid cycle to fuel oxidative phosphorylation in the mitochondria, even in the presence of oxygen. This phenotype is a common feature of malignant cells and is also observed in some highly proliferative normal tissues. The selective advantage provided by this phenotype is not entirely clear. Adopting this metabolic state may allow tumor cells to balance their need for ATP, biosynthetic precursor molecules, and reducing power in order to respond to growth and proliferation signals and may provide a selective advantage in the hypoxic and acidic microenvironments that are often a feature of solid tumors. Oncogenic signaling pathways and responses to the local microenvironment combine to produce this metabolic phenotype via a number of molecular mechanisms. A better understanding of these mechanisms in both tumor and normal tissues and a more complete understanding of how the Warburg effect interacts with the rest of the tumor metabolic network should provide opportunities for novel clinical intervention.

  2. Cancer predisposition in children: genetics, phenotypes & screening

    NARCIS (Netherlands)

    Hopman, S.M.J.

    2014-01-01

    This thesis describes the genetic, phenotypic and screening aspects of tumor predisposition syndromes in childhood cancer patients. In tumor predisposition syndromes, the same constitutional molecular defects that lead to the clinical phenotype predispose the patient to develop specific cancers.

  3. Detection of RNA in the Plasma of Patients with Sporadic Creutzfeldt–Jakob Disease, Gerstmann–Straüssler Syndrome and Other Non-Transmissible Spongiform Encephalopathy Brain Disorders

    Directory of Open Access Journals (Sweden)

    Kazuo Tsukui

    2010-01-01

    Full Text Available The infectious agent of transmissible spongiform encephalopathy (TSE was assumed to be the aggregate of abnormal prion protein isoform (PrPsc. We observed that lowering the pH of 3% SDS-inoculated plasma or brain homogenate after PK digestion to 4.5 (acidic SDS condition enabled to precipitate proteinase K-resistant prion protein (PrPres in plasma as well as PrPres in the brain with synthetic poly-A RNA as affinity aggregate. Therefore, we determined if RNA molecules could be used for discriminating TSE patients from healthy individuals. We also examined the plasma of patients with classical Creutzfeldt–Jakob disease (CJD and other brain disorders who were not diagnosed with TSE. The results indicated that RNA approximately 1.5–2.0 kb in length was commonly observed in the plasma of patients with brain disorders but was not detected in the plasma of healthy volunteers. Enhanced expression of RNA and its protection from endogenous nucleases might occur in the former group of patients. Moreover, we speculate that the non-transmissible neuronal disorders overlap with prion diseases.

  4. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  5. The Human Phenotype Ontology in 2017

    International Nuclear Information System (INIS)

    Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie

    2016-01-01

    Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

  6. Delineating SPTAN1 associated phenotypes

    DEFF Research Database (Denmark)

    Syrbe, Steffen; Harms, Frederike L; Parrini, Elena

    2017-01-01

    De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1...... contact site exhibited severe and progressive brain, brainstem and cerebellar atrophy, with hypomyelination in most. We used fibroblasts from five patients to study spectrin aggregate formation by Triton-X extraction and immunocytochemistry followed by fluorescence microscopy. αII/βII aggregates and α...

  7. The thrifty phenotype hypothesis revisited

    DEFF Research Database (Denmark)

    Vaag, A A; Grunnet, L G; Arora, G P

    2012-01-01

    Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2...... of the underlying molecular mechanisms. Type 2 diabetes is a multiple-organ disease, and developmental programming, with its idea of organ plasticity, is a plausible hypothesis for a common basis for the widespread organ dysfunctions in type 2 diabetes and the metabolic syndrome. Only two among the 45 known type 2...

  8. Phenotypic variability in Patau syndrome.

    Science.gov (United States)

    Caba, Lavinia; Rusu, Cristina; Butnariu, Lacramioara; Panzaru, Monica; Braha, Elena; Volosciuc, M; Popescu, Roxana; Gramescu, Mihaela; Bujoran, C; Martiniuc, Violeta; Covic, M; Gorduza, E V

    2013-01-01

    Patau syndrome has an incidence of 1/10.000-20.000, the clinical diagnosis being suggested by the triad cleft lip and palate, microphthalmia/anophthalmia and postaxial polydactyly. Most frequent cytogenetic abnormality is free and homogeneous trisomy 13 (80.0%), rarely being detected trisomy mosaics or Robertsonian translocations. The objective of the study was to identify phenotypic features of trisomy 13. The retrospective study was conducted on a trial group of 14 cases diagnosed cytogenetically with trisomy 13 between January 2000 and December 2012 at lasi Medical Genetics Centre. Of the 14 cases, 3 were evaluated pathologically (two aborted foetuses and one stillborn), 8 cases were detected in the neonatal period, and 3 in infancy. Clinical diagnosis was supported by the identification of a model of abnormal development, mainly characterized by: maxillary cleft (lip and palate--5 cases; lip--1 case), ocular abnormalities (microphthalmia/anophthalmia--7 cases; cyclopia--1 case), postaxial polydactyly (7 cases), scalp defects (6 cases), congenital heart anomalies (10 cases, 6 patients with atrial septal defect), complete holoprosencephaly (4 cases), ear abnormalities (11 cases), broad nasal root (10 cases). An important issue in confirming the phenotypic variability of Patau syndrome is that the classic clinical triad was identified only in one case. Patau syndrome is a disease with variable expression and is characterized by a pattern of abnormal prenatal development characterized by facial dysmorphia, polydactyly and severe birth defects (heart, brain) that generate an increased in utero and perinatal mortality.

  9. A comparison of the risk of bovine spongiform encephalopathy infectivity in beef from cattle younger than 21 months in Japan with that in beef from the United States as assessed by the carcass maturity score.

    Science.gov (United States)

    Sugiura, Katsuaki; Smith, Gary C

    2008-04-01

    After the detection of the first case of bovine spongiform encephalopathy (BSE) in the United States in December 2003, the Japanese government halted all imports of U.S. beef. The BSE risk in beef is partly dependent on the slaughter age of the cattle from which it is derived. In Japan, all cattle 21 months old and older are screened using a rapid diagnostic test, while in the United States, routine BSE testing is not done at any age of slaughter cattle. In the United States, there is no nationally mandated cattle identification system that enables cattle younger than 21 months to be identified. Therefore, all beef potentially produced for export to Japan must be from cattle that are age verified as younger than 21 months old or be classified by the U.S. Department of Agriculture using a carcass maturity score, which in turn is related to the age of the animal from which the beef is derived. After consulting the Food Safety Commission, the Japanese government decided on 12 December 2005 to allow importation of beef from the United States derived from cattle with a carcass maturity score of < or =A40 and from which specified risk materials are removed. In this study, a stochastic model was used to simulate the interval of time from slaughter to the predicted clinical onset of BSE in an infected animal. A simulation result, based on the assumption that the BSE prevalence is equivalent in the two countries, revealed that there was no increased risk of BSE infectivity in beef coming from carcasses with a maturity score of < or =A40 in the United States, compared with beef from cattle younger than 21 months slaughtered in Japan.

  10. Evolution of phenotypic plasticity in colonizing species.

    Science.gov (United States)

    Lande, Russell

    2015-05-01

    I elaborate an hypothesis to explain inconsistent empirical findings comparing phenotypic plasticity in colonizing populations or species with plasticity from their native or ancestral range. Quantitative genetic theory on the evolution of plasticity reveals that colonization of a novel environment can cause a transient increase in plasticity: a rapid initial increase in plasticity accelerates evolution of a new optimal phenotype, followed by slow genetic assimilation of the new phenotype and reduction of plasticity. An association of colonization with increased plasticity depends on the difference in the optimal phenotype between ancestral and colonized environments, the difference in mean, variance and predictability of the environment, the cost of plasticity, and the time elapsed since colonization. The relative importance of these parameters depends on whether a phenotypic character develops by one-shot plasticity to a constant adult phenotype or by labile plasticity involving continuous and reversible development throughout adult life. © 2014 John Wiley & Sons Ltd.

  11. Phenotypic Plasticity and Species Coexistence.

    Science.gov (United States)

    Turcotte, Martin M; Levine, Jonathan M

    2016-10-01

    Ecologists are increasingly interested in predicting how intraspecific variation and changing trait values impact species interactions and community composition. For many traits, much of this variation is caused by phenotypic plasticity, and thus the impact of plasticity on species coexistence deserves robust quantification. Partly due to a lack of sound theoretical expectations, empirical studies make contradictory claims regarding plasticity effects on coexistence. Our critical review of this literature, framed in modern coexistence theory, reveals that plasticity affects species interactions in ways that could impact stabilizing niche differences and competitive asymmetries. However, almost no study integrates these measures to quantify the net effect of plasticity on species coexistence. To address this challenge, we outline novel empirical approaches grounded in modern theory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Refined Phenotyping of Modic Changes

    Science.gov (United States)

    Määttä, Juhani H.; Karppinen, Jaro; Paananen, Markus; Bow, Cora; Luk, Keith D.K.; Cheung, Kenneth M.C.; Samartzis, Dino

    2016-01-01

    Abstract Low back pain (LBP) is the world's most disabling condition. Modic changes (MC) are vertebral bone marrow changes adjacent to the endplates as noted on magnetic resonance imaging. The associations of specific MC types and patterns with prolonged, severe LBP and disability remain speculative. This study assessed the relationship of prolonged, severe LBP and back-related disability, with the presence and morphology of lumbar MC in a large cross-sectional population-based study of Southern Chinese. We addressed the topographical and morphological dimensions of MC along with other magnetic resonance imaging phenotypes (eg, disc degeneration and displacement) on the basis of axial T1 and sagittal T2-weighted imaging of L1-S1. Prolonged severe LBP was defined as LBP lasting ≥30 days during the past year, and a visual analog scale severest pain intensity of at least 6/10. An Oswestry Disability Index score of 15% was regarded as significant disability. We also assessed subject demographics, occupation, and lifestyle factors. In total, 1142 subjects (63% females, mean age 53 years) were assessed. Of these, 282 (24.7%) had MC (7.1% type I, 17.6% type II). MC subjects were older (P = 0.003), had more frequent disc displacements (P disability. The strength of the associations increased with the number of MC. This large-scale study is the first to definitively note MC types and specific morphologies to be independently associated with prolonged severe LBP and back-related disability. This proposed refined MC phenotype may have direct implications in clinical decision-making as to the development and management of LBP. Understanding of these imaging biomarkers can lead to new preventative and personalized therapeutics related to LBP. PMID:27258491

  13. The phenotypic variance gradient - a novel concept.

    Science.gov (United States)

    Pertoldi, Cino; Bundgaard, Jørgen; Loeschcke, Volker; Barker, James Stuart Flinton

    2014-11-01

    Evolutionary ecologists commonly use reaction norms, which show the range of phenotypes produced by a set of genotypes exposed to different environments, to quantify the degree of phenotypic variance and the magnitude of plasticity of morphometric and life-history traits. Significant differences among the values of the slopes of the reaction norms are interpreted as significant differences in phenotypic plasticity, whereas significant differences among phenotypic variances (variance or coefficient of variation) are interpreted as differences in the degree of developmental instability or canalization. We highlight some potential problems with this approach to quantifying phenotypic variance and suggest a novel and more informative way to plot reaction norms: namely "a plot of log (variance) on the y-axis versus log (mean) on the x-axis, with a reference line added". This approach gives an immediate impression of how the degree of phenotypic variance varies across an environmental gradient, taking into account the consequences of the scaling effect of the variance with the mean. The evolutionary implications of the variation in the degree of phenotypic variance, which we call a "phenotypic variance gradient", are discussed together with its potential interactions with variation in the degree of phenotypic plasticity and canalization.

  14. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    NARCIS (Netherlands)

    Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have

  15. Phenotype and genotype differentiation between flathead grey ...

    African Journals Online (AJOL)

    This study aimed to study the phenotype and genotype differentiation and to compare the amount of differences in phenotype based on morphometric character indices and meristic counts with the amount of differences in genotype based on random amplified polymorphic DNA (RAPD) fingerprinting between two Mugilidae, ...

  16. REVIEW ARTICLE One gene, many phenotypes

    African Journals Online (AJOL)

    salah

    One gene, many phenotypes. A- Modifier causing less severe (re- duced) phenotype of Beta thalassemia. The severity of anemia in beta thalas- semia reflects the degree of globin chain imbalance. The excess of alpha globin chain precipitates in red cell pre- cursors leading to ineffective erythro- poiesis. This imbalance can ...

  17. Phenotype Development in Adolescents With Tourette Syndrome

    DEFF Research Database (Denmark)

    Groth, Camilla; Debes, Nanette Mol; Skov, Liselotte

    2017-01-01

    Tourette syndrome (TS) is a neurodevelopmental disorder characterized by frequent comorbidities and a wide spectrum of phenotype presentations. This study aimed to describe the development of phenotypes in TS and tic-related impairment in a large longitudinal study of 226 children and adolescents...

  18. Human pancreatic islet progenitor cells demonstrate phenotypic ...

    Indian Academy of Sciences (India)

    2009-04-24

    Apr 24, 2009 ... Phenotypic plasticity is a phenomenon that describes the occurrence of 2 or more distinct phenotypes under diverse conditions. This article discusses the work carried out over the past few years in understanding the potential of human pancreatic islet-derived progenitors for cell replacement therapy in ...

  19. Developing and emerging clinical asthma phenotypes

    NARCIS (Netherlands)

    Hekking, Pieter-Paul W.; Bel, Elisabeth H.

    2014-01-01

    For more than a century, clinicians have attempted to subdivide asthma into different phenotypes based on triggers that cause asthma attacks, the course of the disease, or the prognosis. The first phenotypes that were described included allergic asthma, intrinsic or nonallergic asthma, infectious

  20. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping of at...

  1. Emerging semantics to link phenotype and environment

    Directory of Open Access Journals (Sweden)

    Anne E. Thessen

    2015-12-01

    Full Text Available Understanding the interplay between environmental conditions and phenotypes is a fundamental goal of biology. Unfortunately, data that include observations on phenotype and environment are highly heterogeneous and thus difficult to find and integrate. One approach that is likely to improve the status quo involves the use of ontologies to standardize and link data about phenotypes and environments. Specifying and linking data through ontologies will allow researchers to increase the scope and flexibility of large-scale analyses aided by modern computing methods. Investments in this area would advance diverse fields such as ecology, phylogenetics, and conservation biology. While several biological ontologies are well-developed, using them to link phenotypes and environments is rare because of gaps in ontological coverage and limits to interoperability among ontologies and disciplines. In this manuscript, we present (1 use cases from diverse disciplines to illustrate questions that could be answered more efficiently using a robust linkage between phenotypes and environments, (2 two proof-of-concept analyses that show the value of linking phenotypes to environments in fishes and amphibians, and (3 two proposed example data models for linking phenotypes and environments using the extensible observation ontology (OBOE and the Biological Collections Ontology (BCO; these provide a starting point for the development of a data model linking phenotypes and environments.

  2. Auditory Phenotype of Smith-Magenis Syndrome

    Science.gov (United States)

    Brendal, Megan A.; King, Kelly A.; Zalewski, Christopher K.; Finucane, Brenda M.; Introne, Wendy; Brewer, Carmen C.; Smith, Ann C. M.

    2017-01-01

    Purpose: The purpose of this study was to describe the auditory phenotype of a large cohort with Smith-Magenis syndrome (SMS), a rare disorder including physical anomalies, cognitive deficits, sleep disturbances, and a distinct behavioral phenotype. Method: Hearing-related data were collected for 133 individuals with SMS aged 1-49 years. Audiogram…

  3. The Cognitive Phenotype of Spina Bifida Meningomyelocele

    Science.gov (United States)

    Dennis, Maureen; Barnes, Marcia A.

    2010-01-01

    A cognitive phenotype is a product of both assets and deficits that specifies what individuals with spina bifida meningomyelocele (SBM) can and cannot do and why they can or cannot do it. In this article, we review the cognitive phenotype of SBM and describe the processing assets and deficits that cut within and across content domains, sensory…

  4. Adjusting phenotypes by noise control.

    Directory of Open Access Journals (Sweden)

    Kyung H Kim

    2012-01-01

    Full Text Available Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks.

  5. Nordic research infrastructures for plant phenotyping

    Directory of Open Access Journals (Sweden)

    Kristiina Himanen

    2018-03-01

    Full Text Available Plant phenomics refers to the systematic study of plant phenotypes. Together with closely monitored, controlled climates, it provides an essential component for the integrated analysis of genotype-phenotype-environment interactions. Currently, several plant growth and phenotyping facilities are under establishment globally, and numerous facilities are already in use. Alongside the development of the research infrastructures, several national and international networks have been established to support shared use of the new methodology. In this review, an overview is given of the Nordic plant phenotyping and climate control facilities. Since many areas of phenomics such as sensor-based phenotyping, image analysis and data standards are still developing, promotion of educational and networking activities is especially important. These facilities and networks will be instrumental in tackling plant breeding and plant protection challenges. They will also provide possibilities to study wild species and their ecological interactions under changing Nordic climate conditions.

  6. Federated Tensor Factorization for Computational Phenotyping

    Science.gov (United States)

    Kim, Yejin; Sun, Jimeng; Yu, Hwanjo; Jiang, Xiaoqian

    2017-01-01

    Tensor factorization models offer an effective approach to convert massive electronic health records into meaningful clinical concepts (phenotypes) for data analysis. These models need a large amount of diverse samples to avoid population bias. An open challenge is how to derive phenotypes jointly across multiple hospitals, in which direct patient-level data sharing is not possible (e.g., due to institutional policies). In this paper, we developed a novel solution to enable federated tensor factorization for computational phenotyping without sharing patient-level data. We developed secure data harmonization and federated computation procedures based on alternating direction method of multipliers (ADMM). Using this method, the multiple hospitals iteratively update tensors and transfer secure summarized information to a central server, and the server aggregates the information to generate phenotypes. We demonstrated with real medical datasets that our method resembles the centralized training model (based on combined datasets) in terms of accuracy and phenotypes discovery while respecting privacy. PMID:29071165

  7. Phenotypic plasticity of the Drosophila transcriptome.

    Directory of Open Access Journals (Sweden)

    Shanshan Zhou

    Full Text Available Phenotypic plasticity is the ability of a single genotype to produce different phenotypes in response to changing environments. We assessed variation in genome-wide gene expression and four fitness-related phenotypes of an outbred Drosophila melanogaster population under 20 different physiological, social, nutritional, chemical, and physical environments; and we compared the phenotypically plastic transcripts to genetically variable transcripts in a single environment. The environmentally sensitive transcriptome consists of two transcript categories, which comprise ∼15% of expressed transcripts. Class I transcripts are genetically variable and associated with detoxification, metabolism, proteolysis, heat shock proteins, and transcriptional regulation. Class II transcripts have low genetic variance and show sexually dimorphic expression enriched for reproductive functions. Clustering analysis of Class I transcripts reveals a fragmented modular organization and distinct environmentally responsive transcriptional signatures for the four fitness-related traits. Our analysis suggests that a restricted environmentally responsive segment of the transcriptome preserves the balance between phenotypic plasticity and environmental canalization.

  8. Targeting phenotypically tolerant Mycobacterium tuberculosis

    Science.gov (United States)

    Gold, Ben; Nathan, Carl

    2016-01-01

    While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

  9. PHENOTYPIC TRAITS IN ZAGORJE TURKEY

    Directory of Open Access Journals (Sweden)

    Z. Janječić

    2007-06-01

    Full Text Available Production of turkeys in the region of Hrvatsko zagorje began in second half of 16th century, when there was a little influence of other turkey breeds from other region. Recently, interest for protection and preservation of autochthonous poultry breeds in Croatia is growing and in that sense this investigation was set to determine the phenotypic traits of Zagorje turkey. One hundred 10-month old turkeys (5 males and 20 females of four strains (bronze, black, grey and pale were measured, while egg production data were collected by a poll among the breeders. Average body weight of bronze, black, grey and pale strain males were 7.08, 6.88, 6.10 and 6.09 kg, respectively, while in females the average values were 4.02, 4.07, 3.63, and 3.68 kg. Generally, according to body measures of male birds, other than body weight, of all of the strains of Zagorje turkey, the black one is the biggest, as it had the highest values for body length, length of sternum, length of drumstick, length of shank, depth of chest and head measures. At the same time, the bronze strain had the highest value for carcass width. Body measures mentioned previously were not so different in females. Number of reared chicks was lowest in the pale strain. From the body measures assessed it is possible to conclude that Zagorje turkeys are rather uniform within the strain but differences in most of the breed traits are present between the strains, especially in males of bronze and black strain, when compared to gray and pale strain.

  10. ACE phenotyping in human heart.

    Science.gov (United States)

    Tikhomirova, Victoria E; Kost, Olga A; Kryukova, Olga V; Golukhova, Elena Z; Bulaeva, Naida I; Zholbaeva, Aigerim Z; Bokeria, Leo A; Garcia, Joe G N; Danilov, Sergei M

    2017-01-01

    Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10-15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. "Conformational fingerprint" of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk.

  11. Modelling the trend of bovine spongiform encephalopathy prevalence in France: Use of restricted cubic spline regression in age-period-cohort models to estimate the efficiency of control measures.

    Science.gov (United States)

    Sala, Carole; Morignat, Eric; Ducrot, Christian; Calavas, Didier

    2009-07-01

    An age-period-cohort (APC) analysis was used to assess the trend in prevalence of bovine spongiform encephalopathy (BSE) in France over time in relation to the control measures adopted since onset of the epidemic. Restricted cubic regression splines were used to model the functional forms of the non-linear effects of age at screening, birth cohort and date of diagnosis of the tested animals. The data of the 2001-2007 period of surveillance was analysed using 1-year categorisation. A categorical analysis was performed as control to check the accuracy of the sets of knots in the spline models, which were selected according to the Akaike Information Criterion (AIC). Knot selection was based on a priori knowledge of the disease and the dates of implementation of the five main BSE control measures. It was assumed that disease prevalence was a function of exposure to BSE and that changes in the exposure of cattle to BSE were mainly due to the control measures. The effects of the five main control measures were discussed in relation to the trend in BSE risk for the successive birth cohorts. The six selected models confirmed that all measures participated in disease control. However, characterization of the respective effect of individual measures was not straightforward due to the very low disease prevalence, incompletely tested cohorts and probably cumulative and overlapping effects of successive measures. The ban of importation of meat and bone meal (MBM) from the UK and the ban of use of MBM in bovines were insufficient to control the epidemic. The decline in the BSE epidemic more likely originated from implementation of the ban of MBM use in all ruminants in 1994, whose effect was probably reinforced by the evolution in perception of the BSE risk following evidence of BSE transmission to humans. Finally, the respective effects of the last two measures (prohibition of the use of specific risk material in 1996 and total MBM ban in 2000) could not be characterized as

  12. Evolution of molecular phenotypes under stabilizing selection

    Science.gov (United States)

    Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

    2013-01-01

    Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes.

  13. Integrating phenotype ontologies with PhenomeNET

    KAUST Repository

    Rodriguez-Garcia, Miguel Angel

    2017-12-19

    Background Integration and analysis of phenotype data from humans and model organisms is a key challenge in building our understanding of normal biology and pathophysiology. However, the range of phenotypes and anatomical details being captured in clinical and model organism databases presents complex problems when attempting to match classes across species and across phenotypes as diverse as behaviour and neoplasia. We have previously developed PhenomeNET, a system for disease gene prioritization that includes as one of its components an ontology designed to integrate phenotype ontologies. While not applicable to matching arbitrary ontologies, PhenomeNET can be used to identify related phenotypes in different species, including human, mouse, zebrafish, nematode worm, fruit fly, and yeast. Results Here, we apply the PhenomeNET to identify related classes from two phenotype and two disease ontologies using automated reasoning. We demonstrate that we can identify a large number of mappings, some of which require automated reasoning and cannot easily be identified through lexical approaches alone. Combining automated reasoning with lexical matching further improves results in aligning ontologies. Conclusions PhenomeNET can be used to align and integrate phenotype ontologies. The results can be utilized for biomedical analyses in which phenomena observed in model organisms are used to identify causative genes and mutations underlying human disease.

  14. Redefining Aging in HIV Infection Using Phenotypes.

    Science.gov (United States)

    Stoff, David M; Goodkin, Karl; Jeste, Dilip; Marquine, Maria

    2017-10-01

    This article critically reviews the utility of "phenotypes" as behavioral descriptors in aging/HIV research that inform biological underpinnings and treatment development. We adopt a phenotypic redefinition of aging conceptualized within a broader context of HIV infection and of aging. Phenotypes are defined as dimensions of behavior, closely related to fundamental mechanisms, and, thus, may be more informative than chronological age. Primary emphasis in this review is given to comorbid aging and cognitive aging, though other phenotypes (i.e., disability, frailty, accelerated aging, successful aging) are also discussed in relation to comorbid aging and cognitive aging. The main findings that emerged from this review are as follows: (1) the phenotypes, comorbid aging and cognitive aging, are distinct from each other, yet overlapping; (2) associative relationships are the rule in HIV for comorbid and cognitive aging phenotypes; and (3) HIV behavioral interventions for both comorbid aging and cognitive aging have been limited. Three paths for research progress are identified for phenotype-defined aging/HIV research (i.e., clinical and behavioral specification, biological mechanisms, intervention targets), and some important research questions are suggested within each of these research paths.

  15. Evolution of molecular phenotypes under stabilizing selection

    International Nuclear Information System (INIS)

    Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

    2013-01-01

    Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes. (paper)

  16. The nature of stable insomnia phenotypes.

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L

    2015-01-01

    We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Longitudinal. Urban, community-based. Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). None. At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the 'neither criterion' phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With the exception of daytime sleepiness, few clinical differences are apparent across stable phenotypes.

  17. Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma

    NARCIS (Netherlands)

    Eisenhofer, G.; Pacak, K.; Huynh, T.T.; Qin, N.; Bratslavsky, G.; Linehan, W.M.; Mannelli, M.; Friberg, P.; Grebe, S.K.; Timmers, H.J.L.M.; Bornstein, S.R.; Lenders, J.W.M.

    2011-01-01

    Phaeochromocytomas and paragangliomas (PPGLs) are highly heterogeneous tumours with variable catecholamine biochemical phenotypes and diverse hereditary backgrounds. This analysis of 18 catecholamine-related plasma and urinary biomarkers in 365 patients with PPGLs and 846 subjects without PPGLs

  18. Phenotypic profiles of Armenian grape cultivars

    Directory of Open Access Journals (Sweden)

    Aroutiounian Rouben

    2015-01-01

    Full Text Available The conservation and sustainable use of grapevine biodiversity in Armenia is particularly important due to the large number of traditional local varieties. Being partially different from European grapevine gene pool, the material of Armenian local cultivars significantly contributes to the understanding of the genetic variation and is valuable source for target selection. During last years many Armenian grapevine cultivars have been already described and their genotypes determined, but some local varieties and wild accessions remain unidentified and their phenotypic characteristics overlooked. The comprehensive analysis of phenotypes is essential for research, including genetic association studies, cultivar evaluation and selection. The goal of our research was the phenotyping on the base of reproductive, carpological and analytical characteristics of 80 Armenian aboriginal and new grape cultivars. Description of phenotypic profiles is important step towards identification and conservation of genetic resources of Armenian grapes. In future, these data can be applied for breeding of improved grape varieties targeted to fresh consumption and wine production.

  19. Phenotypic diversity and phylogenetic relationship between the ...

    African Journals Online (AJOL)

    Phenotypic diversity and phylogenetic relationship between the Bakosi/Baweri and other pig breeds ( Sus scrofa Domesticus ) in the humid forest with monomodal rainfall agro-ecological zone of Cameroon.

  20. Mining skeletal phenotype descriptions from scientific literature.

    Directory of Open Access Journals (Sweden)

    Tudor Groza

    Full Text Available Phenotype descriptions are important for our understanding of genetics, as they enable the computation and analysis of a varied range of issues related to the genetic and developmental bases of correlated characters. The literature contains a wealth of such phenotype descriptions, usually reported as free-text entries, similar to typical clinical summaries. In this paper, we focus on creating and making available an annotated corpus of skeletal phenotype descriptions. In addition, we present and evaluate a hybrid Machine Learning approach for mining phenotype descriptions from free text. Our hybrid approach uses an ensemble of four classifiers and experiments with several aggregation techniques. The best scoring technique achieves an F-1 score of 71.52%, which is close to the state-of-the-art in other domains, where training data exists in abundance. Finally, we discuss the influence of the features chosen for the model on the overall performance of the method.

  1. Phenotypic variation in plants: Roles for epigenetics

    OpenAIRE

    Lauss, K.

    2017-01-01

    Besides genetics, also epigenetics can play a role in shaping the characteristics of a plant (phenotype). Epigenetics refers to chemical modifications of DNA and proteins associated with the DNA that can influence gene activity (the ‘epigenome’) and can be passed on through cell divisions and following generations. This thesis aimed to explore relationships between epigenome and phenotype in plants. The focus is DNA methylation, an epigenetic modification that occurs on cytosine bases in the ...

  2. A Regulatory RNA Inducing Transgenerationally Inherited Phenotypes

    DEFF Research Database (Denmark)

    Jensen, Lea Møller

    . The variation in Arabidopsis enables different regulatory networks and mechanisms to shape the phenotypic characteristics. The thesis describes the identification of regulatory RNA encoded by an enzyme encoding gene. The RNA regulates by inducing transgenerationally inherited phenotypes. The function of the RNA...... is dependent on the genetic background illustrating that polymorphisms are found in either interactors or target genes of the RNA. Furthermore, the RNA provides a mechanistic link between accumulation of glucosinolate and onset of flowering....

  3. Plant phenotypic plasticity in a changing climate

    OpenAIRE

    Nicotra, Adrienne B.; Atkin, Owen K.; Bonser, Stephen P.; Davidson, Amy M.; Finnegan, Jean; Mathesius, Ulrike; Poot, Pieter; Purugganan, Michael D.; Valladares, Fernando; van Kleunen, Mark

    2010-01-01

    Climate change is altering the availability of resources and the conditions that are crucial to plant performance. One way plants will respond to these changes is through environmentally induced shifts in phenotype(phenotypic plasticity). Understanding plastic responses is crucial for predicting and managing the effects of climate change on native species as well as cropplants. Here,we provide a toolbox with definitions of key theoretical elements and a synthesis of the current understanding ...

  4. Important discoveries from analysing bacterial phenotypes

    OpenAIRE

    Bochner, Barry R; Giovannetti, Luciana; Viti, Carlo

    2008-01-01

    The ability to test hundreds to thousands of cellular phenotypes in a single experiment has opened up new avenues of investigation and exploration and led to important discoveries in very diverse applications of microbiological research and development. The information provided by global phenotyping is complementary to, and often more easily interpretable than information provided by global molecular analytical methods such as gene chips and proteomics. This report summarizes advances present...

  5. Phenex: ontological annotation of phenotypic diversity.

    Directory of Open Access Journals (Sweden)

    James P Balhoff

    2010-05-01

    Full Text Available Phenotypic differences among species have long been systematically itemized and described by biologists in the process of investigating phylogenetic relationships and trait evolution. Traditionally, these descriptions have been expressed in natural language within the context of individual journal publications or monographs. As such, this rich store of phenotype data has been largely unavailable for statistical and computational comparisons across studies or integration with other biological knowledge.Here we describe Phenex, a platform-independent desktop application designed to facilitate efficient and consistent annotation of phenotypic similarities and differences using Entity-Quality syntax, drawing on terms from community ontologies for anatomical entities, phenotypic qualities, and taxonomic names. Phenex can be configured to load only those ontologies pertinent to a taxonomic group of interest. The graphical user interface was optimized for evolutionary biologists accustomed to working with lists of taxa, characters, character states, and character-by-taxon matrices.Annotation of phenotypic data using ontologies and globally unique taxonomic identifiers will allow biologists to integrate phenotypic data from different organisms and studies, leveraging decades of work in systematics and comparative morphology.

  6. Bovine Spongiform Encephalopathy: Production and Inspection

    Science.gov (United States)

    ... brain, skull, eyes trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum) and ...

  7. [Therapeutic prospects for subacute transmissible spongiform encephalopathies].

    Science.gov (United States)

    Seman, M; Adjou, K T

    1999-05-01

    There is currently no effective therapy available for Creutzfeldt-Jakob disease. However, a limited number of drugs such as polyanions, the amyloid-binding dye Congo red, amphotericin B and anthracyclines have been found to delay the appearance of the clinical signs in experimental prion diseases. Today, the most promising agent appears to be less toxic derivative the amphotericin B, MS-8209. Indeed this compound has a wide spectrum of anti-prion activity and constitute the unique molecule able to prolong survival time when treatment is performed at the late stages of infection. This result represents an important progress in therapeutical approaches of prion diseases and justify the development of new polyene antibiotic derivatives.

  8. Phenotypic plasticity and diversity in insects.

    Science.gov (United States)

    Moczek, Armin P

    2010-02-27

    Phenotypic plasticity in general and polyphenic development in particular are thought to play important roles in organismal diversification and evolutionary innovation. Focusing on the evolutionary developmental biology of insects, and specifically that of horned beetles, I explore the avenues by which phenotypic plasticity and polyphenic development have mediated the origins of novelty and diversity. Specifically, I argue that phenotypic plasticity generates novel targets for evolutionary processes to act on, as well as brings about trade-offs during development and evolution, thereby diversifying evolutionary trajectories available to natural populations. Lastly, I examine the notion that in those cases in which phenotypic plasticity is underlain by modularity in gene expression, it results in a fundamental trade-off between degree of plasticity and mutation accumulation. On one hand, this trade-off limits the extent of plasticity that can be accommodated by modularity of gene expression. On the other hand, it causes genes whose expression is specific to rare environments to accumulate greater variation within species, providing the opportunity for faster divergence and diversification between species, compared with genes expressed across environments. Phenotypic plasticity therefore contributes to organismal diversification on a variety of levels of biological organization, thereby facilitating the evolution of novel traits, new species and complex life cycles.

  9. Phenotypes of organ involvement in sarcoidosis.

    Science.gov (United States)

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

    2018-01-01

    Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies. Copyright ©ERS 2018.

  10. Serum Biochemical Phenotypes in the Domestic Dog.

    Directory of Open Access Journals (Sweden)

    Yu-Mei Chang

    Full Text Available The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species.

  11. Overeating phenotypes in overweight and obese children.

    Science.gov (United States)

    Boutelle, Kerri N; Peterson, Carol B; Crosby, Ross D; Rydell, Sarah A; Zucker, Nancy; Harnack, Lisa

    2014-05-01

    The purpose of this study was to identify overeating phenotypes and their correlates in overweight and obese children. One hundred and seventeen treatment-seeking overweight and obese 8-12year-old children and their parents completed the study. Children completed an eating in the absence of hunger (EAH) paradigm, the Eating Disorder Examination interview, and measurements of height and weight. Parents and children completed questionnaires that evaluated satiety responsiveness, food responsiveness, negative affect eating, external eating and eating in the absence of hunger. Latent profile analysis was used to identify heterogeneity in overeating phenotypes in the child participants. Latent classes were then compared on measures of demographics, obesity status and nutritional intake. Three latent classes of overweight and obese children were identified: High Satiety Responsive, High Food Responsive, and Moderate Satiety and Food Responsive. Results indicated that the High Food Responsive group had higher BMI and BMI-Z scores compared to the High Satiety Responsive group. No differences were found among classes in demographics or nutritional intake. This study identified three overeating phenotypes, supporting the heterogeneity of eating patterns associated with overweight and obesity in treatment-seeking children. These finding suggest that these phenotypes can potentially be used to identify high risk groups, inform prevention and intervention targets, and develop specific treatments for these behavioral phenotypes. Copyright © 2014. Published by Elsevier Ltd.

  12. Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen.

    Science.gov (United States)

    Adissu, Hibret A; Estabel, Jeanne; Sunter, David; Tuck, Elizabeth; Hooks, Yvette; Carragher, Damian M; Clarke, Kay; Karp, Natasha A; Newbigging, Susan; Jones, Nora; Morikawa, Lily; White, Jacqueline K; McKerlie, Colin

    2014-05-01

    The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD) we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30) or without (n=20) clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3%) in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14%) presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice.

  13. A New Method to Infer Causal Phenotype Networks Using QTL and Phenotypic Information

    NARCIS (Netherlands)

    Wang, H.; Eeuwijk, van F.

    2014-01-01

    In the context of genetics and breeding research on multiple phenotypic traits, reconstructing the directional or causal structure between phenotypic traits is a prerequisite for quantifying the effects of genetic interventions on the traits. Current approaches mainly exploit the genetic effects at

  14. Plant phenotypic plasticity in a changing climate.

    Science.gov (United States)

    Nicotra, A B; Atkin, O K; Bonser, S P; Davidson, A M; Finnegan, E J; Mathesius, U; Poot, P; Purugganan, M D; Richards, C L; Valladares, F; van Kleunen, M

    2010-12-01

    Climate change is altering the availability of resources and the conditions that are crucial to plant performance. One way plants will respond to these changes is through environmentally induced shifts in phenotype (phenotypic plasticity). Understanding plastic responses is crucial for predicting and managing the effects of climate change on native species as well as crop plants. Here, we provide a toolbox with definitions of key theoretical elements and a synthesis of the current understanding of the molecular and genetic mechanisms underlying plasticity relevant to climate change. By bringing ecological, evolutionary, physiological and molecular perspectives together, we hope to provide clear directives for future research and stimulate cross-disciplinary dialogue on the relevance of phenotypic plasticity under climate change. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Semi-supervised Learning for Phenotyping Tasks.

    Science.gov (United States)

    Dligach, Dmitriy; Miller, Timothy; Savova, Guergana K

    2015-01-01

    Supervised learning is the dominant approach to automatic electronic health records-based phenotyping, but it is expensive due to the cost of manual chart review. Semi-supervised learning takes advantage of both scarce labeled and plentiful unlabeled data. In this work, we study a family of semi-supervised learning algorithms based on Expectation Maximization (EM) in the context of several phenotyping tasks. We first experiment with the basic EM algorithm. When the modeling assumptions are violated, basic EM leads to inaccurate parameter estimation. Augmented EM attenuates this shortcoming by introducing a weighting factor that downweights the unlabeled data. Cross-validation does not always lead to the best setting of the weighting factor and other heuristic methods may be preferred. We show that accurate phenotyping models can be trained with only a few hundred labeled (and a large number of unlabeled) examples, potentially providing substantial savings in the amount of the required manual chart review.

  16. The phenotype of murine wound macrophages.

    Science.gov (United States)

    Daley, Jean M; Brancato, Samielle K; Thomay, Alan A; Reichner, Jonathan S; Albina, Jorge E

    2010-01-01

    The phenotype of wound macrophages has not been studied by direct examination of these cells, yet macrophages recruited to sites of injury are described as alternatively activated macrophages, requiring IL-4 or IL-13 for phenotypic expression. This study characterized wound macrophage phenotype in the PVA sponge wound model in mice. Eighty-five percent of wound macrophages isolated 1 day after injury expressed Gr-1, but only 20% of those isolated at 7 days expressed this antigen. Macrophages from 1-, 3-, and 7-day wounds expressed markers of alternative activation,including mannose receptor, dectin-1, arginase 1,and Ym1, but did not contain iNOS. Day 1 wound macrophages produced more TNF-alpha, more IL-6, and less TGF-beta than Day 7 wound macrophages. Wound macrophages did not produce IL-10. The cytokines considered necessary for alternative activation of macrophages,IL-4 and IL-13, were not detected in the wound environment and were not produced by wound cells.Wound macrophages did not contain PStat6. Wound fluids inhibited IL-13-dependent phosphorylation of Stat6 and contained IL-13Ralpha2, a soluble decoy receptor for IL-13. The phenotype of wound macrophages was not altered in mice lacking IL-4Ralpha, which is required for Stat6-dependent signaling of IL-4 and IL-13.Wound macrophages exhibit a complex phenotype,which includes traits associated with alternative and classical activation and changes as the wound matures.The wound macrophage phenotype does not require IL-4 or IL-13.

  17. Relationship between endophenotype and phenotype in ADHD

    Directory of Open Access Journals (Sweden)

    Buitelaar Jan K

    2008-01-01

    Full Text Available Abstract Background It has been hypothesized that genetic and environmental factors relate to psychiatric disorders through the effect of intermediating, vulnerability traits called endophenotypes. The study had a threefold aim: to examine the predictive validity of an endophenotypic construct for the ADHD diagnosis, to test whether the magnitude of group differences at the endophenotypic and phenotypic level is comparable, and to investigate whether four factors (gender, age, IQ, rater bias have an effect (moderation or mediation on the relation between endophenotype and phenotype. Methods Ten neurocognitive tasks were administered to 143 children with ADHD, 68 non-affected siblings, and 120 control children (first-borns and 132 children with ADHD, 78 non-affected siblings, and 113 controls (second-borns (5 – 19 years. The task measures have been investigated previously for their endophenotypic viability and were combined to one component which was labeled 'the endophenotypic construct': one measure representative of endophenotypic functioning across several domains of functioning. Results The endophenotypic construct classified children with moderate accuracy (about 50% for each of the three groups. Non-affected children differed as much from controls at the endophenotypic as at the phenotypic level, but affected children displayed a more severe phenotype than endophenotype. Although a potentially moderating effect (age and several mediating effects (gender, age, IQ were found affecting the relation between endophenotypic construct and phenotype, none of the effects studied could account for the finding that affected children had a more severe phenotype than endophenotype. Conclusion Endophenotypic functioning is moderately predictive of the ADHD diagnosis, though findings suggest substantial overlap exists between endophenotypic functioning in the groups of affected children, non-affected siblings, and controls. Results suggest other

  18. A new method to infer causal phenotype networks using QTL and phenotypic information.

    Directory of Open Access Journals (Sweden)

    Huange Wang

    Full Text Available In the context of genetics and breeding research on multiple phenotypic traits, reconstructing the directional or causal structure between phenotypic traits is a prerequisite for quantifying the effects of genetic interventions on the traits. Current approaches mainly exploit the genetic effects at quantitative trait loci (QTLs to learn about causal relationships among phenotypic traits. A requirement for using these approaches is that at least one unique QTL has been identified for each trait studied. However, in practice, especially for molecular phenotypes such as metabolites, this prerequisite is often not met due to limited sample sizes, high noise levels and small QTL effects. Here, we present a novel heuristic search algorithm called the QTL+phenotype supervised orientation (QPSO algorithm to infer causal directions for edges in undirected phenotype networks. The two main advantages of this algorithm are: first, it does not require QTLs for each and every trait; second, it takes into account associated phenotypic interactions in addition to detected QTLs when orienting undirected edges between traits. We evaluate and compare the performance of QPSO with another state-of-the-art approach, the QTL-directed dependency graph (QDG algorithm. Simulation results show that our method has broader applicability and leads to more accurate overall orientations. We also illustrate our method with a real-life example involving 24 metabolites and a few major QTLs measured on an association panel of 93 tomato cultivars. Matlab source code implementing the proposed algorithm is freely available upon request.

  19. Haptoglobin Phenotypes and Hypertension in Indigenous Zambians ...

    African Journals Online (AJOL)

    Objectives: The aim of the study was to investigate the association between presence of haptoglobin phenotypes and hypertension in indigenous Zambian patients attending outpatient medical clinic at the University Teaching Hospital in Lusaka, Zambia. Methodology: The study was a descriptive, noninterventional, ...

  20. Hypospadias: risk factor patterns and different phenotypes.

    NARCIS (Netherlands)

    Brouwers, M.M.; Zanden, L.F.M. van der; Gier, R.P.E. de; Barten, E.J.; Zielhuis, G.A.; Feitz, W.F.J.; Roeleveld, N.

    2010-01-01

    OBJECTIVE: To obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case-referent study in which a distinction was made between different phenotypes. PATIENTS AND METHODS: Cases and referents were 305 boys with hypospadias and 629 boys with

  1. Phenotypic and Molecular Characterization of Plasmid- Encoded ...

    African Journals Online (AJOL)

    Purpose: To investigate the distribution of plasmid-encoded extended spectrum beta-lacatamases (ESBLs) in Lahore, Pakistan using different phenotypic and molecular methods. Methods: Escherichia coli and Klebsiella spp were obtained over a period of nineteen months (June 2007 to December 2008). Both were tested ...

  2. phenotype correlation of methylene tetrahydrofolate reductase ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-06-21

    Jun 21, 2014 ... ORIGINAL ARTICLE. Study of genotype–phenotype correlation of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in a sample of Egyptian autistic children. Rabah M. Shawky a,. *, Farida El-baz b. , Tarek M. Kamal c. , Reham M. Elhossiny b. ,. Mona A. Ahmed b. , Ghada H. El Nady d.

  3. Phenotypic characterization of Lactobacillus strains isolated from ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-05

    Oct 5, 2009 ... fermented foods. By considering phenotypic tests, this work aims at iden- tifying new LAB strains isolated from human, animal or vegetal biotopes and to ..... Lactobacillus strains identified based on the pH achieved after 6 and 24 h of culture. Time (h). Cause of the variations. DFa. SSEb. MSc. Fd. Pe. 6.

  4. Phenotypic variation in plants : Roles for epigenetics

    NARCIS (Netherlands)

    Lauss, K.

    2017-01-01

    Besides genetics, also epigenetics can play a role in shaping the characteristics of a plant (phenotype). Epigenetics refers to chemical modifications of DNA and proteins associated with the DNA that can influence gene activity (the ‘epigenome’) and can be passed on through cell divisions and

  5. Constraints on the evolution of phenotypic plasticity

    DEFF Research Database (Denmark)

    Murren, Courtney J; Auld, Josh R.; Callahan, Hilary S

    2015-01-01

    Phenotypic plasticity is ubiquitous and generally regarded as a key mechanism for enabling organisms to survive in the face of environmental change. Because no organism is infinitely or ideally plastic, theory suggests that there must be limits (for example, the lack of ability to produce an opti...

  6. Phenotypic and molecular characterization of Salmonella serotypes ...

    African Journals Online (AJOL)

    The presence of Salmonella and human pathogens in unpasteurized milk remains a public health hazard. The study reported the phenotypic and molecular characterization of Salmonella serotypes in cow raw milk, cheese and traditional yoghurt marketed for man's consumption in Nigeria. Isolation of Salmonella was done ...

  7. Radiofrequency treatment alters cancer cell phenotype

    Science.gov (United States)

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana

    2015-07-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

  8. Phenotypic Characteristics of Zambian patients with Parkinson's ...

    African Journals Online (AJOL)

    Genomic DNA was extracted from peripheral blood leukocytes according to standard procedures from patients and controls, respectively. Results: In total 46 patients for phenotype and 46 controls were matched with patients for age, gender, and area of residence. The mean age of patients at onset of the disease was 53.8 ...

  9. Phenotypic characterisation and molecular polymorphism of ...

    African Journals Online (AJOL)

    The study of the phenotypic characterisation and molecular polymorphism of local chicken populations was carried out in Benin on 326 chickens of the Forest ecological area and 316 of the Savannah ecological area, all were 7 months old at least. The collection of blood for the molecular typing was achieved on 121 ...

  10. Restoration of normal phenotype in cancer cells

    Science.gov (United States)

    Bissell, Mina J.; Weaver, Valerie M.

    1998-01-01

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

  11. Phenotypic characterization of Lactobacillus strains isolated from ...

    African Journals Online (AJOL)

    Thirty three strains of Lactobacillus were isolated from human milk and infant faeces, animal (cow and goat) milks and from plants (Anagalis arvensis and Bromus mango species). The various strains were identified based on phenotypic tests. Amongst them, 12 strains belonged to group 1, which comprised L. acidophilus, ...

  12. Restoration of normal phenotype in cancer cells

    Science.gov (United States)

    Bissell, M.J.; Weaver, V.M.

    1998-12-08

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying {beta}{sub 1} integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive. 14 figs.

  13. Colorectal Cancer "Methylator Phenotype": Fact or Artifact?

    Directory of Open Access Journals (Sweden)

    Charles Anacleto

    2005-04-01

    Full Text Available It has been proposed that human colorectal tumors can be classified into two groups: one in which methylation is rare, and another with methylation of several loci associated with a "CpG island methylated phenotype (CIMP," characterized by preferential proximal location in the colon, but otherwise poorly defined. There is considerable overlap between this putative methylator phenotype and the well-known mutator phenotype associated with microsatellite instability (MSI. We have examined hypermethylation of the promoter region of five genes (DAPK, MGMT, hMLH1, p16INK4a, and p14ARF in 106 primary colorectal cancers. A graph depicting the frequency of methylated loci in the series of tumors showed a continuous, monotonically decreasing distribution quite different from the previously claimed discontinuity. We observed a significant association between the presence of three or more methylated loci and the proximal location of the tumors. However, if we remove from analysis the tumors with hMLH1 methylation or those with MSI, the significance vanishes, suggesting that the association between multiple methylations and proximal location was indirect due to the correlation with MSI. Thus, our data do not support the independent existence of the so-called methylator phenotype and suggest that it rather may represent a statistical artifact caused by confounding of associations.

  14. Cognitive Phenotype of Velocardiofacial Syndrome: A Review

    Science.gov (United States)

    Furniss, Frederick; Biswas, Asit B.; Gumber, Rohit; Singh, Niraj

    2011-01-01

    The behavioural phenotype of velocardiofacial syndrome (VCFS), one of the most common human multiple anomaly syndromes, includes developmental disabilities, frequently including intellectual disability (ID) and high risk of diagnosis of psychotic disorders including schizophrenia. VCFS may offer a model of the relationship between ID and risk of…

  15. The Behavioural Phenotype of Angelman Syndrome

    Science.gov (United States)

    Horsler, K.; Oliver, C.

    2006-01-01

    Background: The purpose of this review is to examine the notion of a behavioural phenotype for Angelman syndrome and identify methodological and conceptual influences on the accepted presentation. Methods: Studies examining the behavioural characteristics associated with Angelman syndrome are reviewed and methodology is described. Results:…

  16. Phenotypic characterisation and molecular polymorphism of ...

    African Journals Online (AJOL)

    PRECIOUS

    2010-01-18

    Jan 18, 2010 ... The study of the phenotypic characterisation and molecular polymorphism of local chicken populations was carried out in Benin on 326 chickens of the Forest ecological area and 316 of the Savannah ecological area, all were 7 months old at least. The collection of blood for the molecular typing was.

  17. Worm Phenotype Ontology: Integrating phenotype data within and beyond the C. elegans community

    Directory of Open Access Journals (Sweden)

    Yook Karen

    2011-01-01

    Full Text Available Abstract Background Caenorhabditis elegans gene-based phenotype information dates back to the 1970's, beginning with Sydney Brenner and the characterization of behavioral and morphological mutant alleles via classical genetics in order to understand nervous system function. Since then C. elegans has become an important genetic model system for the study of basic biological and biomedical principles, largely through the use of phenotype analysis. Because of the growth of C. elegans as a genetically tractable model organism and the development of large-scale analyses, there has been a significant increase of phenotype data that needs to be managed and made accessible to the research community. To do so, a standardized vocabulary is necessary to integrate phenotype data from diverse sources, permit integration with other data types and render the data in a computable form. Results We describe a hierarchically structured, controlled vocabulary of terms that can be used to standardize phenotype descriptions in C. elegans, namely the Worm Phenotype Ontology (WPO. The WPO is currently comprised of 1,880 phenotype terms, 74% of which have been used in the annotation of phenotypes associated with greater than 18,000 C. elegans genes. The scope of the WPO is not exclusively limited to C. elegans biology, rather it is devised to also incorporate phenotypes observed in related nematode species. We have enriched the value of the WPO by integrating it with other ontologies, thereby increasing the accessibility of worm phenotypes to non-nematode biologists. We are actively developing the WPO to continue to fulfill the evolving needs of the scientific community and hope to engage researchers in this crucial endeavor. Conclusions We provide a phenotype ontology (WPO that will help to facilitate data retrieval, and cross-species comparisons within the nematode community. In the larger scientific community, the WPO will permit data integration, and

  18. [Genotype/phenotype correlation in autism: genetic models and phenotypic characterization].

    Science.gov (United States)

    Bonnet-Brilhault, F

    2011-02-01

    Autism spectrum disorders are a class of conditions categorized by communication problems, ritualistic behaviors, and deficits in social behaviors. This class of disorders merges a heterogeneous group of neurodevelopmental disorders regarding some phenotypic and probably physiopathological aspects. Genetic basis is well admitted, however, considering phenotypic and genotypic heterogeneity, correspondences between genotype and phenotype have yet to be established. To better identify such correspondences, genetic models have to be identified and phenotypic markers have to be characterized. Recent insights show that a variety of genetic mechanisms may be involved in autism spectrum disorders, i.e. single gene disorders, copy number variations and polygenic mechanisms. These current genetic models are described. Regarding clinical aspects, several approaches can be used in genetic studies. Nosographical approach, especially with the concept of autism spectrum disorders, merges a large group of disorders with clinical heterogeneity and may fail to identify clear genotype/phenotype correlations. Dimensional approach referred in genetic studies to the notion of "Broad Autism Phenotype" related to a constellation of language, personality, and social-behavioral features present in relatives that mirror the symptom domains of autism, but are much milder in expression. Studies of this broad autism phenotype may provide a potentially important complementary approach for detecting the genes involved in these domains. However, control population used in those studies need to be well characterized too. Identification of endophenotypes seems to offer more promising results. Endophenotypes, which are supposed to be more proximal markers of gene action in the same biological pathway, linking genes and complex clinical symptoms, are thought to be less genetically complex than the broader disease phenotype, indexing a limited aspect of genetic risk for the disorder as a whole. However

  19. Invasion strategies in clonal aquatic plants: Are phenotypic differences caused by phenotypic plasticity or local adaptation?

    DEFF Research Database (Denmark)

    Riis, Tenna; Lambertini, Carla; Olesen, Birgit

    2010-01-01

    populations may facilitate ecotypic differentiation in the future cannot be excluded. These results thus indicate that invasive clonal aquatic plants adapt to new introduced areas by phenotypic plasticity. Inorganic carbon, nitrogen and phosphorous were important in controlling plant size of E. canadensis...... range of habitats in introduced areas by phenotypic plasticity rather than local adaptation. © 2010 The Author. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved....

  20. PhenDisco: phenotype discovery system for the database of genotypes and phenotypes

    OpenAIRE

    Doan, Son; Lin, Ko-Wei; Conway, Mike; Ohno-Machado, Lucila; Hsieh, Alex; Feupe, Stephanie Feudjio; Garland, Asher; Ross, Mindy K; Jiang, Xiaoqian; Farzaneh, Seena; Walker, Rebecca; Alipanah, Neda; Zhang, Jing; Xu, Hua; Kim, Hyeon-Eui

    2013-01-01

    The database of genotypes and phenotypes (dbGaP) developed by the National Center for Biotechnology Information (NCBI) is a resource that contains information on various genome-wide association studies (GWAS) and is currently available via NCBI's dbGaP Entrez interface. The database is an important resource, providing GWAS data that can be used for new exploratory research or cross-study validation by authorized users. However, finding studies relevant to a particular phenotype of interest is...

  1. Advanced phenotyping and phenotype data analysis for the plant growth and development study

    Directory of Open Access Journals (Sweden)

    Md. Matiur eRahaman

    2015-08-01

    Full Text Available Due to increase in the consumption of food, feed, fuel and to ensure global food security for rapidly growing human population, there is need to breed high yielding crops that can adapt to future climate. To solve these global issues, novel approaches are required to provide quantitative phenotypes to elucidate the genetic basis of agriculturally import traits and to screen germplasm with super performance in function under resource-limited environment. At present, plant phenomics has offered and integrated suite technologies for understanding the complete set of phenotypes of plants, towards the progression of the full characteristics of plants with whole sequenced genomes. In this aspect, high-throughput phenotyping platforms have been developed that enables to capture extensive and intensive phenotype data from non-destructive imaging over time. These developments advance our view on plant growth and performance with responses to the changing climate and environment. In this paper, we present a brief review on currently developed high-throughput plant phenotyping infrastructures based on imaging techniques and corresponding principles for phenotype data analysis.

  2. Elucidating the genotype–phenotype map by automatic enumeration and analysis of the phenotypic repertoire

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2015-01-01

    Background: The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. Methods: The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Results: Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Conclusions: Starting with a system’s relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy. PMID:26998346

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

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

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

  4. Automated multidimensional phenotypic profiling using large public microarray repositories

    Science.gov (United States)

    Xu, Min; Li, Wenyuan; James, Gareth M.; Mehan, Michael R.; Zhou, Xianghong Jasmine

    2009-01-01

    Phenotypes are complex, and difficult to quantify in a high-throughput fashion. The lack of comprehensive phenotype data can prevent or distort genotype–phenotype mapping. Here, we describe “PhenoProfiler,” a computational method that enables in silico phenotype profiling. Drawing on the principle that similar gene expression patterns are likely to be associated with similar phenotype patterns, PhenoProfiler supplements the missing quantitative phenotype information for a given microarray dataset based on other well-characterized microarray datasets. We applied our method to 587 human microarray datasets covering >14,000 samples, and confirmed that the predicted phenotype profiles are highly consistent with true phenotype descriptions. PhenoProfiler offers several unique capabilities: (i) automated, multidimensional phenotype profiling, facilitating the analysis and treatment design of complex diseases; (ii) the extrapolation of phenotype profiles beyond provided classes; and (iii) the detection of confounding phenotype factors that could otherwise bias biological inferences. Finally, because no direct comparisons are made between gene expression values from different datasets, the method can use the entire body of cross-platform microarray data. This work has produced a compendium of phenotype profiles for the National Center for Biotechnology Information GEO datasets, which can facilitate an unbiased understanding of the transcriptome-phenome mapping. The continued accumulation of microarray data will further increase the power of PhenoProfiler, by increasing the variety and the quality of phenotypes to be profiled. PMID:19590007

  5. Phenotypic signatures arising from unbalanced bacterial growth.

    Science.gov (United States)

    Tan, Cheemeng; Smith, Robert Phillip; Tsai, Ming-Chi; Schwartz, Russell; You, Lingchong

    2014-08-01

    Fluctuations in the growth rate of a bacterial culture during unbalanced growth are generally considered undesirable in quantitative studies of bacterial physiology. Under well-controlled experimental conditions, however, these fluctuations are not random but instead reflect the interplay between intra-cellular networks underlying bacterial growth and the growth environment. Therefore, these fluctuations could be considered quantitative phenotypes of the bacteria under a specific growth condition. Here, we present a method to identify "phenotypic signatures" by time-frequency analysis of unbalanced growth curves measured with high temporal resolution. The signatures are then applied to differentiate amongst different bacterial strains or the same strain under different growth conditions, and to identify the essential architecture of the gene network underlying the observed growth dynamics. Our method has implications for both basic understanding of bacterial physiology and for the classification of bacterial strains.

  6. New genes as drivers of phenotypic evolution.

    Science.gov (United States)

    Chen, Sidi; Krinsky, Benjamin H; Long, Manyuan

    2013-09-01

    During the course of evolution, genomes acquire novel genetic elements as sources of functional and phenotypic diversity, including new genes that originated in recent evolution. In the past few years, substantial progress has been made in understanding the evolution and phenotypic effects of new genes. In particular, an emerging picture is that new genes, despite being present in the genomes of only a subset of species, can rapidly evolve indispensable roles in fundamental biological processes, including development, reproduction, brain function and behaviour. The molecular underpinnings of how new genes can develop these roles are starting to be characterized. These recent discoveries yield fresh insights into our broad understanding of biological diversity at refined resolution.

  7. Phenotyping animal models of diabetic neuropathy

    DEFF Research Database (Denmark)

    Biessels, G J; Bril, V; Calcutt, N A

    2014-01-01

    of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted......NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy....... The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current...

  8. New genes as drivers of phenotypic evolution

    Science.gov (United States)

    Chen, Sidi; Krinsky, Benjamin H.; Long, Manyuan

    2014-01-01

    During the course of evolution, genomes acquire novel genetic elements as sources of functional and phenotypic diversity, including new genes that originated in recent evolution. In the past few years, substantial progress has been made in understanding the evolution and phenotypic effects of new genes. In particular, an emerging picture is that new genes, despite being present in the genomes of only a subset of species, can rapidly evolve indispensable roles in fundamental biological processes, including development, reproduction, brain function and behaviour. The molecular underpinnings of how new genes can develop these roles are starting to be characterized. These recent discoveries yield fresh insights into our broad understanding of biological diversity at refined resolution. PMID:23949544

  9. Multiple Phenotypic Changes Define Neutrophil Priming

    Science.gov (United States)

    Miralda, Irina; Uriarte, Silvia M.; McLeish, Kenneth R.

    2017-01-01

    Exposure to pro-inflammatory cytokines, chemokines, mitochondrial contents, and bacterial and viral products induces neutrophils to transition from a basal state into a primed one, which is currently defined as an enhanced response to activating stimuli. Although, typically associated with enhanced generation of reactive oxygen species (ROS) by the NADPH oxidase, primed neutrophils show enhanced responsiveness of exocytosis, NET formation, and chemotaxis. Phenotypic changes associated with priming also include activation of a subset of functions, including adhesion, transcription, metabolism, and rate of apoptosis. This review summarizes the breadth of phenotypic changes associated with priming and reviews current knowledge of the molecular mechanisms behind those changes. We conclude that the current definition of priming is too restrictive. Priming represents a combination of enhanced responsiveness and activated functions that regulate both adaptive and innate immune responses. PMID:28611952

  10. Multiple Phenotypic Changes Define Neutrophil Priming

    Directory of Open Access Journals (Sweden)

    Irina Miralda

    2017-05-01

    Full Text Available Exposure to pro-inflammatory cytokines, chemokines, mitochondrial contents, and bacterial and viral products induces neutrophils to transition from a basal state into a primed one, which is currently defined as an enhanced response to activating stimuli. Although, typically associated with enhanced generation of reactive oxygen species (ROS by the NADPH oxidase, primed neutrophils show enhanced responsiveness of exocytosis, NET formation, and chemotaxis. Phenotypic changes associated with priming also include activation of a subset of functions, including adhesion, transcription, metabolism, and rate of apoptosis. This review summarizes the breadth of phenotypic changes associated with priming and reviews current knowledge of the molecular mechanisms behind those changes. We conclude that the current definition of priming is too restrictive. Priming represents a combination of enhanced responsiveness and activated functions that regulate both adaptive and innate immune responses.

  11. Multiple Phenotypic Changes Define Neutrophil Priming.

    Science.gov (United States)

    Miralda, Irina; Uriarte, Silvia M; McLeish, Kenneth R

    2017-01-01

    Exposure to pro-inflammatory cytokines, chemokines, mitochondrial contents, and bacterial and viral products induces neutrophils to transition from a basal state into a primed one, which is currently defined as an enhanced response to activating stimuli. Although, typically associated with enhanced generation of reactive oxygen species (ROS) by the NADPH oxidase, primed neutrophils show enhanced responsiveness of exocytosis, NET formation, and chemotaxis. Phenotypic changes associated with priming also include activation of a subset of functions, including adhesion, transcription, metabolism, and rate of apoptosis. This review summarizes the breadth of phenotypic changes associated with priming and reviews current knowledge of the molecular mechanisms behind those changes. We conclude that the current definition of priming is too restrictive. Priming represents a combination of enhanced responsiveness and activated functions that regulate both adaptive and innate immune responses.

  12. Diagnosis, assessment, and phenotyping of COPD

    DEFF Research Database (Denmark)

    Lange, Peter; Halpin, David M; O'Donnell, Denis E

    2016-01-01

    COPD is now widely recognized as a complex heterogeneous syndrome, having both pulmonary and extrapulmonary features. In clinical practice, the diagnosis of COPD is based on the presence of chronic airflow limitation, as assessed by post-bronchodilator spirometry. The severity of the airflow...... limitation, as measured by percent predicted FEV1, provides important information to the physician to enable optimization of management. However, in order to accurately assess the complexity of COPD, there need to be other measures made beyond FEV1. At present, there is a lack of reliable and simple blood...... biomarkers to confirm and further assess the diagnosis of COPD. However, it is possible to identify patients who display different phenotypic characteristics of COPD that relate to clinically relevant outcomes. Currently, validated phenotypes of COPD include alpha-1 antitrypsin deficiency, and "frequent...

  13. Phenotype development in TgHD minipigs

    Czech Academy of Sciences Publication Activity Database

    Ellederová, Zdeňka; Vidinská, Daniela; Mačáková, Monika; Kučerová, S.; Bohuslavová, Božena; Sedláčková, M.; Lišková, Irena; Valeková, Ivona; Baxa, Monika; Ardan, Taras; Juhás, Štefan; Motlík, Jan

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 11-11 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : phenotype * minipig model of Huntington´s disease * reproductive failure Subject RIV: EB - Genetics ; Molecular Biology

  14. Molecular and phenotypic characterization of anamorphic fungi

    OpenAIRE

    Madrid Lorca, Hugo

    2011-01-01

    Anamorphic fungi (those reproducing asexually) are a big part of kingdom Fungi. Most of them occur as saprobes in nature, but numerous species are pathogenic to plants and animals including man. With the aim of contributing to the knowledge of the diversity and distribution of anamorphic fungi, we performed a phenotypic and molecular characterization of environmental and clinical isolates of these fungi. Based on a polyphasic taxonomy approach which included morphology, physiology and DNA seq...

  15. Connectomic intermediate phenotypes for psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Alex eFornito

    2012-04-01

    Full Text Available Psychiatric disorders are phenotypically heterogeneous entities with a complex genetic basis. To mitigate this complexity, many investigators study so-called intermediate phenotypes that putatively provide a more direct index of the physiological effects of candidate genetic risk variants than overt psychiatric syndromes. Magnetic resonance imaging (MRI is a particularly popular technique for measuring such phenotypes because it allows interrogation of diverse aspects of brain structure and function in vivo. Much of this work however, has focused on relatively simple measures that quantify variations in the physiology or tissue integrity of specific brain regions in isolation, contradicting an emerging consensus that most major psychiatric disorders do not arise from isolated dysfunction in one or a few brain regions, but rather from disturbed interactions within and between distributed neural circuits; i.e., they are disorders of brain connectivity. The recent proliferation of new MRI techniques for comprehensively mapping the entire connectivity architecture of the brain, termed the human connectome, has provided a rich repertoire of tools for understanding how genetic variants implicated in mental disorder impact distinct neural circuits. In this article, we review research using these connectomic techniques to understand how genetic variation influences the connectivity and topology of human brain networks. We highlight recent evidence from twin and imaging genetics studies suggesting that the penetrance of candidate risk variants for mental illness, such as those in SLC6A4, MAOA, ZNF804A and APOE, may be higher for intermediate phenotypes characterised at the level of distributed neural systems than at the level of spatially localised brain regions. The findings indicate that imaging connectomics provides a powerful framework for understanding how genetic risk for psychiatric disease is expressed through altered structure and function of

  16. Delineating the GRIN1 phenotypic spectrum

    DEFF Research Database (Denmark)

    Lemke, Johannes R; Geider, Kirsten; Helbig, Katherine L

    2016-01-01

    with a dominant-negative effect. In addition, we describe 2 homozygous GRIN1 mutations (1 missense, 1 truncation), each segregating with severe neurodevelopmental phenotypes in consanguineous families. CONCLUSIONS: De novo GRIN1 mutations are associated with severe intellectual disability with cortical visual......, severe intellectual disability with absent speech, muscular hypotonia, hyperkinetic movement disorder, oculogyric crises, cortical blindness, generalized cerebral atrophy, and epilepsy. Mutations cluster within transmembrane segments and result in loss of channel function of varying severity...

  17. Phenotyping Cowpeas for Adaptation to Drought

    OpenAIRE

    Hall, Anthony E.

    2012-01-01

    Methods for phenotyping cowpeas for adaptation to drought are reviewed. Key factors involve achieving optimal time of flowering and cycle length, and appropriate morphology for different types of cultivars as they relate to their utilization for dry grain, hay, and fresh pea production. Strong resistance to vegetative-stage drought is available and should be incorporated. The extreme ability of extra-early erect cowpea cultivars to escape terminal drought should be exploited in zones with ver...

  18. Associations between phenotypes of preeclampsia and thrombophilia.

    Science.gov (United States)

    Berks, Durk; Duvekot, Johannes J; Basalan, Hillal; De Maat, Moniek P M; Steegers, Eric A P; Visser, Willy

    2015-11-01

    Preeclampsia complicates 2-8% of all pregnancies. Studies on the association of preeclampsia with thrombophilia are conflicting. Clinical heterogeneity of the disease may be one of the explanations. The present study addresses the question whether different phenotypes of preeclampsia are associated with thrombophilia factors. Study design We planned a retrospective cohort study. From 1985 until 2010 women with preeclampsia were offered postpartum screening for the following thrombophilia factors: anti-phospholipid antibodies, APC-resistance, protein C deficiency and protein S deficiency, hyperhomocysteineamia, factor V Leiden and Prothrombin gene mutation. Hospital records were used to obtain information on phenotypes of the preeclampsia and placental histology. We identified 844 women with singleton pregnancies who were screened for thrombophilia factors. HELLP complicated 49% of pregnancies; Fetal growth restriction complicated 61% of pregnancies. Early delivery (preeclampsia was associated with protein S deficiency (p=0.01). Fetal growth restriction was associated with anti-phospholipid antibodies (ppreeclampsia was associated with anti-phospholipid antibodies (p=0.01). Extensive placental infarction (>10%) was associated with anti-phospholipid antibodies (ppreeclampsia, especially if complicated by fetal growth restriction, are associated with anti-phospholipid antibodies. Other phenotypes of preeclampsia, especially HELLP syndrome, were not associated with thrombophilia. We advise only to test for anti-phospholipid antibodies after early onset preeclampsia, especially if complicated by fetal growth restriction. We suggest enough evidence is presented to justify no further studies are needed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Phenotypic variability of Cat-Eye syndrome.

    Science.gov (United States)

    Berends, M J; Tan-Sindhunata, G; Leegte, B; van Essen, A J

    2001-01-01

    Cat-Eye syndrome (CES) is a disorder with a variable pattern of multiple congenital anomalies of which coloboma of the iris and anal atresia are the best known. CES is cytogenetically characterised by the presence of an extra bisatellited marker chromosome, which represents an inverted dicentric duplication of a part of chromosome 22 (inv dup(22)). We report on three CES-patients who carry an inv dup(22) diagnosed with FISH studies. They show remarkable phenotypic variability. The cause of this variability is unknown. Furthermore, we review clinical features of 71 reported patients. Only 41% of the CES-patients have the combination of iris coloboma, anal anomalies and pre-auricular anomalies. Therefore, almost 60% of the CES-patients are hard to recognize by their phenotype alone. Mild to moderate mental retardation was found in 32% (16/50) of the cases. Mental retardation occurs more frequently in male CES-patients. There is no apparent phenotypic difference between mentally retarded and mentally normal CES-patients.

  20. Cluster analysis in phenotyping a Portuguese population.

    Science.gov (United States)

    Loureiro, C C; Sa-Couto, P; Todo-Bom, A; Bousquet, J

    2015-09-03

    Unbiased cluster analysis using clinical parameters has identified asthma phenotypes. Adding inflammatory biomarkers to this analysis provided a better insight into the disease mechanisms. This approach has not yet been applied to asthmatic Portuguese patients. To identify phenotypes of asthma using cluster analysis in a Portuguese asthmatic population treated in secondary medical care. Consecutive patients with asthma were recruited from the outpatient clinic. Patients were optimally treated according to GINA guidelines and enrolled in the study. Procedures were performed according to a standard evaluation of asthma. Phenotypes were identified by cluster analysis using Ward's clustering method. Of the 72 patients enrolled, 57 had full data and were included for cluster analysis. Distribution was set in 5 clusters described as follows: cluster (C) 1, early onset mild allergic asthma; C2, moderate allergic asthma, with long evolution, female prevalence and mixed inflammation; C3, allergic brittle asthma in young females with early disease onset and no evidence of inflammation; C4, severe asthma in obese females with late disease onset, highly symptomatic despite low Th2 inflammation; C5, severe asthma with chronic airflow obstruction, late disease onset and eosinophilic inflammation. In our study population, the identified clusters were mainly coincident with other larger-scale cluster analysis. Variables such as age at disease onset, obesity, lung function, FeNO (Th2 biomarker) and disease severity were important for cluster distinction. Copyright © 2015. Published by Elsevier España, S.L.U.

  1. Aberrant phenotypes in peripheral T cell lymphomas.

    Science.gov (United States)

    Hastrup, N; Ralfkiaer, E; Pallesen, G

    1989-01-01

    Seventy six peripheral T cell lymphomas were examined immunohistologically to test their reactivity with a panel of monoclonal antibodies against 11 T cell associated antigens (CD1-8, CD27, UCHL1, and the T cell antigen receptor). Sixty two (82%) lymphomas showed aberrant phenotypes, and four main categories were distinguished as follows: (i) lack of one or several pan-T cell antigens (49, 64% of the cases); (ii) loss of both the CD4 and CD8 antigens (11, 15% of the cases); (iii) coexpression of the CD4 and CD8 antigens (13, 17% of the cases); and (iv) expression of the CD1 antigen (eight, 11% of the cases). No correlation was seen between the occurrence of aberrant phenotypes and the histological subtype. It is concluded that the demonstration of an aberrant phenotype is a valuable supplement to histological assessment in the diagnosis of peripheral T cell lymphomas. It is recommended that the panel of monoclonal antibodies against T cell differentiation antigens should be fairly large, as apparently any antigen may be lost in the process of malignant transformation. Images Figure PMID:2469701

  2. Dissecting phenotypic variation among AIS patients

    International Nuclear Information System (INIS)

    Wang Minghua; Wang Jiucun; Zhang Zhen; Zhao Zhimin; Zhang Rongmei; Hu Xiaohua; Tan Tao; Luo Shijing; Luo Zewei

    2005-01-01

    We have created genital skin fibroblast cell lines directly from three patients in a Chinese family affected by androgen insensitivity syndrome (AIS). All patients in the family share an identical AR Arg 840 Cys mutant but show different disease phenotypes. By using the cell lines, we find that the mutation has not influenced a normal androgen-binding capacity at 37 deg C but has reduced the affinity for androgens and may cause thermolability of the androgen-receptor complex. The impaired nuclear trafficking of the androgen receptor in the cell lines is highly correlated with the severity of donors' disease phenotype. The transactivity of the mutant is substantially weakened and the extent of the reduced transactivity reflects severity of the donors' disease symptom. Our data reveal that although etiology of AIS is monogenic and the mutant may alter the major biological functions of its wild allele, the function of the mutant AR can also be influenced by the different genetic backgrounds and thus explains the divergent disease phenotypes

  3. The phenotypic spectrum of congenital Zika syndrome.

    Science.gov (United States)

    Del Campo, Miguel; Feitosa, Ian M L; Ribeiro, Erlane M; Horovitz, Dafne D G; Pessoa, André L S; França, Giovanny V A; García-Alix, Alfredo; Doriqui, Maria J R; Wanderley, Hector Y C; Sanseverino, Maria V T; Neri, João I C F; Pina-Neto, João M; Santos, Emerson S; Verçosa, Islane; Cernach, Mirlene C S P; Medeiros, Paula F V; Kerbage, Saile C; Silva, André A; van der Linden, Vanessa; Martelli, Celina M T; Cordeiro, Marli T; Dhalia, Rafael; Vianna, Fernanda S L; Victora, Cesar G; Cavalcanti, Denise P; Schuler-Faccini, Lavinia

    2017-04-01

    In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV. © 2017 Wiley Periodicals, Inc.

  4. MPHASYS: a mouse phenotype analysis system

    Directory of Open Access Journals (Sweden)

    Mian I

    2007-06-01

    Full Text Available Abstract Background Systematic, high-throughput studies of mouse phenotypes have been hampered by the inability to analyze individual animal data from a multitude of sources in an integrated manner. Studies generally make comparisons at the level of genotype or treatment thereby excluding associations that may be subtle or involve compound phenotypes. Additionally, the lack of integrated, standardized ontologies and methodologies for data exchange has inhibited scientific collaboration and discovery. Results Here we introduce a Mouse Phenotype Analysis System (MPHASYS, a platform for integrating data generated by studies of mouse models of human biology and disease such as aging and cancer. This computational platform is designed to provide a standardized methodology for working with animal data; a framework for data entry, analysis and sharing; and ontologies and methodologies for ensuring accurate data capture. We describe the tools that currently comprise MPHASYS, primarily ones related to mouse pathology, and outline its use in a study of individual animal-specific patterns of multiple pathology in mice harboring a specific germline mutation in the DNA repair and transcription-specific gene Xpd. Conclusion MPHASYS is a system for analyzing multiple data types from individual animals. It provides a framework for developing data analysis applications, and tools for collecting and distributing high-quality data. The software is platform independent and freely available under an open-source license 1.

  5. Genetic variants influencing phenotypic variance heterogeneity.

    Science.gov (United States)

    Ek, Weronica E; Rask-Andersen, Mathias; Karlsson, Torgny; Enroth, Stefan; Gyllensten, Ulf; Johansson, Åsa

    2018-03-01

    Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene × gene or gene × environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.

  6. Syndromic (phenotypic diarrhea in early infancy

    Directory of Open Access Journals (Sweden)

    Bodemer Christine

    2008-02-01

    Full Text Available Abstract Syndromic diarrhea (SD, also known as phenotypic diarrhea (PD or tricho-hepato-enteric syndrome (THE, is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN. To date, no epidemiological data are available. The estimated prevalence is approximately 1/300,000–400,000 live births in Western Europe. Ethnic origin does not appear to be associated with SD. Infants are born small for gestational age and present with facial dysmorphism including prominent forehead and cheeks, broad nasal root and hypertelorism. Hairs are woolly, easily removed and poorly pigmented. Severe and persistent diarrhea starts within the first 6 months of life (≤ 1 month in most cases and is accompanied by severe malabsorption leading to early and relentless protein energy malnutrition with failure to thrive. Liver disease affects about half of patients with extensive fibrosis or cirrhosis. There is currently no specific biochemical profile, though a functional T-cell immune deficiency with defective antibody production was reported. Microscopic analysis of the hair show twisted hair (pili torti, aniso- and poilkilotrichosis, and trichorrhexis nodosa. Histopathological analysis of small intestine biopsy shows non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria, and no specific histological abnormalities involving the epithelium. The etiology remains unknown. The frequent association of the disorder with parental consanguinity and/or affected siblings suggests a genetic origin with an autosomal recessive mode of transmission. Early management consists of total PN. Some infants have a rather milder phenotype with partial PN dependency or require only enteral feeding. Prognosis of this syndrome is poor, but most patients now survive, and about half of the patients may be weaned from PN at adolescence, but experience failure to thrive and final short stature. Disease name

  7. MRI phenotypes of localized intravascular coagulopathy in venous malformations

    International Nuclear Information System (INIS)

    Koo, Kevin S.H.; Dowd, Christopher F.; Hess, Christopher P.; Mathes, Erin F.; Frieden, Ilona J.; Rosbe, Kristina W.; Hoffman, William Y.

    2015-01-01

    The incidence of localized intravascular coagulopathy (LIC) in venous malformations varies with lesion size and location, as well as the presence of palpable phleboliths. The development of LIC can cause pain and hemorrhage and can progress to disseminated intravascular coagulopathy (DIC) and thromboembolic disease resulting in death in some cases. Early recognition of LIC can relieve symptoms and prevent progression to life-threatening complications. The aim of this work was to identify MRI features of venous malformation associated with LIC. We hypothesized that venous malformations with larger capacitance, slower flow and less physiological compression (greater stasis) were more likely to be associated with LIC. In this HIPAA-compliant and IRB-approved study, we retrospectively reviewed clinical records and MRI for consecutive patients undergoing evaluation of venous malformations at our multidisciplinary Birthmarks and Vascular Anomalies Center between 2003 and 2013. Inclusion required consensus diagnosis of venous malformation and availability of laboratory data and MRI; patients on anticoagulation or those previously undergoing surgical or endovascular treatment were excluded. LIC was diagnosed when D-dimer exceeded 1,000 ng/mL and/or fibrinogen was less than 200 mg/dL. Two board-certified radiologists assessed the following MRI features for each lesion: morphology (spongiform vs. phlebectatic), presence of phleboliths, size, location (truncal vs. extremity), and tissue type(s) involved (subcutis, muscle, bone and viscera). Univariate logistic regression analyses were used to test associations between LIC and MRI findings, and stepwise regression was applied to assess the significance of the individual imaging predictors. Seventy patients, 37 with LIC, met inclusion criteria during the 10-year study period (age: 14.5 +/- 13.6 years [mean +/- standard deviation]; 30 male, 40 female). Both elevated D-dimer and low fibrinogen were associated with the presence of

  8. MRI phenotypes of localized intravascular coagulopathy in venous malformations

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Kevin S.H. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Dowd, Christopher F.; Hess, Christopher P. [University of California, San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Mathes, Erin F.; Frieden, Ilona J. [University of California, San Francisco, Department of Dermatology, San Francisco, CA (United States); Rosbe, Kristina W. [University of California, San Francisco, Department of Otolaryngology, San Francisco, CA (United States); Hoffman, William Y. [University of California, San Francisco, Department of Surgery, San Francisco, CA (United States)

    2015-10-15

    The incidence of localized intravascular coagulopathy (LIC) in venous malformations varies with lesion size and location, as well as the presence of palpable phleboliths. The development of LIC can cause pain and hemorrhage and can progress to disseminated intravascular coagulopathy (DIC) and thromboembolic disease resulting in death in some cases. Early recognition of LIC can relieve symptoms and prevent progression to life-threatening complications. The aim of this work was to identify MRI features of venous malformation associated with LIC. We hypothesized that venous malformations with larger capacitance, slower flow and less physiological compression (greater stasis) were more likely to be associated with LIC. In this HIPAA-compliant and IRB-approved study, we retrospectively reviewed clinical records and MRI for consecutive patients undergoing evaluation of venous malformations at our multidisciplinary Birthmarks and Vascular Anomalies Center between 2003 and 2013. Inclusion required consensus diagnosis of venous malformation and availability of laboratory data and MRI; patients on anticoagulation or those previously undergoing surgical or endovascular treatment were excluded. LIC was diagnosed when D-dimer exceeded 1,000 ng/mL and/or fibrinogen was less than 200 mg/dL. Two board-certified radiologists assessed the following MRI features for each lesion: morphology (spongiform vs. phlebectatic), presence of phleboliths, size, location (truncal vs. extremity), and tissue type(s) involved (subcutis, muscle, bone and viscera). Univariate logistic regression analyses were used to test associations between LIC and MRI findings, and stepwise regression was applied to assess the significance of the individual imaging predictors. Seventy patients, 37 with LIC, met inclusion criteria during the 10-year study period (age: 14.5 +/- 13.6 years [mean +/- standard deviation]; 30 male, 40 female). Both elevated D-dimer and low fibrinogen were associated with the presence of

  9. Social Cognition, Social Skill, and the Broad Autism Phenotype

    Science.gov (United States)

    Sasson, Noah J.; Nowlin, Rachel B.; Pinkham, Amy E.

    2013-01-01

    Social-cognitive deficits differentiate parents with the "broad autism phenotype" from non-broad autism phenotype parents more robustly than other neuropsychological features of autism, suggesting that this domain may be particularly informative for identifying genetic and brain processes associated with the phenotype. The current study…

  10. Is the turbidimetric immunoassay of haptoglobin phenotype-dependent?

    NARCIS (Netherlands)

    Rijn, H.J.M. van; Wilt, W. van der; Stroes, J.W.; Schrijver, J.

    Comparison of the turbidimetric immunoassay of haptoglobin with a reference method (the RID technique with appropriate correction for phenotype) clearly showed the turbidimetric assay to be phenotype-dependent. Correction factors for the three main phenotypes were calculated and reference values

  11. Chronic obstructive pulmonary disease phenotypes: the future of COPD

    DEFF Research Database (Denmark)

    Han, MeiLan K; Agusti, Alvar; Calverley, Peter M

    2010-01-01

    prognostic or therapeutic characteristics, but significant variation and confusion surrounds use of the term "phenotype" in COPD. Phenotype classically refers to any observable characteristic of an organism, and up until now, multiple disease characteristics have been termed COPD phenotypes. We, however...... our understanding and management of the complexity implicit to this disease....

  12. The other side of phenotypic plasticity: a developmental system that ...

    Indian Academy of Sciences (India)

    Prakash

    On the one hand, we would like to understand how the environment induces phenotypic changes (the study of phenotypic plasticity). On the other hand, we may ask how a development system maintains a stable and precise phenotypic output despite the .... for egg laying and mating with males. Defects in this reproductive ...

  13. New approach to phenotypic variability and karyotype-phenotype correlation in Turner syndrome.

    Science.gov (United States)

    Miguel-Neto, Jamil; Carvalho, Annelise B; Marques-de-Faria, Antonia Paula; Guerra-Júnior, Gil; Maciel-Guerra, Andréa T

    2016-04-01

    Phenotypic variability of Turner syndrome (TS) challenges clinicians, and undiagnosed mosaicism may lead to conflicting results of karyotype-phenotype correlations. This study assessed the extent of phenotypic variability and investigated the presence of karyotype-phenotype correlations. The sample comprised 80 patients with ≥50 cells analyzed in karyotype. Twenty were 45,X/46,X,+mar; three groups of 20 patients were constructed by matching those girls with the nearest-aged patient with 45,X, 45,X/46,XX and 45,X/46,X,i(Xq) or 46,X,i(Xq) karyotype. Data were obtained on height z-score, dysmorphic features, echocardiogram and urinary system sonography. The number of dysmorphic features ranged from one to 16 and was not correlated to age at diagnosis or height. The groups did not differ in height, number of dysmorphic features, cardiovascular and urinary system anomalies and frequency of any specific feature, except for short fourth metacarpal. Wide phenotypical variability of TS may be objectively described and its clinical picture is not correlated to karyotype.

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

    Directory of Open Access Journals (Sweden)

    Eva Y. G. De Vilder

    2017-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

    Grosskinsky, D. K.; Svensgaard, J.; Christensen, S.; Roitsch, Thomas

    2015-01-01

    Roč. 66, č. 18 (2015), s. 5429-5440 ISSN 0022-0957 Institutional support: RVO:67179843 Keywords : External phenotype * genome–environment–management interaction * genome–phenome map * internal phenotype * phenomics * physiological traits * physiology * plant phenotyping * predictors Subject RIV: EH - Ecology, Behaviour Impact factor: 5.677, year: 2015

  16. Invasion strategies in clonal aquatic plants: are phenotypic differences caused by phenotypic plasticity or local adaptation?

    Science.gov (United States)

    Riis, Tenna; Lambertini, Carla; Olesen, Birgit; Clayton, John S.; Brix, Hans; Sorrell, Brian K.

    2010-01-01

    Background and Aims The successful spread of invasive plants in new environments is often linked to multiple introductions and a diverse gene pool that facilitates local adaptation to variable environmental conditions. For clonal plants, however, phenotypic plasticity may be equally important. Here the primary adaptive strategy in three non-native, clonally reproducing macrophytes (Egeria densa, Elodea canadensis and Lagarosiphon major) in New Zealand freshwaters were examined and an attempt was made to link observed differences in plant morphology to local variation in habitat conditions. Methods Field populations with a large phenotypic variety were sampled in a range of lakes and streams with different chemical and physical properties. The phenotypic plasticity of the species before and after cultivation was studied in a common garden growth experiment, and the genetic diversity of these same populations was also quantified. Key Results For all three species, greater variation in plant characteristics was found before they were grown in standardized conditions. Moreover, field populations displayed remarkably little genetic variation and there was little interaction between habitat conditions and plant morphological characteristics. Conclusions The results indicate that at the current stage of spread into New Zealand, the primary adaptive strategy of these three invasive macrophytes is phenotypic plasticity. However, while limited, the possibility that genetic diversity between populations may facilitate ecotypic differentiation in the future cannot be excluded. These results thus indicate that invasive clonal aquatic plants adapt to new introduced areas by phenotypic plasticity. Inorganic carbon, nitrogen and phosphorous were important in controlling plant size of E. canadensis and L. major, but no other relationships between plant characteristics and habitat conditions were apparent. This implies that within-species differences in plant size can be explained

  17. Weight in Parkinson's Disease: Phenotypical Significance.

    Science.gov (United States)

    Sharma, Jagdish C; Lewis, Anna

    2017-01-01

    Body weight in Parkinson's disease (PD) is a significant nonmotor feature. Weight homeostasis is a complex physiological process and gets deranged in PD patients leading to changes in weight. While both the low and high body weight have been reported as risk factors for PD, the majority of PD patients have a lower weight and a subset of patients lose weight during the course of the disease, while a small proportion gain weight. A number of clinical parameters such as older age, impaired cognition, severity of disease, and an imbalance of food intake determined by satiety and hunger hormones have been reported to be associated with but not the cause of weight change. Low body weight and weight loss have a negative impact on disease severity, dyskinesia quality of life, and mortality indicative of disease progression. An early assessment of olfactory impairment seems to identify patients at risk of weight loss, the patients with more severe olfactory loss-anosmic group, lose weight as compared to the patients with some preservation of olfaction, the hyposmic group. Higher levodopa dose per kilogram body weight increases the risk of dyskinesia, higher body weight seems to be protective against this complication. The identification of PD patients according to the nonmotor phenotype of "Park-olfaction-weight-phenotype" and the "olfaction-weight-dyskinesia" triad should help to develop strategies to prevent weight reduction and improve general health and complications of PD patients. The phenotype seems to reflect a differential prodromal pathology and influence clinical disease. Higher body weight patients would benefit from life style changes to achieve a healthy profile. Weight monitoring and weight orientated approach to management of PD patients should help to improve their outcome. Body weight change might be a surrogate to disease progression and may be used to investigate neuroprotection strategies. © 2017 Elsevier Inc. All rights reserved.

  18. The phenotypic plasticity of developmental modules

    Directory of Open Access Journals (Sweden)

    Aabha I. Sharma

    2016-08-01

    Full Text Available Abstract Background Organisms develop and evolve in a modular fashion, but how individual modules interact with the environment remains poorly understood. Phenotypically plastic traits are often under selection, and studies are needed to address how traits respond to the environment in a modular fashion. In this study, tissue-specific plasticity of melanic spots was examined in the large milkweed bug, Oncopeltus fasciatus. Results Although the size of the abdominal melanic bands varied according to rearing temperatures, wing melanic bands were more robust. To explore the regulation of abdominal pigmentation plasticity, candidate genes involved in abdominal melanic spot patterning and biosynthesis of melanin were analyzed. While the knockdown of dopa decarboxylase (Ddc led to lighter pigmentation in both the wings and the abdomen, the shape of the melanic elements remained unaffected. Although the knockdown of Abdominal-B (Abd-B partially phenocopied the low-temperature phenotype, the abdominal bands were still sensitive to temperature shifts. These observations suggest that regulators downstream of Abd-B but upstream of DDC are responsible for the temperature response of the abdomen. Ablation of wings led to the regeneration of a smaller wing with reduced melanic bands that were shifted proximally. In addition, the knockdown of the Wnt signaling nuclear effector genes, armadillo 1 and armadillo 2, altered both the melanic bands and the wing shape. Thus, the pleiotropic effects of Wnt signaling may constrain the amount of plasticity in wing melanic bands. Conclusions We propose that when traits are regulated by distinct pre-patterning mechanisms, they can respond to the environment in a modular fashion, whereas when the environment impacts developmental regulators that are shared between different modules, phenotypic plasticity can manifest as a developmentally integrated system.

  19. Wolfram Syndrome: New Mutations, Different Phenotype

    Science.gov (United States)

    Pasquali, Lorenzo; Lugani, Francesca; Perri, Katia; Russo, Chiara; Tallone, Ramona; Ghiggeri, Gian Marco; Lorini, Renata; d'Annunzio, Giuseppe

    2012-01-01

    Background Wolfram Syndrome (WS) is an autosomal recessive neurodegenerative disorder characterized by Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness identified by the acronym “DIDMOAD”. The WS gene, WFS1, encodes a transmembrane protein called Wolframin, which recent evidence suggests may serve as a novel endoplasmic reticulum calcium channel in pancreatic β-cells and neurons. WS is a rare disease, with an estimated prevalence of 1/550.000 children, with a carrier frequency of 1/354. The aim of our study was to determine the genotype of WS patients in order to establish a genotype/phenotype correlation. Methodology/Principal Findings We clinically evaluated 9 young patients from 9 unrelated families (6 males, 3 females). Basic criteria for WS clinical diagnosis were coexistence of insulin-treated diabetes mellitus and optic atrophy occurring before 15 years of age. Genetic analysis for WFS1 was performed by direct sequencing. Molecular sequencing revealed 5 heterozygous compound and 3 homozygous mutations. All of them were located in exon 8, except one in exon 4. In one proband only an heterozygous mutation (A684V) was found. Two new variants c.2663 C>A and c.1381 A>C were detected. Conclusions/Significance Our study increases the spectrum of WFS1 mutations with two novel variants. The male patient carrying the compound mutation [c.1060_1062delTTC]+[c.2663 C>A] showed the most severe phenotype: diabetes mellitus, optic atrophy (visual acuity 5/10), deafness with deep auditory bilaterally 8000 Hz, diabetes insipidus associated to reduced volume of posterior pituitary and pons. He died in bed at the age of 13 years. The other patient carrying the compound mutation [c.409_424dup16]+[c.1381 A>C] showed a less severe phenotype (DM, OA). PMID:22238590

  20. Wolfram syndrome: new mutations, different phenotype.

    Directory of Open Access Journals (Sweden)

    Concetta Aloi

    Full Text Available BACKGROUND: Wolfram Syndrome (WS is an autosomal recessive neurodegenerative disorder characterized by Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness identified by the acronym "DIDMOAD". The WS gene, WFS1, encodes a transmembrane protein called Wolframin, which recent evidence suggests may serve as a novel endoplasmic reticulum calcium channel in pancreatic β-cells and neurons. WS is a rare disease, with an estimated prevalence of 1/550.000 children, with a carrier frequency of 1/354. The aim of our study was to determine the genotype of WS patients in order to establish a genotype/phenotype correlation. METHODOLOGY/PRINCIPAL FINDINGS: We clinically evaluated 9 young patients from 9 unrelated families (6 males, 3 females. Basic criteria for WS clinical diagnosis were coexistence of insulin-treated diabetes mellitus and optic atrophy occurring before 15 years of age. Genetic analysis for WFS1 was performed by direct sequencing. Molecular sequencing revealed 5 heterozygous compound and 3 homozygous mutations. All of them were located in exon 8, except one in exon 4. In one proband only an heterozygous mutation (A684V was found. Two new variants c.2663 C>A and c.1381 A>C were detected. CONCLUSIONS/SIGNIFICANCE: Our study increases the spectrum of WFS1 mutations with two novel variants. The male patient carrying the compound mutation [c.1060_1062delTTC]+[c.2663 C>A] showed the most severe phenotype: diabetes mellitus, optic atrophy (visual acuity 5/10, deafness with deep auditory bilaterally 8000 Hz, diabetes insipidus associated to reduced volume of posterior pituitary and pons. He died in bed at the age of 13 years. The other patient carrying the compound mutation [c.409_424dup16]+[c.1381 A>C] showed a less severe phenotype (DM, OA.

  1. Mechanistic phenotypes: an aggregative phenotyping strategy to identify disease mechanisms using GWAS data.

    Directory of Open Access Journals (Sweden)

    Jonathan D Mosley

    Full Text Available A single mutation can alter cellular and global homeostatic mechanisms and give rise to multiple clinical diseases. We hypothesized that these disease mechanisms could be identified using low minor allele frequency (MAF<0.1 non-synonymous SNPs (nsSNPs associated with "mechanistic phenotypes", comprised of collections of related diagnoses. We studied two mechanistic phenotypes: (1 thrombosis, evaluated in a population of 1,655 African Americans; and (2 four groupings of cancer diagnoses, evaluated in 3,009 white European Americans. We tested associations between nsSNPs represented on GWAS platforms and mechanistic phenotypes ascertained from electronic medical records (EMRs, and sought enrichment in functional ontologies across the top-ranked associations. We used a two-step analytic approach whereby nsSNPs were first sorted by the strength of their association with a phenotype. We tested associations using two reverse genetic models and standard additive and recessive models. In the second step, we employed a hypothesis-free ontological enrichment analysis using the sorted nsSNPs to identify functional mechanisms underlying the diagnoses comprising the mechanistic phenotypes. The thrombosis phenotype was solely associated with ontologies related to blood coagulation (Fisher's p = 0.0001, FDR p = 0.03, driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse genetics models were enriched in DNA repair functions (p = 2×10-5, FDR p = 0.03 (POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L while the additive model showed enrichment related to chromatid segregation (p = 4×10-6, FDR p = 0.005 (KIF25, PINX1. We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms.

  2. Unique phenotypic expression of glucosephosphate isomerase deficiency.

    Science.gov (United States)

    Paglia, D E; Paredes, R; Valentine, W N; Dorantes, S; Konrad, P N

    1975-01-01

    Studies of a Mexican kindred present evidence for a unique phenotype of erythrocyte glucosephosphate isomerase, GPI Valle Hermoso. The proband was apparently the homozygous recipient of a mutant autosomal allele governing production of an isozyme characterized by decreased activity, marked thermal instability, normal kinetics and pH optimum, and normal starch gel electrophoretic patterns. Unlike previously known cases, leukocyte and plasma GPI activities were unimpaired. This suggested that the structural alteration primarily induced enzyme instability without drastically curtailing catalytic effectiveness, thereby allowing compensation by cells capable of continued protein synthesis. Age-related losses of GPI, however, were not evident by density-gradient fractionation of affected erythrocytes.

  3. Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies

    Directory of Open Access Journals (Sweden)

    Qiong Yang

    2012-01-01

    Full Text Available Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical or different types of components (e.g., some are continuous and others are categorical. We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.

  4. Phenotypic characterization of canine Malassezia spp., isolates

    Directory of Open Access Journals (Sweden)

    Angélica Hurtado-Suárez

    2016-09-01

    Full Text Available Objective. To characterize and identify yeasts of the genus Malassezia by phenotypic features. Materials and methods. First, the macroscopic and microscopic morphological characteristics were described. In addition we performed biochemical and physiological assays as Tweens and Cremophor, including more. Results. Our results evidenced of 105 isolates obtained from dogs diagnosed with external otitis, it was possible to identify two distinct species from 46 isolates within the Malassezia genus: 36.19% (n=38 were identified as M. pachydermatis and 7.62% (n=8 as M. furfur. According to phenotypic patterns the remaining 56.19% (n=59 were reported as Malassezia spp., possibly corresponding to M. furfur and/or M. pachydermatis. Conclusions. Results emphasize the necessity to characterize according to species. It is not feasible to define Malassezia by species based on morphological, biochemical, and physiological findings. Therefore, molecular genotyping should be performed to identify markers allowing a more precise isolate identification. This would broaden our epidemiological knowledge regarding different species involved in canine otitis pathologies.

  5. Senescence-like Phenotypes in Human Nevi

    Science.gov (United States)

    Joselow, Andrew; Lynn, Darren; Terzian, Tamara; Box, Neil F.

    2016-01-01

    Summary Cellular senescence is an irreversible arrest of cell proliferation at the G1 stage of the cell cycle in which cells become refractory to growth stimuli. Senescence is a critical and potent defense mechanism that mammalian cells have to suppress tumors. While there are many ways to induce a senescence response, oncogene-induced senescence (OIS) remains key to inhibiting progression of cells that have acquired oncogenic mutations. In primary cells in culture, OIS induces a set of measurable phenotypic and behavioral changes, in addition to cell cycle exit. Senescence-associated β-Galactosidase (SA-β-Gal) activity is a main hallmark of senescent cells, along with morphological changes that may depend on the oncogene that is activated, or on the primary cell type. Characteristic cellular changes of senescence include increased size, flattening, multi-nucleation, and extensive vacuolation. At the molecular level, tumor suppressor genes such as p53 and p16INK4a may play a role in initiation or maintenance of OIS. Activation of a DNA damage response and a senescence-associated secretory phenotype could delineate the onset of senescence. Despite advances in our understanding of how OIS suppresses some tumor types, the in vivo role of OIS in melanocytic nevi and melanoma remains poorly understood and not validated. In an effort to stimulate research in this field, we review in this chapter the known markers of senescence and provide experimental protocols for their identification by immunofluorescent staining in melanocytic nevi and malignant melanoma. PMID:27812879

  6. Evolution of phenotypic plasticity in extreme environments.

    Science.gov (United States)

    Chevin, Luis-Miguel; Hoffmann, Ary A

    2017-06-19

    Phenotypic plasticity, if adaptive, may allow species to counter the detrimental effects of extreme conditions, but the infrequent occurrence of extreme environments and/or their restriction to low-quality habitats within a species range means that they exert little direct selection on reaction norms. Plasticity could, therefore, be maladaptive under extreme environments, unless genetic correlations are strong between extreme and non-extreme environmental states, and the optimum phenotype changes smoothly with the environment. Empirical evidence suggests that populations and species from more variable environments show higher levels of plasticity that might preadapt them to extremes, but genetic variance for plastic responses can also be low, and genetic variation may not be expressed for some classes of traits under extreme conditions. Much of the empirical literature on plastic responses to extremes has not yet been linked to ecologically relevant conditions, such as asymmetrical fluctuations in the case of temperature extremes. Nevertheless, evolved plastic responses are likely to be important for natural and agricultural species increasingly exposed to climate extremes, and there is an urgent need to collect empirical information and link this to model predictions.This article is part of the themed issue 'Behavioural, ecological and evolutionary responses to extreme climatic events'. © 2017 The Author(s).

  7. Refractory versus resistant hypertension: Novel distinctive phenotypes

    Science.gov (United States)

    Dudenbostel, Tanja; Siddiqui, Mohammed; Gharpure, Nitin; Calhoun, David A.

    2017-01-01

    Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed. PMID:29034321

  8. Catalase deletion promotes prediabetic phenotype in mice.

    Science.gov (United States)

    Heit, Claire; Marshall, Stephanie; Singh, Surrendra; Yu, Xiaoqing; Charkoftaki, Georgia; Zhao, Hongyu; Orlicky, David J; Fritz, Kristofer S; Thompson, David C; Vasiliou, Vasilis

    2017-02-01

    Hydrogen peroxide is produced endogenously and can be toxic to living organisms by inducing oxidative stress and cell damage. However, it has also been identified as a signal transduction molecule. By metabolizing hydrogen peroxide, catalase protects cells and tissues against oxidative damage and may also influence signal transduction mechanisms. Studies suggest that acatalasemic individuals (i.e., those with very low catalase activity) have a higher risk for the development of diabetes. We now report catalase knockout (Cat -/- ) mice, when fed a normal (6.5% lipid) chow, exhibit an obese phenotype that manifests as an increase in body weight that becomes more pronounced with age. The mice demonstrate altered hepatic and muscle lipid deposition, as well as increases in serum and hepatic triglycerides (TGs), and increased hepatic transcription and protein expression of PPARγ. Liver morphology revealed steatosis with inflammation. Cat -/- mice also exhibited pancreatic morphological changes that correlated with impaired glucose tolerance and increased fasting serum insulin levels, conditions consistent with pre-diabetic status. RNA-seq analyses revealed a differential expression of pathways and genes in Cat -/- mice, many of which are related to metabolic syndrome, diabetes, and obesity, such as Pparg and Cidec. In conclusion, the results of the present study show mice devoid of catalase develop an obese, pre-diabetic phenotype and provide compelling evidence for catalase (or its products) being integral in metabolic regulation. Copyright © 2016. Published by Elsevier Inc.

  9. Cell Phenotype Transitions in Cardiovascular Calcification

    Directory of Open Access Journals (Sweden)

    Luis Hortells

    2018-03-01

    Full Text Available Cardiovascular calcification was originally considered a passive, degenerative process, however with the advance of cellular and molecular biology techniques it is now appreciated that ectopic calcification is an active biological process. Vascular calcification is the most common form of ectopic calcification, and aging as well as specific disease states such as atherosclerosis, diabetes, and genetic mutations, exhibit this pathology. In the vessels and valves, endothelial cells, smooth muscle cells, and fibroblast-like cells contribute to the formation of extracellular calcified nodules. Research suggests that these vascular cells undergo a phenotypic switch whereby they acquire osteoblast-like characteristics, however the mechanisms driving the early aspects of these cell transitions are not fully understood. Osteoblasts are true bone-forming cells and differentiate from their pluripotent precursor, the mesenchymal stem cell (MSC; vascular cells that acquire the ability to calcify share aspects of the transcriptional programs exhibited by MSCs differentiating into osteoblasts. What is unknown is whether a fully-differentiated vascular cell directly acquires the ability to calcify by the upregulation of osteogenic genes or, whether these vascular cells first de-differentiate into an MSC-like state before obtaining a “second hit” that induces them to re-differentiate down an osteogenic lineage. Addressing these questions will enable progress in preventative and regenerative medicine strategies to combat vascular calcification pathologies. In this review, we will summarize what is known about the phenotypic switching of vascular endothelial, smooth muscle, and valvular cells.

  10. Angioedema Phenotypes: Disease Expression and Classification.

    Science.gov (United States)

    Wu, Maddalena Alessandra; Perego, Francesca; Zanichelli, Andrea; Cicardi, Marco

    2016-10-01

    Due to marked heterogeneity of clinical presentations, comprehensive knowledge of angioedema phenotypes is crucial for correct diagnosis and choosing the appropriate therapeutic approach. One of the ways to a meaningful clinical distinction can be made between forms of angioedema occurring "with or without wheals." Angioedema with wheals (rash) is a hallmark of urticaria, either acute or chronic, spontaneous or inducible. Angioedema without wheals may still be manifested in about 10 % of patients with urticaria, but it may also occur as a separate entity. Several classifications of angioedema as part of urticaria were published over time, while a latest one, released in 2014 (HAWK group consensus, see below), provided a classification of all forms of "angioedema without wheals" distinct from urticaria, which will be the focus of the present review. At this time, the HAWK consensus classification is the best in terms of covering the pathophysiology, mediators involved, angioedema triggers, and clinical expression. According to this classification, three types of hereditary angioedema (genetic C1-INH deficiency, normal C1-INH with factor XII mutations, and unknown origin) and four types of acquired angioedema (C1-INH deficiency, related to ACE inhibitors intake, idiopathic histaminergic, and idiopathic non-histaminergic) are presented. We will review the distinctive clinical features of each phenotype in details.

  11. Nunukan Chicken: Genetic Characteristics, Phenotype and Utilization

    Directory of Open Access Journals (Sweden)

    Tike Sartika

    2006-12-01

    Full Text Available Nunukan chicken is a local chicken from East Kalimantan which spreads out in Tarakan and Nunukan Islands . The chicken has a specific buff color and Columbian type feather and also has very late feathering (VLF trait . The Nunukan cocks and hens have no wing and tail primary feather; the tail feathers are short and fragile . The VLF trait is known to have association with a K gene on the Z chromosome. The chicken is efficient in protein metabolism . Sulfur amino acids (cystine and methionine that needed for feather growth, could be utilized for meat and egg production . The egg production of Nunukan chicken was better than the Kampung chicken . The average of hen day, hen house and peak production of Nunukan chicken was 45 . 39.1 and 62%, respectively, while the Kampung chicken was 35 .9, 30 .9 and 48%, respectively . Based on genetic analysis, the external genotype characteristic of the Nunukan chicken is ii ce ss Idld pp. It means that the phenotype appearance of the Nunukan chicken was columbian and gold feathering type, yellow and white shank color and single comb type. This phenotype is similar to Merawang Chicken . The genetic introgression of the Nunukan chicken is affected by the Rhode Island Red with the genetic introgression value of 0.964 .

  12. Associating Symptom Phenotype and Genotype in Preeclampsia.

    Science.gov (United States)

    Founds, Sandra A; Tsigas, Eleni; Ren, Dianxu; Barmada, M Michael

    2018-03-01

    Preeclampsia is a complex genetic disorder with an incompletely understood pathogenesis. Its phenotype may be better elucidated by integrating symptoms. This study aimed to identify symptoms by gestational age and associations with novel preeclampsia candidate genes. Women with a history of preeclampsia recruited from The Preeclampsia Registry completed clinical/demographic, symptom surveys and provided medical records. DNA extracted from saliva was processed with multiplexed assays for eight single-nucleotide polymorphisms (SNPs) selected to tag candidate genes and/or located in symptom susceptibility regions. Groups with versus without symptoms were compared using χ 2 . Associations between SNPs and symptoms were analyzed as genotype categories and presence/absence of the variant allele. Logistic regression modeling was conducted with exploratory p = .05. In 114 participants, 113 reported at least 1 of the 18 symptoms. Symptoms varied by trimester. Nine symptoms were associated with seven SNPs. Visual disturbances were associated with three SNPs and nausea/vomiting with two SNPs. Modeling adjustment for maternal age and parity resulted in 15 associations between 9 symptoms and 8 SNPs. Medical records demonstrated 100% concordance with self-reported diagnosis and 48% concordance with reported severity. Findings indicated novel symptom-genotype associations in preeclampsia. The small sample was self-selected, but results support future studies including medical records review. When validated, these results may lead to holistic phenotyping of women to characterize subsets of preeclampsia. This approach may optimize health in pregnancy and later life for mothers and offspring through prediction, prevention, and precision nursing care.

  13. Developmental sculpting of social phenotype and plasticity.

    Science.gov (United States)

    Sakata, Jon T; Crews, David

    2004-04-01

    Early developmental variables engender behavioral and neural variation, especially in species in which embryonic environment determines gonadal sex. In the leopard gecko, Eublepharis macularius, the incubation temperature of the egg (IncT) determines gonadal sex. Moreover, IncT affects the sexual differentiation of the individual and, consequently, within-sex variation. Individuals hatched from eggs incubated at an IncT that produces predominantly males are more masculinized than same-sex counterparts from IncTs that produce predominantly females. Here we review how gonadal sex and IncT interact to affect behavioral, endocrinological, and neural phenotype in the leopard gecko and influence phenotypic plasticity following hormone administration or social experience. We discuss the hormonal dependence of sex- and IncT-dependent behavioral and neural morphological and metabolic differences and highlight the parallels between IncT effects in geckos and intrauterine position effects in rodents. We argue that the leopard gecko is an important model of how the process of sex determination can affect sexual differentiation and of selection forces underlying the evolution of sex ratios. Copyright 2004 Elsevier Ltd.

  14. A vestibular phenotype for Waardenburg syndrome?

    Science.gov (United States)

    Black, F. O.; Pesznecker, S. C.; Allen, K.; Gianna, C.

    2001-01-01

    OBJECTIVE: To investigate vestibular abnormalities in subjects with Waardenburg syndrome. STUDY DESIGN: Retrospective record review. SETTING: Tertiary referral neurotology clinic. SUBJECTS: Twenty-two adult white subjects with clinical diagnosis of Waardenburg syndrome (10 type I and 12 type II). INTERVENTIONS: Evaluation for Waardenburg phenotype, history of vestibular and auditory symptoms, tests of vestibular and auditory function. MAIN OUTCOME MEASURES: Results of phenotyping, results of vestibular and auditory symptom review (history), results of vestibular and auditory function testing. RESULTS: Seventeen subjects were women, and 5 were men. Their ages ranged from 21 to 58 years (mean, 38 years). Sixteen of the 22 subjects sought treatment for vertigo, dizziness, or imbalance. For subjects with vestibular symptoms, the results of vestibuloocular tests (calorics, vestibular autorotation, and/or pseudorandom rotation) were abnormal in 77%, and the results of vestibulospinal function tests (computerized dynamic posturography, EquiTest) were abnormal in 57%, but there were no specific patterns of abnormality. Six had objective sensorineural hearing loss. Thirteen had an elevated summating/action potential (>0.40) on electrocochleography. All subjects except those with severe hearing loss (n = 3) had normal auditory brainstem response results. CONCLUSION: Patients with Waardenburg syndrome may experience primarily vestibular symptoms without hearing loss. Electrocochleography and vestibular function tests appear to be the most sensitive measures of otologic abnormalities in such patients.

  15. Ocean acidification challenges copepod phenotypic plasticity

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    A. Vehmaa

    2016-11-01

    Full Text Available Ocean acidification is challenging phenotypic plasticity of individuals and populations. Calanoid copepods (zooplankton are shown to be fairly plastic against altered pH conditions, and laboratory studies indicate that transgenerational effects are one mechanism behind this plasticity. We studied phenotypic plasticity of the copepod Acartia sp. in the course of a pelagic, large-volume mesocosm study that was conducted to investigate ecosystem and biogeochemical responses to ocean acidification. We measured copepod egg production rate, egg-hatching success, adult female size and adult female antioxidant capacity (ORAC as a function of acidification (fCO2  ∼  365–1231 µatm and as a function of quantity and quality of their diet. We used an egg transplant experiment to reveal whether transgenerational effects can alleviate the possible negative effects of ocean acidification on offspring development. We found significant negative effects of ocean acidification on adult female size. In addition, we found signs of a possible threshold at high fCO2, above which adaptive maternal effects cannot alleviate the negative effects of acidification on egg-hatching and nauplii development. We did not find support for the hypothesis that insufficient food quantity (total particulate carbon < 55 µm or quality (C : N weakens the transgenerational effects. However, females with high-ORAC-produced eggs with high hatching success. Overall, these results indicate that Acartia sp. could be affected by projected near-future CO2 levels.

  16. Root phenotyping: from component trait in the lab to breeding.

    Science.gov (United States)

    Kuijken, René C P; van Eeuwijk, Fred A; Marcelis, Leo F M; Bouwmeester, Harro J

    2015-09-01

    In the last decade cheaper and faster sequencing methods have resulted in an enormous increase in genomic data. High throughput genotyping, genotyping by sequencing and genomic breeding are becoming a standard in plant breeding. As a result, the collection of phenotypic data is increasingly becoming a limiting factor in plant breeding. Genetic studies on root traits are being hampered by the complexity of these traits and the inaccessibility of the rhizosphere. With an increasing interest in phenotyping, breeders and scientists try to overcome these limitations, resulting in impressive developments in automated phenotyping platforms. Recently, many such platforms have been thoroughly described, yet their efficiency to increase genetic gain often remains undiscussed. This efficiency depends on the heritability of the phenotyped traits as well as the correlation of these traits with agronomically relevant breeding targets. This review provides an overview of the latest developments in root phenotyping and describes the environmental and genetic factors influencing root phenotype and heritability. It also intends to give direction to future phenotyping and breeding strategies for optimizing root system functioning. A quantitative framework to determine the efficiency of phenotyping platforms for genetic gain is described. By increasing heritability, managing effects caused by interactions between genotype and environment and by quantifying the genetic relation between traits phenotyped in platforms and ultimate breeding targets, phenotyping platforms can be utilized to their maximum potential. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Ontology-based validation and identification of regulatory phenotypes

    KAUST Repository

    Kulmanov, Maxat

    2018-01-31

    Motivation: Function annotations of gene products, and phenotype annotations of genotypes, provide valuable information about molecular mechanisms that can be utilized by computational methods to identify functional and phenotypic relatedness, improve our understanding of disease and pathobiology, and lead to discovery of drug targets. Identifying functions and phenotypes commonly requires experiments which are time-consuming and expensive to carry out; creating the annotations additionally requires a curator to make an assertion based on reported evidence. Support to validate the mutual consistency of functional and phenotype annotations as well as a computational method to predict phenotypes from function annotations, would greatly improve the utility of function annotations Results: We developed a novel ontology-based method to validate the mutual consistency of function and phenotype annotations. We apply our method to mouse and human annotations, and identify several inconsistencies that can be resolved to improve overall annotation quality. Our method can also be applied to the rule-based prediction of phenotypes from functions. We show that the predicted phenotypes can be utilized for identification of protein-protein interactions and gene-disease associations. Based on experimental functional annotations, we predict phenotypes for 1,986 genes in mouse and 7,301 genes in human for which no experimental phenotypes have yet been determined.

  18. Diabetic encephalopathy-related depression: experimental evidence that insulin and clonazepam restore antioxidant status in rat brain.

    Science.gov (United States)

    Wayhs, Carlos Alberto Yasin; Mescka, Caroline Paula; Guerreiro, Gilian; Moraes, Tarsila Barros; Jacques, Carlos Eduardo Diaz; Rosa, Andrea Pereira; Ferri, Marcelo Kneib; Nin, Maurício Schüler; Dutra-Filho, Carlos Severo; Barros, Helena Maria Tannhauser; Vargas, Carmen Regla

    2014-12-01

    There is increasing evidence suggesting that oxidative stress plays an important role in the development of many chronic and degenerative conditions such as diabetic encephalopathy and depression. Considering that diabetic rats and mice present higher depressive-like behaviour when submitted to the forced swimming test and that treatment with insulin and/or clonazepam is able to reverse the behavioural changes of the diabetic rats, the present work investigated the antioxidant status, specifically total antioxidant reactivity and antioxidant potential of insulin and clonazepam, as well as the effect of this drugs upon protein oxidative damage and reactive species formation in cortex, hippocampus and striatum from diabetic rats submitted to forced swimming test. It was verified that longer immobility time in diabetic rats and insulin plus clonazepam treatment reversed this depressive-like behaviour. Moreover, data obtained in this study allowed to demonstrate through different parameters such as protein carbonyl content, 2'7'-dichlorofluorescein oxidation, catalase, superoxide dismutase, glutathione peroxidase assay, total radical-trapping antioxidant potential and total antioxidant reactivity that there is oxidative stress in cortex, hippocampus and striatum from diabetic rats under depressive-like behaviour and highlight the insulin and/or clonazepam effect in these different brain areas, restoring antioxidant status and protein damage. Copyright © 2014 John Wiley & Sons, Ltd.

  19. The flora phenotype ontology (FLOPO): tool for integrating morphological traits and phenotypes of vascular plants

    KAUST Repository

    Hoehndorf, Robert

    2016-11-14

    Background The systematic analysis of a large number of comparable plant trait data can support investigations into phylogenetics and ecological adaptation, with broad applications in evolutionary biology, agriculture, conservation, and the functioning of ecosystems. Floras, i.e., books collecting the information on all known plant species found within a region, are a potentially rich source of such plant trait data. Floras describe plant traits with a focus on morphology and other traits relevant for species identification in addition to other characteristics of plant species, such as ecological affinities, distribution, economic value, health applications, traditional uses, and so on. However, a key limitation in systematically analyzing information in Floras is the lack of a standardized vocabulary for the described traits as well as the difficulties in extracting structured information from free text. Results We have developed the Flora Phenotype Ontology (FLOPO), an ontology for describing traits of plant species found in Floras. We used the Plant Ontology (PO) and the Phenotype And Trait Ontology (PATO) to extract entity-quality relationships from digitized taxon descriptions in Floras, and used a formal ontological approach based on phenotype description patterns and automated reasoning to generate the FLOPO. The resulting ontology consists of 25,407 classes and is based on the PO and PATO. The classified ontology closely follows the structure of Plant Ontology in that the primary axis of classification is the observed plant anatomical structure, and more specific traits are then classified based on parthood and subclass relations between anatomical structures as well as subclass relations between phenotypic qualities. Conclusions The FLOPO is primarily intended as a framework based on which plant traits can be integrated computationally across all species and higher taxa of flowering plants. Importantly, it is not intended to replace established

  20. Phenotypic and immunohistochemical characterization of sarcoglycanopathies

    Directory of Open Access Journals (Sweden)

    Ana F. B. Ferreira

    2011-01-01

    Full Text Available INTRODUCTION: Limb-girdle muscular dystrophy presents with heterogeneous clinical and molecular features. The primary characteristic of this disorder is proximal muscular weakness with variable age of onset, speed of progression, and intensity of symptoms. Sarcoglycanopathies, which are a subgroup of the limb-girdle muscular dystrophies, are caused by mutations in sarcoglycan genes. Mutations in these genes cause secondary deficiencies in other proteins, due to the instability of the dystrophin-glycoprotein complex. Therefore, determining the etiology of a given sarcoglycanopathy requires costly and occasionally inaccessible molecular methods. OBJECTIVE: The aim of this study was to identify phenotypic differences among limb-girdle muscular dystrophy patients who were grouped according to the immunohistochemical phenotypes for the four sarcoglycans. METHODS: To identify phenotypic differences among patients with different types of sarcoglycanopathies, a questionnaire was used and the muscle strength and range of motion of nine joints in 45 patients recruited from the Department of Neurology - HC-FMUSP (Clinics Hospital of the Faculty of Medicine of the University of São Paulo were evaluated. The findings obtained from these analyses were compared with the results of the immunohistochemical findings. RESULTS: The patients were divided into the following groups based on the immunohistochemical findings: a-sarcoglycanopathies (16 patients, b-sarcoglycanopathies (1 patient, y-sarcoglycanopathies (5 patients, and nonsarcoglycanopathies (23 patients. The muscle strength analysis revealed significant differences for both upper and lower limb muscles, particularly the shoulder and hip muscles, as expected. No pattern of joint contractures was found among the four groups analyzed, even within the same family. However, a high frequency of tiptoe gait was observed in patients with a-sarcoglycanopathies, while calf pseudo-hypertrophy was most common in

  1. Recommendations for using standardised phenotypes in genetic association studies

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    Naylor Melissa G

    2009-07-01

    Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  2. Phenotyping common beans for adaptation to drought

    Science.gov (United States)

    Beebe, Stephen E.; Rao, Idupulapati M.; Blair, Matthew W.; Acosta-Gallegos, Jorge A.

    2013-01-01

    Common beans (Phaseolus vulgaris L.) originated in the New World and are the grain legume of greatest production for direct human consumption. Common bean production is subject to frequent droughts in highland Mexico, in the Pacific coast of Central America, in northeast Brazil, and in eastern and southern Africa from Ethiopia to South Africa. This article reviews efforts to improve common bean for drought tolerance, referring to genetic diversity for drought response, the physiology of drought tolerance mechanisms, and breeding strategies. Different races of common bean respond differently to drought, with race Durango of highland Mexico being a major source of genes. Sister species of P. vulgaris likewise have unique traits, especially P. acutifolius which is well adapted to dryland conditions. Diverse sources of tolerance may have different mechanisms of plant response, implying the need for different methods of phenotyping to recognize the relevant traits. Practical considerations of field management are discussed including: trial planning; water management; and field preparation. PMID:23507928

  3. Associations between Mycobacterium tuberculosis Strains and Phenotypes

    Science.gov (United States)

    Brown, Timothy; Nikolayevskyy, Vladyslav; Velji, Preya

    2010-01-01

    To inform development of tuberculosis (TB) control strategies, we characterized a total of 2,261 Mycobacterium tuberculosis complex isolates by using multiple phenotypic and molecular markers, including polymorphisms in repetitive sequences (spoligotyping and variable-number tandem repeats [VNTRs]) and large sequence and single-nucleotide polymorphisms. The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: >5 copies at exact tandem repeat (ETR) A, >2 at mycobacterial interspersed repetitive unit 24, and >3 at ETR-B associated with the East African–Indian and M. bovis strains. All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum. These findings can be used as a model of pathogen global diversity. PMID:20113558

  4. Morphologies and phenotypes in Bacillus subtilis biofilms.

    Science.gov (United States)

    Wang, Xiaoling; Meng, Shuo; Han, Jingshi

    2017-08-01

    In this study, we explored Bacillus subtilis biofilm growth under various conditions such as the use of substrates with different stiffnesses and nutrient levels using a well-developed optical imaging technique to spatially and temporally track biofilm growth. We also developed a quantitative method to characterize B. subtilis biofilm morphologies under various growth conditions. To determine biofilm rim irregularities, we used the dimensionless P2A ratio, defined as P 2 /4πA, where P is the perimeter and A is the area of the biofilm. To estimate biofilm thickness from transmission images, we developed a calibration procedure based on Beer- Lambert's law and cross sectioning. Furthermore, to determine the distributions of different B. subtilis cell phenotypes during biofilm growth, we used a triple-fluorescence-labeled B. subtilis strain that expressed motility, matrix production, and sporulation. Based on this work, we are able to tune biofilm growth by changing its growing environment.

  5. Sheep models of polycystic ovary syndrome phenotype

    Science.gov (United States)

    Veiga-Lopez, Almudena

    2012-01-01

    Polycystic ovary syndrome (PCOS) is a fertility disorder affecting 5–7% of reproductive-aged women. Women with PCOS manifest both reproductive and metabolic defects. Several animal models have evolved, which implicate excess steroid exposure during fetal life in the development of the PCOS phenotype. This review addresses the fetal and adult reproductive and metabolic consequences of prenatal steroid excess in sheep and the translational relevance of these findings to PCOS. By comparing findings in various breeds of sheep, the review targets the role of genetic susceptibility to fetal insults. Disruptions induced by prenatal testosterone excess are evident at both the reproductive and metabolic level with each influencing the other thus creating a self-perpetuating vicious cycle. The review highlights the need for identifying a common mediator of the dysfunctions at the reproductive and metabolic levels and developing prevention and treatment interventions targeting all sites of disruption in unison for achieving optimal success. PMID:23084976

  6. Do convergent developmental mechanisms underlie convergent phenotypes?

    Science.gov (United States)

    Wray, Gregory A.

    2002-01-01

    Convergence is a pervasive evolutionary process, affecting many aspects of phenotype and even genotype. Relatively little is known about convergence in developmental processes, however, nor about the degree to which convergence in development underlies convergence in anatomy. A switch in the ecology of sea urchins from feeding to nonfeeding larvae illustrates how convergence in development can be associated with convergence in anatomy. Comparisons to more distantly related taxa, however, suggest that this association may be limited to relatively close phylogenetic comparisons. Similarities in gene expression during development provide another window into the association between convergence in developmental processes and convergence in anatomy. Several well-studied transcription factors exhibit likely cases of convergent gene expression in distantly related animal phyla. Convergence in regulatory gene expression domains is probably more common than generally acknowledged, and can arise for several different reasons. Copyright 2002 S. Karger AG, Basel.

  7. Phenotyping Cowpeas for Adaptation to Drought

    Directory of Open Access Journals (Sweden)

    Anthony eHall

    2012-05-01

    Full Text Available Methods for phenotyping cowpeas for adaptation to drought are reviewed. Key factors involve achieving optimal time of flowering and cycle length, and appropriate morphology for different types of cultivars as they relate to their utilization for dry grain, hay and fresh pea production. The strong resistance to vegetative-stage drought that is available, resistance to mid-season drought, escaping terminal drought, the delayed-leaf-senescence trait, water-use-efficiency, deeper rooting and heat tolerance are discussed. Diseases and pests that influence adaptation to drought are considered. Use of varietal intercrops and rotations are examined. Breeding and experimental field strategies for enhancing the adaptation to drought of cowpeas are described.

  8. Phenotypic characteristics of early Wolfram syndrome.

    Science.gov (United States)

    Marshall, Bess A; Permutt, M Alan; Paciorkowski, Alexander R; Hoekel, James; Karzon, Roanne; Wasson, Jon; Viehover, Amy; White, Neil H; Shimony, Joshua S; Manwaring, Linda; Austin, Paul; Hullar, Timothy E; Hershey, Tamara

    2013-04-27

    Wolfram Syndrome (WFS:OMIM 222300) is an autosomal recessive, progressive, neurologic and endocrinologic degenerative disorder caused by mutations in the WFS1 gene, encoding the endoplasmic reticulum (ER) protein wolframin, thought to be involved in the regulation of ER stress. This paper reports a cross section of data from the Washington University WFS Research Clinic, a longitudinal study to collect detailed phenotypic data on a group of young subjects in preparation for studies of therapeutic interventions. Eighteen subjects (ages 5.9-25.8, mean 14.2 years) with genetically confirmed WFS were identified through the Washington University International Wolfram Registry. Examinations included: general medical, neurologic, ophthalmologic, audiologic, vestibular, and urologic exams, cognitive testing and neuroimaging. Seventeen (94%) had diabetes mellitus with the average age of diabetes onset of 6.3 ± 3.5 years. Diabetes insipidus was diagnosed in 13 (72%) at an average age of 10.6 ± 3.3 years. Seventeen (94%) had optic disc pallor and defects in color vision, 14 (78%) had hearing loss and 13 (72%) had olfactory defects, eight (44%) had impaired vibration sensation. Enuresis was reported by four (22%) and nocturia by three (17%). Of the 11 tested for bladder emptying, five (45%) had elevated post-void residual bladder volume. WFS causes multiple endocrine and neurologic deficits detectable on exam, even early in the course of the disease. Defects in olfaction have been underappreciated. The proposed mechanism of these deficits in WFS is ER stress-induced damage to neuronal and hormone-producing cells. This group of subjects with detailed clinical phenotyping provides a pool for testing proposed treatments for ER stress. Longitudinal follow-up is necessary for establishing the natural history and identifying potential biomarkers of progression.

  9. Phenotype heterogeneity in cancer cell populations

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luis [CNRS UMR 7598, LJLL, & INRIA MAMBA team, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, luis@ann.jussieu.fr (France); Chisholm, Rebecca [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, rebecca.chisholm@gmail.com (Australia); Clairambault, Jean [INRIA MAMBA team & LJLL, UMR 7598, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, jean.clairambault@inria.fr, Corresponding author (France); Escargueil, Alexandre [INSERM “Cancer Biology and Therapeutics”, Sorbonne Universités, UPMC Univ Paris 06, UMR-S 938, CDR St Antoine, Hôpital St Antoine, 184 Fbg. St Antoine, 75571 Paris cedex 12, France, alexandre.escargueil@upmc.fr (France); Lorenzi, Tommaso [CMLA, ENS Cachan, 61, Av. du Président Wilson, 94230 Cachan cedex & INRIA MAMBA team, & LJLL, UMR 7598, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, tommaso.lorenzi@gmail.com (France); Lorz, Alexander [Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598 & INRIA Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, alex.lorz@ann.jussieu.fr (France); Trélat, Emmanuel [Institut Universitaire de France, Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598, Boîte courrier 187, UPMC Univ Paris 06, 4 Pl. Jussieu, 75252 Paris cedex 05, France, emmanuel.trelat@upmc.fr (France)

    2016-06-08

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  10. Genetic Regulation of Phenotypic Plasticity and Canalisation in Yeast Growth.

    Directory of Open Access Journals (Sweden)

    Anupama Yadav

    Full Text Available The ability of a genotype to show diverse phenotypes in different environments is called phenotypic plasticity. Phenotypic plasticity helps populations to evade extinctions in novel environments, facilitates adaptation and fuels evolution. However, most studies focus on understanding the genetic basis of phenotypic regulation in specific environments. As a result, while it's evolutionary relevance is well established, genetic mechanisms regulating phenotypic plasticity and their overlap with the environment specific regulators is not well understood. Saccharomyces cerevisiae is highly sensitive to the environment, which acts as not just external stimulus but also as signalling cue for this unicellular, sessile organism. We used a previously published dataset of a biparental yeast population grown in 34 diverse environments and mapped genetic loci regulating variation in phenotypic plasticity, plasticity QTL, and compared them with environment-specific QTL. Plasticity QTL is one whose one allele exhibits high plasticity whereas the other shows a relatively canalised behaviour. We mapped phenotypic plasticity using two parameters-environmental variance, an environmental order-independent parameter and reaction norm (slope, an environmental order-dependent parameter. Our results show a partial overlap between pleiotropic QTL and plasticity QTL such that while some plasticity QTL are also pleiotropic, others have a significant effect on phenotypic plasticity without being significant in any environment independently. Furthermore, while some plasticity QTL are revealed only in specific environmental orders, we identify large effect plasticity QTL, which are order-independent such that whatever the order of the environments, one allele is always plastic and the other is canalised. Finally, we show that the environments can be divided into two categories based on the phenotypic diversity of the population within them and the two categories have

  11. Predicting phenotypic diversity and the underlying quantitative molecular transitions.

    Directory of Open Access Journals (Sweden)

    Claudiu A Giurumescu

    2009-04-01

    Full Text Available During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render approximately 500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network

  12. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities

    OpenAIRE

    Chong, Jessica X.; Buckingham, Kati J.; Jhangiani, Shalini N.; Boehm, Corinne; Sobreira, Nara; Smith, Joshua D.; Harrell, Tanya M.; McMillin, Margaret J.; Wiszniewski, Wojciech; Gambin, Tomasz; Coban Akdemir, Zeynep H.; Doheny, Kimberly; Scott, Alan F.; Avramopoulos, Dimitri; Chakravarti, Aravinda

    2015-01-01

    Discovering the genetic basis of a Mendelian phenotype establishes a causal link between genotype and phenotype, making possible carrier and population screening and direct diagnosis. Such discoveries also contribute to our knowledge of gene function, gene regulation, development, and biological mechanisms that can be used for developing new therapeutics. As of February 2015, 2,937 genes underlying 4,163 Mendelian phenotypes have been discovered, but the genes underlying ∼50% (i.e., 3,152) of...

  13. Accurate phenotyping: Reconciling approaches through Bayesian model averaging.

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    Carla Chia-Ming Chen

    Full Text Available Genetic research into complex diseases is frequently hindered by a lack of clear biomarkers for phenotype ascertainment. Phenotypes for such diseases are often identified on the basis of clinically defined criteria; however such criteria may not be suitable for understanding the genetic composition of the diseases. Various statistical approaches have been proposed for phenotype definition; however our previous studies have shown that differences in phenotypes estimated using different approaches have substantial impact on subsequent analyses. Instead of obtaining results based upon a single model, we propose a new method, using Bayesian model averaging to overcome problems associated with phenotype definition. Although Bayesian model averaging has been used in other fields of research, this is the first study that uses Bayesian model averaging to reconcile phenotypes obtained using multiple models. We illustrate the new method by applying it to simulated genetic and phenotypic data for Kofendred personality disorder-an imaginary disease with several sub-types. Two separate statistical methods were used to identify clusters of individuals with distinct phenotypes: latent class analysis and grade of membership. Bayesian model averaging was then used to combine the two clusterings for the purpose of subsequent linkage analyses. We found that causative genetic loci for the disease produced higher LOD scores using model averaging than under either individual model separately. We attribute this improvement to consolidation of the cores of phenotype clusters identified using each individual method.

  14. Epistatic Mutations And Unpredictable Phenotypes In Pseudomonas Aeruginosa

    DEFF Research Database (Denmark)

    Andresen, Eva Kammer; Abou Hachem, Maher; Jelsbak, Lars

    2015-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen, able to adapt to stressful environments such as the cystic fibrosis (CF) airways. Adaptation of P. aeruginosa to the CF environment is associated with phenotypic changes, such as switch in mucoidy, antibiotic resistance and loss of virulence...... factors. The phenotypic changes arise from mutations in trans-regulatory elements but are nearly impossible to predict from sequence data alone. Often, the combinatorial effects of few mutations in global regulators give rise to unexpected phenotypes. To understand the epistatic effect and how unexpected...... phenotypes arise from seemingly unrelated mutations, we have studied two mutations in P. aeruginosa transcriptional regulators, sigma factor rpoD and algT....

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    of the internal phenotype into high-throughput phenotyping of whole plants and canopies. By this means, complex traits can be broken down into individual components of physiological traits. Since the higher resolution of physiological phenotyping by ‘wet chemistry’ is inherently limited in throughput, high......-throughput non-invasive phenotyping needs to be validated and verified across scales to be used as proxy for the underlying processes. Armed with this interdisciplinary and multidimensional phenomics approach, plant physiology, non-invasive phenotyping, and functional genomics will complement each other......Plants are affected by complex genome×environment×management interactions which determine phenotypic plasticity as a result of the variability of genetic components. Whereas great advances have been made in the cost-efficient and high-throughput analyses of genetic information and non...

  16. Determining Multiple Sclerosis Phenotype from Electronic Medical Records.

    Science.gov (United States)

    Nelson, Richard E; Butler, Jorie; LaFleur, Joanne; Knippenberg, Kristin; C Kamauu, Aaron W; DuVall, Scott L

    2016-12-01

    Multiple sclerosis (MS), a central nervous system disease in which nerve signals are disrupted by scarring and demyelination, is classified into phenotypes depending on the patterns of cognitive or physical impairment progression: relapsing-remitting MS (RRMS), primary-progressive MS (PPMS), secondary-progressive MS (SPMS), or progressive-relapsing MS (PRMS). The phenotype is important in managing the disease and determining appropriate treatment. The ICD-9-CM code 340.0 is uninformative about MS phenotype, which increases the difficulty of studying the effects of phenotype on disease. To identify MS phenotype using natural language processing (NLP) techniques on progress notes and other clinical text in the electronic medical record (EMR). Patients with at least 2 ICD-9-CM codes for MS (340.0) from 1999 through 2010 were identified from nationwide EMR data in the Department of Veterans Affairs. Clinical experts were interviewed for possible keywords and phrases denoting MS phenotype in order to develop a data dictionary for NLP. For each patient, NLP was used to search EMR clinical notes, since the first MS diagnosis date for these keywords and phrases. Presence of phenotype-related keywords and phrases were analyzed in context to remove mentions that were negated (e.g., "not relapsing-remitting") or unrelated to MS (e.g., "RR" meaning "respiratory rate"). One thousand mentions of MS phenotype were validated, and all records of 150 patients were reviewed for missed mentions. There were 7,756 MS patients identified by ICD-9-CM code 340.0. MS phenotype was identified for 2,854 (36.8%) patients, with 1,836 (64.3%) of those having just 1 phenotype mentioned in their EMR clinical notes: 1,118 (39.2%) RRMS, 325 (11.4%) PPMS, 374 (13.1%) SPMS, and 19 (0.7%) PRMS. A total of 747 patients (26.2%) had 2 phenotypes, the most common being 459 patients (16.1%) with RRMS and SPMS. A total of 213 patients (7.5%) had 3 phenotypes, and 58 patients (2.0%) had 4 phenotypes mentioned

  17. Mapping gene associations in human mitochondria using clinical disease phenotypes.

    Directory of Open Access Journals (Sweden)

    Curt Scharfe

    2009-04-01

    Full Text Available Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects

  18. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.

    Science.gov (United States)

    Chong, Jessica X; Buckingham, Kati J; Jhangiani, Shalini N; Boehm, Corinne; Sobreira, Nara; Smith, Joshua D; Harrell, Tanya M; McMillin, Margaret J; Wiszniewski, Wojciech; Gambin, Tomasz; Coban Akdemir, Zeynep H; Doheny, Kimberly; Scott, Alan F; Avramopoulos, Dimitri; Chakravarti, Aravinda; Hoover-Fong, Julie; Mathews, Debra; Witmer, P Dane; Ling, Hua; Hetrick, Kurt; Watkins, Lee; Patterson, Karynne E; Reinier, Frederic; Blue, Elizabeth; Muzny, Donna; Kircher, Martin; Bilguvar, Kaya; López-Giráldez, Francesc; Sutton, V Reid; Tabor, Holly K; Leal, Suzanne M; Gunel, Murat; Mane, Shrikant; Gibbs, Richard A; Boerwinkle, Eric; Hamosh, Ada; Shendure, Jay; Lupski, James R; Lifton, Richard P; Valle, David; Nickerson, Deborah A; Bamshad, Michael J

    2015-08-06

    Discovering the genetic basis of a Mendelian phenotype establishes a causal link between genotype and phenotype, making possible carrier and population screening and direct diagnosis. Such discoveries also contribute to our knowledge of gene function, gene regulation, development, and biological mechanisms that can be used for developing new therapeutics. As of February 2015, 2,937 genes underlying 4,163 Mendelian phenotypes have been discovered, but the genes underlying ∼50% (i.e., 3,152) of all known Mendelian phenotypes are still unknown, and many more Mendelian conditions have yet to be recognized. This is a formidable gap in biomedical knowledge. Accordingly, in December 2011, the NIH established the Centers for Mendelian Genomics (CMGs) to provide the collaborative framework and infrastructure necessary for undertaking large-scale whole-exome sequencing and discovery of the genetic variants responsible for Mendelian phenotypes. In partnership with 529 investigators from 261 institutions in 36 countries, the CMGs assessed 18,863 samples from 8,838 families representing 579 known and 470 novel Mendelian phenotypes as of January 2015. This collaborative effort has identified 956 genes, including 375 not previously associated with human health, that underlie a Mendelian phenotype. These results provide insight into study design and analytical strategies, identify novel mechanisms of disease, and reveal the extensive clinical variability of Mendelian phenotypes. Discovering the gene underlying every Mendelian phenotype will require tackling challenges such as worldwide ascertainment and phenotypic characterization of families affected by Mendelian conditions, improvement in sequencing and analytical techniques, and pervasive sharing of phenotypic and genomic data among researchers, clinicians, and families. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. How phenotypic plasticity made its way into molecular biology

    Indian Academy of Sciences (India)

    Prakash

    A rapid exploration in Medline shows that phenotypic plasticity became a fashionable expression quite recently, in the last five years. Obviously, there is currently a tendency to favour increasing use of the expressions phenotypic plasticity and developmental plasticity. My objective in this contribution is to disentangle the ...

  20. COMPUTER APPROACHES TO WHEAT HIGH-THROUGHPUT PHENOTYPING

    Directory of Open Access Journals (Sweden)

    Afonnikov D.

    2012-08-01

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

  1. Genetic and phenotypic parameters of reproduction and lactation ...

    African Journals Online (AJOL)

    This study was done to estimate genetic and phenotypic parameters for Friesian x Boran crossbred dairy cattle of Kagera region. Parameters estimated were heritability, repeatability and phenotypic correlations of various lactation and reproductive traits. Variance component (VARCOMP) procedure and general linear ...

  2. Phenotypic and seed protein analysis in 31 Lima bean ( Phaseolus ...

    African Journals Online (AJOL)

    Phenotypic and seed protein analyses were performed on 31 accessions of Lima bean assembled in Ghana. Data on 16 phenotypic characters consisting of eight quantitative and eight qualitative were analysed. There were significant differences among the accessions based on the eight quantitative characters.

  3. The Down Syndrome Behavioural Phenotype: Taking a Developmental Approach

    Science.gov (United States)

    Fidler, Deborah; Most, David; Philofsky, Amy

    2009-01-01

    Individuals with Down syndrome are predisposed to show a specific behavioural phenotype, or a pattern of strengths and challenges in functioning across different domains of development. It is argued that a developmental approach to researching the Down syndrome behavioural phenotype, including an examination of the dynamic process of the unfolding…

  4. Determinants of asthma phenotypes in supermarket bakery workers.

    NARCIS (Netherlands)

    Baatjies, R.; Lopata, A.L.; Sander, I.; Raulf-Heimsoth, M.; Bateman, E.D.; Meijster, T.; Heederik, D.J.J.; Robins, T.G.; Jeebhay, M.F.

    2009-01-01

    While baker's asthma has been well described, various asthma phenotypes in bakery workers have yet to be characterised. Our study aims to describe the asthma phenotypes in supermarket bakery workers in relation to host risk factors and self-reported exposure to flour dust. A cross-sectional study of

  5. Determinants of asthma phenotypes in supermarket bakery workers

    NARCIS (Netherlands)

    Baatjies, R.; Lopata, A.L.; Sander, I.; Raulf-Heimsoth, M.; Batemane, E.D.; Meijster, T.; Heederik, D.; Robins, T.G.; Jeebhay, M.F.

    2009-01-01

    While baker's asthma has been well described, various asthma phenotypes in bakery workers have yet to be characterised. Our study aims to describe the asthma phenotypes in supermarket bakery workers in relation to host risk factors and self-reported exposure to flour dust. A cross-sectional study of

  6. Phenotype modulation of airway smooth muscle in asthma

    NARCIS (Netherlands)

    Wright, David B.; Trian, Thomas; Siddiqui, Sana; Pascoe, Chris D.; Johnson, Jill R.; Dekkers, Bart G. J.; Dakshinamurti, Shyamala; Bagchi, Rushita; Burgess, Janette K.; Kanabar, Varsha; Ojo, Oluwaseun O.

    The biological responses of airway smooth muscle (ASM) are diverse, in part due to ASM phenotype plasticity. ASM phenotype plasticity refers to the ability of ASM cells to change the degree of a variety of functions, including contractility, proliferation, migration and secretion of inflammatory

  7. Adaptation to different climates results in divergent phenotypic ...

    Indian Academy of Sciences (India)

    E-mail: bcbitner@biologia.ufrj.br. As a first approximation, the fact that the same genotype can produce different phenotypes might appear an obstacle to evolution by natural selection. It might, however, contribute to geographical adaptation itself, if there is genetic variation for plasticity. The way a phenotype behaves along ...

  8. Phenotypic plasticity and local adaptation in two extreme ...

    African Journals Online (AJOL)

    We investigated differences in adaptive phenotypic plasticity as well as local adaptations measured by reaction norms of two extreme populations (Leeu Gamka, arid Karoo and Richards Bay, subtropical coastal forest) of the extremely phenotypically plastic tree species Acacia karroo in a common-garden experiment.

  9. Chronic obstructive pulmonary disease phenotypes: the future of COPD

    DEFF Research Database (Denmark)

    Han, MeiLan K; Agusti, Alvar; Calverley, Peter M

    2010-01-01

    to clinical outcome is determined. Although this schema represents an ideal construct, we acknowledge any phenotype may be etiologically heterogeneous and that any one individual may manifest multiple phenotypes. We have much yet to learn, but establishing a common language for future research will facilitate...

  10. One gene, many phenotypes | Shawky | Egyptian Journal of Medical ...

    African Journals Online (AJOL)

    Phenotype descriptions are valuable information right at the interface of medicine and biology. With the rapid advancement in the fi eld of genetics, thousands of genes involved in human diseases have been cloned. It was expected that knowledge of mutations would lead to consistent genotype-phenotype correlations.

  11. Is there any relationship between haptoglobin phenotypes and ...

    African Journals Online (AJOL)

    This study was conducted to examine the possible association between Haptoglobin (Hp) phenotypes and diabetes retinopathy in some Ghanaians to determine whether a specific Hp phenotype predisposes diabetics to retinopathy. A total of 110 diabetics were enrolled into the study. Blood samples were taken from each ...

  12. Phenotypic plasticity and reaction norms of abdominal bristle ...

    Indian Academy of Sciences (India)

    Genetic correlations; growth temperature; heritability; isofemale lines; phenotypic correlation; reaction norms. Abstract. The phenotypic plasticity of abdominal bristle number (segments 3 and 4 in females) was investigated in 10 isofemale lines from a French population, grown at 7 constant temperatures, ranging from 12° to ...

  13. How phenotypic plasticity made its way into molecular biology

    Indian Academy of Sciences (India)

    2009-08-03

    Aug 3, 2009 ... Phenotypic plasticity has been fashionable in recent years. It has never been absent from the studies of evolutionary biologists, although the availability of stable animal models has limited its role. Although opposed by the reductionist and deterministic approach of molecular biology, phenotypic plasticity ...

  14. Distribution of Kell phenotype among pregnant women in Sokoto ...

    African Journals Online (AJOL)

    The distribution of Kell phenotype among the pregnant subjects was compared based on ethnicity. The prevalence of Kell antigen was significantly higher among the Hausa ethnic group (3.2%) compared to other ethnic groups which indicated zero prevalence (p=0.001). Kell negative phenotype was ≥ 96.8% among all the ...

  15. Migraine with prolonged aura: phenotype and treatment.

    Science.gov (United States)

    Viana, Michele; Afridi, Shazia

    2018-01-01

    We review the published literature on migraine with prolonged aura (PA), specifically with regards to the phenotype and treatment options. PA is not uncommon. A recent study found that about 17% of migraine auras are prolonged and that 26% of patients with migraine with aura have experienced at least one PA. The characteristics of PA are similar to most typical auras with the exception of a higher number of aura symptoms (in particular sensory and/or dysphasic). There are no well-established treatments at present which target the aura component of migraine. Other than case reports, there have been open-label studies of lamotrigine and greater occipital nerve blocks. The only randomised, blinded, controlled trial to date has been of nasal ketamine showing some reduction in aura severity but not duration. A small open-labelled pilot study of amiloride was also promising. Larger randomised, controlled trials are needed to establish whether any of the existing or novel compounds mentioned are significantly effective and safe.

  16. Switching between phenotypes and population extinction

    Science.gov (United States)

    Lohmar, Ingo; Meerson, Baruch

    2011-11-01

    Many types of bacteria can survive under stress by switching stochastically between two different phenotypes: the “normals” who multiply fast, but are vulnerable to stress, and the “persisters” who hardly multiply, but are resilient to stress. Previous theoretical studies of such bacterial populations have focused on the fitness: the asymptotic rate of unbounded growth of the population. Yet for an isolated population of established (and not very large) size, a more relevant measure may be the population extinction risk due to the interplay of adverse extrinsic variations and intrinsic noise of birth, death and switching processes. Applying a WKB approximation to the pertinent master equation of such a two-population system, we quantify the extinction risk, and find the most likely path to extinction under both favorable and adverse conditions. Analytical results are obtained both in the biologically relevant regime when the switching is rare compared with the birth and death processes, and in the opposite regime of frequent switching. We show that rare switches are most beneficial in reducing the extinction risk.

  17. The Metabolic Phenotype of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Eric Eidelman

    2017-06-01

    Full Text Available Prostate cancer is the most common non-cutaneous cancer in men in the United States. Cancer metabolism has emerged as a contemporary topic of great interest for improved mechanistic understanding of tumorigenesis. Prostate cancer is a disease model of great interest from a metabolic perspective. Prostatic tissue exhibits unique metabolic activity under baseline conditions. Benign prostate cells accumulate zinc, and this excess zinc inhibits citrate oxidation and metabolism within the citric acid cycle, effectively resulting in citrate production. Malignant cells, however, actively oxidize citrate and resume more typical citric acid cycle function. Of further interest, prostate cancer does not exhibit the Warburg effect, an increase in glucose uptake, seen in many other cancers. These cellular metabolic differences and others are of clinical interest as they present a variety of potential therapeutic targets. Furthermore, understanding of the metabolic profile differences between benign prostate versus low- and high-grade prostate cancers also represents an avenue to better understand cancer progression and potentially develop new diagnostic testing. In this paper, we review the current state of knowledge on the metabolic phenotypes of prostate cancer.

  18. Chromatin regulators, phenotypic robustness and autism risk

    Directory of Open Access Journals (Sweden)

    Reut eSuliman

    2014-04-01

    Full Text Available Though extensively characterized clinically, the causes of autism spectrum disorder (ASD remain a mystery. ASD is known to have a strong genetic basis, but it is genetically very heterogeneous. Recent studies have estimated that de novo disruptive mutations in hundreds of genes may contribute to ASD. However, it is unclear how it is possible for mutations in so many different genes to contribute to ASD. Recent findings suggest that many of the mutations disrupt genes involved in transcription regulation that are expressed prenatally in the developing brain. De novo disruptive mutations are also more frequent in girls with ASD, despite the fact that ASD is more prevalent in boys. In this paper, we hypothesize that loss of robustness may contribute to ASD. Loss of phenotypic robustness may be caused by mutations that disrupt capacitors that operate in the developing brain. This may lead to the release of cryptic genetic variation that contributes to ASD. Reduced robustness is consistent with the observed variability in expressivity and incomplete penetrance. It is also consistent with the hypothesis that the development of the female brain is more robust, and it may explain the higher rate and severity of disruptive de novo mutations in girls with ASD.

  19. Ameloblastoma Phenotypes Reflected in Distinct Transcriptome Profiles

    Science.gov (United States)

    Hu, Shijia; Parker, Joel; Divaris, Kimon; Padilla, Ricardo; Murrah, Valerie; Wright, John Timothy

    2016-01-01

    Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic epithelium and presents with diverse phenotypes yet to be characterized molecularly. High recurrence rates of 50–80% with conservative treatment in some sub-types warrants radical surgical resections resulting in high morbidity. The objective of the study was to characterize the transcriptome of ameloblastoma and identify relevant genes and molecular pathways using normal odontogenic tissue (human “dentome”) for comparison. Laser capture microdissection was used to obtain neoplastic epithelial tissue from 17 tumors which were examined using the Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct molecular clusters that were associated with pre-secretory ameloblast and odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the follicular type while 6/7 of the samples in the odontoblast cluster were of the plexiform type (p ameloblastoma sub-types and have implications for the use of tailored treatment. PMID:27491308

  20. The spatial patterns of directional phenotypic selection

    KAUST Repository

    Siepielski, Adam M.

    2013-09-12

    Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta-analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. © 2013 John Wiley & Sons Ltd/CNRS.

  1. [Phenotype characterization of environmental Cryptococcus neoformans isolates].

    Science.gov (United States)

    Huérfano, Sandra; Cepero, Maria Caridad; Castañeda, Elizabeth

    2003-09-01

    Cryptococcosis is caused by the three varieties of C. neoformans with physiological and virulence differences, some of which have been studied to determine biological aspects of this microorganism. The phenotypical aspects of environmental isolates from varieties grubii and gattii were evaluated to establish differences associated with their life cycle and virulence. To this end, 28 and 31 strains of C. neoformans serotypes A (var. grubii) and C (var. gattii) were studied. The microscopic and macroscopic morphology on Sabouraud agar and soils, growth rate at 37 degrees C, production of 22 extracellular enzymes, haploid fructification, mating type, killer toxin sensitivity patterns and virulence in BALB/c mice were evaluated. No differences were observed between the two varieties regarding microscopic and macroscopic morphology or growth at 37 degrees C (p > 0.05). However, a decrease in the cellular and capsular sizes of yeast in soil, as compared to Sabouraud, was observed (p enzimatic activity of proteases, phospholipases, phenoloxidase and beta-glucosidase was observed in var. grubii isolates as compared to var. gattii (p enzimatic activity of var. grubii can be associated with the virulence in the animal model.

  2. Phenotyping cowpeas for adaptation to drought.

    Science.gov (United States)

    Hall, Anthony E

    2012-01-01

    Methods for phenotyping cowpeas for adaptation to drought are reviewed. Key factors involve achieving optimal time of flowering and cycle length, and appropriate morphology for different types of cultivars as they relate to their utilization for dry grain, hay, and fresh pea production. Strong resistance to vegetative-stage drought is available and should be incorporated. The extreme ability of extra-early erect cowpea cultivars to escape terminal drought should be exploited in zones with very short rainfall seasons. In zones with the possibility of limited rainfall in the middle of the growing season, resistance to mid-season drought, and the delayed-leaf-senescence trait can be valuable. Breeding for water-use efficiency, deeper rooting, and heat tolerance are discussed. Diseases and pests that influence adaptation to drought are considered. Resistance to the organism causing ashy stem blight disease should be incorporated because this disease can destroy cowpea seedlings under hot, dry soil conditions. The value of varietal intercrops with contrasting types of cowpea cultivars in enhancing adaptation to drought is described. Implications of cowpea/cereal rotations for cowpea breeding are discussed. Breeding strategies for enhancing cowpea adaptation to drought are described.

  3. A review of imaging techniques for plant phenotyping.

    Science.gov (United States)

    Li, Lei; Zhang, Qin; Huang, Danfeng

    2014-10-24

    Given the rapid development of plant genomic technologies, a lack of access to plant phenotyping capabilities limits our ability to dissect the genetics of quantitative traits. Effective, high-throughput phenotyping platforms have recently been developed to solve this problem. In high-throughput phenotyping platforms, a variety of imaging methodologies are being used to collect data for quantitative studies of complex traits related to the growth, yield and adaptation to biotic or abiotic stress (disease, insects, drought and salinity). These imaging techniques include visible imaging (machine vision), imaging spectroscopy (multispectral and hyperspectral remote sensing), thermal infrared imaging, fluorescence imaging, 3D imaging and tomographic imaging (MRT, PET and CT). This paper presents a brief review on these imaging techniques and their applications in plant phenotyping. The features used to apply these imaging techniques to plant phenotyping are described and discussed in this review.

  4. Design of synthetic bacterial communities for predictable plant phenotypes.

    Science.gov (United States)

    Herrera Paredes, Sur; Gao, Tianxiang; Law, Theresa F; Finkel, Omri M; Mucyn, Tatiana; Teixeira, Paulo José Pereira Lima; Salas González, Isaí; Feltcher, Meghan E; Powers, Matthew J; Shank, Elizabeth A; Jones, Corbin D; Jojic, Vladimir; Dangl, Jeffery L; Castrillo, Gabriel

    2018-02-01

    Specific members of complex microbiota can influence host phenotypes, depending on both the abiotic environment and the presence of other microorganisms. Therefore, it is challenging to define bacterial combinations that have predictable host phenotypic outputs. We demonstrate that plant-bacterium binary-association assays inform the design of small synthetic communities with predictable phenotypes in the host. Specifically, we constructed synthetic communities that modified phosphate accumulation in the shoot and induced phosphate starvation-responsive genes in a predictable fashion. We found that bacterial colonization of the plant is not a predictor of the plant phenotypes we analyzed. Finally, we demonstrated that characterizing a subset of all possible bacterial synthetic communities is sufficient to predict the outcome of untested bacterial consortia. Our results demonstrate that it is possible to infer causal relationships between microbiota membership and host phenotypes and to use these inferences to rationally design novel communities.

  5. Plant phenotyping: from bean weighing to image analysis.

    Science.gov (United States)

    Walter, Achim; Liebisch, Frank; Hund, Andreas

    2015-01-01

    Plant phenotyping refers to a quantitative description of the plant's anatomical, ontogenetical, physiological and biochemical properties. Today, rapid developments are taking place in the field of non-destructive, image-analysis -based phenotyping that allow for a characterization of plant traits in high-throughput. During the last decade, 'the field of image-based phenotyping has broadened its focus from the initial characterization of single-plant traits in controlled conditions towards 'real-life' applications of robust field techniques in plant plots and canopies. An important component of successful phenotyping approaches is the holistic characterization of plant performance that can be achieved with several methodologies, ranging from multispectral image analyses via thermographical analyses to growth measurements, also taking root phenotypes into account.

  6. A Review of Imaging Techniques for Plant Phenotyping

    Directory of Open Access Journals (Sweden)

    Lei Li

    2014-10-01

    Full Text Available Given the rapid development of plant genomic technologies, a lack of access to plant phenotyping capabilities limits our ability to dissect the genetics of quantitative traits. Effective, high-throughput phenotyping platforms have recently been developed to solve this problem. In high-throughput phenotyping platforms, a variety of imaging methodologies are being used to collect data for quantitative studies of complex traits related to the growth, yield and adaptation to biotic or abiotic stress (disease, insects, drought and salinity. These imaging techniques include visible imaging (machine vision, imaging spectroscopy (multispectral and hyperspectral remote sensing, thermal infrared imaging, fluorescence imaging, 3D imaging and tomographic imaging (MRT, PET and CT. This paper presents a brief review on these imaging techniques and their applications in plant phenotyping. The features used to apply these imaging techniques to plant phenotyping are described and discussed in this review.

  7. A Review of Imaging Techniques for Plant Phenotyping

    Science.gov (United States)

    Li, Lei; Zhang, Qin; Huang, Danfeng

    2014-01-01

    Given the rapid development of plant genomic technologies, a lack of access to plant phenotyping capabilities limits our ability to dissect the genetics of quantitative traits. Effective, high-throughput phenotyping platforms have recently been developed to solve this problem. In high-throughput phenotyping platforms, a variety of imaging methodologies are being used to collect data for quantitative studies of complex traits related to the growth, yield and adaptation to biotic or abiotic stress (disease, insects, drought and salinity). These imaging techniques include visible imaging (machine vision), imaging spectroscopy (multispectral and hyperspectral remote sensing), thermal infrared imaging, fluorescence imaging, 3D imaging and tomographic imaging (MRT, PET and CT). This paper presents a brief review on these imaging techniques and their applications in plant phenotyping. The features used to apply these imaging techniques to plant phenotyping are described and discussed in this review. PMID:25347588

  8. Relationship among phenotypic plasticity, phenotypic fluctuations, robustness, and evolvability; Waddington's legacy revisited under the spirit of Einstein.

    Science.gov (United States)

    Kaneko, Kunihiko

    2009-10-01

    Questions on possible relationship between phenotypic plasticity and evolvability, and that between robustness and evolution have been addressed over decades in the field of evolution-development. Based on laboratory evolution experiments and numerical simulations of gene expression dynamics model with an evolving transcription network, we propose quantitative relationships on plasticity, phenotypic fluctuations, and evolvability. By introducing an evolutionary stability assumption on the distribution of phenotype and genotype, the proportionality among phenotypic plasticity against environmental change, variances of phenotype fluctuations of genetic and developmental origins, and evolution speed is obtained. The correlation between developmental robustness to noise and evolutionary robustness to mutation is analysed by simulations of the gene network model. These results provide quantitative formulation on canalization and genetic assimilation, in terms of fluctuations of gene expression levels.

  9. A mathematical model of cancer cells with phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Da Zhou

    2015-12-01

    Full Text Available Purpose: The phenotypic plasticity of cancer cells is recently becoming a cutting-edge research area in cancer, which challenges the cellular hierarchy proposed by the conventional cancer stem cell theory. In this study, we establish a mathematical model for describing the phenotypic plasticity of cancer cells, based on which we try to find some salient features that can characterize the dynamic behavior of the phenotypic plasticity especially in comparison to the hierarchical model of cancer cells. Methods: We model cancer as population dynamics composed of different phenotypes of cancer cells. In this model, not only can cancer cells divide (symmetrically and asymmetrically and die, but they can also convert into other cellular phenotypes. According to the Law of Mass Action, the cellular processes can be captured by a system of ordinary differential equations (ODEs. On one hand, we can analyze the long-term stability of the model by applying qualitative method of ODEs. On the other hand, we are also concerned about the short-term behavior of the model by studying its transient dynamics. Meanwhile, we validate our model to the cell-state dynamics in published experimental data.Results: Our results show that the phenotypic plasticity plays important roles in both stabilizing the distribution of different phenotypic mixture and maintaining the cancer stem cells proportion. In particular, the phenotypic plasticity model shows decided advantages over the hierarchical model in predicting the phenotypic equilibrium and cancer stem cells’ overshoot reported in previous biological experiments in cancer cell lines.Conclusion: Since the validity of the phenotypic plasticity paradigm and the conventional cancer stem cell theory is still debated in experimental biology, it is worthy of theoretically searching for good indicators to distinguish the two models through quantitative methods. According to our study, the phenotypic equilibrium and overshoot

  10. High throughput phenotypic analysis of Mycobacterium tuberculosis and Mycobacterium bovis strains' metabolism using biolog phenotype microarrays.

    Directory of Open Access Journals (Sweden)

    Bhagwati Khatri

    Full Text Available Tuberculosis is a major human and animal disease of major importance worldwide. Genetically, the closely related strains within the Mycobacterium tuberculosis complex which cause disease are well-characterized but there is an urgent need better to understand their phenotypes. To search rapidly for metabolic differences, a working method using Biolog Phenotype MicroArray analysis was developed. Of 380 substrates surveyed, 71 permitted tetrazolium dye reduction, the readout over 7 days in the method. By looking for ≥5-fold differences in dye reduction, 12 substrates differentiated M. tuberculosis H37Rv and Mycobacterium bovis AF2122/97. H37Rv and a Beijing strain of M. tuberculosis could also be distinguished in this way, as could field strains of M. bovis; even pairs of strains within one spoligotype could be distinguished by 2 to 3 substrates. Cluster analysis gave three clear groups: H37Rv, Beijing, and all the M. bovis strains. The substrates used agreed well with prior knowledge, though an unexpected finding that AF2122/97 gave greater dye reduction than H37Rv with hexoses was investigated further, in culture flasks, revealing that hexoses and Tween 80 were synergistic for growth and used simultaneously rather than in a diauxic fashion. Potential new substrates for growth media were revealed, too, most promisingly N-acetyl glucosamine. Osmotic and pH arrays divided the mycobacteria into two groups with different salt tolerance, though in contrast to the substrate arrays the groups did not entirely correlate with taxonomic differences. More interestingly, these arrays suggested differences between the amines used by the M. tuberculosis complex and enteric bacteria in acid tolerance, with some hydrophobic amino acids being highly effective. In contrast, γ-aminobutyrate, used in the enteric bacteria, had no effect in the mycobacteria. This study proved principle that Phenotype MicroArrays can be used with slow-growing pathogenic mycobacteria

  11. Facial phenotypes in subgroups of prepubertal boys with autism spectrum disorders are correlated with clinical phenotypes

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    Aldridge Kristina

    2011-10-01

    Full Text Available Abstract Background The brain develops in concert and in coordination with the developing facial tissues, with each influencing the development of the other and sharing genetic signaling pathways. Autism spectrum disorders (ASDs result from alterations in the embryological brain, suggesting that the development of the faces of children with ASD may result in subtle facial differences compared to typically developing children. In this study, we tested two hypotheses. First, we asked whether children with ASD display a subtle but distinct facial phenotype compared to typically developing children. Second, we sought to determine whether there are subgroups of facial phenotypes within the population of children with ASD that denote biologically discrete subgroups. Methods The 3dMD cranial System was used to acquire three-dimensional stereophotogrammetric images for our study sample of 8- to 12-year-old boys diagnosed with essential ASD (n = 65 and typically developing boys (n = 41 following approved Institutional Review Board protocols. Three-dimensional coordinates were recorded for 17 facial anthropometric landmarks using the 3dMD Patient software. Statistical comparisons of facial phenotypes were completed using Euclidean Distance Matrix Analysis and Principal Coordinates Analysis. Data representing clinical and behavioral traits were statistically compared among groups by using χ2 tests, Fisher's exact tests, Kolmogorov-Smirnov tests and Student's t-tests where appropriate. Results First, we found that there are significant differences in facial morphology in boys with ASD compared to typically developing boys. Second, we also found two subgroups of boys with ASD with facial morphology that differed from the majority of the boys with ASD and the typically developing boys. Furthermore, membership in each of these distinct subgroups was correlated with particular clinical and behavioral traits. Conclusions Boys with ASD display a facial phenotype

  12. Population FBA predicts metabolic phenotypes in yeast.

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    Piyush Labhsetwar

    2017-09-01

    Full Text Available Using protein counts sampled from single cell proteomics distributions to constrain fluxes through a genome-scale model of metabolism, Population flux balance analysis (Population FBA successfully described metabolic heterogeneity in a population of independent Escherichia coli cells growing in a defined medium. We extend the methodology to account for correlations in protein expression arising from the co-regulation of genes and apply it to study the growth of independent Saccharomyces cerevisiae cells in two different growth media. We find the partitioning of flux between fermentation and respiration predicted by our model agrees with recent 13C fluxomics experiments, and that our model largely recovers the Crabtree effect (the experimentally known bias among certain yeast species toward fermentation with the production of ethanol even in the presence of oxygen, while FBA without proteomics constraints predicts respirative metabolism almost exclusively. The comparisons to the 13C study showed improvement upon inclusion of the correlations and motivated a technique to systematically identify inconsistent kinetic parameters in the literature. The minor secretion fluxes for glycerol and acetate are underestimated by our method, which indicate a need for further refinements to the metabolic model. For yeast cells grown in synthetic defined (SD medium, the calculated broad distribution of growth rates matches experimental observations from single cell studies, and we characterize several metabolic phenotypes within our modeled populations that make use of diverse pathways. Fast growing yeast cells are predicted to perform significant amount of respiration, use serine-glycine cycle and produce ethanol in mitochondria as opposed to slow growing cells. We use a genetic algorithm to determine the proteomics constraints necessary to reproduce the growth rate distributions seen experimentally. We find that a core set of 51 constraints are essential but

  13. Phenotypic heterogeneity in modeling cancer evolution.

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    Ali Mahdipour-Shirayeh

    Full Text Available The unwelcome evolution of malignancy during cancer progression emerges through a selection process in a complex heterogeneous population structure. In the present work, we investigate evolutionary dynamics in a phenotypically heterogeneous population of stem cells (SCs and their associated progenitors. The fate of a malignant mutation is determined not only by overall stem cell and non-stem cell growth rates but also differentiation and dedifferentiation rates. We investigate the effect of such a complex population structure on the evolution of malignant mutations. We derive exactly calculated results for the fixation probability of a mutant arising in each of the subpopulations. The exactly calculated results are in almost perfect agreement with the numerical simulations. Moreover, a condition for evolutionary advantage of a mutant cell versus the wild type population is given in the present study. We also show that microenvironment-induced plasticity in invading mutants leads to more aggressive mutants with higher fixation probability. Our model predicts that decreasing polarity between stem and non-stem cells' turnover would raise the survivability of non-plastic mutants; while it would suppress the development of malignancy for plastic mutants. The derived results are novel and general with potential applications in nature; we discuss our model in the context of colorectal/intestinal cancer (at the epithelium. However, the model clearly needs to be validated through appropriate experimental data. This novel mathematical framework can be applied more generally to a variety of problems concerning selection in heterogeneous populations, in other contexts such as population genetics, and ecology.

  14. NGF steers microglia toward a neuroprotective phenotype.

    Science.gov (United States)

    Rizzi, Caterina; Tiberi, Alexia; Giustizieri, Michela; Marrone, Maria Cristina; Gobbo, Francesco; Carucci, Nicola Maria; Meli, Giovanni; Arisi, Ivan; D'Onofrio, Mara; Marinelli, Silvia; Capsoni, Simona; Cattaneo, Antonino

    2018-02-23

    Microglia are the sentinels of the brain but a clear understanding of the factors that modulate their activation in physiological and pathological conditions is still lacking. Here we demonstrate that Nerve Growth Factor (NGF) acts on microglia by steering them toward a neuroprotective and anti-inflammatory phenotype. We show that microglial cells express functional NGF receptors in vitro and ex vivo. Our transcriptomic analysis reveals how, in primary microglia, NGF treatment leads to a modulation of motility, phagocytosis and degradation pathways. At the functional level, NGF induces an increase in membrane dynamics and macropinocytosis and, in vivo, it activates an outward rectifying current that appears to modulate glutamatergic neurotransmission in nearby neurons. Since microglia are supposed to be a major player in Aβ peptide clearance in the brain, we tested the effects of NGF on its phagocytosis. NGF was shown to promote TrkA-mediated engulfment of Aβ by microglia, and to enhance its degradation. Additionally, the proinflammatory activation induced by Aβ treatment is counteracted by the concomitant administration of NGF. Moreover, by acting specifically on microglia, NGF protects neurons from the Aβ-induced loss of dendritic spines and inhibition of long term potentiation. Finally, in an ex-vivo setup of acute brain slices, we observed a similar increase in Aβ engulfment by microglial cells under the influence of NGF. Our work substantiates a role for NGF in the regulation of microglial homeostatic activities and points toward this neurotrophin as a neuroprotective agent in Aβ accumulation pathologies, via its anti-inflammatory activity on microglia. © 2018 The Authors GLIA Published by Wiley Periodicals, Inc.

  15. Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders.

    Directory of Open Access Journals (Sweden)

    Tallulah Andrews

    2015-03-01

    Full Text Available Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far behind. Exploiting deep and systematic phenotyping of a cohort of 197 patients presenting with heterogeneous developmental disorders and whose genomes harbour de novo CNVs, we systematically applied a range of commonly-used functional genomics approaches to identify the underlying molecular perturbations and their phenotypic impact. Grouping patients into 408 non-exclusive patient-phenotype groups, we identified a functional association amongst the genes disrupted in 209 (51% groups. We find evidence for a significant number of molecular interactions amongst the association-contributing genes, including a single highly-interconnected network disrupted in 20% of patients with intellectual disability, and show using microcephaly how these molecular networks can be used as baits to identify additional members whose genes are variant in other patients with the same phenotype. Exploiting the systematic phenotyping of this cohort, we observe phenotypic concordance amongst patients whose variant genes contribute to the same functional association but note that (i this relationship shows significant variation across the different approaches used to infer a commonly perturbed molecular pathway, and (ii that the phenotypic similarities detected amongst patients who share the same inferred pathway perturbation result from these patients sharing many distinct phenotypes, rather than sharing a more specific phenotype, inferring that these pathways are best characterized by their pleiotropic effects.

  16. Phenotype ontologies and cross-species analysis for translational research.

    Directory of Open Access Journals (Sweden)

    Peter N Robinson

    2014-04-01

    Full Text Available The use of model organisms as tools for the investigation of human genetic variation has significantly and rapidly advanced our understanding of the aetiologies underlying hereditary traits. However, while equivalences in the DNA sequence of two species may be readily inferred through evolutionary models, the identification of equivalence in the phenotypic consequences resulting from comparable genetic variation is far from straightforward, limiting the value of the modelling paradigm. In this review, we provide an overview of the emerging statistical and computational approaches to objectively identify phenotypic equivalence between human and model organisms with examples from the vertebrate models, mouse and zebrafish. Firstly, we discuss enrichment approaches, which deem the most frequent phenotype among the orthologues of a set of genes associated with a common human phenotype as the orthologous phenotype, or phenolog, in the model species. Secondly, we introduce and discuss computational reasoning approaches to identify phenotypic equivalences made possible through the development of intra- and interspecies ontologies. Finally, we consider the particular challenges involved in modelling neuropsychiatric disorders, which illustrate many of the remaining difficulties in developing comprehensive and unequivocal interspecies phenotype mappings.

  17. Proportion of Rh phenotypes in voluntary blood donors.

    Science.gov (United States)

    Sarkar, R S; Philip, Joseph; Mallhi, R S; Yadav, Pramod

    2013-10-01

    The Rh system is the major blood group system besides ABO system. Even after proper blood grouping and cross matching there is a possibility of alloimmunization and antibody production in the recipients against the Rh or minor blood group antigens like Kell, MNSs, Duffy etc. Keeping in view the heavy financial burden of complete phenotyping of blood; the determination of only Rh phenotypes can play a major role in preventing alloimmunization and adverse events in multitransfusion cases. To determine the proportion of Rh phenotypes in voluntary blood donors with a view to generate blood bank data for constitution of panel of blood donors for multipurpose utilities. Identification of Rhesus factors (Rh) was done by the antigen antibody agglutination test by the test tube method on 10,133 healthy voluntary donors. The phenotypic frequencies of Rh blood groups in the studied population were D-92.25%, C-87.55%, E-26.55%, c-51.06% and e-98.42%. Thus 'e' was the most common and E was the least common of all the Rh types. Phenotypically DCCee group was the most common phenotype and dccee was least common type. Determination of Rh phenotypes can play a major role in preventing alloimmunization and avoiding adverse events in multitransfusion cases.

  18. Microbial genotype-phenotype mapping by class association rule mining.

    Science.gov (United States)

    Tamura, Makio; D'haeseleer, Patrik

    2008-07-01

    Microbial phenotypes are typically due to the concerted action of multiple gene functions, yet the presence of each gene may have only a weak correlation with the observed phenotype. Hence, it may be more appropriate to examine co-occurrence between sets of genes and a phenotype (multiple-to-one) instead of pairwise relations between a single gene and the phenotype. Here, we propose an efficient class association rule mining algorithm, netCAR, in order to extract sets of COGs (clusters of orthologous groups of proteins) associated with a phenotype from COG phylogenetic profiles and a phenotype profile. netCAR takes into account the phylogenetic co-occurrence graph between COGs to restrict hypothesis space, and uses mutual information to evaluate the biconditional relation. We examined the mining capability of pairwise and multiple-to-one association by using netCAR to extract COGs relevant to six microbial phenotypes (aerobic, anaerobic, facultative, endospore, motility and Gram negative) from 11,969 unique COG profiles across 155 prokaryotic organisms. With the same level of false discovery rate, multiple-to-one association can extract about 10 times more relevant COGs than one-to-one association. We also reveal various topologies of association networks among COGs (modules) from extracted multiple-to-one correlation rules relevant with the six phenotypes; including a well-connected network for motility, a star-shaped network for aerobic and intermediate topologies for the other phenotypes. netCAR outperforms a standard CAR mining algorithm, CARapriori, while requiring several orders of magnitude less computational time for extracting 3-COG sets. Source code of the Java implementation is available as Supplementary Material at the Bioinformatics online website, or upon request to the author. Supplementary data are available at Bioinformatics online.

  19. Enabling phenotypic big data with PheNorm.

    Science.gov (United States)

    Yu, Sheng; Ma, Yumeng; Gronsbell, Jessica; Cai, Tianrun; Ananthakrishnan, Ashwin N; Gainer, Vivian S; Churchill, Susanne E; Szolovits, Peter; Murphy, Shawn N; Kohane, Isaac S; Liao, Katherine P; Cai, Tianxi

    2018-01-01

    Electronic health record (EHR)-based phenotyping infers whether a patient has a disease based on the information in his or her EHR. A human-annotated training set with gold-standard disease status labels is usually required to build an algorithm for phenotyping based on a set of predictive features. The time intensiveness of annotation and feature curation severely limits the ability to achieve high-throughput phenotyping. While previous studies have successfully automated feature curation, annotation remains a major bottleneck. In this paper, we present PheNorm, a phenotyping algorithm that does not require expert-labeled samples for training. The most predictive features, such as the number of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes or mentions of the target phenotype, are normalized to resemble a normal mixture distribution with high area under the receiver operating curve (AUC) for prediction. The transformed features are then denoised and combined into a score for accurate disease classification. We validated the accuracy of PheNorm with 4 phenotypes: coronary artery disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. The AUCs of the PheNorm score reached 0.90, 0.94, 0.95, and 0.94 for the 4 phenotypes, respectively, which were comparable to the accuracy of supervised algorithms trained with sample sizes of 100-300, with no statistically significant difference. The accuracy of the PheNorm algorithms is on par with algorithms trained with annotated samples. PheNorm fully automates the generation of accurate phenotyping algorithms and demonstrates the capacity for EHR-driven annotations to scale to the next level - phenotypic big data. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  20. Metformin treatment in different phenotypes of polycystic ovary syndrome.

    Science.gov (United States)

    Hosseini, Marzieh Agha; Alleyassin, Ashraf; Sarvi, Fatemeh; Safdarian, Leila; Kokab, Abas; Fanisalek, Mehran

    2013-11-01

    The aim of this study was to evaluate the effectiveness of Metformin on ovulation and eventual clinical pregnancy in different phenotypes of polycystic ovary syndrome (PCOS). A total of 359 subjects who had proven PCOS according to Rotterdam criteria were prospectively selected. Patients' PCOS phenotypes were determined and recorded. All patients were younger than 35 years. Clinical and biochemical assays in all patients were initially obtained. Then patients were divided into two separate groups. One group received both 1,500 mg of Metformin and 1 mg of folic acid per day and the other group received only 1 mg of folic acid for a total of 2 months. Subsequently, all patients underwent ovulation stimulation with 5 mg of Letrozole per day for 5 days followed by an intra-uterine insemination. Finally, ovulation and pregnancy rates were evaluated for all four PCOS phenotypes. Effect of Metformin therapy was evaluated for each group and each phenotype. The pregnancy rate in Metformin and non-Metformin groups were, respectively, as follows: in phenotype A (39.2 vs. 33.7 %, p = 0.270), phenotype B (43.8 vs. 20 %, p = 0.210), phenotype C (44 vs. 20 %, p = 0.064), and phenotype D (36.5 vs. 28.6 %, p = 0.279). Although there was a little improvement in ovulation and pregnancy rates among patients with B and C phenotypes, there was not a statistically significant difference between the two groups. Based on our study, Metformin therapy does not change the ovulation and pregnancy rate.

  1. Evaluation of pyridoacridine alkaloids in a zebrafish phenotypic assay.

    Science.gov (United States)

    Wei, Xiaomei; Bugni, Tim S; Harper, Mary Kay; Sandoval, Imelda T; Manos, Elizabeth J; Swift, Jennifer; Van Wagoner, Ryan M; Jones, David A; Ireland, Chris M

    2010-06-02

    Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1), 3-hydroxy-deoxyamphimedine (2), debromopetrosamine (3), and three known compounds, amphimedine (4), neoamphimedine (5) and deoxyamphimedine (6), have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1-6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4) was the only compound that caused a phenotype in zebrafish embryos at 30 muM. No phenotype other than death was observed for compounds 1-3, 5, 6.

  2. Evaluation of Pyridoacridine Alkaloids in a Zebrafish Phenotypic Assay

    Directory of Open Access Journals (Sweden)

    Xiaomei Wei

    2010-06-01

    Full Text Available Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1, 3-hydroxy-deoxyamphimedine (2, debromopetrosamine (3, and three known compounds, amphimedine (4, neoamphimedine (5 and deoxyamphimedine (6, have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1–6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4 was the only compound that caused a phenotype in zebrafish embryos at 30 µM. No phenotype other than death was observed for compounds 1–3, 5, 6.

  3. Mitochondrial Haplogroups Define Two Phenotypes of Osteoarthritis

    Science.gov (United States)

    Fernández-Moreno, Mercedes; Soto-Hermida, Angel; Oreiro, Natividad; Pértega, Sonia; Fenández-López, Carlos; Rego-Pérez, Ignacio; Blanco, Francisco J.

    2012-01-01

    Objective: To assess a mitochondrion-related phenotype in patients with osteoarthritis (OA). Methods: Serum levels of the following OA-related biomarkers: matrix metalloproteinase-1 (MMP-1); MMP-3; MMP-13; myeloperoxidase (MPO); a peptide of the alpha-helical region of type II collagen, Coll2-1, and its nitrated form Coll2-1NO2; a C-terminal neoepitope generated by the collagenase-mediated cleavage of collagen type II triple helix, C2C; the C-propeptide of collagen type II, CPII; hyaluronic acid (HA); human cartilage glycoprotein 39, YKL-40; cartilage oligomeric matrix protein; and cathepsin K were analyzed in 48 OA patients and 52 healthy controls carrying the haplogroups H and J. Logistic regression models and receiver operating characteristic (ROC) curves were performed to predict the onset of OA. Results: MMP-13 was the only biomarker significantly increased in OA patients compared to healthy controls in both haplogroups H and J. The collagen type II biomarkers, Coll2-1, Coll2-1NO2, the Coll2-1NO2/Coll2-1 ratio, C2C, CPII, and the C2C:CPII ratio were significantly increased in OA patients carrying haplogroup H compared to OA carriers of the haplogroup J. Two logistic regression models for diagnosis were constructed and adjusted for age, gender, and body mass index. For haplogroup H, the biomarkers significantly associated with OA were MMP-13 and Coll2-1; the area under the curve (AUC) of the ROC curve for this model was 0.952 (95% CI = 0.892–1.012). For haplogroup J, the only biomarker significantly associated with OA was MMP-13; the AUC for this model was 0.895 (95% CI = 0.801–0.989). Conclusion: The mitochondrial DNA haplogroups are potential complementary candidates for biomarkers of OA; their genotyping in conjunction with the assessment of classical protein molecular markers is recommended. PMID:22593743

  4. HLA phenotype polymorphism in the Lebanese population.

    Science.gov (United States)

    Mansour, I; Klaymé, S; Naman, R; Loiselet, J; Hallé, L; Kaplan, C

    1996-01-01

    The HLA-A, -B, -DR and DQ phenotypes have been defined in a panel of 217 Lebanese. These subjects were all unrelated, belonged to different religious communities and originated from the various provinces of Lebanon. All the broad class I specificities tested, except splits A25(10), B54(22) and B56(22), were present in this panel. When HLA-A and -B antigen frequencies were compared with data on the Caucasoids, Negroids and Orientals, several similarities in antigen frequencies could be found between some frequencies observed in the Lebanese and those observed in the Negroids and/or Orientals. There were no frequencies equivalent to those particular to the Caucasoids. In addition, two groups of class I antigens could be distinguished: a first group (A32, B14, B18, B35, B38, B39, B41 and B50) showing higher frequencies, and a second group (A31, B27, B60 and B62) showing lower frequencies than those observed in the Caucasoids, Negroids and Orientals. However, when analysed separately, several mediterranean ethnic groups, notably the Greeks and Italians, have a frequency profile equivalent to that of the Lebanese, with the exception of the B41 specificity, which is particularly high in the Lebanese (14.2%). The data concerning the class II antigens are the most interesting. All the specificities were present in the panel. The HLA-DR5 is the highest frequency of DR antigens in the present panel (58.9%) and nearly all DR5 positive individuals are DR11. The DR11 allele accounts for 33.1% of the total DR gene frequency. The highest DQ antigen frequency is that of DQ3 (76.4%), the majority of which is DQ7 (66.4%). We observed a high DR11-DQ7 haplotype frequency (29.4%) with a significant delta value for linkage disequilibrium. There is no linkage disequilibrium between B41 and DR11. The commonly observed linkage disequilibrium between the DQ5 allele, and the DR1, DR2, DR10 and DR14 alleles are not significant in this Lebanese panel.

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

    Directory of Open Access Journals (Sweden)

    Michael Hiller

    2012-10-01

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

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

    Science.gov (United States)

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

    2017-12-10

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

  7. Modeling Phenotypes of Tuberous Scerosis in the Mouse

    National Research Council Canada - National Science Library

    Shipley, James M

    2007-01-01

    The overall goal of this project is to generate a mouse model of the smooth muscle-related facets of tuberous sclerosis, specifically in an attempt to model the lung phenotype seen in a subset of TS...

  8. Modeling Phenotypes of Tuberous Sclerosis in the Mouse

    National Research Council Canada - National Science Library

    Shipley, James M

    2006-01-01

    The overall goal of this project is to generate a mouse model of the smooth muscle-related facets of tuberous sclerosis specifically in an attempt to model the lung phenotype seen in a subset of TS...

  9. TSC2 Happloinsufficiency Leads to a Mutator Phenotype

    National Research Council Canada - National Science Library

    Walker, Cheryl

    2007-01-01

    .... The goal of this award was to determine whether Tsc2 haploinsufficiency generated a mutator phenotype in target tissues in vivo that possibly contributed to early events in tumorigenesis within TSC2...

  10. TSC2 Happloinsufficiency Leads to a Mutator Phenotype

    National Research Council Canada - National Science Library

    Short, John D

    2006-01-01

    .... The goal of this award was to determine whether Tsc2 haploinsufficiency generated a mutator phenotype in target tissues in vivo that possibly contributed to early events in tumorigenesis within TSC2...

  11. Behavioral phenotyping of minipigs transgenic for the Huntington gene

    Czech Academy of Sciences Publication Activity Database

    Schramke, S.; Schuldenzucker, V.; Schubert, R.; Frank, F.; Wirsig, M.; Ott, S.; Motlík, Jan; Fels, M.; Kemper, N.; Hölzner, E.; Reilmann, R.

    2016-01-01

    Roč. 265, S1 (2016), s. 34-45 ISSN 0165-0270 Institutional support: RVO:67985904 Keywords : animal models * minipig * phenotyping * behavioral * motor Subject RIV: FH - Neurology Impact factor: 2.554, year: 2016

  12. Differential Impact of Lactose/Lactase Phenotype on Colonic Microflora

    Directory of Open Access Journals (Sweden)

    Andrew Szilagyi

    2010-01-01

    Full Text Available BACKGROUND: The ability to digest lactose divides the world’s population into two phenotypes that may be risk variability markers for several diseases. Prebiotic effects likely favour lactose maldigesters who experience lactose spilling into their colon.

  13. distribution and phenotypic variability aspects of some quantitative ...

    African Journals Online (AJOL)

    Administrator

    DISTRIBUTION AND PHENOTYPIC VARIABILITY ASPECTS OF SOME QUANTITATIVE. TRAITS AMONG DURUM WHEAT A CCESSIONS. AYED SOUROUR and SLIM-AMARA HAJER. Genetic and Plant Breeding Laboratory, Department of Agronomy and Biotechnology. National Agronomic. Institute of Tunisia.

  14. Chronic obstructive pulmonary disease phenotypes: the future of COPD

    DEFF Research Database (Denmark)

    Han, MeiLan K; Agusti, Alvar; Calverley, Peter M

    2010-01-01

    , propose the following variation on this definition: "a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression, or death)." This more......Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although FEV(1) inadequately describes this heterogeneity, a clear alternative has not emerged. The goal of phenotyping is to identify patient groups with unique...... prognostic or therapeutic characteristics, but significant variation and confusion surrounds use of the term "phenotype" in COPD. Phenotype classically refers to any observable characteristic of an organism, and up until now, multiple disease characteristics have been termed COPD phenotypes. We, however...

  15. The duplication 17p13.3 phenotype

    DEFF Research Database (Denmark)

    Curry, Cynthia J; Rosenfeld, Jill A; Grant, Erica

    2013-01-01

    . Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype......Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34...... was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome....

  16. Estimating the variation, autocorrelation, and environmental sensitivity of phenotypic selection

    NARCIS (Netherlands)

    Chevin, Luis-Miguel; Visser, Marcel E.; Tufto, Jarle

    Despite considerable interest in temporal and spatial variation of phenotypic selection, very few methods allow quantifying this variation while correctly accounting for the error variance of each individual estimate. Furthermore, the available methods do not estimate the autocorrelation of

  17. Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

    DEFF Research Database (Denmark)

    Song, Yong; Schwager, Michelle J; Backer, Vibeke

    2017-01-01

    The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically s...

  18. The genotypic and phenotypic spectrum of MTO1 deficiency

    NARCIS (Netherlands)

    O'Byrne, James J.; Tarailo-Graovac, Maja; Ghani, Aisha; Champion, Michael; Deshpande, Charu; Dursun, Ali; Ozgul, Riza K.; Freisinger, Peter; Garber, Ian; Haack, Tobias B.; Horvath, Rita; Barić, Ivo; Husain, Ralf A.; Kluijtmans, Leo A. J.; Kotzaeridou, Urania; Morris, Andrew A.; Ross, Colin J.; Santra, Saikat; Smeitink, Jan; Tarnopolsky, Mark; Wortmann, Saskia B.; Mayr, Johannes A.; Brunner-Krainz, Michaela; Prokisch, Holger; Wasserman, Wyeth W.; Wevers, Ron A.; Engelke, Udo F.; Rodenburg, Richard J.; Ting, Teck Wah; McFarland, Robert; Taylor, Robert W.; Salvarinova, Ramona; van Karnebeek, Clara D. M.

    2018-01-01

    Background: Mitochondrial diseases, a group of multi-systemic disorders often characterized by tissue-specific phenotypes, are usually progressive and fatal disorders resulting from defects in oxidative phosphorylation. MTO1 (Mitochondrial tRNA Translation Optimization 1), an evolutionarily

  19. Evaluation of some genetic factors influencing the phenotypic ...

    African Journals Online (AJOL)

    Evaluation of some genetic factors influencing the phenotypic severity of β thalassemia Egyptian patients. Ibtessam R Hussein, Amina M Medhat, Samir F Zohny, Alice K Abd El-Aleem, Ghada Y El-Kammah, Bardees M Foda ...

  20. Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma.

    LENUS (Irish Health Repository)

    Teo, Minyuen

    2013-03-01

    A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

  1. Phenotypic and molecular genetic analysis of Pyruvate Kinase ...

    African Journals Online (AJOL)

    Phenotypic and molecular genetic analysis of Pyruvate Kinase deficiency in a Tunisian family. Jaouani Mouna, Hamdi Nadia, Chaouch Leila, Kalai Miniar, Mellouli Fethi, Darragi Imen, Boudriga Imen, Chaouachi Dorra, Bejaoui Mohamed, Abbes Salem ...

  2. Audiologic phenotype of osteogenesis imperfecta: use in clinical differentiation.

    NARCIS (Netherlands)

    Swinnen, F.K.R.; Dhooge, I.J.; Coucke, P.J.; D'Eufemia, P.; Zardo, F.; Garretsen, T.J.; Cremers, C.W.R.J.; Leenheer, E.M. De

    2012-01-01

    OBJECTIVES: To describe the audiologic phenotype in osteogenesis imperfecta (OI). STUDY DESIGN: Observational study. SETTING: Tertiary referral center. PATIENTS: One hundred eighty-two patients with genetically confirmed OI, aged 3 to 89 years. INTERVENTION: Diagnostic hearing evaluation through

  3. Phenotypes and genotypes in individuals with SMC1A variants

    DEFF Research Database (Denmark)

    Huisman, Sylvia; Mulder, Paul A; Redeker, Egbert

    2017-01-01

    SMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed...... of cognitive and adaptive functioning. Self-injurious behavior is more frequent and more severe in the NIPBL group. In the Dutch group 5 of 13 individuals (all females) had a phenotype that shows a remarkable resemblance to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability......, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group...

  4. Cornelia de Lange Syndrome: Evolution of the Phenotype

    Science.gov (United States)

    Passarge, Eberhard; And Others

    1971-01-01

    The medical case history of a 2-year-old girl who developed, during the second year of life, the classical phenotype (typical appearance) indicative of the deLange syndrome, with both mental and physical impairment. (KW)

  5. FeNO as biomarker for asthma phenotyping and management.

    Science.gov (United States)

    Ricciardolo, Fabio L M; Sorbello, Valentina; Ciprandi, Giorgio

    2015-01-01

    The current review aims to revisit literature on exhaled nitric oxide (FeNO) in asthma phenotyping and management to clarify the utility of this test in clinical practice. It is increasingly evident that multiple profiles characterize asthma as a complex disease for which is necessary to find tools able to discriminate among these phenotypes to achieve the best therapeutic strategy for all asthmatic patients. Current findings indicate that FeNO, a noninvasive and easy-to-obtain biomarker, can be considered a useful tool in predicting asthma developing and exacerbation, in identifying specific asthma phenotypes, in improving asthma diagnosis and management in a selected population, and in monitoring efficacy of standard corticosteroid and biologic therapy. Based on this evidence, FeNO might become an appropriate tool for physicians to better define specific asthma phenotypes and to better deal with asthma worsening.

  6. Complement C4 phenotypes in dementia of the Alzheimer type

    NARCIS (Netherlands)

    Eikelenboom, P.; Goetz, J.; Pronk, J. C.; Hauptmann, G.

    1988-01-01

    Complement C4 phenotype distribution was studied in 64 patients with dementia of the Alzheimer type. In contrast to reported findings we failed to find a significant association between C4B2 gene frequency and Alzheimer's dementia

  7. Growth Control by Ethylene: Adjusting Phenotypes to the Environment

    NARCIS (Netherlands)

    Pierik, R.; Sasidharan, R.; Voesenek, L.A.C.J.

    2007-01-01

    Plants phenotypically adjust to environmental challenges, and the gaseous plant hormone ethylene modulates many of these growth adjustments. Ethylene can be involved in environmentally induced growth inhibition as well as growth stimulation. Still, ethylene has long been considered a growth

  8. Prevalence of sexual dimorphism in mammalian phenotypic traits.

    Science.gov (United States)

    Karp, Natasha A; Mason, Jeremy; Beaudet, Arthur L; Benjamini, Yoav; Bower, Lynette; Braun, Robert E; Brown, Steve D M; Chesler, Elissa J; Dickinson, Mary E; Flenniken, Ann M; Fuchs, Helmut; Angelis, Martin Hrabe de; Gao, Xiang; Guo, Shiying; Greenaway, Simon; Heller, Ruth; Herault, Yann; Justice, Monica J; Kurbatova, Natalja; Lelliott, Christopher J; Lloyd, K C Kent; Mallon, Ann-Marie; Mank, Judith E; Masuya, Hiroshi; McKerlie, Colin; Meehan, Terrence F; Mott, Richard F; Murray, Stephen A; Parkinson, Helen; Ramirez-Solis, Ramiro; Santos, Luis; Seavitt, John R; Smedley, Damian; Sorg, Tania; Speak, Anneliese O; Steel, Karen P; Svenson, Karen L; Wakana, Shigeharu; West, David; Wells, Sara; Westerberg, Henrik; Yaacoby, Shay; White, Jacqueline K

    2017-06-26

    The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans.

  9. Extended phenotype: nematodes turn ants into bird-dispersed fruits

    DEFF Research Database (Denmark)

    Hughes, D P; Kronauer, D J C; Boomsma, J J

    2008-01-01

    A recent study has discovered a novel extended phenotype of a nematode which alters its ant host to resemble ripe fruit. The infected ants are in turn eaten by frugivorous birds that disperse the nematode's eggs.......A recent study has discovered a novel extended phenotype of a nematode which alters its ant host to resemble ripe fruit. The infected ants are in turn eaten by frugivorous birds that disperse the nematode's eggs....

  10. Phenotypic and functional characterization of earthworm coelomocyte subsets

    DEFF Research Database (Denmark)

    Engelmann, Péter; Hayashi, Yuya; Bodo, Kornélia

    2016-01-01

    Flow cytometry is a common approach to study invertebrate immune cells including earthworm coelomocytes. However, the link between light-scatter- and microscopy-based phenotyping remains obscured. Here we show, by means of light scatter-based cell sorting, both subpopulations (amoebocytes...... amoebocytes and eleocytes, with the former being in favor of bacterial engulfment. This study has proved successful in linking flow cytometry and microscopy analysis and provides further experimental evidence of phenotypic and functional heterogeneity in earthworm coelomocyte subsets....

  11. Surrogate-assisted feature extraction for high-throughput phenotyping.

    Science.gov (United States)

    Yu, Sheng; Chakrabortty, Abhishek; Liao, Katherine P; Cai, Tianrun; Ananthakrishnan, Ashwin N; Gainer, Vivian S; Churchill, Susanne E; Szolovits, Peter; Murphy, Shawn N; Kohane, Isaac S; Cai, Tianxi

    2017-04-01

    Phenotyping algorithms are capable of accurately identifying patients with specific phenotypes from within electronic medical records systems. However, developing phenotyping algorithms in a scalable way remains a challenge due to the extensive human resources required. This paper introduces a high-throughput unsupervised feature selection method, which improves the robustness and scalability of electronic medical record phenotyping without compromising its accuracy. The proposed Surrogate-Assisted Feature Extraction (SAFE) method selects candidate features from a pool of comprehensive medical concepts found in publicly available knowledge sources. The target phenotype's International Classification of Diseases, Ninth Revision and natural language processing counts, acting as noisy surrogates to the gold-standard labels, are used to create silver-standard labels. Candidate features highly predictive of the silver-standard labels are selected as the final features. Algorithms were trained to identify patients with coronary artery disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis using various numbers of labels to compare the performance of features selected by SAFE, a previously published automated feature extraction for phenotyping procedure, and domain experts. The out-of-sample area under the receiver operating characteristic curve and F -score from SAFE algorithms were remarkably higher than those from the other two, especially at small label sizes. SAFE advances high-throughput phenotyping methods by automatically selecting a succinct set of informative features for algorithm training, which in turn reduces overfitting and the needed number of gold-standard labels. SAFE also potentially identifies important features missed by automated feature extraction for phenotyping or experts. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please

  12. Latent cluster analysis of ALS phenotypes identifies prognostically differing groups.

    Directory of Open Access Journals (Sweden)

    Jeban Ganesalingam

    2009-09-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes.Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method.The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001. Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb and time from symptom onset to diagnosis (p<0.00001.The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research.

  13. The geometry of the Pareto front in biological phenotype space

    Science.gov (United States)

    Sheftel, Hila; Shoval, Oren; Mayo, Avi; Alon, Uri

    2013-01-01

    When organisms perform a single task, selection leads to phenotypes that maximize performance at that task. When organisms need to perform multiple tasks, a trade-off arises because no phenotype can optimize all tasks. Recent work addressed this question, and assumed that the performance at each task decays with distance in trait space from the best phenotype at that task. Under this assumption, the best-fitness solutions (termed the Pareto front) lie on simple low-dimensional shapes in trait space: line segments, triangles and other polygons. The vertices of these polygons are specialists at a single task. Here, we generalize this finding, by considering performance functions of general form, not necessarily functions that decay monotonically with distance from their peak. We find that, except for performance functions with highly eccentric contours, simple shapes in phenotype space are still found, but with mildly curving edges instead of straight ones. In a wide range of systems, complex data on multiple quantitative traits, which might be expected to fill a high-dimensional phenotype space, is predicted instead to collapse onto low-dimensional shapes; phenotypes near the vertices of these shapes are predicted to be specialists, and can thus suggest which tasks may be at play. PMID:23789060

  14. Informatics and machine learning to define the phenotype.

    Science.gov (United States)

    Basile, Anna Okula; Ritchie, Marylyn DeRiggi

    2018-03-01

    For the past decade, the focus of complex disease research has been the genotype. From technological advancements to the development of analysis methods, great progress has been made. However, advances in our definition of the phenotype have remained stagnant. Phenotype characterization has recently emerged as an exciting area of informatics and machine learning. The copious amounts of diverse biomedical data that have been collected may be leveraged with data-driven approaches to elucidate trait-related features and patterns. Areas covered: In this review, the authors discuss the phenotype in traditional genetic associations and the challenges this has imposed.Approaches for phenotype refinement that can aid in more accurate characterization of traits are also discussed. Further, the authors highlight promising machine learning approaches for establishing a phenotype and the challenges of electronic health record (EHR)-derived data. Expert commentary: The authors hypothesize that through unsupervised machine learning, data-driven approaches can be used to define phenotypes rather than relying on expert clinician knowledge. Through the use of machine learning and an unbiased set of features extracted from clinical repositories, researchers will have the potential to further understand complex traits and identify patient subgroups. This knowledge may lead to more preventative and precise clinical care.

  15. 3D Laser Triangulation for Plant Phenotyping in Challenging Environments.

    Science.gov (United States)

    Kjaer, Katrine Heinsvig; Ottosen, Carl-Otto

    2015-06-09

    To increase the understanding of how the plant phenotype is formed by genotype and environmental interactions, simple and robust high-throughput plant phenotyping methods should be developed and considered. This would not only broaden the application range of phenotyping in the plant research community, but also increase the ability for researchers to study plants in their natural environments. By studying plants in their natural environment in high temporal resolution, more knowledge on how multiple stresses interact in defining the plant phenotype could lead to a better understanding of the interaction between plant responses and epigenetic regulation. In the present paper, we evaluate a commercial 3D NIR-laser scanner (PlantEye, Phenospex B.V., Herleen, The Netherlands) to track daily changes in plant growth with high precision in challenging environments. Firstly, we demonstrate that the NIR laser beam of the scanner does not affect plant photosynthetic performance. Secondly, we demonstrate that it is possible to estimate phenotypic variation amongst the growth pattern of ten genotypes of Brassica napus L. (rapeseed), using a simple linear correlation between scanned parameters and destructive growth measurements. Our results demonstrate the high potential of 3D laser triangulation for simple measurements of phenotypic variation in challenging environments and in a high temporal resolution.

  16. Field Phenotyping of Soybean Roots for Drought Stress Tolerance

    Directory of Open Access Journals (Sweden)

    Berhanu A. Fenta

    2014-08-01

    Full Text Available Root architecture was determined together with shoot parameters under well watered and drought conditions in the field in three soybean cultivars (A5409RG, Jackson and Prima 2000. Morphology parameters were used to classify the cultivars into different root phenotypes that could be important in conferring drought tolerance traits. A5409RG is a drought-sensitive cultivar with a shallow root phenotype and a root angle of <40°. In contrast, Jackson is a drought-escaping cultivar. It has a deep rooting phenotype with a root angle of >60°. Prima 2000 is an intermediate drought-tolerant cultivar with a root angle of 40°–60°. It has an intermediate root phenotype. Prima 2000 was the best performing cultivar under drought stress, having the greatest shoot biomass and grain yield under limited water availability. It had abundant root nodules even under drought conditions. A positive correlation was observed between nodule size, above-ground biomass and seed yield under well-watered and drought conditions. These findings demonstrate that root system phenotyping using markers that are easy-to-apply under field conditions can be used to determine genotypic differences in drought tolerance in soybean. The strong association between root and nodule parameters and whole plant productivity demonstrates the potential application of simple root phenotypic markers in screening for drought tolerance in soybean.

  17. Probing phenotypic growth in expanding Bacillus subtilis biofilms.

    Science.gov (United States)

    Wang, Xiaoling; Koehler, Stephan A; Wilking, James N; Sinha, Naveen N; Cabeen, Matthew T; Srinivasan, Siddarth; Seminara, Agnese; Rubinstein, Shmuel; Sun, Qingping; Brenner, Michael P; Weitz, David A

    2016-05-01

    We develop an optical imaging technique for spatially and temporally tracking biofilm growth and the distribution of the main phenotypes of a Bacillus subtilis strain with a triple-fluorescent reporter for motility, matrix production, and sporulation. We develop a calibration procedure for determining the biofilm thickness from the transmission images, which is based on Beer-Lambert's law and involves cross-sectioning of biofilms. To obtain the phenotype distribution, we assume a linear relationship between the number of cells and their fluorescence and determine the best combination of calibration coefficients that matches the total number of cells for all three phenotypes and with the total number of cells from the transmission images. Based on this analysis, we resolve the composition of the biofilm in terms of motile, matrix-producing, sporulating cells and low-fluorescent materials which includes matrix and cells that are dead or have low fluorescent gene expression. We take advantage of the circular growth to make kymograph plots of all three phenotypes and the dominant phenotype in terms of radial distance and time. To visualize the nonlocal character of biofilm growth, we also make kymographs using the local colonization time. Our technique is suitable for real-time, noninvasive, quantitative studies of the growth and phenotype distribution of biofilms which are either exposed to different conditions such as biocides, nutrient depletion, dehydration, or waste accumulation.

  18. Metalloproteins during development of Walker-256 carcinosarcoma resistant phenotype

    Directory of Open Access Journals (Sweden)

    V. F. Chekhun

    2015-04-01

    Full Text Available The study was focused on the detection of changes in serum and tumor metal-containing proteins in animals during development of doxorubicin-resistant phenotype in malignant cells after 12 courses of chemotherapy. We found that on every stage of resistance development there was a significant increase in content of ferritin and transferrin proteins (which take part in iron traffick and storage in Walker-256 carcinosarcoma tissue. We observed decreased serum ferritin levels at the beginning stage of the resistance development and significant elevation of this protein levels in the cases with fully developed resistance phenotype. Transferrin content showed changes opposite to that of ferritin. During the development of resistance phenotype the tumor tissue also exhibited increased ‘free iron’ concentration that putatively correlate with elevation of ROS generation and levels of MMP-2 and MMP-9 active forms. The tumor non-protein thiol content increases gradually as well. The serum of animals with early stages of resistance phenotype development showed high ceruloplasmin activity and its significant reduction after loss of tumor sensitivity to doxorubicin. Therefore, the development of resistance phenotype in Walker-256 carcinosarcoma is accompanied by both the deregulation of metal-containing proteins in serum and tumor tissue and by the changes in activity of antioxidant defense system. Thus, the results of this study allow us to determine the spectrum of metal-containing proteins that are involved in the development of resistant tumor phenotype and that may be targeted for methods for doxorubicin sensitivity correction therapy.

  19. Digging deep into Golgi phenotypic diversity with unsupervised machine learning.

    Science.gov (United States)

    Hussain, Shaista; Le Guezennec, Xavier; Yi, Wang; Dong, Huang; Chia, Joanne; Yiping, Ke; Khoon, Lee Kee; Bard, Frédéric

    2017-12-01

    The synthesis of glycans and the sorting of proteins are critical functions of the Golgi apparatus and depend on its highly complex and compartmentalized architecture. High-content image analysis coupled to RNA interference screening offers opportunities to explore this organelle organization and the gene network underlying it. To date, image-based Golgi screens have based on a single parameter or supervised analysis with predefined Golgi structural classes. Here, we report the use of multiparametric data extracted from a single marker and a computational unsupervised analysis framework to explore Golgi phenotypic diversity more extensively. In contrast with the three visually definable phenotypes, our framework reproducibly identified 10 Golgi phenotypes. They were used to quantify and stratify phenotypic similarities among genetic perturbations. The derived phenotypic network partially overlaps previously reported protein-protein interactions as well as suggesting novel functional interactions. Our workflow suggests the existence of multiple stable Golgi organizational states and provides a proof of concept for the classification of drugs and genes using fine-grained phenotypic information. © 2017 Hussain, Le Guezennec, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  20. Discordant phenotype in siblings with X-linked agammaglobulinemia

    Energy Technology Data Exchange (ETDEWEB)

    Bykowsky, M.J.; Veksler, K.S.; Sullivan, K.E. [Children`s Hospital, Philadelphia, PA (United States)] [and others

    1996-03-01

    X-linked agammaglobulinemia (XLA) is a congenital humoral immunodeficiency caused by a defect in a B-cell-specific signaling molecule, Btk. There has been little concordance of phenotype with genotype in this disorder, and defects in Btk cause immunodeficiencies that range from mild impairment to complete inability to produce antibodies. The factors modifying the phenotype of XLA are not understood. The current study is the first description of two male siblings with identical T{sup 134}{yields}C mutations in the translation initiation ATG of Btk who have different clinical phenotypes as well as different laboratory phenotypes. The proband lacks immunoglobulins and B cells and has recurrent infections, while the elder, affected brother has normal levels of IgG and IgM and very few infections. Both have undetectable levels of Btk kinase activity in circulating mononuclear cells. Complete sequencing of Btk gene transcripts in both brothers revealed no additional mutations to account for the discordant phenotypes. This description provides unequivocal evidence that the phenotype of XLA is influenced by factors additional to the Btk gene. 39 refs., 3 figs., 3 tabs.

  1. Application of Phenotype Microarray technology to soil microbiology

    Science.gov (United States)

    Mocali, Stefano

    2016-04-01

    It is well established that soil microorganisms are extremely diverse and only a small fraction has been successfully cultured in the laboratory. Furthermore, addressing the functionality of genomes is one of the most important and challenging tasks of today's biology. In particular the ability to link genotypes to corresponding phenotypes is of interest in the reconstruction and biotechnological manipulation of metabolic pathways. High-throughput culture in micro wells provides a method for rapid screening of a wide variety of growth conditions and commercially available plates contain a large number of substrates, nutrient sources, and inhibitors, which can provide an assessment of the phenotype of an organism. Thus, over the last years, Phenotype Microarray (PM) technology has been used to address many specific issues related to the metabolic functionality of microorganisms. However, computational tools that could directly link PM data with the gene(s) of interest followed by the extraction of information on gene-phenotype correlation are still missing. Here potential applications of phenotype arrays to soil microorganisms, use of the plates in stress response studies and for assessment of phenotype of environmental communities are described. Considerations and challenges in data interpretation and visualization, including data normalization, statistics, and curve fitting are also discussed. In particular, here we present DuctApe, a suite that allows the analysis of both genomic sequences and PM data, to find metabolic differences among PM experiments and to correlate them with KEGG pathways and gene presence/absence patterns.

  2. Stress-Driven Selection of Novel Phenotypes

    Science.gov (United States)

    Fox, George E.; Stepaov, Victor G.; Liu, Yamei

    2011-01-01

    A process has been developed that can confer novel properties, such as metal resistance, to a host bacterium. This same process can also be used to produce RNAs and peptides that have novel properties, such as the ability to bind particular compounds. It is inherent in the method that the peptide or RNA will behave as expected in the target organism. Plasmid-born mini-gene libraries coding for either a population of combinatorial peptides or stable, artificial RNAs carrying random inserts are produced. These libraries, which have no bias towards any biological function, are used to transform the organism of interest and to serve as an initial source of genetic variation for stress-driven evolution. The transformed bacteria are propagated under selective pressure in order to obtain variants with the desired properties. The process is highly distinct from in vitro methods because the variants are selected in the context of the cell while it is experiencing stress. Hence, the selected peptide or RNA will, by definition, work as expected in the target cell as the cell adapts to its presence during the selection process. Once the novel gene, which produces the sought phenotype, is obtained, it can be transferred to the main genome to increase the genetic stability in the organism. Alternatively, the cell line can be used to produce novel RNAs or peptides with selectable properties in large quantity for separate purposes. The system allows for easy, large-scale purification of the RNAs or peptide products. The process has been reduced to practice by imposing sub-inhibitory concentrations of NiCl2 on cells of the bacterium Escherichia coli that were transformed separately with the peptide library and RNA library. The evolved resistant clones were isolated, and sequences of the selected mini-gene variants were established. Clones resistant to NiCl2 were found to carry identical plasmid variants with a functional mini-gene that specifically conferred significant nickel

  3. Testing evolutionary hypotheses for phenotypic divergence using landscape genetics.

    Science.gov (United States)

    Funk, W Chris; Murphy, Melanie A

    2010-02-01

    Understanding the evolutionary causes of phenotypic variation among populations has long been a central theme in evolutionary biology. Several factors can influence phenotypic divergence, including geographic isolation, genetic drift, divergent natural or sexual selection, and phenotypic plasticity. But the relative importance of these factors in generating phenotypic divergence in nature is still a tantalizing and unresolved problem in evolutionary biology. The origin and maintenance of phenotypic divergence is also at the root of many ongoing debates in evolutionary biology, such as the extent to which gene flow constrains adaptive divergence (Garant et al. 2007) and the relative importance of genetic drift, natural selection, and sexual selection in initiating reproductive isolation and speciation (Coyne & Orr 2004). In this issue, Wang & Summers (2010) test the causes of one of the most fantastic examples of phenotypic divergence in nature: colour pattern divergence among populations of the strawberry poison frog (Dendrobates pumilio) in Panama and Costa Rica (Fig. 1). This study provides a beautiful example of the use of the emerging field of landscape genetics to differentiate among hypotheses for phenotypic divergence. Using landscape genetic analyses, Wang & Summers were able to reject the hypotheses that colour pattern divergence is due to isolation-by-distance (IBD) or landscape resistance. Instead, the hypothesis left standing is that colour divergence is due to divergent selection, in turn driving reproductive isolation among populations with different colour morphs. More generally, this study provides a wonderful example of how the emerging field of landscape genetics, which has primarily been applied to questions in conservation and ecology, now plays an essential role in evolutionary research.

  4. Multiparametric classification links tumor microenvironments with tumor cell phenotype.

    Directory of Open Access Journals (Sweden)

    Bojana Gligorijevic

    2014-11-01

    Full Text Available While it has been established that a number of microenvironment components can affect the likelihood of metastasis, the link between microenvironment and tumor cell phenotypes is poorly understood. Here we have examined microenvironment control over two different tumor cell motility phenotypes required for metastasis. By high-resolution multiphoton microscopy of mammary carcinoma in mice, we detected two phenotypes of motile tumor cells, different in locomotion speed. Only slower tumor cells exhibited protrusions with molecular, morphological, and functional characteristics associated with invadopodia. Each region in the primary tumor exhibited either fast- or slow-locomotion. To understand how the tumor microenvironment controls invadopodium formation and tumor cell locomotion, we systematically analyzed components of the microenvironment previously associated with cell invasion and migration. No single microenvironmental property was able to predict the locations of tumor cell phenotypes in the tumor if used in isolation or combined linearly. To solve this, we utilized the support vector machine (SVM algorithm to classify phenotypes in a nonlinear fashion. This approach identified conditions that promoted either motility phenotype. We then demonstrated that varying one of the conditions may change tumor cell behavior only in a context-dependent manner. In addition, to establish the link between phenotypes and cell fates, we photoconverted and monitored the fate of tumor cells in different microenvironments, finding that only tumor cells in the invadopodium-rich microenvironments degraded extracellular matrix (ECM and disseminated. The number of invadopodia positively correlated with degradation, while the inhibiting metalloproteases eliminated degradation and lung metastasis, consistent with a direct link among invadopodia, ECM degradation, and metastasis. We have detected and characterized two phenotypes of motile tumor cells in vivo, which

  5. Simultaneous detection and estimation of trait associations with genomic phenotypes.

    Science.gov (United States)

    Morrison, Jean; Simon, Noah; Witten, Daniela

    2017-01-01

    SummaryGenomic phenotypes, such as DNA methylation and chromatin accessibility, can be used to characterize the transcriptional and regulatory activity of DNA within a cell. Recent technological advances have made it possible to measure such phenotypes very densely. This density often results in spatial structure, in the sense that measurements at nearby sites are very similar. In this article, we consider the task of comparing genomic phenotypes across experimental conditions, cell types, or disease subgroups. We propose a new method, Joint Adaptive Differential Estimation (JADE), which leverages the spatial structure inherent to genomic phenotypes. JADE simultaneously estimates smooth underlying group average genomic phenotype profiles and detects regions in which the average profile differs between groups. We evaluate JADE's performance in several biologically plausible simulation settings. We also consider an application to the detection of regions with differential methylation between mature skeletal muscle cells, myotubes, and myoblasts. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Refining mimicry: phenotypic variation tracks the local optimum.

    Science.gov (United States)

    Mérot, Claire; Le Poul, Yann; Théry, Marc; Joron, Mathieu

    2016-07-01

    Müllerian mimicry between chemically defended preys is a textbook example of natural selection favouring phenotypic convergence onto a shared warning signal. Studies of mimicry have concentrated on deciphering the ecological and genetic underpinnings of dramatic switches in mimicry association, producing a well-known mosaic distribution of mimicry patterns across geography. However, little is known about the accuracy of resemblance between natural comimics when the local phenotypic optimum varies. In this study, using analyses of wing shape, pattern and hue, we quantify multimodal phenotypic similarity between butterfly comimics sharing the so-called postman pattern in different localities with varying species composition. We show that subtle but consistent variation between populations of the localized species, Heliconius timareta thelxinoe, enhance resemblance to the abundant comimics which drive the mimicry in each locality. Those results suggest that rarer comimics track the changes in the phenotypic optimum caused by gradual changes in the composition of the mimicry community, providing insights into the process by which intraspecific diversity of mimetic pattern may arise. Furthermore, our results suggest a multimodal evolution of similarity, with coordinated convergence in different features of the phenotype such as wing outline, pattern and hue. Finally, multilocus genotyping allows estimating local hybridization rates between H. timareta and comimic H. melpomene in different populations, raising the hypothesis that mimicry refinement between closely related comimics may be enhanced by adaptive introgression at loci modifying the accuracy of resemblance. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

  7. Phenoliner: A New Field Phenotyping Platform for Grapevine Research.

    Science.gov (United States)

    Kicherer, Anna; Herzog, Katja; Bendel, Nele; Klück, Hans-Christian; Backhaus, Andreas; Wieland, Markus; Rose, Johann Christian; Klingbeil, Lasse; Läbe, Thomas; Hohl, Christian; Petry, Willi; Kuhlmann, Heiner; Seiffert, Udo; Töpfer, Reinhard

    2017-07-14

    In grapevine research the acquisition of phenotypic data is largely restricted to the field due to its perennial nature and size. The methodologies used to assess morphological traits and phenology are mainly limited to visual scoring. Some measurements for biotic and abiotic stress, as well as for quality assessments, are done by invasive measures. The new evolving sensor technologies provide the opportunity to perform non-destructive evaluations of phenotypic traits using different field phenotyping platforms. One of the biggest technical challenges for field phenotyping of grapevines are the varying light conditions and the background. In the present study the Phenoliner is presented, which represents a novel type of a robust field phenotyping platform. The vehicle is based on a grape harvester following the concept of a moveable tunnel. The tunnel it is equipped with different sensor systems (RGB and NIR camera system, hyperspectral camera, RTK-GPS, orientation sensor) and an artificial broadband light source. It is independent from external light conditions and in combination with artificial background, the Phenoliner enables standardised acquisition of high-quality, geo-referenced sensor data.

  8. Secondary contact seeds phenotypic novelty in cichlid fishes.

    Science.gov (United States)

    Nichols, Paul; Genner, Martin J; van Oosterhout, Cock; Smith, Alan; Parsons, Paul; Sungani, Harold; Swanstrom, Jennifer; Joyce, Domino A

    2015-01-07

    Theory proposes that genomic admixture between formerly reproductively isolated populations can generate phenotypic novelty for selection to act upon. Secondary contact may therefore be a significant promoter of phenotypic novelty that allows species to overcome environmental challenges and adapt to novel environments, including during adaptive radiation. To date, this has largely been considered from the perspective of interspecific hybridization at contact zones. However, it is also possible that this process occurs more commonly between natural populations of a single species, and thus its importance in adaptive evolution may have been underestimated. In this study, we tested the consequences of genomic introgression during apparent secondary contact between phenotypically similar lineages of the riverine cichlid fish Astatotilapia calliptera. We provide population genetic evidence of a secondary contact zone in the wild, and then demonstrate using mate-choice experiments that both lineages can reproduce together successfully in laboratory conditions. Finally, we show that genomically admixed individuals display extreme phenotypes not observed in the parental lineages. Collectively, the evidence shows that secondary contact can drive the evolution of phenotypic novelty, suggesting that pulses of secondary contact may repeatedly seed genetic novelty, which when coupled with ecological opportunity could promote rapid adaptive evolution in natural circumstances.

  9. Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia

    Directory of Open Access Journals (Sweden)

    Stephanie A. Amici

    2017-11-01

    Full Text Available Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2 macrophages has been widely used. However, the complexity of macrophage function can only be achieved by the existence of varied, plastic and tridimensional macrophage phenotypes. Understanding how tissue macrophages integrate environmental signals via molecular programs to define pathogen/injury inflammatory responses provides an opportunity to better understand the multilayered nature of macrophages, as well as target and modulate cellular programs to control excessive inflammation. This is particularly important in MS and other neuroinflammatory diseases, where chronic inflammatory macrophage and microglial responses may contribute to pathology. Here, we perform a comprehensive review of our current understanding of how molecular pathways modulate tissue macrophage phenotype, covering both classic pathways and the emerging role of microRNAs, receptor-tyrosine kinases and metabolism in macrophage phenotype. In addition, we discuss pathway parallels in microglia, novel markers helpful in the identification of peripheral macrophages versus microglia and markers linked to their phenotype.

  10. Red hair is the null phenotype of MC1R.

    Science.gov (United States)

    Beaumont, Kimberley A; Shekar, Sri N; Cook, Anthony L; Duffy, David L; Sturm, Richard A

    2008-08-01

    The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.

  11. Mutations and phenotype in isolated glycerol kinase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Walker, A.P.; Muscatelli, F.; Stafford, A.N.; Monaco, A.P. [Inst. of Molecular Medicine, Oxford (United Kingdom)] [and others

    1996-06-01

    We demonstrate that isolated glycerol kinase (GK) deficiency in three families results from mutation of the Xp21 GK gene. GK mutations were detected in four patients with widely differing phenotypes. Patient 1 had a splice-site mutation causing premature termination. His general health was good despite absent GK activity, indicating that isolated GK deficiency can be silent. Patient 2 had GK deficiency and a severe phenotype involving psychomotor retardation and growth delay, bone dysplasia, and seizures, similar to the severe phenotype of one of the first described cases of GK deficiency. His younger brother, patient 3, also had GK deficiency, but so far his development has been normal. GK exon 17 was deleted in both brothers, implicating additional factors in causation of the severe phenotype of patient 2. Patient 4 had both GK deficiency with mental retardation and a GK missense mutation (D440V). Possible explanations for the phenotypic variation of these four patients include ascertainment bias; metabolic or environmental stress as a precipitating factor in revealing GK-related changes, as has previously been described in juvenile GK deficiency; and interactions with functional polymorphisms in other genes that alter the effect of GK deficiency on normal development. 36 refs., 4 figs., 1 tab.

  12. Determinants of asthma phenotypes in supermarket bakery workers.

    Science.gov (United States)

    Baatjies, R; Lopata, A L; Sander, I; Raulf-Heimsoth, M; Bateman, E D; Meijster, T; Heederik, D; Robins, T G; Jeebhay, M F

    2009-10-01

    While baker's asthma has been well described, various asthma phenotypes in bakery workers have yet to be characterised. Our study aims to describe the asthma phenotypes in supermarket bakery workers in relation to host risk factors and self-reported exposure to flour dust. A cross-sectional study of 517 supermarket bakery workers in 31 bakeries used a questionnaire, skin prick tests, and specific immunoglobulin E to wheat, rye and fungal alpha-amylase and methacholine challenge testing. The prevalence of probable occupational asthma (OA, 13%) was higher than atopic (6%), nonatopic (6%) and work-aggravated asthma (WAA, 3%) phenotypes. Previous episodes of high exposure to dusts, fumes and vapours causing asthma symptoms were more strongly associated with WAA (OR 5.8, 95% CI 1.7-19.2) than OA (2.8, 1.4-5.5). Work-related ocular-nasal symptoms were significantly associated with WAA (4.3, 1.3-13.8) and OA (3.1, 1.8-5.5). Bakers with OA had an increased odds ratio of reporting adverse reactions to ingested grain products (6.4, 2.0-19.8). OA is the most common phenotype among supermarket bakery workers. Analysis of risk factors contributes to defining clinical phenotypes, which will guide ongoing medical surveillance and clinical management of bakery workers.

  13. Strategy revealing phenotypic differences among synthetic oscillator designs.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2014-09-19

    Considerable progress has been made in identifying and characterizing the component parts of genetic oscillators, which play central roles in all organisms. Nonlinear interaction among components is sufficiently complex that mathematical models are required to elucidate their elusive integrated behavior. Although natural and synthetic oscillators exhibit common architectures, there are numerous differences that are poorly understood. Utilizing synthetic biology to uncover basic principles of simpler circuits is a way to advance understanding of natural circadian clocks and rhythms. Following this strategy, we address the following questions: What are the implications of different architectures and molecular modes of transcriptional control for the phenotypic repertoire of genetic oscillators? Are there designs that are more realizable or robust? We compare synthetic oscillators involving one of three architectures and various combinations of the two modes of transcriptional control using a methodology that provides three innovations: a rigorous definition of phenotype, a procedure for deconstructing complex systems into qualitatively distinct phenotypes, and a graphical representation for illuminating the relationship between genotype, environment, and the qualitatively distinct phenotypes of a system. These methods provide a global perspective on the behavioral repertoire, facilitate comparisons of alternatives, and assist the rational design of synthetic gene circuitry. In particular, the results of their application here reveal distinctive phenotypes for several designs that have been studied experimentally as well as a best design among the alternatives that has yet to be constructed and tested.

  14. Epigenetic reversion of breast carcinoma phenotype is accompaniedby DNA sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Sandal, Tone; Valyi-Nagy, Klara; Spencer, Virginia A.; Folberg,Robert; Bissell, Mina J.; Maniotis, Andrew J.

    2006-07-19

    The importance of microenvironment and context in regulation of tissue-specific genes is finally well established. DNA exposure to, or sequestration from, nucleases can be used to detect differences in higher order chromatin structure in intact cells without disturbing cellular or tissue architecture. To investigate the relationship between chromatin organization and tumor phenotype, we utilized an established 3-D assay where normal and malignant human breast cells can be easily distinguished by the morphology of the structures they make (acinus-like vs tumor-like, respectively). We show that these phenotypes can be distinguished also by sensitivity to AluI digestion where the malignant cells are resistant to digestion relative to non-malignant cells. Reversion of the T4-2 breast cancer cells by either cAMP analogs, or a phospatidylinositol 3-kinase (P13K) inhibitor not only reverted the phenotype, but also the chromatin sensitivity to AluI. By using different cAMP-analogs, we show that the cAMP-induced phenotypic reversion, polarization, and shift in DNA organization act through a cAMP-dependent-protein-kinase A-coupled signaling pathway. Importantly, inhibitory antibody to fibronectin also reverted the malignant phenotype, polarized the acini, and changed chromatin sequestration. These experiments show not only that modifying the tumor microenvironment can alter the organization of tumor cells but also that architecture of the tissues and the global chromatin organization are coupled and yet highly plastic.

  15. Natural variation of model mutant phenotypes in Ciona intestinalis.

    Directory of Open Access Journals (Sweden)

    Paolo Sordino

    Full Text Available BACKGROUND: The study of ascidians (Chordata, Tunicata has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. CONCLUSIONS/SIGNIFICANCE: Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity.

  16. Alloantigenic phenotype of radiation-induced thymomas in the mouse

    International Nuclear Information System (INIS)

    Hogarth, P.M.; Henning, M.M.; McKenzie, I.F.C.

    1982-01-01

    The alloantigenic phenotype of 21 radiation-induced thymomas is described. Monoclonal antibodies and conventional antisera, absorbed to remove contaminating antibodies, were used to test the thymomas directly for the presence of H-2, Ia, Ly-1, Ly-2, Ly-4, Ly-5, Ly-6, Ly-9, Ly-15, Thy-1, TL, and Qa-2 antigens, and for surface immunoglobulin. The phenotypes obtained by direct tests were also confirmed by absorption studies. The tumors were all of T-cell origin (Thy-1 + Ig - ) and showed a restricted heterogeneity of their cell surface phenotype, concordant with the known alloantigenic phenotypes of functional T-cells. Thus the thymomas could be classified into 7 groups based on the differing expressions of Ia, Ly-1, Ly-2, Ly-4, and Ly-6 specificities; all tumors were H-2 + , Ly-5 + , Ly-9 + , and Ly-15 + . Thus a wide variety of phenotypically diverse tumors could be detected; if these represent the clonal expansion of different functional subsets, they could provide a valuable set of functional T-cells

  17. Social-cognition and the broad autism phenotype: identifying genetically meaningful phenotypes.

    Science.gov (United States)

    Losh, Molly; Piven, Joseph

    2007-01-01

    Strong evidence from twin and family studies suggests that the genetic liability to autism may be expressed through personality and language characteristics qualitatively similar, but more subtly expressed than those defining the full syndrome. This study examined behavioral features of this 'broad autism phenotype' (BAP) in relation to performance on a measure of social-cognition in an attempt to tease out this complex clinical picture and identify markers of underlying neuropsychological systems of genetic significance to autism. We hypothesized that mild social-cognitive impairment would be associated with clinically defined social characteristics of the BAP (aloof personality style, lower quality social relationships, and impaired pragmatic language use). Forty-eight parents of individuals with autism (13 of whom were identified as 'aloof'), and 22 control parents, were administered the 'Eyes Test', a social-cognitive measure that taps the ability to read complex psychological states from viewing only the eye region of faces. Whereas social-cognitive ability was unimpaired among parents of autistic children in general, the subgroup of parents defined as 'aloof' displayed significant social-cognitive deficits on the 'Eyes Test'. Impaired social-cognitive ability was associated with low quality of friendships and problems with pragmatic language use, associations which mirror those documented in autism. Findings suggest that social-cognitive impairments co-segregate with conceptually related personality, social, and language features that constitute the BAP, and point towards performance on the Eyes Test as a genetically meaningful endophenotype.

  18. Effect of Surface Modification and Macrophage Phenotype on Particle Internalization

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daniel [Iowa State University; Phan, Ngoc [Iowa State University; Isely, Christopher [Iowa State University; Bruene, Lucas [Iowa State University; Bratlie, Kaitlin M [Ames Laboratory

    2014-11-10

    Material properties play a key role in the cellular internalization of polymeric particles. In the present study, we have investigated the effects of material characteristics such as water contact angle, zeta potential, melting temperature, and alternative activation of complement on particle internalization for pro-inflammatory, pro-angiogenic, and naïve macrophages by using biopolymers (~600 nm), functionalized with 13 different molecules. Understanding how material parameters influence particle internalization for different macrophage phenotypes is important for targeted delivery to specific cell populations. Here, we demonstrate that material parameters affect the alternative pathway of complement activation as well as particle internalization for different macrophage phenotypes. Here, we show that the quantitative structure–activity relationship method (QSAR) previously used to predict physiochemical properties of materials can be applied to targeting different macrophage phenotypes. These findings demonstrated that targeted drug delivery to macrophages could be achieved by exploiting material parameters.

  19. Phenotype of asthma-chronic obstructive pulmonary disease overlap syndrome.

    Science.gov (United States)

    Rhee, Chin Kook

    2015-07-01

    Many patients with asthma or chronic obstructive pulmonary disease (COPD) have overlapping characteristics of both diseases. By spirometric definition, patients with both fixed airflow obstruction (AO) and bronchodilator reversibility or fixed AO and bronchial hyperresponsiveness can be considered to have asthma-COPD overlap syndrome (ACOS). However, patients regarded to have ACOS by spirometric criteria alone are heterogeneous and can be classified by phenotype. Eosinophilic inflammation, a history of allergic disease, and smoke exposure are important components in the classification of ACOS. Each phenotype has a different underlying pathophysiology, set of characteristics, and prognosis. Medical treatment for ACOS should be tailored according to phenotype. A narrower definition of ACOS that includes both spirometric and clinical criteria is needed.

  20. Phenotypic Bias and Ethnic Identity in Filipino Americans*

    Science.gov (United States)

    Kiang, Lisa; Takeuchi, David T.

    2009-01-01

    Objective Links between phenotypes (skin tone, physical features) and a range of outcomes (income, physical health, psychological distress) were examined. Ethnic identity was examined as a protective moderator of phenotypic bias. Method Data were from a community sample of 2,092 Filipino adults in San Francisco and Honolulu. Results After controlling for age, nativity, marital status, and education, darker skin was associated with lower income and lower physical health for females and males. For females, more ethnic features were associated with lower income. For males, darker skin was related to lower psychological distress. One interaction was found such that females with more ethnic features exhibited lower distress; however, ethnic identity moderated distress levels of those with less ethnic features. Conclusions Phenotypic bias appears prevalent in Filipino Americans though specific effects vary by gender and skin color versus physical features. Discussion centers on the social importance of appearance and potential strengths gained from ethnic identification. PMID:20107617

  1. Body Temperature Measurements for Metabolic Phenotyping in Mice

    Directory of Open Access Journals (Sweden)

    Carola W. Meyer

    2017-07-01

    Full Text Available Endothermic organisms rely on tightly balanced energy budgets to maintain a regulated body temperature and body mass. Metabolic phenotyping of mice, therefore, often includes the recording of body temperature. Thermometry in mice is conducted at various sites, using various devices and measurement practices, ranging from single-time probing to continuous temperature imaging. Whilst there is broad agreement that body temperature data is of value, procedural considerations of body temperature measurements in the context of metabolic phenotyping are missing. Here, we provide an overview of the various methods currently available for gathering body temperature data from mice. We explore the scope and limitations of thermometry in mice, with the hope of assisting researchers in the selection of appropriate approaches, and conditions, for comprehensive mouse phenotypic analyses.

  2. The Fragile X Syndrome: Behavioral Phenotype and Learning Disabilities

    Directory of Open Access Journals (Sweden)

    Claudia GRAU RUBIO

    2016-04-01

    Full Text Available In this article, we describe the behavioral phenotype of individuals with Fragile X Syndrome and its impact in the educational scope. This syndrome is characterized by difficulties in sensory integration, cognitive deficits (verbal reasoning, abstract/ visual and cuantitative skills, short term memory, sequential processing, attention and executive processes, language disorders (phonetic-phonologicals, semanticals, morphosyntacticals and pragmaticals and communication disorders, social anxiety, general hyperarousal, autism, non autistic social difficulties, attention deficit and hyperactivity, and learning disabilities. The behavioral phenotype is highly variable and depends on sex, age, and mutation status (full mutation or premutation. The behavioural phenotype has important repercussions in education, as it enables us to understand the learning disabilities and to develop specific intervention strategies.

  3. Atopic dermatitis phenotypes and the need for personalized medicine

    Science.gov (United States)

    Cabanillas, Beatriz; Brehler, Ann-Christin; Novak, Natalija

    2017-01-01

    Purpose of review To describe recent developments in therapies which target the molecular mechanisms in atopic dermatitis. Recent findings Current advances in the understanding of the molecular basis of atopic dermatitis are leading to the stratification of different atopic dermatitis phenotypes. New therapies offer the option to target-specific molecules involved in the pathophysiology of atopic dermatitis. Current new therapies under investigation aim to modulate specific inflammatory pathways associated with distinctive atopic dermatitis phenotypes, which would potentially translate into the development of personalized, targeted-specific treatments of atopic dermatitis. Summary Despite the unmet need for well tolerated, effective, and personalized treatment of atopic dermatitis, the current standard treatments of atopic dermatitis do not focus on the individual pathogenesis of the disease. The development of targeted, phenotype-specific therapies has the potential to open a new promising era of individualized treatment of atopic dermatitis. PMID:28582322

  4. Root Traits and Phenotyping Strategies for Plant Improvement

    Directory of Open Access Journals (Sweden)

    Ana Paez-Garcia

    2015-06-01

    Full Text Available Roots are crucial for nutrient and water acquisition and can be targeted to enhance plant productivity under a broad range of growing conditions. A current challenge for plant breeding is the limited ability to phenotype and select for desirable root characteristics due to their underground location. Plant breeding efforts aimed at modifying root traits can result in novel, more stress-tolerant crops and increased yield by enhancing the capacity of the plant for soil exploration and, thus, water and nutrient acquisition. Available approaches for root phenotyping in laboratory, greenhouse and field encompass simple agar plates to labor-intensive root digging (i.e., shovelomics and soil boring methods, the construction of underground root observation stations and sophisticated computer-assisted root imaging. Here, we summarize root architectural traits relevant to crop productivity, survey root phenotyping strategies and describe their advantages, limitations and practical value for crop and forage breeding programs.

  5. Light pigmentation phenotype is correlated with increased substantia nigra echogenicity.

    Science.gov (United States)

    Rumpf, Jost-Julian; Schirmer, Maria; Fricke, Christopher; Weise, David; Wagner, Justinus Aspasios; Simon, Jan; Classen, Joseph

    2015-11-01

    This study was undertaken to address the question of whether pigmentation may be mechanistically linked with Parkinson's disease. In a cross-sectional, observational study, 116 healthy subjects received transcranial sonography of the substantia nigra. Pigmentation phenotype was assessed using the Fitzpatrick skin phototype classification, and five additional phenotypic pigmentation traits as well as a photographic method (Melanin index) in a subgroup of 46 subjects. Lighter skin phototype was associated with larger echogenic substantia nigra area and increased prevalence of abnormally enlarged echogenic substantia nigra area. The strongest association of substantia nigra echogenicity and phenotypic pigmentation traits was found for hair color and facial tanning. Findings suggest an increasing prevalence of structural abnormality of substantia nigra with decreasing darkness of skin and thus may provide additional evidence in favor of a pathogenic link of pigmentation and Parkinson's disease. © 2015 International Parkinson and Movement Disorder Society.

  6. Association Between Vitamin D Status and COPD Phenotypes

    DEFF Research Database (Denmark)

    Moberg, M.; Ringbaek, T.; Roberts, N. B.

    2014-01-01

    It has been suggested that identifying phenotypes in chronic obstructive pulmonary disease (COPD) might improve treatment outcome and the accuracy of prediction of prognosis. In observational studies vitamin D deficiency has been associated with decreased pulmonary function, presence of emphysema...... and osteoporosis, upper respiratory tract infections, and systemic inflammation. This could indicate a relationship between vitamin D status and COPD phenotypes. The aim of this study was to assess the association between vitamin D levels and COPD phenotypes. In addition, seasonality of vitamin D levels...... was examined. A total of 91 patients from a Danish subpopulation of the "Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points" cohort took part in a biomarker substudy. Vitamin D concentration was measured from blood samples taken at two visits, approximately 6 months apart...

  7. Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

    DEFF Research Database (Denmark)

    Song, Yong; Schwager, Michelle J; Backer, Vibeke

    2017-01-01

    The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically s......-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases.......The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically...... residing either in the westernized environment of Denmark or in the rural area of Greenland. Our results showed that lung function was associated with genetic variants in ORMDL3, with polymorphisms having a significant interaction with place of residence. LT-α SNP rs909253 and rs1041981 were significantly...

  8. Body Temperature Measurements for Metabolic Phenotyping in Mice

    Science.gov (United States)

    Meyer, Carola W.; Ootsuka, Youichirou; Romanovsky, Andrej A.

    2017-01-01

    Endothermic organisms rely on tightly balanced energy budgets to maintain a regulated body temperature and body mass. Metabolic phenotyping of mice, therefore, often includes the recording of body temperature. Thermometry in mice is conducted at various sites, using various devices and measurement practices, ranging from single-time probing to continuous temperature imaging. Whilst there is broad agreement that body temperature data is of value, procedural considerations of body temperature measurements in the context of metabolic phenotyping are missing. Here, we provide an overview of the various methods currently available for gathering body temperature data from mice. We explore the scope and limitations of thermometry in mice, with the hope of assisting researchers in the selection of appropriate approaches, and conditions, for comprehensive mouse phenotypic analyses. PMID:28824441

  9. Correlation between Duffy blood group phenotype and breast cancer incidence

    International Nuclear Information System (INIS)

    Liu, Xiao-feng; Li, Lian-fang; Ou, Zhou-luo; Shen, Rong; Shao, Zhi-min

    2012-01-01

    Different ethnicities have different distribution of Duffy blood group (DBG) phenotypes and different breast cancer morbidity. A study in our lab demonstrated that Duffy antigen/receptor for chemokines (DARC, also known as DBGP, the Duffy protein phenotype), led to the inhibition of tumorigenesis. Therefore, we tested the hypothesis that DBGP is correlated with breast cancer occurrence. DBGP proteins were examined by indirect antiglobulin testing with anti-FYa and anti-FYb antibodies. The phenotypes were classified into four groups according to the agglutination reactions: FYa + FYb+, FYa + FYb-, FYa-FYb + and FYa-FYb-. The phenotypes and pathological diagnosis of consecutively hospitalized female patients (n = 5,022) suffering from breast cancer at the Shanghai Cancer Hospital and Henan Province Cancer Hospital were investigated. The relationships between DBGP expression with breast cancer occurrence, axillary lymph status, histological subtype, tumor size pathological grade and overall survival were analyzed. The incidence of breast cancer was significantly different between FYa + FYb + (29.8%), FYa + FYb- (33.2%), FYa-FYb + (45.6%) and FYa-FYb- (59.1%; P = 0.001). Significant different numbers of breast cancer patients had metastases to the axillary lymph nodes in the FYa + FYb + group (25.1%), FYa + FYb- (36.9%), FYa-FYb + (41.0%) and FYa-FYb- (50.0%, (P = 0.005). There was a statistical significance (p = 0.022) of the overall survival difference between patients with difference phenotypes. No significant difference was observed in cancer size (t-test, p > 0.05), histological cancer type (Fisher's exact test, p > 0.05) or histological grade (Fisher's exact test, p > 0.05) between every each DBGP group. DBGP is correlated with breast cancer incidence and axillary lymph node metastasis and overall survival. Further investigations are required to determine the underlying mechanism of Duffy blood group phenotype on breast cancer risk

  10. Robust and sensitive analysis of mouse knockout phenotypes.

    Directory of Open Access Journals (Sweden)

    Natasha A Karp

    Full Text Available A significant challenge of in-vivo studies is the identification of phenotypes with a method that is robust and reliable. The challenge arises from practical issues that lead to experimental designs which are not ideal. Breeding issues, particularly in the presence of fertility or fecundity problems, frequently lead to data being collected in multiple batches. This problem is acute in high throughput phenotyping programs. In addition, in a high throughput environment operational issues lead to controls not being measured on the same day as knockouts. We highlight how application of traditional methods, such as a Student's t-Test or a 2-way ANOVA, in these situations give flawed results and should not be used. We explore the use of mixed models using worked examples from Sanger Mouse Genome Project focusing on Dual-Energy X-Ray Absorptiometry data for the analysis of mouse knockout data and compare to a reference range approach. We show that mixed model analysis is more sensitive and less prone to artefacts allowing the discovery of subtle quantitative phenotypes essential for correlating a gene's function to human disease. We demonstrate how a mixed model approach has the additional advantage of being able to include covariates, such as body weight, to separate effect of genotype from these covariates. This is a particular issue in knockout studies, where body weight is a common phenotype and will enhance the precision of assigning phenotypes and the subsequent selection of lines for secondary phenotyping. The use of mixed models with in-vivo studies has value not only in improving the quality and sensitivity of the data analysis but also ethically as a method suitable for small batches which reduces the breeding burden of a colony. This will reduce the use of animals, increase throughput, and decrease cost whilst improving the quality and depth of knowledge gained.

  11. Contribution of different relapse phenotypes to disability in multiple sclerosis.

    Science.gov (United States)

    Stewart, Tamasine; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Duquette, Pierre; Girard, Marc; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, Francois; Grammond, Pierre; Sola, Patrizia; Shaygannejad, Vahid; Hupperts, Raymond; Alroughani, Raed; Oreja-Guevara, Celia; Pucci, Eugenio; Boz, Cavit; Lechner-Scott, Jeannette; Bergamaschi, Roberto; Van Pesch, Vincent; Iuliano, Gerardo; Ramo, Cristina; Taylor, Bruce; Slee, Mark; Spitaleri, Daniele; Granella, Franco; Verheul, Freek; McCombe, Pamela; Hodgkinson, Suzanne; Amato, Maria Pia; Vucic, Steve; Gray, Orla; Cristiano, Edgardo; Barnett, Michael; Sanchez Menoyo, Jose Luis; van Munster, Erik; Saladino, Maria Laura; Olascoaga, Javier; Prevost, Julie; Deri, Norma; Shaw, Cameron; Singhal, Bhim; Moore, Fraser; Rozsa, Csilla; Shuey, Neil; Skibina, Olga; Kister, Ilya; Petkovska-Boskova, Tatjana; Ampapa, Radek; Kermode, Allan; Butzkueven, Helmut; Jokubaitis, Vilija; Kalincik, Tomas

    2017-02-01

    This study evaluated the effect of relapse phenotype on disability accumulation in multiple sclerosis. Analysis of prospectively collected data was conducted in 19,504 patients with relapse-onset multiple sclerosis and minimum 1-year prospective follow-up from the MSBase cohort study. Multivariable linear regression models assessed associations between relapse incidence, phenotype and changes in disability (quantified with Expanded Disability Status Scale and its Functional System scores). Sensitivity analyses were conducted. In 34,858 relapses recorded during 136,462 patient-years (median follow-up 5.9 years), higher relapse incidence was associated with greater disability accumulation (β = 0.16, p < 0.001). Relapses of all phenotypes promoted disability accumulation, with the most pronounced increase associated with pyramidal (β = 0.27 (0.25-0.29)), cerebellar (β = 0.35 (0.30-0.39)) and bowel/bladder (β = 0.42 (0.35-0.49)) phenotypes (mean (95% confidence interval)). Higher incidence of each relapse phenotype was associated with an increase in disability in the corresponding neurological domain, as well as anatomically related domains. Relapses are associated with accumulation of neurological disability. Relapses in pyramidal, cerebellar and bowel/bladder systems have the greatest association with disability change. Therefore, prevention of these relapses is an important objective of disease-modifying therapy. The differential impact of relapse phenotypes on disability outcomes could influence management of treatment failure in multiple sclerosis.

  12. Genetic ancestry affects the phenotype of normogonadotropic anovulatory (WHOII) subfertility.

    Science.gov (United States)

    Valkenburg, O; Lao, O; Schipper, I; Louwers, Y; Uitterlinden, A G; Kayser, M; Laven, J S E

    2011-07-01

    Normogonadotropic (World Health Organization category II) anovulation is the most frequent cause of reduced fertility. Anovulation is associated with endocrine changes, i.e. hyperandrogenism, obesity, and insulin resistance. However, the phenotype is notoriously heterogeneous, depending on population characteristics and diagnostic criteria. Our objective was to study the phenotype of normogonadotropic anovulatory women among various ethnic subgroups that coexist in an urban community (The Netherlands). Moreover, we studied whether genetic ancestry testing can be used to identify bio-geographic ancestry and predict the phenotype of individual patients. A standardized clinical and endocrine examination was performed in 1517 normogonadotropic anovulatory women. Bio-geographic ancestry was ascertained by questionnaire and genetic testing (637 cases), using a set of 10 previously validated ancestry informative markers. Subgroups constituted individuals from northwestern European (n = 774), Mediterranean European (north of Sahara and Middle East, n = 220), African (n = 111), Southeast Asian (n = 53), and Hindustani (n = 83) origin. Phenotypic differences included fasting insulin levels, androgen levels, and the frequency of hyperandrogenism (ranging from 76% in Mediterranean-European women to 41% in northwestern European women). Genetic ancestry testing was able to identify population structure on a continental level, i.e. European, African and Southeast Asian descent. We did not observe improved informativeness when genotype data were added to the prediction model. Population differences add to the phenotype of normogonadotropic anovulation and need to be taken into account when evaluating the individual patient. Although effective on a continental level, the present set of ancestry markers was not sufficiently effective to describe all ethnic variation in the phenotype of anovulatory subfertility.

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

    Science.gov (United States)

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

    2017-04-01

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

  14. Genotypic richness predicts phenotypic variation in an endangered clonal plant

    Directory of Open Access Journals (Sweden)

    Suzanna M. Evans

    2016-02-01

    Full Text Available Declines in genetic diversity within a species can affect the stability and functioning of populations. The conservation of genetic diversity is thus a priority, especially for threatened or endangered species. The importance of genetic variation, however, is dependent on the degree to which it translates into phenotypic variation for traits that affect individual performance and ecological processes. This is especially important for predominantly clonal species, as no single clone is likely to maximise all aspects of performance. Here we show that intraspecific genotypic diversity as measured using microsatellites is a strong predictor of phenotypic variation in morphological traits and shoot productivity of the threatened, predominantly clonal seagrass Posidonia australis, on the east coast of Australia. Biomass and surface area variation was most strongly predicted by genotypic richness, while variation in leaf chemistry (phenolics and nitrogen was unrelated to genotypic richness. Genotypic richness did not predict tissue loss to herbivores or epiphyte load, however we did find that increased herbivore damage was positively correlated with allelic richness. Although there was no clear relationship between higher primary productivity and genotypic richness, variation in shoot productivity within a meadow was significantly greater in more genotypically diverse meadows. The proportion of phenotypic variation explained by environmental conditions varied among different genotypes, and there was generally no variation in phenotypic traits among genotypes present in the same meadows. Our results show that genotypic richness as measured through the use of presumably neutral DNA markers does covary with phenotypic variation in functionally relevant traits such as leaf morphology and shoot productivity. The remarkably long lifespan of individual Posidonia plants suggests that plasticity within genotypes has played an important role in the longevity of

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

    LENUS (Irish Health Repository)

    FitzGerald, Oliver

    2015-05-07

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

  16. Desmoplakin truncations and arrhythmogenic left ventricular cardiomyopathy: characterizing a phenotype.

    Science.gov (United States)

    López-Ayala, Jose María; Gómez-Milanés, Ivan; Sánchez Muñoz, Juan José; Ruiz-Espejo, Francisco; Ortíz, Martín; González-Carrillo, Josefa; López-Cuenca, David; Oliva-Sandoval, M J; Monserrat, Lorenzo; Valdés, Mariano; Gimeno, Juan R

    2014-12-01

    Risk stratification for sudden death in arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging in clinical practice. We lack recommendations for the risk stratification of exclusive left-sided phenotypes. The aim of this study was to investigate genotype-phenotype correlations in patients carrying a novel DSP c.1339C>T, and to review the literature on the clinical expression and the outcomes in patients with DSP truncating mutations. Genetic screening of the DSP gene was performed in 47 consecutive patients with a phenotype of either an ARVC (n = 24) or an idiopathic dilated cardiomyopathy (DCM), who presented with ventricular arrhythmias or a family history of sudden death (n = 23) (aged 40 ± 19 years, 62% males). Three unrelated probands with DCM were found to be carriers of a novel mutation (c.1339C>T). Cascade family screening led to the identification of 15 relatives who are carriers. Penetrance in c.1339C>T carriers was 83%. Sustained ventricular tachycardia was the first clinical manifestation in six patients and nine patients were diagnosed with left ventricular impairment (two had overt severe disease and seven had a mild dysfunction). Cardiac magnetic resonance revealed left ventricular involvement in nine cases and biventricular disease in three patients. Extensive fibrotic patterns in six and non-compaction phenotype in five patients were the hallmark in imaging. DSP c.1339C>T is associated with an aggressive clinical phenotype of left-dominant arrhythmogenic cardiomyopathy and left ventricular non-compaction. Truncating mutations in desmoplakin are consistently associated with aggressive phenotypes and must be considered as a risk factor of sudden death. Since ventricular tachycardia occurs even in the absence of severe systolic dysfunction, an implantable cardioverter-defibrillator should be indicated promptly. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please

  17. Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation.

    Science.gov (United States)

    Posey, Jennifer E; Harel, Tamar; Liu, Pengfei; Rosenfeld, Jill A; James, Regis A; Coban Akdemir, Zeynep H; Walkiewicz, Magdalena; Bi, Weimin; Xiao, Rui; Ding, Yan; Xia, Fan; Beaudet, Arthur L; Muzny, Donna M; Gibbs, Richard A; Boerwinkle, Eric; Eng, Christine M; Sutton, V Reid; Shaw, Chad A; Plon, Sharon E; Yang, Yaping; Lupski, James R

    2017-01-05

    Whole-exome sequencing can provide insight into the relationship between observed clinical phenotypes and underlying genotypes. We conducted a retrospective analysis of data from a series of 7374 consecutive unrelated patients who had been referred to a clinical diagnostic laboratory for whole-exome sequencing; our goal was to determine the frequency and clinical characteristics of patients for whom more than one molecular diagnosis was reported. The phenotypic similarity between molecularly diagnosed pairs of diseases was calculated with the use of terms from the Human Phenotype Ontology. A molecular diagnosis was rendered for 2076 of 7374 patients (28.2%); among these patients, 101 (4.9%) had diagnoses that involved two or more disease loci. We also analyzed parental samples, when available, and found that de novo variants accounted for 67.8% (61 of 90) of pathogenic variants in autosomal dominant disease genes and 51.7% (15 of 29) of pathogenic variants in X-linked disease genes; both variants were de novo in 44.7% (17 of 38) of patients with two monoallelic variants. Causal copy-number variants were found in 12 patients (11.9%) with multiple diagnoses. Phenotypic similarity scores were significantly lower among patients in whom the phenotype resulted from two distinct mendelian disorders that affected different organ systems (50 patients) than among patients with disorders that had overlapping phenotypic features (30 patients) (median score, 0.21 vs. 0.36; P=1.77×10 -7 ). In our study, we found multiple molecular diagnoses in 4.9% of cases in which whole-exome sequencing was informative. Our results show that structured clinical ontologies can be used to determine the degree of overlap between two mendelian diseases in the same patient; the diseases can be distinct or overlapping. Distinct disease phenotypes affect different organ systems, whereas overlapping disease phenotypes are more likely to be caused by two genes encoding proteins that interact within

  18. Machine learning and computer vision approaches for phenotypic profiling.

    Science.gov (United States)

    Grys, Ben T; Lo, Dara S; Sahin, Nil; Kraus, Oren Z; Morris, Quaid; Boone, Charles; Andrews, Brenda J

    2017-01-02

    With recent advances in high-throughput, automated microscopy, there has been an increased demand for effective computational strategies to analyze large-scale, image-based data. To this end, computer vision approaches have been applied to cell segmentation and feature extraction, whereas machine-learning approaches have been developed to aid in phenotypic classification and clustering of data acquired from biological images. Here, we provide an overview of the commonly used computer vision and machine-learning methods for generating and categorizing phenotypic profiles, highlighting the general biological utility of each approach. © 2017 Grys et al.

  19. Structural genomic variation in childhood epilepsies with complex phenotypes

    DEFF Research Database (Denmark)

    Helbig, Ingo; Swinkels, Marielle E M; Aten, Emmelien

    2014-01-01

    A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role...... of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened...

  20. Karyologic Variation in Different Phenotypes of Sciurus granatensis (Rodentia, Sciuridae

    Directory of Open Access Journals (Sweden)

    Carolina Arango

    2007-08-01

    Full Text Available Seven specimens of Sciurus granatensis (redtailed squirrel rescued from illegal fauna traffic in Colombia were studied; they had different phenotypes according to colour. G, C, Q, R and NOR chromosome banding was used, being found a 2n=42 diploid number for the Sciurus granatensis Colombian squirrels. There were 3 karyomorphs according to fundamental number (FN and different chromosomal characteristics caused by rearregement, suggesting that S. granatensis represents a complex of species. Relationships between karyotype and phenotype were not observed. The variation in the colour of sqirrels' fur was probably due to environmental conditions.

  1. PhenoTips: Patient Phenotyping Software for Clinical and Research Use.

    OpenAIRE

    Girdea, Marta; Dumitriu, Sergiu; Fiume, Marc; Buske, Orion; Bowdin, Sarah; Boycott, Kym M.; Chénier, Sébastien; Chitayat, David; Faghfoury, Hanna; Meyn, Stephen; Ray, Peter N.; So, Joyce; Stavropoulos, Dimitri J.; Brudno, Michael

    2014-01-01

    We have developed PhenoTips, a deep phenotyping tool and database, specifically designed for phenotyping patients with genetic disorders. Our tool closely mirrors clinician workflows so as to facilitate the recording of observations made during the patient encounter. Phenotypic information is represented using the Human Phenotype Ontology; however, the complexity of the ontology is hidden behind a user interface, which combines simple selection of common phenotypes with error-tolerant, predic...

  2. A comparison of power to detect a QTL in sib-pair data using multivariate phenotypes, mean phenotypes, and factor scores

    NARCIS (Netherlands)

    Boomsma, D.I.; Dolan, C.V.

    1998-01-01

    The power to detect a quantitative trait locus (QTL) in sib-pair data is investigated. We assume that we have at our disposal 3 or 4 related phenotypic measures in a sample of sib-pairs. Individual differences in these phenotypes are due to a common QTL and specific (i.e., unique to each phenotype)

  3. Comparative Analysis of the ABO and Rh CDE Phenotype ...

    African Journals Online (AJOL)

    Data presented in this report further evaluate the distribution and inter-ethnic phenotypic variability of the ABO and Rh blood groups among students of a tertiary institution in Port Harcourt. Standard haemagglutination procedures were used. ABO blood group frequencies were obtained as follows: 23.8% for blood group A, ...

  4. Lymphomatoid papulosis with a natural killer-cell phenotype

    NARCIS (Netherlands)

    Bekkenk, M. W.; Kluin, P. M.; Jansen, P. M.; Meijer, C. J.; Willemze, R.

    2001-01-01

    Lymphomatoid papulosis (LyP) is defined as a recurrent self-healing papulonodular eruption with the histological features of a (CD30+) cutaneous T-cell lymphoma. The atypical cells usually have a CD3+/-, CD4+/-, CD8-, CD30+, CD56- T-cell phenotype. We report an unusual case of LyP, in which the

  5. Lymphomatoid papulosis with a natural killer-cell phenotype

    NARCIS (Netherlands)

    Bekkenk, MW; Kluin, PM; Jansen, PM; Meijer, CJLM; Willemze, R

    Lymphomatoid papulosis (LyP) is defined as a recurrent self-healing papulonodular eruption with the histological features of a (CD30+) cutaneous T-cell lymphoma. The atypical cells usually have a CD3+/-, CD4+/-, CD8-, CD30+, CD56- T-cell phenotype. We report an unusual case of LyP, in which the

  6. 1. Association between Presence of Haptoglobin Phenotypes and ...

    African Journals Online (AJOL)

    RICHY

    1. Medical Journal of Zambia, Vol. 42, No. 1: 1- 6 (2015). ABSTRACT. Objectives: The aim of the study was to investigate the association between presence of haptoglobin phenotypes and hypertension in indigenous Zambian patients attending outpatient medical clinic at the University. Teaching Hospital in Lusaka, Zambia.

  7. Iris phenotypes and pigment dispersion caused by genes influencing pigmentation.

    Science.gov (United States)

    Anderson, Michael G; Hawes, Norman L; Trantow, Colleen M; Chang, Bo; John, Simon W M

    2008-10-01

    Spontaneous mutations altering mouse coat colors have been a classic resource for discovery of numerous molecular pathways. Although often overlooked, the mouse iris is also densely pigmented and easily observed, thus representing a similarly powerful opportunity for studying pigment cell biology. Here, we present an analysis of iris phenotypes among 16 mouse strains with mutations influencing melanosomes. Many of these strains exhibit biologically and medically relevant phenotypes, including pigment dispersion, a common feature of several human ocular diseases. Pigment dispersion was identified in several strains with mutant alleles known to influence melanosomes, including beige, light, and vitiligo. Pigment dispersion was also detected in the recently arising spontaneous coat color variant, nm2798. We have identified the nm2798 mutation as a missense mutation in the Dct gene, an identical re-occurrence of the slaty light mutation. These results suggest that dysregulated events of melanosomes can be potent contributors to the pigment dispersion phenotype. Combined, these findings illustrate the utility of studying iris phenotypes as a means of discovering new pathways, and re-linking old ones, to processes of pigmented cells in health and disease.

  8. Phenotypic and physiological aspects related to drought tolerance in ...

    African Journals Online (AJOL)

    Drought is one of the major limitations to crop productivity worldwide. Identifying suitable screening tools and quantifiable traits would facilitate the crop improvement process for drought tolerance in sorghum. This study evaluated phenotypic characteristics and physiological parameters determine which cultivars are more ...

  9. Some insights into the phenotypic and genetic diversity of ...

    African Journals Online (AJOL)

    Deon

    Abstract. Indigenous pigs in southern Africa are mainly owned by economically vulnerable groups in marginal areas where they are used as a source food, income and security. A study was carried out to achieve three objectives: to describe pig production systems, get a phenotypic description of the pigs and to characterize.

  10. Phenotypic plasticity of body size in a temperate population of ...

    Indian Academy of Sciences (India)

    ture, however, wild-collected flies show a large phenotypic variance in size, implying a ... bigger in the cold (Partridge and Coyne 1997; Pétavy et al. 1997; Bochdanovits and ..... One is to consider the whole matrix of isofemale lines data, corresponding to 210 mean values (30 lines × 7 temperatures). The other is to consider ...

  11. In vitro phenotypic differentiation towards commensal and pathogenic oral biofilms

    NARCIS (Netherlands)

    Janus, M.M.; Keijser, B.J.F.; Bikker, F.J.; Exterkate, R.A.M.; Crielaard, W.; Krom, B.P.

    2015-01-01

    Commensal oral biofilms, defined by the absence of pathology-related phenotypes, are ubiquitously present. In contrast to pathological biofilms commensal biofilms are rarely studied. Here, the effect of the initial inoculum and subsequent growth conditions on in vitro oral biofilms was studied.

  12. Phenotypic switching of populations of cells in a stochastic environment

    Science.gov (United States)

    Hufton, Peter G.; Lin, Yen Ting; Galla, Tobias

    2018-02-01

    In biology phenotypic switching is a common bet-hedging strategy in the face of uncertain environmental conditions. Existing mathematical models often focus on periodically changing environments to determine the optimal phenotypic response. We focus on the case in which the environment switches randomly between discrete states. Starting from an individual-based model we derive stochastic differential equations to describe the dynamics, and obtain analytical expressions for the mean instantaneous growth rates based on the theory of piecewise-deterministic Markov processes. We show that optimal phenotypic responses are non-trivial for slow and intermediate environmental processes, and systematically compare the cases of periodic and random environments. The best response to random switching is more likely to be heterogeneity than in the case of deterministic periodic environments, net growth rates tend to be higher under stochastic environmental dynamics. The combined system of environment and population of cells can be interpreted as host-pathogen interaction, in which the host tries to choose environmental switching so as to minimise growth of the pathogen, and in which the pathogen employs a phenotypic switching optimised to increase its growth rate. We discuss the existence of Nash-like mutual best-response scenarios for such host-pathogen games.

  13. Phenotypic plasticity and reaction norms of abdominal bristle ...

    Indian Academy of Sciences (India)

    Unknown

    The phenotypic plasticity of abdominal bristle number (segments 3 and 4 in females) was investigated in 10 iso- female lines from a French population, grown at 7 constant temperatures, ranging from 12° to 31°C. Overall concave reaction norms were obtained with a maximum around 20°–21°C. Intraclass correlation ...

  14. Phenotypic and genetic parameters for selected production and ...

    African Journals Online (AJOL)

    Phenotypic and genetic parameters for selected production and reproduction traits of Mpwapwa cattle in low-input production systems. ... Genetic parameters were estimated using an animal model procedure with ASReml software. The heritability for LMY and 305LMY were moderately high (0.33 ± 0.11–0.44 ± 0.04) and ...

  15. Genetic and phenotypic variation of some reproductive traits in ...

    African Journals Online (AJOL)

    The objectives of this study were to determine the effects of season, year of calving and parity on lactation period, calving interval, number of days open and dry period in Egyptian buffalo, and to estimate genetic and phenotypic parameters for these traits using a multi-trait animal model. Season of calving, year of calving ...

  16. Genetic and phenotypic variation of some reproductive traits in ...

    African Journals Online (AJOL)

    Unknown

    Abstract. The objectives of this study were to determine the effects of season, year of calving and parity on lactation period, calving interval, number of days open and dry period in Egyptian buffalo, and to estimate genetic and phenotypic parameters for these traits using a multi-trait animal model. Season of calving, year.

  17. A simple algorithm for the identification of clinical COPD phenotypes

    NARCIS (Netherlands)

    Burgel, Pierre-Régis; Paillasseur, Jean-Louis; Janssens, Wim; Piquet, Jacques; ter Riet, Gerben; Garcia-Aymerich, Judith; Cosio, Borja; Bakke, Per; Puhan, Milo A.; Langhammer, Arnulf; Alfageme, Inmaculada; Almagro, Pere; Ancochea, Julio; Celli, Bartolome R.; Casanova, Ciro; de-Torres, Juan P.; Decramer, Marc; Echazarreta, Andrés; Esteban, Cristobal; Gomez Punter, Rosa Mar; Han, MeiLan K.; Johannessen, Ane; Kaiser, Bernhard; Lamprecht, Bernd; Lange, Peter; Leivseth, Linda; Marin, Jose M.; Martin, Francis; Martinez-Camblor, Pablo; Miravitlles, Marc; Oga, Toru; Sofia Ramírez, Ana; Sin, Don D.; Sobradillo, Patricia; Soler-Cataluña, Juan J.; Turner, Alice M.; Verdu Rivera, Francisco Javier; Soriano, Joan B.; Roche, Nicolas

    2017-01-01

    This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses. Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of

  18. Prevalence of Rh Phenotypes among Blood Donors in Kano, Nigeria

    African Journals Online (AJOL)

    Background: The Rh antigens have been reported to cause acute and delayed haemolytic transfusion reactions apart from the dreadful Haemolytic Disease of the Newborn. The aim of this study was determine the prevalence of Rh phenotypes that would serve as a baseline data towards provision of safe blood transfusion ...

  19. Improving Phenotypic Prediction by Combining Genetic and Epigenetic Associations

    NARCIS (Netherlands)

    Shah, S.; Bonder, M.J.; Marioni, R.E.; Zhu, Z.; McRae, A.F.; Zhernakova, A.; Harris, S.E.; Liewald, D.C.M.; Henders, A.K.; Mendelson, M.M.; Liu, C.; Joehanes, R.; Liang, L.; Boomsma, D.I.; Pool, R.; van Dongen, J.; Hottenga, J.J.; Levy, D.; Martin, N.G.; Starr, J.M.; Wijmenga, C.; Wray, N.R.; Yang, J.; Montgomery, G.W.; Franke, L.; Deary, I.J.; Visscher, P.M.

    2015-01-01

    We tested whether DNA-methylation profiles account for inter-individual variation in body mass index (BMI) and height and whether they predict these phenotypes over and above genetic factors. Genetic predictors were derived from published summary results from the largest genome-wide association

  20. Maternal Vitamin D Levels and the Autism Phenotype among Offspring

    Science.gov (United States)

    Whitehouse, Andrew J. O.; Holt, Barbara J.; Serralha, Michael; Holt, Patrick G.; Hart, Prue H.; Kusel, Merci M. H.

    2013-01-01

    We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks' pregnancy. The mothers of the three children with a clinical diagnosis of autism spectrum disorder had 25(OH)-vitamin D concentrations above the population mean.…

  1. Sex Differences in Genetic Architecture of Complex Phenotypes?

    NARCIS (Netherlands)

    Vink, J.M.; Bartels, M.; van Beijsterveldt, C.E.M.; van Dongen, J.; van Beek, J.H.D.A.; Distel, M.A.; de Moor, M.H.M.; Smit, D.J.A.; Minica, C.C.; Ligthart, R.S.L.; Geels, L.M.; Abdellaoui, A.; Middeldorp, C.M.; Hottenga, J.J.; Willemsen, G.; de Geus, E.J.C.; Boomsma, D.I.

    2012-01-01

    We examined sex differences in familial resemblance for a broad range of behavioral, psychiatric and health related phenotypes (122 complex traits) in children and adults. There is a renewed interest in the importance of genotype by sex interaction in, for example, genome-wide association (GWA)

  2. Phenotypic plasticity, clonal architecture and biomass partitioning in ...

    African Journals Online (AJOL)

    Shahzada

    2013-05-08

    May 8, 2013 ... traits, clonal architecture and biomass partitioning to different plant parts was observed between standing and running water ..... and life-history. Trends Plant Sci. 5: 537-542. Sultan SE (2003).Phenotypic plasticity in plants: a case study in ecological development. Evol. Dev. 5: 25-33. Willson MF (1983).

  3. Studying disease-linked phenotypes using haploid genetics

    NARCIS (Netherlands)

    Blomen, Vincent A.

    2017-01-01

    Although genes are unequivocally important for the development of both common and rare human diseases, the connection between the genotype (an individual’s genetic makeup) and phenotype (an individual’s observable traits) is often ill-defined. Even genetic disorders caused by a defect in only a

  4. Risk Prediction Models for Oral Clefts Allowing for Phenotypic Heterogeneity

    Directory of Open Access Journals (Sweden)

    Yalu eWen

    2015-08-01

    Full Text Available Oral clefts are common birth defects that have a major impact on the affected individual, their family and society. World-wide, the incidence of oral clefts is 1/700 live births, making them the most common craniofacial birth defects. The successful prediction of oral clefts may help identify sub-population at high risk, and promote new diagnostic and therapeutic strategies. Nevertheless, developing a clinically useful oral clefts risk prediction model remains a great challenge. Compelling evidences suggest the etiologies of oral clefts are highly heterogeneous, and the development of a risk prediction model with consideration of phenotypic heterogeneity may potentially improve the accuracy of a risk prediction model. In this study, we applied a previously developed statistical method to investigate the risk prediction on sub-phenotypes of oral clefts. Our results suggested subtypes of cleft lip and palate have similar genetic etiologies (AUC=0.572 with subtypes of cleft lip only (AUC=0.589, while the subtypes of cleft palate only (CPO have heterogeneous underlying mechanisms (AUCs for soft CPO and hard CPO are 0.617 and 0.623, respectively. This highlighted the potential that the hard and soft forms of CPO have their own mechanisms despite sharing some of the genetic risk factors. Comparing with conventional methods for risk prediction modeling, our method considers phenotypic heterogeneity of a disease, which potentially improves the accuracy for predicting each sub-phenotype of oral clefts.

  5. Dissecting the correlation structure of a bivariate phenotype ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 84; Issue 2. Dissecting the correlation structure of a bivariate phenotype: common genes or shared environment? ... High correlations between two quantitative traits may be either due to common genetic factors or common environmental factors or a combination of both.

  6. KBG syndrome and the establishment of its neuropsychological phenotype

    NARCIS (Netherlands)

    Egger, J.I.M.; Dongen, L.C.M. van; Stumpel, C.; Wingbermühle, P.A.M.; Kleefstra, T.

    2017-01-01

    Objective: KBG syndrome is caused by a mutation in the ANKRD11 gene, characterized by short stature and specific dental, craniofacial and skeletal anomalies. Scarce literature on the phenotypical presentation mention delayed speech and motor development as well as mild to moderate intellectual

  7. Identifying Neurobiological Markers of the Broader Autism Phenotype

    Science.gov (United States)

    2015-01-01

    with ASD and their families. Keywords: Autism Spectrum Disorders (ASD), Broader Autism Phenotype (BAP), nonverbal emotions , social cognition... emotional recall/imagery (Beauregard, et al., 2001; Eippert, et al., 2007; Phan, et al., 2002; Schutter & Honk, 2009). Our findings may therefore reflect...vocal emotions expressed by others (Aziz-Zadeh, et al., 2010; Gallese, 2007). Accordingly, our neuroimaging paradigm provides an exciting new

  8. Maxillofacial and mandibular phenotypes in the skulls of red Sokoto ...

    African Journals Online (AJOL)

    This work examined phenotypic expressions in the anatomy of the mandible and maxillofacial region of the Red Sokoto and Sahel goats in Nigeria. The infraorbital foramen was placed above premolar two (PM2) in Red Sokoto but above premolar one (PM1) in Sahel. The Red Sokoto displayed interdigital septa (ruggae) ...

  9. Phenotypic Detection and Antibiogram of β‑lactamase‑producing ...

    African Journals Online (AJOL)

    None of the isolates were resistant to piperacillin‑tazobactam. P. penneri isolates exhibited high resistance to most of the antibiotics. Conclusions: A high prevalence of ESBL and AmpC β‑lactamases was found that concurrently showed MDR. Phenotypic methods for the detection of β‑lactamases are easy and simple and ...

  10. Alpha-1 antitrypsin phenotypes in patients with Klinefelter's syndrome

    Indian Academy of Sciences (India)

    Klinefelter's syndrome (KS) is the most common human sex chromosome disorder, with a prevalence of 1 in 660 men. The phenotype is variable, but the most constant findings are small and firm testes, decreased testosterone level, infertility, eunuchoid body proportion, increased height, and learning disabilities, due to the ...

  11. Efficient learning of microbial genotype-phenotype association rules.

    Science.gov (United States)

    MacDonald, Norman J; Beiko, Robert G

    2010-08-01

    Finding biologically causative genotype-phenotype associations from whole-genome data is difficult due to the large gene feature space to mine, the potential for interactions among genes and phylogenetic correlations between genomes. Associations within phylogenetically distinct organisms with unusual molecular mechanisms underlying their phenotype may be particularly difficult to assess. We have developed a new genotype-phenotype association approach that uses Classification based on Predictive Association Rules (CPAR), and compare it with NETCAR, a recently published association algorithm. Our implementation of CPAR gave on average slightly higher classification accuracy, with approximately 100 time faster running times. Given the influence of phylogenetic correlations in the extraction of genotype-phenotype association rules, we furthermore propose a novel measure for downweighting the dependence among samples by modeling shared ancestry using conditional mutual information, and demonstrate its complementary nature to traditional mining approaches. Software implemented for this study is available under the Creative Commons Attribution 3.0 license from the author at http://kiwi.cs.dal.ca/Software/PICA

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

    DEFF Research Database (Denmark)

    Li, Shuxia; Duan, Hongmei; Pang, Zengchang

    2013-01-01

    modeling was performed on full and nested models with the best fitting models selected. Results: Heritability estimates were compared between Danish and Chinese samples to identify differential genetic influences on each of the phenotypes. Except for hip circumference, all other body measures exhibited...

  13. Some insights into the phenotypic and genetic diversity of ...

    African Journals Online (AJOL)

    Deon

    objectives: to describe pig production systems, get a phenotypic description of the pigs and to characterize ... aimed at combining data on production systems, physical attributes and genetic diversity in order to build a .... condition scores of pigs and chemical composition of pig feed resources in a semi-arid smallholder.

  14. Genotypic and phenotypic diversity among Bacillus species isolated ...

    African Journals Online (AJOL)

    DIRECTOR

    2013-03-20

    Mar 20, 2013 ... representatives of eight species (licheniformis, polymyxa, laterosporus, cereus, circulans, subtilis, pumilus and brevis) were studied. Results of genotypic analyses were not concurrent with previous phenotypic identification. Bacillus from different species were able to cluster together to form phylogenetic ...

  15. Study on common phenotypic traits for purchasing sheep and their ...

    African Journals Online (AJOL)

    A study was conducted in 2008 to assess the relationship between common phenotypic traits most considered for marketing sheep and the body weight and price of sheep at markets of four towns in East Showa zone. Six hundred randomly selected sheep purchased for various purposes were studied. The study methods.

  16. Functional adaptation and phenotypic plasticity at the cellular and ...

    Indian Academy of Sciences (India)

    2009-08-10

    Aug 10, 2009 ... The ability to adaptively alter morphological, anatomical, or physiological functional traits to local environmental variations using external environmental cues is especially well expressed by all terrestrial and most aquatic plants. A ubiquitous cue eliciting these plastic phenotypic responses is mechanical ...

  17. Genotypic and phenotypic diversity among Bacillus species isolated ...

    African Journals Online (AJOL)

    Dichotomous keys based on morphological, cultural and biochemical tests have long been used to identify Bacillus species. The analysis of 16S rDNA is suggested to be used for identification that is more exact. The present study was carried out to compare a conventional phenotypic method with the analysis of the 16S ...

  18. Not in their genes: Phenotypic flexibility, behavioural traditions and ...

    Indian Academy of Sciences (India)

    2005-03-11

    Mar 11, 2005 ... Behavioural transmission; bonnet macaque; cultural evolution; Macaca radiata; phenotypic flexibility; social traditions ... National Institute of Advanced Studies, Indian Institute of Science Campus, Bangalore 560 012, India; Indian Association for the Cultivation of Science, 2A-2B Raja S C Mullick Road, ...

  19. Estimating genetic correlations based on phenotypic data: a ...

    Indian Academy of Sciences (India)

    effects. [Zintzaras E. 2011 Estimating genetic correlations based on phenotypic data: a simulation-based method. J. Genet. 90, 51–58]. Introduction. The evolutionary ... sibs); and (iii) shared environmental effects are absent, equa- tion (1) can ..... the averages of WL and WW in each fly following Becker. (1984). Table 1 gives ...

  20. Phenotypic Characterization of the Bunaji Cattle Breed in Oyo State ...

    African Journals Online (AJOL)

    STD), body length (BLT), heart girth (HTG), height at withers (HTW), canon circumference (CCR), tail length (TLT), horn length (HLT) and ear length (ELT). Phenotypic traits such as dewlap, coat color, horn type, ear type, hump type and navel flap ...

  1. Endocannabinoids drive the acquisition of an alternative phenotype in microglia.

    Science.gov (United States)

    Mecha, M; Feliú, A; Carrillo-Salinas, F J; Rueda-Zubiaurre, A; Ortega-Gutiérrez, S; de Sola, R García; Guaza, C

    2015-10-01

    The ability of microglia to acquire diverse states of activation, or phenotypes, reflects different features that are determinant for their contribution to homeostasis in the adult CNS, and their activity in neuroinflammation, repair or immunomodulation. Despite the widely reported immunomodulatory effects of cannabinoids in both the peripheral immune system and the CNS, less is known about how the endocannabinoid signaling system (eCBSS) influence the microglial phenotype. The general aim of the present study was to investigate the role of endocannabinoids in microglia polarization by using microglia cell cultures. We show that alternative microglia (M2a) and acquired deactivated microglia (M2c) exhibit changes in the eCB machinery that favor the selective synthesis of 2-AG and AEA, respectively. Once released, these eCBs might be able to act through CB1 and/or CB2 receptors in order to influence the acquisition of an M2 phenotype. We present three lines of evidence that the eCBSS is critical for the acquisition of the M2 phenotype: (i) M2 polarization occurs on exposure to the two main endocannabinoids 2-AG and AEA in microglia cultures; (ii) cannabinoid receptor antagonists block M2 polarization; and (iii) M2 polarization is dampened in microglia from CB2 receptor knockout mice. Taken together, these results indicate the interest of eCBSS for the regulation of microglial activation in normal and pathological conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Fire coral clones demonstrate phenotypic plasticity among reef habitats.

    Science.gov (United States)

    Dubé, Caroline E; Boissin, Emilie; Maynard, Jeffrey A; Planes, Serge

    2017-08-01

    Clonal populations are often characterized by reduced levels of genotypic diversity, which can translate into lower numbers of functional phenotypes, both of which impede adaptation. Study of partially clonal animals enables examination of the environmental settings under which clonal reproduction is favoured. Here, we gathered genotypic and phenotypic information from 3,651 georeferenced colonies of the fire coral Millepora platyphylla in five habitats with different hydrodynamic regimes in Moorea, French Polynesia. In the upper slope where waves break, most colonies grew as vertical sheets ("sheet tree") making them more vulnerable to fragmentation. Nearly all fire corals in the other habitats are encrusting or massive. The M. platyphylla population is highly clonal (80% of the colonies are clones), while characterized by the highest genotype diversity ever documented for terrestrial or marine populations (1,064 genotypes). The proportion of clones varies greatly among habitats (≥58%-97%) and clones (328 clonal lineages) are distributed perpendicularly from the reef crest, perfectly aligned with wave energy. There are six clonal lineages with clones dispersed in at least two adjacent habitats that strongly demonstrate phenotypic plasticity. Eighty per cent of the colonies in these lineages are "sheet tree" on the upper slope, while 80%-100% are encrusting or massive on the mid slope and back reef. This is a unique example of phenotypic plasticity among reef-building coral clones as corals typically have wave-tolerant growth forms in high-energy reef areas. © 2017 John Wiley & Sons Ltd.

  3. Phenotypic characterization of DFNA24: prelingual progressive sensorineural hearing impairment.

    NARCIS (Netherlands)

    Santos, R.L.; Hafner, F.M.; Huygen, P.L.M.; Linder, T.E.; Schinzel, A.; Spillmann, T.; Leal, S.M.

    2006-01-01

    This article describes the hearing impairment (HI) phenotype which segregates in a large multi-generation Swiss-German family with autosomal dominant nonsyndromic HI. The locus segregating within this pedigree is located on chromosome 4q35-qter and is designated as DFNA24. For this pedigree,

  4. Panic and phobic anxiety: defining phenotypes for genetic studies.

    Science.gov (United States)

    Smoller, J W; Tsuang, M T

    1998-09-01

    With recent advances in molecular genetics, the rate-limiting step in identifying susceptibility genes for psychiatric disorders has become phenotype definition. The success of psychiatric genetics may require the development of a "genetic nosology" that can classify individuals in terms of the heritable aspects of psychopathology. The authors' aim is to begin to apply this analysis to the anxiety disorders, focusing on panic and phobic disorders. Two parallel traditions of defining anxiety phenotypes are reviewed: the first, more closely identified with clinical psychiatry, has identified categorical diagnoses (e.g., panic disorder and social phobia). The other, more closely identified with psychological studies of personality development, has examined dimensional traits (e.g., neuroticism) and anxious temperament (e.g., behavioral inhibition). The authors suggest that a genetic nosology of panic and phobic disorders may incorporate features of both traditions and discuss strategies for optimizing genetic approaches to anxiety including 1) studying phenotypic extremes, 2) identifying biological trait markers, and 3) using animal models to identify candidate loci. An important dividend from the effort to define the boundaries of heritable phenotypes for genetic studies of anxiety may be a refinement of the nosology of anxiety disorders.

  5. Genetic Dissection of Behavioral Phenotypes. Lost & Found in Translation

    NARCIS (Netherlands)

    Bruining, H.

    2011-01-01

    This thesis shows that the exploration of human genetic disorders and animal genetic models can bring understanding of the causes and mechanisms of common psychiatric disorders. The first part of the thesis contains studies on genetic behavioral phenotypes in boys with Klinefelter syndrome, a human

  6. Prevalence of coat colour phenotypes and its influence on mange ...

    African Journals Online (AJOL)

    Prevalence of coat colour phenotypes and its influence on sarcoptic mange infestation of West African Dwarf (WAD) goats reared extensively by subsistence farmers in South-west Nigeria was investigated from March to October, 2011. The total number of goats randomly sampled from different villages within the same ...

  7. Nicolaides-Baraitser Syndrome: Delineation of the Phenotype

    NARCIS (Netherlands)

    Sousa, Sérgio B.; Abdul-Rahman, Omar A.; Bottani, Armand; Cormier-Daire, Valérie; Fryer, Alan; Gillessen-Kaesbach, Gabriele; Horn, Denise; Josifova, Dragana; Kuechler, Alma; Lees, Melissa; Macdermot, Kay; Magee, Alex; Morice-Picard, Fanny; Rosser, Elizabeth; Sarkar, Ajoy; Shannon, Nora; Stolte-Dijkstra, Irene; Verloes, Alain; Wakeling, Emma; Wilson, Louise; Hennekam, Raoul C. M.

    2009-01-01

    Nicolaides-Baraitser syndrome (NBS) is an infrequently described condition, thus far reported in five cases. In order to delineate the phenotype and its natural history in more detail, we gathered data on 18 hitherto unreported patients through a multi-center collaborative study, and follow-up data

  8. Nicolaides-Baraitser Syndrome : Delineation of the Phenotype

    NARCIS (Netherlands)

    Sousa, Sergio B.; Abdul-Rahman, Omar A.; Bottani, Armand; Cormier-Daire, Valerie; Fryer, Alan; Gillessen-Kaesbach, Gabriele; Horn, Denise; Josifova, Dragana; Kuechler, Alma; Lees, Melissa; MacDermot, Kay; Magee, Alex; Morice-Picard, Fanny; Rosser, Elizabeth; Sarkar, Ajoy; Shannon, Nora; Stolte-Dijkstra, Irene; Verloes, Alain; Wakeling, Emma; Wilson, Louise; Hennekam, Raoul C. M.

    Nicolaides-Baraitser syndrome (NBS) is an infrequently described condition, thus far reported in five cases. In order to delineate the phenotype and its natural history in more detail, we gathered data on 18 hitherto unreported patients through a multi-center collaborative study, and follow-up data

  9. Phenotypic characterization of camels and their production system ...

    African Journals Online (AJOL)

    The objectives of the study were to characterize the production system of camel in Yabello and Melka Soda districts and to characterize phenotypically camel based on quantitative and qualitative traits. A total of 192 households were selected for characterization of the production system and 300 camels were sampled ...

  10. In vitro Phenotypic Antibiotic Susceptibility Profiles Of Food Indicator ...

    African Journals Online (AJOL)

    The Gram-negative bacteria from granulated sugar samples had 7.69% phenotypic resistance profiles while the Gram-negative bacteria from table salt samples had between 13.3% and 20.0% resistance profiles. The resistance profiles of Gram-positive bacteria from granulated sugar samples was between 8.0% and 19.0% ...

  11. Genotype phenotype mapping in RNA viruses - disjunctive normal form learning.

    Science.gov (United States)

    Wu, Chuang; Walsh, Andrew S; Rosenfeld, Roni

    2011-01-01

    RNA virus phenotypic changes often result from multiple alternative molecular mechanisms, where each mechanism involves changes to a small number of key residues. Accordingly, we propose to learn genotype-phenotype functions, using Disjunctive Normal Form (DNF) as the assumed functional form. In this study we develop DNF learning algorithms that attempt to construct predictors as Boolean combinations of covariates. We demonstrate the learning algorithm's consistency and efficiency on simulated sequences, and establish their biological relevance using a variety of real RNA virus datasets representing different viral phenotypes, including drug resistance, antigenicity, and pathogenicity. We compare our algorithms with previously published machine learning algorithms in terms of prediction quality: leave-one-out performance shows superior accuracy to other machine learning algorithms on the HIV drug resistance dataset and the UCIs promoter gene dataset. The algorithms are powerful in inferring the genotype-phenotype mapping from a moderate number of labeled sequences, as are typically produced in mutagenesis experiments. They can also greedily learn DNFs from large datasets. The Java implementation of our algorithms will be made publicly available.

  12. Do plants and animals differ in phenotypic plasticity?

    Indian Academy of Sciences (India)

    2004-11-30

    Nov 30, 2004 ... A true comparison between the plant and animal phenotype would be a comparison between plants and sessile photo-synthesizing colonial invertebrates. Such comparisons are lacking. However, they would provide important insights into the adaptive significance of plasticity in these groups. It is also ...

  13. Milder phenotypes of glucose transporter type 1 deficiency syndrome

    NARCIS (Netherlands)

    Anand, G.; Padeniya, A.; Hanrahan, D.; Scheffer, H.; Zaiwalla, Z.; Cox, D.; Mann, N.; Hewertson, J.; Price, S.; Nemeth, A.; Arsov, T.; Scheffer, I.; Jayawant, S.; Pike, M.; McShane, T.

    2011-01-01

    Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a treatable condition resulting from impaired glucose transport into the brain. The classical presentation is with infantile-onset epilepsy and severe developmental delay. Non-classical phenotypes with movement disorders and early-onset

  14. Language Phenotypes and Intervention Planning: Bridging Research and Practice

    Science.gov (United States)

    Fidler, Deborah J.; Philofsky, Amy; Hepburn, Susan L.

    2007-01-01

    This paper focuses on the communication and language phenotypes associated with three genetic disorders: Down syndrome, Williams syndrome, and fragile X syndrome. It is argued that there is empirical evidence that these disorders predispose children to specific profiles of strength and weakness in some areas of speech, language, and communication,…

  15. Near-fatal asthma phenotype in the ENFUMOSA Cohort

    NARCIS (Netherlands)

    Romagnoli, M.; Caramori, G.; Braccioni, F.; Ravenna, F.; Barreiro, E.; Siafakas, N. M.; Vignola, A. M.; Chanez, P.; Fabbri, L. M.; Papi, A.; Bel, E. H.

    2007-01-01

    BACKGROUND: Near-fatal asthma (NFA) is characterized by severe asthma attacks usually requiring intensive care unit admission. This phenotype of asthma has been studied mainly in acute conditions. METHODS: The aim of our study was to compare the clinical, functional and inflammatory characteristics

  16. Evaluation of Post-Operative Antibiotic Administration on Phenotypic ...

    African Journals Online (AJOL)

    But baseline data to judge effects of long-term post-operative antibiotic administration in clinical and surgical canine health conditions are currently lacking in Nigeria. This study aimed at providing vital baseline antibiotic profiles of canine bacteria of veterinary and public health importance. Phenotypic antibiotic susceptibility ...

  17. maxillofacial and mandibular phenotypes in the skulls of red sokoto ...

    African Journals Online (AJOL)

    James

    SUMMARY. This work examined phenotypic expressions in the anatomy of the mandible and maxillofacial region of the Red Sokoto and Sahel goats in Nigeria. The infraorbital foramen was placed above premolar two (PM2) in Red Sokoto but above premolar one. (PM1) in Sahel. The Red Sokoto displayed interdigital ...

  18. Genetic analysis of antibiotic production and other phenotypic traits ...

    African Journals Online (AJOL)

    So, the present study made an attempt to study the genetics of production of antibiotic and other phenotypic properties was demonstrated by plasmid DNA curing analysis. The DNA-intercalating agent ethidium bromide was used to eliminate plasmid DNA from streptomycetes and effects of curing agent (EB) on the antibiotic ...

  19. Phenotypic and molecular characterization of six Sudanese camel ...

    African Journals Online (AJOL)

    The objective of this study was to sequence the growth hormone (GH) gene in Sudanese camel breeds (Kenani, Lahwee, Rashaidi, Anafi, Bishari and Kabbashi) searching for single nucleotide polymorphisms (SNPs) and contribute to the phenotypic characterization of the multitude of camel ecotypes in Sudan. This will also ...

  20. Estimate of genetic and phenotypic parameters for litter size and ...

    African Journals Online (AJOL)

    Data on 964 and 1150 weaning weight and litter size records respectively, collected over a 10-year period on Yankasa Sheep breeding project at the National Animal Production Research Institute (N.A.P.R.I.), Zaria, were used in this study. The analysis was for estimation of genetic and phenotypic parameters for litter size ...

  1. Phenotypic and nuclear DNA variation in Tunisian cultivars of date ...

    African Journals Online (AJOL)

    The aim of this study was to assess the morphological diversity of the five most important and widely consumed Tunisian date palm (Phoenix dactylifera L.) cultivars and the possible relationship between phenotypic variation and genome size and ploidy, since polyploidy can occur in this species. Five Tunisian palm date ...

  2. Modulating the ecology and phenotype of in vitro oral biofilms

    NARCIS (Netherlands)

    Janus, M.M.

    2017-01-01

    Chapter 2 describes the development of a complex healthy biofilm model compared to a cariogenic biofilm model and a biofilm model for periodontal disease. The addition of different nutrients and different incubation times were used to create phenotypically different biofilms. These in vitro models

  3. Phenotypic correlations between egg weight and some egg quality ...

    African Journals Online (AJOL)

    Eggs were examined for both internal and external egg quality traits.Data obtained were subjected to one-way analysis of variance using the general linear procedure of SAS (2012). Differences in means were ranked using the Duncan's multiple Range test. Phenotypic correlations between egg weight and other egg quality ...

  4. Phenotypic Correlations of Backfat Thickness with Meatiness Traits ...

    African Journals Online (AJOL)

    The aim of the present study was to determine the phenotypic correlations of backfat thickness with meatiness traits and intramuscular fat, cholesterol and fatty acid composition in the longissimus muscle of pigs. For this study, 60 barrows and 60 gilts (Pietrain × Duroc boars and Polish Large White crossbred sows) were ...

  5. Dystrophic Cardiomyopathy: Complex Pathobiological Processes to Generate Clinical Phenotype

    Directory of Open Access Journals (Sweden)

    Takeshi Tsuda

    2017-09-01

    Full Text Available Duchenne muscular dystrophy (DMD, Becker muscular dystrophy (BMD, and X-linked dilated cardiomyopathy (XL-DCM consist of a unique clinical entity, the dystrophinopathies, which are due to variable mutations in the dystrophin gene. Dilated cardiomyopathy (DCM is a common complication of dystrophinopathies, but the onset, progression, and severity of heart disease differ among these subgroups. Extensive molecular genetic studies have been conducted to assess genotype-phenotype correlation in DMD, BMD, and XL-DCM to understand the underlying mechanisms of these diseases, but the results are not always conclusive, suggesting the involvement of complex multi-layers of pathological processes that generate the final clinical phenotype. Dystrophin protein is a part of dystrophin-glycoprotein complex (DGC that is localized in skeletal muscles, myocardium, smooth muscles, and neuronal tissues. Diversity of cardiac phenotype in dystrophinopathies suggests multiple layers of pathogenetic mechanisms in forming dystrophic cardiomyopathy. In this review article, we review the complex molecular interactions involving the pathogenesis of dystrophic cardiomyopathy, including primary gene mutations and loss of structural integrity, secondary cellular responses, and certain epigenetic and other factors that modulate gene expressions. Involvement of epigenetic gene regulation appears to lead to specific cardiac phenotypes in dystrophic hearts.

  6. Patterns of genetic structure and phenotypic diversity in sorghum ...

    African Journals Online (AJOL)

    Multivariate QSTand FSTvalues revealed two subgroups of quantitative traits that underwent either stabilizing or divergent selection among MG scale. These results underline the role of farmer practices in phenotypic and genetic evolution of sorghum. This concept should be well considered in sorghum breeding programs.

  7. A standardized clinical evaluation of phenotypic diversity in diabetic polyneuropathy.

    Science.gov (United States)

    Scholz, Joachim; Rathmell, James P; David, William S; Chad, David A; Broderick, Alithia C; Perros, Stephen G; Shin, Naomi S; Wells, Jenna L; Davis, John B; DiMaggio, Charles J; Wang, Shuang; Tate, Simon N

    2016-10-01

    Diabetic polyneuropathy (DPN) is a major cause of neuropathic pain and a frequent target condition in analgesic treatment trials. Differences in the clinical symptoms and signs associated with DPN suggest distinct pathophysiological mechanisms underlying nerve damage and dysfunction that are likely to have therapeutic relevance. The aim of this study was to develop a tool for the bedside assessment of painful neuropathies such as DPN that captures the diversity of phenotypes. Sixty-one patients with type 2 diabetes and painful neuropathy, 19 patients with painless DPN, 25 patients with type 2 diabetes but no clinical evidence of neuropathy, and 20 healthy control subjects completed a structured interview (47 items) and a standardized physical examination (39 items). After analyzing critical features of pain and painless symptoms and examining the outcome of physical tests of sensory function, we determined principal components of the phenotypic variance among patients. Increased sensitivity to mechanical or thermal stimuli and, to a lesser extent, the sensory quality of pain or paresthesia were the most discriminating elements of DPN phenotypes. Correlation patterns of symptoms and signs indicated the involvement of functionally distinct nerve fiber populations. We combined interview questions and physical tests identifying these differences in a shortened assessment protocol that we named Standardized Evaluation of Pain and Somatosensory Function (StEPS). The protocol StEPS generates a phenotypic profile of patients with neuropathy. Separate intensity ratings for spontaneous painful symptoms and pain evoked by standard stimuli support a detailed documentation of neuropathic pain and its response to analgesic treatment.

  8. Thermal phenotypic plasticity of body size in Drosophila ...

    Indian Academy of Sciences (India)

    Thermal phenotypic plasticity of body size in Drosophila melanogaster: sexual dimorphism and genetic correlations. Jean R. David Amir Yassin ... Thirty isofemale lines collected in three different years from the same wild French population were grown at seven different temperatures (12–31°C). Two linear measures, wing ...

  9. Phenotypic Correlations of Body Weight and Linear Body Traits in ...

    African Journals Online (AJOL)

    Data on 126 Sigmond strain of Japanese quail chicks consisting of 42 each of heavy, medium and low body weight lines were used to estimate phenotypic correlations (rp ) among body weight (BWT) and linear body traits at 2, 4 and 6 weeks of age. The linear body traits considered were breast girth (BG), shank length (SL), ...

  10. Genetic Mechanisms Involved in the Phenotype of Down Syndrome

    Science.gov (United States)

    Patterson, David

    2007-01-01

    Down syndrome (DS) is the most common genetic cause of significant intellectual disability in the human population, occurring in roughly 1 in 700 live births. The ultimate cause of DS is trisomy of all or part of the set of genes located on chromosome 21. How this trisomy leads to the phenotype of DS is unclear. The completion of the DNA…

  11. Plasticity of airway smooth muscle phenotype in airway remodeling

    NARCIS (Netherlands)

    Gosens, Reinoud

    2004-01-01

    Isolated smooth muscle cells in culture do not immediately start dividing, even in a medium containing all nutrients required. Before entering the cell cycle, the cells first accomodate their phenotype to their new environment. They lose their contractile properties and modulate to a proliferative

  12. Determination of Isoniazid Acetylator Phenotype and its Clinical ...

    African Journals Online (AJOL)

    After a 2-month treatment of the TB patients, the sputum smear cultures were negative in about 81% independent of the acetylator or HIV status. Early side effects experienced were dominated by peripheral neuropathies mostly in slow and intermediate acetylators. Key words: Acetylator, isoniazid, phenotype, tuberculosis, ...

  13. Phenotypic plasticity of body size in a temperate population of ...

    Indian Academy of Sciences (India)

    Phenotypic plasticity was analysed after development at seven different constant temperatures, ranging from 12°C to 31°C. The three year samples exhibited similar reaction norms, suggesting a stable genetic architecture in the natural population. The whole sample (30 lines) was used to determine precisely the shape of ...

  14. Supplementary data: Genotype–phenotype relationship of F7 ...

    Indian Academy of Sciences (India)

    Genotype–phenotype relationship of F7 R353Q polymorphism and plasma FVII.c levels in Asian Indian families predisposed to coronary artery disease. Jayashree Shanker, Ganapathy Perumal, Arindam Maitra, Veena S. Rao, B. K. Natesha, Shibu John,. Sridhar Hebbagodi and Vijay V. Kakkar. J. Genet. 88, 291–297.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  16. Muscle phenotype in patients with myotonic dystrophy type 1

    DEFF Research Database (Denmark)

    Andersen, Grete; Orngreen, Mette C; Preisler, Nicolai

    2013-01-01

    Introduction: The pathogenesis of muscle involvement in patients with myotonic dystrophy type 1 (DM1) is not well understood. In this study, we characterized the muscle phenotype in patients with confirmed DM1. Methods: In 38 patients, muscle strength was tested by hand-held dynamometry. Myotonia...

  17. Cell phenotypes, immunoglobulins and complement in lesions of ...

    African Journals Online (AJOL)

    ... stained positive for CD68. Type III reaction consisted of a discrete epithelioid granuloma without wellformed grains. IgG, IgM and C3 were found on the surface of the grain and the hyphae . Keywords: Madurella mycetomatis lesion, cell phenotypes, immunoglobulins, complement. Sudanese Journal of Dermatology Vol.

  18. Original Paper Patterns of genetic structure and phenotypic diversity ...

    African Journals Online (AJOL)

    Diversity levels in ten local sorghum guinea varieties (25 panicles per variety) collected from different farms in ... results underline the role of farmer practices in phenotypic and genetic evolution of sorghum. This concept should be well considered ... varietal needs and preferences: applying research station-based breeding ...

  19. 3. Phenotypic Characteristics of Zambian patients with Parkinson's

    African Journals Online (AJOL)

    Esem

    ABSTRACT. Objective: To describe the phenotypic characteristics of adult Zambian patients with newly diagnosed Parkinson's disease (PD) at University Teaching Hospital (UTH). Background: The genetic basis of idiopathic Parkinson's disease is remains unknown. Little information is available regarding the genotype and ...

  20. Phenotypic and genetic diversification of Pseudanabaena spp. (cyanobacteria)

    NARCIS (Netherlands)

    Acinas, S.G.; Haverkamp, T.H.A.; Huisman, J.; Stal, L.J.

    2009-01-01

    Pseudanabaena species are poorly known filamentous bloom-forming cyanobacteria closely related to Limnothrix. We isolated 28 Pseudanabaena strains from the Baltic Sea (BS) and the Albufera de Valencia (AV; Spain). By combining phenotypic and genotypic approaches, the phylogeny, diversity and

  1. Dissecting the correlation structure of a bivariate phenotype ...

    Indian Academy of Sciences (India)

    Unknown

    We use Monte-Carlo simulations to evaluate the performance of the proposed test under different trait parameters and quantitative trait distributions. An application of the method is illustrated using data on two alcohol-related phenotypes from a project on the collaborative study on the genetics of alcoholism. [Ghosh S 2005 ...

  2. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

    NARCIS (Netherlands)

    Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

    1999-01-01

    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia

  3. Method for restoration of normal phenotype in cancer cells

    Science.gov (United States)

    Bissell, Mina J.; Weaver, Valerie M.

    2000-01-01

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

  4. Thermal phenotypic plasticity of body size in Drosophila melanogaster

    Indian Academy of Sciences (India)

    2011-08-19

    Aug 19, 2011 ... 2006a), we analysed the phenotypic plasticity of a French population by considering three different samples, each of 10 isofemale lines collected in three different years. This paper was mostly dedicated to the analysis of the shapes of the reaction norms of two size traits, wing and thorax length, and of their ...

  5. Phenotypic correlations between wool traits of a Dohne Merino flock

    African Journals Online (AJOL)

    Merino's as determined by Brorvn & Turner (1968), Turner. & Young (1969) as well as Heydenrych (1975). Clean fleece production proved to have a slightly higher relationship than greasy fleece mass with bodymass (r : 0,32, P s 0,01). The phenotypic correlation between staple length and clean wool production was 0,30, ...

  6. How phenotypic plasticity made its way into molecular biology

    Indian Academy of Sciences (India)

    2009-08-03

    Aug 3, 2009 ... Although opposed by the reductionist and deterministic approach of molecular biology, phenotypic plasticity has nevertheless recently made its way into this discipline, in particular through the limits of the molecular description. Its resurrection has been triggered by a small group of theoreticians, the rise of ...

  7. A Computational Study of Phenotype Switching in Bacillus Subtilis Biofilm

    Science.gov (United States)

    Smith, Howard; Wang, Xiaoling; Jiang, Yi

    Bacillus Subtilis (B. Subtilis), is known to differentiate into three main phenotypes during biofilm growth. Novel techniques to track the spatial and temporal evolution of the three main phenotypes exhibited by B. Subtilis have been developed. However, the techniques do not explain the environmental causes of the phenotype switching and how this leads to the spatiotemporal organization of the biofilm. We hypothesize that cells switch their phenotype according to nutrients and autoinducer levels. We test the hypothesis using a hybrid agent-based and continuous model. The bacteria in our model are individual cells that can (i) grow and divide by the intake of nutrients, (ii) produce and secrete EPS, (iii) form spores and (iv) produce an auto inducer. Using a threshold for nutrient and thresholds for autoinducers, we were able to reproduce the experimental spatiotemporal dynamics. From our simulations we observed that in order to reproduce experimental results, two different autoinducers were necessary. The results also suggest that low-EPS producing biofilms generally obtained higher cell populations. Furthermore, most of the cells that become spore forming cells arise from matrix producing cells.

  8. Study on common phenotypic traits for purchasing sheep and their ...

    African Journals Online (AJOL)

    A study was conducted in 2008 to assess the relationship between common phenotypic traits most considered for marketing sheep and the body weight and price of sheep at markets of four towns in East Showa zone. Six hundred randomly selected sheep purchased for various purposes were studied. The study methods ...

  9. Thoracic Outlet Syndrome: A Significant Family Genetic Phenotypic Presentation.

    Science.gov (United States)

    Janák, David; Novotný, Karel; Roček, Miloslav; Rohn, Vilém

    We report on a very rare case of diagnosis and successful surgical treatment of three young family members with a four-fold presentation of thoracic outlet syndrome. In the relevant family case, we are considering and discussing the population incidence, a possible HOX genes disorder, and a significant phenotypic presentation.

  10. Sickle cell disease clinical phenotypes in children from South ...

    African Journals Online (AJOL)

    More children with a history of asthma had ACS. Furthermore, high steady.state white blood cell count was associated with severe disease. Conclusion: The clinical phenotypes of SCD in children from South.Western Nigeria are highly variable with the disease manifesting very early and about 10% having significant ...

  11. Phenotypic and genotypic screening of rice genotypes at seedling ...

    African Journals Online (AJOL)

    Selection for salinity tolerance genotypes of rice based on phenotypic performance alone is less reliable and will delay progress in breeding. Recent advent of molecular markers, microsatellites or simple sequence repeats (SSRs) are used to find out salt tolerant rice genotypes. Three selected SSR markers; RM7075, ...

  12. Phenotype in 18 Danish subjects with genetically verified CHARGE syndrome

    DEFF Research Database (Denmark)

    Husu, E; Hove, Hd; Farholt, Stense

    2013-01-01

    problems (12/15) were other frequent cranial nerve dysfunctions. Three-dimensional reconstructions of MRI scans showed temporal bone abnormalities in >85%. CHARGE syndrome present a broad phenotypic spectrum, although some clinical features are more frequently occurring than others. Here, we suggest...

  13. How phenotypic plasticity made its way into molecular biology

    Indian Academy of Sciences (India)

    Prakash

    also to internal variations such as those resulting from gene mutations (Morange 2001). On the other hand, phenotypic plasticity can generate a huge change in the properties of an organism in response to moderate changes in the environment. In the latter case, it can generate alternative states, a phenomenon described ...

  14. Estimating genetic correlations based on phenotypic data: a ...

    Indian Academy of Sciences (India)

    effects. [Zintzaras E. 2011 Estimating genetic correlations based on phenotypic data: a simulation-based method. J. Genet. 90, 51–58]. Introduction. The evolutionary ... Also affiliated to Institute for Clinical. Research and Health Policy Studies, Tufts Medical Center, Tufts University. School of Medicine, 800 Washington Street, ...

  15. Disease phenotype at diagnosis in pediatric Crohn's disease

    DEFF Research Database (Denmark)

    de Bie, Charlotte I; Paerregaard, Anders; Kolacek, Sanja

    2013-01-01

    It has been speculated that pediatric Crohn's disease (CD) is a distinct disease entity, with probably different disease subtypes. We therefore aimed to accurately phenotype newly diagnosed pediatric CD by using the pediatric modification of the Montreal classification, the Paris classification....

  16. Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype.

    NARCIS (Netherlands)

    Guyant-Marechal, L.; Verrips, A.; Girard, C.; Wevers, R.A.; Zijlstra, F.; Sistermans, E.A.; Vera, P.; Campion, D.; Hannequin, D.

    2005-01-01

    Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disease caused by a deficiency of the mitochondrial enzyme 27-sterol hydroxylase (CYP27). We report a 53-year-old man, with an unusual phenotype of CTX. He had xanthomas since adolescence. He had no mental retardation and

  17. Phenotype prediction for mucopolysaccharidosis type I by in silico analysis.

    Science.gov (United States)

    Ou, Li; Przybilla, Michael J; Whitley, Chester B

    2017-07-04

    Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease due to deficiency of α-L-iduronidase (IDUA), a lysosomal enzyme that degrades glycosaminoglycans (GAG) heparan and dermatan sulfate. To achieve optimal clinical outcomes, early and proper treatment is essential, which requires early diagnosis and phenotype severity prediction. To establish a genotype/phenotype correlation of MPS I disease, a combination of bioinformatics tools including SIFT, PolyPhen, I-Mutant, PROVEAN, PANTHER, SNPs&GO and PHD-SNP are utilized. Through analyzing single nucleotide polymorphisms (SNPs) by these in silico approaches, 28 out of 285 missense SNPs were predicted to be damaging. By integrating outcomes from these in silico approaches, a prediction algorithm (sensitivity 94%, specificity 80%) was thereby developed. Three dimensional structural analysis of 5 candidate SNPs (P533R, P496R, L346R, D349G, T374P) were performed by SWISS PDB viewer, which revealed specific structural changes responsible for the functional impacts of these SNPs. Additionally, SNPs in the untranslated region were analyzed by UTRscan and PolymiRTS. Moreover, by investigating known pathogenic mutations and relevant patient phenotypes in previous publications, phenotype severity (severe, intermediate or mild) of each mutation was deduced. Collectively, these results identified potential candidate SNPs with functional significance for studying MPS I disease. This study also demonstrates the effectiveness, reliability and simplicity of these in silico approaches in addressing complexity of underlying genetic basis of MPS I disease. Further, a step-by-step guideline for phenotype prediction of MPS I disease is established, which can be broadly applied in other lysosomal diseases or genetic disorders.

  18. Noise-induced Min phenotypes in E. coli.

    Directory of Open Access Journals (Sweden)

    David Fange

    2006-06-01

    Full Text Available The spatiotemporal oscillations of the Escherichia coli proteins MinD and MinE direct cell division to the region between the chromosomes. Several quantitative models of the Min system have been suggested before, but no one of them accounts for the behavior of all documented mutant phenotypes. We analyzed the stochastic reaction-diffusion kinetics of the Min proteins for several E. coli mutants and compared the results to the corresponding deterministic mean-field description. We found that wild-type (wt and filamentous (ftsZ- cells are well characterized by the mean-field model, but that a stochastic model is necessary to account for several of the characteristics of the spherical (rodA- and phospathedylethanolamide-deficient (PE- phenotypes. For spherical cells, the mean-field model is bistable, and the system can get trapped in a non-oscillatory state. However, when the intrinsic noise is considered, only the experimentally observed oscillatory behavior remains. The stochastic model also reproduces the change in oscillation directions observed in the spherical phenotype and the occasional gliding of the MinD region along the inner membrane. For the PE- mutant, the stochastic model explains the appearance of randomly localized and dense MinD clusters as a nucleation phenomenon, in which the stochastic kinetics at low copy number causes local discharges of the high MinD(ATP to MinD(ADP potential. We find that a simple five-reaction model of the Min system can explain all documented Min phenotypes, if stochastic kinetics and three-dimensional diffusion are accounted for. Our results emphasize that local copy number fluctuation may result in phenotypic differences although the total number of molecules of the relevant species is high.

  19. Inflammatory genes and psychological factors predict induced shoulder pain phenotype.

    Science.gov (United States)

    George, Steven Z; Parr, Jeffrey J; Wallace, Margaret R; Wu, Samuel S; Borsa, Paul A; Dai, Yunfeng; Fillingim, Roger B

    2014-10-01

    The pain experience has multiple influences, but little is known about how specific biological and psychological factors interact to influence pain responses. The current study investigated the combined influences of genetic (pro-inflammatory) and psychological factors on several preclinical shoulder pain phenotypes. An exercise-induced shoulder injury model was used, and a priori selected genetic (IL1B, TNF/LTA region, and IL6 single nucleotide polymorphisms (SNP)) and psychological (anxiety, depression symptoms, pain catastrophizing, fear of pain, and kinesiophobia) factors were included as the predictors of interest. The phenotypes were pain intensity (5-d average and peak reported on numerical rating scale), upper extremity disability (5-d average and peak reported on the Quick Disabilities of the Arm, Shoulder and Hand instrument), and duration of shoulder pain (d). After controlling for age, sex, and race, the genetic and psychological predictors were entered separately as main effects and interaction terms in regression models for each pain phenotype. Results from the recruited cohort (n = 190) indicated strong statistical evidence for the interactions between 1) TNF/LTA SNP rs2229094 and depression symptoms for average pain intensity and duration and 2) IL1B two SNP diplotype and kinesiophobia for average shoulder pain intensity. Moderate statistical evidence for prediction of additional shoulder pain phenotypes included interactions of kinesiophobia, fear of pain, or depressive symptoms with TNF/LTA rs2229094 and IL1B. These findings support the combined predictive ability of specific genetic and psychological factors for shoulder pain phenotypes by revealing novel combinations that may merit further investigation in clinical cohorts to determine their involvement in the transition from acute to chronic pain conditions.

  20. Population dynamics of metastable growth-rate phenotypes.

    Directory of Open Access Journals (Sweden)

    Lindsay S Moore

    Full Text Available Neo-Darwinian evolution has presented a paradigm for population dynamics built on random mutations and selection with a clear separation of time-scales between single-cell mutation rates and the rate of reproduction. Laboratory experiments on evolving populations until now have concentrated on the fixation of beneficial mutations. Following the Darwinian paradigm, these experiments probed populations at low temporal resolution dictated by the rate of rare mutations, ignoring the intermediate evolving phenotypes. Selection however, works on phenotypes rather than genotypes. Research in recent years has uncovered the complexity of genotype-to-phenotype transformation and a wealth of intracellular processes including epigenetic inheritance, which operate on a wide range of time-scales. Here, by studying the adaptation dynamics of genetically rewired yeast cells, we show a novel type of population dynamics in which the intracellular processes intervene in shaping the population structure. Under constant environmental conditions, we measure a wide distribution of growth rates that coexist in the population for very long durations (>100 generations. Remarkably, the fastest growing cells do not take over the population on the time-scale dictated by the width of the growth-rate distributions and simple selection. Additionally, we measure significant fluctuations in the population distribution of various phenotypes: the fraction of exponentially-growing cells, the distributions of single-cell growth-rates and protein content. The observed fluctuations relax on time-scales of many generations and thus do not reflect noisy processes. Rather, our data show that the phenotypic state of the cells, including the growth-rate, for large populations in a constant environment is metastable and varies on time-scales that reflect the importance of long-term intracellular processes in shaping the population structure. This lack of time-scale separation between the